Synthesis and antimicrobial activity of some new oxazolone derivatives of 4,5-disubstituted-2-aminothiazoles

: Some new 4-arylidcne-2-(4' ·(4",5" -disub~tlluted-2" -thiawlylaminol-3-nitrophcnyl)-4,5-dihydro-o"'a.tolc-5-ones have been synthesized and screened for their antimicrobial activity.

The biological activity of thiazoles has been studied extensively and they have been reported to exhibit antibacterial, antifungal, anti-inflammatory, antiviral and anticancer activities•. Oxazoles and oxadiazoles 2 are other classes of compounds reported to possess immense pharmaceutical potential. In continuation with our work on these azoles we report here the synthesis of the compounds incorporating these systems with a view to obtain pharmacologically more potential heterocyclic systems.

Results and discussion
3-N itro-4-( 4' -phenylthiazol-2-yl-amino )benzoic acid (3a) was converted to the acid chloride by reacting with thionyl chloride and further with glycine in methanolic solution of KOH forming N-(4-(4' -phenylthiazol-2yl)amino-3-nitrobenzoyl)glycine (Sa). Infrared spectrum of 3a showed characteristic vibrations at 1680 cm-1 for the carbonyl group of the carboxylic group, at 3310 cm· 1 for the -NH bond and at a higher frequency, 3400 em·• for the non H-bonded -OH group. In another derivative (3c) where a carbethoxy group was present at 5-position of the thiazole nucleus, another band at 1720 cm· 1 for the carbonyl group of the ester was observed. The PMR spectrum of 3a showed a singlet at~ 7.63 for 5-H of the thiazole ring, singlet at 3 9.55 for the -NH and another singlet downtield at 3 10.22 for the single proton of the hydroxyl group which confirmed the formation of this derivative.
In compound Sa, the infrared spectrum showed vibrations at 1670 cm-1 which indicated the presence of an amido group while an absorption band at 1685 cm· 1 was observed due to the carbonyl group vibration of the carboxyl group. The PMR spectrum showed a triplet at ~ 8.23 for one proton and a doublet at ~ 4.24 integrating  for two protons. This confirmed the presence of -NIICII 2 moiety being introduced on reaction with glycine. In lhe next step conversion to the oxazolone derivatives took place by reacting with benzaldehyde in presence of sodium acetate and acetic anhydride. In IR spectrum of 4ary lidene-2-( 4' -( 4" -methyl-2" -th iazo I y lam i no)-3nitrophenyl)-4,5-dihydrooxazol-5-one (6d) a stretching vibration at 1800 cm· 1 indicated the presence of a cyclic keto group and at 1640 cm· 1 for an olefinic bond C = Cll. In the PMR spectrum signal at 15 5.82 as a singlet was visible for a single proton i.e. C=CH, which supported the formation of the oxazolone derivative.
The antibacterial activity was done by the disc diffusion technique 4 at 250 and 500 (.!g/disc with Ampicillin and Streptomycin as the standard drugs. The gram negative strains of bacteria taken were E. coli, Klebsiella species, S. typhi, the gram positiveS. aureus and S. a/bus. The antifungal activity was conducted against a single strain of fungi A. flavus and yeast C. albicans with Griesofulvin as the reference drug. Compounds Sa, Sb, Sd, Se, Sf, Sg (E. coli), Sa and Se (S. aureus) and Sb and Sc (S. typ/11) gave zone of inhibition comparable to the standard drugs. One derivative Sg (S. a/bus), while two other compounds Sd and Sc against S. typhi and also against Klebsiella species displayed a lesser zone of inhibition.
Against Alpergillus flavus, Sa, Sc, Sg and Sh were very active while Sc and Sf also inhibited the growth of Candida albicans comparable to the standard drug Griesofulvin.

Experimental
The IR spectra were recorded on Shimadzu B I 01 A

4-Arylidene
N-( 4-( 4'-Phenylthiazo 1-2-yl) amino-3 -nitrobenzoyl)glycine (0.01 mol), benzaldehyde (0.01 mol) and (0.02 mol) of anhydrous sodium acetate in acetic anhydride (5 mL) were fused together on an electric hot plate. When the contents liquified, further heating was done on a water bath for 2-3 h. After cooling. the conrents were diluted with ethanol and left in a freezer overnight. The solid so obtained was filtered, washed with hot water,