Hey guys, as you can tell this is my first post and its a big one!
Iv been doing a lot of research into practical LSD production, specifically, using (a mix) of ergot alkaloids from natural sources (HBWR, purpurea ergots, paspali broth). Id like to share some thoughts as well as some criticizes of common processes and shed some light on the necessity of perfecting an alternative method.
The method using hydrazine is perfect for a mix of natural alkaloids, the mixed alkaloid feedstock is converted directly to lysergic acid hydrazide and it goes on from there. This avoids lossy hydrolysis and works with even very impure feedstock, I read hoffman got clean product from the scrapings of an old ergot fermenter. The downsides of course is the use of hydrazine for practicality and safety reasons.
Most other processes thoroughly described in literature start with a hydrolysis to lysergic acid which then requires forming a salt, then freebase again and inevitably involves serious mechanical losses. hydrazine or methyl ester methods produce a precipitant directly, which is much better for purity/logistics... get that dirty mother liquor out of here! Standard hydrolysis seems to work best with pure single component feedstock like commercially diverted alkaloids. The methyl ester method seems to be superior for a natural source of feedstock.
I am going to quote the erowid article so you guys can get an understanding of the manipulations involved in this. For scaling this reaction the patent explains a route avoiding the use of p-toluenesulfonic acid and instead using 13N HCl in methanol, but requires much lower temperatures. The solvent volume is tiny this way though, 50g can be easily worked up in a 2L flask!
I don't expect anyone actively doing this work to get online and explain their progress but usually when these types of methods (explained in literature but not reproduced clandestinely to the communities knowledge) are explored (peptide coupling etc) at some point a knowledgeable person will pop in and throw everyone a bone, at least mentioning if it was successful or any major pitfalls preventing it. But im also interesting in hearing theoretical discussion. I would love to know what you guys think of this route. P.S. how much isomerization should be expected from the last reaction? It seems pretty mild.. Also, whats in estimate of the expected d/l ratios?
http://www.erowid.org/archive/rhodium/chemistry/lysergic.amides.html
-DrZeus
Iv been doing a lot of research into practical LSD production, specifically, using (a mix) of ergot alkaloids from natural sources (HBWR, purpurea ergots, paspali broth). Id like to share some thoughts as well as some criticizes of common processes and shed some light on the necessity of perfecting an alternative method.
The method using hydrazine is perfect for a mix of natural alkaloids, the mixed alkaloid feedstock is converted directly to lysergic acid hydrazide and it goes on from there. This avoids lossy hydrolysis and works with even very impure feedstock, I read hoffman got clean product from the scrapings of an old ergot fermenter. The downsides of course is the use of hydrazine for practicality and safety reasons.
Most other processes thoroughly described in literature start with a hydrolysis to lysergic acid which then requires forming a salt, then freebase again and inevitably involves serious mechanical losses. hydrazine or methyl ester methods produce a precipitant directly, which is much better for purity/logistics... get that dirty mother liquor out of here! Standard hydrolysis seems to work best with pure single component feedstock like commercially diverted alkaloids. The methyl ester method seems to be superior for a natural source of feedstock.
I am going to quote the erowid article so you guys can get an understanding of the manipulations involved in this. For scaling this reaction the patent explains a route avoiding the use of p-toluenesulfonic acid and instead using 13N HCl in methanol, but requires much lower temperatures. The solvent volume is tiny this way though, 50g can be easily worked up in a 2L flask!
I don't expect anyone actively doing this work to get online and explain their progress but usually when these types of methods (explained in literature but not reproduced clandestinely to the communities knowledge) are explored (peptide coupling etc) at some point a knowledgeable person will pop in and throw everyone a bone, at least mentioning if it was successful or any major pitfalls preventing it. But im also interesting in hearing theoretical discussion. I would love to know what you guys think of this route. P.S. how much isomerization should be expected from the last reaction? It seems pretty mild.. Also, whats in estimate of the expected d/l ratios?
http://www.erowid.org/archive/rhodium/chemistry/lysergic.amides.html
Quote
making the lysergic acid ester:
(US Patent 4524208)
"A mixture of 2.5 g of lysergic acid amide and 2.5 g of isolysergic acid amide in 500 ml of methanol is heated with 100 g of p-toluenesulfonic acid for 4 hours to 50 deg. C. Then half of the solvent is removed by distillation, the residue is poured into a mixture of 200 ml of concentrated ammonia and ice, and extracted with methylene chloride. The organic phase is dried with sodium sulfate ...(skipping crystallization and proceeding directly to the next step if decently clean)"
~80% yield!
lysergic acid methyl ester to lysergic acid diethylamide
(Tetrahedron Letters No. 8, pp 4171-4174, 1977.)
"In a typical experiment 0.8 ml (2.0 mmol) of a 2.5 M solution of trimethylaluminum in hexane was slowly added at room temperature to a solution of 2.0 mmol of (diethyl)amine in 5 ml of dry methylene chloride under nitrogen. The mixture was stirred at room temperature for 15 min and 2.0 mmol of ester was added. The misture was warmed at 25-41 degrees under nitrogen until TLC indicated that the reaction had gone to completion. The reaction was carefully quenched with dilute HCL and extracted with methylene chloride. The organic extract was dried (MgSO4) and concentrated to afford the carboxamide which could be recrystallized, if necessary."
-DrZeus
