I.J. Kobylianskii et al. / Journal of Fluorine Chemistry 132 (2011) 175–180
179
4.36 mmol). The product was isolated by column chromatography
(eluent hexane – Et2O, 3:1) followed by recrystallization from
CH2Cl2–hexane: a yellow solid, mp 232–234 8C. 1H NMR (DMSO-
5.80 mmol). The product was isolated by column chromatography
(eluent hexane – Et2O, 3:1) followed by recrystallization from
CH2Cl2–hexane: a yellow solid, mp 119–121 8C. 1H NMR (DMSO-
d6):
(1H, t, J = 7.3 Hz, Ph), 7.82 (2H, d, J = 7.3 Hz, Ph), 7.97 (1H, s, H-8),
8.53 (1H, d, J = 7.3 Hz, H-5). 13C NMR (DMSO-d6):
81.7 (d,
J = 7.7 Hz, C-2), 82.9 (d, J = 3.1 Hz, C-1), 110.1 (J = 4.6 Hz, CN), 112.6
(J = 2.0 Hz, CN), 114.1, 120.6, 122.7, 128.72, 128.73, 128.8, 129.6,
132.6, 133.3, 135.9, 142.9 (d, J = 279.3 Hz, C-3), 192.9 (COPh). 19F
d
7.39 (1H, d, J = 7.3 Hz, H-6), 7.59 (2H, t, J = 7.3 Hz, Ph), 7.74
d6):
d
7.31 (1H, dd, J = 7.4, 1.1 Hz, H-6), 8.51 (1H, d, J = 7.4 Hz, H-5),
82.6 (d, J = 8.0 Hz, C-2),
8.53 (1H, br s, H-8). 13C NMR (DMSO-d6):
d
d
83.7 (d, J = 3.0 Hz, C-1), 107.5 (CN), 109.3 (d, J = 4.0 Hz, CN), 111.6
(d, J = 2.0 Hz, CN), 114.5, 116.4, 122.9, 125.0, 127.7 (d, J = 4.0 Hz),
142.8 (d, J = 280.7 Hz, C-3). 19F NMR (DMF):
d
ꢀ128.5. IR (CHCl3);
n
2250 (CN) cmꢀ1. Anal. Calcd. for C11H3FN4: C, 62.9; H, 1.4; N, 26.7.
Found: C, 62.8; H, 1.4; N, 26.8.
NMR (DMF):
d
ꢀ129.7. IR (CHCl3);
n 2260, 2240 (CN), 1720
(C55O) cmꢀ1. Anal. Calcd. for C17H8FN3O: C, 70.6; H, 2.8; N, 14.5.
Found: C, 70.4; H, 2.7; N, 14.5.
5.8. Dimethyl 6-cyano-3-fluoroindolizine-1,2-dicarboxylate (3g) and
dimethyl 8-cyano-3-fluoroindolizine-1,2-dicarboxylate (3h)
5.4. 7-Ethyl-1,2-dimethyl 3-fluoroindolizine-1,2,7-tricarboxylate (3c)
A 1:1 mixture of indolizines 3g and 3h (0.125 g, 16%) was
obtained from pyridine-3-carbonitrile (0.3 g, 2.88 mmol) and
dimethyl maleate (0.83 g, 5.76 mmol). The mixture was isolated
by column chromatography (eluent hexane – Et2O, 3:1). After
additional separation by column chromatography (eluent hexane –
EtOAc, 5:1) followed by recrystallization from CH2Cl2–hexane
analytically pure samples of indolizines 3g and 3h were obtained.
Indolizine 3c (0.196 g, 23%) was obtained from ethyl pyridine-
4-carboxylate (0.4 g, 2.65 mmol) and dimethyl maleate (0.763 g,
5.3 mmol). The product was isolated by column chromatography
(eluent hexane – EtOAc, 5:1) followed by recrystallization from
Et2O–hexane: a yellow solid, mp 91–93 8C. 1H NMR (CDCl3):
d 1.42
(3H, t, J = 7.3 Hz, CH3), 3.94 (3H, s, CH3O), 3.96 (3H, s, CH3O), 4.41
(2H, q, J = 7.3 Hz, CH2), 7.38 (1H, d, J = 7.3 Hz, H-6), 7.86 (1H, d,
Compound 3g: a yellow solid, mp 119–121 8C. 1H NMR (CDCl3):
3.94 (3H, s, CH3), 3.98 (3H, s, CH3), 7.07 (1H, d, J = 9.8, H-8), 8.20
(1H, d, J = 9.8 Hz, H-7), 8.31 (1H, s, H-5). 13C NMR (CDCl3):
51.9
d
J = 7.3 Hz, H-5), 8.79 (1H, s, H-8). 13C NMR (CDCl3):
d 14.2 (CH3),
51.8 (CH3O), 52.5 (CH3O), 61.6 (CH2), 102.5 (d, J = 5.5 Hz, C-2),
103.4 (C-1), 112.8, 119.1 (d, J = 1.5 Hz), 123.4, 124.2 (d, J = 2.0 Hz),
125.9 (d, J = 2.5 Hz), 140.3 (d, J = 275.8 Hz, C-3), 162.2 (d, J = 4.0 Hz,
CO2Me), 163.3 (d, J = 3.0 Hz, CO2Me), 164.7 (CO2Et). 19F NMR
d
(CH3), 52.8 (CH3), 100.5, 102.2, 102.8 (d, J = 4.5 Hz, C-1), 104.8,
115.8, 121.1 (d, J = 2.0 Hz), 121.2, 126.3 (d, J = 6.0 Hz), 139.8 (d,
J = 277.3 Hz, C-3), 161.7 (d, J = 4.0 Hz, C55O), 163.0 (d, J = 3.0 Hz,
(DMF):
d
ꢀ137.6. IR (CHCl3);
n
1720 (C55O) cmꢀ1. Anal. Calcd. for
C55O). 19F NMR (DMF):
d
ꢀ134.6. Anal. Calcd. for C13H9FN2O4: C,
C15H14FNO6: C, 55.7; H, 4.4; N, 4.3. Found: C, 55.8; H, 4.3; N, 4.3.
56.5; H, 3.3; N, 10.1. Found: C, 56.3; H, 3.3; N, 10.0.
Compound 3h: a yellow solid, mp 152–154 8C. 1H NMR (CDCl3):
5.5. Ethyl 1,2-dicyano-3-fluoroindolizine-7-carboxylate (3d)
d
3.95 (3H, s, CH3), 4.01 (3H, s, CH3), 6.83 (1H, dd, J = 7.3, 6.5 Hz, H-
6), 7.44 (1H, d, J = 6.9 Hz, H-7), 8.03 (1H, d, J = 7.3 Hz, H-5). 13C NMR
(CDCl3): 52.0 (CH3), 52.5 (CH3), 101.0 (d, J = 4.5 Hz, C-2), 104.6,
Indolizine 3d (0.190 g, 28%) was obtained from ethyl 4-pyridine-
4-carboxylate (0.4 g, 2.65 mmol) and fumaronitrile (0.41 g,
5.28 mmol). The product was isolated by column chromatography
(eluent hexane – Et2O, 3:1) followed by recrystallization from
CH2Cl2–hexane: a cream-coloured solid, mp 139–141 8C. 1H NMR
d
104.8, 111.9, 115.1, 119.4, 123.6 (d, J = 2.0 Hz), 131.0 (d, J = 1.5 Hz),
140.2 (d, J = 277.3 Hz, C-3), 161.5 (d, J = 4.5 Hz, C55O), 162.9 (d,
J = 2.5 Hz, C55O). 19F NMR (DMF):
d
ꢀ132.5. Anal. Calcd. for
C
13H9FN2O4: C, 56.5; H, 3.3; N, 10.1. Found: C, 56.5; H, 3.3; N, 10.1.
(CDCl3):
7.56 (1H, dd, J = 7.3, 1.5 Hz, H-6), 7.99 (1H, d, J = 7.3 Hz, H-5), 8.37
(1H, br s, H-8). 13C NMR (CDCl3):
14.2 (CH3), 62.3 (CH2), 83.3 (d,
d 1.45 (3H, t, J = 7.3 Hz, CH3), 4.45 (2H, q, J = 7.3 Hz, CH2),
5.9. Dimethyl 1-fluoropyrrolo[1,2-a]quinoxaline-2,3-dicarboxylate
d
(6)
J = 7.8 Hz,C-2), 85.0(d, J = 2.6 Hz, C-1), 109.0(d, J = 4.5 Hz,CN), 111.8
(CN), 114.6, 120.0, 120.9, 126.5 (d, J = 4.5 Hz), 129.1 (d, J = 3.6 Hz),
Compound 3j (0.090 g, 10%) was obtained from quinoxaline
(0.386 g, 2.97 mmol) and dimethyl maleate (0.887 g, 6.16 mmol).
The product was isolated by column chromatography (eluent
hexane – Et2O, 3:1) followed by recrystallization from Et2O–
142.4 (d, J = 281.5 Hz, C-3), 163.5 (C55O). 19F NMR (DMF):
d
ꢀ127.6.
2260, 2240 (CN), 1730 (C55O) cmꢀ1. Anal. Calcd. for
13H8FN3O2: C, 60.7; H, 3.1; N, 16.3. Found: C, 60.8; H, 3.2; N, 16.3.
IR (CHCl3);
C
n
hexane: a yellow-red solid, mp 160–162 8C. 1H NMR (CDCl3):
(6H, s, 2CH3), 7.56–7.63 (2H, m), 8.00–8.03 (1H, m), 8.20–8.24 (1H,
m), 9.32 (1H, d, J = 2.9 Hz). 13C NMR (CDCl3):
52.2 (CH3), 52.5
d 3.98
5.6. Dimethyl 7-cyano-3-fluoroindolizine-1,2-dicarboxylate (3e)
d
Indolizine 3e (0.378 g, 48%) was obtained from pyridine-4-
carbonitrile (0.3 g, 2.88 mmol) and dimethyl maleate (0.83 g,
5.76 mmol). The product was isolated by column chromatography
(eluent hexane – Et2O, 3:1) followed by recrystallization from
(CH3), 101.5 (d, J = 8.0 Hz, C-2), 107.3 (C-3), 116.3, 116.4, 124.8 (d,
J = 3.0 Hz), 127.4, 129.0 (d, J = 4.0 Hz), 130.4, 136.5, 144.5 (d,
J = 282.7 Hz, C-1), 145.2, 161.8 (d, J = 4.0 Hz, C55O), 162.7 (d,
J = 3.0 Hz, C55O). 19F NMR (CDCl3):
d
ꢀ121.5. IR (CHCl3);
n 1720
Et2O–hexane: a yellow solid, mp 174–176 8C. 1H NMR (CDCl3):
3.94 (3H, s, CH3), 3.97 (3H, s, CH3), 6.91 (1H, dd, J = 7.3, 1.5 Hz, H-6),
7.92 (1H, d, J = 7.3 Hz, H-5), 8.51 (1H, br s, H-8). 13C NMR (CDCl3):
d
(C55O) cmꢀ1. Anal. Calcd. for C15H11FN2O4: C, 59.6; H, 3. 7; N, 9.3.
Found: C, 59.6; H, 3.8; N, 9.1.
d
52.0 (CH3), 52.7 (CH3), 103.4 (d, J = 6.0 Hz, C-2), 104.1 (CN), 105.2
(d, J = 2.0 Hz, C-1), 113.2, 117.3, 120.3, 124.6 (d, J = 2.0 Hz), 127.5,
140.5 (d, J = 276.3 Hz, C-3), 161.6 (d, J = 4.0 Hz, C55O), 162.6 (d,
Acknowledgements
We gratefully acknowledge Federal Targeted Programme
‘‘Scientific and Scientific-Pedagogical Personnel of the Innovative
Russia in 2009–2013’’ (contract no. 16.740.11.0442) and the
Russian Foundation for Basic Research (project no. 11-03-00186)
for support of this research.
J = 3.0 Hz, C55O). 19F NMR (DMF):
d
ꢀ132.8. IR (CHCl3);
n 1730
(C55O) cmꢀ1. Anal. Calcd. for C13H9FN2O4: C, 56.5; H, 3.3; N, 10.1.
Found: C, 56.5; H, 3.3; N, 10.0.
5.7. 3-Fluoroindolizine-1,2,7-tricarbonitrile (3f)
References
Indolizine 3f (0.260 g, 43%) was obtained from pyridine-4-
carbonitrile (0.3 g, 2.88 mmol) and fumaronitrile (0.45 g,
[1] R.W. Fessenden, R.H. Schuler, J. Chem. Phys. 43 (1965) 2704–2712.