Solvent-Dependent Conformational Switching of N-Methyl-N,N'-diarylsquaramide

Kimiko Tanaka; Fumi Takeda; Midori Kanda; Masatoshi Kawahata; Shinya Fujii; Kosuke Katagiri; Hyuma Masu; Hiroyuki Kagechika; Aya Tanatani

doi:10.1021/acs.joc.3c00918

Solvent-Dependent Conformational Switching of N-Methyl-N,N'-diarylsquaramide

J Org Chem. 2023 Sep 1;88(17):12289-12293. doi: 10.1021/acs.joc.3c00918. Epub 2023 Aug 11.

Authors

Kimiko Tanaka¹, Fumi Takeda¹, Midori Kanda¹, Masatoshi Kawahata², Shinya Fujii³, Kosuke Katagiri⁴, Hyuma Masu⁵, Hiroyuki Kagechika³, Aya Tanatani¹

Affiliations

¹ Department of Chemistry, Faculty of Science, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan.
² Faculty of Pharmaceutical Science, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan.
³ Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
⁴ Department of Chemistry of Functional Molecules, Faculty of Science and Engineering, Konan University, 8-9-1 Okamoto, Higashinada, Kobe, Hyogo 658-8501, Japan.
⁵ Center for Analytical Instrumentation, Chiba University, 1-33 Yayoi, Inage, Chiba 263-8522, Japan.

PMID: 37565781
DOI: 10.1021/acs.joc.3c00918

Abstract

N,N'-Diarylsquaramide and N,N'-dialkylsquaramide are conformationally stable linkers with extended (trans, trans) and folded (cis, cis) structures, respectively, independently of external conditions. Here, we show that N-monomethylated N,N'-diarylsquaramides generally take a (trans, cis) structure in the crystal but show a solvent-dependent conformational equilibrium in solution. In particular, the stable conformer of N-methyl-N,N'-bis(1-naphthyl)squaramide (1f) changes depending upon the solvent. Thus, aromatic N-monomethylated squaramides could find application as components of environment-responsive molecular switches.