A Remarkable Two-Step Synthesis of Diverse 1,4-Benzodiazepine-2,5-diones Using the Ugi Four-Component Condensation
- 1 January 1996
- journal article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 61 (25) , 8935-8939
- https://doi.org/10.1021/jo961517p
Abstract
A two-step, general synthesis of 1,4-benzodiazepine-2,5-diones (BZDs) is presented. This synthesis employs an Ugi four-component condensation using a convertible isocyanide (1-isocyanocyclohexene), followed by an acid-activated cyclization reaction. This synthesis represents a dramatically improved route to BZDs over those currently in the literature. In addition, since amino acids are not used as inputs, the potential for molecular diversity is much greater than that with existing syntheses. It was also found that BZDs substituted with methylenes at the C-3 and N-4 positions display conformational isomerism in the NMR spectra at room temperature. Variable-temperature NMR experiments support this observation and offer the interesting conclusion that the BZD core structure, in certain examples, might not be as rigid as previously supposed.Keywords
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