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Výroba LSD z námelu

Neèekejte, e se vám ho povede vyrobit doma v kuchyni - je to nároèná práce pro dobøe vybav
laboratoø. Myslím, e není tøeba to pøekládat - pokud nìkdo disponuje potøebným vybavením,
tì bude rozumìt. Vybral jsem nejednodu í postup a doplnil pár komentáøù. Námel parazituje
dá se u nás celkem dobøe najít. Místo námelu lze pou ít i ergotamin extrahovaný z nìkterých
rénám (Bellaspon ..), ale je to nároènìj í. Potøebné vybavení by stálo s rezervou okolo 50
blémovìj í je vakuová odparka a aparatura na chromatografii.
1. Pøíprava kyseliny lysergové z námelu 10 g of any lysergic acid amide from various nat
ural sources dissolved in 200 ml of methanolic KOH solution and the methanol rem
oved immediately in vacuo. The residue is treated with 200 ml of an 8% aqueous s
olution 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 neu
tral to congo red with tartaric acid, filtered, cleaned by extraction with ether
, the aqueous solution filtered and evaporated. Digest the MeOH to remove some o
f the coloured material from the crystals of lysergic acid.
Arrange the lighting in the lab similarly to that of a dark room. Use photograph
ic red and yellow safety lights, as lysergic acid derivatives are decomposed whe
n light is present. Rubber gloves must be worn due to the highly poisonous natur
e of ergot alkaloids. A hair drier, or, better, a flash evaporator, is necessary
to speed up steps where evaporation is necessary.
2. Syntéza LSD isomerù z kyseliny lysergové
Step I. Use Yellow light
5.36 g of d-lysergic acid are suspended in 125 ml of acetonitrile and the suspen
sion cooled to about -20 C in a bath of acetone cooled with dry ice. To the susp
ension is added a cold (-20 C) solution of 8.82 g of trifluoroacetic anhydride i
n 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 mixe
d 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 mixtu
re is held in the dark at room temperature for about 2 hours. The acetonitrile i
s evaporated in vacuo, leaving a residue of LSD-25 plus other impurities. The re
sidue is dissolved in 150 ml of chloroform and 20 ml of ice water. The chlorofor
m layer is removed and the aqueous layer is extracted with several portions of c
hloroform. 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 anhydr
ous Na2SO4 and evaporated in vacuo.
Vzniklo LSD s pøímìsí isomerù, zpùsobujících bolesti hlavy, nevolnost a dal í ne ádoucí efe
vní je pouze d-stereoizomer. Nutno provést purifikaci podle bodu 3.
3. Oddìlení èistého LSD od isomerù
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 c
hromatography 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 an
d carefully add an aliquot of the LSD-solvent solution containing 50 ml of solve
nt and 1 g LSD. Run this through the column, following the fastest moving fluore
scent band. After it has been collected, strip the remaining material from the c
olumn by washing with MeOH. Use the UV light sparingly to prevent excessive dama
ge to the compounds. Evaporate the second fraction in vacuo and set aside for St
ep II. The fraction containing the pure LSD is concentrated in vacuo and the syr
up will crystallise slowly. This material may be converted to the tartrate by ta
rtaric 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 mini
mum amount of alcohol. Add twice that volume of 4 N alcoholic KOH solution and a
llow the mixture to stand at room temperature for several hours. Neutralise with
dilute HCl, make slightly basic with NH4OH and extract with chloroform as in #2
. Evaporate in vacuo and chromatograph as in the previous step.
Note: Lysergic acid compounds are unstable to heat, light and oxygen. In any for
m it helps to add ascorbic acid as an anti- oxidant, keeping the container tight
ly closed, light-tight with aluminum foil, and in a refrigerator.
N-acetyl-LSD : známé jako ALD-52, hor í ne LSD, zhruba 90% úèinnost, mírné potlaèení nervo
klidnìj í, ménì intenzivní prùbìh, nìkdy je na tripech místo LSD
N-methyl-LSD : lep í ne klasické LSD, dokonalej í pùsobení na nervovou soustavu

Lysergic Acid Diethylamide (LSD) Syntheses

from "Recreational Drugs" by Professor Buzz
--------------------------------------------------------------------------------
Introduction
LSD is, without a doubt, the king of hallucinogens. It is rather difficult to ma
ke by total synthesis, but with the right starting materials (lysergic acid, erg
otamine) it is as easy to produce as your average THC or amphetamine. I call it
the king because of the awesome potency, the usual hallucinogenic dose being abo
ut 100 to 400 micrograms orally. The amphetamine DOM (STP), which is 100 times m
ore powerful than mescaline, requires a dose of 5 milligrams. This gives one gra
m of LSD the potential to contain 4,000 to 10,000 doses. With an average of abou
t 6,000 doses per gram, the street value (based on $5 a hit) of one gram of LSD
is $30,000.
LSD Synthesis
As with the rest of this book, I will deal only with the synthetic manufacture o
f drugs (LSD included). If you want to grow the ergot alkaloids that begin the t
otal synthesis of LSD, then you will have to go to the Merck Index and look up t
he references to the operation. Michael V. Smith's book, Psychedelic Chemistry,
has a section on growing Claviceps purpurea, which yield ergot compounds. This s
ection is very complete and informative, but I think that you should also look u
p the dangers of growing this fungus before doing it, as it causes a type of gan
grene that can kill you (not to mention making your arms and legs fall off) upon
contamination of your body. As Mr. Smith's book states, this fungus is very tem
peramental, hard to obtain, even harder to grow and diffficult to work with. Smi
th's book gives many references and many formulas that you will not see here, bu
t which are of great interest in the making of all hallucinogens (not just LSD).
This does not make my book incomplete. On the contrary, I have given more than
enough information to make every major type of drug.
My book is not intended to cut in on Smith's book sales. It is intended to give
you information and formulas that Smith's book lacks. Where he gives many differ
ent types of formulas, I give only the fast, simple and high yielding formulas.
Also, you will not see the same formula in both his and my book, unless it is a
general method and not specific. What his book lacks, my book gives (equipment,
methods, basic chemistry, a wider variety of types of different classes of drugs
, glossary terms, easier to understand wordage, how to buy and make precursors,
etc.). What my book lacks, his book gives (more variety of hallucinogenic formul
as, cultivation of pot and ergot, tests for activity, etc.). I feel it would be
a good idea to buy his book and try some of these harder formulas after learning
the basics and practicing some of the formulas from my book, for complete under
standing first.
Forgive me for wandering from the subject of LSD synthesis. As this first chapte
r of formulas is for psychedelics, I felt it necessary to explain the difference
of the only other book of this type. If you are sharp, and have carefully read
my chapter on buying precursors, you should be able to get lysergic acid from a
supplier. Be warned, that the DEA must be informed of the purchase by the suppli
er, according to laws requiring them to do so. Lysergic acid can be made. Follow
ing is the general method to give you a very good idea of the procedure and chem
icals involved.
Synthesis of Lysergic Acid
By reacting N-benzoyl-3-(B-carboxyethyl)-dihydroindole (see JCS, 3158 (1931) for
the preparation of this compound) with thionyl chloride, followed by aluminum c
hloride gives 1-benzoyl-5-keto-1,2,2a,3,4,5-hexahydrobenzindole. This is then br
ominated to give the 4-bromo-derivative, which is converted to the ketol-ketone
by reacting with methylamine acetone ethylene ketol. This is then hydrolized by
acid to yield the diketone and treated with sodium methoxide to convert it to th
e tetracyclic ketone. Acetylate and reduce this ketone with sodium borohydride t
o get the alcohol, which is converted to the hydrochloride form, as usual.
The above hydrochloride is treated with thionyl chloride in liquid sulfur dioxid
e, to produce an amorphous chloride hydro chloride, which is converted to the ni
trile with sodium cyanide in liquid hydrogen cyanide. Methanolysis then gives th
e ester of the nitrile. Alkaline hydrolysis of this last compound, followed by c
atalytic dehydrogenation in water using a deactivated Raney Nickle catalyst (see
JOC. 13, 455 1948) gives dl-lysergic acid.
Total Synthesis Of Lysergic Acid
This is the easiest way to totally synthesize lysergic acid. There are other way
s, but after reviewing other methods, I found this to be superior. It is quite c
omplicated and it takes good modern equipment.
JACS, 78, 3087 (1956). 3-Indolepropionic acid, 94.5 g (0.5 mole) is dissolved in
600 ml of water containing 20 g of NaOH. The solution is mixed with 100 g of Ra
ney Nickle catalyst and hydrogenated at room temp in a steel bomb at about 3,500
psi until the uptake of hydrogen stops (about 20-30 hours). Filter off the cata
lyst and wash it with a little water to remove the product that is clinging to i
t. Add 85 ml of concd HCl acid to the filtrate, and cool. If your reduction is i
ncomplete, you will now have unreacted starting material separate, and this must
be removed by filtration. Benzoylate the filtrate (the Schotten and Baumann met
hod is preferable), using 210 ml of 12 N NaOH 180 ml of benzoyl chloride. Keep t
he solution alkaline throughout the benzoylation, and keep the temp below 40°C by
cooling. When the benzoyl chloride is fully reacted, the reaction mixture is coo
led and acidified with 300 ml of HCl acid. Filter the crude product by filtratio
n, wash with water, and extract with four 1 liter portions of hot water. Separat
e, and crystallize the resulting syrupy product from a few volumes of methanol.
Filter and wash with a little cold methanol to get a little over 100 g that melt
s at 151-153°. This is l-Benzoyl-3-beta-carboxyethyl-2,3-dihydroindole. This can b
e purchased to eliminate this step.
1-Benzoyl-5-keto-1,2,2a,3,4,5,-hexahydrobenzindole. 118 g of the above product (
1-benzoyl-3-B-carboxyethyl-2,3-dihydroindole) is mixed with 200 ml of pure thion
yl chloride. This solution is allowed to stand for 30 min, then it is warmed gen
tly for 15-21 min on a steam bath. Excess thionyl chloride is completely evapora
ted with the temp maintained between 22-26°C in vacuo. The crude acid chloride is
dissolved in dry carbon disulfate. This solution is added, in a thin stream, to
a well stirred suspension of 240 g of aluminum chloride in 1750 ml of carbon dis
ulfate in a 5,000 cc flask. Note: this must be done under a fume hood. A complex
will separate and bog down the stirring device. Heat this mixture under reflux
with stirring for 1 hour. Decompose this mixture by adding 500 g of ice, 250 ml
of concd HCl acid, and 500 ml of water, all while good stirring is continued. Co
oling of this operation is affected by periodic distillation of the carbon disul
fate in vacuo. After the decomposition is complete, any remaining carbon disulfa
te is removed completely in vacuo, and the product is extracted with 2 liters of
benzene. The extract is washed well with 500 ml of 2 N NaOH in three portions,
and then with water. Dry (with the usual magnesium sulfate), and evaporate to a
small volume in vacuo. Add this small volume to several portions of ether to get
the ketone to crystallize (add slowly), and filter, then wash with ether to get
85 g of pure title product, mp: 146-147°C.
1-Benzoyl-4-bromo-5-keto-1,2,2a,3,4,5-hexahydrobenzindole. A solution of the abo
ve indole (305 g) in 2,200 ml of glacial acetic acid is warmed to 40°C. While the
reaction is illuminated with a 250 watt bulb, 352 g of pyridine hydrobromide per
bromide is added in portions, over 5 min with shaking. The solution is then heat
ed to 60° and is held between there and 55°C for 30 min. Treat the mixture with carb
on, and evaporate to a small volume in vacuo. The residue is taken up with 2,200
ml of chloroform, and wash this solution with several portions of water, dry as
above, and concentrate in vacuo. Crystallize the residue from 2,200 ml of 50% a
cetic acid and 50% ether to get 270 g of title product that melts at 180.5-181.5°C
. Another crop can be obtained from concentrating the fltrates. Yield: 30 g of l
ess pure product.
1-Benzoyl-2,2a,3,4-tetrahydro-4-methyl-2-methyl-1,3-dioxolan-2-yl-methyl-aminobe
nzindol-5-(1H)one. A solution of the last indole product above (270 g) and 307 g
of methylaminoacetone ethylene ketol in 4,500 ml of dry benzene is refluxed for
21 hours under a slow stream of nitrogen. The mixture is cooled and 151 g of me
thylaminoacetone ethylene ketol hydrobromide is filtered off. The filtrate is wa
shed with ice water, then extracted with 2.5 liters of cold dilute HCl acid cont
aining 150 ml of the concd acid. The acid extracts are immediately added to an e
xcess of ice cold dilute NaOH. Extract with 1 1iter of chloroform, dry over magn
esium sulfate, treat with carbon and concentrate by evaporation in vacuo. The re
sidual ketol-ketone is crystallized from acetone to yield 220 g, mp: 135-136°C.
5-Keto-4-N-methyl-N-acetonylamino-1,2,2a,3,4,5-hexahydrobenzindole. 20 g of the
above product is dissolved in a mixture of 250 ml of concd HCl acid and 250 ml o
f water, and the solution is kept under nitrogen for 5 days at 37°. Cool the mixtu
re, treat with carbon, filter, and concentrate the filtrate in vacuo to a small
volume. Treat the residue with an excess of sodium bicarbonate, extract with col
d chloroform, and remove the chloroform by evaporation in vacuo at room temp. Th
e crude diketone is powdered, slurried with 75 ml of benzene-ether, and filtered
. Yield: 9.8 g, mp: 105-107°C.
9-keto-7-methyl-4,5,5a,6,6a,7,8,9-octahydroindolo-(4,3)isoquinoline. 25 g of the
 above product is mixed with 550 ml of absolute ethanol. Stir this mixture under
nitrogen and cool to -15° with an external freezing mixture. Sodium methoxide is
added (17 g) and the mixture is stirred for 10 min at -10 to -12°. Cool to -25°, and
the product is filtered and washed (while still in the funnel) with cold ethano
l and ether. Without exposure to air the crude ketone is immediately slurried wi
th a little ice water and filtered. Wash with ice water, ethanol, then ether (al
l cold) to yield 16 g of product melting at 145-147°.
4-Acetyl-9-keto-7-methyl-4,5,5a,6,6a,7,8,9-octahydroindolo-4,3-quinoline. 24 g o
f the last product is added to 80 ml of cold acetic anhydride. The mixture is he
ld at 25° for about 5 min, then thoroughly cooled, filtered, and the product (a so
lid) washed with ether to yield 20.5 g, mp: 169-170°. A second crop is obtained by
concentrating the mother liquor by evaporation.
A mixture of the last product (1.0 g) and 10 g of palladium carbon (5%), in 35 m
l of xylene, is heated under reflux for 4 hours. The catalyst is filtered and ex
tracted with hot methanol and chloroform. The combined extract filtrates and the
initial filtrate are combined and evaporated in vacuo. The residue is recrystal
lized from water to give 0.6 g of a monohydrate product that melts at 255-256°. Th
is product is called 4-acetyl-4,5,5a,6-tetrahydro-9-hydroxy-7-methylindolo-(4,3f
g)-quinolinium hydroxide betaine.
4-Acetyl-9-hydroxy-7-methyl-4,5,5a,6,7,8,9,10-octahydroindolo-(4,3fg)-quinoline.
1 g of the above betaine in a mixture of 20 ml of ethanol and 5 ml of water, is
treated with 0.08 g of sodium borohydride, and this solution is refluxed for 10
min and kept at 25° for 1 hour after the reflux is finished. The solvent is disti
lled off, and the residue is taken up in a mixture of chloroform and water. The
chloroform solution is separated, dried as above, and then the solvent is distil
led off. The residue is recrystallized from a nitromethane-ethyl acetate mixture
to yield 0.2 g (21%), mp 193-196°. Not only is this a small scale, but it is a po
or yield, requiring you to perform it several times to get enough product to per
form the next step. When you have more than enough, convert the product into its
hydrochloride form by dissolving in dry methanol and precipitating with dry hyd
rogen chloride.
4-acetyl-9-chloro-7-methyl-4,5,5a,6,6a,7,8,9-octahydroindolo-(4,3fg)-quinoline h
ydrochloride. 3.1 g of the above product in its hydrochloride form is dissolved
in 75 ml of liquid sulfur dioxide contained in a glass lined, high pressure bomb
, or autoclave. Thionyl chloride (1.2 ml) is added and the vessel is sealed and
kept at 25° for 6 hours. Vent the vessel carefully and remove the mixture. Evapora
te the sulfur dioxide while keeping the volume of the solution constant by the s
low addition of dry ether. The amorphous chloro hydrochloride is filtered, washe
d with ether (dry) and dried by evaporating in vacuo to give 3.5 g of product, m
p:130-135°.
4-Acetyl-9-cyano-7-methyl-4,5,5a,6,6a,7,8,9-octahydroindolo-(4,3fg)-quinoline. 4
0 g of dry, powdered sodium cyanide, is added to ice cold liquid hydrogen cyanid
e and stirred gently with ice bath cooling. Speed up the stirring, continue the
cooling, and add 7.5 g of the amorphous product directly above. Continue stirrin
g for 30 min, then the hydrogen cyanide is distilled under enough reduced pressu
re to keep it coming over the condenser at a temp below 10-12°. The residue is mix
ed with chloroform and ice water, and the resulting mixture is filtered. The org
anic layer of the filtrate is separated and the aqueous layer is extracted with
two separate portions of chloroform. The combined extracts (this would include t
he separated chloroform, as usual) are dried over magnesium sulfate, decolorized
, and the solvent removed by distillation in vacuo. Crystallize the product in e
thyl acetate. Yield: 3.3 g, mp: 173-174°. Recrystallize again for extra purity.
9-Carbomethoxy-7-methyl-4,5,5a,6,6a,7,8,9-octahydroindolo-(4,3fg)-quinoline. 1 g
of the last product is mixed with 15 ml of methanol and 0.25 ml of water. With
external (ice bath) cooling add 2 ml of concd sulfuric acid slowly. Seal this so
lution in a high pressure bomb with a glass liner (or in a glass tube taking saf
ety precautions in case of explosion) with a nitrogen atmosphere, and heat at 10
0° for 23-24 hours. Note: I have seen a big pressure cooker (like gramma cans peas
with) work for some of these bomb procedures. I do not recommend it, but here i
s how to do it right, if you feel you must. Use only the great big heavy duty mo
dels, in excellent condition, set the pop off (relief valve) for near maximum po
sition; never, ever tamper or modify this valve to get more pressure. Put the pr
oduct in a glass beaker, put it in the cooker, flush with nitrogen, heat and sta
y in a different house during the reaction. Carefully turn off heat, notice or r
ecord pressure gauge after time has elapsed. Wait until pressure drops noticeabl
y, bleed off remaining pressure and get product.
Treat the mixture with decolorizing carbon and then evaporate in vacuo to 10 ml.
Pour onto a mixture of 30 ml of chloroform, ice, and 10 g of sodium bicarbonate
. Separate the chloroform layer, and extract the aqueous phase with three 10 ml
portions of chloroform. The combined chloroforms are dried, evaporated to drynes
s in vacuo, and the product is crystallized from benzene to give 1/2 g of produc
t that melts at 159-160°. You may purify more by recrystallizing from ethyl acetat
e. This is not very much product. As with the procedure 4 steps back, you will h
ave to perform this step over and over. If you try to double or triple the amoun
ts given, you may get more product, but you will hurt the yield.
dl-Lysergic acid. 3.9 g of the last product is mixed with 78 ml of 1.5% potassiu
m hydroxide solution. Reflux for 30 min under nitrogen. 8.5 g of hydrogen sodium
arsonate, and Raney Nickle (16 g wet), that has previously been deactivated by
boiling in xylene suspension (see JOC, 455 (1948) to deactivate), is added and t
he mixture is refluxed and stirred under a nitrogen atmosphere for 20 hours. The
solution is treated with carbon, and the crude lysergic acid is precipitated by
neutralization to pH 5.6, and then filter it off and wash with water. Yield: 1.
04 g. A second crop is obtained in the usual manner (0.15 g). Purify by dissolvi
ng in dilute ammonium hydroxide, treat with decolorizing carbon, and reprecipita
te with carbon dioxide to get a mp of 242-243°. You may be able to get an analytic
al or laboratory consultant to make one of these products near the final step, t
hereby eliminating the need to go through all of the steps as described. This wi
ll save you much time, but as these people are highly trained, their time will b
e costly.
Lysergic acid can be made from many ergot derivatives by hydrolysis of these com
pounds. These compounds include ergonovine, ergotamine, ergokryptine, ergosine,
methysergide, ergine, and a few others. Total synthesis of these compounds is im
practical, as lysergic acid is made before the alkaloid. You could stop the oper
ation as soon as you reach lysergic acid, otherwise you will have to hydrolyze a
s described below. There are many analogs of these alkaloids that end with the i
ne suffix. These are not as suspicious as the former because they lead to an ina
ctive iso-LSD. They will look like this: the ergotamine isomer = ergotaminine, t
he ergonovine isomer = ergonovinine, etc. These analogs are easily converted to
the active forms or they may be used exactly as the non-iso versions to give the
iso-LSD, which is converted very easily to LSD as also described below.
Lysergic Acid From Ergot Alkaloids.
Dissolve 20 g of the alkaloid (use any of the above or one of its isomers or a c
ombination) in 200 ml of 1 M methanolic KOH solution (this is made by dissolving
14 g of KOH in 250 ml of dry methanol) in a 1 1iter evaporation flask (heavy wa
lled construction). Evaporate the methanol off. Add 400 ml of 8% aqueous (water)
KOH solution to the residue and boil for one hour under a slow stream of nitrog
en that is allowed to flow through a small orifice for exhausting purposes. Cool
, acidify with dilute sulfuric acid, and shake in a separatory funnel with 1 1it
er of dry ether. Separate the lower aqueous layer and filter it with vacuum assi
st. Wash the precipitate with 20 ml of dilute sulfuric acid. This is lysergic ac
id; store as described later in this chapter.
There remains a small amount of lysergic acid in the filtrate solution. Remove i
t by basifying the solution with sodium carbonate, and then bubbling CO2 through
it. Filter it off and add it to the other lysergic acid. Now you will need to p
recipitate the iso-lysergic acid out and convert it. If you did not use any iso-
alkaloid then you will have very little iso-lysergic acid, but it is still worth
converting. If you used iso-alkaloid, this is a must.
Precipitate the iso-lysergic acid by adding some 10% HNO3, filter, add more port
ions until no more precipitate forms. Convert it to lysergic acid by adding 3 ml
of 10% KOH per every 0.1 g of iso-lysergic acid, heat on steam bath for 1 hour
under a nitrogen atmosphere. Precipitate the changed lysergic acid by acidifying
with glacial acetic acid. The total yield of this entire operation (including t
he iso change) is a little under 10 grams. As stated earlier, you may use only i
so-alkaloid in the hydrolysis step above to get iso-lysergic acid which can be u
sed in the synthesis of LSD to get iso-LSD, which can be changed to the active L
SD as described later. Note: iso-LSD is not active.
Some sources say that lysergic acid does not need to be purifed. I feel that eve
rything should be purified. In the event that something should go wrong with the
formula, you can immediately rule out impurities as the cause. Also, impurities
create unwanted byproducts which can be poisonous, creating dangers for the dru
g user. Purification of lysergic acid is very easy. Dissolve the acid in dilute
ammonium hydroxide, treat with decolorizing carbon, reprecipitate (after filteri
ng off and washing product from the carbon) with carbon dioxide.
Convert iso-LSD to LSD. Add 50 ml of ethanol and 5 ml of 4 N KOH per every gram
of iso-LSD. Let this mixture stand for 2 hours at room temp. Evaporate in vacuo
to get the LSD.
Separate iso-LSD from LSD. Dissolve the residue of the mixture of LSDs from the
end of the formula in 120 ml of benzene and 40 ml of chloroform. Add tartaric or
maleic acid to precipitate the LSD, filter off, add a little ether and put in r
efrigerator for several days to get a little more LSD, which is filtered off and
added to the rest. Evaporate the filtrate in vacuo to get the iso-LSD and conve
rt as above.
LSD from Lysergic Acid. This is based on the formula taken from CA, 50, 10803d (
1956) Dissolve 5.5 g of dry lysergic acid in 125 ml of acetonitrile that has bee
n cooled to -10° and cool further to -20° with an external freezing mixture. Add 8.8
g of trifluoroacetic anhydride in 75 ml of acetonitrile (this solution must be
cooled to -20° before the addition). Be careful making this addition, so as not to
raise the temp, etc. Let stand at -20° until all the lysergic acid dissolves (abo
ut 1/2 hours). Add 7.6 g of diethylamine (or analog) in 150 ml of acetonitrile a
nd allow to set at room temp in darkness for 2 hours. Evaporate in vacuo to get
the LSD, which can be separated from the iso-LSD as above.
LSD From Lysergic Acid
This is taken from CA, 57, 5979 (1962). It is designed by Hofmann to give 1-meth
yl-D-lysergic acid, and is modified to give LSD and iso-LSD. Dissolve 0.54 g of
lysergic acid in 10 ml of freshly distilled phosphorous oxychloride, stir 0.42 g
of powdered, fresh phosphorous pentachloride. Allow to stand at room temp for 2
min, then at 90° for 2 min, then evaporate in vacuo. Extract the residue with hex
ane to give lysergic acid chloride hydrochloride. To save time you may extract t
he reaction mixture without evaporating. Add 2.5 g of the hydrochloride to a coo
led solution of 7 ml of diethylamine (or analog) in 25 ml of methylene chloride
that is cooled to 0° Note This solution is cooled to 0° before the addition. With st
irring add 13.75 ml of dry pyridine and stir for 30 min with cooling to keep the
temp at 0° or a little below. Warm to room temp and continue the stirring for 90
min. Evaporate in vacuo to get the LSDs. Separate as already described.
LSD From Lysergic Acid Monohydrate
This is, in my opinion, the best of all the methods. It was designed to be used
to experiment with different types of amines, so if you would like to substitute
diethylamine with another amine this would be the best bet. It also gives good
yields (50% or better) and is very easy. The reference that gives it (JMC, 16, 5
32 (1973)), also gives potency data for many lysergamides and many of their form
ulas. The reading is good, interesting, informative, and the method given below
gives no useful amount of iso-LSD, so separation of that product is not necessar
y. Both method A and B were from JMC, 16, 532.
Method A. A slurry of 3.15 g d-lysergic acid monohydrate (monohydrate means dry)
and 7.3 g of diethylamine (or 0.1 mole of similar amine) in 150 ml of pure chlo
roform is heated to reflux. After the lysergic acid is dissolved (a few min) coo
l the mixture down to where reflux has stopped by removing the heat. Before the
mixture cools any further 2 ml of phosphorous oxychloride is added at such a rat
e as to give reflux (about 2 min). After addition, reflux for 4-5 min further un
til an amber-colored solution results. Cool to room temp and wash the mixture wi
th 200 ml of 1 M ammonium hydroxide. The chloroform solution was dried with MgSO
4 (this would have to be after separation), filtered, and concentrated by evapor
ation in vacuo under a temp of 38° (at no time let the temp go over 40°). The last t
races of solvent are removed at 2-5 mm. Dissolve the residue in a minimum amount
of methanol and acidify with freshly prepared solution of 20% maleic acid in me
thanol (not aqueous) to precipitate the LSD in its maleate form. Filter the fluf
fy white needles, wash with cold methanol and air dry to get 2.2 g of LSD that r
equires no further purification.
Method B. This is proven to be more effective for using substituted amines. Mix
the following slurry; 3.15 g of dry d-lysergic acid in 150 ml of chloroform and
reflux in a 3 necked flask. As soon as you have the reflux adjusted add 7.3 g of
diethylamine (or 0.1 mole of analog) in 25 ml of chloroform and at the same tim
e, from another addition funnel mounted in the opposite neck of the flask, add 2
ml of phosphorous oxychloride so that both the additions begin at the same time
. The additions should be timed so that they both finish after 2-3 min. Keep at
reflux with gentle heating for another 3-5 min until a clear amber-colored solut
ion results. Cool thesolution to room temp and finish the work up, as in method
A directly above, to get 2 g of LSD maleate. As in method A, this method gives v
ery little or no iso-LSD, so don't worry about removing that.
Lysergic Acid Monohydrate
I put this formula in this book specifically for the two methods (A and B) direc
tly above, however, lysergic acid monohydrate can be used on any of the LSD form
ulas with possible success. I feel this may be easier than the first method give
n at the beginning of this chapter.
Dissolve 175 g of KOH in 1,750 ml of water in a flask of 5 liters volume equippe
d with a reflux condenser and a gas inlet tube. If a stirring device is not requ
ired, it should be removed and the open neck stoppered. Heat the mixture to 80° un
der a stream of nitrogen and add 500 g of ergotamine tartrate. Hold the temp at
80° for 2 1/2 hours with bubbling from the nitrogen filled gas inlet tube. Pour th
e mixture into a 5 gallon polyethylene bucket (made from the same material as a
plastic gas can) filled with about 6 liters of ice. Put the bucket in a cooling
mixture to cool below 10°. Neutralize the mixture by adding cold dilute sulfuric a
cid to a congo red end point (pH 4.2). Lysergic acid and potassium sulphate will
be seen to precipitate. Let stand for 2-3 hours in the 5-10° cooling mixture. Fil
ter with vacuum assist, and let vacuo suck as dry as possible. Break up the filt
er cake and put in a 2 liter beaker. Make a solution from 150 ml of liquid ammon
ia and 2.5 liters of very cold dry denatured ethanol and add to the reaction mix
ture. Stir for 1 hour and filter. Keep the fltrate and treat the filter cake to
1/2 the ammonia ethanol mixture as above. This second extract is filtered and th
e cake is washed with 250 ml of the ammoniacal ethanol mixture. Combine the fitr
ates, and evaporate to total dryness with a strong vacuum and gently heating. Do
not heat at too high of a temp. Scrape the product from the vacuum vessel and p
ut into a mortar. Mix 113 ml of methanol with 38 ml of water, and rinse the rest
of the residue from the evaporation vessel and dump into the mortar with the re
st of the product. The slurry in the mortar is ground up well and filtered. Wash
the flter cake with 150 ml of cold water and use vacuum to suck dry for 1 hour.
Break up the filter cake and dry at 80-85° under a high vacuum to get about 65-75
g of cream-white to gray-white powder. This is lysergic acid monohydrate.
I think that if you dry the lysergic acid (obtained from the ergot alkaloids by
hydrolysis as described earlier) it will also work in methods A and B. This is h
ow you dry lysergic acid: dry under high vacuum at 140-145° for 2-3 hours.
LSD From Ergot Alkaloids
This was invented by Hofmann and is a superior method because you may proceed fr
om the ergot alkaloids to LSD without isolating the lysergic acid. CA, 57, 12568
(1962).
Add 1.2 g of ergotamine hydrochloride to 4 ml of anhydrous hydrazine and heat 1
hour at 90°. Add 20 ml of water and evaporate in vacuo, to get d-iso-lysergic acid
hydrazine. 1 g of the lysergic hydrazine is powdered well and added to 40 ml of
0.1 N (ice cold) HC1 acid. To this, cooled to 0°, is added 4 ml of 1 N Na nitrite
, with good stirring. Over 2-3 min, add 40 ml of 0.1 N HC1 acid to get pH to 5.
Let stand for 5 min, basify with 1 N NaHCO3, extract with 100 ml of ether, and t
hen with 50 ml of ether. Wash the ether layer with water and dry, then evaporate
in vacuo at 10°. Dissolve the resulting yellow azide in about 5 ml of diethylamin
e at 0° and then heat in a metal bomb at 60° for 1 hour. If a bomb is unavailable yo
u may get by with heating for 3-4 hours at 45° in a vented flask under a nitrogen
atmosphere. Also, I would flush the bomb with nitrogen before sealing and heatin
g. Remove heat after time elapses and let stand (after bleeding off pressure for
bomb method) for 2 hours and evaporate in vacuo to get 0.7 g of LSD and 0.15 g
of iso-LSD. The iso-LSD will not do anything (good or bad) if consumed, so you m
ay leave it in with the LSD. You may also separate it and convert it to LSD as i
n the formulas ahove.
LSD From Lysergic Acid JOC, 24, 368 (1959)
This is a simple method that gives good yields of LSD with very little (if any)
iso-LSD. You will be required to purchase sulfur trioxide from Allied Chemical a
nd Dye Corp (ask for Sulfan B, or SO3), but this is not a suspicious chemical so
ordering is not a problem.
Sulfur trioxide-Dimethylformamide complex (SO3-DMF). This is a reagent required
for this method of LSD production. A completely dry 22 liter flask (round bottom
) in an ice cooling bath is fitted with a condenser, stirring device, addition f
unnel, then is filled with 10-11 liters of DMF (dimethylformamide) that has been
freshly distilled under reduced vacuum. Use drying tubes to protect the reactio
n from all moisture (including atmospheric moisture). 2 pounds of sulfur trioxid
e (SO3) are then added, with a great deal of caution, over 4-5 hours with stirri
ng, dropwise. The temp must be held between 0°-5° during this addition. Stir for 1-2
hours after the addition until some separated, crystalline SO3-DMF complex has
dissolved. Store in the dark in a suitable vessel, in a refrigerator for not mor
e than 3 months. Upon storage, the complex will turn yellow and then orange. Thi
s is normal. As long as it is less than 3-4 months, it is still good. This mixtu
re gives a molarity of 1 (1 M) and can be made using 1/2 or 1/4 of the amounts a
bove to scale down the version, still giving a 1 M solution.
Lysergic Acid Diethylamide. A solution of 7.1 g of lysergic acid monohydrate. As
with any of the formulas calling for the monohydrate, you may substitute dry or
 anhydrous lysergic acid in place of the lysergic acid monohydrate by using a sm
aller amount of the dry lysergic acid. I have found that dividing the amount of
the monohydrate by the constant of 1.1 gives a close amount of dry lysergic to u
se, e.g., 7.1 divided by 1.1 = 6.5 g, to substitute in the formula. Likewise, th
e monohydrate can be figured into a formula calling for dry lysergic, 6.5 times
1.1 = 7.1 g. Also, if a formula does not specify if the lysergic acid is to be d
ry, e.g., add 0.54 g of d-lysergic acid, then always use dry or monohydrate as a
ny water will kill the yield. Dry as stated above. As a general rule dry your ly
sergic acid as soon as you plan to use it (because it collects H2O from air). 1
g of lithium hydroxide hydrate in 200 ml of methanol is prepared. Distill off th
e solvent (methanol) on a low temp steam bath under reduced pressure, or evapora
te under vacuum. The resulting glass-like lithium lysergate residue, is dissolve
d in 400 ml dry dimethylformamide (DMF). 200 ml of this DMF is distilled off wit
h 15 mm pressure through a 12 inch helices-packed fractional column. Cool the re
sulting solution to 0°, and with stirring, quickly add the SO3-DMF solution (50 ml
of 1 M). The mixture is stirred with cooling for 10 min and 125.0 mmol. of the
desired amine is added (that would be 9.05 g of diethylamine). The stirring and
cooling are continued for 10 min after the amine addition, and then the reaction
is decomposed by adding 400 ml of water. After stirring thoroughly the reaction
mixture is treated with a saturated solution of NaCl. Table salt and water are
fine for this if the salt is not iodized. Use 200 ml of the saturated solution o
n the reaction mixture. Extract the amide (LSD) with repeated portions of ethyle
ne dichloride. Test for completeness of extraction with Van Urk test or hold ext
ract under black light briefly and look for fluorescence as compared with non-ex
tracted ethylene dichloride, or use any indole test. The combined extracts are d
ried (with MgSO4 as usual), and then evaporated under vacuo to a syrup. Keep the
temp below at least room temp. Dissolve the residue in about 60 ml of dry metha
nol, acidify with solid maleic acid, treat to turbidity with dry ether, and refr
igerate for 3-6 hours to get colorless soft needles of LSD maleate which are fil
tered from the mother liquor. More crystals may be obtained by evaporating the m
other liquor in a cool, dark place under vacuum.
Things To Remember When Working With Ergot Alkaloids, Lysergic Acid, And LSD
These compounds are very sensitive and even unstable. This means that the follow
ing steps must be taken to keep from ruining your compound or yield.
Always use red or yellow photographic dark room light bulbs during any step of L
SD manufacture. Direct sunlight, electric filament, or fluorescent light bulbs (
etc.) will hurt the above compounds. Dark room bulbs are cheap and are a must.
Keep all forms of H2O out of the reaction. Thoroughly dry all the glass ware to
be used. Use a drying tube filled with anhydrous MgSO4 (calcium chloride reacts
with amines in an unfavorable way and should not be used). I can't be there to h
old your hand and guide you through every step, so unless the formula says to ad
d water, the drying tube should be in use, and after the water addition is over,
the drying tube goes back on. This way the reaction is always protected even if
it does not need to be. Better safe than sorry. Also, if you're not sure if you
should use dry reagents, use dry reagents anyway. Also dry the lysergic acid (a
s described above) and any other precursors in whatever drying process required
for that compound before use. Dry the finished LSD or even any intermediate alon
g the way after you have completed the product. Likewise, dry an intermediate th
at you may have purchased from a chemical supplier.
Keep oxidizing agents from these items. Even the oxygen in the air can oxidize s
ome of these compounds. The formula states that during some of the reactions abo
ve, an inert gas (nitrogen) must be used for an atmosphere inside the reaction v
essel. Nitrogen can be obtained in small bottles (tanks) at a very reasonable fe
e, without any questions asked. Make sure you use a regulator and introduce a sl
ow stream into the vessel by way of a gas inlet tube or an equivalent. Always fl
ush the vessel before putting any reagents into it (flush the air out with nitro
gen). I would use a nitrogen atmosphere from the very beginning of the formula t
o the very end, even if the formula did not specify its use. Very few of the abo
ve formulas call for a nitrogen atmosphere during evaporation, but I feel this m
ay be bad for yield and or potency. LSD has many doses per gram, and if you lose
1/2 g because you were too cheap to use three dollars worth of nitrogen, you ha
ve lost about 2,000 doses at $5 a dose = $10,000 of LSD wasted. Better safe than
sorry? Also, any precursors you make or buy should be stored in a nitrogen atmo
sphere, as should LSD. This can be done by poking a gas inlet tube into the vess
el trust above or a little below the substance) flushing the air out with a mode
rate stream of nitrogen then quickly reinstall the cap or stopper.
The best way to store LSD is by producing it in the maleate form. This not only
makes it resistant to oxidation, but it purifies it, too. Use the procedure abov
e (JOC, 24, 368, or CA, 57, 5979) when you get to the last dry-and-evaporate-in-
vacuo step, then treat the residue as specified.
Never subject these compounds to excessive heat, or any type of temperature warm
er than the inside of your refrigerator. Even LSD maleate will decompose in exce
ss heat, so store in a refrigerator. Keep evaporation procedures cooled. This wi
ll slow the evaporation process down, but that is better than losing the product
. Some of the above formulas require heat for a reaction. This is Ok, but do not
exceed the temp stated at any time and never heat longer than needed. Also, nit
rogen atmospheres are used during heating operation.
Substituents
LSD analogs (lysergic acid amides) can be prepared by substituting amines in pla
ce of diethylamine. The potency usually drops anywhere from 33% to 75% depending
on the substituent. Diethylamine is highly suspicious, and the substituent will
produce a lysergamide that is most likely legal, as legislation has only single
d out lysergic acid diethylamide. Little work has been done on the potency of su
bstituted Iysergamides, so a little experimentation by you may be in order. Pers
onally, I would like to try substituting a potent phenethylamine or phenylisopro
pylamine such as DOM (STP) or 4-bromo-2,5-dimethoxyamphetamine. If I could get a
government grant, or maybe a grant from a major pharmaceutical corporation, lik
e Upjohn or Lilly, then I could play around with such experiments.
The following substituents give lysergamides with potencies as indicated in dose
s per gram (remember that LSD gives about 6,000 to 9,000 doses):
Ethylpropylamine 2,000 to 5,000
Morpholide 600 to 2,000
Methylpropylamine 600 to 1,000
Dipropylamine 600 to 1,000
Methylethylamine 400 to 600
Dimethylamine 300 to 400
Pyrrolidide 300 to 400
As a point of reference, DOM (STP) is one of the most powerful amphetamines, at
200 doses per gram. At $5 a line, its value is about 5 times 200 = $1,000 a gram
. For more info see JMC, 16, 532 (1973).
Claviceps purpurea is not the only place to get d-lysergic amides. The plant gro
up of Convolvulacea has been found to posses lysergic acid amides such as ergine
and several others. These Convolvulacea type of plants do not cause the dreaded
St. Anthony's fire, as does claviceps purpurea, and as a matter of fact, they a
re hallucinogenic if eaten in large doses. Care must be taken that the seeds hav
e not been treated with poison to discourage usage as a mind alterant, or treate
d with methyl mercury to prevent spoilage.
When these seeds are to be used for LSD syntheses, make sure to clean off the wh
ite layer that surrounds them by singeing or mild burning. Also, ask for Hawaiia
n Rose Wood, as these are the only ones that contain an appreciable amount of ly
sergic related compounds. These compounds must be extracted as below, hydrolyzed
(like ergotamine) as above, and then used in any of the formulas that require d
-lysergic acid or possibly used directly in the Hofmann hydrazine method; CA, 57
, 12568 (1962). These seeds have very little amide, so you can plan on quite a l
ot of work in the extraction step. According to A. Hoffer and H. Osmond, the mos
t amide plentiful species (Woodrose) has a minute 3 to 6 mg of amide per every g
ram of seed. This means that if you extract very thoroughly, you will require a
little over 200 g of seeds to get 1 g of amide, which will be reduced further af
ter hydrolysis to give you about 0.5 g of usable d-lysergic acid. Extract as fol
lows.
Pulverize the seeds in a clean blender until they are a fine powder. Put this po
wder into a beaker, add 1 1iter of petroleum ether to every 900 to 1000g of powd
ered seeds, stopper the beaker to prevent evaporation and let set for 3 days. Fi
lter off the petroleum ether and let evaporate to make sure no amides were extra
cted (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. Filte
r 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 fo
r 3 or 4 days.
Filter as before and extract again with about 300 ml of methanol. Combine the re
sidues of all extractions and hydrolyze.