M. Gruttadauria, L. A. Bivona, P. Lo Meo, S. Riela, R. Noto
FULL PAPER
7.48 (d, J = 8.1 Hz, 2 H), 7.61 (d, J = 8.1 Hz, 2 H), 7.73 (d, J = 2-{[4Ј-(Diphenylamino)-1,1Ј-biphenyl-4-yl]methylene}malononitrile
1
9.0 Hz, 2 H), 8.29 (d, J = 9.0 Hz, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 20.8, 27.4, 39.1, 55.6, 75.2, 124.5, 127.8, 127.9, 128.0,
(9d): M.p. 53–55 °C; yield 258 mg (65%). H NMR (CDCl3): δ =
7.10–7.19 (m, 8 H), 7.30–7.36 (m, 4 H), 7.55 (d, J = 8.7 Hz, 2 H),
7.73–7.76 (m, 2 H, overlapped with 7.76 s, 1 H), 7.98 (d, J = 8.4 Hz,
2 H) ppm. 13C NMR (75 MHz), (CDCl3): δ = 81.3, 113.5, 114.6,
123.0, 124.2, 125.5, 127.5, 128.4, 129.6, 129.8, 129.9, 131.9, 132.0,
128.1, 138.7, 142.8, 147.5, 147.6, 223.3 ppm. IR (nujol): ν
=
˜
max
3450, 1712 cm–1. C18H17NO4 (311.12): calcd. C 69.44, H 5.50, N
4.50; found C 69.39, H 5.48, N 4.53.
147.2, 147.5, 149.4, 159.6 ppm. IR (nujol): νmax = 2225, 1576 cm–1.
˜
(S)-2-{(R)-Hydroxy[4Ј-methyl-1,1Ј-biphenyl-4-yl]methyl}cyclopent-
anone (4b): M.p. 85–88 °C. [α]3D1 = –103Ϯ2; yield 121 mg (43%).
1H NMR CDCl3: δ = (mixture of diastereoisomers) 1.50–2.60 (m,
7 H), 2.44 (s, 3 H), 4.60 (s, 1 H, OH), 4.77 (d, J = 9.0 Hz, 1 H,
anti), 5.35 (s, 1 H, syn), 7.26 (d, J = 8.1 Hz, 2 H), 7.40 (d, J =
8.1 Hz, 2 H), 7.50 (d, J = 8.1 Hz, 2 H), 7.58 (d, J = 8.1 Hz, 2 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 20.8, 21.5, 27.4, 39.2, 55.7,
75.4, 127.3, 127.4, 129.9, 137.5, 138.3, 140.6, 141.2, 223.5 ppm. IR
C28H19N3 (397.16): calcd. C 84.61, H 4.82, N 10.57; found C 84.66,
H 4.78, N 10.62.
2-{[4Ј-Methyl-1,1Ј-biphenyl-4-yl]methylene}malononitrile (9e): M.p.
1
168–170 °C; yield 149 mg (61%). H NMR (CDCl3): δ = 2.44 (s, 3
H), 7.32 (d, J = 8.4 Hz, 2 H), 7.57 (d, J = 8.4 Hz, 2 H), 7.75 (d, J
= 8.4 Hz, 2 H), 7.77 (s, 1 H), 7.98 (d, J = 8.4 Hz, 2 H) ppm. 13C
NMR (75 MHz), (CDCl3): δ = 21.7, 82.0, 113.3, 114.4, 127.5,
128.1, 129.9, 130.3, 131.9, 136.3, 140.0, 147.7, 159.7 ppm. IR (nu-
(nujol): νmax = 3480, 1717 cm–1. C19H20O2 (280.15): calcd. C 81.40,
˜
jol): νmax = 2226, 1583 cm–1. C17H12N2 (244.29): calcd. C 83.58, H
˜
H 7.19; found C 81.46, H 7.22.
4.95, N 11.47; found C 83.65, H 5.03, N 11.51.
(E)-Methyl 3-(4-{(R)-Hydroxy[(S)-2-oxocyclopentyl]methyl}phenyl)-
acrylate (6): M.p. 83–86 °C. [α]2D7 = –113Ϯ1; yield 192 mg (70%).
1H NMR CDCl3: δ = (mixture of diastereoisomers) 1.45–1.55 (m,
1 H), 1.65–1.78 (m, 2 H), 1.90–2.02 (m, 1 H), 2.16–2.30 (m, 1 H),
2.36–2.47 (m, 2 H), 3.79 (s, 3 H), 4.61 (s, 1 H, OH), 4.73 (d, J =
9.0 Hz, 1 H, anti), 5.28 (s, 1 H, syn), 6.42 (d, J = 15.9 Hz, 1 H),
7.35 (d, J = 8.1 Hz, 2 H), 7.49 (d, J = 8.1 Hz, 2 H), 7.67 (d, J =
15.9 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 20.4, 26.9,
38.7, 51.7, 55.2, 74.8, 117.9, 127.1, 128.2, 134.1, 143.8, 144.4, 167.4,
2-{[3Ј-Methoxy-1,1Ј-biphenyl-4-yl]methylene}malononitrile
(9f):
M.p. 124–126 °C; yield 192 mg (74%). 1H NMR (CDCl3): δ = 3.89
(s, 3 H), 7.00 (d, J = 8.1 Hz, 1 H), 7.16 (s, 1 H), 7.23 (d, J = 8.1 Hz,
1 H), 7.42 (dd, J = 8.1 and 8.1 Hz, 1 H), 7.74 (d, J = 8.1 Hz, 2 H),
7.77 (s, 1 H), 7.97 (d, J = 8.1 Hz, 2 H) ppm. 13C NMR (75 MHz),
(CDCl3): δ = 55.8, 82.3, 113.3, 113.5, 114.4, 114.7, 120.1, 128.5,
130.3, 130.7, 131.8, 140.7, 147.5, 159.7, 160.6 ppm. IR (nujol): ν
˜
max
= 2228, 1579 cm–1. C17H12N2O (260.09): calcd. C 78.44, H 4.65, N
10.76; found C 78.50, H 4.61, N 10.70.
222.6 ppm. IR (nujol): ν
= 3450, 1715, 1705 cm–1. C16H18O4
˜
max
(E)-Ethyl 2-Cyano-3-(4Ј-nitro-1,1Ј-biphenyl-4-yl)acrylate (9g): M.p.
(274.12): calcd. C 70.06, H 6.61; found C 70.10, H 6.66.
1
181–183 °C; yield 210 mg (65%). H NMR (CDCl3): δ = 1.42 (t, J
Typical Procedure for the Sequential Suzuki/Knoevenagel Reaction:
In a round-bottomed flask the aryl halide (1 mmol), the aryl-
boronic acid (1.1 mmol), ethanol (1.2 mL), water (1.2 mL), K2CO3
(165.8 mg, 1.2 mmol) and SiO2-Pd-1 (2 mg, 0.2 mol-%) were
placed. The reaction mixture was stirred at 50 °C for 6 h (R = NO2,
OCH3) or 23 h (R = H). After completion of the reaction two pro-
cedures were followed: a) the reaction mixture was cooled to room
temperature, then water (3 mL) and malononitrile (1.1 mmol) were
added and the mixture was stirred for further 23 h or b) ethyl cya-
noacetate (1.1 mmol) was added and the reaction mixture was
stirred for further 2 h at 50 °C. After this time the reaction mixture
was extracted with dichloromethane. The organic phase was dried
(Na2SO4), concentrated under reduced pressure and purified by
column chromatography (petroleum ether/ethyl acetate, 5:1). Com-
pound 9d was prepared following the Suzuki procedure reported in
the literature.[15] After completion of the reaction, water (3 mL) and
malononitrile (1.1 mmol) were added and the mixture stirred for
23 h. Work-up and purification were carried out as described
above.
= 7.2 Hz, 3 H), 4.40 (q, J = 7.2 Hz, 2 H), 7.74–7.82 (m, 4 H), 8.12
(d, J = 8.1 Hz, 2 H), 8.29–8.35 (m, 3 H) ppm. 13C NMR (75 MHz),
(CDCl3): δ = 14.6, 21.6, 63.3, 104.2, 115.8, 124.7, 128.5, 128.6,
132.2, 143.5, 146.1, 148.1, 154.2, 162.7 ppm. IR (nujol): ν
=
˜
max
2226, 1729, 1593 cm–1. C18H14N2O4 (322.31): calcd. C 67.07, H
4.38, N 8.69; found C 67.14, H 4.43, N 8.71.
(E)-Ethyl 2-Cyano-3-(4Ј-methoxy-1,1Ј-biphenyl-4-yl)acrylate (9h):
M.p. 104–106 °C; yield 246 mg (80%). 1H NMR (CDCl3): δ = 1.40
(t, J = 7.2 Hz, 3 H), 3.86 (s, 3 H), 4.38 (q, J = 7.2 Hz, 2 H), 7.00
(d, J = 8.7 Hz, 2 H), 7.58 (d, J = 8.7 Hz, 2 H), 7.67 (d, J = 8.4 Hz,
2 H), 8.03 (d, J = 8.4 Hz, 2 H), 8.23 (s, 1 H) ppm. 13C NMR
(75 MHz), (CDCl3): δ = 14.6, 55.8, 63.0, 102.1, 114.9, 116.3, 127.4,
128.7, 130.1, 132.0, 132.2, 145.9, 154.9, 160.2, 163.1 ppm. IR (nu-
jol): ν
= 2225, 1720, 1590 cm–1. C19H17NO3 (307.12): calcd. C
˜
max
74.25, H 5.58, N 4.56; found C 74.30, H 5.60, N 4.51.
(E)-Ethyl 2-Cyano-3-[4Ј-(diphenylamino)-1,1Ј-biphenyl-4-yl]acrylate
(9i): M.p. 154–156 °C; yield 360 mg (81%). 1H NMR (CDCl3): δ =
1.43 (t, J = 7.2 Hz, 3 H), 4.41 (q, J = 7.2 Hz, 2 H), 7.06–7.18 (m,
8 H), 7.28–7.34 (m, 4 H), 7.54 (d, J = 9.0 Hz, 2 H), 7.71 (d, J =
8.4 Hz, 2 H), 8.07 (d, J = 8.4 Hz, 2 H), 8.27 (s, 1 H) ppm. 13C
NMR (75 MHz), (CDCl3): δ = 14.6, 62.7, 101.5, 116.0, 123.0,
123.7, 125.1, 128.0, 129.5, 132.0, 145.6, 147.2, 148.8, 154.6, 162.7
2-{[4Ј-Nitro-1,1Ј-biphenyl-4-yl]methylene}malononitrile (9b): M.p.
200–203 °C; yield 242 mg (88%). 1H NMR (CDCl3): δ = 7.79–7.84
(m, 5 H, ArH + CH), 8.06 (d, J = 8.5 Hz, 2 H), 8.37 (d, J = 9.0 Hz,
2 H) ppm. 13C NMR (75 MHz), (CDCl3): δ = 84.0, 112.9, 113.9,
124.8, 128.5, 128.9, 131.5, 131.8, 144.9, 145.5, 148.4, 159.1 ppm.
ppm. IR (nujol): ν
= 2225, 1726, 1589 cm–1. C30H24N2O2
˜
max
(444.52): calcd. C 81.06, H 5.44, N 6.30; found C 81.14, H 5.51, N
6.25.
IR (nujol): ν
= 2224, 1583 cm–1. C16H9N3O2 (275.07): calcd. C
˜
max
69.81, H 3.30, N 15.27; found C 69.92, H 3.38, N 15.21.
(E)-Ethyl 2-Cyano-3-(4Ј-methyl-1,1Ј-biphenyl-4-yl)acrylate (9j):
M.p. 134–136 °C; yield 186 mg (64%). 1H NMR (CDCl3): δ = 1.41
(t, J = 7.2 Hz, 3 H), 2.41 (s, 3 H), 4.38 (q, J = 7.2 Hz, 2 H), 7.27
(d, J = 8.1 Hz, 2 H), 7.53 (d, J = 8.1 Hz, 2 H), 7.68 (d, J = 8.4 Hz,
2 H), 8.04 (d, J = 8.4 Hz, 2 H), 8.23 (s, 1 H) ppm. 13C NMR
(75 MHz), (CDCl3): δ = 14.6, 21.6, 63.1, 102.4, 116.2, 127.4, 127.8,
130.2, 130.4, 132.2, 136.7, 139.1, 146.2, 154.8, 163.0 ppm. IR (nu-
2-{[4Ј-Methoxy-1,1Ј-biphenyl-4-yl]methylene}malononitrile
(9c):
M.p. 155–156 °C; yield 242 mg (93%). 1H NMR (CD3)2CO: δ =
3.86 (s, 3 H), 7.07 (d, J = 9.0 Hz, 2 H), 7.75 (d, J = 9.0 Hz, 2 H),
7.87 (d, J = 9.0 Hz, 2 H), 8.08 (d, J = 9.0 Hz, 2 H), 8.26 (s, 1 H)
ppm. 13C NMR [75 MHz, (CD3)2CO]: δ = 56.2, 81.9, 114.6, 115.5,
115.9, 128.2, 129.7, 131.1, 132.3, 132.8, 147.5, 161.2, 162.0 ppm.
IR (nujol): ν
= 2224, 1571 cm–1. C17H12N2O (260.09): calcd. C
jol): ν
= 2225, 1714, 1596 cm–1. C19H17NO2 (291.34): calcd. C
˜
˜
max
max
78.44, H 4.65, N 10.76; found C 78.48, H 4.68, N 10.80.
78.33, H 5.88, N 4.81; found C 78.23, H 5.86, N 4.71.
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Eur. J. Org. Chem. 2012, 2635–2642