Synth.esis of alkoxyphthalimide derivatives of 5-arylidene-2-( 6' -chlorobenzothiazol-2' -yl-imino )-4-thiazolidinones

Synthesis and characterization of ulkoxyphthalimide derivatives of 5-arylidenc-2-(6'-chlorohcnzothiazol-2'-yl-imino)-4-thiazolidinoncs arc dcsuihcd. 2-Amino-6-chlorobcnzothiazolc 1 was converted to corresponding thiourcas 2 hy reacting with benzoyl thiocyanate and hydrolysing the product with sodium hydroxide. Compound 2 reacted with chloroacctic acid and anhydrous sodium acetate in ethanol to furnish corresponding thiazulidinonc J. The reactive methylene group on the thiazolidinone ring was condensed with various substituted hcnzaldchydcs to give 5-arylidene-2-(6'-chlorohenzothiazol-2' -yl-imino)-4-thiazolidinoncs 4 which on condensation with w-hromoalkuxyphthalimidcs Sa-c gave their alkoxyphthalimide derivatives 6 in good yields. All new compounds were chara cterized from 1 II NMR, IR, MS spectra and elemental analysis.

Thiazolidinones are important compounds due to their broad range of biological activities 1 • We have reported here some compounds with amino-oxy moiety containing thiazoly I th iazol idi nones.
Results and discussion 2-Amino-6-chlorobenzothiazole on reacting with benzoyl thiocyanate and hydrolysing the product with sodium hydroxide gave the .:orresponding thiocarbamide 2 in 68% yield. Cyclisation of 2 with chloroacetic acid in the presence of anhydrous sodium acetate in absolute alcohol furnished the corresponding thiazolidinone 3. IR, mass and NMR studies contirmeu the formation of 3. The intense band at 1656 cm-1 for this showed C=N stretching for the phenylimino group attached to the thiazolidinone nucleus while the ring C=O group appeared at 1710 cm-1 • Compound 3 on condensation with para-substituted benzaldehydes in acetic acid in presence of sodium acetate gave 4ac. Formation of products was contirmed by disuppearance of the IR bund at 2lJ3l) cm-1 and NMR signal at 8 4.4 (singlet) for the CH 2 group of the thiazolidinone nucleus in 3 and appearance of new IR band at 1642 cm-1 and NMR signal at 8 6.4 (singlet) of C=CHAr in 4a. w-Bromoalkoxyphthali mides Sa-c were prep•tred by rep01ted methods. Condensation of 4a-c with w-bromoalkoxyphthalimides Sac in absolute alcohol gave their alkoxyphthalimide derivatives 6a-c in good yields. IR. mass and NMR spectra confirmed the condensation of Sa-c with 4a-c at the N atom. Free stretching vibration band for -NH group at 3300-3100 cm-1 which was present in its precursors 4a-c due to NHCO group, had disappeared anu a strong band at 1300-1160 cm-1 appeared for the C-N stretching of the CH 2 NCO group contirmed the formation of a new C-N bond. Furthermore, C=O stretching of the thiazolidinone ring was still present which confirmed the formation of the final compounds.

Antimicrobial activity :
The titled compounds were screened for their antibacterial and antifungal activities using cup or wellmethod 2 . Antibacterial activity of compounds have been evaluated against four bacterial strains viz. B. subtilis, E. coli, K. pneumoniae and P. aeruginosa. Sterilized nutrient agar medium was poured in Petri dishes and after soliditication. these Petri dishes were inoculated with 0.2 ml suspensior~ of organism employing spread plate method 3 . Two wells were made in each Petri plate and tilleu with two different concentrations viz. 500 ppm and I 000 ppm. The zones of inhibition were recorued after 24 h of incubation. Almost all compounds showed low to moderate activity against K. pneumoniae and P. aeruginosa and majority of the compounds were inactive against E. coli and B. subtilis as compared to the standard drug (Ciprotloxacin) used.
tive against A jiunigalus and other were good active while compounds 6d, 6c and 6f were not exhibited activity against A. jionigaws but they were found to be moderately active against C. albicans. So these thiazolidinones are found to exhibit good antifungal activity rather then antibacterial activity. Although in the present findings, the antibacterial and antifungal activity could not be directly related to the structure yet some conclusions have been drawn thut increused antimicrobiul activity was observed when urylidene unit w<ts attached to the thiazolidinone nucleus but activity was found to be del:reased when hydroxyl group was present at p-position in the arylidene unit and an inl:rease in the number of cm·bon atoms in the alkoxyphthalimide moiety also increased the activity.

Experimental
Melting points were determined in open capillaries. IR spectra (KBr disl:) were rewrded on Perkin-Elmer 1800 and Shimadzu 8201 PC (4000-350 cm-1 ) FTIR spectrophotometer. NMR spectra (CDCI~) were recorded on Perkin-Elmer R-32 (90 MHz) NMR spectrometer using TMS as internal standard. Mass spectra were determined on Joel D-300 (EI) and Joel SX-102 (FAB) spectrometers. Purity of compounds was checked by TLC using silica gei-G plates and benzene-methanol or toluene-methanol as developing solveiit and the spots were exposed in iodine chamber. Compounds 1 and 5a-c 4 were prepared according to literatun: prol:edures.

N'-(6-Ch/orobenzothiazol-2-y/) thiourea (2) :
A solution of ammonium thiocyanate (9 g) in acetone (50 ml) was taken inside a three necked tlask provided with a reflux condenser, a dropping funnel and a mechanical stir-rer. Benzoyl chloride (13 ml) was added dropwise with stirring. A solution of 2-amino-6-chlorobenzothiazole (0.1 M) in acetone (50 rnl) was added dropwise so that the solution was retluxed at its own temperature. The whole reaction mixture was poured into cold water (I L) and the resulting precipitate was filtered off and hydrolysed by boiling with solution of NaOH (30 g) in water (300 ml). It was filtered and the filterate was acidified wit~ cone. HCI and made basic with ammonium hydroxide. The solid obtained was filtered, dried and crystallized from alcohol.· Yield 65%, m.p. 220"C.