(Stranger)
01-05-03 15:36
No 395639
(Rated as: excellent)
All of the different synthesises I find makes no difference which method you use. None are easier than others as to saving steps or equipment, chemicals etc. The internet is not to be trusted, info gathered from chemical journals, patent info are to be followed.
Svensk Farmaetisk Tideschrift Vol.75,933-40.(1971)
Die suspension von 1.34g.(5mmol) wasserfreier D-Lysergsaure in 80ml. Dimethylformamid wurde bei 20 degrees mit der Losung von 0.89g.(5.5mmol) N,N'-Carbonyldiimidazol in 25ml. desselben Losungsmittels versetzt und das Reaktionsgemisch wurde sodann 30 min bei 20 degrees im Dunkeln geruhrt. Die klare Losung wurde nun mit der Losung von 0.40g.(5.5mmol) Diathylamin in 5ml. Dimethylformamid versetzt, und das Gemisch wurde zunachst 2 Stunden bei 20 degrees, sodann noch 20 Stunden bei 5 degrees stehengelassen. Aus der braunlichen Losung wurde das Dimethylformamid im Vakuum der Wasserstrahlpumpe bei 50-60 degrees abdestilliert. Der Abdampfruckstand wurde in 250ml. 2%iger wassriger Weinsaurelosung gelost und mit Ather ausgeschuttelt, der wassrige Anteil wurde nach Versetzen mit einer geringen Menge Ostacol abgesaugt und mit Ammoniak auf pH 8 alkalisiert. Die freigesetzten Basen wurden in das Gemisch Ather-Athanol (9:1) aufgenommen, und die organische Schicht wurde nach dem Trocknen vom Losungsmittel befreit Man erhielt 2.3g Rohprodukt, das neben 57% Amiden D-Lysergsaure (I) und D-Isolysergsaure (II)(81% berechnet auf die Ausgangssaure) vor allem Imidazol enthielt. Der qualitativen papierchromatographischen Bewertung zufolge enthielt das Rohprodukt nur die Amide I und II sowie Spuren von D-Lysergsaure und einem Zersetzungsprodukt.
Das Rohbasengemisch wurde in 10 ml. Benzol mit 1%Aceton gelost und einer Aluminiumoxydsaule (50g; Aktivitat III-IV) unter Verwendung desselben Losungsmittelgemisches zur Elution der substanzen getrennt. Aus den ersten Fraktionen erhielt man .93g. sehr reines Amid I [a]20/D +26 degrees(c 0.30; Pyridin). Das normale Tartrat des Amids I entsprach nach Umkristallisieren aus Methanol in sienen Eigenschaften einer authentischen Dr.Probe. Smp. 198-200 degrees.[a]20/D 31 degrees (c 0.92; Wasser). Beim Troknen bei 100 degrees/0.2mm verlor die substanz 5.02% an Gewicht. Fur (C20H25N3O)2.C4H6o^ (796.9) berechnet:10.55%N; gefunden: 10.48% N.
(I'm Yust a Typo)
01-05-03 15:41
No 395641
>The internet is not to be trusted
Right said!
(Stranger)
01-05-03 18:24
No 395665
When I saw the name of the author I also thought that the text was swedish. Actually, it is German, but the special characters have gone. If someone thinks that it is from benefit, I can translate it.
(Stranger)
01-05-03 18:33
No 395666
Where do you have this text from? I took a brief look at it and noticed mistakes in orthography and punctuation - usually not a good sign: If the author is already careless with the rules of writing, he's often even more careless with the content of the text and the procedure wasn't taken from the literature for sure. That's at least my experience.
Edit: I just noticed that it would be possible that you typed this text out of a book. That would explain everything
Is this the case?
(Chief Bee)
01-05-03 19:34
No 395675
(Rated as: excellent)
A suspension of 1.34g (5mmol) anhydrous D-Lysergic Acid in 80ml DMF was mixed at 20°C with a solution of 0.89g (5.5mmol) N,N'-Carbonyldiimidazole in 25ml DMF and the reaction mixture was then stirred for 30 min at 20°C in the dark. The clear solution was then mixed with a solution of 0.40g (5.5mmol) Diethylamine in 5ml DMF, and the mixture allowed to stand for 2h at 20°C followed by 20h at 5°C. The resulting amber solution was freed from DMF by evaporation at 50-60°C under aspirator vacuum, the residue dissolved in 250mL 2% aqueous tartaric acid and the solution washed with diethyl ether. To the aqueous phase was added a small amount of Ostacol (activated carbon), the solution filtered with suction and basified to pH 8 with aqueous ammonium hydroxide. The liberated freebase was extracted with a 9:1 ether/ethanol mixture, and after separation and drying of the organic phase, the solvent was evaporated in vacuo to give 2.3g of crude product, which consisted of 57 weight% of the diethylamides of D-Lysergic acid (I) and D-Isolysergic acid (II) (81% yield calculated on the starting acid) and the rest being chiefly Imidazole. According to qualitative TLC analysis the crude product contained only the amides (I) and (II) as well as traces of D-Lysergic acid and a decomposition product.
The crude base mixture was dissolved in 10ml 99:1 benzene/acetone and chromatographed on 50g alumina (activity III-IV) using the same solvent mixture as eluent to separate the different fractions. From the first fractions, 0.93g very pure D-Lysergic acid Diethylamide, [a]20/D+26° (c=0.30; Pyridine). Following recrystallization from methanol, the physical properties of the neutral D-Lysergic Acid Diethylamide L-Tartrate was found to be identical to an authentic sample; mp 198-200°C, [a]20/D 31° (c=0.92; Water). Upon drying in a vacuum dessiccator at 100°C/0.2mmHg the substance lost 5.02% of its weight. For (C20H25N3O)2.C4H6O6 (796.9 g/mol) calculated: 10.55% N; found: 10,48% N.
Reference: Svensk Farmaceutisk Tidskrift Vol. 75, pp. 933-40 (1971)
(Hive Bee)
01-06-03 11:42
No 395870
Post 390003 (flipper: "LSD from LSA synth qeustion", Tryptamine Chemistry)
57,5% yield
This sentence is strange:
to give 2.3g of crude product, which consisted of 57 weight% of the diethylamides of D-Lysergic acid (I) and D-Isolysergic acid (II) (81% yield calculated on the starting acid) and the rest being chiefly Imidazole.
I dont understand it. He says that it's a 81% yield calculated on the starting acid. That 57% puzzles me but it's a weight percentage and not molar. 
(Chief Bee)
01-06-03 12:06
No 395873
Wow - whoever translated the article in that post did a very bad job - the 81% yield refers to the combined yield of LSD and iso-LSD *before* isolation and purification...
(Stranger)
01-06-03 17:48
No 395989
I typed it in from the journal, therefore the german signs are missing.
(Chief Bee)
01-06-03 17:53
No 395991
bbell: Could you please check your reference again and see if the specific rotation of the LSD tartrate is +31° or not, your writeup lacks a +/- sign there. Good job otherwise!
(Stranger)
01-06-03 20:22
No 396017
yes the article states m.p 198-200 degrees.[a]2/D +31 degrees (c .92; water) sorry for the ommission. There may be a small spelling mistake or two. But other wise is word for word.
I also have Hofmann and Stoll's article's from Helvitica Chemica Acta vol.38,421-33(1955);vol.26,922-28 and pages 944-65(1943) in German concerning LSD synthesis
(Hive Bee)
01-07-03 09:10
No 396168
from the mid 1960's that was used by a infamous chemist to make the LSD that turned on the Beatles & Rolling Stones, Leary & Alpert, NYC and half of Europe.
However the method listed here leaves out very important details:
The reaction between Lysergic Acid and the N,N Carbonyl Diimidazole must be done under absolutely anhydrous conditions! The Lysergic Acid MUST be dried in a vacuum oven first, and the reaction itself should preferably be done in an isolation chamber (large glove box) and in the dark! N,N Carbonyl Diimidazole, as well as the Lysergic Acid Imidazolate, deteriorate RAPIDLY when exposed to even small amounts of moisture. Any moisture and you have worthless crap within seconds!
Personally, I think the POCl3 method is simpler and straight forward.
(Master Whacker)
01-07-03 09:53
No 396175
The Lysergic Acid MUST be dried in a vacuum oven first
Not true, lysergic acid monohydrate reacts just fine with the coupling reagents contrary to this widely believed erroneous information.
(Hive Bee)
01-07-03 15:23
No 396257
just fine.
Correct me if I'm wrong, but N,N Carbonyl Diimidazole immediately breaks down on contact with H2O into imidazole and CO2. Sure I guess you don't have to dry the Lysergic Acid, but I'll bet the yields will go to hell....
(Newbee)
05-26-03 18:40
No 435756
Source is right from the journal, a typo or may be possible.A.Hofmann is the author.Title of journal is Svensk Farmaceutisk Tidskrift.
(Stranger)
05-30-03 19:36
No 436690
pyBOP and DIEA I would say is the easiest. Just use 2 eq of pyBOP and 4 of the DIEA. Run in DMF. Maybe EDC and DIEA in DCM as solvent would be easier or would the chlorine from the DCM fuck up the LSD molecule?
respect...
(Newbee)
06-19-03 18:01
No 441173
As I far as I am concerned no one method is better than another. You are working with a few grams of material.One method uses phosgene deadly poison.Once you have D-lysergic acid or iso-L.A. anything goes
(Stranger)
06-19-03 23:04
No 441228
> As I far as I am concerned no one method is better than another.
sure there is. if you cant get your hands on the chems needed, that particular synth is useless.
(Stranger)
06-26-03 05:43
No 442672
Well, I dicovered that CHCL3 is indeed a lousy solvent for egometrine freebase.(Even with a 5 % soln.of NH4OH) I will let you know how ethylene dichloride works.And keep you posted if and how the POCL3 rxn works,as soon as I have the chems...
Bad Karma? Yes please, you hypokrats!!!
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