N. Suthiwangcharoen, A. C. Bean, M. Hassan, C. K. Eidell, and C. E. Stephens
Vol 000
1-(2-Chlorobenzyl)-5-hydroxy-4,5-dimethyl-2-oxo-2,5-
dried (Na2SO4) and evaporated onto silica gel (high
vacuum). Column chromatography (SiO2) eluting with
hexanes:EtOAc (2:1) gave, after concentration of pure
dihydro-1H-pyrrole-3-carbonitrile (3c).
This compound
was obtained as pale golden crystals, mp 143–144°C
(diethyl ether); IR (cmÀ1): 3235, 2988, 2232, 1678, 1432,
fractions, the product as
a
yellow/brown solid
1
1394, 1163, 1050, 1038, 949, 746; H NMR: 1.30 (s, 3H),
(0.185 g, 78%), mp 128–129°C. Recrystallization from
EtOH/water gave an olive green solid, mp 130–131°C
(Lit mp: 130–131°C) [14]. A second recrystallization
from a larger volume of hexanes gave fine yellow
crystals, mp 131–133°C; IR (cmÀ1): 3058, 3009,
2968, 2939, 2225, 1715, 1633, 1612, 1354, 1190,
1129, 865, 760, 706, 640; 1H NMR: 2.32 (s, 3H),
2.78 (t, 2H), 3.79 (t, 2H), 5.48 (d, J = 2.9 Hz, 1H),
5.51 (d, J = 2.9 Hz, 1H), 7.18–7.26 (m, 5H); 13C
NMR: 12.0, 33.5, 40.6, 101.8, 105.8, 112.4, 126.3,
128.2, 128.7, 138.1, 143.4, 158.9, 163.2. This reaction
could also be accomplished in comparable yield using
POCl3.
2.22 (s, 3H), 4.51 (s, 2H), 6.65 (s, 1H), 7.23–7.30 (m, 3H),
7.41–7.45 (m, 1H); 13C NMR: 12.7, 21.9, 39.3, 89.8,
107.0, 112.4, 127.2, 128.5, 128.7, 129.1, 131.4, 134.7,
162.9, 176.0. Anal. Calcd. for C14H13ClN2O2 (276.72): C,
60.77; H, 4.74; N, 10.12. Found: C, 60.60; H, 4.87; N, 10.04.
1-(2-Bromobenzyl)-5-hydroxy-4,5-dimethyl-2-oxo-2,5-
dihydro-1H-pyrrole-3-carbonitrile (3d).
This compound
was obtained as a fine golden crystalline solid, mp 154–
156°C (diethyl ether); IR (cmÀ1): 3253, 2988, 2232,
1
1674, 1436, 1393, 1162, 1028, 950, 744; H NMR: 1.31
(s, 3H), 2.24 (s, 3H), 4.49 (s, 2H), 6.68 (s, 1H), 7.19–
7.25 (m, 2H), 7.32–7.37 (m, 1H), 7.61 (d, J = 7.8 Hz,
1H); 13C NMR: 12.7, 21.9, 41.9, 89.7, 106.9, 112.4,
121.6, 127.7, 128.4, 128.9, 132.3, 136.2, 162.9, 176.0.
Anal. Calcd. for C14H13BrN2O2 (321.17): C, 52.36; H,
4.08; N, 8.72. Found: C, 52.34; H, 4.05; N, 8.62.
Acknowledgments. We thank undergraduate students Reshma
Benny and Allyson Knapp for technical lab assistance. We also
thank our department for partial funding of this work.
5-Hydroxy-4,5-dimethyl-2-oxo-1-phenethyl-2,5-dihydro-1H-
pyrrole-3-carbonitrile (3e). This compound was obtained as
a pale orange crystalline solid, mp 136–137°C (diethyl ether);
REFERENCES AND NOTES
IR (cmÀ1): 3262, 3020, 2996, 2940, 2232, 1681, 1416, 1158,
1
1103, 753, 701; H NMR: 1.32 (s, 3H), 2.17 (s, 3H), 2.88
[1] Roth, H. J.; Eger, K. Arch Pharm 1975, 308, 179.
(t, 2H), 3.49 (t, 2H), 6.53 (s, 1H), 7.17–7.33 (m, 5H); 13C
NMR: 12.6, 21.7, 34.5, 89.7, 106.9, 112.4, 126.2, 128.4,
128.6, 139.0, 162.3, 175.6 (one signal obscured by DMSO
peaks). Anal. Calcd. for C15H16N2O2 (256.30): C, 70.29; H,
6.29; N, 10.93. Found: C, 70.36; H, 6.19; N, 10.94.
[2] Laks, J. S.; Ross, J. R.; Bayomi, S. M.; Sowell, J. W. Synthesis
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[3] Mattson, R. J.; Wang, L. C.; Sowell, J. W. J Heterocyclic
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1-Butyl-5-hydroxy-4,5-dimethyl-2-oxo-2,5-dihydro-1H-
pyrrole-3-carbonitrile (3f). This compound was obtained
[5] Ross, J. R.; Laks, J. S.; Wang, D. L.; Sowell, J. W. Synthesis
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as golden micro-needles, mp 76–78°C (diethyl
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ether/hexanes); IR (cmÀ1): 3324, 2961 2875, 2231, 1688,
1
[7] Ross, J. R.; Vishwakarma, L. C.; Sowell, J. W. J Heterocyclic
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1449, 1409, 1375, 1153, 1095, 766; H NMR: 0.87 (t,
3H), 1.27 (m, 2H), 1.39 (s, 3H), 1.52 (m, 2H), 3.14 (m,
1H), 3.26 (m, 1H), 6.44 (s, 1H); 13C NMR: 12.6, 13.7,
19.8, 21.9, 30.7, 38.3, 89.8, 107.0, 112.6, 162.2, 175.4.
Anal. Calcd. for C11H16N2O2 (208.26): C, 63.44; H, 7.74;
N, 13.45. Found: C, 63.28; H, 7.61; N, 13.18.
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DEHYDRATION OF LACTAM 3E TO
5-METHYLENE-γ-LACTAM 4E
[13] Suthiwangcharoen, N.; Pochini, S. M.; Sweat, D. P.; Stephens,
C. E. J Heterocyclic Chem 2011, 48, 706.
4-Methyl-5-methylene-2-oxo-1-phenethyl-2,5-dihydro-1H-
[14] Adhikari, R.; Jones, D. A.; Liepa, A. J.; Nearn, R. H. Aust J
Chem 2005, 58, 882.
pyrrole-3-carbonitrile (4e).
To
a
solution of 5-
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hydroxylactam 3e (0.256 g, 1.0 mmol) in dry acetonitrile
(5 mL) was added thionyl chloride (0.1 mL, 1.37 mmol)
and the mixture was refluxed for 40 min. The darkened
solution was then concentrated in vacuo to a brown oil,
which was dissolved in EtOAc and washed with
sodium bicarbonate solution. The solution was then
[16] Cirrincione, G.; Dattolo, G.; Almerico, A. M.; Aiello, E.;
Jones, R. A.; Dawes, H. M.; Hursthouse, M. B. J Chem Soc Perkin Trans
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[17] Hawkins, R. A.; Stephens, C. E. Tetrahedron Lett 2010,
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet