180 lines
8.5 KiB
Plaintext
180 lines
8.5 KiB
Plaintext
LSD-25 Synthesis from "Psychedelic Guide to the Preparation of
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the Eucharist":
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Preparatory arrangements:
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Starting material may be any lysergic acid derivative,
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from ergot on rye grain or from culture, or morning glory
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seeds or from synthetic sources. Preparation #1 uses any
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amide, or lysergic acid as starting material. Preparations #2
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and #3 must start with lysergic acid only, prepared from the
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amides as follows:
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10 g of any lysergic acid amide from various natural
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sources dissolved in 200 ml of methanolic KOH solution and the
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methanol removed immediately in vacuo. The residue is treated
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with 200 ml of an 8% aqueous solution of KOH and the mixture
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heated on a steam bath for one hour. A stream of nitrogen gas
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is passed through the flask during heating and the evolved NH3
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gas may be titrated is HCl to follow the reaction. The
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alkaline solution is made neutral to congo red with tartaric
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acid, filtered, cleaned by extraction with ether, the aqueous
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solution filtered and evaporated. Digest with MeOH to remove
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some of the coloured material from the crystals of lysergic
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acid.
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Arrange the lighting in the lab similarly to that of a
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dark room. Use photographic red and yellow safety lights, as
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lysergic acid derivatives are decomposed when light is
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present. Rubber gloves must be worn due to the highly
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poisonous nature of ergot alkaloids. A hair drier, or, better,
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a flash evaporator, is necessary to speed up steps where
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evaporation is necessary.
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Preparation #1
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Step I. Use Yellow light
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Place one volume of powdered ergot alkaloid material in a
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tiny roundbottom flask and add two volumes of anhydrous
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hydrazine. An alternate procedure uses a sealed tube in which
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the reagents are heated at 112 C. The mixture is refluxed (or
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heated) for 30 minutes. Add 1.5 volumes of H2O and boil 15
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minutes. On cooling in the refrigerator, isolysergic acid
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hydrazide is crystallised.
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Step II. Use Red light
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Chill all reagents and have ice handy. Dissolve 2.82 g
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hydrazine rapidly in 100 ml 0.1 N ice-cold HCl using an ice
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bath to keep the reaction vessel at 0 C. 100 ml ice-cold 0.1 N
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NaNO2 is added and after 2 to 3 minutes vigorous stirring, 130
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ml more HCl is added dropwise with vigorous stirring again in
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an ice bath. After 5 minutes, neutralise the solution with
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NaHCO3 saturated sol. and extract with ether. Remove the
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aqueous solution and try to dissolve the gummy substance in
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ether. Adjust the ether solution by adding 3 g diethylamine
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per 300 ml ether extract. Allow to stand in the dark,
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gradually warming up to 20 C over a period of 24 hours.
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Evaporate in vacuum and treat as indicated in the purification
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section for conversion of iso-lysergic amides to lysergic acid
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amides.
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Preparation #2
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Step I. Use Yellow light
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5.36 g of d-lysergic acid are suspended in 125 ml of
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acetonitrile and the suspension cooled to about -20 C in a
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bath of acetone cooled with dry ice. To the suspension is
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added a cold (-20 C) solution of 8.82 g of trifluoroacetic
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anhydride in 75 ml of acetonitrile. The mixture is allowed to
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stand at -20 C for about 1.5 hours during which the suspended
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material dissolves, and the d-lysergic acid is converted to
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the mixed anhydride of lysergic and trifluoroacetic acids. The
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mixed anhydride can be separated in the form of an oil by
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evaporating the solvent in vacuo at a temperature below 0 C,
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but this is not necessary. Everything must be kept anhydrous.
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Step II. Use Yellow light
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The solution of mixed anhydrides in acetonitrile from
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Step I is added to 150 ml of a second solution of acetonitrile
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containing 7.6 g of diethylamine. The mixture is held in the
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dark at room temperature for about 2 hours. The acetonitrile
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is evaporated in vacuo, leaving a residue of LSD-25 plus other
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impurities. The residue is dissolved in 150 ml of chloroform
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and 20 ml of ice water. The chloroform layer is removed and
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the aqueous layer is extracted with several portions of
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chloroform. The chloroform portions are combined and in turn
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washed with four 50 ml portions of ice-cold water. The
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chloroform solution is then dried over anhydrous Na2SO4 and
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evaporated in vacuo.
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Preparation #3
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This procedure gives good yield and is very fast with
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little iso-lysergic acid being formed (its effect are mildly
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unpleasant). However, the stoichometry must be exact or yields
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will drop.
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Step I. Use White light
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Sulfur trioxide is produced in anhydrous state by
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carefully decomposing anhydrous ferric sulfate at
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approximately 480 C. Store under anhydrous conditions.
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Step II. Use White light
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A carefully dried 22 litre RB flask fitted with an ice
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bath, condenser, dropping funnel and mechanical stirrer is
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charged with 10 to 11 litres of dimethylformamide (freshly
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distilled under reduced pressure). The condenser and dropping
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funnel are both protected against atmospheric moisture. 2 lb
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of sulfur trioxide (Sulfan B) are introduced dropwise, very
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cautiously stirring, during 4 to 5 hours. The temperature is
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kept at 0-5 C throughout the addition. After the addition is
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complete, the mixture is stirred for 1-2 hours until some
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separated, crystalline sulfur trioxide-dimethylformamide
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complex has dissolved. The reagent is transferred to an air-
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tight automatic pipette for convenient dispensing, and kept in
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the cold. Although the reagent, which is colourless, may
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change from yellow to red, its efficiency remains unimpaired
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for three to four months in cold storage. An aliquot is
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dissolved in water and titrated with standard NaOH to a
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phenolphthalein end point.
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Step III. Use Red light
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A solution of 7.15 g of d-lysergic acid mono hydrate (25
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mmol) and 1.06 g of lithium hydroxide hydrate (25 mmol) in 200
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ml of MeOH is prepared. The solvent is distilled on the steam
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bath under reduced pressure. the residue of glass-like lithium
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lysergate is dissolved in 400 ml of anhydrous dimethyl
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formamide. From this solution about 200 ml of the dimethyl
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formamide is distilled off at 15 ml pressure through a 12 inch
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helices packed column. the resulting anhydrous solution of
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lithium lysergate left behind is cooled to 0 C and, with
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stirring, treated rapidly with 500 ml of SO3-DMF solution
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(1.00 molar). The mixture is stirred in the cold for 10
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minutes and then 9.14 g (125.0 mmol) of diethylamine is added.
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The stirring and cooling are continued for 10 minutes longer,
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when 400 ml of water is added to decompose the reaction
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complex. After mixing thoroughly, 200 ml of saturated aqueous
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saline solution is added. The amide product is isolated by
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repeated extraction with 500 ml portions of ethylene
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dichloride. the combined extract is dried and then
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concentrated to a syrup under reduced pressure. Do not heat up
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the syrup during concentration. the LSD may crystallise out,
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but the crystals and the mother liquor may be chromatographed
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according to the instructions on purification.
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Purification of LSD-25
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The material obtained by any of these three preparations
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may contain both lysergic acid and iso-lysergic acid amides.
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Preparation #1 contains mostly iso-lysergic diethylamide and
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must be converted prior to separation. For this material, go
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to Step II first.
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Step I. Use darkroom and follow with a long wave UV
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The material is dissolved in a 3:1 mixture of benzene and
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chloroform. Pack the chromatography column with a slurry of
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basic alumina in benzene so that a 1 inch column is six inches
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long. Drain the solvent to the top of the alumina column and
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carefully add an aliquot of the LSD-solvent solution
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containing 50 ml of solvent and 1 g LSD. Run this through the
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column, following the fastest moving fluorescent band. After
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it has been collected, strip the remaining material from the
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column by washing with MeOH. Use the UV light sparingly to
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prevent excessive damage to the compounds. Evaporate the
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second fraction in vacuo and set aside for Step II. The
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fraction containing the pure LSD is concentrated in vacuo and
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the syrup will crystallise slowly. This material may be
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converted to the tartrate by tartaric acid and the LSD
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tartrate conveniently crystallised. MP 190-196 C.
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Step II. Use Red light
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Dissolve the residue derived from the methanol stripping
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of the column in a minimum amount of alcohol. Add twice that
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volume of 4 N alcoholic KOH solution and allow the mixture to
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stand at room temperature for several hours. Neutralise with
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dilute HCl, make slightly basic with NH4OH and extract with
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chloroform or ethylene dichloride as in preparations #1 or #2.
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Evaporate in vacuo and chromatograph as in the previous step.
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Note: Lysergic acid compounds are unstable to heat, light and
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oxygen. In any form it helps to add ascorbic acid as an anti-
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oxidant, keeping the container tightly closed, light-tight
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with aluminum foil, and in a refrigerator.
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