NNHPh Ph Cl N NH NNH2 S Ph SMe Ph + H2NNHC(S)SMe –HCl 1 2 N N S Ph NNH2 Ph N N S Ph NNO Ph 3 4 N N S Ph NN Ph 5 PhCHO Zn–AcOH H2NNHC(S)NH2 CHPh + MeSH O Me Cl NNHPh O Me S NNHPh SMe H2NN 6c 7 + 2 N S N SMe Me NNHPh 8 –H2O NNHPh Ph Cl 1 NNHC(S)SR2 R1 Me + N N N Ph NHC(S)SR2 Me R1 Ph N N S Ph SR2 Ph NHN C(R1)Me N N S Ph Ph NN C(R1)Me 12 –R2SH 11 13a R1 = 2-C4H3S b R1 = 2-C4H3O c R1 = 2-C5H4N d R1 = 3-C5H4N a R1 = 2-C4H3S, R2 = Me b R1 = 2-C4H3O, R2 = Me c R1 = 2-C5H4N, R2 = Me d R1 = 3-C5H4N, R2 = Me 9 a R1 = 2-C4H3S, R2 = Et b R1 = 2-C4H3O, R2 = Et 10 12 J.CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 12–13 J. Chem. Research (M), 1998, 0169–0179 Reactions with Hydrazonoyl Halides. Part 15.1 A Synthetic Approach to 2,3-Dihydrothiadiazoles Hussein A. Emam,a Hussein F. Zohdib and Adbou O. Abdelhamid*b aDepartment of Chemistry, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt bDepartment of Chemistry, Faculty of Science, Cairo University, Giza, Egypt Hydrazonoyl halides 1 and 6a–f reacted with methyl hydrazinecarbodithioate (2) and methyl 3-[1-(aryl)alkylmethylidene] hydrazinecarbodithioates (9a–d or 10a,b), in ethanolic triethylamine solution, to afford the corresponding 2-hydrazono- 3,5-diphenyl-2,3-dihydro-1,3,4-thiadiazoles (3), 5-methyl-2-methylsulfanyl-6-phenylhydrazono-1,3,4-thiadiazine (8) and 2,3-dihydro-1,3,4-thiadiazoles 17–20a–f, respectively.It has been reported that dithiocarbazoic acid reacts with haloacetophenones2 and a-halo compounds3 to give 1,3,4-thiadiazines and 2-halomethyl-1,3,4-thiadiazoles, which have been reported to exhibit antiprotozoal,4 antiviral,5 bactericidal6 and fungicidal7 properties.However, the reaction of hydrazonoyl halides with dithiocarbazoate has not yet been reported.8 In this paper, we report a study of this reaction. Treatment of N-phenylbenzohydrazonoyl chloride (1) with methyl hydrazinecarbodithioate (2) in ethanolic triethylamine afforded a product which gave analytical and spectral data in accord with its formulation as 2-hydrazono-3,5-diphenyl- 2,3-dihydro-1,3,4-thiadiazole (3).Compound 3 was authentically obtained by other routes: (a) via reaction9 of 1 with thiosemicarbazide; (b) by reduction of 2-nitrosoimino- 3,5-diphenyl-2,3-dihydro-1,3,4-thiadiazole10 (4). Also, 3 reacted with benzaldehyde to give the corresponding hydrazone 5 (see Scheme 1). In contrast to the above results, 1-chloro-2-phenylhydrazonopropan-2-one (6c) reacted with 2 to give a product formulated as 5-methyl-2-methylsulfanyl- 6-phenylhydrazono-1,3,4-thiadiazine (8) according to elemental analysis and spectral data (see Scheme 2).Treatment of N-phenylbenzohydrazonoyl chloride (1) with methyl 3-[1-(2-thienyl)ethylidene]hydrazinecarbodithioate (9a) in ethanolic triethylamine at room temperature gave the 2,3-dihydro-1,3,4-thiadiazole 13a (see Scheme 3). In contrast, treatment of 1 with ethyl 3-[1-(2-thienyl)ethylidene]hydrazinecarbodithiote 10a), at room temperature, produced the same product (13a).These results indicate the following facts: (a) structure 12 is not the final product; (b) 13a is formed via loss of methane-(or ethane-)thiol; (c) structure 11 is ruled out (see Scheme 3). Similarly, compounds 9b–d reacted with 1 to give 2,3-dihydro-1,3,4-thiadiazole derivatives 13b–d, respectively. The products 13a–d are assumed to be formed via elimination of alkanethiol from the corresponding cycloadduct 12, resulting from 1,3-dipolar cycloaddition of nitrile imide to the C�S of the methyl or ethyl dithiocarbazoate [similar to the reaction of hydrazonoyl halides with substituted thiourea9] (see Scheme 4).The formation of 13a–d can also be explained by the reaction of a dithiocarbazoate of general formula 9 (or 10) with the hydrazonoyl chloride 1, in the presence of a base such as triethylamine or potassium hydroxide. The corresponding 2,3-dihydro-1,3,4-thiadiazole can be easily obtained through the nucleophilic attack of the thiolate group followed by ring closure and methane-(or ethane-)thiol elimination.The elimination of the thiole moiety was confirmed by isolation of the same product (13a) when using 10a and 1, respectively. All attempts to isolate the hydrazone 14 were *To receive any correspondence. Scheme 1 Scheme 2 Scheme 3N N N S Ph SR2 N R1 Me Ph H 14 12 S N N Ph N H N Me R1 Ph SR2 Me(R1)C NNHC(S)R2 9(10) PhC NNPh 9(10) + – 1 + Et3N N N S Ph Ph N N C(R1)Me 13 –R2SH 1 base N N S Ph NNH2 Ph S Me O + S Me NNHCSNH2 13a 1 + 3 15 16 (1) R3CO Cl(Br) NNHPh N N S R3CO Ph NN C(R1)Me 17–20a–f + 9a–d(10a,b) 17 R1 = 2-C4H3S 18 R1 = 2-C4H3O 19 R1 = 2-C5H4N 20 R1 = 3-C5H4N a R3 = EtO b R3 = PhNH c R3 = Me d R3 = Ph e R3 = 2-C4H3O f R3 = 2-C4H3S 6,17–20 6a–f J.CHEM. RESEARCH (S), 1998 13 unsuccessful. Unequivocal support for structure 13 was provided by the preparation of 13a via two routes.The first involves the reaction of 5-hydrazino-2,4-diphenyl-1,3,4-thiadiazole 3 with 2-acetylthiophene (15), in propan-2-ol, the second by the reaction of N-phenylbenzohydrazonoyl chloride (1) with 1-[1-(2-thienyl)ethylidene]thiosemicarbazide (16), in boiling ethanol. All the products were identical with 13a [see eqn. (1)]. In order to study the effect of a carbonyl group on the reactivity of the hydrazonoyl halides, the reaction of a-oxohydrazonoyl halides 6a–f with 9a–d, in ethanolic triethylamine at room temperature, was investigated and found to give the corresponding 2,3-thiadiazoles 17–20a–f.The structures of the products were confirmed by their spectra and alternative synthesis. Thus, the reaction of 10a,b with 6a,b in ethanol containing equimolar amounts of triethylamine gave products identical with 17a,b and 18a,b respectively (see Scheme 5). Techniques used: 1H NMR, IR, mass spectrometry Tables: 2 References: 23 Received, 16th July 1997; Accepted, 19th September 1997 Paper E/7/05088G References cited in this synopsis 1 Part 14: H.F. Zohdi, H. A. Emam and A. O. Abdelhamid, Phosphorus, Sulfur, Silicon Relat. Elem., in press. 2 I. Ya. Postovskii, A. D. Sinegibskaya, A. P. Novilova and L. P. Sidorova, Tezisy Dokl. Nauchn. Sess. Khim. Tekhnol. Org. Soedin. Sery Sernistykh Neftei, 14th, ed. I. G. Bakhtalze, 1975 (pub. 1976), pp. 207–208 (Chem. Abstr., 1978, 88, 190771q). 3 W. Thiel, H. Viola and R. Mayer, Ger. (East) Pat., DD 211,450 (Cl. C07D285/12), 1984 (Chem. Abstr., 1985, 102, 9565d). 4 S. K. Mallick, A. R. Martin and R. G. Lingard, J. Med. Chem., 1971, 14, 528. 5 A. Andolsek, B. Stanovnik, M. Tisler and P. Schauer, J. Med. Chem., 1971, 3. 6 P. N. Dahl, T. E. Achary and A. Nayak, Indian J. Chem., 1975, 3. 7 S. R. Smith, J. Indian Chem. Soc., 1975, 52, 734. 8 A. S. Shawali, Chem. Rev., 1993, 93, 2731. 9 P. Wolkoff, S. T. Nemeth and M. S. Gibson, Can. J. Chem, 1975, 53, 3211. 10 A. S. Shawali and H. M. Hassaneen, Indian J. Chem., 1976, 14B, 425. Scheme 4 Scheme