N-Substituted γ-Methylene γ-Lactams
889
4.97, 5.18 (1H, 1H, d, d, each J 2.4, =CH2), 7.20 & 7.42 (2H, 2H, each
d, J 8.8, 4 ArH). δC (CDCl3) 11.5, 14.2, 61.1, 98.1, 122.2, 129.0, 129.5,
132.7, 133.6, 145.9, 153.5, 163.1, 175.1.
(2H, s, CH2), 5.12, 5.21 (1H, 1H, each d, J 2, =CH2), 6.6–7.0 (3H, m,
3ArH). δC (CDCl3) 12.1, 43.4, 55.75, 55.82, 100.0, 107.5, 110.5, 111.0,
111.8, 119.5, 128.3, 144.1, 148.6, 149.2, 157.9, 163.9.
1-(2-(3,4-Dimethoxyphenyl)ethyl)-5-hydroxy-4,5-dimethyl-2-oxo-
2,5-dihydro-1H-pyrrole-3-carbonitrile 3q
1-Cyclohexyl-2-oxo-2,4,5,6-tetrahydro-1H-indole-3-
carbonitrile 5
Recrystallized from isopropyl alcohol to give the hydroxy compound
(44% yield) as colourless needles, mp 146–148◦C. (Found: C 64.6, H
6.2, N 8.8. C17H20N2O4 requires C 64.5, H 6.4, N 8.9%). δH (CDCl3)
1.38, 2.22 (3H, 3H, each s, 2Me), 2.83 (2H, m, ArCH2), 3.47 (2H, m,
NCH2), 3.77 (6H, s, 2OMe), 6.71 (3H, br s, 3ArH). δC (CDCl3) 12.8,
21.6, 34.1, 41.2, 55.0 (overlapping signals), 90.3, 108.4, 111.53, 111.56,
112.2, 120.8, 131.2, 147.6, 148.9, 163.3, 174.5.
Obtained from the reaction between cyclohexane-2,3-dione and
1j, followed by extraction of the crude hydroxy compound with
dichloromethane and dehydration overnight as a solution in formic acid,
mp 131–132◦C (67%, colourless prisms from ethanol). (Found: C 74.2,
H7.4, N11.3. C15H18N2OrequiresC74.4, H7.5, N11.6%). δH (CDCl3)
1.08–1.46 (3H, m), 1.61–2.3 (9H, m), 2.44 (2H, dd, J 5.8), 2.81 (2H,
m), 3.8–4.1 (1H, m, N–CH), 6.11 (1H, t, J 4.8, CH2–CH=). δC (CDCl3)
22.2, 24.3, 24.8, 25.2, 26.0, 30.3, 52.3, 102.0, 112.3, 118.4, 137.3, 157.1,
164.2.
8,9-Dimethoxy-1,10b-dimethyl-3-oxo-3,5,6,10b-
tetrahydropyrrolo[2,1-a]isoquinoline-2-carbonitrile 6
The hydroxy compound 3q (0.63 g) was dissolved in formic acid
(3 mL, 95%), the solution left to stand for 6 h, and then diluted with
water (10 mL). The precipitate was collected by filtration and purified
by chromatography over silica gel. The material obtained by eluting
with light petroleum/ethyl acetate (25/75) was recrystallized from ethyl
acetate/light petroleum to give the product as colourless needles (0.36 g,
61%), mp 194–195◦C. (Found: C 68.5, H 6.0, N 9.5. C17H18N2O3
requires C 68.4, H 6.1, N 9.4%). δH (CDCl3) 1.68, 2.73 (3H, 3H, each s,
2 × Me), 2.5–2.7 (1H, m, –CHHCH2–), 2.8–3.2 (2H, m, –NCHHCH2–),
3.81, 3.88 (6H, each s, 2 × OMe), 4.4–4.5 (1H, m, –NCHHCH2–), 6.60,
7.79 (1H, 1H, each s, 2ArH). δC (CDCl3) 15.3, 26.7, 29.8, 36.3, 55.9,
56.3, 67.3, 109.1, 109.8, 111.9, 112.3, 126.2, 126.5, 147.1, 148.8, 164.8,
176.8.
Reversible Sulfinate Addition to 1-(4-Chlorophenyl)-4-methyl-
5-methylene-2-oxo-2,5-dihydro-1H-pyrrole-3-carbonitrile 4b
Sodium 4-toluenesulfinate (200 mg) was added to a suspension of 4b
(100 mg) in formic acid (1.5 mL). The mixture was warmed to 90◦C for
5 min, cooled to room temperature, and the precipitate was filtered off
to yield the crude adduct (116 mg). δH (CDCl3/CF3COOH 10/1) 2.44,
2.53 (3H, 3H, s, 2Me), 3.66 (2H, d, J 3.7, CH2CH), 5.24 (1H, t, J 3.7,
CH2CH), 7.03 (2H, d, J 8.6, 2ArH), 7.35 (2H, d, J 8.6, 2ArH), 7.49 (2H,
d, J 8.2, 2ArH), 7.72 (2H, d, J 8.2, 2ArH), peaks characteristic of the
methylene lactam starting material were evident in the spectrum at 5.27
(1H, d, J 2.7, =C(H)H) and 5.60 (1H, d, J 2.7, =C(H)H), which inte-
grated for 15–20% of the total material. Chromatography of a solution
of this crude adduct (80 mg) in dichloromethane over silica gel resulted
in elution of 4b (30 mg, 61%).
5-Hydroxy-4,5-dimethyl-2-oxo-1-(2-(phenyl)ethyl)-2,5-dihydro-
1H-pyrrole-3-carbonitrile 3r
Acknowledgments
The hydroxy compound (37%) crystallized from ethyl acetate/light
petroleum as woolly needles, mp 135–136◦C. (Found: C 70.2, H 6.1, N
10.6. C15H16N2O2 requires C 70.3, H 6.3, N 10.9%). δH (CDCl3) 1.37,
2.21 (3H, 3H, each s, 2Me), 2.8–3.2 (2H, m, PhCH2), 3.4–3.8 (2H, m,
NCH2), 7.2 (5H, m, Ph). δC (CDCl3) 12.9, 21.5, 34.6, 41.3, 90.3, 108.5,
111.6, 126.7, 128.7, 128.8, 138.6, 163.4, 174.5.
We thank E. I. DuPont de Nemours and Co., Agricultural
Products Department, for biological screening of these
compounds.
References
4-Methyl-5-methylene-2-oxo-1-(2-phenylethyl)-2,5-dihydro-
[1] W. N. Speckamp, Rec. Trav. Chim. Pays-Bas 1981, 100, 345.
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1H-pyrrole-3-carbonitrile 4r
The action of formic acid on 3r over 48 h gave the methylene lactam
(56%), mp 130–131◦C (aqueous ethanol). (Found: C 75.4, H 6.0, N
11.6. C15H14N2O requires C 75.6, H 5.9, N 11.8%). δH (CDCl3) 2.35
(3H, s, Me), 2.87 (2H, t, J 10, PhCH2), 3.86 (2H, t, J 10, CH2N), 4.96,
5.14 (1H, 1H, each d, J 2, =CH2), 7.1–7.4 (5H, m, Ph). δC (CDCl3)
12.2, 34.5, 41.6, 98.5, 108.0, 111.8, 126.8, 128.67, 128.72, 137.9, 144.5,
157.5, 163.7.
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[4] (a) Y. Hayashi, M. Shoji, J. Yamaguchi, K. Sato, S. Yamaguchi,
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2,5-dihydro-1H-pyrrole-3-carbonitrile 3s
Condensation of the cyanoacetamide 1s and butane-2,3-dione in the
usual way gave the hydroxy compound (52%), mp 138–139◦C (ethanol).
(Found: C 63.4, H 65.7, N 9.1. C16H18N2O4 requires C 63.6, H 6.0, N
9.3%). δH (CDCl3) 1.31, 2.19 (3H, 3H, each s, 2Me), 3.78, 4.06 (3H,
3H, each s, 2OMe), 4.38 (1H, br s, OH), 4.46, 4.61 (1H, 1H, each d, J
16, CH2), 6.7–7.0 (3H, m, 3ArH). δC (CDCl3) 12.7, 22.3, 42.1, 55.8,
55.9, 90.6, 108.1, 111.1, 111.4, 111.5, 120.5, 130.0, 148.3, 148.8, 163.5,
175.1.
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1-(3,4-Dimethoxyphenyl)methyl-4-methyl-5-methylene-2-oxo-
2,5-dihydro-1H-pyrrole-3-carbonitrile 4s
[5] R. E. Valters, W. Flitsch, Ring-Chain Tautomerism 1985, p. 49
(Plenum Press: New York, NY).
A solution of the hydroxy compound (0.45 g) in trifluoroacetic acid
(2 mL) was diluted with water (3 mL) after 16 h, the precipitate was
filteredoff, washedwithwater, andrecrystallizedfromisopropylalcohol
to give the methylene lactam 4s (0.33 g, 79%), mp 116–117◦C. (Found:
C 67.5, H 5.4, N 9.8. C16H16N2O3 requires C 67.6, H 5.7, N 9.9%).
δH (CDCl3) 2.33 (3H, s, Me), 3.87, 3.89 (3H, 3H, each s, 2OMe), 4.86
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