Molecular and crystal structure of trans and cis isomers of 3-cyano-4-[2-(4-methoxyphenyl)vinyl]-6,6-dimethyl-5,6-dihydro-2H-pyran

Article abstract of DOI:10.1007/s10593-009-0279-6

Monocrystals of the trans and cis isomers of 3-cyano-4-[2-(4-methoxyphenyl) vinyl]-6,6-dimethyl-5,6-dihydro-2H-pyran have been obtained and an X-ray structural analysis of them has been carried out. Both compounds have a molecular structure corresponding

Full text of DOI:10.1007/s10593-009-0279-6

Chemistry of Heterocyclic Compounds, Vol. 45, No. 4, 2009
MOLECULAR AND CRYSTAL STRUCTURE
OF trans AND cis ISOMERS OF 3-CYANO-4-[2-(4-METHOXY-
PHENYL)VINYL]-6,6-DIMETHYL-5,6-DIHYDRO-2H-PYRAN*
S. Belyakov1, M. Fleisher1**, D. Jansone1, L. Leite1, and E. Lukevics1
Monocrystals of the trans and cis isomers of 3-cyano-4-[2-(4-methoxyphenyl)vinyl]-6,6-dimethyl-
5,6-dihydro-2H-pyran have been obtained and an X-ray structural analysis of them has been carried
out. Both compounds have a molecular structure corresponding to symmetry group C1. The heterocyclic
ring is in a distorted envelope conformation. The crystals of the trans isomer are rhombic and have a
fir-tree type of packing. The crystal packing of the cis isomer is formed by pairs of molecules, each of
which consists of only one enantiomer.
Keywords: 3-cyano-4-[2-(4-methoxyphenyl)vinyl]-6,6-dimethyl-5,6-dihydro-2H-pyran, X-ray structural
analysis, AM1.
Many synthetic and natural derivatives of δ-lactones possess a broad spectrum of biological activity, in
particular bactericidal [1], cardiotonic [2], and cytotoxic [3] properties, are used in clinical practice as
anticonvulsants [4], serve as agents for the treatment of hypercholesterolemia [5], oncological diseases [6], and
are also used as plant growth stimulators [7-9]. With the aim of searching for new pharmacologically active
compounds of this class, 3-cyano-4-[2-(4-methoxyphenyl)vinyl]-6,6-dimethyl-5,6-dihydro-2H-pyran (1) has
been synthesized by the condensation of 3-cyano-4,6,6-trimethyl-5,6-dihydro-2-pyranone with 4-methoxy-
benzaldehyde in EtOH in the presence of catalytic quantities of NaOH. The synthesized compound was
1
identified on the basis of spectral data and elemental analysis [3]. According to data of H NMR spectra the
vinyl fragment of the compound has a trans configuration (J = 15.9 Hz). X-ray structural analysis is the most
objective method to establish the three-dimensional structure of chemical compounds in detail. Crystals of two
forms were obtained on recrystallizing compound 1 from ethanol, viz. pale-green needles and yellow prisms.
Spatial models of molecules of both compounds were obtained by X-ray structural analysis (Fig. 1). The
basic geometric characteristics are given in Tables 1 and 2. It was established that the crystals of the first form
are trans isomers and the crystals of the prismatic form are cis isomers of compound 1. In the condensed phase
both isomers have a molecular structure pertaining to the point group of symmetry C1.
_______
* Dedicated to deeply respected Professor Hank van der Plas in connection with his jubilee.
** To whom correspondence should be addressed, e-mail: misha@osi.lv.
1Latvian Institute of Organic Synthesis, Riga LV-1006, Latvia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 535-540, April, 2009. Original
article submitted December 5, 2008.
0009-3122/09/4504-0417©2009 Springer Science+Business Media, Inc.
417

a
b
Fig. 1. Spatial models of (a) the trans isomer and (b) the cis isomer of the compound 1 molecule according
to X-ray structural analysis, with ellipsoids of thermal vibrations and numbering of atoms.
The phenyl ring, the atoms of the vinyl group, the basic atoms of the heterocyclic ring, the cyano group,
and the oxygen atom of the carbonyl group of the trans isomer lie in one plane. The oxygen atom of the
methoxy group occupies the cis position relative to the C(15)–C(16) bond. The dihedral angle C(4)–C(10)–
C(11)–C(12), characterizing the trans form of compound 1, is equal to 178.9o.
The heterocyclic ring has the conformation of a distorted half-chair. The emergence of atom C(6) from
the plane of the other ring atoms was equal to 0.655(6) Å, and the angle of fold of the C(5)–C(6)–O(1) plane
was 43.4(4)° The pseudo-plane C(20)–C(6)–C(21), containing the carbon atoms of the methyl groups, was
practically orthogonal to the basic plane of the heterocycle (91.7(4)°).
TABLE 1. Main Bond Lengths (l) in trans and cis Isomers of Compound 1,
Determined by X X-ray structural analysis and Calculated by AM1
l, Å
trans-1
X-ray structural
cis-1
X-ray structural
Bond
АМ1
АМ1
analysis
analysis
O(1)–C(2)
1.334(6)
1.478(7)
1.350(6)
1.505(6)
1.511(7)
1.467(7)
1.434(7)
1.336(6)
1.449(6)
1.437(6)
1.374
1.474
1.360
1.489
1.530
1.442
1.448
1.346
1.449
1.423
1.340(3)
1.468(3)
1.356(3)
1.504(3)
1.517(3)
1.470(2)
1.452(3)
1.339(3)
1.461(3)
1.429(3)
1.373
1.475
1.357
1.489
1.529
1.443
1.453
1.340
1.450
1.424
C(2)–C(3)
C(3)–C(4)
C(4)–C(5)
C(5)–C(6)
C(6)–O(1)
C(4)–C(10)
C(10)–C(11)
C(11)–C(12)
O(18)–C(19)
418

TABLE 2. Main Valence Angles (ω) in trans and cis Isomers of
Compound 1, Determined by X-ray structural analysis and Calculated by
the AM1 Method
ω, deg
trans-1
X-ray structural
cis-1
X-ray structural
Angle
АМ1
АМ1
analysis
analysis
C(3)–C(4)–C(5)
C(4)–C(5)–C(6)
C(5)–C(6)–O(1)
C(6)–O(1)–C(2)
O(1)–C(2)–C(3)
C(2)–C(3)–C(4)
C(4)–C(10)–C(11)
C(10)–C(11)–C(12)
C(19)–O(18)–C(15)
116.7(4)
113.1(4)
110.4(4)
119.6(4)
117.7(5)
123.3(5)
125.3(4)
127.0(4)
118.2(4)
118.7
112.5
111.8
118.3
119.8
120.6
124.0
125.1
116.3
115.5(2)
111.8(2)
109.3(2)
120.3(2)
117.5(2)
123.6(2)
129.5(2)
130.3(2)
118.1(2)
119.2
112.4
111.9
118.5
119.7
120.4
127.3
127.7
116.2
In the crystal, the molecules of the trans isomer form fir-tree packing, from which significant
intermolecular interactions are absent, which causes the relatively low density of the substance (1.211 g/cm3)
(Table 3).
TABLE 3. Crystallographic Characteristics of trans and cis Isomers of
Compound 1 and Refinement Parameters of the Crystal Structures
Parameters
trans-1
cis-1
Empirical formula
Molecular mass
Crystal shape
Crystal size, mm
System
C17H17NO3
C17H17NO3
283.327
283.327
Needles
Prisms
0.05×0.07×0.43
Rhombic
0.12×0.19×0.31
Monoclinic
Unit cell parameters:
a, Å
b, Å
c, Å
20.820(2)
13.8366(11)
5.3925(4)
90.0
12.4206(6)
8.4972(5)
14.0206(9)
94.631(2)
β, deg
Unit cell volume, V, Å3
Space group
1553.5(2)
Pna21
4
1474.91(15)
P 21/n
4
Number of molecules in unit cell, Z
F(000)
600
600
Density of substance, ρcalc, g/cm3
Maximum angle 2θmax, deg
Miller index intervals
1.211
46.0
1.276
55.0
–22≤h≤22
–14≤k≤15
–5≤l≤5
–15≤h≤16
–10≤k≤11
–18≤l≤18
Absorption coefficient, µ, mm-1
0.08
0.09
Number of reflections
overall
independent
with I > 3σ(I)
1921
1268
826
5845
3836
1732
R-Factor
0.049
0.048
R-Indexes for all reflections (R1, wR2)
0.095, 0.121
190
0.084, 0.197
258
Number of parameters refined
GOOF
1.330
1.267
(∆/σ)max
0.007
0.002
419

Parameter c of the crystal unit cell was significantly less than the two other parameters (Table 3). In
similar cases crystal growth occurs preferentially in the direction perpendicular to the small parameter (Gibbs–
Currie–Wulff theorem [10]), as a result of which fine needle-shaped crystals are formed.
The molecule of the cis isomer of 1 may not have a planar conformation due to the mutual repulsion of
the hydrogen atoms at C(5) and C(17), consequently the molecule is characterized by a helical conformation
with an absolute value of the C(12)–C(11)–C(10)–C(4) torsion angle of 13.4(2)° (Fig 1b). The phenyl ring is
turned relative to the plane containing the vinyl group by 33.3(2)°. The heterocyclic ring has, as in the case of
the trans isomer, the shape of a distorted half-chair. The O(1) atom emerges from the plane of the C(3)–C(4)–
C(5) atoms by 0.264 Å, and the C(6) atom emerges by 0.755(2) Å in the same direction.
Although the molecule of the cis isomer does not have asymmetric atoms it is nonetheless chiral since it
may have both a left helical conformation or a right. The crystal consists of a mixture of equal amounts of the
two enantiomers (torsion angle C(12)–C(11)–C(10)–C(4) is -13.4(2)° and +13.4(2) °). The special feature of the
structure of the crystals of the cis isomer is the packing, consisting of pairs of molecules each of which is formed
only of one of the enantiomers (Fig. 2). In each pair the molecules are disposed in such a way that the phenyl
ring of one of them is almost parallel to the heterocyclic ring of the other (the angle between the planes of the
rings is equal to 13.3(2)°).
Fig. 2. Projection of the crystal structure of the cis isomer of compound 1
along the direction of the x axis.
To obtain a representation of the structure of the isolated molecules in the gas phase quantum-chemical
calculations were carried out of the isomers with complete optimization of their geometry by the AM1
semiempirical method [11]. Bond lengths and valence angles obtained experimentally (X-ray structural analysis)
and found theoretically (AM1) differed insignificantly (Tables 1 and 2). A shortening of the valence bond of the
heteroatom to the carbon atom of the carbonyl group on going into the crystalline state amounted to only
0.040 Å for the trans isomer and 0.033 Å for the cis isomer.
A more significant difference concerned the C(12)–C(11)–C(10)–C(4) torsion angle in the cis isomer,
describing the extent of rotation of the heterocycle around the C(4)–C(10) bond. According to the calculations
this angle is equal to 54.1° in the isolated molecule, while in the crystal, due to the effect of the molecular
packing, it was reduced to 13.4(2)°.
420

EXPERIMENTAL
3-Cyano-4-[2-(4-methoxyphenyl)vinyl]-6,6-dimethyl-5,6-dihydro-2H-pyran (1) was synthesized by the
procedure reported in [3]. Monocrystals of the trans and cis isomers of the compound were obtained by
recrystallization of the reaction products from ethyl alcohol.
Quantum-chemical calculations were carried out by the AM1 method [11] using the MOPAC2007 set of
programs [12]. The optimized structures are minimum points on the potential energy surface of the molecular
systems.
The diffraction picture for monocrystals was obtained on a Bruker-Nonius KappaCCD automatic X-ray
diffractometer. Interpretation of the crystal structure was carried out by the method developed previously in the
Latvian Institute of Organic Synthesis [13]. The initial R-factor (after interpretation) obtained for the models of
the structures was 25-30%. Further refinement was effected with a full matrix least squares method in an
anisotropic approximation for all non-hydrogen atoms using the maXus set of programs [14]. Positions of
hydrogen atoms were localized on the basis of Fourier difference syntheses of electron density and were refined
in an isotropic approximation using a "rider" model. The crystallographic characteristics of the compound 1
isomers and the structural refinement parameters are given in Table 3.
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