Oxidative Coupling of Halogenated-Acetanilides with Acrylates
COMMUNICATIONS
and dried to give 4 as a beige solid; yield: 2.9 g (70%); mp>
2608C; 1H NMR (500 MHz, DMSO-d6): d¼2.07 (3H, s), 3.49
(1H, br), 3.92 (3H, s), 6.65–6.68 (1H, d, J¼15 Hz), 7.47 (2H,
s), 7.64–7.67 (1H, d, J¼15 Hz), 9.78 (1H, s); 13C NMR
(500 MHz, DMSO-d6): d¼22.95, 56.45, 109.67, 120.95,
122.66, 128.11, 128.94, 130.33, 138.51, 152.31, 167.53, 169.04;
MS (ESI): m/z¼270 (MþH); HR-MS (ESI): m/z¼270.0538
(calcd. for C12H13ClNO4: 270.0533).
1.43 (2H, m, J¼7 Hz), 1.60–1.65 (2H, m, J¼7 Hz), 2.09 (3H,
s), 2.32 (3H, s), 4.15–4.17 (2H, t, J¼7 Hz), 6.59–6.62 (1H, d,
J¼15 Hz), 7.54 (1H, s), 7.72–7.75 (1H, d, J¼15 Hz), 7.85
(1H, s), 9.89 (1H, s); 13C NMR (500 MHz, DMSO-d6): d¼
13.61, 18.64, 18.88, 23.11, 30.26, 63.73, 119.18, 126.06, 126.98,
128.94, 132.66, 134.75, 135.86, 139.01, 166.15, 168.85; MS
(ESI): m/z¼310 (MþH); HR-MS (ESI): m/z¼310.1205
(calcd. for C16H21ClNO3: 310.1210).
Butyl 3-[2-(Acetylamino)-4-fluoro-5-methoxyphenyl]-2-
(2E)-propenoate (14): White solid; mp 180.5–181.58C; 1H
NMR (500 MHz, DMSO-d6): d¼0.91–0.94 (3H, t, J¼7 Hz),
1.38–1.43 (2H, m, J¼7 Hz), 1.61–1.66 (2H, m, J¼7 Hz),
2.07 (3H, s), 3.91 (3H, s), 4.15–4.18 (2H, t, J¼7 Hz), 6.70–
6.73 (1H, d, J¼15 Hz), 7.29–7.31 (1H, d, J¼12 Hz), 7.54–
7.56 (1H, d, J¼9 Hz), 7.72–7.75 (1H, d, J¼15 Hz), 9.83 (1H,
s); 13C NMR (500 MHz, DMSO-d6): d¼13.48, 18.64, 22.91,
30.28, 56.31, 63.66, 111.03, 114.17, 114.30, 118.85, 125.19,
130.67, 130.73, 139.09, 145.12, 145.19, 151.34, 152.99, 166.34,
168.88; MS (ESI): m/z¼310 (MþH); HR-MS (ESI): m/z¼
310.1450 (calcd. for C16H21FNO4: 310.1455).
Butyl 3-[2-(Acetylamino)-4-fluoro-5-methylphenyl]-2-
(2E)-propenoate (16): White solid; mp 151–1528C; 1H NMR
(500 MHz, DMSO-d6): d¼0.91–0.94 (3H, t, J¼7 Hz), 1.36–
1.41 (2H, m, J¼7 Hz), 1.60–1.65 (2H, m, J¼7 Hz), 2.09 (3H,
s), 2.22 (3H, s), 4.14–4.16 (2H, t, J¼7 Hz), 6.53–6.56 (1H, d,
J¼15 Hz), 7.29–7.31 (1H, d, J¼7 Hz), 7.74–7.68 (1H, d, J¼
15 Hz), 7.79–7.81 (1H, d, J¼7 Hz), 9.90 (1H, s); 13C NMR
(500 MHz, DMSO-d6): d¼13.49, 13.63, 18.64, 23.16, 30.27,
63.65, 63.65, 112.13, 112.30, 118.28, 121.66, 121.79, 124.06,
136.47, 136.54, 139.14, 160.47, 162.12, 166.25, 168.80; MS
(ESI): m/z¼294 (MþH); HR-MS (ESI): m/z¼294.1494
(calcd. for C16H21FNO3: 294.1505).
General Procedure for the Preparation of Acetanilides
To a pre-cooled (08C) solution of aniline (0.21 mol), triethyl-
amine (0.6 mol), N,N-dimethylaminopyridine (0.2 g) and ethyl
acetate (500 mL), a solution of acetic anhydride (0.2 mol) in
ethyl acetate (80 mL) was added slowly over 1 h. The hazy mix-
ture was warmed up to 228C and stirred at room temperature
for 17 h to give a thick suspension. The reaction mixture was
quenched with water (150 mL). The top organic layer was
washed in sequence with saturated aqueous NaCl solution
(150 mL), 2 N HCl solution (150 mL) and saturated NaCl
aqueous solution (150 mL). The organic layer was dried over
MgSO4, filtered, and concentrated at 558C under vacuum to
leave a viscous oil. Hexane (150 mL) was added to obtain a
thick suspension at 228C. Acetanilides (1, 11, 13, 15, 17, 19,
21, 23 and 25) were collected by filtration as white solids. The
yield were 85–95%.
General Procedure for the Oxidative Coupling of
Acetanilides with n-Butyl Acrylate
Butyl 3-[2-(Acetylamino)-4-bromo-5-methylphenyl]-2-
(2E)-propenoate (18): White solid; mp 168–1698C; 1H NMR
(500 MHz, DMSO-d6): d¼0.91–0.94 (3H, t, J¼7 Hz), 1.35–
1.41 (2H, m, J¼7 Hz), 1.60–1.65 (2H, m, J¼7 Hz), 2.09 (3H,
s), 2.34 (3H, s), 4.14–4.17 (2H, t, J¼7 Hz), 6.61–6.64 (1H, d,
J¼15 Hz), 7.69 (1H, s), 7.70–7.73 (1H, d, J¼15 Hz), 7.85
(1H, s), 9.88 (1H, s); 13C NMR (500 MHz, DMSO-d6): d¼
13.51, 18.64, 21.66, 23.11, 30.26, 63.74, 119.24, 125.57, 127.54,
128.63, 129.31, 134.52, 135.83, 139.11, 166.15, 168.88; MS
(ESI): m/z¼354 (MþH); HR-MS (ESI): m/z¼354.0722
(calcd. for C16H21BrNO3: 354.0705).
Into a homogeneous mixture of acetanilide (30 mmol), 1,4-
benzoquinoline (30 mmol), p-toluenesulfonic acid monohy-
drate (30 mmol), palladium acetate (1.5 mmol) and acetic
acid (75 mL), a solution of n-butyl acrylate (33 mmol) in tol-
uene (23 mL) was added over 2 min. The flask was capped
with a rubber septum, and the mixture was stirred at room tem-
perature for 17 h. Water (150 mL) and ethyl acetate (400 mL)
were added into the mixture and stirred for 15 min. Tetrahy-
drofuran (150 mL) was added to dissolve all insoluble solids
(if necessary). The top organic layer was washed in a sequence,
with water (100 mL), saturated aqueous Na2CO3 solution
(150 mL) and saturated NaCl solution (150 mL). The organic
layer was dried with MgSO4, filtered, and concentrated at
558C under vacuum. The resulting solids were purified by silica
gel column chromatography to yield the corresponding oxida-
tively coupled products (10, 12, 14, 16, 18, 20, 22, 24 and 26).
Butyl 3-[2-(Acetylamino)-4-chloro-5-methoxyphenyl]-2-
(2E)-propenoate (10): White solid; mp 186–1878C; 1H NMR
(500 MHz, DMSO-d6): d¼0.91–0.94 (3H, t, J¼7 Hz), 1.38–
1.43 (2H, m, J¼7 Hz), 1.61–1.66 (2H, m, J¼7 Hz), 2.07 (3H,
s), 3.93 (3H, s), 4.16–4.18 (2H, t, J¼7 Hz), 6.75–6.78 (1H, d,
J¼15 Hz), 7.47–7.49 (2H, d, J¼15 Hz), 7.70–7.72 (1H, d,
J¼15 Hz), 9.77 (1H, s); 13C NMR (500 MHz, DMSO-d6): d¼
14.01, 18.70, 20.66, 30.26, 56.48, 63.75, 109.73, 119.72, 122.93,
128.04, 128.70, 130.54, 139.08, 152.32, 166.25, 168.91; MS
(ESI): m/z¼326 (MþH); HR-MS (ESI): m/z¼326.1159
(calcd. for C16H21ClNO4: 326.1159).
Butyl
3-[2-(Acetylamino)-4-methyl-5-iodophenyl]-2-
(2E)-propenoate (20): White solid; mp 191–1928C; 1H NMR
(500 MHz, DMSO-d6): d¼0.91–0.93 (3H, t, J¼7 Hz), 1.35–
1.41 (2H, m, J¼7 Hz), 1.59–1.62 (2H, m, J¼7 Hz), 2.07 (3H,
s), 2.35 (3H, s), 4.13–4.16 (2H, t, J¼7 Hz), 6.59–6.62 (1H, d,
J¼15 Hz), 7.39 (1H, s), 7.62–7.65 (1H, d, J¼15 Hz), 8.23
(1H, s), 9.84 (1H, s); 13C NMR (500 MHz, DMSO-d6): d¼
13.53, 18.63, 23.11, 27.47, 30.26, 63.71, 97.35, 119.08, 127.49,
128.19, 136.27, 137.09, 138.47, 143.25, 166.18, 168.68; MS
(ESI): m/z¼402 (MþH); HR-MS (ESI): m/z¼402.0579
(calcd. for C16H21INO3: 402.0566).
Butyl 3-[2-(Acetylamino)-5-chlorophenyl]-2-(2E)-prope-
noate (22): White solid; mp 140–1418C; 1H NMR (500 MHz,
DMSO-d6): d¼0.91–0.94 (3H, t, J¼7 Hz), 1.36–1.41 (2H,
m, J¼7 Hz), 1.60–1.65 (2H, m, J¼7 Hz), 2.09 (3H, s), 3.32
(3H, s), 4.15–4.17 (2H, t, J¼7 Hz), 6.66–6.69 (1H, d, J¼
15 Hz), 7.43–7.47 (2H, m), 7.69–7.72 (1H, d, J¼15 Hz), 7.91
(1H, s), 9.87 (1H, s); 13C NMR (500 MHz, DMSO-d6): d¼
11.18, 16.29, 20.75, 27.90, 61.47, 117.96, 124.01, 125.73, 127.62,
Butyl 3-[2-(Acetylamino)-4-chloro-5-methylphenyl]-2-
(2E)-propenoate (12): White solid; mp 143–1448C; 1H NMR
(500 MHz, DMSO-d6): d¼0.91–0.94 (3H, t, J¼7 Hz), 1.38–
Adv. Synth. Catal. 2005, 347, 1921 – 1924
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1923