Instruments and characterization:
All substrates and solvents were purchased from commercial sources and used without further purification unless otherwise stated. Also all products were obtained in microwave conditions with the microwave digestion device model, Ethos 1 from Millstone Company. TLC was performed on Merck 60 F254 silica gel plates, visualization by a UV lamp (254 nm). Melting points were obtained by Barnstead Electro thermal 9200 apparatus and are uncorrected. IR spectra were recorded on a Bruker FT-IR Equinax-55 spectrophotometer in KBr with absorption in cm-1. All of the NMR spectra were recorded on a Varian model UNITYInova 500 MHz spectrometer (1H: 500 13C: 125, 19F: 470.3 MHz) in DMSO using TMS as an internal standard. Chemical shifts of 1H and 13C NMR are reported in parts per million (ppm) from tetramethylsilane as an internal standard and for 19F NMR in parts per million (ppm) from CFCl3 as an internal standard, in DMSO-d6 as a solvent; the coupling constants J are given in Hz and spectra were recorded in parts per million (ppm). Elemental analyses were performed using a Carlo Erba EA 1108 instrument.
General procedure for the synthesis of compounds 2a-s.
A mixture of primary aromatic amine, trifluoroacetic acid, triphenylphosphine, and triethylamine in CCl4 as solvent under reflux to give trifluoromethylimidoyl chlorides 2 according to the reported procedure.[36] Distillation and work-up provided the target imidoyl chlorides in good to great yields.
General procedure for the synthesis of compounds 4a-s.
A mixture of hydrazine hydrate 3 (1.25 mmol) and trifluoromethylimidoyl chloride 2 (1 mmol), triethylamine (1 mmol) in 5 mL diethyl ether was stirred for 3 h at room temperature. After completion of the reaction, determined by TLC. The reaction mixture was filtered and removal of the solvent under reduced pressure. After the resulting crude product was purified by washing with n-hexane several times.[35]
General procedure for the synthesis of compounds 6a-n.
To an oven-dried Schlenk tube equipped with a magnetic stirring bar, were added the appropriate 2,2,2-trifluoro-N′′-phenylacetimidohydrazide 4 (1 mmol), carbon disulfide 5 (5 mmol), and DMF (1 mL) and then was irradiated in a microwave oven at 700 W for 20 min. After completion of the reaction, as indicated by TLC (3:1 n-hexane/EtOAc), the reaction mixture was added to a 10% sodium bicarbonate solution and ice, and then filter the precipitate formed. The product was purified by washing with diethyl ether several times.
4-(P-tolyl)-3-(trifluoromethyl)-1H-1,2,4-triazole-5(4H)-thione (6a).
Yield: 0.227 g (90%); cream colored solid; mp 169–171°C. 1H-NMR (500 MHz, DMSO d6) δ = 9.56 (s, 1H, NH), 7.33 (d, 2H, JHH= 8.2 Hz, HAr), 7.11 (d, 2H, JHH= 8.2 Hz, HAr), 2.27 (s, 3H, Me). 13C-NMR (125 MHz, DMSO d6) δ = 180.16, 160.68 (q, 2JCF= 37.7 Hz), 137.33, 134.05, 129.30, 126.82 (q, 1JCF= 283.1 Hz), 124.32, 20.95 (Me). 19F-NMR (DMSO d6, 470.33 MHz) δ = -58.32. IR KBr (ῡmax, cm− 1): 704, 758, 810 (CF3), 1140 (C = S), 1588 (C = N), 3150 (NH). Anal.Calcd for (C10H8F3N3S); C, 46.33; H, 3.11; N, 16.21%. Found: C, 46.65; H, 3.19; N, 15.97%.
4-(m-tolyl)-3-(trifluoromethyl)-1H-1,2,4-triazole-5(4H)-thione (6b).
Yield: 0.209 g (81%); cream colored solid; mp 157–159°C. 1H-NMR (500 MHz, DMSO d6) δ = 9.69 (s, 1H, NH), 7.24–7.31 (m, 2H, HAr), 7.19 (t, 1H, JHH= 7.8 Hz, HAr), 6.92 (d, 1H, JHH= 7.8 Hz, HAr) 2.27 (s, 3H, Me). 13C-NMR (125 MHz, DMSO d6) δ = 179.90, 148.16 (q, 2JCF= 36.1 Hz), 139.91, 138.07, 128.65, 125.52, 124.63, 121.31, 115.32 (q, 1JCF= 255.4 Hz), 21.49 (Me). 19F-NMR (DMSO d6, 470.33 MHz) δ = -61.47. IR KBr (ῡmax, cm− 1): 700, 748, 783 (CF3), 1164 (C = S), 1588 (C = N), 3349 (NH). Anal.Calcd for (C10H8F3N3S); C, 46.33; H, 3.11; N, 16.21%. Found: C, 46.70; H, 2.97; N, 16. 37%.
4-(o-tolyl)-3-(trifluoromethyl)-1 H -1,2,4-triazole-5(4 H )-thione (6c)
Yield: 0.202 g (78%); cream colored solid; mp 170–172°C. 1H-NMR (500 MHz, DMSO d6) δ = 9.12 (s, 1H, NH), 7.24 (m, 2H, HAr), 7.16 (2H, HAr), 2.24 (s, 3H, Me). 13C-NMR (125 MHz, DMSO d6) δ = 181.70, 138.27, 135.48, 135.44 (q, 2JCF= 46.4 Hz), 130.74, 129.35 (q, 1JCF= 238.7 Hz), 128.66, 126.99, 126.55, 18.23 (Me). 19F-NMR (DMSO d6, 470.33 MHz) δ = -60.81. IR KBr (ῡmax, cm− 1): 718, 737, 756 (CF3), 1154 (C = S), 1527 (C = N), 3336 (NH). Anal.Calcd for (C10H8F3N3S); C, 46.33; H, 3.11; N, 16.21%. Found: C, 46.09; H, 3.43; N,16.57%.
4-(3,4-dimethylphenyl)-3-(trifluoromethyl)-1H-1,2,4-triazole-5(4H)-thione (6d).
Yield: 0.232 g (85%); cream colored solid; mp 149–151°C. 1H-NMR (500 MHz, DMSO d6) δ = 9.45 (s, 1H, NH), 7.18 (s, 1H, HAr), 7.14 (dd, 1H, JHH= 8.0, 2.0 Hz, HAr), 7.05 (d, 1H, JHH= 8.0 Hz, HAr), 2.18 (s, 3H, Me), 2.17 (s, 3H, Me). 13C-NMR (125 MHz, DMSO d6) δ = 180.09, 179.22 (q, 2JCF = 39.8 Hz), 153.02 (q, 1JCF = 263.5 Hz), 137.49, 136.51, 132.89, 129.77, 125.63, 121.96, 19.89 (Me), 19.23 (Me). 19F NMR (DMSO d6, 470.33 MHz) δ = -58.30. IR KBr (ῡmax, cm− 1): 680, 720, 811 (CF3), 1024 (C = S), 1586 (C = N), 3250 (NH). Anal.Calcd for (C11H10F3N3S); C, 48.35; H, 3.69; N, 15.38%. Found: C, 48.67; H, 3.71; N, 15.42%.
4-(2,5-dimethylphenyl)-3-(trifluoromethyl)-1H-1,2,4-triazole-5(4H)-thione (6e).
Yield: 0.229 g (84%); cream colored solid; mp 175–177°C. 1H-NMR (500 MHz, DMSO d6) δ = 9.28 (s, 1H, NH), 7.08 (d, 1H, JHH= 7.5 Hz, HAr), 7.05 (s, 1H, HAr), 6.94 (d, 1H, JHH= 7.5 Hz, HAr), 2.24 (s, 3H, Me), 2.18 (s, 3H, Me). 13C-NMR (125 MHz, DMSO d6) δ = 181.65, 173.26 (q, 2JCF = 36.1 Hz), 138.09, 135.45, 132.11, 130.47, 129.00, 127.48, 126.24 (q, 1JCF = 284.2 Hz), 20.92 (Me), 17.87 (Me). 19F NMR (DMSO, 470.33 MHz) δ = -58.40. IR KBr (ῡmax, cm− 1): 717, 780, 806 (CF3), 1153 (C = S), 1578 (C = N), 3346 (NH). Anal.Calcd for (C11H10F3N3S); C, 48.35; H, 3.69; N, 15.38%. Found: C, 48.23; H, 3.83; N, 15.50%.
4-mesityl-3-(trifluoromethyl)-1H-1,2,4-triazole-5(4H)-thione (6f).
Yield: 0.246 g (86%); cream colored solid; mp 181–183°C. Major isomer: 1H-NMR (500 MHz, DMSO d6) δ = 8.10 (s, 1H, NH), 6.99 (s, 2H, H-Ar), 2.30 (s, 3H, Me), 1.96 (s, 6H, 2Me).Minor isom er: 1H-NMR (500 MHz, DMSO d6) δ = 8.64 (s, 1H, NH), 6.77 (s, 2H, HAr), 2.19 (s, 3H, Me), 1.86 (s, 6H, 2Me). Major isomer: 13C-NMR (125 MHz, DMSO d6) δ = 171.82, 162.83 (q, 2JCF = 33.0 Hz), 155.81, 140.26, 135.94, 128.99, 109.52 (q, 1JCF = 280.0 Hz), 20.95, 17.27. Minor isomer: 13C-NMR (125 MHz, DMSO d6) δ = 172.50, 164.08 (q, 2JCF = 45.0 Hz), 159.44, 145.25, 136.18, 129.38, 125.63 (q, 1JCF = 290.2 Hz), 21.08, 17.92. Major isomer: 19F NMR (DMSO, 470.33 MHz) δ = -63.00. Minor isomer: 19F NMR (DMSO, 470.33 MHz) δ = -67.23. IR KBr (ῡmax, cm− 1): 753, 851, 928 (CF3), 1148 (C = S), 1526 (C = N), 3373 (NH). Anal.Calcd for (C12H12F3N3S); C, 50.17; H, 4.21; N, 14.63%. Found: C, 50.03; H, 4.29; N, 14.37%.
4-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-1,2,4-triazole-5(4H)-thione (6g).
Yield: 0.238 g (87%); cream colored solid; mp 189–191°C. 1H-NMR (500 MHz, DMSO d6) δ = 9.57 (s, 1H, NH), 7.31 (d, 2H, JHH= 8.9 Hz, H-Ar), 6.78 (d, 2H, JHH= 8.9 Hz, H-Ar), 3.72 (s, 3H, OMe). 13C-NMR (125 MHz, DMSO d6) δ = 180.66, 156.89, 132.84, 126.27, 115.45 (q, 2JCF = 35.8 Hz), 114.07, 109.78 (q, 1JCF = 261.8 Hz), 55.71 (OMe). 19F NMR (DMSO, 470.33 MHz) δ = 62.65. IR KBr (ῡmax, cm− 1): 723, 756, 786 (CF3), 1032 (C = S), 1550 (C = N), 3219 (NH). Anal.Calcd for (C10H8F3N3OS); C, 43.64; H, 2.93; N, 15.27%. Found: C, 43.90; H, 3.09; N,15.45%.
4-(4-fluorophenyl)-3-(trifluoromethyl)-1H-1,2,4-triazole-5(4H)-thione (6h).
Yield: 0.202 g (77%); cream colored solid; mp 183–185°C. 1H-NMR (500 MHz, DMSO d6) δ = 9.83 (s, 1H, NH), 7.48–7.46 (m, 2H, H-Ar), 7.17–7.14 (m, 2H, H-Ar). 13C-NMR (125 MHz, DMSO d6) δ = 182.59 (q, 2JC,F = 43.7 Hz), 180.85, 159.61 (d, 1JC,F = 239.9 Hz), 136.16, 131.73 (q, 1JC,F = 285.7 Hz), 126.58 (d, 3JC,F = 8.1 Hz), 115.45 (d, 2JC,F = 22.3 Hz). 19F NMR (DMSO, 470.33 MHz) δ = -60.36, -61.58. IR KBr (ῡmax, cm− 1): 672, 720, 764 (CF3), 1087 (C = S), 1550 (C = N), 3220 (NH). Anal.Calcd for (C9H5F4N3S); C, 41.07; H, 1.91; N, 15.96%. Found: C, 41.26; H, 2.13; N, 16.28%.
4-(4-chlorophenyl)-3-(trifluoromethyl)-1H-1,2,4-triazole-5(4H)-thione (6i).
Yield: 0.219 g (79%); cream colored solid; mp 182–184°C. 1H-NMR (500 MHz, DMSO d6) δ = 10.92 (s, 1H, NH), 7.64 (d, 2H, JHH= 8.7 Hz, H-Ar), 7.36 (d, 2H, JHH= 8.7 Hz, H-Ar). 13C-NMR (125 MHz, DMSO d6) δ = 179.73, 172.01 (q, 2JCF = 45.6 Hz), 162.74, 142.36 (q, 1JCF = 242.5 Hz), 138.99, 128.63, 124.85. 19F NMR (DMSO, 470.33 MHz) δ = -58.39. IR KBr (ῡmax, cm− 1): 673, 728, 804 (CF3), 1012 (C = S), 1591 (C = N), 3211 (NH). Anal.Calcd for (C9H5ClF3N3S); C, 38.65; H, 1.80; N, 15.02%. Found: C, 38.33; H, 1.67; N, 15.19%.
4-(3-chloro-4-fluorophenyl)-3-(trifluoromethyl)-1H-1,2,4-triazole-5(4H)-thione (6j).
Yield: 0.219 g (74%); cream colored solid; mp 150–152°C. 1H-NMR (500 MHz, DMSO d6) δ = 10.94 (s, 1H, NH), 7.91 (dd, 1H, JHH= 8.0, 2.5 Hz, HAr), 7.47–7.50 (m, 1H, HAr), 7.38 (t, 1H, JHH= 8.0 Hz, HAr). 13C-NMR (125 MHz, DMSO d6) δ = 180.25, 154.46 (d, 1JCF = 242.5 Hz), 137.05, 125.24, 124.14, 119.12 (d, 3JCF = 18.4 Hz), 116.93 (d, 3JCF = 22.0 Hz), 115.54 (q, 2JCF = 28.5 Hz), 114.61 (q, 1JCF = 203.2 Hz). 19F NMR (DMSO, 470.33 MHz) δ = -58.31, -121.53. IR KBr (ῡmax, cm− 1): 721, 773, 818 (CF3), 1059 (C = S), 1597 (C = N), 3179 (NH). Anal.Calcd for (C9H4ClF4N3S); C, 36.32; H, 1.35; N, 14.12%. Found: C, 36.60; H, 1.39; N,14.00%.
4-(3-nitrophenyl)-3-(trifluoromethyl)-1H-1,2,4-triazole-5(4H)-thione (6k).
Yield: 0.237 g (82%); yellow colored solid; mp 172–174°C. 1H-NMR (500 MHz, DMSO d6) δ = 10.24 (s, 1H, NH), 8.52 (s, 1H, H-Ar), 7.93 (dd, 2H, JHH= 8.7, 4.8 Hz, H-Ar), 7.61 (t, 1H, 8.7 Hz, H-Ar). 13C-NMR (125 MHz, DMSO d6) δ = 180.54, 155.95 (q, 2JCF = 33.7 Hz), 140.05, 140.92, 130.23, 130.21, 119.51, 119.18 (q, 1JCF = 296.6 Hz), 118.29. 19F NMR (DMSO, 470.33 MHz) δ = -61.55. IR KBr (ῡmax, cm− 1): 680, 735, 799 (CF3), 1090 (C = S), 1599 (C = N), 3338 (NH). Anal.Calcd for (C9H5F3N4O2S); C, 37.25; H, 1.74; N, 19.30%. Found: C, 37.38; H, 1.80; N,19.57%.
4-(4-nitrophenyl)-3-(trifluoromethyl)-1H-1,2,4-triazole-5(4H)-thione (6l).
Yield: 0.243 g (84%); yellow colored solid; mp 149–151°C. 1H-NMR (500 MHz, DMSO d6) δ = 7.92 (d, 2H, JHH= 9.1 Hz, HAr), 6.67 (s, 1H, NH), 6.58 (d, 2H, JHH= 9.1 Hz, HAr). 13C-NMR (125 MHz, DMSO d6) δ = 186.11, 163.66 (q, 2JCF = 46.8 Hz), 156.11, 136.18, 126.77, 112.83, 107.43 (q, 1JCF = 275.1 Hz). 19F NMR (DMSO, 470.33 MHz) δ = -61.32. IR KBr (ῡmax, cm− 1): 631, 697, 752 (CF3), 1112 (C = S), 1631 (C = N), 3481 (NH). Anal.Calcd for (C9H5F3N4O2S); C, 37.25; H, 1.74; N, 19.30%. Found: C, 37.03; H, 1.88; N,19.18%.
4-(naphthalen-1-yl)-3-(trifluoromethyl)-1H-1,2,4-triazole-5(4H)-thione (6m).
Yield: 0.238 g (81%); cream colored solid; mp 200–202°C. 1H-NMR (500 MHz, DMSO d6) δ = 10.02 (s, 1H, NH), 8.06 (d, 1H, JHH= 8.0 Hz, HAr), 7.95 (d, 1H, JHH= 8.0 Hz, HAr), 7.84 (d, 1H, JHH= 8.0 Hz, HAr), 7.47–7.65 (m, 4H, HAr). 13C-NMR (125 MHz, DMSO d6) δ = 183.40, 174.07 (q, 2JCF = 28.9 Hz), 135.80, 134.36, 130.62, 128.53, 127.15, 126.56, 126.50, 126.14, 126.04, 123.65. 19F NMR (DMSO, 470.33 MHz) δ = -60.21. IR KBr (ῡmax, cm− 1): 601, 638, 660 (CF3), 1157 (C = S), 1626 (C = N), 3338 (NH). Anal.Calcd for (C13H8F3N3S); C, 52.88; H, 2.73; N, 14.23%. Found: C, 53.09.; H, 2.65; N, 14.49%.
3-(trifluoromethyl)-4-(3-(trifluoromethyl)phenyl)-1H-1,2,4-triazole-5(4H)-thione (6n).
Yield: 0.231 g (74%); cream colored solid; mp 207–209°C. 1H-NMR (500 MHz, DMSO d6) δ = 10.45 (s, 1H, NH), 7.94–7.98 (m, 1H, HAr), 7.76–7.77 (m, 1H, HAr), 7.56–7.59 (m, 1H, HAr), 7.46–7.49 (m, 1H, HAr). 19F NMR (DMSO, 470.33 MHz) δ = -58.28, 61.21.IR KBr (ῡmax, cm− 1): 730, 810, 883 (CF3), 1115 (C = S), 1579 (C = N), 3359 (NH). Anal.Calcd for (C10H5F6N3S); C, 38.35; H, 1.61; N, 13.42%. Found: C, 38.19; H, 1.75; N,13.18%.