80% |
With trifluoroacetic acid In ethanol at 20℃; |
General procedure for preparation of compounds 6
General procedure: Compounds 2-4 were synthesized according previously reported procedures, compound 2 is described in Ref. 26, compounds 3 and 4 are described in Ref. 27. TFA (1 equiv) was added to a mixture of compound 4 (0.40 g, 1 equiv) and aldehyde 5 (1.1 equiv) in ethanol (5 mL), at room temperature under stirring. When TLC showed the absence of the reagent, the solid was filtered and washed with ethanol and was identified as 5. Compound 6a: Yield 70%; mp: 236-238°C; IR (Nujol mull) (νmax/cm-1): 3299, 2229, 1586, 1519. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 10.01 (s, 1H, OH), 9.49 (s, 1H, OH), 8.71 (s, 1H, N=CH), 7.78 (s, 1H, H-2), 7.44 (d, J=1.8Hz, 1H, ArH), 7.26 (dd, J=8.3/1.8Hz, 1H, ArH), 6.88 (d, J=8.4Hz, 1H, ArH), 3.59 (s, 3H, Me). 13C NMR (DMSO-d6, 100MHz): δC (ppm) 164(Cimin), 151, 148(C-5), 146, 138(C-2), 127, 124, 117, 116(CN), 114, 97(C-4), 31. Anal. Calcd for C12H10N4O2: C, 59.50; H, 4.13; N, 23.14. Found: C, 59.55; H, 4.34; N, 22.98. Compound 6b: Yield 80%; mp: 242-244°C; IR (Nujol mull) (νmax/cm-1): 3555, 3270, 2215, 1586, 1533, 1515. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 9.39 (br s, 2H, OH), 9.19 (br s, 1H, OH), 8.63 (s, 1H, N=CH), 7.78 (s, 1H, H-2), 6.95 (s, 2H, ArH), 3.59 (s, 3H, Me). 13C NMR (DMSO-d6, 100MHz): δC (ppm) 165(Cimin), 148(C-5), 146, 139, 138(C-2), 125, 117(CN), 109, 97(C-4), 31. Anal. Calcd for C12H10N4O3.0.9H2O: C, 52.65; H, 4.43; N, 20.72. Found: C, 52.52; H, 4.30; N, 20.42. Compound 6c: Yield 70%; mp: >275 (dec.) °C; IR (Nujol mull) (νmax/cm-1): 3453, 3120, 2227, 1636, 1601, 1525. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 11.25 (s, 1H, OH), 10.18 (s, 1H, OH), 8.71 (br s, 1H, OH), 8.98 (s, 1H, N=CH), 7.79 (s, 1H, H-2), 7.14 (d, J=8.7Hz, 1H, ArH), 6.48 (d, J=8.7Hz, 1H, ArH), 3.60 (s, 3H, Me). 13C NMR (DMSO-d6, 100MHz): δC (ppm) 164(Cimin), 152, 150, 147(C-5), 138(C-2), 133, 123, 116(CN), 113, 109, 98(C-4), 31. Anal. Calcd for C12H10N4O3: C, 55.81; H, 3.87; N, 21.70. Found: C, 55.74; H, 4.05; N, 21.58. Compound 6d: Yield 68%; mp: >260 (dec.) °C; IR (Nujol mull) (νmax/cm-1): 3364, 3108, 2227, 1648, 1609, 1577, 1564. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 11.62 (s, 2H, OH), 10.51 (s, 1H, OH), 9.24 (s, 1H, N=CH), 7.76 (s, 1H, H-2), 5.87 (s, 2H, ArH), 3.56 (s, 3H, Me). 13C NMR (DMSO-d6, 100 MHz): δC (ppm) 166(Cimin), 163, 161, 147(C-5), 138(C-2), 117(CN), 102, 98(C-4), 95, 31. Anal. Calcd for C12H10N4O3.0.1H2O: C, 55.43; H, 3.93; N, 21.56. Found: C, 55.47; H, 4.26; N, 21.18. Compound 6e: Yield 55%; mp: 285-287°C; IR (Nujol mull) (νmax/cm-1): 3433, 3127, 2231, 1611, 1591, 1521. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 9.97 (s, 1H, OH), 9.90 (s, 1H, OH), 9.47 (s, 1H, OH), 8.72 (s, 1H, N=CH), 8.01 (s, 1H, H-2), 7.30 (d, J=7.0Hz, 2H, ArH), 7.27 (d, J=2.1Hz, 1H, ArH), 7.17 (dd, J=8.4/2.1Hz, 1H, ArH), 6.88 (d, J=7.0Hz, 2H, ArH), 6.85 (d, J=8.4Hz, 1H, ArH). 13C NMR (DMSO-d6, 100MHz): δC (ppm) 165(Cimin), 158, 151, 148(C-5), 146, 137(C-2), 127, 126.6, 126, 124, 117(CN), 116, 114, 115.7, 98(C-4). Anal. Calcd for C17H12N4O3.0.4H2O: C, 62.52; H, 3.89; N, 17.16. Found: C, 62.39; H, 3.96; N, 16.92. Compound 6f: Yield 81%; mp: 285-287°C; IR (Nujol mull) (νmax/cm-1): 3309, 2238, 1605, 1586, 1519. 1H NMR (DMSO-d6, 400MHz): δH (ppm) δ 9.91 (s, 1H, OH), 9.37 (br s, 2H, OH), 9.16 (br s, 1H, OH), 8.64 (s, 1H, N=CH), 7.99 (s, 1H, H-2), 7.29 (d, J=9.0Hz, 2H, ArH), 6.88 (d, J=9.0Hz, 2H, ArH), 6.82 (s, 2H, ArH). 13C NMR (DMSO-d6, 100MHz): δC (ppm) 165(Cimin), 158, 149(C-5), 146, 139, 137(C-2), 127, 126, 125, 117(CN), 116, 109, 98(C-4). Anal. Calcd for C17H12N4O4: C, 60.71; H, 3.57; N, 16.67. Found: C, 60.55; H, 3.71; N, 16.69. Compound 6g: Yield 98%; mp: 289-291°C; IR (Nujol mull) (νmax/cm-1): 3355, 3126, 2218, 1633, 1606, 1524, 1501. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 11.24 (s, 1H, OH), 10,15 (s, 1H, OH), 8.99 (s, 1H, N=CH),9.97 (s, 1H, OH), 8.68 (s, 1H, OH), 8.01 (s, 1H, H-2), 7.32 (d, J=8.7Hz, 2H, ArH), 7.01 (d, J=9.0Hz, 1H, ArH), 6.89 (d, J=8.7Hz, 2H, ArH), 6.45 (d, J=9.0Hz, 1H, ArH). 13C NMR (DMSO-d6, 100MHz): δC (ppm) 165(Cimin), 158, 152, 150, 147(C-5), 138(C-2), 132, 127, 125, 124, 117(CN), 116, 112, 109, 99(C-4). Anal. Calcd for C17H12N4O4.1.8H2O: C, 55.37; H, 4.23; N, 15.20. Found: C, 55.10; H, 4.34; N, 15.08. Compound 6h: Yield 86%; mp: 300°C (dec.); IR (Nujol mull) (νmax/cm-1): 3368, 3302, 3141, 2227, 1652, 1609, 1582, 1568, 1522. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 11.43 (s, 2H, OH), 10.48 (s, 1H, OH), 9.96 (s, 1H, OH), 9.31 (s, 1H, N=CH), 7.96 (s, 1H, H-2), 7.29 (d, J=9.0Hz, 2H, ArH), 6.88 (d, J=9.0Hz, 2H, ArH), 5.79 (s, 2H, ArH). 13C NMR(DMSO-d6, 100MHz): δC (ppm) 166(Cimin), 163, 161, 158, 147(C-5), 137(C-2), 127, 125, 117(CN), 116, 102, 98(C-4), 95. Anal. Calcd for C17H12N4O4.0.6H2O: C, 58.82; H, 3.81; N, 16.15. Found: C, 58.74; H, 3.91; N, 16.15. Compound 6i: Yield 42%; mp: 253-255°C; IR (Nujol mull) (νmax/cm-1): 3475, 3133, 2223, 1608, 1584. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 9.70 (br s, 2H, OH), 8.73 (s, 1H, N=CH), 8.05 (s, 1H, H-2), 7.44 (d, J=6.9Hz, 2H, ArH), 7.26 (d, J=1.8Hz, 1H, ArH), 7.17 (dd, J=8.1/1.8Hz, 1H, ArH), 7.08 (d, J=6.9Hz, 2H, ArH), 6.84 (d, J=8.1Hz, 1H, ArH), 3.81 (s, 3H, Me). 13C NMR (DMSO-d6, 100MHz): δC (ppm) 165(Cimin), 159, 151, 149(C-5), 146, 138(C-2), 127, 126.7, 126.5, 124, 116(CN), 115.7, 115, 114, 98(C-4), 56. Anal. Calcd for C18H14N4O3: C, 64.67; H, 4.19; N, 16.77. Found: C, 64.52; H, 4.18; N, 16.90. Compound 6j: Yield 91%; mp: 265-267°C; IR (Nujol mull) (νmax/cm-1): 3306, 2238, 1606, 1584, 1538, 1519. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 9.00 (br s, 3H, OH), 8.66 (s, 1H, N=CH), 8.04 (s, 1H, H-2), 7.43 (d, J=8.7Hz, 2H, ArH), 7.08 (d, J=9.0Hz, 2H, ArH), 6.82 (s, 2H, ArH), 3.81 (s, 3H, Me). 13C NMR (DMSO-d6, 100MHz): δC (ppm) 166(Cimin), 159, 149(C-5), 146, 139, 137(C-2), 127, 126.7, 125, 116(CN), 114, 109, 98(C-4), 56. Anal. Calcd for C18H14N4O4: C, 61.71; H, 4.00; N, 16.00. Found: C, 61.70; H, 4.25; N, 16.15. Compound 6k: Yield 80%; mp: >232°C (dec.); IR (Nujol mull) (νmax/cm-1): 3310, 3125, 2112, 2221, 1633, 1602, 1585, 1531, 1519. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 10.80 (br s, 3H, OH), 8.99 (s, 1H, N=CH), 8.04 (s, 1H, H-2), 7.46 (d, J=8.7Hz, 2H, ArH), 7.09 (d, J=9.0Hz, 2H, ArH), 7.02 (d, J=8.7Hz, 1H, ArH), 6.45 (d, J=8.7Hz, 1H, ArH), 3.81 (s, 3H, Me). 13C NMR (DMSO-d6, 100MHz): δC (ppm) 165(Cimin), 159, 152, 150, 147(C-5), 138(C-2), 133, 128, 127, 124, 116(CN), 115, 112, 109, 99(C-4), 56. Anal. Calcd for C18H14N4O4: C, 61.71; H, 4.00; N, 16.00. Found: C, 61.51; H, 4.11; N, 15.97. Compound 6l: Yield 98%; mp: 269-270°C; IR (Nujol mull) (νmax/cm-1): 3331, 3125, 3112, 2225, 1633, 1602, 1585, 1531, 1519. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 11.42 (s, 2H, OH), 10.49 (s, 1H, OH), 9.31 (s, 1H, N=CH), 7.99 (s, 1H, H-2), 7.44 (d, J=9.0Hz, 2H, ArH), 7.09 (d, J=9.0Hz, 2H, ArH), 5.79 (s, 2H, ArH), 3.81 (s, 3H, Me). 13C NMR (DMSO-d6, 100MHz): δC (ppm) 166(Cimin), 163, 161, 160, 147(C-5), 137(C-2) 127, 126, 116(CN), 115, 102, 98(C-4), 95, 56. Anal. Calcd for C18H14N4O4.H2O: C, 58.69; H, 4.35; N, 15.21. Found: C, 58.63; H, 4.41; N, 15.06. Compound 6m: Yield 98%; mp: 234-236°C; IR (Nujol mull) (νmax/cm-1): 3491, 3120, 2219, 1614, 1586, 1514. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 10.22 (s, 1H, OH), 8.80 (s, 1H, N=CH), 8.08 (s, 1H, H-2), 7.47 (d, J=9.0Hz, 2H, ArH), 7.40 (d, J=1.8Hz, 1H, ArH), 7.34 (dd, J=8.3/2.1Hz, 1H, ArH), 7.08 (d, J=9.0Hz, 2H, ArH), 6.89 (d, J=8.3Hz, 1H, ArH), 3.80 (s, 3H, MeO), 3.78 (s, 3H, MeO), 13C NMR (DMSO-d6, 100MHz): δC (ppm) 165(Cimin), 159, 152, 149(C-5), 148, 137(C-2), 127, 126.6, 126.5, 125, 116(CN), 115.7, 114, 111, 98(C-4), 56, 55.6. Anal. Calcd for C19H16N4O3: C, 65.52; H, 4.60; N, 16.09. Found: C, 65.54; H, 4.52; N, 16.17. Compound 6n: Yield 80%; mp: 271-273°C; IR (Nujol mull) (νmax/cm-1): 3549, 3132, 2222, 1605, 1586, 1515, 1529, 1519. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 9.48 (br s, 2H, OH), 8.76 (s, 1H, N=CH), 8.12 (s, 1H, H-2), 7.60 (dd, J=8.0/4.8Hz, 2H, ArH), 7.41 (t, J=9.0Hz, 2H, ArH), 7.28 (d, J=2.1Hz, 1H, ArH), 7.19 (dd, J=8.3/1.8Hz, 2H, ArH), 6.86 (d, J=8.3Hz, 1H, ArH). 13C NMR (DMSO-d6, 100MHz): δC (ppm) 165(Cimin), 162, 151, 149(C-5), 146, 137(C-2), 131, 128, 127, 125, 117(CN), 116, 115.7, 114, 98(C-4). Anal. Calcd for C17H11N4O2F.0.3H2O: C, 62.31; H, 3.54; N, 17.10. Found: C, 62.34; H, 3.41; N, 17.17. Compound 6o: Yield 93%; mp: 260-262°C; IR (Nujol mull) (νmax/cm-1): 3525, 3225, 2224, 1605, 1582, 1512. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 9.38 (br s, 2H, OH), 9.21 (s, 1H, OH), 8.68 (s, 1H, N=CH), 8.11 (s, 1H, H-2), 7.60 (dd, J=9.0/4.8Hz, 2H, ArH), 7.41 (t, J=9.0Hz, 2H, ArH), 6.83 (s, 2H, ArH). 13C NMR (DMSO-d6, 100MHz): δC (ppm) 166(Cimin), 162, 149(C-5), 146, 140, 137(C-2), 131, 128, 125, 117(CN), 116, 108.8, 98(C-4). Anal. Calcd for C17H11N4O3F.1.7H2O: C, 55.34; H, 3.91; N, 15.19. Found: C, 55.35; H, 4.39; N, 15.12. Compound 6p: Yield 97%; mp: 266-268°C; IR (Nujol mull) (νmax/cm-1): 3377, 3145,2219, 1633, 1605, 1583, 1528. 1H NMR (DMSO-d6, 400MHz): δH (ppm) 11.04 (s, 1H, OH), 10.19 (s, 1H, OH), 9.02 (s, 1H, N=CH), 8.68 (s, 1H, OH), 8.11 (s, 1H, H-2), 7.64 (dd, J=9.0/4.8Hz, 2H, ArH), 7.43 (t, J=9.0Hz, 2H, ArH), 7.04 (d, J=9.0Hz, 1H, ArH), 6.46 (d, J=9.0Hz, 1H, ArH). 13C NMR (DMSO-d6, 100MHz): δC (ppm) 165(Cimin), 162, 153, 150, 147(C-5), 138(C-2), 133, 130, 128, 124, 117, 116(CN), 113, 109, 99(C-4). Anal. Calcd for C17H11N4O3F.0.05H2O: C, 60.19; H, 3.27; N, 16.52. Found: C, 60.19; H, 3.54; N, 16.72. |