Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) A new ring transformation in the series of 1,2,3-thiadiazoles. Synthesis of 5H-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazines Yury Yu. Morzherin,a Tatiana V. Glukhareva,a Irina N. Slepukhina,a Vladimir S. Mokrushin,a Alexey V. Tkachevb and Vasiliy A. Bakulev*a a Department of Technology of Organic Synthesis, Urals State Technical University, 620002 Ekaterinburg, Russian Federation.Fax: +7 3432 745483; e-mail: morjerine@htf.ustu.ru b N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russian Federation. Fax: +7 3832 34 4752; e-mail: atkachev@nioch.nsc.ru DOI: 10.1070/MC2000v010n01ABEH001218 The first example of the ring transformation of 1,2,3-thiadiazoles involving four atoms of the side chain to form 5H-[1,2,3]triazolo- [5,1-b][1,3,4]thiadiazines is presented.Several types of ring transformation reactions and rearrangements of 1,2,3-thiadiazoles leading to various heterocyclic compounds have been discovered.1 These processes are governed by the following factors: (i) the facile cleavage of the weak N–S bond, (ii) the existence of an equilibrium between 1,2,3-thiadiazoles and a-diazo thiocarbonyl compounds and (iii) the capacity of both thiocarbonyl and diazo groups to cyclise onto electrophilic and nucleophilic functionalities.It was shown that 1,2,3-thiadiazoles could be transformed with involvement of one (Dimroth type rearrangement),2 two (Conforth type)3 or three (L’abbé type)4 atoms of the side chain.This paper presents the first example of the ring transformation of 1,2,3-thiadiazoles with the participation of four atoms of the side chain. Starting compounds 2a–d for this novel ring transformation were obtained by one pot synthesis from 5-N-nitrosylamino- 1,2,3-thiadiazole5 1 (Scheme 1).† We found that compounds 2 are transformed to ethyl 6-aryl-5-chloro-5H-[1,2,3]triazolo[5,1-b]- [1,3,4]thiadiazin-3-carboxylates 4a–d in moderate yields by a treatment with thionyl chloride at room temperature for 1 h.The structures of products 4a–d were assigned on the basis of elemental analyses, IR, mass and NMR spectra.‡ We have also found that this reaction being carried out at –80 °C for 30 min leads to intermediate compounds 3a–d that could be transformed further into 4a–d under similar conditions.The structures of compounds 3a–d obtained as triazolothiazines were confirmed by 1H NMR and mass spectrometry.§ The fact that the melting points and NMR spectra of 3a,b were found to be identical to those of compounds obtained earlier by the reaction of ethyl 1-amino-5-mercapto-1,2,3-thiadiazol-4-carboxylate with bromoacetophenones6 also confirmed the structures of 3a–d.The rearrangement probably involves a Dimroth rearrangement and chlorination by thionyl chloride. The order in which these processes occur is not clear and will be the subject of a further study. † The 1H and 13C NMR spectra were recorded in [2H6]DMSO solutions with a Bruker DRX-500 instrument (500 MHz for 1H and 125 MHz for 13C), and the IR spectra were recorded in KBr using a UR-20 spectrometer.Synthesis of 2. A suspension of N-nitrosoamine 1 (4 g, 0.02 mol) in 200 ml of 1 M HCl was treated with SnCl2 (4.7 g, 0.025 mol) at 10–15 °C. After stirring for 3 h, the reaction mixture was filtered. To the filtrate 0.02 mol of a ketone and 0.1 g of Et4NCl were added, and the mixture was stirred at room temperature for 12 h.The precipitate of 2 was filtered off and recrystallised from ethanol. For 2a: yield 62%, mp 120–122 °C. 1H NMR, d: 10.45 (s, 1H, NH), 7.79–7.83 (m, 2H, ArH), 7.44–7.48 (m, 3H, ArH), 4.44 (q, 2H, OCH2, J 7.3 Hz), 2.42 (s, 3H, Me), 1.40 (t, 3H, Me, J 7.3 Hz). For 2b: yield 57%, mp 190–192 °C. 1H NMR, d: 10.47 (s, 1H, NH), 7.81 (d, 2H, ArH, J 8.85 Hz), 7.52 (d, 2H, ArH, J 8.85 Hz), 4.43 (q, 2H, OCH2, J 7.0 Hz), 2.40 (s, 3H, Me), 1.40 (t, 3H, Me, J 7.3 Hz).For 2c: yield 65%, mp 144–146 °C. 1H NMR, d: 10.41 (s, 1H, NH), 7.70 (d, 2H, ArH, J 8.24 Hz), 7.27 (d, 2H, ArH, J 8.24 Hz), 4.43 (q, 2H, OCH2, J 7.0 Hz), 2.38 (s, 3H, Me), 1.39 (t, 3H, Me, J 7.0 Hz). For 2d: yield 49%, mp 205–206 °C. 1H NMR, d: 10.6 (s, 1H, NH), 8.54–8.55 (m, 1H, ArH), 8.20–8.28 (m, 2H, ArH), 7.69–7.76 (m, 1H, ArH), 4.46 (q, 2H, OCH2, J 7.3 Hz), 2.50 (s, 3H, Me), 1.44 (t, 3H, Me, J 7.3 Hz).‡ Synthesis of 4. A suspension of hydrazone 1 (0.02 mol) in 50 ml of SOCl2 was stirred for 2 h at room temperature, and the excess of SOCl2 was removed at a reduced pressure. The product was recrystallised from ethanol. For 4a: yield 45%, mp 150–152 °C. 1H NMR, d: 8.05–8.15 (m, 2H, ArH), 7.62–7.74 (m, 3H, ArH), 7.57 (1H, s, CHCl), 4.39 (q, 2H, OCH2, J 7.3 Hz), 1.36 (t, 3H, Me, J 7.3 Hz). MS, m/z: 324 (9%, M + 2), 322 (20%, M+). For 4b: yield 55%, mp 196–198 °C. 1H NMR, d: 8.14 (d, 2H, ArH, J 10.0 Hz), 7.65 (d, 2H, ArH, J 10 Hz), 7.50 (1H, s, CHCl), 4.41 (q, 2H, OCH2, J 7.5 Hz), 1.42 (t, 3H, Me, J 7.5 Hz). 13C NMR, d: 159.9 (CO), 149.0 (C3a), 139.7 (CArCl), 134.8 (C3), 129.8 (CArH), 129.0 (CArH), 128.9 (CAr), 122.2 (C6), 61.8 (OCH2), 46.2 (C5), 14.1 (Me).MS, m/z: 359 (3.5%, M + 2), 357 (8.3%, M+). For 4c: yield 65%, mp 162–164 °C. 1H NMR, d: 8.03 (d, 2H, ArH, J 8.24 Hz), 7.44 (d, 2H, ArH, J 8.24 Hz), 7.46 (1H, s, CHCl), 4.40 (q, 2H, OCH2, J 7.3 Hz), 1.42 (t, 3H, Me, J 7.3 Hz). MS, m/z: 338 (4.5%, M + 2), 336 (8.3%, M+).For 4d: yield 48%, mp 215–216 °C. 1H NMR, d: 8.91–8.93 (m, 1H, ArH), 8.44–8.58 (m, 2H, ArH), 7.91–7.98 (m, 1H, ArH), 7.74 (s, 1H, CHCl), 4.44 (q, 2H, OCH2, J 10.0 Hz), 1.43 (t, 3H, Me, J 10.0 Hz). MS, m/z: 369 (1.5%, M + 2), 367 (2.3%, M+). § Synthesis of 3. A suspension of hydrazone 1 (0.02 mol) in 50 ml of SOCl2 was stirred at –80 °C for 30 min, and the excess of SOCl2 was removed at a reduced pressure.The product was recrystallised from ethanol. For 3a: yield 35%, mp 183–185 °C (lit.,6 185 °C). 1H NMR (CDCl3) d: 7.95–8.15 (m, 2H, ArH), 7.46–7.54 (m, 3H, ArH), 4.40 (q, 2H, OCH2, J 7.0 Hz), 3.95 (s, 2H, CH2), 1.45 (t, 3H, Me, J 7.0 Hz). MS, m/z: 288 (8%, M). For 3b: yield 23%, mp 215–216 °C (lit.,6 216 °C). 1H NMR (CDCl3) d: 8.05 (d, 2H, ArH), 7.52 (d, 2H, ArH), 4.45 (q, 2H, OCH2, J 7.3 Hz), 3.95 (s, 2H, CH2), 1.40 (t, 3H, Me, J 7.3 Hz).MS, m/z: 324 (9%, M + 2), 322 (20%, M+). For 3c: (mixture with 4c) 1H NMR, d: 7.98 (d, 2H, ArH, J 7.9 Hz), 7.36 (d, 2H, ArH, J 7.9 Hz), 4.36 (q, 2H, OCH2, J 7.3 Hz), 4.26 (s, 2H, CH2), 2.26 (s, 3H, Me), 1.31 (t, 3H, Me, J 7.3 Hz). MS, m/z: 302 (19%, M). For 3d: (mixture with 4d) 1H NMR, d: 8.87 (dd, 1H, ArH), 8.55 (dd, 1H, ArH), 8.47 (dd, 1H, ArH), 7.87 (dd, 1H, ArH), 4.37 (q, 2H, OCH2, J 7.0 Hz), 4.41 (s, 2H, CH2), 1.40 (t, 3H, Me, J 7.0 Hz).MS, m/z: 333 (10%, M). N N S COOEt NH NO 1 N N S COOEt NH NH2 i ii N N S COOEt NH N 2a–d Ar Me N S N N N COOEt Ar H H N S N N N COOEt Ar Cl H iii iv 3a–d 4a–d a Ar = Ph b Ar = 4-ClC6H4 c Ar = 4-MeC6H4 d Ar = 3-NO2C6H4 Scheme 1 Reagents and condition: i, SnCl2, 1 M HCl, 3 h, room temperature; ii, ArCOMe, 1 M HCl, Et4NCl, 10 h, room temperature; iii, SOCl2, –80 °C, 30 min; iv, SOCl2, room temperature, 2 h.Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) Thus, we have found the first example of the ring transformation of 1,2,3-thiadiazole where four atoms of the side chain take part in the reaction to afford 5H-[1,2,3]triazolo[5,1-b]- [1,3,4]thiadiazine.This work was supported by the Russian Foundation for Basic Research (grant no. 98-03-33045a). References 1 G. L’abbé, B. 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