Indian Journal of Chemistry Vol. 57B, June 2018, pp. 823-829 A facile and simple synthesis of novel isoxazolyl benzo[ f][1,4]oxazepin-3-(2H)- ones and their antimicrobial activity Ramu Kakkerla* a , Srinivas Marri b , M P S Murali Krishna c & M V Rajam d a Department of Chemistry, Satavahana University, Karimnagar 505 001, India b Department of Chemistry, Siddhartha Degree and P.G. College, Narsampet, Warangal 506 132, India c Department of Chemistry, Andhra Polytechnic College, Kakinada 533 003, India d Department of Genetics, University of Delhi, South Campus, New Delhi 110 021, India E-mail: kakkerla2001@yahoo.co.in Received 16 November 2017; accepted (revised) 14 March 2018 A series of novel isoxazolyl benzo[f][1,4]oxazepin-3-(2H)-ones (9a-h) have been synthesized by adopting a facile and simple methodology. The reaction of 3-amino-5-methylisoxazole (5) with salicylaldehydes (6), followed by reduction with NaBH 4 , and in situ chloroacetylation and cyclization with chloroacetyl chloride and triethyl amine affords isoxazolyl benzo[f][1,4]oxazepin-3-(2H)-ones (9a-h). The newly synthesized compounds (7-9) have been characterized by spectral (IR, 1 H and 13 C NMR, and HRMS) data. The title compounds (9a-h) have been evaluated for their in vitro antimicrobial activity against different bacterial and fungal strains. Compounds 9b, 9f and 9g show excellent antimicrobial activity, when compared to the respective standard drugs. Keywords: Isoxazolyl benzo[f][1,4]-oxazepin-3-(2H)-ones, oxazepins, reductive amination, antimicrobial activity The development of new synthetic methods leading to hybrid structures, which consists of different biologically active molecules in a single frame work, has attracted much attention. The heterocyclic pharmacophores are selected on the basis of their known bio profiles, so that successive hybrid molecules may exhibit synergetic or additive pharmacological activities 1,2 . Benzo-1,4-oxazepines are quite attractive drug targets due to their biological activities. For example, N-pyrrolidinyl derivatives of benzo-1,4-oxazepins-3-ones (1) appear to have tranquilizer and analgesic activity 3 . Benzo-1,4- oxazepin-5-ones (2) exhibit antihistaminic activity 4 , whereas benzo-1,4-oxazepin-3,5-diones (3) were found to be suitable for use as psychotropics 5 . Some novel benzo-1,4-oxazepin-5-ones (4) were found to act as 5-HT 1 A receptor agonists, and show anti-ischemic effects 6 (Figure 1). Similarly, biological activity of substituted isoxazoles has made them the focus of medicinal chemists over the years. Isoxazoles are found to posses analgesic and anti-inflammatory 7 , antiviral 8,9 , anticonvulsant 10 , antimicrobial 11 , and anticancer 12,13 activities. Benzo-1,4-oxazepin-3-ones were synthesized by conventional methods starting from (i) 2-hydroxy benzophenones via 2-hydroxy benzhydrylamines followed by O-alkylation with halo esters and thermal ring closure 14 (ii) N-substituted derivatives were obtained from phenols via amido alkylation with 2- chloro-N-(hydroxymethyl)acetamide and a subsequent ring closure 15 , (iii) 2-formyl phenocarboxylic acid by reaction with primary amines and isocyanides by Ugi 3CC reaction 16 , and (iv) salicylaldehyde and anilines via reduction, further reaction with chloroacetyl O N O N O N O N O O R NR 2 (H 2 C) 5 O O R (CH 2 ) 4 O N R N N N N R (1) (2) (3) (4) Figure 1 — Biologically active benzo-1,4-oxazepinones