
From: "John Payne" 
Subject: Re: using sodium cyanoborohydride to synthesize meth.
Date: 1997/03/26
Message-ID: <01bc398a$a409b160$027b3a8e@nameserver.sfu.ca>#1/3
References: <01bc344f$01c85c20$LocalHost@default>
Organization: Big Black Vagina Anonynous Internet Remailer
Newsgroups: alt.drugs,alt.drugs.chemistry,rec.drugs.chemistry


Skunky  wrote in article
<01bc344f$01c85c20$LocalHost@default>...
> I was very interested at reading Uncle Festers reductive alkylation using
> aluminum amalgam to make meth.   This was quite a while back and since I
> have
> come across  similar methods using sodium cyanoborohydride for the
> reduction but mainly for synthesizing MDA & MDMA.   
>       I am pretty sure I can work out the reaction conditions for myself
> but would not like to give it a go without someone with experience to
> advise me first.  I'm not quite up to deducing my own procedure.   
>        So if anyone can e-mail me or post up some info on using sodium
> cyanoborohydride for synthesizing methamphetamine I'd be infinitely
> grateful.   

It is interesting that you mention Uncle Fester as a preamble to discussing
the use of sodium cyanoborohydride for the reductive amination in the
synthesis of MDA & MDMA. Actually sodium cyanoborohydride is most useful
for the synthesis of MDMA and methamphetamine, less so for MDA. However,
Uncle Fester says that sodium cyanoborohydride gives him poor yields and he
dismisses its usefulness. Uncle Fester is wrong on this count and on other
points. Sodium cyanoborohydride reductive amination of phenylacetone or
3,4MDP2P can give up to 98% yield in very large batches with no side
reactions. Alexander Shulgin in PiHKAL discusses the use of sodium
cyanoborohydride reductive amination but only for very small batches. In
fairness to both authors it should be said that Fester is a good read but
is often wrong, whereas Shulgin is a difficult read but is often deficient.
Uncle Fester presents the use of activated aluminium for reductive
amination and so does Shulgin. Aluminium may be the best way to go, but
since I have not yet had the opportunity to try it, I am not in a position
to comment.

Let us start with theory. Why do reductive amination at all? Many poor
thinkers advocate the bromination of safrole with hydrobromic acid followed
by amination with methylamine. What could be simpler? What could be more
stupid? Chemists have been synthesising various amphetamines for nearly one
hundred years now using various sophisticated approaches and only now is
the simplistic route being promoted. The problems these people fail to
address are two fold. 1) Hydrobromination of saffrole is problematic. 2)
The nucleophilic potential of an amine goes up with the degree of
substitution. That means the reaction will not stop at the secondary amine
MDMA but will aminate one or two more bromosafrole molecules to give a
tertiary or quaternary amine and not the product you want.

Reductive amination using sodium cyanoborohydride address this issue
properly. Sodium borohydride is more accessible than sodium
cyanoborohydride, but it will reduce the ketone to the secondary alcohol
and so it is not used. Sodium cyanoborohydride used at neutral pH has the
property that it will reduce the imine (Schiff base) formed between the
ketone and methylamine much much faster that the imine. It is a selective
reducing agent of the first rank.

For research purposes the place to start for primary literature is the
Merck Index. The entry for  will lead you to the original literature which
details the synthesis of sodium cyanoborohydride and also the typical
procedures used in reductive amination or other selective reductions.
Sodium cyanoborohydride can be made by reacting equimolar quantities of
sodium borohydride and hydrogen cyanide in THF. One gram of hydrogen
cyanide can kill one hundred men so do not attempt this unless you are a
first rank chemist like me. The hydrogen cyanide is made following a
procedure found in Organic Synthesis, Collective Edition. Work at the 50
-100 gram scale in a distillation apparatus with ground glass joints. Emil
Fischer established the practice where you must smoke cigarettes while you
do this work. Nicotine accentuates the taste of HCN to give you an early
warning of danger. In the absence of a fumehood wear scuba gear when
disassembling the glassware. Store the liquid HCN frozen in the freezer.
Combine equimolar quantities of NaBH4 and HCN in THF and allow the reaction
to go to completion with the evolution of H2. Remove the THF with a rotary
evaporator. If you do not own a rotary evaporator go out and buy one right
now. The NaCNBH3 you made fresh is better than any you can buy. If you
don't mind the heat, go out and buy the NaCNBH3 instead.

More theory: the reductive amination of the ketone can lead to higher
amines but this can be overcome with the use a five times molar excess of
methylamine. That means that for this reaction you are going to want to
make a large quantity of methylamine hydrochloride. 40% aqueous methylamine
is easy to get and work with. Take equimolar quantities of 40% MeNH2 and
concentrated HCl and make them as cold as you can in a deep freeze. Do the
next part outdoors, clandestine and at night to avoid detection. Combine
the two cold liquids quickly in a 1000 ml beaker. It will get real hot real
quick and a lot of MeNH3CL smoke will be given off but you can put a cover
on the beaker and the smoke will dissipate real quick so the neighbours
will be unaware of what you did. Take the solution inside cool it and then
remove all the water with your rotary evaporator to yield a good crop of
white methylamine hydrochloride as a cake in your flask.

So now you are all set to do your reductive amination of your ketone. You
start with either phenylacetone or with 3,4MDP2P. Organic Synthesis,
Collective Edition describes to methods for making the phenylacetone. One
involves the condensation of acetic anhydride with benzylcyanide using
sodium ethoxide, the other, the tube furnace method from phenylacetic acid.
Or you made the 3,4MDP2P from isosafrole, 30% H2O2 and formic acid
following the "Japanese Method" detailed somewhere in Chemical Abstracts.
You can also find more details of the methods by using DejaNews to wade
through the last several years of this newsgroup.

More theory: sodium cyanoborohydride is a selective reducing agent and it
evolves hydrogen at a slow rate in solution. So you do not want to want to
react at reflux. Reductive amination with sodium cyanoborohydride is best
done in methanol at room temperature. The reaction is mostly over in a day
and a half and 98% yield can be achieved in three days of waiting. Starting
with a given molar quantity of ketone use a 25-50% molar excess of NaCNBH3
based on moles of hydrogen and a five times molar quantity of MeNH3CL in
sufficient methanol to bring everything into solution. The beauty of this
reaction is that you do not need expensive glassware of fixed capacity. You
can work at humungous scale using even a plastic garbage can.

After three days neutralize any unreacted NaCNBH3 using a calculated
quantity of dilute HCl or acetic acid. Remove all of the methanol using
your rotary evaporator. Then dissolve all of the cake in H2O. Add
sufficient 5 N NaOH to cause the desired amine product to separate as a
slightly brown layer floating on top of the aqueous layer. Here is where
the work up can be slightly different depending on whether the product is
methamphetamine or MDMA. The meth cook will sample the meth and continue
his work in an energized manner for many more hours or days. Good meth
cooks tend to be fastidious about the quality of the meth he makes and
does. It is possible to just separate the top layer using a separatory
funnel and to carry on. A better approach is to steam distill the amine out
of the pot. The water in the aqueous layer is sufficient. The steam
distillate is collected. Separation is enhanced by the addition of just
sufficient 5 N NaOH. The floating amine layer is now clear. The top layer
is removed with a separatory funnel an the bottom layer is washed a couple
of times with a small quantity of ethyl ether which is combined with the
top layer. You now have liquid meth with a small quantity of ether, a
little dissolved water and perhaps some MeNH2 or unreacted ketone as a
water white oily liquid. It is traditional to dry this over anhydrous NaSO4
or equivalent. Now set up your vacuum distillation apparatus with a water
aspirator vacuum pump. If you do not own a distillation apparatus with
ground glass joints go out and buy one right now. Depending on your vacuum
the product will distill at 130 C or so and the liquid MDMA somewhat
higher.

With the pure liquid meth it is now time to create the hydrochloride. Many
people think it is possible to create crystal meth using gaseous hydrogen
chloride. I have never seen this to be true. What is obtained instead is an
amorphous product. Why bother. Instead use your HCL gas generator to
produce a quantity of anhydrous methanolic HCL in the case of MDMA or you
can use aqueous HCL for meth. Combine equimolar quantities of HCl solution
and amine product in methanol to neutrality. Use your rotary evaporator to
remove solvent to yield a white cake in your flask. This is crude though
pure methamphetamine HCl or MDMA HCL.

It is now time to recrystallize your immensely valuable product. Dissolve
the cake in the minimum quantity of hot isopropyl alcohol. Cool the IPA
solution in the fridge. Crystallization may begin. Layer the solution on
top with an equal quantity of anhydrous diethyl ether and put beaker into
freezer overnight. I am told it is also possible to use methanol and MEK as
solvent pairs. Overnight the ether layer will be seen to diffuse into the
IPA and a massive crystallization has occurred. Stir if necessary. Some
crystals will be needles upto one mm in length. You are laughing. Separate
solvent from filter mass using a buchner filter and vacuum. Air dry for a
while and then remove residual using a vacuum desiccator. You have a world
class crystalline product. You have money in the bank.


