N-benzoyl- and N-sulfonyl-1,5-benzodiazepines: comparison of their atropisomeric and conformational properties.
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).
Faculty of Pharma Sciences, Teikyo University , 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Tetsuya
T
Yoneda
Hidetsugu
H
Tabata
Jun
J
Nakagomi
Tomohiko
T
Tasaka
Tetsuta
T
Oshitari
Hideyo
H
Takahashi
Hideaki
H
Natsugari
D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008968:Molecular Conformation; D060327:Solid-Phase Synthesis Techniques; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014105:Tosyl Compounds / Q000138:chemical synthesis / Q000737:chemistry*
C418322:1,5-benzodiazepin-2-one; C000593435:N-p-tosyl-1,5-benzodiazepin-2-one; D014105:Tosyl Compounds; D001569:Benzodiazepines