Molecular and crystal structure of 2,4-diethoxycarbonyl-5-hydroxy-5-methyl-3-phenyl-N-(3-chlorophenyl)-1-cyclohexenylamine

Article abstract of DOI:10.1007/s10947-009-0138-4

Arylamination of 2,4-diethoxycarbonyl-5-hydroxy-5-methyl-3-phenylcyclohexanone affords 2,4-diethoxycarbonyl-5-hydroxy-5-methyl-3-phenyl-N-(3-chlorophenyl)-1-cyclohexenylamine. A distorted semi-chair conformation with psedoequatorial orientation of all sub

Full text of DOI:10.1007/s10947-009-0138-4

Journal of Structural Chemistry. Vol. 50, No. 5, pp. 926-929, 2009
Original Russian Text Copyright © 2009 by A. P. Kriven’ko, É. A. Grigor’eva, A. V. Grigor’ev, V. V. Sorokin, and S. F. Solodovnikov
MOLECULAR AND CRYSTAL STRUCTURE
OF 2,4-DIETHOXYCARBONYL-5-HYDROXY-
5-METHYL-3-PHENYL-N-(3-CHLOROPHENYL)-
1-CYCLOHEXENYLAMINE
A. P. Kriven’ko,1 É. A. Grigor’eva,1 A. V. Grigor’ev,2
V. V. Sorokin,1 and S. F. Solodovnikov3
UDC 543.442.3:547.592.15
Arylamination of 2,4-diethoxycarbonyl-5-hydroxy-5-methyl-3-phenylcyclohexanone affords 2,4-
diethoxycarbonyl-5-hydroxy-5-methyl-3-phenyl-N-(3-chlorophenyl)-1-cyclohexenylamine. distorted
A
semi-chair conformation with psedoequatorial orientation of all substituents except the pseudoaxial Ɉɇ-
group is established based on the spectral and single crystal XRD data. The presence of an intramolecular
N–ɇ…Ɉ=C hydrogen bond is noted.
Keywords: X-ray structural analysis, enaminoesters, cyclohexenes.
Earlier we have prepared a number of 3-Ar-2,4-diethoxycarbonyl-5-hydroxy-5-methylcyclohexenyl-N-R-amines by
the interaction of aryl-, cyclohexyl-, benzylamines with diethoxy-substituted cyclohexanolones [1]. This work presents the
data on the synthesis and structural examination of a new member of these series: 2,4-diethoxycarbonyl-5-hydroxy-5-methyl-
3-phenyl-N-(3-chlorophenyl)-1-cyclohexenylamine (1).
Experimental. Compound 1 was prepared by amination of 2,4-diethoxycarbonyl-5-hydroxy-5-methyl-3-phenyl-
cyclohexanone with m-chloroaniline in boiling benzene solution under a ketol:amine ratio of 1:2 with addition of a catalytic
amount of acetic acid
A solution of 0.01 mole of 2,4-diethoxycarbonyl-5-hydroxy-5-methyl-3-phenyl-cyclohexanone and 0.013 mole of
m-chloroaniline in 50 ml of benzene was added with 1 ml of glacial acetic acid. The reaction mixture was boiled for 18 h;
light-gray crystals of 1 precipitated on cooling. Tm 161-162qɋ (from ethanol). Yield 2.32 g (68%). Found, %: ɋ 66.15, ɇ
6.32, N 3.27, Cl 8.05. ɋ25ɇ28N1Ɉ5Cl. Calculated, %: ɋ 65.57, ɇ 6.12, N 3.06, Cl 7.76.
The IR spectra of the compounds were recorded on a Fourier spectrometer FSM-1201 (thin layer: Vaseline oil,
hexachlorobutadiene). The 1H NMR spectra were measured on a Bruker AC-300 spectrometer (300 MHz for 1ɇ) in DMSO-d6
2
3
1Saratov State University; sorokinvv@info.sgu.ru. NITA-FARM Co. Ltd, Saratov. A. V. Nikolaev Institute of
Inorganic Chemistry, Siberian Division, Russian Academy of Sciences, Novosibirsk. Translated from Zhurnal Strukturnoi
Khimii, Vol. 50, No. 5, pp.963-966, November-December, 2009. Original article submitted August 13, 2008.
926
0022-4766/09/5005-0926 © 2009 Springer Science+Business Media, Inc.

TABLE 1. Positional (u104) and Equivalent Isotropic Thermal Parameters (Å2u103) of Non-Hydrogen Atoms
in the Structure of 1
Atom
x/a
y/b
z/c
U(eq)*
Atom
x/a
y/b
z/c
U(eq)*
Cl
5000
2819(2)
526(4)
5000
89(1)
58(2)
55(2)
64(2)
67(2)
51(2)
43(2)
39(2)
37(3)
41(3)
42(3)
42(3)
44(3)
44(3)
49(3)
60(3)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
C(19)
C(20)
C(21)
C(22)
C(23)
C(24)
C(25)
5619(5)
5619(5)
5022(6)
2344(6)
1179(5)
503(5)
2103(5)
2343(5)
1956(6)
1356(6)
1113(6)
1492(5)
2774(5)
2848(6)
3472(6)
4175(5)
1302(7)
468(8)
45(7)
–265(7)
170(7)
–307(8)
–2266(6)
–2186(6) –658(12)
–2573(7) –1979(14)
–2994(7) –1800(13)
–3075(8) –273(15)
–2679(7) 1026(13)
–3500(7) 3362(13)
–5131(6) 3238(14)
–5696(7) 3516(15)
–2980(6) 4623(11)
4025(13)
3305(14)
2745(13)
1668(13)
1269(15)
1216(16)
893(11)
59(3)
64(3)
54(3)
49(3)
82(4)
120(6)
40(3)
55(3)
71(4)
73(4)
83(4)
63(3)
48(3)
80(4)
106(5)
53(3)
O(1)
O(2)
O(3)
O(4)
O(5)
N
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
2494(3)
1690(4)
2334(4)
3079(4)
3324(4)
3753(4)
3501(5)
2818(5)
2544(5)
3101(5)
3630(5)
3997(4)
4396(5)
4388(5)
5013(6)
1217(9)
1772(9)
4291(9)
2770(9)
5530(9)
2340(11)
2575(11)
2139(11)
–494(4)
–3554(4)
–4224(4)
–1983(4)
101(5)
–765(6)
–956(6)
–1914(7) 2387(12)
–2634(6) 2852(12)
–2240(6) 4108(13)
–1440(6) 3369(11)
475(6)
1342(6)
1720(6)
2904(13)
3612(12)
4193(14)
*U(eq) is defined as one third of the trace of the orthogonalized tensor Uij.
(TMS as internal standard). The reaction course and product purity were monitored by TLC on Silufol UV-254 foils, eluent:
hexane–ethylacetate–chloroform 2:2:1, iodine staining, UV radiation.
X-ray diffraction data for unit cell refinement and structure solution of compound 1 were collected by the standard
method at room temperature on an Enraf-Nonius CAD-4 automatic diffractometer (OMoKD, graphite monochromator, Z/2T-
scanning with variable scan rate, 2T d 55q) from a prismatic crystal with a size of 0.10u0.15u0.52 mm. The compound
crystallizes in the monoclinic crystal system; chemical formula C25H28NOCl, M = 457.93; space group Cc; ɚ = 19.606(2) Å,
b = 14.646(2) Å, c = 8.304(2) Å; E = 94.55(1)q, V = 2377.0(7) Å3, Z = 4, dcalc = 1.280 g/cm3. Absorption correction was not
applied because of a small linear extinction coefficient (P = 0.196 mm–1).
The structure was solved by the direct method and refined with full-matrix least squares techniques in the
anisotropic approximation for non-hydrogen atoms using the SHELXTL-97 program package [2]. Almost all hydrogen atoms
were located from the difference Fourier syntheses and refined with isotropic thermal parameters. Final convergence factors
for 300 parameters and 4 restraints on the C–H, N–H, O–H distances were: R(F) = 0.0405, wR(F2) = 0.0526 for 782 observed
reflections [I > 2V(I)]; R(F) = 0.1169, wR(F2) = 0.0790 for all 1953 reflections; goodness-of-fit S = 0.742.
The refined positional parameters of independent atoms and equivalent isotropic thermal parameters are listed in
Table 1; intramolecular bond distances and angles are in Table 2. Crystallographic information has been deposited to the
Cambridge Structural Database, deposition number CCDC 719586, address deposit@ccdc.cam.ac.uk.
Results and discussion. The IR spectrum of enamine 1 exhibits stretching vibrations of a secondary amine group
(3310 cm–1), hydroxyl (3568 cm–1) and non-conjugated carbonyl groups (1710 cm–1). The bathochromic shift of the carbonyl
group vibration at 1639 cm–1 is due to the conjugation and intramolecular C=O…H–N hydrogen bonding, similarly to
structurally analogous compounds [3, 4].
1
The ɇ NMR spectrum exhibits the signals of protons of the hydroxyl (3.24 ppm), amine (11.71 ppm) functions,
geminal protons of the ɋ6 carbon at 2.63 ppm as a doublet of doublets, 1H each, SSCC J6ea 17.7 Hz indicating their magnetic
non-equivalence. Relying on the non-equivalence of the geminal protons and according to the work [5], we accepted the
distorted semi-chair confirmation of the cyclohexene ring with the pseudoaxial hydroxyl group.
927

TABLE 2. Bond Lengths d, Å and Angles M, deg in the Molecule of 1
Distance
d
Distance
d
Distance
d
Distance
d
C(1)–C(2)
C(1)–N
1.39(1)
1.38(1)
1.50(1)
1.52(1)
1.41(1)
1.54(1)
1.54(1)
1.53(1)
1.50(1)
C(5)–C(6)
C(5)–O(5)
C(5)–C(25)
N–C(7)
C(7)–C(8)
C(8)–C(9)
C(9)–C(10)
C(9)–Cl
1.53(1)
1.42(1)
1.56(1)
1.42(1)
1.40(1)
1.39(1)
1.35(1)
1.74(1)
1.36(1)
C(11)–C(12)
C(12)–C(7)
C(13)–O(1)
C(13)–O(2)
O(2)–C(14)
C(14)–C(15)
C(16)–C(17)
C(17)–C(18)
1.37(1)
1.39(1)
1.26(1)
1.34(1)
1.43(1)
1.50(1)
1.41(1)
1.40(1)
C(18)–C(19)
C(19)–C(20)
C(20)–C(21)
C(21)–C(16)
C(22)–O(3)
C(22)–O(4)
O(4)–C(23)
C(23)–C(24)
1.38(1)
1.39(1)
1.39(1)
1.35(1)
1.20(1)
1.33(1)
1.47(1)
1.48(1)
C(1)–C(6)
C(2)–C(3)
C(2)–C(13)
C(3)–C(4)
C(3)–C(16)
C(4)–C(5)
C(4)–C(22)
C(10)–C(11)
Angle
Angle
Angle
M
M
M
C(2)–C(1)–C(6)
N–C(1)–C(2)
N–C(1)–C(6)
124(1)
120(1)
116(1)
122(1)
120(1)
118(1)
112(1)
114(1)
108(1)
114(1)
110(1)
110(1)
111(1)
112(1)
109(1)
106(1)
C(4)–C(5)–C(25)
C(6)–C(5)–C(25)
C(1)–C(6)–C(5)
C(1)–N–C(7)
C(12)–C(7)–C(8)
C(12)–C(7)–N
110(1)
108(1)
112(1)
129(1)
119(1)
124(1)
117(1)
118(1)
123(1)
120(1)
117(1)
119(1)
122(1)
120(1)
120(1)
125(1)
O(2)–C(13)–C(2)
C(13)–O(2)–C(14)
O(2)–C(14)–C(15)
C(21)–C(16)–C(17)
C(21)–C(16)–C(3)
C(17)–C(16)–C(3)
C(18)–C(17)–C(16)
C(19)–C(18)–C(17)
C(18)–C(19)–C(20)
C(21)–C(20)–C(19)
C(16)–C(21)–C(20)
O(3)–C(22)–O(4)
O(3)–C(22)–C(4)
O(4)–C(22)–C(4)
C(22)–O(4)–C(23)
O(4)–C(23)–C(24)
115(1)
118(1)
107(1)
118(1)
122(1)
120(1)
119(1)
121(1)
120(1)
118(1)
123(1)
123(1)
126(1)
111(1)
118(1)
106(1)
C(1)–C(2)–C(13)
C(1)–C(2)–C(3)
C(13)–C(2)–C(3)
C(2)–C(3)–C(16)
C(2)–C(3)–C(4)
C(16)–C(3)–C(4)
C(22)–C(4)–C(5)
C(22)–C(4)–C(3)
C(5)–C(4)–C(3)
O(5)–C(5)–C(4)
O(5)–C(5)–C(6)
C(4)–C(5)–C(6)
O(5)–C(5)–C(25)
C(8)–C(7)–N
C(9)–C(8)–C(7)
C(10)–C(9)–C(8)
C(10)–C(9)–Cl
C(8)–C(9)–Cl
C(9)–C(10)–C(11)
C(10)–C(11)–C(12)
C(11)–C(12)–C(7)
O(1)–C(13)–O(2)
O(1)–C(13)–C(2)
Figure 1 shows a general view of the molecule of 1. The cyclohexene ring has the shape of a distorted semi-chair. The
fragment of the ring near the double bond is almost planar: the C(6)–C(1)–C(2)–C(3) torsion angle is 3q. The configuration of
the “saturated” part of the ring approaches to the cyclohexane one: the C(3)–C(4)–C(5)–C(6) torsion angle is 64q.
The aryl substituent at C3 (C(3) in Fig. 1) and ester substituents are in the pseudo-equatorial positions. The angles
between the plane of the aryl substituent at C3 and the planes defined by C(3), C(4), C(5) and C(1), C(2), C(3) atoms are 110q
and 120q respectively. The C(4)–C(3)–C(16)–C(21) and C(2)–C(3)–C(16)–C(21) torsion angles are 99q and 134q
respectively. Therefore, the aryl substituent is positioned almost perpendicularly to the “plane” of the cyclohexene ring. The
molecule has an intramolecular hydrogen bond between the amine hydrogen and oxygen of the ester function at ɋ2. The
Ɉ(1)…ɇ(1) distance is 1.86(6) Å; Ɉ(1)…N is 2.64(9) Å; N–H(1) is 0.82(4) Å; the O(1)…H(1)–N(1) angle is 159(6)q. The
hydroxyl group is pseudo-axial. The torsion angle between the vicinal trans-diequatorial ester group and the phenyl
substituent (C(16)–C(3)–C(4)–C(22)) equals to 54(1)q, evidencing the diaxial arrangement of the methine hydrogens at ɋ(3)
and ɋ(4). The torsion angle between the vicinal trans-diequatorial ester group and the methyl substituent (C(22)–C(4)–C(5)–
C(25)) is 54(1)q. The N-aryl cycle is not coplanar to the enaminocarbonyl fragment, though not perpendicular to it (C(1)–
N(1)–C(7)–C(12) torsion angle is 49(2)q) admitting partial conjugation.
Therefore, the molecule of compound 1 is geometrically similar to the molecule of 2,4-diacetyl-5-hydroxy-5-
methyl-3-(2-chlorophenyl)-N-(4-methylphenyl)-1-cyclohexenylamine that we described previously in the work [6].
928

Fig. 1. Geometry of the molecule of 1 according to XRD data.
A difference in the substituents (acetyl, ethoxycarbonyl) does not significantly affect the overall geometry of the molecule:
the shape of the cyclohexene ring, twist angles of the aryl groups at the nitrogen and carbon atoms. The dissimilarity consists
in the absence of the intramolecular hydrogen bond between the hydroxyl and the adjacent ester group in enamine 1 caused
by the switching of the ɇ(5) atom of the hydroxyl group to the intermolecular bond with the Ɉ(1) oxygen atom of the ester
function. The Ɉ(1)…ɇ(5c), Ɉ(1)…Ɉ(5c), and Ɉ(5c)–H(5c) distances are 2.15(9) Å, 2.77(1) Å, and 0.96(4) Å respectively; the
O(1)…H(5c)–Ɉ(5c) angle is 119(5)q. The presence of this intermolecular hydrogen bond strengthens molecular packing in the
structure along the ɫ axis.
This study was supported by the grant of the President of the Russian Federation for support of young scientists
(MK-9885.2006.3.).
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