Practical LSD
Manufacture
by Uncle
Fester
Loompanics Unlimited Port
Townsend, Washington
This book is sold for information purposes only. Neither the
author nor the publisher will be held accountable for the use or
misuse of the information contained in this book.
Practical LSD Manufacture
. 1995 by Uncle Fester
All rights reserved. No part of this book may be reproduced or
stored in any form whatsoever without the prior written consent of
the publisher. Reviews may quote brief passages without the
written consent of the publisher as long as proper credit is
given.
Published by:
Loompanics Unlimited
PO Box 1197
Port Townsend, WA 98368
Loompanics Unlimited is a division of Loompanics Enterprises, Inc.
Cover design by Shaun Hayes-Holgate Illustrations by
John Megahan/The Technical Sketch and Kevin Martin
ISBN 1-55950-123-5
Library of Congress Card Catalog 95-75543
Contents
Preface..................................................................................................!
1. LSD Production: An Overview................................................... 1
2. Sources Of The Lysergic Amides.............................................. 5
3.
Extraction And Isolation Of
The Lysergic Acid Amides ................................................15
4.
LSD Directly From The Lysergic Amides —
The One Pot Shot...............................................................23
5. Lysergic Acid ...........................................................................41
6. LSD From Lysergic Acid And SO3..........................................47
7.
LSD From Lysergic Acid And
Trifluoroacetic Anhydride..................................................57
8. LSD From Lysergic Acid And Phosgene ................................61
9. Method X .................................................................................65
10. Solvent Management ...............................................................69
11. Keeping Out Of Trouble..........................................................71
12. Studies On The Production Of TMA-2 ...................................77
Appendix
Know Your Essential Oils ...........................................................97
Precursor And Essential Chemicals.............................................99
Waste Exchanges....................................................................... 101
Distributors................................................................................. 105
Love Letters From The Heat...................................................... 107
A Few Words Concerning Calamus by Cousin
Lester..................................................................... 113
Preface
Preface
The DBA has recently estimated the total number of
clandestine LSD labs operating in the United States at only 100,
with most of them located in northern California. This
alarmingly low number of labs leaves the supply of LSD in this
country at constant peril. Further, the concentration of
production in so few hands has left us awash in a mediocre
swill comparable to the beer spewed out by the major brewers.
This distressing situation results from the convergence of a
series of factors. The botanical sources of lysergic acid are not
easily available in large quantities. The actual production of
LSD from these botanical sources is a touchy and involved
operation. These roadblocks, however, pale in comparison to
the most important factor — the inaccessibility of good
information to those motivated to put it into action.
I can think of no other area of organic chemistry which, to
we common working pot-boilers, is shrouded in as much
mystery, or is as thoroughly obfuscated as the production of
LSD. The scientific articles dealing with this topic are barely
readable by the typical person with an undergraduate degree in
chemistry. They assume a level of understanding of the arcane
Practical LSD Manufacture
field of lysergic chemistry not generally possessed by even
those skilled in the "cooking arts."
The "underground publications" covering this topic have
done little to clean up this situation. They have merely
regurgitated the original unintelligible works until they have
become like mantras, repeatedly chanted and not understood.
It is here that this book shall break new ground. Rather than
presenting this field as a magic act, the sources of lysergic acid
raw materials in nature shall be detailed, and their mystery
removed. The processes required to isolate this raw material
and move it on in pure form to LSD shall be expounded upon.
Common threads shall be drawn between the various
procedures to show what variations in technique are acceptable,
and which produce the disappointing commercial product we
are all too often cursed with.
A special added feature of this book will be the result of my
own investigations into the production of the most wonderful
psychedelic: TMA-2, derived form the roots of the calamus
plant. For those unable or unwilling to wade through the
difficulties that attend cultivating ergot, or growing crops of
morning glories, digging up the roots of this common plant
offers a most convenient and low-profile route to an awe-
inspiring substance. You will be quite pleased, I'm sure.
Fester
7 LSD Production: An
Overview
LSD Production:
An Overview
The synthesis of LSD is not a task to be undertaken lightly by the
novice wannabe drug chemist. It requires a level of skill roughly
double that needed to produce more conventional drugs such as
methamphetamine. A person contemplating this task should be well
trained prior to beginning the attempt, as learning while "on the job" is
likely to lead not only to failure, but also the probable poisoning of the
said wannabe drug chemist.
This fact of life is due to both the nature of the product itself, and
the involved procedures required to convert ergot, morning glory
seeds, or Hawaiian baby woodrose seeds into LSD. The potency of
LSD is truly phenomenal — 10,000 doses per gram — and is easily
absorbed through the skin. This is how Albert Hofmann, the
discoverer of LSD, got his first trip. He was skilled enough that his
boo-boo involved a small enough dose that his brain was not fried.
Beginner chemists tend to get the stuff they are cooking all over
themselves, and would not be so lucky.
Lysergic acid, its precursors, and LSD are all very fragile
molecules, and quite prone to destruction by light, air and heat. The
common makeshift basement lab set-ups used by most clandestine
operators will not do for anyone contemplating LSD synthesis. Real
laboratory equipment is needed, such as a distilling kit with ground
Practical LSD Manufacture
glass joints for doing reactions in, and for distilling home synthesized
reagents to an acceptable degree of purity. A vacuum desiccator is
essential to dry lysergic compounds without burning them. A vacuum
pump rather than an aspirator is the only acceptable source of vacuum
for this desiccator. One must be prepared to spend about $5000 up
front to equip such a lab, but the paybacks are potentially enormous if
one avoids detection. See my Third Edition of Secrets of
Methamphetamine Manufacture for many useful tips on how to obtain
chemicals and equipment, set up shop and move the product without
getting caught. The wise operator will never pass up the opportunity to
use the five-finger-discount method, industry contacts, waste
exchanges and the surplus market to stock his or her lab.
The minimum level of skill I would trust to undertake this task
would be at least a full year of college organic chemistry lab, and a
few biology courses with lab where the use of chromatography was
taught to isolate biological substances from complex mixtures. Sterile
culture technique in these biology classes is a real plus if the plan is to
cultivate ergot in a rye field. Long gone are the days when a guy like
Owsley, with only a little training and a smart wife, could buy pure
ergotamine tartarate and all the other chemicals needed to brew
legendary acids like White Lightning and Orange Sunshine. Today's
operator must be prepared to isolate lysergic acid precursors from
materials like ergot, morning glory seeds, or Hawaiian baby woodrose
seeds. He must also be ready and able to synthesize in pure form
closely watched organic reagents like diethylamine.
There is a constant and unyielding maxim in organic chemistry:
GIGO — garbage in, garbage out. If the materials used in an organic
synthesis are not pure to a reasonable degree, the result is a complex
mixture in which the desired product comprises only a small
proportion. Even a seemingly very simple reaction cannot escape this
law. Case in point is the hydriodic acid and red phosphorus reduction of
ephedrine to methamphetamine. If in this reaction the ephedrine is not
fairly free of the fillers and binders found in the stimulant pills from
which it is extracted, the result at the end of the reaction is a heavy
reduction in the yield of product, and the formation of a most stubborn
emulsion from which the desired meth is extracted only with
LSD Production: An Overview
great difficulty. This is the origin of the revolting peanut butter
consistency of most meth seen on the market. Similarly, one can only
expect success in the production of high-grade LSD if care is taken
throughout the procedure to ensure that the materials used meet the
requirement of a reasonable degree of purity.
The actual synthesis of LSD is an exquisite combination of
farming skills, biology, biochemistry and organic chemistry. In its
preferred embodiment, a scheme for the large-scale manufacture of
LSD would center around someone playing weekend hobby farmer on an
acre or two of land. On this land, our happier-than-most farmer
would plant either rye to be infested with the Claviceps fungus to
produce a crop of ergot; morning glories for the eventual harvest of
their seeds; or, if local weather conditions permit, Hawaiian baby
woodrose, also for the harvest of its seeds.
Mother Nature's bounty is then squirreled off to the lab site for
the biochemical phase of the process — the isolation of the lysergic
alkaloids. Here one or more of a series of alkaloids are freed from the
very complex plant matrix and hopefully isolated in a pure form.
These alkaloids all have one thing in common — they are amides of
lysergic acid. See the structures of the major naturally occurring
amides pictured below:
Practical LSD Manufacture
They all contain the lysergic acid molecule shown below:
The lysergic acid molecule is the key to all known methods of
LSD production. The common thread that all the synthetic routes to
LSD share is that the path they travel starts with the naturally
occurring alkaloids, the amide linkage is lopped off to give lysergic
acid, and then the lysergic acid is reacted with diethylamine to give
LSD shown below:
The nuts and bolts of how this is done will be explained in the
succeeding chapters.
2 Sources Of The Lysergic Amides
2
Sources Of The
Lysergic Amides
Let me begin this chapter by nuking an oft-chanted mantra, this
mantra being the claim that a person can grow ergot fungus in a
culture medium and get it to produce lysergic acid amides to feed into
LSD production. This claim as seen in Psychedelic Chemistry and
other publications I read while in college is pure BS. It is truly
unfortunate that nature does not cooperate in this manner, since this
would obviously be the best way to set up a large-scale production
operation, as the logistical complications of crop growth and harvest
would then be eliminated.
Let me give a science and literature reading lesson to those who
have made these claims. See Proceedings of the Royal Society of
London, Series B, Volume 155, pages 26 to 54 (1961). Also see US
Patent 3,219,545. You will note while reading these articles detailing
how to get lysergic amide production in a culture medium that these
guys had to scour the globe to find that rare strain of claviceps fungus
that will cooperate in this manner. The vast majority of claviceps
fungi just will not produce these alkaloids while being cultured. See
the following articles to convince yourself of just how futile it is to
collect a wild strain of claviceps and try to get it to produce lysergic
acid amides in culture: Ann. Rep. Takeda Res. Lab Volume 10, page 73
(1951); and Farmco, Volume 1, page 1 (1946); also Arch. Pharm. Berl.
Volume 273, page 348 (1935); also American Journal of
Practical LSD Manufacture
Botany, Volume 18, page 50 (1931); also Journal of the American
Pharmacy Association Volume 40, page 434 (1951); also US patent
2,809,920; also Canadian Journal of Microbiology, Volume 3, page
55 (1957), and Volume 4, page 611 (1958) and Volume 6, page 355
(1960); also Journal of the American Pharmacy Society Volume 44,
page 736 (1955).
With this matter disposed of, it is time to move on to what
actually are viable sources of lysergic acid amides for the production of
LSD. This is the farming end of the acid business. It is only through
raising ergot-infested rye, or growing morning glories and Hawaiian
baby woodrose that the required feedstocks of lysergic compounds
can be obtained without making a target of oneself. I have for years
seen ads in High Times offering morning glory seeds and Hawaiian
baby woodrose seeds for sale, but these are offered in small amounts at
high prices. I would bet my bottom dollar that these outfits, if they are
not front operations, will at least report to the heat any large orders they
get. To avoid detection, the aspiring LSD manufacturer must be ready
to get his hands dirty, and spend some time as a farmer.
The most difficult farming choice, and as luck would have it, the
one that gives the purest acid, is to grow a patch of ergot-infested rye.
The reason why ergot is superior to growing morning glory seeds or
woodrose seeds is that these seeds have a considerable amount of
another type of alkaloid in them besides the ones that yield lysergic
acid. These other alkaloids are of the clavine type, meaning that they
have the lysergic-acid skeleton, but lack the carboxyl grouping. In its
place will be a methyl grouping, an alcohol grouping, a methyl
alcohol grouping or combinations of the above. These clavine
alkaloids will likely be carried all the way through into the product,
producing both the GIGO situation during the synthetic operations
and a contaminated product when finished. I will present my ideas on
how to remove them, but they are best avoided in the first place.
Ergot is the name given to a dark brown to purplish black horn-
shaped growth occasionally seen nestled amongst the healthy grains in
the head of the rye plant. It is typically in the neighborhood of 10 to 15
mm long, and can reach diameters of about 5 mm. The ergot
consists of tightly interwoven hyphae of the fungus Claviceps
2 Sources Of The Lysergic Amides
purpurea, and it grows parasitically upon the rye plant. During the
Middle Ages, when ergot infested rye was quite common, great
poisoning epidemics called St. Anthony's Fire or ignis sacer would
break out among the people who ate it. For some reason that escapes
me, they never, over the course of hundreds of years, connected this
most lamentable malady to eating the ergot infesting their rye. The
usual response to an outbreak was to burn a witch or two in the hope
that this display of piety would so please God that they would be
saved.
A most wonderful book has been written on the topic of ergot, and
upon the history of these mass poisoning outbreaks. The book is titled
Ergot and Ergotism by G. Barger, and it is absolute must reading for
anyone seriously contemplating growing ergot. In this book you will
find a series of pictures of ergot growing on rye in the wild, and a
much more detailed presentation of both the chemistry of ergot and its
life cycle than will be given here.
You may well have noticed that outbreaks of ergot poisoning are no
longer commonplace. This is mostly because modem farming
practices such as plowing, crop rotation, drainage of fields and the use of
fungus-resistant seed strains make the present day crop of rye a
much less hospitable place for the ergot to grow in than the sloppily
run dumps that our peasant ancestors presided over. Yet, the
occasional head of ergot is still there to be found in fields of rye, and a
field trip to a patch of rye to gather some ergot is the necessary first
step of purposely growing your own patch of rye just overrun with
ergot. Such field trips are made considerably easier thanks to the fact
that wild ergot on a modern farm will be mostly growing around the
edges of the field. There is no need to run all over the farmer's rye,
and cause him to want to ventilate you for trampling his crop.
When a few dozen heads of wild ergot have been collected, the
stage is set for you to begin growing truly worthwhile crops of ergot
rather than the pitiful scattered kernel or two found on your typical
farm. To get these bountiful yields of ergot, biological skills will be
called upon to get an infestation rate in your own crop of rye that far
exceeds that seen in even the most slovenly days of Dark Ages
serfdom.
Practical LSD Manufacture
To grow ergot successfully, one must have some knowledge of the
life cycle of the Claviceps fungus. The kernel of ergot seen growing
on the rye plant is the form this fungus takes to make it through the
winter. In the wild state, the ergot falls off of the rye plant when the
grain matures, and lays there on top of the dirt until the following
spring. Then, when warm weather returns, the kernel of ergot sprouts
off a bunch of tiny growths that look for all the world like so many
minute mushrooms. In the head of each of these little mushroom
growths are millions of spores. These spores are the fungus equivalent of
seeds.
When the mushroom growths have reached a length of about 20
mm, they are mature, and the head of the mushroom explodes,
sending the millions of spores floating through the air. These spores,
either by luck of air currents or by hitching a ride upon insects, find
their way into the flower of the rye plants growing nearby. The flower of
the rye plant is nothing spectacular. Rye is a grass, and its flowers look
like most other grass flowers — just a filamentaceous dab of color
scattered over the head of the plant which soon grows into seeds.
Upon being deposited into the flower of the rye plant, the spore
germinates and takes over the flower. The fungus then grows by
sucking nutrients out of the rye plant, until a new kernel of ergot has
been formed to repeat the process again next year.
The biological sciences are made to order to take the hit-and-miss
aspect out of the process of rye flower infestation. Instead of the
random action of air currents or insects to bring spores into contact
with their new home, one may germinate these spores in a sterile
culture medium, grow them until they have multiplied a million-fold,
then spray them onto the rye plants just as they are blooming to ensure a
heavy infestation with ergot. This method has been in use since the
1920s with great success in the commercial production of ergot. See
the reference by Hecke (pages 1921-1922) in the back of the Ergot
and Ergotism book mentioned above for complete experimental
details. Yields of ergot using this method average a few hundred
pounds per acre. A couple of acres could supply most of the United
States with high-grade acid.
2 Sources Of The Lysergic Amides
To put this plan into action, the few dozen kernels of ergot are kept
cool and dry during the winter, then as spring approaches they are made
ready to germinate by putting them in the refrigerator for one month to
six weeks with the temperature held steady from just above freezing to
3° C. This will make the ergot think that it has gone through winter, and
works better than actually freezing the stuff. Without this treatment, the
ergot will not germinate to form the mushroom stage of its life cycle.
After our artificial winter has passed for the ergot, we must make it
think that it is at home in the dirt. To do this, a terrarium is thoroughly
cleaned out with bleach water and several rinses. Then a layer of clean
sand about an inch thick is put in the bottom of the terrarium, and the
ergot is sprinkled on top of the sand. Finally, a little more sand is
sprinkled over the top of the ergot until they are each just covered up.
The terrarium is kept at room temperature, with an occasional misting
with water to keep the sand moist but not soaking wet.
After about a month in the terrarium, the ergot begins to sprout. In
the case of ergot, sprout means to grow a bunch of the little mushrooms
mentioned before. They grow towards the light, starting out short and
fat, and becoming increasingly thin as they grow. The heads of these
mushrooms will be covered with what appear to be warts when they are
ripe. Misting with water must be continued during the sprouting of the
ergot to keep it growing.
When the mushrooms sprouting from a particular grain of ergot are
ripe, they should be harvested. The individual grains will not all sprout
or ripen at the same time, so this is a harvest one-grain-at-a-time
operation. The ripe grain is carefully scooped out of the sand with a
spoon, and the sand is then dilute-bleach-water-misted away to leave the
bare grain covered with mushrooms. Care must be taken when handling
the sprouted ergot, as rough handling will cause the ripe heads of the
mushrooms to explode and spew forth their load of spores.
From this point onward, best results are going to be had using
sterile-culture technique. The next objective is to remove the spores
from the heads of the mushrooms growing out of the ergot, and put
Practical LSD Manufacture
them into a sterile culture medium made from diluted malt extract,
where they will grow for a week or so producing a culture broth
loaded with germinated spores which can be sprayed onto the
blooming heads of rye, yielding a heavy infection rate of ergot in your
patch of rye.
I have some helpful observations to share on the matter of home
sterile-culture technique, based upon my own experiences. It has been
my observation that keeping one's cultures free from contamination by
freeloading wild germs is often considerably more difficult in the
kitchen than it is in a biology lab. The typical university lab is
supplied with filtered air from the central heating and air conditioning
unit. The amount of dust particles and animal dander floating in the
air is much smaller than usually seen in the home. This is especially
true if your housekeeping is bad, like mine. The threat from wild
contamination is most severe if you live in a warm, moist area, like the
eastern half of the US in the summer. When doing home cultures, the
sterile transfers should be done in an air-conditioned room with an
effective air filter.
To begin the sterile culture portion of ergot farming, a series of
2000 ml conical flasks are filled about one inch deep with nutrient
broth made by diluting malt extract with 5 volumes of water. Malt
extract is found at stores and outlets catering to the home brewer. It
comes in cans, and is a very thick liquid. Avoid the crystalline version of
malt extract. The tops of the conical flasks are loosely plugged with
cotton, and then sterilized in a pressure cooker at 15 Ibs. pressure for a
little over l/2 hour.
When they have cooled down to room temperature they are moved
into the room in which the sterile transfers will be done. The spores
from the heads of the mushrooms are sterilely transferred into these
flasks for growth. This is done by taking a microscope slide cover slip,
and while holding it with a tweezers, passing the cover slip through
the flame of an alcohol lamp. Then, when the cover slip has cooled
down, it is impregnated with spores by holding the cover slip over the
head of a mushroom with a sterilized tweezer and lancing the
mushroom head with a similarly sterilized needle. Remember that the
heads of these mushrooms are ready to explode when ripe. The spore
2 Sources Of The Lysergic Amides
impregnated cover slip is then dropped into the conical flask, and the
cotton plug replaced. In this manner, a whole series of flasks can be
seeded with Claviceps fungus from a single ergot grain.
The spores germinate shortly after landing in the nutrient broth.
From there they grow into a slimy film floating on the surface of the
broth. The best growth is obtained at a temperature of 25-30° C. This
fungus needs oxygen to grow, but a few days of growth in the 2000 ml
flask will not exhaust the supply there. Longer periods of incubation
would require that some fresh oxygen be supplied to the flasks.
Best results are obtained when the fungus is actively growing
when it is sprayed onto the rye plants. This means that the whole ergot
sprouting and culturing operation must be timed to coincide with the
flowering of the rye plants. In my own state of Wisconsin, the rye
comes into bloom in early to mid-June, depending upon the weather.
The blooming of rye lasts for about a week, so timing is critical. It is
possible to spray a little before the onset of blooming, but spraying too
late is mostly a waste of time.
The spraying is a very simple operation. A metal or plastic hand
pump sprayer with a capacity of about 3 gallons is filled about half
full of water. The contents of one of those conical culture flasks are
then put into the sprayer, and mixed around thoroughly by shaking.
Then more water is added to fill the sprayer, and the solution is then
sprayed onto the crop. This is best done early in the morning, while
dew is still on the plants. The aim should be to get a fairly light
misting over the entire crop. This can be repeated every day for the
week that the rye is in bloom.
From here nature takes over, producing kernels of ergot identical to
the ones harvested the year before. There is general agreement that the
most potent ergot grows during very hot summers. No farmer has
control of the weather, but if there is a choice as to where our ergot
farmer sets up shop, it would then be best to choose a state with very
hot summers, or at least the southward-facing slope of a hill. It is also
generally agreed that the ergot is at its most potent about a week or so
before the rye grain are fully ripe. This is when the rye crop should be
harvested.
Practical LSD Manufacture
The harvesting of the rye (ergot) crop should not be done with a
combine, as these machines pass the grains through a sieve. Most of
the ergot would then be lost, as it is much larger than the rye kernels.
Rather, the rye plants should be cut down using a hand or mechanical
sickle, and they should then be gathered up into shocks as seen in old
time pictures or paintings of grain harvesting. Next, the grains should be
beaten off the rye plants into a container such as a bushel basket. We
are talking about old time farming here! The ergot is then
separated from the rye kernels by dumping the bushel basket full of
grain into a tank full of saturated salt solution in water. The ergot
floats to the top of the salt water, while the rye sinks. The ergot is
skimmed off the top of the water, rinsed, and immediately spread out to
dry in the sun. The ergot must not be allowed to get moldy, as this ruins
its potency.
This procedure is the preferred source for the lysergic acid
amides. It is preferable both to growing morning glory seeds and
Hawaiian baby woodrose seeds because the alkaloid content of the
ergot is about 10 times higher, and also because the ergot has very
small amounts of the clavine alkaloids contaminating it. The case can be
made that the simplicity of the seed growing operations as
compared to growing ergot argues in favor of using that method. My
thoughts on this matter are that ergot is needed for really high quality
acid, and that if a person wants an easy drug to make, he should check
out my recipe for Cat in the third edition of Secrets Of
Methamphetamine Manufacture.
There is an excellent alternative source of ergot for those living
close to the Gulf coast, the Atlantic coast south of New York, and the
Pacific Northwest's Puget Sound. In the saltwater marshes along the
coast, the marsh grass Spartina is subject to a very heavy infestation
with wild ergot. Yields of wild ergot in the range of 150 pounds per
acre are pretty common in areas that have been disturbed, such as by
ditches or in "spoil areas." (See Mycologia, Volume 66, pages 978 to
986 (1974) for full details and pictures.) Harvesting the ergot in this
case would probably be best done in a manner similar to that used by
Native Americans to harvest wild rice. They simply travel through the
2 Sources Of The Lysergic Amides
13
grass in a shallow-draft rowboat, bend the heads of grain into their
boats, and beat it off with a stick.
If the choice is made to fuel LSD production using morning glory
seeds, one should be aware that not all varieties are created equal.
Some types of morning glories contain little or no ergot alkaloids. The
best varieties to choose are Heavenly Blues, Pearly Gates or Flying
Saucers. The only growing tips I have to share are to give the plants a
moderate dose of nitrogen fertilizer when they are young to encourage
heavy growth, then switch to organic fertilizers so as not to mess up
the plant's hormonal balance during flowering and seed production.
There have been recent reports of a wholly new source of lysergic
acid amides. The so called Sleepy Grass (Stipa robusta) of the desert
areas of the American West is reported to have an alkaloid content
approaching that of ergot, and should be a good source of raw
material to feed into acid production. See Discover magazine, Dec.
92.
Additional Reading On Growing Ergot:
Gulf Res. Rep. 3(1), pages 105-109 (1970), "Observations on
Claviceps purpurea on Spartina alterflora." Canadian Journal of
Botany Vol. 35, pages 315-320 (1957), "Studies
on Ergot in Gramineous Hosts." Pharmacognosy (1965), pages 321
327. Agricultural Gazette of New South Wales Vol. 52, pages 571581
(1941), "Artificial Production of Ergot." Pythopathology Volume
35, pages 353-360 (1945), "The Field
Inoculation of Rye With Claviceps purpurea." American Journal of
Botany Volume 18, pages 50-78 (1931), "The
Reactions of Claviceps purpurea to Variations in Environment."
3
Extraction And Isolation Of
The Lysergic Acid Amides
15
3
Extraction And Isolation Of
Lysergic Acid Amides
After the harvest of the crops, the farming phase of acid
production is now over. This is a good news/bad news situation for
the acid chemist. The good news is that the voluminous pile of crop
will in short order be reduced in size to a quantity more conveniently
handled in the lab. For example, ergot typically contains from V* to
￥2% alkaloids by weight. A 200 pound harvest of ergot will, after
extraction, yield Vi to a full pound of lysergic acid amides. This
quantity is worth several millions of dollars if moved wholesale at a
dollar per dose. The yield from a similar amount of morning glory
seeds will be reduced by a factor of about 5, but still be substantial.
Hawaiian baby woodrose seeds are intermediate between the two.
The bad news takes several forms. A significant amount of
solvents will be needed to perform the extraction from the crop. It is at
this juncture that the acid chemist will need to employ industrial
contacts, theft, or the formation of a front operation to get the several
55-gallon drums of solvents needed to execute the extraction. The
aroma that solvents give off also precludes doing this procedure in a
residential neighborhood. A shed back on the farm site or a business
front setting is much more suitable.
It is also at this phase that the delicate natures of the lysergic
molecules express themselves. While they are locked up in ergot or in
seeds, these molecules are pretty stable, so long as the crop is kept
Practical LSD Manufacture
cool, dry, and free from mold. Once they are released, they are prey to
light, heat, air, and bad chemical handling. A clock begins to tick on
the shelf life of your product. Once the extraction is begun, the
chemist must consider himself committed to the task, and not allow
himself to be distracted by other matters while the product spoils.
There are several alternate procedures for the extraction of the
amides from ergot. They all produce roughly similar results. This is
fortunate, as it allows the acid chemist to choose the materials used
based upon availability rather than being rigidly locked into using a
certain set of materials.
The first step in the extraction procedure, regardless of whether
ergot or seeds are being extracted, is a thorough grinding. A blender is
suitable for this job, and a coffee grinder may work as well if it gives a
fine grind. Once the crop has been ground up, it is immediately
vulnerable to attack by light and air, so as soon as it is ground it
should be wetted with the solvent chosen for use in the next step:
defatting.
Defatting is a very important step in the isolation of pure alkaloid.
The fats and oils present in the crop must be removed because if they
were left in, a tenacious emulsion would form during the extraction of
the alkaloid, and you could forget about ever getting even close to a
pure amide extract. For all practical purposes, all that would be
extracted would be garbage.
Defatting can be done with any one of several very common and
easily available solvents. For a 200 pound crop, one can count on
using at least one, and possibly two 55 gallon drums of solvent. The
defatting can be done with either hexane, petroleum ether (not ethyl
ether) mineral spirits or naphtha. The preferred procedure for small
scale extractions is to put the ground-up, solvent-soaked crop into a
burette, and then keep dripping fresh solvent onto the top of the
material until the solvent coming out at the bottom of the burette does
not leave a grease stain on filter paper when the solvent dries. This is
easily scaled up for our 200 pound crop by replacing the burette with
clean pipes about 4 inches in diameter, and about 4 feet long, with
suitable valves and filters at the bottom to prevent everything from
falling out. (See Figure 1). When all the fats have been removed from
3
Extraction And Isolation Of
The Lysergic Acid Amides
17
the crop, the best procedure is to
evaporate the remaining defatting
Cotton
solvent from the crop under a
vacuum. This is not practical for
a large crop, so letting the
Crop
remainder drip out of the bed
over a period of a few hours is
called for.
With the fats removed, the
Cotton over filter paper
ergot alkaloids can be extracted
Threaded cap and valve
from the crop. Note here the
word alkaloid. This is the key to
all variations of the extraction Note use of copper brass or bronze
not allowed on any part'
procedure. There is a piperidine
nitrogen atom in the lysergic
Figure 1 Apparatus
portion of
for large-scale defatting
these molecules that possesses
basic properties similar to ammonia and amines. This atom allows
the lysergic molecules to form salts with acids, and also causes the
solubility characteristics of the molecule to change depending upon
whether the molecule is in acid or basic solution. It further allows the
lysergic amides, including LSD, to form crystals from solution.
The lysergic amides as found in our crop are tied up in the plant
material in association with acidic substances. To get the amides to
extract out in a solvent, this salt must be free-based. There are two
preferred solvent and basing agent combinations. Choice number one is
used in the USP procedure. This combination is ammonia as the
free-basing agent in a solvent of chloroform. The other preferred
combination was used extensively in Europe. This combination used
MgO (magnesia) as the basing agent with a solvent of ethyl ether or
benzene. There have been comparisons of the two methods, and the
European variation gives an extraction that is about 25% more
complete than the USP method. It is, however, not nearly as practical
Practical LSD Manufacture
as the USP method for large-scale extractions because it would be
necessary to dump the crop out of the extraction pipes, and then grind
the solid MgO into an intimate mixture with the crop prior to
extraction with ether. The USP method allows the much simpler
procedure that follows:
The extraction solvent is made up by adding one-tenth gallon
strong ammonia (28% NH3OH; 56% NHtOH) to nine-tenths gallon
methanol. After mixing, this is added to nine gallons of chloroform to
give 10 gallons of extraction solvent. The use of methanol is
necessary because without it the ammonia does not mix into the
chloroform. Instead, it would float on top of the chloroform giving an
unhomogenous mixture.
The extraction is done by trickling this extraction solvent into the
top of the bed of crop, allowing it to flow downward through the crop,
and collecting the extract as it flows out the bottom of the pipe. This
extract must be protected from light to prevent its destruction. The
extraction of a 200 pound crop requires about 150 gallons of solvent.
One can monitor the extraction by catching a little bit of the solvent
coming out the bottom of the pipes in a watch glass, and shining a
black light upon it in a darkened room. The lysergic amides in the
crop fluoresce a bluish color. When this color no longer appears in the
extract, the extraction is complete.
Next, the approximately 150 gallons of solvent must be
evaporated down to a more convenient amount. If one's crop was not so
bountiful as 200 pounds, this is a lot simpler, and can be done in
laboratory glassware. For a large crop, a more industrial approach
must be taken. The two main precautions to prevent damage to the
product are the same in either case. The evaporation must be done
with a vacuum, so that the product is not exposed to heating above 40°C
(105° F), and the product must not be exposed to light.
To evaporate the large industrial quantity of solvent, a 55-gallon
steel drum is filled about two-thirds full of the extraction solvent. On
the top of the drum are two threaded openings. Opening number one is
secured with the original bung. The other opening is tightly stuffed with
a rubber stopper. This rubber stopper has a hole drilled in it, and a
section of pipe is put through the hole in the stopper so that it
3
Extraction And Isolation Of
The Lysergic Acid Amides
19
extends about an inch below the stopper. To this pipe, a line of
vacuum tubing is attached, leading to a vacuum pump. This pump
should be the typical shop pump that can pull a vacuum of about 21
inches of mercury out of the possible 30 inches. This is enough to
greatly speed the evaporation without causing the chloroform to boil.
Boiling may raise a head of foam that would carry product along with it,
causing great losses.
On a laboratory scale, a stronger vacuum can be used from an
aspirator. By using red or yellow darkroom light bulbs for
illumination, damage to the product can be kept to a minimum. The
stronger vacuum speeds up the process quite a bit. Use boiling chips to
prevent bumping.
As the chloroform evaporates away, more of the extraction solvent
may be added to either the 55-gallon drum or the distilling flask,
depending upon the scale of production. The evaporation is continued
until the extraction solvent has been reduced to one-fifteenth its
original volume. For the 200-pound crop, the 150 gallons of extraction
solvent has been reduced to 10 gallons.
An accessory which may speed up and smooth out this
evaporation is a capillary air bubbler. This is made by taking a section of
glass tubing, and poking it through a rubber stopper. The end of the
glass tubing is then heated to redness in a flame, and pulled into a
very fine capillary. The tubing is then stuck into the solution being
evaporated, extending nearly to the bottom. The vacuum will pull a
fine stream of air bubbles through the solution and aid evaporation.
When the chloroform has been reduced to one-fifteenth of its
original volume, it must be diluted with ether. The reason for this is
that the next step is extraction of the ergot alkaloids into a tartaric-acid
solution, and it has been found that this is very difficult from pure
chloroform. When the solution is predominantly ether, the transfer of
the alkaloids into the tartaric-acid solution can be done efficiently. For
the drum-sized batch, add 30 gallons of ether and two gallons of
alcohol. Similarly, for smaller batches add three volumes of ether and a
little alcohol.
At this point, an important matter must be addressed. This matter is
central snoopervision of chemical transactions. Note the "Love
Practical LSD Manufacture
Letters From The Heat" section at the end of this book concerning the
Chemical Diversion Trafficking Act of 1988, and its amendments
since then. This federal law requires chemical dealers to "identify
their customers, maintain retrievable records, and report suspicious
transactions" for a list of chemicals compiled at the end of this book.
Ether is on the mandatory snitch list in amounts above 25 gallons, and
you can take it to the bank that regular chemical outlets will be
following the letter of the law. You can also bet that connections met
through the waste exchanges are mostly concerned with getting the
stuff off their hands, not kissing up to the DBA. The serious
experimenter may wish to try substituting benzene for ether, since it is
not now on the mandatory snitch list.
The alkaloids are next extracted out of the ether solution into
decimolar (15 grams per liter) tartaric acid in water. The alkaloids
form a salt with the tartaric acid that is soluble in water, and leave the
extraneous plant compounds in the ether. This extraction should be
done four times with a volume of tartaric-acid solution that is one-
seventh the volume of the ether solution. For example, with about 40
gallons of ether solution in a drum, extract with about 6 gallons of
tartaric acid solution four times. This means a fresh six gallons on
each extraction. If a stubborn emulsion forms, the addition of a little
alcohol to the mix will break it.
Tartaric acid is the preferred acid for this extraction because the
tartaric acid salt of the alkaloids is relatively stable in light. A .2N
solution of sulfuric acid can be used instead if precautions are taken to
protect the solution from exposure to light. This method may be
preferable because it has become a hassle to buy tartaric acid.
Recently, at my place of work, I had occasion to order one pound of
Rochelle salts (potassium sodium tartarate) from a major chemical
supplier. This material was for use in a laboratory scale cyanide
copper plating bath, where the Rochelle salt acts as a complexor. To
get them to sell me this material, I had to answer a battery of
questions, in spite of the fact that the firm at which I work has had a
long customer relationship with this major chemical supplier. Less
scrutiny of tartaric acid purchases would likely be encountered from a
firm which supplies chemicals to the plating industry. To get tartaric
3
Extraction And Isolation Of
The Lysergic Acid Amides
21
acid from Rochelle salts, just dissolve them in water, and then add
hydrochloric acid until the pH of the decimolar solution reaches 2.
The tartaric-acid solution containing the alkaloids should now be
free-based, preferably with ammonia. The ammonia should be added
slowly with vigorous stirring until the pH of the solution reaches 8 to
8.5. A higher pH must be avoided, since at these pHs racemization to
the inactive iso form of lysergic occurs.
The free-based alkaloids can now be extracted out of the water
solution into ether. The extraction should be done four times, each
time with a volume of ether 1A that of the water solution. The
combined ether extracts should be dried over some magnesium sulfate
previously wetted with ether to prevent it from absorbing alkaloid
during the drying process.
Finally, the ether is evaporated away under a vacuum to yield a
residue of fairly pure alkaloids. The alkaloids in this form are very
fragile, and must be immediately transferred to a freezer for storage.
4
LSD Directly From The Lysergic Amides —
The One Pot Shot
23
4
LSD Directly From The
Lysergic Amides
— The One-Pot Shot
When the lysergic amides have been extracted in pure form from
the crop, work should begin without delay to convert it to LSD.
Diligence in this matter is very important because possession of the
extracted amides is strong evidence of intent to manufacture LSD.
Further, mere possession of lysergic acid or ergine is prohibited as
they are federal "controlled substances." The goal must be to get the
hot potato out of one's hands and convert it to cash as fast as possible.
There are several possible methods to follow in the conversion of
the lysergic amides to LSD. The first two presented in this book are
excellent, and highly recommended. The third one is OK. Beyond
that, we are talking last resort. In all cases, the overriding factor which
must take precedence is ease of availability of the required chemicals. A
bottle of trifluoroacetic anhydride in hand beats homemade
anhydrous hydrazine in the bush.
The first LSD manufacture method presented here is what I like to
call "the one-pot shot." It can be found in US patent 3,239,530 and
US patent 3,085,092, both granted to Albert Hofmann. This method
uses anhydrous hydrazine to cleave the ergot amides to produce
lysergic acid hydrazide. The hydrazide is then isolated by extraction,
Practical LSD Manufacture
and reacted with acetylacetone (2,4-pentanedione) to form a pyrazole
intermediate, which is then reacted with diethylamine to form LSD.
This method at first glance seems complicated, but the actual
manipulations involved here are less challenging than proceeding
through lysergic acid. Further, the yields are higher with this method
than those proceeding through lysergic acid, and there is less
formation of the inactive iso-LSD than with other methods. Iso-LSD is
not a complete loss since it can be converted to the active LSD, but it is
best to avoid its formation in the first place.
This method has a serious drawback. Anhydrous hydrazine is not
available off the shelf at your local hardware store, and attempts to
procure it through normal channels are likely to catch the attention of
those shit-eating dogs at the DBA. I include in this chapter directions for
making your own anhydrous hydrazine, but be warned here that
failure to use a nitrogen atmosphere during the distillation of
anhydrous hydrazine will likely lead to an explosion. On that cheery
note, let's begin!
Step One:
Conversion of Ergot Amides
to Lysergic Acid Hvdrazide
The reaction above is illustrated for ergotamine, but the process is
just as valid when a mixture of amides is used as extracted from the
4
LSD Directly From The Lysergic Amides —
The One Pot Shot
25
crop. Further, the crop amides have been left in the freebase form, so
the procedure given in example 5 in US patent 3,239,530 is used. This is
superior to trying to make a hydrochloride salt of the amides, as
suggested in example 1, because this would expose the active
ingredients to loss and destruction during the unnecessary handling.
There are three main precautions to be followed while executing
this procedure. Water must be rigorously excluded from the reaction
mixture, as hydrazine hydrate will react with the amides to form
racemic lysergic acid hydrazide rather than our desired product. To
ensure the exclusion of water from the reaction, the glassware should be
baked in an electric oven prior to use, and be allowed to cool off in a
dessicator. A drying tube should be attached to the top of the
condenser used, to prevent humidity in the air from getting in the mix.
Naturally, the hydrazine used had better be anhydrous.
Another danger to success is exposure to light. Work should be
done under a dim red darkroom bulb. The flask containing the
reaction mixture should be wrapped in aluminum foil to exclude light.
Procedures such as extractions and filtering should be done as rapidly as
possible without causing spills.
Finally, this reaction should be done under a nitrogen atmosphere,
as hot hydrazine and oxygen do not get along too well.
In a 500 ml round-bottom flask place a magnetic stirring bar, 10
grams of the ergot amide mixture (dried in a vacuum dessicator to
ensure its freedom from water), 50 ml of anhydrous hydrazine, and 10 ml
of glacial acetic acid. A condenser equipped with a drying tube is then
attached to the flask, and the flask wrapped in a single layer of
aluminum foil. The flask is then lowered into a glass dish containing
cooking oil heated to 140° C on a magnetic-stirrer hot-plate. When the
flask goes into the oil, the heat should be backed off on the hot-plate so
that both oil and flask meet each other in the middle at 120° C.
Monitor the warming of the contents of the flask by occasional
insertion of a thermometer. Stir at moderate speed. In about 10
minutes, the desired temperature range is reached, and some gentle
boiling begins. Maintain the temperature of the oil bath at 120-125° C,
and heat the batch for 30 minutes.
Practical LSD Manufacture
When 30 minutes heating at 120° C is complete, add 200 ml
water to the batch, increase the oil temperature to 140° C, and rig the
glassware for simple distillation. Distill off between 200 to 250 ml
water, hydrazine hydrate and acetic acid mixture. Then remove the
flask from the heated oil, and allow it to cool. Use of an aspirator
vacuum to assist the distillation is highly recommended.
When the flask has cooled, add 100 ml of decimolar tartaric-acid
solution (1.5 grams tartaric acid in 100 ml water) to the flask, and 100
ml ether. Stopper the flask, and shake vigorously for a few minutes,
with frequent breaks to vent off built-up pressure from the flask. If the
stirring bar bangs too violently in the flask, remove it with a magnet
rather than break the flask.
Pour the contents of the flask into a 250 ml sep funnel, and drain
the lower layer (water solution of lysergic acid hydrazide tartarate)
into a 250 ml Erlenmeyer flask wrapped in foil. To the ether layer still in
the sep funnel, add 50 ml fresh decimolar tartaric-acid solution, and
shake. Examine the water layer for the presence of lysergic acid
hydrazide with a black light. If there is a significant amount, add this
also to the Erlenmeyer flask.
Place the magnetic stirring bar in the Erlenmeyer flask, and stir it
moderately. Monitor the pH of the solution with a properly calibrated
pH meter, and slowly add .5M (20 grams per liter) sodium hydroxide
solution until the pH has risen to the range of 8-8.5. Higher pH will
cause racemization. The freebase is then extracted from the water
solution with chloroform. Two extractions with 100 ml of chloroform
should complete the extraction, but check a third extraction with the
black light to ensure that most all of the product lysergic acid
hydrazide has been extracted.
The chloroform extracts should be evaporated under a vacuum in a
500 ml flask to yield the product. This is best done by rigging the 500
ml flask for simple distillation, and applying an aspirator vacuum to
remove the chloroform. Assume that the yield from this procedure will
be about 5 grams of lysergic acid hydrazide if ergot was the crop used.
Assume that the yield will be about 7.5 grams if seeds were used.
The difference here is due to the fact that in ergot, the amides
4
LSD Directly From The Lysergic Amides —
The One Pot Shot
27
are largely composed of substances in which the portion lopped off is
about as large as the lysergic acid molecule. Seeds tend to be more
conservative as to their building upon the lysergic molecule. A careful
weighing on a sensitive scale comparing the weight of the flask before
and after would give a more exact number.
Both of these choices are really very poor, because lysergic acid
hydrazide, unlike most other lysergic compounds, crystallizes very
well with negligible loss of product. At the hydrazide stage of LSD
manufacture, one has a perfect opportunity to get an exceedingly pure
product, freed from clavine alkaloids and other garbage compounds
carried in from the extraction of the complex plant material.
I refer the reader to US patent 2,090,429 issued to Albert
Hofmann and Arthur Stoll, the dynamic duo of lysergic chemistry,
dealing with lysergic acid hydrazide. In this patent, they describe in a
rather excited state how they were able to produce pure lysergic acid
hydrazide from tank scrapings that were otherwise impure junk.
Lysergic acid hydrazide has the following properties: it dissolves
easily in acid, but is very difficultly soluble in water, ether, benzene
and chloroform. In hot absolute ethanol it is slightly soluble, and is
crystallizable in this solvent to yield "beautiful, compact, clear, on six-
sided cut-crystal plates that melt with decomposition at 235-240° C."
This is obviously the way to go. The hydrazide should be
recrystallized from absolute ethanol, and then dried under a vacuum to
remove residual alcohol clinging to the crystals. About 300 ml of hot
ethanol is required to dissolve each gram of lysergic acid hydrazide
during the crystallization. Upon cooling, a first crop of pure lysergic
acid hydrazide is obtained. Then, by boiling away half of the mother
liquor and cooling, an additional crop is obtained. This process can be
continued as long as the crystals obtained look nice.
Practical LSD Manufacture
Step Two: Lysergic Acid
Pyrazole
In this reaction, one mole of lysergic acid hydrazide is dissolved in
an inert, water-miscible solvent like ethanol. Then an excess of 1-molar
hydrochloric acid is added to form a salt with the lysergic acid
hydrazide. To this mixture is then added two moles of acetylacetone
(2,4-pentanedione), which forms the desired pyrazole. This reaction is
not nearly as touchy as the formation of the hydrazide. The presence of
traces of moisture from the air poses no problem. 2,4-pentanedione finds
use in analytical chemistry as a chelating agent for transition metals,
and as such should be available without raising too many red flags.
Synthesis of this compound is not hard, and directions for doing so are
found in US Patents 2,737,528 and 2,834,811.
To do the reaction, the flask containing the 5 grams of hydrazide is
wrapped in a single layer of foil to exclude light. Then a magnetic
stirring bar is added, along with 18 ml of ethanol, 18 ml water, 20 ml 1molar
HC1 (made by adding one part 37% HC1 to 11 parts water) and
this mixture is stirred for a few minutes. Then 3.5 grams (3.5 ml) of
2,4-pentanedione is added at room temperature, and the stirring
continued for an hour or so.
The product is recovered from solution by the slow addition with
stirring of 20 ml 1-molar NaOH (40 grams per liter). This
neutralization throws the pyrazole out of solution as a solid. The solid is
collected by filtration through a Buchner funnel, and rinsed off with
LSD Directly From The Lysergic Amides —
The One Pot Shot 29
some water. The crystals are then dried under a vacuum, preferably
with the temperature elevated to 60° C. Further purification can be
done by crystallization. If so desired, dissolve the crystals in
chloroform, then add 8-10 volumes of ether to precipitate the product. I
do not feel this is necessary if the hydrazide used was reasonably
pure, since all the reagents used in the last step are soluble in water.
The water rinse should have carried them away. Further, alcohol and
2,4-pentanedione are volatile, and would be removed in the vacuum
drying.
Step Three:
LSD
CH,
This simple and easy reaction is done as follows: In a flask
wrapped in a single layer of foil are placed 1 gram lysergic acid
pyrazole, and 30 ml diethylamine. Diethylamine is a definite "do not
purchase" item. Easy directions for its synthesis are given in this
chapter. The two ingredients are swirled until mixed, then allowed to
stand at room temperature for about a day.
The excess diethylamine is then distilled off, and saved for use in
future batches. Dimethylpyrazole is a high-boiling-point substance,
and easily separated from diethylamine. When most of the
diethylamine has been distilled off, a vacuum is applied, and the
residue is evaporated to dryness. The evaporation is completed by
Practical LSD Manufacture
warming the flask in boiling water for a few minutes with continued
application of vacuum. The residue is almost pure LSD.
Purification and Storage
At this point, the process has yielded LSD freebase. In this state,
the substance is quite unstable and not suitable for storage. A
judgment as to the purity of the product is therefore needed in quick
order, because which method of further processing to use is dependent
upon the purity of the product. If there is reason to believe that a
significant amount of iso-LSD is mixed in with the product, the
following chromatographic separation is called for. The iso-LSD can
then be recovered and converted to the active LSD, which greatly
increases the value of the product. Iso-LSD can be expected to be
formed using the process in this chapter if the additions of sodium
hydroxide were not sufficiently slow, and local areas of high pH
developed in the solution. Using methods in other chapters proceeding
through lysergic acid, a large amount of the iso product can be
expected if lysergic acid was made by use of hydrazine hydrate or HOH.
Also, some of the natural alkaloids are of the iso form and yield iso-
LSD. The procedure for acid production using trifluoroacetic anhydride
will always make a lot of the iso product. The best procedure I can
recommend is: whatever method has been used, check the product
through chromatography for the presence of the iso-LSD. The following
procedure is taken from US patent 2,736,728.
3.5 grams of LSD freebase is dissolved in 160 ml of a 3-1 mixture of
benzene and chloroform (120 ml benzene, 40 ml chloroform).
Next, a chromatography column is constructed from a burette. It must
hold about 240 grams of basic alumina (not acidic alumina), so a 100
ml burette is called for. A wad of cotton and filter paper is stuffed
down the burette against the stopcock to keep the particles of alumina
from flowing out. The 240 grams of basic alumina are then poured
into the burette with tapping to assure it is well packed. The alumina
should then be wetted with some 3-1 benzene-chloroform.
LSD Directly From The Lysergic Amides —
The One Pot Shot 31
Now the 160 ml of benzene-chloroform containing the LSD is run
slowly into the burette, followed by more benzene-chloroform to
develop the chromatogram. As the mixture flows downward through
the alumina, two zones that fluoresce blue can be spotted by
illumination with a black light. The faster-moving zone contains LSD,
while the slower-moving zone is iso-LSD.
When the zone containing LSD reaches the spigot of the burette, it
should be collected in a separate flask. About 3000 ml of the 3-1
benzene-chloroform is required to get the LSD moved down the
chromatography column, and finally eluted.
The iso-LSD is then flushed from the column by switching the
solvent being fed into the top of the column to chloroform. This
material is collected in a separate flask, and the solvent removed
under a vacuum. The residue is iso-LSD, and should be stored in the
freezer until conversion to LSD is undertaken. Directions for this are
also given in this chapter.
For the fraction containing the LSD, conversion to LSD tartrate
must be done to make it water soluble, improve its keeping
characteristics, and to allow crystallization. Tartaric acid has the
ability to react with two molecules of LSD. Use, then, of a 50% excess of
tartaric acid dictates the use of about 1 gram of tartaric acid to 3
grams of LSD. The three grams of LSD would be expected from a
well-done batch out of a total 3.5 LSD/iso-LSD mix.
The crystalline tartrate is made by dissolving one gram of tartaric
acid in a few mis of methanol, and adding this acid solution to the
benzene-chloroform elute from the chromatography column.
Evaporation of the solvent to a low volume under a vacuum gives
crystalline LSD tartrate. Crystals are often difficult to obtain. Instead,
an oil may result due to the presence of impurities. This is not cause
for alarm; the oil is still likely 90%+ pure. It should be bottled up in
dark glass, preferably under a nitrogen atmosphere, and kept in a
freezer until moved.
If chromatography reveals that one's chosen cooking method
produces little of the iso products, then the production of the tartrate
salt and crystallization is simplified. The residue obtained at the end
Practical LSD Manufacture
of the batch is dissolved in a minimum amount of methanol. To this is
then added tartaric acid. The same amount is added as above: one gram
tartaric acid to three grams LSD. Next, ether is slowly added with
vigorous stirring until a precipitate begins to form. The stoppered flask is
then put in the freezer overnight to complete the precipitation. After
filtering or centrifuging to isolate the product, it is transferred to a dark
bottle, preferably under nitrogen, and kept in the freezer until moved.
LSD from (so-LSD
Two variations on this procedure will be presented here. The first is
the method of Smith and Timmis from The Journal of the
Chemistry Society Volume 139, H pages 1168-1169 (1936). The other is
found in US patent 2,736,728. Both use the action of a strong
hydroxide solution to convert iso material into a mixture that contains
active and iso material. At equilibrium, the mixture contains about 2/3
active material and 1/3 iso material. These substances are separated by
chromatography, and the iso material saved to be added to the batch
the next time isomerization is done. In this way, eventually all of the
product becomes active material.
Method One
The iso-LSD as eluted from the chromatography column is first
evaporated under a vacuum to remove the solvent. The residue is then
dissolved in 1-molar alcoholic KOH, and boiled under reflux,
preferably with a nitrogen atmosphere, for 30 minutes.
The mixture is next cooled and diluted with 3 volumes of water. It is
next acidified with HC1, then made alkaline again with sodium
carbonate. The product is now extracted from solution with ether or
chloroform. After removal of the solvent, the product can be chromatographed
as previously described.
LSD Directly From The Lysergic Amides —
The One Pot Shot 33
Method Two
The iso-LSD as eluted from the chromatography is first
evaporated under a vacuum to remove the solvent. The residue is
dissolved in the minimum amount of alcohol, and then one half
volume of 4-molar KOH in 100 proof vodka is added. The mixture is
allowed to sit at room temperature for a couple of hours, then the
alkali is neutralized by adding dry ice. The solvents are next removed
under a vacuum, and the residue chromatographed as previously
described.
Preparation of Anhydrous Hydrazine
Anhydrous hydrazine can be made from the easily available raw
materials: bleach, ammonia, sulfuric acid and potassium hydroxide.
This is not a task to be undertaken lightly, as there are dangers
inherent in the process. Hydrazine will likely detonate during
distillation if the distillation is not done in a nitrogen atmosphere.
Also, hydrazine is a vicious poison prone to absorption through the
skin or by inhalation of its vapors. It is very corrosive to living tissue,
and its burning effects may be delayed. Hydrazine can also be
assumed to be a carcinogen. All steps in its preparation must be done
with proper ventilation, and protection of the body from spills.
Step One: Hydrazine Sulfate
2NH3
+ NaOCI ——> NH2 NH2 + H2O + NaCI NH2NH2
+ H2S04 ——> NH2NH2H2S04
Into a 3-quart-capacity glass baking dish (Pyrex) put 750 ml
strong ammonia (28% NH3), 350 ml distilled water, 190 ml 10%
gelatine solution, and 700 ml 12.5% bleach. This strength of bleach is
Practical LSD Manufacture
available from pool supply companies and makers of cleaners. The
5.25% strength Clorox will not do here. One must also be aware that
traces of iron and copper have a very bad effect upon the yield, so do
not dispense with the use of distilled water. The bleach is another
possible source of iron. In checking out this reaction, the Pro
Chemicals brand of bleach worked fine. I can't vouch for other
brands. If all else fails, the bleach can be made from chlorine and
NaOH in distilled water. (See Organic Syntheses Collective Volume 1,
page 309.) The Pro Chemicals brand of bleach analyzed at 10 ppm iron
by atomic absorption, and this amount did not interfere with the
reaction. One must also check the bleach to make sure it is alkaline, as
free chlorine prevents the formation of hydrazine.
When the ingredients have been mixed in the baking dish, it is
heated as rapidly as possible until it has been boiled down to one-third of
its original volume. Being a wimp and boiling it down too slowly
reduces the yield. Take not more than two hours.
The dish is then removed from the heat, and allowed to cool.
When the dish nears room temperature, it should be nestled in ice to
chill thoroughly. The solution should then be filtered to remove
suspended particles from the solution.
The filtered solution is next put in a beaker, and nestled in ice
°
mixed with salt until the temperature of the solution reaches 0 C.
When that temperature is reached, 10 ml of concentrated sulfuric acid
for each 100 ml of solution is slowly added with constant stirring. If
the stirring is not strong, or if the filtering was poorly done, a product
contaminated with brown particles results. If done well, hydrazine
sulfate precipitates as white crystals. The mixture is allowed to stand in
the cold for a few hours to complete the precipitation. The crystals are
then filtered by suction, and the crystals rinsed off with cold
alcohol. The yield is 25 to 30 grams of hydrazine sulfate.
LSD Directly From The Lysergic Amides —
The One Pot Shot 35
Step Two:
Hydrazine Hydrate
Mix 100 grams dry hydrazine sulfate with 100 grams powdered
KOH and place the mixture into a copper and silver retort. Then add 15
ml water, and distill off the hydrazine hydrate formed though a
downward-inclined glass condenser. There is little need for heat to be
applied at the beginning of the distillation because so much heat is
generated in the reaction between the KOH and the sulfate. Later,
strong heating is required to distill out the last of the hydrazine
hydrate.
This crude product contains water beyond the monohydration of
hydrazine. It is purified by fractional distillation. Pure hydrazine
hydrate boils at 117° C to 119° C. The forerun contains the excess
water. It should be converted back to hydrazine sulfate by addition of
sulfuric acid as done in step one. The yield is 10 grams of hydrazine
hydrate.
During the fractional distillation, there are some precautions
which should be followed. Hydrazine hydrate attacks rubber and cork,
so the use of these materials must be avoided in the distillation. It also
attacks most kinds of stopcock grease. The distillation is most safely
done under nitrogen. Nitrogen should be introduced into the distilling
flask, and the system flushed of air for about 15 minutes. Then the
rate of nitrogen flow is reduced, and distillation commenced. The
product will also attack glass, albeit slowly. It should be stored in 304 or
347 stainless steel. 316 stainless is not acceptable.
Step Three:
Anhydrous Hydrazine
100 grams (100 ml) of hydrazine hydrate is mixed with 140 grams
powdered sodium hydroxide. The apparatus is thoroughly flushed
with nitrogen, then the rate of nitrogen addition to the distilling flask
Practical LSD Manufacture
is slowed, and fractional distillation is commenced through an
efficient fractionating column of about 15 theoretical plates.
Anhydrous hydrazine distills at 112° C to 114° C. Anhydrous
hydrazine is obtained at 99%+ purity.
Another method for producing anhydrous hydrazine exists which
gives a higher yield of product, but it uses anhydrous ammonia and
more complicated glassware and procedures. See Journal of the
American Chemical Society Volume 73, page 1619 (1951), and
Volume 76, page 3914 (1954). Also see Hydrazine by C.C. Clark, The
Chemistry of Hydrazine by L.F. Audrieth, and Industrial and
Engineering Chemistry Volume 45, pages 2608 and 2612 (1953).
Also see Inorganic Syntheses Volume 1, page 90 (1939).
Anhydrous hydrazine can be stored in dark glass bottles under
refrigeration for years.
Other variations on the alkali hydroxide dehydration of hydrazine
hydrate exist which give higher yields of less-pure hydrazine. See
pages 48-54 in the Chemistry of Hydrazine mentioned above. It lists
many references. Especially interesting is Journal of the American
Chemical Society Volume 71, pages 1644-47 (1949).
Preparation of Diethvlamine
NH3 + CH3CH2I —s> xHI + CH3CH2NH2
+ (CH3CH2)2NH +
(CH3CH2)3N
The reaction which produces diethylamine also yields as by-
products ethylamine and triethylamine. The relative amounts of each
compound produced depends upon the molar ratio of the two starting
materials. Use of only a little ethyl iodide favors the formation of
mostly ethylamine. Use of a lot of the ethyl iodide favors the
formation of triethylamine. Somewhere in the middle, a roughly even
split occurs. This will be done here. See Journal of the American
Chemical Society Volume 69, pages 836 to 838 (1947).
LSD Directly From The Lysergic Amides —
The One Pot Shot 37
A section of clean steel pipe 2l/2 to 3 inches in diameter is
obtained, and fine threads are cut into each end so that a cap may be
screwed onto each end. A really nice touch would be to have all the
pieces plated with a half-thousandths-inch of electroless nickel, but
the plater may think you are constructing a pipe bomb when he sees
the pipe and caps.
The bottom of the pipe is secured by screwing the cap on over
threads coated with Teflon tape. Welding may also be used. The pipe is
then nestled into a Styrofoam cooler, and is then filled about Vi full of
rubbing alcohol, and then to this solvent dry ice is added, slowly at first
to prevent it from boiling over, then more rapidly. The top of the pipe
should be covered to prevent frost from forming inside the pipe as it
cools down.
Next, add 175 ml of ethyl iodide to the pipe, and let it cool down. It
will not freeze, as its melting point is about 100° below O° C. Then liquid
ammonia is added to the pipe. This is best done by inverting a cylinder
of liquid ammonia, attaching plastic tubing to the valve, and cracking
open the valve to feed the liquid into the pipe. About 525 ml of liquid
ammonia is called for. In a 3-inch-diameter pipe, that plus the ethyl
iodide will fill it half full. This is not an operation to be done in a
residential neighborhood, as the fumes are tremendous. A rural setting
with beaucoup ventilation is more proper.
Now secure the top of the pipe by screwing on the cap tightly over
Teflon tape. The pipe is now moved into a tub of ice water, and
allowed to sit in this ice water for 45 minutes to an hour to warm up to 0 °
C.
When the pipe has warmed to O° C, it should be shaken to mix the
two reactants, and returned to the ice water. This shaking should be
repeated a few times at 5-minute intervals. When 30 minutes have
passed from the first shaking, the pipe should be returned to the dry
ice bath and allowed to cool.
When the pipe has cooled, the cap on the top of the pipe is
loosened. Then the pipe is returned to the tub of ice water, and the
ammonia is allowed to slowly evaporate away. This will take
overnight, and raise great plumes of stink.
Practical LSD Manufacture
After most of the ammonia has evaporated, the contents of the
pipe should be emptied into a beaker. The foul substance is a mixture of
ammonia, ethlyamine, diethylamine, triethylamine, and the hydriodides
thereof. The best route to follow is to cool this mixture in ice, and
slowly add with stirring 90 grams of sodium hydroxide dissolved
in 100 ml of water. This neutralizes the HI in the mix, yielding the
freebases of all.
This mixture should be extracted several times with toluene.
Toluene is chosen because it is available at the hardware store, and its
boiling point is higher than any of the amines. The extracts should be
filtered, and dried over sodium hydroxide pellets.
The toluene extracts should then be transferred to a flask, and the
mixture fractionally distilled through an efficient column. Ethylamine
distills at 16° C, diethylamine distills at 55° C, and triethlyamine
distills at 89° C. The diethylamine fraction should be collected over a
20-degree range centered on 55° C, and this fraction then redistilled to
get the pure product. The yield of diethylamine is about 40 ml.
Absolute freedom from water in the product can be assured by letting
the crude distillate sit over a few chips of KOH for a few hours prior to
the final distillation.
Preparation of Tartaric Acid
My experience with the chemical scrutinizers while ordering a
pound of Rochelle salts should serve as a lesson to those embarking
upon LSD manufacture. Substances which are useful for this purpose
will raise red flags if obtained through normal channels. It must then be
the highest priority to avoid these normal channels, or to subvert their
scrutiny by preparing yourself those substances with direct use in the
synthesis.
The most low-profile method for getting tartaric acid is to follow
the procedure given below. It uses cream of tartar from the grocery
store and gives good results. See Chemical Engineering Progress
Volume 43, page 160 (1947). Also Organic Syntheses Collective
Volume 1 for alternate procedures. I worked out this procedure by
LSD Directly From The Lysergic Amides —
The One Pot Shot 39
myself in my lab, and it gives good results. That such a simple procedure,
using such easily obtained materials, so effectively subverts the feds'
control over tartaric acid shows what a bunch of ninnies they really are.
To make tartaric acid suitable for use in making the tartaric salt of
LSD, weigh out 10 grams of cream of tartar, and put it into a 100 ml
beaker. I used McCormick brand, and it was nicely white and fluffy.
Other brands will do, so long as they too are white and fluffy.
To the 10 grams of cream of tartar, add water until the 50 ml mark is
reached in the beaker. This produces a milky white suspension. Stir for a
while to try to dissolve as much as possible, then add 10 ml 37% lab-
grade hydrochloric acid. The mixture of calcium tartarate and potassium
hydrogen tartarate that comprises cream of tartar reacts to form tartaric
acid, along with KC1 and CaCl2- A clear solution results after about a
minute of stirring.
Now the water and excess hydrochloric acid are removed by vacuum
evaporation. It is preferable to use a vacuum here, as heating at normal
pressure may result in isomerization of the tartaric acid, and the
replacement of some of the hydroxyl groupings in tartaric acid with
chlorine. Also, hydrochloric acid was used here instead of sulfuric
because the reaction is much faster, and the excess HC1 is removed
during the evaporation. The solution should be evaporated down to a
volume of about 10 ml. It will be yellowish in color, and have crystals of
tartaric acid floating around in it, along with KC1 and CaCl2.
Next, add 100 ml of 91% isopropyl alcohol, and dissolve the crystals
of tartaric acid. KC1 and CaCh will not dissolve, and should be filtered
out. 91% isopropyl alcohol is chosen because it is available at the
drugstore, is not too good a solvent for tartaric acid for crystallization,
and is less likely to form esters with tartaric acid than ethyl or methyl
alcohol.
The isopropyl alcohol is evaporated under a vacuum to 50 ml
volume, and the first crop of white crystals of tartaric acid collected. This
amounts to about 4 grams after drying. Further evaporation yields
additional crops of crystals. Vacuum evaporation is used so that
Practical LSD Manufacture
heating does not contribute to the formation of the ester isopropyl
tartrate.
5 Lysergic Acid
5
Lysergic Acid
All of the production methods from here on out use lysergic acid
as the starting material. These methods may be preferable if the
alkaloids have been extracted from seeds rather than ergot, because
the crystallization of lysergic acid affords an excellent opportunity to
remove the clavine alkaloids present in the seeds.
Two methods will be presented here. Method number one uses
easily available KOH and methanol to cleave the amides to lysergic
acid. Method number two uses hydrazine hydrate, which can be made
from bleach and ammonia according to the directions in the previous
chapter. The first method gives about 50% yield, while the yield in the
second method is better. Both methods give a mixture of regular and
iso lysergic acid, leading to mixtures of regular and iso-LSD. This
makes the chromatographic separation procedure a must for all
methods using the lysergic produced according to the directions given
here.
Method One
Ten grams of lysergic amides extracted from the crops are dissolved in
200 ml of methanol containing 11 grams KOH. The methanol is
Practical LSD Manufacture
then removed at once by distillation under a vacuum. To the residue in
the flask, then add 200 ml of an 8% solution of KOH in water. This
mixture should then be heated on a steam bath for one hour.
Next, the reaction mixture should be cooled, and sulfuric acid
added to it until it reaches pH 3. This results in the precipitation of
crude lysergic acid having a dark color.
The acid solution should next be extracted several times with
ether. These extractions remove a lot of the lopped off portions of the
lysergic amides, and lighten up the color of the lysergic acid. The acid
suspension should next be filtered to yield dark colored crude crystals of
lysergic acid.
These crude crystals should be transferred to a beaker, and taken up
in solution with two 200 ml portions of ethyl alcohol containing a few
mis of strong ammonia. The residue which does not dissolve is
inorganic, and can be discarded.
The alcohol solution of lysergic acid should be evaporated to
dryness under a vacuum. The crystals should be ground quickly while
soaking for a short period of time in 50 ml methanol to remove
colored impurities, then filtered. This yields about 2Y2 grams lysergic
acid. It should be dried in a vacuum dessicator, then stored in the
freezer. The lysergic acid even after vacuum-drying holds one
molecule of water as part of the crystal structure. This is not a
problem if the method given in Chapter 6 is used. Other synthesis
methods require the removal of this water of crystallization, and it is
tough. A vacuum of 2 mm Hg and a temperature of 140° C is needed to
remove it. Such methods are best avoided if possible. Reference: Journal
of Biological Chemistry, Volume 104, page 547.
Method Two
As mentioned before, this method gives higher yields, and so it is
highly recommended. An increase in yield from 50% to 75%
translates into 50% more LSD produced from the crops. This is well-
worth the hassle involved with scrounging up or making some
hydrazine hydrate.
5 Lysergic Acid
To do the hydrolysis, 15 grams of lysergic amides from the crops is
put into a 500 ml flask along with a solution made up of 150 ml ethyl
alcohol, 150 ml water, and 100 grams KOH. Next, 15 ml of hydrazine
hydrate is added. This hydrazine should be the monohydrate, which is
64% hydrazine. If a weaker variety has been scrounged up, this can be
made to work by adding more, and using less water.
Now the flask should be fitted with a condenser, and flushed with
nitrogen. Then heat the flask in an oil bath to gentle boiling for 4
hours. A slow stream of nitrogen to the flask during the reflux averts
the danger from hydrazine.
The flask is next cooled, and the contents poured into a sep funnel of
at least 1000 ml capacity. The batch is then extracted with 600 ml
ether, followed by 600 ml of an 85-15% mix of ether and alcohol.
Finally, one more extraction with 600 ml of 85-15% ether-alcohol is
done.
All of the desired product should now be extracted into the
solvent, and out of the water. This fact should be checked using a
black light to look for the characteristic blue fluorescence.
The combined solvent extracts should now be lowered to a pH of
about 2 using HC1. At this point, a precipitate should form, and it
should be filtered out. The precipitate should be washed free of
entrained product with 4-1 ether-alcohol, and the washing added to
the rest of the filtered solvent.
Now 2750 ml of water should be added to the solvent, and the
mixture placed in a gallon and a half glass jug or 5000 ml beaker. To
this should be added 3 portions of cation exchange resin in H* cycle.
Cation exchange resin is a common item of commerce used in
deionized water systems. Check the yellow pages under "water" and
see which of the local Culligan men offer deionized water systems.
The deionizers come in two-tank systems with one tank packed with
cation exchange resin to remove calcium, magnesium and sodium
from the water. The other tank has an anion exchange resin to remove
chlorides, sulfates, and so on. It is no great task to buy cation
exchange resin from these outlets. The resin consists of tiny plastic
beads coated with the exchanger. In the case of the cation exchangers,
Practical LSD Manufacture
this is generally a sulfonate. "In H* cycle" means that the resin is
charged up and ready to go. This is generally done by soaking the
resin in 20% sulfuric acid in water for a while, then rinsing with
distilled water. Check the directions on the container of resin. Steer
clear of mixed resins that contain both anion and cation exchangers. If
the Culligan man is too stupid to know the difference, or doesn't
know what he has, keep looking until you find one who knows his
business.
The treatment with three portions of cation exchange resin in H*
cycle should be done as follows: Each portion of resin should weigh
about 15 grams. The first portion is added, and then the mixture
should be stirred strongly or shaken for about 10 minutes. The product
will come out of the liquid, and stick to the resin. The resin should be
filtered out, and kept in the fridge while similar treatment proceeds
with the next two portions of cation exchange resin.
All of the product should now be out of the liquid and on the
resin. This should again be checked using the blacklight.
The resin portions are now combined, and soaked in 300 ml of
10% NRjOH in water for 30 minutes with stirring. This brings the
product off the resin, and into the ammonia solution. The slurry
should now be filtered to give a brown liquid which is kept in the
fridge. The resin should be treated again with 300 ml of 10% NHtOH,
and filtered.
Now the 600 ml of ammonia solution containing lysergic acid
should be evaporated down in a vacuum to a volume of 50 ml, and
this remaining liquid kept in the fridge overnight at 4 C to yield a
precipitate of about 5'/z grams of 96% pure lysergic acid. It consists of
lysergic acid and iso-lysergic acid in about a two-to-one ratio.
The resin can be used over and over again by recharging in 20%
sulfuric acid solution, and rinsing with distilled water.
Reference: Chem Abstracts, Volume 69, column 36323 (1968) Czech
patent 123,689
5 Lysergic
Acid
Notes:
1.
The blacklight is your friend, and is very useful in spotting the
product, but don't overuse it as UV is quite harmful to the
product. The blacklight should be a fluorescent tube, and not
some black painted light bulb.
2.
All work described in this chapter should be done under red or
yellow darkroom lighting.
6 LSD From Lysergic Acid And SO}
6
LSD from Lysergic Acid
and S03
This is the second of the two excellent methods of LSD synthesis. It
gives very good yields of high-quality product, if two precautions are
followed. The first point on which success hinges is the
requirement that a rather strict stoichiometry (stoichiometry concerns
the proportions of different chemicals used in reactions) be followed in
both the amount of alkali reacted with the lysergic acid to form the salt
of lysergic acid, and the amount of SOs then added to form the mixed
anhydride of lysergic acid.
The other key precaution is the need to maintain strictly
anhydrous conditions in both the production of the SO3-solvent
complex, and the reaction of that complex with the lysergic acid salt to
produce the mixed anhydride. The reason for this is that SOs is the
anhydride of sulfuric acid, and any traces of moisture will react with it to
produce sulfuric acid. Sulfuric acid does not react with lysergic acid
to form an anhydride. Instead, it just messes up the stoichiometry of the
reaction, leading to greatly reduced yields.
To prevent moisture from interfering with the reaction, glassware
should be baked in an electric oven for an hour or so, and then
allowed to cool down in a dessicator. High humidity must be avoided, so
this is not work suitable for a damp basement or even reasonably
Practical LSD Manufacture
humid days. Air conditioning, or winter's dry indoor heated air are
best. Solvents and reagents must be free of water. The reaction works as
follows:
Preparation of Sulfur Trioxide Complex
Work begins with the preparation and standardization of SOssolvent
complex. SOs is available from a couple of sources. There is a
6 LSD From Lysergic Acid And SO}
form of pure stabilized SOs called Sulfan B. If this material can be had
off of some unguarded shelf, it is superior to the other source of SOa,
fuming sulfuric acid.
To make the SOs-solvent complex using Sulfan, a 2000 ml flask is
charged with a magnetic stirring bar and 1000 ml acetonitrile.
Dimethylformamide can also be used as the solvent, but the authors of
the patent for this process evidently preferred acetonitrile for the
production of LSD. The solvent should come from a freshly-opened
bottle made by a reputable manufacturer. The bottle will list the water
content, generally a few-hundredths percent. This amount of water
will not pose a problem.
Next, the flask is fitted with a condenser and a dropping funnel,
both being equipped with a drying tube to prevent the atmospheric
moisture from infiltrating the reagents. The flask is nestled into a
plastic or Styrofoam tub containing ice water, and the solvent allowed to
cool down. When the temperature in the flask gets down to 5-C,
stirring is begun, and 40 grams of Sulfan should be put into the
dropping funnel. The Sulfan should be dripped into the solvent slowly
and cautiously over a period of an hour or two, while maintaining the
temperature inside the flask in the 0-5° C range. A crystalline
precipitate may form during the addition. If it does, continue stirring
for another hour or so to bring it into solution. If it still fails to
dissolve, add more solvent. Acetonitrile-SOs complex is generally
used at a strength of .5 molar, while dimethylformamide-SOs complex is
used at 1 molar strength. 80 grams per liter SOs is 1 molar. Using
Sulfan fresh from the bottle, it is not necessary to analyze the strength of
the resulting SOs-solvent complex so long as complete dissolution is
achieved.
The procedure for making SO3-solvent complex from fuming
sulfuric acid is more complicated, but less likely to arouse suspicion
since fuming sulfuric acid has a lot more uses than Sulfan. It is also far
more likely to be available via the five-finger discount method.
Fuming sulfuric acid comes in a variety of strengths, but the ACS
reagent contains 30% SO3 or oleum. Pure SOs boils at 45° C, and at
room temperature has a vapor pressure of over 400 mm Hg. That is
Practical LSD Manufacture
why the stuff fumes, and why the stuff can be removed from the
sulfuric acid in which it is dissolved. A simple although time-
consuming method for preparing SOa-solvent complex from fuming
sulfuric acid is to use an adapter such as the one pictured in Figure 2.
With all glass
ware thoroughly
dry, one can attach
a 1000 ml flask on
one side of this
adapter and put
500 ml of fuming
sulfuric acid in it.
figure 2 '— On
tne other side
Adapter used in preparing SOj-solvent complex of the adapter, a 2000
from fuming sulfuric acid. ml flask can be attached
containing 1000 ml of
acetonitrile or dimethylformamide. The use of stopcock grease
should be avoided, as SOs will attack it. Rather the joints should be
sealed by wrapping parafilm around them.
There will be a tendency for the two solutions to come into a
vapor equilibrium. 30% oleum contains about 580 grams per liter
SOa. The vapors will over time work their way into the solvent and
form complexes. It will take some time, depending upon the
temperature, for enough fumes from the sulfuric acid to work their
way out of the acid and into the solvent. Slow magnetic stirring in the
solvent helps to maintain a homogenous mixture, and speeds
absorption of SOa fumes. Cooling the solvent in ice can't hurt either.
Analysis of the solvent should be done after about 12 hours have
passed. The need for stirring is especially crucial here so a
representative sample is taken. To analyze, remove exactly 2 ml of
solvent with a pipette and squirt it into 50 ml of distilled water. Add
some phenolphthalein indicator, or monitor pH with a meter. Now
titrate with .IN NaOH (prepared by dissolving exactly 4 grams of
NaOH pellets in one liter of water) until the color of the solution turns
6 LSD From Lysergic Acid And SO3
pink, or the pH meter shows pH 7. Record the amount of NaOH
solution used.
Molarity SO, in solvent = mis NaOH used / 40
So a 1-molar SO3 complex will require 40 ml of .IN NaOH to
neutralize it. Two equivalents of NaOH react per sulfuric acid.
If after 12 hours, the solvent has still not absorbed enough SO),
just let the process continue. The complex formed need not be exactly
.5M in acetonitrile, or 1 M in dimethlyformamide, just close to those
values. What is important is that the exact strength of complex formed
be known, because that dictates just how much of SOa solution is
used. That is crucially important to the success of the reaction.
When the SOa-solvent complex has reached the desired strength,
the flask containing it should be stoppered with a glass or Teflon
stopper, and kept in the fridge. It will gradually darken first to yellow
and then orange, but it is good for at least 3 or 4 months.
The argument can be made that this procedure is wasteful of
fuming sulfuric acid. After all, maybe only 2 liters of 1-molar SO3
complex can be reasonably made from a pint of fuming sulfuric acid
by this passive fume-absorption method. When one considers that this is
enough SO3 to make 3 million doses, however, such objections are silly.
Batch Production
With SO3 complex in solvent prepared and carefully standardized to
evaluate its exact strength, attention can be turned to LSD synthesis
using lysergic acid and SO3 complex. Exact weighing of ingredients,
and assuring that they are free from water are the two main concerns in
this synthesis. To that end, the lysergic acid crystals obtained by the
methods given in Chapter 5 should be dried without heating under a
vacuum for about an hour. This will remove all but the water of
crystallization, which poses no problem. The scale used to portion out
Practical LSD Manufacture
the ingredients for this synthesis should at least be a very sensitive
triple-beamer, and its accuracy should be checked using new
corrosion-free brass weight standards. Atmospheric humidity is a very
real threat. NaOH, KOH, and lysergic acid will all pull water from the
air. This not only makes accurate weighing impossible, but it also
introduces water to the batch. For this reason, air conditioning or the
dry indoor heat of winter are best during the unavoidable handling
and weighing of reagents.
Two methods will be presented here, the first being the specific
synthetic method for LSD given in example ten of US Patent
2,774,763. The other is the general method given in Journal of
Organic Chemistry Volume 24, pages 368 to 372. Both are authored by
William Garbrecht, a true hero of LSD synthesis. The patent dates from
1955, while the Journal article dates from 1958.1 leave it to the serious
experimenter to decide which is more advanced. No doubt, both are
operable.
Patent Method
15 grams of lysergic acid is quickly weighed out, and placed in a
dried 1000 ml flask equipped with a magnetic stirring bar. 200 ml of
methanol is added to dissolve the acid, then the flask is stoppered while
either 2.22 grams lithium hydroxide hydrate, or 2.09 grams sodium
hydroxide pellets or 2.94 grams KOH pellets is weighed out and
dissolved in 200 ml methanol. The use of lithium hydroxide is preferred
because it doesn't absorb water from the air, thereby messing up the
weighing. Lithium hydroxide, on the other hand, is not a very common
item, and will raise red flags that attract unwelcome attention.
NaOH and KOH, however, are very mundane items. Further, a
freshly opened bottle containing them can safely be assumed to be free
of water. Quick weighing under low humidity will not add appreciable
amounts of water to it. If the choice was mine to make, I would use
NaOH or KOH.
6 LSD From Lysergic Acid And SO3
The LiOH or NaOH or KOH solution is now added to the
methanol solution containing lysergic acid. After a period of stirring to
assure complete reaction to the metal salt of lysergic acid, the
solvent is distilled off under a vacuum, leaving a bubbly residue
clinging to the glass at the bottom of the flask. If the lysergic acid is
pure, such as that made by method 2 in Chapter 5, this residue will
have a glassy appearance. No heat stronger than steam or hot water
should be used to drive the distillation.
The residue in the flask still contains traces of water and
methanol. The water comes from the reaction of the hydroxide with
the acid, and from the lithium hydroxide, if that was used. This is
removed azeotropically. Add 500 ml of hexane to the flask, and distill
off about half of it, using a fractionating column. Both water and
methanol form azeotropes with hexane.
The approximately 250 mis of solution left in the flask is now
cooled in an ice bath to about 5° C. When that temperature is reached, . 1
mole of SOa-acetonitrile complex is added. If the solution prepared is .5molar
strength, that requires the addition of 200 ml. This
addition should be done with strong magnetic stirring, and slowly
enough that the temperature does not climb too much. After the SOa
has been added, allow the reaction to come to completion for about 5
minutes, then add 18 grams of diethylamine (26 ml) dissolved in 250
ml of anhydrous ether.
A further 5 minutes of reaction time is then allowed with stirring,
before pouring the whole reaction mixture into a 2000 ml sep funnel.
Now 1000 ml of water is slowly poured into the sep funnel with
swirling. This addition of water generates a lot of heat as the SOs
reacts to make sulfuric acid, and then gets diluted. Over a period of
time work up to shaking the sep funnel. The LSD goes into the water
layer. Separate it off, and extract four more times with 1000 ml
portions of water.
The combined water extracts (5000 ml in all) are now saturated
with salt, then extracted five times with 1000 ml portions of ethylene
dichloride (1,2-dichloro-ethane). Ethylene dichloride is heavier than
water, so it forms the lower layer in the sep funnel.
