Synthesis of 4-methyl-5-arylpyrimidines and 4-arylpyrimidines: route speci®c markers for the Leuckardt preparation of amphetamine, 4-methoxyamphetamine, and 4-methylthioamphetamine

Abstract General synthetic routes to 4-methyl-5-arylpyrimidines and 5-arylpyrimidines are described. 4-Benzylpyrimidine, 4-methyl-5-phenylpyrimidine, 4-(4-methoxybenzyl)pyrimidine, and 4-methyl-5-(4-methoxyphenyl)pyrimidine have been positively identi®ed as route-speci®c by-products in the Leuckardt preparations of amphetamine and 4-methoxyamphetamine. Using headspace solid phase microextraction (SPME) 4-(4-methoxybenzyl)pyrimidine and 4-methyl-5-(4-methoxyphenyl)pyrimidine have been identi®ed in illicit tablets containing 4-methoxyamphetamine. This is an indication that illicit laboratories use the Leuckardt method for the preparation of 4-methoxyamphetamine. Flatliner tablets containing 4-methylthioamphetamine have been screened for the presence of 4-(4-methylthiobenzyl)pyrimidine and 4-methyl-5-(4-methylthiophenyl)pyrimidine using both headspace and aqueous phase SPME. As these pyrimidines were not detected it would appear likely that illicit laboratories are not using the Leuckardt method for the preparation of 4-methylthioamphetamine.

A theoretical study of the mechanism of rearrangement of dihydropyrimidines into pyrroles

Pyrimidines, pyrroles, cycloreversion,CO extrusion, Two possible mechanisms for the transformation of a 1,4-dihydropyrrolo[3,2-b]pyrrole derivative into a tetrasubstituted pyrrole have been studied theoretically and one of them has been found in reasonable accord with the experimental data. This mechanismis part of the very rare example of rearrangement of dihydropyrimidines into pyrroles

Deep Eutectic Solvents as Non-innocent and Environmentally Responsible Reaction Media for the Divergent Synthesis of Valuable N-Heterocycles from Azides

The increasing demand for environmentally friendly chemical processes has led to the development of more efficient and profitable strategies for the preparation of heterocyclic compounds with a low ecological footprint. Over the last few years, our group focused on the sustainable synthesis of functionalized heterocycles such as tetrahydrofuran, thiophene, pyridyl and indolyl derivatives in the so-called Deep Eutectic Solvents (DESs), which represent an emerging generation of bio-based solvents. In this communication, we report the divergent synthesis of a collection of valuable N-heterocycles like 2,5-diarylpyrazines, 2-aroylimidazoles, 2,4-diaroyl-6-arylpyrimidines, and 1,2,3-triazoles, which are important scaffolds in many biologically active and pharmaceutically relevant molecules,6 simply starting from substituted azides as substrates, and using DESs as both biodegradable solvents and effective catalysts, under mild conditions

4-(5-tert-Butyl-1,3-dithian-2-yl)-5-chloro-2-phenyl-1,3-oxazole

In the title mol­ecule, C17H20ClNOS2, the phenyl and oxazole rings are nearly coplanar with an average deviation of 0.022 Å from the mean plane (M). The 1,3-dithiane ring adopts a chair conformation and is twisted in such a way that the C—CBu fragment lies in M (deviations are 0.031 and 0.010 Å, respectively, for the two C atoms)

‘APAAN in the neck’ - A reflection on some novel impurities found in seized materials containing amphetamine in Ireland during routine forensic analysis.

This perspective examines amphetamine importations into Ireland. Some novel by-products were detected and linked to a change in the method of production of P2P from APAAN. These by-products remained present during subsequent Leuckart reaction conditions. Novel by-products from substituted cathinone synthesis reactions were also isolated and characterized

Novel 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidine derivatives and their antitrypanosomal activities against T.brucei

Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense and is invariably fatal unless treated. Current therapies present limitations in their application, parasite resistance, or require further clinical investigation for wider use. Our work, informed by previous findings, presents novel 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidine derivatives with promising antitrypanosomal activity. In particular, 32 exhibits an in vitro EC50 value of 0.5 µM against Trypanosoma brucei rhodesiense, and analogues 29, 30 and 33 show antitrypanosomal activities in the <1 µM range. We have demonstrated that substituted 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidines present promising antitrypanosomal hit molecules with potential for further preclinical development

A NEW AND FACILE SYNTHESIS OF 5-ARYLPYRIMIDINES AND 4-ARYLPYRAZOLES

A condensation of 2-aryl-3-(methylthio)acroleins (3a)-(3e), a new masked form of arylmalondialdehydes, with amidines yielded the corresponding 5-arylpyrimidines (4a)-(4k). Similarly, the reaction of 3 with N-substituted hydrazines gave the corresponding 1-substituted 4-arylpyrzolone.s (5a)-(5j)