Synlett 2015; 26(13): 1804-1807
DOI: 10.1055/s-0034-1380677
letter
© Georg Thieme Verlag Stuttgart · New York

A Novel One-Pot Method for Highly Regioselective Synthesis of Triazoloapyrimidinedicarboxylates Using Silica Sodium Carbonate

Bahador Karami*
Department of Chemistry, Yasouj University, Yasouj, Iran   eMail: karami@mail.yu.ac.ir
,
Mahnaz Farahi
Department of Chemistry, Yasouj University, Yasouj, Iran   eMail: karami@mail.yu.ac.ir
,
Zohreh Banaki
Department of Chemistry, Yasouj University, Yasouj, Iran   eMail: karami@mail.yu.ac.ir
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Publikationsverlauf

Received: 18. Februar 2015

Accepted after revision: 02. April 2015

Publikationsdatum:
08. Mai 2015 (online)


Abstract

A novel synthesis of dimethyl 4,5-dihydro-5-aryl-[1,2,4]triazolo[1,5-a]pyrimidine-6,7-dicarboxylates is reported. This methodology consists of the one-pot condensation of 3-amino-1H-1,2,4-triazole, dimethyl acetylenedicarboxylate, and aryl aldehydes using silica sodium carbonate as a solid base catalyst. The use of silica sodium carbonate as a heterogeneous reusable catalyst makes this procedure mild, convenient, and environmentally benign.

Supporting Information

 
  • References and Notes

  • 1 Dias LR. S, Santos MB, De Albuquerque S, Castro HC, De souza AM. T, Freitas AC. C, Di Vaio MA. V, Cabral LM, Rodrigues CR. Bioorg. Med. Chem. 2007; 15: 211
  • 2 Magedov IV, Manpadi M, Van Slambrouck S, Steelant WF. A, Rozhkova E, Przheval’skii NM, Rogelj S, Kornienko A. J. Med. Chem. 2007; 50: 5183
  • 3 Chernyshev VM, Sokolov AN, Taranushich VA. Russ. J. Appl. Chem. 2006; 79: 1134
  • 4 Sakhno YI, Desenko SM, Shishkina SV, Shishkin OV, Musatov VI, Chebanov VI. Synthesis 2011; 1120
  • 5 Chebanov VA, Gura KA, Desenko SM. Top. Heterocycl. Chem. 2010; 23: 41
  • 6 Fischer G. Adv. Heterocycl. Chem. 1993; 57: 81
  • 7 Ryabukhin SV, Plaskon AS, Boron SY, Volochnyuk DM, Tolmachev AA. Mol. Diversity 2011; 15: 189
  • 8 Magan R, Marin C, Rosales MJ, Salas JM. Pharmacology 2005; 73: 41
  • 9 Ovchinnikova IG, Valova MS, Matochkina EG, Kodess MI, Tumashov AA, Slepukhin PA, Fedorova OV, Rusinov GL, Charushin VN. Russ. Chem. Bull. 2011; 60: 965
  • 10 Rudenko RV, Komykhov SA, Musatov VI, Desenko SM. J. Heterocycl. Chem. 2009; 46: 285
  • 11 Chebanov VA, Muravyova EA, Desenko SM, Musatov VI, Knyazeva IV, Shishkina SV, Shishkin OV, Kappe CO. J. Comb. Chem. 2006; 8: 427
  • 12 Shaabani A, Maleki A, Rezayan AH, Sarvary A. Mol. Diversity 2011; 15: 41
  • 13 Simon C, Constantieux T, Rodriguez J. Eur. J. Org. Chem. 2004; 4957
  • 14 Isambert I, Del Mar Sanchez Duque M, Plaquevent JC, Génisson Y, Rodriguez J, Constantieux T. Chem. Soc. Rev. 2011; 40: 1347
  • 15 Tang Y, Xu J, Gu X. J. Chem. Sci. 2013; 125: 313
  • 16 Gupta M, Gupta R, Anand M. Beilstein J. Org. Chem. 2009; 5: 1
  • 17 Eskandari K, Karami B, Khodabakhshi S. Catal. Commun. 2014; 54: 124
  • 18 Karami B, Ghashghaee V, Khodabakhshi S. Catal. Commun. 2012; 20: 71
  • 19 Karami B, Eskandari K, Khodabakhshi S. ARKIVOC 2012; (ix): 76
  • 20 Karami B, Khodabakhshi S, Eskandari K. Tetrahedron Lett. 2012; 53: 1445
  • 21 Karami B, Khodabakhshi S, Akrami S, Farahi M. Tetrahedron Lett. 2014; 55: 3581
  • 22 Karami B, Khodabakhshi S, Eskandari K. Synlett 2013; 24: 998
  • 23 Preparation of Silica Sodium Carbonate (SSC) 17 To a 250 mL round-bottom flask equipped with a reflux condenser, silica gel 60 (10 g) that had been previously dried at 120 °C for 6 h was added. Then SOCl2 (40 mL) was added dropwise with cooling in an ice bath (caution). After the addition of the SOCl2, the reaction mixture was removed from the ice bath and stirred for 0.5 h at r.t. and 48 h under reflux conditions. The mixture was then filtered to obtain the silica chloride. Subsequently, to a stirred 250 mL round-bottom flask containing NaHCO3 (10 g) and n-hexane (25 mL) under reflux, 10 g of silica chloride (after drying at 120 °C for 6 h) was added. After 24 h, the reaction mixture was filtered to separate the catalyst, and the solid product was washed with distilled H2O (10×), using 5 mL each time until filtrate neutral, in order to remove the remaining NaHCO3. Finally, after drying the catalyst at 100 °C for 12 h, 14 g of SSC was obtained.
  • 24 General Experimental Procedure for the Synthesis of Compounds 4a–j To a stirred solution of 3-amino-1H-1,2,4-triazole (1 mmol), aryl aldehyde (1 mmol), and DMAD (1 mmol) in CHCl3 (5 ml) SSC (10 mol%, 0.2 g) was added. The resulting mixture was stirred for 60–120 min at r.t. After completion of the reaction, the solvent was evaporated. Next, boiling EtOAc (10 mL) was added, and the catalyst was separated by filtration. Further purification was achieved by recrystallization from EtOH. Dimethyl 5-Phenyl-4,5-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine-6,7-dicarboxylate (4a) White solid (0.28 g, 90%); mp 228–231 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 8.44 (d, J =8.8 Hz, 1 H), 8.23 (s, 1 H), 7.88 (d, J = 8.0 Hz, 2H), 7.74 (t, J = 7.2 Hz, 2 H), 7.56 (t, J = 7.2 Hz, 1 H), 4.05 (d, J = 8.8 Hz, 1 H), 3.43 (s, 3 H), 2.99 (s, 3 H) ppm. 13C NMR (100 MHz, DMSO-d 6): δ = 166.87, 159.34, 156.10, 152.66, 139.47, 136.88, 128.58, 127.92, 127.87, 127.43, 56.58, 55.61, 55.58 ppm. IR (KBr): νmax = 3201, 1729, 1698 cm–1. Anal. Calcd for C15H14N4O4: C, 58.06; H, 4.55; N, 27.08. Found: C, 58.01; H, 4.63; N, 27.01. Dimethyl 5-(4-Chlorophenyl)-4,5-dihydro-[1,2,4]triazolo-[1,5-a]pyrimidine-6,7-dicarboxylate (4c) Yellow solid (0.32 g, 92%); mp 235–237 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 8.47 (d, J = 8.0 Hz, 1 H), 7.85 (s, 1 H), 7.43 (d, J = 8.0 Hz, 2 H), 7.19 (d, J = 8.0 Hz, 2 H), 4.69 (d, J = 8.0 Hz, 1 H), 3.04 (s, 3 H), 2.62 (s, 3 H) ppm.13C NMR (100 MHz, DMSO-d 6): δ = 160.01, 159.83, 157.91, 155.05, 154.06, 145.66, 131.62, 129.41, 128.88, 120.41, 57.52, 52.20, 51.72 ppm. IR (KBr): νmax = 3215, 1731, 1705 cm–1. Anal. Calcd for C15H13ClN4O4: C, 51.66; H, 3.76; N, 16.07. Found: C, 51.60; H, 3.78; N, 16.10. Dimethyl 5-(m-Tolyl)-4,5-dihydro-[1,2,4]triazolo[1,5-a]-pyrimidine-6,7-dicarboxylate (4e) Pale yellow solid (0.30 g, 89%); mp 223–225 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 8.91 (d, J = 8 Hz, 1 H), 8.59 (s, 1 H), 7.98 (s, 1 H), 7.60–7.67 (m, 1 H), 7.18 (d, J = 7.6 Hz, 2 H), 4.89 (d, J = 8.0 Hz, 1 H), 3.22 (s, 3 H), 2.91 (s, 3 H), 2.63 (s, 3 H) ppm. 13C NMR (100 MHz, DMSO-d 6): δ = 160.23, 159.75, 157.92, 155.14, 153.77, 148.23, 147.97, 134.53, 130.66, 122.33, 122.03, 120.22, 56.74, 56.16, 49.19, 30.49 ppm. IR (KBr): νmax = 3220, 1729, 1710 cm–1. Anal. Calcd for C16H16N4O5: C, 55.81; H, 4.68; N, 16.27. Found: C, 55.82; H, 4.69; N, 16.29. Dimethyl 5-(4-Nitrophenyl)-4,5-dihydro -[1,2,4]triazolo[1,5-a]pyrimidine-6,7-dicarboxylate (4i) Yellow solid (0.34 g, 95%); mp 264–266 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 8.86 (d, J = 8.0 Hz, 1 H), 8.34 (s, 1 H), 8.21 (d, J = 8.0 Hz, 2 H), 6.96 (d, J = 8.0 Hz, 2 H), 4.87 (d,J = 8.0 Hz, 1 H), 3.73 (s, 6 H) ppm. 13C NMR (100 MHz, DMSO-d 6): δ = 160.01, 159.81, 157.94, 154.95, 153.76, 144.66, 131.62, 129.44, 128.85, 120.41, 57.50, 50.15, 50.00 ppm. IR (KBr): νmax = 3106, 1728, 1708 cm–1. Anal. Calcd for C15H13N5O6: C, 50.14; H, 3.65; N, 19.49. Found: C, 50.15; H, 3.67; N, 19.48.