The Utility Of Suzuki-Miyaura Cross-Coupling Reaction In The Synthesis Of Angular Benzo[A]Phenothiazine And Benzo[A]Phenoxazine Derivatives And Their Anti-Microbial Screening

ABSTRACT

Palladium-catalysed Suziki-Miyaura cross-coupling (SMC) reactions of 6-chloro-5H

benzo[a]phenothiazin-5-one, 11-amino-6-chloro-9-thio-5H-naphtho[2,1-b]pyrimido[5,4-e][1,4]

oxazin-5-one and 6-chloro-5H-naphtho[2,1-b]pyrido[2,3-e][1,4]oxazin-5-one with phenylboronic

acid and 3-nitophenylboronic acid were thoroughly investigated. The above intermediates were

prepared by the reactions of 2-aminothiophenol, 4,5-diamino-6-hydroxylpyrimidine-2-thiol and 2-

aminpyridin-3-ol respectively with 2,3-dichloronaphthalene-1,4-dione in a basic medium using

benzene/DMF as the solvent. Thereafter, each was subjected to the SMC reactions with

phenylboronic acid and 3-nitrophenyl boronic acid, refluxing for 7-8 h at 110 oC using

tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3), SPhos, potassium phosphate (K3PO4), and

toluene as the catalyst, ligand, base and solvent correspondingly to yield 6-phenyl-5Hbenzo[

a]phenothiazin-5-one and 6-(3-nitrophenyl)-5H-benzo[a]phenothiazin-5-one;11-amino-9-

mercapto-6-phenyl-5H-naphtho[2,1-b]pyrimido[5,4-e][1,4]oxazin-5-one and 11-amino-9-

mercapto-6-(3-nitrophenyl)-5H-naphtho[2,1-b]pyrimido[5,4-e][1,4]oxazin-5-one; and 6-phenyl-

5H-naphtho[2,1-b]pyrido[2,3-e][1,4]oxazin-5-one and 6-(3-nitrophenyl)-5H-naphtho[2,1-

b]pyrido[2,3-e][1,4]oxazin-5-one. Structures of the compounds were characterized using

UV/visible spectrophotometry, FT-IR, 1H-NMR and 13C-NMR spectroscopy and elemental

analysis. Using Ciprofloxacin (antibacterial) and Ketoconazole (antifungal) as reference drugs, the

compounds were screened against six (6) micro-organisms, viz: Bacillus subtitis, Staphylococcus

aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albican and Aspergillus niger; and were found to show significant activity against some gram-positive bacteria.