Preparation of Evidence in Illicit Amphetamine

Manufacturing Prosecutions
CECIL L. H I D E R
Criminalist, S a n Mateo County Sheriff's Dept., Redwood City, California

A discussion of the technique utilized in the illicit manufacture of amphetamine

i s presented. T h e chemical precursors and catalytic agents which m a y be encountered
are described. Due to the nature of the material, it i s suggested that the laboratory
staff be directly responsible for the collection, preservation, and presentation of
evidence seized in investigations of illicit amphetamine production.
During the years 1962-1963, the abuse of adrenergic or sympathomimetic
amines, and d-methylamphetamine in particular, reached an all time high in
California. This was in part due to its clandestine availability from some
doctors and pharmacists in the State. In 1964, newly enacted State statutes,
coupled with withdrawal of the compound from all but hospital use by one of
the leading manufacturers, led to the first illicit processing of the drug. The
first illicit processing in California was apparently by a few individuals who
procured the pure drug in salt form from the Eastern portion of the United
States. The drug was then dissolved in water and packaged in vials, similar
in appearance to the product marketed by the leading licit manufacturer. In
1966, Federal laws regulating certain restricted drugs, including the ampheta-
mines, rendered it virtually impossible for the illicit processor to obtain the drug.
By late 1966 and early 1967, much evidence of the illicit synthesis of ampheta-
mine was apparent. The most popular drug manufactured illicitly appears to be
methylamphetamine.
The most common chemical precursors used in illicit manufacturing are
methylamine and phenyl-2-propanone (phenylacetone). Precursor chemicals
often will be found in bottles labelled as such, or as by-products from the com-
pleted synthesis. The completed amphetamine product will normally appear
as a wine-red liquid, ye!low ethereal solution, or granular light brown powder.
On rare occasions the manufacturer will utilize activated charcoal to produce a
white product which is difficult or impossible to distinguish from legitimate
sources. I t is frequently observed that an illicit manufacturer, unsure of his
results by any given method, will acquire supplies for more than one method.
Many chemical supply houses will now notify authorities if amphetamine pre-
cursors are ordered or purchased, although possession of these materials does
not violate California or Federal laws. Cheap, superfluous chemicals are often
ordered in order t o avoid detection.
The practice of illicit amphetamine manufacturing has become prevalent in
several areas. This is in part due to the fact that the cookbook-like procedures
have been passed from hand t o hand, thereby providing many persons with an
ability to manufacture these drugs without actually possessing a detailed know-
ledge of chemical principles.
The most apparent feature noted by the analyst or investigator a t the scene
of an illicit laboratory will be the odor of diethyl ether or other solvents. The
equipment being utilized and the precursors will generally indicate whether
amphetamine or methylamphetamine is being manufactured. Precursors
which may be encountered, other than methylamine and phenylacetone, would
include ephedrine, benzylcyanide, and phenylacetic acid.
Diverse catalytic agents have been encountered in the illicit manufacture of
amphetamine and methylamphetamine. The most commonly employed
catalysts, however, are salts of nickel, platinum, and palladium. One may
occasionally expect to encounter thionyl chloride as well as salts of cobalt,
75
copper, and chromium serving as catalysts. The most common reducing
agent encountered is hydrogen, although several metals, such as sodium, are
easily employed.
In many instances the chemical precursors are not found, as illicit operators
often purchase only those amounts of chemicals necessary for one synthesis.
The precursors and other reactants may still be isolated, however, from the
finished amphetamine product or mother solutions. I n view of the nature of
the evidence in these cases, it is recommended that the analyst personally
collect or supervise the collection of evidence.
The following mechanisms depict the most common methods encountered in
cases involving illicit amphetamine manufacture :

Method 1

Phenylacetone Methylamine Methylamphetamine

This method involves reduction of a mixture of phenylacetone and aqueous

methylamine in ether. The reduction is accomplished by using hydrogen with
salt of palladium as the catalyst.

Phenylacetone Methylamine blethylamphetamine

In this method, the condensation products of phenylacetone and methyla-

mine are reduced by sodium metal in the presence of ethyl alcohol, and requires
approximately four weeks to react. Initially, ethyl alcohol, methylamine, and
phenylacetone are left at room temperature in a stoppered bottle and allowed
to react for approximately four weeks. Sodium metal, together with an excess
of ethyl alcohol, is added to this mixture for reduction. After reduction, water
is added, the ethyl alcohol evaporated, and the resultant solution steam dis-
tilled until the mother solution is no longer alkaline. Hydrochloric acid is used
for neutralization, and the insoluble portion is then extracted with ether. The
extract is condensed and precipitated with mercuric chloride. The mercury salt is
decomposed wit11 hydrogen sulfide, leaving the free base of methylamphetamine.

-
Ephedrine hle thylamphetarnine
 111 the third method, the catalytic hydrogenation of ephedrine is performed
in acetic acid containing a, small quantity of perchloric acid as an activator.
The hydrogenation is carried out between 80 and 90°C using palladium black
as the catalyst. Perchloric acid is removed as the insoluble potassium salt.
The product is distilled under reduced pressure to remove acetic acid. To the
aqueous solution of the residue is added an etheral solution of hydrochloric acid
to precipitate methylamphetamine.

Method 4

0'
\ / CHgirH3
Ephedrine
+ SOCl2

Thionyl chloride
CH3

-
Catalyst
Qcr2cxmcH3
I
CH3

In this synthesis, the replacement of the hydroxyl group of ephedrine

by the halogen atom is accomplished through the use of thionyl chloride. The
catalytic hydrogenation of the newly formed intermediate products yields
methylamphetamine.

Method 5

Phenylacetic acid Acetic acid Phenylacet one

Fomamide
Formic acid

This method involves the thermal acetylation and decarboxylation of phenyl-

acetic acid to phenylacetone. The phenylacetone is then subjected to the
Leuckart reaction, a reductive amination with formamide, formic acid, and
ammonium formate. The derivative from this reaction is hydrolyzed with
strong acid to yield amphetamine.
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 Method 6

Phenylacetone Amphetamine

The sixth synthesis employs the reductive amination of phenylacetone in the

presence of nickel catalyst and ammonia under pressure to deliver amphetamine.

Method 7

~ C % C O O H

Phenylacetic a c i d
+
Acetic
-0
( C H ~ C O ~ ) ~ ~
NaOAc
145-150°C
C%COCH~

Phenylacetone
anhydride

Hydroxylamine Oxime of Amphetamine

phenylacetone

I n this synthesis, phenylacetic acid is reacted with acetic anhydride and

sodium acetate between 145 and 150°C to prepare phenylacetone. Phenylace-
tone is then converted to its oxime by its reaction with hydroxylamine. The
oxime is then reduced to amphetamine.

hde thod 8

EtOAc
- H2S04

Benz y l c y a n i d e Phenylcyano
acetone

Phenylacetone Amphetamine

In this method, phenylacetone is prepared from benzylcyanide and ethyl

acetate in the presence of sodium alcoholate, through the intermediate formation
of phenylcyanoacetone. The phenylcyanoacetone is hydrolyzed by dilute
sulfuric acid t o phenylacetone, which is then converted to amphetamine by
methods outlined above.
78
 I t is apparent from the several methods and many reductive-catalytic systems
that the chemicals and apparatus found a t any given illicit laboratory site may
vary to a considerable extent. Once the method or methods of preparation
has been determined it will be necessary to insure by analysis that the yield
product was in fact prepared by that method for purposes of court testimony.
Many analytical techniques are available for the analysis. The presence of
primary or secondary amines may be determined, a separation of primary and
secondary amines may be effected through the use of the Hinsberg test, and
catalyst, precursors, and by-products identified. Final identification may be
accomplished by use of one or more tests which may involve microchemical
tests, infrared spectroscopy, gas or thin layer chromatography, and refracto-
metry.
In order to insure the thoroughness of preparation of the case for court
purposes, and in consideration of the technical nature of the evidence which
may be encountered, it is suggested that the responsibility for the collection,
preservation, and court presentation of evidence in illicit manufacturing of
amphetamine cases should rest with the laboratory staff.
References
AUGUSTINE, ROBERTL., 1965, Catalytic Hydrogenation, Marcel Dekker, New
York.
BURGER, ALFRED,1960, Medicinal Chemistry, 2nd Edition, Inter-science, New
York.
CALDWELL, D., and NORMAN EVERS,1959, The Chemistry of Drugs, 3rd Edition,
Interscience, New York.
MARTIN,ERIC W., et al, 1965, Remington's Pharmaceutical Sciences, 13th
Edition, Mack Publishing Co., Easton, Pa.