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Sulfite‐Induced N ‐Alkylation and Thioketonization of Azoles Enable Access to Diverse Azole Thiones
Author(s) -
Deng JianChao,
Chen JiaHao,
Zhang JunRong,
Lu TingTing,
Tang RiYuan
Publication year - 2018
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201801166
Subject(s) - chemistry , azole , combinatorial chemistry , alkylation , molecule , organic chemistry , antifungal , catalysis , medicine , dermatology
The direct modification of azole skeletons enables access to drug‐like molecules. The development of a highly compatible reaction platform for this pursuit still remains challenging. Herein, we report the use of sulfite as the single electron transfer (SET) reducing agent for the activation of functionalized bromoalkanes, elemental sulfur, and imidazoliniums for the transition metal‐free and base‐free N ‐alkylation and thioketonization of azoles. Excellent functional group tolerance and high synthetic efficiency proved particularly advantageous for the rapid assembly of a large array of pharmaceutically‐oriented azole thiones, many of which contain synthetically and biologically useful functional groups. The direct transformation of drug molecules (such as Ketoconazole, Econazole, and Fluconazole) into their corresponding azole thiones has also been successfully achieved. Reactions with selenium also proceeded smoothly under the optimized conditions. Successful gram‐scale reactions demonstrate the good applicability of this methodology.