G. Elgemeie, A. M. Elzanaty, Α. Η. H. Elghandour,
2002
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Journal
Heterocyclic Communications
Abstract
The novel 2-(yV-acetoarylsulfonylhydrazide)-2-thiazolin-4-ones 4 and their corresponding thiazolo[2,3-a]pyridine derivatives 10 were prepared by the reaction of arylsulphonylcyanoacetohydrazides 2 with thioglycolic acid followed by condensation with arylmethylidinemalononitri les 6. As a part of our program directed for development of an efficient procedure for the synthesis of azoles and fused azoles of potential biological activity ~, w e have previously reported several new approaches for the synthesis o f condensed heterocycles utilizing the 2-substituted methyl azolyl derivatives as starting materials '. In the present part w e are reported the utility o f reactions of arylsulphonylcyanoacetohydrazides with thioglycolic acid for the synthesis o f 2-(Nacetoarylsulfonylhydrazide)-2-thiazolen-4-ones. Moreover , the scope and limitation of our procedure for the synthesis of thiazoles are also reported. Thus, it has been found that arylsulphonylcyanoacetohydrazides 2 react with thioglycolic acid in refluxing pyridine for 2h to give a condensation products 4 by water elimination. The analytical data for the product 4a revealed a molecular formula C11H11N3S2O4 (NT 313). T w o tautomeric structures were considered in solutions. The structure of the 2-functionally substituted methyl-2-thiazoline-4-one form was readily rolled out based on *H N M R spectra, which revealed one proton signal at δ = 5.49 ppm. This signal can be only interpreted in terms of the 2-substituted methylidine form. T h e formation of 4 by the reaction of 2 with thioglycolic acid is assumed to proceed via the intermediacy of 3, which formed by addition of thioglycolic acid to the cyano group in compounds 2. C o m p o u n d s 4 bearing latent functional substituents were found useful to synthesize its fused ring derivatives. Thus, compounds 4 readily reacted with aldehydes in ref luxing ethanol containing a catalytic amount of piperidine in a 1 : 2 molar ratio to give the corresponding diarylidine derivatives 5. Compounds 4 reacted with arylmethylidinemalononitri les 6 to yield products for which structures 8-10 were assigned. The possibility that the reaction products are the pyranothiazoles 8 resulting f rom the cyclization of 7 was eliminated based on the IR spectrum which revealed, in each case, two bands for two carbonyl groups. Also, structure 9 was rolled out based on 'H N M R spectra, which revealed a pyridine H 4 signal at 4.8-5.1 ppm. This signal can only interpreted in terms of the structure 10. I'ol. S. No. 6. 2002 Reaction oflhioglycolic acid with N-cyunoacetoaiylsulphonylhydrazides: Novel synthesis of2-(N-acetoarylsiilfonylliydra:ide)-2-lhia:<>lin-4-ones and their Moreover, the IR spectrum revealed the presence of two carbonyl groups The formation of 10 by the reaction of 4 with 6 may be assumed to proceed via formation of 1 : 2 Micheal adduct intermediates 7, which cyclize with loss of malononitrile to give compounds 10. Analytical data for compound 10g revealed a molecular formula C29H23N5S2O4 (NT 569) 'H NMR spectroscopy was used to confirm this structure for the product. Thus, 'H NMR spectra for 10g revealed the presence of a singlet band at δ = 4.89 ppm assigned to the pyridine H-4 proton and three broad bands at δ = 6.55, 10 82 and 12.2 ppm assignable to the NH2 and two NH groups, respectively. Compounds 10 could also be obtained via direct reaction of 5 with malononitrile. In summary, we have achieved a regiospecific synthesis of novel 2-(/V-acetoarylsulfonylhydrazide)-2-thiazolin-4-ones and their corresponding thiazolo[2,3-a]pyridine derivatives. The products obtained are currently under biological evaluation studies. EXPERIMENTAL All melting points are uncorrected. IR spectra were obtained (KBr disk) on a Perkin Elmer 11650 FT-IR instrument. The 'H NMR spectra were measured on a Varian 400 MHz spectrometer for solutions in (CD3)2 SO using Si(CH3y)4 as an internal standard. Mass spectra were recorded on a Varian MAT 112 spectrometer. Analytical data were obtained from the Microanalytical Data Center at Cairo Univerisity. 2-ArylsulphonylhydrazidomethyI-2-thiazoline-4-ones (4a-b) General procedure: A mixture of an equimolar amounts of arylsulphonylhydrazides 2 and mercaptoacetic acid was refluxed in pyridine solution for 2 h. The reaction mixture was then cooled, poured over ice-water mixture and neutralized with dil. HCl solution. The formed solid product was filtered off and recrystaliized from ethanol. 4a: Buff (50 %), m. p. 270 °C, w / cm ' (KBr) 3454 and 3055 (NH), 1736 (CO) and 1680 (CO) ! H NMR (DMSO): δ = 3.62 (s, 2H, CH2), 5.49 (s, 1H, CH), 7.55-7 80 (m, 5H, C6H5), 9 70 (s, br, 1H, NH), 9.80 (s, br, 1H, NH) and 11.37 (s, br, 1H, NH); n C NMR (DMSO): δ = 31.98 (CH2), 89.07 (CH), 127.57-132.85 (CeHj); 165.51 (C-2), 174.07 (2CO), m/z 313 (Calcd for CnHnN 3 S204: C, 42.2, H, 3 5, N, 13.4; S, 20.4. Found: C, 41.7; H, 3.1; N, 13.6, S, 20.8 %). 4b: Buff (55 %), m. p. 240 °C, vmax / cm" (KBr) 3564 and 3228 (NH), 1707 (CO) and 1655 (CO); 'H NMR (DMSO): δ = 2.38 (s, 311, CHj), 3.63 (s, 2H, CH2), 5.49 (s, 1H, CH), 7.35-7.68 (m, 5H, C6H4), 9.60 (s, br, 1H, NH), 9.70 (s, br, 1H, NH) and 11.35 (s, br, 1H, NH); n C NMR (DMSO): δ = 21.06 (CH3), 31.98 (CH2), 89.16 (CH), 127.63-129.30 (CeR,), 165.52 (C-2), 174 06 (2CO); m/z 327 (Calcd for C12H13N3S2O4: C, 44.0; H, 4.0; N, 12.8; S, 19.6. Found: C, 43.8, H, 3.5; N, 13.1; S, 20.0%).