3.2.2. Preparation Procedure for the Target Compounds 3a–3h
To a 50 mL round bottom flask equipped with a magnetic stirrer, intermediate
2 (0.02 mol) was dissolved in DMF (10 mL), and then substituted phenylamine (0.02 mol), dimethylaminopyridine (DMAP, 0.0002 mol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 0.03 mol) were added. The reactions were performed overnight at room temperature. Upon completion of the reaction (determined by TLC), the mixture was quenched with distilled water (50 mL) and the precipitated residues were filtered, dried under vacuum, and recrystallized from methanol to give the pure racemic target compounds
3a–
3h. The physical characteristics,
1H NMR,
13C NMR, and HRMS data for the target compounds
3a–
3h are shown below. The
1H NMR,
13C NMR, and HRMS spectra for the target compounds
3a–
3h are shown in
Supplementary Materials.
Data for 6-chloro-4-oxo-N-phenylthiochromane-2-carboxamide (3a). Yellow solid; mp 121–123 °C; Yield 76%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.33 (s, 1H, CONH), 7.88 (d, J = 2.4 Hz, 1H, Ph-H), 7.54–7.48 (m, 3H, Ph-H), 7.38 (d, J = 8.4 Hz, Ph-H), 7.28 (t, J = 8.0 Hz, 2H, Ph-H), 7.04 (t, J = 7.2 Hz, 1H, Ph-H), 4.36 (t, J = 4.4 Hz, 1H, SCH), 3.22 (dd, 1J = 4.4 Hz, 2J= 17.2 Hz, 1H, CH2), 3.13 (dd, 1J = 4.8 Hz, 2J = 16.8 Hz, 1H, CH2); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 191.56, 169.01, 139.05, 137.29, 133.56, 132.07, 130.52, 129.77, 129.33, 127.09, 124.10, 119.48, 42.62, 40.41; HRMS (ESI) [M + Na]+ calcd.. for C16H12ClNO2S: 340.01695, found 340.01728.
Data for 6-chloro-N-(4-fluorophenyl)-4-oxothiochromane-2-carboxamide (3b). Brown solid; mp 211–213 °C; Yield 72%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.41 (s, 1H, CONH), 7.54–7.49 (m, 3H, Ph-H), 7.38 (d, J = 8.8 Hz, 1H, Ph-H), 7.16–7.09 (m, 2H, Ph-H), 4.35 (t, J = 4.8 Hz, 1H, SCH), 3.22 (dd, 1J = 4.0 Hz, 2J = 16.8 Hz, 1H, CH2), 3.13 (dd, 1J = 4.8 Hz, 2J = 16.8 Hz, 1H, CH2); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 191.53, 168.91, 158.60 (d, J = 239.0 Hz), 137.24, 135.45, 135.45, 135.43, 133.57, 132.07, 130.55, 129.76, 127.11, 121.33, 121.25, 116.04, 115.81, 42.58, 40.42; HRMS (ESI) [M + Na]+ calcd.. for C16H11ClFNO2S: 358.00753, found 358.00755.
Data for 6-chloro-N-(4-chlorophenyl)-4-oxothiochromane-2-carboxamide (3c). Brown solid; mp 234–235 °C; Yield 81%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.43 (s, 1H, CONH), 7.88 (d, J = 2.4 Hz, 1H, Ph-H), 7.54–7.49 (m, 3H, Ph-H), 7.38 (d, J = 8.4 Hz, 1H, Ph-H), 7.16–7.11 (m, 2H, Ph-H), 4.35 (t, J = 4.4 Hz, 1H, SCH), 3.22 (dd, 1J = 4.4 Hz, 2J = 16.8 Hz, 1H, CH2), 3.13 (dd, 1J = 4.4 Hz, 2J = 16.8 Hz, 1H, CH2); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 191.53, 168.91, 159.80, 157.41, 137.23, 135.42, 133.56, 132.06, 130.55, 129.76, 127.11, 121.32, 116.03, 42.58, 40.41; HRMS (ESI) [M + Na]+ calcd. for C16H11Cl2NO2S: 373.97798, found 373.98073.
Data for 6-chloro-4-oxo-N-(p-tolyl)thiochromane-2-carboxamide (3d). Brown solid; mp 216–218 °C; Yield 74%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.24 (s, 1H, CONH), 7.88 (d, J = 2.8 Hz, 1H, Ph-H), 7.52 (dd, 1J = 2.4 Hz, 2J = 8.4 Hz, 1H, Ph-H), 7.38 (d, J = 8.8 Hz, 3H, Ph-H), 7.08 (d, J = 8.0 Hz, 2H, Ph-H), 4.33 (t, J = 4.4 Hz, 1H, SCH), 3.21 (dd, 1J = 4.4 Hz, 2J = 16.8 Hz, 1H, CH2), 3.12 (dd, 1J = 4.8 Hz, 2J = 16.8 Hz, 1H, CH2), 2.23 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 191.57, 168.75, 137.35, 136.54, 133.53, 133.06, 132.09, 130.49, 129.74, 129.69, 127.08, 119.48, 40.60, 40.42, 20.88; HRMS (ESI) [M + Na]+ calcd. for C17H14ClNO2S: 354.03260, found 354.03258.
Data for 6-methyl-4-oxo-N-phenylthiochromane-2-carboxamide (3e). Yellow solid; mp 178–179 °C; Yield 75%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.32 (s, 1H, CONH), 7.79 (d, J = 0.8 Hz, 1H, Ph-H), 7.51 (dd, 1J = 0.8 Hz, 2J = 8.4 Hz, 2H, Ph-H), 7.30–7.26 (m, 3H, Ph-H), 7.20 (d, J = 8.0 Hz, 1H, Ph-H), 7.04 (t, J = 7.6 Hz, 1H, Ph-H), 4.32 (t, J = 4.8 Hz, 1H, SCH), 3.16 (dd, 1J = 4.0 Hz, 2J = 16.4 Hz, 1H, CH2), 3.09 (dd, 1J = 5.2 Hz, 2J = 16.8 Hz, 1H, CH2), 2.29 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 192.57, 169.25, 138.13, 135.29, 134.85, 134.78, 130.57, 129.21, 128.24, 127.59, 127.55, 121.02, 42.79, 40.98, 20.83; HRMS (ESI) [M + Na]+ calcd. for C17H15NO2S: 320.07157, found 320.07151.
Data for N-(4-fluorophenyl)-6-methyl-4-oxothiochromane-2-carboxamide (3f). Yellow solid; mp 206–207 °C; Yield 79%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.39 (s, 1H, CONH), 7.79 (d, J = 1.2 Hz, 1H, Ph-H), 7.29 (dd, 1J = 1.6 Hz, 2J = 8.0 Hz, 1H, Ph-H), 7.20 (d, J = 8.0 Hz, 1H, Ph-H), 7.16–7.10 (m, 2H, Ph-H), 4.31 (t, J = 4.4 Hz, 1H, SCH), 3.17 (dd, 1J = 4.4 Hz, 2J = 16.8 Hz, 1H, CH2), 3.09 (dd, 1J = 4.8 Hz, 2J = 16.8 Hz, 1H, CH2), 2.29 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 192.62, 168.99, 158.55 (d, J = 239.0 Hz), 135.58, 135.56, 135.25, 134.91, 134.83, 130.58, 128.24, 127.58, 121.25, 121.18, 115.99, 115.77, 42.79, 41.06, 20.82; HRMS (ESI) [M + Na]+ calcd. for C17H14FNO2S: 338.06215, found 338.06226.
Data for N-(4-chlorophenyl)-6-methyl-4-oxothiochromane-2-carboxamide (3g). Yellow solid; mp 209–210 °C; Yield 70%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.46 (s, 1H, CONH), 7.78 (s, 1H, Ph-H), 7.53 (d, J = 8.8 Hz, 2H, Ph-H), 7.34 (d, J = 8.8 Hz, 2H, Ph-H), 7.29 (d, J = 8.0 Hz, 1H, Ph-H), 7.20 (d, J = 8.0 Hz, 1H, Ph-H), 4.31 (t, J = 4.8 Hz, 1H, SCH), 3.16 (dd, 1J = 4.0 Hz, 2J = 16.8 Hz, 1H, CH2), 3.09 (dd, 1J = 4.8 Hz, 2J = 16.8 Hz, 1H, CH2), 2.29 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 192.57, 169.25, 138.13, 135.29, 134.85, 134.78, 130.57, 129.21, 128.24, 127.59, 121.02, 42.79, 40.98, 20.83; HRMS (ESI) [M + Na]+ calcd. for C17H14ClNO2S: 354.03260, found 354.03244.
Data for 6-methyl-4-oxo-N-(p-tolyl)thiochromane-2-carboxamide (3h). Yellow solid; mp 199–200 °C; Yield 68%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.22 (s, 1H, CONH), 7.78 (d, J = 1.2 Hz, 1H, Ph-H), 7.39 (d, J = 8.4 Hz, 2H, Ph-H), 7.28 (dd, 1J = 1.6 Hz, 2J = 8.0 Hz, 1H, Ph-H), 7.19 (d, J = 8.0 Hz, 1H, Ph-H), 7.08 (d, J = 8.0 Hz, 2H, Ph-H), 4.29 (t, J = 4.8 Hz, 1H, SCH), 3.15 (d, J = 4.0 Hz, 2J = 16.8 Hz, 1H, CH2), 3.07 (dd, 1J = 4.2 Hz, 2J = 16.8 Hz, 1H, CH2), 2.29 (s, 3H, CH3), 2.23 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 192.66, 168.83, 136.68, 135.18, 135.03, 134.81, 132.93, 130.60, 129.65, 128.21, 127.56, 119.43, 42.82, 41.11, 20.88, 20.83; HRMS (ESI) [M + Na]+ calcd. for C18H17NO2S: 334.08722, found 334.08714.
3.2.3. Preparation Procedure for the Target Compounds 4a–4x
To a 50 mL round bottom flask equipped with a magnetic stirrer, a mixture of compound
3 (10 mmol), R
3ONH
2·HCl (15 mmol), pyridine (10 mL), and ethanol (10 mL) were added and reacted under a reflux temperature for 3–5 h. Upon completion of the reaction (determined by TLC), the mixture was cooled to room temperature and the precipitated residues were dried under vacuum and recrystallized from ethanol to give the pure racemic target compounds
4a–
4x. The physical characteristics,
1H NMR,
13C NMR, and HRMS data for the target compounds
4a–
4x are shown below. The
1H NMR,
13C NMR, and HRMS spectra for the target compounds
4a–
4x are shown in
Supplementary Materials.
Data for 6-chloro-4-(hydroxyimino)-N-phenylthiochromane-2-carboxamide (4a). White solid; mp 235–237 °C; Yield 80%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 11.73 (s, 1H, OH), 10.29 (s, 1H, CONH), 7.86 (t, J = 1.6 Hz, 1H, Ph-H), 7.54 (d, J = 1.2 Hz, 1H, Ph-H), 7.52 (s, 1H, Ph-H), 7.31 (d, J = 1.2 Hz, 2H, Ph-H), 7.29 (d, J = 8.0 Hz, 2H, Ph-H), 7.05 (t, J = 7.2 Hz, 1H, Ph-H), 4.18 (dd, 1J = 4.8 Hz, 2J = 7.2 Hz, 1H, SCH), 3.29 (dd, 1J = 7.2 Hz, 2J = 18.0 Hz, 1H, CH2), 3.15 (dd, 1J = 4.4 Hz, 2J = 18.0 Hz, 1H, CH2); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.38, 149.92, 139.16, 132.55, 131.57, 130.63, 130.26, 129.28, 129.05, 129.45, 124.05, 119.60, 42.67, 28.32; HRMS (ESI) [M + Na]+ calcd. for C16H13ClN2O2S: 355.02785, found 355.02769.
Data for 6-chloro-4-(methoxyimino)-N-phenylthiochromane-2-carboxamide (4b). White solid; mp 197–198 °C; Yield 85%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.45 (s, 1H, CONH), 7.86 (d, J = 1.6 Hz, 1H, Ph-H), 7.53 (d, J = 8.0 Hz, 2H, Ph-H), 7.36–7.27 (m, 4H, Ph-H), 7.05 (t, J = 7.2 Hz, 1H, Ph-H), 4.24 (t, J = 5.6 Hz, 1H, SCH), 4.00 (s, 3H, CH3), 3.33 (dd, 1J = 6.4 Hz, 2J = 18.0 Hz, 1H, CH2), 3.09 (dd, 1J = 4.4 Hz, 2J = 18.0 Hz, 1H, CH2); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.37, 150.63, 143.08, 139.19, 131.91, 131.39, 130.66, 130.36, 129.62, 129.25, 127.44, 124.68, 124.02, 119.57, 62.79, 40.03, 28.54; HRMS (ESI) [M + Na]+ calcd. for C17H15ClN2O2S: 369.04350, found 369.04279.
Data for 6-chloro-4-(ethoxyimino)-N-phenylthiochromane-2-carboxamide (4c). White solid; mp 191–192 °C; Yield 88%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.31 (s, 1H, CONH), 7.87 (d, J = 1.2 Hz, 1H, Ph-H), 7.52 (d, J = 7.6 Hz, 2H, Ph-H), 7.36–7.27 (m, 4H, Ph-H), 7.05 (t, J = 7.2 Hz, 1H, Ph-H), 4.25 (q, J = 7.2 Hz, 2H, CH2CH3), 4.18 (dd, 1J = 4.8 Hz, 2J = 6.8 Hz, 1H, SCH), 3.32 (dd, 1J = 6.8 Hz, 2J = 18.0 Hz, 1H, CH2), 3.11 (dd, 1J = 4.8 Hz, 2J = 18.0 Hz, 1H, CH2), 1.29 (t, J = 7.2 Hz, 3H, CH2CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.29, 150.34, 139.13, 131.84, 131.71, 130.71, 130.38, 129.54, 129.28, 124.70, 119.57, 70.35, 42.26, 28.78, 15.14; HRMS (ESI) [M + Na]+ calcd. for C18H17ClN2O2S: 383.05915, found 383.05883.
Data for 6-chloro-N-(4-fluorophenyl)-4-(hydroxyimino)thiochromane-2-carboxamide (4d). Light yellow solid; mp 225–227 °C; Yield 74%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 11.73 (s, 1H, OH), 10.36 (s, 1H, CONH), 7.85 (d, J = 1.2 Hz, 1H, Ph-H), 7.57–7.53 (m, 2H, Ph-H), 7.31 (d, J = 0.8 Hz, 2H, Ph-H), 7.14 (t, J = 8.8 Hz, 2H, Ph-H), 4.16 (dd, 1J = 4.4 Hz, 2J = 7.2 Hz, 1H, SCH), 3.28 (dd, 1J = 7.2 Hz, 2J = 17.6 Hz, 1H, CH2), 3.15 (dd, 1J = 4.4 Hz, 2J = 18.0 Hz, 1H, CH2); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.30, 158.60 (d, J = 239.0 Hz), 149.88, 135.55, 132.55, 131.51, 130.65, 130.26, 129.19, 129.06, 124.49, 121.44, 121.36, 115.98, 115.76, 42.61, 28.31; HRMS (ESI) [M + Na]+ calcd. for C16H12ClFN2O2S: 373.01843, found 373.01799.
Data for 6-chloro-N-(4-fluorophenyl)-4-(methoxyimino)thiochromane-2-carboxamide (4e). White solid; mp 195–196 °C; Yield 68%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.35 (s, 1H, CONH), 7.86 (d, J = 1.6 Hz, 1H, Ph-H), 7.55–7.51 (m, 2H, Ph-H), 7.36–7.31 (m, 2H, Ph-H), 7.15–7.11 (m, 2H, Ph-H), 4.16 (dd, 1J = 4.8 Hz, 2J = 6.8 Hz, 1H, SCH), 4.00 (s, 3H, CH3), 3.32 (dd, 1J = 6.8 Hz, 2J = 18.0 Hz, 1H, CH2), 3.10 (dd, 1J = 4.8 Hz, 2J = 18.0 Hz, 1H, CH2); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.22, 158.60 (d, J = 239.0 Hz), 150.59, 135.50, 131.79, 131.40, 130.72, 130.37, 129.64, 124.70, 121.3841, 121.34, 115.98, 115.76, 62.78, 41.99, 28.52; HRMS (ESI) [M + Na]+ calcd. for C17H14ClFN2O2S: 387.03408, found 387.03343.
Data for 6-chloro-4-(ethoxyimino)-N-(4-fluorophenyl)thiochromane-2-carboxamide (4f). White solid; mp 200–201 °C; Yield 78%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.37 (s, 1H, CONH), 7.87 (d, J = 1.2 Hz, 1H, Ph-H), 7.56–7.52 (m, 2H, Ph-H), 7.36–7.31 (m, 2H, Ph-H), 7.16–7.11 (m, 2H, Ph-H), 4.25 (dd, J = 7.2 Hz, 2H, CH2CH3), 4.17 (dd, 1J = 4.8 Hz, 2J = 7.2 Hz, 1H, SCH), 3.31 (dd, 1J = 7.2 Hz, 2J = 18.0 Hz, 1H, CH2), 3.12 (dd, 1J = 4.8 Hz, 2J = 18.0 Hz, 1H, CH2), 1.29 (t, J = 7.2 Hz, 3H, CH2CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.21, 158.60 (d, J = 239.0 Hz), 150.31, 135.53, 131.78, 131.71, 130.74, 130.78, 129.55, 124.71, 121.38 (d, J = 8.0 Hz), 115.98, 115.76, 70.35, 42.20, 28.77, 15.14; HRMS (ESI) [M + Na]+ calcd. for C18H16CLFN2O2S: 401.04973, found 401.04886.
Data for 6-chloro-N-(4-chlorophenyl)-4-(hydroxyimino)thiochromane-2-carboxamide (4g). Light yellow solid; mp 239–240 °C; Yield 79%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 11.73 (s, 1H, OH), 10.44 (s, 1H, CONH), 7.85 (s, 1H, Ph-H), 7.56 (d, J = 8.8 Hz, 2H, Ph-H), 7.35 (d, J = 8.8 Hz, 1H, Ph-H), 7.31 (d, J = 1.2 Hz, 3H, Ph-H), 4.17 (dd, 1J = 4.8 Hz, 2J = 7.2 Hz, 1H, SCH), 3.30 (dd, 1J = 6.8 Hz, 2J = 18.0 Hz, 1H, CH2), 3.13 (dd, 1J = 4.4 Hz, 2J = 18.0 Hz, 1H, CH2); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.57, 149.83, 138.11, 132.56, 131.35, 130.86, 130.27 129.19, 129.06, 127.60, 124.44, 121.16, 42.51, 28.20; HRMS (ESI) [M + Na]+ calcd. for C16H12Cl2N2O2S: 388.98888, found 388.98813.
Data for 6-chloro-N-(4-chlorophenyl)-4-(methoxyimino)thiochromane-2-carboxamide (4h). Light pink solid; mp 216–218 °C; Yield 76%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.45 (s, 1H, CONH), 7.86 (d, J = 1.6 Hz, 1H, Ph-H), 7.54 (dd, 1J = 2.4 Hz, 2J = 7.2 Hz, 2H, Ph-H), 7.36–7.33 (m, 4H, Ph-H), 4.17 (dd, 1J = 1.6 Hz, 2J = 5.6 Hz, 1H, SCH), 4.00 (s, 3H, CH3), 3.34 (dd, 1J = 6.4 Hz, 2J = 18.0 Hz, 1H, CH2), 3.07 (dd, 1J = 4.4 Hz, 2J = 18.0 Hz, 1H, CH2); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.50, 150.54, 138.08, 131.63, 131.40, 130.75, 129.65, 129.20, 127.60, 124.69, 121.14, 62.79, 41.90, 28.41; HRMS (ESI) [M + Na]+ calcd. for C16H12Cl2N2O2S: 403.00453, found 403.00421.
Data for 6-chloro-N-(4-chlorophenyl)-4-(ethoxyimino)thiochromane-2-carboxamide (4i). White solid; mp 200–202 °C; Yield 79%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.45 (s, 1H, CONH), 7.87 (d, J = 1.2 Hz, 1H, Ph-H), 7.55 (dd, 1J = 2.0 Hz, 2J = 6.4 Hz, 2H, Ph-H), 7.34 (dd, 1J = 2.0 Hz, 2J = 9.2 Hz, 4H, Ph-H), 4.25 (q, J = 7.2 Hz, 2H, CH2CH3), 4.17 (dd, 1J = 4.8 Hz, 2J = 6.8 Hz, 1H, SCH), 3.33 (dd, 1J = 6.8 Hz, 2J = 18.0 Hz, 1H, CH2), 3.10 (dd, 1J = 4.8 Hz, 2J = 18.0 Hz, 1H, CH2), 1.28 (t, J = 7.2 Hz, 3H, CH2CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.48, 150.26, 138.09, 131.71, 131.62, 130.77, 130.39, 129.55, 129.20, 127.60, 124.70, 121.14, 70.36, 42.11, 28.66, 15.15; HRMS (ESI) [M + Na]+ calcd. for C18H16Cl2N2O2S: 417.02018, found 417.01923.
Data for 6-chloro-4-(hydroxyimino)-N-(p-tolyl)thiochromane-2-carboxamide (4j). While solid; mp 249–250 °C; Yield 73%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 11.72 (s, 1H, OH), 10.20 (s, 1H, CONH), 7.85 (t, J = 1.6 Hz, 1H, Ph-H), 7.41 (d, J = 8.4 Hz, Ph-H), 7.31 (d, J = 1.2 Hz, 2H, Ph-H), 7.10 (d, J = 8.0 Hz, 2H, Ph-H), 4.15 (dd, 1J = 4.4 Hz, 2J = 7.2 Hz, 1H, SCH), 3.26 (dd, 1J = 7.2 Hz, 2J = 18.0 Hz, 1H, CH2), 3.14 (dd, 1J = 4.4 Hz, 2J = 18.0 Hz, 1H, CH2), 2.24 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.10, 149.94, 136.64, 133.01, 132.53, 131.67, 130.60, 129.64, 129.04, 124.45, 119.61, 42.73, 28.37, 20.90; HRMS (ESI) [M + Na]+ calcd. for C17H15ClN2O2S: 369.04350, found 369.04307.
Data for 6-chloro-4-(methoxyimino)-N-(p-tolyl)thiochromane-2-carboxamide (4k). While solid; mp 215–216 °C; Yield 79%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.21 (s, 1H, CONH), 7.86 (d, J = 1.6 Hz, 1H, Ph-H), 7.40 (d, J = 8.8 Hz, 2H, Ph-H), 7.36–7.30 (m, 2H, Ph-H), 7.09 (d, J = 8.4 Hz, 2H, Ph-H), 4.15 (dd, 1J = 4.8 Hz, 2J = 6.8 Hz, 1H, SCH), 3.98 (s, 3H, CH3), 3.31 (dd, 1J = 6.8 Hz, 2J = 18.0 Hz, 1H, CH2), 3.09 (dd, 1J = 4.4 Hz, 2J = 18.0 Hz, CH2), 2.23 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.03, 150.65, 136.62, 133.01, 131.95, 131.38, 130.66, 130.35, 129.64, 124.69, 119.58, 62.78, 42.10, 28.57, 20.89; HRMS (ESI) [M + Na]+ calcd. for C18H17ClN2O2S: 383.05915, found 383.05886.
Data for 6-chloro-4-(ethoxyimino)-N-(p-tolyl)thiochromane-2-carboxamide (4l). Light yellow solid; mp 196–198 °C; Yield 72%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.21 (s, 1H, CONH), 7.86 (d, J = 2.0 Hz, 1H, Ph-H), 7.40 (d, J = 8.4 Hz, 2H, Ph-H), 7.35–7.32 (m, 2H, Ph-H), 7.09 (d, J = 8.4 Hz, 2H, Ph-H), 4.24 (q, J = 6.8 Hz, 2H, CH2CH3), 4.16 (dd, 1J = 4.8 Hz, 2J = 7.2 Hz, 1H, SCH), 3.29 (dd, 1J = 7.2 Hz, 2J = 18.0 Hz, 1H, CH2), 3.11 (dd, 1J = 4.8 Hz, 2J = 18.0 Hz, 1H, CH2), 2.25 (s, 3H, CH3), 1.28 (t, J = 7.2 Hz, 3H, CH2CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.01, 150.37, 136.62, 133.01, 131.95, 131.69, 130.68, 130.36, 129.64, 129.53, 124.70, 119.59, 70.34, 42.32, 28.83, 20.90, 15.14; HRMS (ESI) [M + Na]+ calcd. for C19H19ClN2O2S: 397.07480, found 397.07433.
Data for 4-(hydroxyimino)-6-methyl-N-phenylthiochromane-2-carboxamide (4m). Light pink solid; mp 237–238 °C; Yield 79%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 11.46 (s, 1H, OH), 10.26 (s, 1H, CONH), 7.71 (s, 1H, Ph-H), 7.54 (d, J = 8.0 Hz, 2H, Ph-H), 7.30 (t, J = 8.0 Hz, 2H, Ph-H), 7.15 (d, J = 8.0 Hz, 1H, Ph-H), 7.09–7.03 (m, 2H, Ph-H), 4.10 (t, J = 6.4 Hz, 1H, SCH), 3.20 (d, J = 1.6 Hz, 2H, CH2), 2.28 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.48, 150.85, 139.22, 135.40, 130.73, 130.26, 129.42, 129.26, 128.41, 125.74, 124.00, 119.60, 43.42, 29.13, 21.19; HRMS (ESI) [M + Na]+ calcd. for C17H16N2O2S: 335.08247, found 335.08237.
Data for 4-(methoxyimino)-6-methyl-N-phenylthiochromane-2-carboxamide (4n). Yellow solid; mp 142–144 °C; Yield 82%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.26 (s, 1H, CONH), 7.71 (s, 1H, Ph-H), 7.53 (d, J = 7.6 Hz, 2H, Ph-H), 7.29 (t, J = 7.6 Hz, 2H, Ph-H), 7.17 (d, J = 8.0 Hz, 1H, Ph-H), 7.11 (dd, 1J = 1.2 Hz, 2J = 8.0 Hz, 1H, Ph-H), 7.05 (t, J = 7.2 Hz, 1H, Ph-H), 4.11 (dd, 1J = 4.8 Hz, 2J = 7.2 Hz, 1H, SCH), 3.96 (s, 3H, CH3), 3.26 (dd, 1J = 7.6 Hz, 2J = 18.0 Hz, 1H, CH2), 3.15 (dd, 1J = 4.8 Hz, 2J = 18.0 Hz, 1H, CH2), 2.28 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.38, 151.69, 139.21, 135.56, 130.86, 129.70, 129.63, 129.26, 128.53, 125.93, 124.00, 119.57, 62.49, 42.77, 29.37, 21.10; HRMS (ESI) [M + Na]+ calcd. for C18H18N2O2S: 349.09812, found 349.09763.
Data for 4-(ethoxyimino)-6-methyl-N-phenylthiochromane-2-carboxamide (4o). Yellow solid; mp 178–180 °C; Yield 80%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.27 (s, 1H, CONH), 7.71 (s, 1H, Ph-H), 7.53 (d, J = 7.6 Hz, 2H, Ph-H), 7.29 (t, J = 7.2 Hz, 2H, Ph-H), 7.17 (d, J = 8.0 Hz, 1H, Ph-H), 7.11 (dd, 1J = 1.6 Hz, 2J = 8.0 Hz, 1H, Ph-H), 7.05 (t, J = 7.2 Hz, 1H, Ph-H), 4.22 (q, J = 7.2 Hz, 2H, CH2CH3), 4.11 (dd, 1J = 4.8 Hz, 2J = 7.6 Hz, 1H, SCH), 3.24 (dd, 1J = 8.0 Hz, 2J = 18.0 Hz, 1H, CH2), 3.16 (dd, 1J = 4.8 Hz, 2J = 18.0 Hz, 1H, CH2), 2.28 (s, 3H, CH3), 1.28 (t, J = 6.8 Hz, 3H, CH2CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.37, 151.40, 139.20, 135.58, 130.77, 129.94, 129.70, 129.26, 128.55, 125.96, 124.01, 119.57, 69.99, 43.02, 29.64, 21.13, 15.19; HRMS (ESI) [M + Na]+ calcd. for C19H20N2O2S: 363.11377, found 363.11337.
Data for N-(4-fluorophenyl)-4-(hydroxyimino)-6-methylthiochromane-2-carboxamide (4p). White solid; mp 227–228 °C; Yield 75%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 11.46 (s, 1H, OH), 10.33 (s, 1H, CONH), 7.70 (s, 1H, Ph-H), 7.57–7.54 (m, 2H, Ph-H), 7.17–7.07 (m, 4H, Ph-H), 4.09 (t, J = 6.8 Hz, 1H, SCH), 3.20 (d, J = 6.8 Hz, 2H, CH2), 2.28 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.40, 158.58 (d, J = 239.0 Hz), 150.82, 135.43, 130.73, 130.27, 129.36, 128.41, 125.74, 121.43, 121.35, 115.96, 115.74, 43.33, 29.11, 21.19; HRMS (ESI) [M + Na]+ calcd. for C17H15FN2O2S: 353.07305, found 353.07262.
Data for N-(4-fluorophenyl)-4-(methoxyimino)-6-methylthiochromane-2-carboxamide (4q). White solid; mp 184–185 °C; Yield 70%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.32 (s, 1H, CONH), 7.71 (s, 1H, Ph-H), 7.56–7.52 (m, 2H, Ph-H), 7.18–7.10 (m, 4H, Ph-H), 4.09 (dd, 1J = 4.8 Hz, 2J = 7.6 Hz, 1H, SCH), 3.96 (s, 3H, CH3), 3.25 (dd, 1J = 7.6 Hz, 2J = 18.0 Hz, 1H, CH2), 3.14 (dd, 1J = 4.8 Hz, 2J = 18.0 Hz, 1H, CH2), 2.28 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.30, 158.60 (d, J = 239.0 Hz), 151.66, 135.60, 130.87, 129.63, 128.54, 125.94, 12140, 121.32, 115.96, 115.74, 62.50, 42.68, 29.35, 21.10; HRMS (ESI) [M + Na]+ calcd. for C18H17FN2O2S: 367.08870, found 367.08810.
Data for 4-(ethoxyimino)-N-(4-fluorophenyl)-6-methylthiochromane-2-carboxamide (4r). White solid; mp 168–170 °C; Yield 77%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.33 (s, 1H, CONH), 7.71 (s, 1H, Ph-H), 7.56–7.53 (m, 2H, Ph-H), 7.18–7.10 (m, 4H, Ph-H), 4.22 (q, J = 7.2 Hz, 2H, CH2CH3), 4.09 (dd, 1J = 4.8 Hz, 2J = 7.6 Hz, 1H, SCH), 3.24 (dd, 1J = 7.6 Hz, 2J = 18.0 Hz, 1H, CH2), 3.16 (dd, 1J = 4.8 Hz, 2J = 18.0 Hz, 1H, CH2), 2.28 (s, 3H, CH3), 1.28 (t, J = 7.2 Hz, 3H, CH2CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.29, 158.58 (d, J = 240.0 Hz), 135.61, 130.78, 129.94, 128.55, 125.96, 121.41, 121.33, 115.96, 115.74, 70.00, 42.92, 29.61, 21.12, 15.19; HRMS (ESI) [M + Na]+ calcd. for C19H19FN2O2S: 381.10435, found 381.10381.
Data for N-(4-chlorophenyl)-4-(hydroxyimino)-6-methylthiochromane-2-carboxamide (4s). White solid; mp 235–236 °C; Yield 78%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 11.46 (s, 1H, OH), 10.41 (s, 1H, CONH), 7.71 (s, 1H, Ph-H), 7.58–7.55 (m, 2H, Ph-H), 7.37–7.32 (m, 2H, Ph-H), 7.15 (d, J = 8.0 Hz, 1H, Ph-H), 7.08 (dd, 1J = 2.0 Hz, 2J = 8.0 Hz, 1H, Ph-H), 4.01 (dd, 1J = 5.6 Hz, 2J = 7.2 Hz, 1H, SCH), 3.22 (dd, 1J = 7.2 Hz, 2J = 18.0 Hz, 1H, CH2), 3.17 (dd, 1J = 5.2 Hz, 2J = 18.0 Hz, 1H, CH2), 2.28 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.68, 150.77, 138.18, 135.45, 130.75, 130.27, 129.18, 128.41, 127.55, 125.73, 121.16, 43.22, 29.00, 21.19; HRMS (ESI) [M + Na]+ calcd. for C17H15ClN2O2S: 369.04350, found 369.04330.
Data for N-(4-chlorophenyl)-4-(methoxyimino)-6-methylthiochromane-2-carboxamide (4t). White solid; mp 197–199 °C; Yield 70%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.41 (s, 1H, CONH), 7.71 (s, 1H, Ph-H), 7.55 (dd, 1J = 2.0 Hz, 2J = 6.8 Hz, 2H, Ph-H), 7.34 (dd, 1J = 2.0 Hz, 2J = 6.4 Hz, 2H, Ph-H), 7.16 (d, J = 8.0 Hz, 1H, Ph-H), 7.11 (dd, 1J = 1.2 Hz, 2J = 8.0 Hz, 1H, Ph-H), 4.11 (dd, 1J = 4.8 Hz, 2J = 7.2 Hz, 1H, SCH), 3.96 (s, 3H, CH3), 3.27 (dd, 1J = 7.2 Hz, 2J = 18.0 Hz, 1H, CH2), 3.13 (dd, 1J = 4.8 Hz, 2J = 18.0 Hz, 1H, CH2), 2.28 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.59, 151.61, 138.16, 135.62, 130.88, 129.64, 129.46, 129.17, 128.53, 127.54, 125.92, 121.13, 62.50, 42.58, 29.23, 21.10; HRMS (ESI) [M + Na]+ calcd. for C18H17ClN2O2S: 383.05915, found 383.05863.
Data for N-(4-chlorophenyl)-4-(ethoxyimino)-6-methylthiochromane-2-carboxamide (4u). White solid; mp 169–170 °C; Yield 79%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.41 (s, 1H, CONH), 7.71 (s, 1H, Ph-H), 7.56 (dd, 1J = 2.0 Hz, 2J = 7.2 Hz, 2H, Ph-H), 7.36 (d, J = 3.2 Hz, 1H, Ph-H), 7.34 (d, J = 2.0 Hz, 1H, Ph-H), 7.17 (d, J = 8.0 Hz, 1H, Ph-H), 7.10 (d, J = 8.4 Hz, 1H, Ph-H), 4.22 (q, J = 7.2 Hz, 2H, CH2CH3), 4.10 (dd, 1J = 4.8 Hz, 2J = 7.6 Hz, 1H, SCH), 3.26 (dd, 1J = 7.6 Hz, 2J = 18.0 Hz, 1H, CH2), 3.15 (dd, 1J = 4.8 Hz, 2J = 18.0 Hz, 1H, CH2), 2.28 (s, 3H, CH3), 1.28 (t, J = 7.2 Hz, 3H, CH2CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.57, 151.31, 138.16, 135.63, 130.78, 129.95, 129.46, 129.18, 128.54, 127.55, 125.95, 121.14, 70.00, 42.81, 29.49, 21.13, 15.19; HRMS (ESI) [M + Na]+ calcd. for C19H19ClN2O2S: 397.07480, found 397.07421.
Data for 4-(hydroxyimino)-6-methyl-N-(p-tolyl)thiochromane-2-carboxamide (4v). White solid; mp 237–239 °C; Yield 76%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 11.45 (s, 1H, OH), 10.17 (s, 1H, CONH), 7.70 (s, 1H, Ph-H), 7.42 (d, J = 8.4 Hz, 2H, Ph-H), 7.17–7.07 (m, 3H, Ph-H), 7.15 (d, J = 8.0 Hz, 1H, Ph-H), 7.17–7.07 (m, 4H, Ph-H), 4.08 (dd, 1J = 5.6 Hz, 2J = 7.2 Hz, 1H, SCH), 3.22 (dd, 1J = 5.6 Hz, 2J = 18.4 Hz, 1H, CH2), 3.16 (dd, 1J = 8.0 Hz, 2J = 18.0 Hz, 1H, CH2), 2.27 (s, 3H, CH3), 2.24 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.20, 150.88, 136.71, 135.37, 132.95, 130.72, 130.25, 129.62, 128.40, 125.74, 119.61, 43.50, 29.20, 21.19, 20.90; HRMS (ESI) [M + Na]+ calcd. for C18H18N2O2S: 349.09812, found 349.09779.
Data for 4-(methoxyimino)-6-methyl-N-(p-tolyl)thiochromane-2-carboxamide (4w). White solid; mp 205–207 °C; Yield 73%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.17 (s, 1H, CONH), 7.71 (s, 1H, Ph-H), 7.41 (d, J = 8.4 Hz, 2H, Ph-H), 7.16 (d, J = 8.0 Hz, 1H, Ph-H), 7.12 (d, J = 1.6 Hz, 1H, Ph-H), 7.09 (d, J = 8.0 Hz, 2H, Ph-H), 4.09 (dd, 1J = 5.2 Hz, 2J = 8.0 Hz, 1H, SCH), 3.96 (s, 3H, CH3), 3.24 (dd, 1J = 7.6 Hz, 2J = 18.0 Hz, 1H, CH2), 3.14 (dd, 1J = 4.8 Hz, 2J = 18.0 Hz, 1H, CH2), 2.28 (s, 3H, CH3), 2.24 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.10, 151.72, 136.69, 135.53, 132.95, 130.86, 129.81, 129.62, 128.52, 125.94, 119.59, 62.49, 42.85, 29.43, 21.10, 20.90; HRMS (ESI) [M + Na]+ calcd. for C19H20N2O2S: 363.11377, found 363.11303.
Data for 4-(ethoxyimino)-6-methyl-N-(p-tolyl)thiochromane-2-carboxamide (4x). White solid; mp 198–200 °C; Yield 78%; 1H NMR (400 MHz, DMSO-d6, ppm) δ: 10.18 (s, 1H, CONH), 7.71 (s, 1H, Ph-H), 7.42 (d, J = 8.4 Hz, 2H, Ph-H), 7.16 (d, J = 8.0 Hz, 1H, Ph-H), 7.11 (d, J = 1.6 Hz, 1H, Ph-H), 7.09 (d, J = 8.4 Hz, 2H, Ph-H), 4.22 (q, J = 6.8 Hz, 2H, CH2CH3), 4.09 (dd, 1J = 5.2 Hz, 2J = 7.6 Hz, 1H, SCH), 3.23 (dd, 1J = 8.0 Hz, 2J = 18.4 Hz, 1H, CH2), 3.16 (dd, 1J = 5.2 Hz, 2J= 18.0 Hz, 1H, CH2), 2.28 (s, 3H, CH3), 2.24 (s, 3H, CH3), 1.28 (t, J = 7.2 Hz, 3H, CH2CH3); 13C NMR (100 MHz, DMSO-d6, ppm) δ: 168.08, 151.43, 136.69, 135.55, 132.96, 130.76, 129.92, 129.82, 129.62, 128.53, 125.96, 119.59, 69.99, 43.11, 29.70, 21.12, 20.90, 15.19; HRMS (ESI) [M + Na]+ calcd. for C20H22N2O2S: 377.12942, found 377.12911.