Structure, z′ = 2 crystal packing features of 3-(2-chlorobenzylidene)-5-(p-tolyl)furan-2(3h)-one

Article abstract of DOI:10.3390/molecules26082137

3-(2-Chlorobenzylidene)-5-(p-tolyl)furan-2(3H)-one (1), C₁₈H₁₃ClO₂, crystallizes with Z = 8 and Z^′ = 2, and the structure at 100 K has orthorhombic (Pna2₁) symmetry. Each kind of molecule takes part in π–π stacking interactions to form infinite chains parallel to the c axis. We believe that the existence of two forms can be explained by the probable rotation around a single C–C bond. The quantum chemical modeling reveals that these molecules are almost equivalent energetically, and they can be described as the two most stable conformers (rotamers) with a minor rotational barrier of about 0.67 kcal/mol.

Full text of DOI:10.3390/molecules26082137

molecules
Article
Structure, Z0 = 2 Crystal Packing Features of
3-(2-Chlorobenzylidene)-5-(p-tolyl)furan-2(3H)-one
Vyacheslav S. Grinev 1,2,
*
, Oksana A. Mayorova 1, Tatyana V. Anis’kova 2, Alexandra S. Tikhomolova 2
and Alevtina Yu. Yegorova 2
1
Institute of Biochemistry and Physiology of Plants and Microorganisms RAS, Prospekt Entuziastov 13,
410049 Saratov, Russia; beloousova011@yandex.ru
Institute of Chemistry, N.G. Chernyshevsky Saratov National Research State University, Ulitsa
2
Astrakhanskaya 83, 410012 Saratov, Russia; aniskovatv@mail.ru (T.V.A.);
bondartsova.alexandra@ya.ru (A.S.T.); yegorovaay@gmail.com (A.Y.Y.)
*
Correspondence: grinev@ibppm.ru; Tel.: +7-845-297-0403; Fax: +7-845-297-0383
Abstract: 3-(2-Chlorobenzylidene)-5-(p-tolyl)furan-2(3H)-one (
and Z0 = 2, and the structure at 100 K has orthorhombic (Pna21) symmetry. Each kind of molecule
takes part in stacking interactions to form infinite chains parallel to the c axis. We believe that
1), C18H13ClO2, crystallizes with Z = 8
π–π
the existence of two forms can be explained by the probable rotation around a single C–C bond. The
quantum chemical modeling reveals that these molecules are almost equivalent energetically, and
they can be described as the two most stable conformers (rotamers) with a minor rotational barrier of
about 0.67 kcal/mol.
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Keywords: crystal structure; crystallographically independent forms; rotamers; quantum chemical
modeling; rotational barrier; 3-arylidene-5-arylfuran2(3H)-one
Citation: Grinev, V.S.; Mayorova, O.A.;
Anis’kova, T.V.; Tikhomolova, A.S.;
Yegorova, A.Y. Structure, Z0 = 2
Crystal Packing Features of 3-(2-
Chlorobenzylidene)-5-(p-tolyl)furan-
2(3H)-one. Molecules 2021, 26, 2137.
https://doi.org/10.3390/
1. Introduction
Much attention is paid to the study of the biological active compounds containing both
furan-2(3H)-one and substituted benzene rings linked via “spacers” of various length and
molecules26082137
rigidity, which are capable of adopting different conformations adapting to receptors [1–8].
Academic Editors: Irina A. Balova
and Alexander S. Antonov
There are several ways to obtain such compounds using 5-aryl substituted furan-2(3H)-ones
as initial substrates. Among them there is an azo coupling reaction of aryldiazonium salts
based on the substituted anilines giving rise to arylazohydrazones of furan-2(3H)-ones with
an azo group as a spacer demonstrating anti-inflammatory and analgesic activity [9–15].
Another approach to obtain structural information on hydrazones with a shorter
spacer is a condensation of substituted aromatic aldehydes with furan-2(3H)-ones result-
ing in corresponding arylmethylidene derivatives. Both hydrazones and arylmethyli-
dene derivatives of furan-2(3H)-ones are of interest for studying their Z/E-tautomeric
equilibrium and conformational preferences. Arylmethylidene (arylidene) derivatives of
furan-2(3H)-ones are also structural fragments of various biologically active compounds.
The 2-(2-nitrobenzylidene) malonate and some related structures were synthesized and
studied as a novel group of TLR4 signaling inhibitors to reveal the mechanism of their
inhibitory effect [16]. Recently, some structural, spectroscopic, and photophysical proper-
ties of alkylamino substituted 2-arylidene and 2,5-diarylidene cyclopentanone dyes were
studied [17]. Arylmethylidene derivatives are also available as scaffolds for the synthesis
of various heterocyclic compounds of different complexity. These substances combine the
properties of unsaturated carbonyl compounds and esters, allowing the implementation
of reactions with various C-nucleophiles such as acetoacetic ester [18], acetylacetone [19],
Received: 18 February 2021
Accepted: 6 April 2021
Published: 8 April 2021
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4.0/).
cyclohexanone [20], and mono- and N,N-binucleophiles [21
a conjugated double bond, arylidene derivatives can easily add azides [23
give rise corresponding epoxides [25]), and halogen [26]. Many of the studied reactions
,22]. Owing to the presence of
,
24] oxygen (to
Molecules 2021, 26, 2137. https://doi.org/10.3390/molecules26082137
https://www.mdpi.com/journal/molecules

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are stereoselective, and the configuration of the resultant products is associated with the
structure of the reagents.
Recently, we reported basic crystal structural features of the arylmethylidene com-
pound
1
, which is one of the representatives of hydrazones, namely (E)-3-[2-(2-nitrophenyl)-
, Figure 1). It has been shown that azo
hydrazineylidene]-5-phenylfuran-2(3H)-one (
2
coupling with compounds containing an active methylene group leads to the possible
existence of several tautomeric forms due to prototropic tautomerism due to the migration
of a proton from the C(2) carbon atom to the N(2) nitrogen atom or O(2) oxygen atom.
Compound (2) exists in the crystal in the E-hydrazo tautomeric form, which was confirmed
by the corresponding interatomic distances N(1)–N(2) of 1.3437(16) Å and N(1)–C(2) of
1.2984(18) Å.
Figure 1. General view of molecules: non-flat arylidene (1, current study) and flat hydrazone (2) derivatives of furan-
2(3H)-one in a crystal. Atoms are represented by thermal vibration ellipsoids (P = 50%). The H-bond is indicated by
a dotted line.
X-ray diffraction analysis of (2) showed that the hydrazone tautomeric form is favor-
able for the intermolecular H-bond of the corresponding substituents in the aryl fragment
since an additional stabilization of the E-configuration is possible. The entire molecule lies
almost in one plane due to the extended conjugation chain covering the phenyl ring at
position 5, the double bond and the lactone carbonyl group in the furanone ring, as well as
the 2-nitrophenylhydrazo fragment [5].
3-Arylmethylidene derivatives also have the ability to exist in the E- and Z-configuration
relative to the exocyclic C=C bond. The introduction of a bulky substituent in an ortho-
position of the benzene ring as well as the closeness of the H-atoms of mentioned benzene
ring and at the C-4 atom in furan-2(3H)-one moiety may cause some hindrance during the
rotation around single bonds to give rise to some stable rotational structures (rotamers),
which are bonded by non-covalent π–π stacking interactions in the crystal. The study of the
conformational preferences of some o-substituted heterocyclic systems is important from
the point of view of structure–activity relationships (SAR), because different conformers
may have non-equivalent receptor affinities [27–29]. For the study of the conformational
features of different compounds, a number of techniques have been used, including NMR,
UV–Vis, FTIR spectroscopy, X-ray diffraction, and quantum chemical calculations. Inter-
molecular interactions have been implicated in the formation of high Z0 structures [30].
Today, scientists pay great attention to crystals with Z0
≥
2. From the one hand, crystals
containing more than one independent molecule exhibit lower symmetry [31]. On the other
hand, there is an approach based on a topological analysis of the experimental distribution
of electron density which allows one to investigate the response of the single molecule in
crystals with Z0
≥
2 to the surroundings [32] even caused by the weak interactions [33,34].
In this study, we present the results of X-ray diffraction of the titled compound
demonstrating a Z = 2 crystal packing. To reveal some reasons of the existence of a mixture
0
of two forms in the condensed state, we performed DFT modeling. We also suggest that

Molecules 2021, 26, 2137
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the intrinsic rotation around simple C–C bond is a possible mechanism of the transition
of these two forms from one to another and evaluated the intrinsic rotation barrier in the
gaseous phase.
2. Results and Discussion
2.1. Solving Structure Attempts
Our attempts to solve the structure in the higher symmetry space group (including
in the centrosymmetric space group Pnam) were unsuccessful and failed to establish a
reasonable structural model. The ADDSYM (PLATON) program did not indicate any
missed symmetry for the structure solved in Pna21. Furthermore, the ADDSYM analysis
for the structure of (1) solved in P1 only suggested the centrosymmetric space group Pna21.
Solving the structure using the SUPERFLIP and SHELXT programs having algorithms for
determining the space group gave the same results.
2.2. Crystal Structure Analysis
The content of the asymmetric unit of (1), along with the atom-labeling scheme, is
shown on Figure 2. This structure has been deposited in the Cambridge Crystallographic
Data Centre with the deposition number CCDC 1456486. These data can be obtained free
of charge via https://www.ccdc.cam.ac.uk/structures/ (accessed date 19 March 2021, or
from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ,
UK; Fax: +44-1223-336033).
Figure 2. The geometry of the two crystallographically independent forms of (
ellipsoids are drawn at the 50% probability level.
1) in the asymmetric unit. Displacement
Compound (1
) crystallizes with Z = 8 and Z0 = 2 in the orthorhombic crystal system,
space group Pna21. In the asymmetric unit, two crystallographically independent forms
0
are found. These two molecules reveal structural closeness. Most authors determine the Z
0
parameter as the number of symmetry independent molecules [30]. Z > 1 may be formally
presented as a co-crystallization where the two components are chemically the same. On
the one hand, applying the inversion symmetry operation to one of these forms, one can
see a significant similarity in the overlay diagram, especially in the part of molecules
containing the flat furan-2(3H)-one ring with the p-tolyl substituent (Figure 3). On the other
hand, these twins can be represented as rotamers of (1), because aryl-substituted furan
moieties of two forms are very similar, and the most pronounced distinction is the location
of the arylmethylidene substituent, which can be illustrated by the values of the C(2)–C(5)–
◦
C(6)–C(7) and C(2A)–C(5A)–C(6A)–C(7A) torsion angles which are –144.5(5) (rotamer 1a
)
◦
and 157.6(5) (rotamer 1b), respectively. As a result, there are differences in the interatomic
distances between chlorine and hydrogen atoms in forms (1a) and (1b). In (1a), the con-
tacts Cl(1)···H(5A) and H(5A)···O(2) are 2.785 and 2.714 Å, respectively, and the distance

Molecules 2021, 26, 2137
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H(11A)···H(3A) is 2.301 Å. The corresponding distances in (1b) are shorter by 0.1–0.2 Å
(2.649, 2.629 and 2.150 Å, respectively). The C(5)H···Cl(1)/C(5A)H···Cl(1A) contacts are sig-
nificantly shorter than the sum of Bondi’s vdw (Van der Waals)radii (in non-bonded contact
distances) of 2.95 Å [35], indicating a pronounced electrostatic attraction between chlorine
and hydrogen atoms. The O(2)···C(5)H/O(2A)···C(5A)H contacts are close to the sum of
the vdw radii (2.72 Å), and in (1b), the attraction between hydrogen and oxygen atoms
is greater. The C(3)H···C(11)
H
/C(3A)H···C(11A)
H contacts [2.30118(8)/2.14979(7) Å] are
significantly shorter than the sum of the vdw radii (2.38–2.40 Å), especially for the 1b twin,
which indicates a repulsion between hydrogen atoms leading to the distortion of planarity
of the whole molecule (
play an important role in defining molecular conformation and crystal packing [36].
1
) in the single crystal and we note that short H···H distances often
Figure 3. The overlay diagram of the two crystallographically independent forms of 1 in the asym-
metric unit. Displacement ellipsoids are drawn at the 50% probability level.
The molecule of (
hydrazono]-5-phenylfuran-2(3H)-one (
2(3H)-one moieties and differ in the substituents at position 3.
According to the position of the substituents and rings towards the C(2)–C(5) double
bond, the molecules of ( ) are E-isomers. It was known that the arylidene derivatives of
1) is structurally related to the recently described 3-[2-(2-nitrophenyl)-
2
) [ ]. Both compounds ( ) and ( ) include 5-arylfuran-
5
1
2
1
five-membered heterocycles may be Z-configurational isomers as well as in the E-form
at the exocyclic C=C double bond. This mostly depends not on the steric volume of a
substituent but on the ability of the substituent to form non-covalent interactions within
the molecule, as well as between neighboring molecules [37
network of the hydrogen bonds in the crystal and the non-covalent interaction between
the H-atom of the methoxy group and the -system of the other substituent allows one to
,38]. The presence of the wide
π
stabilize the E-form of 3-phenyl-4-(2,4,6-trimethoxybenzylidene)isoxazol-5(4H)-one, while
the corresponding 3-phenyl-4-(2,4,6-trimethylbenzylidene)isoxazol-5(4H)-one is in the Z-
form as the more common configuration of such arylidene substituted molecules in the
solid state [37].
The p-tolyl substituent at position 5 and the furan-2(3H)-one ring in (
plane, as they also are in (2). In contrast, in 3-phenyl-4-arylidene-isoxazol-5(4H)-ones, the
3-phenylisoxazolone fragments are non-coplanar [37]. Hydrazone ( ) is almost flat owing
to the presence of an extended conjugation along the whole molecule. In the furanone
ring of ( ), the heteroatom O(1) is coming out of the plane, and the C(2)–C(3)–C(4)–O(1)
torsion angle is 1.25(14)◦. The furanone ring of (
) is more flat, the deviations from the
1) are in one
2
2
1
plane of the ring of atoms are minimal, and the absolute values of the corresponding
C(2)–C(3)–C(4)–O(1) torsion angle are less than 1◦. The 2-nitrophenyl substituent slightly
deviates from the plane of the furanone ring, and the N(1)–N(2)–C(11)–C(12) torsion angle
is 8.08(17)◦. At the same time, the molecule of (
1) is non-planar, and the arylmethylidene

Molecules 2021, 26, 2137
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substituent is characterized by the C(2)–C(5)–C(6)–C(7)/C(2A)–C(5A)–C(6A)–C(7A) torsion
angles of –144.5(5)◦ and 157.6(5)◦, respectively, which are greater than the corresponding
angle of –18.41(18)◦ [the O(3)–N(3)–C(16)–C(11) torsion angle] in (
2
). This is probably due
to the more pronounced flexibility of the arylhydrazone substituent, as well as to the longer
distance between the nitroaromatic and furanone fragments in ( ), while the arylmethyli-
dene substituent is located closer to the furanone ring in ( ). An additional factor that
2
1
does not permit the most advantageous position for conjugation, in which all the aromatic
rings of the molecule would be in one plane, is the presence of the bulky chlorine atom
as the substituent in the ortho position of the benzene ring. Nevertheless, the interatomic
distances C(1)–C(2)/C(1A)–C(2A) of 1.480(6)/1.477(6) Å and C(5)–C(6)/C(5A)–C(6A) of
1.461(6)/1.451(6) Å are significantly shorter than the corresponding distances in alkanes
(typically about 1.541
jugated olefins (about 1.466
At the same time, the interatomic distances C(2)–C(5)/C(2A)–C(5A) of 1.354/1.351 Å are
slightly longer than the corresponding average value of the isolated double bond in olefins
±
0.003 Å) and are close to the average single bond length of con-
0.005 Å), which shows their partial double-bond character.
±
(about 1.335
±
0.002 Å) and they are of partly single-bonded character. The interatomic
distances C(1)–O(2)/C(1A)–O(2A) with their values of 1.201(5)/1.202(5) Å are typical of an
average C=O bond length of 1.200 Å [39]. These facts point to the presence of conjugation
in the molecules of (1). Moreover, in system (2) there is an intramolecular hydrogen bond
between the hydrogen atom at N(2) and the O(3) atom of the nitro group, which is absent
from structure (1).
2.3. Packing and π–π Stacking Interactions
The unit cell volume of (
[1373.71(3) Å3 for the unit cell of (
whereas the unit cell of ( ) contains only four molecules. In the projection along the c axis,
it can be seen that the molecules are arranged in a checkerboard pattern—each form, (1a
1
) [2776.3(3) Å3] is relatively large for this type of molecule
)]. The cell unit of ( ) contains four pairs of rotamers,
2
1
2
)
and/or (1b), is surrounded by the molecules of another one from four sides (Figure 4). The
molecules 1a only interacting with symmetry-related 1a molecules (and similarly for 1b).
Considering the packing of the molecules along the a axis, one may note that each rotamer
is arranged with another form head-to-head or tail-to-tail.
Figure 4 is an extended packing diagram showing that the rotamers of each kind
are linked into infinite chains parallel to the c axis via π–π stacking interactions between
the chlorophenyl rings, the benzene rings of the p-tolyl substituents at position 5, and
furan-2(3H)-one rings. The intercentroid distances between all rings of each type are
identical and are 3.8037(2) Å for both rotamers. Such parameters of stacking interactions as
interplanar distances, ring offsets, and angles
θ for all three types of rings differ not only
among themselves within each form but also between the same rings of the other type. The
major parameters of π–π stacking interactions are presented in Table 1.
The smallest intercentroid distance and the maximum angle
case of the p-tolyl substituents of (1a). The maximal interplanar distance and accordingly,
the minimal angle , were observed in the o-chlorobenzene rings of (1b). In general, the
θ are observed in the
θ
values of the interplanar distances are in the range of 3.3803(7)–3.519(3) Å, and the angles
θ
are in the range of 22.33(8)–27.31(4)◦, which is typical of stacked carbo- and heterocyclic
molecules, which are relatively small and almost flat [40–43].
In contrast to the non-flat arylmethylidene (
1
), the planar hydrazone (
2) shows only in-
tramolecular H-bonds in a crystal as non-covalent interactions and reveals no
(Figure 5).
π–π
stacking

Molecules 2021, 26, 2137
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Figure 4. Extended packing diagram of the stacked molecules of (1), showing non-covalent interactions by dotted cylinders
resulting in infinite chains parallel to the c axis. Hydrogen atoms omitted for clarity. One (1a) molecules is marked blue, and
one (1b) molecule is marked green.
Table 1. Parameters of the stacking interactions in the single crystal of (1a); (1b).
◦
Ring
Angle θ,
Interplanar Distance, Å
Intercentroid Distance, Å
Ring Offset, Å
1a
o-Cl-Ar
Fur-2(3H)-one
p-Tol
3.470(3)
3.478(4)
3.380(3)
3.8037(2)
3.8037(2)
3.8037(2)
1.559(7)
1.540(8)
1.745(7)
24.19(5)
23.89(3)
27.31(4)
1b
o-Cl-Ar
Fur-2(3H)-one
p-Tol
3.519(3)
3.453(4)
3.464(3)
3.8037(2)
3.8037(2)
3.8037(2)
1.444(7)
1.596(8)
1.572(7)
22.33(8)
24.81(8)
24.41(9)

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Figure 5. Extended packing diagram of molecules of (2), view along the a axis. Hydrogen atoms omitted for clarity.
Centroid–centroid distance of the benzene and furan-2(3H)-one rings of 7.47720(10) Å and ring offset of 6.675(2) Å indicate
no non-covalent interactions between molecules.
2.4. Theoretical Investigation of the Rotational Barrier
The existence of two types of molecules, (1a) and (1b), in the crystal state can be
illustrated by the rotation around the single C–C bond. The similarity of the aryl-substituted
furan moieties of two forms suggests that the rotation is a likely reason for the presence of
two forms of (1), which we call rotamers. To quantify the rotational barrier energy in (1),

Molecules 2021, 26, 2137
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we performed the quantum chemical calculations of both rotamers in vacuum, separately
at the B3LYP/6-311++G(d,p) level of theory. The curve expressing the dependence of the
relative values of the system’s energy on the value of the C(2)–C(5)–C(6)–C(7) torsion
angle is symmetric and there are two global minima, two local minima, two local maxima,
and one global maximum (Figure 6). All important contacts in the extrema of the energy
rotational curves of rotamers (1a) and (1b) are in Table 2.
Figure 6. Relative energy profiles for the rotation around the C(5)–C(6)/C(5A)–C(6A) bond in rotamers (1a) and (1b). The
difference between relative energies of the two rotamers multiplied by 25 is shown by the dotted line.
Table 2. Important contacts (Å) in the extrema of the energy rotational curves of rotamers (1a) and (1b).
Contact
Angle
C(5)H–Cl(1)
C(3)H–C(11)H
C(5)H–C(11)H
C(3)H–Cl(1)
Extremum
1a
1b
1a
1b
1a
1b
1a
1b
Global min
Local max
Local min
Global max *
Local min
Local max
Global min
Local max **
−
152.303
−
147.749
2.690
3.647
4.065
4.409
4.105
3.536
2.723
2.543
2.722
3.535
4.105
4.409
4.065
3.648
2.690
2.543
2.242
4.095
4.852
5.551
4.932
3.900
2.308
1.968
2.307
3.899
4.932
5.551
4.853
4.097
2.243
1.968
3.711
3.014
2.536
2.070
2.483
3.120
3.692
3.807
3.692
3.121
2.483
2.070
2.535
3.013
3.711
3.807
5.657
3.776
2.943
2.502
2.880
3.994
5.581
6.009
5.583
3.995
2.881
2.502
2.942
3.774
5.655
6.010
−82.303
−52.303
−2.303
47.697
87.697
147.697
177.697
−87.749
−47.749
2.2511
52.251
82.2509
152.251
−
177.749
* major barrier; ** minor barrier.
The structures of both rotamers found in the crystal of (
with corresponding models (a comparison of geometrical parameters are listed in Table 3
and correspond to the two global minima in the relative energy curve (Figure 6) with
1) demonstrate good correlation
)

Molecules 2021, 26, 2137
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calculated values for the dihedral angles at these minima of –152.303◦ and 152.251◦ for
(
1a) and (1b), respectively. The most energetically disadvantageous structure represents
a rotamer with the torsion angle of about 0◦. This structure is completely flat, despite
the fact that a maximum conjugation of multiple bonds should be expected for such
structure as a stabilization factor. The flat configuration of the molecule is not possible due
to the C(5)H···C(11)H/C(5A)H···C(11A)H close contacts of about 2.07 Å, as well as the
C(3)H···Cl(1)/C(3A)H···Cl(1A) distances of about 2.50 Å, which are significantly shorter
than the corresponding sums of the vdw radii, illustrating strong repulsion between
these atoms. The local maxima corresponded to torsion angles of about
±
90◦. In this
configuration, all important contacts are greater than the corresponding sums of the vdw
radii, but the structure exhibits no conjugation of the furanone ring with the arylmethylene
fragment and this affects the total energy of the system. The difference between the energies
of (1a) or (1b), as compared with their optimized structures, is about 3.88 kcal/mol. The
two local minima between local and global maxima correspond to the structures with
torsion angles of about
±
50◦. The rotational barrier, calculated as the difference between
the energies of the global maximum and global minimum, is about 5.66 kcal/mol. The
transition of rotamer (1a) to (1b) and back is possible ◦through a rotation around the
C(5)–C(6)/C(5A)–C(6A) single bond by approximately 50 , with transfer to the second flat
state, corresponding to the local maximum, halfway through the rotation. This rotamer
is characterized by C(3)H···C(11)H/C(3A)H···C(11A)H distances of about 1.97 Å and
C(5)H···Cl(1)/C(5A)H···Cl(1A) contacts of about 2.54 Å, close contacts, which are smaller
than the corresponding sums of the vdw radii. These distances are similar to those in the
most disadvantageous structure. The barrier of this transition as the difference between
the energies of the local maximum structure and the global minimum state is only about
0.67 kcal/mol.
Table 3. Comparison of some important geometrical parameters (bonds and interatomic distances
(Å), and angles and torsions (◦)) of the rotamers from the X-ray study and calculations of each
rotamer separately.
Experimental
Calculated
Geometrical
Parameter
1a
1b
1a
1b
C(2)–C(5)
C(2)–C(3)
C(5)–C(6)
1.354(4)
1.437(5)
1.461(5)
2.714(4)
2.785(3)
2.303(5)
124.4(3)
−144.5(3)
1.351(5)
1.447(5)
1.452(4)
2.628(4)
2.651(3)
2.151(5)
128.4(3)
157.6(4)
1.356
1.442
1.457
2.629
2.690
2.242
127.858
1.356
1.442
1.457
2.629
2.690
2.243
127.843
152.251
O(2)···C(5)H
C(5)H···Cl(1)
C(3)H···C(11)H
C(2)–C(5)–C(6)
C(2)–C(5)–C(6)–C(7)
−152.303
3. Material and Methods
3.1. Physical Measurements
The 1H (400 MHz) and 13C NMR (100 MHz) spectra in acetone-d6 were recorded with
a Varian (Agilent) 400 spectrometer (Agilent Technologies, Santa Clara, CA, USA), internal
standard was tetramethylsilane (TMS). Chemical shifts (δ) are reported in ppm. Elemental
analysis was performed on a CHNS analyzer “Elementar Vario MICRO cube” (Elementar
Analysensysteme GmbH, Hanau, Germany). The melting point was determined on a
Boetius table. The progress of the reaction and the purity of the synthesized compound
were monitored by TLC on ALUGRAM® SIL G UV254 plates (MACHEREY-NAGEL GmbH
& Co. KG, Düren, Germany), and a hexane–ethyl acetate–acetone (2:2:1) mixture was
the eluent.

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3.2. Synthesis, Characterization, and Crystallization
The 3-(2-chlorobenzylidene)-5-(p-tolyl)furan-2(3H)-one (1) was obtained by the proce-
dure described in [40] (Scheme 1):
A mixture of 1 g (5.2 mmol) of 4-oxo-4(p-tolyl)butanoic acid, 0.73 g (5.2 mmol) of
2-chlorobenzaldehyde, and 0.43 g (5.2 mmol) of anhydrous sodium acetate was heated in
12 mL of acetic anhydride for 45 min. After being cooled, the reaction mixture was poured
into water, and the precipitate of (I) was filtered, recrystallized from 96% ethanol, and
dried. Yellow crystals (aq. EtOH) yield 1.17 g (76%), mp 151–153 ◦C; 1H NMR (400 MHz,
acetone):
Ar), 7.53–7.59 (m, 2H, Ar, CH=), 7.79 (d, J = 8.3 Hz, 2H, p-Tol), 8.01 (dd, J = 7.6, 1.8 Hz, 1H,
Ar). 13C NMR (100 MHz, acetone):
20.6, 96.0, 124.5, 125.5, 127.5, 129.6, 129.9, 130.3, 130.5,
δ 2.40 (s, 3H, Me), 6.70 (s, 1H, Fu). 7.33 (d, J = 8.0 Hz, 2H, p-Tol), 7.39–7.50 (m, 2H,
δ
133.3, 133.31, 134.1, 134.71, 140.3, 147.4, 170.3. Anal. calcd. for C18H13ClO2: C: 72.86%;
H: 4.42%; Cl: 11.95%; found: C: 72.35%; H: 4.51%; Cl: 12.06%.
Scheme 1. Synthesis of the titled compound (1).
A suitable single crystal of (1) was obtained by slowly cooling a hot 96% EtOH solution.
The crystal was washed with cooled EtOH and dried in vacuum. The dimensions of the
crystal were 0.30 × 0.05 × 0.05 mm3.
3.3. Crystal Structure Determinations and Refinement
An X-ray diffraction study of (
diffractometer (CuK radiation, graphite monochromator,
absorption corrections were made using the SADABS program [44
1
) was performed on a Bruker SMART APEX II CCD
-scan) at 100 K. Empirical
47]. The structure was
α
ω
–
solved by a direct method and was refined by full-matrix least-squares versus F2hkl with
anisotropic displacement parameters for all non-hydrogen atoms. The hydrogen atoms
were placed in the calculated positions and were refined geometrically by using a riding
model with Uiso(H) = 1.2Ueq(C) and Uiso(H) = 1.5Ueq(C) for methyl groups.
The refinement was performed with the SHELX SHELXL-2014/7 software package
version [48]. The structure was refined as an inversion twin (batch scale factor, BASF = 0.36).
The crystal data, data collection, and structure refinement details are summarized in Table 4
.
The packing diagram and parameters of non-covalent interactions were obtained using
Mercury 3.0 software [49].
3.4. DFT Calculations
The coordinates from the X-ray data were used as the initial coordinates. All structures
were fully optimized by using tight convergence criteria and Becke’s three-parameter
hybrid functional combined with the Lee–Yang–Parr correlation functional (B3LYP [50–52])
with the 6-311++G(d,p) basis set. The optimized coordinates of each of the two forms were
used separately for relaxed scans of the C(2)–C(5)–C(6)–C(7)/C(2A)–C(5A)–C(6A)–C(7A)
torsion angle with an increment of 10◦. The energy profiles of the rotation processes were
analyzed for extrema to evaluate the rotational barrier energy.

Molecules 2021, 26, 2137
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Table 4. Experimental details.
Crystal data
Chemical formula
C18H13ClO2
Mr
296.73
Orthorhombic, Pna21
Crystal system, space group
Temperature (K)
a, b, c (Å)
V (Å3)
100
28.2038(14), 25.8791(14), 3.8037(2)
2776.3(3)
Z
8
2
0
Z
Radiation type
CuKα
2.44
−1
µ (mm
)
Crystal size (mm)
0.30 × 0.05 × 0.05
Data collection
Bruker APEX II CCD (charge-coupled device) area detector’
Diffractometer
diffractometer
Absorption correction
No. of measured, independent, and observed [I > 2σ(I)]
reflections
Multi-scan SADABS
26,357, 4925, 4084
Rint
0.083
0.618
−1
(sin θ/λ)max (Å
)
Refinement
R[F2 > 2σ(F2)], wR(F2), S
No. of reflections
0.051, 0.119, 1.00
4925
382
1
No. of parameters
No. of restraints
H-atom treatment
∆ρmax, ∆ρmin (e Å
Absolute structure
Absolute structure parameter
H-atom parameters constrained
−3
0.24, −0.42
)
Refined as an inversion twin
0.36(2)
4. Conclusions
The two crystallographically independent forms for (1) have similar geometries but
are not superimposable. Thus, while the flat furan-2(3H)-one parts are superimposable, the
mean planes of the terminal and substituted phenyl groups are rotated to different extents
with respect to the plane of the furan ring in the two.
The quantum-chemical modeling of two non-flat forms (1a) and (1b) found in the
single crystal of arylmethylidene derivative of furan-2(3H)-one (1) describes them well
as rotamers by the presence of two almost energetically equivalent global minima on
the energy curve as a function of the C(2)–C(5)–C(6)–C(7)/C(2A)–C(5A)–C(6A)–C(7A)
dihedral angle. The close H···H and H···Cl contacts in rotamers of (
1) are the reason for
their non-planar structures. According to the quantum chemical calculations, the energy
curve for the rotation along the single C(5)-C(6)/C(5A)-C(6A) bond of each rotamer reveals
two unequal rotational barriers of 5.66 kcal/mol and 0.67 kcal/mol. That each rotamer can
◦
easily transform to the other during the rotation by 50 is the cause for the co-crystallization
of these rotamers.
Author Contributions: Conceptualization, methodology, software, V.S.G.; validation, T.V.A., V.S.G.;
formal analysis, investigation, resources and data curation, T.V.A., V.S.G., O.A.M., A.S.T.; writing—
original draft preparation, V.S.G.; writing—review and editing, V.S.G.; visualization, V.S.G., O.A.M.;
supervision, A.Y.Y.; project administration, A.Y.Y.; funding acquisition, O.A.M. All authors have read
and agreed to the published version of the manuscript.
Funding: This work was supported by the Russian Foundation for Basic Research (grant no. 19-33-
60038 to O.A. Mayorova).
Data Availability Statement: The data presented in this study are available on request from the
corresponding author.

Molecules 2021, 26, 2137
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Acknowledgments: The authors thank Ekaterina S. Prikhozhdenko (Saratov National Research State
University) for valuable comments and Maxim V. Dmitriev (Perm State University) for help in the
preparation of the twinning description section.
Conflicts of Interest: The authors declare no conflict of interest.
Sample Availability: Sample of the compound (1) is available from the authors.
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