HaCKeRz KrOnIcKLeZ 3/HaCKeRz_KrOnIcKLeZ.iso/drugs/lsd.synthesis

Text File | 1996-05-06 | 9KB | 180 lines

LSD-25 Synthesis from "Psychedelic Guide to the Preparation of
the Eucharist":

Preparatory arrangements:
     Starting material may be any lysergic acid derivative,
from ergot on rye grain or from culture, or morning glory
seeds 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 1-2 hours until some
separated, crystalline sulfur trioxide-dimethylformamide
complex has dissolved. The reagent is transferred to an air-
tight automatic pipette for convenient dispensing, and kept in
the cold. Although the reagent, which is colourless, may
change from yellow to red, its efficiency remains unimpaired
for three to four months in cold storage. An aliquot is
dissolved in water and titrated with standard NaOH to a
phenolphthalein end point.

Step III. Use Red light
     A solution of 7.15 g of d-lysergic acid mono hydrate (25
mmol) and 1.06 g of lithium hydroxide hydrate (25 mmol) in 200
ml of MeOH is prepared. The solvent is distilled on the steam
bath under reduced pressure. the residue of glass-like lithium
lysergate is dissolved in 400 ml of anhydrous dimethyl
formamide. From this solution about 200 ml of the dimethyl
formamide is distilled off at 15 ml pressure through a 12 inch
helices packed column. the resulting anhydrous solution of
lithium lysergate left behind is cooled to 0 C and, with
stirring, treated rapidly with 500 ml of SO3-DMF solution
(1.00 molar). The mixture is stirred in the cold for 10
minutes and then 9.14 g (125.0 mmol) of diethylamine is added.
The stirring and cooling are continued for 10 minutes longer,
when 400 ml of water is added to decompose the reaction
complex. After mixing thoroughly, 200 ml of saturated aqueous
saline solution is added. The amide product is isolated by
repeated extraction with 500 ml portions of ethylene
dichloride. the combined extract is dried and then
concentrated to a syrup under reduced pressure. Do not heat up
the syrup during concentration. the LSD may crystallise out,
but the crystals and the mother liquor may be chromatographed
according to the instructions on purification.

Purification of LSD-25
     The material obtained by any of these three preparations
may contain both lysergic acid and iso-lysergic acid amides.
Preparation #1 contains mostly iso-lysergic diethylamide and
must be converted prior to separation. For this material, go
to Step II first.

Step I. Use darkroom and follow with a long wave UV
     The material is dissolved in a 3:1 mixture of benzene and
chloroform. Pack the chromatography column with a slurry of
basic alumina in benzene so that a 1 inch column is six inches
long. Drain the solvent to the top of the alumina column and
carefully add an aliquot of the LSD-solvent solution
containing 50 ml of solvent and 1 g LSD. Run this through the
column, following the fastest moving fluorescent band. After
it has been collected, strip the remaining material from the
column by washing with MeOH. Use the UV light sparingly to
prevent excessive damage to the compounds. Evaporate the
second fraction in vacuo and set aside for Step II. The
fraction containing the pure LSD is concentrated in vacuo and
the syrup will crystallise slowly. This material may be
converted to the tartrate by tartaric acid and the LSD
tartrate conveniently crystallised. MP 190-196 C.

Step II. Use Red light
     Dissolve the residue derived from the methanol stripping
of the column in a minimum amount of alcohol. Add twice that
volume of 4 N alcoholic KOH solution and allow the mixture to
stand at room temperature for several hours. Neutralise with
dilute HCl, make slightly basic with NH4OH and extract with
chloroform or ethylene dichloride as in preparations #1 or #2.
Evaporate in vacuo and chromatograph as in the previous step.

Note: Lysergic acid compounds are unstable to heat, light and
oxygen. In any form it helps to add ascorbic acid as an anti-
oxidant, keeping the container tightly closed, light-tight
with aluminum foil, and in a refrigerator.