An Efficient Aromatization of 2-Amino-4,5,6,7-tetrahydrobenzo-[b]thiophene-3-carboxylates in Dimethyl Sulfoxide Catalyzed by p-Toluenesulfonic Acid

Abstract

A novel oxidation–aromatization of alkyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylates is reported. The Gewald product, obtained from three-component condensation reaction between a cyclohexanone, an alkyl cyanoacetate, and sulfur, underwent an oxidation reaction in dimethyl sulfoxide in the presence of a catalytic amount of p-toluenesulfonic acid to give the corresponding alkyl 2-aminobenzo[b]thiophene-3-carboxylate in excellent yield.

Key words

2-aminobenzo[b]thiophene-3-carboxylates - Gewald reaction - oxidation–aromatization - dimethyl sulfoxide - p-toluenesulfonic acid

• References and Notes

• 1 Abreu AS, Ferreira PM. T, Monteiro LS, Queiroz MJ. R. P, Ferreira IC. F. R, Calhelha RC, Estevinho LM. Tetrahedron 2004; 60: 11821
• 2 Raga MM, Moreno-Mañas M, Cuberes MR, Palacín C, Castelló JM, Ortiz JA. Arzneim. Forsch. 1992; 42: 691
• 3 Mourey RJ, Burnette BL, Brustkern SJ, Daniels JS, Hirsch JL, Hood WF, Meyers MJ, Mnich SJ, Pierce BS, Saabye MJ, Schindler JF, South SA, Webb EG, Zhang J, Anderson DR. J. Pharmacol. Exp. Ther. 2010; 333: 797
• 4 Black LJ, Jones CD, Falcone JF. Life Sci. 1983; 32: 1031
• 5a Chen Z, Mocharla VP, Farmer JM, Pettit GR, Hamel E, Pinney KG. J. Org. Chem. 2000; 65: 8811
• 5b Flynn BL, Flynn GP, Hamel E, Jung MK. Bioorg. Med. Chem. Lett. 2001; 11: 2341
• 6 Markwell RE, Smith SA, Ward RW. US 4548948 (A), 1985
• 7 Burkart SE, Davis SG, Lutomski KA, Meier GA, Phillips RB, Roush DM. US 5073564 (A), 1991
• 8 Tao ZF, Hasvold LA, Leverson JD, Han EK, Guan R, Johnson EF, Stoll VS, Stewart KD, Stamper G, Soni N, Bouska JJ, Luo Y, Sowin TJ, Lin NH, Giranda VS, Rosenberg SH, Penning TD. J. Med. Chem. 2009; 52: 6621
• 9 Laporte MG, Lessen TA, Leister L, Cebzanov D, Amparo E, Faust C, Ortlip D, Bailey TR, Nitz TJ, Chunduru SK, Young DC, Burns CJ. Bioorg. Med. Chem. Lett. 2006; 16: 100
• 10a Arndt HD. Angew. Chem. 2006; 118: 4664
• 10b Kellen JA. In Vivo 2001; 15: 459
• 10c Jordan VC. J. Med. Chem. 2003; 46: 1081
• 10d Detre S, Riddler S, Salter J, A’Hern R, Dowsett M, Johnston SR. D. Cancer Res. 2003; 63: 6516
• 10e Rossi A, Pergola C, Koeberle A, Hoffmann M, Dehm F, Bramanti P, Cuzzocrea S, Werz O, Sautebin L. Br. J. Pharmacol. 2010; 161: 555
• 10f Qin Z, Kastrati I, Chandrasena RE. P, Liu H, Yao P, Petukhov PA, Bolton JL, Thatcher GR. J. J. Med. Chem. 2007; 50: 2682
• 10g Liu H, Liu J, van Breemen RB, Thatcher GR, Bolton JL. Chem. Res. Toxicol. 2005; 18: 162
• 11a Fouad I, Mechbal Z, Chane-Ching KI, Adenier A, Maurel F, Aaron JJ, Vodicka P, Cernovska K, Kozmik V, Svoboda J. J. Mater. Chem. 2004; 14: 1711
• 11b Jung KH, Kim KH, Lee DH, Jung DS, Park CE, Choi DH. Org. Electron. 2010; 11: 1584
• 12a Tietze LF, Lohmann JK, Stadler C. Synlett 2004; 1113
• 12b Tietze LF, Thede K, Schimpf R, Sannicolo F. Chem. Commun. 2000; 583
• 13 Nakamaya J In Comprehensive Heterocyclic Chemistry II . Vol. 2. Katritzky AR, Rees CW, Scriven EF. V. Chapt. 11 Pergamon Press; London: 1996: 607-677 ; and references cited therein
• 14 Sato O, Nakayama J In Comprehensive Heterocyclic Chemistry III . Vol 3. Katritzky AR, Ramsden CA, Scriven EF. V, Taylor RJ. K. Chapt. 11 Elsevier Science; Oxford: 2008: 843-922 ; and references cited therein
• 15a Kim S, Dahal N, Kesharwani T. Tetrahedron Lett. 2013; 54: 4373
• 15b Teplyakov FS, Vasileva TG, Petrov ML, Androsov DA. Org. Lett. 2013; 15: 4038
• 15c Romagnoli R, Baraldi PG, Lopez-Cara C, Preti D, Aghazadeh Tabrizi M, Balzarini J, Bassetto M, Brancale A, Fu XH, Gao Y, Li J, Zhang SZ, Hamel E, Bortolozzi R, Basso G, Viola G. J. Med. Chem. 2013; 56: 9296
• 15d Lyapunova AG, Androsov DA, Petrov ML. Tetrahedron Lett. 2013; 54: 3427
• 15e Hari DP, Hering T, König B. Org. Lett. 2012; 14: 5334
• 15f Han J, Wang Q, Chang X, Liu Y, Wang Y, Meng J. Tetrahedron 2011; 67: 8865
• 15g Mésangeau C, Fraise M, Delagrange P, Caignard DH, Boutin JA, Berthelot P, Yous S. Eur. J. Med. Chem. 2011; 46: 1835
• 15h Duan Z, Ranjit S, Liu X. Org. Lett. 2010; 12: 2430
• 15i Isloor AM, Kalluraya B, Pai KS. Eur. J. Med. Chem. 2010; 45: 825
• 15j Kobayashi K, Horiuchi M, Fukamachi S, Konishi H. Tetrahedron 2009; 65: 2430
• 15k Pradhan TK, De A. Tetrahedron Lett. 2005; 46: 1493
• 16 Zhang X, Zhou X, Kisliuk RL, Piraino J, Cody V, Gangjee A. Bioorg. Med. Chem. 2011; 19: 3585
• 17 Seio K, Tanaka H, Kohara T, Hashimoto K, Fujimura M, Horiuchi H, Yasumatsu Y, Kimura K. US 6271225 (B1), 2001
• 18 Eiden F, Felbermeir G. Arch. Pharm. 1984; 317: 675
• 19 Gewald N, Neumann G, Böttcher H. Z. Chem. 1966; 6: 261
• 20a Adib M, Sheikhi E, Haghshenas P, Rajai-Daryasarei S, Bijanzadeh HR. Zhu L. G. Tetrahedron Lett. 2014; 55: 4983
• 20b Adib M, Sheikhi E, Bagheri M, Bijanzadeh HR, Amanlou M. Tetrahedron 2012; 68: 3237
• 20c Adib M, Sheikhi E, Rezaei N. Tetrahedron Lett. 2011; 52: 3191
• 20d Adib M, Ansari S, Bijanzadeh HR. Synlett 2011; 619
• 20e Adib M, Karimzadeh M, Mahdavi M, Sheikhi E, Mirzaei P. Synlett 2011; 834
• 21 Adib M, Bayanati M, Soheilizad M, Janatian Ghazvini H, Tajbakhsh M, Amanlou M. Synlett 2014; 25: 2918
• 22 General Procedure for the Preparation of Methyl 2-Aminobenzo[b]thiophene-3-carboxylate (7a) A mixture of cyclohexanone (0.196 g, 2.0 mmol), methyl cyanoacetate (0.198 g, 2.0 mmol), elemental sulfur (0.064 g, 2.0 mmol), and morpholine (0.174 g, 2.0 mmol) was heated at 75 °C for 1 h. After nearly complete conversion into the corresponding 2-aminothiophene, as was indicated by TLC monitoring, the reaction mixture was cooled to r.t., and the solid residue was recrystallized from EtOH to afford methyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (6a ). Then a solution of 6a (0.211 g, 1 mmol) and TsOH (0.052 g, 0.3 mmol) in DMSO (1 mL) was heated at 190 °C for 45 min in a silicone oil bath. Progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to r.t., H₂O (4 mL) was added to the mixture, which then was extracted with CH₂Cl₂ (3 × 5 mL). The extract was dried with Na₂SO₄, and the solvent was removed. The residue was crystallized from n-hexane–EtOAc (5:1) to afford the pure product as pale yellow crystals, mp 126–128 °C, yield 0.203 g, 98% (on the basis of 6a). IR (KBr): ν_max = 3395, 3280 and 3167 (NH), 1647 (C=O), 1591, 1493, 1464, 1431, 1372, 1275, 1231, 1146, 1011, 779, 741, 662 cm^–1. MS: m/z (%) = 207 (95) [M⁺], 175 (100), 147 (40), 121 (37), 103 (8), 77 (9), 69 (6). ¹H NMR (500.1 MHz, CDCl₃): δ = 3.97 (s, 3 H, CH₃), 6.55 (br s, 2 H, NH₂), 7.16 (td, J = 7.6, 1.2 Hz, 1 H, CH), 7.34 (td, J = 7.8, 1.2 Hz, 1 H, CH), 7.52 (d, J = 8.0 Hz, 1 H, CH), 8.10 (d, J = 8.0 Hz, 1 H, CH). ¹³C NMR (100.6 MHz, CDCl₃): δ = 51.1 (OCH₃), 99.7 (CCO₂), 121.4, 122.4, 122.5 and 125.5 (4 × CH), 128.8 and 137.3 (2 × C), 164.5 (SCN), 166.7 (C=O).