Synthesis of 2-Alkoxy/Thioalkoxy Benzo[d]imidazoles and 2-Thione Benzo[d]imidazoles via a Phase-Based, Chemoselective Reaction

ACS Combinatorial Science
Hyo-Jeong YoonYoung-Dae Gong

Abstract

2-Alkoxy/thioalkoxy benzo-[d]-imidazole and 2-thione benzo-[d]-imidazole libraries were constructed in solution phase and on solid phase, respectively. The key step in this work is the phase-based chemoselective reaction of the 2-mercaptobenzo-[d]-imidazole intermediate with benzyl chloride (solution phase) and Merrifield resin (solid phase). In the solution-phase case, benzyl chloride reacted with the thiol group of 2-mercaptobenzo-[d]-imidazole, whereas in the solid-phase case, Merrifield resin was introduced at an internal amine group of benzo-[d]-imidazole. To afford the desired 2-alkoxy/thioalkoxy benzo-[d]-imidazole analogues, we used various alkyl halides, alcohols, and thiols in solution phase, and to obtain 2-thione benzo-[d]-imidazole derivatives on solid phase, we used diverse alkyl halides and boronic acids. Finally, to measure the drug potential to be orally active and the molecular diversity in three-dimensional (3D) space, we calculated physicochemical properties and displayed energy-minimized 3D structures. As a result, the libraries from solution phase and solid phase show distinct features in physicochemical properties and skeletal diversities in 3D space.

References

Jan 10, 2002·Chemical Reviews·Viktor Krchnák, Mark W Holladay
Feb 1, 1996·Chemical Reviews·Lorin A. Thompson, Jonathan A. Ellman
Apr 1, 1997·Chemical Reviews·Adel NefziRichard A. Houghten
May 18, 2005·Bioorganic & Medicinal Chemistry·Xueqing WangAndrew O Stewart
Sep 12, 2006·Journal of Combinatorial Chemistry·Roland E DolleJoseph M Salvino
Sep 20, 2007·Journal of Combinatorial Chemistry·Roland E DolleWei Zhang
Jan 29, 2008·Journal of Combinatorial Chemistry·J Phillip KennedyCraig W Lindsley
Jun 11, 2010·Journal of Combinatorial Chemistry·Young-Dae Gong, Taeho Lee
Jun 28, 2011·Nature Reviews. Drug Discovery·David C Swinney, Jason Anthony
Jun 5, 2013·Bioorganic & Medicinal Chemistry Letters·Jaime Pérez-VillanuevaRafael Castillo
Dec 25, 2013·Organic Letters·Hannah BaarsCarsten Bolm
Nov 5, 2014·Journal of Medicinal Chemistry·Jean-Christophe CarryCécile Combeau
Jan 15, 2015·The Journal of Organic Chemistry·Devulapally MaheshTharmalingam Punniyamurthy
Jul 15, 2015·Bioorganic & Medicinal Chemistry Letters·Shridevi D DoddaramappaJavarasetty Chethan

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