A Mild and Versatile Synthesis
of Thioamides

K. A. Mahammed; V. P. Jayashankara; N. Premsai 
Rai; K. Mohana 
Raju; P. N. Arunachalam

doi:10.1055/s-0029-1217711

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Synlett 2009(14): 2338-2340
DOI: 10.1055/s-0029-1217711

LETTER

A Mild and Versatile Synthesis of Thioamides

K. A. Mahammed^a,b, V. P. Jayashankara^a, N. Premsai Rai^a, K. Mohana Raju^b, P. N. Arunachalam*^a
^a Syngene International Ltd., Biocon Park, Plot Nos. 2 & 3, Bommasandra-Jigani Road, Bangalore 560 100, India
e-Mail: pn.arunachalam@syngeneintl.com;
^b Synthetic Polymer Laboratories, Department of Polymer Science, Sri Krishnadevaraya University, Anantapur 515 003, India

Further Information

Publication History

Received 13 May 2009
Publication Date:
31 July 2009 (online)

Abstract
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Abstract

Aliphatic and aromatic nitriles react with thioacetic acid in the presence of calcium hydride to give the corresponding thioamides in good to excellent yields. The examples studied include haloaryl nitriles in which the halogen is facile towards S_NAr reactions under other conditions.

Key words

thioamides - nitriles - thioacetic acid - calcium hydride

References and Notes

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20

General Procedure for the Synthesis of Thioamide To a mixture of aryl nitrile (1 equiv) and CaH₂ (1 equiv) was taken in a two-necked 50 mL round-bottomed flask, and the content was cooled to 0 ˚C and added thioacetic acid (1.5 equiv). After stirring for 15 min the reaction mixture was heated in an oil bath at 80 ˚C for the given period of time (Table [¹] ). After the completion of the reaction, the contents were cooled to r.t., 50% aq EtOAc (2 × 10 mL) was added and stirred for some time till the layers separated. Extraction was done once again with EtOAc, and the combined organic layer was filtered through Celite pad, and concentrated under reduced pressure to get the crude product. It was then purified by crystallization using PE and EtOAc (9:1). All the novel products were characterized by NMR and MS analysis.
4-Bromo-2-chlorobenzenecarbothioamide (2b)
^¹H NMR (400 MHz, DMSO-d ₆): δ = 7.31 (d, 1 H), 7.50 (q, 1 H), 7.75 (s, 1 H), 9.73 (br s, 1 H), 10.23 (br s, 1 H) ppm. ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 126.5, 129.1, 129.7, 133.3, 136.6, 141.3, 188.5 ppm. Anal. Calcd (%) for C₇H₅BrClNS: C, 33.56; H, 2.01; N, 5.59. Found: C, 33.54; H, 2.22; N, 5.55. MS: m/z = 251.0 [M⁺].
4-Chloro-3-nitrobenzenecarbothioamide (2d) ^¹H NMR (400 MHz, DMSO-d ₆): δ = 7.8 (d, 1 H), 8.1 (d, 1 H), 8.5 (s, 1 H), 9.8 (br s, 1 H), 10.2 (br s, 1 H) ppm.
^¹³C NMR (100 MHz, DMSO-d ₆): δ = 124.7, 128.0, 131.8, 132.4, 139.6, 147.2, 196.5 ppm. Anal. Calcd (%) for C₇H₅ClN₂O₂S: C, 33.81; H, 2.33; N, 12.93. Found: C, 33.76; H, 2.38; N, 12.96. MS: m/z = 214.9 [M⁺].
2-(3,4-Dichlorophenyl)ethanethioamide (2f) ^¹H NMR (400 MHz, DMSO-d ₆): δ = 3.8 (s, 2 H), 7.2 (d, 1 H), 7.5 (s, 1 H), 7.6 (d, 1 H), 9.4 (s, 1 H), 9.5 (s, 1 H) ppm. ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 50.5, 129.6, 129.8, 130.6, 131.1, 131.2, 138.8, 204.9 ppm. Anal. Calcd (%) for C₈H₇Cl₂NS: C, 43.65, H, 3.21, N, 6.36. Found: C, 43.76, H, 3.28, N, 6.34; MS: m/z = 219.9 [M⁺].
3-(4-Iodophenyl)propanethioamide (2g) ^¹H NMR (400 MHz, DMSO-d ₆): δ = 3.7 (s, 2 H), 7.1 (d, 2 H), 7.6 (d, 2 H), 9.3 (br s, 1 H), 9.4 (br s, 1 H) ppm. ^¹³C NMR: (100 MHz, DMSO-d ₆): δ = 50.7, 93.0, 131.6, 137.3, 137.6, 205.4 ppm. Anal. Calcd (%) for C₈H₈INS: C, 34.67; H, 2.91; N, 5.05. Found: C, 34.65; H, 2.98; N, 5.11. MS: m/z = 277.8 [M⁺].
2-[4-(Trifluoromethoxy)phenyl]ethanethioamide (2i) ^¹H NMR (400 MHz, DMSO-d ₆): δ = 3.8 (s, 2 H), 7.2 (d, 2 H), 7.4 (d, 2 H), 9.4 (br s, 1 H), 9.5 (br s, 1 H) ppm. ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 50.5, 116.7, 131.0, 131.3, 136.8, 137.3, 147.6, 147.7, 205.4 ppm. Anal. Calcd (%) for C₉H₈F₃NOS: C, 45.95; H, 3.43; N, 5.95. Found: C, 45.98; H, 3.48; N, 5.98. MS: m/z = 235.8 [M⁺].
Propanethioamide (2t) ^¹H NMR (400 MHz, DMSO-d ₆): δ = 1.2 (t, 3 H) 2.6 (q, 2 H), 7.2 (s, 1 H), 8.0 (s, 1 H) ppm. ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 15.0, 42.1, 208.6 ppm. Anal. Calcd (%) for C₃H₇NS: C, 40.41; H, 7.91; N, 15.71. Found: C, 40.45; H, 7.98; N, 15.78. GC-MS: m/z = 89.1 [M⁺].
2,2-Dimethylpropanethioamide (2v) ^¹H NMR (400 MHz, DMSO-d ₆): δ = 1.3 (s, 9 H) 7.0 (br s, 1 H), 7.7 (br s, 1 H) ppm. ^¹³C NMR: (100 MHz, DMSO-d ₆): δ = 32.5, 48.8, 221.8 ppm. Anal. Calcd (%) for C₅H₁₁NS: C, 51.23; H, 9.46; N, 11.95. Found: C, 51.31; H, 9.48; N, 11.98. MS: m/z = 118.0 [M⁺].