The power of nonconventional phenyl C-H?N hydrogen bonds: Supportive crystal-packing force and dominant supramolecular engineering force

Article abstract of DOI:10.1021/cg5014076

The role of phenyl C-H···N interactions in crystal engineering is explored with a variety of fluorinated phenyl-containing compounds. In particular, we show that this interaction can guide the formation of one-dimensional phenyl C-H···N hydrogen-bonded ribbons with, for example, 4-(2,3,5,6-tetrafluorophenylethynyl)pyridine. The interaction is shown to also control the formation of self-complementary homodimers with 3-(2,3,4,5-tetrafluorophenylethynyl)pyridine. We also demonstrate that the phenyl C-H···N hydrogen bond interaction is capable of enticing co-crystallization of molecules such as 2,3,5,6,2′,3′,5′,6′-octafluorobiphenyl and 4,4′-dipyridyl. Finally, we describe the use of an intramolecular scaffold to evaluate the effect of electron-withdrawing substituents on the strength of a phenyl C-H···N hydrogen bond.

Full text of DOI:10.1021/cg5014076

Article
pubs.acs.org/crystal
The Power of Nonconventional Phenyl C−H···N Hydrogen Bonds:
Supportive Crystal-Packing Force and Dominant Supramolecular
Engineering Force
Eric Bosch,*,† Nathan P. Bowling,‡ and Jeffery Darko†
†Department of Chemistry, Missouri State University, 901 S. National Avenue, Springfield, Missouri 65804, United States
‡Department of Chemistry, University of Wisconsin-Stevens Point, 2001 Fourth Avenue, Stevens Point, Wisconsin 54481, United
States
S
* Supporting Information
ABSTRACT: The role of phenyl C−H···N interactions in
crystal engineering is explored with a variety of fluorinated
phenyl-containing compounds. In particular, we show that this
interaction can guide the formation of one-dimensional phenyl
C−H···N hydrogen-bonded ribbons with, for example, 4-
(2,3,5,6-tetrafluorophenylethynyl)pyridine. The interaction is
shown to also control the formation of self-complementary
homodimers with 3-(2,3,4,5-tetrafluorophenylethynyl)-
pyridine. We also demonstrate that the phenyl C−H···N
hydrogen bond interaction is capable of enticing co-
crystallization of molecules such as 2,3,5,6,2′,3′,5′,6′-octafluorobiphenyl and 4,4′-dipyridyl. Finally, we describe the use of an
intramolecular scaffold to evaluate the effect of electron-withdrawing substituents on the strength of a phenyl C−H···N hydrogen
bond.
crystallization of tricyanobenzene with hexamethylbenzene is
also a classic example which features multiple phenyl C−H···N
nitrile interactions.9 Significantly, the structure of the hindered
compound 2-(2,4,6-trifluorophenyl)pyridine, which was deter-
mined to provide proof of structure related to a synthetic
methodology paper, also exhibites a relatively strong sp2 C−
H···N hydrogen bond with N···H and N···C bond distances of
2.389 and 3.305 Å with a C−H···N angle of 161.98°.10
Thus, it is fair to say that, while the sp2 C−H···N interaction
is common and although it plays a well-recognized role in
crystal packing, it has seldom been exploited as one of the
major intermolecular interactions in crystal engineering. These
few examples do, however, suggest that the phenyl C−H···N
interaction can be a major control element in supramolecular
chemistry and crystal engineering. Furthermore, we were
prompted to explore this interaction following the unexpected
observation of a C−H···N hydrogen bonding interaction which
seemed to trump a C−Br···N halogen bonding interaction in a
separate study.11
INTRODUCTION
■
The importance of the supportive role of weak interactions
between organic molecules has long been recognized in crystal
engineering.1 One of these weaker interactions is the
nonconventional C−H···N hydrogen bond. We have been
particularly interested in exploring and maximizing these weak
interactions with select molecules that contain phenyl and
pyridyl rings due to the rigid and well-defined geometric
environment in these moieties. Our first investigation using this
methodology involved sp1 C−H···N hydrogen bonding where
we were able to demonstrate that the interaction was strong
enough to promote co-crystallization of a series of diynes with a
series of dipyridines.2,3 It should be noted that the strength of
the C−H···N hydrogen bond is predicted to decrease with
changing hybridization of the C atom in the order sp1 > sp2 >
sp3.4 A recent search of the Cambridge structural database5
reveals more than 2000 reports of close phenyl C−H···N
interactions of which there are 338 reports with a H···N
distance 0.3 Å less than the sum of the van der Waals radii of
nitrogen (1.55 Å) and hydrogen (1.20 Å).6 Most of these
reports correspond to coincidental observation of short C−H···
N interactions in structures in which other intermolecular
forces or coordination bonds are the dominant intermolecular
interactions. Clear examples of the more dominant role of sp2
C−H···N in crystallization include the co-crystallization of
pyridine and 3,5-dinitrobenzonitrile7 and crystallization of 4-(2-
(2,4,6-trinitrophenyl)vinyl)pyridine,8 which both feature a fairly
strong phenyl C−H···N pyridine hydrogen bond. The co-
In this study, we explore the sp2 C−H···N hydrogen bond
between phenyl hydrogen atoms and pyridines. We reasoned
that the most acidic phenyl hydrogens would provide the
strongest phenyl C−H···N hydrogen bonding and, therefore,
provide the best opportunity for this interaction to be the major
Received: September 19, 2014
Revised: February 15, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/cg5014076
Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design
Article
raphy with a 2:1 mixture of hexane and ethyl acetate as eluant. The
product was isolated as a colorless solid (0.080 g, 24%) which was
recrystallized from absolute ethanol.
and controlling intermolecular interaction in crystallization and
co-crystallization. Furthermore, it is well-documented that the
acidity of a phenyl proton is drastically increased on
fluorination of the benzene ring. For example, the pKa of a
proton on benzene is estimated at about 43, while the pKa of
the hydrogen in pentafluorobenzene is reduced to 24.12 Indeed,
a theoretical investigation by Radom et al. indicated that fluoro
substitution would increase the strength of the sp2 C−H···N
hydrogen bond between ethylene and ammonia from 1.7 kJ/
mol to 8.1−8.6 kJ/mol for the interaction between α,β-
difluoroethylene and ammonia.13 This rationale, and acidity
data, was supported by electrostatic potential calculations
performed with Spartan.14 The electrostatic potential of
benzene and pentafluorobenzene is shown in Figure 1, where
the enhanced polarity/acidity of the pentafluorophenyl hydro-
gen is striking.
1H NMR: (400 MHz, CDCl3) δ 8.66 (br d, J ∼ 5 Hz, 2H), 7.44 (d,
J = 5.6 Hz, 2H), 7.17 (dddd, J = 2.4, 5.6, 9.6, 16.0 Hz, 1H). 13C NMR:
83.65 (m), 93.26 (m), 107.4 (m), 114.4 (dd, J = 3.7, 21.6 Hz), 125.5,
129.8, 141.0 (dddd, J = 4.4, 12.5, 17.0, 254.1 Hz), 141.5 (dddd, J = 3.0,
12.5,15.3, 257.8 Hz, 146.9 (tdd, J = 3.0, 10.4, 248.2 Hz), 148.4 (dddd,
J = 2, 3.5, 11.1, 256.3 Hz), 149.9. 19F NMR: −134.2 (dm, J = 20.7 Hz
1F), −138.5 (m, 1F), −151.7 (ddt, J = 4.5, 8.0, 20.5 Hz, 1F), −154.3
(tt, J = 2.5, 20.5 Hz, 1H).
Synthesis of 3-(2,3,4,5-tetrafluorophenylethynyl)pyridine, 3.
3-Ethynylpyridine (0.27 g, 2.6 mmol), 1-bromo-2,3,4,5-tetrafluoro-
benzene (0.60 g, 2.6 mmol), PdCl2(PPh3)2 (49 mg), CuI (6.5 mg),
and triethylamine (15 mL) were reacted under an argon atmosphere at
50 °C. The reaction mixture was diluted with CH2Cl2 (50 mL) and
washed with water (4 × 50 mL). The organic layer was separated,
dried over anhydrous Na2SO4, filtered, and the solvent was evaporated.
The crude product was purified using flash chromatography with a 2:1
mixture of hexane and ethyl acetate as eluant, and the product was
isolated as an off-white solid (0.504 g, 76%) which was recrystallized
from absolute ethanol.
1H NMR: (400 MHz, CDCl3) δ 7.16 (m, 1H), 7.32 (ddd, J = 1, 5, 8
Hz, 1H), 7.83 (td, J = 2.0, 8.0 Hz, 1H), 8.61 (dd, J = 1.6, 4.8 Hz, 1H),
8.78 (br d, J = 1.2 Hz, 1H). 13C NMR: 82.6 (m), 92.8 (m), 107.6 (m),
114.2 (dd, J = 3.5, 20.6 Hz), 119.0, 128.4 (d, J = 12.5 Hz), 132.0 (d, J
= 9.6 Hz), 141.0 and 141.2 (overlapping dm, each J = 250 Hz), 146.2
(dddd, J = 2.5, 3.7, 10.3, 248.2 Hz), 148.24 (dddd, J = 2.5, 3.7, 9.6, 250
Hz), 149.5, 152.2. 19F NMR: −134.8 (dddd, J = 5.4, 6.7, 11.5, 21.8 Hz,
1F), −138.9 (dddd, J = 2.8, 10.3, 12.9, 23.3, 1F), −152.6 (ddt, J = 4.6,
8.0, 20.1, 1F), −154.7 (tt, J = 2.9, 20.1, 1F).
Synthesis of 9. A one-pot modification of the procedure reported
by Bunz et al. was used.16 Thus, 2-ethynylpyridine, (1.03 g, 10 mmol),
4,5-diiodoveratrole (4.84 g, 12.4 mmol), PdCl2(PPh3)2 (101 mg), and
CuI (26 mg) were reacted in triethylamine (15 mL) under an argon
atmosphere at 40 °C until TLC indicated that all the 2-ethynylpyridine
was consumed. 3 mL of trimethylsilyl acetylene was then added, and
the reaction was heated for 3 days when another 1.5 mL of
trimethylsilylacetylene was added. After 7 days total reaction time, the
reaction was worked up and the crude product was purified using flash
chromatography and increasingly polar mixtures of hexane and ethyl
acetate as eluant. 4,5-Bis(2-trimethylsilylethynyl)veratrole (1.69 g,
41%) was first eluted, followed by the trimethylsilyl-protected 9 (1.27
g, 38%). Finally, the dipyridyl product (0.39 g, 9%) was eluted. The
trimethylsilyl-protected 9 was deprotected using KOH in ethanol to
give 9 as a brown oil in quantitative yield.
Figure 1. Electrostatic potential map of benzene and pentafluor-
obenzene (right) drawn with the same range of −225 to 225 kJ/mol.
Blue indicates positive charge.
EXPERIMENTAL SECTION
■
Chemicals. The dipyridyl ligand, 1,2-bis(4′-pyridyl)ethyne, was
available from an earlier study.2 4,4′-Dipyridine, 1,2-bis(4′-pyridyl)-
ethene, and 2,3,5,6,2′,3′,5′,6′-octafluorobiphenyl were purchased and
used as received.
Synthesis. 3-Ethynylpyridine and 4-ethynylpyridine were prepared
by Sonogashira coupling of the corresponding bromopyridine with
trimethylsilylacetylene, followed by deprotection using potassium
hydroxide in methanol.15
Synthesis of 4-(2,3,5,6-tetrafluorophenylethynyl)pyridine, 1.
4-Ethynylpyridine, (0.098 g, 0.95 mmol), 1-bromo-2,3,5,6-tetrafluoro-
benzene (0.226 g, 1 mmol), PdCl2(PPh3)2 (11 mg), CuI (2 mg), and
triethylamine (1 mL) and THF (0.5 mL) were reacted under an argon
atmosphere at 50 °C for 24 h. The reaction mixture was diluted with
CH2Cl2 (50 mL) and washed with water (4 × 50 mL). The organic
layer was separated, dried over anhydrous Na2SO4, and filtered, and
the solvent was evaporated. The crude product was purified using flash
chromatography with a 2:1 mixture of hexane and ethyl acetate as
eluant. The product was isolated as an off white solid (0.12 g, 51%)
which was recrystallized from absolute ethanol.
Synthesis of 7. Compound 9, (0.20 g, 0.76 mmol), 1-bromo-
2,3,4,5-tetrafluorobenzene (0.24 g, 1.04 mmol), PdCl2(PPh3)2 (22
mg), and CuI (4 mg) were reacted under an argon atmosphere in
triethylamine (15 mL) at 50 °C for 24 h. The crude product was
purified using flash chromatography with a 1:1 mixture of hexane and
ethyl acetate as eluant. The product 7 was isolated as an off-white solid
1
(0.090 g, 29%) which was recrystallized from absolute ethanol. H
NMR: (400 MHz, CDCl3) δ 8.65 (md, J = 5 Hz, 1H), 7.70 (dt, J = 2, 8
Hz, 1H), 7.54 (d, J = 8 Hz, 1H), 7.51 (m, 1H), 7.26 (ddd, J = 1, 5, 8
Hz, 1H), 7.13 (s, 1H), 7.03 (s, 1H), 3.94 (s, 3H), 3.93 (s, 3H). 13C
NMR: 150.1, 149.9, 149.7, 148 (md, J = 250 Hz), 146.9 (md, J = 250
Hz), 143.3, 140.9, 140.8 (md, J = 250 Hz), 136.3, 127.0, 122.9, 118.5,
118.0, 114.9 (dd, J = 3, 21 Hz), 114.5, 113.9, 108.6 (m), 95.2 (dd, J =
2, 4 Hz), 91.9, 87.6, 83.0 (m), 56.15. 19F NMR: −135.5 (m, 1F),
−139.4 (m, 1F), −153.9 (ddt, J = 4, 8, 20 Hz, 1F), −155.4 (tt, J = 3,
20 Hz, 1F).
1H NMR: (400 MHz, CDCl3) δ 7.13 (tt, J = 7.2, 9.8 Hz, 1H), 7.44
(d, J = 5.6 Hz, 2H), 8.67 (br d, J = 5 Hz, 2H). 13C NMR: 78.4 (m),
98.4 (m), 107.4 (t, J=22.8 Hz), 125.6 129.7, 130.37 (dd, J = 11.8, 62.4
Hz), 145.9 (dddd, J = 3.7, 10.3, 13.3, 248.9 Hz), 146.9 (tdd, J = 3.0,
14.6, 254.4 Hz), 150.1. 19F NMR: −135.9 (m, 2F), −138.4 (quintet, J
= 10 Hz, 2F).
Synthesis of 8. Compound 9 (0.25 g, 0.95 mmol), 1-bromo-2,3,4-
trifluorobenzene (0.31 g, 1.2 mmol), PdCl2(PPh3)2 (33 mg), and CuI
(7 mg) were reacted under an argon atmosphere in triethylamine (15
mL) at 50 °C for 24 h. The crude product was purified using flash
chromatography with a 1:1 mixture of hexane and ethyl acetate as
eluant. The product 8 was isolated as an off-white solid (0.37 g, 96%)
Synthesis of 4-(2,3,4,5-tetrafluorophenylethynyl)pyridine, 2.
4-Ethynylpyridine (0.10 g, 1.0 mmol), 1-bromo-2,3,4,5-tetrafluoro-
benzene (0.22 g, 1.0 mmol), PdCl2(PPh3)2 (13 mg), and CuI (2 mg)
were reacted under an argon atmosphere in triethylamine (2 mL) at 50
°C for 12 h. The reaction mixture was diluted with CH2Cl2 (50 mL)
and washed with water (4 × 50 mL). The organic layer was separated,
dried over anhydrous Na2SO4, and filtered, and the solvent was
evaporated. The crude product was purified using flash chromatog-
1
which was recrystallized from absolute ethanol. H NMR: (400 MHz,
CDCl3) δ 8.63 (d, J = 4.8 Hz, 1H), 7.68 (dt, J =2.0, 8.0 Hz, 1H), 7.54
B
DOI: 10.1021/cg5014076
Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design
Article
C
DOI: 10.1021/cg5014076
Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design
Article
(d, J = 7.7 Hz, 1 H), 7.38 (m, 1H), 7.38 (m, 1H), 7.23 (ddd, J = 1, 4.8,
7.6 Hz, 1H), 7.12 (s, 1H), 7.02 (s, 1H), 6.95 (m, 1H), 3.93 (s, 3H),
3.91 (s, 3H). 13C NMR: 151.7 (ddd, J = 255, 10, 4 Hz), 151.4 (ddd,
253, 10, 4 Hz), 150.1, 149.6 (d, J = 3 Hz), 143.5, 140.2 (td, J = 15.4,
252 Hz), 136.2, 127.3 (dd, J = 7, 3 Hz), 127.1 (d, J = 2 Hz), 122.8,
118.3, 118.1, 114.7, 114.0, 112.3 (dd, J = 4, 18 Hz), 110.0 (dd, J = 4,
13 Hz), 94.1 (dd, J = 2, 4 Hz), 91.7, 87.8, 83.7 (dd, J = 2, 4 Hz), 56.12,
56.10. 19F NMR: −130.4 (td, J = 7.5, 20.7 Hz, 1F), −132 (m, 1F),
−159.7 (ddt, J = 2.3, 7, 20.7 Hz).
Preparation of Co-crystals. Solutions of each pair of the
dipyridines (0.1 mmol) with an equivalent amount of 4H,4′H-
octafluorobiphenyl were prepared in dichloromethane (3 mL) in screw
cap vials. Slow evaporation yielded a homogeneous mass of crystals in
each case: 4 (4,4′-dipyridine; 4H,4H′-octafluorobiphenyl); 5 (1,2-
bis(4′-pyridyl)ethyne; 4H,4H′-octafluorobiphenyl); 6 (trans-1,2-bis-
(4′-pyridyl)ethene; 4H,4H′-octafluorobiphenyl).
bond is opposite to that of the pyridine nitrogen. The
formation of linear one-dimensional hydrogen-bonded ribbons
has often been used to showcase weak intermolecular
interactions with molecules that contain the appropriate
donor and acceptor sites.2,20 Compound 2, on the other
hand, was chosen to determine how robust the C−H···N
interaction is since the hydrogen bond donor and hydrogen
bond acceptor do not have the favorable hydrogen bonding
angles that compound 1 has. In contrast, compound 3 was
designed with the expectation that it would form self-
complementary C−H···N hydrogen-bonded dimers due to
the relative placement of the pyridine N and the activated C−H
bond.
Each of the compounds 1, 2, and 3 was prepared in modest
yield by Sonogashira coupling of the appropriate ethynylpyr-
idine with the corresponding iodo- or bromotetrafluoro-
benzene, as detailed in the Experimental Section. This series
of compounds was recrystallized from warm ethanol. X-ray
analysis of each of the clear colorless crystals revealed that the
compounds were all essentially planar in the solid state with the
torsional angle less than 2° in all three structures. The bond
distances and angles in each of the three compounds are
unexceptional.
As we hoped, the molecules of compound 1 formed linear
C−H···N hydrogen-bonded ribbons in the solid state, as shown
in Figure 3. The N1−H11 and C11−N1 distances are 2.299
and 3.244(2) Å, respectively, and the C11−H11−N1 and
C3(para to N)−N1−H11 angles are 172.59° and 175.15°,
respectively. Adjacent strands of the head-to-tail hydrogen-
bonded ribbons have alternating directionality with the
tetrafluorophenyl ring adjacent to the pyridine ring providing
supporting and stabilizing C−H···F interactions. The hydrogen
fluorine distance is 2.593 Å for both F3−H2 and F4−H1,
slightly less than the sum of the van der Waals radii of hydrogen
and fluorine, which is 2.67 Å.6 The C−H−F angles are 128.54°
and 161.46° for C2−H2−F3 and C1−H1−F4, respectively.
These distances and angles compare favorably to those
reported for a series of polyfluorobenzenes reported by
Thallandi et al. in 1998.21 This supporting but weak C−H···F
interaction is consistently observed in this study. Indeed, this is
the major interaction between adjacent C−H···N hydrogen-
bonded ribbons and helps stabilize the formation of two-
dimensional sheets, as shown in Figure 3. The two-dimensional
sheets are π-stacked with π-stacked layers slightly offset with
X-ray Structure Determination. For each compound or co-
crystal, a single crystal was mounted on a Kryoloop using viscous
hydrocarbon oil. Data were collected using a Bruker Apex1 CCD
diffractometer equipped with Mo Kα radiation with λ = 0.71073 Å.
Data collection at low temperature was facilitated by use of a Kryoflex
system with an accuracy of 1 K. Initial data processing was carried
out using the Apex II software suite.17 Structures were solved by direct
methods using SHELXS-2013 and refined against F2 using SHELXL-
2013.18 In all structures, hydrogen atoms were located in the difference
maps but were placed in idealized positions and refined with a riding
model. The program X-Seed was used as a graphical interface.19 The
crystallographic data are collected in Table 1.
RESULTS AND DISCUSSION
Molecular Design, Synthesis, and Evaluation of
Tetrafluorophenylethynylpyridines. The design of the
■
Figure 2. Tetrafluorophenylethynylpyridines prepared to evaluate the
role of phenyl C−H···N interactions in supramolecular chemistry.
molecules in this study was modeled on two of our earlier
studies, the co-crystallization of pyridines and alkynes2 and the
formation of self-complementary halogen-bonded dimers.11
Thus, we prepared compound 1 (Figure 2) expecting that this
would favor the formation of linear ribbons of hydrogen-
bonded molecules because the direction of the activated C−H
Figure 3. View of three adjacent C−H···N hydrogen-bonded ribbons of compound 1, 4-[(2,3,5,6-tetrafluorophenyl)ethynyl]pyridine, forming a two-
dimensional sheet. Select molecules shown as space-filling models to highlight the weak cohesive C−H···F interactions.
D
DOI: 10.1021/cg5014076
Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design
Article
Figure 4. View of adjacent C−H···N hydrogen-bonded ribbons formed from compound 2, 4-[(2,3,4,5-tetrafluorophenyl)ethynyl]pyridine, forming
an essentially planar two-dimensional sheet. Select molecules shown as space-filling models to highlight the weak cohesive C−H···F interactions.
Figure 5. View of a series of adjacent phenyl C−H···N hydrogen-bonded self-complementary dimers formed on crystallization of compound 3, 3-
[(2,3,4,5-tetrafluorophenyl)ethynyl]pyridine.
Figure 6. View of a portion of the one-dimensional C−H···N hydrogen-bonded ribbons in the co-crystals formed between 4H,4H′-
octafluorobiphenyl and 4,4′-bipyridine, 4, in (A); 4H,4H′-octafluorobiphenyl and 1,2-bis(4′-pyridyl)ethyne, 5, in (B); and 4H,4H′-
octafluorobiphenyl and 1,2-bis(4′-pyridyl)ethene, 6, in (C).
alternating head-to-tail arrangement of molecules within the
stack. The interplanar distance is approximately 3.4 Å.
Compound 2 was prepared to evaluate the effect of
positional mismatch on the role of the C−H···N interaction
E
DOI: 10.1021/cg5014076
Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design
Article
Figure 7. Crystal packing of the hydrogen-bonded ribbons of co-crystals formed between 4H,4H′-octafluorobiphenyl and 4,4′-bipyridine, complex 4,
in (A); 4H,4H′-octafluorobiphenyl and 1,2-bis(4′-pyridyl)ethyne, complex 5, in (B); and 4H,4H′-octafluorobiphenyl and 1,2-bis(4′-pyridyl)ethene,
complex 6, in (C) as viewed along the b-axis.
of a good geometric match between the donor and acceptor
sites in this molecule.
The dimers form two-dimensional sheets within which
adjacent dimers have alternating directionality in one
dimension, which maximizes the interactions between the
tetrafluorophenyl ring and the pyridine ring, thereby max-
imizing the supporting and stabilizing C−H···F interactions.
The hydrogen fluorine distances range from 2.554 to 2.780 Å
for F2−H3, F1−H4, F4−H2, F3−H3, and F3−H3 with
carbon−fluorine distances between 3.255(2) and 3.724(2) Å.
In addition, there are several close F···F contacts with distances
Figure 8. Crystal packing of the hydrogen-bonded ribbons of co-
crystals formed between 4H,4H′-octafluorobiphenyl and 4,4′-bipyr-
idine, 4, with the C−H···F interactions shown as dashed lines.
of 2.906(2), 2.721(2), and 2.968(2) Å. The two-dimensional
sheets π-stack, and the dimers are slip-stacked with interplanar
distances around 3.3 Å.
Co-crystallization of Bipyridines and Octafluoro-
biphenyl. Following the observation of relatively strong C−
H···N interactions in the crystalline compounds 1−3, we
thought it reasonable that this interaction could entice the co-
crystallization of separate molecules. In fact, we believe that
weak interaction driven co-crystallization is a more powerful
indication of the potential of these interactions. We decided to
take advantage of the relatively rigid and directional nature of
octafluorobiphenyl and 4,4′bipyridyl, 1,2-bis(4′-pyridyl)ethene
and 1,2-bis(4′-pyridyl)ethyne in order to maximize the
potential for co-crystallization. Separate equimolar solutions
containing octafluorobiphenyl and each of the bipyridyls were
dissolved in dichloromethane and allowed to crystallize over
the period of a week. Clear colorless homogeneous co-crystals
were formed from each of the three mixtures labeled 4, 5, and
6, respectively. X-ray analysis revealed that one-dimensional C−
H···N hydrogen-bonded ribbons were formed with strong C−
H···N hydrogen bonds as the major cohesive force in each of
the three co-crystals. Portions of each of these C−H···N
hydrogen-bonded ribbons are shown in Figure 6.
on its crystallization and crystal structure. Despite the
mismatch, the structure reveals the formation of zigzag phenyl
C−H···N hydrogen-bonded ribbons of 2 shown in Figure 4.
Not surprisingly, the N1−H13 and C13−N1 distances are
slightly longer than the related distances in the structure of
compound 1 at 2.472 and 3.364(3) Å, respectively, while the
C13−H13−N1 and C3−N1−H13 angles of 156.41° and
164.68°, respectively, reflect the imperfect alignment of the
hydrogen bond donor and acceptor.
The packing of adjacent phenyl C−H···N hydrogen-bonded
zigzag ribbons of 2 shown in Figure 4 again highlights multiple
supporting and stabilizing C−H···F and F···F interactions with
F−H distances ranging between 2.493 and 2.628 Å and F···F
distances between 2.890(2) and 3.384(2) Å. The two-
dimensional layers also π-stack with interplanar distances
slightly less than 3.4 Å.
In contrast to these two structures, X-ray analysis of the clear
colorless crystals of compound 3 revealed the formation of an
essentially planar self-complementary dimer, as shown in Figure
5. The short N1−H13 and C13−N1 distances of 2.375 and
3.320(2) Å, respectively, and the C13−H13−N1 and C4−N1−
H13 angles of 173.47° and 164.95°, respectively, are indicative
Relatively short hydrogen bond distances are observed in all
three structures. Thus, in the complex 4 (4,4′bipyridine and
Figure 9. Design of original trans-coordinating ligand for transition metals (A) and as adapted to probe intramolecular C−H···N hydrogen bonding
(B) and their synthesis from common precursor 9.
F
DOI: 10.1021/cg5014076
Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design
Article
Figure 10. View of compounds 7 (A) and 8 (B) showing the intramolecular C−H···N hydrogen bond with thermal ellipsoids drawn at the 50% level
and the asymmetric units labeled.
tively. The corresponding C−F distances are 3.531(3),
3.470(3), 3.553(3), and 3.613(3) Å, respectively.
Table 2. C−H···N Hydrogen Bond Lengths and Angles
́
́
complex
dN−H (Å)
dN−C(Å)
∠NHC (deg)
∠CpNH (deg)
Intramolecular Activated C−H···N Hydrogen Bonding.
We have previously used the 1,2-bis(2-pyridinylethynyl)-
benzene scaffold (A in Figure 9) to prepare ligands for
transition-metal complexation,22 and more recently, we have
adapted this framework to investigate intramolecular halogen
bonding.23 It became apparent that this scaffold is in fact
perfect to investigate intramolecular C−H···N hydrogen
bonding. Accordingly, the ligand was modified to include a
polyfluorophenyl ring in place of one of the pyridyl rings shown
as B in Figure 9. The compounds were prepared using
Sonogashira coupling from the common precursor ethynyl
compound 916 with 1-bromo-2,3,4,5-tetrafluorobenzene and 1-
bromo-2,3,4-trifluorobenzene to synthesize 7 and 8, respec-
tively.
To date, two polyfluoro molecules have been synthesized:
the tetrafluoroderivative 7 and the trifluoroderivative 8. Both
have been crystallized and analyzed by X-ray diffraction. In both
cases, the molecule is essentially planar with evidence for a
strong intramolecular C−H···N hydrogen bond. The two
structures are shown in Figure 10.
As expected, the C−N···H hydrogen bond in the more
activated tetrafluorophenyl compound is slightly stronger than
that in the less activated trifluorophenyl compound. In
compound 7, the N1−H21 and C21−N1 distances are 2.393
and 3.339(2) Å, respectively, whereas in compound 8, the N1−
H21 and C21−N1 distances are 2.559 and 3.505(4) Å,
respectively. The angles about the hydrogen bond are similar in
the two compounds. For compound 7, the angles C21−H21−
N1 and C3−N1−H21 are 173.59° and 161.10°, respectively,
whereas for compound 8, these angles are 174.10° and 163.49°,
respectively. It is clear in both structures that the C−H···N
interaction is strong enough to pull the fluorophenyl and
pyridine rings closer together. This flexing of the ethynyl
linkages is spread over multiple bonds and angles and cannot be
evaluated by simply comparing two angles. Nevertheless, the
nonbonding angle C13−C8···C2 reflects this flexing with
reduced angles of 113.56° in compound 7 and 115.79° in
compound 8.
1
2
3
4
2.299
2.472
2.375
2.300
2.283
2.294
2.304
2.288
2.289
2.393
2.559
3.244(2)
3.364(3)
3.320(2)
3.250(3)
3.233(3)
3.244(4)
3.254(4)
3.232(3)
3.235(3)
3.339(2)
3.505(4)
172.59
156.41
173.47
180
175.15
164.68
164.95
180
180
180
5
6
180
180
180
180
172.11
173.73
173.59
174.10
176.94
177.18
161.10
163.49
7
8
octafluorobiphenyl), the N1−H14, N2−H7 and the N1−C14,
N2−C7 distances are 2.300, 2.283 and 3.250(3), 3.233(3) Å,
respectively. In complex 5, between 1,2-bis(4-pyridyl)ethyne
and octafluorobiphenyl, the N1−H1, N2−H8 and the N1−C1,
N2−C8 distances are 2.294, 2.304 and 3.244(4), 3.254(4) Å,
respectively, and in complex 6, between 1,2-bis(pyridyl)ethyne
and octafluorobiphenyl, the N1−H13, N2−H22 and the N1−
C13, N2−C22 distances are 2.289, 2.288 and 3.235(3),
3.232(3) Å, respectively. In the structures 4 and 5, the atoms
involved in the hydrogen bonding lie on an axis of symmetry,
and therefore, all the angles about the C−H···N hydrogen
bonds are 180°, while in complex 6, the angle C13−H13−N1 is
almost linear at 173.73°. The aromatic rings of each component
in each of the co-crystals are not coplanar. Thus, the torsional
angle between the bipyridyl rings in co-crystal 4 is about 45°
and the angle between the two tetrafluorophenyl rings is about
57°. Similar torsional angles of 51° and 60° are observed in the
complex 5 and angles of about 50° and 59° for complex 6 for
the bipyridyl and biphenyl rings, respectively. This similarity is
clear when the crystal packing is shown viewed along the b-axis,
as shown in Figure 7.
This adoption of a nonplanar geometry by the bipyridyls,
which are generally coplanar in similar hydrogen-bonded
complexes,2 is quite possibly driven by other crystal packing
forces due to the fact that the octafluorobiphenyl is nonplanar
due to the steric interactions between the orthofluorine groups.
In that regard, it is noteworthy that there is a significant
contribution from stabilizing C−H···F interactions between
adjacent pyridyl and fluorophenyl rings. Figure 8 highlights the
C−H···F interactions within the complex 4. In this complex,
the H···F distances are 2.700, 2.636, 2.700, and 2.774 Å for
interactions F1−H1, F2−H2, F3−H5, and F4−H6, respec-
Overview. The phenyl C−H···N hydrogen bond distances
and angles are collected in Table 2. The phenyl C−H···N
hydrogens bonds reported here are among the shortest
reported to date. The hydrogen bonds reported for the
tetrafluorphenyl N···H distance in compounds 1,2 and co-
crystals 4, 5, and 6 are all less than 2.375 Å, while compound 3,
which was designed to have mismatched donor and acceptor
G
DOI: 10.1021/cg5014076
Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design
Article
(10) Chen, J. A.; Cammers-Goodwin, A. Tetrahedron Lett. 2003, 44,
1503−1506.
atom geometry, has a longer N···H distance of 2.490 Å. As
expected based on the reduced acidity of the trifluorophenyl
hydrogens, the intramolecular trifluorophenyl C−H···N hydro-
gen bond in compound 8 was significantly longer (0.166 Å)
than the analogous intermolecular C−H···N tetrafluorophenyl
hydrogen bond in compound 7.
(11) Oburn, S.; Bowling, N.; Bosch, E. Cryst. Growth and Des. 2015,
DOI: 10.1021/cg501406w.
(12) Uneyama, K. Organofluorine Chemistry; Blackwell: Oxford, U.K.,
2006.
(13) Wetmore, S. D.; Schofield, R.; Smith, D. M.; Radom, L. J. Phys.
Chem. A 2001, 105, 8718−8726.
(14) Calculated using Spartan’08: Spartan ’08; Wavefunction, Inc.:
Irvine, CA, 2008.
CONCLUSIONS
■
We have demonstrated that fluoro-activated phenyl hydrogen
atoms can form strong phenyl C−H···N hydrogen bonds and
have the ability to be a dominant force in the crystallization of
simple molecules in which the activated phenyl hydrogen and
the basic nitrogen atom have favorable geometry. Furthermore,
the phenyl C−H···N hydrogen bond is strong enough to
consistently guide the co-crystallization of different molecules.
Finally, we have demonstrated the use of a diphenylpyridyl
scaffold as a means to quantify the activation effect of atoms/
groups on the strength of the C−H···N hydrogen bond, and we
plan to use this to evaluate the relative strengths of activated
phenyl C−H···N interactions. It is also noteworthy that
multiple stabilizing weak phenyl C−H···F interactions are
observed within each of the reported structures.
(15) Holmes, B. T.; Pennington, W. T.; Hanks, T. W. Synth.
Commun. 2003, 33, 2447−2461.
(16) Shotwell, S.; Windscheif, P. M.; Smith, M. D.; Bunz, U. H. F.
Org. Lett. 2004, 6, 4151−4154.
(17) ApexII Suite; Bruker AXS Ltd.: Madison, WI, 2006.
(18) Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112−122.
(19) Barbour, L.; Atwood, J. A. Cryst. Growth Des. 2003, 3, 3−8.
(20) Sarma, J.A. R. P.; Allen, F. H.; Hoy, V. J.; Howard, J. A. K.;
Thaimattam, R.; Desiraju, G. R. Chem. Commun. 1997, 101−102.
(21) Thalladi, V. R.; Weiss, H.-C.; Blaser, D.; Boese, R.; Nangia, A.;
Desiraju, G. R. J. Am. Chem. Soc. 1998, 120, 8702−8710.
(22) Bosch, E.; Barnes, C. L. Inorg. Chem. 2001, 40, 3097−3100.
(23) Widner, D. L.; Knauf, Q. R.; Merucci, M. T.; Fritz, T. R.; Sauer,
J. S.; Speetzen, E. D.; Bosch, E.; Bowling, N. P. J. Org. Chem. 2014, 70,
6269−6278.
Our future studies will further explore this interesting
interaction and will probe the incorporation of this phenyl
C−H···N interaction along with other well-established, and
stronger, crystal engineering forces, into complex co-crystals.
ASSOCIATED CONTENT
* Supporting Information
CIF files of synthesized compounds. This material is available
■
S
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
*Phone: 417-836-4277. Fax: 417-836-5507. E-mail: ericbosch@
missouristate.edu. Web: http://chemistry.missouristate.edu/
31072.htm (E.B.).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Science Foundation for financial
support of this research (RUI Grant No. CHE1306284) and
the Missouri State University Provost Incentive Fund, which
funded the purchase of the X-ray diffractometer. We thank Dr.
C. L. “Chuck” Barnes, University of Missouri, for sage advice.
REFERENCES
■
(1) Desiraju, G. R.; Steiner, T. The Weak Hydrogen Bond in Structural
Chemistry and Biology; IUCR Monographs on Crystallography; Oxford
University Press: New York, 1999; Vol 9.
(2) Bosch, E. Cryst. Growth Des. 2010, 10 (8), 3808−3813.
(3) Bosch, E. J. Chem. Crystallogr. 2014, 44, 287−292.
(4) Hartmann, M.; Wetmore, S. D.; Radom, L. J. Phys. Chem. A 2001,
105, 4470−4479.
(5) Allen, F. H. Acta Crystallogr. 2002, B58, 380−388.
(6) Bondi, A. J. Phys. Chem. 1964, 68, 441−451.
(7) Arora, K. K.; Reddy, J. P.; Pedireddi, V. R. Tetrahedron 2005, 61,
10793−10800.
(8) McHugh, C. J.; Kennedy, A. R.; Smith, W. E.; Graham, D. Analyst
2007, 132, 986−988.
(9) Reddy, D. S.; Goud, B. S.; Panneerselvam, K.; Desiraju, G. R.
Chem. Commun. 1993, 663−664.
H
DOI: 10.1021/cg5014076
Cryst. Growth Des. XXXX, XXX, XXX−XXX