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Clandestine manufacture of 3,4-methylenedioxymethylamphetamine (MDMA)
by low pressure reductive amination

A Mass Spectrometric study of some reaction mixtures

A.M.A. Verweij
Forensic Sci. Int. 45, 91-96 (1990)

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Summary

Attention is paid here to a synthesis of MDMA consisting of a low pressure reductive amination of 3,4-(methylenedioxy)phenylpropanone with methylamine. The structures of several compounds present in reaction mixtures were elucidated by means of mass spectrometry

Introduction

As a result of the increasing popularity amongst drug users of 3,4-methylenedioxymethylamphetamine (MDMA), the drug was brought under the regulations of the Dutch Opium Law in the course of 1988. Rumours began to circulate last Autumn, concerning the production of MDMA (Ecstasy) in this country and these lasted several months until an actively operating production location was discovered and dismantled by police.

The process of synthesizing MDMA followed there can be described as a low pressure reductive amination at slightly elevated temperature. The recipe was: a mixture of 3,4-methylendioxyphenylpropanone and methylamine in alcohol was added slowly and under temperature control to aluminium powder freshly treated with mercuric chloride in EtOH. Then the temperature of the reaction mixture was raised and kept at the boiling temperature of alcohol for several hours. MDMA was isolated by distillation under reduced pressure, and a further cleanup was done by introduction hydrochloric gas into an alcoholic solution of MDMA.

Results are given here of the gas chromatographic-mass spectrometric investigation of several reaction mixtures at different reaction stages of the low pressure reductive amination, found in an illegal laboratory. This was done in order to get a better understanding of the synthesis followed by the producers of illegal MDMA, and to ascertain the impurities which might be present in the final MDMA preparations.

Experimental

Spectroscopic conditions: EI mass spectra at 70 eV were taken on a Finnigan MAT 212 GC-MS combination, coupled to a Kratos DS90 computer system. In the low resolution mode M/dM = 1000 was used. Ion source and GC-MS interface temperature were 250C. The accelerating voltage was 3 kV, whilst an ionization current of 0.8 mA was used. Chromatographic conditions, column: Phase Sep OV-1 on fused silica, length 50 m, inner diameter 0.32 mm and 0.15 um film thickness. The oven was programmed from 50C to 250C at 5C per min. The carrier gas was He, flow rate was approximately 1.8 mL/min and the split ration was 5:1.

Results and discussion

In our previous work regarding impurities in illicit drug preparation1,2 attention was paid principally to the syntheses of amphetamine and methylamphetamine. Especially the Leuckart process for the production of amphetamine was discussed in detail3. A high pressure reductive amination procudure for the production of methylamphetamine was found4 to be operative in this country. Benzylmethylketone and methylamine were the starting materials in that process, and hydrogenation took place with Raney nickely and hydrogen. Impurities like amphetamine, N,N-dimethylamphetamine and phenylpropanol-2 were found in minor quantities in illegal methylamphetamine. The explanation of the existence of phenylpropanol-2 was straightforward, it was thought to originate from the hydrogenation of benzylmethylketone with ammonia or dimethylamine, both impurities are present in the other starting material methylamine.

Tables (1 and 2 combined, MS data dropped)

No. CompoundM.W.
1 1,2-(Methylenedioxy)-4-methylbenzene 136
2 3,4-(Methylenedioxy)benzaldehyde 150
3 Safrole 162
4 Isosafrole 162
5 1,2-(Methylenedioxy)-4-propylbenzene 164
6 3,4-(Methylenedioxy)phenylpropanone 178
7 1,2-Dimethoxy-4-propenylbenzene 178
8 MDA179
9 1-(3,4-Methylenedioxy)phenylpropanol-2 180
10 1,2-(Methylenedioxy)-
4-(2-N-methyliminopropyl)benzene
191
11 MDMA193
12 N,N-dimethyl-(1,2-methylenedioxy)-
4-(2-aminopropyl)benzene
207
13 N-Ethyl-N-methyl-(1,2-methylenedioxy)-
4-(2-aminopropyl)benzene
221

The low pressure reductive amination of 3,4-methylenedioxyphenylpropanone with methylamine under hydrogenation by Al(Hg) in boiling EtOH, is a synthesis of similar nature as the procedure for the production of methylamphetamine. It is to be expected, therefore, that impurities to be found in MDMA, are as common as those in methylamphetamine. In Fig 2 a total ion chromatogram is given of a representative reaction mixture of the reductive amination of 3,4-methylenedioxyphenylpropanone and methylamine. The chromatographic peaks are numbered according to increasing molecular weight of the compounds. The nomenclature used together with molecular weights of the compounds are collected in Table 1. Structure elucidation of the different compounds was obtained by using, if possible, the mass spectra and retention times of standard compounds. Some mass spectra were found in libraries5-7, while in other cases the general properties of mass spectra were applied. The ions m/z 77, 105, 135 (in combination) appeared to be of diagnostic value for the methylenedioxymethylbenzene group, whereas the nitrogen containing compounds were governed by the ions m/z of either 44, 58, 72 or 86 due to charge localisation by nitrogen. In Table 2 and eight peak index of the mass spectra is given. Some additional compounds present in other reaction mixtures than the one mentioned complete the tables.

The nature and the origin of the compounds present in the reaction mixtures deserve some further attention. First the non-nitrogen compounds. The existence of safrole and isosafrole can be interpreted on the basis of the well known method of preparing the starting ketone, 3,4-methylenedioxyphenylpropanone, of the MDMA synthesis by oxidising safrole or isosafrole by hydrogen peroxide in an acid medium. As hydrogenation is a basic step in the reaction they hydrogenated forms of the ketone, the alcohol 1-(3,4-methylenedioxy)phenylpropanol-2 can be present. Further hydrogenation of safrole, isosafrole and the alcohol can give rise to the presence of 1,2-(methylenedioxy)-4-propylbenzene. The aldehyde 3,4-(methylenedioxy)benzaldehyde is thought to be an impurity of the starting ketone, whereas 1,2-(methylenedioxy)-4-methylbenzene is its hydrogenation product. The dimethoxy compound 1,2-(dimethoxy)-4-propenylbenzene is like-wise thought to be an impurity of the starting material.

Finally some remarks are given here on the nitrogen compounds found in the reaction mixtures. The synthesis of MDMA by reductive amination of 3,4-methylenedioxyphenyl-2-propanone and methylamine was not unsuccessful as regards to the yields of MDMA. But a fair amount of nitrogen containing impurities was found to be present in the reaction mixtures (see Fig 2). As a matter of fact the methylamine could have been contaminated with ammonia, dimethylamine and ethylmethylamine, in that way the occurrence of the other nitrogen compounds can be explained. The presence of the imine 1,2-(methylenedioxy)-4-(2-N-methyliminopropyl)benzene, an intermediate product, points specifically to the type of reaction used by the producers of illegal MDMA and can be of importance as "route specific" impurity.

Of course the presence of the compounds as impurities in the final drug preparations, will depend on the degree of the purificiation of MDMA by the illegal producers.

References

  1. A Sinnema et al. Impurities in illegal amphetamine. A review. Bull Narc 33 (1981) 37-54
  2. AMA Verweij et al. Impurities in illegal drug preparations. Amphetamine and methylamphetamine. A review. Forensic Sci. Rev. 1(1), 1-11 (1989)
  3. AM vd Ark et al. Weakly basic impurities in illicit amphetamine. J Forensic Sci 23 (1978) 693-700
  4. AM vd Ark et al. Verunreinigungen in illegalem amphetamin. Arch Krim 162, 171-175 (1978)
  5. An eight peak index of mass spectra. The Royal Society of Chemistry, Nottingham 1983
  6. EPA/NIH Mass spectral data base. US Department of Commerce, Washington 1978
  7. An eight peak index of mass spectra compiled specifically for the use in Forensic Science. HOCRE report 448, Aldermaston 1982