General procedures. Solvent were purified and dried by standard procedures. The boiling range of the petroleum ether used was 40–60 oC. Thin layer chromatography (TLC): silica gel 60 F254 plastic plates (E. Merck, layer thickness 0.2 mm) detected by UV absorption. Elemental analyses were performed on a Flash EA-1112 instrument at the Microanalytical laboratory, Faculty of Science, Suez Canal University, Ismailia, Egypt. Melting points were determined on a Buchi 510 melting-point apparatus and the values are uncorrected. 1H and 13C NMR spectra were recorded at 400 MHz and 100 MHz, respectively (Bruker AC 400) in CDCl3 and DMSO solution with tetramethylsilane as an internal standard. The NMR analyses were performed at Faculty of Science, Sohag University.
General method for the preparation of thiating reagent N-cyclohexyl dithiocarbamate cyclohexyl ammonium salt (2).
To a mixture of freshly distilled cyclohexyl amine (60 mmol) and water (50 mL) was added carbon disulfide (21 mmol) dropwise. The reaction mixture was stirred at room temperature for 2h. The white solid obtained was filtered, washed with water, dried and crystalized from ethanol to provide pure product of cyclohexyl amine cyclohexyl ammonium dithiocarbamate provided the pure compound.
Yield 98% (ethanol 95%) white crystals, mp 188–189°C. 1H NMR spectrum, (400 MHz, DMSO), δ, ppm (J, Hz): 8.01 (3H, bs, 3NH); 4.15–3.95 (1H, m, CH); 3.05–2.96 (1H, m, CH); 1.98–0.96 (20H, m, 10CH2). 13C NMR spectrum, (100.0 MHz, DMSO), δ, ppm: 212.4 (C = S); 55.3 (CH); 50.0 (CH); 32.3 (2CH2); 30.9 (2CH2); 25.8 (CH2); 25.5 (2CH2); 25.1 (CH2); 24.3 (2CH2). Found, %: C, 56.88; H, 9.55; N, 10.21. For C13H26N2S2 (274.2). Calculated, %: C, 56.56; H, 9.43; N, 10.09.
Preparation of cyclohexylcarbamothioic- N -(p -tolyl)benzimidic thioanhydride (8).
A mixture of N-(p-tolyl)benzoamide (5) (2.5 mmol) and thionyl chloride (5 mL) were heated at 70oC for 8 h. The thionyl chloride was removed under reduced pressure and was heated at 120oC under reduced pressure 50 mmHg for 2 extra hrs. to give a yellowish clear colored oil of benzimidoyl chloride 6, which was not further purified and was used directly in the next step. To a solution of benzimidoyl chloride 6 (2.5 mmol) in acetonitrile (10 mL) was added (0.69 g, 2.5 mmol) of N-cyclohexyl dithiocarbamate cyclohexyl ammonium salt (2). The reaction mixture was stirred at room temperature for 1 h. (TLC monitored), then heated for 2h.. The reaction mixture was evaporated under reduced pressure and 25 mL of ethanol was added to the solid residue. The yellowish precipitate was filtered to give 8. The crude compound was purified by crsystalization from ethyl alcohol 95%.
Yield 84% yellow crystals, mp 138–139°C. 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 7.89 (2H, d, J = 8.0, ArH); 7.82 (1H, bs, NH); 7.55–7.48 (5H, m, ArH); 7.19 (2H, d, J = 8.0, ArH); 3.87–3.67 (1H, m, CH); 2.36 (3H, s, CH3); 2.06–1.59 (4H, m, 2CH2); 1.44–1.20 (6H, m, 3CH2). Found, %: C, 68.36; H, 6.48; N, 7.46. For C21H24N2S2 (368.6). Calculated, %: C, 68.44; H, 6.56; N, 7.60; S, 17.40.
General method for the preparation of thiating reagent N-isopropyldithiocarbamate isopropyl ammonium salt (10).
To a mixture of isopropyl amine (60 mmol) and ethyl acetate (50 mL) was added carbon disulfide (21 mmol) dropwise. The reaction mixture was stirred at room temperature for 2h. The white solid obtained was filtered, washed with ethyl acetate, dried and was packed tightly and was pure enough for further reactions.
Yield 95% (acetonitrile) white crystals, mp 85–86°C. 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 8.19 (1H, bs, NH); 6.06–5.75 (3H, bs, 3NH); 3.88–3.75 (1H, m, CH); 3.72–3.51 (1H, m, CH); 1.43–1.08 (12H, m, 4CH3). 13C NMR spectrum, (100.0 MHz, CDCl3), δ, ppm: 211.8 (C = S); 52.7 (CH); 48.3 (CH); 24.5 (2CH3); 22.3 (2CH3). Found, %: C, 43.17; H, 9.23; N, 14.38. For C7H18N2S2 (194.4). Calculated, %: C, 43.26; H, 9.34; N, 14.41; S, 32.99.
General method for the preparation of N-aryl substituted benzthioamide 17–19(a-e)
A mixture of N-aryl substituted benzamide 11–13(a-e) (2.5 mmol) and thionyl chloride (5 mL) were heated at 70oC for 8 h. The thionyl chloride was removed under reduced pressure and was heated at 120oC under reduced pressure 50 mmHg for 2 extra hrs. to give a yellowish clear colored oil of benzimidoyl chloride 14–16(a-e), which was not further purified and was used directly in the next step. To a solution of benzimidoyl chloride 14–16(a-e) (2.5 mmol) in acetonitrile (10 mL) was added (0.49 g, 2.5 mmol) of N-isopropyldithiocarbamate isopropyl ammonium salt (10). The reaction mixture was stirred at room temperature for 1 h. (TLC monitored). The reaction mixture was evaporated under reduced pressure and 25 mL of ethanol was added to the solid residue. The yellowish precipitate was filtered to give the desired N-aryl substituted benzothioamides 17–19(a-e). The crude compounds were pure enough for analytical purposes. Purification of products for analysis was achieved by crystallization from the appropriate solvent.
N -Phenylbenzothioamide (17a).
Yield 89% (ethanol 95%) yellow crystals, mp 100–101°C (lit. [26] 102°C). 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 9.06 (1H, bs, NH); 8.20–7.80 (4H, m, ArH); 7.64–7.29 (6H, m, ArH).13C NMR spectrum, (100.0 MHz, CDCl3), δ, ppm: 197.5 (C = S), 143.5, 139.6, 130.2, 129.3, 128.9, 127.6, 125.8, 124.7. Found, %: C, 73.15; H, 5.17; N, 6.53. For C13H11NS (213.3). Calculated, %: C, 73.20; H, 5.20; N, 6.57; S, 15.03.
N -(p -Tolyl)benzothioamide (17b).
Yield 93% (ethanol 95%) yellow crystals, mp 126–127°C (lit. [8] 130°C). 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 8.99 (1H, bs, NH); 7.88–7.77 (2H, m, ArH); 7.66 (2H, d, J = 8.0, ArH); 7.51 (2H, d, J = 8.0, ArH); 7.42–7.39 (3H, m, ArH); 2.37 (3H, s, CH3).13C NMR spectrum, (100.0 MHz, CDCl3), δ, ppm: 198.8 (C = S), 143.7, 136.7, 135.1, 130.6, 129.9, 128.4, 127.6, 125.9, 124.3, 21.7 (CH3). Found, %: C, 73.93; H, 5.74; N, 6.09. For C14H13NS (227.3). Calculated, %: C, 73.97; H, 5.76; N, 6.16; S, 14.10.
N -(m -Tolyl)benzothioamide (17c).
Yield 76% (ethanol 95%) yellow crystals, mp 87–88°C (lit. [27] 81°C). 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 9.00 (1H, bs, NH); 7.88–7.72 (2H, m, ArH); 7.67–7.54 (2H, m, ArH); 7.46–7.36 (3H, m, ArH); 7.31–7.18 (2H, m, ArH); 2.42 (3H, s, CH3). Found, %: C, 73.89; H, 5.72; N, 6.11. For C14H13NS (227.3). Calculated, %: C, 73.97; H, 5.76; N, 6.16; S, 14.10.
N -(o -Tolyl)benzothioamide (17d).
Yield 84% (ethanol 95%) yellow crystals, mp 148–150°C (lit. [26] 151°C). 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 7.86 (1H, d, J = 6.0, ArH); 7.81 (2H, d, J = 6.0, ArH); 7.59 (1H, bs, NH); 7.59–7.41 (3H, m, ArH); 7.22–7.15 (2H, m, ArH); 7.13 (1H, t, J = 6.0, ArH) 2.27 (3H, s, CH3).13C NMR spectrum, (100.0 MHz, CDCl3), δ, ppm: 198.2 (C = S), 142.9, 139.1, 133.6, 131.8, 131.3, 128.9,126.0, 125.6,125.1, 18.4 (CH3). Found, %: C, 73.85; H, 5.70; N, 6.12. For C14H13NS (227.3). Calculated, %: C, 73.97; H, 5.76; N, 6.16; S, 14.10.
N -(4-Methoxyphenyl)benzothioamide (17e).
Yield 96% (ethanol 95%) yellow crystals, mp 130–131°C (lit. [26] 127°C). 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 8.89 (1H, bs, NH); 7.87–7.76 (2H, m, ArH); 7.54 (2H, d, J = 8.0, ArH); 7.53–7.42 (3H, m, ArH); 6.88 (2H, d, J = 8.0, ArH); 3.73 (3H, s, OCH3).13C NMR spectrum, (100.0 MHz, CDCl3), δ, ppm: 199.6 (C = S), 158.6, 142.8, 131.4, 130.2, 128.3, 127.5, 125.3, 113.8, 55.3 (OCH3). Found, %: C, 69.03; H, 5.36; N, 5.72. For C14H13NOS (243.3). Calculated, %: C, 69.11; H, 5.39; N, 5.76; S, 13.18.
4-Methoxy- N -phenylbenzothioamide (18a).
Yield 82% (ethanol 95%) yellow crystals, mp 145–146°C (lit. [8] 150°C). 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 7.86 (2H, d, J = 6.0, ArH); 7.71 (1H, bs, NH); 7.45–7.36 (2H, m, ArH); 7.34–7.29 (3H, m, ArH); 6.93 (2H, d, J = 6.0, ArH); 3.82 (3H, s, OCH3).13C NMR spectrum, (100.0 MHz, CDCl3), δ, ppm: 199.4 (C = S), 158.4, 139.1, 134.5, 129.0, 127.2, 126.9, 123.4, 114.1, 55.5 (OCH3). Found, %: C, 69.09; H, 5.38; N, 5.72. For C14H13NOS (243.3). Calculated, %: C, 69.11; H, 5.39; N, 5.76; S, 13.18.
4-Methoxy- N -(p -tolyl)benzothioamide (18b).
Yield 93% (ethanol 95%) yellow crystals, mp 172–173°C (lit. [28] 174°C). 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 7.85 (2H, d, J = 6.0, ArH); 7.73 (1H, bs, NH); 7.52 (2H, d, J = 6.0, ArH); 7.19 (2H, d, J = 6.0, ArH); 6.99 (2H, d, J = 6.0, ArH); 3.73 (3H, s, OCH3); 2.36 (3H, s, CH3).13C NMR spectrum, (100.0 MHz, CDCl3), δ, ppm: 200.5 (C = S), 158.7, 136.6, 135.8, 134.1, 129.9, 127.4 124.7, 113.8, 55.7 (OCH3), 21.5 (CH3). Found, %: C, 69.94; H, 5.76; N, 5.38. For C15H15NOS (257.4). Calculated, %: C, 70.01; H, 5.88; N, 5.44; S, 12.46.
4-Methoxy N-(m-tolyl)benzothioamide (18c).
Yield 86% (ethanol 95%) yellow crystals, mp 132–133°C. 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 7.82 (2H, d, J = 6.0, ArH); 7.67 (1H, bs, NH); 7.62–7.54 (2H, m, ArH); 7.31–7.11 (2H, m, ArH); 6.93 (2H, d, J = 6.0, ArH); 3.86 (3H, s, OCH3); 2.39 (3H, s, CH3).13C NMR spectrum, (100.0 MHz, CDCl3), δ, ppm: 200.2 (C = S), 158.5, 138.9, 136.3, 135.4, 134.4, 129.8, 127.6, 125.9, 124.5, 114.6, 21.2 (CH3). Found, %: C, 69.87; H, 5.74; N, 5.36. For C15H15NOS (257.4). Calculated, %: C, 70.01; H, 5.88; N, 5.44; S, 12.46.
4-Methoxy- N -(o -tolyl)benzothioamide (18d).
Yield 94% (ethanol 95%) yellow crystals, mp 125–126°C (lit. [29] 119°C). 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 7.94 (1H, d, J = 6.0, ArH); 7.88 (2H, d, J = 6.0, ArH); 7.64 (1H, bs, NH); 7.29–7.24 (2H, m, ArH); 7.13 (1H, t, J = 6.0, ArH); 7.00 (2H, d, J = 6.0, ArH); 3.98 (3H, s, OCH3); 2.36 (3H, s, CH3).13C NMR spectrum, (100.0 MHz, CDCl3), δ, ppm: 199.1 (C = S), 159.3, 139.2, 136.5, 134.3, 133.6, 130.1, 127.4, 126.4, 125.6, 113.9, 55.5 (OCH3), 18.9 (CH3). Found, %: C, 69.92; H, 5.79; N, 5.41. For C15H15NOS (257.4). Calculated, %: C, 70.01; H, 5.88; N, 5.44; S, 12.46.
4-Methoxy- N -(4-methoxyphenyl)benzothioamide (18e).
Yield 90% (ethanol 95%) yellow crystals, mp 149–150°C (lit. [8] 152°C). 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 7.75 (2H, d, J = 6.0, ArH); 7.61 (1H, bs, NH); 7.44 (2H, d, J = 6.0, ArH); 6.89 (2H, d, J = 6.0, ArH); 6.82 (2H, d, J = 6.0, ArH); 3.82 (3H, s, OCH3); 3.74 (3H, s, OCH3). 13C NMR spectrum, (100.0 MHz, CDCl3), δ, ppm: 202.1 (C = S), 159.7, 157.6, 134.1, 131.3 127.8, 125.6, 114.4, 113.7, 55.6 (OCH3), 55.2 (OCH3). Found, %: C, 65.88; H, 5.51; N, 5.04. For C15H15NO2S (273.4). Calculated, %: C, 65.91; H, 5.53; N, 5.12; S, 11.73.
4-Chloro- N -phenylbenzothioamide (19a).
Yield 92% (ethanol 95%) yellow crystals, mp 157–158°C (lit. [30] 153°C). 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 9.03 (1H, bs, NH); 7.67 (2H, d, J = 6.0, ArH); 7.45–7.36 (4H, m, ArH); 7.34–7.29 (3H, m, ArH).13C NMR spectrum, (100.0 MHz, CDCl3), δ, ppm: 198.6 (C = S), 140.3, 139.8, 135.3, 129.0, 128.5, 127.9, 127.3, 123.6. Found, %: C, 62.89; H, 4.05; N, 5.61. For C13H10ClNS (247.7). Calculated, %: C, 63.03; H, 4.07; Cl, 14.31; N, 5.65; S, 12.94.
4-Chloro- N -(p -tolyl)benzothioamide (19b).
Yield 96% (ethanol 95%) yellow crystals, mp 150–151°C. 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 9.03 (1H, bs, NH); 7.71 (2H, d, J = 6.0, ArH); 7.52 (2H, d, J = 6.0, ArH); 7.42 (2H, d, J = 6.0, ArH); 7.19 (2H, d, J = 6.0, ArH); 2.37 (3H, s, CH3).13C NMR spectrum, (100.0 MHz, CDCl3), δ, ppm: 199.5 (C = S), 141.2, 136.3, 135.6, 134.7, 129.2, 128.9, 127.6, 124.5, 21.3 (CH3). Found, %: C, 64.14; H, 4.59; N, 5.28. For C14H12ClNS (261.8). Calculated, %: C, 64.24; H, 4.62; Cl, 13.54; N, 5.35; S, 12.25.
4-Chloro- N -(m -tolyl)benzothioamide (19c).
Yield 98% (ethanol 95%) yellow crystals, mp 136–137°C. 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 9.01 (1H, bs, NH); 7.67–7.54 (4H, m, ArH); 7.39 (2H, d, J = 6.0, ArH); 5.31–7.13 (2H, m, ArH); 2.36 (3H, s, CH3).13C NMR spectrum, (100.0 MHz, CDCl3), δ, ppm: 199.6 (C = S), 141.5, 138.4, 136.7, 135.6, 134.9, 129.6, 129.0, 127.2, 125.8, 123.4. 21.5 (CH3). Found, %: C, 64.18; H, 4.54; N, 5.29. For C14H12ClNS (261.8). Calculated, %: C, 64.24; H, 4.62; Cl, 13.54; N, 5.35; S, 12.25.
4-Chloro- N -(o -tolyl)benzothioamide (19d).
Yield 73% (ethanol 95%) yellow crystals, mp 129–130°C. 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 9.03 (1H, bs, NH); 7.94 (1H, d, J = 6.0, ArH); 7.67 (2H, d, J = 6.0, ArH); 7.39 (2H, d, J = 6.0, ArH); 7.31–7.24 (2H, m, ArH); 7.16 (1H, t, J = 6.0, ArH); 2.36 (3H, s, CH3). 13C NMR spectrum, (100.0 MHz, CDCl3), δ, ppm: 199.3 (C = S), 140.5, 139.4, 136.5, 134.5, 133.8, 130.5, 128.8, 127.9, 127.3, 125.6, 18.5 (CH3). Found, %: C, 64.12; H, 4.48; N, 5.31. For C14H12ClNS (261.8). Calculated, %: C, 64.24; H, 4.62; Cl, 13.54; N, 5.35; S, 12.25.
4-Chloro- N -(4-methoxyphenyl)benzothioamide (19e).
Yield 85% (ethanol 95%) yellow crystals, mp 166–167°C (lit. [31] 172°C).. 1H NMR spectrum, (400 MHz, CDCl3), δ, ppm (J, Hz): 8.89 (1H, bs, NH); 7.82 (2H, d, J = 6.0, ArH); 7.64 (2H, d, J = 6.0, ArH); 7.36 (2H, d, J = 6.0, ArH); 6.91 (2H, d, J = 6.0, ArH); 3.75 (3H, s, OCH3).13C NMR spectrum, (100.0 MHz, DMSO), δ, ppm: 199.8 (C = S), 158.9, 140.4, 134.2, 131.9, 128.6, 127.6, 126.3, 114.5, 55.4 (OCH3). Found, %: C, 60.49; H, 4.32; N, 4.87. For C14H12NClNOS (277.8). Calculated, %: C, 60.54; H, 4.35; Cl, 12.76; N, 5.04; S, 11.54.