MONTMORILLONITE KSF CATALYZED FACILE SYNTHESIS OF NOVEL SPIRO HETEROCYCLES UNDER MICROWAVE IRRADIATION

The arylidienes of spiro thiazolidines (5) containing a,b-unsaturated function have been used as component of Micheal addition with equimolar amount of 2-aminopyridine (6a) to give novel spiro [indole-3,2¢-pyrido[1,2-a]thiazolo[5,4-e]pyrimidines] (7) in a single step under microwaves in presence of montmorillonite KSF as solid support. The new improved synthetic method for spiro [indole-3, 2¢-thiazolo[4,5-d]pyrimidines] (8) has also been developed involving the reaction of (5) with thiourea under microwaves. Comparison with conventional synthesis indicated the enhanced yield with faster reactions under microwaves.

A perusal of the literature has revealed manifold implications of pyrido [2,3-d] pyrimidines , viz.antibacterial [8] , antifungal [9] and antiallergic, [10] etc.The nucleosides of pyrido [2,3-d] pyrimidines have also been reported as potent antileukemic, [11] anti HIV, [12]anti cancer [13] and dihydrofolate reductase inhibitors.[14] The chemistry of spiro indoles in which an indole ring is joined to sulfur and nitrogen containing heterocycles at the C-3 position through a spiro carbon atom is of great interest due to their physiological and biological activities.[15,16] Spiro [indolethiazolidines] are known to possess various biological activity e.g.anti-inflammatory, [17] fungistatic, [18] bacteriostatic, [19] anticonvulsant activities [20] and used as dyes.[21] The significance of these compounds can be judged from the fact that most of the references of spiro-indoles in the literature are patents.[22] Arylidene derivatives of condensed 4thiazolidinones have been found to be better fungistatic agents than the parent 4thiazolidinones.Besides, condensed 4-thiazolidinones are better antibacterial agents than their thiazole counterparts.[23][24][25] Therefore, it was though of interest to construct a system, which may combine these biolabile rings together in a single molecular framework to see the additive effect towards their biological activities.
9th International Electronic Conference on Synthetic Organic Chemistry.ECSOC-9  5a: X=H, Y=H, Z= 4-N(CH 3 ) 2 reactions [26][27][28] because of their advantages with respect to classical organic chemistry in terms of shorter reaction times, minimum waste, generally higher yields, possibility of carrying out reactions in the absence of solvents and in safe conditions.In view of this, more interest has now been focused on dry media synthesis, involving the coupling of MWI with solid supported reagents.The method provides unique chemical process with special attribute to enhanced reaction time, higher yield, greater selectivity and ease of manipulation.
Literature survey reveals that there is no report on the synthesis of title novel nucleus yet so far.Therefore, it was thought that it would be desirable to develop a facile, efficient, environeconomic, microwave induced method for preparation of novel spiro indolines 7 and 8 by the reaction of arylidiens derivative (5) with 2-aminopyridine (6a) and thiourea (6b) using montmorillonte KSF as solid support under microwaves.
Hence, in continuation of our earlier interest on molecular diversity and search for new leads in drug designing programme in the synthesis of molecules,[29] which are novel yet resemble known biologically active molecules by virtue of the presence of some critical structural features, we wish to report our results on the use of microwave technique in a multistep synthesis of a novel spiro [indole-3,2¢-pyrido[1,2-a]thiazolo [5,4-e]pyrimidines]( 7) and 5¢-thioxo-4,5,6,7-tetrahydro-2H, 3¢H-spiro [indole-3, 2¢-thiazolo [4,5-d]pyrimidines] (8) (Scheme-1) by combining 2-3 steps as a one pot reaction to reduce the pollution at source as important green chemical theme.[30] The required spiro[indole-thiazolidines] (1) were prepared by the multicomponent condensation between indole-2,3-dione,amines and marcaptoacetic acid [31] using montmorillonite KSF as solid support.These on reaction with araldehyde "in situ" by Recent years have witnessed the importance of microwaves in mediating organic

Scheme-2
Conventionally 5, 7 and 8 were synthesized by long refluxing in gl.AcOH and fused sodium acetate in volatile solvents such as dioxane, dry toluene using Dean Strak apparatus with tedious work up process and purification by chromatographic technique with further need of solvent yielding the desired compounds in lower yield.

RESULTS AND DISCUSSION
The structure assigned to arylidiene derivatives (5)

EXPERIMENTAL
Melting points were determined in open glass capillaries and were uncorrected.Thin layer chromatography on silica gel 'G' coated glass plates using benzene, ethyl acetate (8: 2) as eluent was used for monitoring the progress of the reactions.IR spectra (KBr) were recorded on a Magna FT IR-550 spectrophotometer, 1 H and 13 C NMR spectra [CDCl 3 + (CD 3 ) 2 SO ] were taken on a Bruker-300DX spectrometer at 300 and 200 MHz respectively, using TMS as an internal standard for PMR and mass spectra were recorded on Jeol D-300 spectrometer at an ionization potential of 70 e.v.Microwave assisted reactions were carried out on a National panasonic oven with inverter technology operating at fixed frequency 2450 MHz with power out put range 1000w.Table-2: Spectral & analytical data of 5, 7,8 a-d

Spiro [indole-3,2¢-thiazolidine]-2,4¢ (1H)-dione (5) :
These compounds were synthesized in one pot by multicomponent cyclocondensation of equimolar mixture(0.01mol) of indol-2.3-dione,amines and marcaptoacetic acid using montmorillonite KSF as solid support as reported by us.[31] Since tlc studies showed 100% conversion with formation of single product hence it is used as such for further conversion without isolating them.For structure confirmation some products are isolated by desorption with methanol and compared with authentic samples prepared by literature methods.An equimolar mixture of 4a (2.75 g, 0.01 mol), N, N-dimethylbenzaldehyde (1.75 g, 0.01 mol) and anhyd sodium acetate in gl acetic acid (40 ml) was refluxed for 5 hrs.On cooling, the reaction mixture was poured into ice cold water.The solid thus obtained was filtered, washed with water, dried and crystallized from benzene.m.p.=240°C, Yield =58 % (b)Microwave mediated synthesis: N, N-dimethylbenzaldehyde (1.75 g, 0.01 mol) was adsorbed on montmorillonite KSF (70% weight of reactants) and mixed with spiro thiazolidinone (4a) (synthesized "in situ") and irradiated inside microwave oven at 640 watt till completion of reaction (TLC).The product was obtained by desorption with methanol and further recrystallization with ethylacetate gave pure product.m.p =240°C, Yield =95 %

(d)Microwave mediated synthesis:
It was synthesized by reaction of 5a and 6b using montmorillonite KSF as solid support under microwaves.m.p = 212°C, Yield =89 %
dione (7a): It was synthesized by following different ways (a)Conventional method: