General
All organic solvents were purchased from commercial sources and used as received unless otherwise stated. All chemicals were purchased from Merck, Aldrich or Acros and used without further purification, thin-layer chromatography (TLC) was performed on precoated Merck 60 GF254 silica gel plates with a fluorescent indicator, and detection by means of UV light at 254 and 360 nm. All melting points were measured on a Stuart melting point apparatus and are uncorrected. IR spectra were recorded in IR spectra were recorded in the Smart iTR which is an ultra-high-performance, versatile Attenuated Total Reflectance (ATR) sampling accessory on The Nicolet iS10 FT-IR spectrometer. The NMR spectra were recorded on a Varian Mercury VX-300 NMR spectrometer. 1H spectra were run at 300 MHz and 13C spectra were run at 75.46 MHz in dimethyl sulphoxide (DMSO-d6). Chemical shifts were related to that of the solvent. Assignments are made using 1H, 13C, gHMBC, 2D experiments was done using standard Varian methods.
Mass spectra were recorded on the Thermo ISQ Single Quadrupole GC-MS. The resulting products were identified from their retention times by GC–MS analysis. Elemental analyses were carried out on EuroVector instrument C, H, N, S analyzer EA3000 Series. Sonication was performed by Techno-gaz sonicator (with a frequency of 37 kHz and ultrasonic peak max. 320 W).
N-phenyltrifluromethylcarbohydrazonoyl benzenesulfonate (3)[15], α-ketohydrazonoyl halides 10a-f[57] were prepared according to the reported literature.
General procedure and characterization data
Typical procedure for synthesis of pyrazole derivatives 5a,b and 11a-j.
Sonicated reactions
In an Erlenmeyer flask, a mixture of β-diketone (4a,b) (1 mmol) and appropriate hydrazonoyl benzenesulfonate (3) and/or hydrazonyl halides (10a-e) (1 mmol) (3) was taken in absolute ethanol (30 ml) in the presence of Cu(OTf)2/Et3N (5:5 mol%) as catalyst then subjected to ultrasonic irradiations for appropriate time (cf. Tables 1, 2,3). All The reactions were kept at 70–80°C (the temperature inside reaction vessel was 70–76°C and the reaction flask was put in the mid of sonicator bath to to achieve effective cavitations). The sonochemical reactions were continued until the starting materials were no longer detectable by TLC. After the completion of the reaction, EtOAc (30 mL) was added to dilute the reaction solution. Then, the mixture was washed with water. The combined organic phases were dried and concentrated in vacuo, and the remaining residue was purified by recrystalization from ethanol to afford pyrazole derivatives 5a,b and 11a-j. The above reaction was studied also by using various condition and catalysts.
(i) in absence of catalyst: this process was performed as described above and no product formed (ii) in presence of equivalent amount from sodium methoxide, this process was performed as described above and only a trace of product obtained identified as 5a (cf. Table 1) (iii) in presence of different ratio of triethylamine (0.05 mmol) or (0.1 mmol) also, these processes were performed as described above and the progress of the reaction was monitored by TLC, the product formed was identified as 5a in each case (cf. Table 1) in different percent yield, (iv) in presence of different ratio of copper (II) triflate (0.05 mmol) or (0.1 mmol) also, these processes were performed as described above and no product formed.
Silent reactions
These processes were performed on the same scale described above for sonicated reaction. Here the reactant and catalyst were put in ethanol under reflux for suitable time (cf. Tables 2 and 3) until the starting materials were no longer detectable by TLC. The products were obtained and purified as described above in sonicated reaction.
Physical and spectral data of the compounds 5a,b and 11a-j are listed below
4.2.2.1. 4-Acetyl-3,5-di(trifluoromethyl)-1-phenylpyrazole (5a) [58]
M.p. = 211–213°C; IR (KBr): 1712 (C = O), 1611 (C = N) cm-1; 1H NMR (300 MHz, CDCl3) δ: 2.65 (s, 3H, CH3), 6.52-7.23 (m, 5H, ArH’s); 13C NMR (75.46 MHz, CDCl3) δ: 31.42, 112.11, 118.00, 119.58, 123.89, 126.24, 129.30, 136.87, 139.00, 154.62, 191.65. MS (m/z): 322 (M+). (Calc.: C, 48.46; H, 2.50; N, 8.69. C13H8F6N2O Found: C, 48.72; H, 2.38; N,8.55).
4-Benzoyl-3,5-di(trifluoromethyl)-1-phenylpyrazole (5b)
M.p. = 227–228°C; IR (KBr): 1708 (C = O), 1601 (C = N) cm-1; 1H NMR (300 MHz, CDCl3) δ: 7.22-7.69 (m, 10H, ArH’s); 13C NMR (75.46 MHz, CDCl3) δ: 116.05, 119.18, 121.94, 125.54, 126.33, 128.52, 128.53, 129.14, 130.25, 136.89, 139.34, 139.74, 152.87, 193.16. MS (m/z): 384 (M+). (Calc.: C, 56.26; H, 2.62; N, 7.29. C18H10F6N2O Found: C, 56.50; H, 2.52; N,7.15).
3,4-Diacetyl-1-phenyl-5-trifluoromethylpyrazole (11a)
M.p. = 192–194°C; IR (KBr): 1712, 1699 (2 C = O), 1594 (C = N) cm-1; 1H NMR (300 MHz, DMSO-d6) δ: 2.29 (s, 3H, CH3), 2.74 (s, 3H, CH3), 7.31-7.71 (m, 5H, ArH’s); 13C NMR (75.46 MHz, DMSO-d6) δ: 29.15, 31.54, 115.15, 122.01, 125.53, 125.54, 127.41, 129.14, 131.06, 139.98, 150.98, 196.24, 199.09. MS (m/z): 296 (M+). (Calc.: C, 56.76; H, 3.74; N, 9.46. C14H11F3N2O2 Found: C, 56.50; H, 2.52; N,7.15).
3-Acetyl-4-benzoyl-1-phenyl-5-trifluoromethylpyrazole (11b)
M.p. = 213–214°C; IR (KBr): 1710, 1701 (2 C = O), 1599 (C = N) cm-1; 1H NMR (300 MHz, DMSO-d6) δ: 2.24 (s, 3H, CH3), 7.16-7.67 (m, 10H, ArH’s); 13C NMR (75.46 MHz, DMSO-d6) δ: 28.98, 115.24, 120.07, 124.13, 126.22, 128.11, 128.12, 129.85, 133.54, 139.47, 152.00, 194.01, 198.19. MS (m/z): 358 (M+). (Calc.: C, 63.69; H, 3.66; N, 7.82. C19H13F3N2O2 Found: C, 63.96; H, 3.14; N,7.67).
3,4-Diacetyl-1-(4-flurophenyl)-5-trifluoromethylpyrazole (11c)
M.p. = 175–177°C; IR (KBr): 1711, 1697 (2 C = O), 1601 (C = N) cm-1; 1H NMR (300 MHz, DMSO-d6) δ: 2.31 (s, 3H, CH3), 2.59 (s, 3H, CH3), 7.24 (d, 2H, J = 8.4 Hz, ArH’s), 7.55 (d, 2H, J = 8.4 Hz, ArH’s); 13C NMR (75.46 MHz, DMSO-d6) δ: 26.94, 31.20, 113.54, 115.23, 119.08, 123.94, 132.15, 137.65, 152.89, 162.41, 195.00, 198.23. MS (m/z): 314 (M+). (Calc.: C, 53.51; H, 3.21; N, 8.91. C14H10F4N2O2 Found: C, 53.78; H, 3.10; N,8.75).
3-Acetyl-4-benzoyl-1-(4-flurophenyl)-5-trifluoromethylpyrazole (11d)
M.p. = 201–203°C; IR (KBr): 1719, 1701 (2 C = O), 1603 (C = N) cm-1; 1H NMR (300 MHz, DMSO-d6) δ: 2.28 (s, 3H, CH3), 7.21-7.84 (m, 9H, ArH’s); 13C NMR (75.46 MHz, DMSO-d6) δ: 27.98, 112.03, 115.87, 119.26, 125.44, 128.31, 132.05, 135.16, 136.49, 149.97, 162.00, 191.24, 196.20. MS (m/z): 376 (M+). (Calc.: C, 60.64; H, 3.21; N, 7.44. C19H12F4N2O2 Found: C, 60.95; H, 3.07; N,7.27).
3,4-Diacetyl-1-(4-trifluoromethylphenyl)-5-trifluoromethylpyrazole (11e)
M.p. = 194–196°C; IR (KBr): 1707, 1697 (2 C = O), 1600 (C = N) cm-1; 1H NMR (300 MHz, DMSO-d6) δ: 2.26 (s, 3H, CH3), 2.61 (s, 3H, CH3), 7.44 (d, 2H, J = 8.1 Hz, ArH’s), 7.67 (d, 2H, J = 8.1 Hz, ArH’s); 13C NMR (75.46 MHz, DMSO-d6) δ: 29.91, 32.42, 117.21, 123.94, 124.36, 124.85, 126.03, 129.54, 138.03, 143.11, 151.98, 192.10, 196.85. MS (m/z): 364 (M+). (Calc.: C, 49.46; H, 2.77; N, 7.69. C15H10F6N2O2 Found: C, 49.75; H, 2.63; N,7.54).
3-Acetyl-4-benzoyl-1-(4-trifluoromethylphenyl)-5-trifluoromethyl- pyrazole (11f)
M.p. = 210°C; IR (KBr): 1706, 1699 (2 C = O), 1598 (C = N) cm-1; 1H NMR (300 MHz, DMSO-d6) δ: 2.26 (s, 3H, CH3), 7.42-7.85 (m, 9H, ArH’s); 13C NMR (75.46 MHz, DMSO-d6) δ: 27.58, 113.13, 119.26, 121.35, 124.08, 125.65, 127.11, 128.45, 129.69, 132.45, 134.00, 135.04, 143.01, 149.19, 190.98, 196.01. MS (m/z): 426 (M+). (Calc.: C, 56.35; H, 2.84; N, 6.57. C20H12F6N2O2 Found: C, 56.68; H, 2.71; N,6.37).
Ethyl 4-acetyl-1-(4-fluorophenyl)-5-(trifluoromethyl)-1H-pyrazole-3-carboxylate (11 g)
M.p. = 180–182°C; IR (KBr): 1723, 1699 (2 C = O), 1598 (C = N) cm-1; 1H NMR (300 MHz, DMSO-d6) δ: 1.29 (t, 3H, J = 7.2 Hz, CH3), 2.23 (s, 3H, CH3), 4.01(q, 2H, J = 7.2 Hz, CH2), 7.28 (d, 2H, J = 8.4 Hz, ArH’s), 7.65 (d, 2H, J = 8.4 Hz, ArH’s); 13C NMR (75.46 MHz, DMSO-d6) δ: 13.11, 29.18, 58.11, 113.26, 119.01, 125.36, 132.58, 136.00, 148.39, 160.07, 162.37, 192.10. MS (m/z): 344 (M+). (Calc.: C, 52.33; H, 3.51; N, 8.14. C15H12F4N2O3 Found: C, 52.61; H, 3.38; N,7.99).
Ethyl 4-benzoyl-1-(4-fluorophenyl)-5-(trifluoromethyl)-1H-pyrazole-3-carboxylate (11h)
M.p. = 212°C; IR (KBr): 1725, 1701 (2 C = O), 1598 (C = N) cm-1; 1H NMR (300 MHz, DMSO-d6) δ: 0.91 (t, 3H, J = 7.6 Hz CH3), 4.23 (q, 2H, J = 7.6 Hz, CH2), 7.21-7.78 (m, 9H, ArH’s); 13C NMR (75.46 MHz, DMSO-d6) δ: 13.26, 58.25, 112.31, 115.25, 118.01, 119.27, 125.87, 128.97, 131.98, 132.68, 134.85, 137.50, 148.05, 159.98, 163.00, 194.28. MS (m/z): 406 (M+). (Calc.: C, 59.12; H, 3.47; N, 6.89. C20H14F4N2O3Found: C, 59.39; H, 3.34; N,6.75).
Ethyl 4-acetyl-1-(4-trifluoromethylphenyl)-5-(trifluoromethyl)-1H-pyrazole-3-carboxylate (11i)
M.p. = 192–194°C; IR (KBr): 1721, 1699 (2 C = O), 1599 (C = N) cm-1; 1H NMR (300 MHz, DMSO-d6) δ: 0.89 (t, 3H, J = 7.2 Hz, CH3), 2.29 (s, 3H, CH3), 4.00 (q, 2H, J = 7.2 Hz, CH2), 7.67 (d, 2H, J = 7.8 Hz, ArH’s), 7.89 (d, 2H, J = 7.8 Hz, ArH’s); 13C NMR (75.46 MHz, DMSO-d6) δ: 13.56, 28.88, 59.58, 116.48, 121.33, 123.58, 125.47, 126.05, 127.89, 132.11, 141.05, 146.36, 159.87, 192.01. MS (m/z): 394 (M+). (Calc.: C, 48.74; H, 3.07; N, 7.11. C16H12F6N2O3 Found: C, 49.05; H, 2.94; N,6.93).
Ethyl 4-benzoyl-1-(4-trifluoromethylphenyl)-5-(trifluoromethyl)-1H-pyrazole-3-carboxylate (11j)
M.p. = 207–208°C; IR (KBr): 1722, 1701 (2 C = O), 1602 (C = N) cm-1; 1H NMR (300 MHz, DMSO-d6) δ: 1.16 (t, 3H, J = 7.2 Hz CH3), 3.91(q, 2H, J = 7.2 Hz, CH2), 7.51-7.88 (m, 9H, ArH’s); 13C NMR (75.46 MHz, DMSO-d6) δ: 13.98, 59.04, 114.52, 118.12, 121.54, 121.55, 125.87, 126.02, 128.11, 128.95, 132.05, 132.97, 134.23, 142.31, 148.00, 162.45, 196.10. MS (m/z): 456 (M+). (Calc.: C, 55.27; H, 3.09; N, 6.14. C21H14F6N2O3 Found: C, 55.58; H, 2.95; N, 5.97).
Ethyl 4-acetyl-1-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrazole-3-carboxylate (11k)
M.p. = 227–229°C; IR (KBr): 1725, 1705 (2 C = O), 1602 (C = N) cm-1; 1H NMR (300 MHz, DMSO-d6) δ: 1.19 (t, 3H, J = 7.00 Hz, CH3), 2.21 (s, 3H, CH3), 3.95 (q, 2H, J = 7.00 Hz, CH2), 7.60 (d, 2H, J = 7.8 Hz, ArH’s), 7.52 (d, 2H, J = 7.8 Hz, ArH’s); 13C NMR (75.46 MHz, DMSO-d6) δ: 13.52, 28.06, 58.56, 115.18, 121.33, 125.18, 127.51, 132.55, 133.00, 146.15, 159.11, 190.00. MS (m/z): 360 (M+). (Calc.: C, 49.95; H, 3.35; N, 7.77. C15H12ClF3N2O3 Found: C, 50.21; H, 3.27; N,7.59).
Ethyl 4-benzoyl-1-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrazole-3-carboxylate (11 l)
M.p. = 250–251°C; IR (KBr): 1723, 1703 (2 C = O), 1602 (C = N) cm-1; 1H NMR (300 MHz, DMSO-d6) δ: 0.95 (t, 3H, J = 7.2 Hz CH3), 3.99(q, 2H, J = 7.2 Hz, CH2), 7.62-7.95 (m, 9H, ArH’s); 13C NMR (75.46 MHz, DMSO-d6) δ: 13.90, 59.22, 114.00, 117.45, 121.17, 126.89, 128.12, 128.57, 132.00, 133.09, 133.89, 139.11, 147.52, 159.47, 192.13. MS (m/z): 422 (M+). (Calc.: C, 56.82; H, 3.34; N, 6.63. C20H14ClF3N2O3 Found: C, 57.03; H, 3.28; N, 6.48).