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

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posted on 20.06.2014, 00:00 by Tetsuya Yoneda, Hidetsugu Tabata, Jun Nakagomi, Tomohiko Tasaka, Tetsuta Oshitari, Hideyo Takahashi, Hideaki Natsugari
The atropisomeric and conformational properties of 1,5-benzodiazepines with an N-sulfonyl (p-tosyl/mesyl) group (IIa/b) were investigated by comparison with those of the N-benzoyl congeners (I). Similar to I, when the Ar–N­(SO2) axis was frozen by a C9-substitution in the molecules, IIa/b were separated into the (aR)- and (aS)-atropisomers. The conformation of IIa/b revealed that the substituent (p-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., (+)-(aR)-N-p-tosyl-1,5-benzodiazepin-2-one (IIa-2)], whereas that of I is anti to the diazepine ring [e.g., (−)-(aR)-N-benzoyl-1,5-benzodiazepin-2-one (I-2)], which was further supported by a computational study. The stereochemical stability also differed between the two congeners (e.g., ΔG: 104 kJ/mol for I-2 and 132 kJ/mol for IIa-2).