- Cycloaddition of Benzodiazepine Nitrones to Alkynes: Synthesis and X-Ray Analysis of Some Tricyclic Quinoxalines.
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7-Chloro-2-methylamino-5-phenyl-3H-benzodiazepine 4-oxide (chlordiazepoxide) undergoes 1,3-dipolar cycloaddition to electron-deficient alkynes yielding condensed 4-isoxazoline benzodiazepine and pyrrole-fused quinoxaline derivatives.The structure of the reaction products was determined by analytical and spectroscopic methods with the application of LIS and X-ray analysis.The overall process involves an initial addition step, the rate determing one, followed by ring-opening of the 4-isoxazoline intermediate, ring-contraction of the seven-membered nucleus to the quinoxaline system, and subsequent condensation to the tricyclic derivatives.The suitable stereochemistry and the N-O vinylic functionality, forming a good leaving group in the 4-isoxazolines, drive the 1,2-bond migration from carbon to the electron-deficient nitrogen atom of the benzodiazepine ring.The energetics of the condensation steps are discussed on the basis of thermochemical considerations postulating a kinetic effect for the pyrrole-ring closure due to the extended delocalization of the enolate intermediate.
- Capozzi, Giuseppe,Ottana, Rosaria,Romeo, Giovanni,Sindona, Giovanni,Uccella, Nicola,Valle, Giovanni
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p. 2026 - 2048
(2007/10/02)
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- DIHYDROISOXAZOLOBENZODIAZEPINE RING SYSTEM: STEREOCHEMISTRY AND CONFORMATION
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The configurational properties of dihydroisoxazolobenzodiazepine derivatives, obtained by 1,3-dipolar cycloaddition between chlordiazepoxide and various substituted alkynes, have been determined by 1H nmr spectroscopy, largery by computer-simulation of lanthanide induced shifts (LIS).Cycloadducts exist in solution as 3:2 mixture of two interconvertible diastereoisomers, which are the result of heptaatomic ring mobility.The stereochemistry of examined derivatives has been found appropriate to determine the further rearrangement to pyrrole-fused quinoxalines, observed in this new tricyclic system.
- Capozzi, Giuseppe,Ottana, Rosaria,Romeo, Giovanni,Uccella, Nicola
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p. 3087 - 3095
(2007/10/02)
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