Dariusz Błachut

Identification and synthesis of some contaminants present in 4-methoxyamphetamine (PMA) prepared by the Leuckart method

The clandestine synthesis of ring and side chain modified phenylisopropylamines continues to be a major source of these drugs of abuse. One method used for the synthesis of the amphetamine and related compounds involves the treatment of the appropriate ketone with formamide or ammonium formate followed by acid hydrolysis of intermediate N-formyl derivative. In this paper the synthesis of 4-methoxyamphetamine (PMA, 1) by the Leuckart method is investigated. The identification by means of gas chromatography-mass spectrometry (GC-MS) of methoxy derivative of N-(beta-phenylisopropyl)benzaldimine 9, methoxy derivative of N-(beta-phenylisopropyl)benzyl methyl ketimine 5, 1-(4-methoxyphenyl)-N-(4-methoxybenzyl)-2-propanamine 10, (RR/SS) and (RS) 1-(4-methoxyphenyl)-N-[2-(4-methoxyphenyl)-1-methylethyl]-2-propanamine 6a-6c, (RR/SS) and (RS)-1-(4-methoxyphenyl)-N-methyl-N-[2-(4-methoxyphenyl)-1-methylethyl]-2-propanamine 7a-7c, (RR/SS) and (RS)-1-(4-methoxyphenyl)-N-formyl-N-[2-(4-methoxyphenyl)-1-methylethyl]-2-propanamine 8a-8c in crude PMA, are reported. The identity of these compounds was confirmed by independent synthesis of reference compounds. The NMR, MS, IR data, stereochemistry and some chromatographic properties of synthesized compounds are discussed. Finally, the results of the GC-MS analysis of illicitly prepared tablets, containing PMA 1 and 4-methoxymethamphetamine (PMMA, 2), are outlined. The presence of 4-methoxydimethylamphetamine 11, 4-methoxyethylamphetamine 12, and 4-hydroxymethamphetamine 13 are reported in these tablets. The identity of 2, 11, and 12 was confirmed by their independent synthesis.

α-Phenylethylamine in illegally produced amphetamine

The possibility of simultaneous synthesis of α-phenylethylamine and amphetamine from mixture of acetophenone and benzylmethylketone was studied. The structures of specific impurities were predicted and these compounds were synthesized and finally found in reaction mixtures, as well as in the final product. The data collected by gas chromatography, proton and carbon magnetic resonance, Fourier transform infrared spectrometry and mass spectrometry are presented.

The analytical profile of some 4-methylthioamphetamine (4-MTA) homologues

The 4-methylthioamphetamine (4-MTA) is a sulphur-containing amphetamine-type stimulant (ATS), which appeared on the illicit market in Europe at the end of 90s. For the purpose of this study, several N-alkyl homologues of 4-MTA, including 4-methylthiomethamphetamine (4-MTMA), 4-methylthioethylamphetamine (4-MTEA), 4-methylthiodimethamphetamine (4-MTDMA), 4-methylthiopropylamphetamine (4-MTPA) and 4-methylthiobutylamphetamine (4-MTBA) were synthesized. The homologues were characterized by means of gas chromatography/mass spectrometry (GC-MS), infrared (IR) spectroscopy and the magnetic resonance spectroscopy ((1)H and (13)C NMR). The gas chromatography and mass spectrometry properties of their acetyl, trifluoroacyl (TFA), pentafluoropropionyl (PFP) and heptafluorobutyryl (HFB) derivatives were also investigated and discussed.

The synthesis and the structure elucidation of N,O-diacetyl derivative of cyclic 3-hydroxymelatonin

Melatonin was subjected to an oxidation to give 3-hydroxymelatonin. All spectroscopic data for this compound were collected. Ab initio calculations for both possible configurations were performed. X-ray data on N,O-diacetyl derivative of 3-hydroxymelatonin allowed the unambigous structure determination.

(2S)-1-(4-methoxyphenyl)-N-[(1R)-2-(4-methoxyphenyl)-1-methylethyl]-2-propanamine in crude p-methoxyamphetamine (PMA) produced by the Leuckart method

The synthesis and separation of both diastereoisomers of 1-(4-methoxyphenyl)-N-[2- (4-methoxyphenyl)-1-methylethyl]-2-propanamine as markers of clandestine p-methoxyamphetamine have been described. The stereochemistry of the meso diastereomer was established by crystallographic method.

The Thorpe-Ingold Effect in Cyclic Imides. Part III

- Reactivity of phenyllithium with a number of succinimide derivatives were studied. We have shown that the Thorpe-Ingold effect affected both the reaction products distribution and their structures. Regioselectivity of these reactions were rationalized. Structures were confirmed with NMR and crystallographic methods.

The synthesis, mass spectrometric properties and identification of some N,N-di-(β-arylisopropyl)formamides related to the synthesis of ring-modified amphetamines

This study examines the electron impact (EI) induced mass spectrometric behavior of several N,N-di-(β-arylisopropyl)formamides, which are connected to the Leuckart synthesis of some amphetamine analogues. Emphasis is laid on the fragmentation paths, which are common for all compounds under investigation and may be used in construction of the prediction scheme useful for identification of similar impurities, especially in absence of desirable authentic material. On the basis of this scheme several new N,N-di-(β-arylisopropyl)formamides have been identified in selected amphetamine analogues synthesized by the Leuckart method, including 4-methylthioamphetamine (4-MTA), 4-fluoroamphetamine (4-FA), 4-methylamphetamine, 3-trifluoromethylamphetamine, 3,4-methylenedioxyamphetamine (MDA), 2,5-dimethoxyamphetamine (2,5-DMA), 2,4,5- and 3,4,5-trimethoxyamphetamines (2-TMA and 3-TMA).

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

Summary A series of differently substituted 3,5-diaryl-2,4,6-trimethylpyridines were prepared and characterized using the Suzuki–Miyaura coupling reaction with accordingly selected bromo-derivatives and arylboronic acids. The reaction conditions were carefully optimized allowing high yield of isolated products and also the construction of unsymmetrically substituted diarylpyridines, difficult to access by other methods.

Identification of common impurities present in the synthetic routes leading to 4-methylthioamphetamine (4-MTA). Part II: Reductive amination and nitropropene route

In this paper the by-products arising during the synthesis of 4-methylthioamphetamine (4-MTA) by LiAlH(4) reduction of 1-(4-methylthiophenyl)-2-nitropropene (nitropropene route) and reductive amination of 4-methylthiophenyl-2-propanone in the presence of NaCNBH(4) are investigated. The identification of 4-methylthio derivatives of N-(β-phenylisopropyl)benzaldimine, 4-methylthio derivative of N-(β-phenylisopropyl)benzyl methyl ketimine, 1-(4-methylthiophenyl)-N-(4-methylthiobenzyl)-2-propanamine, (RS) and (SS/RR)-N,N-di-[β-(4-methylthiophenyl)isopropyl]amine, 4-methylthiobenzyl ether and methylthiobenzoic acid methyl ester as most prominent impurities in crude 4-MTA synthesised by reductive amination of 4-methylthiophenyl-2-propanone, is reported. Methylthio derivatives of 2-methyl-3-phenylaziridine, 2-benzylaziridine, and 4-methylthio derivative of BMK oxime as route-specific markers of nitropropene route leading to 4-MTA, were also characterized. The identity of these compounds was confirmed by their independent synthesis.

Efficient synthesis of differently substituted triarylpyridines with the Suzuki-Miyaura cross-coupling reaction

A library of differently substituted 3,4,5-triaryl-2,6-dimethylpyridines and 2,3,5-triaryl-4,6-dimethylpyridines were synthesized and characterized using the Suzuki-Miyaura cross-coupling reaction with accordingly selected tribromodimethylpyridines and arylboronic acids. The optimized coupling conditions were found to be general for both isomeric tribromodimethylpyridines and a wide range of arylboronic acids substituted with electro-donating and electro-withdrawing groups.