SHORT COMMUNICATION Domino synthesis of ...

4 downloads 0 Views 158KB Size Report
Nov 24, 2015 - Domino synthesis of novel series of 4-substituted ... thiourazoles) via domino combination of thiophosgene, aliphatic or aromatic amines, and ...

Chemical Papers 66 (11) 1078–1081 (2012) DOI: 10.2478/s11696-012-0228-1

SHORT COMMUNICATION

Domino synthesis of novel series of 4-substituted 5-thioxo-1,2,4-triazolidin-3-one derivatives Arash Ghorbani-Choghamarani*, Sara Sardari Department of Chemistry, Faculty of Science, Ilam University, P.O. Box 69315516, Ilam, Iran Received 18 February 2012; Revised 9 May 2012; Accepted 17 May 2012

The efficient synthesis of 4-substituted 5-thioxo-1,2,4-triazolidin-3-one derivatives (4-substituted thiourazoles) via domino combination of thiophosgene, aliphatic or aromatic amines, and ethyl carbazate is presented. c 2012 Institute of Chemistry, Slovak Academy of Sciences  Keywords: thiourazole, thiophosgene, amine, ethyl carbazate, isothiocyanate

Heterocycles are essential moieties in a wide range of biologically active molecules; it is hardly surprising, therefore, that considerable effort has been channelled towards the development of combinatorial synthetic methodologies for the preparation of heterocyclic libraries (Phoon & Sim, 2002). Urazole derivatives (1,2,4-triazolidine-3,5-diones) are useful five-membered heterocyclic compounds which can provide a wide variety of aliphatic as well as aromatic constituents at position 4 (Mallakpour & Rafiee, 2007). Urazoles were reported as possessing herbicidal and biological properties (Simlot et al., 1994). A thiourazole compound also exhibited herbicidal activity (Shimizu et al., 1995). As part of our ongoing programmes towards the synthesis and modification of heterocyclic compounds (Ghorbani-Choghamarani et al., 2008, 2009a, 2009b, 2010, 2011), we present an efficient route for the synthesis of 4-substituted thiourazole derivatives. Starting amines were purchased from Merck (Darmstadt, Germany) and Acros Organics (Geel, Belgium). Thiophosgene and ethyl carbazate were obtained from Acros Organics (Geel, Belgium). Melting points were determined with an Electrothermal IA 9100 apparatus and are uncorrected. IR spectra (in nujol) were recorded on a Bomem IR spectrometer. 1 H NMR (400 MHz) and 13 C NMR (100.6 MHz) spectra (in DMSO-d6 using TMS as an internal standard) were recorded using Bruker FX

400Q spectrometer. EI mass spectra were measured using Agilent Technologies (HP) mass spectrometer at ionisation energy of 70 eV. General procedure for the synthesis of 4-substituted 5-thioxo-1,2,4-triazolidin-3-ones (IVa–IVj) Thiophosgene (1 mmol) was added in portions over 2–3 min to a mixture of the corresponding amine (RNH2 , Ia–Ij) (1 mmol) and triethylamine (2 mmol) in anhydrous THF (10 mL), and the mixture was stirred at ambient temperature for 1 h. Ethyl carbazate (1.2 mmol) was then added and the reaction mixture was heated under reflux for 2 h followed by evaporation of the solvent to give the corresponding ethyl 2-(R-carbamothioyl)hydrazinecarboxylate (IIIa– IIIj). To this, an aqueous solution of KOH (5 M, 20 mL) was added and the mixure was heated under reflux for 5 h, cooled in an ice bath and concentrated HCl was added (to pH 1). The white crystalline product was collected and dried to afford the corresponding 4-substituted thiourazole (for substituent R, see Table 1). Starting from 4-bromoaniline (Ia) and thiophosgene in the presence of triethylamine in THF as a solvent, 4-bromophenyl isothiocyanate (IIa) was obtained within 1 h. In the next step, IIa and ethyl carbazate in THF were heated under re-

*Corresponding author, e-mail: [email protected], [email protected]

Unauthenticated Download Date | 11/24/15 9:02 AM

1079

A. Ghorbani-Choghamarani, S. Sardari/Chemical Papers 66 (11) 1078–1081 (2012)

Fig. 1. Synthesis of 4-substituted 5-thioxo-1,2,4-triazolidin-3-ones (IVa–IVj). Reaction conditions: i) thiophosgene, triethylamine, THF, 25 ◦C, 1 h; ii) ethyl carbazate, THF, reflux, 2 h; iii) 5 M KOH, reflux, 5 h. Table 1. Characterisation data of newly prepared 4-substituted 5-thioxo-1,2,4-triazolidin-3-ones (IVa–IVj) Formula

Mr

Yieldb /%

M.p./ ◦C

IVa

C8 H6 N3 BrOS

272.12

65

232–235

IVb

C9 H9 N3 OS

207.25

75

213–216

IVc

C11 H13 N3 OS

235.31

55

189–191

IVd

C10 H11 N3 OS

221.28

72

195–198

IVe

C8 H13 N3 OS

199.27

70

181–183

IIIf

C10 H17 N3 OS

227.33

80

228–230

IIIg

C8 H7 N3 OS

193.23

70

190–192c

IIIh

C9 H9 N3 OS

207.25

78

214–216d

IVi

C12 H9 N3 OS

243.28

52

251–254

IIIj

C27 H21 N3 OS

435.54

98

185–189

Compound

Ra

a) See Fig. 1; b) isolated yield after recrystallisation; c) 193.5–195.5 ◦C (reported by Bradsher et al. (1958)); d) 216.5–217.5 ◦C (reported by Bradsher et al. (1958)).

flux for 2 h to afford 1-(4-bromophenyl)-2-thiobiurea (IIIa) (quantitatively) which was dissolved in a 5 M aqueous solution of KOH and heated under reflux to give 4-(4-bromophenyl)-5-thioxo-1,2,4-triazolidin3-one (IVa). Subsequently, transformation of Ia to IVa was performed via a cascade domino reaction (without isolation of intermediates), affording IVa in 65 % yield.

Analogously, a series of new 4-substituted thiourazoles was prepared by cascade domino reaction using different types of starting amines (Fig. 1). The characterisation and spectral data of the compounds prepared are given in Tables 1 and 2, respectively. In the synthesis of thiourazoles as intermediates for the preparation of inhibitors of the c-Jun Nterminal kinase, De et al. (2009) assigned structure

Unauthenticated Download Date | 11/24/15 9:02 AM

1080

A. Ghorbani-Choghamarani, S. Sardari/Chemical Papers 66 (11) 1078–1081 (2012)

Table 2. Spectral data of prepared compounds Compound

Spectral data

IIIa

1 H NMR (DMSO-d ), δ: 9.82 (s, 1H), 9.66 (s, 1H), 9.38 (s, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.8 Hz, 2H), 6 4.08 (q, J = 6.8 Hz, 2H), 1.22 (t, J = 6.8 Hz, 3H) 13 C NMR (DMSO-d ), δ: 181.3, 156.4, 139.1, 131.2, 128.1, 126.1, 61.4, 15.0 6 MS, m/z (Ir /%): 319 (26) (M+ + 2), 317 (21) (M+ ), 273 (5), 215 (87), 213 (76), 104 (100), 57 (18), 41 (13) IR, ν˜/cm−1 : 3134, 2932, 1699, 1515, 1456, 1377, 1301, 1201, 1184, 921, 896, 800 1 H NMR (DMSO-d ), δ: 12.53 (br, 2H), 7.71 (d, J = 7.6 Hz, 2H), 7.27 (d, J = 6.4 Hz, 2H) 6 13 C NMR (DMSO-d ), δ: 167.4, 152.8, 136.9, 132.3, 130.5, 122.2 6 MS, m/z (Ir /%): 274 (2.5) (M+ + 2), 272 (2.3) (M+ ), 260 (17), 167 (17), 151 (100), 149 (42), 83 (29), 64 (60), 57 (47), 41 (36) IR, ν˜/cm−1 : 3137, 2928, 1699, 1646, 1511, 1459, 1372, 1315, 1302, 1245, 1180, 1105, 770 1 H NMR (DMSO-d ), δ: 13.15–12.35 (br, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8 Hz, 2H), 2.35 (s, 3H) 6 13 C NMR (DMSO-d ), δ: 167.4, 152.8, 138.6, 130.7, 129.7, 128.5, 21.2 6 MS, m/z (Ir /%): 207 (82) (M+ ), 178 (2), 149 (100), 133 (21), 107 (18), 91 (24), 57 (34), 43 (24) IR, ν˜/cm−1 : 3285, 2956, 2924, 1714, 1687, 1527, 1462, 1377, 1315, 1248, 1032, 721 1 H NMR (DMSO-d ), δ: 12.71 (br, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 2.95 (sep, J = 6.8 Hz, 6 1H), 1.23 (d, J = 6.8 Hz, 6H) 13 C NMR (DMSO-d ), δ: 167.2, 152.8, 149.2, 130.9, 128.6, 127.1, 33.7, 24.3 6 MS, m/z (Ir /%): 235 (100) (M+ ), 220 (69), 207 (3), 193 (53), 167 (31), 149 (80), 91 (16), 57 (26), 43 (25) IR, ν˜/cm−1 : 3417, 1720, 1651, 1512, 1415, 1258, 1047, 722 1 H NMR (DMSO-d ), δ: 12.50 (br, 2H), 7.34–7.05 (m, 4H), 2.65 (q, J = 7.6 Hz, 2H), 1.21 (t, J = 7.6 Hz, 3H) 6 13 C NMR (DMSO-d ), δ: 167.3, 153.1, 144.8, 130.7, 128.6, 128.4, 28.3, 15.9 6 MS, m/z (Ir /%): 221 (100) (M+ ), 206 (18), 192 (4), 163 (13), 148 (11), 132 (28), 120 (7), 91 (6), 77 (13), 43 (3) IR, ν˜/cm−1 : 3308, 3128, 1668, 1564, 1460, 1370, 1308, 1261, 1228, 986, 891, 721 1 H NMR (DMSO-d ), δ: 12.81–12.11 (br, 2H), 4.32 (m, 1H), 2.21–2.11 (m, 2H), 1.79–1.76 (m, 2H), 1.59–1.56 (m, 6 3H), 1.29–1.08 (m, 3H) 13 C NMR (DMSO-d ), δ: 167.1, 153.1, 53.6, 28.6, 25.8, 25.3 6 MS, m/z (Ir /%): 199 (26) (M+ ), 167 (23), 149 (62), 118 (100), 117 (46), 98 (10), 91 (2), 83 (16), 67 (17), 55 (48), 41 (39) IR, ν˜/cm−1 : 3369, 3165, 1665, 1556, 1456, 1372, 1310, 1080, 754, 716 1 H NMR (DMSO-d ), δ: 12.43 (br, 2H), 4.55 (m, 1H), 2.21 (m, 3H), 1.74–1.47 (m, 11H) 6 13 C NMR (DMSO-d ), δ: 166.2, 153.3, 54.3, 30.8, 26.4, 25.9, 25.0 6 MS, m/z (Ir /%): 227 (25) (M+ ), 216 (3), 177 (1), 149 (4), 118 (100), 117 (33), 111 (11), 95 (10), 91 (2), 81 (18), 69 (57), 67 (20), 55 (33), 41 (33) IR, ν˜/cm−1 : 3395, 3150, 1703, 1456, 1372, 1251, 1084, 1042, 716 1 H NMR (DMSO-d ), δ: 12.66 (br, 2H), 7.51–7.35 (m, 5H) 6 13 C NMR (DMSO-d ), δ: 164.3, 153.7, 132.8, 129.4, 129.1, 128.2 6 MS, m/z (Ir /%): 193 (74) (M+ ), 178 (23), 167 (35), 161 (12), 150 (16), 149 (100), 136 (8), 117 (15), 104 (13), 91 (11), 77 (28), 71 (27), 57 (45), 43 (36), 41 (32) 1 H NMR (DMSO-d ), δ: 12.58 (br, 2H), 7.30–7.26 (m, 5H), 4.81 (s, 2H) 6 13 C NMR (DMSO-d ), δ: 167.8, 158.2, 141.5, 133.6, 132.8, 132.7 6 MS, m/z (Ir /%): 207 (21) (M+ ), 191 (4), 174 (7), 167 (1), 149 (6), 106 (30), 91 (100), 86 (3), 77 (8), 65 (15), 57 (2), 43 (3), 41 (4) IR, ν˜/cm−1 : 3328, 1720, 1650, 1462, 1415 1 H NMR (DMSO-d ), δ: 12.78 (br, 2H), 8.10–8.04 (m, 2H), 7.57–7.51 (m, 5H) 6 13 C NMR (DMSO-d ), δ: 168.1, 153.2, 134.3, 130.4, 130.2, 129.8, 128.8, 128.5, 127.6, 127.0, 126.0, 122.8 6 MS, m/z (Ir /%): 243 (12) (M+ ), 193 (3), 178 (5), 149 (100), 113 (12), 104 (8), 83 (12), 71 (25), 57 (42), 55 (24), 43 (30), 41 (28) IR, ν˜/cm−1 : 3371, 2929, 1711, 1678, 1462, 1377, 1083, 1048, 721 1 H NMR (DMSO-d ), δ: 12.62 (br, 2H), 7.26–7.08 (m, 19H) 6 13 C NMR (DMSO-d ), δ: 169.8.1, 153.7, 147.4, 146.5, 131.4, 130.9, 128.3, 128.0, 127.3, 126.6 6 MS, m/z (Ir /%): 435 (18) (M+ ), 358 (46), 335 (49), 258 (100), 243 (21), 221 (27), 207 (48), 180 (26), 165 (46), 133 (15), 118 (12), 104 (12), 86 (81), 58 (22), 41 (20)

IVa

IVb

IVc

IVd

IVe

IVf

IVg

IVh

IVi

IVj

B to thiourazole tautomer (Fig. 1). By contrast, the 1 H and 13 C spectral data of 4-substituted thiourazoles IVa–IVj indicate tautomeric structure A, similarly to 13 C NMR data observed by Phoon and Sim (2002) for 1,2,4-trisubstituted thiourazoles, which cannot assume the B tautomer structure. In this case, the two most deshielded 13 C resonances for 1,2,4-

trisubstituted thiourazoles occur at δ approximately of 153 and 170 (in CDCl3 ). 13 C NMR spectra of 4substituted thiourazoles IVa–IVj (in DMSO-d6 because they are insoluble in CDCl3 ) showed the most deshielded resonances at δ approximately of 153 and 167, almost identical chemical shifts to those reported by Phoon and Sim (2002).

Unauthenticated Download Date | 11/24/15 9:02 AM

A. Ghorbani-Choghamarani, S. Sardari/Chemical Papers 66 (11) 1078–1081 (2012)

In summary, an efficient method for the synthesis of 4-substituted-5-thioxo-1,2,4-triazolidin-3-ones via a cascade tandem reaction of various amines with thiophosgene and ethyl carbazate was developed. Good to excellent yields of the products can be achieved with aliphatic as well as aromatic amines. Acknowledgements. The authors express their gratitude to the research facilities of Ilam University, Ilam, Iran for financial support for this research.

References Bradsher, C. K., Brown, F. C., & Webster, S. T. (1958). Some 4substituted thiourazoles. The Journal of Organic Chemistry, 23, 618–619. DOI: 10.1021/jo01098a607. De, S. K., Stebbins, J. L., Chen, L. H., Riel-Mehan, M., Machleidt, T., Dahl, R., Yuan, H., Emdadi, A., Barile, E., Chen, V., Murphy, R., & Pellecchia, M. (2009). Design, synthesis, and structure-activity relationship of substrate competitive, selective, and in vivo active triazole and thiadiazole inhibitors of the c-Jun N-terminal kinase. Journal of Medicinal Chemistry, 52, 1943–1952. DOI: 10.1021/jm801503n. Ghorbani-Choghamarani, A., Zolfigol, M. A., Salehi, P., Ghaemi, E., Madrakian, E., Nasr-Isfahani, H., & Shahamirian, M. (2008). An efficient procedure for the synthesis of Hantzsch 1,4-dihydropyridines under mild conditions. Acta Chimica Slovenica, 55, 644–647. Ghorbani-Choghamarani, A., Chenani, Z., & Mallakpour, S. (2009a). Supported nitric acid on silica gel and polyvinyl pyrrolidone (PVP) as an efficient oxidizing agent for the oxidation of urazoles and bis-urazoles. Synthetic Communications, 39, 4264–4270. DOI: 10.1080/00397910902898619.

1081

Ghorbani-Choghamarani, A., Hajjami, M., Goudarziafshar, H., Nikoorazm, M., Mallakpour, S., Sadeghizadeh, F., & Azadi, G. (2009b). Catalytic oxidation of urazoles and bis-urazoles to their corresponding triazolinediones using aluminium nitrate and a catalytic amount of silica sulfuric acid. Monatshefte f¨ ur Chemie, 140, 607–610. DOI: 10.1007/s00706-0080100-8. Ghorbani-Choghamarani, A., Zolfigol, M. A., Hajjami, M., Rastgoo, S., & Mallakpour, S. (2010). Metal-free oxidation of urazole and 1,4-dihydropyridine derivatives under mild and heterogeneous conditions by nitro urea, derived from urea nitrate, and silica sulfuric acid. Letters in Organic Chemistry, 7, 249–254. Ghorbani-Choghamarani, A., Zolfigol, M. A., Hajjami, M., Goudarziafshar, H., Nikoorazm, M., Yousefi, S., & Tahmasbi, B. (2011). Nano aluminium nitride as a solid source of ammonia for the preparation of Hantzsch 1,4-dihydropyridines and bis-(1,4-dihydropyridines) in water via one pot multicomponent reaction. Journal of the Brazilian Chemical Society, 22, 525–531. Mallakpour, S., & Rafiee, Z. (2007). A novel one-pot synthesis of 4-substituted 1,2,4-triazolidine-3,5-diones. Synlett, 2007, 1255–1256. DOI: 10.1055/s-2007-977413. Phoon, C. W., & Sim, M. M. (2002). Solid-phase syntheses of 1,2,4-trisubstituted urazole and thiourazole derivatives. Journal of Combinatorial Chemistry, 4, 491–495. DOI: 10.1021/cc0200134. Shimizu, T., Hashimoto, N., Nakayama, I., Nakao, T., Mizutani, H., Unai, T., Yamaguchi, M., & Abe, H. (1995). A novel isourazole herbicide, fluthiacet-methyl, is a potent inhibitor of protoporphyrinogen oxidase after isomerization by glutathione S-transferase. Plant & Cell Physiology, 36, 625– 632. Simlot, R., Izydore, R. A., Wong, O. T., & Hall, I. H. (1994). Hypolipidemic activity of 4-substituted 1,2-diacyl1,2,4-triazolidine-3,5-diones in rodents. Journal of Pharmaceutical Sciences, 83, 367–371. DOI: 10.1002/jps.2600830320.

Unauthenticated Download Date | 11/24/15 9:02 AM