All reagents, starting materials, and solvents were purchased from Merck AG and were used without treatment unless otherwise indicated. The reactions were performed using microwave oven operating between 200 − 1000 watts of electrical power. The melting points were determined with a Stuart-SMP20 capillary melting point apparatus and are uncorrected. The IR spectra were recorded on a JASCO FTIR spectrometer in KBr. 1H NMR and 13C NMR spectra were obtained on Jeol spectrometer (500 MHz) in CDCl3/DMSO-d6 using tetramethylsilane (TMS) as internal standards and chemical shifts are expressed in ppm. HRMS were recorded on Agilent 6530 ESI-QTOF mass instrument operating in positive ion acquisition mode. All the synthesized chromene derivatives were analyzed by thin-layer chromatography (TLC) using 4:1 hexanes and ethyl acetate.
General procedure for the preparation of chromene derivatives (4a-v, 5a-v and 7a-l): A mixture of malononitrile (2, 1 mmol), aldehyde (3, 1 mmol), α-naphthol (1a)/β-naphthol (1b)/4-hydroxycoumarin (6) (1 mmol) and 5 mg (12 mol%) of NaF were taken in a 10 mL microwave vial. Water (2 mL) was added to this mixture and subjected to microwave irradiation at 200W. The progress of the reaction was monitored by TLC. After completion of the reaction, the solid obtained was filtered and washed with 4 mL of water to remove the NaF. The crude products obtained were purified by recrystallization from MeOH. All the synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR and HRMS. The known compounds melting point values were compared with the literature values and observed a good agreement. Structure of the two compounds were also confirmed by single crystal analysis.
Selected compounds spectral data:
2-Amino-4-(2-fluorophenyl)-4 H -benzo[ h ]chromene-3-carbonitrile (4b): Light brown solid. Melting point: 234–237 oC. IR (υmax, cm− 1): 3434, 3300 (NH2), 3169 (= C-H), 2205 (CN), 1650 (C = C), 1414 (C-F), 1105 (C-O-C). 1H NMR (500 MHz, DMSO-d6): δ 8.24 (d, J = 8.1 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.65–7.55 (m, 3H), 7.30–7.06 (m, 7H), 5.20 (s, 1H). 13C NMR (126 MHz, DMSO-d6): δ 161.0, 160.5, 159.0, 143.1,132.8, (d,131.9, 131.8), (d, 130.2, 130.1), (d, 129.2, 129.1), 127.7, (d, 126.8, 126.7), 125.7, 124.8, 124.0, 122.7, 120.7, 120.3, 116.6, (d, 115.8, 115.7), 54.6, 35.3. HRMS (ESI-QTOF) for C20H13FN2O [M + H]+ calculated 317.1085, found 317.1095.
2-Amino-4-(3-bromophenyl)-4 H -benzo[ h ]chromene-3-carbonitrile (4i): Pale yellow solid. Melting point: 238–240 oC. IR (υmax, cm− 1): 3454, 3340 (NH2), 3189 (= C-H), 2190 (CN), 1655 (C = C), 1100 (C-O-C), 680 (C-Br). 1H NMR (500 MHz, DMSO-d6): δ 8.23 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 8.2 Hz, 1H), 7.65–7.56 (m, 3H), 7.45–7.42 (m, 2H), 7.30–7.23 (m, 4H), 7.12 (d, J = 8.6 Hz, 1H), 4.96 (s, 1H). 13C NMR (126 MHz, DMSO-d6): δ 160.3, 148.4, 142.8, 132.8, 131.0, 130.2, 129.9, 127.7, 126.9, 126.7, 126.0, 124.1, 123.4, 122.7, 121.9, 120.7, 120.3, 117.2, 55.6, 40.4. HRMS (ESI-QTOF) for C20H13BrN2O [M + H]+ calculated 377.0284, found 377.0277.
2-Amino-4-(2-nitrophenyl)-4 H -benzo[ h ]chromene-3-carbonitrile (4k): Brown solid. Melting point: 222–224 oC. IR (υmax, cm− 1): 3464, 3334 (NH2), 3160 (= C-H), 2195 (CN), 1650 (C = C), 1570, 1350 (NO2), 1300 (C-NO2), 1100 (C-O-C). 1H NMR (500 MHz, DMSO-d6): δ 8.37–8.23 (m, 1H), 8.01–7.88 (m, 2H), 7.69–7.57 (m, 4H), 7.50–7.27 (m, 4H), 7.05 (d, J = 8.6 Hz, 1H), 5.45 (s, 1H). 13C NMR (126 MHz, DMSO-d6): δ 160.2, 148.8, 143.1, 138.7, 133.6, 132.9, 131.8, 128.5, 127.7, 127.1, 126.8, 125.5, 124.2, 123.8, 122.7, 120.8, 119.9, 116.1, 55.3, 36.1. HRMS (ESI-QTOF) for C20H13N3O3 [M + Na]+ calculated 366.0849, found 366.0875.
2-Amino-4-(m-tolyl)-4H-benzo[h]chromene-3-carbonitrile (4o): Light yellow solid. Melting point: 195–198 oC. IR (υmax, cm-1): 3429, 3329 (NH2), 3160 (= C-H), 2180 (CN), 1645 (C = C), 1105 (C-O-C). 1H NMR (500 MHz, DMSO-d6): δ 8.21 (d, J = 8.2 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.62–7.53 (m, 2H), 7.27 (d, J = 8.4 Hz, 1H), 7.16–7.11 (m, 2H), 6.95 (d, J = 7.2 Hz, 1H), 6.57 (s, 2H), 6.37 (s, 2H), 5.37 (s, 1H), 2.20 (s, 3H). 13C NMR (126 MHz, DMSO-d6): δ 160.1, 145.6, 142.6, 137.8, 132.6, 128.5, 128.1, 127.6, 127.6, 126.7, 126.6, 126.2, 124.9, 123.8, 122.7, 120.7, 120.5, 117.9, 56.3, 40.9, 21.0. HRMS (ESI-QTOF) for C21H16N2O [M + H]+ calculated 313.1335, found 313.1333.
2-Amino-4-(4-oxo-4 H -chromen-3-yl)-4 H -benzo[ h ]chromene-3-carbonitrile (4v): Pale yellow solid. Melting point: 286–287 oC. IR (υmax, cm− 1): 3424, 3320 (NH2), 3169 (= C-H), 2190 (CN), 1650 (C = C), 1135 (C-O-C). 1H NMR (500 MHz, DMSO-d6): δ 8.64 (s, 1H), 7.90 (dd, J = 28.5, 8.5 Hz, 4H), 7.75–7.72 (m, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.49–7.37 (m, 3H), 7.26 (d, J = 9.0 Hz, 1H), 6.98 (s, 2H), 5.30 (s, 1H). 13C NMR (126 MHz, DMSO-d6): δ 175.5, 161.4, 156.0, 155.3, 148.1, 134.7, 131.1, 130.7, 129.8, 129.1, 127.6, 126.4, 126.0, 125.5, 125.1, 124.1, 123.3, 121.0, 118.9, 117.3, 113.6, 54.6, 31.4. HRMS (ESI-QTOF) for C23H14N2O3 [M + Na]+ calculated 389.0897, found 389.0904.
3-Amino-1-(3-fluorophenyl)-1 H -benzo[ f ]chromene-2-carbonitrile (5c): White solid. Melting point: 286–287 oC. IR (υmax, cm− 1): 3434, 3314 (NH2), 3189 (= C-H), 2190 (CN), 1645 (C = C), 1405 (C-F), 1090 (C-O-C). 1H NMR (500 MHz, DMSO-d6): δ 7.95–7.83 (m, 3H), 7.47–7.26 (m, 4H), 7.04–6.96 (m, 5H), 5.37 (s, 1H). 13C NMR (126 MHz, DMSO-d6): δ 163.2, 161.2, 159.8, (d, 148.6, 148.5), 146.8, (d, 130.8, 130.7), 130.1, 129.7, 128.5, 127.2, 125.0, 123.5, 123.0, 120.3, 116.8, 115.0, (d, 113.7, 113.6), (d, 113.5, 113.3), 57.3, 37.6. HRMS (ESI-QTOF) for C20H13FN2O [M + Na]+ calculated 339.0904, found 339.0920.
3-Amino-1-(2-bromophenyl)-1 H -benzo[f]chromene-2-carbonitrile (5h): Pale yellow solid. Melting point: 247–250 oC. IR (υmax, cm− 1): 3464, 3324 (NH2), 3184 (= C-H), 2190 (CN), 1650 (C = C), 1090 (C-O-C), 660 (C-Br). 1H NMR (500 MHz, DMSO-d6): δ 7.96–7.91 (m, 2H), 7.64–7.61 (m, 2H), 7.48–7.33 (m, 3H), 7.20–7.17 (m, 1H), 7.10–6.90 (m, 4H), 5.67 (s, 1H). 13C NMR (126 MHz, DMSO-d6): δ 159.7, 147.1, 144.2, 132.7, 130.8, 130.1, 130.0, 129.9, 128.8, 128.7, 128.7, 127.4, 125.0, 122.8, 121.7, 119.7, 116.7, 115.0, 56.5, 37.4. HRMS (ESI-QTOF) for C20H13BrN2O [M + H]+ calculated 377.0284, found 377.0271.
3-Amino-1-(3-bromophenyl)-1 H -benzo[ f ]chromene-2-carbonitrile (5i): White solid. Melting point: 240–244 oC. IR (υmax, cm− 1): 3464, 3340 (NH2), 3124 (= C-H), 2190 (CN), 1660 (C = C), 1090 (C-O-C), 660 (C-Br). 1H NMR (500 MHz, DMSO-d6): δ 7.95–7.83 (m, 3H), 7.48–7.33 (m, 5H), 7.23–7.15 (m, 2H), 7.06 (s, 2H), 5.37 (s, 1H). 13C NMR (126 MHz, DMSO-d6): δ 159.8, 148.4, 146.8, 131.0, 130.8, 130.0, 129.8, 129.6, 129.5, 128.5, 127.2, 126.1, 125.0, 123.5, 121.9, 120.2, 116.8, 114.9, 57.3, 37.5. HRMS (ESI-QTOF) for C20H13BrN2O [M + H]+ calculated 377.0284, found 377.0283.
3-Amino-1-(furan-2-yl)-1 H -benzo[ f ]chromene-2-carbonitrile (5t): Black solid. Melting point: 225–227 oC (Literature melting point: 226–227) [47]. IR (υmax, cm− 1): 3454, 3349 (NH2), 3169 (= C-H), 2174 (CN), 1650 (C = C), 1085 (C-O-C). 1H NMR (500 MHz, DMSO-d6): δ 8.05 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 9.0 Hz, 2H), 7.54–7.41 (m, 3H), 7.28 (d, J = 9.0 Hz, 1H), 7.08 (s, 2H), 6.30–6.24 (m, 2H), 5.49 (s, 1H). 13C NMR (126 MHz, DMSO-d6): δ 161.5, 156.6, 147.4, 142.7, 131.1, 130.7, 130.0, 128.9, 127.6, 125.5, 123.8, 120.8, 117.3, 114.1, 110.8, 106.2, 54.7, 32.2. HRMS (ESI-QTOF) for C18H12N2O2 [M + H]+ calculated 289.0972, found 289.0978.
3-Amino-1-(pyridin-4-yl)-1 H -benzo[ f ]chromene-2-carbonitrile (5u): Ash colour solid. Melting point: 230–232 oC (Literature melting point: 228–230) [29]. IR (υmax, cm− 1): 3380, 3304 (NH2), 3140 (= C-H), 2185 (CN), 1645 (C = C), 1085 (C-O-C). 1H NMR (500 MHz, DMSO-d6): δ 8.48–8.44 (m, 2H), 7.98–7.92 (m, 2H), 7.78 (d, J = 8.0 Hz, 1H), 7.47–7.34 (m, 3H), 7.19–7.13 (m, 4H), 5.39 (s, 1H). 13C NMR (126 MHz, DMSO-d6): δ 160.0, 153.7, 150.1, 147.0, 130.8, 130.0, 129.9, 128.5, 127.3, 125.1, 123.4, 122.2, 120.1, 116.8, 114.2, 56.3, 37.2. LC-HRMS (ESI-QTOF) for C19H13N3O [M + H]+ calculated 300.1131, found 300.1153.
3-Amino-1-(4-oxo-4 H -chromen-3-yl)-1 H -benzo[ f ]chromene-2-carbonitrile (5v): Yellow solid. Melting point: 286–287 oC. IR (υmax, cm− 1): 3384, 3324 (NH2), 3174 (= C-H), 2185 (CN), 1645 (C = C), 1080 (C-O-C). 1H NMR (500 MHz, DMSO-d6): δ 8.64 (s, 1H), 7.94–7.86 (m, 4H), 7.75–7.71 (m, 1H), 7.58–7.25 (m, 5H), 6.98 (s, 2H), 5.30 (s, 1H). 13C NMR (126 MHz, DMSO-d6): δ 175.0, 160.9, 155.5, 154.9, 147.6, 134.2, 130.6, 130.2, 129.2, 128.6, 127.1, 125.9, 125.5, 124.9, 124.6, 123.6, 122.8, 120.5, 118.4, 116.8, 113.0, 54.1, 30.9. HRMS (ESI-QTOF) for C23H14N2O3 [M + Na]+ calculated 389.0897, found 389.0910.
2-amino-5-oxo-4-propyl-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (7a): Light brown solid. Melting point: 226–229 oC. IR (υmax, cm− 1): 3414, 3320 (NH2), 3189 (= C-H), 2190 (CN), 1714 (C = O), 1660 (C = C), 1105 (C-O-C). 1H NMR (500 MHz, DMSO-d6): δ 7.79 (dd, J = 7.9, 1.4 Hz, 1H), 7.70–7.66 (m, 1H), 7.46–7.42 (m, 2H), 7.29 (s, 2H), 3.41–3.40 (m, 1H), 1.72–1.49 (m, 2H), 1.31–1.14 (m, 2H), 0.84 (t, J = 7.2 Hz, 3H). 13C NMR (126 MHz, DMSO-d6): δ 159.9, 159.4, 154.1, 152.0, 132.7, 124.6, 122.1, 119.6, 116.5, 112.9, 104.3, 55.1, 36.2, 30.7, 17.6, 13.8. HRMS (ESI-QTOF) for C16H14N2O3 [M + H]+ calculated 283.1077, found 283.1101.
2-Amino-4-(3-fluorophenyl)-5-oxo-4,5-dihydropyrano[3,2- c ]chromene-3-carbonitrile (7c): White solid. Melting point: 255–257 oC. IR (υmax, cm− 1): 3389, 3309 (NH2), 3184 (= C-H), 2194 (CN), 1714 (C = O), 1650 (C = C), 1390 (C-F), 1075 (C-O-C). 1H NMR (500 MHz, DMSO-d6): δ 7.88 (dd, J = 8.0, 1.5 Hz, 1H), 7.72–7.68 (m, 1H), 7.49–7.32 (m, 5H), 7.12–7.04 (m, 3H), 4.50 (s, 1H). 13C NMR (126 MHz, DMSO-d6): δ 163.2, 161.2, 159.6, 158.0, 153.7, 152.2, 146.3, 133.0, 130.5, 124.6, 123.6, 123.5, 122.6, 119.1, 116.4, 114.0, 113.0, 103.2, 57.6, 36.8. HRMS (ESI-QTOF) for C19H11FN2O3 [M + Na]+ calculated 357.0646, found 357.0670.
2-Amino-4-(3,4-dimethoxyphenyl)-5-oxo-4,5-dihydropyrano[3,2- c ]chromene-3-carbonitrile (7i): White solid. Melting point: 234–238 oC. IR (υmax, cm− 1): 3374, 3314 (NH2), 3184 (= C-H), 2194 (CN), 1720 (C = O), 1665 (C = C), 1110 (C-O-C). 1H NMR (500 MHz, DMSO-d6): δ 7.79 (d, J = 7.8 Hz, 1H), 7.60–7.59 (m, 1H), 7.40–7.25 (m, 4H), 6.78–6.74 (m, 2H), 6.64 (dd, J = 8.2, 1.9 Hz, 1H), 4.30 (s, 1H), 3.61 (s, 6H). 13C NMR (126 MHz, DMSO-d6): δ 160.1, 158.4, 153.7, 152.6, 149.0, 148.5, 136.3, 133.3, 125.1, 123.0, 120.2, 119.8, 117.0, 113.5, 112.4, 112.1, 104.6, 58.6, 56.0, 56.0, 37.0. HRMS (ESI-QTOF) for C17H10N2O4 [M + Na]+ calculated 399.0951, found 399.0980.
2-Amino-5-oxo-4-(4-oxo-4 H -chromen-3-yl)-4,5-dihydropyrano[3,2- c ]chromene-3-carbonitrile (7l): Off white solid. Melting point: 258–262 oC. IR (υmax, cm− 1): 3380, 3284 (NH2), 3164 (= C-H), 2250 (CN), 1720 (C = O), 1670 (C = C), 1110 (C-O-C). 1H NMR (500 MHz, DMSO-d6): δ 8.57 (s, 1H), 7.93 (m, J = 26.2, 8.0, 1.5 Hz, 2H), 7.80–7.64 (m, 3H), 7.50–7.40 (m, 5H), 4.39 (s, 1H). 13C NMR (126 MHz, DMSO-d6): δ 175.3, 159.7, 159.4, 155.6, 155.3, 154.4, 152.1, 134.2, 132.9, 125.5, 124.8, 124.6, 123.6, 122.6, 122.3, 119.3, 118.4, 116.5, 113.0, 101.1, 54.3, 30.4. HRMS (ESI-QTOF) for C22H12N2O5 [M + Na]+ calculated 407.0638, found 407.0662.