12-03-03 20:41
No 474518
Going through the different synthesis methods for LSD - it appears that a path to a reasonable yield would be...
Ergotamine Tartrate to Lysergic acid(I) an then use the Cerny and Semonsky method:
"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."
Is this a realistic route? Or would one have better success using the Ergotamine Tartrate with looking at the method outlined by Tihkal?
(Chief Bee)
12-03-03 21:06
No 474525
This seems to be a viable route. What is the source for this experimental?
(Stranger)
12-03-03 22:32
No 474540
I found the Cerny and Semonsky info from MVS. This method seems straight forward for a person with reasonable chemistry background and lab skills.
The hypothesis is to start with HBWR seeds - extract to Ergotamine Tartrate and then to Lysergic Acid.
The chemicals for Cerny and Semonsky synthesis seem a little easier to come by and work with versus POCl3 route.
Any recommendations?
(Hive Bee)
12-04-03 01:13
No 474569
the seeds will give you lysergic acid amine (ergine) not ergotamine. The old Hofmann synthesis starting from ergotamine (or any ergot containing lysergic acid) is as easy as any method. Ergotamine reflux with hydrazine to give racemic L.A.hydrazide. Manufacture the azide with sodium nitirte and HCL to give racemic L.A. azide. In an ether solution the azide is mixed with diethylamine in ethanol to give racemic L.A. diethylamide. Chromatography on alunimium oxide will give racemic iso LSD and racemic LSD. The d-LSD-D-tartrate is made from the racemic LSD with D-tartaric acid in methanol. Don't forget the iso-LSD can be converted to the normal d-LSD. The hydrazine method has several advantages over the alkaline hydrolysis with potasium hydroxide. I am not sure about this but Shulgin's synthesis may need the free base ergotamine as starting material. The instruction for preparation of the free base can be found in:Jacobs and Craig.Journal Biological Chemistry vol.113,245-53(1936).Hofmann and Stoll's method in english can be found in Chemical Abstracts vol38,1499-1502(1944).If you understand german Helvitica Chimica Acta vol 26,922-964(1943)."Rhodium" web page has all the patents you would need to manufacture LSD.
(Moderator)
12-04-03 09:53
No 474613
What is MVS?
(Chief Bee)
12-04-03 10:34
No 474614
Michael Valentine Smith, a.k.a. Michael Starks of "Psychedelic Chemistry" and "Marijuana Chemistry" fame.
(Stranger)
12-04-03 17:36
No 474655
Thanks for the info.
I took a look in the JBC and found:
Walter A. Jacobs and Lyman C. Craig
THE ERGOT ALKALOIDS. IX. THE STRUCTURE OF LYSERGIC ACID
J. Biol. Chem., Apr 1936; 113: 767 - 778.
Going through Docs. at "Rhodium" and elsewhere I can follow using method from MVS for extraction (tartaric acid path). From this I now understand that you will get ergine (lysegic acid amides).
Depending on the next path:
If you follow the route by Hoffman and Stoll, then you can use the above product to start this synthesis - correct?
Or, if you want to not take the hydrazine route and would like to follow the path of Shulgin, which starts with Ergotamine Tartrate and KOH - further using DEA and POCl3, then the Ergine needs to be converted to Ergotamine? This is where I am getting a little confused. I think I have gone through too many articles and text too fast and need to go through it again slower.
Most appealing to me is the route by Cerny and Semonsky, which states that the starting material is Lysergic Acid - again leaves me a little confused about definition of Lysegic Acid specific to this method.
I realize the Hoffman synthesis with Hydrazine is best, but all the literature on this gets one worried about obtaining and working with it.
(pHantasticant)
12-04-03 19:48
No 474676
Most appealing to me is the route by Cerny and Semonsky, which states that the starting material is Lysergic Acid - again leaves me a little confused about definition of Lysegic Acid specific to this method.
A straightforward route to acid from lysergic acid is:
Post 412547 (pHarmacist: "Synthesis of LSD from Lysergic Acid", Tryptamine Chemistry)
http://www.bassdrive.com/BassDrive.m3u
(Stranger)
12-04-03 23:58
No 474703
Ok, just to try and put a full path together.
1. HBWR Extraction - From Rec. Drugs by Prof. Buzz:
Pulverize the seeds in a clean blender until they are a fine powder. Put this powder into a beaker, add 1 1iter of petroleum ether to every 900 to 1000g of powdered seeds, stopper the beaker to prevent evaporation and let set for 3 days. Filter off the petroleum ether and let evaporate to make sure no amides were extracted (there should not be much, if any) from the ether. Add 1 1iter of methanol (dry is best) and let soak for 4 days with vigorous shaking, now and then. Filter off the methanol and evaporate it under vacuo (vacuum speeds the process). In the meantime, add 500 ml of fresh methanol to the powder and extract it again for 3 or 4 days.
Filter as before and extract again with about 300 ml of methanol. Combine the residues of all extractions and hydrolyze.
2. Obtain Lysergic Acid by Hydrolysis of #1 Product using Jacobs and Craig method:
1.0g of ergotinine(or in this case #1 Product) was dissolved in 20ml of N-methyl alcoholic KOH and the methanol was removed at once by distillation at low pressure. The residue was treated with 20ml of an 8% aqueous solution of KOH and the mixture was heated on a steam-bath for 1 hour. A stream of nitrogen was passed through the flask during the heating and basic volatile material from the reaction mix was collected by passing the gas through a solution of dilute HCl acid.
The alkaline solution was made acid to Congo red with sulfuric acid. At this point, a considerable amount of partly crystalline material precipitated. The acid suspension as such was placed in an extractor and exhaustively extracted with ether. The aqueous suspension which remained was then filtered. The dark colored solid was treated successively with 2x20ml portions of ammoniacal ethyl alcohol which left a residue which was inorganic. The filtrate on evaporation to dryness under reduced pressure gave a residue which was digested a short time with 5ml of methyl alcohol to remove colored impurities. After cooling, the undissolved crystals were collected. 0.26g of a slightly colored crystalline solid was obtained which melted with decomposition at 235°C.
3. Lysergic Acid to LSD - Cerny and Semonsky method.
I want to stay on this general path - but think I may be missing some things?
(Hive Bee)
12-06-03 19:27
No 475047
Ergine is L.A. amine this will not convert to ergotamine
Ergot to ergotamine
ergotamine to L.A. hydrazide(better yields than KOH method)
L.A.hydrazide to L.A.azide
L.A.azide to LSD
Sorry the article by Jacobs and Craig for the manufacturing of the free base of ergotamine can be found in J.Organic Chemistry vol 1,245-53.