Synthesis and antimicrobial evaluation of ethoxyphthalimide derivatized spiro [indole-3,5′-(1,3)thiazolo(4,5-c)isoxazol]-2(1H)-ones via ring closure metathesis

The synthesis of 3'-{(4-substituted phenyl-1-N-ethoxyphthalimido-6'-pyridin-2-yl}-3,3a'-dihydro-6'H-spiro[indole-3,5'[1,3]-thiazolo[4,5-c]isoxazol]-2(1H)-ones 6a-d is carried out through a five step pathway starting from acid catalyzed condensation of 2-aminopyridine with isatin yielding 3-(pyridin-2-ylimino)-1,3-dihydro-2H-indol-2-one 1 which on reaction with thioacetic acid in the presence of anhydrous ZnCl2, give 3'-pyridin-2-yl-4'H-spiro[indole-3,2'-[1,3]thiazolidine]-2,4'(1H)-dione 2. Reaction of 2 with various araldehydes 3a-d affords the corresponding 5'-[(4-substituted phenyl)methylidene]-3'-pyridin-2-yl-4'H-spiro-[indole-3,2'-[1,3]thiazolidine]-2,4'(1H)-diones 4a-d. These chalcones are further cyclised with hydroxylamine hydrochloride to furnish 3'-(4-substituted phenyl)-6'-pyridin-2-yl-3,3a'-dihydro-6'H-spiro[indole-3,5'[1,3]thiazolo[4,5-c]isoxazol]-2(1H)-ones 5a-d which are subsequently condensed with omega-bromoethoxyphthalimide to yield the targeted compounds 6a-d. Structural confirmation of the synthesized compounds has been accomplished by IR. H-1 NMR, and mass spectral data. Final compounds have been screened for their antimicrobial activity.