Synthesis and the molecular and crystal structures of methyl 2-substituted 7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylates

Article abstract of DOI:10.1007/s10593-012-1139-3

Methyl 7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylates were obtained as a result of 3-amino-5,5-dimethylcyclohex-2-enone reaction with the methyl esters of acyl(aroyl)pyruvic acids. The structure of methyl 7,7-dimethyl-5-oxo-2-phenyl-5,6,7,8-tetrahydroquinoline-4-carboxylate was established by X-ray structural analysis.

Full text of DOI:10.1007/s10593-012-1139-3

Chemistry of Heterocyclic Compounds, Vol. 48, No. 9, December, 2012 (Russian Original Vol. 48, No. 9, September, 2012)
SYNTHESIS AND THE MOLECULAR AND CRYSTAL
STRUCTURES OF METHYL 2-SUBSTITUTED 7,7-DIMETHYL-
5-OXO-5,6,7,8-TETRAHYDROQUINOLINE-4-CARBOXYLATES
D. A. Rudenko1, M. V. Artemova1, P. A. Slepukhin2,
V. I. Karmanov3, and S. N. Shurov1*
Methyl 7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylates were obtained as a result of
3-amino-5,5-dimethylcyclohex-2-enone reaction with the methyl esters of acyl(aroyl)pyruvic acids. The
structure of methyl 7,7-dimethyl-5-oxo-2-phenyl-5,6,7,8-tetrahydroquinoline-4-carboxylate was
established by X-ray structural analysis.
Keywords: 3-amino-5,5-dimethylcyclohex-2-enone, methyl acyl(aroyl)pyruvates, 2-substituted methyl
7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylates.
It is known that the reaction of methyl aroylpyruvates with aniline begins with attack by the amine
nitrogen atom at the C-2 carbon atom of the ester [1]. In view of this it could be supposed that the products of
the reaction of 3-amino-5,5-dimethylcyclohex-2-enone (1) with methyl acyl(aroyl)pyruvates 2a-f would be methyl
4-aryl-2-[(5,5-dimethyl-3-oxocyclohex-1-en-1-yl)amino]-4-oxo-2-butenoates 3a-f or their dehydration products –
quinolines 4a-f. Moreover, for the enaminone 1 many of its reactions with electrophiles begin with an attack on
the C-2 carbon atom [2]. Therefore, the isomeric 2-substituted methyl 7,7-dimethyl-5-oxo-5,6,7,8-tetra-
hydroquinoline-4-carboxylates 6a-f can be formed in the investigated reaction. As a rule, intermediates of the
5a-f type, the formation of which is postulated for the reactions of the enaminone 1 with β-dicarbonyl
compounds, are not isolated from the reaction mixture [2].
We established that 2-substituted methyl 7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carb-
oxylates 6a-f are formed as a result of the reaction of compounds 1 and 2a-f (Table 1).
Since the data from IR and 1H NMR spectroscopy do not allow to make an unequivocal choice between
the isomeric structures 4 and 6, X-ray structural investigations of a single crystal of compound 6b were
undertaken. The general view of the molecule is shown in Figure 1.
_______
*To whom correspondence should be addressed, e-mail: seshurov@yandex.ru.
1Perm State University, 15 Bukireva St., Perm 614990, Russia.
2I. Ya. Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences, 22 S. Kovalevskoi
St. / 20 Akademicheskaya St., Yekaterinburg 620990, Russia; e-mail: slepukhin@ios.uran.ru.
3Institute of Technical Chemistry, Ural Branch, Russian Academy of Sciences, 3 Akademika Koroleva St., Perm
614013, Russia; e-mail: karmanovvi@rambler.ru.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1418-1421, September, 2012.
Original article submitted July 14, 2011.
0009-3122/12/4809-1321©2012 Springer Science+Business Media New York
1321

O
R
COOMe
+
Me
Me
O
OH
2a–f
NH2
1
EtOH
–H2O

O
O
COOMe
O
R
Me
Me
COR
Me
Me
NH2
N
COOMe
H
5a–f
3a–f
–H2O
–H2O
R
O
COOMe
O
Me
Me
Me
Me
N
R
N
COOMe
6a–f
4a–f
a R = t-Bu, b R = Ph, c R = 4-MeC6H4, d R = 4-MeOC6H4, e R = 4-BrC6H4, f R = 4-O2NC6H4
According to the data from X-ray crystallographic analysis, compound 6b crystallizes in a
centrosymmetric space group of the monoclinic system. The conjugation system of the heterocycle is planar
within 0.05 Å, and the C(3) atom deviates from the ring plane by 0.63 Å. The distribution of the bond lengths
and the valence angles in the molecule is close to standard, and there are no significant shortened
Fig. 1. The general appearance of the molecule of compound 6b with the atoms represented by thermal vibration
ellipsoids of 50% probability.
1322

TABLE 1. The Spectral Characteristics of Compounds 6a-f
IR spectrum,
1Н NMR spectrum, δ, ppm (J, Hz)
Com-
ν, сm-1
pound
7-С(СН3)2 6-CH2 8-CH2
(6H, s) (2H, s) (2H, s) (1H, s) (3H, s)
H-3 OCH3
C=O COOMe
R
1686
1686
1735
1732
1.09
1.12
2.56
2.60
3.06
3.15
7.33
7.86
3.84 1.36 (9Н, s, C(CH3)3)
3.89 7.50-7.54 (3Н, m, H Ph);
8.21-8.24 (2Н, m, H Ph)
3.99 2.40 (3Н, s, СН3);
7.34 (2Н, d,
6a
6b
1689
1741
1.13
2.60
3.15
7.82
6c
J = 9.0, H Ar);
8.14 (2Н, d,
J = 9.0, H Ar)
1679
1736
1.13
2.60
3.13
7.78
3.88 3.87 (3Н, s, ОСН3);
7.07 (2Н, d,
6d
J = 9.0, H Ar);
8.22 (2Н, d,
J = 9.0, H Ar)
1683
1695
1736
1744
1.13
1.15
2.61
2.65
3.16
3.22
7.89
8.05
3.88 7.71 (2Н, d,
J = 9.0, H Ar);
8.19 (2Н, d, J = 9.0, H Ar)
3.90 8.39 (2Н, d,
J = 9.0, H Ar);
6e
6f
8.52 (2Н, d, J = 9.0, H Ar)
contacts in the molecular packing. The residual electron density is characterized by a significant maximum
(0.726 e·Å−3) at х 0.5737, у 0.8412, z 0.4340. The intensity of the peak is higher than the intensity
corresponding to a hydrogen atom location, but significantly lower than the intensity corresponding to a
location of atoms in the middle of the second period. This peak probably appears as a result of the generally
poor quality of the crystal.
Thus, the X-ray investigations have shown that the products from the reaction of 3-amino-5,5-dimethyl-
cyclohex-2-enone with methyl acyl(aroyl)pyruvates are 2-substituted methyl 7,7-dimethyl-5-oxo-5,6,7,8-tetra-
hydroquinoline-4-carboxylates.
EXPERIMENTAL
The IR spectra were recorded in vaseline oil on a Bruker IFS 66ps IR Fourier spectrometer. The
1H NMR spectra were recorded in acetone-d6 on a Varian Mercury 300 Plus instrument (300 MHz) with HMDS
as internal standard (δ 0.059 ppm). Elemental analysis was performed on a LECO CHNS-932 instrument. The
melting points were determined on a PTP instrument.
Methyl 2-(tert-Butyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylate (6a). A mixture of
the ester 2a (4.14 g, 22 mmol) and enaminone 1 (3.10 g, 22 mmol) was refluxed in EtOH (50 ml) for 5 h. The
reaction mixture was cooled to 0°C, and the precipitate was filtered off. Yield 1.09 g (17%). White crystals, mp
135-136°С (MeOH). Found, %: C 70.50; H 7.90; N 4.70. C17H23NO3. Calculated, %: C 70.56; H 8.01; N 4.84.
Methyl 7,7-Dimethyl-5-oxo-2-phenyl-5,6,7,8-tetrahydroquinoline-4-carboxylate (6b). This product
was obtained similarly to the ester 6a from the ester 2b (7.88 g, 38 mmol) and enaminone 1 (5.32 g, 38 mmol).
Yield 7.57 g (64%). Yellow crystals, mp 132-134°С (EtOH). Found, %: C 73.61; H 5.97; N 4.46. C19H19NO3.
Calculated, %: C 73.77; H 6.19; N 4.53.
Methyl 7,7-Dimethyl-2-(4-methylphenyl)-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylate (6c).
This product was obtained similarly to the ester 6a from the ester 2c (4.75 g, 22 mmol) and the enaminone 1
(3.10 g, 22 mmol). Yield 2.61 g (37%). Yellow crystals, mp 139-140°С (EtOH). Found, %: C 74.34; H 6.37;
N 4.34. C20H21NO3. Calculated, %: C 74.28; H 6.55; N 4.33.
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Methyl 2-(4-Methoxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylate (6d). This
product was obtained similarly to the ester 6a from the ester 2d (4.45 g, 19 mmol) and enaminone 1 (2.64 g,
19 mmol). Yield 2.54 g (39%). Pale-yellow crystals, mp 137-139°С (MeOH). Found, %: C 70.64; H 6.00;
N 4.23. C20H21NO4. Calculated, %: C 70.78; H 6.24; N 4.13.
Methyl 2-(4-Bromophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylate (6e).
This product was obtained similarly to the ester 6a from the ester 2e (4.50 g, 16 mmol) and enaminone 1
(2.20 g, 16 mmol). Yield 1.96 g (32%). Colorless crystals, mp 114-115°С (2-PrOH). Found, %: C 59.00;
H 4.50; N 3.55. C19H18BrNO3. Calculated, %: C 58.78; H 4.67; N 3.61.
Methyl 7,7-Dimethyl-2-(p-nitrophenyl)-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylate (6f). This
product was obtained similarly to the ester 6a from the ester 2f (3.00 g, 14 mmol) and enaminone 1 (1.90 g,
14 mmol). Yield 1.50 g (31%). Yellow-brown crystals, mp 131-133°С (EtOH). Found, %: C 64.30; H 5.00;
N 7.82. C19H18N2O5. Calculated, %: C 64.40; H 5.12; N 7.91.
X-Ray Structural Investigation of Compound 6b (C19H19NO3, M 309.37). The investigation was
carried out on an Xcalibur 3 single-crystal diffractometer with a CCD detector and SHELXTL97 software [3]
using the standard procedure (MoKα radiation, T 130(2) K, ω scanning with 1° step). Crystals 0.51×0.46×0.39
mm, colorless, grown in 2-PrOH, monoclinic, space group P21/c, unit cell parameters: a 12.9499(14),
b 7.6102(12), с 17.196(2) Å; β 100.424(10)°; Z 4. Experiment completeness at angles θ ≤ 26.0° is 97.9%. The
number of reflections collected was 4956, independent 3335 (Rint 0.0236), 1768 with I > 2σ(I). The structure
was interpreted by the direct method in isotropic approximation and refined in anisotropic approximation for the
non-hydrogen atoms. The hydrogen atoms were placed at the geometrically calculated positions and were
included in the refinement in isotropic approximation using the "rider" model. A correction for absorption was
not made, μ 0.083 mm-1. The final probability parameters were R1 0.0427, wR2 0.0917 (for reflections with
I > 2σ(I)) with quality factor S 1.006. The maximum and minimum peaks of residual electron density were
0.726 and -0.262 e·Å−3. The results of the X-ray structural investigation were deposited at the Cambridge
Crystallographic Data Center (deposit CCDC 843787).
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2.
3.
Yu. S. Andreichikov, A. P. Kozlov, Yu. A. Nalimova, and S. P. Tendryakova, Zh. Org. Khim., 13, 2559
(1977).
A. Maquestiau, Y. Van Haverbeke, J. J. Vanden Eynde, and N. De Pauw, Bull. Soc. Chim. Belg., 88,
671 (1979).
G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr., A64, 112 (2008).
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