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

다국어 초록 (Multilingual Abstract)

<P>2-Alkoxy/thioalkoxy benzo-[<I>d</I>]-imidazole and 2-thione benzo-[<I>d</I>]-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-[<I>d</I>]-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-[<I>d</I>]-imidazole, whereas in the solid-phase case, Merrifield resin was introduced at an internal amine group of benzo-[<I>d</I>]-imidazole. To afford the desired 2-alkoxy/thioalkoxy benzo-[<I>d</I>]-imidazole analogues, we used various alkyl halides, alcohols, and thiols in solution phase, and to obtain 2-thione benzo-[<I>d</I>]-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.</P><P><B>Graphic Abstract</B>
<IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/acsccc/2017/acsccc.2017.19.issue-12/acscombsci.7b00106/production/images/medium/co-2017-00106q_0015.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/co7b00106'>ACS Electronic Supporting Info</A></P>