Quantum Chemical and Experimental Studies of an Unprecedented Reaction Pathway of Nucleophilic Substitution of 2-Bromomethyl-1,3-thiaselenole with 1,3-Benzothiazole-2-thiol Proceeding Stepwise at Three Different Centers of Seleniranium Intermediates.

Svetlana V Amosova,Nataliya A Makhaeva,Vladimir A Shagun,Irina A Novokshonova,Vladimir A Potapov

doi:10.3390/molecules26216685

Svetlana V Amosova, Nataliya A Makhaeva + Show 3 more

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https://doi.org/10.3390/molecules26216685

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Abstract

The results of quantum chemical and experimental studies of the reaction of 2-bromomethyl-1,3-thiaselenole with 1,3-benzothiazole-2-thiol made it possible to discover the unprecedented pathway of this reaction, which proceeds stepwise at three different centers of seleniranium intermediates. The first stage includes an attack of thiolate anion at the selenium atom of the seleniranium cation accompanied by ring opening with the formation of (Z)-2-[(1,3-benzothiazol-2-ylsulfanyl)selanyl]ethenyl vinyl sulfide, which is converted to six-membered heterocycle, 2-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)-1,3-benzothiazole, in a 99% yield. The latter compound undergoes rearrangement with ring contraction producing five-membered heterocycle, 2-[(1,3-thiaselenol-2-ylmethyl)sulfanyl]-1,3-benzothiazole, in a 99% yield (the thermodynamic product). The formation of 1,2-bis[(Z)-2-(vinylsulfanyl)ethenyl] diselenide is the result of the disproportionation of (Z)-2-[(1,3-benzothiazol-2-ylsulfanyl)selanyl]ethenyl vinyl sulfide. Thus, based on the quantum chemical and experimental studies, a regioselective synthesis of the reaction products in high yields was developed.

Highlights

More than 80% of modern drugs contain heterocyclic fragments in their structures [1].Nitrogen heterocycles are among the most significant structural components of pharmaceuticals
The present work is a necessary continuation of pioneering studies of the new methodology of nucleophilic substitution at three different centers of seleniranium intermediates in reactions of 2-bromomethyl-1,3-thiaselenole (1) with nucleophilic reagents (Scheme 1) [57,58,59,60,61]
It should be emphasized that the reactions of nucleophilic substitution at the selenium atom of seleniranium cations were unknown before our investigations

Summary

Introduction

More than 80% of modern drugs contain heterocyclic fragments in their structures [1]. Nitrogen heterocycles are among the most significant structural components of pharmaceuticals. Thiazole ranks sixth among the 27 classes of the most used nitrogen-containing heterocycles [2]. The thiazole ring is a structural component of more 30 modern drugs including very significant anti-HIV drugs such as ritonavir and cobicistat, each of which contains two thiazole heterocycles with different functional environments [2]. Compounds containing a condensed thiazole ring, 2,3-dihydro[1,3]thiazolo[3,2-a]pyridines and [1,3]thiazolo[3,2-a]quinolines, show high antibacterial [5,6,7,8] and antitumor activity [9,10,11,12]. Platinum group metal complexes containing a benzothiazole moiety exhibit antibacterial [13] and antimicrobial [14] activity

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