Probing the intermolecular interactions of aromatic amides containing N-heterocycles and triptycene

Article abstract of DOI:10.1039/c4ce00089g

A series of aromatic amides incorporated with N-heterocycles or triptycene units are synthesized and studied for probing the effects of such chemical modifications on the intermolecular interactions. Single crystals of a number of heterocyclic amides and the triptycene-containing amide were obtained. Crystal structures, hydrogen bonds, lattice energy, solubility, and melting points were compared amongst relevant molecules. Suitably positioned nitrogen atoms from heterocycles are found to form intramolecular H-bonds with amide NHs at the expense of weakening or disrupting the intermolecular H-bonds. The effects of such H-bonding changes on solubility and melting point are nonetheless limited. Uniquely, the triptycene unit effectively improves the solubility of the amide without tempering the thermal resistance of the molecule. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ce00089g

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Probing the intermolecular interactions of
aromatic amides containing N-heterocycles
Cite this: CrystEngComm, 2014, 16,
and triptycene†
4265
*
Nongyi Cheng, Qifan Yan, Shuai Liu and Dahui Zhao
A series of aromatic amides incorporated with N-heterocycles or triptycene units are synthesized and
studied for probing the effects of such chemical modifications on the intermolecular interactions. Single
crystals of a number of heterocyclic amides and the triptycene-containing amide were obtained. Crystal
structures, hydrogen bonds, lattice energy, solubility, and melting points were compared amongst relevant
molecules. Suitably positioned nitrogen atoms from heterocycles are found to form intramolecular
H-bonds with amide NHs at the expense of weakening or disrupting the intermolecular H-bonds. The
effects of such H-bonding changes on solubility and melting point are nonetheless limited. Uniquely, the
triptycene unit effectively improves the solubility of the amide without tempering the thermal resistance
of the molecule.
Received 14th January 2014,
Accepted 21st February 2014
DOI: 10.1039/c4ce00089g
www.rsc.org/crystengcomm
incorporating nitrogen hetero-atoms on the intermolecular
interactions and crystal structures of these molecules.
Introduction
Amide functionality is of unparalleled importance to both
natural and synthetic materials. Amide (peptide) bond is the
key functional group composing the primary structures and
upholding the secondary structures of proteins. Aliphatic
and aromatic polyamides constitute a large family of commod-
ity and high-performance polymer materials. Among them,
poly(p-phenylene terephthalamide), also known as para-aramid,
PPTA and Kevlar®, is remarkably elite amongst high-performance
fibres,1,2 which boast exceptional mechanical and thermal
properties. In addition to van der Waals interactions, hydrogen
bonds (H-bonds) have long been believed to be of particular
importance for their strong inter-chain forces and appealing
mechanical properties.3–13
In this contribution, we report our recent investigation on
a series of aromatic amides, which comprise three hydro-
carbon or N-heterocyclic aromatic rings connected by an
amide group in two different orientations (Chart 1). Different
heterocycles (pyridine and pyrazine) were introduced at
varied positions in these amide molecules. By comparing the
crystal structures and relevant physical properties of the
heterocyclic amides (1a–d and 2a–d) with those of hydrocarbon
prototypes (1 and 2),14,15 we intend to delineate the effects of
Single crystal structures were obtained for a number of
synthesized molecules, which greatly facilitate the structure
and molecular interaction analyses. As nitrogen atoms in
pyridine and pyrazine are effective H-bonding acceptors, they
may compete with the carbonyl group in forming H-bonds
with amide NH.16–26 H-bonding interactions were hence spe-
cifically examined in our heterocyclic amides. It was found
that suitably positioned N-hetero-atoms can form intramolec-
ular H-bonds with amide NHs. In addition to other crystal
structure variations, the formation of such intramolecular
H-bonds particularly result in substantially weakened or even
completely disrupted intermolecular H-bonds. As the intra-
molecular H-bonds become shorter and stronger, the inter-
molecular ones are observed to become longer and
weaker. Bifurcated H-bonds involving both inter- and intra-
molecular bonding partners are manifested as intermediate
states in this transition. Furthermore, molecules possessing
intramolecular H-bonds display overall better planarity in the
aromatic backbone. The solubility and melting point (mp)
changes upon N-heterocycle incorporation were also studied.
In addition to N-heterocycles, we also examined the effects
of integrating a triptycene unit into the amide scaffold.27
On the one hand, triptycene has a rigid, spatially extended
skeleton which greatly alters the overall geometry and steric
features of the amide molecule. On the other hand, as a
hydrocarbon group triptycene does not significantly change
the electronic properties of the amide backbone. Crystallo-
graphic results show that the amide groups in the triptycene-
containing molecule 3 preserve the intermolecular H-bonding
Beijing National Laboratory for Molecular Sciences, Department of Applied
Chemistry and the Key Laboratory of Polymer Chemistry and Physics of the
Ministry of Education, College of Chemistry, Peking University, Beijing, China.
E-mail: dhzhao@pku.edu.cn
† Electronic supplementary information (ESI) available: Additional characterization
data and copies of NMR spectra. CCDC 942457–942462. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c4ce00089g
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Crystal structure analyses
Attempts were made at growing single crystals for all the pre-
pared amides. However, crystals suitable for X-ray diffraction
analyses were only obtained for molecules 1, 2, 2a, 1b, 2c
and 3 (Table 1 and Fig. 1). Single crystals of 1 and 2 were
acquired by gradually diffusing methanol vapor into DMF
solutions. The rest of the crystals were obtainable by slowly
evaporating solutions of 2a, 1b, 2c and 3 in 1,4-dioxane,
chloroform or methanol (ESI†).
Crystallographic results unambiguously reveal the details
of molecular structures and packing. Particular attention was
paid to H-bonding motifs. Molecules 1 and 2 are known
to form intermolecular H-bonds between the amide NH and
carbonyl (CO) groups.29,30 When heterocyclic pyridine
and pyrazine rings are present, the contained hetero-atoms
may also form H-bonds by competing with amide CO for
the same set of H-bond donors (amide NHs).29 Moreover, in
molecules 2a, 1b, 2c, and 1d nitrogen atoms are located in
suitable positions to possibly form intramolecular H-bonds
with amide NHs via 5-membered cyclic structures.18–26 Evi-
dence for such intramolecular H-bond formation is indeed
shown by crystal structures of 2a, 1b, and 2c. We notice that
it may not be complete coincidence that all the attainable
single crystals comprising heterocycles manifest such intramo-
lecular H-bonds. Evidently, when these heterocyclic nitrogens
do not form intramolecular H-bonds, they would compete
with carbonyl groups to form intermolecular H-bonds. Such
competitions may have impaired the crystallization ability of
relevant molecules (1a, 2b, 1c and 2d) by causing disorder.
Interestingly, 1d is a molecule that is capable of intramolecu-
lar H-bonding while its single crystal is still not obtained. This
is apparently related to the fact that while two of the pyrazine
nitrogens in 1d can form intramolecular H-bonds, there are
two others that are not engaged and may still be involved in
intermolecular H-bonding competition.
Shown by the crystal structures, intermolecular H-bonds
are formed by 1 and 2. The NH⋯O distances between the
NH hydrogen and CO oxygen from neighbouring mole-
cules in 1 and 2 are 2.24 Å and 2.27 Å, respectively (Fig. 1).
Such distances are perceptibly smaller than the sum of mean
van der Waals radii of hydrogen and oxygen atoms (2.72 Å).31
Upon introducing pyridine or pyrazine units in 2a, 1b, and
2c, the intermolecular H-bonds were found to be weakened,
or even disrupted, as intramolecular H-bonds were formed
and strengthened. In the single crystal of 2a, the inter-
molecular NH⋯O distance was extended slightly to 2.38 Å,
while the intramolecular NH⋯N distance between the amide
NH and pyridine nitrogen is 2.42 Å (Table 2 and Fig. 1c),
which is shorter than the sum of mean van der Waals radii
of N and H (2.75 Å).31 Namely, the amide NH in 2a forms
bifurcate H-bonds with both pyridine N in the same molecule
and carbonyl O from an adjacent molecule. While the inter-
molecular H-bonds in 2a are weakened but not completely
disrupted, the corresponding intermolecular NH⋯O dis-
tance in the crystal of 1b is further lengthened to 2.71 Å.
Chart 1 Structures of studied aromatic amides.
ability. Although the number is reduced compared to that in
the unsubstituted analogue 1, the strength of the H-bonds in
3 was relatively enhanced. Moreover, the triptycene incorpora-
tion substantially increases the solubility of the molecule in a
number of organic solvents, but its mp is hardly tempered
compared to that of 1 without substitution.
Taking studied amide molecules as fragmental structures
of aromatic polyamides, our results provide useful informa-
tion for possible chemical modifications to the latter. Namely,
introducing a N-hetero-atom or a triptycene unit in the poly-
mer backbone may effectively improve the solubility and pro-
cessability of relevant polymers without significantly impairing
their mechanical and thermal properties.
Results and discussion
Materials
Two prototype amides 1 and 228 and most modified mole-
cules were synthesized from the corresponding acid chlorides
and amines. The exceptions are 1b, 1d and 2c, which were
prepared by directly coupling relevant amines with the neces-
sary carboxylic acids using triphenyl phosphite as the activat-
ing reagent,29 because the corresponding acid chlorides were
unavailable from commercial resources. The structures of
all the new compounds were characterized and confirmed by
1H and 13C NMR, mass spectroscopy and elemental analyses.
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Table 1 Summary of crystallographic data
Compounds
1
2
2a
1b
2c
3
Chemical formula
Formula mass
Crystal system
a/Å
b/Å
c/Å
α/°
C20H16N2O2
316.35
Monoclinic
18.047(4)
5.2394(10)
7.8799(16)
90.00
C20H16N2O2
316.35
C19H15N3O2
317.34
C18H14N4O2
318.33
Monoclinic
5.6482(11)
15.050(3)
8.6769(17)
90.00
C18H14N4O2
318.33
Monoclinic
4.813(3)
9.377(5)
15.910(9)
90.00
C34H24N2O2
492.55
Monoclinic
5.3070(11)
21.226(4)
6.8830(14)
90.00
Monoclinic
5.4114(11)
20.902(4)
6.7857(14)
90.00
Monoclinic
48.195(10)
13.492(3)
19.716(4)
90.00
β/°
γ/°
94.25(3)
90.00
743.1(3)
173(2)
107.01(3)
90.00
741.5(3)
173(2)
107.29(3)
90.00
732.8(3)
173(2)
93.73(3)
90.00
736.0(3)
173(2)
90.696(9)
90.00
718.1(7)
173(2)
112.39(3)
90.00
11 854(4)
173(2)
Unit cell volume/Å3
Temperature/K
Space group
P2(1)/c
2
1345
P2(1)/n
2
5228
1683
0.0522
0.0640
0.1308
0.0751
0.1369
P2(1)/n
2
5333
1660
0.0530
0.0686
0.1190
0.0795
0.1244
P2(1)/n
2
5270
P2(1)/n
2
4911
C2/c
16
39 572
10 436
0.0909
0.1002
0.2549
0.1407
No. of formula units per unit cell, Z
No. of reflections measured
No. of independent reflections
Rint
Final R1 values (I > 2σ(I))
Final wR(F2) values (I > 2σ(I))
Final R1 values (all data)
Final wR(F2) values (all data)
CCDC number
1345
1659
1631
0.0000
0.0931
0.1685
0.1104
0.1756
942458
0.0444
0.0614
0.1283
0.0664
0.1313
942457
0.0508
0.0623
0.1107
0.0744
0.1163
942460
0.2724
942459
942462
942461
Table 2 H-Bond parameters in crystal structures
Compd
Type
H⋯A (Å)
D⋯A (Å)
∠D–H⋯A (°)
1
N–H⋯O
N–H⋯O
N–H⋯O
N–H⋯N
N–H⋯O
N–H⋯N
N–H⋯N
N–H⋯O
N–H⋯O
2.241
2.270
2.382
2.42
2.708
2.306
2.217
2.040
2.048
3.096
3.091
3.190
2.80
3.450
2.716
2.678
2.892
2.895
163.7
155.2
152.8
106.6
142.8
108.4
112.4
162.4
161.4
2
2aa
1ba
2c
3b
a
Bifurcated H-bonds are observed. b Two types of H-bonds were present.
amide 2c the intramolecular NH⋯N distance is further
reduced to 2.22 Å, corresponding to a relatively strong intra-
molecular H-bond. In the meantime, an intermolecular
NH⋯O distance of more than 4 Å is observed for this molecule
(Fig. 1e), unambiguously indicating completely disrupted inter-
molecular H-bonds. In summary, while the intramolecular
H-bonds progressively gain in strength from 2a to 1b and 2c,
the intermolecular H-bonds are continuously weakened until
they disappear (Table 2). Namely, a gradual transition from
intermolecular H-bonds to intramolecular H-bonds is manifested,
with a bifurcated H-bonding motif as the intermediate state.
Since the amide NH chemical shifts are sensitively influenced
by H-bonding, 1H NMR is employed to provide further evi-
dence for intramolecular H-bond formation. Chloroform-d is
chosen as the solvent since it does not form H-bonds with the
solute molecules. However, except for 1b all other studied molecules
exhibit very low solubility in chloroform, insufficient for
Fig. 1 Crystal structures of 1 (a), 2 (b), 2a (c), 1b (d) and 2c (e) (gray: C;
blue: N; red: O; green: H).
As this value is basically the sum of van der Waals radii of
O and H, it is arguable whether intermolecular H-bonds are
still present in 1b. Meanwhile, the intramolecular NH⋯N
distance is further shortened to 2.31 Å, suggesting even
stronger intramolecular H-bonds (Fig. 1d). Moreover, in
1
recording H NMR spectra. Hence, tert-butyl substituted ana-
logues of 1, 2, 2a and 2c are prepared for NMR study, since
their H-bonding properties should be similar to those of the
respective analogues without t-Bu substitution. Compared to
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the NH chemical shifts at 8.0–8.1 ppm shown by substituted
1 and 2, amide NH resonances are detected at 9.7–10.1 ppm
for 1b and 2c derivatives (Fig. 2). Similarly a downfield
shifted signal is observed for one of the NHs in the 2a ana-
logue. Such results are clear evidence for the occurrence of
intramolecular H-bonds in 2a, 1b and 2c.
Certain characteristics of crystal structures are noticeably
altered along with such H-bonding motif changes. While the
crystal lattices of 1b and 2a still bear great similarity to those
of 1 and 2 respectively (Fig. 1a–d and Table 1), the molecular
packing of 2c is utterly changed (Fig. 1e). Furthermore, as the intra-
molecular H-bonds are increasingly strengthened from 2a to
1b and 2c, an increasing co-planarity among the aromatic
rings is observed in these molecules. Relevant dihedral angles
between the amide bond and adjacent aromatic rings are
measured in the crystals (Table 3). Dihedral angles greater
than 30° are detected between the amide bond and aromatic rings
for 1 and 2, but corresponding dihedral angles involving
H-bonded heterocycles are decreased to about 23°, 14°, and
3° for 2a, 1b and 2c, respectively. Here, the dihedral angle
value appears to correlate with the NH⋯N distance and intra-
molecular H-bond strength. Interestingly, not only the dihe-
dral angles directly associated with intramolecular H-bonds
are considerably narrowed, those between the amide bond
and aromatic rings not engaged in intramolecular H-bonds
are also reduced with similar magnitudes. Particularly for 2c,
a nearly co-planar molecular skeleton is manifested by the
three comprising aromatic rings.
Additional crystal structure differences are observed with
the ring packing motifs. Specifically, in the crystal structures
of 1, 2 and 2a with evident intermolecular H-bonds, a number
of CH–π interactions33,34 are perceived among the aromatic
rings, whereas the number of such edge-on contacts is
reduced significantly as the molecule becomes more and more
planar, as in 1b and 2c (Fig. S1†). Of all the examined crystal
structures, face-to-face aromatic stacking is only observed with
1b (Fig. S2†).32,33
Lattice energy, which indicates the energy difference bet-
ween a molecule in the crystalline state and gas phase,
reflecting the strength of intermolecular forces, is then calcu-
lated for all molecules with single crystal data using the
DFT method at the B3LYP/3-21G theory level (Table 3).34
Heterocyclic amides 1b and 2a show moderately diminished
lattice energy values compared to 1 and 2, while considerably
reduced lattice energy is exhibited by 2c. The magnitude
of lattice energy decreasing also seems to correlates to the
strength of intermolecular H-bonds, but are inconsistent with
the trend of mp changes (vide infra) exhibited by these molecules.
The triptycene unit incorporated into amide 3 was antici-
pated to cause great steric hindrance to intermolecular H-bond
formation. When the crystal structure of amide 3 is revealed,
it is nonetheless found that intermolecular H-bonds are
still effective among the molecules, although the number of
them is reduced to half of those observed with 1 and 2
(Fig. 3). Two sets of (C)O⋯HN contacts with slightly varied
distances of 2.040 Å and 2.048 Å are detected in the crystal
Fig. 2 1H NMR spectra of 1b and tert-butyl substituted analogues of
1, 2, 2a and 2c.
Table 3 Lattice energy and dihedral angle values from crystal structures
Dihedral angle A (°)a
Dihedral angle B (°)a
Lattice energy (kcal mol−1
)
1
30.43
31.84
30.76
13.63
4.10
35.20
−33.52
2
31.43
22.91
15.75
2.81
−34.90
−31.43
−29.13
−22.99
2a
1b
2c
a
Dihedral angles A and B are highlighted in red and blue, respectively.
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Solubility and melting points
The solubility and melting point (mp) changes with N-heterocycle
incorporations are subsequently studied, since the two properties
are pertinent to intermolecular interactions. We are aware
that the melting process is not only governed by intermolecular
forces, but also sensitive to the molecular symmetry. Similarly,
the dissolving process is complex and determined by a
number of factors including solute–solute, solute–solvent,
and solvent–solvent interactions, etc. Nonetheless, with sensi-
ble analyses, mp and solubility can still be useful indices for
assessing intermolecular interactions.
For all the prepared amide molecules, the mp and solubility
in a number of different organic solvents were measured and
compared (Table 4). Consistent with the literature data,28,35
molecules 1 and 2 both show high mp at over 320 °C and
very low solubility in common organic solvents. Among all the
organic solvents tested, N,N-dimethylformamide (DMF) and
dimethylsulfoxide (DMSO) are the only ones that can properly
dissolve the two amide molecules. Upon nitrogen hetero-atom
incorporation, perceptible changes in mp and solubility occur,
the magnitudes of which heavily depend on the number and
position of the hetero-atoms. A general observation is that
lowered mp is accompanied with higher solubility. This trend
is understandable since mp and solubility are both related to
the strength of intermolecular interactions.
Fig.
3 Crystal structure of 3 (viewed from two different angles:
gray, C; blue, N; red, O; green, H).
For all the studied heterocyclic amides, DMF and DMSO
are still the best solvents. Nonetheless, pronounced solubility
improvements are observed in alternative solvents with most
nitrogen-containing molecules. With pyridine unit(s) incor-
porated in the structures, amides 1a–b and 2a–b generally
display lowered mp and improved solubility compared to 1
and 2. Molecules 1b and 2b, comprising two pyridine units,
show higher mp than 1a and 2a having one pyridine unit.
With the introduction of pyrazine unit(s), 1c–d and 2c–d all
display elevated mp and decreased solubility relative to their
pyridine-containing analogues (1a–b and 2a–b). Molecule 1c
exhibits mp at over 280 °C, and the mp of 2c even reaches
over 320 °C, comparable to those of 1 and 2. Notably, 1c and
of 3 (Table 2). The perceptibly shorter bond lengths indicate
that the intermolecular H-bonds among 3 are stronger than
those among 1 and 2. Although no particularly intimate CH–π
or π–π stacking contacts are observed, molecule 3 is packed
relatively compactly in the crystal lattice, as evidenced by the
multiple non-specific aromatic interactions, with a face-to-
face aromatic ring distance of ca. 3.8 Å and CH–π contacts of
2.8–3.0 Å (Fig. S3†). Presumably, both the strong H-bonds
and large van der Waals forces contribute to the desirable thermal
resistance of 3 (vide infra).
Table 4 Melting points and solubility of studied aromatic amides
Solubilityb /mg mL−1
Compd
mp/°Ca
Acetone
CH3CN
MeOH
CHCl3
CH2Cl2
THF
1,4-Dioxane
DMF
DMSO
1
2
324–325
336–338
246–248
257–259
271–272
280–282
284–285
324–325c
364–365
323–326d
314–317
0.1
—
2
—
—
0.7
0.2
0.3
—
—
—
—
—
—
—
2
—
—
—
—
0.5
0.2
2
—
—
0.2
—
—
1
0.1
—
5
5
2
0.7
4
0.2
—
—
—
0.2
0.1
6
>10
2
>10
>10
10
2
10
2
1
3
2
1a
2a
1b
2b
1c
2c
1d
2d
3
0.5
0.5
8
0.2
—
0.3
—
—
>10
>10
>10
5
>10
0.5
2
0.2
0.5
—
0.4
—
—
—
5
—
0.2
—
0.2
—
—
—
4
6
0.7
0.5
5
0.2
0.2
—
—
1
>10
3
>10
>10
0.1
a
b
c
Melting points measured in the air unless otherwise noted. Solubility measured at room temperature (—: <0.1 mg mL−1). Different forms
d
of crystals exist for 2c based on the X-ray diffraction analyses (Fig. S4), with the melting points varying slightly from 321 to 325 °C. Measured
under nitrogen atmosphere since the molecule decomposes at ca. 260 °C in the air.
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2c still demonstrate perceptibly higher solubility in a number
of solvents compared with 1 and 2. For amides 1d and 2d
having two pyrazine units, even higher mp's were exhibited.
Inevitably, very poor solubility is detected for these molecules.
Among all the studied amides, 2d is the only molecule that
decomposes in air at about 260 °C. None of the other amides
decompose before they melt in air. In general, molecules 2 and
2a–d typically show slightly lower solubility than their respec-
tive regio-isomers 1 and 1a–d, suggesting an intrinsic difference
between arenedicarboxamide and dicarboxyl arenediamine.
Comparing the boiling points between benzene (80 °C) and
pyridine/pyrazine (both at 115 °C), nitrogen incorporation
should enhance the strength of intermolecular interactions,
presumably due to the enlarged dipole–dipole interactions.
Molecular symmetry nonetheless sensitively influences the
mp. For example, pyridine of lower molecular symmetry has a
much lower mp (−41.6 °C) than benzene (5.5 °C), but pyrazine
has a much higher mp (52 °C), likely by virtue of both greater
dipole–dipole interactions and suitable molecular symmetry.
Similar molecular symmetry effects are likely experienced by
the currently studied pyridine- and pyrazine-containing amides.
Namely, the lowered mp values of pyridine-containing 1a–b and
2a–b are likely related to the lower molecular symmetry. With
higher molecular symmetry as well as greater van der Waals
forces, mp is amended in 1c–d and 2c–d.
Another influential factor of mp and solubility is the inter-
molecular H-bond. As indicated by the bond lengths from
the crystal structures, the intermolecular H-bonds in 1, 2, 2a
and 1b are only of moderate to weak strength.30 Hence, in
spite of the evident molecular structure and H-bonding motif
changes, their influence over the solubility and mp are
not particularly significant. The set of molecules possessing
intramolecular H-bonds, with weakened or even disrupted
intermolecular H-bonds, do not show collective property distinc-
tions from their respective isomers without intramolecular
H-bonds (in which intermolecular H-bonds are presumably
preserved). For example, amides 1a, 2b, 1c and 2d do not
display consistently higher or lower mp than 2a, 1b, 2c, and
1d, respectively. Amide 2c, with completely annihilated inter-
molecular H-bonds, even possesses a higher mp than 1c,
which should presumably maintain the capability of inter-
molecular H-bonding.
solvents. Particularly improved solubility is displayed in ace-
tone and methanol. Most impressively, in acetonitrile the sol-
ubility of 3 reaches over 10 mg mL−1. Moreover, although the
number of intermolecular H-bonds among 3 is greatly reduced
relative to that among 1, molecule 3 displays a high mp of over
310 °C. This is likely a result of the greater van de Waals
forces and strengthened H-bonds among molecule 3 (vide ante).
The advantage of incorporating such a triptycene unit is evi-
dent. It greatly helps to improve the solubility of the molecule
in common organic solvents, while the thermal resistance is
not significantly compromised. Such properties indicate that
triptycene is a uniquely useful structural unit.
Conclusion
We synthesized a series of aromatic amide molecules con-
taining pyridine/pyrazine heterocycles or the triptycene group.
For probing the effects of such heterocycles and spatially
extended aromatic substituents on the nature and strength of
intermolecular interactions, systematic comparisons are made
among the prototype phenyl amides and modified analogues,
regarding their crystal structures as well as their melting
points and solubility. From the single crystal structures, it is
perceived that when the hetero-atoms are present at suitable
positions, intramolecular H-bonds are formed between amide
NH and heterocyclic nitrogen atoms. Moreover, increasingly
strengthened intramolecular H-bonds are found to progres-
sively weaken or even disrupt the intermolecular H-bonds, as
the two types of H-bonding motifs compete for the same set
of H-bond donors (amide NHs). Bifurcate H-bonds involving
both inter- and intramolecular bonding partners emerge as
an intermediate state in this transition. More planar confor-
mations are exhibited by molecules possessing the intramo-
lecular H-bonds.
The effects of relevant chemical modifications on the solu-
bility and mp are also examined. The influence of H-bonding
motif change over the mp is not quite pronounced. Improved
solubility in common organic solvents and lowered melting
points are generally observed upon pyridine incorporation.
The mp changes are likely related to the lowered molecular
symmetry of pyridine-containing molecules. Pyrazine-containing
amides display more comparable mp to hydrocarbon amides
1 and 2, whereas the solubility is typically lowered with
increasing mp.
Triptycene-containing amide 3 is however an exception.
With a hardly tempered high mp of >310 °C, the solubility
of this molecule in many organic solvents is much higher
compared to its analogue 1 without triptycene substitution.
Due to the presence of the spatially extended triptycene
unit this molecule displays only half the number of inter-
molecular H-bonds exhibited by analogue 1. Shorter H-bond
lengths are nonetheless detected in the crystal structure of 3,
implying stronger bond strength. Very compact molecular
packing is also observed in the crystal of molecule 3. Greater
van der Waals forces resulting from larger molecular mass
might be an important reason for the high mp of the molecule.
The alteration of H-bonding motif in pertinent molecules
appears to have minor effects on the solubility. Molecule 2c
exhibits lower solubility in most examined solvents than its
regio-isomer 1c, but perceptibly higher solubility is observed
for 2c than 1c in dichloromethane and chloroform, which are
incapable of H-bonding with solute molecules. Compared to
the intramolecularly H-bonded amide NH and pyrazine nitro-
gen in 2c, higher solvation energy is possibly required for
accommodating such polar functional groups in 1c by these
solvents incapable of hydrogen-bonding. Similarly, slightly
higher solubility is also observed for 1b than 2b in these two
solvents (Table 4).
Remarkably, triptycene-containing amide 3 demonstrates
much higher solubility than analogue 1 in most examined
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These results suggest that large van der Waals interac-
tions are helpful for achieving desirable thermal properties
from such aromatic amides. When adequate van der Waals
interactions exist, intermolecular H-bonds may not be particu-
larly critical. Furthermore, pyridine, pyrazine, and particularly
triptycene appear to be useful modular units for chemical
modification of aromatic polyamides, which could bestow
improved solubility and processability for relevant materials.
N,N′-(1,4-Phenylene)dipyridine-2-carboxamide (1b). To a
solution of pyridine-2-carboxylic acid (200 mg, 1.62 mmol) in
pyridine (8 mL) were added aniline (87 mg, 0.81 mmol) and
triphenyl phosphite (503 mg, 1.62 mmol). The mixture was
heated at reflux under stirring for 2 h, and then quenched with
water. The precipitate was filtered and washed with water and
1
ethanol to afford 1b as a white solid (93%). H NMR (CDCl3,
300 MHz, ppm): δ 10.06 (s, 2H), 8.63 (d, 2H, J = 4.5 Hz), 8.31
(d, 2H, J = 7.8 Hz), 7.90–7.95 (m, 2H), 7.83 (s, 4H), 7.47–7.51
(m, 2H). 13C NMR (DMSO-d6, 75 MHz, ppm): δ 163.2, 150.9,
149.4, 139.1, 135.3, 127.8, 123.3, 121.5. ESI-TOF-MS: calcd for
C18H14N4O2: 318.1; found: 319.1 (M + H+). Elem. anal.: calcd
for C18H14N4O2: C, 67.91; H, 4.43; N, 17.60. Found: C, 67.64;
H, 4.51; N, 17.59.
N,N′-Di(pyridin-2-yl)terephthalamide (2b). To a solution
of pyridine-2-amine (200 mg, 2.12 mmol) in THF (15 mL)
was added terephthaloyl dichloride (200 mg, 0.985 mmol).
The reaction mixture was heated at reflux under stirring over-
night forming a precipitate. The precipitate was filtered and
washed with water and ethanol to afford 2b as a white solid
(62%). 1H NMR (DMSO-d6, 300 MHz, ppm): δ 10.97 (s, 2H),
8.41 (d, 2H, J = 4.5 Hz), 8.20 (d, 2H, J = 8.4 Hz), 8.13 (s, 4H),
7.84–7.89 (m, 2H), 7.17–7.21 (m, 2H). The 1H NMR data is
consistent with the literature.37
N,N′-(Pyrazine-2,5-diyl)dibenzamide (1c). To a solution of
pyrazine-2,5-diamine38,39 (38 mg, 0.342 mmol) in dry THF
(10 mL) was added benzoyl chloride (150 mg, 1.06 mmol)
dropwise. The reaction mixture was heated at reflux under
stirring for 12 h. The precipitate formed was filtered and
washed with ethyl ether. The crude product was then purified
with column chromatography over silica gel eluted with THF
to afford 1c as a white solid (51%). 1H NMR (DMSO-d6,
300 MHz, ppm): δ 11.18 (s, 2H), 9.26 (s, 2H), 8.07 (d, 4H,
J = 7.8 Hz), 7.52–7.65 (m, 6H). 13C NMR (DMSO-d6, 125 MHz,
ppm): δ 166.7, 145.8, 135.6, 134.3, 133.0, 129.3, 129.0. ESI-TOF-
MS: calcd for C18H14N4O2: 318.1; found: 319.1 (M + H+). Elem.
anal. calcd for C18H14N4O2: C, 67.91; H, 4.43; N, 17.60. Found:
C, 67.83; H, 4.53; N, 17.55.
N,N′-Diphenylpyrazine-2,5-dicarboxamide (2c). To a solution
of pyrazine-2,5-dicarboxylic acid (498 mg, 2.96 mmol) in pyridine
(25 mL) were added aniline (552 mg, 5.93 mmol) and triphenyl
phosphite (1.84 g, 5.93 mmol). The mixture was heated at
reflux under stirring for 1 h, and quenched with water. The
precipitate was filtered, and washed with water and ethanol
to afford 2c as a white solid (63%). 1H NMR (DMSO-d6,
300 MHz, ppm): δ 10.93 (s, 2H), 9.38 (s, 2H), 7.93 (d, 4H,
J = 8.1 Hz), 7.40 (t, 4H, J = 8.1 Hz), 7.17 (t, 2H, J = 7.5 Hz).
13C NMR (DMSO-d6, 125 MHz, ppm): δ 161.9, 147.9, 143.2,
139.0, 129.6, 125.3, 121.6. ESI-TOF-MS: calcd for C18H14N4O2:
318.1; found, 318.2 (M+). Elem. anal.: calcd for C18H14N4O2:
C, 67.91; H, 4.43; N, 17.60. Found: C, 67.84; H, 4.34; N, 17.56.
N,N′-(1,4-Phenylene)dipyrazine-2-carboxamide (1d). To a
solution of pyrazine-2-carboxylic acid (100 mg, 43.5 mmol)
in pyridine (5 mL) were added benzene-1,4-diamine (44 mg,
0.403 mmol) and triphenyl phosphite (250 mg, 0.806 mmol).
The reaction mixture was heated at reflux under stirring for
Experimental
Materials
N,N′-(1,4-Phenylene)dibenzamide (1). To a solution of
benzene-1,4-diamine (370 mg, 3.42 mmol) in THF (25 mL) were
added benzoyl chloride (962 mg, 6.84 mmol) and triethylamine
(2 mL). The reaction mixture was stirred at room temperature
for another 30 min and a white precipitate was formed.
Filtration and washing with water and ethanol afforded 1 as
a white solid (82%). 1H NMR (DMSO-d6, 300 MHz, ppm):
δ 10.25 (s, 2H), 7.96 (d, 4H, J = 6.9 Hz), 7.76 (s, 4H), 7.51–7.62
(m, 6H). The 1H NMR data is consistent with literature.14
N,N′-Diphenylterephthalamide (2). To
a
solution of
terephthaloyl dichloride (200 mg, 0.985 mmol) in THF (20 mL)
was added aniline (183 mg, 1.97 mmol). The mixture was
stirred at room temperature for 43 min. The white precipitate
was filtered and washed with water and ethanol to afford 2
as a white solid (97%). 1H NMR (DMSO-d6, 300 MHz, ppm):
δ 10.40 (s, 2H), 8.10 (s, 4H), 7.80 (d, 4H, J = 8.1 Hz), 7.38
1
(t, 4H, J = 7.5 Hz), 7.13 (t, 2H, J = 7.0 Hz). The H NMR data is
consistent with literature.15
N,N′-(Pyridine-2,5-diyl)dibenzamide (1a). To a solution of
pyridine-2,5-diamine dihydrochloride (100 mg, 0.549 mmol)
in pyridine (20 mL) was added 10 drops of benzoyl chloride.
The mixture was refluxed under stirring for 4 h, and then
poured into water. The white precipitate was filtered and
washed with water and ethanol to afford 1a as a white solid
(67%). 1H NMR (CDCl3, 300 MHz, ppm): δ 8.63 (d, 1H, J = 2.4 Hz),
8.57 (s, 1H), 8.44 (d, 1H, J = 9.0 Hz), 8.11 (dd, 1H, J = 2.4 Hz,
9.0 Hz), 7.89–7.95 (m, 4H), 7.82 (s, 1H), 7.49–7.61 (m, 6H).
The 1H NMR data is consistent with literature.36
N,N′-Diphenylpyridine-2,5-dicarboxamide (2a). To a solution
of pyridine-2,5-dicarboxylic acid (500 mg, 2.99 mmol) in toluene
(40 mL) was added oxalyl dichloride (759 mg, 5.98 mmol).
The solution was stirred and refluxed for 30 min, and aniline
(834 mg, 8.97 mmol) was added. The mixture was stirred for
another 10 min. The precipitate was filtered and washed with
dichloromethane and methanol to afford 2a as a white solid
(67%). 1H NMR (DMSO-d6, 300 MHz, ppm): δ 10.77 (s, 1H),
10.64 (s, 1H), 9.20 (d, 1H, J = 2.1 Hz), 8.56 (dd, 1H, J = 8.4 Hz,
J = 2.1 Hz), 8.31 (d, 1H, J = 8.1 Hz), 7.94 (d, 2H, J = 8.1 Hz),
7.80 (d, 2H, J = 7.8 Hz), 7.36–7.42 (m, 4H), 7.12–7.18 (m, 2H).
13C NMR (DMSO-d6, 75 MHz, ppm): δ 164.3, 162.8, 152.8,
148.8, 139.7, 139.2, 138.3, 133.9, 129.7, 125.2, 123.0, 121.4.
ESI-TOF-MS: calcd for C19H15N3O2, 317.1; found 318.1 (M + H+).
Elem. anal.: calcd for C19H15N3O2: C, 71.91; H, 4.76; N, 13.24.
Found: C, 71.70; H, 4.82, N, 13.21.
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2 h, and then quenched with water forming a precipitate.
The precipitate was filtered and washed with water and etha-
nol to afford 1d as a white solid (45%). 1H NMR (DMSO-d6, 300
MHz, ppm): δ 10.77 (s, 2H), 9.30 (s, 2H), 8.94 (d, 2H, J =
2.4 Hz), 8.82 (d, 2H, J = 2.4 Hz), 7.90 (s, 4H).40 ESI-TOF-MS:
calcd for C16H12N6O2: 320.1; found, 321.1 (M + H+).
N,N′-Di(pyrazin-2-yl)terephthalamide (2d). To a solution
of pyrazine-2-amine (300 mg, 3.15 mmol) in THF (50 mL)
were added terephthaloyl dichloride (320 mg, 1.58 mmol)
and triethylamine (2 mL). The reaction mixture was heated
at reflux under stirring for 22 h, and then quenched with
water forming a precipitate. The precipitate was filtered
and washed with water and ethanol to afford 2d as a white
solid (30%). 1H NMR (DMSO-d6, 300 MHz, ppm): δ 11.33
(s, 2H), 9.44 (s, 2H), 8.46–8.51 (m, 4H), 8.17 (s, 4H). 13C NMR
(DMSO-d6, 125 MHz, ppm): δ 166.4, 143.5, 141.1, 138.4, 137.4,
129.1. ESI-TOF-MS: calcd for C16H12N6O2: 320.1; found, 321.1
(M + H+). Elem. anal. calcd for C16H12N6O2: C, 60.00; H, 3.78;
N, 26.24. Found: C, 59.87; H, 3.84; N, 26.08.
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N,N′-(2,5-Diaminotriptycene)dibenzamide (3). To a solution
of 2,5-diaminotriptycene dihydrochloride41 (962 mg, 2.69 mmol)
in boiling water (700 mL) was added NaOH in portions until
the pH was adjusted to 12. A white solid was formed and
filtered. The white solid was dissolved in THF (100 mL). A mixture
of benzoyl chloride (757 mg, 5.39 mmol) and triethylamine
(2 mL) was added to the solution. The reaction mixture was
heated at reflux under stirring and a nitrogen atmosphere
overnight. The precipitate formed was filtered and washed
with water and ethanol to afford 3 as a white solid (47%).
1H NMR (DMSO-d6, 400 MHz, ppm): δ 10.34 (s, 2H), 8.13
(d, 2H, J = 6.0 Hz), 7.60–7.70 (m, 6H), 7.42–7.44 (m, 4H), 7.03
(s, 2H), 6.98–7.01 (m, 4H), 5.67(s, 2H). 13C NMR (DMSO-d6,
125 MHz, ppm): δ 167.1, 145.9, 142.5, 135.6, 132.5, 131.6,
129.3, 128.8, 125.6, 125.1, 124.0, 50.1. ESI-TOF-MS: calcd for
C34H24N2O2: 492.2; found, 493.2 (M + H+). Elem. anal.: calcd
for C34H24N2O2: C, 82.91; H, 4.91; N, 5.69. Found: C, 82.89;
H, 4.88; N, 5.65.
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Acknowledgements
The work is supported by the Ministry of Science and Technology
(2011CB606106) and the National Natural Science Foundation
of China (projects 21174004 and 21222403).
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