PAPER
Synthesis of b-Oxo Thioamides
1799
13C NMR (125 MHz, CDCl3): d = 21.0, 54.4, 120.6, 123.6, 127.1,
128.8, 129.5, 134.3, 135.0, 138.5, 166.3, 193.9.
tocol very attractive for use in academic research and
practical applications.
Anal. Calcd for C16H16N2OS: C, 67.58; H, 5.67; N, 9.85. Found: C,
67.45; H, 5.81; N, 9.73.
All melting points were determined in open capillary tubes in a
Thiele apparatus and are uncorrected. IR spectra were recorded on
a Magna-560 infrared spectrometer of samples prepared on KBr
plates as neat films. NMR spectra of samples in CDCl3 (unless stat-
ed otherwise) were recorded on a Varian Inova-500 spectrometer.
Elemental analyses were carried out on a Perkin-Elmer PE-2400 an-
alyzer. Starting materials and solvents were obtained from commer-
cial sources and used without treatment.
3-Anilino-N-(2-chlorophenyl)-3-thioxopropanamide (3ea)
White solid; mp 151–152 °C.
1H NMR (500 MHz, CDCl3): d = 4.13 (s, 2 H), 7.11 (t, J = 7.5 Hz,
1 H), 7.29 (d, J = 7.5 Hz, 2 H), 7.41 (t, J = 7 Hz, 3 H), 7.79 (d, J = 8
Hz, 2 H), 8.22 (d, J = 6.5 Hz, 1 H), 8.80 (s, 1 H), 11.08 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 55.6, 122.6, 123.4, 124.7, 125.9,
127.1, 127.5, 128.9, 129.5, 133.7, 138.6, 166.6, 193.2.
3-Anilino-N-phenyl-3-thioxopropanamide (3aa);14 Typical Pro-
cedure
Anal. Calcd for C15H13ClN2OS: C, 59.11; H, 4.30; N, 9.19. Found:
C, 59.36; H, 4.23; N, 9.08
A 50-mL round-bottomed flask was charged with K2CO3 (0.83 g,
6.0 mmol), 3-oxo-N-phenylbutanamide (1a; 0.89 g, 5.0 mmol) and
EtOH (15 mL) at r.t. After the reaction mixture had stirred at r.t. for
0.5 h, PhNCS (2a; 0.68 g, 5.0 mmol) was added dropwise within 10
min. The mixture was heated and stirred under reflux for 1.5 h until
complete conversion had taken place, as indicated by TLC. Then
the resulting mixture was cooled to r.t. and neutralized with dilute
aq HCl. The precipitated solid was collected by filtration, washed
with H2O, and dried in vacuo; this furnished pure product 3aa.
3-Anilino-N-(2-methoxyphenyl)-3-thioxopropanamide (3fa)
White solid; mp 138–140 °C.
1H NMR (500 MHz, CDCl3): d = 3.91 (s, 3 H), 4.06 (s, 2 H), 6.92
(d, J = 8 Hz, 1 H), 6.98 (t, J = 8 Hz, 1 H), 7.12 (t, J = 8 Hz, 1 H),
7.28 (s, 1 H), 7.41 (t, J = 7.5 Hz, 2 H), 7.81 (d, J = 8 Hz, 2 H), 8.28
(d, J = 8.5 Hz, 1 H), 8.39 (s, 1 H), 11.37 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 55.0, 55.8, 110.3, 120.3, 120.8,
Yield: 1.27 g (94%); white solid; mp 147–149 °C.
123.4, 125.0, 126.6, 126.9, 128.8, 138.7, 148.6, 166.4, 193.3.
1H NMR (500 MHz, CDCl3): d = 4.10 (s, 2 H), 7.17 (t, J = 7 Hz, 1
H), 7.28 (t, J = 7.5 Hz, 1 H), 7.34 (t, J = 8 Hz, 2 H), 7.41 (t, J = 8
Hz, 2 H), 7.54 (d, J = 7.5 Hz, 2 H), 7.79 (d, J = 7.5 Hz, 2 H), 8.86
(s, 1 H), 11.33 (s, 1 H).
Anal. Calcd for C16H16N2O2S: C, 63.98; H, 5.37; N, 9.33. Found: C,
64.13; H, 5.44; N, 9.37.
3-Anilino-3-thioxo-N-2-tolylpropanamide (3ga)
White solid; mp 124–125 °C.
13C NMR (125 MHz, CDCl3): d = 54.6, 120.5, 123.6, 125.2, 127.2,
128.9, 129.1, 137.0, 138.4, 166.5, 193.9.
IR (neat): 3285, 3217, 3147, 3108, 1674, 1600, 1537, 1498, 1415,
811, 753, 684 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.30 (s, 3 H), 4.14 (s, 2 H), 7.12
(t, J = 7.5 Hz, 1 H), 7.17 (d, J = 7 Hz, 1 H), 7.21 (d, J = 8 Hz, 1 H),
7.28 (d, J = 7 Hz, 1 H), 7.38 (t, J = 7.5 Hz, 2 H), 7.73 (d, J = 8 Hz,
1 H), 7.78 (d, J = 8 Hz, 2 H), 8.70 (s, 1 H), 11.31 (s, 1 H).
Anal. Calcd for C15H14N2OS: C, 66.64; H, 5.22; N, 10.36. Found:
C, 66.48; H, 5.17; N, 10.48.
3-Anilino-N-(4-chlorophenyl)-3-thioxopropanamide (3ba)
White solid; mp 158–160 °C.
IR (neat): 3246, 3183, 3106, 2951, 1680, 1603, 1541, 1492, 1430,
1398, 826, 735, 686 cm–1.
13C NMR (125 MHz, CDCl3): d = 18.2, 55.4, 123.3, 123.4, 126.1,
126.5, 127.1, 128.8, 130.5, 130.8, 134.9, 138.6, 166.5, 194.1.
1H NMR (500 MHz, CDCl3): d = 4.07 (s, 2 H), 7.29–7.31 (m, 3 H),
7.41 (t, J = 8 Hz, 2 H), 7.48 (d, J = 7 Hz, 2 H), 7.75 (d, J = 8 Hz, 2
H), 8.72 (s, 1 H), 11.02 (s, 1 H).
Anal. Calcd for C16H16N2OS: C, 67.58; H, 5.67; N, 9.85. Found: C,
67.74; H, 5.62; N, 9.94.
3-Anilino-N-(2,4-dimethylphenyl)-3-thioxopropanamide (3ha)
White solid; mp 116–117 °C.
1H NMR (500 MHz, CDCl3): d = 2.25 (s, 3 H), 2.30 (s, 3 H), 4.09
(s, 2 H), 7.00 (t, J = 9 Hz, 2 H), 7.39 (t, J = 7.5 Hz, 2 H), 7.53 (d,
J = 7.5 Hz, 1 H), 7.76–7.78 (m, 3 H), 8.36 (s, 1 H), 11.33 (s, 1 H).
13C NMR (125 MHz, DMSO-d6): d = 55.4, 121.2, 123.4, 126.7,
127.6, 129.1, 129.2, 138.4, 139.9, 166.3, 194.9.
Anal. Calcd for C15H13ClN2OS: C, 59.11; H, 4.30; N, 9.19. Found:
C, 59.34; H, 4.13; N, 9.12.
3-Anilino-N-(4-methoxyphenyl)-3-thioxopropanamide (3ca)
13C NMR (125 MHz, CDCl3): d = 18.1, 20.9, 55.1, 123.3, 123.7,
White solid; mp 131–132 °C.
127.0, 127.1, 128.8, 130.8, 131.4, 132.2, 135.9, 138.7, 166.6, 194.1.
1H NMR (500 MHz, CDCl3): d = 3.81 (s, 3 H), 4.03 (s, 2 H), 6.89
(d, J = 8 Hz, 2 H), 7.42 (d, 5 H), 7.79 (s, 2 H), 8.43 (s, 1 H), 11.33
(s, 1 H).
Anal. Calcd for C17H18N2OS: C, 68.42; H, 6.08; N, 9.39. Found: C,
68.58; H, 6.11; N, 9.45.
3-Anilino-N-(5-chloro-2-methoxyphenyl)-3-thioxopropan-
amide (3ia)
White solid; mp 152–153 °C.
1H NMR (500 MHz, CDCl3): d = 3.90 (s, 3 H), 4.06 (s, 2 H), 6.82
(d, J = 9 Hz, 1 H), 7.07 (q, J = 8.5, 2.5 Hz, 1 H), 7.29 (d, J = 7.5 Hz,
1 H), 7.42 (t, J = 7.5 Hz, 2 H), 7.80 (d, J = 7.5 Hz, 2 H), 8.37 (s, 1
H), 8.53 (s, 1 H), 11.18 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 54.3, 55.5, 114.1, 122.4, 123.5,
127.1, 128.8, 129.9, 138.5, 157.0, 166.4, 193.9.
Anal. Calcd for C16H16N2O2S: C, 63.98; H, 5.37; N, 9.33. Found: C,
63.79; H, 5.42; N, 9.46.
3-Anilino-3-thioxo-N-4-tolylpropanamide (3da)14a
White solid; mp 157–159 °C.
13C NMR (125 MHz, CDCl3): d = 55.2, 56.1, 111.1, 120.1, 123.4,
124.3, 125.8, 127.0, 127.5, 128.9, 138.6, 147.2, 166.4, 193.1.
IR (neat): 3243, 3189, 3111, 3025, 2918, 1677, 1598, 1540, 1511,
1492, 1434, 815, 760, 711 cm–1.
Anal. Calcd for C16H15ClN2O2S: C, 57.40; H, 4.52; N, 8.37. Found:
C, 57.23; H, 4.43; N, 8.51.
1H NMR (500 MHz, CDCl3): d = 2.30 (s, 3 H), 4.02 (s, 2 H), 7.11
(d, J = 8.5 Hz, 2 H), 7.24 (t, J = 7 Hz, 1 H), 7.37 (t, J = 8.5 Hz, 4 H),
7.75 (d, J = 8 Hz, 2 H), 8.35 (s, 1 H), 11.13 (s, 1 H).
Synthesis 2009, No. 11, 1797–1800 © Thieme Stuttgart · New York