Structure of Methyl 1-oxo-3,5-diphenylcyclohexene-6-carboxylate

Introduction

The exploration of a simple molecule with different functionalities for the synthesis of heterocycles is a worthwhile contribution in the chemistry of heterocycles. In fact, 6-ethoxycarbonyl-3,5-diarylcyclohexenone has been used as an effective synthon in some projected syntheses of benzoselenadiazoles/thiadiazoles¹, spirocyclohexanones², carbazole derivatives³, fused isoxazoles and pyrazoles^4,5. The intermediate present in this communication has been chosen by us as a promising starting material to develop pyrazole rings with antimalarial and antibacterial activities⁶.

Compounds 1a,b were synthesised by a base-catalysed Claisen-Schmidt condensation of 4-chlorobenzaldehyde with the appropriate acetophenone. These ketones on treatment with methyl 3-oxobutanoate in the presence of sodium methoxide yield methyl 6-(4-chlorophenyl)-4-(4-methylphenyl)cyclohex-3-en-2-one-1-carboxylate⁷ 1a (R₁: 4-Cl; R₂: 4-Me in Scheme 1) or methyl-1-oxo-3,5-diphenylcyclohexene-6-carboxylate 1b (R₁= R₂: H in Scheme 1, see also Figure 1). In the present communication, we report the formation of 1b and its characterisation by elemental analysis as well as IR, ¹H NMR, ¹³C NMR, COSY, and HETCOR spectral and crystallographic studies. The analysis of 1a has been previously reported⁷.

The IR spectrum of 1b showed bands around 1734, 1657 and 1590 cm^-1 corresponding to α,β-unsaturated carbonyl, carbonyl ester and C=C bonds, respectively. The ¹H NMR spectrum exhibited a doublet and doublet of triplets at 3.06 and 3.13 ppm for H_4a,_4b, respectively, those protons are coupling with the proton in position 2 of the cyclohexene ring. The absence of doublets corresponding to the alkene structure of the starting material indicates that an addition reaction has indeed taken place. ¹³C NMR confirms the presence of carbonyl C atoms of a ketone and an ester at 175 and 194 ppm. The assignments were confirmed by COSY and HETCOR spectra.

Experimental

Melting points were determined on a Thomas micro hot stage apparatus and are uncorrected. Infrared spectra were determined as KBr pellets on a Shimadzu model 470 spectrophotometer. The ¹H NMR, ¹³C NMR, COSY and HETCOR spectra were recorded using a Jeol Eclipse 270 MHz spectrometer. Chemical shifts are expressed relative to residual chloroform. Central Service of Universidad de Málaga, Málaga-España performed elemental analyses, results were within ± 0.4% of predicted values for all compounds. Chemical reagents were obtained from Aldrich Chemical Co., USA. All solvents were distilled and dried with the usual desiccant.

X-ray Crystallographic Data Collection and Structural Determination.

Single-crystal X-ray diffraction measurement of the compounds were carried out with a Bruker Smart 1000 CCD diffractometer equipped with a graphite crystal monochromator situated in the incident beam for data collection at 298(2) K. The lattice parameters were obtained by least-squares refinement of the diffraction data of 9336 reflections, and data collections were performed with Mo Kαradiation (λ= 0.71073 Å) by ω scan mode in the range of 1.96 < θ < 25.10°. All of the measured independent reflections were used in the structural analysis, and semiempirical absorption corrections were applied using the SADABS program. The maximum and minimum transmission factors were 0.980 and 0.961. The program SAINT14 was used for integration of the diffraction profiles. The structure was solved by direct methods using the SHELXS97 program of the SHELXTL package and refined with SHELXL9715. The non-hydrogen atoms were located in successive difference Fourier syntheses. The final refinement was performed by full-matrix least-squares methods with anisotropic thermal parameters for all of the non-hydrogen atoms on F2. All of the hydrogen atoms were generated theoretically onto the specific atoms and refined isotropically with fixed thermal factors. A summary of the crystallographic data and structure refinement of 1b is listed in

Table 1. Crystallographic data for compound 1b

Parameter	Compound 1b	Parameter	Compound 1b
formula	C20 H18 O3	ρ(calcd), g cm-3	1.331
fw	306.34	F(000)	648
lattice	Monoclinic	μ(Mo KR), cm-1	0.089
a, Å	14.885(7)	diffractometer	APEX
b, Å	11.172(5)	radiatn λ, Å	0.71073
c, Å	9.367(4)	temp, °C	25
β, deg	101.161(12)	R (I > 2.00 σ (I)) a	0.3288
V, Å3	1528.2(12)	Rw (all data)b	0.6053
space group	P2(1)/c	no. of observs	2671 (all data)
Z	4	no. of variables	210

, and selected bond lengths and bond angles are listed in

Table 2. Selected bond distances (Å), angles (deg) and torsion angles (deg) for compound 1b at 298 K

Distances
C(15)-O(1)	1.20(2)
C(15)-C(16)	1.41(2)
C(15)-C(14)	1.52(3)
C(13)-O(3)	1.18(3)
C(13)-O(2)	1.24(3)
C(13)-C(14)	1.50(3)
C(1)-C(6)	1.04(3)
C(1)-C(19)	1.36(3)
C(1)-C(2)	1.49(3)
C(7)-C(12)	1.34(3)
C(7)-C(8)	1.37(3)
C(7)-C(17)	1.50(3)
C(8)-C(9)	1.24(3)
angles
O(1)-C(15)-C(16)	126.9(19)
O(1)-C(15)-C(14)	121.1(16)
C(16)-C(15)-C(14)	112.0(18)
O(3)-C(13)-O(2)	127(3)
O(3)-C(13)-C(14)	116(3)
O(2)-C(13)-C(14)	117(3)
torsion angles
C(12)-C(7)-C(8)-C(9)	3(3)
C(17)-C(7)-C(8)-C(9)	-174(2)
C(7)-C(8)-C(9)-C(10)	-4(4)
C(8)-C(9)-C(10)-C(11)	7(4)
C(9)-C(10)-C(11)-C(12)	-10(4)
C(8)-C(7)-C(12)-C(11)	-4(3)
C(17)-C(7)-C(12)-C(11)	172.4(19)
C(10)-C(11)-C(12)-C(7)	8(3)
O(1)-C(15)-C(16)-C(17)	-173(3)
C(14)-C(15)-C(16)-C(17)	8(4)
C(15)-C(16)-C(17)-C(18)	-10(3)
C(15)-C(16)-C(17)-C(7)	174(2)
C(12)-C(7)-C(17)-C(16)	168(2)
C(8)-C(7)-C(17)-C(16)	-15(3)
C(12)-C(7)-C(17)-C(18)	-7(3)
C(8)-C(7)-C(17)-C(18)	169.5(19)
C(16)-C(17)-C(18)-C(19)	21(3)
C(7)-C(17)-C(18)-C(19)	-163.7(18)
C(6)-C(1)-C(19)-C(14)	127(4)
C(2)-C(1)-C(19)-C(14)	-58(4)
C(6)-C(1)-C(19)-C(18)	-75(3)
C(2)-C(1)-C(19)-C(18)	100.6(19)
C(17)-C(18)-C(19)-C(14)	-29(3)
C(17)-C(18)-C(19)-C(1)	167.5(19)
O(3)-C(13)-O(2)-C(20)	-2(5)
C(14)-C(13)-O(2)-C(20)	-179(3)
C(19)-C(1)-C(6)-C(5)	-175(3)
C(2)-C(1)-C(6)-C(5)	10(4)

.

General procedure for the synthesis

A mixture of sodium methoxide (catalytic), freshly distilled methyl 3-oxobutanoate (0.01 mol) and chalcone (0.01 mol) in 20 ml of absolute methanol was stirred at room temperature over night. The resulting precipitate was collected by filtration, washed with methanol and bidistilled water. Crystallization from methanol gave crystals of 1b suitable for single-crystal X-ray diffraction.

Methyl 1-oxo-3,5-diphenylcyclohexene-6-carboxylate (1b)

Yield 90%; m.p. 110-112 °C; IR (cm^-1, KBr): 1734 (CO), 1657 (CO), 1590 (C=C). ¹H NMR CDCl₃: δ 3.06 (d, 1H, H_4a, J:12.5 Hz), 3.13 (dt, 1H, H_4b, J:11,5, 7.71, 1.98 Hz), 3.58 (s, 3H, OCH₃), 3.81 (dd, 2H, H₅,₆, J:5.44, 2.23 Hz), 6.56 (d, 1H, H₂, J:1.98 Hz), 7.42-7.29 (m, 5H, Ar), 7.55-7.51 (m, 5H, Ar). ¹³C NMR: 36.1, 44.1, 52.2, 59.6, 124.1, 126.2, 127.2, 127.6, 128.9, 130.6, 137.7, 141.1, 158.8, 174.8, 194.0. Anal. Calcd. For C₂₀H₁₈O₃: C, 78.41; H, 5.92. Found. C, 78.63; H, 5.84.