First synthesis of 2-alkyl- 5-aryl-3,3-bis(methoxycarbonyl)- 4,5-dihydropyrroles

Full text of DOI:10.1007/s10593-010-0478-1

Chemistry of Heterocyclic Compounds, Vol. 46, No. 1, 2010
FIRST SYNTHESIS OF 2-ALKYL-
5-ARYL-3,3-BIS(METHOXYCARBONYL)-
4,5-DIHYDROPYRROLES
A. O. Chagarovskiy1, E. M. Budynina1, O. A. Ivanova1, and I. V. Trushkov1*
Keywords: donor-acceptor cyclopropanes, nitriles, ∆1-pyrrolines, cycloaddition.
Donor-acceptor cyclopropanes have attracted considerable interest in light of their high reactivity in
various reactions including cycloaddition [1-3]. Until now, the cycloaddition of such cyclopropanes to nitriles
has been studied only for 2-alkoxycyclopropanecarboxylates [4-8]. In the presence of Me3SiOTf, these
compounds form adducts, which, under the reaction conditions, tend to lose an alcohol molecule with the
formation of pyrroles [5-8]. According to Yu and Pagenkopf [5], other cyclopropanes do not react with nitriles.
CO2Me
Ar
SnCl4
CO2Me
CO2Me
RCN
CO2Me
+
Ar
MeNO2
N
R
2a,b
1a–c
3a–e
1a, 3a,d Ar = Ph; 1b, 3b Ar = 4-BrC6H4; 1c, 3c,e Ar = 3,4,5-(MeO)3C6H2;
2a, 3a,c R = Me; 2b, 3b,d,e R = Et
We studied the reaction of 2-arylcyclopropane-1,1-dicarboxylates 1a-c with nitriles 2a and 2b and found
that ∆1-pyrrolines 3a-e were formed when the reaction was carried out in nitromethane with SnCl4 as the
catalyst.
1
The IR spectra were taken on a UR-20 spectrometer for vaseline mulls. The H and 13C NMR spectra
were taken on a Bruker Avance-400 spectrometer at 400 and 100 MHz, respectively for CDCl3 solutions. The
chemical shifts were measured relative to the solvent signals (1H: δ 7.26 ppm, 13C: δ 77.13 ppm). The electron
impact mass spectra were taken on a Finnigan SSQ7000 GC-MS at 70 eV.
2-Arylcyclopropane-1,1-dicarboxylates 1 were prepared according to Corey and Chaykovsky [9].
∆1-Pyrrolines 3a-e. SnCl4 (1.5 mmol) in MeNO2 (2 ml) was added to a solution of nitrile 2 (3.75 mmol)
and cyclopropane 1 (0.75 mmol) in (18 ml) MeNO2. The reaction mixture was stirred for 3 h in an argon
atmosphere at 55°C, poured into 50 ml aqueous sodium carbonate, and extracted with three 40-ml portions of
_______
* To whom correspondence should be addressed, e-mail: itrushkov@mail.ru.
1Chemistry Faculty, M. V. Lomonosov Moscow State University, Moscow 119991 Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 139-141, January, 2010. Original
article submitted November 20, 2009.
120
0009-3122/10/4601-0120©2010 Springer Science+Business Media, Inc.

methylene chloride. The combined organic layer was washed with three 20-ml portions of aqueous Trilon B and
three 20-ml water portions and then dried over anhydrous sodium sulfate. The solvent was evaporated off and
the reaction product was isolated by chromatography on a silica gel column.
Dimethyl Ester of 2-Methyl-5-phenyl-4,5-dihydropyrrole-3,3-dicarboxylic Acid (3a) was obtained
in 74% yield as a colorless oil, Rf 0.31 (4:1 petroleum ether–ethyl acetate). IR spectrum, ν, cm-1: 1740 (C=O),
1
5
2
3
1670 (C≡N). H NMR spectrum, δ, ppm (J, Hz): 2.31 (3H, d, J = 2.3, CH3); 2.37 (1H, dd, J = 13.5, J = 8.1,
2
3
3
CH2); 3.16 (1H, dd, J = 13.5, J = 7.3, CH2); 3.76 (3H, s, OCH3); 3.82 (3H, s, OCH3); 5.12 (1H, ddd, J = 8.1,
3J = 7.3, J = 2.3, CHAr); 7.24-7.29 (3H, m, Ar); 7.30-7.37 (2H, m, Ar). 13C NMR spectrum, δ, ppm (J, Hz):
5
18.17 (1JCH = 128, CH3), 42.62 (1JCH = 137, CH2), 53.05 (1JCH = 136, CH3O), 53.18 (1JCH = 136, CH3O), 72.19
(C), 73.63 (1JCH = 140, CHAr), 126.52 (2CH, Ar), 127.26 (CH, Ar), 128.54 (2CH, Ar), 142.30 (C, Ar), 168.24
(C), 168.38 (C), 169.23 (C). Mass spectrum, m/z (Irel, %): 275 [M] (33), 215 (100), 203 (15), 184 (15), 170 (38),
131 (42), 130 (42), 121 (24), 115 (32). Found, %: C 65.30; H 6.15; N 4.92. C15H17NO4. Calculated, %: C 65.44;
H 6.22; N 5.09.
Dimethyl Ester of 5-(4-Bromophenyl)-2-ethyl-4,5-dihydropyrrole-3,3-dicarboxylic Acid (3b) was
1
obtained in 64% yield as a pale-yellow oil, Rf 0.50 (4:1 petroleum ether–ethyl acetate). H NMR spectrum, δ,
3
2
3
3
ppm (J, Hz): 1.22 (3H, t, J = 7.3, CH3); 2.27 (1H, dd, J = 13.4, J = 8.1, CH2); 2.50-2.60 (2H, qd, J = 7.3,
5J = 2.3, CH2Me); 3.10 (1H, dd, J = 13.4, J = 7.3, CH2); 3.70 (3H, s, OCH3); 3.76 (3H, s, OCH3); 5.04 (1H,
ddd, 3J = 8.1, 3J = 7.3, 5J = 2.3, CHAr); 7.12 (2H, d, 3J = 8.0, Ar); 7.40 (2H, d, 3J =8.0, Ar). 13C NMR spectrum,
δ, ppm: 10.89 (CH), 24.88 (CH2Me), 42.70 (CH2), 53.10 (2CH3O), 72.19 (C), 72.80 (CHAr), 120.99 (C, Ar),
128.29 (2CH, Ar), 131.54 (2CH, Ar), 141.72 (C, Ar), 168.39 (CO2Me), 168.88 (CO2Me), 173.29 (C=N). Found,
%: C 52.46; H 4.78; N 3.98. C16H18BrNO4. Calculated, %: C 52.19; H 4.93; N 3.80.
2
3
Dimethyl Ester of 2-Methyl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydropyrrole-3,3-dicarboxylic Acid
1
(3c) was obtained in 89% yield as a colorless oil, Rf 0.64 (ether). H NMR spectrum, δ, ppm (J, Hz): 2.20 (3H,
br. s, CH3); 2.38 (1H, dd, 2J = 13.6, 3J = 8.1, CH2); 3.16 (1H, dd, 2J = 13.6, 3J = 7.1, CH2); 3.69 (3H, s, OCH3);
3.71 (3H, s, OCH3); 3.73 (3H, s, OCH3); 3.76 (6H, s, 2OCH3); 4.95 (1H, br. dd, 3J = 7.1, 3J = 8.1, CHAr); 6.41
(2H, s, 2CH, Ar). 13C NMR spectrum, δ, ppm: 18.11 (CH3), 42.29 (CH2), 53.06 (CO2CH3), 53.17 (CO2CH3),
55.95 (2OCH3), 60.64 (OCH3), 72.02 (C), 73.66 (CH), 103.53 (2CH), 136.94 (C), 137.90 (C), 153.23 (2C),
168.08 (CO2Me), 168.58 (CO2Me), 169.14 (C=N). Found: C 59.21; H 6.32; N 3.75%. C18H23NO7. Calculated,
%: C 59.17; H 6.34; N 3.83.
Dimethyl Ester of 2-Ethyl-5-phenyl-4,5-dihydropyrrole-3,3-dicarboxylic Acid (3d) was obtained in
65% yield as a pale-yellow oil, Rf 0.45 (4:1 petroleum ether–ethyl acetate). IR spectrum, ν, cm-1: 1740 (C=O),
1
3
2
3
1660 (C=N). H NMR spectrum, δ, ppm, (J, Hz): 1.28 (3H, t, J = 7.3, CH3); 2.38 (1H, dd, J = 13.4, J = 7.9,
CH2); 2.62 (2H, qd, 3J = 7.3, 5J = 2.3, CH2Me); 3.16 (1H, dd, 2J = 13.4, 3J = 7.1, CH2); 3.76 (3H, s, OCH3); 3.82
(3H, s, OCH3); 5.43 (1H, ddd, 3J = 7.9, 3J = 7.3, 5J = 2.3, CHAr); 7.24-7.28 (3H, m, Ar); 7.32-7.37 (2H, m, Ar).
13C NMR spectrum, δ, ppm: 10.96 (CH3), 24.89 (CH2Me), 42.99 (CH2), 53.01 (CH3O), 53.15 (CH3O), 72.23
(C), 73.58 (CHAr), 126.55 (2CH, Ar), 127.25 (CH, Ar), 128.52 (2CH, Ar), 142.60 (C, Ar), 168.61 (CO2Me),
169.41 (CO2Me), 172.75 (C=N). Mass spectrum, m/z (Irel, %): 289 [M]+ (64), 274 (8), 230 (41), 229 (100), 170
(88), 145 (56), 121 (51), 115 (57). Found, %: C 66.47; H 6.84; N 4.82. C16H19NO4. Calculated, %: C 66.42;
H 6.62; N 4.84.
Dimethyl Ester of 2-Ethyl-5-(3,4,5-trimethoxyphenyl)- 4,5-dihydropyrrole-3,3-dicarboxylic Acid
(3e) was obtained in 72% yield as an orange oil, Rf 0.58 (ether). 1H NMR spectrum, δ, ppm (J, Hz): 1.28 (3H, t,
2
3
2
3J = 7.3, CH3); 2.38 (1H, dd, J = 13.4, J = 8.0, CH2); 2.58-2.81 (2H, m, CH2Me); 3.15 (1H, dd, J = 13.4,
3J = 7.4, CH2);; 3.78 (3H, s, OCH3); 3.83 (6H, s, OCH3); 3.86 (6H, s, OCH3); 5.02-5.08 (1H, m, CHAr); 6.49
(2H, s, Ar). 13C NMR spectrum, δ, ppm: 11.01 (CH3), 24.89 (CH2Me), 42.74 (CH2), 53.18 (CH3O), 56.08
(3CH3O), 60.81 (CH3O), 72.17 (C), 73.75 (CHAr), 103.64 (2CH), 137.19 (C), 138.25 (C), 153.33 (2C), 168.54
(CO2Me), 169.46 (CO2Me), 172.82 (C=N). Found, %: C 59.90; H 6.75; N 3.71. C19H25NO7. Calculated, %:
C 60.15; H 6.64; N 3.69.
121

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