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Synlett 2007(17): 2687-2690  
DOI: 10.1055/s-2007-991073
LETTER
© Georg Thieme Verlag Stuttgart · New York

Efficient Synthesis of Thiobenzanilides by Willgerodt-Kindler Reaction with Base Catalysts

Ken Okamotoa,b, Takakazu Yamamotoa, Takaki Kanbara*b,c
a Chemical Resources Laboratory, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan
b Tsukuba Research Center for Interdisciplinary Materials Science (TIMS), University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba 305-8573, Japan
c Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba 305-8573, Japan
Fax: +81(29)8534490; e-Mail: kanbara@ims.tsukuba.ac.jp;
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Publication History

Received 2 July 2007
Publication Date:
25 September 2007 (online)

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Abstract

Willgerodt-Kindler reaction between anilines and benz­aldehydes readily proceeded in the presence of catalytic amount of Na2S·9H2O to give thiobenzanilides in moderate to good yields. The base catalyst was also available for preparation of primary thio­benzamide.

Key words

sulfur - catalysis - condensation - aromatic amines - thioamides

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Experimental Procedure (Table [1] , entry 9): Na2S·9H2O (216 mg, 15 mol%) was added to a mixture of sulfur (160 mg, 5 mmol as elemental sulfur) and aniline (0.55 mL, 6 mmol) in DMF (4 mL), and the suspension was stirred at 115 °C for 0.5 h under nitrogen. After the mixture was cooled to r.t., benzaldehyde (0.41 mL, 4 mmol) was added, and was stirred at 115 °C for 12 h under nitrogen. After cooling to r.t., the resulting solution was quenched with sat. aq NH4Cl solution (50 mL) and extracted with CHCl3 (50 mL). The organic fraction was thoroughly washed with H2O (2 × 50 mL) and dried with anhyd Na2SO4. After concentration, the resulting crude product was purified by chromatography on silica gel with CHCl3 to afford N-phenylthiobenzamide as a yellow powder (780 mg, 91% yield); mp 99 °C, lit.7 99 °C.

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N -(4-Methoxyphenyl)thiobenzamide (Table [2] , entry 2): yellow powder; mp 135 °C, lit.7 135 °C.
4-Methoxy- N -phenylthiobenzamide (Table [2] , entry 3): yellow powder; mp 154 °C, lit.7 153-154 °C.
4-Methoxy- N -(4-methoxyphenyl)thiobenzamide (Table [2] , entry 4): yellow powder; mp 148 °C, lit.7 148 °C.
1,3-Bis(anilinothiocarbonyl)benzene (Table [2] , entry 5): yellow powder; mp 243-244 °C, lit.2a 242-244 °C.


1,4-Bis(anilinothiocarbonyl)benzene (Table [2] , entry 6): yellow powder; mp 280-281 °C, lit.2a 280-282 °C. N -(4-Nitrophenyl)thiobenzamide (Table [2] , entry 7): yellow powder; mp 145-146 °C, lit.13 145 °C.
N -(4-Pyridyl)thiobenzamide (Table [2] , entry 8): yellow powder; mp 187-188 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 11.99 (s, 1 H), 9.59 (d, J = 6.4 Hz, 2 H), 8.00 (d, J = 6.4 Hz, 2 H), 7.78 (d, J = 7.6 Hz, 2 H), 7.55 (t, J = 7.6 Hz, 1 H), 7.47 (t, J = 7.6 Hz, 2 H). 13C{1H} NMR (100 MHz, DMSO-d 6): δ = 199.35, 150.17, 146.64, 142.78, 130.99, 128.00, 127.37, 116.67. Anal. Calcd for C12H10N2S: C, 67.26; H, 4.70; N, 13.07; S, 14.96. Found: C, 67.32; H, 4.52; N, 13.15; S, 14.88.
N -(3-Pyridyl)thiobenzamide (Table [2] , entry 9): yellow powder; mp 140-141 °C, lit.14 140-141 °C.
N -(6-Quinolyl)thiobenzamide (Table [2] , entry 10): orange powder; mp 177-179 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 12.03 (s, 1 H), 8.90 (br, 1 H), 8.56 (br, 1 H), 8.38 (d, J = 8.0 Hz, 1 H), 8.05-8.11 (m, 2 H), 7.89 (d, J = 7.6 Hz, 2 H), 7.53-7.56 (m, 2 H), 7.49 (t, J = 7.6 Hz, 2 H). 13C{1H} NMR (100 MHz, DMSO-d 6): δ = 199.81, 151.99, 147.55, 144.08, 139.55, 137.49, 132.50, 130.65, 129.67, 129.29, 129.08, 128.86, 123.41, 123.00. Anal. Calcd for C16H12N2S: C, 72.70; H, 4.58; N, 10.60; S, 12.13. Found: C, 72.62; H, 4.51; N, 10.60; S, 11.97.
4 - Cyano -N -phenylthiobenzamide (Table [2] , entry 11): orange powder; mp 130-131 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 12.01 (s, 1 H), 7.91-7.93 (br, 4 H), 7.83 (d, J = 8.0 Hz, 2 H), 7.44 (t, J = 8.0 Hz, 2 H), 7.29 (t, J = 8.0 Hz, 1 H). 13C{1H} NMR (100 MHz, DMSO-d 6): δ = 195.16, 146.14, 139.47, 131.96, 128.42, 127.95, 126.42, 123.74, 118.27, 112.54. Anal. Calcd for C14H10N2S: C, 70.56; H, 4.23; N, 11.76. Found: C, 70.85; H, 4.45; N, 11.71.
N -Phenyl-2-pyridinethioamide (Table [2] , entry 12): orange-yellow powder; mp 45 °C, lit.15 45 °C.

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Preparation of Thiobenzamide (Scheme [4] ): Na2S·9H2O (244 mg, 1 mmol) was added to a mixture of sulfur (160 mg, 5 mmol as elemental sulfur) and 28% aq NH3 (3 mL, ca. 44 mmol) in DMF (4 mL), and the suspension was stirred at 115 °C for 0.5 h under nitrogen. After the mixture was cooled to r.t., benzaldehyde (0.41 mL, 4 mmol) was added, and stirred at 115 °C for 12 h under nitrogen. After cooling to r.t., the resulting solution was quenched with sat. aq NH4Cl solution (50 mL) and extracted with CHCl3 (50 mL). The organic fraction was thoroughly washed with H2O (2 × 50 mL) and dried with anhyd Na2SO4. After concentration, the resulting crude material was purified by chromatography on silica gel with CHCl3-Et2O (100:0-20:80) to afford thiobenzamide as a pale yellow powder (270 mg, 49% yield); mp 118 °C, lit.7b 117-118 °C.