<i>N</i>‑Benzoyl-
and <i>N</i>‑Sulfonyl-1,5-benzodiazepines: Comparison
of Their Atropisomeric
and Conformational Properties
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Abstract
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(SO<sub>2</sub>) 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><sup>⧧</sup>: 104 kJ/mol for <b>I-2</b> and
132 kJ/mol for <b>IIa-2</b>)