<i>N</i>‑Benzoyl- and <i>N</i>‑Sulfonyl-1,5-benzodiazepines: Comparison of Their Atropisomeric and Conformational Properties

The atropisomeric and conformational properties of 1,5-benzodiazepines with an <i>N</i>-sulfonyl (<i>p</i>-tosyl/mesyl) group (<b>IIa</b>/<b>b</b>) were investigated by comparison with those of the <i>N</i>-benzoyl congeners (<b>I</b>). Similar to <b>I</b>, when the Ar–N­(SO₂) axis was frozen by a C9-substitution in the molecules, <b>IIa</b>/<b>b</b> were separated into the (a<i>R</i>)- and (a<i>S</i>)-atropisomers. The conformation of <b>IIa</b>/<b>b</b> revealed that the substituent (<i>p</i>-tolyl/methyl group) in the sulfonyl moiety occupies the position over the diazepine ring (folded form) in both the solid and solution states [e.g., (+)-(a<i>R</i>)-<i>N</i>-<i>p</i>-tosyl<b>-</b>1,5-benzodiazepin-2-one (<b>IIa-2</b>)], whereas that of <b>I</b> is <i>anti</i> to the diazepine ring [e.g., (−)-(a<i>R</i>)-<i>N</i>-benzoyl<b>-</b>1,5-benzodiazepin-2-one (<b>I-2</b>)], which was further supported by a computational study. The stereochemical stability also differed between the two congeners (e.g., Δ<i>G</i>^⧧: 104 kJ/mol for <b>I-2</b> and 132 kJ/mol for <b>IIa-2</b>)