RARE CLANDESTINE SYNTHESIS ROUTE FOR

METHYLAMPHETAMINE AND ITS PRECURSOR IN NSW

Todd McBriar and Una Culllinan
Division of Analytical Laboratories (DAL), Sydney, NSW, Australia
BACKGROUND DISCUSSION-SYNTHESIS DISCUSSION-ANALYSIS-CONT
METHYLAMINE SYNTHESIS: The acidic condensation of ammonium chloride (refer to 6a 6b 6c
In December 2009, the NSW police drug squad submitted to the pic 1) with formaldehyde (fig 4a) in a 1:2 molar ratio produces the imine intermediate [X].
NSW illicit drug laboratory a number of items that were related The imine is reduced to methylamine (fig 4b). Obtain 50-95% yield. The excess
to the clandestine manufacture of methylamphetamine (MA) formaldehyde condenses the methylamine to dimethylamine (fig 4c). The dimethylamine
and its controlled precursor-phenyl-2-propanone (P2P). Several impurity in the starting material produces the side-product N,N-dimethylamphetamine in
factors made these submissions worthy of note (Table 1): the finished product. The lower the reflux temperature the better the yield [4] & [5]. 6d 6e 6f 6g
Benzyl cyanide -keto ester
The submission consisted of a commercial quantity of high FIG 4a [X] [X] FIG 4b MA MA
purity methylamphetamine

5.6 kgs of an unusual precursor- -acetylphenylacetonitrile-

which indicated a rare synthesis procedure was being
utilised. Presumably to avoid detection from the relevant
authorities
The identification of two materials that indicated a series of
clandestine procedures to synthesise not only finished
product, but starting reagents and precursors such as P2P
PIC 1
AIMS/OBJECTIVES
To outline the reaction pathway to synthesise starting
materials like methylamine HCL and dimethylamine HCL
FIG 4C Based on 586.1 g of ammonium chloride
submitted. The total amount of methylamine
HCL produced = 370g (assume 50% yield).
Refer to pic 2 for submitted case item.
PIC 2
fingerprint overlay profile of the MA samples. Refer to Table 1 [1] -[5]. Fig
PROFILING ANALYSIS: Preliminary profiling analysis was based on
previous work [1]-[3]. Due to availability, analysis was attempted on DB-17 &
HP-1 columns (vs DB-5 & Ultra 2).The HP-1 proved to be more selective in
resolving impurities vs the DB-17. Samples were dissolved in 4:1 buffer:10%
Na2CO3 and extracted in 0.5mL solvent. GCMS parameters were: 1.0L
pulsed splitless injection, Oven 50oC (1min), then 10oC/min to 300oC (10min).
He carrier gas at 1.0mL/min, inj/transfer line 230oC/300oC. Fig 7a outlines the
7b-7d tentatively indicates the impurities/route markers of the MA synthesis.

To outline the stepwise reaction pathway to synthesise firstly, 7a 7b 7c 7d

-acetylphenylacetonitrile, then P-2-P -acetyl-phenylacetonitrile: Reflux 2 moles of benzyl cyanide and 3 moles of ethyl acetate in a
hot solution of sodium ethoxide for 2 hours, stand overnight (fig 1). The sodium salt product TIC PROFILES OF

To outline and discuss the Schiff base and Leuckart pathways (69-76% yield) is dissolved in water, cooled and acidified. Producing the dry base product (59- MA SAMPLES
[5]
for the synthesis of methylamphetamine 64% yield) [6] & [7] . Refer to pic 3 and pic 3 zoom for submitted case items. N,N-
dimethylamphetamine
[4]
[2]

To present the analytical data (GCMS, UPLC & FTIR) from PIC 3 PIC 3 zoom [1]
the examination of the submitted items [3]

To undertake preliminary qualitative GC-MS profiling based

on previous work by the UNDCP (1999) [1], Zhang et al [2] and
Sasaki et al [3] . This was attempted to ascertain the probable
route used by the illicit chemist
NOTE: The profiling was attempted utilising the current in-
house columns available (30m D-17 & 15 m HP-1)
FIGURE 1
P2P: The dry -keto ester product is distilled with conc H2SO4 and water for several hours. The ketone
layer is separated, washed and filtered (77-86% yield) [7] & [4]. Based on 200g lots of the -keto ester
starting material the submitted quantity of 5.6kgs could yield up to 4.2kgs of P2P.
MA synthesis: The Schiff base pathway involves the condensation of P2P with methylamine, which is
reduced via an imine intermediate to MA (fig 2). The methylamine can be present in solution (40%) or
as a salt. (Typical yield = 70%) [8].
MA synthesis: The Leuckart pathway (fig 3) involves the substitution of a formamide with a ketone.
Based on 4.0g lots of methylamine HCL starting material the submitted quantity of 2.63kg could yield
up to 2.28kg of the formamide (99% yield). Refluxing the formamide with P2P (170-1900C) produces
the N-formyl intermediate which via acid hydrolysis produces MA (Typical yield=43%) [4], [8]-[9] .
MA yield-Schiff base: Based on 4.2kgs of P2P with Al metal would yield 4.07kgs MA HCL (requires
11.76kgs of 40% methylamine). Based on 3.0kgs of methylamine HCL, with NaBH4 would yield 3.0kgs
RESULTS
Synthesis: The use of -acetylphenylacetonitrile to produce P2P is a dated
method that is rarely seen in Australian clandestine operations, and the first to
be seen in NSW. It appears illicit chemists are attempting to avoid detection by
producing starting material in-house rather than importing or diverting it
from other means. Depending on the synthetic route use, Schiff vs Leuckart,
the MA HCL produced varies (4.07kgs vs 2.52kgs).
Profiling: The preliminary findings indicate the MA submitted could possibly
originate from the same batch (7a). Based on the impurities found (7b & 7d)
and the route specific marker/intermediate (7c), the likely synthesis method
was tentatively identified as the Leuckart method (refer to figure 3).
REFERENCES
[1] B.Remberg, A.H. Stead, Drug characterization/impurity profiling, with special focus on methamphetamine: recent work of the United Nations Drug Control Programme, Bull. Narcotics LI
(1999) 97-117.
[2] J.X. Zhang, D. M Zhang, X.G. Han, Identification of impurities and statistical classification of methamphetamine hydrochloride drugs seized in China, Forensic Sci. Int, 182 (2008) 13-19.
[3] T. Sasaki, Y.Makino, Effective injection in pulsed splitless mode for impurity profiling of methamphetamine crystal by GC or GC/MS, Forensic Sci,. Int 160 (2006) 1-10.
[4] U.Fester, Secrets of methamphetamine manufacture, 7th ed Loompanics Unlimited, Washington, Chapter 13 pgs 109-111.
[5] H.I, Jones, The Preparation of Methylamine, J.Am.Chem. Soc, (1918) pgs 411-1515
[6] Organic Syntheses, Coll. Vol. 2, p.487 (1943); Vol. 18, pgs.487-489 (1938).
[7] Organic Syntheses, Coll. Vol. 2, p.487 (1943); Vol. 18, pgs 391-392 (1938).

of MA HCL (requires 2.97kg P2P) . Based on 3.0kgs of methylamine HCL would produce 5.0kgs of 40% [8] M.White, FSS report on methylamphetamine, The ACMD working group on methylamphetamine, Oct 2004.
[9] J.Cappon, Preparation of N-Methylformamide, Rec.Trav.Chim.Pays-Bas (1994) 113,318.
[10] M.Pearson, J.Hugel, T.Evoy, Drug Yield Calculator, Software Application, Ver 7.0.
solution (assume 0.7 density), yielding 1.7kgs MA HCL (requires 1.8kgs of P2P with Al metal) [10].
TABLE 1: INVENTORY OF SUBMITTED ITEMS
MA yield-Leuckart: Based on 4.2kgs of P2P would yield 2.52kgs of MA HCL PACKAGING FORM COMPOUND USE/ROLE MASS %PURITY
(GRAMS)
(requires 10.92kgs of 40% methylamine). Based on 3.0kgs of methylamine
HCL would produce 5.0kgs of 40% solution, yielding 1.15kgs MA HCL plastic bag compressed substance methylamphetamine [1] illicit drug 229.0 77.5

FIGURE 2 (requires 1.9kgs of P2P) [10]. 3 plastic bags compressed substance methylamphetamine [2] illicit drug 286.2 77.0
2 plastic bags compressed substance methylamphetamine [3] illicit drug 57.1 73.5
plastic bag compressed substance methylamphetamine [4] illicit drug 28.4 74.5
DISCUSSION-ANALYSIS plastic bag pasty substance methylamphetamine [5] illicit drug 5.7 61.5
2 plastic bags lumpy substance methylamphetamine illicit drug 231.5 8.5
CASE WORK ANALYSIS: The items in Table 1 were examined using a 7 plastic bags green powder -acetylphenylacetonitrile precursor to 5600 not
combination of GCMS, FTIR & UPLC. Figs 6a-6g outline the typical (REFER PIC 3) P2P determined
results obtained for ammonium chloride (FTIR-6a), -keto ester (FTIR 4 plastic bags compressed or wet methylamine HCL starting material for 2627.9 not
& GCMS-6b, 6e), methylamine HCL (FTIR- 6c) benzyl cyanide (GCMS- crystalline substance (REFER PIC 2) MA synthesis determined
printed by 6d), MA (GCMS & UPLC-6f, 6g).
3 plastic bags & powder ammonium chloride starting material for 586.1 not
www.postersession.com plastic (REFER PIC 1) methylamine synthesis determined
FIGURE 3 container