The Journal of Organic Chemistry
Note
Scheme 2. Proposed Mechanism of the Cyclization Reaction To Form Pyrroles
(E)-Methyl 4-(2-chloroacetoxy)-8-phenyloct-2-en-7-ynoate (1a):
Rf = 0.60 (25% EtOAc in petroleum ether); viscous oil; 1H NMR (400
MHz, CDCl3, ppm) δ 7.39−7.38 (m, 2H), 7.28−7.26 (m, 3H), 6.89
(ddd, J = 7.9 Hz, 5.6 Hz, 0.8 Hz, 1H), 6.07−6.02 (m, 2H), 5.68−5.65
(m, 1H), 4.09 (s, 2H), 3.72 (s, 3H), 2.50 (t, J = 7.2 Hz, 2H), 2.04−
1.99 (m, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 166.2, 165.8,
143.5, 131.4, 128.1, 127.7, 123.2, 122.2, 87.5, 81.8, 73.1, 51.6, 40.6,
32.3, 15.1; IR (KBr) 3002w, 2952 m, 2233vw, 1726s, 1169s cm−1;
LRMS (ESI), m/z 321.2 [M + H]+; HRMS (ESI) calcd for
C17H17ClNaO4 [M + Na]+ 343.0708, found 343.0713.
2926s, 1736s, 1435s, 1155s, 730 m, 698 m cm−1; HRMS (ESI) calcd
for C16H19NO2 [M + H]+ 258.1489, found 258.1496.
Methyl 3-(5-methyl-1-phenethyl-1H-pyrrol-2-yl)propanoate (3c):
1
Rf = 0.30 (10% acetone in petroleum ether); viscous oil; H NMR
(400 MHz, CDCl3, ppm) δ 7.34−7.24 (m, 3H), 7.12 (d, J = 6.8 Hz,
2H), 5.80 (d, J = 6.8 Hz, 2H), 3.99 (t, J = 7.6 Hz, 2H), 3.72 (s, 3H),
2.89 (t, J = 7.6 Hz, 2H), 2.84−2.80 (m, 2H), 2.69−2.65 (m, 2H), 2.15
(s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ 173.4, 138.3, 130.1,
128.8, 128.6, 127.9, 126.7, 105.5, 103.9, 51.7, 45.1, 37.6, 33.0, 21.8,
12.3; IR (KBr) 3026w, 2924s, 1734s, 1615s, 1435s, 1160s, 752 m, 700
m cm−1; HRMS (ESI) calcd for C17H21NO2 [M + H]+ 272.1645,
found 272.1650.
(E)-Methyl 4-(2-chloroacetoxy)oct-2-en-7-ynoate (1b): Rf = 0.60
1
(35% EtOAc in petroleum ether); viscous oil; H NMR (400 MHz,
CDCl3, ppm) δ 6.82 (dd, J = 6.0 Hz, 15.8 Hz, 1H), 6.01 (dd, J = 15.8
Hz, 1.2 Hz, 1H), 4.10 (s, 2H), 3.73 (s, 3H),2.79−2.27 (m, 2H), 2.01
(t, J = 2.8 Hz, 1H), 1.95−1.93 (m, 2H); 13C NMR (100 MHz, CDCl3,
ppm) δ 166.2, 165.8, 143.3, 122.3, 82.0, 72.9, 69.7, 51.7, 40.6, 32.0,
14.2; IR (KBr) 3296s, 2944 m, 2119vw, 1726s, 1169s cm−1; LRMS
(ESI), m/z 262.2 [M + NH4]+; HRMS (ESI) calcd for C11H13ClNaO4
[M + Na]+ 267.0395, found 267.0397.
Methyl 3-(1-allyl-5-methyl-1H-pyrrol-2-yl)propanoate (3d): Rf =
0.33 (10% acetone in petroleum ether); viscous oil; H NMR (400
1
MHz, CDCl3, ppm) δ 5.94−5.85 (m, 1H), 5.83−5.81 (m, 1H), 5.12
(dd, J = 10.4 Hz, 1.2 Hz, 1H), 4.70 (dd, J = 17.2 Hz, 1.2 Hz, 1H),
4.41−4.39 (m, 2H), 3.70 (s, 3H), 2.86−2.82 (m, 2H), 2.68−2.64 (m,
2H), 2.18 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ 173.4, 134.0,
130.4, 128.3, 115.7, 105.3, 104.0, 51.6, 45.4, 33.2, 21.8, 12.1; IR (KBr)
2924s, 2854 m, 1735s, 1616s, 1437s, 1159s cm−1; HRMS (ESI) calcd
for C12H17NO2 [M + H]+ 208.1332, found 208.1329.
(E)-Methyl 4-acetoxy-8-phenyloct-2-en-7-ynoate (1c): Rf = 0.60
1
(25% EtOAc in petroleum ether); viscous oil; H NMR (400 MHz,
CDCl3, ppm) δ 7.40−7.37 (m, 2H), 7.29−7.26 (m, 3H), 6.90 (dd, J =
16.0 Hz, 5.6 Hz, 1H), 6.00 (dd, J = 15.6 Hz, 1.6 Hz, 1H), 5.62−5.57
(m, 1H), 3.74 (s, 3H), 2.50 (t, J = 6.8 Hz, 2H), 2.11 (s, 3H), 1.99 (q, J
= 6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 169.9, 166.3,
144.9, 131.6, 128.2, 127.8, 123.5, 121.7, 88.0, 81.7, 71.4, 51.7, 32.7,
20.9, 15.4; IR (KBr) 2923s, 2853 m, 1728s, 1231s,758 m cm−1; LRMS
(ESI), m/z 304.2 [M + NH4]+; HRMS (ESI) calcd for C17H18NaO4
[M + Na]+ 309.1097, found 309.1096.
Methyl 3-(1-(furan-2-ylmethyl)-5-methyl-1H-pyrrol-2-yl)-
propanoate (3e): Rf = 0.28 (10% acetone in petroleum ether);
1
viscous oil; H NMR (400 MHz, CDCl3, ppm) δ 7.34 (d, J = 1.2 Hz,
1H), 6.29 (dd, J = 3.2 Hz, 1.8 Hz, 1H), 6.03 (d, J = 3.2 Hz, 0.8 Hz,
1H), 5.83−5.82 (m, 2H), 4.95 (s, 2H), 3.70 (s, 3H), 2.96−2.92 (m,
2H), 2.68−2.64 (m, 2H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3,
ppm) δ 173.4, 151.1, 142.2, 130.7, 128.5, 110.3, 107.0, 105.7, 104.3,
51.6, 40.5, 33.1, 21.9, 12.3; IR (KBr) 2923s, 2854 m, 1733s, 1616s,
1436s, 1167s, 747 m, 664 m cm−1; HRMS (ESI) calcd for C14H17NO3
[M + H]+ 248.1281, found 248.1282.
7-Phenylhept-1-en-6-yn-3-yl 2-chloroacetate (1d): Rf = 0.65 (25%
1
EtOAc in petroleum ether); viscous oil; H NMR (400 MHz, CDCl3,
ppm) δ 7.40−7.38 (m, 2H), 7.29−7.25 (m, 3H), 5.85−5.78 (m, 1H),
5.50 (q, J = 6.8 Hz, 1H), 5.35 (d, J = 13.2 Hz, 1H), 5.26 (d, J = 10.4
Hz, 1H), 4.06 (s, 2H), 2.50−2.46 (m, 2H), 2.04−1.92 (m, 2H); 13C
NMR (100 MHz, CDCl3, ppm) δ 166.4, 134.8, 131.5, 128.2, 127.7,
123.5, 118.2, 88.2, 81.4, 75.7, 40.9, 32.8, 15.4; IR (KBr) 3081w, 2927
m, 2230w, 1756s, 1175s, 757 m cm−1; LRMS (ESI), m/z 280.3 [M +
NH4]+; HRMS (ESI) calcd for C15H15ClNaO2 [M + Na]+ 285.0653,
found 285.0652.
Methyl 3-(1-(2-(1H-indol-3-yl)ethyl)-5-methyl-1H-pyrrol-2-yl)-
propanoate (3f): Rf = 0.20 (10% acetone in petroleum ether);
viscous oil; 1H NMR (400 MHz, CDCl3, ppm) δ 8.03 (brs, 1H), 7.56
(d, J = 8.0 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 7.21 (td, J = 8.0 Hz, 0.8
Hz, 1H), 7.14 (td, J = 8.0 Hz, 0.8 Hz, 1H), 5.81 (d, J = 3.2 Hz, 1H),
5.79 (d, J = 3.2 Hz, 1H), 4.06−4.02 (m, 2H), 3.69 (s, 3H), 3.07−3.03
(m, 2H), 2.87 (t, J = 8.0 Hz, 2H), 2.67−2.64 (m, 2H), 2.20 (s, 3H);
13C NMR (100 MHz, CDCl3, ppm) δ 173.5, 136.2, 130.2, 128.0,
Methyl 3-(1,5-dibenzyl-1H-pyrrol-2-yl)propanoate (3a): Rf = 0.28
(10% acetone in petroleum ether); Viscous oil; H NMR (400 MHz,
127.2, 122.1, 122.0, 119.6, 118.5, 112.5, 111.2, 105.4, 103.9, 51.7, 44.2,
33.1, 27.0, 21.9, 12.4; IR (KBr) 3365s, 2923s, 2854 m, 1732s, 1614s,
1432s, 1160s, 744s cm−1; HRMS (ESI) calcd for C19H22N2O2 [M +
H]+ 311.1754, found 311.1747.
Methyl 3-(5-methyl-1-phenyl-1H-pyrrol-2-yl)propanoate (3g): Rf
= 0.25 (10% acetone in petroleum ether); Viscous oil; 1H NMR (400
MHz, CDCl3, ppm) δ 7.50−7.40 (m, 3H), 7.24−7.22 (m, 2H), 5.93
(s, 2H), 3.63 (s, 3H), 2.72−2.68 (m, 2H), 2.52−2.48 (m, 2H), 2.02 (s,
3H); 13C NMR (100 MHz, CDCl3, ppm) δ 173.3, 138.5, 131.6, 129.4,
129.2, 128.3, 128.0, 105.7, 104.8, 51.6, 33.3, 22.4, 12.8; IR (KBr)
3061w, 2950s, 2923s, 2853 m, 1735s, 1618s, 1435s, 1162s, 771 m, 699
m cm−1; HRMS (ESI) calcd for C15H17NO2 [M + H]+ 244.1332,
found 244.1335.
1
CDCl3, ppm) δ 7.27−7.21 (m, 6H), 7.18 (d, J = 7.2 Hz, 2H), 6.81 (d,
J = 7.2 Hz, 2H), 5.90 (d, J = 3.2 Hz, 1H), 5.87 (d, J = 3.2 Hz, 1H),
4.94 (s, 2H), 3.79 (s, 2H), 3.64 (s, 3H), 2.78 (t, J = 8.4 Hz, 2H), 2.60
(t, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 173.3,
139.4, 138.3, 131.5, 131.46, 128.7, 128.5, 128.4, 127.1, 126.2, 125.5,
107.3, 104.6, 51.6, 46.7, 33.2, 33.1, 21.9; IR (KBr) 3027w, 2923s,
1736s, 1164s cm−1; HRMS (ESI) calcd for C21H20N2O4S [M + H]+
397.1217, found 397.1209.
Methyl 3-(1-benzyl-5-methyl-1H-pyrrol-2-yl)propanoate (3b): Rf
1
= 0.25 (10% acetone in petroleum ether); viscous oil; H NMR (400
MHz, CDCl3, ppm) δ 7.30−7.24 (m, 3H), 6.87 (d, J = 7.2 Hz, 2H),
5.89 (d, J = 7.2 Hz, 1H), 5.88 (d, J = 7.2 Hz, 1H), 5.06 (s, 2H), 3.66
(s, 3H), 2.80 (t, J = 8.0 Hz, 2H), 2.62−2.58 (m, 2H), 2.15 (s, 3H); 13C
NMR (100 MHz, CDCl3, ppm) δ 173.3, 138.3, 130.8, 128.8, 127.1,
125.6, 105.7, 104.4, 51.6, 46.6, 33.2, 22.0, 12.3; IR (KBr) 3029w,
Methyl 3-(5-methyl-1-(naphthalen-1-yl)-1H-pyrrol-2-yl)-
propanoate (3h): Rf = 0.22 (10% acetone in petroleum ether);
viscous oil; 1H NMR (400 MHz, CDCl3, ppm) δ 7.94 (dd, J = 8.0 Hz,
4.8 Hz, 2H), 7.59−7.51 (m, 2H), 7.48−7.42 (m, 2H), 7.10 (d, J = 8.4
4169
dx.doi.org/10.1021/jo300374v | J. Org. Chem. 2012, 77, 4167−4170