1,5-Benzoxazepines vs 1,5-Benzodiazepines. One-Pot Microwave-Assisted Synthesis and Evaluation for Antioxidant Activity and Lipid Peroxidation Inhibition

Abstract

Amino-1,5-benzoxazepines 2 and 5 and hydroxyl-1,5-benzodiazepines 3 and 6 have been synthesized in one-pot solvent-free conditions from 2,3-diaminophenol and ketones through microwave assisted acid catalysis, the benzoxazepine/benzodiazepine ratio depending on the R(1) and R(3) aryl substituents. The otherwise inaccessible and unknown 2,2-dimethyl-4-aryl-1,5-benzodiazepines 8 were also prepared in an analogous manner. The reaction mechanism was investigated by means of DFT calculations. Structural assignments of the new compounds as well as complete assignment of (1)H and (13)C NMR signals have been unambiguously achieved on the basis of the analysis of their (1)H and (13)C NMR (1D and 2D), IR, MS, and elemental analysis data, whereas the presence of an amino group in 5 and of a hydroxyl in 6 was confirmed by derivatization. Compounds 2, 3, 5f, 6a, 6c, 6d, 6f, 6h, 8c, and 12 were evaluated as antioxidants and lipid peroxidation inhibitors in vitro. Compound 6f was also evaluated as anti-inflammatory agent in vivo. Compounds 2 and 6f were found to be the most potent as inhibitors of lipoxygenase and of lipid peroxidation, respectively.

Green Synthetic Approaches for Medium Ring-Sized Heterocycles of Biological Interest

“…A recent study aiming at developing a common approach to 1,5-benzoxazepines and 1,5-benzoazepines from the condensation of 2,3-diaminophenol with carbonyl compounds through MW-assisted solvent-free conditions has revealed several interesting features [54]. A recent study aiming at developing a common approach to 1,5-benzoxazepines and 1,5-benzoazepines from the condensation of 2,3-diaminophenol with carbonyl compounds through MW-assisted solvent-free conditions has revealed several interesting features [54].…”

Ultrasound promoted synthesis of chromeno[2,3-b]pyridines and their evaluation as lipid peroxidation inhibitors

“…Thus, they might be able to behave as hybrid molecules in terms of biological activity. Therefore, some of the new compounds were screened for their antioxidant activity according to a previously reported methodology, 23,24 and more specifically, for their reducing ability (RA) by interaction with the stable free radical 1,1-diphenylpicrylhydrazyl (DPPH) and for their inhibition on lipid peroxidation by interaction with the water soluble azo compound 2,2''-azobis(2-amidinopropane) dihydrochloride (AAPH) and the results are compared to well known antioxidant agents e.g. nordihydroguairetic acid (NDGA), and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox).…”

Microwaves in Heterocyclic Chemistry

“…Condensation of azepan-4-ones with 3,5-dinitro-1-methylpyridin-2-ones in the presence of ammonia [144] was found to be a highly efficient method (40-120 • C, 0.5-2 h) for the synthesis of 3-nitro-6,7,8,9-tetrahydro-5H-pyrido [3,2- Amino-1,5-benzoxazepines and hydroxy-1,5-benzodiazepines could be synthesized using solvent-free conditions from 2,3-diaminophenol and 2,3,4-trisubstituted acetophenone though microwave-assisted (80 or 240 W, 2-3 min) acid catalysis (AcOH) [145]. It was shown that the benzoxazepine:benzodiazepine ratio depended on the three aryl substituents of acetophenone.…”