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J. Kozic et al. / Tetrahedron 72 (2016) 2072e2083
J¼2.3 Hz, H40), 3.99 (3H, s, OCH3), 2.28 (3H, s, CH3); 13C NMR
collected, extracted three times with H2O (40 mL) and dried over
Na2SO4. The solvent was removed and obtained compound was
directly used in the next step.27
(DMSO-d6, 125 MHz):
d 162.33, 155.99, 137.78, 132.65, 131.92,
130.37, 130.07, 128.50, 124.97, 124.47, 124.34, 122.31, 114.74, 56.98,
17.26, Anal. Calcd for C15H13Cl2NO2 (310, 18) (%): C 58.08, H 4.22, N
4.52; Found: C 58.25, H 4.39, N 4.38.
Yield: 89.0%, white solid; mp: 64e65 ꢁC; IR: 3400e2300 (b, ʋ
OH), 2977 (ʋas CH3), 2955 (ʋas CH2), 2869 (ʋs CH3),1681 (ʋ CO),1601,
1575, 1488, 1447 (ʋ CC aromatic) cmꢂ1 1H NMR (DMSO-d6,
;
4.5.12. 5-Chloro-N-(5-chloro-2-methylphenyl)-2-methoxybenzothio-
amide (5). The thioamide was prepared according to the procedure
D. Yield: 25.0%, yellow solid; mp: 142e144 ꢁC; IR: 1597, 1577, 1530,
1486, 1463 (ʋ CC aromatic) cmꢂ1. 1H NMR (DMSO-d6, 500 MHz): Z-
300 MHz):
d
12.79 (1H, br s, COOH), 7.76 (1H, d, J¼7.0 Hz), 7.43 (1H,
t, J¼7.5 Hz), 7.33e7.21 (2H, m), 2.90 (2H, q, J¼7.4 Hz, CH2), 1.14 (3H,
t, J¼7.4 Hz, CH3); 13C NMR (DMSO-d6, 75 MHz):
d 169.14, 145.12,
131.96, 130.54, 130.35, 130.34, 126.04, 27.03, 16.32.
conformer:
d
11.58 (1H, s, NH), 7.54 (1H, d, J¼2.7 Hz, H6), 7.46 (1H,
dd, J¼8.9 Hz, J¼2.7 Hz, H4), 7.41 (1H, d, J¼2.2 Hz, H60), 7.35 (1H, d,
J¼8.3 Hz, H30), 7.32 (1H, dd, J¼8.3 Hz, J¼2.2 Hz, H40), 7.15 (1H, d,
J¼8.9 Hz, H3), 3.85 (3H, s, OCH3), 2.25 (3H, s, CH3); E-conformer:
4.5.16. N-(5-Chloro-2-hydroxyphenyl)-2-ethylbenzamide (7a). The
amide was prepared according to the procedure C. Yield: 74.4%,
white solid; mp: 151e152 ꢁC; IR: 3379 (ʋ NH), 3155 (b, ʋ OH), 2972
(ʋas CH3), 1650 (amide I),1593 (ʋ CC aromatic),1525 (amide II),1493
d
12.04 (1H, s, NH), 7.49 (1H, d, J¼2.7 Hz, H6), 7.27 (1H, dd, J¼8.9 Hz,
J¼2.7 Hz, H4), 7.19 (1H, d, J¼8.3 Hz, H30), 7.10 (1H, dd, J¼8.3 Hz,
J¼2.2 Hz, H40), 6.79 (1H, d, J¼2.2 Hz, H60), 6.75 (1H, d, J¼8.9 Hz, H3),
3.39 (3H, s, OCH3), 2.27 (3H, s, CH3). Z/E ratio 88:12. 13C NMR
(ʋ CC aromatic) cmꢂ1; 1H NMR (DMSO-d6, 300 MHz):
d 10.12 (1H, br
s, OH), 9.36 (1H, s, NH), 7.89 (1H, d, J¼2.7 Hz, H60), 7.53e7.37 (2H,
m), 7.37e7.24 (2H, m), 7.05 (1H, dd, J¼8.6 Hz, J¼2.7 Hz, H40), 6.90
(1H, d, J¼8.6 Hz, H30), 2.76 (2H, q, J¼7.5 Hz, CH2), 1.18 (3H, t,
(DMSO-d6, 125 MHz): Z-conformer:
132.34, 130.23, 130.07, 129.28, 127.53, 127.15, 124.03, 113.91, 56.40,
17.18; E-conformer: 198.26, 151.24, 139.60, 132.33, 132.22, 131.68,
129.56, 129.43, 126.92, 126.11, 123.99, 112.98, 55.44, 17.28. Anal.
Calcd for C15H13Cl2NOS (326.24) (%): C 55.22, H 4.02, N 4.29, S 9.83;
Found: C 55.41, H 4.36, N 4.53, S 9.59.
d 195.34, 153.10, 139.47, 133.83,
J¼7.5 Hz, CH3); 13C NMR (DMSO-d6, 75 MHz):
d 168.32, 147.79,
d
141.99, 136.27, 130.24, 129.44, 127.45, 127.44, 125.93, 124.91, 122.62,
122.35, 117.05, 26.06, 16.09; Anal. Calcd for C15H14ClNO2 (275, 73)
(%): C 65.34, H 5.12, N 5.08; Found: C 65.57, H 4.92, N 5.38.
4.5.17. N-(5-Chloro-2-hydroxyphenyl)-2-ethylbenzothioamide
(7). The thioamide was prepared according to the procedure E.
Yield: 39.9%, Yellow-green solid; mp: 140e141 ꢁC, decomposition;
IR: 3351 (ʋ NH), 3144 (b, ʋ OH), 2962 (ʋas CH3), 2930 (ʋas CH2), 2870
(ʋs CH3), 1603, 1530, 1499, 1487, 1453 (ʋ CC aromatic) cmꢂ1. 1H NMR
4.5.13. N-(2-Hydroxyphenyl)-2-methoxybenzamide (6a).26 The am-
ide was prepared according to the procedure C. Yield: 73.2%, white
solid; mp: 200e202 ꢁC; IR: 3294 (ʋ NH), 3201 (b, ʋ OH), 1638
(amide I), 1614, 1598 (ʋ CC aromatic), 1555 (amide II), 1510, 1484,
1455 (ʋ CC aromatic) cmꢂ1; 1H NMR (DMSO-d6, 300 MHz):
d
10.57
(DMSO-d6, 500 MHz): Z-conformer: d 11.32 (1H, s, NH), 10.12 (1H, s,
(1H, s), 10.20 (1H, s), 8.37 (1H, d, J¼7.9 Hz), 8.08 (1H, dd, J¼7.8 Hz,
J¼1.8 Hz), 7.61e7.52 (1H, m), 7.25 (1H, d, J¼8.3 Hz), 7.13 (1H, t,
J¼7.5 Hz), 6.95e6.89 (2H, m), 6.87e6.77 (1H, m), 4.03 (3H, s, OCH3);
OH), 7.56 (1H, d, J¼2.7 Hz, H60), 7.44e7.10 (5H, m, H3, H4, H5, H6,
H40), 6.95 (1H, d, J¼8.7 Hz, H30), 2.81 (2H, q, J¼7.5 Hz, CH2), 1.21 (3H,
t, J¼7.5 Hz, CH3); E-conformer:
d 11.56 (1H, s, NH), 10.28 (1H, s, OH),
13C NMR (DMSO-d6, 75 MHz):
d
162.27, 157.35, 146.46, 133.66,
7.17e7.05 (5H, overlapped by Z-conformer, H3, H4, H5, H6, H40),
6.75 (1H, d, J¼8.7 Hz, H30), 6.64 (1H, d, J¼2.6 Hz, H60), 3.18 (2H, q,
J¼7.6 Hz, CH2), 1.07 (3H, t, J¼7.6 Hz, CH3). Z/E ratio 95:5. 13C NMR
131.54, 127.43, 123.86, 121.58, 121.36, 119.92, 119.45, 114.76, 112.79,
56.63; Anal. Calcd for C14H13NO3 (243.26) (%): C 69.12, H 5.39, N
5.76; Found: C 69.38, H 5.56, N 5.93.
(DMSO-d6, 125 MHz): Z-conformer: d 201.03, 151.24, 144.05, 139.09,
128.73, 128.67, 128.04, 127.78, 127.49, 126.90, 125.55, 121.69, 117.83,
25.41, 15.68; E-conformer: 203.12, 150.42, 141.13, 138.12, 130.65,
4.5.14. N-(2-Hydroxyphenyl)-2-methoxybenzothioamide
(6). The
d
thioamide was prepared according to the procedure E. Yield: 46.7%,
130.22, 128.42, 128.08, 127.79, 126.75, 125.16, 121.52, 117.34, 24.87,
14.72; Anal. Calcd for C15H14ClNOS (291.80) (%): C 61.74, H 4.84, N
4.80, S 10.99; Found: C 61.57, H 4.95, N 4.58, S 11.21.
yellow oil; IR: 3289 (ʋ NH), 3046 (b, ʋ OH), 1585, 1537, 1515, 1489 (ʋ
CC aromatic) cmꢂ1 1H NMR (DMSO-d6, 500 MHz): Z-conformer:
.
d
11.39 (1H, s, NH), 9.97 (1H, s, OH), 8.28 (1H, dd, J¼8.1 Hz, J¼1.6 Hz,
H60), 7.88 (1H, dd, J¼7.8 Hz, J¼1.8 Hz, H6), 7.50e7.39 (1H, m, H4),
7.18e7.08 (2H, m, H3, H40), 7.03 (1H, td, J¼7.5 Hz, J¼1.0 Hz, H5), 6.95
(1H, dd, J¼8.2 Hz, J¼1.4 Hz, H30), 6.85 (1H, td, J¼7.7 Hz, J¼1.4 Hz,
4.5.18. 5-Chloro-N-(2-ethylphenyl)-2-methoxybenzamide (8a). The
amide was prepared according to the procedure B. Yield: 89.3%,
white solid; mp: 114e116 ꢁC; IR: 3341 (ʋ NH), 1663 (amide I), 1614,
1593 (ʋ CC aromatic), 1550 (amide II), 1485, 1474, 1456 (ʋ CC aro-
H50), 3.89 (3H, s, OCH3); E-conformer:
d 11.32 (1H, s, NH), 9.73 (1H,
s, OH), 7.30 (1H, dd, J¼7.6 Hz, J¼1.8 Hz, H6), 7.16 (1H, overlapped by
Z-conformer, H4), 6.99e6.93 (1H, m, H40), 6.84 (1H, overlapped by
Z-conformer, H5), 6.74 (1H, dd, J¼8.1 Hz, J¼1.3 Hz, H30), 6.69 (1H, d,
J¼8.4 Hz, H3), 6.62 (1H, dd, J¼8.3 Hz, J¼1.6 Hz, H60), 6.46 (1H, td,
J¼7.6 Hz, J¼1.3 Hz, H50), 3.43 (3H, s, OCH3). Z/E ratio 88:12. 13C NMR
matic) cmꢂ1 1H NMR (DMSO-d6, 300 MHz):
; d 9.83 (1H, br s, NH),
7.90e7.79 (2H, m), 7.58 (1H, dd, J¼8.9 Hz, J¼2.9 Hz, H4), 7.33e7.22
(2H, m), 7.21 (1H, dd, J¼7.8 Hz, J¼1.8 Hz), 7.15 (1H, dd, J¼7.3 Hz,
J¼1.5 Hz), 3.98 (3H, s, OCH3), 2.65 (2H, q, J¼7.6 Hz, CH2), 1.18 (3H, t,
J¼7.6 Hz, CH3); 13C NMR (DMSO-d6, 75 MHz):
d 162.37, 155.93,
(DMSO-d6, 125 MHz): Z-conformer:
d
193.98, 154.81, 150.42, 132.41,
136.11, 135.76, 132.34, 130.07, 128.83, 126.36, 125.48, 124.94, 124.76,
124.26, 114.62, 56.87, 24.22, 14.29; Anal. Calcd for C16H16ClNO2
(289, 76) (%): C 66.32, H 5.57, N 4.83; Found: C 66.59, H 5.75, N 4.68.
131.87, 131.19, 127.83, 127.63, 125.11, 120.81, 118.91, 116.14, 112.47,
56.46; E-conformer: 199.89, 152.78, 151.30, 131.38, 130.09, 129.47,
d
127.85, 127.42, 126.26, 120.02, 118.19, 115.86, 111.00, 55.08. Anal.
Calcd for C14H13NO2S (259.32) (%): C 64.84, H 5.05, N 5.40, S 12.36;
Found: C 64.68, H 5.36, N 5.73, S 12.49.
4.5.19. 5-Chloro-N-(2-ethylphenyl)-2-methoxybenzothioamide
(8). The thioamide was prepared according to the procedure D.
Yield: 37.3%, Yellow solid; mp: 101e103 ꢁC; IR: 3336 (ʋ NH), 2958
(ʋas CH3), 2930 (ʋas CH2), 2870 (ʋs CH3), 1595, 1569, 1508, 1481,
1464, 1445 (ʋ CC aromatic) cmꢂ1. 1H NMR (DMSO-d6, 500 MHz): Z-
4.5.15. 2-Ethylbenzoic acid (11).27 2-Ethylbenzonitrile (7.6 mmol)
and KOH (24.8 mmol) were suspended in ethane-1,2-diol (10 mL)
and stirred at 170 ꢁC for 7 h. Then, the reaction mixture was cooled
down to rt, H2O (50 mL) was added and the resulting mixture was
extracted three times with ether (30 mL). pH of the aqueous layer
was adjusted to 1 by diluted HCl and the aqueous phase was
extracted three times with ether (40 mL). Organic phases were
conformer:
d
11.50 (1H, s, NH), 7.51 (1H, d, J¼2.7 Hz, H6), 7.45 (1H,
dd, J¼8.8 Hz, J¼2.7 Hz, H4), 7.37e7.25 (4H, m, H30, H40, H50, H60),
7.15 (1H, d, J¼8.8 Hz, H3), 3.86 (3H, s, OCH3), 2.64 (2H, q, J¼7.5 Hz,
CH2), 1.17 (3H, t, J¼7.5 Hz, CH3); E-conformer:
d 11.98 (1H, s, NH),
7.38 (1H, d, J¼2.8 Hz, H6), 7.24e7.22 (1H, m, H4), 7.24e7.15 (1H, m),