trouble getting yields for LSD

[mosh]

I intended to start the exact same procedure (Tihkal) a few days ago but stop every thing waiting for your report.(today I began drying).
As I understand it:
In the converting of the Ergotamine to LSA part
You did not use the 15 % ammonia in Anhydrous ethanol but Et2O   
You used maleic acid instead of the d-tartaric acid.
Did you use the chromatography?

Please send more details I have only 10g of ergotamine cant do any mistake
All my staff are analytical grade so with little help I believe I can make it.
I have a some lab experience.

[El_Zorro]

From Shulgun himself:

This base was dissolved in warm, dry MeOH, using 4 mL per g of product. There was then added dry d-tartaric acid (0.232 g per g of LSD base), and the clear warm solution treated with Et2O dropwise until the cloudiness did not dispel on continued stirring. This opaqueness set to a fine crystalline suspension (this is achieved more quickly with seeding) and the solution allowed to crystallize overnight in the refrigerator. Ambient light should be severely restricted during these procedures. The product was removed by filtration, washed sparingly with cold methanol, with a cold 1:1 MeOH/Et2O mixture, and then dried to constant weight. The white crystalline product was lysergic acid diethylamide tartrate with two molecules of methanol of crystallization, with a mp of about 200 °C with decomposition, and weighed 3.11 g (66%). Repeated recrystallizations from methanol produced a product that became progressively less soluble, and eventually virtually insoluble, as the purity increased. A totally pure salt, when dry and when shaken in the dark, will emit small flashes of white light.
I sell crack for the CIA

[mosh]

The question was not what is written in Shulgins Tihkal but how momtanha do it ?

[montanha]

Ok, this is what's going:
1 - This is correct: I used Et2o instead of anhydrous ethanol in 15% ammonia
2 - I DID use maleic acid instead of tartaric acid
3 - I only chromatographed one trial(2nd), which was the most successful one.

I do not think this success is due to chromatography, but due to my LSA. My first LSA hydrolysis did not have satisfying results, I had a few problems w/ the temperature control and with the vacuum pump.

This last addition was made, and no crystals have formed. I guess that my methanol is NOT dry, after all.

Lilienthal, I'm sorry I didnt listen to you.  I consider this now a potential cause for the crystals not to come out.
I will dry my MeOH before next procedure. Do you think CaO for a few hours is enough?

Flipper - I am pretty sure you can dissolve the freebase in water and drop it wherever you want, but one should crystallyze it to clean it and to check how much you actually have (how could this be done otherwise?)

Mosh, if you get a successful run, please get  to me the details! since I can't, I don;t want to drive you off the way. What I have found is that it seems like everything should be freshly cleaned, dried and distilled, like Buzz's book says. It's really tiring to to all this, but it's not as bad as not having crystals hehehehe

If you want to know how I proceeded for crystallyzation, I only dried the solvents, added a little meoh, (not everything dissolved) then I added a little more (continued dissolving, but some didn't), and then more. Definitely w/ 4ml/gram of freebase will not dissolve the stuff... unless it has to be hot or something...or it takes a hell of a long time. Well, after (almost) everything was in solution ( some stubborn crystals appeared I don't know where from) I added the MeOH (20% maleic acid sol.) and the mixture turned rather quickly into a cloudy mess. Only problem is it continues to be a cloudy mess. I am not sure, but I added some old LSA to complete 3.15 grams, and the solution turned dark in  the last 6 hours. The first attempt resulted in a very dark solution also, w/ apparently lower yields. I am guessing that some ET went in there (either ET or other impurities). I still have a few attempts before I cry, I will definitely chromatograph every run from now on.

[mosh]

Thank you for your replay

My Methanol is 0.03% water.Is it dry enough?

The Ether is dry 0.0075%.

My biggest concern is the dry ammonia because I can;t use pure ammonia where I work

Did you warmed the MeOH?

[montanha]

If these labels tell the truth, I guess your solvents are dry enough.
I am told, though, by a bee, not to trust them.
I have a surprise for all of you. I am very shocked!
I washed my chloroform in nh4oh and then dried it. I am a very lazy person, so I left a tiny little bit of chcl3 in the 2L sep funnel and dried the rest ( which I dilluted in the WARM methanol and then added maleic acid). This didn't give me many crystals yet - maybe the methanol is NOT dry.
Dilluting it in 400ml water, I see that one drop is a fine hit, though. meaning I got this time about 8000 hits. this is fine, I started out from 2.5 grams this time. now I DO have a big surprise. I need expert advidse for this one.
TODAY I was going to wash the sep funnel w/ nh4oh (and the little bit of chcl3) and I noticed a reasonable ammount of STAR-SHAPED CRYSTALS that formed in the funnel! they weighed .4 grams and they have a blue fluorescence!!!!!

I AM DYING TO TRY THEM TONIGHT!
I will dillute it and tomorrow I will come tell you guys what happened.
Might this be freebase crystals? maybe the CHCl3 evaporated and the nh4oh made the Slow crystallyzation form those beautiful stars ( which later, broke into tiny needles)

I would love answers before I take these.
If I don't get them, I will take them anyways. I don't want to wait a week to analyze this. I "bee" too anxious too wait hehehe...
Later

[bujinkan]

like you said, might as well try to dry out the methanol. You have no reason not to.

heheh, oh and i hope you didnt fry yourself...you havent updated us for a while. ( the fear and loathing bathtub scene comes into mind.)

[herbarium]

any news on bioassy?

-herb

[montanha]

actually, I do have some news.
My darn methanol finally showed something.
In the last 30 hours the clowdy mess turned into thicker balls of crystals! Tey're definitely not needles, but it is now clear that something has formed. and it looks like it's more than one gram. I haven't weighed it yet.
I wonder why it took so long.... and I do hope its my product. I will wait another day to see if I get more and I will filter ahd weight tomorrow.

THEN I will try it. What should I do if it works? send samples?! take pictures? jump 2 meters?

[mosh]

Please send your full procedure.Colors, weights, time,temperature etc.
I began today and the first thing I noticed is that the Color didn;t change to yellow Even after the 4 hours in
75°C with nitrogen bubbled into the stuff. The color is light brown.
My ergotamine was white.

[Rhodium]

Do NOT forget to post pictures of your LSD crystals! We want to see a pile of crystals that's enough for a few thousand hits...

[montanha]

Right
I will post the pictures. But I am doing quite a few hydrolysis before I do the next step. I feel that this will save me a lot of time, since I will do an entire clean procedure w/ all fresh materials and all.
when I am going to have good looking crystals I will definitely take pictures of'em. About the procedure... I can take pics of those, but I have to fix a nice lab setup ( my lab looks like shit! ahaha)
see, I'm shy.

but I'll do an effort and I will photograph the procedure.

Mosh is right, The ET does not go yellow in solution, mine remains white and very clear. It's color changes under UV, though. I will try to show these differences.

I'm scared someone might trace me back though.
Rhodium, you mentioned purification of the LSD tartrate from epimers and decomposition products. Is there a further way to purify the LSD other than packed column chromatography?(of course there is, but not using 200 thousand dollars equipment) (THE COLUMN WILL LOOK GREAT ON THE PICTURE ALBUM!)
and what would YOUR plan be to avoid the darned epimerization of the alpha-carbon from happening during reaction?

[mosh]

Can you send written procedure mainly about the ergptamine ==> d-lysergic acid hydrate procedure?
I am very confused about skipping the ammonical ethanol part.

[herbarium]

please publish instead of pm, this is of utmost interrest

-herb

[Rhodium]

I don't recall exactly where the information is located, but I know that among the LSD synthesis documents at my page, there are instructions for minimizing epimerization and how to convert iso-LSD to LSD. Column chromatography is the way to go for purification.

[bujinkan]

"Convert iso-LSD to LSD. Add 50 ml of ethanol and 5 ml of 4 N KOH per every gram of iso-LSD. Let this mixture stand for 2 hours at room temp. Evaporate in vacuo to get the LSD.

Separate iso-LSD from LSD. Dissolve the residue of the mixture of LSDs from the end of the formula in 120 ml of benzene and 40 ml of chloroform. Add tartaric or maleic acid to precipitate the LSD, filter off, add a little ether and put in refrigerator for several days to get a little more LSD, which is filtered off and added to the rest. Evaporate the filtrate in vacuo to get the iso-LSD and convert as above."
above excerpt from

https://www.thevespiary.org/rhodium/Rhodium/chemistry/lsd-buzz.html

[bujinkan]

http://jaxindy.chem.yale.edu/

maybe that can help. i cant find much on lessening epimerization on rhodiums site. maybe im just blind, but are you sure theres something like that there rhod?

[Rhodium]

From the same document as above:


LSD From Lysergic Acid Monohydrate

This is, in my opinion, the best of all the methods. It was designed to be used to experiment with different types of amines, so if you would like to substitute diethylamine with another amine this would be the best bet. It also gives good yields (50% or better) and is very easy. The reference that gives it also gives potency data for many lysergamides and many of their formulas. The reading is good, interesting, informative, and the method given below gives no useful amount of iso-LSD, so separation of that product is not necessary. Both method A and B were from JMC 16, 532.


It was several months ago I last read the documents, so my recollection of the contents was not entirely correct. There were no discussion about how to minimize epimerization other than the above - a note on which method to use. Either my site is becoming too large, or my memory is failing - I can no longer memorize all its contents.

[mosh]

any news ??

[Rhodium]

Epimerization Studies of LSD using 1H Nuclear Magnetic Resonance (NMR) Spectroscopy
S.J. Salamone, Z. Li, A.J. McNally, S. Vitone, and R. Wu

A study was conducted to determine the conditions needed to achieve the equilibrium concentration for the epimerization of d-lysergic acid diethylamide (LSD) to iso-LSD. The reaction was followed by integration of the C-9 resonance of LSD and iso-LSD by proton nuclear magnetic resonance (NMR). The C-9 resonance of LSD and iso-LSD appear as singlets at 6.35 and 6.27 ppm respectively. Starting with pure LSD, the conversion to iso-LSD is attained at temperatures above 37°C and pH levels over 7.0. At a pH of 7.0 or higher, the LSD/iso-LSD ratio of 9:1 is achieved after one week at 45°C or two weeks at 37°C. Starting with iso-LSD, the conversion to LSD requires more vigorous conditions. The 9:1 LSD/iso-LSD ratio is attained only after 6 weeks at a temperature of 45°C and a pH of 9.7. At lower pH levels, the reaction proceeds more slowly. The 9:1 LSD/iso-LSD ratio is achieved whether the starting material is LSD or iso-LSD and therefore represents an equilibrium concentration (K = 9). In addition, the more vigorous conditions needed to achieve equilibrium of iso-LSD to LSD demonstrate the difficulty in extraction of the epimerizable proton of iso-LSD. This study is the first to quantitate the epimerization of LSD by NMR techniques and establishes the conditions needed to induce epimerization in solution.

Ref: Journal of Analytical Toxicology, Volume 21, Number 6, October 1997, pp. 492–497.