R1 CN ArNH SK NCCH(R1)CSNHAr 3 + ArNCS 10a,b 11 N S Ph R1 CN R2 S PhHN COR2 NH2 R1 R1 CN PhNH SK 10a S PhHN CN NH2 R1 16 15 ii iii N S Ph 12 17 S PhHN CO2Et NH2 R1 13 N S Ph 12 R1 CN i 14 R1 CN PhHN SMe 18 N NH R1 NH2 PhHN 19 iv v AcOH N S R1 = a Ar = Ph b Ar = 4-BrC6H4 10,11 15a R1 = Ph b R2 = 2-C4H3S c R2 = 2-C4H3O d R2 = Me O HN R1 CN 240 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 240–241 J. Chem. Research (M), 1997, 1681–1694 A Convenient Synthesis of Thiophene, 1,3-Thiazole, 2,3-Dihydro-1,3,4-thiadiazole and Pyrazole Derivatives Abdou O.Abdelhamid*a and Saad M. Al-Shehrib aDepartment of Chemistry, Faculty of Science, Cairo University, Giza, Egypt bDepartment of Science, King Khalid Military Academy, P.O. Box 22140, Riyadh 11495, Saudi Arabia 3-Aminothiophenes and 2,3-dihydro-1,3,4-thiadiazoles are synthesised via the reaction of 2-cyano-2-[4-(2-naphthyl)- 1,3-thiazol-2-yl]thioacetanilides with a-haloketones or hydrazonoyl halides.The interesting pharmacological properties of thiazole derivatives1 –4 in relation to the various changes in the structure of these compounds is worth studying in order to synthesise less toxic and more potent drugs. Therefore, the fusion of other heterocyclic moieties to the thiazole ring may lead to the fulfilment of this objective. The present investigation deals with the synthesis of some such compounds. In continuation of our interest in the chemistry of the thiazoles,5–8 the syntheses of several new thiazole and dihydrothiadiazole derivatives are described. 2-Bromoacetylnaphthalene (1) reacts with cyanothioacetamide (2) in ethanol to afford [4-(2-naphthyl)-1,3-thiazol- 2-yl]acetonitrile (3). Compound 3 reacted with benzaldehyde, p-tolualdehyde and salicylaldehyde to give the corresponding 3-aryl-2-[4-(2-naphthyl)-1,3-thiazol-2-yl]acrylonitriles 4a,b and 3-[4-(2-naphthyl)-1,3-thiazol-2-yl]coumarin (5). Coumarin 5 was also prepared by boiling coumarin- 3-carbothioamide (6)10 with 1 in ethanol (see Scheme 1).a-Substituted cinnamonitrile reacted with 3 in ethanol containing a catalytic amount of piperidine to give the same product 4a. Compound 4, a typical a,b-unsaturated nitrile, underwent fission at the exocyclic ethylenic double bond on heating with hydrazine or phenylhydrazine in ethanol to give 3 and the corresponding aldehyde hydrazone. Also, compound 3 reacted with benzenediazonium chloride in ethanolic sodium acetate solution to afford 2-cyanocarbonyl- 4-(2-naphthyl)-1,3-thiazole phenylhydrazone (9).Compound 3 reacted with aryl isothiocyanates in the presence of potassium ethoxide solution to give the potassium salts 10a,b which were converted into 2-cyano-2-[4-(2-naphthyl)- 1,3-thiazol-2-yl]thioacetanilides 11a,b by treatment with acetic acid. Treatment of 10a with each of ethyl chloroacetate, a-haloketones or chloroacetonitrile gave the 3-amino-2-substituted thiophenes 13, 15a–d and 16, respectively (see Scheme 2).The IR spectrum of 13 especially revealed bands at 3491, 3315 (NH2) and 1664 cmµ1 (CO) with no cyano absorption band.11 Similarly, 10a reacted with phenacyl bromide, 2- bromoacetylthiophene, 2-bromoacetylfuran, chloroacetone and chloroacetonitrile to give 3-amino-2-acylthiophenes 15a–d and 3-amino-2-cyanothiophene 16, respectively (see Scheme 2). The structures 14 and 17 were ruled out on the basis of spectral studies. The IR spectrum of 15 revealed bands at 3425, 3228, 3103 (NH and NH2), 1650 cmµ1 (CO) and no cyano group absorption band in the region 2100–2300.The IR spectrum of 16 revealed bands at 3402, 3321, 3220 (NH2 and NH), 2187 (CN) and 1630 cmµ1 *To receive any correspondence. Scheme 1 Scheme 2 Reagents: i, ClCH2CO2Et; ii, XCH2CO2R (a) R2=Ph; X=Br; (b) R2=2-C4H3S; X=Br; (c) R2=2-C4H3O; X=Br; (d) R2=Me; X=Cl; iii, ClCH2CN; iv, MeI; v, N2H4R1 CN ArNH SK + Ph NNHPh Cl N N S R1 CN Ar Ph 21 N N S R1 CN Ar Ph 22 10a,b 20 R1 CN ArNH SK R3CO NNHPh X N N S R1 CN COR3 Ar N S R1 CN N Ar O S R1 CN N N N S R1 CN COR3 R3 NPh R3 Ph NPh + 24 10a,b 23a-e 25 26 27 a R3 = Ph, X = Br b R3 = Me, X = Cl c R3 = OEt, X = Cl d R3 = NHPh, X = Cl e R3 = 2-C10H7, X = Br 23 RCOCH2Br + PhSO2Na RCOCH2SO2Ph N N R4 SO2Ph R Ph 29 28 a R4 = Ph b R4 = MeCO c R4 = PhCO d R4 = PhNHCO 29 e R4 = CO2Et f R4 = 2-C4H3OS g R4 = 2-C4H3O2 h R4 = 2-C10H7 29a-h R = 2-C10H7 1 + 20(23) N S RCO SO2Ph Ar R3 N NPh 31 N N S RCO SO2Ph Ar COR3 32 N N S RCO SO2Ph Ph COR3 33 RCO SO2Ph ArHN SK RCOCH2SO2Ph 23 + 28 ArNCS J.CHEM. RESEARCH (S), 1997 241 (C�N). Treatment of compound 10a with methyl iodide in ethanol gave the methylsulfanyl derivative 18. Structure 18 was con- firmed by the following: (a) the IR spectrum revealed bands 3350 (NH) and 2185 (CN) cmµ1; (b) the 1H NMR spectrum showed signals at d 2.14 (s, 3 H, CH3), 6.92 (s, 1 H, thiazole H-5) and 7.15–8.24 (m, 13 H, ArH’s); (c) it is converted into the aminopyrazole 19 upon refluxing with hydrazine hydrate, in ethanol.Treatment of 10a with N-phenylbenzohydrazonoyl chloride (20) gave a single product (TLC). The IR spectrum of the product showed a band at 2192 cmµ1 corresponding to a cyano group. Structure 22 was excluded on the result of the elemental analyses, spectral data and the reaction of 10b with 20, which gave the same product 21 which was obtained before (see Scheme 3). These results indicate that 21 is formed by the loss of aniline and 4-bromoaniline, respectively.The reaction of the a-oxohydrazonoyl halides 23 with 10a,b was also studied. Thus, treatment of 23a with 10a in ethanol gave only a single product 27 (TLC), the structure of which was deduced on the basis of elemental analyses and spectral data. The structure of 27a was further confirmed by the reaction of 10b with 23a which gave the same product 27 (see Scheme 4). According to the above results structures 24–26 were excluded.Similarly, 23b–e reacted with 10a or 10b to give the 2,3-dihydrothiadiazoles 27b–e, respectively. The b-oxo sulfone 28 reacted with the appropriate hydrazonoyl halide 20 or 23a–f to give the pyrazoles 29a–h, respectively (see Scheme 5). The IR spectrum of 29 revealed absorption bands at 1720–1660 cmµ1 due to CO and 1350, 1310 cmµ1 due to SO2 groups. Treatment of 28 with aryl isothiocyanates in the presence of N,N-dimethylformamide containing potassium hydroxide solution formed a non-isolable product, 30a,b, which reacted with hydrazonoyl chloride 23b to give a single product (TLC) of molecular formula C28H20N2O4S (see Scheme 6).The structure of the product was inferred from its spectral data to be 33. The structure was further confirmed by reaction of 30b with 23b under the same experimental conditions as before, which produced the same product 33b. The results indicate that 33b is formed by loss of aniline. Similarly, the reaction of 23a,c,d, with 30a or 30b gave the 2,3-dihydro- 1,3,4-thiadiazoles 33a,c,d, respectively (see Scheme 6).Especially, the IR spectra of 33 showed one absorption band due to a CO group in the region 1720–1660 cmµ1. The structures 31 and 32 were ruled out on the basis of spectral data. The foregoing results indicate that both aryl and aroyl groups have similar effects on the behaviour of hydrazonoyl halides. All new compounds were characterised by elemental analysis, IR, 1H and 13C NMR.Techniques used: IR, 1H and 13C NMR, elemental analysis, TLC References: 19 Tables 1 and 2: Characterisation and spectral data for the newly synthesised derivatives Received, 2nd January 1997; Accepted, 9th April 1997 Paper E/7/00067G References 1 M. K. Route, B. Padhi and N. K. Das, Nature, 1954, 173, 516. 2 A. Makie and A. L. Misra, J. Chem. Soc., 1954, 3919. 3 A. Mostafa, W. Asker, S. Khattab and K. Abou Elazayem, J. Am. Chem. Soc., 1960, 82, 2029. 4 Thiazole and its Derivatives, ed. J. V. Metzger, Wiley, New York, 1979, vol. 39. 5 A. O. Abdelhamid and M. A. Afifi, Sulfur Lett., 1987, 6, 125. 6 A. O. Abdelhamid and A. M. Afifi, Phosphorus Sulfur Relat. Elem., 1988, 36, 129. 7 B. E. Elanadouli, A. O. Abdelhamid and A. S. Shawali, J. Heterocycl. Chem., 1984, 21, 1087. 8 A. O. Abdelhamid and F. A. Attaby, J. Heterocycl. Ch., 1991, 28, 41. 10 J. S. Brunskill, A. De. Z. Elgabar, H. Jeffrey and D. F. Ewing, Synth. Commun., 1978, 8, 533. 11 D. L. Pavia, G. M. Lampman and G. S. Kriz Jr., in Introduction to Spectroscopy, Saunders, Philadelphia, 1979. Scheme 3 Scheme 4 Scheme 5 Scheme 6