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Methyl 2-(5-Chloro-2-methoxybenzoyl)-3-(phenylamino)acryl-
ate (4t). General Procedure A (at room temp.): Yellowish oil (puri-
fied by column chromatography; eluent: hexane/EtOAc, 6:4), yield
85 % (0.20 g). 1H NMR (500 MHz, CDCl3): δ = 0.92 (t, J = 7.3 Hz, 0.75
H), 1.04 (t, J = 7.3 Hz, 0.75 H), 3.75 (s, 3.09 H), 3.87–4.01 (m, 2.04 H),
Methyl 2-(2,4-Dimethoxy-3-methylbenzoyl)-3-(phenyl-
amino)acrylate (4j). General Procedure B (at 100 °C): Yellow solid
(crystallization from iPrOH), yield 67 % (0.19 g), m.p. 121.6–124.3 °C.
1H NMR (500 MHz, [D6]DMSO): δ = 2.05 (s, 2.00 H),2.06 (s, 1.00 H),
3.45 (s, 2.00 H), 3.50 (s, 0.96 H), 3.54 (s, 3.00 H),3.83 (s, 3.05 H), 6.74–
6.77 (d, J = 8.8 Hz, 1.00 H), 3.81 (s, 3.12 H), 4.00–4.12 (m, 2.14 H), 6.84 (m, 1.00 H), 7.12–7.51 (m, 6.07 H), 8.21 (d, J = 13.1 Hz, 0.32 H),
6.71–6.86 (m, 2.02 H), 7.15–7.51 (m, 6.00 H), 8.52–8.60 (m, 0.95 H), 8.44 (d, J = 13.5 Hz, 0.68 H), 10.50 (d, J = 13.1 Hz, 0.31 H), 12.07 (d,
11.00 (d, J = 13.8 Hz, 0.20 H), 12.58 (d, J = 14.1 Hz, 0.72 H) ppm.
J = 13.5 Hz, 0.67 H) ppm. 13C NMR (125 MHz, [D6]DMSO): δ = 8.6,
8.6, 50.6, 50.8, 55.7, 61.4, 61.5, 104.2, 105.7, 105.8, 117.5, 117.8,
13C NMR (125 MHz, CDCl3): δ = 55.1, 51.8, 55.8, 55.9, 56.0, 59.8, 60.1,
104.7, 104.9, 111.8, 111.9, 115.4, 117.5, 118.0, 125.4, 125.6, 125.9, 117.9, 124.5, 125.1, 126.7, 128.0, 128.2, 129.7, 129.7, 139.2, 139.6,
127.9, 128.7, 129.4, 130.0, 130.0, 130.1, 130.3, 133.9, 139.0, 139.1, 149.8, 150.3, 156.5, 159.6, 167.6, 167.2, 192.6 ppm. HRMS (APCI,
151.5, 151.9, 154.9, 155.4, 167.2, 193.2 ppm. HRMS (APCI, m/z): calcd.
m/z): calcd. for C20H22NO5 [M + H] 356.1498, found 356.1492.
for C19H19ClNO4 [M + H] 360.1003, found 360.0995.
Methyl 2-(2-Methoxybenzoyl)-3-(phenylamino)acrylate (4l).
3-(Cyclopropylamino)-2-(2,4-dimethoxybenzoyl)acrylonitrile
General Procedure B (at 100 °C): Yellowish oil (purified by column
(4w). General Procedure A (at 50 °C): Yellow, low freezing (puri- chromatography; eluent: hexane/EtOAc, 6:4), yield 70 % (0.19 g). 1H
fied by column chromatography; eluent: hexane/EtOAc, 6:4), yield
83 % (0.18 g). H NMR (500 MHz, CDCl3): δ = 0.77–0.91 (m, 4.16 H),
NMR (500 MHz, CDCl3): δ = 3.59 (s, 2.41 H), 3.60 (s, 0.55 H), 3.82 (s,
3.00 H), 6.76–7.52 (m, 9.00 H), 8.45 (d, J = 14.0 Hz, 0.20 H), 8.52 (d,
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2.91 (m, 0.98 H), 3.82 (s, 3.00 H), 3.87 (s, 3.07 H), 6.47 (d, J = 2.2 Hz, J = 13.4 Hz, 0.80 H), 10.90 (d, J = 14.0 Hz, 0.17 H), 12.60 (d, J =
0.99 H), 6.50 (dd, J = 8.5, 2.2 Hz, 1.09 H), 7.32 (d, J = 8.5 Hz, 0.93 H),
7.36 (d, J = 8.5 Hz, 0.07 H), 7.21 (d, J = 13.5 Hz, 0.93 H), 8.15 (d, J =
14.8 Hz, 0.04 H), 10.80 (d, J = 13.5 Hz, 0.85 H) ppm. 13C NMR
13.4 Hz, 0.73 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 51.2, 55.6,
55.8, 104.9, 110.5, 110.7, 115.8, 117.3, 117.8, 117.9, 120.7, 125.2,
125.6, 128.3, 129.4, 129.5, 130.0, 131.1, 131.4, 132.2, 139.2, 151.3,
(125 MHz, CDCl3): δ = 6.6, 6.6, 14.3, 21.2, 30.4, 55.6, 55.7, 55.7, 60.5, 151.6 156.4, 167.9, 194.8 ppm. HRMS (APCI, m/z): calcd. for
84.5, 98.8, 104.9, 120.7, 122.1, 130.5, 158.5, 160.3, 163.2, 192.4 ppm. C18H18NO4 [M + H] 312.1236, found 312.1232.
HRMS (APCI, m/z): calcd. for C15H17N2O3 [M + H] 273.1239, found
273.1233.
Ethyl 3-[(3-Chloro-2-methylphenyl)amino]-2-(2,6-dimethoxy-
benzoyl)acrylate (4o). General Procedure B (at 100 °C): White
General Procedure B for Synthesis of Enamines 4f, 4g, 4j, 4l, 4o,
4r, 4u, 4v: To a solution or suspension of 3a–c, 7a–c or 10 (1 mmol)
in toluene (4 mL) was added corresponding arylamine (1.2 mmol)
and the mixture was stirred at temperatures from r.t. to 100 °C. The
reaction was checked by TLC and the typical reaction time was 12 h.
The residue after evaporation was either crystallized or purified by
column chromatography giving 4f, 4g, 4j, 4l, 4o, 4r, 4u, 4v.
solid (precipitated after cooling), yield 55 % (0.11 g), m.p. 162.7–
168.8 °C. H NMR (500 MHz, CDCl3): δ = 0.90 (t, J = 7.1 Hz, 0.52 H),
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0.94 (t, J = 7.3 Hz, 2.44 H), 2.43 (s, 0.50 H), 2.51 (s, 2.45 H), 3.74–3.79
(m, 6.00 H), 3.94–4.06 (m, 1.99 H), 6.53–6.60 (m, 2.13 H), 7.14–7.32
(m, 4.00 H), 8.56 (d, J = 13.6 Hz, 0.82 H), 8.65 (d, J = 13.2 Hz, 0.16
H), 11.36 (d, J = 13.2 Hz, 0.13 H), 13.09 (d, J = 13.6 Hz, 0.67 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 13.6, 13.9, 14.3, 14.6, 56.1, 56.2, 59.9,
104.0, 104.1, 106.0, 114.7, 114.7, 121.7, 126.1, 126.4, 126.6, 127.7,
127.8, 129.6, 129.8, 136.0, 139.5, 152.5, 153.3, 156.7, 156.9, 166.9,
194.5 ppm. HRMS (APCI, m/z): calcd. for C21H23ClNO5 [M + H]
404.1265, found 404.1260.
Methyl 2-(2,4-Dimethoxybenzoyl)-3-(p-tolylamino)acrylate (4f).
General Procedure B (at 100 °C): Brown, low freezing oil (purified
by column chromatography; eluent: hexane/EtOAc, 4:1 and crystalli-
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zation from iPrOH), yield 66 % (0.44 g), m.p. 94.3–96.7 °C. H NMR
(500 MHz, CDCl3): δ = 2.33 (s, 0.51 H), 2.34 (s, 2.53 H), 3.58 (s, 3.00
H), 3.75–3.78 (m, 3.00 H), 3.84 (s, 2.54 H), 3.86 (s, 0.61 H), 6.40 (d,
J = 2.0 Hz, 1.00 H), 6.53 (dd, J = 8.5, 2.0 Hz, 1 H), 7.03 (d, J = 8.5 Hz,
0.34 H), 7.10 (d, J = 8.41 Hz, 1.69 H), 7.16 (d, J = 8.5 Hz, 0.34 H),
7.18 (d, J = 8.6 Hz, 1.69 H), 7.39 (d, J = 8.5 Hz, 0.84 H), 7.53 (d, J =
8.6 Hz, 0.17 H), 8.32 (d, J = 13.6 Hz, 0.16 H), 8.40 (d, J = 13.5 Hz,
0.84 H), 10.68 (d, J = 13.6 Hz, 0.16 H), 12.40 (d, J = 13.5 Hz, 0.80
Ethyl 2-(2,5-Dimethoxybenzoyl)-3-(mesitylamino)acrylate (4r).
General Procedure B (at 100 °C): Yellowish oil (purified by column
chromatography; eluent: hexane/EtOAc, 4:1), yield 70 % (0.20 g). 1H
NMR (500 MHz, CDCl3): δ = 0.94–1.02 (m, 2.94 H), 2.22–2.35 (m, 9.00
H), 3.71–3.79 (m, 6.17 H), 3.93–4.01 (m, 2.00 H), 6.74–6.95 (m, 5.00
H), 7.91 (d, J = 14.2 Hz, 0.21 H), 8.05 (d, J = 13.7 Hz, 0.21 H), 10.41
(d, J = 14.1 Hz, 0.21 H), 12.03 (d, J = 13.7 Hz, 0.21 H) ppm. 13C NMR
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 20.8, 50.8, 51.1, 55.4, 55.4, (125 MHz, CDCl3): δ = 13.8, 13.9, 14.1, 18.4, 18.5, 20.9, 43.3, 55.7,
55.4, 55.6, 97.9, 104.4, 117.0, 117.5, 125.0, 130.3, 130.3, 130.3, 135.1, 55.8, 56.2, 56.4, 59.6, 59.7, 60.4, 103.5, 111.9, 112.2, 113.2, 113.3,
136.8, 150.6, 162.6, 168.3, 193.1 ppm. HRMS (APCI, m/z): calcd. for 113.8, 115.9, 116.0, 129.6, 129.6, 132.4, 133.3, 135.2, 136.8, 136.9,
C20H22NO5 [M + H] 356.1498, found 356.1499.
150.5, 153.5, 158.8, 159.4, 167.6, 194.2 ppm. HRMS (APCI, m/z): calcd.
for C23H28NO5 [M + H] 398.1967, found 398.1973.
Methyl 2-(2,4-Dimethoxybenzoyl)-3-{[4-(trifluoromethyl)-
phenyl]amino}acrylate (4g). General Procedure B (at 100 °C):
White solid (crystallization from iPrOH), yield 76 % (0.31 g), m.p.
Ethyl 3-[(2-Bromo-4-methylphenyl)amino]-2-(5-chloro-2-meth-
oxybenzoyl)acrylate (4u). General Procedure B (at 100 °C): Yel-
low, low freezing oil (purified by column chromatography; eluent:
hexane/EtOAc, 6:4), yield 58 % (0.17 g). 1H NMR (500 MHz, CDCl3):
δ = 0.91 (t, J = 7.3 Hz, 0.87 H), 1.00 (t, J = 7.1 Hz, 2.26 H), 2.31–2.36
(m, 3.00 H), 3.76 (s, 3.06 H), 3.99–4.08 (m, 2.04 H), 6.75–6.82 (m, 1.00
H), 7.13–7.22 (m, 1.04 H), 7.27–7.50 (m, 3.86 H), 8.42–8.52 (m, 1.00
H), 11.21 (d, J = 13.8 Hz, 0.25 H), 12.74 (d, J = 13.1 Hz, 0.72 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 13.8, 14.0, 20.6, 20.7, 55.9, 56.0,
60.0, 60.2, 105.7, 105.0, 111.7, 111.8, 113.7, 114.1, 116.2, 116.4, 125.7,
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119.6–127.2 °C. H NMR (500 MHz, CDCl3): δ = 3.60 (s, 3.00 H), 3.76
(s, 3.00 H), 3.85 (s, 3.00 H), 6.40 (d, J = 2.4 Hz, 1.00 H), 6.55 (dd, J =
8.6, 2.4 Hz, 1.00 H), 7.27 (d, J = 8.6 Hz, 2.00 H), 7.45 (d, J = 8.6 Hz,
0.87 H), 7.63 (d, J = 8.6 Hz, 2.00 H), 8.28 (d, J = 12.9 Hz, 0.06 H),
8.38 (d, J = 12.8 Hz, 0.91 H), 10.68 (d, J = 12.9 Hz, 0.06 H), 12.27 (d,
J = 12.8 Hz, 0.89 H) ppm. 13C NMR (500 MHz, CDCl3): δ = 51.3, 55.3,
55.4, 97.9, 98.0, 104.6, 104.7, 106.98, 116.5, 117.0, 120.7 (q, JC,F
272 Hz, CF3), 122.9 (q, JC,F = 272 Hz, CF3), 124.3, 125.0 (q, JC,F
=
=
272 Hz, CF3), 126.54, 126.8, 127.1, 127.1, 127.2 (q, JC,F = 272 Hz, CF3), 125.7, 128.3, 128.8, 129.6, 129.7, 130.4, 130.5, 133.7, 133.8, 134.0,
127.2, 127.2, 130.8, 142.2, 148.8, 158.5, 163.2.168.0, 193.3 ppm. 19F 135.2, 135.2, 136.2, 136.7, 150.1, 150.4, 155.0, 155.6, 167.3, 168.5,
NMR (500 MHz, CDCl3): δ = –62.15 ppm. HRMS (APCI, m/z): calcd.
190.5, 192.9 ppm. HRMS (APCI, m/z): calcd. for C20H20BrClNO5 [M +
for C20H19F3NO5 [M + H] 410.1215, found 410.1217.
H] 452.0264, found 452.0262.
Eur. J. Org. Chem. 2016, 2336–2350
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim