# Ergot spores



## Token (Aug 16, 2008)

Is there any place that sells them, or can you buy/grow ray and put it in a place with really high humidity and see if it grows?


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## nashbar (Aug 17, 2008)

not gonna happen

buy lsd like everyone does


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## Capita (Aug 19, 2008)

fucking around with ergot fungus is very very dangerous and can kill you.. and to grow cultures large enough to use for lsd you have to have to grow it in a sterile room in a pea tree dish.. much more equipment and work than a reg person would have


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## Token (Aug 20, 2008)

But it would be worth it to learn yet another trade. Try growing the fungus an another house for safety. Or can you synthesis it from lsa?


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## nashbar (Aug 20, 2008)

i encourage you to prove me wrong. please, keep me posted on your progress.

aside from any dangers and pitfalls you might come across...

1. you'll never find ergot spores
2. you'll never isolate ergot fungi
3. you'll never grow any substantial amoutn of fungal matter
4. you'll never be able to extract ergot alkaloids
5. you'll never have the chemicals to process the alkaloids to LSD
6. you'll never have the equipment to process the alkaloids
7. you'll never have the conditions to process the alkaloids

this is all assuming you actually know what you're doing with chemistry, actual chemistry, not the anarchists cookbook or whatever method you would follow.

as for LSA, #3-#7 apply, substituting ergot for morning glory or whatever seeds you're thinking.

i'll give you a hint, google "ergotamine tartrate". move to a third world country, buy as much as you want and then start dabbling in chemical synthesis.

really, i fully support your efforts. you WILL fail, but you'll probably learn something.


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## OnEcrazysoul (Aug 20, 2008)

The knowledge would be good but I don't think it would be worth it imo. I am not sure about the lsa, but I am pretty sure you cant.


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## OnEcrazysoul (Aug 20, 2008)

nashbar said:


> i encourage you to prove me wrong. please, keep me posted on your progress.
> 
> aside from any dangers and pitfalls you might come across...
> 
> ...


Sometimes the truth hurts...


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## kdox88 (Aug 21, 2008)

lol, many lives have been lost to ergot. i believe it feeds on grains and was the reason for many deaths back in the day, i mean way back.
try using Hawaiian baby woodrose seeds. you can get lsa fairly easily as for lsd, unless you are a top notch chemist you'll probably end up fucking up horribly. the chemicals involved are very dangerous, you could end up with some sort of poisoning, catch something on fire, blow something up, or producing something that will kill or sicken any person who ingests it. not to mention the cost of supplies, that shit can be outrageously expensive.


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## Token (Aug 21, 2008)

kdox88 said:


> lol, many lives have been lost to ergot. i believe it feeds on grains and was the reason for many deaths back in the day, i mean way back.
> try using Hawaiian baby woodrose seeds. you can get lsa fairly easily as for lsd, unless you are a top notch chemist you'll probably end up fucking up horribly. the chemicals involved are very dangerous, you could end up with some sort of poisoning, catch something on fire, blow something up, or producing something that will kill or sicken any person who ingests it. not to mention the cost of supplies, that shit can be outrageously expensive.


I've already done that and sold the lsa extract for 70 bucks for like 15 hit's lift, I've already got a half ass lab set up until I move then I can set up a real one when I get into my house, lately I've been doing dmt lsa mescaline opium morphine codeine and ephedrine extraction, so I do know little bit about chemistry and organic chemistry!

also I remember when I was in the UK that one of the lords wife ate some bread with ergot in it and tripped, riding her horse through the town naked, so It can't be that bad to grow some. 

ps I've never read the anarchist cook book, I found listening to your parents/family can be very helpful.

I'm just going to keep doing research til i fill ready to embark on this adventure


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## kdox88 (Aug 21, 2008)

Token said:


> I've already done that and sold the lsa extract for 70 bucks for like 15 hit's lift, I've already got a half ass lab set up until I move then I can set up a real one when I get into my house, lately I've been doing dmt lsa mescaline opium morphine codeine and ephedrine extraction, so I do know little bit about chemistry and organic chemistry!
> 
> also I remember when I was in the UK that one of the lords wife ate some bread with ergot in it and tripped, riding her horse through the town naked, so It can't be that bad to grow some.
> 
> ...


producing lsd is alot more difficult than extractions.
this might help you.
Erowid Online Books : "TIHKAL" - #26 LSD-25
or try this site
LSD-25 Synthesis
u might want to take some chemistry classes.... alot of chemistry classes
it really takes an expert chemist.
think about it. if it were easy everyone would do it themselves. since the active dose is so small and if a bunch of people made it, it would be everywhere. that is why their are only a few chemists who cook up some lsd. it is difficult.


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## Token (Aug 21, 2008)

I think I would need a few more chemicals and a organic chemistry class and I got this.


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## TreeMoss (Oct 29, 2008)

I think you could pull it off and someone saying not so is not being very cool (just thinking he is by thinking it is impossible).

A good bit of the worship for me with drugs is no longer worshiping or holding as an idol those that can provide for me what I can not, so even pharmi companies are something I'd rather not rely on.

Sure, you could isolate and keep pure Ergot for growth; any fungus can be contained and controlled in an environment.

Having the ergot tartrate pre made cuts down your work a great deal, since growing the fungus and seperating the alkaloid that you want (I do think there are several as nature travels with pals).

Ergot isn't that dangerous if you aren't putting the solution that you are growing it in into squirt guns and playing I'm on fire tripping till someone becomes toxic, or eating the stuff.

Not that it's good lab procedure to spill anything on yourself, but even a drop wouldn't be the end of your life (just a little uneasy for awhile). Anyone who knows good lab safety can have a good result, sadly I would never try (a good thing, only sad since it cost a lot of money) to provide the very costly equipment to varify results (just having crystals emit light when shaken in the dark is a fine and dandy test but uncertian on the way to that point if you are no pro learning the ropes).

A mass spec and what it takes to isolate the alkaloid from the ergot you desire (some form of chromatographer I am not sure whitch) are hard to come by if you aren't in college or don't have lab access with freedom to preform such an illegal operation.

they aren't illegal to obtain although a bit sketchy to have at a "in the dark" lab but nobody is really watching those and really are costly but not impossible to invest in.

The ammount of chemicals you could make with those two forms of equipment is simply huge right now and not getting smaller.

Don't get me wrong, having some of this stuff is way cool and not to show off so it's not like showing a pot plant to a "friend"....more like a life investment for small personal batches of what ever...hell, you could by a nice car or a down payment on a house for what it cost to own these fancy toys (well, not a toy but as we grow older they are; just not for kids to tinker with and break).

Face it, an ergot tartrate maker in the US underground has a good start; nothing to get caught with crossing the border (that is a doulbe no no). Basically mafia type things moved most of that in the past and not everyone wants to rely on such motives....more interested in the fundamentals than simply production and making money (which some did quite good with apparently before getting caught).


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## ballo (Oct 29, 2008)

nice...my sister has told me a little bit about ergot and shes actually majoring in molecular biology and one the pre req's is organic chemistry...i wonder if she'll know whats up lol


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## TreeMoss (Nov 2, 2008)

Wow, for some stupid reason I never knew untill a few weeks ago that she actually fruits little mushrooms. I guess I never heard that much in popular culture, plus it's a real damn shame that we forget to tell very often that LSD comes from ERgot....it's not really a chemy.......something just wiped up in a labatory with no roots back to nature........and that is everything to me, well; not much more than understanding the affects and how there is safe uses.

I wish I knew as much as my brother in law, he's damn close to becoming a Professer in Organic Chem...Phd and all that (could make anything known to man perfectly with that kind of experience.)


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## Funnyfunguy (May 23, 2013)

Capita said:


> fucking around with ergot fungus is very very dangerous and can kill you.. and to grow cultures large enough to use for lsd you have to have to grow it in a sterile room in a pea tree dish.. much more equipment and work than a reg person would have



Shameless necro: 

This is patently false. Most Claviceps fungus species do not produce the precursor alkaloids when cultured on a medium. In the experiments detailed in _Proceedings of the Royal Society ofLondon, Series B, Volume 155, pages 26 to 54 (1961) and USPatent 3,219,545 _they explain that they had to search high and low for the unique varieties That are capable of producing the right chemicals while being cultured. Successful LSD production would include cropping a field of rye and infecting the flowers with a solution of liquid culture generated from ergot collected in the wild. The isolated chunks of ergot would need to be winterized prior to spawning into a terrarium. If you don't cool the ergot it will not germinate. At this point it's very similar to growing regular mushrooms, which is the goal. Once the tiny mushrooms grow and reach maturation they are picked just before exploding (thus releasing spores). At this point the fruit is moved to a sterile environment, such as a still air box, a shmuvbox or a flow hood. The cap is lanced, while suspended over a piece of sterile glass, such as a lens slide. A liquid culture medium is created, sterilized by pressure cooking, and inoculated with the spores. The result is a jug of germinated spores looking for a rye plant to infect. Load the mixture into a spray tank (think a pump action tank you can carry around with a misting wand). Dilute down and spray the flowers in your target field of rye with the liquid culture and wait. When it's time to harvest, use an old school sickle so you don't lose your crop to a combine (can break up the pieces prematurely and cause yield loss). Once you have everything gathered, shake the ergot off each stalk and put aside. The yield must be dried immediately to prevent loss due to mold. Once dried it will keep for a little while, but should be utilized ASAP. Big time growers will have 1-2 acres dedicated strictly to growing rye so they have a constant supply of the important alkaloid precursor.

Info is from uncle fester's guide which is a great read if you haven't checked it out.


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## rory420420 (May 23, 2013)

Hahaha...I'm not a scientist,chemist..I have background education...I don't know you,or your background/knowledge...you may be the next mensa god for all I know..what I also know is unless you got MAD $$$$ then this is a pipe dream in an aspect..althogh obtainable(I seen a precurser for mdma in a shampoo formula the other day)..its highly unlikely you will achieve chemicals synth..but I salute your effort and hope you achieve your goal!!!


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## rory420420 (May 24, 2013)

Uncle fester.....lol


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## rory420420 (May 24, 2013)

I'm 34,and disproved techs in his guide when I was 14 by asking my biology teacher in highschool..there is no need for wood alcohol in any extraction,let alone egot substance...not an expert but what I've learned..who knows?duck?


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## KushKrew (May 24, 2013)

Token said:


> I've already done that and sold the lsa extract for 70 bucks for like 15 hit's lift, I've already got a half ass lab set up until I move then I can set up a real one when I get into my house, lately I've been doing dmt lsa mescaline opium morphine codeine and ephedrine extraction, so I do know little bit about chemistry and organic chemistry!
> 
> also I remember when I was in the UK that one of the lords wife ate some bread with ergot in it and tripped, riding her horse through the town naked, so It can't be that bad to grow some.
> 
> ...


Dude do you have ANY CLUE how hardcore makin acid is? A half-assed lab?! Bro, you need to be kitted out with a vacuum-chamber just so your de-hydrating agent doesn't make stuff catch fire if it spills (yup). 

Don't talk SHIT nobody you know ate ergot and tripped bro, I don't believe it for a second. Ergot poisoning cuts off all circulation to the extremities resulting in severe pain akin to frostbite, the loss of limbs and such. Fingers falling off guy. There is absolutely NO way you can eat bread with ergot in it and go have a happy time. Not one that would make you want to go through it anyhow. 

Acid is so hard to make that the real deal is becoming harder to find than a good lab-grown DMT crystal. Mostly guys are eating weak-ass DOB paper and thinking 'whoooa strong acid'. Post 90's acid is a JOKE. Can't even give us PROPA DOB anymore, you know, hallucinations for 28 hours kinda TRIPPIN'

Let it go man, for your own health and safety. 

If you REALLY insist on Ergot, I can save your life for you. Dr Albert Hoffman himself isolated a pure LSA Ergot strain with no poisoning, whereby pretty much solving the mystery of the Eulysian Mystery Schools. It is found in a tiny area only, you'll find clues to how to find it in Graham Hancock's Supernatural. If you want ergot, don't be a douche and go about it all willy-nilly, you go poisoning yourself and your mates and it's BAD NEWS FOR THE REST OF US bro. 

The White Rabbit is one of the very very few to have cracked the 'code' and it is still Owlsley's methods being handed down in the circles than know. 

Children should stay away from matches is all I'm sayin'.


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## KushKrew (May 24, 2013)

And UNCLE FESTER??? LOL LOL LOL.....


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## MrEDuck (May 24, 2013)

I've found enough dangerous errors in Fester's work to not a trust a single thing he says. The man's book on LSD suggested that propionic anhydride was some secret reagent used in a synth of LSD because the reporting threshold was 1g like for the acid precursors. Ever hear of fentanyl uncle fester? It was around when you were cooking meth.
Kushkrew why the hell would someone want to use hydrazine to synthesize LSD? That procedure has been obsolete my entire life. Even SOCl2 or POCl3 is less dangerous. Peptide coupling reagents are the way to make LSD.


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## KushKrew (May 24, 2013)

Well I don't claim to know much about any form of chemistry, but I gave Fester's 'book' to a mate who was studying to become a chemical engineer... I didn't understand much of the banter at all, I could however gather that Uncle Fester is bit of a joke (it got passed around as a work of comedy) but little details like chemicals that make shit catch fire kinda stuck and made me think: This ain't no a/b extraction. Leave it be... 
So not claiming to know much, but I DO know that even trained (or in training) engineers found the idea less than feasible for them. All I can think in a case like that is what da fuk would a layman be doing even attempting it?...


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## KushKrew (May 24, 2013)

Acid is cheap enough to leave it to the pros, I have my source and will untill I die. And if it dries up I'm sure I'll find a new one, with some tenacity and a lot of psychedelic spirit


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## MrEDuck (May 24, 2013)

Well Bear never finished a degree in a chemical science, and managed to figure it out and teach Scully and Sand. It's still tedious and requires good lab technique and a fair amount of squinting because of the low light but it is doable for the self taught. Just not if they look to learn anything from Fester's books.


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## rory420420 (May 24, 2013)

The psychedelic community needs another silo.


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## MrEDuck (May 24, 2013)

Getting LSD precursors is no easy thing, especially in that kind of bulk. Not to mention the start up capital you need for an operation like that. I really doubt anyone would set up a shop like that in the US if they were building a new lab. Canada and Europe have far better laws if you get caught.


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## Moldy (May 24, 2013)

KushKrew said:


> Dude do you have ANY CLUE how hardcore makin acid is? A half-assed lab?! Bro, you need to be kitted out with a vacuum-chamber just so your de-hydrating agent doesn't make stuff catch fire if it spills (yup).
> 
> Don't talk SHIT nobody you know ate ergot and tripped bro, I don't believe it for a second. Ergot poisoning cuts off all circulation to the extremities resulting in severe pain akin to frostbite, the loss of limbs and such. Fingers falling off guy. There is absolutely NO way you can eat bread with ergot in it and go have a happy time. Not one that would make you want to go through it anyhow.
> 
> ...


Owsley's acid was supreme, never had anything come close except Sunshine / Orange crush came in about 1/2 as good. I only got it once in Estes Park, Co in the mid 60's. Never ever forget it either. It was more like a scary fun movie with all of the affects.


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## MrEDuck (May 24, 2013)

Owsley believed that his state of mind while performing the synthesis was the absolutely crucial point of the synthesis, and would probably have felt that was more important than the method followed by the chemist.


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## rory420420 (May 25, 2013)

Sunshine was ald52....id love to go blind squinting at an ounce of pure lsd...duck,any idea how/why the silo had axcess to the huge amount of these precursers? What are legitimate uses for these same chems/substances...evident that $ talks when it comes to these things,why else would the 90s be the subject of question when it comes to lsd manufacture/use...


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## MrEDuck (May 26, 2013)

Occam's razor says that it's because money talks. Ergotamine is used legitimately as a treatment for migraines but hasn't been common since the introduction of the tryptans, it's also used to make dihydroergotamine which is also used to treat migraines but can't be used to make LSD.


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## rory420420 (May 26, 2013)

Could the dihydro be be extracted to leave just ergotamine? Any ideas on how pickard obtained these precursers in such large quantities,or did he preform complete synthesis?


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## Damnecro (May 26, 2013)

Ergot is easily found growing on leftover rye grain/wheat spikes in several of the fields in the portland metro area begin looking after first good cooling rain in september - november. sterilized rye/wheat will cultivate the fungus just like setting up pftek for cubensis but use the grain.. Sure its dangerous, If your gonna wash the infected grain wear some safety equipment. be mindful of the contact toxicity of your extraction. oh and don't .... 


How to make LSA
Liquid LSD is merely dissolved crystal lsd, and the grain seed extract is LSA, not LSD.
(extracting D-lysergic acid amide) LSA
Items needed: 1. About 200 grams of infected grain
2. 200 cc. of petroleum ether (make sure it's PETROLEUM ether)
3. Small piece of window screen or strainer.
4. A couple of large glasses.
5. One old cookie tray.
6. 260 cc. of wood alcohol.
What to do:
1. Grind up about 170 grams of seeds. (Wash the seeds in water first)
2. In 145 cc. of petroleum ether, soak the seeds for two to three days.
3. With screen, filter the liquid and save the seed mush. Allow the mush to dry.
4. Let the mush soak in 130 cc. of wood alcohol for two days.
5. Filter the solution again. Save the liquid in a glass jar.
6. Soak the same mush again in another 130 cc. of wood alcohol for two more days.
7. Filter out the mush and throw it away. Save the liquid.
8. Now, pour both saved glass containers with the liquid in them, into a cookie sheet.
9. Let the liquid dry in to a yellowish gum.
Scrap the yellow gum into pill capsules and take. 

*lsa / lsd*
Arrange the lighting in the lab similarly to that of a dark room. Use photographic red and yellow safety lights,
as lysergic acid derivatives are decomposed when light is present. Rubber gloves must be worn due to the
highly poisonous nature of ergot alkaloids. A hair drier, or, better, a flash evaporator, is necessary to speed
up steps where evaporation is necessary.
Preparation #1
Step I. Use Yellow light
Place one volume of powdered ergot alkaloid material in a tiny roundbottom flask and add two volumes of
anhydrous hydrazine. An alternate procedure uses a sealed tube in which the reagents are heated at 112 C.
The mixture is refluxed (or heated) for 30 minutes. Add 1.5 volumes of H2O and boil 15 minutes. On cooling
in the refrigerator, isolysergic acid hydrazide is crystallised.
Step II. Use Red light
Chill all reagents and have ice handy. Dissolve 2.82 g hydrazine rapidly in 100 ml 0.1 N ice-cold HCl using
an ice bath to keep the reaction vessel at 0 C. 100 ml ice-cold 0.1 N NaNO2 is added and after 2 to 3
minutes vigorous stirring, 130 ml more HCl is added dropwise with vigorous stirring again in an ice bath.
After 5 minutes, neutralise the solution with NaHCO3 saturated sol. and extract with ether. Remove the
aqueous solution and try to dissolve the gummy substance in ether. Adjust the ether solution by adding 3 g
diethylamine per 300 ml ether extract. Allow to stand in the dark, gradually warming up to 20 C over a period
of 24 hours. Evaporate in vacuum and treat as indicated in the purification section for conversion of isolysergic
amides to lysergic acid amides.
Preparation #2
Step I. Use Yellow light
5.36 g of d-lysergic acid are suspended in 125 ml of acetonitrile and the suspension cooled to about -20 C in
a bath of acetone cooled with dry ice. To the suspension is added a cold (-20 C) solution of 8.82 g of
trifluoroacetic anhydride in 75 ml of acetonitrile. The mixture is allowed to stand at -20 C for about 1.5 hours
during which the suspended material dissolves, and the d-lysergic acid is converted to the mixed anhydride
of lysergic and trifluoroacetic acids. The mixed anhydride can be separated in the form of an oil by
evaporating the solvent in vacuo at a temperature below 0 C, but this is not necessary. Everything must be
kept anhydrous.
Step II. Use Yellow light
The solution of mixed anhydrides in acetonitrile from Step I is added to 150 ml of a second solution of
acetonitrile containing 7.6 g of diethylamine. The mixture is held in the dark at room temperature for about 2
hours. The acetonitrile is evaporated in vacuo, leaving a residue of LSD-25 plus other impurities. The residue
is dissolved in 150 ml of chloroform and 20 ml of ice water. The chloroform layer is removed and the
aqueous layer is extracted with several portions of chloroform. The chloroform portions are combined and in
turn washed with four 50 ml portions of ice-cold water. The chloroform solution is then dried over anhydrous
Na2SO4 and evaporated in vacuo.
Preparation #3
This procedure gives good yield and is very fast with little iso-lysergic acid being formed (its effect are mildly
unpleasant). However, the stoichometry must be exact or yields will drop.
Step I. Use White light
Sulfur trioxide is produced in anhydrous state by carefully decomposing anhydrous ferric sulfate at
approximately 480 C. Store under anhydrous conditions.
Step II. Use White light
A carefully dried 22 litre RB flask fitted with an ice bath, condenser, dropping funnel and mechanical stirrer is
charged with 10 to 11 litres of dimethylformamide (freshly distilled under reduced pressure). The condenser
and dropping funnel are both protected against atmospheric moisture. 2 lb of sulfur trioxide (Sulfan B) are
introduced dropwise, very cautiously stirring, during 4 to 5 hours. The temperature is kept at 0-5 C
throughout the addition. After the addition is complete, the mixture is stirred for 1-2 hours until some
separated, crystalline sulfur trioxide-dimethylformamide complex has dissolved. The reagent is transferred to
an air- tight automatic pipette for convenient dispensing, and kept in the cold. Although the reagent, which is
colourless, may change from yellow to red, its efficiency remains unimpaired for three to four months in cold
storage. An aliquot is dissolved in water and titrated with standard NaOH to a phenolphthalein end point.
Step III. Use Red light
A solution of 7.15 g of d-lysergic acid mono hydrate (25 mmol) and 1.06 g of lithium hydroxide hydrate (25
mmol) in 200 ml of MeOH is prepared. The solvent is distilled on the steam bath under reduced pressure. the
residue of glass-like lithium lysergate is dissolved in 400 ml of anhydrous dimethyl formamide. From this
solution about 200 ml of the dimethyl formamide is distilled off at 15 ml pressure through a 12 inch helices
packed column. the resulting anhydrous solution of lithium lysergate left behind is cooled to 0 C and, with
stirring, treated rapidly with 500 ml of SO3-DMF solution (1.00 molar). The mixture is stirred in the cold for 10
minutes and then 9.14 g (125.0 mmol) of diethylamine is added. The stirring and cooling are continued for 10
minutes longer, when 400 ml of water is added to decompose the reaction complex. After mixing thoroughly,
200 ml of saturated aqueous saline solution is added. The amide product is isolated by repeated extraction
with 500 ml portions of ethylene dichloride. the combined extract is dried and then concentrated to a syrup
under reduced pressure. Do not heat up the syrup during concentration. the LSD may crystallise out, but the
crystals and the mother liquor may be chromatographed according to the instructions on purification.
Purification of LSD-25
The material obtained by any of these three preparations may contain both lysergic acid and iso-lysergic acid
amides. Preparation #1 contains mostly iso-lysergic diethylamide and must be converted prior to separation.
For this material, go to Step II first.
Step I. Use darkroom and follow with a long wave UV
The material is dissolved in a 3:1 mixture of benzene and chloroform. Pack the chromatography column with
a slurry of basic alumina in benzene so that a 1 inch column is six inches long. Drain the solvent to the top of
the alumina column and carefully add an aliquot of the LSD-solvent solution containing 50 ml of solvent and
1 g LSD. Run this through the column, following the fastest moving fluorescent band. After it has been
collected, strip the remaining material from the column by washing with MeOH. Use the UV light sparingly to
prevent excessive damage to the compounds. Evaporate the second fraction in vacuo and set aside for Step
II. The fraction containing the pure LSD is concentrated in vacuo and the syrup will crystallise slowly. This
material may be converted to the tartrate by tartaric acid and the LSD tartrate conveniently crystallised. MP
190-196 C.
Step II. Use Red light
Dissolve the residue derived from the methanol stripping of the column in a minimum amount of alcohol. Add
twice that volume of 4 N alcoholic KOH solution and allow the mixture to stand at room temperature for
several hours. Neutralise with dilute HCl, make slightly basic with NH4OH and extract with chloroform or
ethylene dichloride as in preparations #1 or #2. Evaporate in vacuo and chromatograph as in the previous
step.
Note: Lysergic acid compounds are unstable to heat, light and oxygen. In any form it helps to add ascorbic
acid as an anti- oxidant, keeping the container tightly closed, light-tight with aluminum foil, and in a
refrigerator.



I don't recommend trying this unless you are trained in lab procedure or are just balls awesome as fuck and never screw up.


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## Damnecro (May 26, 2013)

LSD 


by Michael Valentine Smith
Since Hofmann's first trip in 1943, great deal of interest has been generated in the occurrence and properties of various lysergic acid derivatives. Fungi of the genus Claviceps, which grow on rye wheat, rice and other grasses, were the first natural source of these alkaloids to be discovered. In recent years related compounds have been found in the genera Penicillium (the blue-green mold that also produces penicillin), Aspergillus, and Rhizobus (the black bread mold). These compounds are now produced commercially by culturing certain strains of Clavicebs which produce as much as 4 g of ergotamine per Liter of culture medium. Growing pure cultures of fungi is not for amateurs, but those interested will find these references useful: JPS 58,143(1969); App. Microbiol. 18,464 (1969); HCA 47,1052(1964); Lloydia 32,327,401(1969); Can. J. Microbiol. 16,923(1970); CA 61,15314c-f, 67,84858e, 69, 36323w; Biotech. Bioeng. 13,331(1971); CA 76,57736(1972); U.S. Patent 3,483,086; Planta Med. 23,330(1973); J. Pharm. Educ. 36,598(1972); CA 78,41492(1973); French Patent 1,531, 205; German Patents 1,806,984 and 1,909,216; British Patent 1,158,380. For a description of a wild American Claviceps species see Mycologia 66,978(1974).


The occurrence of hallucinogens in the seeds (and to a lesser degree in the leaves and stems) of various members of the family Convolvulaceae (morning glories, etc.) was known to the Aztecs. Seeds of the genera Rivea, Impomoea, and Argyria (Hawaiian baby woodrose) contain lysergic acid derivatives; the woodrose being champion with about one hundred times as much as the other genera (about 7 mg alkaloids/g seeds). In view of the low yield (maximum 10 mg alkaloids/ 100 g seeds) even the famed pearly gates variety of morning glory is not worthwhile extracting, and the trip is commonly a bummer, resembling that produced by scopolamine or ibogaline and unlike that of LSD. However, the lysergic acid amide, etc., can be extracted, hydrolyzed to lysergic acid (as described below for ergot alkaloid hydrolysis), and converted to LSD by any of the methods described. For species variation of alkaloid content see Lloydia 29,35(1966). Crude ergot or woodrose seeds should yield ca. 1 g LSD/kg after conversion of the isolated alkaloids.


Alkaloid Extraction (short method)


Finely grind seeds (preferably woodrose) and add NaHCO3. Extract with ethyl acetate by soaking about one day. Filter and extract the ethyl acetate with tartaric acid solution. Basify the extract with NaHCO3 and extract it with ethyl acetate. Dry and evaporate in vacuum the ethyl acetate to get the alkaloids. Repeat this procedure on the seeds until no more residue is obtained. Alternatively, add 100 ml petroleum ether to 100 g finely ground seeds and let soak about two days. Filter, discard petroleum ether and let seeds dry. Add 100 ml methanol to the seeds and let soak about two days. Filter, repeat extraction with another 100 ml methanol and evaporate in vacuum the combined methanol extracts. The residual yellow oil contains the alkaloids.


For chromatographic purification of ergot alkaloids from seed extracts see Phytochem. 11,1479( 1972). For ergot extraction and separation see also Fr. Patent 2,089,081 (11 Feb 1972) and CA 79,105,457(1973). For a recent review of the ergot alkaloids see R. Manske (Ed.) The Alkaloids, vol. 15: 1-40(1975).


Extraction of Lysergic Acid Amides from Woodrose Seeds or Powdered Ergot


Reduce the seed material to a fine powder in a blender, and spread it out to dry. Grind it again if it is not fine enough after the first time due to dampness. Saturate the powdered seed material with lighter fluid, naphtha or ligroine. When completely saturated, it should have the consistency of soup. Pour it in a chromatography column and let it sit overnight. Remove the fatty oils from the material by dripping the lighter fluid or other solvent through the column slowly and keep testing the liquid that comes through for fats by evaporating a drop on clean glass until it leaves no greasy film. It will take several ounces of solvent for each ounce of seeds. Mix 9 volumes of chloroform with 1 volume of concentrated ammonium hydroxide and shake it in a separatory funnel. When it settles the chloroform layer will be on the bottom. Drain off the chloroform layer. Discard the top layer. Drip the chloroform wash through the column and save the extract. Test continuously by evaporating a drop on clean glass until it ceases to fluoresce under a black light. Evaporate the chloroform extracts and dissolve the residue in the minimum amount of a 3% tartaric acid solution. If all the residue doesn't dissolve, place it into suspension by shaking vigorously. Transfer the solution to a separatory funnel and wash the other vessel with acid in order to get all the alkaloid out. Pour the washings in the funnel also. Basify by adding sodium bicarbonate solution, and add an equal volume of chloroform. Shake this thoroughly, let it settle, remove the bottom layer and set it aside. Once again, add an equal portion of chloroform, shake, let it settle and remove the bottom layer. Combine the chloroform extracts (bottom layers) and evaporate to get the amides.


The Culture and Extraction of Ergot Alkaloids


Make up a culture medium by combining the following ingredients in about 500 milliliters of distilled water in a 2 liter, small-neck flask:


Sucrose..........................100 grams
Chick pea meal...................50 grams
Calcium nitrate..................1 gram
Moriopotassium phosphate.........0.25 grams
Magnesium sulphate...............0.25 grams
Potassium chloride...............0.125 grams
Ferrous sulphate heptahydrate....8.34 milligrams
Zinc sulphate heptahydrate.......3.44 milligrams


Add water to make up one liter, adjust to pH 4 with ammonia solution and citric acid. Sterilize by autoclaving. Inoculate the sterilized medium with Claviceps purpurea under sterile conditions, stopper with sterilized cotton and incubate for two weeks periodically testing and maintaining pH 4. After two weeks a surface culture will be seen on the medium. Large-scale production of the fungus can now begin. Obtain several ordinary 1 gallon jugs. Place a two-hole stopper in the necks of the jugs. Fit a short (6 inch) glass tube in one hole, leaving 2 inches above the stopper. Fit a short rubber tube to this. Fill a small (500 milliliter) Erlenmeyer flask with a dilute solution of sodium hypochlorite, and extend a glass tube from the rubber tube so the end is immersed in the hypochlorite. Fit a long, glass tube in the other stopper hole. It must reach near the bottom of the jug and have about two inches showing above the stopper. Attach a rubber tube to the glass tube as short or as long as desired, and fit a short glass tube to the end of the rubber tube. Fill a large, glass tube (1 inch x 6 inches) with sterile cotton and fit 1-hole stoppers in the ends. Fit the small, glass tube in end of the rubber tube into 1 stopper of the large tube. Fit another small glass tube in the other stopper. A rubber tube is connected to this and attached to a small air pump obtained from a tropical fish supply store. You now have a set-up for pumping air from the pump, through the cotton filter, down the long glass tube in the jug, through the solution to the air space in the top of the jug, through the short glass tube, down to the bottom of the Erlenmeyer flask and up through the sodium hypochlorite solution into the atmosphere. With this aeration equipment you can assure a supply of clean air to the Clauiceps purpurea fungus while maintaining a sterile atmosphere inside the solution. Dismantle the aerators. Place all the glass tubes, rubber tubes, stoppers and cotton in a paper bag, seal tight with wire staples and sterilize in an autoclave. Fill the 1-gallon jugs 2/3 to 3/4 full with the culture medium and autoclave. While these things are being sterilized, homogenize in a blender the culture already obtained and use it to inoculate the media in the gallon jugs. The blender must be sterile. Everything must be sterile. Assemble the aerators. Start the pumps. A slow bubbling in each jug will provide enough oxygen to the cultures. A single pump can, of course, be connected to several filters. Let everything sit at room temperature (25øC.) in a fairly dark place (never expose ergot alkaloids to bright light -- they decompose) for a period of ten days. After ten days adjust the cultures to 1% ethanol using 95% ethanol under sterile conditions. Maintain growth for another two weeks. After a total of 24 days growth period the culture should be considered mature. Make the culture acidic with tartaric acid and homogenize in a blender for one hour. Adjust to pH 9 with ammonium hydroxide and extract with benzene or chloroform/iso-butanol mixture. Extract again with alcoholic tartaric acid and evaporate in a vacuum to dryness. The dry material is the salt (i.e., the tartaric acid salt, the tartrate) of the ergot alkaloids, and is stored in this form because the free basic material is too unstable and decomposes readily in the presence of light, heat, moisture and air. To recover the free base for extraction of the amide or synthesis to LSD, make the tartrate basic with ammonia to pH 9, extract with chloroform and evaporate in vacuo. If no source of pure Claviceps purpurea fungus can be found, it may be necessary to make a field trip to obtain the ergot growths from rye or other cereal grasses. Rye grass is by far the best choice. The ergot will appear as a blackish growth on the tops of the rye where the seeds are. They are approximately the same shape as the seeds and are referred to as "heads of ergot." From these heads of ergot sprout the Claviceps purpurea fungi. They have long stems with bulbous heads when seen under a strong glass or microscope. It is these that must be removed from the ergot, free from contamination, and used to inoculate the culture media. The need for absolute sterility cannot be overstressed. Consult any elementary text on bacteriology for the correct equipment and procedures. Avoid prolonged contact with ergot compounds, as they are poisonous and can be fatal.


LSD Identification


Since LSD is an indole derivative, it gives a positive reaction (violet color) to the tests given in the indole section. LSD also fluoresces under an ultraviolet light (black light), but so do many other compounds. For infrared spectra of LSD and related compounds, see JACS 78,3087(1956) and J. Forensic Sci.12,538 (1967). For other information on identification see JPS 56,1526 (1967) and JAOAC 50,1362(1967), 51,1318(196. For a microcrystalloscopic test see J. Pharm. Pharmacol. 22,839(1970). In order to make LSD, lysergic acid is needed. This can sometimes be obtained, but generally one of the lysergic acid containing ergot alkaloids such as ergotamine is more readily available. Ergot is the dried sclerotium of various species of fungi which infect rye (and other grasses), leading to the formation of large purple growths in place of the rye grains. These growths are collected, dried, powdered and the alkaloids extracted. For the extraction procedure see HCA 28,1283(1945), J. Pharm. Pharmacol. 7,1 (1955), JPS 50,201(1961), CA 75,137422(1971). Proc. Indian Acad. Sci. 71B,28,33(1970) gives production from artificially infected rye. Ergot is produced mainly in Europe (especially Switzerland) but some has been grown in the USA (e.g., in Minnesota). This production occurs primarily because of the use of ergotamine and related compounds in medicine (contracting the post-partum uterus, terminating migraineheadaches, etc.). Many of the ergot alkaloids are derivatives (amides) of lysergic acid. Unfortunately, these compounds have little hallucinogenic activity and it is necessary to hydrolyze (split with water) off the amide, producing lysergic acid, and to synthesize a different amide with greater psychedelic activity. This hydrolysis can be done with any of the following compounds or a mixture of them: ergometrine, ergine, ergotamine, ergosine, ergocristine, ergokryptine, ergonovine (ergo- metrine) and methysergide (Sansert). When -ine is added to the name (e.g., ergotaminine) this indicates the isomers which will lead to the production of the inactive iso-LSD. The papers cited here give simple techniques for converting these to the active forms (or see the technique for converting iso-LSD to LSD in method 1 following): HCA 37,820,2039(1954); CA 69,36322(196; CCCC 34,694 (1969). For a review of the ergot alkaloids see THE ALKALOIDS, Manske and Holmes (Eds.), 8,725(1965), and F. Bove, THE STORY OF ERGOT (1970).


Ergot Alkaloid Hydrolysis


JBC 104,549(1934); HCA 47,1929(1964). Perhaps the best method is Hofmann's modern hydrazine hydrolysis given later, since this disposes of the necessity for isolating the lysergic acid (I); otherwise the following alkaline hydrolysis can be used: Dissolve 20 g of the alkaloid (e.g., ergotamine) in 200 ml 1M KOH in methanol (i.e., dissolve 56 g KOH pellets in 1L 100% methanol) in a 1 L heavy walled vacuum flask and evaporate in vacuum the methanol at room temperature. To prevent the solution from cooling, and thus greatly prolonging the evaporation time, put the flask in a pan of water kept at room temperature by gentle heating or by running warm water through it. Add 400 ml 8% KOH in water to the residue and boil for one hour (under N2 if possible, this can be done by filling the flask with a N2 stream and loosely stoppering or by allowing a gentle stream of N2 to flow through during heating). Cool, acidify with dilute sulfuric acid and shake in separatory funnel with 1 L ether. Discard the upper ether layer and filter with vacuum the aqueous suspension of lysergic acid (I). Wash precipitate with 20 ml dilute sulfuric acid. To recover the small amount of (I) remaining in solution, basify with Na carbonate and bubble C02 through it. Filter and add precipitate to first batch. Some isolysergic acid will remain in solution and can be precipitated by adding 10% HNO3. It can be converted to (I) by adding 3 ml 10% KOH for each 0.1 g acid, boiling on steam bath for one hour under N2 (if possible) and precipitating by acidifying with glacial acetic acid. Maximum yield is about 9 g (I) for 20 g ergotamine. A shorter method of hydrolysis which may work as well follows: dissolve 20 g alkaloid in 300 ml methanol and 300 ml 40% KOH and reflux two hours under N2 (if possible). Cool, saturate with CO2 and evaporate in vacuum. Extract the residue with hot ethanol three times and dry, evaporate in vacuum the combined ethanol extracts to get (I). Under ordinary conditions, about 20% of (I) will be converted by the action of hot water, etc., to the inactive isolysergic acid. Most of this remains in solution and can be isomerized to (I) as described above, or it can be converted to iso-LSD by any of the methods described later and isomerized to LSD (see method 1). It is unnecessary to purify (I), but this can be done as follows: dissolve 9 g (I) in 20 ml NH4OH, filter and concentrate in vacuum at room temperature to precipitate (I). After filtering, the grey crystals can be further purified by dissolving in boiling water and cooling in ice bath to precipitate (I). Melting point should be about 240o (decomposes). Alternatively, the dark-colored (I) resulting from hydrolysis can be shaken with 2x400 ml 2 M NH4OH in ethanol, and the combined extracts evaporated in vacuum to give (I). Dissolve the remaining residue in 500 ml hot methanol, cool to 0ø and filter out the (I) (recrystallize-water). Can remove colored impurities by shaking solution with decolorizing carbon and filtering. Recently a method for increasing the yield of (I) about 10% using 2.5% hydrazine hydrate was described (CA 69,36323(196). Dissolve 7 g alkaloid in 200 ml 6 N KOH in methanol and 200 ml ethanol, add 10 ml hydrazine hydrate and boil four hours under N2 (if possible) and proceed as above. Finally, the (I) must be thoroughly dried by heating at about 110ø/1 mm for two hours or 150ø if ordinary lab vacuum of 15 mm is used. A forced water vacuum (about 25 mm) can be used here as elsewhere. An oil bath (e.g., mineral oil) will allow temperature regulation.


LSD Synthesis


Dangers


There are certain aspects of LSD production which are common to all synthetic methods. The first is a certain degree of danger; each uses dangerous reagents and solvents. Hydrazine and hydrazine hydrate are both violent poisons, and each can cause severe skin burns and eye damage. The vapor of each is irritating, and can cause severe eye irritation as well as liver and blood damage, but the symptoms don't always manifest right away, sometimes appearing three or four days after exposure, so it is easy for exposure to be much more dangerous than is immediately realized. In addition, anhydrous hydrazine is a sensitive and violent explosive, the explosion of which can be set off by certain types of stainless steel and such common things as wood and rust. Both trifluoroacetic acid and sulfur trioxide will cause very severe skin burns, and their vapors are extremely irritating. Sulfur trioxide is such a strong dehydrating agent that it chars organic material, and its heat of dehydration is so high that it will start a fire if spilled on wood, which could prove fatal were flammable solvents in use at the time or stored nearby. Phosgene is very poisonous; so insidious that it was used as a war gas in World War I. One deep breath can cause immediate collapse and death, and as it is not irritating there is no gag reflex to prevent one from taking that deep breath. Doses which are not high enough to be immediately lethal may not be noticed at all at the time of exposure, yet lead to death within 24 hours. Sub-lethal doses cause pulmonary edema and serious respiratory disability; again, the symptoms can appear well after an exposure which was hardly noticed. Diethylamine, used in every LSD synthesis, has a very low flash point, and its vapor is irritating. The vapor of DMF is also irritating, and prolonged exposure can cause liver damage. In fact, most of the solvents used in LSD production are either flammable or toxic or both. In addition to all the above, the starting material, the ergot alkaloids, is as a class quite toxic, and clean working conditions are necessary when working with it. Ergot alkaloid poisoning, known in the Middle Ages as Saint Antony's fire, can actually cause one's limbs to blacken, shrivel, and fall off! Any woman working with these compounds should also be aware that many of them are oxytoxics, that is, they cause uterine contractions, and are so used to induce labor, etc.


Working Conditions


There are certain procedures common to all syntheses of LSD which are based upon the sensitive nature of ergot compounds in general. Natural ergot alkaloids, lysergic acid, LSD, and the intermediate products associated with the various syntheses are all to a varying degree unstable. Even the most stable of these compounds will readily decompose under any but moderate conditions. Thus precautions must be taken against light, moisture, oxygen, and heat. Light of the ultraviolet region promotes addition of water at the delta-9-10 double bond to form the lumi-compounds. Thus reactions are best carried out in the light of red or yellow photographic darkroom bulbs, and storage should be in opaque or amber bottles. Most of the reactions involved in LSD synthesis require anhydrous conditions for good yield, and so protection must be made against moisture during the actual production. Furthermore, the final product must be thoroughly dried to prevent possible formation during storage of the lumi-compounds as mentioned above. Oxidizing agents, including atmospheric oxygen, will decompose ergot compounds. For this reason, all reactions are carried out in an atmosphere of an inert gas such as nitrogen. The danger of oxidation increases with temperature, so this precaution is of course most important with those reactions proceeding at elevated temperature. Various methods have been devised to prevent oxidation during storage. The most obvious is to store the LSD in nitrogen filled containers, but the excellent protection thus afforded is of course lost when the bottle or ampule is opened. Another method is to use an antioxidant; Brown and Smith recommend ascorbic acid. A more sophisticated method, recommended on the highest authority, is to make LSD maleate rather than the tartrate. Both maleic and tartaric acids are dicarboxylic, but the pK2 of maleic acid is too low to form a salt with LSD. Thus there is a free carboxyl group in LSD maleate, which group will serve to prevent oxidative decomposition. Excessive heat will cause decomposition of LSD and its precursors, and will also increase the possibility of racemization. Thus reactions at elevated temperature are not unnecessarily prolonged, nor are temperatures unnecessarily raised. All drying is done in vacuo in an inert atmosphere, and long term storage should be under refrigeration.


Legal Acid


I want to emphasize that "legal acid" can be obtained if other amines are substituted for diethylamine in LSD synthesis. These other lysergamides should give identical trips, but most of them are less potent than LSD. Precise potency data do not exist, so it remains for an enterprising chemist to gain immortality by adding each of the following amines (and any others that come to mind) to separate aliquots of the final step of LSD synthesis (they could easily be done simultaneously), isolating the tartrates and assaying them for potency: piperidine, diisopropylamine, ethylisopropylamine, ethylpropylamine, methylethylamine, methylisopropylamine, tetrahydrooxythiazine, tetrahydroisoxazine, dioxazole, 2-methylmorpholine, 2,5-dimethyl (or dimethoxy) pyrrolidine, cyclo-butyl-amine, cyclopentylamine, etc. Published potency data expressed as a fraction of LSD activity follow: pyrrolidide (1/20), dimethylamide (1/20), morpholide (1/10 or 1/3), ethylpropyl (1/3), dipropyl (1/10), methylethyl (less than 1/10), methylpropyl (less than 1/10).


Methods


LSD via the Hydrazide HCA 38,429(1955), HCA 26,953(1943)
CA 57,12568(1962), U.S. Patent 3,239,530(1966).


Perhaps the simplest method is the following devised by Hofmann, which proceeds directly from the ergot alkaloid via hydrazine, and is not to be confused with his earlier use of hydrazine under more violent conditions which led to a racemized product and reduction of the yield by one-half.


Add 1.16 g ergotamine HCl to 4 ml anhydrous hydrazine and heat one hour at 90ø. Add 20 ml water and evaporate in vacuum. Can proceed to the next step or can purify by adding ether and aqueous tartaric acid, basify the aqueous phase and extract aqueous phase with CHCl3 to get mainly d-iso-lysergic hydrazide (I). Can chromatograph on alumina and elute with 0.5% ethanol in CHCl3 to purify. To 1 g (I), finely ground, in 40 ml 0.1 N ice cold HCl, add with good stirring at 0ø 4 ml 1N Na nitrite. Quickly over two-three minutes, add 40 ml 0.1 N HCl so pH is about 5. Let stand five minutes, basify with 1N NaHCO3 and extract with 100 ml ether, then 50 ml ether. Wash ether with water and dry and evaporate in vacuum at 10ø. Dissolve the resulting yellow azide in about 5 ml diethylamine (DEA) at 0ø and heat one hour at 60ø in a bomb (sealed metal pipe), or heat 3 to 4 hours at 45øC in a vented flask. Let stand several hours and evaporate in vacuum to get about 0.7 g d-LSD and 0.15 g d-iso-LSD (which can be converted to d-LSD as described in method 1 following). Alternatively, the DEA can be added to the cooled ether solution of the azide and let stand several hours or overnight at room temperature in the dark in a vented flask. An alternate method of proceeding from the hydrazide follows (U.S. Patent 3,085,092). To a solution of 1.4 g (I) in 5.5 ml 1 N HCl, 5 ml water, 5 ml EtOH, add 1 g acetylacetone (2,4 pentanedione), let stand 1 hour at room temperature and neutralize with 5.5 ml 1 N NaOH. Filter off the lysergyl pyrazole (II) and wash with water. Can purify by drying in vacuum at 60øC and recrystallizing from chloroform by the addition of ether. Heat 0.4 g (ll) and 2.5 ml DEA at 100ø C for 2 hours (or let stand 15 hours at room temperature, evaporate to dryness and heat a few minutes at 100øC in vacuum). Can recrystallize from CHCl3, petroleum ether or as described elsewhere here.


Technical Scale Details For This Method // Hydrazide Production


In dim yellow light, (preferably) three tared and fully dried 250 ml round-bottom flasks containing stirring bars are each charged with 30 g dry ergotamine tartrate and 120 ml anhydrous hydrazine. The flasks are fitted with gas inlet tubes adjusted to just above the liquid level and streams of nitrogen passed through, the exhaust gas being led through wash bottles equipped with traps and containing dilute acid to remove hydrazine vapors. The flasks are lowered into oil baths preheated to 90øC, and heated with slow stirring for one hour. The contents of the three reaction flasks are then emptied into a 2000 ml beaker containing 900 ml distilled water, and this solution transferred to a 3000 ml two-neck round bottom flask. An additional 900 ml water is used to rinse the residue in the flasks, beaker, etc. into the 3000 ml flask. This large flask is fitted with siphon tube, gas inlet tube, and gas outlet connected to wash bottle and trap. The aqueous hydrazide solution is evaporated from a tared 2000 ml flask on an efficient rotary evaporator, using a bath temperature of 40øC and an ice-cooled condenser; the 3000 ml siphon flask assembly is used as storage for the vacuum feed. The weight of the crude hydrazide so obtained is determined, it is dissolved in about 170 ml 1 N tartaric acid, the aqueous solution washed with three 30 ml portions ether, made alkaline with 190 ml 1 N ammonium hydroxide, and exhaustively extracted with successive portions of chloroform, the first two portions being 100 ml each, the following 50 ml. Completeness is ensured by testing with UV light, extraction ceasing only when the chloroform extract exhibits no blue fluorescence. The chloroform solution is washed with three 30 ml portions distilled water, dried over chloroform moistened magnesium sulfate, and the hydrazide recovered by vacuum evaporation in tared 500 ml flasks, one such flask being used for each two 90 g batches. These flasks are flushed with nitrogen, stoppered, and stored in a dark and dry refrigerator. As the hydrazide is stable, all the ergotamine tartrate will be converted to it prior to the next step. Theoretical yield from 1000 g ergotamine tartrate is 429.65 g; 80% yield is 343 g.


Pyrazole Production


In dim red light, the weighed hydrazide contained in one of the 500 ml flasks (ca. 67 g; 95% of theory) is washed into a 1000 ml beaker with 263 ml 1N hydrochloric acid. 239 ml distilled water, 239 ml ethanol (95%), and 37 ml 2,4-pentanedione are added, and the well-mixed solution left to stand in the dark at room temperature until the reaction is complete, i.e., about 30 minutes. The reaction mixture is neutralized with the addition of 263 ml 1 N sodium hydroxide, and the beaker covered with parafilm and refrigerated to ensure complete precipitation. The pyrazole is filtered at the pump, the mother liquor being returned to the beaker and used to wash out the last few crystals, washed with cold water, and sucked dry under a stream of dry nitrogen. The product is dried in vacuo over barium oxide or phosphorus pentoxide for at least twelve hours before proceeding to the next step, wherein anhydrous conditions will increase yield. Hofmann calls for drying the pyrazole in vacuo at 60øC, which indicated the product to be fairly stable. So all the hydrazide is converted prior to aminization.


Amide Production


In dim red light, 50 g of the well-dried pyrazole and 700 ml freshly dried diethylamine are placed in a tared and well-dried 1500 ml flask equipped with gas inlet tube and stirring bar. The flask is lowered into a bath preheated to 45øC, and the contents stirred under a stream of nitrogen for four hours. On a rotary evaporator, using a 6 atm temperature of 40øC and an ice-cooled condenser, the diethylamine is removed in vacuo and set aside for purification and re-use. Briefly and in high vacuum the flask is heated to 100øC, the split-off pyrazole being thereby driven off. The residue so obtained is immediately placed in solution with methanolic potassium hydroxide to effect interconversion of the stereoisomers. Amination and Transposition will proceed simultaneously, the first batch being transposed while the second is aminated.


Production Scale Isomerization of iso-LSD to LSD


In dim red light, the amide residue from the last step is dissolved in the least possible amount of dry methanol and washed into a 1500 ml round-bottom flask. A two-fold volume of 4 N methanolic potassium hydroxide is added, and the well-mixed solution left to stand at room temperature, in the dark and under a slow stream of nitrogen, for four hours. At the end of this period, the solution is neutralized with methanolic hydrogen chloride (ca. 5 N), washed into a 4000 ml Erlenmeyer flask, and dried over methanol-moistened anhydrous magnesium sulfate (0.10 g MgSO4 per ml KOH solution). The methanolic acid should be added slowly and with good stirring to prevent possible hydration of the 9-10 double bond to give lumi-LSD. Together with 100 ml dry isopropanol (to remove the last trace of water azeotropicly) the dried solution is transfered to a 3000 ml siphon flask assembly, and the solvent removed in vacuo in a tared 500 ml two-part freeze-dry flask. The weighed gummy residue is scraped into the thimble of a Soxhlet extractor, the adhering residue being washed into the thimble with portions of warm chloroform, the total volume of which is 12.5 ml per gram amide (total weight minus weight KCl). A 3000 ml flask is used with the extracter, and it is previously charged with 37.5 ml dry benzene per gram amide. Under a stream of dry nitrogen, the solvent is in vacuo at 40øC refluxed through the thimble, thus extracting the amide from the inorganic salt and at the same time preparing the solution for use in the chromatographic separation of the stereoisomers. The above solution is stored over a small amount of benzene-moistened calcium sulfate in a nitrogen flushed flask which is placed in a dark refrigerator. All the pyrazole is converted to this benzene-chloroform solution prior to separation of the isomers.


The following methods all proceed from lysergic acid (I). Methods 1, 2, 4, and 6 give less than 20% iso-LSD in the product but methods 2, 5, and 9 seem to have the highest total yield (about 80%) of LSD plus iso-LSD. Since unreacted lysergic acid can be recovered and run through the synthesis again, and iso-LSD isomerized to LSD as described here, it is probably best to use the simplest methods. These comparative yields come mostly from the reference to method 9.


From Lysergic Acid - Method 1 CA 50,10803d( 1956) (Pioch)


Dissolve 5.3 g dry (I) in 125 ml acetonitrile (or dimethylformamide or proprionitrile) and cool to -20ø (freezer or dry ice-acetone or ethanol mixture). Add 8.82 g trifluoroacetic anhydride in 75 ml acetonitrile cooled to -20ø carefully. Let stand at -20ø 1 1/2 hours or until all the (I) dissolves. Then add 7.6 g DEA in 150 ml acetonitrile and let stand at room temperature in dark two hours. Evaporate in vacuum to get LSD. If purification is desired, dissolve the residue in 150 ml CHCl3 and add 20 ml ice water. Pour into 1/2 L separatory funnel and drain out the lower CHCl3 layer into a beaker (after shaking). Add 50 ml CHCl3 to funnel, shake and drain bottom layer into same beaker. Repeat with 3x50 ml CHCl3 and discard the water. Extract the combined CHCl3 extracts with 4x50 ml ice cold water and dry, evaporate in vacuum the CHCl3 to get 3.5 g d-LSD. This is composed partly of the inactive d-iso-LSD, which, while it will not effect the trip, can be recovered and converted to d-LSD as follows: dissolve the residue in 120 ml benzene and 40 ml CHCl3 (or 200 ml methanol), add tartaric or maleic acid and shake to precipitate mainly d-LSD (add a little ether and cool in refrigerator several days if necessary to ensure complete precipitation; evaporate in vacuum the solvent to get d-iso-LSD. Add 50 ml ethanol and 5 ml 4N KOH per g iso-LSD and let stand at room temperature two hours; evaporate in vacuum (or extract with CHCl3 as above) to get LSD. 4 hours in 2.66 N methanolic KOH is said to be optimal for isomerization.


From Lysergic Acid - Method 2 JOC 24,368(1959) (Galbrecht)


This method is supposed to give little iso-LSD but it gives some of the monomethylamide. Add 1 L dimethylformamide (freshly distilled, if possible) to dry flask fitted with stirrer, ice bath, dropping funnel and condenser, both protected from water by Ca chloride drying tubes. Add dropwise with stirring over four-five hours at 0ø 0.21 lbs (90.7 g) SO3 (sulfuric anhydride, available as Sulfan from Allied Chem. Co.). If precipitate forms, stir until it dissolves. Sulfan may be made in larger amounts and is good for several months if kept dry and cool. Molarity of fresh 503-DMF reagent should be about 1M, but for precise determination, add a little water to an aliquot and titrate with standard NaOH to phenolphthalein end point. Add 6.45 g dry (I) (or 7.15 g (I) monohydrate) and 1.06 g LiOH hydrate (or NaOH or KOH but these absorb water so they must be dissolved in absolute methanol, titrated and added in equimolar amounts) to 200 ml methanol in a 1 L vacuum flask and evaporate in vacuum. Dissolve residue in 400 ml anhydrous dimethylformamide and distill off 200 ml DMF at about 15 mm Hg through a twelve inch column packed with glass helices or other material. Cool to 0øC and rapidly add 50 ml SO3-DMF solution (1 M). Stir at 0øC for ten minutes and add 91.5 g (12.9 ml) DEA and stir ten minutes. Add 400 ml of water stir and add 200 ml saturated NaCl. Extract the LSD by shaking with several 500 ml portions ethylene dichloride (can use indole test given in indole section to show completeness of extraction). Combine extracts (lower layer in separatory funnel) and dry, evaporate in vacuum to get LSD (can purify as above).


From Lysergic Acid - Method 3 JOC 24,368(1959) (Garbrecht)


This route is said to give a lower yield than method 2. Dissolve 13.4 g dry (I) in 250 ml dry dimethylformamide and cool to 0ø. Add cooled solution of 3.4 ml 0.35 M methane-sulfonic acid anhydride in dry dimethylformamide. After thirty minutes at 0øC add 14.6 g (20.4 ml) DEA and keep at 0øC one hour. Evaporate in vacuum to get LSD and proceed as above.


From Lysergic Acid - Method 4 CA 57,5979(1962) (Hofmann)


Dissolve 0.536 g (I) in 10 ml freshly distilled POCl3; stir and add 416 mg powdered, freshly sublimed PCl5. Hold two minutes at room temperature, two minutes at 90øC, and evaporate in vacuum. Extract the residue with hexane to give the lysergic acid chloride-HCl (can also extract the reaction mixture with hexane instead of evaporating in vacuum). Alternatively, use 6 ml POCl3 and 240 mg SOCl2 and heat three minutes at 90øC to get the acid chloride. To 5 g of the acid chloride add 1.4 ml DEA in 50 ml methylene chloride and cool to 0ø. Stir and add 27.5 ml pyridine and stir one-half hour at 0øC. Warm to room temperature and stir 1 1/2 hours; evaporate in vacuum to get LSD.


From Lysergic Acid - Method 5
CCCC 27,1590(1962) (Cerny and Semonsky) cf. CA 75,77110(1971)


To a suspension of 13.4 g dry (I) in 800 ml dry dimethylformamide (DMF) in a 2 L vacuum flask at 20ø, add a solution of 8.9 g N,N'-carbonyldiimidazole in 250 ml DMF and stir at 20ø in dark for one-half hour. Add a solution of 4 g DEA in 50 ml DMF and let stand two hours at 20ø; then twenty hours at 5ø. Evaporate in vacuum to get LSD. Can purify as above or dissolve residue in 2 1/2 L 2% tartaric acid; extract with ether and discard ether. Filter, basify with NH4OH and extract with a 9:1 solution of ether:ethanol. Dry and evaporate in vacuum to get LSD in 81% yield.


From Lysergic Acid - Method 6 JMC 16,532(1973) (Johnson et al)


This method gives very little iso-LSD.


To a refluxing slurry of 3.15 g dry (I) or monohydrate) in 150 ml CHCl3 add 0.1 mole of the amine in 25 ml CHCl3 and 2 ml POCl3 simultaneously from separate dropping funnels over 2 to 3 minutes. Reflux 3 to 5 minutes more till a clear amber solution results. Cool to room temperature and wash with 200 ml 1M NH4OH. Dry and evaporate in vacuum (below 40ø). Can dissolve in the minimum amount of methanol and acidify with a fresh solution of 20% maleic acid in methanol. Filter and wash crystals with cold methanol to get the LSD or other amide. This method works with a wide variety of amines. For LSD itself, the POCl3 can be added first. The yield is about 50%.


From Lysergic Acid - Method 7 German Patent 1.965,896 (1970) (Julia et al.)


See end of total synthesis of LSD given below.


From Lysergic Acid - Method 8 U.S. Patent 3,141,887 (Patelli and Bernardi)


Note: Phosgene is very hazardous and only professional chemists working with a fume hood should even think about using this method. It can be dissolved in a weighed container of DMF (dimethylformamide) and a second weighing will give the phosgene concentration. 0.5 g anhydrous lysergic acid suspended in 10 ml DMF or acetonitrile at -10øC are reacted with 2 ml of DMF containing 0.34 g of the phosgene-DMF complex for 20 minutes. Add 0.7 g diethylamine in 10 ml DMF (or acetonitrile), keep at -10øC for ten minutes and then at room temperature for 10 minutes. Dilute with chloroform, wash with NaOH (1 normal), then water and distill off the solvent in a vacuum. Dissolve the oily residue in methanol, acidify with tartaric or maleic acid; add ether to start crystallization. Keep overnight at 0øC, filter and wash with ether. Dissolve the product in methanol, decolorize with charcoal and precipitate with ether to obtain the tartrate or maleate (tartrate melts 192-198 C). D20 = + 25ø (C = 1 in water).


From Lysergic Acid - Method 9 CT 13,373(197 (Losse and Mahlberg)


This method gives about 2/3 iso-LSD, and about 80% total yield.


Add 134 mg (0.5 mM) dry (I), 103 mg (0.SmM) N,N-dicyclohexylcarbo- diimide, 90 mg (0.67mM) 1-hydroxybenzotriazol (N-hydroxybenzotriazol) and 0.5 mM diethylamine to 2.5 ml CH2Cl2 and 2.5 ml tetrahydrofuran and stir in the dark at 20ø C for 24 hours. filter, wash precipitate with CH2Cl2 and evaporate the filtrate at 15 mm Hg, 30ø C to get LSD.


LSD Via SO3 METHOD I


This and the following method are expanded versions of Garbrecht's method. My own prejudice is that it makes much more sense to use one of the other, simpler methods since the unreacted lysergic acid can be recycled, and the initial yield is consequently of little import. However, the details as presented here derive from the practical experience of underground chemists and contain many points of interest for any technique.


Notes on Processes:


1. Chemicals to process one kilogram of ergotamine tartrate:


Alumina, Activity II, 100-200 mesh...................8 Lbs.
Benzene, Reagent..................................20 Liters
Charcoal, activated powder, Norit A...............100 Grams
Congo red papers.....................................1 Vial
Dichloromethane (methylene chloride), Purified....60 Liters
Diethylamine, Reagent..................500 Grams or 725 ml.
Dimethylformamide, Reagent........................12 Liters
Ergotamine tartrate..............................1 Kilogram
Ether, Absolute......................................5 Lbs.
Ethyl alcohol, Anhydrous, Denatured................10Liters
Lithium hydroxide hydrate, Reagent................200 Grams
Methanol, Reagent..................................24 Pints
Molecular sieve, Linde 4 A............................1 Lb.
Petroleum ether, B.P. 40ø=70øC...................2.5 Liters
Phenolpthalein, White................................1 Gram
Phosphorus pentoxide, Reagent.....................100 Grams
Potassium hydroxide, Reagent.........................2 Lbs.
Sodium Chloride, Reagent.............................5 Lbs.
Sulfuric acid, Fuming 33%............................3 Lbs.
Sulfuric acid, Reagent...............................4 Lbs.
Tartaric acid, natural, powder, Reagent...........200 Grams


2. Cylinder gasses:
Ammonia, anhydrous...................................1 Lb.
Nitrogen, Dry.....................1 small welding cylinder


3. Notes on preparing reagents:


Ammoniacal ethanol is prepared by chilling ten liters of anhydrous denatured ethyl alcohol as commercially purchased in a freezer to well below 0ø C. Next, 600 to 750 ml of liquid ammonia is drawn from a pressure cylinder into a 1000 ml graduate in a well ventilated area. The contents of the graduate are carefully poured into the chilled alcohol. The solution is then stirred to mix and warmed to room temperature. The solution should be at least two molar as determined by titration against standard acid solution to a methyl red endpoint. If titration is to be attempted, a little methyl red should be added to the chemical list. Dilute sulfuric acid is prepared by pouring 750 ml of sulfuric acid into about 11.25 liters of ice cold water in a large acid resistant container such as a polyethylene jug or 5 gallon gasoline container, etc. Anhydrous dimethylformamide for making up sulfur trioxide-DMF reagent is prepared by shaking three liters of reagent dimethylformamide with 100 to 200 grams of Linde molecular sieve, and allowing the mixture to stand overnight with occasional shaking. Next, the dimethylformamide is decanted off and poured into a five liter boiling flask. The flask is fitted with a helices packed fractionating column and distilled at 25 millimeters pressure. 800 ml is distilled off as a forerun and discarded or re-dried over molecular sieve. The next fraction of about two liters is collected and kept so as to protect from atmospheric moisture (drying tube, etc.). A little dimethylformamide is left in the boiling flask. Dimethylformamide when prepared in this manner is excellent for preparing the sulfur trioxide reagent. Commercially available spectro-quality or pesticide quality dimethylformamide may also be used if the water content is specified to be less than .O5%, but the reagent obtained from these products has always appeared darker in color than that made by the above method. Commercial reagent quality dimethylformamide is suitable for the main reaction.


4. Preparation of the sulfur trioxide-dimethylformamide reagent (503-DMF).


Sulfur trioxide is distilled from fuming sulfuric acid. About 200 grams are necessary and can be obtained from varying amounts of fuming sulfuric acid depending upon the concentration of sulfur trioxide in the commercially available product. Occasionally it is possible to purchase fuminþ sulfuric acid which contains as much as 70% sulfur trioxide (S03). Fuming sulfuric acid containing 30-33% is usually easily available and 200 grams of 503 can be obtained by distilling about one kilogram of it. The distillation is done at atmospheric pressure in a simple distillation apparatus which utilizes a large bore condenser of the West or similar typ;. The receiving flask should be connected to the condenser in a closed fashion as in a vacuum distillation and vented to the atmosphere through a drying tube or similar device. Corks, rubber stoppers and any kind of joint grease cannot be used in contact with sulfur trioxide or fuming sulfuric acid as they will char. Tapered glass fittings should be used throughout without grease. All fittings should be cleaned in benzene to remove grease before distilling. Sulfur trioxide fumes are very irritating and good ventilation is a must. Glass stoppers and small empty flasks with tapered fittings should be used to close openings in the distilling apparatus when changing receiving or boiling flasks. This will help considerably to keep fumes out of the atmosphere.


Experimental procedure:


200 grams of sulfur trioxide are distilled from the appropriate amount of fuming sulfuric acid. The boiling range should be 5ø or less. The 200 grams are collected in a small round bottom flask previously weighed with a glass stopper in place. Next, a small unweighed portion of phosphorus pentoxide is added to the sulfur trioxide in the flask (1 teaspoonful). The flask is swirled and then placed on the distilling apparatus as the boiling flask. A forerun of 5 ml is distilled into a small receiving flask. This is returned to the boiling flask and the apparatus is fitted with a receiving flask (3 liter boiling flask) already containing 1500 ml anhydrous dimethyl-formamide and a magnetic stirring bar teflon coated. The flask is surrounded by an ice water bath in a nonmagnetic container and a magnetic stirring motor is placed underneath to rotate the stirring bar in the flask. The remaining sulfur trioxide is distilled into the receiving flask containing the dimethylformamide. The receiving flask should be absolutely dry before filling it with the dimethyl-formamide. The sulfur trioxide should distill off over a 2ø boiling range the second time. A hot water bath or an oil bath is convenient when heating the boiling flask and prevents overheating. When the distillation is complete, the receiving flask is removed carefully and stoppered. The flask is warmed and swirled to dissolve any crystalline material and then cooled to around 5øC. and left several hours. If any material precipitates, a little anhydrous dimethyl-formamide is added to dissolve the residue. The flask is swirled and the contents decanted into a storage bottle. The temperature in the storage bottle is recorded and a ten milliliter aliquot withdrawn with a pipette. The aliquot is run into a 250 ml Erlenmeyer flask and diluted with 10 ml water to decompose the complex. The mixture is then titrated to a phenolpthalein endpoint with a standard base solution. A convenient standard base solution can be made by dissolving 1 mole of lithium hydroxide hydrate (41.96 gr) in distilled water to make one liter in a volumetric flask. Three consecutive titrations should be done and an average taken. One mole of sulfur trioxide reacts with two moles of lithium hydroxide. The reagent bottle should be labeled as to sulfur trioxide concentration (about 1.5 molar) and the temperature at which the concentration was determined since the reagent has a rather high coefficient of expansion.


If at any time during the distillation of the sulfur trioxide, crystals of solid sulfur trioxide form in the condenser or receiving flask, they may be melted by careful local heating with a propane torch flame or by running hot water through the condenser jacket. The water in the condenser should be above 23øC during distillation of sulfur trioxide to prevent crystallization of sulfur trioxide polymers.


5. Notes on changing the scale of reactions:


The ergotamine to lysergic acid reaction may be scaled up or down by multiplying the quantities involved by a proportionality constant: all quantities should be multiplied by the same constant. It has been found that the quantities of water and potassium hydroxide used in the hydrolysis of ergotamine are not particularly critical and their relative concentrations may be varied somewhat to meet other considerations. As a rule, ergotamine should be hydrolysed with about a 1.5 to 2.5 molar potassium hydroxide solution. The lysergic acid to lysergic acid amide reaction has been designed to utilize minimal quantities of solvents in order to squeeze as much material as possible into ordinary laboratory glassware. Some workers have suggested that the quantity of dichloromethane (or chloroform) can be further reduced and still effectively extract the amide, but this may prove difficult, especially if emulsions are encountered. When scaling down the reaction, if desired, the quantities of methanol, dimethylformamide, saline solution, and dichloromethane may be in greater quantity than calculated by direct proportion to the other reagents. The proportional relationship between lysergic acid, lithium hydroxide and sulfur trioxide must be strictly adhered to. The molar proportions are: lysergic acid, 1 mole; lithium hydroxide, 1 mole; sulfur trioxide, 2 moles. Diethylamine should be added in at least five molar equivalents. 6.5 equivalents are used in the example given. In general, two thirds of the dimethylformamide should be distilled off from the lithiumlysergate solution. It is convenient to do the reaction in a small quantity of dimethylformamide if doing large quantities of lysergic acid since the product is contained in smaller volume and extraction may be done with less solvent.


6. Notes on purification of amide


The chromatography detailed in the example has been used and works fairly well, however, the removal of all colored impurities is not achieved and there is room for improvement. It is suggested that further experimentation be done to improve the process. An ultraviolet light is indispensable when doing experimentation with these compounds. The lysergic acid amide displays a blue fluorescence. Benzene has been used successfully as an eluant on activity 4 alumina, but the results were no better than the example given. Chloroform and chloroform-benzene mixtures also have been used on varying grades of alumina but no useful data is available.


7. Notes on crystallization of tartrate


Methanol and methanol-ether mixtures have both been used to crystallize the amide tartrate. Crystallization proceeds more readily if ether is present. Usually, the quantity of solvent from which the tartrate is crystallized should be around 4.0 to 6.0 times the weight of the free base amide (in grams) expressed in milliliters. For example, if the free base lysergamide weighs 20 grams, then the crystallization should be done in 80 to 120 milliliters of solvent. The purer the free base amide, the less solvent that may be effectively used and the higher the yield. The solvent is reagent grade methanol containing 10% to 25% ethyl ether. It is usually preferable to dissolve the amide in the methanol and then to add the ether. Ether should not be added after the tartaric acid is added since it precipitates the impurities at the site of addition. Crystallization occurs more slowly with impure preparations. Considerable time should be allowed in the cold before filtering. Overnight is excellent.


Lysergic Acid Monohydrate


350 grams of potassium hydroxide are dissolved in 3500 ml of water in a five liter three-neck boiling flask equipped with a reflux condenser and a small tube introducing a slow stream of nitrogen gas. The mixture is then heated to about 80øC, when 500 grams of ergotamine tartrate is added to the flask. The temperature is maintained at 80ø for about 2 1/2 hours while continuously bubbling nitrogen gently through the mixture. The reaction mixture is next poured into a ten liter polyethylene bucket and diluted by addition of ice to an approximate volume of six liters. The bucket is then placed in an ice water bath and the mixture cooled below 10øC, after which the mixture is slowly neutralized by the careful addition of cold dilute sulfuric acid (15 parts water:1 part acid) to a congo red endpoint (pH 4.0 - 4.4). Lysergic acid and considerable potassium sulfate precipitates at this time. The bucket is allowed to stand in the ice water bath several hours when the precipitate is filtered off on a large buchner funnel (15 cm or larger) and sucked as dry as possible on the funnel. The slightly moist filter cake is broken up and placed in a four liter beaker containing 2 1/2 liters of two molar ammoniacal ethanol (about 300 ml liquid ammonia poured into 5.0 liters of chilled anhydrous denatured ethanol). The contents of the beaker are stirred for one hour and then filtered. The filtrate is kept and the filter cake is broken up and extracted in the previous manner with a second portion of two liters ammoniacal ethanol. This extract is filtered using 500 ml of ammoniacal ethanol to wash down the filter cake and the combined filtered extracts are taken to total dryness in a rotary vacuum evaporator over a boiling water bath. The tan colored residue is easily scraped from the sides of the evaporator flask by means of two bent wire rods, one bent less than 90ø and one bent greater than 90ø. The residue is scraped into a large mortar as well as possible with the bent rods and then 225 ml of methanol mixed with 75 ml of water is used in divided portions to wash the remaining residue in the flask into the mortar. The last portion of the methanol-water mixture (about 100 ml) is left in the evaporator flask to be used to wash the mortar clean later. The slurry in the mortar is ground with a pestle to an even consistency free of lumps when it is then poured and scraped into a large Buchner funnel (15 cm or larger) and filtered. The remaining portion of the methanol-water mixture is used to wash down the mortar and the filter cake. Next the filter cake is washed with at least 250 ml of water and sucked dry for an hour. The filter cake is broken up and dried to a constant weight under high vacuum at 90øC in a dessicator.


Yield: 125 to 150 grams of lysergic acid monohydrate, MW.286.35. A slightly off-white powder.


N,N-Diethyllysergamide (LSD)


143.20 grams of lysergic acid monohydrate (0.5 mole) and 21.0 grams of lithium hydroxide hydrate (0.5 mole) are dissolved in 2500 ml of methanol with stirring and warming in a four liter beaker. When the lysergic acid is completely dissolved, the contents of the beaker are admitted to a rotary vacuum evaporator and taken to total dryness over a boiling water bath. A little methanol is used to rinse any lysergate residue that may remain in the beaker into the evaporator. The crumbly, tan colored dry residue is dissolved and rinsed into a five liter boiling flask with three liters of anhydrous dimethylformamide. Considerable care should be exercised when transferring solutions from one vessel to another to avoid loss of lysergate since small deviations from the calculated quantities of reagents result in considerable reduction in overall yield. The five liter flask is next fitted with a 600 mm helices packed fractionating column and about 2050 ml of dimethylformamide is carefully distilled off at 10.0 millimeters pressure to remove water from the lysergate solution. The boiling flask containing lithium lysergate in the remaining dimethylformamide is tightly stoppered and chilled in an ice water bath to below 5øC. 1.0 mole of sulfur trioxide is now added to the flask by addition of the appropriate amount of sulfur trioxide-dimethylformamide reagent (previously prepared by double distilling sulfur trioxide from fuming sulfuric acid and slowly adding it to anhydrous dimethylformamide to make a solution of approximately 1.5 molar strength as determined by titration against standard base solution). Cooling and swirling are continued for 15 minutes when 335 ml of diethylamine is added. Cooling and swirling are continued 15 minutes longer when the reaction mixture is poured into 3800 ml of a 20% saline (sodium chloride) solution to break the reaction complex. The reaction mixture is now extracted with 10.0 to 12.0 liters of methylene chloride (dichloromethane) or chloroform in divided portions in a separatory funnel. A scheme for division of the extraction solvent is as follows:


Extract Quantity Total Solvent Used
First 2000ml 2000ml
Second 1800 3800
third 1500 5300
Fourth 1200 6500
Fifth 1000 7500
Sixth 1000 8500
Seventh 800 9300
Eighth 700 10,000
etc. etc. etc.
Continue until clear lower layer appears.


The extracts from the reaction are combined and shaken up with a little anhydrous magnesium sulfate (120 grams) and filtered. The filtrate is evaporated to dryness in the rotary vacuum evaporator, care being taken not to heat the extracts or the residual syrup above 55øC. A good mechanical vacuum pump and effective cold traps in the line are necessary to remove the residual dimethylformamide from the residue. A brown to black bubbly residue should remain when evaporation is complete. This residue contains the amide product and considerable impurities. A general method of purifying the amide follows.


Method A


The material to be purified (the above residue or other material containing N,N-diethyl lysergamide) is taken up in 1200 ml of methylene chloride containing 20% benzene and applied to a chromatographic column containing two pounds of basic alumina 100-200 mesh Brockmann activity two or three. The column is eluted with nine liters of methylene chloride containing 20% benzene. At this point, the column when viewed with visible light should display three distinct color bands. The uppermost band will be a dark brown or greyish color, the next band will be a reddish brown color, and the lowest band will be a light brown or tan color. The eluant should be amber colored. The column may now be eluted with about one liter methylene chloride containing 0.5% methanol. This will bring the reddish band nearly to the bottom of the column. At no time should any portion of the reddish band be eluted from the column. If any of the reddish band reaches the bottom of the column, elution should be stopped. Next, the total eluant is shaken up with 30 grams of activated charcoal (Norit A) mixed with 30 grams of alumina and filtered. The filter is washed with 600 ml of methylene chloride and the total filtrate taken to dryness on the rotary vacuum evaporator. Care is taken not to heat the residue or solution above 55ø C. The residue is taken up in one liter of benzene and immediately taken to near dryness when another liter of benzene is added to dissolve the residue and the solution is again taken to near dryness. This procedure is repeated until four to five liters of benzene have been added and evaporated. The residue is finally taken to complete dryness at about 45ø C. If sufficient benzene has been added and evaporated, a light tan bubbly, crystalline material will fill the interior of the evaporator flask. It is important that this residue be completely dry before proceeding. The evaporation of benzene from the residue aids removal of solvents and other volatile materials (as azeotropes) which promotes formation of the bubbly crystalline structure in the residue. 700 ml of petroleum ether is next added to the evaporator flask which is then removed from the evaporator and tightly stoppered. The flask is shaken vigorously to loosen the residue from the sides of the flask. Usually all the material comes loose from the flask and forms a slurry in the petroleum ether. If necessary, a bent wire rod may be used to scrape material from the flask. The slurry is now decanted into a buchner funnel and filtered. The filtrate is used to further wash material from the flask into the filter funnel. The filter cake is sucked as dry as possible and then dried to a constant weight under high vacuum at 45øC in a dessicator.


Yield: approximately 130 grams N,N-diethyllysergamide MW 323.42.


The material remaining on the column may be removed with methanol, evaporated in a vacuum and recycled through the isomerization and subsequent procedures by itself or combined with fresh material. Also, all leftover solutions and residues may be neutralized with sodium bicarbonate, evaporated in vacuo, extracted with ammoniacal chloroform, the extract evaporated to dryness, and the residue re-used.


N,N-Diethyllysergamide Tartrate


130 grams of N,N-diethyllysergamide is dissolved in 400 ml methanol and filtered. The filter is washed with 30 ml methanol and the filtrate and washing is poured into a one liter beaker. 30 ml more methanol is used to further wash the filter and filter flask and the wash is also poured into the beaker. 130 ml of diethyl ether is now added to the contents of the beaker. The beaker is gently warmed on a hot plate and 32.0 grams of tartaric acid are then added with constant stirring and warming until they are completely dissolved. The beaker is then allowed to cool. Crystallization of the tartrate usually begins as soon as the tartaric acid dissolves completely. The beaker and contents are refrigerated for at least four hours. Occasional stirring of the crystallizing solution will produce smaller crystals, whereas if the solution is left unstirred during the crystallization, larger crystals will grow. Either is satisfactory. After the beaker has been allowed to stand in the cold four hours or more, the contents are filtered off on a 110 mm buchner funnel with suction. The crystals are washed on the funnel with first 200 ml of a two part methanolne part ether mixture, and then with 250 ml of a two part etherne part methanol mixture. Next the crystals are washed with 600 ml of ether and sucked dry. The filter cake is broken up and allowed to air dry in a warm, dark place.


First crop yield: Approximately 80 grams pale yellow to white needles.


The mother liquors and the two washes containing methanol are collected and combined. A one normal solution of potassium hydroxide in methanol is added in approximately equal volume to the combined washes and mother liquors. The solution is then filtered and the filter washed with a few ml of methanol. The filtrates are allowed to stand at room temperature for two to three hours to re-equilibrate the iso-lysergic acid amides from the mother liquors. About 500 ml of water is then added and the mixture extracted with 2.5 liters of methylene chloride in divided portions in a separatory funnel. The combined extracts are shaken with 25 grams of anhydrous magnesium sulfate and filtered. The filtrate is taken to dryness on the rotary vacuum evaporator, care taken not to heat above 55øC. The material is purified in the same manner as that from the original reaction mixture using approximately one fourth the quantities of solvents and alumina as for the original.


Second crop yield: Approximately 20 grams white needles.


The mother liquors may again be worked up as before, or alternatively, they may be saved and included in subsequent batches.


Third crop yield: Approximately 5 grams white needles.


Total yield: Approximately 105 grams N,N-diethyllysergamide tartrate MW = 430.51 (includes one mole methanol per mole of amide).


Method B


The residue from the previous step is taken up in two liters of chloroform and filtered with suction through a column 50 millimeters in diameter packed with 400 grams of basic alumina, Brockman activity 1. The filtrate is then refiltered through the same column in the same manner four or five times until the filtrate appears light amber and further repetition of this process fails to remove significant color from the filtrate. The column is now eluted by adding several liters of fresh chloroform to the top and sucking it through into the previous filtrate. Sufficient chloroform should be added to remove all blue fluorescent material from the column but not greenish or yellow (use a blacklight in a darkened room). A band of greenish yellow material should remain in the upper 2/3 of the column when viewed in ultraviolet light (blacklight). The total filtrate is taken to dryness in vacuo in a three liter round bottom flask on a rotary evaporator over a 60ø hot water bath. The residue is taken up in 500 ml of benzene and again taken to dryness in the same manner. 500 ml of benzene is again added and taken to dryness. The flask is left on the evaporator under full vacuum for a considerable length of time after the residue appears dry to remove any traces of dimethylformamide that may still remain. A bubbly, crystalline residue should fill the interior of the flask at the end of this step. If any tarry, gummy appearing material appears to remain on the sides of the flask, repeat the addition of 500 ml of benzene and evaporate to dryness again to get a glassy, crystalline appearance. When the material in the flask is totally dry, remove the flask from the evaporator and add sufficient petroleum ether (a commercial mixture of hexanes is excellent for this purpose) to the flask to be able to swirl the crysþalline material around and loosen it from the sides of the flask. Filter this slurry on the buchner funnel with a fritted glass disk and use the filtrate to further wash the remaining material from the evaporator flask into the buchner funnel. Suck the material dry on the funnel and then place in a vacuum dessicator and dry to a constant weight. Record the dry weight of this material N. Calculate the weight of one equivalent of tartaric acid as follows:


Weight of tartaric acid =.232N


Add methanol to a small beaker in a quantity equal to four times N in milliliters. Dissolve the dried material of weight N in this. Dissolve one equivalent of tartaric acid in the same solution, warming the solution gently and stirring. Slowly with stirring, add ether to the solution in the quantity of no greater than.5 N ml. Addition of ether causes a precipitate which dissolves quickly. Ether should be added dropwise with stirring between drops to dissolve any precipitate before addition of the next drop. Crystallization of LSD tartrate should begin shortly after or during addition of the ether. This precipitate does not dissolve and should not be confused with the precipitate caused by the addition of ether. The mixture should be stirred until the solution becomes thickened by formation of crystals. Once crystallization of LSD tartrate is begun it is unnecessary to continue addition of ether. The beaker should be refrigerated several hours and the contents then filtered on a buchner funnel with a fritted glass disk. The crystals are sucked dry and washed with 2.0 N milliters of methanol previously chilled below -5øC and then with 4 N milliliters of a 1:1 mixture of cold ether and methanol. The crystals are sucked completely dry, washed with 8 N ml of ether, sucked dry, and placed in a vacuum dessicator to remove last traces of solvent.


The total filtrates from the crystals (mother liquors plus washings) are made basic by addition of 2 molar ammoniacal ethanol in approximately equal volume and allowed to stand several days at room temperature when the mixture is filtered and taken to dryness and treated in the same manner as the residue from step 2 for a second crop of crystals.


LSD Via SO3 Method 2
Lysergic Acid


Ergotamine tartrate (10g) is added to a stirred de-aerated (nitrogen stream) solution of 38 g potassium hydroxide in 100 ml of methanol and 200 ml of water. The solution turns pink to red. The solution is heated to reflux and the methanol is slowly removed using a partial takeoff. Methanol is allowed to distill until the pot temperature reaches 90-95ø C. The mixture is then maintained at total reflux until the evolution of ammonia ceases (hold pH paper in outlet of reflux condenser to test for ammonia). Nitrogen should be bubbled through the mixture to entrain the ammonia. The hot dark solution is then allowed to cool somewhat and then cautiously acidified with a mixture of 60 ml acetic acid and 60 ml water. The resulting hot solution is quickly treated with Norite "A" decolorizing carbon and filtered hot. The clear purple-hued filtrate is allowed to cool to room temperature (crystallization begins) and then in an ice bath or refrigerator. The crystalline precipitate of lysergic acid (grey to purplish white) is collected, washed with a small amount of cold water (5 ml), followed by cold methanol (5 ml) and ether. Yield 3.2 to 3.8 g. Digestion of the crude acid with about 50 ml of methanol (to remove some of the colored impurities) gave after cooling to 0-10øC and filtering an almost quantitative recovery of lighter colored acid. This material is suitable for conversion into LSD.


Lysergic Acid Diethylamide


1. Sulfur Trioxide-Dimethylformamide Comþlex


Into a carefully dried two liter three necked round bottomed flask fitted with a mechanical stirrer, thermometer and a pressure equalizing dropping funnel protected from the atmosphere with a CaCl2 drying tube, was placed approximately one (I) liter of freshly distilled dimethylformamide (DMF) (a one to three degree fraction BP ca. 62-63øC/20 mm). The DMF was cooled to 0-5ø C by means of an external ice-salt-water bath. Sulfur trioxide (Sulfan B) (ca. 100 g) was then placed in the dropping funnel and added dropwise over a period of 30 to 40 minutes to the stirred DMF. The temperature is carefully maintained between 0 and 5ø C throughout the course of the addition. Stirring is continued thereafter until all of the crystalline material is brought into solution. The resulting reagent solution is then transferred into a suitable reservoir fitted with an automatic burette (protected from the atmosphere with a Drierite tube) and refrigerated. If kept dry, the reagent will be good for a month or two even though it will turn yellow and then orange in color. The molarity of the reagent is then determined by titration against standard base. An aliquot (1 or 5 ml) is first diluted with water (20 or 100 ml) to convert the sulfur trioxide-DMF complex into sulfuric acid. The resulting solution is titrated to phenolphtalein end-point with standard 0.1 or 0.01 N aqueous alkali (NaOH or KOH) to determine the molarity (1/2 of the Normality). It should be in the range of 0.9 to 1.2 depending on the amounts of 503 and DMF used.


2. Lysergic Acid Diethylamide (LSD)


For best results all lysergic acid and LSD solutions should be protected from direct light (yellow light is non-damaging) and the working temperatures should never exceed 25ø C. Lysergic acid monohydrate (7.15 g, 25.0 mmol on a 100% basis) and lithium hydroxide monohydrate (1.06 g, 25.0 mmol) were added to 200 ml of anhydrous methanol and stirred until complete solution occurs. Use magnetic stirrer and keep solution under dry nitrogen in the dark. The solvent methanol is then removed by evaporation under reduced pressure to leave a frothy glass-like residue of lithium lysergate. A solution of the calculated amount of tartaric acid is prepared in methanol (ca. 8 ml/g). Approximately 1/2 of the methanol to be used and 20% of the tartaric acid solution is added to the flask containing the LSD base. The flask is swirled and/or shaken until the solid material has dissolved (5-10 minutes) and the solution is then transferred into an Erlenmeyer flask. The balance of the methanol, in two portions, is used to complete the transfer. At this point the rest of the tartaric acid solution is added. lt may be helpful to titrate the solution to an end-point pH of 5.3, since adding excess tartaric acid solution inhibits crystallization somewhat. However this is optional. If seed crystals are available, they should be added at this point. Crystallization should begin within a 1/2 hour: The flask should then be refrigerated for 12-24 hours at 5-10ø C and then for another 12 hours at -10 to -20øC. For 5 g of LSD base 1 g of tartaric acid in 7-8 ml methanol and an additional 17-18 ml of methanol are used. The crystalline mass of needles is broken up and the cold solution filtered (suction). The filter cake is sucked dry and then washed with anhydrous ether. lf necessary the product may be recrystallized from methanol using 5 ml for each gram. The snow white product melts at 198-200øC.


3. Recrystallization Procedure


The crude tartrate (10 g) is placed in a 125 ml Erlenmeyer flask and boiling methanol (50 ml) is added and the mixture stirred and heated for a minute or two (no longer) until solution is complete. The hot solution is quickly filtered through a previously warmed buchner funnel and the filtrate cooled immediately by swirling in a cold water bath until the temperature drops to 25ø C. Crystallization should be well on the way by this time. The mixture is further cooled to 5 to 10øC and then to -10 to -20øC as previously described, to complete the crystallization. Recovery is between 50 and 70%.


4. Additional Crops of Crystals


The mother liquors from initial crystallizations and from re-crystallizations of LSD can be concentrated by evaporation under reduced pressure to produce additional crops of crystals. The second and third crops of crystals are usually dirty enough to require re-crystallization. After three crops, the mother liquors usually become very syrup-like. They then contain mostly iso-LSD (as the tartrate salt). The iso-LSD salt can be converted back into the base by the addition of methanolic KOH or potassium methoxide to the mother liquor. The resulting mixture should be added to a separatory funnel containing salt solution and ethylene dichloride. The LSD base is extracted into the ethylene dichloride layer (the lower layer). The lower layer is removed and fresh ethylene dichloride used to extract the last traces of LSD base from the salt water-base mixture. The ethylene dichloride extracts are combined, dried with MgSO4, decolorized and filtered through diatomaceous earth as earlier. The resulting ethylene dichloride solution may be combined with the chloroform solutions of iso-LSD which eluted from the chromatographic column. The combined solution may be evaporated to dryness under reduced pressure.


5. Isomerization


The dry iso-LSD base can then be dissolved in methanol and potassium methoxide added. The resulting mixture is stirred for about 30 minutes. During this time isomerization takes place; about 70% of the iso-LSD is converted into the desired "normal" form of LSD. The methanolic solution is poured into a separatory funnel containing salt water solution and ethylene dichloride. The salt water layer is repeatedly extracted with ethylene dichloride to separate the LSD base from the water-base mixture. The ethylene dichloride extracts are combined, dried with MgSO4, decolorized and filtered. The ethylene dichloride solution is then evaporated to dryness under reduced pressure. The resulting dry LSD base is chromatographed on basic alumina (activity grade 1) as previously described. The blue band is collected as before, evaporated and converted into the tartrate salt. The iso-LSD band may be collected and saved for further re-cycling. NOTE: If you only have mother liquors to isomerize, the second mixing with potassium methoxide is unnecessary. Simply prolong the initial mixing to about 1/2 hour.


Total Synthesis of Lysergic Acid


Of the many attempts at the total synthesis of lysergic acid from simple starting materials, only two have been successful (JACS 78,3087(1956), which is very complicated, and CA 74,3762 (1970), which follows). However, it is very likely that some of the intermediates in each attempt are psychedelic. ln fact, this is one of the most promising and least investigated areas of psychedelic chemistry. Following are some references to the synthesis of intermediates: CCCC 33,1576(196; HCA 33,67,375,1796, 2254,2257(1950), 34,382(1951), 35,1249,2095(1952), 36,839 1125,1137(1953), 37,1826(1954), 38,463,468(1955), 44,1531 (1961); JCS 3399,3403(1954); BSC 861(1965); JOC 10,76 (1945), 26,4441(1961), 29,843(1964); Chem. and Ind. 1151 (1953); CJC 41,2585(1963); CPB 12,1405,1493(1964),13,420 (1965), 14,1227(1966); JACS 61,2891(1939), 67,76(1945), 71,761(1949), 73,2402(1951), 78,3087(1956), 79,102(1957), 82,1200(1960), 88,3941 (1966); BER 86,25,404(1953), 87,882 (1954), 88,370,550(1955), 89,270,2783(1956), 90,1980,1984 (1957), 93,2024,2029 (1960), 96,1618(1963),100,2427(1967), 101,2605(196; JMC 8,200(1965); C.R. Acad. Sci. Paris 264 (C), I 18(1967), 265 (C), 110( 1967); BSC 1071 (196; CJC 41,2585(1963); CPB 12,1405,1493(1964), 13,420(1965), 14, 1227(1966); JCS (P.T.1.) 1121(1972), 760(1973), 438(1973); CA 78,71830,72200(1973).


Various analogs containing part of the LSD structure have been synthesized, but few have any activity. See JPS 60,809(1971) for a review of these compounds. For other LSD analogs see JMC 16,804,1015(1973); BSC 2046(1973); CA 48,4489(1954); JPS 62,1881(1973). Some other useful references on LSD chemistry: U.S. Patents 3,856,821 and 3,856,822; Swiss Patent 517,680(1970); Belgian Patent 738,926; French Patent 1,368,420 and addition 91,948 (196. Total Synthesis of LSD German Patent 1,965,896 (1 Oct 1970). German Patent 1,947,063 is the same as 1,965,896. For synthesis of 5-Br-isatin from isatin see CA 33,2516(1939) or BER 40,2492(1907). For the use of cycloaliphatic or aromatic esters in place of methyl- 6-methylnicotinate or of isatin or 4 or 5 chloroisatin or 4-bromoisatin in place of 5-bromoisatin see French Patent Addition #2,052,237 (14 May 1971).


Total yield of LSD from starting materials is probably about 1%


Mix 32.8 g (0.217M) methyl-6-methylnicotinate (other alkyl groups can replace either methyl group) with 45.2 g (0.2M) 5-bromoisatin (apparently 4-Br or 4 or 5 Cl isatin will also work) in a 250 ml flask at 100ø in an oil bath and raise the temperature of the bath to 180ø over 15 minutes. Lower temperature to 170ø and let react for 70 minutes. Cool and then grind the solid as fine as possible in a mortar. Recrystallize from 150 ml dimethylformamide and wash with ether to get 40 g (57%) methyl-a(5-bromo-3-isatylidene)-6-methylnicotinate (I). Suspend 10 g (I) in 250 ml glacial acetic acid and heat to boiling. Add in small portions over 30 minutes excess powdered zinc. Reflux 1 hour, filter and evaporate in vacuum and recrystallize the residue from dioxane to get 9.7 g (95%) methyl-a-(5-bromo-2-oxindol-3-yl)-6-methylnicotinate (II). To a suspension of 18 g dry NaBH4 in 300 ml dry tetrahydrofuran add with stirring at 0ø over 30 minutes about 75 g BF3 etherate. Stir 3 hours at 0ø, add 18 g (II) and heat exactly 20 minutes at precisely 22-24ø. Add carefully 150 ml concentrated HCl while cooling in an ice bath. Add 200 ml water and stir 12 hours. Basify, extract the product with ethyl acetate and dry, evaporate in vacuum to get 11 g of residue which recrystallizes from methanol to give methyl-a-(2,3-dihydro-5-bromo-3-indolyl)-6-methylnictotinate (111).


The following step may be unnecessary but it gives stability to (III). The acetyl group can be split off at the end of synthesis, but this is unnecessary since the 1-acetyl-LSD is as active as LSD.


Treat 12 g (Ill) at room temperature for 24 hours with acetic anhydride then hydrolyze and extract to get 11.5 g residue which is ground in petroleum ether and recrystallized from cyclohexane (can chromatograph on alumina and elute with petroleum ether to wash out an oil, then with benzene containing 5% ethyl acetate to elute the produce) to give methyl-a-(1-acetyl-5-bromo-2,3-dihydro-3-indolyl)-6-methylnicotinate (IV). Heat 5 g (IV),12.5 ml acetone,12.5 ml methanol and 1.8 ml methyl iodide for 18 hours in a Carius tube at 70-80ø. Cool, filter, wash with acetone and recrystallize from methanol to get methyl-a(1-acetyl-2,3-dihydro-5-bromo-3- indolyl)-1,6-dimethylnicotinate iodide (V). To 9.4 g (V) in 250 ml water and 250 ml methanol at 35ø add over 5 minutes 2.9 g KBHþ and stir 10 minutes. Add 2.9 g more KBH4 and stir 30 minutes. Evaporate in vacuum and extract the residue with methylene chloride to get 6.2 g oily mixture containing about 2 g of the d isomer (can separate by chromatography if desired) of methyl-a(1-acetyl-2,3-dihydro-5-bromo-3-indolyl)-6-methyl- 1,2,5,6-tetrahydronicotinate (VI). To a suspension of finely powdered NaNH2 (6.1 g) in 2 liters dry ammonia, add with stirring 8 g (VI) in 50 ml dry tetrahydrofuran. Stir 1 hour, add NH4Cl and evaporate the ammonia as fast as possible in a nitrogen stream. Extract at pH 8 with methylene chloride to get 6 g (can chromatograph on 300 g silica gel and 250 g Celite and elute with 98% benzene-2% absolute ethanol and evaporate in vacuum) of methyl-1-acetyl-2,3-dihydro-lysergate (VII). (VII) can be converted to 2,3-dihydro-LSD (not to be confused with 9,10-dihydro-LSD, which is inactive), which is about ten times less active than LSD. (VII) can be converted to lysergic acid prior to conversion to LSD, which will triple the yield in terms of LSD activity (considering 30% yield). The process (which follows) is somewhat complicated and an easier dehydrogenation process may work. 2,3-dihydro-LSD can be converted directly to 12-hydroxy-LSD, which has about the same activity as LSD and this process is also given below.


Lysergic Acid from 2,3-Dihydrolysergic Acid JACS 78,3114 (1956)


Dissolve 4 g (VII) in 78 ml 1.5% KOH and reflux five minutes (under N2 if possible). Add 8.5 g Na arsenate hydrate and 16 g Raney-Ni (wet) (deactivated by boiling in xylene suspension - see JOC 13,455(194) and reflux twenty hours (under N2 if possible). Filter, precipitate lysergic acid by taking pH to 5.6 with HCl; filter and wash precipitate with water to get 1 g lysergic acid. Evaporate in vacuum the filtrate to get more product.


12-Hydroxylysergamides from 2,3-dihydrolysergamides HCA 47,756(1964)


Warm to dissolve 1.5 g 2,3-dihydro-LSD in 5 ml acetone, 40 ml water and 40 ml saturated NaHCO3. Cool to 20ø and add all at once with vigorous stirring 2.46 g potassium nitro-sodisulfonate dissolved in 90 ml water and 10 mI saturated NaHCO3. After 1 minute, extract 7 times with ethylacetate, wash the combined extracts with water, dry and carefully remove solvent to get a mixture of 12-OH-LSD, LSD and starting material which can be chromatographed to give about 0.2 g 12-OH-LSD. The following method of converting (IV) to the diethylamide (which can probably be used in place of (IV) to give the diethylamide of (V), (VI), and (VII)) will probably also work admirably for (VII) or lysergic acid. Reflux 0.5 g (IV) with 0.5 g KOH in 30 ml methanol for 4 hours. Evaporate in vacuum and add water to the residue. Adjust the pH to between 5 and 6 and filter or centrifuge to get 0.3 g of the free acid. Suspend 1.8 g of the acid in 125 ml chloroform, cool to -5ø and add 0.5 g triethylamine, then 0.6 g ethylchloroformate and stir 45 minutes. Add 2 ml diethylamine and stir 3 hours at room temperature to get, after the usual workup, 1 g of the diethylamide (recrystallize from benzene).


Summary of Procedures and Materials For 1 Kilogram Ergotamine


* Starred chemicals are carefully watched.
**** diethylamine 500 g (725 ml)
methylethylamine 50 g (75 ml)
ethylisopropylamine 50 g (75 ml)
diethyl ether 5 lbs
potassium hydroxide pellets 2 Ibs
methanol 5 L
activated charcoal powder 100 g
tartaric or maleic acid powder 200 g
small cylinder N2 or N2O or freon 
HCL or sulphuric acid concentrated 500 ml
chloroform 5 L (optional but desirable)
ethanol 9 L (optional but desirable)
NH4OH concentrated 500 ml (optional but desirable)
IN ADDITION AT LEAST ONE OF THE FOLLOWING SETS OF REAGENTS


First choice


N,N-dicyclohexylcarbodiimide 500 g
N-hydroxybemotriazol 500 g
(1-hydroxybenzotriazol) 
tetrahydrofuran 10 L
methylene chloride 10 L
Second choice


N,N carbonyldiimidazole 200 g
dimethylformamide 15 L
Third choice


** anhydrous hydrazine 4 L
HCl conc. 1 L
sodium nitrite 1 kg
Fourth choice


** phosphorous oxychloride 200 ml
chloroform 10 L
methanol 5 L
Fifth choice


acetonitrile or DMF 15 L
** trifluoroacetic anhydride 500 g


----------



## Damnecro (May 26, 2013)

Discussions on the synthesis of LSD


Taken from the Hive & Usenet
Plus some reference Lists at the end


HTML by Rhodium


Kaff (posted 05-16-9


It just occurred to me that noone ever mentions acid. I have Fester's book Practical LSD Manufacture but that's about as practical as buying a wheat farm just to make acid. Yeah right Hawaiin Baby woodrose seeds and morning glory seeds have some lysergic acid, but why aren't there any new methods?


drone 342 (posted 05-16-9


I agree, Fester's LSD book was a major disappointment -- yet one more reason to loath the guy. There is an advancement, one which Fester didn't include, which is the use of POCl3 as a dehydrating reagent in the condensation of lysergic acid with diethylamine. Check out Rhodium's page, as well as hyperreal for more info on this new developement.


The wierdest part about it is that it was developed by our friends over at the Edgewood Arsenal in Maryland during the mid-seventies -- the good people who lead the world in cutting-edge chemical warfare technology and supply the intelligence community with all the wierd shit they use. These are the same folks who stockpiled QNB in multi-kilo quantities right into the eighties, as well as the freaky things they don't tell anyone about. Some day, I want a tour of that place.


Anyways, the important thing to keep in mind, which really shows yet again how much Fester talks out of his ass, is that all the seeds, fungi, and other biomass is NOT the way to allocate your lysergic compounds for this reaction. Anybody who makes it on a big scale is using most liekely ergot alkaloids from a commercial source -- foreign pharmacy companies, etc. Its not that hard to get your hands on an ounce or two of ergotamine or ergonovine if you put your noggin to it. Hell, even bromocryptine will work (remove the bromine by maing the grignard out of it, then hydrolyzing it. As long as its done gently, no funky additions, olgermizations or whatever, will happen.)


I've been waiting for someone to bring this subject up. Ask and you shall recieve.


KrZ (posted 05-17-9


Whats wrong with Hawaiin Baby Woodrose? When your making something where 1 dose=50 micrograms a pound of HWBR goes a long ways... Does fester talk about culturing as a source in an incubator?


Fan of Shulgin (posted 05-17-9


IMHO culturing the ergot fungus in the best method by far for producing LSD. Even someone with absolutely no knowledge of microbiology can culture ergot. And as to obtaining the fungus, it can be found in most large fields of rye. This is no joke, wait just until harvest time and go out and have a look for the 'heads'. The beauty of growing the Claviceps is that you can keep it alive for ever if you are careful, and thus have an almost never ending supply of raw material.


It is worth noting, that this is the method that most illegal acid labs operate (look up operation Julie in the UK!). Even producing acid on a small scale requires you to prepare shit loads of the precursors, because even working under red light at low temperatures and low humidity does not have that great an effect on keeping yields high (a 20% yield in LSD manufacture is considered a great success). Remember LSD is inherantly unstable!


Anyway - LSD synthesis, Claviceps cultivation etc are one of the most talked about drug manufacturing methods on the net. Have a good long search around!


drone 342 (posted 05-17-9


I'm telling you guys, mushroom cultivation IS NOT where its at! As far as I can tell, this is not as common of a procedure as people believe. Why? Ever look at the amount of solvents entailed in extracting the stuff? This is a way too involved process that uses far too many resources. MAYBE there's some lab that does this, but it's just not practical. Besides, this bioproduction entails the chemist mastering a whole bunch more skills than the tricky ones already required.


I stand by my procedure as THE ONE TRUE WAY(tm), or at least the best of the one true ways. Think about it: Bromocryptine into bromolysergic acid. Bromolysergic acid into bromolysergic acid diethylamide. Bromolsyergic acid diethylamide into its respective grignard reagent. Grignard reagent decomposition into LSD. Add a dash of tartaric acid, and chromatograph it. All pretty simple procedures -- relatively speaking.


Bromocryptine is easy to get in reasonable quantities. Other ergot alkaloids are also available, and would alow the chemist to skip a debromination step or two as well.


While some believe that LSD is only worthwhile on a mega-huge scale of ounces at a time, I contend that using the sources I suggest, that a gram-size batch would still be a very attractive endevor.


HBWR seeds might be a decent way to go, I agree, but I prefer pill extracting any day. Considering also the price and notriousness of this as a source, other sources should be investigated more thotoughly. How much does a kilo of seeds go for nowadays?


Still, here's another source. Grain companies have a lot of fancy-shmancy equiptment I've been told, soley to remove claviceps from our food supply. This means that every harvest season, your local grain elevator has got pounds of ergot-ladden grain that they normally throw away. This I heard from a friend of mine who worked in a grain elevator -- lost contact with him since my chemical skills were upgraded. This is worth some investigating.


Anyways, I agree that far too little research is being done into these matters, and I'd like to see more discussion of the chemistry of Hoffmann's baby. The chemistry IS above kitchen production conditions, but not out of reach for the semi-elite of The Hive's Chemical Guard. By eliminating the riduculous, over-complicated bullshit procedures out there, and replacing them with simpler, more practical means, the small circle of people willing-and-able to perform this most sacred of chemistry is widended considerably.


KrZ (posted 05-18-9


Drone, c'mon, we are not talking about mushrooms here, wake up son... Mushrooms growing right on top of rye plants, that would look prety silly.. All you need is a sample, some .2% agar plates and some sterile technique, not exactly skill-requiring stuff..


drone 342 (posted 05-18-9


KrZ said: Drone, c'mon, we are not talking about mushrooms here, wake up son... Mushrooms growing right on top of rye plants, that would look prety silly. All you need is a	sample, some .2% agar plates and some sterile technique, not exactly skill-requiring stuff.


KrZ:


Sorry, I suffer from a mild case of irony deficiency, and so its hard for me to tell when folks are pulling my leg. I wholeheartedly aprove of and endorse mushroom cultivation -- provided it is of my favorite basidiomycetes genus that starts with the letter "p".


However, I think you'll discover claviceps is harder than you think. Ever try to get a pure culture of that stuff? If you go through any of the research collections or biotech companies, you're going to have to fill out more paperwork than you'd believe -- not because its laden with ergot goodness, but because its considered a agriculturally harmful organism. It's about as involved as filling out forms for the purchasing of an encapsulating machine. If you choose to isolate your own strain from the field, good luck. You got a 2-month or so window of time to collect it, and then comes the isolation process. Then once you have pure claviceps, you're going to have to isolate a decent-producing heterokaryote from your collection, which you may or may not have. Once you manage THAT, then comes the petri dish phase, followed by the initial submerged culture for producing seed stock, then finally the large-scale submerged culture to yield a a sludge of filaments you gotta strain out, dry, then extract.


Yuck. There are a lot of professional folks out there who's entire days, nay, entire careers relovle around ergot production. I rather rely on the fruits of their labor and save all the schmassle that this project would otherwise entail.


Think about it. I honestly feel the main detractor from more people producing LSD is this ergot culturing myth. Yeah, everyone says "Boy, I sure wish I could make some good acid. All I gotta do is get a chemistry degree under my belt, get a good lab space, and on top of that, raise a culture of some fucked-up saprophytic fungus that'll give me gangrene in the process." This is obviously daunting. If you disagree and say its not too much of a bother, then why aren't more people kicking out kilos of "L"? What I'm proposing is that this fungus cultivation idea is more of a detriment to acid production than an advantage. Just extract the shit from pills, or go to the third world where the stuff is cheap, and you can buy it in its straight uncut powder form for pharmaceutical outlets (there are several countries where you can do this when you know a good pharmacist and have the cake to do some bribing; believe me, I've looked.)


As simple as ergot cultivation sounds, there's plenty of reasons its not done commonly.


drone 342 (posted 05-18-9


Oh yeah, and I almost forgot. With bromocriptine, you can do that grignard degredation process as your first couple steps; this wil cut down on the amounts of POCl3 and Et2N required in the amidation and save you precious resources. Grignards don't readily add to amides, so you can take advantage of that.


drone 342 (posted 05-20-9


Okay, so of available precursors for acid, we got:


HBWR
Ipomoea sp.
Claviceps sp.
Ergot alkaloid pills (ergotamine, ergonovine, etc.)
bromocriptine
a few other misc. plants
Seems to me the chemistry and methodology is pretty cut-and-dry -- the main problem is precursor aquisition. So what other exciting sources might be out there for the ergoloid ring?


drone 342 (posted 05-20-9


Actually, I just stumbled across the articles I was looking for:


J. Ass. Off. Anal. Chem. 53(1), 123-127 (1970)
J. Pharm. Sci. 62(4), 588-591 (1973)
Commodium (posted 05-20-9


Yeah, looks like (according to that Journal of the AOAC article) Hawaiian Baby Wood Rose is 0.04 to 0.30 % LSA, by weight.


drone 342 (posted 05-20-9


Incidentally, I looked into the possible utilization of sleepy grass, butit looked like it was full of all sorts of other alkaloid garbage aside from lisergic acid and its amides. Chanoclavines, Pyridines, etc. This might be a good source if anybody knows a good way of separating the wheat from the chaff in this case. What else besides HPLC will do the trick? (I have an HPLC machine for my amusement, but I can only do tiny volumes; besides, half the point of this research is figuring out ways of doing this kind of stuff successfully garage-style rather than just in the lab.)


Also, does anybody else harbor the same loathing for Fester and his piece-o-shit-excuse-for-an-acid-book as I do? I mean, he completely missed the POCl3 method, and left "method X" a mystery (even though its probobly just as full of shit as the rest of the book.) In addition, he mistakenly thought propionic anhydride had something to do with acid chemistry, and then didn't even give a particularily meaningful synthesis for it. All his methods looked like rehashes of patents from the earlier part of this century (available in half a dozen other publications already,) and the only lysergic acid source he offers is buying a goddam wheat farm and raising a crop of moldy rye grain! Even his claviceps raising would take over a year to accomplish!


So, his book only would be practical for a farmer with a couple years on his hands, a few 55-gallon barrels of tech-grade solvents, a lab full of large-scale equiptment for advanced organic chemical procedures, and some rather extensive training in organic chemistry. If a person had all those resources available to them at the same time, they'd be an idiot if they couldn't find a better way of going about things than that.


buzzz (posted 05-20-9


I haven't looked over it a great deal but, the book Psychedelic Chemistry by Michael Valentine Smith gives detailed info on lysergic acid and extractions for ergot extraction from HBWS and states that the seeds yield 7mg alkaloids/100 g of seeds and that thru the usual steps to reach the end point of lsd that you get roughly 1g LSD / kg of seed. the book can be ordered from Loompanics.


drone 342 (posted 05-20-9


Got a copy of that one already; what library would be complete without MVS's book? Nothing too earth-shattering, but still I like it; there's an aura of honesty to it that you don't see in many other underground drug books. MVS is sure no formally-trained chemist, but at least he knew how to operate a copying machine and give credit where it was due.


Your numbers don't add up. (7mg ergot/100g HBWR)×(1000g/1kg) does not equal even 1g of ergot, but I get the general gist of it. I'll give it a look-see. Thanks for the tip. Considering that a kilo can be boughten for around $300-$400 dollars, it looks like it would almost be a good investment (I prefer the chemistry of drugs where the profit margin is closer to 95-99% rather a mere 75-80%, but hey, its acid.)


KrZ (posted 05-21-9


LSD Manufacture: Illegal LSD Production


LSD has been manufactured illegally since the 1960's. A limited number of chemists, probably less than a dozen, are believed to be manufacturing nearly all of the LSD available in the United States. Some of these manufacturers probably have been operating since the 1960's.


LSD manufacturers and traffickers can be separated into two groups. The first, located in northern California, is composed of chemists (commonly referred to as 'cooks') and traffickers who work together in close association; typically, they are major producers capable of distributing LSD nationwide. The second group is made up of independent producers who, operating on a comparatively limited scale, can be found throughout the country. As a group, independent producers pose much less of a threat than the northern California group inasmuch as their production is intended for local consumption only.


Drug law enforcement officials have surmised that LSD chemists and top echelon traffickers form an insider's fraternity of sorts. They successfully have remained at large because there are so few of them. Their exclusivity is not surprising given that LSD synthesis is a difficult process to master. Although cooks need not be formally trained chemists, they must adhere to precise and complex production procedures. In instances where the cook is not a chemist, the production recipe most likely was passed on by personal instruction from a formally trained chemist. Further supporting the premise that most LSD manufacture is the work of a small fraternity of chemists, virtually all the LSD seized during the 1980's was of consistently high purity and sold in relatively uniform dosages of 20 to 80 micrograms.


LSD commonly is produced from lysergic acid, which is made from ergotamine tartrate, a substance derived from an ergot fungus on rye, or from lysergic acid amide, a chemical found in morning glory seeds. Although theoretically possible, manufacture of LSD from morning glory seeds is not economically feasible and these seeds never have been found to be a successful starting material for LSD production. Lysergic acid and lysergic acid amide are both classified in Schedule III of the Controlled Substances Act. Ergotamine tartrate is regulated under the Chemical Diversion and Trafficking Act.


Ergotamine tartrate is not readily available in the United States, and its purchase by other than established pharmaceutical firms is suspect. Therefore, ergotamine tartrate used in clandestine LSD laboratories is believed to be acquired from sources located abroad, most likely Europe, Mexico, Costa Rica, and Africa.11 The difficulty in acquiring ergotamine tartrate may limit the number of independent LSD manufacturers. By contrast, illicit manufacture of methamphetamine and phencyclidine is comparatively more prevelant in the United States because, in part, precursor chemicals can be procured easily.


Only a small amount of ergotamine tartrate is required to produce LSD in large batches. For example, 25 kilograms of ergotamine tartrate can produce 5 or 6 kilograms of pure LSD crystal that, under ideal circumstances, could be processed into 100 million dosage units, more than enough to meet what is believed to be the entire annual U.S. demand for the hallucinogen. LSD manufacturers need only import a small quantity of the substance and, thus, enjoy the advantages of ease of concealment and transport not available to traffickers of other illegal drugs, primarily marijuana and cocaine.


Cooking LSD is time consuming; it takes from 2 to 3 days to produce 1 to 4 ounces of crystal. Consequently, it is believed that LSD usually is not produced in large quantities, but rather in a series of small batches. Production of LSD in small batches also minimizes the loss of precursor chemicals should they become contaminated during the synthesis process.


LSD crystal produced clandestinely can be as much as 95- to 100-percent pure. At this purity-and assuming optimum conditions during dilution and application to paper-1 gram of crystal could produce 20,000 dosage units of LSD. However, analysis of LSD crystal seized in California over the past 3 years revealed an average purity of only 62 percent. Moreover, LSD degrades quickly when exposed to heat, light, and air and is most susceptible to degradation during the application process and once it is in paper form. As a result, under less than optimal, real-life conditions, actual yields are significantly below the theoretically possible yield: 1 gram of LSD crystal genarally yields 10,000 dosage units of LSD, or approximately 10 million dosage units per kilogram.


Over the past 30 years, the traditional dilution factor for manufacturing LSD has been 10,000 doses per 1 gram of crystal. Therefore, dosage units yielded from high-purity (95- to 100-percent pure) LSD crystal would contain 100 micrograms. However, dosages currently seen contain closer to 50 micrograms. This discrepancy stems in part from production impurities: during the sythesis process, manufacturers generally fail to perform a final 'clean-up' step to remove by-products, thereby lowering the crystal's purity. Further, though average purity of tested LSD crystal samples is, as noted, 62 percent, the average potency of doses analyzed is approximately 50 micrograms rather than 62 micrograms, as would be expected. The diminished potency can be attributed to distributors who, when applying the crystal to paper, often 'cheat' by diluting 1 gram of crystal to produce up to 15,000 or more dosage units.


Pure, high-potency LSD is a clear or white, odorless crystalline material that is soluble in water. It is mixed with binding agents, such as spray-dried skim milk, for producing tablets or is dissolved and diluted in a solvent for application onto paper or other materials. Variations in the manufacturing process or the presence of precursors or by-products can cause LSD to range in color from clear or white, in its purest form, to tan or even black, indicating poor quality or degradation. To mask product difficiencies, distributors often apply LSD to off-white, tan, or yellow paper to disguise discoloration.


At the highest levels of the traffic, where LSD crystal is purchased in gram or multigram quantities from wholesale sources of supply, it rarely is diluted with adulterants, a common practice with cocaine, heroin, and other illicit drugs. However, to prepare the crystal for production in retail dosage units, it must be diluted with binding agents or dissolved and diluted in liquids. The dilution of LSD crystal typically follows a standard, predetermined recipe to ensure uniformity of the final product. Excessive dilution yields less potent dosage units that soon become unmarketable.


LSD crystal usually is converted into tablet form ('microdots' that are 3/32 inch or smaller in diameter), thin squares of gelatin ('window panes'), or applied to sheets of prepared paper (blotter paper-initially used as a medium-has been replaced by a variety of paper types). LSD most frequently is encountered in paper form, still commonly referred to as blotter paper or blotter acid. It consists of sheets of paper soaked in or otherwise impregnated with LSD. Often these sheets are covered with colorful designs or artwork and are usually perforated into one-quarter inch square, individual dosage units.


KrZ (posted 05-21-9


Taken from Michael Valentine Smith: Psychedelic Chemistry, pages 105-107:


The Culture and Extraction of Ergot Alkaloids




Sucrose .................................... 100 g
Chick pea meal .............................. 50 g
Calcium nitrate .............................. 1 g
Monopotassium phosphate ...................... 250 mg
Magnesium sulphate ........................... 250 mg
Potassium chloride ........................... 125 mg
Ferrous sulphate heptahydrate ................ 8.34 mg
Zinc sulphate heptahydrate ................... 3.44 mg
Make up a culture medium by combining the following ingredients in about 500 milliliters of distilled water in a 2 liter, small-neck flask:


Add water to make up one liter, adjust pH 4 with ammonia solution and citric acid. Sterile by autoclaving.


Inoculate the sterilized medium with Claviceps purpurea under sterile conditions, stopper with sterilized cotton and incubate for two weeks periodically testing and maintaining pH 4. After two weeks a surface culture will be seen on the medium. Large-scale production of the fungus can now begin.


Obtain several ordinary 1 gallon jugs. Place a two-hole stopper in the necks of the jugs. Fit a short (6 inch) glass tube in one hole, leaving 2 inches above the stopper. Fit a short rubber tube to this. Fill a small (500 milliliter) Erlenmeyer flask with a dilute solution of sodium hypochlorite, and extend a glass tube from the rubber tube so the end is immersed in the hypochlorite. Fit a long, glass tube in the other stopper hole. It must reach near the bottom of the jug and have about two inches showing above the stopper. Attach a rubber tube to the glass tube as short or as long as desired, and fit a short glass tube to the end of the rubber tube. Fill a large, glass tube (1 inch x 6 inches) with sterile cotton and fit 1-hole stoppers in the ends. Fit the small, glass tube in end of the rubber tube into 1 stopper of the large tube. Fit another small glass tube in the other stopper. A rubber tube is connected to this and attached to a small air pump obtained from a tropical fish supply store. You now have a set-up for pumping air from the pump, through the cotton filter, down the long glass tube in the jug, through the solution to the air space in the top of the jug, through the short glass tube, down to the bottom of the Erlenmeyer flask and up through the sodium hypochlorite solution into the atmosphere. With this aeration equipment you can assure a supply of clean air to the Claviceps purpurea fungus while maintaining a sterile atmosphere inside the solution.


Dismantle the aerators. Place all the glass tubes, rubber tubes, stoppers and cotton in a paper bag, seal tight with wire staples and sterilize in an autoclave.


Fill the 1-gallon jugs 2/3 to 3/4 full with the culture medium and autoclave.


While these things are being sterilized, homogenize in a blender the culture already obtained and use it to inoculate the media in the gallon jugs. The blender must be sterile. Everything must be sterile.


Assemble the aerators. Start the pumps. A slow bubbling in each jug will provide enough oxygen to the cultures. A single pump can, of course, be connected to several filters.


Let everything sit a room temperature (25 C) in a fairly dark place (never expose ergot alkaloids to bright light - they decompose) for a period of ten days.


After ten days adjust the culture to 1% ethanol using 95% ethanol under sterile conditions. Maintain growth for another two weeks.


After total of 24 days growth period the culture should be considered mature. Make the culture acidic with tartaric acid and homogenize in a blender for one hour.


Adjust to pH 9 with ammonium hydroxide and extract with benzene or chloroform/iso-butanol mixture.


Extract again with alcoholic tartaric acid and evaporate in a vacuum to dryness. The dry material in the salt (i.e., the tartaric acid salt, the tartrate) of the ergot alkaloids, and is stored in this form because the free basic material is too unstable and decomposes readily in the presence of light, heat, moisture and air.


To recover the free base for extraction of the amide of synthesis to LSD, make the tartrate basic with ammonia to pH 9, extract with chloroform and evaporate in vacuo.


If no source of pure Claviceps purpurea fungus can be found, it may be necessary to make a field trip to obtain the ergot growths from rye or other cereal grasses. Rye grass is by far the best choice. The ergot will appear as a blackish growth on the tops of the rye where the seeds are and are referred to as "heads of ergot." From these heads of ergot sprout the Claviceps purpurea fungi. They have long steams with bulbous heads when seen under a strong glass or microscope. It is these that must be removed from the ergot, free from contamination, and used to inoculate the culture media. The need for absolute sterility cannot be overstressed. Consult any elementary text on bacteriology for the correct equipment and procedures. Avoid prolonged contact with ergot compounds, as they are poisonous and can be fatal.


The whole part with the pump is unecessary, you can get micropore 1-gallon jugs from http://www.fungi.com and alot of the gear you would need, obtaining a pure strain sounds like the tricky part, culturing and selection of pure-looking samples a couple times should do it. LSD must be synthesized, it's such a beautiful molecule...


Piglet (posted 05-21-9


Fan of Shulgin: I checked out the 'Operation Julie' book and it says that the Ergot compounds were ALL bought. Initially by simply driving to Switzerland and paying cash (those were the days!) and later using fake companies and from underground sources (Brotherhood of Eternal Love with Leary et all).


I have never read of any large LSD manufacturers making there own. It is quite a skill & is quite dangerous (ergot IS classed as a poison, do you like your extremeties? Do you want them to go black and drop off? Don't try growing ergot without knowing the safety rules)


Someone I know was in prison with Kemp (the Julie main-man) and Kemp is a 1 in a million brainiac.


Ergot compounds appear in certain prescription migraine medications (all made by Sandoz, fancy that!)


The book 'Operation Julie' has a few pictures of the chemistry setup. It was pretty involved stuff. One small hilight was a brown bottle featured slap-bang in the middle of one picture. It said 'NaNO2'. Fester says that this 'might' be a replacement for acetyl-acetone. It is. THAT was the Method-X bit. It's not even a secret.


drone 342 (posted 05-21-9


Here's a thought:


What about using DCC as your dehydrating reagent for forming an amide bond? High yields and low temps means better product in larger quantities.


Ref: Encyclopedia for Organic Synthesis, Paquett, L.A., Ed; Wiley, 1995; vol. 3, p. 1731


also check your Merck (of course)


Much of the fancy-schmancy technology devoted to peptide synthesis is equally applicable in this situation as well. There's a ton of ways to go from an acid to an amide, and its good to have as many as possible in one's repetoire.


oh yeah, DCC is "DiCyclohexylCarbodiimide".


Structure: (C6H12)-N=C=N-(C6H12)


The reaction converts this to dicyclohexylurea.


KrZ posted (05-22-9


JLF sells pure claviceps purpea 1 gm for 10.00.


drone 342 (posted 05-22-9


Re: Claviceps. That doesn't sound like too good of a deal. Do they have better prices when you buy in bulk? Even at half the price, that really isn't too good a deal. Considering the tiny percentage of ergot alkaloids in a gram, then considering how much less you have after hydrolyzing off those useless peptides, and how much less you have still after the dehydration of the acid with ethylamine, ten dollars is way more than street prices. This isn't even counting in labor as a cost (most chemists I know like to get paid.)


josh (posted 05-22-9


Hey drone, would you post a synth. for lsd using bromocryptine.This synthesis that you have briefly described is very interesting.This bee would greatly appreciate it.


Ritter (posted 05-22-9


I'm no expert on Grignards, however do you really feel you could get the -Br to react w/ Mg to make the Grignard? My experience has been that its pretty freakin' difficult to make tender complicated multi-cyclic molecules such as bromocryptine undergo Grignard formation. I only skimmed your comments above and may be reiterating what you stated but I think the best way to go about this would be to hydrolyze off the peptide garbage leaving bromo lysergic acid and then subject this to Grignard's reaction. I think the appropriate time to form the amide is after the Grignard because a carboxyl group will probably be less reactive than an amide group towards the Grignard.


drone 342 (posted 05-24-9


Ritter,


Yes, Grignard will work wonders in this case, and no, it actually is easy to get it to do it. All that multicyclic studd simply doesn't appeal to the grignard substituent -- its looking for an electron-deficient site labile and with nowhere to run to. Amides are surpisingly sturdy to these condsitions, and will not readily react at all. As far as I see it, that would really be the only concern (regarding the carbonyls found therin.)The reason for this is that the nitrogen is electron donating, whereas in any other carbonyl, it doesn't have this luxury, and will react readliy with a Grignard. Conditions are a snap, just a nice dry ether soultion or Benzene solution (with light being thoroughly eliminatined from the envronment around the flask) of the free base of your ergot caompound in question will do. If you're still worried about that reaction affecting the peptide, just save it for the last step -- make bromo-LSD, then do it. I guaruntee that the amide will be safe.


Quirks,


Thank you. This is the useful type of information we need buckets of if we want to end the war on drugs (my strategy: an all-out assault; a psychedelic blitzkrieg. Hey, now that's a catchy phrase!)


drone 342 (posted 05-24-9


Fan of Shulgin,


Where can you get a living 1-gram clean specimen of claviceps purpurea? Are you sure its alive? How do you know this works, or is this strictly speculation?


Josh,


Tell you what; I'll give the ref's, and anybody with the resources to actually perform this should also have plenty of access to the library. Actually, all you need is a copy of a decent lab manual describing the synthesis of grignard reagents, and follow the general guidelines for producing a Grignard intermediate. Then, add water. You now have ergocriptine. Hydrolyze it and condense with diethylamine according to the proceedures listed in TiHKAL.


Alternatively, one could use DCC. From the Encyclopedia of Reagents for Organic Synthesis:


Typically, DCC (1.1 equiv) is added to a concentrated solution (0.1-1.0M) of the carboxylic acid (1.0 equiv), amine (1.0 equiv), and catalyst (when used) in methylene chloride or acetonitrile at 0°C. The hydrated DCC adduct, dicyclohexylurea (DCU), quickly precipitates and the reaction is generally complete within 1 h at rt..."


Downsides: THF and DMF screw things up by slowing things down and ecouraging the production of side-products, as well as racemizing the carboxylic acid. The other downside is in some solvents, a trace of DCU can disolve in with your product, requiring purification (nothing flash chromatography wouldn't take care of quite easily, which you have to do anyways if you want to be a good person.)


Further refs:


J. Am. Chem. Soc. 77, 1067 (1955)
Chem & Ind (London) 1087 (1955)
Badanszky, M. Peptide Chemistry: A Practical Textbook; Springer: NY, 1988
J. Org. Chem. 36,1909 (1971)
Piglet (posted 05-26-9


Fan Of Shulgin: When I typed about the dangers of ergot, I meant to to guy producing it. The actual amount of ergot needed to produce 'St. Antonys Fire' immediately seem quite low. It was estimated from the last outbreaks (after WW2 when people were starving and would eat ANYTHING including infested rye) that about 30mg causes SEVERE reactions. I know you would never ingest such amounts of ANY substence in a lab, but growing your own ergot is not a lab technique. I did check out that old chestnut about growing in culture. Most of the researchers had little success. I think it CAN be produced in culture, but only by someone who REALLY knows there stuff. Sandoz grow rye to this day!


drone 342 (posted 06-10-9


Piglet, where did you get this information about Sandoz? As far as I know, Claviceps is one of those organisms that researchers have spent a lot of time, money, and energy in getting it to grow in submerged culture on a large scale -- and have come up with a successful means of doing so. I've heard some similar things in publications from times past, but I suspect that in modern industry, the transition has been made.


Cherrie Baby (posted 06-11-9


"Where can you get a living 1-gram clean specimen of claviceps purpurea?"


During late summer have a look at the Rye grass in the local park. You'll notice a purple-brown "ear" growing on the rye seeds - this stuff is Claviceps purpurea. It grows in my back garden. If you have some experience with shrooms this is easy to grow. The big catch is that nearly all the LSA producing ergot has been from particular strains which you'll have to get from a lab that stocks pure cultures. I don't think wild ergot would work when making LSA's. I've been told that you can grow the ergot (easily) but it won't make LSA unless it's the right strain!


Are there any biochemists out there who know the answer to this one way or another?


Forest Gump (Posted Dec. 24, 1997)


The book that you refer to "Practical LSD Manufacture" by Uncle Fester, now in its 2nd Ed. isn't completely about LSD, although from the title one could get that impression. The first edition contianed 115 pages, of which only about 70 pages actually had anything to do with LSD synthesis, the rest mostly about Fester's pet project: TMA-2 synthesis. The second edition contains 142 pages, almost all the extra pages going to his pet project -- which now consumes about halve the book -- while the LSD portion remains virtually unchanged (all the errors and mistakes of the first edition were remarkably well preserved into the second). A naive person could be forgiven for mistakenly thinking the book of being just a vehicle for his pet project -- but of course we know better.


Before I list just some of those errors let me preface it with this: it is obvious that not only does Fester not have any practical experience with Lysergic chemistry, but that he is also confused by it.


Isomer Confusion. In chapter 4 Fester makes repeated mistakes as to chirality. On page 24, in reference to the anhydrous hydrazine degradation method, he tells us that this procedure produces very little iso- compound, when in fact it produces predominately iso- material. On page 25 he informs us of the importance of maintaining anhydrous conditions to avoid getting racemic product -- on further reading it is obvious that by "racemic" he means iso/normal mixtures, as nowhere is there to be found any reference to the l (levo) compound. 


The older hydrazine hydrate method produced a 1/1 mixture of d and l compounds; the l compounds are inactive and represent a total loss, as there is no convenient method to convert them into the desired d compound. The anhydrous hydrazine method is a newer improvement upon this which avoids the l compound, but it still gives about 2/3 of the iso- compound which is also inactive; 2/3 inactive product sounds real bad, but it's not nearly as bad as the older method because the iso- compound is easily isomerized into the active compound in about 2/3 yield. When Hofmann refers to this new method as not producing any "racemic" material what he means is that it doesn't produce any of the useless l compound, not that it doesn't produce iso- compound. 


Also, the amidation procedure he gives in the same chapter produces some iso- compound, although nowhere does he mention that. Indeed, from reading the purifacation procedure, he seems to think that this amidation method also preserves chirality.




Continuum Error. The first paragraph on page 27 (i.e., "Both of these choices are really very poor, ...") picks up from nowhere, and we're left to wonder what he's refering to. Chalk this one up to bad proofreading (this is Loompanics we're talking about after all).




Outdated Methods. The four amidation methods in the book have long since been superseded by the phosphorus oxychloride in chloroform method, which is not in the book.




Method X. In the book a big deal is made about his erroneous discovery of a "superior" LSD method which he calls "method x". I'll spare you all the convoluted details and inane logic of how he came about this "discovery" except for this one statement of his: "Note that propionic anhydride is a listed chemical under the Chemical Diversion Act, with a reporting threshold of 1 gram. There is only one substance in the field of clandestine drug manufacture where 1 gram is a significant amount -- LSD"
I'm sure not a few DEA chemists must have laughed there ass off after having read that. Propionic anhydride is used to make fentanyl and its analogues. Some fentanyl analogues are 10 times more potent than LSD!!!!


And that is just some of the errors contained within that book. And with that I'll leave you, hopefully a little bit more knowlegable.


FX (Posted Dec. 25, 1997):


Hey, thanks a lot. You seem to know quite a bit about LSD chemistry. I'm sure that Fester's book has some errors, but I am not aware of any other book in existence on practical LSD manufacture. Are you? It is amazing how few people know anything about LSD synth, apparently it is the hardest recreational drug to manufacture of them all, much much harder than ectacy or meth. Why is this? How should someone go about learning about LSD manufacture assuming that they don't have PhDs in chemistry? According to DEA, almost all of the LSD made in the United States is made but just a handful of chemists in california! Can you believe that? A half a dozen people make amost 100 million hits per year, and they have been doing it since the 1960s! This almost blows the mind!


Forest Gump (Posted Dec. 25, 1997):


Below are all the books that are in print that I know of which contain LSD synthesis procedures:


The Anarchist Cookbook, William Powell (1971)
The Book of Acid, Adam Gottlieb (1975)
Psychedelic Chemistry, Michael V. Smith (2nd Ed., 1981)
Recreational Drugs, Prof. Buzz (1989)
Practical LSD Manufacture, Uncle Fester (2nd Ed., 1997)
TIHKAL: The Continuation, Alexander Shulgin (1997)
So, which ones do I recomend for someone serious about LSD chemistry? Well, all of them! But not for the reasons you might think at first.


Most of these books contain serious errors. The Anarchist Cookbook for example has a method of "Making LSD in the kitchen" which is incorrect of course, although it does give an accurate procedure which is merely a reprint of the first part of Pioch's patent method. The Book of Acid calls to use sodium nitrate in one method, when in fact it is sodium nitrite which is used in that procedure. Recreational Drugs doesn't really contain anything that wasn't already in Psychedelic Chemistry, although it does give an incorrect LSD structure. All these books can go a long way in developing one's critical faculties though -- which is an important attribute for an LSD researcher to have, considering the B.S. factor that surrounds LSD.


So, which of these books do I think are the most important to have? All the books listed below, in order of importance:


Psychedelic Chemistry
Practical LSD Manufacture
TIHKAL
Again, not for all the obvious reasons. Number 1 and 2 contain many journal references, and so can be a good step-off point to the real gold mine: the chemical journals at your nearest university science library. TIHKAL and #1 both have the most up-to-date method, although that's the only method TIHKAL has.


Believe it or not, you can probably start learning about LSD chemistry right now if you have a chemistry text-book or are near any library. Just look-up the following (numbered in order of importance):


carboxyl group;
carboxylic acids;
amides;
amines;
also, look-up:


acid halides;
anhydrides;
mixed anhydrides;
hydrazides;
azides;
azoles;
esters;
and of course, alkaloids.


You see, LSD is an amide. LSD is usually made from lysergic acid which is a carboxylic acid and diethylamine which is an amine. Lysergic acid is in turn usually made by degradation of an amide, such as ergotamine.


All of these procedures involve the changing of one functional group: the carboxyl group. A good LSD chemistry researcher will devote much (MUCH) study to this group.


I hope that this has been helpful.




Forest Gump:


CB: (2) Another dodgy thing about Fester's "Practical LSD Manufacture" is his recommendation to make LSAs by growing ergot on rye and to plant your own rye field in order to do this! Is the man mad? Fester appears to be ignorant of the existence of C. paspali.


FG: Yes, Fester is a bit loopy to think that prospective LSD chemists are going to become Farmer for a Year. Although the method certaintly works, the labor and amount of solvents required make it impractical for one or two people.


Some more references:


CB: (4) In D. M. Perrine's book "The chemistry of mind-altering drugs" pages 274-278 outline syntheses of LSD. He includes both modern total synthetic methods and clandestine methods [he figures that lysergic acid is made from either growing C. paspali to produce paspalic acid OR by diverting LSA from medicines]


Some of Perrine's references are:


Kornfeld et al; JACS 1956, 78, 3087-114 [early obsolete method]
Horwell; Tetrahedron 1980, 36, 3123-49 [review of early synth]
Oppolzer et al; Helv. Chim. Acta 1981, 64, 478-81 [modern total synth]
Oppolzer et al; Tetrahedron 1983, 39, 3695 [modern total synth]
Rebek & Tai; Tet Lett 24, 859-60 (1983), (and refs therein) "A New Synthesis of Lysergic Acid", [from tryptophan]
Rebek, Tai & Shue; JACS 106, 1813-19 (1984) "Synthesis of Ergot Alkaloids from Tryptophan"
Kobel et al; Helv. Chim. Acta 1964, 47, 1052 [paspalic acid form C. paspali]
Troxler; Helv. Chim. Acta 1968, 51, 1372 [Isomerisation of paspalic acid to lysergic acid]
CB: (5) In M. V. Smith's "Psychedelic Chemistry" growth of C purpurea on synthetic media is described. Just about everyone claims that C purpurea will only grow on grain in a field. What's Up Doc?


FG: Getting species of Claviceps to grow in culture is easy. Getting species of Claviceps to grow in culture and produce lysergamides' is what's hard. I'm sure M. V. Smith's method in said book will work just fine for growing Claviceps species, but it will all be for nought, as no lysergamides' will be produced by it.


Successful culture methods have been developed which use specific strains of both C. paspali and C. purpurea to produce as much as 2 to 5 g of lysergamides per liter of culture!!!!


I direct you to "Biosynthesis of Ergot Alkaloids and Related Compounds", Tetrahedron, Vol. 32, pp. 873-912 (1976). On page 883 under the heading "Industrial production of ergolines" it gives a brief overview of what I just mentioned, and gives references to those procedures.


I hope that this has been helpful for you.




Subject: Lysergic Acid references as promised... 
From: [email protected] (aankrom) 
Date: Thu, 7 Apr 1994


FN Johnson et al, J. Med. Chem. 16, 532 (1973), "Emetic Activity of Reduced Lysergamides"


(LSAs using amine and POCl3) JACS 76, 5256; Tet. Lett. 1569 (1969)


Biosynthesis of ergot in submerged culture: 
Arcamone et al, 
Proc. Roy. Soc. B155, 26 (1961)


Stoll & Hofmann - In "The Alkaloids" - ed Manske & Holmes, vol 8, 725-83.


Fetoclavine & fumigaclavine in Aspergillus fumigatus
Fres, Spilsbury & Wilkinson 
Fumigaclavine in Rhizopus nigricans - Yamano et al, 1962, 1961


KrZ - posted 06-21-98


http://www.alltheway.com/html/ergot.html


CA: 7169351y : Describes mutants of strain NRRL 3027 producing 2270mg/l of ergoline compounds of which 85% were amides of lysergic and isolysergic acids. (Swiss patent application)


CA: 77156333n : Describes a method used to get 9.75g pure lysergamides from a 10 litre fermentation originally containing an estimated 15g.


CA: 94:13992r : Reference Indian Drugs; 1980; 17( 228-31 (Eng.)


CA: 90:118108c : Reference Indian Drugs; 1979; 16(4) 88-93 (Eng.)


CA: 102:219574y : Serbo-Croat areticle describing 2.2g/l prod. by C. paspali Stevens and Hall (1984).


Life History and Poisonous Properties of Claviceps paspali; 
H. B. Brown (Mississippi Agricultural Experiment Station); 
Journal of Agricultural Research, Vol. 7, No. 9, pp 401-405. 
Describes on brief glance through it - germination of the yellowish-grey sclerotia found on Paspalum dilatatum Poir. observed in the region of the Mississippi Agricultural College. Also contains reference to Stevens and Halls' original article (1910).


Biotechnological Exploitation of the Ergot Fungus (Claviceps Purpurea); 
Karl Esser and Andrea Duvell; Process Biochemistry, August 1984 pgs 142-149.
Synopsis: "The alkaloids of the ergot fungus C. purpurea and related species already known as drugs in the middle ages are still finding many uses in medical therapy (he he). Since the supply of natural grown ergots is not sufficient, the biotechnological production of ergot alkaloids has gained in importance. This requires not only an undestanding of physiological and environmental conditions, but also concerted breeding in order to increase and stabilize the production level".


Biology of Claviceps; Willard A. Taber; Chapter 15 (sorry - i don't remember which book this came from, but it should be indexed under Taber in Biological Abstracts) pgs 449-486. 
"If one desires isolates of C. paspali (which are high producers of simple amides), one must go to paspalum grass. ... C. paspali differs from all other species in possesing a yellowish tan cauliflower- shaped sclerotium rather than the purplish banana-shaped sclerotium, and it has been suggested that this species be trasnsferred to the genus Mothesia."


The Ergot Alkaloids; A. Stoll and A. Hofmann (THE); 
Chapter 21, The Alkaloids, Manske (ed. ?) vol. VIII, pgs 725-779+. 
Describes lots and lots and lots of chemical detail regarding everything from biogenesis to complete chemical synthesis as a means of confirming structure. Also has a section completely devoted to "Derivatives of Ergot Alkaloids" in which the following processes for synthesizing amides are discussed:


The azide process.
DMF-SO3 mixed anhydride method.
mixed Lysergic acid trifluoroacetic anhydride.
Lysergic acid chloride hydrochloride method.
N,N'-carbonyldiimidazole as condensing agent (Best IMHO).
Kobel, Schreier, Rutschmann. Helv. Chim. Acta, 47, 1052 (1964)




Subject: LSD in the Literature


Certainly making LSD from 'scratch' is not currently thought to be cost effective, however, a variety of publications exist describing how. I realize that this compilation may be above most of your heads however some of the more serious of you might be interested in some of the literature describing various LSD syntheses. If you know of others please post them.


A short synthesis of the 8-azaergoline ring system by intramolecular tandem decarboxylation-cyclization of the Minisci-type reaction
Doll MKH 
J Org Chem 64, 1372-1374 (1999)


Enantiospecific synthesis of (R)-4-amino-5-oxo-1,3,4,5-tetrahydrobenz[cd]indole, an advanced intermediate containing the tricyclic core of the ergots 
Hurt CR, Lin RH, Rapoport H 
J Org Chem 64, 225-233 (1999)


Practical synthesis of 8-alpha-amino-2,6-dimethylergoline: An industrial perspective 
Baenziger M, Mak CP, Muehle H, et al. 
Org Process Res Dev 1(6), 395-406 (1997)


New synthesis and characterization of (+)-lysergic acid diethylamide (LSD) derivatives and the development of a microparticle-based immunoassay for the detection of LSD and its metabolites 
Li Zy, Gocszkutnicka K, McNally AJ, et al. 
Bioconjugate Chem 8(6) 896-905 (1997)


Total synthesis of 2,6-dimethylergolin-8 alpha-amines
Waldvogel F, Engeli P, Kusters E 
Helv Chim Acta 80(7), 2084-2099 (1997)


A new synthesis of indoles 
Murphy JA, Scott KA, Sinclair RS, et al. 
Tetrahedron Lett 38(41), 7295-7298 (1997)


An attempted total synthesis of lysergic acid via an alkene/N-sulfonylimine cyclization 
Ralbovsky JL, Scola PM, Sugino E, et al. 
Heterocycles 43(7), 1497-1512 (1996)


Enzymatic Synthesis Of Beta-N-Acetylhexosaminides Of Ergot Alkaloids 
Kren V, Scigelova M, Prikrylova V, Et Al. 
Biocatalysis 10(1-4), 181-193 (1994)


Synthesis Of Lysergic-Acid Derivatives By Tandem Radical Cyclization Reactions
Ozlu Y, Cladingboel De, Parsons Pj 
Synlett (5), 357-358 (1993)


A New Synthesis Of (±)-Lysergic Acid 
Kurihara T, Terada T, Yoneda R
Chem Pharm Bull 34(1), 442-443 (1986)


A New Synthesis Of Lysergic Acid 
Rebek J, Tai Df 
Tetrahedron Lett 24(9), 859-860 (1983)


A New Synthesis Of (±)-Lysergic Acid 
Kiguchi T, Hashimoto C, Naito T, Et Al. 
Heterocycles 19(12), 2279-2282 (1982)


Total Synthesis Of (±)-Lysergic Acid By An Intramolecular Imino-Diels-Alder Reaction 
Oppolzer W, Francotte E, Battig K 
Helv Chim Acta 64(2), 478-481 (1981)




Synthesis of LSD-25


Originally published in 1967 as "The Psychedelic Guide to Preparation Eucharist" by Robert E. Brown.


Preparatory arrangements


Starting material may be any lysergic acid derivative,from Claviceps purpures(ergot) on rye grain or from culture, from Ipomea (morning glory) seeds, or from synthetic sources. Preparation #1 uses any amide, or lysergic acid as starting material. Preparations #2 and #3 must start with lysergic acid only, prepared from the amides as follows:


10 g of any lysergic acid amide from various natural sources is dissolved in 200ml of mathanoic KOH solution and the methanol removed immediately in vacuum. The residue is treated with 200ml of an 8% aqueous solution of KOH and the mixture heated on a steam bath for one hour. A stream of N2 gas is passed through the flask during heating and the evolved NH3 in the gas stream may be titrated in HCL to follow the reaction. The alkaline solution is made neutral to congo red with tartaric acid,filtered,cleaned by extracting with ether, the aqueous solution filtered and evaporated. Digest with MeOH to remove some of the colored material from the crystals of lysergic acid.


Arrange the lighting in the laboratory similarly to that of a darkroom. Use photographic red and yellow safety lights since lysergic acid derivatives are decomposed by light. A weak, long wave ultraviolet source is conveniently made from the purple glass filter used in the 1950 ford dash lighting system. A small tungsten bulb will provide enough light.


Have plenty of aluminum foil handy to cover reagents and products when light is present. Rubber gloves must be worn due to the highly poisonous nature of ergot alkaloids. A hair dryer, or, much better, a flash evaporator, is necessary to speed up steps where evaporation is necessary.


Preparation #1


Step I - Use Yellow Light


Place one volume of powdered ergot alkaloid material in a tiny roundbottom flask and add two volumes of anhydrous hydrazine. An alternate procedure uses a sealed tube in which the reagents are heated at 112°C. The mixture is refluxed (or heated) for 30 minutes. With an open condenser, keep an inert atmosphere on the reaction. Add 1.5 volumes H2O and boil 15 minutes. On cooling in the refrigerator, isolysergic acid hydrazide is crystallized.


Step II - Use Red Light


Chill all reagents and have ice handy. Dissolve 2.82 g of the hydrazide rapidly in 100ml 0.1 N ice-cold HCl using an ice bath to keep the reaction vessel at 0°C. 100ml ice-cold 0.1 N NaNO2 is added and after 2 to 3 minutes vigorous stirring, 130ml more HCl is added dropwise with vigorous stirring again in an ice bath. After 5 minutes, neutralize the solution with NaHCO3 saturated sol. and extract with ether. Remove the aqueous solution and try to dissolve the gummy substance in ether. Adjust the ether solution by adding 3 g diethylamine per 39ml ether extract. Allow to stand in dark, gradually warming up to 20°C over a period of 24 hours. Evaporate in vacuum and treat as indicated in the purification section for conversion of iso-lysergic amides to lysergic acid amides.


Preparation # 2


Step I - Use Yellow Light


5.36 g of d-lysergic acid are suspended in 125ml of actonitrile and the suspension cooled to about -20°C in a bath of acetone cooled with dry ice. To the suspension is added a cold -20°C solution of 8.82 g of trifluoroacetic anhydride in 75ml of acetonitrile. The mixture is allowed to stand at -20°C for about 1.5 hours during which time the suspended material dissolves, and the d-lysergic acid is converted to the mixture anhydride of lysergic and trifluoroacetic acids. The mixed anhydride can be separated in the form of an oil by evaporating the solvent in vacuum at a temperature below about 0°C. Everything must be kept anhydrous.


Step II - Use Red Light


The solution of mixed anhydrides in acetonitrile from Step I is added to 150ml of acetonitrile containing 7.6 g of diethylamine. The mixture is held in the dark at room temperature for about 2 hours. The acetonitrile is evaporated in vacuum, leaving a residue of LSD-25 plus other impurities. The residue is dissolved in 150ml of chloroform and 20ml of ice water. The chloroform layer is removed and the aqueous layer is extracted with several portions of chloroform. The chloroform portions are combined and in turn,washed with four 50ml portions of ice-water. The chloroform solution is then dried over anhydrous Na2SO4 and evaporated in vacuum.


Preparation # 3


The following procedure gives good yield and is very fast with little iso-lysergic acid being produced, however, the stoichometry must be exact or yields will drop.


Step I - Use White Light


Sulfur trioxide is produced in an anhydrous state by carefully decomposing anhydrous ferric sulfate at approximately 480°C. Store under anhydrous conditions.


Step II - Use White Light


A carefully dried 22 liter RB flask fitted with an ice bath, condenser, dropping funnel and mechanical stirrer is charged with 10 to 11 liters of dimethyformamide (freshly distilled under reduced pressure). The condenser and dropping funnel are both protected against atmospheric moisture. 2 lb. of sulfur trioxide (Sulfan B) are introduced dropwise, very cautiously with stirring, during 4 to 5 hours. The temperature is kept at 0-5 degrees throughout the addition. After the addition is complete, the mixture is stirred for 1-2 hours until some separated,crystalline sulfur trioxide-dimethylformamide complex has dissolved. The reagent is transferred to an air-tight automatic pipette for convenient dispensing, and kept in the cold. Although the reagent, which is colorless may change to yellow and red, its efficiency remains unimpaired for three to four months in cold storage. An aliguot is dissolved in water and titrated with standard NaOH to a phenolphthalein end point.


Step III - Use Red Light


A solution of 7.15 g of d-lysergic acid monohydrate (25 mmol) and 1.06 g of lithium hydroxide hydrate (25 mmol) in 200 L of MeOH is prepared. The solution is distilled on the steam bath under reduced pressure. The residue of glass-like lithium lysergate is dissolved in 400ml of anhydrous dimethyl formamide. From this solution about 200ml of the dimethyl formamide is distilled off at 15mm pressure through a 12- inch helices packed column. The resulting anhydrous solution of lithium lysergate left behind is cooled to 0 degrees and, with stirring, treated rapidly with 500ml of SO3-DMF solution (1.00 M soln). The mixture is stirred in the cold for 10 minutes and then 9.14 g (125.0 mmol) of diethylamine is added. The stirring and cooling are continued for 10 minutes longer, when 400ml of water is added to decompose the reaction complex. After mixing thoroughly, 200ml of saturated aqueous NaCl solution is added. The amide product is isolated by repeated extraction with 500ml portions of ethylene dicloride. The combined extract is dried and then concentrated to a syrup under reduced pressure. Do not heat the syrup during concentration. The LSD may crystallize out, but the crystals and the mother liquor may be chromatographed according to the instructions on purification.


Purification of LSD-25


The material obtained by any of these three preparations may contain both lysergic acid and iso-lysergic acid amides. Preparation #1 contains mostly iso-lysergic diethylamide and must be converted prior to separation. For this material, go to Step II first.


Step I - Use Darkroom and follow with Long Wave UV


The material is dissolved in a three to one mixture of benzene in chloroform. Pack a chromatography column with a slurry of basic alumina in benzene so that a one-inch column is six inches long. Drain the solvent to the top of the alumina column and carefully add an aliquot of the LSD-solvent solution containing 50ml of solvent and 1 g LSD. Run this solution through the column, following the fastest moving blue fluorescent band. After it has been collected, strip the remaining material from the column by washing with MeOH. Use the UV light sparingly during this procedure to prevent excessive damage to the compounds. Evaporate the second fraction in vacuum and set aside for Step II. The fraction containing the pure LSD is concentrated in vacuum and the syrup will crystallize slowly. This material may be converted to the tartaric acid and the LSD tartrate conveniently crystallized, mp 190-196°C


Step II - Use Red Light


Dissolve the residue derived from the methanol stripping of the column in a minimum amount of alcohol. Add twice that volume of 4 N alcoholic KOH solution and allow the mixture to stand at room temperature for several hours. Neutralize with dilute HCl, make slightly basic with NH4OH and extract with chloroform or ethylene dicloride as in preparations #1 or #2. Evaporate in vacuum and chromatograph as in the previous step.


Salvage


Neutralize all leftover solutions and residues with NaHCO3 and evaporate in vacuum to low volume. Extract with ammoniacal chloroform and evaporate the extract to dryness. This residue may be run through the whole process again and more LSD will be produced.


Storage and use


Lysergic acid compounds (among them LSD) are unstable to heat, light and oxygen. In any form it helps to add ascorbic acid as an anti-oxidant, keeping the container tightly closed, light-tight with aluminum foil, and in refrigerator.


Packaging for use presents many possibilities, partially due to the incredibly small dosage involved. First a bio-assay of the solvent is made, then it may be measured by the volume of the solvent it is in. The solvent may be evaporated onto a weighed, calculated amount of some inactive powder such as chalk. sugar or baking soda. This bulky powder may be easily encapsulated in weightable portions. It is advantageous to add a trace of dry ascorbic acid to the dried powders. Sugar cubes offer a handy but extremely notorious method of dispensing. Other methods are without number, here being offered just a few occasionally used by the criminal element. Gelatin capsules are coated with the liquid solution and the capsules filled with an inert substance. Decoys such as this inert mixture might include a trace of brown color, a trace of quinine for fluorescence, and a trace of some relatively non-toxic compound which nearly mimicas the infra-red spectrum of LSD. For transport, a smuggler might evaporate a considerable amount onto a pocket handkerchief or onto a sheet of paper, providing the solution was properly decolorized before such treatment. These underhanded methods are used by criminals to avoid punitive action by law enforcement enthusiasts.


One gram of pure LSD, if used in a truly enlightened, careful manner can be the door to a magnificent experience to nearly 3,000 individuals. Used furtively and in ignorance, the same amount may bring terrible confusion and abject terror to nearly one-third of these.


Bibliography


Chem. Abstracts 44, 10740
Chem. Abstracts 38, 1499c
Chem. Abstracts 41, 2450d
J. Org. Chem. 24, 368-372 (195
J. Biol. Chem. 104, 547 (1934)
US Patent 2,736,728
Ergot Culture and Extraction of Lysergic Acid Derivatives


Chem. Abstracts 57, 13021
Chem. Abstracts 60, 11345


Synthesis of d-LSD maleate or tartrate from lysergic acid with POCl3


Emetic Activity of Reduced Lysergamides
Johnson, Ary, Teiger, Kassel. J
Journal of Medicinal Chemistry 16(5), 532-537 (1973)


Related:


Drug Discrimination and Receptor Binding Studies of N-Isopropyl Lysergamide Derivates 
Huang, Marona-Lewicka, Pfaff, Nichols 
Pharmacology, Biochmistry and Behavior 47(3), 667-673 (1994)


Stereoselective LSD-like Activity in d-Lysergic Acid Amides of (R)- and (S)-2-Aminobutane 
Oberlender, Pfaff, Johnson, Huang, Nichols 
Journal of Medicinal Chemistry 35(2), 203-211 (1992)


Synthesis and LSD-like Descriminative Stimulus Properties in a Series of N6-alkyl Nor-LSD Derivates 
Hoffman-AJ, Nichols 
Journal of Medicinal Chemistry 28, 1252-1255 (1985)


Note: JMC 35(2), 203-211 (1992) has some amazing stereoviews of LSD which might interest non-chemists who like to cross their eyes...




From: [email protected]


As a public service to alt.drugs I have posted the following with some comments by myself. The following is a good example of the credo: A handful of refs does not a chemist make. I found this on one of the drug info sites. I've number the lines for commenting.


LSD Synthesis


Under reduced light (or red light) a stirred solution of 3.15g (11mmol)
of d-lysergic acid monohydrate and 4.45g (99 mmol) of diethylamine was
brought to reflux by heating. Heat was removed, and reflux was maintained
by the addition of 2 mL (3.4g, 22mmol) of phosphorous oxychloride (POCl3)
over a 2 minute period. The mixture was then refluxed for an additional
4-5 mins until an amber-colored solution resulted. The solution was
brought to room temperature and was washed with 200ml of 1M NH4OH.
The CHCl3 solution was dried (MgSO4), filtered, and concentrated under vacuum
(not allowing the solution to exceed 40°C). The last traces of the solvent were removed at 2-5 mmHg. The viscious residue was dissolved in a minimum amount of MeOH and acidified with a freshly prepared 20% solution of maleic acid in MeOH. Crystallization occured spontaneously. The needles were filtered, washed with cold MeOH and air-dried. Yield was 66% after further purification by column chromatography over alumina (Brockman) and elution with 3:1 benzene-chloroform. The chromatography takes appx 8-9 hours. Alternatively, it can be crystallized as the (+)-tartrate from MeOH. After crystallizing from cold MeOH, it is diluted with ethyl acetate, filtered and the the crystals are washed with ethyl acetate.
This procedure also works for primary amines and small dialkyl amines. LSD, however, probably remains the most worthwhile product. Other interesting amines might be the N-ethyl-N-propyl derivative (LEP) and the morpholide (LSM-775). 75µg of the morpholide have been reported to have been as effective as 50µg of d-LSD but with 45 min onset (vs 1 hour) and a 1 hour peak (vs 4 hours). The procedure would probably work well for LEP, but yields would be reduced for the morpholide. Other N20-alkyl-lysergic acid derivatives tend to be more than 10 times less potent than LSD if not effectively inactive. N6-ethyl- (and allyl/propyl) derivates of LSD may be more active than LSD itself, but synthetic routes to these chemicals presently start with LSD and yields would probably inhibit their appearance on the illicit market. (N6 is the other nitrogen on the ring structure in addition to the N1 pyrrole/indole nitrogen). Derivatives of LSD (besides LSA/LA-111 and lysergic acid) are not scheduled, but would be prosecutable under the designer drugs act after testimony from a DEA agent that in their opinion the defendant was planning to distribute them.


Comments:


Line 1: suppose to be a refluxing slurry according to ref: [Johnson, Ary, Teiger, Kassel. "Emetic Activity of Reduced Lysergamides." Journal of Medicinal Chemistry 16(5), 532-537 (1973)] Method B


Line 2: The 3.25g of d-lysergic acid monohydrate is suppose to be dissolved in 150ml of CHCl3. 96mmol of diethylamine is supposed to be used and 96mmol of this is ~7.1g, not 4.45g...(where's a good periodic chart when you need one?). The 7.1g of diethylamine is supposed to be dissolved in 25ml of CHCl3.


Line 3-4: To the 3.25g of d-lysergic acid monohydrate dissolved in 150ml of CHCl3 that is undergoing reflux is added the diethylamine/CHCl3 solution and 2 ml of POCl3. These are added simultaneously from separate dropping funnels over 2-3 minutes. Method B


Line 8: The CHCl3 is dried... What? Yes, it's dried but this is the first time that the procedure that was given in this "how to" even makes mention of it! Of course, all of this is made very clear in the ref: [Johnson, Ary, Teiger, Kassel. "Emetic Activity of Reduced Lysergamides." Journal of Medicinal Chemistry 16(5), 532-537 (1973)]


It's pretty clear that this "how to" was posted by someone with little or no chemical expertise who had a couple of refs in hand, ran to the local college library, photocopied the papers, typed up this mess and posted it for the benefit (ha!) of others.


So, do you still want to attempt a synthesis of LSD? Yes? Well get the refs and get the whole story. A few chemistry classes wouldn't hurt either.




From: [email protected] 
Subject: Re: How to Make LSD File 2 
Date: Mon, 4 Apr 1994


When I saw the subjects relating to the synthesis of LSD, I knew the information would be outdated. It's humourous to see people who think they're in the know giving out info that was outdated even in the 70's.


Lysergic acid amides are commonly made by a simple and efficient procedure using POCl3 and the desired amine in CHCl3 solution. I doubt that this procedure is used by the majority of clandestine chemists, but since I don't know any, I wouldn't know. By the description of the procedure, it's simple and uses relatively safe reagents (I have a reference, but not handy...) And you won't find it in any obvious places even in the most recent Merck because LSD is not the product of focus in the article.


This is why I doubt that unsavvy clandestine chemists would be using this procedure. But according to the article, the method has a broad scope and has been used by Nichols and Oberlender for some other lysergic acid amides. (The article in question regards 9,10-saturated derivatives tested for emetic properties). It's time to stop turning to those stupid "how to make your very own drug" guides and learn how to read real chemsitry literature. If you can't, don't bother...


Even the synthesis of lysergic acid is outdated. Rebek has described an extremely elegant synthesis of methyl lysergate from L-tryptophan which gives only the natural isomer of lysergic acid. It's still a several step procedure, but most of the reagents are fairly common and the yields are greatly improved over past syntheses.


This brings me to an interesting side-note. Several years ago, analogues of LSD that were 2 and 3 times as potent as LSD were synthesized. These went largely unnoticed and would most likely prove of little interest to clandestine chemists because LSD was the precursor used and the loss in synthesis outweighed the gain in potency. But using Rebek's synthesis, one could simply alter the procedure slightly and intorduce the groups that make the compounds more potent. When the 6N-methyl group is replaced by ethyl or allyl, it becomes 2 and 3 times as potent respectively.


I am posting this for general information. I may post references if I decide it would be prudent. Requests will be ignored and I ask you not to send e-mail requesting references. But if you just want to chat about them and maybe speculate on subjective effects or other avenues of substitution... I don't know if I'll ever see the day that research in this area is open and legal, but I'd love to...




From: [email protected] 
Subject: References as promised... 
Date: Thu, 7 Apr 1994


OK. The references that I mentioned, here they come...


Synthesis of Ergot Alkaloids from Tryptophan 
J Rebek Jr., et al, 
J. Am. Chem. Soc. 106, 1813 (1984)


A New Synthesis of Lysergic Acid 
J. Rebek Jr., et al, 
Tet. Lett. 24(9), 859-860 (1983)
(and refs. therein.)


Emetic Activity of Reduced Lysergamides 
FN Johnson et al, 
J. Med. Chem. 16, 532 (1973)
(Lysergamides using s-amine and POCl3)


I still feel like making a disclaimer that I am not encouraging this information to be used to synthesize illegal compounds, but for personal enlightenment. It's time to pull chem-wannabe's out of the Dark Ages!


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## Impman (May 27, 2013)

your the man. All these other whiners and you come through the the damn business. nice!


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## canndo (May 28, 2013)

6700 said:


> this would be your best bet, with a DEA license and some social engineering you could buy LSD https://www.sigmaaldrich.com/catalog/product/sigma/l7007?lang=en&region=US



$99 a mg? kinda high isn't it?


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## Damnecro (May 31, 2013)

Impman said:


> your the man. All these other whiners and you come through the the damn business. nice!


Thank you, but the gentlemen in this thread are merely looking out for you bud. alot of people under estimate the severity of such synthesis and the consequences can be horrific. the fear in someones eyes when a spill occurs is definitely a bad time and from there it can just become worse. the legal aspect pales as a friend's ID is in play and despite yer efforts only parts return back from the ether. Temper the ability to do with the mindfulness if you should.


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## thechemist513 (Jun 14, 2013)

ive collected wild ergot spurs with my hands it didnt effect me i wouldnt recommend it its mostly consumption there are 
ways to make ergott extacts that are
safe to a degree to consume but there is alot of misnformatiot and scare tactics out there


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## thechemist513 (Jun 14, 2013)

i have paspali and ergot spores leave a reply


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## [email protected] (Mar 24, 2016)

Ergot does not survive in America or many parts of Asia due to competing molds in the atmosphere. Anyone that can give you spores would be from Europe. And you should not mess with them. Spores may not be illegal, but St. Anthony's Fire is not a fun thing to encounter.


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## hockeybry2 (Mar 24, 2016)

Plenty or ergot on rye in the us


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## bluntmassa1 (Mar 24, 2016)

thechemist513 said:


> ive collected wild ergot spurs with my hands it didnt effect me i wouldnt recommend it its mostly consumption there are
> ways to make ergott extacts that are
> safe to a degree to consume but there is alot of misnformatiot and scare tactics out there


Yeah their must be a way I read somewhere that the ancient Greeks used to trip on it not sure how it was prepared though. I do kind of want to take a chemistry class though if I learn enough to make LSD I can be a millionaire.


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## hockeybry2 (Mar 24, 2016)

It'd be easier to make mdma


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## [email protected] (Mar 24, 2016)

No, the spores are not natural in the US. Most of your "end product" in the US comes from spores from a greenhouse in the far north of Norway. Nobody can hardly get there to do anything about it, but everyone knows it is there.
As to the Greeks, lysergic acid can be extracted from ergot easily enough. In fact, your body will do it for you if you take in ergot and alcohol at the same time.
Trust me, your average doctor in America hasn't the vaguest idea about what to do for exposure to the actual fungus. It is not natural here. Anybody with half a brain can look it up on wikipedia. Spores definitely come from Europe.


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## mikek420 (Mar 24, 2016)

bluntmassa1 said:


> Yeah their must be a way I read somewhere that the ancient Greeks used to trip on it not sure how it was prepared though. I do kind of want to take a chemistry class though if I learn enough to make LSD I can be a millionaire.


http://tohigherconsciousness.com/eleusinian-mysteries-lsd-and-ancient-greece/


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## DaSprout (Mar 24, 2016)

An interesting blast from the past.


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## DaSprout (Mar 24, 2016)

mikek420 said:


> http://tohigherconsciousness.com/eleusinian-mysteries-lsd-and-ancient-greece/


Good link.


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## bluntmassa1 (Mar 25, 2016)

hockeybry2 said:


> It'd be easier to make mdma


But would it be better? Not to mention I never seen sassafras oil for sale I'd probably need to go to Cambodia and smuggle it back. Ergot I can grow then make ergotamine and then LSD right here. Might be able to grow sassafras trees probably would need to be in Florida though and then wait 20 years just to harvest some and still would be best to wait at least 50 years. Weed won't be so profitable come legalization already the price has dropped pretty good but there is a big demand for LSD and I only hear about it coming around occasionally if it's not 2c knock offs.


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## hockeybry2 (Mar 25, 2016)

You can purchase precursors such catechol which are unregulated, just gotta have some chem background. But you're right saffrole is near impossible to get


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## AZgreenthumb (Mar 26, 2016)

bluntmassa1 said:


> But would it be better? Not to mention I never seen sassafras oil for sale I'd probably need to go to Cambodia and smuggle it back. Ergot I can grow then make ergotamine and then LSD right here. Might be able to grow sassafras trees probably would need to be in Florida though and then wait 20 years just to harvest some and still would be best to wait at least 50 years. Weed won't be so profitable come legalization already the price has dropped pretty good but there is a big demand for LSD and I only hear about it coming around occasionally if it's not 2c knock offs.


You can find sassafras oil if you know where to look I've seen it for sale on DNM markets before. It's expensive but you can still find it but the large scale chemists in Canada just get straight MDP2P from China and convert it directly to MDMA. That being said ecstacy is way easier and less risky to synthesize compared to LSD. With LSD you need way more chemicals not to mention all the complicated glassware and specialty equipment like roto evaporators and you have to maintain a compleatly inert atmosphere during reactions this kind of synthesis is for a phd level chemist.


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## iHearAll (Mar 26, 2016)

http://textfiles.com/drugs/make.txt

Lsa into lysergic acid into iso-lsd and lastly into lsd 25

Not toooo complex. You can start with kash's lsa extraction. But make sure you keep the acetone anhydrous with epsom salt. Then gravity filter it.



Starting with lsa will eliminate the ever scarey ergot culturing. Id wear a hazmat suit if if i were to start with ergot....


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## bluntmassa1 (Mar 26, 2016)

AZgreenthumb said:


> You can find sassafras oil if you know where to look I've seen it for sale on DNM markets before. It's expensive but you can still find it but the large scale chemists in Canada just get straight MDP2P from China and convert it directly to MDMA. That being said ecstacy is way easier and less risky to synthesize compared to LSD. With LSD you need way more chemicals not to mention all the complicated glassware and specialty equipment like roto evaporators and you have to maintain a compleatly inert atmosphere during reactions this kind of synthesis is for a phd level chemist.


That's why I would learn chemistry before making LSD and it's not really that hard if you know chemistry. Not to mention after the bunk DMT fuck the darknet guy had good reviews except for mine but most reviews the people didn't even try it yet. Not like a real dealer where they try to fuck around and you demand your money back like when I was sold fake micro dots and that fake ass red rock opium. Lol

I do like MDMA but I don't really want to make it LSD I would love to make bigger demand really at least for me.


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## AZgreenthumb (Mar 26, 2016)

I don't think people understand just how difficult it is to synthesize LSD. Most of the people who make LSD are experienced organic chemists working in fully equipped laboratories. One will usually need precursor chemicals, such as lysergic acid amides, which you can pretty much only obtain with a DEA license. Or you could specifically harvest the ergot fungus and chemically extract its alkaloids, then process those into the specific amides, then finally LSD. For this you would need thousands and thousands of dollars worth of lab equipment, experience in harvesting microscopic fungi, weeks worth of time, proper growing chambers in a completely sterile environment, all the necessary chemicals, a great amount of experience in organic chemisty, etc. You cannot make LSD without a fully equipped lab. Don't try to make LSD unless you have a phd in organic chemistry and hundreds of thousands of dollers to set up your own lab. Its estimated all of the LSD produced is made by a handful of people. These people have years of lab experience, a fully functional lab, $, connections for precursors, and higher level chem degrees or been trained by one of the few cooks before them.


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## AZgreenthumb (Mar 26, 2016)

Until you have all of these things making your own LSD is just a pipe dream your more then likely going to get yourself killed. Leave it to the professionals they will train a new generation of chemists to take their place. Not trying to be a downer but LSD synthesis is nothing to take lightly you can seriously hurt yourself or other people around you.


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## bluntmassa1 (Mar 26, 2016)

AZgreenthumb said:


> Until you have all of these things making your own LSD is just a pipe dream your more then likely going to get yourself killed. Leave it to the professionals they will train a new generation of chemists to take their place. Not trying to be a downer but LSD synthesis is nothing to take lightly you can seriously hurt yourself or other people around you.


Why you got to be such a Debbie downer? I actually mentioned taking chemistry classes I already have a few chemistry books just haven't read them yet. But it ain't like I'm going to start tomorrow and I think I can afford the lab equipment just need to learn chemistry. Maybe I won't be able to make it but worse case scenario I will be able to make the best DMT pure crystals among other things. I doubt an actual PhD is needed just enough to actually be able to read the books and understand what they are talking about cause just skimming through a lot of that shit is like wtf but if I learn enough to understand that shit I can probably do it and I would probably use a rabbit as my guinea pig just in case I fucked up so I wouldn't kill myself.

Also if I can't buy some ingredients well I imagine I can grab it outside the USA and come to think of it I can smuggle a little bit of liquid in a damn cologne bottle. So yeah it's very doable I can probably get ergotamine and all just in Mexico with just a little bribe money.


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## [email protected] (Mar 26, 2016)

Sassafras is everywhere. It makes root beer. Disgusting stuff.
You know it was LSD that started the Iraq war? Yah, someone started slipping it to devout Islams, and they were pissed. At first, they blamed America because it was an American woman that started it. But the she died, and they figured out it was made in Europe. So that is why they attack Europe now. If you cross reference drug trade with terrorist attacks you can clearly see the correspondence.


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## AZgreenthumb (Mar 27, 2016)

bluntmassa1 said:


> Why you got to be such a Debbie downer? I actually mentioned taking chemistry classes I already have a few chemistry books just haven't read them yet. But it ain't like I'm going to start tomorrow and I think I can afford the lab equipment just need to learn chemistry. Maybe I won't be able to make it but worse case scenario I will be able to make the best DMT pure crystals among other things. I doubt an actual PhD is needed just enough to actually be able to read the books and understand what they are talking about cause just skimming through a lot of that shit is like wtf but if I learn enough to understand that shit I can probably do it and I would probably use a rabbit as my guinea pig just in case I fucked up so I wouldn't kill myself.
> 
> Also if I can't buy some ingredients well I imagine I can grab it outside the USA and come to think of it I can smuggle a little bit of liquid in a damn cologne bottle. So yeah it's very doable I can probably get ergotamine and all just in Mexico with just a little bribe money.


I'm not trying to be a downer my last post applies to everyone. I'm trying to keep people from getting themselves killed. To many idiots out there that think they can handle the deadly chemicals involved in LSD synthesis or any other type of drug synthisis for that matter and they end up getting themselves or somebody else hurt. And make no mistake you don't want to attempt a synthisis like this just because you read some books you need real world lab experience way beyond what a bachlors degree can provide you why do you think only a handful of people in the world manufacture it? And where are you going to find a connection for pure ergotamine tartarate outside the country? It's not like you can just go to Mexico and find it its an extremely rare chemical. Unless you can find another LSD chemist to take you under his wing I wouldent attempt this type of thing. But don't take my word for it head over to the organic chemistry section on reddit there you can ask actual professional chemists why you shouldn't try to make LSD. https://www.reddit.com/r/OrganicChemistry/

I highly suggest you go talk to a certified organic chemist about this wether online or at your local community collage they can go into more detail about the chemicals and glassware involved.


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## Olive Drab Green (Mar 27, 2016)

Ergot can kill you, can't it? I know it grows from rye being tainted and may have been responsible for the Salem Witch Hunts and Trials.


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## Olive Drab Green (Mar 27, 2016)

[email protected] said:


> Sassafras is everywhere. It makes root beer. Disgusting stuff.
> You know it was LSD that started the Iraq war? Yah, someone started slipping it to devout Islams, and they were pissed. At first, they blamed America because it was an American woman that started it. But the she died, and they figured out it was made in Europe. So that is why they attack Europe now. If you cross reference drug trade with terrorist attacks you can clearly see the correspondence.


Except the first one started because we were trying to keep Saddam from invading Kuwait as well as killing a bunch of Kurds, and the second one was nepotism.


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## bluntmassa1 (Mar 27, 2016)

AZgreenthumb said:


> I'm not trying to be a downer my last post applies to everyone. I'm trying to keep people from getting themselves killed. To many idiots out there that think they can handle the deadly chemicals involved in LSD synthesis or any other type of drug synthisis for that matter and they end up getting themselves or somebody else hurt. And make no mistake you don't want to attempt a synthisis like this just because you read some books you need real world lab experience way beyond what a bachlors degree can provide you why do you think only a handful of people in the world manufacture it? And where are you going to find a connection for pure ergotamine tartarate outside the country? It's not like you can just go to Mexico and find it its an extremely rare chemical. Unless you can find another LSD chemist to take you under his wing I wouldent attempt this type of thing. But don't take my word for it head over to the organic chemistry section on reddit there you can ask actual professional chemists why you shouldn't try to make LSD. https://www.reddit.com/r/OrganicChemistry/


I was joking about the Debbie Downer cause you mentioned you were not trying to be a downer. Lol


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## AZgreenthumb (Mar 27, 2016)

Olive Drab Green said:


> Ergot can kill you, can't it? I know it grows from rye being tainted and may have been responsible for the Salem Witch Hunts and Trials.


Yes ergot can kill you
ergotism causes a nervous system dysfunction such as writhing, tremors, or convulsions. It can cause temporary or a permanent psychosis. Hallucinations, particularly in adolescents, are produced with mild poisoning with ergotism. Ergotism can be very lethal: for survivors, there is a 'reverse immunity' of sorts: a victim who survives the first exposure is even more susceptible the next time.




bluntmassa1 said:


> I was joking about the Debbie Downer cause you mentioned you were not trying to be a downer. Lol


For sure hard to read people emotions online. But I wish you all the best in your journey when you feel you have enough chemistry experiance try to synthesize MDMA first. Then once you master that move on to a more complicated drug synthisis like DMT or Mescaline then move on to LSD. Food for thought.


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## Olive Drab Green (Mar 27, 2016)

AZgreenthumb said:


> Yes ergot can kill you
> ergotism causes a nervous system dysfunction such as writhing, tremors, or convulsions. It can cause temporary or a permanent psychosis. Hallucinations, particularly in adolescents, are produced with mild poisoning with ergotism. Ergotism can be very lethal: for survivors, there is a 'reverse immunity' of sorts: a victim who survives the first exposure is even more susceptible the next time.
> 
> 
> ...


Sounds similar to strychnine?


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## Olive Drab Green (Mar 27, 2016)

AZgreenthumb said:


> Yes ergot can kill you
> ergotism causes a nervous system dysfunction such as writhing, tremors, or convulsions. It can cause temporary or a permanent psychosis. Hallucinations, particularly in adolescents, are produced with mild poisoning with ergotism. Ergotism can be very lethal: for survivors, there is a 'reverse immunity' of sorts: a victim who survives the first exposure is even more susceptible the next time.
> 
> 
> ...


Sassafras oil for MDMA, peyote buttons from cactus, DMT from touch-me-nots and some kind of grass, LSD is from.. What is lysergic acid diethylamide derived from?


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## AZgreenthumb (Mar 27, 2016)

Olive Drab Green said:


> Sassafras oil for MDMA, peyote buttons from cactus, DMT from touch-me-nots and some kind of grass, LSD is from.. What is lysergic acid diethylamide derived from?


Ergotamine Tartarate is converted into LSA (*d-lysergic acid amide) and then the LSA is converted into LSD. *


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## Olive Drab Green (Mar 27, 2016)

AZgreenthumb said:


> Ergotamine Tartarate is converted into LSA (*d-lysergic acid amide) and then the LSA is converted into LSD. *


Gotcha.


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## Olive Drab Green (Mar 27, 2016)

Interesting how the dextrorotary isomer would become a chiral compound. I want to see the chemistry behind it.


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## iHearAll (Mar 27, 2016)

AZgreenthumb said:


> I don't think people understand just how difficult it is to synthesize LSD. Most of the people who make LSD are experienced organic chemists working in fully equipped laboratories. One will usually need precursor chemicals, such as lysergic acid amides, which you can pretty much only obtain with a DEA license. Or you could specifically harvest the ergot fungus and chemically extract its alkaloids, then process those into the specific amides, then finally LSD. For this you would need thousands and thousands of dollars worth of lab equipment, experience in harvesting microscopic fungi, weeks worth of time, proper growing chambers in a completely sterile environment, all the necessary chemicals, a great amount of experience in organic chemisty, etc. You cannot make LSD without a fully equipped lab. Don't try to make LSD unless you have a phd in organic chemistry and hundreds of thousands of dollers to set up your own lab. Its estimated all of the LSD produced is made by a handful of people. These people have years of lab experience, a fully functional lab, $, connections for precursors, and higher level chem degrees or been trained by one of the few cooks before them.


You definitely don't NEED a phd to follow a lab proceedure. Especially if you aren't starting with ergot. If you started with lsa it's a whole different ball game. I think a good chunk of stoners have vacuum pumps and.anyone with 1-200$ can get the necessary glass to use. Granted im not suggesting someone go from making bho to thinking lsd?yea i got this. And then they wear no gas mask and have lung cancer aand still messed up somewhere. 


Olive Drab Green said:


> Ergot can kill you, can't it? I know it grows from rye being tainted and may have been responsible for the Salem Witch Hunts and Trials.


Then don't start with ergot. Purify lsa first.


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## bluntmassa1 (Mar 27, 2016)

iHearAll said:


> You definitely don't NEED a phd to follow a lab proceedure. Especially if you aren't starting with ergot. If you started with lsa it's a whole different ball game. I think a good chunk of stoners have vacuum pumps and.anyone with 1-200$ can get the necessary glass to use. Granted im not suggesting someone go from making bho to thinking lsd?yea i got this. And then they wear no gas mask and have lung cancer aand still messed up somewhere.
> 
> Then don't start with ergot. Purify lsa first.


So you can really turn LSA into LSD? Basically just extract Hawaiian Baby Woodrose seeds then no need for ergotamine? 

Will that really work to make the same quality LSD as Timothy Leary and Albert Hoffman?


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## AZgreenthumb (Mar 27, 2016)

iHearAll said:


> You definitely don't NEED a phd to follow a lab proceedure. Especially if you aren't starting with ergot. If you started with lsa it's a whole different ball game. I think a good chunk of stoners have vacuum pumps and.anyone with 1-200$ can get the necessary glass to use. Granted im not suggesting someone go from making bho to thinking lsd?yea i got this. And then they wear no gas mask and have lung cancer aand still messed up somewhere.
> 
> Then don't start with ergot. Purify lsa first.


 are you kidding 1-200 dollars were talking about reacting chemicals under an inert atmosphere your going to need a lot more money then that here read this synthisis here this is not something that can be done for 200$ or 20,000$ for that matter. https://www.erowid.org/archive/rhodium/pdf/lsd.garbrecht.pdf
The processes are so complex, the intermediate products so fragile, and the by-products of many of the steps so toxic, that the majority of university chemistry labs in the nation would be ill equipped to undergo such a procedure. I can say that without a doubt in my mind that there are likely only a handful recognized research labs in the country with the means to produce pure lsd safely.


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## AZgreenthumb (Mar 27, 2016)

Mabey someone with more chemistry knowledge then myself can weigh in @MrEDuck are you there?


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## iHearAll (Mar 27, 2016)

AZgreenthumb said:


> are you kidding 1-200 dollars were talking about reacting chemicals under an inert atmosphere your going to need a lot more money then that here read this synthisis here this is not something that can be done for 200$ or 20,000$ for that matter. https://www.erowid.org/archive/rhodium/pdf/lsd.garbrecht.pdf
> The processes are so complex, the intermediate products so fragile, and the by-products of many of the steps so toxic, that the majority of university chemistry labs in the nation would be ill equipped to undergo such a procedure. I can say that without a doubt in my mind that there are likely only a handful recognized research labs in the country with the means to produce pure lsd safely.


That's from ergot.


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## iHearAll (Mar 27, 2016)

Well im done anyway. The easy kids way is posted in this thread a dozen times if you so wish to start making lsd25. Which i really don't recommend. Just worth the conversation/perspective headbutt. Sorry if i came across negative at all.


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## iHearAll (Mar 27, 2016)

bluntmassa1 said:


> So you can really turn LSA into LSD? Basically just extract Hawaiian Baby Woodrose seeds then no need for ergotamine?
> 
> Will that really work to make the same quality LSD as Timothy Leary and Albert Hoffman?


It's in the proceedure on the previous page.


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## iHearAll (Mar 27, 2016)

For sake of the wrong person making too much lsd and polluting water supplies, ill go with it's impossible......


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## bluntmassa1 (Mar 27, 2016)

AZgreenthumb said:


> are you kidding 1-200 dollars were talking about reacting chemicals under an inert atmosphere your going to need a lot more money then that here read this synthisis here this is not something that can be done for 200$ or 20,000$ for that matter. https://www.erowid.org/archive/rhodium/pdf/lsd.garbrecht.pdf
> The processes are so complex, the intermediate products so fragile, and the by-products of many of the steps so toxic, that the majority of university chemistry labs in the nation would be ill equipped to undergo such a procedure. I can say that without a doubt in my mind that there are likely only a handful recognized research labs in the country with the means to produce pure lsd safely.


I don't think it's that complex I'm pretty sure it was a documentary I seen but it was a fairly basic lab setup that either Timothy Leary or Albert Hoffman used but I don't think they made the ergotamine just turned it into LSD and the reason LSD ain't around like it used to is it's a lot harder to get ergotamine. 

But just cause you can't buy ergotamine in the USA don't mean you can't get it just give a pharmacist in Mexico cash and they will give you oxycontin and steroids so ergotamine ain't impossible to get.


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## HeatlessBBQ (Mar 27, 2016)

Token said:


> But it would be worth it to learn yet another trade. Try growing the fungus an another house for safety. Or can you synthesis it from lsa?


What is Your intention ?
Are You learning or are You experienced ?


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## Mr. Bongwater (Mar 27, 2016)

nashbar said:


> not gonna happen
> 
> buy lsd like everyone does





nashbar said:


> i encourage you to prove me wrong. please, keep me posted on your progress.
> 
> aside from any dangers and pitfalls you might come across...
> 
> ...


so how the hell do people actually make lsd then? somebody out there has to make it if its around in small quanities


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## AZgreenthumb (Mar 28, 2016)

bluntmassa1 said:


> I don't think it's that complex I'm pretty sure it was a documentary I seen but it was a fairly basic lab setup that either Timothy Leary or Albert Hoffman used but I don't think they made the ergotamine just turned it into LSD and the reason LSD ain't around like it used to is it's a lot harder to get ergotamine.
> 
> But just cause you can't buy ergotamine in the USA don't mean you can't get it just give a pharmacist in Mexico cash and they will give you oxycontin and steroids so ergotamine ain't impossible to get.


Here are some pics of actual LSD labs and keep in mind this is just a small fraction of the glassware in these labs. Do these look like 200$ setups to you? I read a story about a LSD chemist who was busted in the UK he spent 49,000 USD on chemicals alone. I'm not saying you can't synthisize LSD on your own one day it's just going to take lots of education, Hands on experiance, and lots and lots of money go about this smart and don't believe anyone who tells you your going to be able to buy all the glassware you need for 200$.

FYI the last pic is of an MDMA lab but you get the idea.


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## AZgreenthumb (Mar 28, 2016)

As for the ergotamine tartarate you can't buy pure ergotamine from a pharmacist. You can buy ergotamine tartarate pills but they are an impractical source of ergotamine do to the extremely low concentration of ergotamine in these pills. And the high ratio of filler would make them nearly impossible to extract any decent amount of precursor. 

You can only acquire pure ergotamine from a company that provides chemicals to pharmaceutical companies such as Sigma-Aldrich. And if you tried to order from a company like that you would be reciving a knock on your door from a DEA agent wanting to know why you tried to order a schedule 1 chemical. 

As I said before the chemists who are making this have some serious high level precursor connections because ergotamine is nearly impossible to find nowadays. 

It's way beyond what you will find at any Mexican pharmacy. Although a lot of people I know have been going to Mexico buying shit tons of XANAX and reselling it for 5 a pop something to keep in mind if you want to make some quick cash.


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## HeatlessBBQ (Mar 28, 2016)

AZgreenthumb said:


> Here are some pics of actual LSD labs and keep in mind this is just a small fraction of the glassware in these labs. Do these look like 200$ setups to you? I read a story about a LSD chemist who was busted in the UK he spent 49,000 USD on chemicals alone. I'm not saying you can't synthisize LSD on your own one day it's just going to take lots of education, Hands on experiance, and lots and lots of money go about this smart and don't believe anyone who tells you your going to be able to buy all the glassware you need for 200$.View attachment 3643579View attachment 3643580View attachment 3643582View attachment 3643583
> 
> FYI the last pic is of an MDMA lab but you get the idea.


and MDMA is easier to synthesize than LSD... 
Thank You for spreading the truth and educating Us on what is what.
Instead of sugar coating it.


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## iHearAll (Mar 28, 2016)

http://textfiles.com/drugs/make.txt

I honestly dont know why im trying to prove this.to apparently one person but anyway lets do a budget check for a 2016 lsa to lsd25 extract. We are not using ergotomine. And i strongly advise that this is educational only. Lsd25 is a felony and manufacturing is rape fucking you in the butt for life.

Ok. So here we go.
Equipment only.

White crystaline Lsa extraction you simply need a seperatory funnel, some sort of glass measuring instruments (i suggest various size graduated cylinders and a liter size round bottom flask), glass stir rod, unbleached coffee filters or fritted glass filters

Lsa is now isolated from the final volitile solvent with a vacuum chamber. Which i assumed you had already cuz you're a pot head who makes their own hash.

To continue you need a bag of ice large plastic bowl, ice, various colored lights i wont go into, hot water, reflux column (optional).

The rest is cake walk but time consuming.


Seperatory funnel 16$
Round bottom flask 10$
Graduated cylinders 20$
Plasitic bowl (ptfe would be nice) 20$
Glass stsir rod is maybe 1$
Heated stir plate handmade 15$
Fritted glass filter 2$
Glass funnel 3$
A bag of ice and hot water.

Well you get the point. The picture is from the 80s or something when the best option was an ergotomine alkaloid.

Now you'll get effed in the a of you go and buy diethylamine, hcl, sodium nitrite, acetone, naptha, toluene, hydrazine, and. epsom salt with your credit card. So i would recommend getting an education and do something useful your life. But since im bored and watching supergirl i wrote up a shopping cart for nobody. Har dardardardar

Edit. Let's toss in a vacuum chamber to bump the cost up to something scarier. Oh and a glass reflux column (chemistry diatiller). God damnit i'm so broke now


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## iHearAll (Mar 28, 2016)

How much acid are you suggesting someone needs to make? Lol those flasks are gallon size. That's like fuck, idk, alot of god damn acid. Final step to making acid is dipping your finger in it and giving it a taste.


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## iHearAll (Mar 28, 2016)

Shit this guys a narc!!!!!! Nigga doesn't want anyone to make some acid maaaaaaaaaaaaan.

Uhuhuhuh narc


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## Noinch (Mar 28, 2016)

iHearAll said:


> http://textfiles.com/drugs/make.txt
> 
> I honestly dont know why im trying to prove this.to apparently one person but anyway lets do a budget check for a 2016 lsa to lsd25 extract. We are not using ergotomine. And i strongly advise that this is educational only. Lsd25 is a felony and manufacturing is rape fucking you in the butt for life.
> 
> ...


 its extremely difficult to go from LSA to LSD and also very unsafe


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## canndo (Mar 29, 2016)

Noinch said:


> It's really not that difficult, its extremely difficult to go from LSA to LSD and also very unsafe





bluntmassa1 said:


> So you can really turn LSA into LSD? Basically just extract Hawaiian Baby Woodrose seeds then no need for ergotamine?
> 
> Will that really work to make the same quality LSD as Timothy Leary and Albert Hoffman?


Leary never made LSD.


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## Noinch (Mar 29, 2016)

canndo said:


> Leary never made LSD.


Ignore the first part of what i said, forgot to backspace. What i said about LSA to LSD is very true


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## canndo (Mar 29, 2016)

Noinch said:


> Ignore the first part of what i said, forgot to backspace. What i said about LSA to LSD is very true



I really wouldn't know.


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## AZgreenthumb (Mar 29, 2016)

iHearAll said:


> http://textfiles.com/drugs/make.txt
> 
> I honestly dont know why im trying to prove this.to apparently one person but anyway lets do a budget check for a 2016 lsa to lsd25 extract. We are not using ergotomine. And i strongly advise that this is educational only. Lsd25 is a felony and manufacturing is rape fucking you in the butt for life.
> 
> ...


Dude seriously? If LSD was that cheap and simple to make everyone would be making it. All the procedures you'll find on the internet are mainly all either.
A) Out of Date
B) Theoretical
C) Worthless crap
LSA is not the name of a particular chemical, it is an abreviation of "Lysergic acid Amides". Im NOT referring to the many LSA's found in HBWS. It would not be sensible or viable to form LSD from an extract of HBWS. It contains many Lysergic-acid Amides and even if one wanted to isolate one for the synthesis it would take too long and the yields just wouldnt be worth it. I mean your posting a tech that was written in the 1970s but go head an set up your cheap little lab and try it out see what happens. I'm not going to waste anymore time arguing this point.


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## canndo (Mar 29, 2016)

Clandestine chemical manufacturing always has the same dynamic. 

Drugs are made underground mostly as a response to absolute prohibition. In other words, drugs are usually made when there is no other way, people don't often make oxycodone, for example. 


When a clandestine operation begins, precursor chemicals can be gotten easily. These chemicals are cheap (relatively), plentiful and pure. 

As law enforcement tracks the paths of manufacture, precursor chemicals are watched, then closely monitored. 

The clandestine labs are forced to make their own precursors. 

The process of making these precursors is watched and finally the precursors of those precursors are closely monitored. 

Hell, this cycle commonly extends to things like hydrochloric acid and acetone. 

I figure eventually water will make the list. 

So now the clandestine manufacturer discovers a novel way to produce the drug using different precursors. 

The cycle starts again. 

But there are only so many ways a chemical can reasonably be produced and eventually this clandestine lab runs out of conventional optionsoptions. 

It either finds holes in the watched or limited precursor chemical supply chain or it closes up. 

This battle has been going on over LSD since the first day it's synthesis was made illegal. 

Over forty years. 

Now what has the average person, passionate as he is, believe he can dive in now and make any headway at all? 

It's nice to dream and very nice to dream big but.


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## losfalcor (Dec 23, 2017)

HEY ALL. this is probably gonna be the only post i ever make on this fourm, but i wanted to point out alota misinformation.

First off, ergot is only dangerous if ingested. its safe to handle with your hands, just dont eat it and i wouldn't think you would.

Now finding ergot is actually quiet easy and likely nearby. Ive found plenty in the neighborhood bayous or fields that arent frequently mowed. Some fields dont have rye, but alot of them do, so its hit and miss. However, i remain confident if you try you will find that little black fungi that your looking for..

OK, so now that you've found your ergot, you need to attempt an isolation. You wash the ergot grain in a bit of alcohol or peroxide and attempt an isolation on a petri dish with malt agar. Once isolated, transfer to liquid culture. Just so you guys know. That 'nutrient recipe' thats often described in may post across the internet (i think its from the book of acid) is just a complicated, outdated formula for liquid culture. Nowadays we use dilute malt agar and karo so forget that complicated jargon. You can make several gallon jugs.

then you basify the LC and extract with a solvent.

Now im not gonna go into great detail, you guys need to do your own research, but mostly every chemical required to make LSD is available over the counter. There are a couple exceptions for a few of the chems that are immediately available, but not all are illegal to buy or own, just not common and not impossible to get. This would include potassium hydroxide, toluene and chloroform (if you choose to use it). The main one to worry about would be the bonding agent. The two most plausible bonding agents would be PYPOB or red phosphorous. Now there are companies out there that sell these chemicals that supply to colleges.

Anyways, the rest is left to you guys. Im out


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## Olive Drab Green (Dec 23, 2017)

You could also just grow Psilocybe mushrooms like a normal person.


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## 3rdeyefind (Jun 8, 2021)

nashbar said:


> not gonna happen
> 
> buy lsd like everyone does


And how might I go about doing this as I live in a rural area and believe me it's a rare commodity.


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## minatozzz (Jun 24, 2021)

[QUOTE = "thechemist513, post: 9211587, membro: 626429"]
eu tenho esporos de paspali e ergot, deixe uma resposta
[/ CITAR]
[QUOTE = "thechemist513, post: 9211587, membro: 626429"]
eu tenho esporos de paspali e cravagem deixe uma resposta
[/CITAR]
Olá salvador desconhecido, posso comprá-los de você?


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## minatozzz (Jun 24, 2021)

I believe that those who know a lot do not tell the truth or tell the outdated truth... the human intellect is the greatest weapon we have and knowledge must be shared! I leave my doubts here:

*Currently, is there any simpler method than the one discovered by Hoffman to go from the claviceps material straight to the lysergic acid diethylamide without isolating the lysergic acid? if so, which one?

* we know that there are a range of fungi and seed sources of lysergic acid amides and alkaloids, but what is the best source? the one that yields the most. I heard it's claviceps paspali is it true?
that is... high yield and purity with practicality!!

- SIMPLICITY IS THE ULTIMATE DEGREE OF
SOPHISTICATION

gratitude, this topic is aggrandizing. light


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