C...π interaction of non-hydrogen bond type

Article abstract of DOI:10.1039/c2nj20903a

An unusual C...π interaction of non-hydrogen bond type has been found for the first time in ethyl (2Z)-2-cyano-3-[(3-fluoro-4-methoxyphenyl) amino]prop-2-enoate and is rationalized by ab initio computations as being the result of electrostatic interactions. The database analysis has shown its scarcity. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.

Full text of DOI:10.1039/c2nj20903a

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LETTER
CÁ Á Áp interaction of non-hydrogen bond typew
Zhenfeng Zhang,*a Hongbo Tong,b Yanbo Wu*b and Guisheng Zhanga
Received (in Victoria, Australia) 20th October 2011, Accepted 21st November 2011
DOI: 10.1039/c2nj20903a
An unusual CÁ Á Áp interaction of non-hydrogen bond type has
been found for the first time in ethyl (2Z)-2-cyano-3-[(3-fluoro-4-
methoxyphenyl)amino]prop-2-enoate and is rationalized by ab initio
computations as being the result of electrostatic interactions.
The database analysis has shown its scarcity.
Noncovalent interactions, such as hydrogen bonding, aromatic
stacking and cationÁ Á Áp interactions, play a dominant role in
many forefront areas of modern chemistry, from materials
design to molecular biology.1–7 Wherever present, they often
strongly influence many chemical and biochemical phenomena;
therefore, a complete understanding of these chemical and
biochemical processes will often demand a complete under-
standing of the interactions too. It is not surprising that a great
deal of interest has been generated in the study of such
interactions. Under the class of the XÁ Á Áp interactions, where
the p-cloud of the benzene interacts with an electropositive
atom X, the HÁ Á Áp and cationÁ Á Áp systems form two separate
classes, and have received a great deal of attention in recent
Fig. 1 Part of the packing diagram of ethyl (2Z)-2-cyano-3-[(3-fluoro-
times. By contrast, the NÁ Á Áp, OÁ Á Áp, SÁ Á Áp etc. interactions7,8
involving the benzene p-electrons have been significantly
underrated due to their rarity.
4-methoxyphenyl)-amino]prop-2-enoate, 1, showing the formation of the
double CÁÁÁp interactions between C1 and C5–C10 ring with a C1ÁÁÁCg
distance of 3.425 A (Cg is the centroid of the C5–C10 ring). Atoms
marked with an asterisk (*) are at the symmetry position: Àx, 1 À y, Àz.
The CÁ Á Áp interactions of non-hydrogen bond type are more
rare for two reasons. First, unlike the H atom in the HÁ Á Áp
system or the cation in the cationÁ Á Áp unit, atom C is usually
not sufficiently electron-deficient (electropositive) to serve as the
p-electrons acceptor. Second, atom C is not often situated in
sterically-unhindered positions. This communication shows that
in spite of these limitations, an electropositive olefinic C atom
forms an electrostatic acceptor–donor interaction with an electron-
rich aromatic ring, thus contributing to crystal stability.
A striking example of such an CÁÁ Áp interaction is found in the
crystal structure of ethyl (2Z)-2-cyano-3-[(3-fluoro-4-methoxy-
phenyl)amino]prop-2-enoate, 1 (Fig. 1). The planar sp2 vinyl
atom C1 lied nearly vertically (o51) over or under the phenyl
ring centroid of the neighboring molecule. The distance of C1 to
the centroid of the C5*–C10* ring is only 3.425(2) A, which is
markedly shorter than the upper limit of the sum of van der
Waals radii, 3.6 A (the phenyl ring half-thickness, taken as
1.7–1.9 A, being half the centroid–centroid distance in parallel
phenyl rings).9 The geometric parameters suggest a stronger
CÁ Á Áp interaction. Here the electron-deficient atom C1 acts as a
p-electron acceptor and the p-cloud of the electron-rich phenyl
ring acts as a p-electron donor. Though the anilino group is
bonded to the vinyl atom C2, atom C1 still exhibits relatively
lower electron density due to the presence of two strong electron-
withdrawing substituents with substantial negative electrostatic
potential held by the C2–N1, C3RN2 and ester carbonyl
groups, respectively, around the ‘‘positively charged C1 atom’’.
This can be verified by the shorter C2–N1, C3RN2 and
C4QO1 bonds [1.324, 1.143 and 1.221 A, respectively]. The
feature in charge distribution is similar to some extent to that of
the perfluorobenzene,10 with reduced electron-density on the
centroid of the phenyl ring and high electron-density on the
edge (perfluorobenzene model). As such, here the feature of
a College of Chemistry and Environmental Science,
Henan Normal University, Xinxiang 453007, P. R. China.
E-mail: zzf5188@sohu.com; Fax: +86 373-3326336;
Tel: +86 373-3326335
b Institute of Molecular Science, Key Laboratory of Chemical Biology
and Molecular Engineering of Education Ministry,
Shanxi University, Taiyuan, 030006, Shanxi, P. R. China.
E-mail: wyb@sxu.edu.cn
w CCDC reference number 837545. For crystallographic data in CIF
or other electronic format see DOI: 10.1039/c2nj20903a
c
44 New J. Chem., 2012, 36, 44–47
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charge distribution facilitates the formation of the intermolecular
CÁ Á Áp interaction between the electron-deficient C1 atom and
the electron-rich C5–C10 ring.
within 51 of being directly above the centroid. Therefore, the
DFT calculations have presented compelling theoretical evidence
for the CÁÁ Áp interaction, and simultaneously given us valuable
insight into the nature and energetic profiles of the interaction.
We have also probed the vibrational characteristics of the
CQC bond in an attempt to observe this interaction in
solution and the solid state. IR spectroscopic measurements
of the nCQC stretching frequency in the solid crystalline
material and in solution of CH2Cl2 show dramatic changes;
the FTIR spectra of the crystalline sample in KBr showed
Recent studies have shown the existence of cationÁ Á Áp inter-
actions between an electron-deficient cation and an electron-
rich arene. Systems hosting such interactions have been found
in the CSD and have been the subject of recent papers.11–13
However, most of the work on this subject still remain
theoretical.14–16 Computational study shows that the inter-
actions between cations such as Li+, Na+, K+, NH4+, Al+,
Ag+ etc. and p-systems such as C6H6, C6H5CH3 or C6H5OH
were found to be energetically favourable,7 and that energy
minima were found to lie along the principal symmetry axis of
the molecule and the binding energy increases with the increase
of p-electron density.
n
CQC at 1650 cmÀ1, and a significant red shift (1635 cmÀ1) was
observed in CH2Cl2. This indicated that the intermolecular
CÁ Á Áp interaction in 1 does have a significant effect on the
vibrational frequency of the CQC bond.
In order to further probe the generality of the novel CÁ Á Áp
interaction, a systematic search of CSD (version 5.32 2011)
was performed. Considering the requirement of the steric
hindrance, the ‘above ring’ carbon atom is constrained to be
sp2 hybridized, lie within 101 of being above the phenyl ring
center and no more than 3.6 A far away from the center. The
angle parameter of 101 for the database search seems to be too
restrictive, however, when the search angle is beyond the
scope, such as in the range of 10–251, all the hits give common
examples of offset pÁ Á Áp interactions; the 3.6 A cut-off was
chosen based on the van der Waals radius of carbon, taken as
1.7 A, and the phenyl ring half-thickness of 1.7–1.9 A.9 Under
the constraints, a total of 135 hits were retained; these hits were
always scrutinized manually; and those obviously inappropriate
compounds including disordered structures were eliminated.
With these stipulations, only thirteen unambiguous CÁ Á Áp
interactions were found (Table 1), out of which three are
present in organic crystals, and ten in metal complexes. Though
these systems differ from our studied structure 1, the CÁ Á Áp
interactions in nature are identical to each other. The database
analysis also reveals that, for those CÁ Á Áp systems, the ‘above
ring’ carbon atom is located within about 71 of being vertically
above or under the centroid of the aromatic ring, and the
average distance to the centroid is 3.44 A. Obviously, the
average CÁÁÁp bond geometry is consistent with that found in 1.
Therefore, the results from the CSD search, the crystallo-
graphic study, theoretical calculation and IR spectra analysis
of structure 1 have confirmed that CÁ Á Áp interaction, though
rare, can actually occur between an adequately electron-deficient
C atom and an electron-rich aromatic ring, and is structurally
significant when it does occur.
A model of the CÁ ÁÁp interaction can be reasoned out from the
cationÁÁ Áp interactions, though the systems differ in parameters
such as the distance of the C atom with respect to the principal
axis (or rather the pseudo axis considering the loss of symmetry
in our system) of the aromatic ring. As such, the CÁ ÁÁp inter-
action can be predicted to be energetically favorable between an
electron-deficient C atom and a p-electron-rich benzene ring.
Interestingly, such a prediction comes true for the first time in
compound 1.
To further seek theoretical evidence for the CÁ Á Áp, the
density functional theory (DFT) calculations at the
BLYP17,18/6-31+G(d) level with the long-range correction
scheme of Hirao and coworkers19 (LCBLYP/6-31+G(d))
were performed on compound 1. The monomer and the dimers
formed by CÁ Á Áp interaction were studied. All the calculations
were carried out using the GAUSSIAN 09 package.20 According
to our DFT calculations, atom C1 carries the largest Mulliken
positive charge (0.747, Fig. 2) and the benzene ring as a whole
carries high negative charge (À0.266). The feature in charge
distribution is in good accordance with our crystallographically
induced conclusion, therefore, from which it is demonstrated
again that the interaction between the electron-deficient C1 and
the electron-rich C5–C10 ring is attractive in nature and the
formation of the CÁ Á Áp interaction should be mainly attributed
to electrostatic interactions. The calculated attractive force
for dimer I, including the zero-point energy corrections, is
À12.9 kcal molÀ1. The calculation also shows that the CÁ Á Áp
interaction geometry (Fig. 2) is in good accordance with that
found in the crystal structure; the distance between C1 atom
and the centroid of C5–C10 ring is 3.422 A, and atom C1 is
The crystal structure also exhibits an intramolecular
hydrogen bond of N–HÁÁÁO type (Fig. 1), the distance H1ÁÁÁO1
Table 1 Results of database analysis of CÁ Á Áp interactions
Mean geometric parameters
db/A
ac/1
No. of entries
CÁ Á Áp interactions 13a
Refcodes: BEFRUA, BEGCEW, FAKBID, HIVQEI, PARKAU,
SADPUJ, QIHPUS, VAPNEF, BUTVAO, GUYZIK, FOSWOA,
3.44
7.1
a
Fig. 2 The dimeric structure I of compound 1 optimized within the
DFT method, LC-BLYP/6-31+G(d) level of theory, showing the
Mulliken charge distribution on C1 and the benzene ring as a whole,
and the resulting CÁ Á Áp interaction. For the sake of clarity, some
hydrogen atoms have been omitted.
b
PIZCEH, VIVKIV. The distance from the ‘above ring’ carbon to
c
the ring centroid. The angle between the ‘above ring’ carbon–ring
centroid vector and the vector perpendicular to the C6–aromatic ring.
c
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New J. Chem., 2012, 36, 44–47 45

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Fig. 5 Part of crystal structure of compound 1, showing the forma-
tion of a two-dimensional sheet via combination of CÁ Á Áp, OÁ Á Áp
interactions and C–HÁ Á ÁN hydrogen bonds. For the sake of clarity,
H atoms not involved in the motif shown have been omitted, and
selected atoms are labeled. Symmetry code: Àx, 2 À y, Àz.
Fig. 3 Part of packing diagram of compound 1, showing the double
OÁÁ Áp interactions between O2 and C5–C10 ring with a O2ÁÁÁCg distance
of 3.486 A (Cg is the centroid of the C5–C10 ring). Atoms marked with
an asterisk (*) are at the symmetry position: 1 À x, 1 À y, Àz.
being 2.06 A, and the associated angle N1–H1Á Á ÁO1 1331. This
strong intramolecular H-bond fixes the Z configuration of the
C1QC2 bond and contributes to maintain a planar conformation
to the molecule’s main skeleton, thus allowing the p-electrons
of the sp2-hybridized N1 to localize sufficiently and finally in
favor of the formation of the ‘perfluorobenzene model’ in charge
distribution. This sets the stage for the CÁ Á Áp, as well as the
following OÁ Á Áp interactions observed within the crystal lattice.
Besides the CÁ Á Áp interaction, the structure also exhibits
geometric characters once expected for an OÁ Á Áp interaction of
non-hydrogen bond type (Fig. 3).8a The ethoxy atom O2 is
found to locate vertically above or under the centre, and
3.486 A away from the centre. The distance is slightly longer
than the upper limit of Svdw radii, 3.42 A. Despite this, the
OÁ Á Áp interaction is still shown to be attractive in nature by
the density functional theory (DFT) calculations at the
BLYP17,18/6-31+G(d) level with the long-range correction
scheme of Hirao and coworkers19 (LCBLYP/6-31+G(d)). The
calculated interacting energy for dimer II (Fig. 4), including the
zero-point energy corrections, is À11.0 kcal molÀ1. In addition,
the calculated OÁ Á Áp geometry closely resembles that in the
crystal structure (Fig. 3 and 4); the distance between atom O2
and the C5–C10 ring centroid is 3.372 A, and O2 is located
within 51 of being directly above the centroid. The ethoxy atom
O2 serves as a p-electron acceptor and the p-cloud of the
aromatic ring acts as an electron donor. The reduced p-electron
density on O2, due to the resonance of a lone pair over the bonded
ester carbonyl group, favors the formation of electrostatic
acceptor–donor interactions of OÁ Á Áp type. Like CÁ Á Áp inter-
action, the OÁ Á Áp interaction is also uncommon in the literature,
though a number of CQOÁ Á Áp types have been reported
recently,21–26 the nature of which is nothing but a lone-pairÁ Á Áp
interaction. In the case of compound 1, the OÁ Á Áp interaction,
however, occurs between the electron-density-reduced alkoxy
oxygen and the aromatic p-electrons, the former distinctly
NOT being an electron-rich carbonyl O atom.
In addition to the CÁ Á Áp and OÁ Á Áp interactions, the aromatic
C6–H and the olefinic C2–H cooperatively form a pair of
conventional bifurcated C–HÁ Á ÁN hydrogen bonds to the
cyano nitrogen atom of the neighboring molecule related by
centrosymmetry (Fig. 5), the distances H2Á Á ÁN2 and H6Á Á ÁN2
being 2.51 and 2.61 A, respectively, and the associated angles
C2–H2Á Á ÁN2 and C6–H6Á Á ÁN2 being 153 and 1611, respec-
tively. These noncovalent interactions, including CÁ Á Áp, OÁ Á Áp,
C–HÁ Á ÁN and N–HÁ Á ÁO, assist each other synergistically and
constitute a two-dimensional sheet (Fig. 5).
In conclusion, the detailed structural analysis has revealed
an unusual CÁ Á Áp interaction occurring between an electron-
deficient C atom and an electron-rich aromatic ring. Ab initio
computations performed at the LC-BLYP/6-31+G(d) level
and IR spectra gave effective supporting data for the CÁ Á Áp
interaction. The database analysis has shown its scarcity. We
believe that the present work may be the first systematic study
on the CÁ Á Áp interaction.
Experimental
Synthesis of ethyl (2Z)-2-cyano-3-[(3-fluoro-4-
methoxyphenyl)amino]prop-2-enoate, 1
A mixture of 3-fluoro-4-methoxyaniline (0.02 mol), ethyl
2-cyano-3-ethoxyacrylate (0.02 mol) and toluene (10 ml) was
heated at reflux for ca. 10 min. The reaction mixture was then
cooled to room temperature. The precipitate was collected by
filtration and washed with ethanol. Crystals suitable for an
X-ray analysis were obtained by slow cooling of a hot toluene
solution of the crude product.
X-Ray structure determination
The selected crystal was mounted in inert oil on glass fibers. Data
were measured using Mo-Ka radiation on a Bruker SMART
1000 CCD diffractometer. Data collection at 296 K and
reduction were performed using SMART and SAINT software.27
Absorption correction was applied using the multi-scan method
(SADABS).28 The crystal structure of 1 was solved by direct
methods and refined by full matrix least-squares on F2 using the
SHELXTL program package.29 All non-hydrogen atoms were
subjected to anisotropic refinement, and all H atoms were placed
Fig. 4 The dimeric structure II of compound 1 optimized within the
DFT method, LC-BLYP/6-31+G(d) level of theory, showing theo-
retically the formation of the OÁ Á Áp interaction.
c
46 New J. Chem., 2012, 36, 44–47
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%
C13H13FN2O3, M = 264.25, triclinic, P1, a = 7.145(1),
b = 7.580(1), c = 13.441(1) A, a = 83.394(2), b = 78.094(2),
g = 70.208(2)1, V = 669.3(1) A3, Z = 2, T = 296(2) K,
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(Rint = 0.017), 1681 observed with I 4 2(I); final R = 0.0340,
wR2 = 0.0975, goodness-of-fit S = 1.01.
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c
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