[D-lysergic acid diethylamide](LSD)
Preparatory arrangements:
Starting material may be any lysergic acid derivative, from ergot on rye grain or from culture, 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 dissolved in 200 ml of methanolic KOH solution and the methanol removed immediately in vacuo. The residue is treated with 200 ml of an 8% aqueous solution of KOH and the mixture heated on a steam bath for one hour. A stream of nitrogen gas is passed through the flask during heating and the evolved NH3 gas may be titrated is HCl to follow the reaction. The alkaline solution is made neutral to congo red with tartaric acid, filtered, cleaned by extraction with ether, the aqueous solution filtered and evaporated. Digest with MeOH to remove some of the coloured material from the crystals of lysergic acid.
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 iso-lysergic 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
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