A Base-Free Multicomponent Domino Approach: One-Pot Synthesis of 2-Iminothiazolines via Oxy-Iodination of Arylacetylenes

Abstract

A simple and an efficient multicomponent domino protocol is developed for the synthesis of 2-iminothiazolines starting from simple and readily available arylacetylenes, amines, and phenyl isothiocyanates under base-free conditions. The present method involves oxy-iodination­ of the arylacetylenes with ammonium iodide and hydrogen peroxide, followed by cyclization processes. A number of diversely functionalized 2-iminothiazolines are synthesized in good to excellent yields.

Key words

arylacetylenes - amines - isothiocyanates - multicomponent reactions - base-free - metal-free conditions

• References and Notes

• 1a Nagasaki F, Yamada T, Takahashi E, Kitagawa Y, Hatano R. JP 63250371, 1988 ; Chem. Abstr. 1989, 110, 192810
• 1b Hoelzel H, Creuzburg D, Stohr P, Dehne H, Teller J, Kranz L, Luthardt H, Roethling T, Kaestner A. DD 258168, 1988 ; Chem. Abstr. 1989, 111, 2681g.
• 2a Ivanov YY, Tkachenko SE, Proshin AN, Bachurin SO. Biomed. Khim. 2003; 49: 92
• 2b Manaka A, Sato M, Aoki M, Tanaka M, Ikeda T, Toda Y, Yamane Y, Nakaike S. Bioorg. Med. Chem. 2001; 11: 1031
• 2c Aamer S, Sabah Z, Maryam J, Bushra M. Turk. J. Chem. 2008; 32: 585
• 2d Misra VS, Saxena A. J. Indian Chem. Soc. 1970; 47: 23
• 2e Hassan HY, El-Kousi NA, Farghaly ZS. Chem. Pharm. Bull. 1998; 46: 863
• 2f Bae S, Hahn HG, Nam KD, Mah H. J. Comb. Chem. 2005; 7: 7
• 2g Kim DS, Jeong YM, Park IK, Hahn HG, Lee HK, Kwon SB, Jeong JH, Yang SJ, Sohn UD, Park KC. Biol. Pharm. Bull. 2007; 30: 180
• 2h Manaka A, Sato M, Aoki M, Tanaka M, Ikeda T, Toda Y, Yamang Y, Nakaike S. Bioorg. Med. Chem. Lett. 2001; 11: 1031
• 2i Sondhi SM, Singh N, Lahoti AM, Bajaj K, Kumar A, Lozach O, Meijer L. Bioorg. Med. Chem. 2005; 13: 4291
• 3a Hantzsch A, Weber JH. Chem. Ber. 1887; 20: 3118
• 3b Traumann V. Liebigs Ann. Chem. 1888; 31
• 3c Svetlik J. J. Org. Chem. 1990; 55: 4740
• 3d D’hooghe M, Waterinckx A, De Kimpe N. J. Org. Chem. 2005; 70: 227
• 3e Sanemitsu Y, Kawamura S, Satoh J, Katayama T, Hashimoto S. J. Pestic. Sci. 2006; 31: 305
• 3f De Kimpe N, Boelens M, Declercq JP. Tetrahedron 1993; 49: 3411
• 3g De Kimpe N, De Cock W, Keppens M, De Smaele D, Meszaros A. J. Heterocycl. Chem. 1996; 33: 1179
• 3h Ingle ST, Kapley SM, Chande MS. Proc. Indian Acad. Sci., Chem. Sci. 1980; 89: 295
• 3i Wang X, Wang F, Quan Z, Zhang Z, Wang M. Synth. Commun. 2006; 36: 2453
• 3j Xia M, Lu Y.-D. Synth. Commun. 2006; 36: 1637
• 3k Manaka A, Ishii T, Takahashi K, Sato M. Tetrahedron Lett. 2005; 46: 419
• 3l Heravi MM, Moghimi S. Tetrahedron Lett. 2012; 53: 392
• 4 Murru S, Singh CB, Kavala V, Patel BK. Tetrahedron 2008; 64: 1931
• 5a Backvall JE. Modern Oxidation Methods . 2nd ed. Wiley-VCH; Weinheim: 2011
• 5b Lane BS, Burgess K. Chem. Rev. 2003; 103: 2457
• 5c Sanderson WR. Pure Appl. Chem. 2000; 72: 1289

For reviews on multicomponent reactions, see:
• 6a Zhu JP, Bienaymé H. Multicomponent Reactions . Wiley-VCH; Weinheim: 2005
• 6b Ramón DJ, Yus M. Angew. Chem. Int. Ed. 2005; 44: 1602
• 6c Simon C, Constantieux T, Rodriguez J. Eur. J. Org. Chem. 2004; 4957
• 6d Muravyova EA, Shishkina SV, Musatov VI, Knyazeva IV, Shishkin OV, Desenko SM, Chebanov VA. Synthesis 2009; 1375
• 6e Maggi R, Ballini R, Sartori G, Sartorio R. Tetrahedron Lett. 2004; 45: 2297
• 6f Dömling A, Ugi I. Angew. Chem. Int. Ed. 2000; 39: 3169
• 6g Khodaei MM, Khosropour AR, Moghanian H. Synlett 2006; 916
• 6h Huang S, Pan Y, Zhu Y, Wu A. Org. Lett. 2005; 7: 3797
• 6i Kumar R, Raghuvanshi K, Verma RK, Singh MS. Tetrahedron Lett. 2010; 51: 5933
• 6j Prajapati D, Gohain D. Beilstein J. Org. Chem. 2006; 2: 11

For reviews on domino reactions, see:
• 7a Tietze LF, Brasche G, Gericke K. Domino Reactions in Organic Synthesis . Wiley-VCH; Weinheim: 2006
• 7b Tietze LF. Chem. Rev. 1996; 96: 115
• 7c Nicolaou KC, Montagnon T, Snyder SA. Chem. Commun. 2003; 551
• 8a Kumar GS, Ragini SP, Meshram HM. Tetrahedron Lett. 2013; 54: 5974
• 8b Chandrasekhara Rao L, Meshram HM, Satish Kumar N, Nageswara Rao N, Jagadhheesh Babu N. Tetrahedron Lett. 2014; 55: 1127
• 8c Meshram HM, Babu BM, Kumar GS, Thakur PB, Bangade VM. Tetrahedron Lett. 2013; 54: 2296
• 9 Narender N, Reddy KS. K, Krishna Mohan KV. V, Kulkarni SJ. Tetrahedron Lett. 2007; 48: 6124
• 10 Thiazol-2-imines 4; General Procedure A 30% aq solution of H₂O₂ (2.2 mmol) was added dropwise to a vigorously stirred solution of NH₄I (2.2 mmol) and arylacetylene 1 (1 mmol) in AcOH (3 mL), and the resulting mixture was allowed to stir at r.t. After 6 h, amine 2 and isothiocyanate 3 were added and the mixture was stirred at 70 °C for 1 h. After completion of the reaction, the mixture was filtered, and the filtrate treated with aq Na₂S₂O₃ solution and then extracted with EtOAc. The combined organic layer was dried over Na₂SO₄ and evaporated under reduced pressure. Purification by column chromatography (hexane–EtOAc, 9.5:0.5) furnished the corresponding thiazol-2-imine 4. All the obtained products were characterized from their IR, ¹H NMR, ¹³C NMR, MS and HRMS spectral data. (Z)-N-[4-(4-Fluorophenyl)-3-phenylthiazol-2(3H)-ylidene]aniline (4b) Yield: 249.20 mg (72%); pale yellow solid; mp 172–174 °C. IR (KBr): 703, 752, 1099, 1267, 1402, 1589, 1621 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 5.92 (s, 1 H), 6.88 (t, J = 8.54 Hz, 2 H), 6.99–7.10 (m, 5 H), 7.22–7.27 (m, 3 H), 7.28–7.35 (m, 4 H). ¹³C NMR (75 MHz, CDCl₃): δ = 97.1, 115.2 (d, ² J _C–F = 21.7 Hz), 121.5, 123.2, 127.6, 127.7 (d, ⁴ J _C–F = 2.7 Hz), 128.8, 128.9, 129.3, 129.9 (d, ³ J _C–F = 8.1 Hz), 137.7, 138.8, 151.7, 159.9, 162.4 (d, ¹ J _C–F = 248.8 Hz). MS (ESI): m/z = 347 [M + H]⁺. HRMS (ESI): m/z [M + H]⁺calcd for C₂₁H₁₆N₂FS: 347.1012; found: 347.1004.
• 11 For a review on 2-iminothiazolidines (i.e., compounds related to 2-iminothiazolines), see: D’hooghe M, De Kimpe N. Tetrahedron 2006; 62: 513