An Efficient Synthesis of 2,4,6-Triarylpyridines via Solvent-Free Reaction between Acetophenoneoximes and Aldehydes

Abstract

An efficient synthesis of 2,4,6-triarylpyridines is described. Heating a mixture of an acetophenoneoxime and an aldehyde under solvent-free conditions afforded Kröhnke pyridines in excellent yields. In this method acetophenoneoximes are directly used for the preparation of Kröhnke pyridines under metal-free conditions.

Key words

2,4,6-triarylpyridines - acetophenoneoximes - aldehydes - solvent-free synthesis - cyclizations - heterocycles

• References and Notes

• 1 Kim BY, Ahn JB, Lee HW, Kang SK, Lee JH, Shin JS, Ahn SK, Hong CI, Yoon SS. Eur. J. Med. Chem. 2004; 39: 433
• 2 Enyedy IJ, Sakamuri S, Zaman WA, Johnson KM, Wang S. Bioorg. Med. Chem. Lett. 2003; 13: 513
• 3 Pillai AD, Rathod PD, Franklin PX, Patel M, Nivsarkar M, Vasu KK, Padh H, Sudarsanam V. Biochem. Biophys. Res. Commun. 2003; 301: 183
• 4 Klimešová V, Svoboda M, Waisser K, Pour M, Kaustová J. Farmaco 1999; 54: 666
• 5 Balasubramanian M, Keay JG In Comprehensive Heterocyclic Chemistry II . Vol. 5. Katritzky AR, Rees CW, Scriven EV. F. Chapt. 6 Pergamon Press; London: 1996: 245-300 ; and references cited therein
• 6 McAteer CH, Balasubramanian M, Murugan R In Comprehensive Heterocyclic Chemistry III . Vol. 7. Katritzky AR, Ramsden CA, Scriven EF. V, Taylor RJ. K. Chapt. 6 Elsevier Science; Oxford: 2008: 309-334 ; and references cited therein
• 7 Kröhnke F. Synthesis 1976; 1
• 8 Fang AG, Mello JV, Finney NS. Tetrahedron 2004; 60: 11075
• 9 Chelucci G, Thummel RP. Chem. Rev. 2002; 102: 3129
• 10 Islam A, Sugihara H, Arakawa H. J. Photochem. Photobiol., A 2003; 158: 131
• 11a Han H, Hurley LH. Trends Pharmacol. Sci. 2000; 21: 136
• 11b Borman S. Chem. Eng. News 2002; 80: 9
• 12a Li JL, Harrison RJ, Reszka AP, Brosh RM, Bohr VA, Neidle S, Hickson ID. Biochemistry 2001; 40: 15194
• 12b Siddiqui-Jain A, Grand CL, Bearss DJ, Hurley LH. Proc. Natl. Acad. Sci. 2002; 99: 11593
• 12c Kelland LR. Eur. J. Cancer 2005; 41: 971
• 12d Chang CC, Chu JF, Kaol FJ, Chiu YC, Lou PJ, Chen HC, Chang TC. Anal. Chem. 2006; 78: 2810
• 12e Dexheimer TS, Sun D, Hurley LH. J. Am. Chem. Soc. 2006; 128: 5404
• 13 Schaefer P, Hamprecht G, Heistracher E, Klintz R, Koenig H, Harreus A, Goetz N, Walter H, Westphalen K.-O, Misslitz U. US 5733850, 1998 ; Chem. Abstr. 1996, 125, 167792w
• 14a Wang P, Moorefield CN, Newkome GR. Angew. Chem. Int. Ed. 2005; 44: 1679
• 14b Constable EC, Dunphy EL, Housecroft CE, Kylberg W, Neuberger M, Schaffner S, Schofield ER, Smith CB. Chem. Eur. J. 2006; 12: 4600
• 14c Newkome GR, Wang PC, Moorefield N, Cho TJ, Mohapatra PP, Li S, Hwang SH, Lukoyanova O, Echegoyen L, Palagallo JA, Iancu V, Hla SW. Science 2006; 312: 1782
• 15a Kobayashi T, Kakiuchi H, Kato H. Bull. Chem. Soc. Jpn. 1991; 64: 392
• 15b Kobayashi T, Kawate H, Kakiuchi H, Kato H. Bull. Chem. Soc. Jpn. 1990; 63: 1937
• 15c Kiselyov AS. Tetrahedron Lett. 1995; 36: 9297
• 15d Wenkert E, Hanna JM, Leftin MH. Jr, Michelotti EL, Potts KT, Usifer D. J. Org. Chem. 1985; 50: 1125
• 15e Tewari RS, Awasthi AK. Synthesis 1981; 314
• 15f Katritzky AR, Chermprapai A, Patel RC, Terraga-Tomas A. J. Org. Chem. 1982; 47: 492
• 15g Potts KT, Cipullo MJ, Ralli P, Theodoridis G. J. Am. Chem. Soc. 1981; 103: 3584
• 15h Palacios F, de Retana AM. O, Oyarzabal J. Tetrahedron Lett. 1996; 37: 4577
• 15i Katritzky AR, Abdel-Fattah AA. A, Tymoshenko DO, Essawy SA. Synthesis 1999; 2114
• 15j Cave GW. V, Raston CL. Chem. Commun. 2000; 2199
• 15k Tu S, Li T, Shi F, Fang F, Zhu S, Wei X, Zong Z. Chem. Lett. 2005; 34: 732
• 16a Winter A, van den Berg AM. J, Hoogenboom R, Kickelbick G, Schubert US. Synthesis 2006; 2873
• 16b Shinde PV, Labade VB, Gujar JB, Shingate BB, Shingare MS. Tetrahedron Lett. 2012; 53: 1523
• 16c Khosropour AR, Mohammadpoor-Baltork I, Kiani F. C. R. Chimie 2011; 14: 441
• 17 Ren ZH, Zhang ZY, Yang BQ, Wang YY, Guan ZH. Org. Lett. 2011; 13: 5394 ; and references cited therein
• 18a Adib M, Sheikhi E, Bagheri M, Bijanzadeh HR, Amanlou M. Tetrahedron 2012; 68: 3237
• 18b Adib M, Sheikhi E, Bijanzadeh HR, Zhu LG. Tetrahedron 2012; 68: 3377
• 18c Adib M, Sheikhi E, Rezaei N. Tetrahedron Lett. 2011; 52: 3191
• 18d Adib M, Ansari S, Bijanzadeh HR. Synlett 2011; 619
• 18e Adib M, Karimzadeh M, Mahdavi M, Sheikhi E, Mirzaei P. Synlett 2011; 834
• 18f Adib M, Ansari S, Feizi S, Bijanzadeh HR. Synlett 2010; 921
• 18g Adib M, Ansari S, Fatemi S, Bijanzadeh HR, Zhu LG. Tetrahedron 2010; 66: 2723
• 18h Adib M, Ansari S, Mohammadi A, Bijanzadeh HR. Tetrahedron Lett. 2010; 51: 30
• 18i Adib M, Ansari S, Feizi S, Asgarian Damavandi J, Mirzaei P. Synlett 2009; 3263
• 18j Adib M, Mahdavi M, Ansari S, Malihi F, Zhu LG, Bijanzadeh HR. Tetrahedron Lett. 2009; 50: 7246
• 18k Adib M, Sheibani E, Zhu LG, Bijanzadeh HR. Tetrahedron Lett. 2009; 50: 4420
• 19 Adib M, Tahermansouri H, Aali Koloogani S, Mohammadi B, Bijanzadeh HR. Tetrahedron Lett. 2006; 47: 5957
• 20 General Procedure for the Preparation of 2,4,6-Triarylpyridines (3) A mixture of the appropriate acetophenoneoxime (2 mmol) and the appropriate aldehyde (1.2 mmol) was stirred within a sealed tube in a silicone oil bath at 200 °C for 3 h. Progress of the reaction followed by TLC monitoring. Then the reaction mixture cooled to r.t., and the residue was purified by column chromatography using n-hexane–EtOAc (4:1) as eluent. The solvent was removed, and the solid residue was recrystallized from absolute EtOH. 2,4,6-Triphenylpyridine (3a) Yield: 92%; colorless crystals; mp 136 °C. IR (KBr): 3061, 3033, 2923, 1598, 1549, 1595, 1445, 1399, 1237, 1027, 873, 757, 692 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 7.40–7.60 (m, 9 H, 9 × CH), 7.78 (d, J = 8.0 Hz, 2 H, 2 × CH), 7.92 (s, 2 H, 2 × CH), 8.23 (d, J = 8.0 Hz, 4 H, 4 × CH). ¹³C NMR (125.8 MHz, CDCl₃): δ = 117.2, 127.2, 127.3 and 128.8 (4 × CH), 129.0 (C), 129.1 and 129.2 (2 × CH), 139.1 (C), 139.6 (CH), 150.2 and 157.5 (2 × C). MS (EI): m/z (%) = 307 (100) [M⁺], 289 (6), 276 (5), 230 (68), 207 (15), 202 (44), 179 (5), 165 (6), 151 (7), 127 (6), 102 (8), 77 (28), 51 (12).
• 21a Lombard R, Stephan J.-P. Bull. Soc. Chim. Fr. 1958; 1458
• 21b Huang XQ, Li HX, Wang JX, Jia XF. Chin. Chem. Lett. 2005; 16: 607
• 22 Tu S, Jia R, Jiang B, Zhang J, Zhang Y, Yao C, Ji S. Tetrahedron 2007; 63: 381
• 23 Tu S, Li T, Shi F, Wang Q, Zhang J, Xu J, Zhu X, Zhang X, Zhu S, Shi D. Synthesis 2005; 3045