General
Reagents and solvents used were of analytical grade. Melting points were determined via Bock-monoscop-M melting point apparatus. IR spectra were recorded on IRPrestige-21 spectrophotometer (Shimadzu) in the range of 4000–400 cm−1. The NMR spectra were either measured on Avance 300 MHz NMR Spectrometer (Bruker) or Avance 400 MHz NMR Spectrometer (Bruker) in deuterated solvents. Chemical shift values are being reported in ppm (parts per million). Designations to the aromatic protons in the intermediate compounds (3a–3f) were made as; protons ortho to the aldehydic group were designated as 1, 1′ while meta as 2,2′; protons from the other aromatic ring (from acid halide) were designated in a clockwise manner throughout with the letters 3, 4, 5 and 6. These designations were maintained in the final products (4a–4l) as well for easy understanding. Mass spectra were recorded using JEOL JMS 600-H machine. For elemental analysis, Vario EL III CHNS-O Elemental Analyzer was used. X-ray diffraction analyses were carried out with a Bruker APEX II DUO diffractometer using graphite-monochromated MoKα radiation (0.71073 Å) from a sealed tube operating at 50 kV and 30 mA. Temperature of the sample was set at 200 (± 2) K with an Oxford Instruments Cryojet system 700 series. Images were recorded by phi and omega scans using APEX2 software [30]. All collected data were corrected for Lorentz, polarization effects and for absorption. The structures were solved by direct methods and refined applying the full-matrix least-squares on F2 method using SHELXS and SHELXL2014 [31] software, respectively. ORTEP plots were drawn with the program PLATON [32]. All non-hydrogen atoms were refined with anisotropic displacement parameters. Hydrogen atoms were placed at their idealized positions with distances of 0.95 Å for C–HAr. The Uiso values for the hydrogen atoms were fixed at 1.2 times the Ueq of the carrier atom (C). Hydrogen atoms of the N–H groups were found from Fourier difference map and treated with riding model. Full crystallographic tables (including structure factors) for compounds 4d and 4j have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC 1579201–1579202. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif.
Synthesis of pyrazine-2-carbohydrazides (1 and 2)
Pyrazine-2-carbohydrazide (1) and 5-methylpyrazine-2-carbohydrazide (2) were prepared following the literature known procedure [24].
General procedure for the synthesis of esters (3a–3f)
Aldehyde (8.0 mmol) was dissolved in tetrahydrofuran (40 mL) and triethyl amine (24.0 mmol) was added to it. The mixture was stirred for 15 min and then kept in an ice bath. Acid halide (8.0 mmol) dissolved in tetrahydrofuran (40 mL) was added dropwise to the reaction mixture. Reaction was stirred for 2 h and then filtered. The filtrate was concentrated and the residue was recrystallized from chloroform in petroleum ether.
4-Formylphenyl 2-fluorobenzoate (3a)
Colour: off-white solid; yield: 0.76 g, 3.1 mmol, 39%; Rf: 0.45 (40% acetone in n-hexane); mp 145–146 °C; IR (\(\bar{\nu }\), cm−1): 1745, 1699, 1253, 1207; 1H NMR (400 MHz, CDCl3): δ 7.19–7.24 (1H, m, H-5), 7.27–7.30 (1H, m, H-3), 7.41–7.43 (2H, m, H-2,2′), 7.60–7.63 (1H, m, H-4), 7.95–7.97 (2H, m, H-1,1′), 8.08–8.11 (1H, m, H-6), 10.01 (1H, s, CHO).
4-Formylphenyl 2-chlorobenzoate (3b)
Colour: off-white solid; yield: 1.67 g, 6.4 mmol, 80%; Rf: 0.45 (40% acetone in n-hexane); mp 92–93 °C; IR (\(\bar{\nu }\), cm−1): 1739, 1695, 1253, 744; 1H NMR (300 MHz, CDCl3): δ 7.41–7.49 (3H, m, H-3,4,5), 7.55–7.57 (2H, m, H-2,2′), 7.98–8.03 (2H, m, H-1,1′), 8.07–8.10 (1H, m, H-6), 10.05 (1H, s, CHO).
4-Formylphenyl 3-chlorobenzoate (3c)
Colour: off-white solid; yield: 1.0 g, 3.8 mmol, 48%; Rf: 0.45 (40% acetone in n-hexane); mp 97–99 °C; IR (\(\bar{\nu }\), cm−1): 1728, 1699, 1253, 732; 1H NMR (300 MHz, CDCl3): δ 7.40 (2H, d, J = 8.4 Hz, H-2,2′), 7.47–7.49 (1H, m, H-5), 7.61–7.64 (1H, m, H-4), 7.97 (2H, d, J = 8.4 Hz, H-1,1′), 8.06–8.09 (1H, m, H-6), 8.17 (1H, s, H-3), 10.02 (1H, s, CHO).
4-Formylphenyl 4-chlorobenzoate (3d)
Colour: white crystals; yield: 1.57 g, 6.0 mmol, 75%; Rf: 0.45 (40% acetone in n-hexane); mp 116–118 °C; IR (\(\bar{\nu }\), cm−1): 1728, 1683, 1261, 746; 1H NMR (300 MHz, CDCl3): δ 7.43 (2H, d, J = 8.7 Hz, H-4,5), 7.53 (2H, d, J = 8.7 Hz, H-3,6), 8.00 (2H, d, J = 8.4 Hz, H-2,2′), 8.16 (2H, d, J = 8.4 Hz, H-1,1′), 10.05 (1H, s, CHO).
4-Formylphenyl 3-bromobenzoate (3e)
Colour: off-white solid; yield: 1.15 g, 3.8 mmol, 47%; Rf: 0.45 (40% acetone in n-hexane); mp 98–100 °C; IR (\(\bar{\nu }\), cm−1): 1728, 1697, 1253, 513; 1H NMR (400 MHz, CDCl3): δ 7.40 (2H, d, J = 8.4 Hz, H-2,2′), 7.41–7.42 (1H, m, H-5), 7.77–7.79 (1H, m, H-4), 7.97 (2H, d, J = 8.4 Hz, H-1,1′), 8.11–8.13 (1H, m, H-6), 8.33 (1H, s, H-3), 10.02 (1H, s, CHO).
4-Formylphenyl 4-bromobenzoate (3f)
Colour: off-white solid; yield: 1.76 g, 5.8 mmol, 72%; Rf: 0.45 (40% acetone in n-hexane); mp 172–174 °C; IR (\(\bar{\nu }\), cm−1) 1741, 1699, 1265, 520; 1H NMR (400 MHz, CDCl3): δ 7.39 (2H, d, J = 8.4 Hz, H-2,2′), 7.66 (2H, d, J = 8.4 Hz, H-4,5), 7.96 (2H, d, J = 8.4 Hz, H-3,6), 8.05 (2H, d, J = 8.4 Hz, H-1,1′), 10.01 (1H, s, CHO).
General procedure for the synthesis of iminobenzoates (4a–4l)
The hydrazide (3.00 mmol) was dissolved in methanol (50 mL) and added dropwise to a methanolic (50 mL) solution of the ester (3.00 mmol). Reaction mixture was refluxed for 5 h. The solid formed was filtered, washed with cold methanol, dried over anhydrous CaCl2 under vacuum and recrystallized from chloroform in n-hexane.
4-[(E)-(Pyrazine-2-carboylimino)methyl]phenyl 2-fluorobenzoate (4a)
Colour: white shiny crystals; yield: 0.6 g, 1.6 mmol, 56%; Rf: 0.3 (40% acetone in n-hexane); mp 281–290 °C; IR (\(\bar{\nu }\), cm−1): 3300, 1728, 1674, 1600, 1290, 1228, 1018; 1H NMR (300 MHz, DMSO): δ 7.41–7.48 (4H, m, H-1,1′,2,2′), 7.76–7.87 (3H, m, H-3,4,5), 8.09–8.15 (1H, m, H-6), 8.68 (1H, s, HC=N), 8.80 (1H, d, J = 2.4 Hz, H-5 pyrazine), 8.93 (1H, d, J = 2.4 Hz, H-6 pyrazine), 9.28 (1H, s, H-3 pyrazine), 12.36 (1H, s, CONH); MS (EI, m/z): 364 [M+], 243, 123, 109, 81, 61.
4-[(E)-(Pyrazine-2-carboylimino)methyl]phenyl 2-chlorobenzoate (4b)
Colour: white shiny flakes; yield: 0.9 g, 2.4 mmol, 80%; Rf: 0.82 (50% acetone in n-hexane); mp 262–265 °C; IR (\(\bar{\nu }\), cm−1): 3288, 1743, 1674, 1560, 1244, 1199, 1020, 750; 1H NMR (400 MHz, DMSO): δ 7.44 (2H, d, J = 8.4 Hz, H-2,2′), 7.54–7.58 (1H, m, H-3), 7.84–7.86 (2H, m, H-4,5), 7.85 (2H, d, J = 8.4 Hz, H-1,1′), 8.10–8.12 (1H, m, H-6), 8.69 (1H, s, HC=N), 8.80 (1H, d, J = 2.4 Hz, H-5 pyrazine), 8.93 (1H, d, J = 2.4 Hz, H-6 pyrazine), 9.27 (1H, s, H-3 pyrazine), 12.33 (1H, s, CONH); MS (EI, m/z): 380 [M+], 139, 123, 111, 75, 52.
4-[(E)-(Pyrazine-2-carboylimino)methyl]phenyl 3-chlorobenzoate (4c)
Colour: Lemon green powder; yield: 1.0 g, 2.6 mmol, 89%; Rf: 0.41 (40% acetone in n-hexane); mp 265–272 °C; IR (\(\bar{\nu }\), cm−1): 3302, 1728, 1678, 1610, 1261, 1020, 736; 1H NMR (400 MHz, DMSO): δ 7.44 (2H, d, J = 8.4 Hz, H-2,2′), 7.64–7.68 (1H, m, H-3), 7.83–7.85 (3H, m, H-4,5,6), 8.10 (2H, d, J = 8.4 Hz, H-1,1′), 8.69 (1H, s, HC=N), 8.80 (1H, d, J = 2.4 Hz, H-5 pyrazine), 8.93 (1H, d, J = 2.4 Hz, H-6 pyrazine), 9.27 (1H, s, H-3 pyrazine), 12.32 (1H, s, CONH); MS (EI, m/z): 380 [M+], 139, 123, 111, 80, 52.
4-[(E)-(Pyrazine-2-carboylimino)methyl]phenyl 4-chlorobenzoate (4d)
Colour: white shiny crystals; yield: 0.95 g, 2.5 mmol, 84%; Rf: 0.4 (40% acetone in n-hexane); mp 287–295 °C; IR (\(\bar{\nu }\), cm−1): 3292, 1732, 1674, 1591, 1253, 1197, 1012, 738; 1H NMR (400 MHz, DMSO): δ 7.42 (2H, d, J = 8.4 Hz, H-2,2′), 7.70 (2H, d, J = 8.4 Hz, H-1,1′), 7.84 (2H, d, J = 8.8 Hz, H-4,5′), 8.15 (2H, d, J = 8.8 Hz, H-3,6′), 8.68 (1H, s, HC=N), 8.80 (1H, d, J = 2.4 Hz, H-5 pyrazine), 8.93 (1H, d, J = 2.4 Hz, H-6 pyrazine), 9.27 (1H, s, H-3 pyrazine), 12.32 (1H, s, CONH); MS (EI, m/z): 380 [M+], 139, 123, 111, 80, 44.
4-[(E)-(Pyrazine-2-carboylimino)methyl]phenyl 3-bromobenzoate (4e)
Colour: white crystals; yield: 0.55 g, 1.3 mmol, 44%; Rf: 0.5 (40% acetone in n-hexane); mp 252–260 °C; IR (\(\bar{\nu }\), cm−1): 3292, 1734, 1683, 1560, 1249, 1031, 509; 1H NMR (400 MHz, DMSO): δ 7.45 (2H, d, J = 8.4 Hz, H-2,2′), 7.57–7.61 (1H, m, H-5), 7.84 (2H, d, J = 8.4 Hz, H-1,1′), 7.98 (1H, d, J = 8 Hz, H-4), 8.14 (1H, d, J = 8 Hz, H-6), 8.26 (1H, s, H-3), 8.69 (1H, s, HC=N), 8.80 (1H, d, J = 2.4 Hz, H-5 pyrazine), 8.93 (1H, d, J = 2.4 Hz, H-6 pyrazine), 9.27 (1H, s, H-3 pyrazine), 12.32 (1H, s, CONH); MS (EI, m/z): 426 [M+], 183, 157, 123, 104, 80.
4-[(E)-(Pyrazine-2-carboylimino)methyl]phenyl 4-bromobenzoate (4f)
Colour: white shiny crystals; yield: 0.91 g, 2.1 mmol, 72%; Rf: 0.42 (40% acetone in n-hexane); mp 295–307 °C; IR (\(\bar{\nu }\), cm−1): 3286, 1732, 1674, 1585, 1257, 1010, 511; 1H NMR (400 MHz, DMSO): δ 7.42 (2H, d, J = 8.4 Hz, H-2,2′), 7.84 (4H, d, J = 8.4 Hz, H-3,4,5,6), 8.07 (2H, d, J = 8.4 Hz, H-1,1′), 8.68 (1H, s, HC=N), 8.80 (1H, d, J = 2.4 Hz, H-5 pyrazine), 8.93 (1H, d, J = 2.4 Hz, H-6 pyrazine), 9.27 (1H, s, H-3 pyrazine), 12.32 (1H, s, CONH); MS (EI, m/z): 426 [M+], 183, 157, 123, 104, 80.
4-[(E)-(5-Methylpyrazine-2-carboylimino)methyl]phenyl 2-fluorobenzoate (4g)
Colour: Pale yellow powder; yield: 0.48 g, 1.3 mmol, 42%; Rf: 0.4 (40% acetone in n-hexane); mp 250–257 °C; IR (\(\bar{\nu }\), cm−1): 3304, 1716, 1683, 1560, 1249, 1031, 509; 1H NMR (400 MHz, DMSO): δ 2.62 (3H, s, CH
3
), 7.40–7.44 (4H, m, H-1,1′,2,2′), 7.76–7.84 (3H, m, H-4,5,6), 8.09–8.13 (1H, m, H-3), 8.68 (1H, s, H-6 pyrazine), 8.68 (1H, s, HC=N) 9.13 (1H, s, H-3 pyrazine), 12.25 (1H, s, CONH); MS (EI, m/z): 378 [M+], 257, 137, 123, 95, 75.
4-[(E)-(5-Methylpyrazine-2-carboylimino)methyl]phenyl 2-chlorobenzoate (4h)
Colour: white shiny flakes; yield: 0.94 g, 2.4 mmol, 79%; Rf: 0.42 (40% acetone in n-hexane); mp 213–220 °C; IR (\(\bar{\nu }\), cm−1): 3296, 1737 (C=O, ester), 1674, 1595 (C=N), 1242, 1197, 1033, 742 (C–Cl aromatic); 1H NMR (400 MHz, DMSO): δ 2.63 (3H, s, CH
3
), 7.43 (2H, d, J = 8.4 Hz, H-2,2′), 7.55–7.58 (1H, m, H-5), 7.68–7.69 (2H, m, H-3,4), 7.84 (2H, d, J = 8.4 Hz, H-1,1′), 8.11 (1H, d, J = 8 Hz, H-6), 8.68 (2H, s, HC=N, H-6 pyrazine), 9.11 (1H, s, H-3 pyrazine), 12.27 (1H, s, CONH); MS (EI, m/z): 394 [M+], 139, 121, 111, 94, 75.
4-[(E)-(5-Methylpyrazine-2-carboylimino)methyl]phenyl 3-chlorobenzoate (4i)
Colour: Lemon green powder; yield: 0.92 g, 2.3 mmol, 77%; Rf: 0.41 (40% acetone in n-hexane); mp 253–260 °C; IR (\(\bar{\nu }\), cm−1): 3302, 1728, 1678, 1602, 1257, 1199, 1020, 721; 1H NMR (400 MHz, DMSO): δ 2.63 (3H, s, CH
3
), 7.43 (2H, d, J = 8.4 Hz, H-2,2′), 7.64–7.68 (1H, m, H-3), 7.82–7.85 (3H, m, H-4,5,6), 8.10 (2H, d, J = 8.4 Hz, H-1,1′), 8.68 (2H, s, HC=N, H-6 pyrazine), 9.13 (1H, s, H-3 pyrazine), 12.25 (1H, s, CONH); MS (EI, m/z): 394 [M+], 139, 121, 111, 94, 75.
4-[(E)-(5-Methylpyrazine-2-carboylimino)methyl]phenyl 4-chlorobenzoate (4j)
Colour: white shiny crystals; yield: 0.98 g, 2.5 mmol, 82%; Rf: 0.45 (40% acetone in n-hexane); mp 265–272 °C; IR (\(\bar{\nu }\), cm−1): 3300, 1734, 1670, 1560, 1261, 1012, 752; 1H NMR (400 MHz, DMSO): δ 2.63 (3H, s, CH
3
), 7.42 (2H, d, J = 8.4 Hz, H-2,2′), 7.69 (2H, d, J = 8.4 Hz, H-1,1′), 7.82 (2H, d, J = 8.4 Hz, H-4,5′), 8.15 (2H, d, J = 8.4 Hz, H-3,6′), 8.68 (2H, s, HC=N, H-6 pyrazine), 9.13 (1H, s, H-3 pyrazine), 12.24 (1H, s, CONH); MS (EI, m/z): 394 [M+], 139, 121, 111, 94, 66.
4-[(E)-(5-Methylpyrazine-2-carboylimino)methyl]phenyl 3-bromobenzoate (4k)
Colour: white solid; yield: 0.85 g, 1.9 mmol, 64%; Rf: 0.42 (40% acetone in n-hexane); mp 265–276 °C; IR (\(\bar{\nu }\), cm−1): 3292, 1732, 1683, 1560, 1247, 1031, 511; 1H NMR (400 MHz, DMSO): δ 2.63 (3H, s, CH
3
), 7.43 (2H, d, J = 8.4 Hz, H-2,2′), 7.57–7.61 (1H, m, H-5), 7.83 (2H, d, J = 8.4 Hz, H-1,1′), 7.98 (1H, d, J = 8 Hz, H-4), 8.14 (1H, d, J = 8 Hz, H-6), 8.26 (1H, s, H-3), 8.68 (2H, s, HC=N, H-6 pyrazine), 9.14 (1H, s, H-3 pyrazine), 12.25 (1H, s, CONH); MS (EI, m/z): 438 [M+], 183, 155, 137, 121, 94.
4-[(E)-(5-Methylpyrazine-2-carboylimino)methyl]phenyl 4-bromobenzoate (4l)
Colour: white powder; yield: 0.81 g, 1.8 mmol, 61%; Rf: 0.5 (40% acetone in n-hexane); mp 293–297 °C; IR (\(\bar{\nu }\), cm−1): 3284, 1735, 1670, 1590, 1261, 1008, 516; 1H NMR (400 MHz, DMSO): δ 2.63 (3H, s, CH
3
), 7.42 (2H, d, J = 8.4 Hz, H-2,2′), 7.81–7.85 (4H, m, H-3,4,5,6), 8.07 (2H, d, J = 8.4 Hz, H-1,1′), 8.68 (2H, s, HC=N, H-6 pyrazine), 9.13 (1H, s, H-3 pyrazine), 12.25 (1H, s, CONH); MS (EI, m/z): 440 [M+], 185, 156, 137, 121, 94.