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By means of GC-MS analysis three impurities, amphetamine, N,N-dimethylamphetamine and phenyl-2-propanol could be found in methylamphetamine synthesized by a high pressure reductive amination of methylamine and benzylmethylketone.
ln the last two years several workshop equipped for the production of illicit amphetamine were discovered in the Netherlands. The amphetamine was produced mainly to supply the Scandinavian drugmarket, but a minor portion of it was sold in Holland.
It appeared that the substance was off-white and sometimes a bit yellow and mostly it smelled peculiar.
In nearly all cases the amphetamine was synthesized by means of a Leuckart reaction in which benzylmethylketone is heated at elevated temperatures with twice its volume of formamide. It is clear that incomplete conversions and side reactions can easily take place in this type of condensation reactions and many impurities could thus be expected in illegal amphetamine, the actual presence depending on the fact whether or not the crude amphetamine is purified in the right way. By means of Mass spectrometry and NMR spectroscopy we succeeded in identification of two pyrimidines1, a dihydropyridone2 and five pyridines3,4,5 as impurities in Leuckart amphetamine.
Until now methylamphetamine has not been produced in this country by the Leuckart synthesis, as is usually done in the USA, although recently a production location was discovered, in which methylamphetamine is as synthesized by a reductive amination. The general procedure was a follows: In a high pressure vessel supplied with an external heating mantle, hydrogen at high pressure was let in a heated mixture of benzylmethylketone, methylamine and Raney nickel in methanol. After a short time the reaction had taken place and the methylamphetamine was distilled from the filtered reaction mixture under lowered pressure. Furtheron the methyl amphetamine was treated with hydrochloric acid, recrystallized and dried.
In this report we describe amphetamine, N,N-dimethylamphetamine and phenyl-2-propanol as impurities in methylamphetamine obtained by high pressure reductive amination. As the impurities in methylamphetamine produced by the Leuckart method are of quite different nature: compounds like α-benzyl-N-methylphenethylamine, N-methyldiphenethylamine, α,α-dimethyldiphenethylamine and N,α,α-trimethyldiphenethylamine are known from literature6, we are of opinion that differentiating between the two modes of synthesizing methylamphetamine is possible by merely comparing the impurities.
A portion of the acidic reaction mixture was concentrated on a waterbath and extracted alter cooling with diethyl ether. Next the water layer was made alkaline and extracted with diethyl ether again. The organic layer was re-extracted under acidic conditions (pH 2.0) and the water layer which was made alkaline (pH 9.0) was extracted again with diethyl ether.
One microliter of the latter extract was injected in a Varian MAT 111 GC-MS combination fitted with a Varian MAT Spectro System 100 MS, giving rise to the reconstructed chromatogram of Figure (see Abb. 1 German Version). The chromatographic conditions were: column two meter s.s., 1/8" diam. filled with Apiezon L KOH 10%/10% on Chromosorb G DMCS 80-100 mesh; Column oven-temperature 100°C.; carrier gas helium, flowrate 10 ml/min. 70 eV Electron impact mass spectra were taken.
From the mass spectra and the retention times of the pure compounds it could be concluded that the peaks appeared to be phenyl-2-propanol (I), amphetamine (II), methylamphetamine (III) and N,N-dimethylamphetamine (IV).
So far we discussed the impurities found in the reaction mixture, but they are present too in the final product, being more or less purified. Apart from the described impurities caffeine was found in the latter, this substance was mixed with methylamphetamine — in percentages up till ten — by the producer for unclear reasons.
The explanation of the existence of phenyl-2-propanol, the major impurity — to be found in percentages of the total weight — is straight forward. It can be thought in originating by hydrogenation of benzylmethylketone, one of the starting products. rhe occurrence of the other two impurities found in much smaller quantities - tenths of percent - present more difficulties. In our view these substances emanate from reductive amination with ammonia and dimethylamine present in the other starting material methylamine, which is processed in bulk by the reaction of ammonia and methanol.
Although the occurrence of N,N-dimethylamphetamine in methylamphetamine produced by Leuckart reaction is known6, we believe that the simultaneously presence of the above mentioned impurities gives us a good means in differentiating of methylamphetamine synthesized by reductive amination and the Leuckart reaction. The more as complicated impurities like phenethylamines6 should be found in the latter case.