Synthetic studies on some 3-[(5-arylidene-4-oxo-1,3-thiazolidin-2-yliden)amino]-2-phenylquinazolin-4(3 H )-ones and their ethoxyphthalimide derivatives

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Introduction
Quinazolone derivatives have evoked considerable attention in recent years as these are endowed with wide range of pharmaceutical activities.3H-Quinazolin-4-one represents a useful nucleus for preparation of some new sedative/ hypnotic and anticonvulsant agents, since such a heterocyclic system possesses the pharmacophoric moiety 1 .Of the various quinazolines reported, the C-2 and N-3 disubstituted quinazolines exhibited interesting pharmacological activities like analgesic, anti-inflammatory 2 , antibacterial 3 , anticonvulsant 4 etc. 2,3-Disubstituted quinazolones have been demonstrated to be associated with potent antiviral and antihypertensive acitivities 5 .Characterization of potential NMDA and cholecystokinin antagonist II-lipophilicity studies on quinazolones are also documented 6 .
Furthermore, 4-thiazolidinones have been synthesized 7 and used for the treatment of cardiac 8 diseases.Modifications on 2,3,4 and 5 positions of 4-thiazolidinone give out antidiabetic drugs and potent aldose reductase inhibitors, which are used in the treatment of diabetic complications like catracts, nephropathy, neuropathy 9 .4-Substituted thiazolidinone derivatives have been synthesized and reported to show a variety of pharmacological and microbiological activities such as antibacterial 10 , antifungal, analgesic etc. Significant antiparkinsonian activity against tremor, rigidity, hypokinesia and catatonia has been evaluated "in vivo" in rats and mice in quinazolinylthiazolidinone 11 .Anticonvulsant 12 and anticancer 13 activities have been observed in many alkoxyphthalimide derivatives.Many amino-oxy compounds have been tested for their ability to inhibit the growth of the malaria parasite Plasmodium falciparum in vitro 14 .Heterocyclic rings attached to alkoxyphthalimide group have been synthesized 15 and tested for antimicrobial and antimalarial 16 activities.
Led by above facts, coupled with our desire of synthesizing alkoxyphthalimide derivatives, we report herein the synthesis of some new heterocycles incorporating above moieties together in order to prepare the molecules having enhanced biological activity.

Results and Discussion
In the present work, an attempt has been made to undertake the synthesis of ethoxyphthalimide derivatives of some thiazolidinoquinazolinones through a multi step process.For this purpose, the required 2-phenyl-3,1-benzoxazin-4(3H)-one (1) was prepared by cyclisation reaction between anthranilic acid and benzoyl chloride using pyridine as a solvent and also a base.Formation of the product was confirmed by a sharp band at 1720 cm -1 for C=O group along with a peak at 1180 cm -1 for C-O stretching in IR spectra.Benzoxazine (1) was converted to quinazolinylthiourea (2) by its nucleophilic substitution reaction with thiosemicarbazide.Insertion of nitrogen in the ring was characterized by disappearance of band at 1180 cm -1 of C-O and shift of carbonyl band from 1720 to 1692 cm -1 .Appearance of new peaks near 3400 and 3300 cm -1 for N-H stretching also helped in assigning structure of (2).When (2) was treated with chloroacetic acid in presence of sodium acetate as a base, nucleophilic reaction took place at the thiourea site of molecule and thiazolidinone ring was formed as a result, to yield a new heterocyclic compound (3) having two free different heterocyclic rings namely quinazolone and thiazolidinone in it.New band in IR at 2983 cm -1 and a singlet in NMR at δ 3.5 for methylene protons and a singlet at δ 5.3 for NH proton were in accordance with the structure of thiazolidinone ring.Its condensation with different aldehydes (4a-f) afforded corresponding arylidene derivatives (5a-f) in quantitative yield.
Formation of (5a) was confirmed by appearance of carbonyl peak at 1665 cm -1 , which is due to α,β-unsaturated carbonyl group.Disappearance of singlet at δ 3.5 (active CH 2 ) and appearance of new singlet at δ 6.0 (C=CH-Ar) also confirm its formation.

Experimental Section
General Procedure.Melting points of all synthesized compounds were taken in open capillaries and are uncorrected.IR spectra (KBr) were recorded on a Perkin-Elmer 1300 FT IR spectrometer and 1 H NMR were determined on a Bruker WM-400 (400 MHz FT NMR) spectrometer using TMS as internal standard.Mass spectra were recorded on Jeol D-300 (EI) and Jeol Sx-102 (FAB) spectrometer.Purity of compounds was checked by elemental analysis and TLC using silica gel-'G' as adsorbent and visualization was accomplished with iodine.Compound (6) was synthesized as given in literature methods 17 .