Synthesis 2021; 53(24): 4682-4688
DOI: 10.1055/s-0040-1720865
paper

Atropisomeric Properties of 9-Methyl-1,4-benzodiazepin-2-ones

Ryoko Tanaka
a   Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan
,
Kosho Makino
a   Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan
,
Hidetsugu Tabata
b   Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan
,
Tetsuta Oshitari
b   Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan
,
Hideaki Natsugari
c   Graduate School of Pharmaceutical Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
,
Hideyo Takahashi
a   Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan
› Author Affiliations
This work was supported in part by a Grant-in-Aid for Scientific Research (C) (19K06980) from the Japan Society for the Promotion of Science. H.T. is grateful for financial support from the Hoansha Foundation.


Abstract

The atropisomeric and conformational properties of 1,4-benzodiazepin-2-ones were investigated by freezing the conformation with a methyl group at the C9 of 1,4-benzodiazepine. It was revealed that 1,4-benzodiazepin-2-ones exist only as a pair of enantiomers [(a1 R, a2 S) and (a1 S, a2 R)], which was confirmed by X-ray analysis. The absolute configuration of each atropisomer was deduced by comparing the [α]D and CD data with those of (–)-N-methoxycarbonylmethylated 9-methyl-5-phenyl-1,4-benzodiaepin-2-one derivative. It was elucidated that the corresponding N-methylated derivative showed similar CD spectra, although the rotational direction of [α]D was opposite to that of others.

Supporting Information



Publication History

Received: 28 June 2021

Accepted after revision: 26 July 2021

Article published online:
27 August 2021

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