PAPER
Synthesis of Ethyl 3-Amino-4-arylfuran-2-carboxylates
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2-(3,4-Dichlorophenyl)-3-hydroxyacrylonitrile Sodium Salt
(7c)
Ethyl 3-Amino-4-(3,4-dimethoxyphenyl)furan-2-carboxylate
(4b)
From (3,4-dichlorophenyl)acetonitrile (8c;1 8.6 g); white powder
(18.41 g, 78%); mp >260 °C.
IR (KBr): 2172 cm–1 (CN).
From 7b (11.4 g); yellow powder (5.4 g, 37%); mp 117 °C.
IR (KBr): 3467 (NH), 3370 (NH), 2962 (CH), 1670 cm–1 (C=O).
1H NMR (CDCl3): = 1.41 (t, 3 H, J = 7.1 Hz, CH3), 3.88 (s, 3 H,
OCH3), 3.90 (s, 3 H, OCH3), 4.39 (q, 2 H, J = 7.1 Hz, CH2), 4.69 (br
s, 2 H, NH2), 6.82 (s, 1 H, H-2phenyl), 6.95 (m, 2 H, H-5 and
H-6phenyl), 7.36 (s, 1 H, Hfuran).
2-(4-Bromophenyl)-3-hydroxyacrylonitrile Sodium Salt (7d)
From (4-bromophenyl)acetonitrile (8d; 19.6 g); beige powder
(17.71 g, 72%); mp >260 °C.
IR (KBr): 2170 cm–1 (CN).
Anal. Calcd for C15H17NO5: C, 61.85; H, 5.88; N, 4.81. Found : C,
61.87; H, 5.92; N, 4.96.
2-(4-Fluorophenyl)-3-hydroxyacrylonitrile Sodium Salt (7e)
From (4-fluorophenyl)acetonitrile (8e; 13.5 g); beige powder (15.55
g, 84%); mp >260 °C.
IR (KBr): 2175 cm–1 (CN).
Ethyl 3-Amino-4-(3,4-dichlorophenyl)furan-2-carboxylate (4c)
From 7c (11.8 g); yellow powder (4.6 g, 31%); mp 81 °C.
IR (KBr): 3450 (NH), 3339 (NH), 2989 (CH), 1674 cm–1 (C=O).
1H NMR (CDCl3): = 1.39 (t, 3 H, J = 7.1 Hz, CH3), 4.38 (q, 2 H,
J = 7.1 Hz, CH2), 4.69 (br s, 2 H, NH2), 7.27 (d, 1 H, J = 8.4 Hz, H-
5phenyl), 7.40 (s, 1 H, Hfuran), 7.51 (s, 1 H, H-2phenyl), 7.53 (d, 1 H,
J = 8.4 Hz, H-6phenyl).
3-Hydroxy-2-(4-methoxyphenyl)acrylonitrile Sodium Salt (7f)6
From (4-methoxyphenyl)acetonitrile (8f; 14.7 g); white powder
(10.25 g, 52%); mp >260 °C.
IR (KBr): 2170 cm–1 (CN).
Anal. Calcd for C13H11Cl2NO3: C, 52.02; H, 3.69; N, 4.67. Found :
C, 52.07; H, 3.97; N, 5.05.
3-Hydroxy-2-(4-methylphenyl)acrylonitrile Sodium Salt (7g)6
From (4-methylphenyl)acetonitrile (8g;13.1 g); white powder
(11.77 g, 65%); mp >260 °C.
Ethyl 3-Amino-4-(4-bromophenyl)furan-2-carboxylate (4d)
From 7d (12.3 g); beige powder (4.3 g, 28%); mp 65 °C.
IR (KBr): 3453 (NH), 3356 (NH), 2978 (CH), 1675 cm-1 (C=O).
IR (KBr): 2180 cm-1 (CN).
1H NMR (CDCl3): = 1.41 (t, 3 H, J = 7.2 Hz, CH3), 4.39 (q, 2 H,
J = 7.2 Hz, CH2), 4.67 (br s, 2 H, NH2), 7.30 (d, 2 Hphenyl, J = 8.4
Hz), 7.39 (s, 1 Hfuran), 7.57 (d, 2 Hphenyl, J = 8.4 Hz).
3-Hydroxy-2-(pyridin-2-yl)acrylonitrile Sodium Salt (7h)
From (2-pyridinyl)acetonitrile (8h; 11.8 g); beige powder (10.26 g,
61%); mp >260 °C.
IR (KBr): 2171 cm–1 (CN).
Anal. Calcd for C13H12BrNO3: C, 50.34; H, 3.90; N, 4.52. Found: C,
50.35; H, 4.12; N, 4.69.
3-Hydroxy-2-(thien-2-yl)acrylonitrile Sodium Salt (7i)
From (2-thienyl)acetonitrile (8i; 12.3 g); white powder (14.20 g,
82%); mp >260 °C.
IR (KBr): 2168 cm–1 (CN).
Ethyl 3-Amino-4-(4-fluorophenyl)furan-2-carboxylate (4e)
From 7e (9.3 g); yellow powder (4.7 g, 38%); mp 98 °C.
IR (KBr): 3440 (NH), 3339 (NH), 2984 (CH), 1673 cm–1 (C=O).
1H NMR (CDCl3): = 1.41 (t, 3 H, J = 7.2 Hz, CH3), 4.39 (q, 2 H,
J = 7.2 Hz, CH2), 4.64 (br s, 2 H, NH2), 7.14 (m, 2 Hphenyl), 7.35 (s,
1 Hfuran), 7.39 (m, 2 Hphenyl).
3-Hydroxy-2-(thien-3-yl)acrylonitrile Sodium Salt (7j)
From (3-thienyl)acetonitrile (8j; 12.3 g); white powder (14.72 g,
85%); mp >260 °C.
IR (KBr): 2170 cm–1 (CN).
Anal. Calcd for C13H12FNO3: C, 62.65; H, 4.85; N, 5.62. Found: C,
62.73; H, 4.98; N, 5.74.
Ethyl 3-Amino-4-(4-methoxyphenyl)furan-2-carboxylate (4f)
From 7f (9.9 g); yellow powder (4.4 g, 34%), mp 87 °C.
IR (KBr): 3465 (NH), 3368 (NH), 2954 (CH), 1667 cm–1 (C=O).
1H NMR (CDCl3): = 1.33 (t, 3 H, J = 7.1 Hz, CH3), 4.32 (q, 2 H,
J = 7.1 Hz, CH2), 4.58 (br s, 2 H, NH2), 6.90 (d, 2 Hphenyl, J = 8.8
Hz,), 7.24 (s, 1 Hfuran), 7.26 (d, 2 Hphenyl, J = 8.8 Hz).
Ethyl 3-Amino-4-arylfuran-2-carboxylates 4a–j; General Pro-
cedure
To 2-aryl-3-hydroxyacrylonitrile sodium salt 7a–j (50 mmol) in
DMF (80 mL) was added diethyl chloromalonate (8.9 mL, 55
mmol). The reaction mixture was allowed to stir for 5 h at r.t. and
then the solvent was removed under reduced pressure. The dark oil
was extracted with CH2Cl2 (100 mL), the organic layer was washed
with H2O (2 100 mL), dried (CaCl2) and evaporated to give an or-
ange syrup. The syrup was dissolved in EtOH (50 mL) to which 1.5-
diazabicyclo[4.3.0]non-5-ene (6.8 mL, 55 mmol) was added and the
mixture was allowed to stir overnight. The solution was concentrat-
ed and an analytical sample was prepared by silica gel chromatog-
raphy (EtOAc–cyclohexane, 1:2).
Anal. Calcd for C14H15NO4: C, 64.36; H, 5.79; N, 5.36. Found: C,
64.48; H, 5.82; N, 5.55.
Ethyl 3-Amino-4-(4-methylphenyl)furan-2-carboxylate (4g)
From 7g (9.1 g); yellow powder (3.8 g, 31%); mp 68 °C.
IR (KBr): 3478 (NH), 3380 (NH), 2963 (CH), 1672 cm–1 (C=O).
1H NMR (CDCl3): = 1.41 (t, 3 H, J = 7.2 Hz, CH3), 2.39 (s, 3 H,
CH3), 4.38 (q, 2 H, J = 7.2 Hz, CH2), 4.69 (br s, 2 H, NH2), 7,25 (d,
2 Hphenyl, J = 8.1 Hz), 7.31 (d, 2 Hphenyl, J = 8.1 Hz), 7.36 (s, 1 Hfuran).
Ethyl 3-Amino-4-phenylfuran-2-carboxylate (4a)2
From 7a (8.4 g); yellow powder (1.7 g, 15%); mp 67–68 °C.
IR (KBr): 3472 (NH), 3369 (NH), 2961 (CH), 1671 cm–1 (C=O).
1H NMR (CDCl3): = 1.28 (t, 3 H, J = 7.1 Hz, CH3), 4.27 (q, 2 H,
J = 7.1 Hz, CH2), 4.51 (br s, 2 H, NH2), 7.37 (m, 6 H, Hphenyl and
Anal. Calcd for C14H15NO3: C, 68.56; H, 6.16; N, 5.71. Found: C,
68.59; H, 6.41; N, 5.89.
Hfuran).
Ethyl 3-Amino-4-(pyridin-2-yl)furan-2-carboxylate (4h)
From 7h (8.4 g); yellow powder (3.7 g, 32%); mp 154 °C.
IR (KBr): 3392 (NH), 3284 (NH), 2969 (CH), 1678 cm–1 (C=O).
Synthesis 2002, No. 6, 753–756 ISSN 0039-7881 © Thieme Stuttgart · New York