Microwave Irradiation for Accelerating Synthesis of [1,2,4]Triazole[4,3-a]-pyrimidines Based on Isoflavones

Abstract

Microwave irradiation was used to accelerate the cyclocondensation of isoflavones and 3-amino-1,2,4-triazoles in the presence of sodium methoxide to produce 6,7-diphenyl[1,2,4]-triazolo[4,3-a]pyrimidines in good to moderate yields.

isoflavone - triazole - [1,2,4]triazolo[4,3-a]pyrimidine - microwave

References and Notes

1 Yang G.-L. inventors; CN  200710301577.6. 

2 Prakash O. Bhardwaj V. Kumar R. Tyagi P. Aneja KR. Eur. J. Med. Chem.  2004,  39:  1073 

3 Bradbury RH. Major OS. Oldham AA. Rivett JE. Roberts DA. Slater AM. Timms D. Waterson D. J. Med. Chem.  1990,  33:  2335 

4 Babichev FS. Kovtunenko VA. Khim. Geterotsikl. Soedin.  1977,  147 

5 Allen CFH. Beilfuss HR. Burness DM. Reynolds GA. Tinker JF. Van Allan JA. J. Org. Chem.  1959,  24:  787 

6 Kottke K. Kuhmstedt K. Knoke D. Pharmazie  1983,  38:  25 

7 El-Sherief HA. Abdel-Rachman AE. El-Naggar GM. Mahmoud AM. Bull. Chem. Soc. Jpn.  1983,  56:  1227 

8 Bower JD. Doyle FP. J. Chem. Soc.  1957,  727 

9 Oganisyan ASh. Noravyan AS. Karapetyan AA. Aleksanyan MS. Struchkov YuT. Khim. Geterotsikl. Soedin.  2004,  85 

10 Lalezari I. Jabari-Sahbari MH. J. Heterocycl. Chem.  1978,  15:  873 

11 Vas’kevich RI. Savitskii PV. Zborovskii YuL. Staninets VI. Rusanov EB. Chernega AN. Russ. J. Org. Chem.  2006,  42:  1403 

12 Zhang Z.-T. Tan D.-J. Xue D. HeIv. Chim. Acta  2007,  90:  2096 

13 Zhang Z.-T. Xu F.-F. Gao M.-X. Qiu L. J. Comb. Chem.  2009,  11:  880 

14 Zhang Z.-T. Qiu L. Xue D. Wu J. Xu F.-F. J. Comb. Chem.  2010,  12:  225 

15 Lidstrom P. Tierney J. Wathey B. Westman J. Tetrahedron  2001,  57:  9225 

16 Mingos DMP. Baghurst DR. Chem. Soc. Rev.  1991,  20:  1 

17 Abramovitch RA. Org. Prep. Proced. Int.  1991,  23:  683 

18

6-Phenyl-7-(2-hydroxy-4-isopropoxyphenyl)[1,2,4]-triazolo[4,3- a ]pyrimidine (3a)
Mp 228-230 ˚C. IR (KBr): ν = 3083, 2982, 2679, 2586, 1610, 1504, 1440, 1381, 1292, 1264, 1180, 1115, 989, 921, 846, 791, 757, 703, 652, 573, 506, 461 cm^-¹. ^¹H NMR (300 MHz, DMSO-d ₆): δ = 1.26 (d, J = 5.9 Hz, 6 H), 4.56 (m, 1 H), 6.39 (d, J = 8.2 Hz, 2 H), 7.03 (d, J = 8.2 Hz, 1 H), 7.33 (m, 5 H), 8.60 (s, 1 H), 8.95 (s, 1 H), 9.86 (s, 1 H) ppm.
^¹³C NMR (75 MHz, DMSO-d ₆): δ = 21.8, 69.4, 102.6, 106.4, 118.7, 125.0, 127.8, 128.3, 129.4, 131.6, 134.4, 144.2, 154.3, 155.5, 155.9, 156.9, 160.2 ppm. MS (EI): m/z (rel intensity) = 369 (62) [M + Na], 347 (100) [M + 1], 305 (66). Anal. Calcd for C₂₀H₁₈N₄O₂: C, 69.35; H, 5.24; N, 16.17. Found: C, 69.18; H, 5.31; N, 16.25.

19

Representative Procedure for the Preparation of 6-Phenyl-7-(2-hydroxy-4-isopropoxy-phenyl)[1,2,4]-triazolo[4,3- a ]-pyrimidine (3a) and 3-Hydroxy-6-phenyl-7-(2-hydroxy-4-isopropoxyphenyl)[1,2,4]triazolo[4,3- a ]pyrimidine (3s)
The ipriflavone (1a, 1.5 mmol, 420 mg), 2a (2.1 mmol, 118 mg) and NaOMe (4.5 mmol, 3 equiv) were mixed in DMSO (8 mL). The mixture was heated by the microwave irradiation (output 240 W, 100 ˚C) for 10 min. Reaction was monitored by TLC, in which the disappearance of 1a indicated the completeness of reaction. The mixture was added into H₂O (30 mL) and adjusted to neutrality with the solution of 5% HCl. Precipitate appeared and was filtered. Finally, 3a (374mg, 72%) was obtained by purifying the precipitate on silica gel column chromatography (PE 60-90-EtOAc = 2:1); 3s was obtained by the same way, except that the equivalent of NaOMe (6.0 mmol, 4 equiv) was different when 2b was instead of 2a.

20 Varga M. Bátori S. Kövári-Rádkai M. Prohászka-Német I. Vitányi-Morvai M. Böcskey Z. Bokotey S. Simon K. Hermecz I. Eur. J. Org. Chem.  2001,  20:  3911