Original scientific paper

Chiral 1,4-Benzodiazepines. X. Further Investigations of Configurational Stability of the Chiral Centre C(3)

V. Šunjić ; Department of Biomedical and Biochemical Research, CRC, Compagnia di Ricerca Chimica, 33048 San Giovanni al Natisone (UD), Italy
A. Lisini ; Department of Biomedical and Biochemical Research, CRC, Compagnia di Ricerca Chimica, 33048 San Giovanni al Natisone (UD), Italy
T. Kovač ; Department of Biomedical and Biochemical Research, CRC, Compagnia di Ricerca Chimica, 33048 San Giovanni al Natisone (UD), Italy
B. Belin ; Department of Biomedical and Biochemical Research, CRC, Compagnia di Ricerca Chimica, 33048 San Giovanni al Natisone (UD), Italy
F. Kajfež ; Department of Biomedical and Biochemical Research, CRC, Compagnia di Ricerca Chimica, 33048 San Giovanni al Natisone (UD), Italy
L. Klasinc ; Ruder Boskovic Institute, 41001 Zagreb, Croatia, Yugoslavia

Abstract

For various at C(3)-chiral 1,4-benzodiazepin-2-ones rate determinations
of racemisation (ka.- for C(3)-0CH3 derivative ( + )-1),
degenerate nucleophilic exchange (k0
- for rac. 1 and rac. 2), and
solvolysis (k5
- for C(3)-hemisuccinyl derivative 4) have been performed.
These investigations revealed; (a) retention of .configuration
during methanolysis of ( + )-3, (b) slow racemisation of
( + )-1 during solvolytic degenerate nucleophilic substitution (kefko. -
- 4), (c} no participation of SNl retentive reaction, possible via
intramolecular transfer of the methoxy group within intermediary
compounds 4-6, (d) thermodi:namic parameters for racemisation
of ( + )-1 between 20-40 °c; liH"" = 18.0 ± 0.8 kcal/moll**, liS"" =
= - 7.2 ± 2.5 e. u.*** Mechanistic scheme is offered which accounts
for all experimental results. The effect of the electrocyclic equilibrium
on the electronic structure of N(4) protonated benzodiazepines,
and its possible consequences for their mechanisms of biological
activity on the central nervous system (CNS), have briefly been
discussed.

Keywords

Hrčak ID:

196347

URI

https://hrcak.srce.hr/196347

Publication date:

20.7.1977.

Visits: 390 *