Lysergic acid diethylamide

Directory

Introduction ................................................................................................................................. 1
Synthesis overview ....................................................................................................................... 2
Chemicals..................................................................................................................................... 3
Equipment ................................................................................................................................... 4
Process ........................................................................................................................................ 5
Safety precautions.…………………………………………………….....................................................................6

Disclaimer………………………………………………………………………………………………………………………………………7

1
1. Introduction

LSD or D-lysergic acid diethylamide is a remarkable compound with a unique

chemical structure as well as fascinating pharmacological effects. First
synthesized in 1938 by Albert Hofmann, this substance rapidly gained notoriety
as an untamable catalyst of the Sixties
counterculture.
With the end of the hippie era, the death of Grateful
Dead singer Jerry García, the arrests of various large
scale LSD manufacturers and the discovery of new
potent and easy to synthesize psychedelics, the
production of LSD has declined to its trough (2010).

In spite of everything the demand has not decreased. Due to the fact that the
illicit market for LSD has historically never been profit oriented, this pestering
demand remains unsatisfied. One gram of pure D-lysergic diethylamide will, at
a dosage of 100µg per use, theoretically suffice for 10 000 cosmic experiences,
which leads to the legitimate question since the required dosage is so low, why
is there not more LSD available?
The most common assumptions are the high penalties for LSD production and
distribution, the difficulty of obtaining watched precursors and the high
financial effort involved in the construction of an adequate laboratory. I will
show you, that all of these assumptions are true (you didn’t think it would be
that easy ;-), but nonetheless conquerable if one has the dedication.
If you read this document carefully, it will provide you a valuable overview of
the processes involved, which should be understandable even without
extensive prior knowledge. It is not, however, a guide to manufacture LSD with
household chemicals in your garage without prior laboratory experience! (Sorry
laymen)

2
2. Synthesis Overview

I chose to illustrate Alexander Shulgin’s route: ergotamine tartrate via D-

lysergic acid hydrate to D-lysergic acid diethylamide tartrate, because it is a
simple, relatively safe and well-yielding synthesis route. It has unfortunately
two major downsides if one has limited access to chemicals:
1. ergotamine tartrate, which is closely watched as an obvious precursor for
illicit LSD production and
2. POCl3, which is closely watched because it is a precursor in the production of
the nerve gas sarin.
But even those two are far from being unavailable, if one remembers the fact
that regulations differ in definition and execution throughout the various
places on this planet. Furthermore, numerous people completely disregard the
idea that any regulations apply to them whatsoever, they just follow the law of
business. Thus a dedicated individual simply needs to exploit the failures of this
capitalistic system - which is not a hard task as these are abundant - in order to
procure the necessary ingredients for the very substance that has the ability to
disassemble this ugly construct.

For the synthesis summary please refer to TIHKAL by Alexander Shulgin

(chemical #26). This section of the book is also widely available on the internet.
Install ambient yellow light in the room that you work in and for the especially
sensitive stage switch to red light to minimize the formation of lumi-LSD
[inactive] that occurs under the presence of light.

This synthesis can be done in three days.

The scale is rather manageable and the
required amounts of chemicals are low.
Nonetheless the yield can potentially be
3g of pure LSD, which would mean 30.000
trips at a dosage of 100µg.

3
An accurate working manner and a problem-free synthesis are of course
required to ensure the highest possible yield.
Great focus should be placed on the preparation and on the chemist’s ability to
improvise. Although many issues can be worked out before hand, coincidence
always plays a part and it is therefore important to have a fast and critical mind
when attempting any organic synthesis. One should be able to adapt the
calculations of ratios on the spot, recognize dangerous developments [e.g.: a
light blue liquid is seen in the cold trap -> liquid O2 condensed in the cold trap,
highly explosive!] and always have spare glassware at reach.

Purification at the end of the synthesis is essential for safe product. A very good
article about LSD purity and the issues concerned with unidentified
components of LSD samples can be found here.
It indicates that, if thorough purification is neglected, the final product may be
contaminated with substantial amounts of iso-LSD and unreacted ergotamine
tartrate, which would pose serious health risks and may be an explanation for
the harsh somatic effects occasionally attributed to samples of street LSD
[i.e.: ‘bad acid’].

4
 3.Chemicals

All Solvents should be anhydrous!

C4H6O6
D-tartaric
tartaric acid (anhydrous)

C33H35N5O5
Ergotamine tartrate

C4H11N
Diethylamine

POCl3
Phosphoryl chloride

CHCl3
Chloroform

C6H6
Benzene

5
 Et2O
Diethyl ether

EtOH
Ethanol

MeOH
Methanol

H2SO4
Sulfuric acid

NH3
Ammonia

Al2O3 (or silica))

Aluminium oxide

MgSO4
Magnesium sulfate

NH4OH
Ammonium hydroxide

KOH
Potassium Hydroxide
Hydroxid

H2O (deionized)
Water

All Solvents should be anhydrous!

6
4. Equipment

Magnetic stirrer, incl. heating

cost: 250$

Rotary reflux, vacuum evaporator (incl. vacuum controller

and vacuum pump) *
cost: 5 000 $

Chromatography apparatus (column will be easiest)

cost: 40 $

Precision balances *
cost: 3000 $
and

7
 Melting point measurement apparatus *
cost: 1000 $

Refri
Refrigerator
cost:
ost: 800 $

Hand UV light
cost:
ost: 30 $

Long wave light (red, yellow)

and

Filters (paper,
paper, glass or other filtration methods)

Ice bath - simply ice cubes

bes in water, or cold acetone

8
 Glassware

pH meter
cost: 150 $ *

For the maintenance of an inert atmosphere:

Argon (inert gas)

High vacuum pump

cost: 1000 $

One of the following two options:

Schlenk line **
cost: 4000

9
 or:

Glove box **
cost: 18 000 $

* These prices are for new and unused equipment as sold by leading laboratory
supply firms. Considerable savings (I’m sure a reduction to just 3/5 (60%) of the
listed prices is quite possible) can be made when buying these devices in used
but fully functional condition at laboratory clearance sales, auctions or
university sellouts; the use of a rotary evaporator, for instance, is not
necessary, but it greatly reduces work effort, is clean and accurate; a simple
vacuum evaporation setup would suffice;

** if one is in fact constructing a personal laboratory financial and spatial

reasons are a concern and it would be highly advisable to refrain from the
purchase of a glove box (if it actually was under consideration) and instead use
a Schlenk line for the synthesis steps under an inert atmosphere; the cost of a
good Schlenk line are proportional to the size of the setup, and the listed price
includes all necessary glassware; an oil bubbler, a high quality manifold, a cold
trap and a high vacuum pump are essential and required though;
While simple methods for the establishment of an inert atmosphere exist (e.g.:
flushing with argon an then closing vessel with argon filled balloon] one should
never follow such procedures without the required knowledge and proficiency.

Note: Working with vacuum is very dangerous! Adequate practical chemistry

abilities are required to prevent injury and to ensure a successful synthesis.
Implosions and explosions are possible if caution is not applied, serious injuries
and death can occur! Careful inspection of glassware has to be made prior to
the experiment to ensure the absence of cracks in the glass! There must always
be a pressure relief! (usually oil bubbler)

10
5. Process

Important note: Before attempting the synthesis, everything should already be

set in place, calculations should be complete, sufficient availability of all
required chemicals should be confirmed, apparatuses should be checked for
functionality, safety precautions should be taken and at least a second person
should be present. Sobriety and undisturbed concentration are very important!

1. Install your setup of choice for the inert atmosphere

2. Put 100ml of H2O and a stirring bar in a suitable flask on a hot

plate; under stirring gradually add 6.7g KOH; set the temperature
to 75 °C

3. Add 10g of Ergotamine tartrate and leave the mixture stirring for 4
hours; the Et should be completely dissolved after about an hour;

4. After 4 hours cool the reaction mixture to 10 °C with an external

ice bath; use a ph meter and add H2SO4 (2.5 N -> 1.25 mol/L)
dropwise until the pH drops to 3.0, this should require about 60ml
of H2SO4; white solids will fall out of solution;

5. Leave the reaction mixture cooled over night;

6. [Next day:] Remove the solids by filtration and wash the filter cake
with 10ml Et2O; Place the dry solids in a beaker with a stirring bar;

7. Prepare a solution of anhydrous EtOH with 15% Ammonia;

8. Add 50ml of this solution to the beaker containing the solids; Stir
this mixture for 1 hour, then separate by decantation;

9. Repeat step 8 (with the leftover solids), combine the two

decantations and remove the solids by filtration; discard the solids
(a few hundred mg) as they are unwanted;

10.Place the clear filtrate under vacuum to remove solvent until dry
solids are left in the flask;
11
11.Prepare a solution of 1% aqueous Ammonia and add 50ml of it to
the flask to dissolve the solids; acidify this mixture again with
H2SO4 (1.25 mol/L) like in step 4 [dropwise to pH 3.0];

12.Solids will precipitate and are then to be removed by filtration and

washed with Et2O until they are free of color; dry these solids
under vacuum; this should leave around 3.5g of D-lysergic acid
hydrate; Store it cold, dry, dark and in the absence of air!

13.Suspend 3.15g of D-lysergic acid hydrate and 7.1g of diethylamine

in 150ml of CHCl3; bring this mixture to reflux with stirring and
heating (60 °C
bp of CHCl3);

14.Remove the heating and very slowly add 3.4g of POCl3 over the
course of 2 minutes, sufficient enough to maintain reflux
conditions;

15.After additional 5 minutes of reflux everything should have gone

into solution; let this solution return to room temperature;

16.Prepare a solution of 200ml NH4OH (1N
1mol/L) and to this add

the solution from step 15 after it has cooled down to room
temperature;

17.Two phases will be visible, separate and discard the inorganic

phase;

18.Dry the organic phase over anhydrous MgSO4 [to remove residual
water], filter the now clumpy MgSO4 and discard it; then remove
the solvent under vacuum; this will leave a residue;

19.Set up a chromatography column [different chromatographic

methods may be chosen] with alumina as stationary phase and
prepare enough of a 3:1 C6H6/CHCl3 eluent mixture;
chromatograph the residue from step 18 [use UV light sparingly to
follow the fraction] and remove any residual solvent from the
collected fraction [LSD free-base] under vacuum;

12
 20.Recrystallize the LSD base from C6H6; Melting point should be
between 87 – 92 °C;
Store it cold, dry, dark and in the absence of air!

21.Weigh the LSD free-base and per gram of LSD base separately
prepare 0.232g of dry D-tartaric acid and 4mL of warm, anhydrous
MeOH;

22.Dissolve the LSD base under stirring in the prepared warm MeOH
[4mL per gram of LSD base] and add dry D-tartaric acid [0.232g per
gram of LSD base];

23.To this clear and warm solution add Et2O dropwise until the
cloudiness does not dispel on continued stirring;

24.Put the solution in the refrigerator overnight; Crystals will form;

Prepare a 1:1 MeOH/Et2O mixture in one flask and in a separate
flask just MeOH and put these two flasks also in the refrigerator;

25.[Next day:] Remove the crystals by filtration, wash them sparingly

with cold methanol and with the cold 1:1 MeOH/Et2O mixture,
then let the product dry;

26.This product is impure D-lysergic acid diethylamide tartrate!

Melting point should be around 200 °C;

27.To purify the material, perform repeated recrystallizations from

methanol which will produce a product that becomes
progressively less soluble, and eventually virtually insoluble, as the
purity increases;
Store it cold, dark, dry and in the absence of air!

Note: Prior to contemplating a bioassay of the product, its actual composition

and purity should be determined by HPLC or other precise methods (e.g.: GC /
MS) and the material has to be further purified if considerable impurities are
present!

13
6. Safety precautions

Ergot alkaloids are extremely poisonous substances and any direct contact
(skin, inhalation, ingestion) must be avoided at all times, or serious injury and
death could be the consequence! In case of ergot poisoning medical attention
has to be sought immediately to prevent fatality!
Rubber gloves have to be worn during the synthesis and caution has to be
applied when taking them of (don’t ever touch the gloves with your bare
hands!).
Always wear safety glasses!
Two fire extinguishers should be placed not too far from the work area;
vacuum evaporations do pose a relevant risk of fire hazard!
Never use a cell phone in the laboratory!
A reliable and powerful ventilation system has to be installed in the laboratory
to prevent a dangerous accumulation of toxic volatile chemicals.
Consider situating your Schlenk line behind a vertically sliding safety glass wall
to decrease the risk of injuries in case of an implosion or explosion!
[Slide it up just so high that your hands fit through and reasonably comfortable
work is possible]
Animals and uninvolved, irresponsible and/or incalculable individuals are
strictly prohibited in the laboratory!
Smoking is strictly forbidden in the laboratory (and harmful everywhere else
too)!
Sobriety and full concentration are essential during every visit to the
laboratory, even when one is not working on a synthesis!

14
7. Disclaimer

This work is nothing more than a convenient summary of information that was
discovered and gathered by brilliant minds. Credit has to be given to those
people for their ability to discover what lay unwatched before and to introduce
it to mankind.
The prohibition of drugs is without a doubt the outcome of the fact that
intelligent and conscious people have historically declined societal leadership
positions, partly because they do not need to be lead by anyone and thus
decide to completely refrain from this hierarchical system. The devastating
impact that stupidity has on this planet has become more than obvious in
recent years and it is now the time to completely eradicate selfishness.
I do not endorse the foul play of lying. It has to be pointed out that in my
perception it is marginal what substance or what action anybody else, who
does not at least exhibit the mental capacities or is afraid to understand
him/herself respectively views as “forbidden”. It seems to be the prevalent
method amongst the mentally retarded and paranoid to declare things and
concepts that exceed their understanding as “dangerous” and “forbidden”.
If you want to judge me, I ask you: what am I? Am I the photo and the name on
my driving license? The genetic code that is imprinted in the base sequence of
my DNA? Am I the concepts and contemplations that constitute what is
referred to as my consciousness? Am I a mere product of society? It can not be
determined. Identity is a flowing illusion and a common misconception of those
that lack the prerequisites for deeper insights. In any way, a judgment on the
bases of words is inadequate in a world that so miraculously surmounts the
narrow limitations of language. We are all one and everything, always.

Yours sincerely,
The Universe

PS.: Should you need any further information, please do not hesitate to contact me.

15