Industrial Secrets of L-Ephedrine Production

Chapter 20 & 21
Dedication: This publication is dedicated to the head of the DEA Chuck
Rosenberg, head of the Sinaloa Cartel Joaquin Guzman (El Chapo), his attorneys
Juan Pablo Badillo and Jose Refugio Rodriguez, as well as the numerous victims
of a futile and fragile drug war. None offered anything to prevent publication of
these books.

20. Methylamine Manufacturer

Although there are many ways of producing methylamine, this procedure for
producing L-ephedrine requires a methylamine of high purity. The standard
commercial reaction, using methanol and ammonia compressed over a zeolite
catalyst, also produces dimethylamine and trimethylamine. These compounds
will interfere with the ephedrine production unless they are fractionally distilled
beforehand.
Refluxing ammonium chloride with formaldehyde for several hours is an easy
and safe method to produce methylamine hydrochloride salt, but this reaction
will not convert all of the ammonium chloride. The higher the formaldehyde
concentration, the higher the overall yield.
This procedure is desirable in the sense that it does not require the use of
explosive or highly flammable substances such as nitromethane. The
disadvantage is the relatively low conversion rate, which requires much boiling,
separation through crystallization, basifying of the solution to liberate gas,
drying of the evolving gas, then finally purification by condensation of the
methylamine gas, and the remaining ammonia gas is converted back into
ammonium chloride in solution. The ingredients are very easy to acquire and
these boils are relatively safe. There is only about a 50-60% conversion to
methylamine hydrochloride in the reaction, so it is important later to remove the

ammonia gas caused by basifying the methylamine. This is relatively easy with
a condenser coil kept at -15C to -20C, as methylamine liquefies at -6C and
ammonia gas at -33.4C. This is enough of a temperature difference, that
fractional distillation probably isnt necessary. It is however believed necessary
to use dry gas during condensation, as moisture in the condensation will lead to
azeotropes with water, making the ammonia and methylamine gases more
difficult to separate. Therefore, the use of the drying tube/canister described in
FIG. 24 is necessary for a clean separation of the methylamine.
Wet methylamine gas first flows through the top center of the device and down
to the bottom of the vessel. The gas is evenly dispersed around the bottom of the
device and forced by pressure upwards and through the dry magnesium sulfate,
passing through a perforated stainless steel bottom. The dry gas now exits
through the top portion of the device after the dry magnesium sulfate has
absorbed. A stainless steel moisture meter should be welded into the top portion
of the apparatus, and extend into the magnesium sulfate. This will allow for an
external reading and estimation when desiccant requires replacement, as the
magnesium sulfate will become more conductive as it absorbs water.
Combine the formaldehyde (37% Formalin) and ammonium chloride at a 2:1
weight ratio in whatever quantities you wish. Start boiling and refluxing for 8
hours, and your methylamine hydrochloride is made. Separation however is
more difficult.
Physically, ammonium chloride and methylamine hydrochloride are very easy
to identify and separate by color and texture. Ammonium chloride crystalizing
from solution will look as dull white crystals, while methylamine hydrochloride
crystals are yellow and shiny when wet. Of course a mix of them will produce
dull white crystals and yellow crystals. The first cooling of the solution will
precipitate exclusively white ammonium chloride crystals, which can be
recycled into the next batch. As long as you boiled down all the way until near

half the original volume, the second crystallization will yield a mix of
ammonium chloride and mostly methylamine hydrochloride crystals, while third
crystallizations produce the highest quality methylamine hydrochloride. I have
found that a water aspirator pulling a strong vacuum is necessary to boil down
this far. You will see much ammonium chloride crystalizing out even at 100C,
before you end the first boil and allow the solution to cool.
Here is a proven recipe:
Place 3 kg of Ammonium Chloride and 6 kg of technical Formaldehyde (37%,
Formalin) into a 20L round bottom reflux setup. Steady boil and reflux the
solution at 91C 100C for 8 hours depending on altitude. Allow the solution
to cool slightly from the boil and then replace the reflux condenser with a
vacuum adapter connected to a water aspirator. Heat the mixture and boil off the
solution near 100C under vacuum until the solution is close to half the original
volume. Ammonium chloride will have already started to precipitate even at this
temperature.
Next, the reaction flask should be cooled rapidly to room temperature by
immersion into first a warm water bath (60C) swirled, and then an ice bath, or
simply allow the solution to cool at room temperature over several hours then
ice, or even use a refrigeration system in a commercial operation.

Much

ammonium chloride will precipitate from the solution.

Filter the solution first by decanting (pouring off) and saving the liquid without
any settled ammonium chloride, where the remaining liquid is poured through a
vacuum Buchner funnel to recover ammonium chloride crystals. The liquid
solution is again set aside and saved. Boil the liquid solution again under aspirator

vacuum until the solution is concentrated to nearly half again (1/4 the original
volume) or less.
The solution is allowed to cool to room temperature or below, where some
ammonium chloride but mostly methylamine hydrochloride will precipitate from
solution. The wet yellow crystals are filtered by Buchner funnel, where the
remaining liquid is boiled down once again to crystalize more methylamine
hydrochloride upon cooling. The second crop of methylamine hydrochloride will
be of the highest purity. Combine all the remaining concentrated solutions and
boil down for a yet another methylamine crop.
Basifying the resulting product with sodium hydroxide (lye) solution will result
in ammonia gas being produced along with methylamine gas, as some ammonium
chloride will be present. A stainless steel pressure balancing apparatus for
liberating the gas has been shown in FIG. 23. Heating the pressure balancing
apparatus to near 90C will liberate any gas dissolved in solution and gasify any
methylamine or ammonia.
The ammonia gas will interfere with the ephedrine production during amination
and needs to be removed for decent yields. One practical way to separate the
methylamine gas from the ammonia gas is to use a custom welded stainless steel
condenser coil apparatus connected to the gas output of the drying canister, which
is connected to the pressure balancing apparatus. Anti-freeze fluid from a
refrigeration system is well circulated through the cooling coil as shown in FIG.

25. However, the evolving gas should be first dried in an in-line drying tube filled
with fresh, dry magnesium sulfate before reaching the condenser FIG. 24 to
remove water that will cause the gases to form azeotropes with the water.
Azeotropes from water will make ammonia and methylamine much more difficult
to separate.
The temperature of the anti-freeze solution should be maintained between -15C
to -20C with a proper explosion proof thermostat (no sparking). Because
methylamine gas condenses at -6C at standard atmospheric pressure, while
ammonia doesnt condense until -33.3C, the remaining gas can be bubbled into
a diluted HCL water solution to form ammonium chloride, while the liquefied
methylamine that is collected can be periodically drained off from a stainless steel
valve, and mixed into a cold methanol solution. Dont ever use brass fittings or
copper fittings, which will be rapidly corroded by the methylamine.
Again, I recommend an auto-dosing pH control system to maintain the weak acid
level. In this case, maintain a low pH of 3-4. The anti-freeze should also be
circulated around or through the methylamine collection area, as to keep the
methylamine from warming and re-boiling. Dont use dry ice or anything with a
temperature less then -20C, or ammonia gas will liquefy too.
A theorized modification to this procedure will likely result in a higher conversion
rates of ammonium chloride into methylamine hydrochloride. Place the mixed 2:1
w/w formaldehyde/ammonium chloride solution into a steel scuba cylinder with
the valve removed, leaving a 20% air gap to ensure hydraulic pressure doesnt
explode the cylinder upon heating. Use a threaded steel plug with Teflon tape to
seal the cylinder shut (Remove any galvanizing from the plug with a weak HCL
bath). Use a large oil bath fitted with a drum heater and filled with brake fluid to
heat the cylinders to 150C for 8 hours. The increase in both pressure and
temperature should provide for a higher conversion rate, but one should test for
the presence of di or tri methylamines that may be formed. Do not be in the room

when these cylinders are heated or during heating, as they are known on occasion
to explode. This scuba tank is an experimental procedure that has not been tested.
The best option for producing relatively pure methylamine gas from the
beginning, which will yield the highest amount of ephedrine in animation, is
through the reduction of nitromethane into methylamine hydrochloride, then the
subsequent basifying of the product with sodium hydroxide (lye) solution. The
additions of a lye solution will produce much evolving methylamine gas, where a
stainless steel pressure balancing apparatus that directs a portion of the evolving
gas to the top of the dripping lye solution is described in FIG. 23. Use Teflon
seals for an access port, as methylamine is highly corrosive to most seals. The
evolving gas can be bubbled through Teflon tubing although HDPE works as well,
through an optional canister containing desiccant medium such as chunks of dry
magnesium sulfate FIG. 24, then into a cold methanol solution infused with dry
ice. The methylamine will rapidly liquefy and dissolve into the solution at these
low temperatures.
Assemble a 20L round of flat bottom glass flask with the corresponding
heating/magnetic stirring mantel, where the flask should have a 24/40 adapter for
a stainless steel temperature probe, and a separate reflux condenser perhaps 40/50
or some larger size.
Drop a stirrer magnet into the solution, then add 1050g of 40 Mesh iron filings,
2250 ml of water and 10g of Ferric Chloride. Next, add 350ml of concentrated
Hydrochloric Acid ("muriatic acid" is ok). When the bubbling ceases, add 310g
of nitromethane. Obtaining nitromethane is dsecribed in a few paragraphs.

Heat the reaction mixture to reflux with a glass condenser coil and stir at 100C
and hold the refluxfor 14 hours. Then allow the solution to cool to room
temperature.
When the solution has cooled, pour the solution into a HDPE plastic vessel with
an overhead, explosion proof stirrer. The vessel should have a chemical resistant
pH probe fitted into a sturdy location. Under strong stirring, the pH should be
raised with the addition of a medium concentration lye solution. The pH should
be brought up to 5-7 before pouring into the stainless steel pressure balancing
vessel shown in FIG. 23, as an acidic solution over time could cause a rupture in
the pressure balancing apparatus. This procedure will produce some methylamine
gas, so stirring will even out the pH and precipitate evolving gas back into the
methylamine salt again.
Nitromethane is highly flammable and the addition of sodium hydroxide prior to
reduction forms a shock sensitive explosive. So always ensure your product has
been properly reduced before basifying. Caution with this procedure is warranted.
The ammonium chloride/formaldehyde method is probably the safest, but the
nitromethane reduction route produces the purest methylamine.
One easy way to test a questionable product that you did not manufacture, to
determine if the questionable product is methylamine hydrochloride, or at least in
portion, is to leave a sample in a humid area. After several hours, the product will
turn from a solid powder to a yellow liquid, as methylamine is highly hygroscopic
(absorbs water).
Nitromethane is easily obtained using race track fuel or fuel for remote control
model cars. Hobby stores carry volumes of these products, which are almost
always mixed with methanol. It is necessary to distill away most of the methanol
first, which boils at 64.7C while nitromethane doesnt boil until 101.1C, so it is
very easy to separate the two by distillation. It is not enough to simply distill the

methanol, as one must still distill the nitromethane after, to separate the
nitromethane from lubricants and oils which are often found in the fuel mixture.
To determine when one has achieved a 10% w/w methylamine solution through
gas bubbling, one can first observe and record the increase in liquid volume.
Second, one needs to extract 10 ml of properly mixed methanol/methylamine
solution from the bubbling apparatus and add to 100 ml of distilled or reverse
osmosis water. Perform a titration from a buret filled with analytical grade 1 N
HCL (hydrochloric acid), adding a very small amount of phenylphthalein solution
(a few drops) to the methylamine/alcohol/water solution as a pH indicator. As 1N
HCL is slowly added under stirring or swirling, the reaction will turn from pink to
clear when the neutralization point is reached (About 25.6 ml of 1 N HCL for a
10% methylamine solution).
Originally obtained from below:

Add a few drops of phenolpthalein indicator (1% in alcohol) and watch the
mixture
turn pink. Now, titrate with 1 N HCl, with lots of swirling (magnetic stir if you
have one)
to a colorless endpoint
Each 1 ml of titrant will neutralize one millimole of methylamine, or 31 mg.
So, [(ml titrated x 0.031)/weight of the 10 ml of methylamine
solution in grams or 7.92] X100 = w/w conc of methyamine in %. It is best
to use analytical grade 1 N HCL from a chemical
chemical supplier, as the concentration of the acid is precise and known.
Pressure Balancing Apparatus
For the liberation and purification of methylamine gas, it is necessary to have
a piece of equipment known as a pressure balancing apparatus depicted in
FIG. 23. These devices are generally made of glassware or stainless steel
depending on the contents. For example, a dry HCL generator requires that it
be made from glass, as the acid will react with and eat holes through stainless
steel quite quickly. Glass is fragile on the other hand, therefore stainless steel
vessels, tuning, ports, and valves are desirable in every application where glass
isnt required. Teflon seals work excellent and are unaffected by
methylamine/ammonia gas.
The first component is the pressure balanced separatory funnel similar to what
is shown in FIG. 23. Again, the pressure balancer should be manufactured in
stainless steel for methylamine gas liberation or wherever possible. The
separatory funnel is not used to actually separate layers, but rather to regulate
the steady solution into a pressurized reaction vessel through a valve.
Otherwise, the solution will simply flow erratically or not at all because of the
pressure created by the evolving gas. With a pressure balancer, the pressure

on the top of the separatory funnel contents is equal to the pressure inside the
reaction vessel and therefore the fluid will flow by gravity freely.
The reaction vessel should be as large as required for your scale of operation,
where Ive found pressure welded, stainless steel cylinders with a capacity of
10-20 liters to be ideal for an average person to operate and dismantle for
cleaning. There should be a decent size stainless steel access port, sealable by
clamp, and again a Teflon gasket to ensure proper sealing. The top center of
the reaction vessel should have a welder stainless steel tube that has been
welded vertically, where to 5/8 stainless steel tubing should be used.
Stainless steel valves with pressure fittings should be used to connect the
valves to the stainless steel tubing.
An inline stainless steel check valve is absolutely necessary for the exit gas,
as back flow is a common problem with these systems. Without one, your
methylamine/methanol solution will most certainly be sucked back into the
pressure balancer or the drying tube. Again, the use of chemical resistant
valves on this apparatus is a must. If the valve is resistant to ammonia
according to a chart, it will very likely be resistant to methylamine as well.
21. Safety Considerations
Because we are using many chemicals, some toxic, corrosive, and poisonous
in high concentrations, it is necessary and relatively easy to exercise safe
procedure for both the workers and the environment.
Full face masks with the proper, corresponding filter cartridges, are a bare
minimum in this work environment while using hazardous chemicals. When
hazardous chemicals are not being used, particle masks should be worn at all
times to avoid contamination of the yeast cultures or fermenters.

Filter cartridges only remove the majority of the pollutants, and really never
all the pollutants, so for certain times this can present a problem. Overall, it is
healthier and sometimes a better idea to use supplied air. Working around
methylamine in particular warrants the use of supplied air, or during times of
very high bleach concentrations in the facility.
A supplied air system is shown in FIG. 26. The face mask is always positively
pressurized with air, so there is generally no possibility of breathing any of the
pollutants unless the mask isnt fitted properly.
Supplied air comes from an air compressor, where we have been quite
successful using electric air compressors intaking outside air. An Egress bottle
is a small compressed air cylinder worn on the workers belt, so that a loss of
air pressure will still allow several minutes of breathable air and time to exit a
toxic environment.
The main concern is that you avoid using a gas/fuel operated compressor, or a
compressor would have means of bringing in polluted air. Wherever the
compressor is located, clean air must be a priority. Also, wearing an Egress
bottle on the operators waste will allow for some air while he/she is walking
to the air hose, where complete protection from environmental air is a priority.
Gloves are always a concern. I prefer to have several different types of gloves
for different parts of any process.
So for example, thin neoprene gloves are the best option for tedious tasks that
dont require working with strong chemicals, such as when one is in the clean
room inoculating Petri dishes. On the other hand, thick chemical resistant
gloves that extend almost up to the elbow is necessary when dealing with some
chemicals such as solvents, acids, and bases.

FIG. 26