A New Synthesis Strategy for Rhodanine and Its Derivatives

Abstract

Rhodanine and its derivatives have been known as privileged structures in pharmacological research because of their wide spectrum of biological activities, but the synthesis method of rhodanine skeleton is limited. In this paper, not only rhodanine skeleton, but also N-aryl rhodanines can be directly prepared via the reaction of thioureas and thioglycolic acid in one step catalyzed by protic acid, which provides a new approach of the synthesis of rhodanine and its derivatives. The developed strategy is straightforward, efficient, atom economical, and convenient in good yields.

Key words

rhodanine - thiourea - thioglycolic acid - thiazolidone - heterocycle

• References and Notes

• 1 Chen HX, Fan DL, Huang JM, Huang WJ, Zhang GY, Huang L. Sci. Adv. Mater. 2020; 12: 665
• 2 Kazemi M, Ghobadi M, Mirzaie A. Nanotechnol. Rev. 2018; 7: 43
• 3 Fadhel AZ, Pollet P, Liotta CL, Eckert CA. Molecules 2010; 15: 8400
• 4 Gao NS, Cheng BZ, Hou H, Zhang RH. Mater. Lett. 2018; 212: 243
• 5 Nagahora N, Kitahara K, Mizuhata Y, Tokitoh N, Shioji K, Okuma K. J. Org. Chem. 2020; 85: 7748
• 6 Yang LF, Zhang N, Han Y, Zou Y, Qiao YJ, Chang DD, Zhao Y, Lu XF, Wu JS, Liu YQ. Chem. Commun. 2020; 56: 9990
• 7 Harry NA, Ujwaldev SM, Aneeja T, Anilkumar G. Curr. Org. Chem. 2021; 25: 248
• 8 Utreja D, Kaur J, Kaur K, Jain P. Mini-Rev. Org. Chem. 2020; 17: 991
• 9 Sharma PK, Amin A, Kumar M. Open Med. Chem. J. 2020; 14: 49
• 10 Azizmohammadi M, Khoobi M, Ramazani A, Emami S, Zarrin A, Firuzi O, Miri R, Shafiee A. Eur. J. Med. Chem. 2013; 59: 15
• 11 Chen L, Noory-Fajer A, Yessimbekov Z, Kazemi M, Mohammadi M. J. Sulfur Chem. 2019; 40: 451
• 12 Wu XM, Huang B, Wang QG, Wang Y. Chem. Eng. J. 2020; 380: 122456
• 13 Brahmbhatt H, Molnar M, Pavić V, Rastija V. Med. Chem. 2019; 15: 840
• 14 Tomasic T, Masic LP. Curr. Med. Chem. 2009; 16: 1596
• 15 Hajibabaei K. Synlett 2014; 25: 2083
• 16 Li W, Zheng CJ, Sun LP, Song MX, Wu Y, Li YJ, Liu Y, Piao HR. Arch. Pharm. Res. 2014; 37: 852
• 17 Zvarec O, Polyak SW, Tieu W, Kuan K, Dai H, Pedersen DS, Morona R, Zhang L, Booker GW, Abell AD. Bioorg. Med. Chem. Lett. 2012; 22: 2720
• 18 Villain-Guillot P, Gualtieri M, Bastide L, Roquet F, Martinez J, Amblard M, Pugniere M, Leonetti JP. J. Med. Chem. 2007; 50: 4195
• 19 Tejchman W, Orwat B, Korona-Głowniak I. RSC Adv. 2019; 9: 39367
• 20 Dolezel J, Hirsova P, Opletalova V, Dohnal J, Marcela V, Kunes J, Jampilek J. Molecules 2009; 14: 4197
• 21 Sortino M, Delgado P, Juárez S, Quiroga J, Abonía R, Insuasty B, Nogueras M, Rodero L, Garibotto FM, Enriz RD, Zacchino SA. Bioorg. Med. Chem. 2007; 15: 484
• 22 Singh P, Jindal B, Surolia A, Panda D. Biochemistry 2012; 51: 5434
• 23 Sinko W, Wang Y, Zhu W, Zhang Y, Feixas F, Cox CL, Mitchell DA, Oldfield E, McCammon JA. J. Med. Chem. 2014; 57: 5693
• 24 Murugan R, Anbazhagan S, Lingeshwaran S, Sriman Narayanan S. Eur. J. Med. Chem. 2009; 44: 3272
• 25 Nitsche C, Schreier VN, Behnam MA, Kumar A, Bartenschlager R, Klein CD. J. Med. Chem. 2013; 56: 8389
• 26 Jadav SS, Sinha BN, Hilgenfeld R, Pastorino B, Lamballerie X, Jayaprakash V. Eur. J. Med. Chem. 2015; 89: 172
• 27 Min G, Lee SK, Kim HN, Han YM, Lee RH, Jeong DG, Han DC, Kwon BM. Bioorg. Med. Chem. Lett. 2013; 23: 3769
• 28 Ge X, Wakim B, Sem DS. J. Med. Chem. 2008; 51: 4571
• 29 Alegaon SG, Alagawadi KR, Sonkusare PV, Chaudhary SM, Dadwe DH, Shah AS. Bioorg. Med. Chem. Lett. 2012; 22: 1917
• 30 He XY, Lu L, Qiu J, Zou P, Yu F, Jiang XK, Li L, Jiang S, Liu S, Xie L. Bioorg. Med. Chem. 2013; 21: 7539
• 31 Ramkumar K, Yarovenko VN, Nikitina AS, Zavarzin IV, Krayushkin MM, Kovalenko LV, Esqueda A, Odde S, Neamati N. Molecules 2010; 15: 3958
• 32 Berczyński P, Kładna A, Piechowska T, Kruk I, Bozdağ-Dündar O, Aboul-Enein HY, Ceylan-Unlusoy M, Ertan R. Luminescence 2014; 29: 1107
• 33 Polshettiwar V, Luque R, Fihri A, Zhu H, Bouhrara M, Basset JM. Chem. Rev. 2011; 111: 3036
• 34 Zeng L, Chen G, Chen HX. Materials 2020; 13: 1780
• 35 Hashemi OR, Kargar MR, Raoufi F, Moghimi A, Aghabozorg H, Ganjali MR. Microchem. J. 2001; 69: 1
• 36 Ramirez MA, Borja NL. Pharmacotherapy 2008; 28: 646
• 37 Horiuchi T, Miura H, Sumioka K. J. Am. Chem. Soc. 2004; 126: 12218
• 38 Ito S, Miura H, Uchida S. Chem. Commun. 2008; 41: 5194
• 39 Zhang Q, Kan B, Liu F. Nat. Photonics 2014; 9: 35
• 40 Ojeka EO, Iyun JF. Global J. Pure Appl. Sci. 2004; 10: 577
• 41 Barakat A, Al-Majid AM, Al-Najjar HJ, Mabkhot YN, Ghabbourc HA, Func H.-K. RSC Adv. 2014; 4: 4909
• 42 Subhedar DD, Shaikh MH, Nawale L, Yeware A, Sarkar D, Shingate BB. Res. Chem. Intermed. 2016; 42: 6607
• 43 Subhedar DD, Shaikh MH, Shingate BB, Nawale L, Sarkar D, Khedkar VM, Kalam Khan FA, Sangshetti JN. J. Med. Chem. 2017; 125: 385
• 44 Subhedar DD, Shaikh MH, Nawale L, Yeware A, Sarkar D, Kalam Khan FA, Sangshetti JN, Shingate BB. Bioorg. Med. Chem. Lett. 2016; 26: 2278
• 45 Evans BE, Rittle KE, Bock MG, DiPardo RM, Freidinger RM, Whiter WL, Lundell GF, Veber DF, Anderson PS, Chang RS. L, Lottie VJ, Cerino DJ, Chen TB, Kling PJ, Kunkel KA, Springer JP, Hirshfield J. J. Med. Chem. 1988; 31: 2235
• 46 Alizadeh A, Zohreh N. Synlett 2009; 2146
• 47 Halimehjani AZ, Hosseinkhany S. Synthesis 2015; 47: 3147
• 48 Attanasi OA, De Crescentini L, Favi G, Filippone P, Giorgi G, Mantellini F, Moscatelli G, Behalo MS. Org. Lett. 2009; 11: 2265
• 49 Rostamniaa S, Doustkhaha E, Hassankhanib A. Supramol. Chem. 2015; 27: 1
• 50 Singh SJ, Chauhan SM. S. Tetrahedron Lett. 2013; 54: 2484
• 51 Razi MK, Javahershenas R, Adelzadeh M, Ghobadi M, Kazemi M. Synth. Commun. 2020; 50: 3739
• 52 Nitsche C, Klein CD. Tetrahedron Lett. 2012; 53: 5197
• 53 Radi M, Botta L, Casaluce G, Bernardini M, Botta M. J. Comb. Chem. 2010; 12: 200
• 54 Lesyk RB, Zimenkovsky BS. Curr. Org. Chem. 2004; 8: 1547
• 55 Quan W, An WK, Li Z, Wu LL, Jiang S, Pan ZL. Henan Science 2019; 37: 361
• 56 General Experimental Procedures To a solution of thiourea (10 mmol) and thioglycolic acid (10 mmol) in toluene (20 mL) was added hydrochloric acid (12 mmol). The reaction mixture was heated to 110 °C under stirring monitored by TLC. The mixture was then quenched by the addition of H₂O and extracted with toluene. The isolated organic phase was dried over Na₂SO₄, filtered, concentrated in vacuo, and purified by column chromatography on silica gel eluting with ethyl acetate–hexane.
• 57 Characterization Data
  2-Thioxothiazolidin-4-one Light yellow solid, mp 169–170 ℃. ¹H NMR (DMSO-d ₆, 400 MHz): δ = 13.15 (s, 1 H), 4.27 (s, 2 H). 3-Methyl-2-thioxothiazolidin-4-one Light yellow solid, mp 69–70 ℃. ¹H NMR (DMSO-d ₆, 400 MHz): δ = 4.25 (s, 2 H), 3.32–3.23 (s, 3 H). 3-Phenyl-2-thioxothiazolidin-4-one Light yellow solid, mp 188–190 ℃. ¹H NMR (DMSO-d ₆, 400 MHz): δ = 7.55–7.46 (m, 3 H), 7.28–7.26 (d, 2 H), 4.39 (s, 2 H). 3-(4-Methylphenyl)-2-thioxothiazolidin-4-one Light yellow solid, mp 169–170 ℃. ¹H NMR (DMSO-d ₆, 400 MHz): δ = 7.33–7.31 (d, 2 H), 7.14–7.12 (d, 2 H), 4.38 (s, 2 H), 2.50–2.25 (s, 3 H). 3-[3-(Trifluoromethyl)phenyl]-2-thioxothiazolidin-4-one Yellow solid, mp 176–177 ℃. ¹H NMR (DMSO-d ₆, 400 MHz): δ = 7.89–7.87 (d, 1 H), 7.81–7.78 (m, 2 H), 7.67–7.61 (m, 1 H), 4.38 (s, 2 H). 3-(2-Chlorophenyl)-2-thioxothiazolidin-4-one Yellow solid, mp 122–123 ℃. ¹H NMR (DMSO-d ₆, 400 MHz): δ = 7.69–7.66 (m, 1 H), 7.58–7.50 (m, 2 H), 7.49–7.45 (m, 1 H), 4.65–4.44 (dd, 2 H). 5-Methyl-3-phenyl-2-thioxothiazolidin-4-one Light yellow solid, mp 118–119 ℃. ¹H NMR (CDCl₃, 400 MHz): δ = 7.55–7.47 (m, 3 H), 7.21–7.19 (m, 2 H), 4.43–4.37 (q, 1 H), 1.80–1.78 (d, 3 H). 5-Methyl-3-(2-chlorophenyl)-2-thioxothiazolidin-4-one Light yellow sticky oil. ¹H NMR (CDCl₃, 400 MHz): δ = 7.58–7.56 (m, 1 H), 7.47–7.45 (m, 2 H), 7.26–7.25 (m, 1 H), 4.52–4.40 (m, 1 H), 1.85–1.80 (m, 3 H). 3,5-Diphenyl-2-thioxothiazolidin-4-one Light yellow solid, mp 132–133 ℃. ¹H NMR (CDCl₃, 400 MHz): δ = 7.58–7.57 (m, 3 H), 7.45–7.43 (m, 4 H), 7.36–7.34 (m, 3 H), 5.89 (s, 1 H). 5-Phenyl-3-[3-(trifluoromethyl)phenyl]-2-thioxothiazolidin-4-one Light yellow sticky. ¹H NMR (CDCl₃, 400 MHz): δ = 8.04–8.02 (t, 1 H), 7.45–7.41 (m, 4 H), 7.36–7.27 (m, 4 H), 5.90 (s, 1 H)