P. Langer, R. Schroeder
FULL PAPER
1H NMR (200 MHz, [D6]DMSO): δ ϭ 1.31 (t, J ϭ 7 Hz, 3 H, as a colourless solid (1.10 g, 48%), m.p. 104Ϫ105 °C. IR (KBr):
CH3), 2.14 (s, 3 H, CH3), 2.26 (s, 3 H, CH3), 4.30 (q, J ϭ 7 Hz, 2 ν˜ ϭ 755 (m), 1014 (w), 1290 (m), 1458 (w), 1532 (m), 1706 (s), 2938
H, CH2), 7.00 (d, 1 H, Ar), 7.02 (s, 1 H, Ar), 7.18 (d, 1 H, Ar)
ppm. 13C NMR (50 MHz, [D6]DMSO): δ ϭ 13.77, 17.49, 20.43,
62.18, 125.46, 126.56, 130.86, 132.05 132.65, 135.62, 155.82, 160.83
ppm. C12H15NO3 (221.26): calcd. C 65.14, H 6.83, N 6.33; found
C 64.81, H 6.85, N 6.19.
(w), 2938 (w), 3333 (m) cmϪ1. MS (EI, 70 eV): m/z ϭ 262 (21)
[Mϩ], 225 (25), 134 (100), 105 (63), 91 (86), 77 (24). 1H NMR
(200 MHz, CDCl3): δ ϭ 1.45 (t, J ϭ 7 Hz, 3 H, CH3), 2.28 (s, 3
H, CH3), 4.32 (q, J ϭ 7 Hz, 2 H, CH2), 7.09Ϫ7.28 (m, 3 H, Ar),
7.92 (d, 1 H, Ar), 8.19 (s, 1 H, NH) ppm. 13C NMR (50 MHz,
CDCl3): δ ϭ 14.32, 17.29, 65.67, 107.75, 122.26, 125.97, 127.06,
129.06, 130.59, 134.22, 160.39 ppm. C11H13Cl2NO2 (262.01): calcd.
C 50.42, H 4.96, N 5.34; found C 50.62, H 5.30, N 5.61.
Ethyl 2-[(3Ј,5Ј-Dimethylphenyl)amino]-2-oxoacetate (3e): Starting
with 1 (1.36 g, 10.0 mmol) and 3,5-xylidine (10.0 mmol), 3e was
isolated as a colourless solid (1.50 g, 68%), m.p. 130 °C. IR (KBr):
ν˜ ϭ 719 (s), 859 (s), 1017 (m), 1204 (s), 1267 (s), 1366 (w), 1474
(s), 1559 (s), 1698 (s), 2980 (m), 3349 (s) cmϪ1. MS (EI, 70 eV):
m/z ϭ 221 (87) [Mϩ], 147 (100), 120 (39), 104 (49), 77 (14). 1H
NMR (200 MHz, [D6]DMSO): δ ϭ 1.43 (t, J ϭ 7 Hz, 3 H, CH3),
2.31 (s, 6 H, CH3), 4.41 (q, J ϭ 7 Hz, 2 H, CH2), 6.80 (s, 1 H, Ar),
7.29 (m, 2 H, Ar), 10.52 (s, 1 H, NH) ppm. 13C NMR (50 MHz,
[D6]DMSO): δ ϭ 13.75, 20.96, 62.22, 118.14, 126.17, 137.24,
137.72, 155.53, 160.74 ppm. C12H15NO3 (221.26): calcd. C 65.14,
H 6.83, N 6.33; found C 65.09, H 6.83, N 6.10.
Ethyl 2,2-Dichloro-2-(4Ј-tolylamino)acetate (4c): Starting with 3c
(2.07 g, 10.0 mmol) and PCl5 (2.08 g, 10.0 mmol), 4c was isolated
as a colourless solid (0.80 g, 31%), m.p. 100Ϫ101 °C. IR (KBr):
ν˜ ϭ 498 (m), 703 (w), 817 (m), 1178 (m), 1295 (s), 1368 (w), 1522
(m), 1543 (m), 1599 (w), 1706 (s), 2983 (w), 3336 (s) cmϪ1. MS (EI,
70 eV): m/z ϭ 262 (27) [Mϩ], 225 (39), 134 (100), 105 (92), 91 (61),
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77 (35). H NMR (200 MHz, CDCl3):δ ϭ 1.44 (t, J ϭ 7 Hz, 3 H,
CH3), 2.33 (s, 3 H, CH3), 4.31 (q, J ϭ 7 Hz, 2 H, CH2), 7.16 (d, 2
H, Ar), 7.47 (d, 2 H, Ar), 8.14 (s, 1 H, NH) ppm. 13C NMR
(50 MHz, CDCl3):δ ϭ 14.38, 20.93, 65.85, 107.77, 120.17, 129.68,
133.67, 135.20, 160.18 ppm. C11H13Cl2NO2 (262.01): calcd. C
50.42, H 4.96, N 5.34; found C 50.61, H 4.98, N 5.43.
Ethyl 2-[(p-Methoxyphenyl)amino]-2-oxoacetate (3f): Starting with
1 (1.36 g, 10.0 mmol) and p-anisidine (1.24 g, 10.0 mmol), 3f was
isolated as a colourless solid (1.40 g, 62%), m.p. 113 °C. IR (KBr):
ν˜ ϭ 508 (w), 704 (m), 838 (s), 1021 (s), 1195 (s), 1243 (2), 1294 (s),
1368 (m), 1442 (m), 1512 (s), 1543 (s), 1696 (s), 3352 (s) cmϪ1. MS
Ethyl 2,2-Dichloro-2-[(2Ј,4Ј-dimethylphenyl)amino]acetate (4d):
Starting with 3d (2.21 g, 10.0 mmol) and PCl5 (2.08 g, 10.0 mmol),
4d was isolated as a colourless solid (1.35 g, 48%), m.p. 139 °C. IR
(KBr): ν˜ ϭ 807 (m), 986 (w), 1150 (m), 1291 (m), 1698 (s), 1700
(s), 3272 (w), 3400 (w) cmϪ1. MS (EI, 70 eV): m/z ϭ 276 (19) [Mϩ],
147 (100), 120 (66), 29 (69). 1H NMR (200 MHz, CDCl3): δ ϭ 1.43
(t, J ϭ 7 Hz, 3 H, CH3), 2.23 (s, 3 H, CH3), 2.30 (s, 3 H, CH3),
4.30 (q, J ϭ 7 Hz, 2 H, CH2), 7.03 (d, 2 H, Ar), 7.73 (d, 1 H, Ar),
8.11 (s, 1 H, NH) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 14.25,
17.18, 20.84, 65.58, 107.78, 122.43, 127.44, 129.28, 131.18, 131.50,
135.70, 160.33 ppm. C12H15Cl2NO2 (276.02): calcd. C 52.21, H
5.43, N 5.07; found C 52.04, H 6.45, N 5.03.
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(EI, 70 eV): m/z ϭ 223 (67) [Mϩ], 148 (100), 122 (85), 28 (51). H
NMR (200 MHz, [D6]DMSO): δ ϭ 1.27 (t, J ϭ 7 Hz, 3 H, CH3),
3.65 (s, 3 H, OCH3), 4.25 (q, J ϭ 7 Hz, 2 H, CH2), 6.88 (d, 2 H,
Ar), 7.63 (d, 2 H, Ar), 10.60 (s, 1 H, NH) ppm. 13C NMR (50 MHz,
[D6]DMSO): δ ϭ 13.76, 55.14, 62.21, 113.83, 121.83, 130.47,
155.11, 156.22, 160.81 ppm. C11H13NO4 (223.11): calcd. C 59.21,
H 5.82, N 6.27; found C 59.41, H 5.69, N 6.24.
Ethyl 2-[(p-Nitrophenyl)amino]-2-oxoacetate (3g): Starting with 1
(1.36 g, 10.0 mmol) and p-nitroaniline (1.38 g, 10.0 mmol), 3g was
isolated as a colourless solid (1.90 g, 84%), m.p. 173 °C. IR (KBr):
ν˜ ϭ 698 (w), 859 (m), 1177 (s), 1305 (s), 1345 (s), 1509 (s), 1561
(m), 1604 (s), 1710 (s), 3343 (s) cmϪ1. MS (EI, 70 eV): m/z ϭ 238
Ethyl 2,2-Dichloro-2-[(3Ј,5Ј-dimethylphenyl)amino]acetate (4e):
Starting with 3e (2.21 g, 10.0 mmol) and PCl5 (2.08 g, 10.0 mmol),
4e was isolated as a colourless solid (1.70 g, 71%), m.p. 159 °C. IR
(KBr): ν˜ ϭ 719 (s), 859 (s), 1017 (s), 1204 (s), 1267 (s), 1474 (s),
1559 (s), 1615 (s), 1695 (s), 2980 (m), 3349 (s) cmϪ1. MS (EI,
70 eV): m/z ϭ 275.7 (18) [Mϩ], 147 (100), 104 (51), 77 (29), 29 (80).
1H NMR (200 MHz, CDCl3): δ ϭ 1.45 (t, J ϭ 7.2 Hz, 3 H, CH3),
2.31 (s, 6 H, CH3), 4.29 (q, J ϭ 7.2 Hz, 2 H, CH2), 6.82 (s, 1 H,
Ar), 7.24 (d, 2 H, Ar), 8.11 (s, 1 H, NH) ppm. 13C NMR (50 MHz,
CDCl3): δ ϭ 15.05, 21.26, 31.82, 65.78, 107.75, 117.50, 117.84,
127.10, 127.21, 135.98, 138.88, 160.12 ppm. C12H15NO2Cl2
(276.02): calcd. C 52.21, H 5.43, N 5.07; found C 53.38, H 6.28,
N 4.97.
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(82) [Mϩ], 165 (100), 138 (24). H NMR (200 MHz, [D6]DMSO):
δ ϭ 1.33 (t, J ϭ 7.2 Hz, 3 H, CH3), 4.33 (q, J ϭ 7.2 Hz, 2 H, CH2),
8.02 (d, 2 H, Ar), 8.22 (d, 2 H, Ar), 11.30 (s, 1 H, NH) ppm.
13C NMR (50 MHz, [D6]DMSO): δ ϭ 13.73, 62.63, 120.33, 124.60,
143.29, 143.54, 155.97, 159.92 ppm. C10H10N2O5 (238.20): calcd.
C 50.42, H 4.23, N 11.76; found C 50.18, H 4.33, N 11.60.
General Procedure for the Synthesis of Ethyl 2-Amino-2,2-dichloro-
acetates (4): A toluene solution (30 mL) of 3 (10.0 mmol) and of
PCl5 (10.0 mmol) was refluxed for 5 h. The solution was concen-
trated to 15 mL to give a precipitate. The latter was isolated by
filtration and recrystallized from n-heptane to give 4 as a colour-
less solid.
Ethyl 2,2-Dichloro-2-[(4Ј-methoxyphenyl)amino]acetate (4f): Start-
ing with 3f (2.23 g, 10.0 mmol) and PCl5 (2.08 g, 10.0 mmol), 4f
was isolated as a colourless solid (1.20 g, 50%), m.p. 90Ϫ91 °C. IR
(KBr): ν˜ ϭ 834 (s), 1143 (s), 1295 (m), 1512 (s), 1539 (s), 1690 (s),
3271 (m), 3352 (m) cmϪ1. MS (EI, 70 eV): m/z ϭ 278 (13) [Mϩ],
241 (21), 148 (100), 122 (83), 77 (11), 29 (49). 1H NMR (200 MHz,
CDCl3): δ ϭ 1.44 (t, J ϭ 7 Hz, 3 H, CH3), 3.80 (s, 3 H, OCH3),
4.42 (q, J ϭ 7 Hz, 2 H, CH2), 6.90 (d, 2 H, Ar), 7.55 (d, 2 H, Ar),
8.78 (s, 1 H, NH) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 14.30,
55.42, 65.79, 107.75, 114.22, 121.33, 121.85, 129.20, 157.13, 160.17
ppm. C11H13Cl2NO3 (278.01): calcd. C 47.52, H 4.67, N 5.03;
found C 47.25, H 4.66, N 5.25.
Ethyl 2,2-Dichloro-2-(phenylamino)acetate (4a): Starting with 3a
(1.93 g, 10.0 mmol) and PCl5 (2.08 g, 10.0 mmol), 4a was isolated
as a colourless solid (1.10 g, 54%). IR (KBr): ν˜ ϭ 491 (w), 760,
(m), 1019, (w), 1178, (s), 1293, (s), 1540, (s), 1703 (s), 3344 (s) cmϪ1
.
MS (EI, 70 eV): m/z ϭ 248 (4) [Mϩ], 246 (8), 119 (100), 91 (31), 77
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(41), 27 (64). H NMR (200 MHz, CDCl3): δ ϭ 1.45 (t, J ϭ 7 Hz,
3 H, CH3), 4.30 (q, J ϭ 7 Hz, 2 H, CH2), 7.15 (t, 1 H, Ar), 7.38
(t, 2 H, Ar), 7.58 (d, 2 H, Ar), 8.21 (s, 1 H, NH) ppm. 13C NMR
(50 MHz, CDCl3): δ ϭ 14.37, 65.88, 107.68, 120.18, 125.47, 129.19,
136.16, 160.21 ppm. C10H11Cl2NO2 (248.00): calcd. C 48.42, H
4.43, N 5.64; found C 50.36, H 4.43, N 6.03.
Ethyl 2,2-Dichloro-2-(2Ј-tolylamino)acetate (4b): Starting with 3b
Ethyl 2,2-Dichloro-2-[(4Ј-nitrophenyl)amino]acetate (4g): Starting
(2.07 g, 10.0 mmol) and PCl5 (2.08 g, 10.0 mmol), 4b was isolated with 3g (2.38 g, 10.0 mmol) and PCl5 (2.08 g, 10.0 mmol), 4g was
Eur. J. Org. Chem. 2004, 1025Ϫ1032