Abstract
A new and efficient synthesis of unsaturated benzoxazepines using sodium metabisulfite and potassium permanganate as oxidative reagents
Highlights
1,4-Benzoxazepines are of pharmacological interest due to their activity on the central nervous system, as enzyme inhibitors, or as analgesics and antitussives.1 The 1,4-oxazepine structure is the parent core of medicinal drugs like amoxapine, loxapine and sintamil.2,4 It was reported that 1,4-oxazepine derivatives exhibit biological activity as histone deacetylase inhibitors and as antitumor agents.5,6 The privileged 5,6
In continuation of our research program regarding the synthesis of biologically active nitrogen heterocycles, we describe development of new and straightforward approaches for preparation of 5,6dihydroimidazobenzoxazepines 20-26 and 6,7-dihydrobenzo[f]benzimidazoloxazepines 35-39, in good yields (Figure 2)
Silica gel 60 for column chromatography was obtained from Fluka
Summary
1,4-Benzoxazepines are of pharmacological interest due to their activity on the central nervous system, as enzyme inhibitors, or as analgesics and antitussives. The 1,4-oxazepine structure is the parent core of medicinal drugs like amoxapine, loxapine and sintamil. It was reported that 1,4-oxazepine derivatives exhibit biological activity as histone deacetylase inhibitors and as antitumor agents. The privileged 5,6-. Among these approaches are: (i) treatment of benzaldehydes with glyoxal and ammonia followed by bis-alkylation with 1,2-dibromoethane; (ii) magnesium ethoxide-promoted conversion of nitriles into amidines and its application in 5,6dihydroimidazobenzoxazepine synthesis; (iii) treatement of 2-(2-formylphenoxy)acetic acid with ophenylenediamine using manganese(II) complex tetrasulfophthalocyanine complex supported on natural silk as catalyst; (iv) condensation of various ortho-phenylenediamines with 2-(prop-2-yn-1-yloxy)benzaldehydes to produce imidazole derivatives followed by intramolecular cyclization forming 7-methylene-6,7dihyrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepines; (v) condensation between 1,2-diketones, 2-formyl phenoxy acetic acids, and ammonium acetate in acetic acid under reflux conditions; (vi) condensation of salicylaldehyde with ortho-phenylenediamine using sodium metabisulfite as a catalyst which forms a benzimidazole phenol followed reaction with 1,2-dibromoethane in the presence of base; (vii) a one-pot combination of condensation, Mannich, oxidation, and aza-Michael addition reactions, employing a variety of functionalized anilines and aldehydes suitably poised with a Michael acceptor. Levan et al reported the isolation and characterization of the unsubstituted 1,2,3,4,5,6,11-hexahydro imidazo-[1,2-d]benzoxazepine as a by-product in a tedious route and without mentioning the product yield.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
