Identification and synthesis of by-products found in 4-methylthioamphetamine (4-MTA) produced by the Leuckart method

Forensic Science International

Volumn 216, Issue 1-3, 2012, Pages 108-120

  Błachut, Dariusz ^a   Wojtasiewicz, Krystyna ^b   Krawczyk, Krzysztof ^b   Maurin, Jan ^c,d   Szawkało, Joanna ^b   Czarnocki, Zbigniew ^b  

^a Agencja Bezpieczenstwa Wewnetrznego Warszawa   (Poland)

^b UNIVERSITY OF WARSAW   (Poland)

^c NATIONAL MEDICINES INSTITUTE   (Poland)

^d INSTITUTE OF ATOMIC ENERGY   (Poland)

Author keywords

Amphetamine analogues; Impurities; Leuckart synthesis

Indexed keywords

2,4 DIMETHYL 3,5 DI(4' METHYLTHIOPHENYL)PYRIDINE; 2,6 DIMETHYL 3,5 DI(4' METHYLTHIOPHENYL)PYRIDINE; 4 (4' METHYLTHIOBENZYL)PYRIMIDINE; 4 METHYL 5 (4' METHYLTHIOPHENYL)PYRIMIDINE; 4 METHYLBENZALDEHYDE; 4 METHYLTHIOAMPHETAMINE; 4 METHYLTHIOPHENYLACETONE; AMMONIUM FORMATE; AMPHETAMINE DERIVATIVE; FORMAMIDE; FORMIC ACID; N,N DI[BETA (4 METHYLTHIOPHENYL)ISOPROPYL]AMINE; N,N DI[BETA (4 METHYLTHIOPHENYL)ISOPROPYL]FORMAMIDE; N,N DI[BETA (4 METHYLTHIOPHENYL)ISOPROPYL]METHYLAMINE; SCHIFF BASE; UNCLASSIFIED DRUG;

ACID HYDROLYSIS; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CHEMICAL REACTION; CONTAMINATION; CONTROLLED STUDY; CRYSTALLOGRAPHY; HYDROLYSIS; LEUCKART METHOD; MASS FRAGMENTOGRAPHY; MASS SPECTROMETRY; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; STEREOCHEMISTRY; SYNTHESIS;

EID: 84857503340     PISSN: 03790738     EISSN: 18726283     Source Type: Journal    
DOI: 10.1016/j.forsciint.2011.09.005     Document Type: Article

References (50)

1. Rösner P., Quednow B., Girreser U., Junge Th. Isomeric: fluoro-methoxy-phenylalkylamines: a new series of controlled-substance analogues (designer drugs). Forensic Sci. Int. 2005, 148:143-156.
2. Westphal F., Rösner P., Junge Th. Differentiation of regioisomeric ring-substituted fluorophenethylamines with product ion spectrometry. Forensic Sci. Int. 2010, 194:53-59.
3. Mahar H.M., Awad T., DeRuiter J., Clark C.R. GC-MS and GC-IRD studies on dimethoxyamphetamines (DMA) regioisomers related to 2,5-DMA. Forensic Sci. Int. 2009, 192:115-125.
4. Shulgin A.T., Sargent T., Naranjo C. Structure-activity relationships of one-ring psychotomimetics. Nature 1969, 221:537-541.
5. Shulgin A.T., Dyer D.C. Psychotomimetic phenylisopropylamines. 5. 4-Alkyl-2,5-dimethoxyphenylisopropylamines. J. Med. Chem. 1975, 18:1201-1204.
6. Staack R.F., Maurer H.H. New designer drug 1-(3,4-methylenedioxybenzyl)piperazine (MDBP): studies on its metabolism and toxicological detection in rat urine using gas chromatography/mass spectrometry. J. Mass. Spectrom. 2004, 39:255-261.
7. Abdel-Hay K.M., Awad T., DeRuiter J., Clark C.R. Differentiation of methylenedioxypiperazines (MDBP) by GC-IRD and GC-MS. Forensic Sci. Int. 2010, 195:78-85.
8. Westphal F., Junge T., Girreser U., Stobbe S., Pérez S.B. Structure elucidation of a new designer benzylpiperazine: 4-bromo-2,5-dimethoxybenzylpiperazine. Forensic Sci. Int. 2009, 187:87-96.
9. Cimbura G. PMA deaths in Ontario. Can. Med. Assoc. J. 1974, 110:1263-1267.
10. Holland G.F., Buck C.J., Weissman A. Anorexigenic agents: aromatic substituted 1-phenyl-2-propylamines. J. Med. Chem. 1963, 6:519-524.
11. European Monitoring Centre for Drugs and Drug Addiction Report on the Risk Assessment of 2C-I, 2C-T-2 and 2C-T-7 in the Framework of the Joint Action on New Synthetic Drugs 2004, Office for official publication of the European Communities, Luxembourg.
12. Miyajima M., Matsumoto T., Ito S. Letter to editor: 2C-T-4 intoxication: acute psychosis caused by a designer drug. Psychiatry Clin. Neurosci. 2008, 62:243.
13. Huang X., Marona-Lewicka D., Nichols D.E. p-Methylthioamphetamine is a potent new non-neurotoxic serotonin-releasing agent. Eur. J. Pharmacol. 1992, 229:31-38.
14. Li Q., Murakami I., Stall S., Levy A.D., Brownfield M.S., Nichols D.E., Van de Kar L.D. Neuroendocrine pharmacology of three serotonin releasers: 1-(1,3-benzodioxol-5-yl)-2-(methylamino)-butane (MBDB), 5-methoxy-6-methyl-2-aminoindan (MMAI) and p-methylthioamphetamine (MTA). J. Pharmacol. Exp. Ther. 1996, 279:1261-1267.
15. Poortman A.J., Lock E. Analytical profile of methylthioamphetamine (4-MTA), a new street drug. Forensic Sci. Int. 1999, 100:221-233.
16. de Letter E.A., Coopman V.A.E., Cordonnier J.A.C.M., Piette M.H.A. One fatal and seven non-fatal cases of 4-methylthioamphetamine (4-MTA) intoxication: clinico-pathological findings. Int. J. Legal Med. 2001, 114:352-356.
17. Kirkbride K.P., Ward A.D., Jenkins N.F., Klass G., Coumbaros J.C. Synthesis of 4-methyl-5-arylpyrimidines and 4-arylpyrimidines: route specific markers for the Leuckart preparation of amphetamine, 4-methoxyamphetamine and 4-methylthioamphetamine. Forensic Sci. Int. 2001, 115:53-67.
18. Cloonan S.M., Keating J.J., Corrigan D., O'Brien J.E., Kavanagh P.V., Wiliams D.C., Meegan M.J. Synthesis and in vitro toxicity of 4-MTA, it characteristic synthesis by-products and related sulfur substituted α-alkylthioamphetamines. Bioorg. Med. Chem. 2010, 18:4009-4031.
19. Błachut D., Wojtasiewicz K., Czarnocki Z. Identification and synthesis of some contaminants present in 4-methoxyamphetamine (PMA) prepared by the Leuckart method. Forensic Sci. Int. 2002, 127:45-62.
20. Błachut D., Danikiewicz W., Wojtasiewicz K., Olejnik M., Kalinowska I., Szawkało J., Czarnocki Z. The synthesis, mass spectrometric properties and identification of some N,N-di-(β-aryloisopropyl)formamides related to the synthesis of ring-substituted amphetamines. Forensic Sci. Int. 2011, 206:197-206.
21. Allinger N.L., Wang G.L., Dewhurst B.B. Kinetic and mechanistic studies of the Dakin-West reaction. J. Org. Chem. 1974, 39:1730-1735.
22. Shulgin A., Shulgin A., Pihk A.L. A Chemical Love Story 1997, Transform Press, Berkeley, CA.
23. Yamanaka H., Sakamoto T., Nishimura S. Studies on pyrimidine derivatives. XXXIX. Site-selectivity in the reaction of 5-substituted and 4,5-disubstituted pyrimidine N-oxides with trimethylsilyl cyanide. Chem. Pharm. Bull. 1987, 35:3119-3126.
24. Błachut D., Wojtasiewicz K., Czarnocki Z. Some pyridine derivatives as route specific markers in 4-methoxyamphetamine (PMA) prepared by the Leuckart method. Studies on the role of the aminating agent in their distribution in the final product. Forensic Sci. Int. 2005, 152:157-173.
25. Błachut D., Czarnocki Z., Wojtasiewicz K., Suzuki-Miyaura A. Approach to s series of forensically relevant pyridines. Synthesis 2006, 2855-2865.
26. Uematsu N., Fuji A., Hashigichi S., Ikariya T., Noyori R. Asymmetric transfer hydrogenation of imines. J. Am. Chem. Soc. 1996, 118:4916-4917.
27. Huizer H., Brussee H., Poortman-van der Meer A.J. Di-(β-phenylisopropyl)amine in illicit amphetamine. J. Forensic Sci. 1985, 30:427-438.
28. Bailey K., Boulanger J.G., Legault D., Taillefer S.L. Identification and synthesis of di-(1-phenylisopropyl)methylamine. J. Pharm. Sci. 1974, 63:1575-1578.
29. Kram T.C. Reidentification of major impurity in illicit amphetamine. J. Forensic Sci. 1979, 24:596-599.
30. Theeuwen A.B.E., Verweij A.M.A. Impurities in illicit amphetamine. 7. Identification of benzyl-methyl ketone phenylisopropyloimine and benzyl methyl ketone benzylimine in amphetamine. Forensic Sci. Int. 1980, 15:237-241.
31. van der Ark A.M., Verweij A.M., Sinnema A. Weakly basic impurities in illicit amphetamine. J. Forensic Sci. 1978, 23:693-700.
32. Verweij A.M.A. Impurities in illicit drug preparation: amphetamine and methamphetamine. Forensic Sci. Rev. 1989, 1:1-11.
33. Anderson K., Lock E., Jalava K., Huizer H., Jonson S., Kaa E., Lopes A., Poortman-van der Meer A., Sippola E., Dujourdy L., Dahlén J. Development of a harmonised method for the profiling of amphetamines VI. Evaluation of the methods for comparison of amphetamine. Forensic Sci. Int. 2007, 169(8):6-99. (and earlier parts cited herein).
34. Lukaszewski T. Spectroscopic and chromatographic identification of precursors, intermediates, and impurities of 3,4-methylenedioxyamphetamine synthesis. J. Assoc. Off. Anal. Chem. 1982, 61:951-967.
35. Bohn M., Bohn G., Blaschke G. Synthesis markers in illegally manufactured 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymetamphetamine. Int. J. Legal Med. 1993, 106:19-23.
36. Hoffmann R.W. Allylic 1,3-strain as a controlling factor in stereoselective transformations. Chem. Rev. 1989, 89:1841-1860.
37. Eliel E.E., Wilen S.H. Stereochemistry of Organic Compounds 1994, John Wiley & Sons Inc., New York.
38. Szabo A., Ostlund N.S. Modern Quantum Chemistry: Introduction to Advanced Electronic Structure Theory 1982, Macmillan Publishing Co., Inc., New York.
39. Roszkowski P., Wojtasiewicz K., Leniewski A., Maurin J.K., Lis T., Czarnocki Z. Enantioselective synthesis of 1-substituted tetrahydro-β-carboline derivatives via the asymmetric transfer hydrogenation. J. Mol. Catal. A: Chem. 2005, 232:143-149.
40. Szawkało J., Czarnocki Z. Enantioselective synthesis of some tetracyclic isoquinoline alkaloids by asymmetric transfer hydrogenation catalysed by a chiral ruthenium complex. Monatsh. Chem. 2005, 136:1619-1627.
41. Sheldrick G.M. SHELXS98. Program for Solving Crystal Structures 1998, University of Goettingen, Germany.
42. Sheldrick G.M. SHELXL98. Program for Crystal Structure Refinement 1998, University of Goettingen, Germany.
43. Barder T.E., Walker S.D., Martinelli J.R., Buchwald S.L. New catalysts for Suzuki-Miyaura coupling processes: scope and studies of the effect of ligand structure. J. Am. Chem. Soc. 2005, 127:4685-4696.
44. Metzger A., Schade M.A., Knochel P. LiCl-mediated preparation of highly functionalized benzylic zinc chlorides. Org. Lett. 2008, 10:1107-1110.
45. Waumans D., Bruneel N., Tytgat J. Anise oil as para-methoxyamphetamine (PMA) precursor. Forensic Sci. Int. 2003, 133:159-170.
46. The ortho-effect in electron induced fragmentation of some heterocycles related to the chemistry of amphetamine analogues. 23rd Informal Meeting on Mass Spectrometry, Fiera di Primiero, Italy, 15-19 May 2005. Abstract Book (Poster P36).
47. Cohen T., Deets G.R. Trapping of picolyl cations in the reaction of 2- and 4-picoline N-oxide with acetic anhydride. J. Am. Chem. Soc. 1972, 94:932-938.
48. Płaziak A.S., Spychała J., Golankiewicz K. Stabilization of even-electron ions in 4-amino-substituted cytosines. Appearance of the strong ortho effect between an aryl substituent and the pyrimidinyl ring. Org. Mass Spectrom. 1989, 24:1045-1050.
49. Jariwala F.B., Figus M., Attygale A.B. Ortho effect in electron ionization mass spectrometry of N-acylanilines bearing a proximal halo substituent. J. Am. Soc. Mass Spectrom. 2008, 16:1114-1118.
50. Baldwin M.A., Loudon A.G., Maccoll A., Smith D. The formation of a five-membered-ring ion on electron impact. Chem. Commun. 1967, 35:0-351.