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Synlett 2013; 24(14): 1825-1829
DOI: 10.1055/s-0033-1339333
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© Georg Thieme Verlag Stuttgart · New York

A Simple One-Pot Procedure for the Synthesis of 1,2,4-Triazolo[1,5-a]pyrid-ines via Pseudo Five-Component Reactions Catalyzed by Molecular Iodine

Abdolali Alizadeh*
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Fax: +98(21)88006544   Email: abdol_alizad@yahoo.com   Email: aalizadeh@modares.ac.ir
,
Vahid Saberi
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Fax: +98(21)88006544   Email: abdol_alizad@yahoo.com   Email: aalizadeh@modares.ac.ir
,
Javad Mokhtari
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Fax: +98(21)88006544   Email: abdol_alizad@yahoo.com   Email: aalizadeh@modares.ac.ir
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Further Information

Publication History

Received: 23 April 2013

Accepted after revision: 10 June 2013

Publication Date:
01 August 2013 (online)

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Abstract

In this paper we report the synthesis of the 1,2,4-triazolo[1,5-a]pyridine ring system. The reaction between benzylidenehydrazines, dialkyl acetylenedicarboxylates, benzaldehydes, and malononitrile proceeds in EtOH at reflux in the presence of molecular iodine as catalyst in good to excellent yields.

Key words

benzylidenehydrazine - dialkyl acetylenedicarboxylate - benzaldehyde - malononitrile - 1,2,4-triazolo[1,5-a]pyridine - catalyst - iodine - multicomponent reaction
 

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  • 11 Typical Procedure for the Preparation of Dimethyl 7-(4-Chlorophenyl)-8-cyano-2-phenyl-[1,2,4]triazolo[1,5-a]pyridine-5,6-dicarboxylate (4a)A solution of benzaldehyde (0.212 g, 2 mmol) and hydrazine hydrate (0.16 g, 1 mmol) was magnetically stirred in EtOH (5 mL) for 20 min. Then a solution of DMAD (0.142 g, 1 mmol) was added, and the mixture was stirred for 3 min. At this point, the condensation product of 4-chlorobenz-aldehyde (0.140 g, 1 mmol) and malononitrile (6a, 0.066 g, 1 mmol) was added, and the reaction mixture was stirred for 3 h under reflux and progress was followed by TLC. After completion, the reaction mixture was cooled to r.t., I2 (0.1 mmol) was added, and the mixture was stirred for a further 2 h. The progress of the reaction was again followed by TLC and, after completion, the solvent was removed under reduced pressure, and the residue was purified by column chromatography (n-hexane–EtOAc, 5:1). All products gave satisfactory spectroscopic data in accordance with the assigned structures.Representative Spectroscopic Data
    Dimethyl 7-(4-Chlorophenyl)-8-cyano-2-phenyl-[1,2,4]triazolo[1,5-a]pyridine-5,6-dicarboxylate (4a)    White powder; yield: 0.26 g (59%); mp 263–265 °C. IR (KBr): 2358 (CN), 1748 (CO2Me), 1538 and 1443 (Ar), 1251 (C–O of ester) cm–1. 1H NMR (500.13 MHz, CDCl3): δ = 3.65 (3 H, s, OCH3), 4.17 (3 H, s, OCH3), 7.38 (2 H, d, 3 J HH = 8.0 Hz, 2 CH of Ar), 7.52–7.54 (5 H, m, 5 CH of Ar), 8.37 (2 H, d, 3 J HH = 8.0 Hz, 2 CH of Ar) ppm. 13C NMR (125.75 MHz, CDCl3): δ = 53.4 (OCH3), 54.3 (OCH3), 102.4 (C8), 112.6 (C5), 118.6 (CN), 128.3 (2 CH meta of Ph), 128.8 (2 CH of Ar), 128.9 (C6), 129.2 (2 CH of Ar), 129.7 (2 CH ortho of Ph), 131.5 (CH para of Ph), 132.8 (C ipso of Ph), 135.3 (C–Cl), 136.5 (C ipso of Ar), 147.6 (C8a), 150.77 (C7), 159.9 (C2),163.6 (C=O), 167.8 (C=O) ppm. MS (EI, 70 eV): m/z (%) = 446 (22) [M+], 367 (35), 298 (31), 224 (22), 190 (36), 167 (22), 149 (57), 111 (28), 97 (46), 81 (57), 69 (100), 57 (65). Anal. Calcd (%) for C23H15ClN4O4 (446.85): C, 61.82; H, 3.38; N, 12.54. Found: C, 61.79; H, 3.39; N, 12.55.Dimethyl 2,7-Bis(4-chlorophenyl)-8-cyano-[1,2,4]triazolo[1,5-a]pyridine-5,6-dicarboxylate (4f)White powder; yield: 0.24 g (51%); mp 281–283 °C. IR (KBr): 2357 (CN), 1746 (CO2Me), 1440 (Ar), 1259 (C–O of ester) cm–1. 1H NMR (400.13 MHz, CDCl3): δ = 3.66 (3 H, OCH3), 4.17 (3 H, OCH3), 7.38 (2 H, d, 3 J HH = 8.0 Hz, 2 CH of Ar), 7.50 (2 H, d, 3 J HH = 8.0 Hz, 2 CH of Ar), 7.54 (2 H, d, 3 J HH = 8.0 Hz, 2 CH of Ar), 8.32 (2 H, d, 3 J HH = 8.0 Hz, 2 CH of Ar) ppm. 13C NMR (100.61 MHz, CDCl3): δ = 53.4 (OCH3), 54.40 (OCH3), 102.4 (C8), 112.5 (C5), 118.8 (CN), 127.3 (C6), 129.1 (2 CH of Ar), 129.2 (2 CH of Ar), 129.5 (2 CH of Ar), 129.6 (2 CH of Ar), 132.6 (C ipso of Ar), 135.2 (C–Cl), 136.7 (C ipso of Ar), 137.7 (C–Cl) 147.7 (C8a), 150.7 (C7), 159.7 (C2), 163.5 (C=O), 166.7 (C=O) ppm. MS (EI, 70 eV): m/z (%) = 481 (31) [M+], 480 (100) [M+ – 1], 449 (22), 364 (51), 190 (22), 163 (22), 138 (72), 102 (30), 75 (53), 59 (33). Anal. Calcd (%) for C23H14Cl2N4O4 (481.30): C, 57.40; H, 2.93; N, 11.64. Found: C, 57.42; H, 2.92; N, 11.65.Dimethyl 7-(3-Bromophenyl)-8-cyano-2-p-tolyl-[1,2,4]triazolo[1,5-a]pyridine-5,6-dicarboxylate (4h)White powder; yield: 0.25 g (55%); mp 287–289 °C. IR (KBr): 2359 (CN), 1742 (CO2Me), 1441 (Ar), 1264 (C–O of ester) cm–1. 1H NMR (400.13 MHz, CDCl3): δ = 2.45 (3 H, s, Me), 3.66 (3 H, OCH3), 4.17 (3 H, OCH3), 7.33 (2 H, d, 3 J HH = 8.0 Hz, 2 CH of Ar), 7.38 (2 H, d, 3 J HH = 8.0 Hz, 2 CH of Ar), 7.54 (2 H, d, 3 J HH = 8.0 Hz, 2 CH of Ar), 8.27 (2 H, d, 3 J HH = 8.0 Hz, 2 CH of Ar) ppm. 13C NMR (100.61 MHz, CDCl3): δ = 29.7 (Me), 53.3 (OCH3), 54.3 (OCH3), 100.2 (C8), 112.7 (C5), 118.3 (CN), 126.0 (C6), 128.2 (2 CH of Ar), 129.2 (2 CH of Ar), 129.5 (2 CH of Ar), 129.6 (2 CH of Ar), 132.4 (C ipso of Ar), 135.6 (C–Cl), 136.5 (C ipso of Ar), 140.6 (C–Me), 142.0 (C8a), 151.8 (C7), 155.0 (C2), 164.6 (C=O), 166.0 (C=O) ppm. MS (EI, 70 eV): m/z (%) = 460 (53) [M+], 422 (38), 391 (27), 364 (89), 199 (43), 163 (43), 138 (100), 111 (49), 75 (46), 59 (58) (32). Anal. Calcd (%) for C24H17ClN4O4 (460.87): C, 62.55; H, 3.72; N, 12.16. Found: C, 62.53; H, 3.73; N, 12.14.