The following synthesis is not meant to be carried out by a
novice chemist, although it is not terribly difficult. For descriptions of how
to carry out the procedures, you should buy a standard lab procedures reference
manual (or preferably you should take college organic chemistry).
Method 1
To a well stirred, cooled mixture of 34g of 30% H202 (hydrogen peroxide) in 150g
80% HCO2H (formic acid) there was added, dropwise, a solution of 32.4g
isosafrole in 120ml acetone at a rate that kept the reaction mixture from
exceeding 40 deg C. This required a bit over 1 hour, and external cooling was
used as necessary. Stirring was continued for 16 hours, and care was taken that
the slow exothermic reaction did not cause excess heating. An external bath with
running water worked well. During this time the solution progressed from an
orange color to a deep red. All volatile components were removed under vacuum
which yielded some 60g of a very deep residue. This was dissolved in 60ml of
MeOH (methyl alcohol -- methanol), treated with 360ml of 15% H2SO4 (sulfuric
acid), and heated for 3 hours on the steam bath. After cooling the mixture was
extracted with 3x75ml Et2O (diethyl ether) or C6H6 (benzene). Its recommended
that, the pooled extracts can washed -- first with H2O and then with dilute NaOH
(sodium hydroxide). Then the solvent is removed under vacuum to afford 20.6g
3,4-methylenedioxyphenylacetone (3,4-methylenedioxybenzyl methyl ketone). The
final residue may be distilled at 2.0mm/108-112 deg C, or at about 160 deg C at
the water pump.
Add 23g 3,4-methylenedioxyphenylacetone to 65g HCONH2 (formamide) and heat at
190 deg for five hours. Cool, add 100ml H20, extract with C6H6 (benzene) and
evaporate in vacuum the extract. Add 8ml MeOH (methyl alcohol -- methanol) and
75ml 15% HCl to residue, heat on water bath two hours and extract in vacuum (or
basify with KOH and extract the oil with benzene and dry, evaporate in vacuum)
to get 11.7 g 3,4-methylenedioxyamphetamine (MDA).
To produce MDMA substitute N-methylformamide for formamide in the above
synthesis.
Method 2
This is a less yealding method usually producing only MDA. It is a two step
procedure first reacting safrole with hydrobromic acid to give 3,4-methylenedi-
oxyphenyl-2-bromopropane, and then taking this material and reacting it with
either ammonia or methylamine to yield MDA or MDMA respectively. This procedure
has the advantages of not being at all sensitive to batch size, nor is it likely
to "run away" and produce a tarry mess. It shares with the Ritter
reaction the advantage of using cheap, simple, and easily available chemicals.
The sole disadvantage of this method is the need to do the final reaction with
ammonia or methylamine inside a sealed pipe. This is because the reaction must
be done in the temperature range of 120- 140 C, and the only way to reach this
temperature is to seal the reactants up inside of a bomb. This is not
particularly dangerous, and is quite safe if some simple precautions are taken.
The first stage of the conversion, the reaction with hydrobromic acid, is quite
simple, and produces almost a 100% yield of the bromi- nated product. See the
Journal of Biological Chemistry, Volume 108 page 619. The author is H.E. Carter.
Also see Chemical Abstracts 1961, column 14350. The following reaction takes
place:
To do the reaction, 200 ml of glacial acetic acid is poured into a champagne
bottle nestled in ice. Once the acetic acid has cooled down, 300 grams (200 ml)
of 48% hydrobromic acid is slowly added with swirling. Once this mixture has
cooled down, 100 grarns of safrole is slowly added with swirling. Once the
safrole is added, the cheap plastic stopper of the champagne bottle is wired
back into place, and the mixture is slowly allowed to come to room temperature
with occasional shaking. After about 12 hours the original two layers will merge
into a clear red solution. In 24 hours, the reaction is done. The chemist
carefully removes the stopper from the bottle, wearing eye protection. Some acid
mist may escape from around the stopper.
The reaction mixture is now poured onto about 500 grams of crushed ice in a 1000
or 2000 ml beaker. Once the ice has melted, the red layer of product is
separated, and the water is extracted with about l00 ml of petroleum ether or
regular ethyl ether. The ether extract is added to the product, and the combined
product is washed first with water, and then with a solution of sodium carbonate
in water. The purpose of these washings is to remove HBr from the product. One
can be sure that all the acid is removed from the product when some fresh
carbonate solution does not fizz in contact with the product.
Once all the acid in the product is removed, the ether must be removed from it.
This is important because if the ether were allowed to remain in it, too much
pressure would be generated in the next stage inside of the bomb. Also, it would
interfere with the formation of a solution between the product and methylamine
or ammonia. It is not necessary to distill the product because with a yield of
over 90%, the crude product is pure enough to feed into the next stage. To
remove the ether from the product, the crude product is poured into a flask, and
a vacuum is applied to it. This causes the ether to boil off. Some gentle
heating with hot water is quite helpful to this process. The yield of crude
product is in the neighborhood of 200 grams.
With the bromo compound in hand, it is time to move onto the next step which
gives MDA or MDMA. The bromo compound reacts with ammonia or methylamine to give
MDA or MDMA.
To do the reaction, 50 grams of the bromo compound is poured into a beaker, and
200 ml of concentrated ammonium hydroxide (28% NH3) or 40% methylamine is added.
Next, isopropyl alcohol is added with stirring until a nice smooth solution is
formed. It is not good to add too much alcohol because a more dilute solution
reacts slower. Now the mixture is poured into a pipe "bomb." This pipe
should be made of stainless steel, and have fine threads on both ends. Stainless
steel is preferred because the HBr given off in the reaction will rust regular
steel. Both ends of the pipe are securely tightened down. The bottom may even be
welded into place. Then the pipe is placed into cooking oil heated to around 130
C. This temperature is maintained for about 3 hours or so, then it is allowed to
cool. Once the pipe is merely warm, it is cooled down some more in ice, and the
cap unscrewed.
The reaction mixture is poured into a distilling flask, the glass- ware rigged
for simple distillation, and the isopropyl alcohol and excess ammonia or
methylamine is distilled off. When this is done, the residue inside the flask is
made acid with hydrochloric acid. If indicating pH paper is available, a pH of
about 3 should be aimed for. This converts the MDA to the hydrochloride which is
water soluble. Good strong shaking of the mixture ensures that this conversion
is complete. The first stage of the purification is to recover unreacted bromo
compound. To do this, 200 to 300 ml of ether is added. After some shaking, the
ether layer is separated. It contains close to 20 grams of bromo compound which
may be used again in later batches.
Now the acid solution containing the MDA is made strongly basic with lye
solution. The mixture is shaken for a few minutes to ensure that the MDA is
converted to the free base. Upon sitting for a few minutes, the MDA floats on
top of the water as a dark colored oily layer. This layer is separated and
placed into a distilling flask. Next, the water layer is extracted with some
toluene to get out the remaining MDA free base. The toluene is combined with the
free base layer, and the toluene is distilled off. Then a vacuum is applied, and
the mixture is fractionally distilled. A good aspirator with cold water will
bring the MDA off at a temperature of 150 to 160 C. The free base should be
clear to pale yellow, and give a yield of about 20 ml. This free base is made
into the crystalline hydrochloride by dissolving it in ether and bubbling dry
HCl gas through it.
Biology Common Forms Other Names
Back to MDMA Back to List of Drugs Back to list of topics MAIN
