The Journal of Organic Chemistry
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pressure, and the crude mixture was purified using flash column
chromatography (EtOAc/petrol (1:1)) to give product 4h (1.076 g,
98%) as a colorless viscous oil: Rf = 0.44 (EtOAc/petrol (1:1)); IR
(neat) νmax 3397, 3042, 2934, 2852, 2234, 1607, 1589, 1464, 1368,
CHAr), 68.8 (CHN), 49.8 (2 × CH2N), 26.6 (2 × CH2), 24.6 (CH2);
HRESIMS calcd for C20H22NO (M + H)+ 292.1701; found 292.1710.
1-(2-Benzylidene-2,3-dihydrobenzofuran-3-yl)pyrrolidine
(5c). A mixture of AgNO3 (229 mg, 1.35 mmol) and 4c (1.883 g, 6.79
mmol) in anhydrous DMF (30 mL) was heated under N2 at 60 °C for
1 h. The solvent was removed under reduced pressure, and the crude
mixture was purified using flash column chromatography (EtOAc/
petrol (1:19)) to give product 5c (1.221 g, 65%) as a brown viscous
oil: Rf = 0.23 (EtOAc/petrol (1:4)); IR (neat) νmax 3053, 2965, 2811,
1686, 1611, 1594, 1461, 1347, 1228, 1210, 1069, 748, and 692 cm−1;
1H NMR (300 MHz) δ 7.72 (2H, d, J = 7.5 Hz, ArH), 7.41 (1H, d, J =
7.0 Hz, ArH), 7.35 (2H, J = 7.5 Hz, d, ArH), 7.25 (1H, t, J = 7.5 Hz,
ArH), 7.04 (1H, d, J = 7.5 Hz, ArH), 7.00 (1H, t, J = 7.0 Hz, ArH),
5.83 (1H, s, CCHAr), 5.16 (1H, s, CHN), 2.77−2.62 (4H, m, 2 ×
CH2N), 1.78−1.72 (4H, m, 2 xCH2); 13C NMR (75 MHz) δ 158.3
(CCHAr), 154.8 (ArCO), 135.2 (ArC), 129.5 (ArCH), 128.6 (2 ×
ArCH), 128.5 (2 × ArCH), 126.3 (ArCH), 126.2 (ArCH), 125.6
(ArC), 122.2 (ArCH), 110.3 (ArCH), 105.7 (CCHAr), 63.9
(CHN), 48.2 (2 × CH2N), 23.5 (2 × CH2); HRESIMS calcd for
C19H20NO (M + H)+ 278.1545; found 278.1544.
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1274, 1246, 1154, 1058, 981, 858, and 805 cm−1; H NMR (500
MHz) δ 7.44 (1H, d, J = 8.00 Hz, ArH), 7.18 (1H, t, J = 8.00 Hz,
ArH), 6.84−6.80 (2H, m, ArH), 4.82 (1H, s, CHN), 3.81 (2H, t, J =
6.0 Hz, CH2CH2OH), 2.63−2.58 (4H, m, 2 × CH2N), 2.50−2.47 (2H
m, CH2), 1.86 (2H, quint, J = 6.5 Hz, CH2), 1.64 (4H, brs, 2 × CH2),
1.50 (2H, brs, CH2); 13C NMR (125 MHz) δ 157.7 (ArCOH), 129.3
(ArCH), 128.4 (ArCH), 121.9 (ArC), 119.0 (ArCH), 116.3 (ArCH),
89.5 (CCCH2), 73.4 (CCCH2), 61.8 (CH2OH), 60.8 (CHN),
31.8 (CH2), 26.0 (2 × CH2), 24.1 (CH2), 15.5 (CH2), [signals for 2 ×
CH2N were not observed due to line broadening]; HRESIMS calcd for
C17H24NO2 (M + H)+ 274.1807; found 274.1796.
2-(1-(Dibutylamino)-3-phenylprop-2-yn-1-yl)phenol (4i). A
mixture of Zn(OAc)2·2H2O (88 mg, 0.4 mmol), salicylaldehyde
(489 mg, 4.0 mmol), phenylacetylene (613 mg, 6.0 mmol), and
dibutylamine (672 mg, 5.2 mmol) in anhydrous toluene (10 mL) was
heated under N2 at 120 °C for 18 h. The solvent was removed under
reduced pressure, and the crude mixture was purified using flash
column chromatography (EtOAc/petrol (1:19)) to give product 4i
(1.20 g, 90%) as a yellow viscous oil: Rf = 0.20 (EtOAc/petrol (1:4));
IR (neat) νmax 3054, 2961, 2848, 2232, 1588, 1473, 1257, 1245, 1115,
1-(2-Benzylidene-2,3-dihydrobenzofuran-3-yl)pyrrolidine
(5c) and 1-(Benzofuran-2-yl(phenyl)methyl)pyrrolidine (6c). A
mixture of AgNO3 (35 mg, 0.21 mmol) and 4c (285 mg, 1.03 mmol)
in anhydrous DMF (5 mL) was heated under N2 at 100 °C for 18 h.
The solvent was removed under reduced pressure, and the crude
mixture was purified using flash column chromatography (5% EtOAc/
petrol) to give 5c (102 mg, 35.8%) and 6c (6 mg, 2.1%). Compound
6c: a viscous yellow oil; Rf = 0.38 (20% EtOAc/petrol); IR (neat) νmax
3052, 3029, 2965, 2874, 2786, 1584, 1492, 1452, 1251, 1134, 801, 744,
1
1072, 689, and 636 cm−1; H NMR (300 MHz) δ 11.35 (1H, brs,
ArOH), 7.60 (1H, d, J = 7.5 Hz, ArH), 7.55−7.52 (2H, m, ArH),
7.34−7.32 (3H, m, ArH), 7.23 (1H, t, J = 7.5 Hz, ArH), 6.88−6.83
(4H, m, 2 × CH2N) 5.30 (1H, s,CHN), 2.72−2.52 (4H, m, 2 ×
CH2N), 1.68−1.49 (4H, m, 2 × CH2); 1.48−1.21 (4H, m, 2 × CH2),
0.90 (6H, t, J = 7.5 Hz, 2 × CH2CH3); 13C NMR (75 MHz) δ 157.4
(ArCO), 131.9 (2 × ArCH), 129.4 (ArCH), 128.6 (2 × ArCH), 128.4
(2 × ArCH), 122.7 (ArC), 122.0 (ArC), 119.1 (ArCH), 116.4 (ArCH),
89.2 (CCAr), 82.8 (CCAr), 57.1 (CHN), 51.0 (2 × CH2N), 30.0
(2 × CH2CH2CH2), 20.7 (2 × CH2CH3), 14.0 (2 × CH2CH3);
HRESIMS calcd for C23H30NO (M + H)+ 336.2327; found 336.2343.
4-(2-Benzylidene-2,3-dihydrobenzofuran-3-yl)morpholine
(5a). A mixture of AgNO3 (240 mg, 1.41 mmol) and 4a (2.00 g, 6.82
mmol) in anhydrous DMF (30 mL) was heated under N2 at 60 °C for
1 h. The solvent was removed under reduced pressure, and the crude
mixture was purified using flash column chromatography (EtOAc/
petrol (1:4)) and then crystallization with EtOAc/petrol to give
product 5a (1.80 g, 90%) as colorless crystals: mp 104−106 °C; Rf =
0.23 (EtOAc/petrol (1:19)); IR (neat) νmax 3035, 2939, 2849, 1681,
1
and 701 cm−1; H NMR (CDCl3, 300 MHz) δ 7.56 (2H, d, J = 7.50
Hz, ArH), 7.46 (2H, t, J = 7.50 Hz, ArH), 7.34−7.16 (5H, m, ArH),
6.63 (1H, s, CCH), 4.42 (1H, s, CHN), 2.52 (4H, brs, 2 × CH2N),
1.80 (4H, brs, 2 × CH2); 13C NMR (CDCl3, 75 MHz) δ 158.8 (OC
CH), 154.9 (ArCO), 140.6 (ArC), 128.5 (2 × ArCH), 128.3 (ArC),
128.3 (2 × ArCH), 127.7 (ArCH), 123.8 (ArCH), 122.7 (ArCH),
120.8 (ArCH), 111.5 (ArCH), 103.6 (OCCH), 69.4 (CHN), 53.5
(2 × CH2N), 23.5 (2 × CH2); HRESIMS calcd for C19H20NO (M +
H)+ 278.1545; found 278.1553.
4-(2-(4-Fluorobenzylidene)-2,3-dihydrobenzofuran-3-yl)-
morpholine (5d). A mixture of AgNO3 (22 mg, 0.13 mmol) and 4d
(203 mg, 0.65 mmol) in anhydrous DMF (5 mL) was heated under N2
at 60 °C for 1 h. The solvent was removed under reduced pressure,
and the crude mixture was purified using flash column chromatog-
raphy (EtOAc/petrol (15:85)) and then crystallization with EtOAc/
petrol to give product 5d (165 mg, 81%) as a pale yellow solid: mp
128−130 °C; Rf = 0.15 (EtOAc/petrol (1:4)); IR (neat) νmax 3063,
2973, 2932, 2823, 1690, 1593, 1508, 1457, 1340, 1228, 1210, 1106,
909, and 850 cm−1; 1H NMR (300 MHz) δ 7.71−7.66 (2H, m, ArH),
7.43 (1H, d, J = 7.8 Hz, ArH), 7.30 (1H, t, J = 7.8 Hz, ArH), 7.09−
7.02 (4H, m, ArH), 5.84 (1H, s,CCHAr), 4.98 (1H, s, CHN), 3.71−
3.68 (4H, m, 2 × CH2O), 2.79−2.72 (2H, m, CH2N), 2.58−2.51 (2H,
m, CH2N); 13C NMR (CDCl3, 75 MHz) δ 161.4 (d, J = 245 Hz,
ArCF), 158.2 (ArCO), 153.5 (CCHAr), 131.2 (ArC), 130.2
(ArCH), 130.1 (ArCH), 129.8 (ArCH), 126.3 (ArCH), 124.5 (ArC),
122.4 (ArCH), 115.5 (d, J = 21 Hz, ArCH), 115.2 (ArCH), 110.3
(ArCH), 104.6 (CCHAr), 68.2 (CHN), 67.5 (2 × CH2O), 48.8 (2
× CH2N); HRESIMS calcd for C19H19NO2F (M + H)+ 312.1400;
found 312.1413.
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1608, 1447, 1339, 1229, 1209, 1109, 727, and 690 cm−1; H NMR
(300 MHz) δ 7.70 (2H, d, J = 8.0 Hz, ArH), 7.35 (1H, d, J = 7.0 Hz,
ArH), 7.34 (2H, t, J = 7.5 Hz, ArH), 7.25 (1H, t, J = 7.5 Hz, ArH),
7.17 (1H, t, J = 7.0 Hz, ArH), 7.00 (1H, d, J = 8.0 Hz, ArH), 6.99 (1H,
d, J = 7.5 Hz, ArH), 5.85 (1H, s, CCHAr), 4.95 (1H, s, CHN),
3.75−3.65 (4H, m, 2 × CH2O), 2.80−2.66 (2H, m, CH2N), 2.60−2.50
(2H, m, CH2N); 13C NMR (75 MHz) δ 158.2 (ArC), 153.8 (C
CHAr), 135.0 (ArC), 129.7 (ArCH), 128.5 (2 × ArCH), 128.46 (2 ×
ArCH), 126.4 (ArCH), 126.2 (ArCH), 124.4 (ArC), 122.3 (ArCH),
110.3 (ArCH), 105.7 (CCHAr), 68.2 (CHN), 67.4 (2 × CH2O),
48.8 (2 × CH2N); HRESIMS calcd for C19H20NO2 (M + H)+
294.1494; found 294.1490.
1-(2-Benzylidene-2,3-dihydrobenzofuran-3-yl)piperidine
(5b). A mixture of AgNO3 (161 mg, 0.95 mmol) and 4b (1.385 g, 4.75
mmol) in anhydrous DMF (25 mL) was heated under N2 at 60 °C for
1 h. The solvent was removed under reduced pressure, and the crude
mixture was purified using flash column chromatography (EtOAc/
petrol (1:9)) to give product 5b (1.086 g, 78%) as a pale yellow solid:
mp 78−80 °C; Rf = 0.25 (EtOAc/petrol (1:9)); IR (neat) νmax 3050,
2942, 2808, 1686, 1606, 1590, 1459, 1331, 1227, 1209, 753, and 691
4-(Benzofuran-2-yl(4-methoxyphenyl)methyl)morpholine
(6e). A mixture of AgNO3 (21 mg, 0.12 mmol) and 4e (203 mg, 0.63
mmol) in anhydrous DMF (5 mL) was heated under N2 at 60 °C for 1
h. The solvent was removed under reduced pressure, and the crude
mixture was purified using flash column chromatography (EtOAc/
petrol (1:9)) to give product 6e (137 mg, 68%) as a viscous yellow oil:
Rf = 0.28 (EtOAc/petrol (1:4)); IR (neat) νmax 3065, 3035, 2956,
2851, 2806, 1607, 1509, 1452, 1247, 1172, 1114, 1032, 1005, 811, and
1
cm−1; H NMR (300 MHz) δ 7.73 (2H, d, J = 8.0 Hz, ArH), 7.42−
7.33 (3H, m, ArH), 7.26−7.19 (2H, m, ArH), 7.04−7.01 (2H, m,
ArH), 5.85 (1H, s, CCHAr), 4.96 (1H, s, CHN), 2.72−2.63 (2H, m,
CH2N), 2.52−2.42 (2H, m, CH2N), 1.59−1.50 (4H, m, 2 × CH2),
1.43−1.34 (2H, m, CH2); 13C NMR (75 MHz) δ 158.2 (ArCO), 154.9
(OCCH), 135.4 (ArC), 129.4 (ArCH), 128.5 (2 × ArCH), 126.2 (2
× ArCH), 125.4 (ArC), 122.1 (ArCH), 110.1 (ArCH), 105.0 (C
1
746 cm−1; H NMR (300 MHz) δ 7.50−7.42 (4H, m, ArH), 7.23−
7.14 (2H, m, ArH), 6.86 (2H, d, J = 8.7 Hz, ArH), 6.63 (1H, s, C
CHAr), 4.45 (1H, s, CHN), 3.76 (3H, s, OCH3), 3.72 (4H, t, J = 4.5
Hz, 2 × CH2O), 2.52−2.38 (2H, m, 2 × CH2N); 13C NMR (CDCl3,
1144
dx.doi.org/10.1021/jo302554v | J. Org. Chem. 2013, 78, 1138−1148