Unexpected course for the reaction of 1-di(ethoxycarbonyl)methyl-1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridinium bromide with dimethyl acetylenedicarb- oxylate in the presence of triethylamine

Full text of DOI:10.1007/s10593-010-0442-0

Chemistry of Heterocyclic Compounds, Vol. 45, No. 11, 2009
UNEXPECTED COURSE FOR THE REACTION OF
1-DI(ETHOXYCARBONYL)METHYL-1-METHYL-
4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINIUM
BROMIDE WITH DIMETHYL ACETYLENEDICARB-
OXYLATE IN THE PRESENCE OF TRIETHYLAMINE
S. A. Soldatova1*, A. T. Soldatenkov1, R. R. Suleimanov1,
N. M. Kolyadina1, and V. N. Khrustalev1
Keywords: 1-di(ethoxycarbonyl)methyl-4-phenyl-1,2,3,6-tetrahydropyridine, N-ylide, pyrrolidine,
sigmatropic rearrangement.
Using acetylenedicarboxylic ester in the presence of base it has been possible to show for the first time
that reaction of 2,3-dihydro-1H-indeno[2,1-c]pyridinium [1] and 1,2,3,4-tetrahydro-γ-carbolinium [2] quaternary
salts to tetrahydroindenoazonines and hexahydroazoninoindoles respectively can occur with expansion of the six
membered ∆3-piperidine ring (with an alkoxycarbonylmethyl substituent on the nitrogen atom) to a nine
membered ring [1, 2]. In this work we have studied the reaction of 1-di(ethoxycarbonyl)methyl-1-methyl-
4-phenyl-1,2,3,6-tetrahydropyridinium bromide (1) with dimethyl acetylenedicarboxylate (2) in the presence of
triethylamine under analogous conditions (20ºC, 32 h). However, in place of the expected azonine derivative,
column chromatography of the reaction mixture unexpectedly gave a 25% yield of the substituted
pyrrolidine 3, the 2-ethenyl group of which contains three alkoxycarbonyl substituents. Its structure was
Ph
Ph
MeO2C
CO2Me
CO2Et
–
2
Br
+
N
N
CO2Et
CO2Me
CO2Et
Et3N
Me
Me
MeO2C
CO2Et
1
3
_______
* To whom correspondence should be addressed, e-mail: sa.soldatova@googlemail.com.
1Peoples' Friendship University of Russia, Moscow 117198, Russia.
2A. N. Nesmeyanov Institute for Organoelemental Compounds, Russian Academy of Sciences, Moscow 119991,
Russia; e-mail: vkh@xrlab.ineos.ac.ru.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No.11, pp. 1749-1751, November, 2009.
Original article submitted October 30, 2009.
1408
0009-3122/09/4511-1408©2009 Springer Science+Business Media, Inc.

1
unambiguously proved by X-ray crystallographic analysis, from its H and IR spectra, and by chromato-mass
spectrometry (detailed data from the X-ray structural analysis will be presented in a separate report).
Such a surprising conversion of salt 1 to pyrrolidine 3 involves migration of a ethoxycarbonyl group and
this can be rationalized by the following reaction steps. The electrophilic acetylene dicarboxylate ester 2 adds to
the initially formed N-ylide and the 1,4-zwitterion formed evidently undergoes a 1→3 acyl shift of one of the
ethoxycarbonyl groups to the carbanion center. This shift leads to a new ylide which can undergo a
[3,2]-sigmatropic rearrangement with recyclization of the piperidine ring to a pyrrolidine.
1
The H NMR spectra were recorded on a Bruker WP-400 (400 MHz) spectrometer using DMSO-d6
(compound 1) or CDCl3 (compound 3) with the residual deuterated solvent protons as internal standard. IR
Spectra were taken on an Infralum FT-801 spectrometer for KBr tablets. An Agilent 1100 liquid chromatograph
with DAD, ELSD Sedex 75 detectors combined with an Agilent LC/MSD VL mass spectrometer with
electrospray ionization was used to monitor the reaction mixtures and the purity of the separated compound 3.
X-ray structural analysis of compound 3 was carried out by a direct method on a Bruker SMART 1000 CCD
diffractometer with MoKα radiation, graphite monochromator, and with θ- and ω-scanning. The starting
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was prepared as in method [6].
1-Di(ethoxycarbonyl)methyl-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium Bromide (1). Bromo-
malonate ester (2.8 g, 10 mmol) was added to a solution of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (2.1 g,
10 mmol) in absolute THF (20 ml) and the mixture was held with refluxing under a nitrogen atmosphere for 3 h. The
cooled reaction mixture was treated with hexane (50 ml) and the precipitate formed was separated and recrystallized
from acetone to give compound 1 with mp 78ºC. IR spectrum, ν, cm-1: 1753 and 1741 sh (C=O), 1629 (C=C). 1H
NMR spectrum, δ, ppm (J, Hz): 1.27 (6H, t, J = 7.2, OCH2CH3); 2.92 (2H, m, H-3); 3.35 (3H, s, NCH3); 3.86 (2H,
m, H-2); 4.33 (4H, m, OCH2CH3); 4.41 and 4.53 (each 1H, both br. d, J = 16.5, H-6); 6.03 (1H, s, NCHCOO); 6.15
(1H, br. s, H-5); 7.18-7.61 (5H, m, C6H5). Found, %: Br 19.52; N 3.42. C19H26BrNO4. Calculated, %: Br 19.42;
N 3.39.
2-(2-Ethoxycarbonyl-1-methyl-3-phenyl-3-vinylpyrrolidin-2-yl)-1-ethoxycarbonyl-1,2-di(methoxy-
carbonyl)ethene (3). Triethylamine (1.8 ml, 14 mmol) was added to a suspension of the quaternary salt 1 (2.0 g,
5 mmol) and acetylenedicarboxylic ester 2 (1.5 g, 10 mmol) in absolute dioxane (30 ml) and stirred at 20ºC under a
nitrogen atmosphere for 32 h. Solvent was evaporated in vacuo and the residue was column chromatographed on
SiO2 in the system hexane-ethyl acetate using a gradient from 1: 0 to 1: 10 to give compound 3 (0.67 g, 25%) as
colorless crystals with mp 112-113ºC. IR spectrum, ν, cm-1: 1731 sh, 1727 (C=O), 1631 (C=C). 1H NMR spectrum,
δ, ppm (J, Hz): 1.20 (3H, t, J = 7.6, OCH2CH3); 1.30 (3H, t, J = 7.6, OCH2CH3); 2.24 (3H, s, NCH3); 2.68 (2H, m,
H-4); 2.86 and 3.33 (each 1H, both m, H-5); 3.45 (3H, s, OCH3); 3.52 (1H, s, OCH3); 4.08 and 4.22 (each 2H, both
q, J = 7.6, OCH2CH3); 4.72 (1H, d, J = 17.2, CH=CH-cis H-trans); 5.05 (1H, d, J = 10.8, CH=CH-cis H trans);
6.94 (1H, dd, J = 17.2 and 10.8, CH=CH-cis H-trans); 7.17-7.58 (5H, m, C6H5). Mass spectrum, m/z: 474 [M+H]+.
Found, %: C 63.12; H 6.71; N 3.02. C25H31NO8. Calculated, %: C 63.42; H 6.55; N 2.96. M 473.
REFERENCES
1.
2.
A. T. Soldatenkov, S. V. Volkov, and S. A. Soldatova, Khim. Geterotsikl. Soedin., 613 (2007). [Chem.
Heterocycl. Comp., 43, 508 (2007)].
G. S. Gimranova, S. A. Soldatova, E. G. Prokudina, A. T. Soldatenkov, and K. B. Polyanskii, Zh. Org.
Khim., 44, 1416 (2008).
3.
4.
5.
S. Mageswaram, W. D. Ollis, and I. O. Sutherland, J. Chem. Soc., Perkin Trans. 1, 1953 (1981).
J. B. Sweeney, A. Tavassoli, N. B. Carter, and J. F. Hayes, Tetrahedron, 58, 10113 (2002).
S. A. Soldatova, G. S. Gimranova, Zh. A. Mamyrbekova, K. B. Polyanskii, S. V. Akbulatov, and
A. T. Soldatenkov, Khim. Geterotsikl. Soedin., 1670 (2007). [Chem. Heterocycl. Comp., 43, 1420 (2007)].
C. J. Schmidle and R. C. Mansfield, J. Am. Chem. Soc., 76, 425 (1956).
6.
1409