Extended structures controlled by intramolecular and intermolecular hydrogen bonding: A case study with pyridine-2,6-dicarboxamide, 1,3-benzenedicarboxamide and N,N'-dimethyl-2,6-pyridinedicarboxamide

Article abstract of DOI:10.1016/S0022-2860(00)00673-6

The small organic molecule pyridine-2,6-dicarboxamide, although known in the literature for some time, exhibits interesting and previously unexplored intermolecular and intramolecular hydrogen bonding both in solid state and in solution. With the aid of X-ray crystallography and variable-temperature NMR spectroscopy, we here demonstrate the presence of a very strong hydrogen bonding network for this molecule both in condensed state and solution. Furthermore, a novel extended hydrogen bonding graph-set has been derived for this molecule in crystalline state. Comparison of pyridine-2,6-dicarboxamide with 1,3-benzenedicarboxamide, where the intramolecular hydrogen bonding to the pyridine ring in the former has been removed, yields a different intermolecular hydrogen bonded structure in the solid state. A new graph-set has been determined for the extended structure of 1,3-benzenedicarboxamide in the solid state. In solution, 1,3-benzenedicarboxamide is shown to maintain a hydrogen bonding pattern that is weaker than that observed with pyridine-2,6-dicarboxamide. Replacement of one hydrogen on each carboxamide nitrogen of pyridine-2,6-dicarboxamide by a methyl group also alters the extended structure to a significant extent. In N,N'-dimethyl-2,6-pyridinedicarboxamide, the three-dimensional hydrogen bonding pattern observed with pyridine-2,6-dicarboxamide all but collapses to one-dimensional chains. (C) 2000 Elsevier Science B.V.

Full text of DOI:10.1016/S0022-2860(00)00673-6

Journal of Molecular Structure 554 (2000) 211±223
www.elsevier.nl/locate/molstruc
Extended structures controlled by intramolecular and
intermolecular hydrogen bonding: a case study with
pyridine-2,6-dicarboxamide, 1,3-benzenedicarboxamide and
N,N0-dimethyl-2,6-pyridinedicarboxamide
D.S. Marlina, M.M. Olmsteadb, P.K. Mascharaka,
*
aDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
bDepartment of Chemistry, University of California, Davis, Davis, CA 95616, USA
Received 14 February 2000; accepted 24 May 2000
Abstract
The small organic molecule pyridine-2,6-dicarboxamide, although known in the literature for some time, exhibits interesting
and previously unexplored intermolecular and intramolecular hydrogen bonding both in solid state and in solution. With the aid
of X-ray crystallography and variable-temperature NMR spectroscopy, we here demonstrate the presence of a very strong
hydrogen bonding network for this molecule both in condensed state and solution. Furthermore, a novel extended hydrogen
bonding graph-set has been derived for this molecule in crystalline state. Comparison of pyridine-2,6-dicarboxamide with 1,3-
benzenedicarboxamide, where the intramolecular hydrogen bonding to the pyridine ring in the former has been removed, yields
a different intermolecular hydrogen bonded structure in the solid state. A new graph-set has been determined for the extended
structure of 1,3-benzenedicarboxamide in the solid state. In solution, 1,3-benzenedicarboxamide is shown to maintain a
hydrogen bonding pattern that is weaker than that observed with pyridine-2,6-dicarboxamide. Replacement of one hydrogen
on each carboxamide nitrogen of pyridine-2,6-dicarboxamide by a methyl group also alters the extended structure to a
signi®cant extent. In N,N0-dimethyl-2,6-pyridinedicarboxamide, the three-dimensional hydrogen bonding pattern observed
with pyridine-2,6-dicarboxamide all but collapses to one-dimensional chains. q 2000 Elsevier Science B.V. All rights
reserved.
Keywords: Hydrogen bonding; Graph-sets; Pyridine-2,6-dicarboxamide; N,N0-dimethyl-2,6-pyridinedicarboxamide; 1,3-benzenedicarboxa-
mide
1. Introduction
been an enormous effort in recent years to control
hydrogen bond formation [2±6]. The hydrogen
bond is one of the most effective and common
forces by which self-assembly and self-organiza-
tion can be achieved to form discrete assemblies
and extended lattices both in solid state and in
solution [2±6] Hydrogen bonding in liquids
governs the formation of liquid crystals, molecular
layers, ®lms, mesophases, as well as molecular
One does not need to look far into the chemical
literature to note the intense interest that interac-
tions between molecules, in particular hydrogen
bonds, have generated [1±22]. Indeed, there has
0022-2860/00/$ - see front matter q 2000 Elsevier Science B.V. All rights reserved.
PII: S0022-2860(00)00673-6

212
D.S. Marlin et al. / Journal of Molecular Structure 554 (2000) 211±223
recognition [2±7]. In solid state, crystalline archi-
tectures built upon hydrogen bonding networks are
®nding utility in crystal engineering and new
materials [7±10]. Hydrogen bonding interactions,
especially those of amides, are also important in
medicinal chemistry. In one avenue of this ®eld,
molecules with speci®c hydrogen bond donors and
acceptors are being used to interact with DNA in
desired ways [11±15].
A graph-set formalism has been established to
understand and communicate ®ndings in the area of
intermolecular hydrogen bonding [16±22]. Rules for
assigning graph-sets to particular networks of
hydrogen bonds in organic crystals have been
described elsewhere [16,22] Attempts have also
been made to use graph-sets in predicting hydrogen
bonding patterns in solid state structures of small
organic molecules with multiple hydrogen bond
donors and acceptors [22]. In recent years, reports
on the mathematical foundation for such pursuit and
the necessary software developments have appeared
[23].
In our effort to synthesize designed ligands with
carboxamide nitrogens as donors, we recognized
the high propensity of pyridine-2,6-dicarboxamide
to form very stable hydrogen bonding networks
both in solid state and in solution. The robust
hydrogen bonding pattern and the associated
graph-set for the extended structure of this
compound are unusual. In order to determine the
factors that give rise to such structures, we have
also looked into the structures of 1,3-benzenedi-
carboxamide and N,N0-dimethyl-2,6-pyridinedicar-
boxamide. The former compound was selected to
determine the effect of intramolecular hydrogen
bonding on the overall structure. This benzene
derivative forms an interesting extended solid
state structure governed by intermolecular
hydrogen bonds. N,N0-dimethyl-2,6-pyridinedicar-
boxamide was studied to elucidate what changes
in the extended structure occur when the extent of
intermolecular hydrogen bonding is reduced. Here
we report the extended structures of all three
compounds in the solid state, the hydrogen
bonding patterns associated with these structures,
and the results of variable-temperature NMR
studies for pyridine-2,6-dicarboxamide and 1,3-
benzenedicarboxamide.
2. Experimental section
Pyridine-2,6-dicarboxylic
acid,
methylamine
(2.0 M in THF), isophthaloyl dichloride, and thionyl
chloride were purchased from Aldrich Chemical Co.
and were used without further puri®cation. Ethanol
was distilled from magnesium ethoxide and THF
was distilled from sodium and benzophenone prior
to use. Pyridine-2,6-dicarboxamide was prepared
accord0ing to a published procedure [24].
N,N -dimethyl-2,6-pyridinedicarboxamide: A batch
of 3 g (18 mmol) of pyridine-2,6-dicarboxylic acid
was added to 10 ml of thionyl chloride and heated
to re¯ux until completely dissolved. The volatiles
were then removed under vacuum and the residue
was triturated twice with THF. The remaining solid
was then dissolved in 30 ml of THF and added drop-
wise to a solution of methylamine (15.0 ml of 2.0 M
THF solution) in THF (50 ml) at 08C. After the addi-
tion was complete, the mixture was warmed to room
temperature and stirred for 5 h. The precipitate that
formed during this step was removed by ®ltration, and
redissolved in 40 ml of water. This aqueous solution
was then made basic with K2CO3 and extracted with
methylene chloride ꢀ3 £ 30 ml†: The extracts were
combined, dried over MgSO4 and the solvent was
®nally removed by rotary evaporation. The residue
was recrystallized from methylene chloride (overall
1
yield: 2.0 g, 64%). H NMR (500 MHz, [D6]DMSO,
258C, TMS), dꢀppm† ˆ 2:89 (d, 6H), 8.15 (m, 3H),
9.27 (q, 2H). Selected IR bands (KBr pellet, cm21):
3323 (s, nNH), 3294 (s, nNH), 1687 (s, nCO), 1659 (s,
nCO), 1543 (s), 1443 (vs), 1401 (s), 1243 (m) 1165
(m), 740 (m), 681 (s), 645 (m).
1,3-Benzenedicarboxamide:
(9.9 mmol) of isophthaloyl dichloride was dissolved
in 10 ml of ethanol and warmed to 608C for 2 h. The
volatiles were then removed in vacuum and the
residue was taken up in10 ml of water. This solution
was cooled to 08C and to this was slowly added a
solution of aqueous ammonium hydroxide (40 ml).
The mixture was heated to 1008C for 2 h and then
allowed to cool to room temperature and ®ltered.
The precipitate was washed twice with water
(10 ml) and dried under vacuum. The white solid
was recrystallized from water (overall yield: 1.3 g,
80%). 1H NMR (500 MHz, [D6]DMSO, 258C,
TMS), dꢀppm† ˆ 7:46 (s, 2H), 7.53 (t, 1H), 8.00 (d,
A
batch of 2 g

D.S. Marlin et al. / Journal of Molecular Structure 554 (2000) 211±223
213
Table 1
Crystallographic data for pyridine-2,6-dicarboxamide (prisms), 1,3-benzenedicarboxamide and N,N0-dimethyl-2,6-pyridinedicarboxamide
Pyridine-2,6-dicarboxamide
1,3-benzene-dicarboxamide
NN0-dimethyl-2,6-
pyridinedicarboxamide
Empirical formula
Crystal habit
Mr
C7H7N3O2
prism
C8H8N2O2
block
C9H11N3O2
plate
165.16
164.16
193.21
Crystal system
Space group
monoclinic
C2/c
monoclinic
C2/c
orthorhombic
Pbca
Ê
a(A)
Ê
b(A)
Ê
c(A)
12.3963(9)
7.6380(6)
8.6729(6)
90
7.0231(10)
7.1749(12)
14.7014(19)
90
12.4186(8)
9.8810(7)
15.7409(10)
90
a (8)
b (8)
g (8)
120.2800(10)
90
93.927(11)
90
90
90
1931.5(2)
90(2)
Ê 3
V(A )
709.14(9)
90(2)
739.06(19)
133(2)
T (K)
Z
4
4
8
Crystal size (mm)
rcalcd (g cm23
0:36 £ 0:20 £ 0:16
1.547
0:10 £ 0:10 £ 0:10
1.475
0:37 £ 0:13 £ 0:04
1.329
)
Ê
Radiation l (A)
m (mm23
0.71073
0.118
1.54178
0.908
0.71073
0.097
)
Max. and min. transm.
R1a (obs'd data)
wR2b (all data)
0.9814 and 0.9589
0.0460
0.9146 and 0.9146
0.0309
0.9961 and 0.9650
0.0448
0.1339
0.0841
0.1016
P
P
a
R1 ˆ iFo 2 Fci= uFou:
P
P
wR2 ˆ ꢀ ꢀwꢀFo2 2 Fc2† †= ꢀwꢀFo2† ††
:
b
2
2
1=2
2H), 8.04 (s, 2H), 8.38 (s, 1H). Selected IR bands
(KBr pellet, cm21): 3367 (s, nNH), 3155 (s, nNH),
1659 (s, nCO), 1627 (s), 1575 (m), 1395 (s), 1128
(s), 797 (m), 643 (s), 620 (m).
solution of the compound in methylene chloride.
X-ray data for N,N0-dimethyl-2,6-pyridinedicar-
boxamide and the prisms of pyridine-2,6-dicarbox-
amide were collected on a Bruker SMART 1000
system with the use of MoKa radiation. The low
temperature N2 stream was generated by a CryoIn-
dustries apparatus. No decay in the intensities
from 50 remeasured frames was detected. For
1,3-benzenedicarboxamide, data were obtained on
a Siemens P4 diffractometer equipped with a
Siemens rotating copper anode, nickel ®lter, and
LT-2 low temperature device. A linear scale to the
intensities was applied to accomodate a 3.4%
decay in the intensities of two standard re¯ections.
All structures were solved by direct methods
(SHELXS-97) and re®ned using all data, based
on F2 (shelxl-97). No absorption corrections
were applied. Hydrogen atoms were located on
difference maps and freely re®ned.
Instrumentation: A Perkin±Elmer 1600 FTIR spec-
trophotometer was employed to monitor the IR
1
spectra and the H NMR spectra were monitored on
a Varian 500 MHz Unity Plus instrument interfaced
with a Sun OS 4.1.3 computer.
X-ray structure determination: Needles of pyri-
dine-2,6-dicarboxamide were grown from a satu-
rated solution of H2O or by layering H2O on a
DMSO solution of the compound and allowing
for slow diffusion at room temperature. Prisms
of this compound were grown by slow cooling
of saturated solutions of this compound in ethanol,
pyridine, or nitromethane. The crystal used for X-
ray data collection was grown from pyridine.
Large colorless blocks of 1,3-benzenedicarboxa-
mide were grown from H2O. In case of N,N0-
Crystal data and data collection parameters are
summarized in Table 1, while selected bond distances
are included in Fig. 1. A list of hydrogen bond
dimethyl-2,6-pyridinedicarboxamide, colorless
plates were grown from slow evaporation of a

214
D.S. Marlin et al. / Journal of Molecular Structure 554 (2000) 211±223
Fig. 1. Drawings of pyridine-2,6-dicarboxamide (structure a), 1,3-benzenedicarboxamide (structure b), and N,N0-dimethyl-2,6-pyridinedicar-
boxamide (structure c) showing the unique set of hydrogen bonds, the atom numbering scheme, and thermal elliposids at the 50% probability
0
Ê
level. Selected hydrogen bond distances (A) are shown. In structure a, intermolecular hydrogen bonds originating from N(2 ) are omitted for
clarity. Similarly, intermolecular hydrogen bonds originating from O, O0 and N0 are omitted in structure b.

D.S. Marlin et al. / Journal of Molecular Structure 554 (2000) 211±223
215
Table 2
Hydrogen bonding distances and angles for pyridine-2,6-dicarboxamide, 1,3-benzenedicarboxamide and N,N0-dimethyl-2,6-pyridinedicarbox-
amide. The hydrogen bond donor atoms are denoted as D and the acceptors as A
D±H´´´Aa
DHA (8)
Ê
d(D±H) (A)
Ê
d(H´´´A) (A)
Ê
d(D´´´A) (A)
Pyridine-2,6-dicarboxamide
N(2)±H(2A)´´´O(100)#2
N(2)±H(2B)´´´O(1000)#3
1,3-benzenedicarboxamide
N±H(1A)´´´O00#2
0.917(15)
0.967(16)
2.251(15)
1.940(17)
3.0691(11)
2.8653(11)
148.3(14)
159.4(13)
0.889(18)
0.89(2)
2.096(19)
2.01(2)
2.9035(17)
2.8998(18)
150.4(15)
173.7(18)
N±H(1B)´´´O000#3
N,N0-dimethyl-2,6-pyridinedicarboxamide
N(1)±H(1)´´´O(20)#1
N(3)±H(3)´´´O(20)#1
0.894(16)
0.901(17)
2.193(17)
2.071(18)
3.0302(16)
2.8802(15)
155.7(14)
149.0(14)
a
Symmetry transformations used to generate equivalent atoms: #1, 2x, y, 2z 1 1=2; #2, x 1 1=2; y 2 1=2; z; and #3, 2x 1 1=2; 2y 1 1=2; 2z.
distances and angles is provided in Table 2. The rest
of the crystallographic data has been submitted as
supplementary material.
dimethyl-2,6-pyridinedicarboxamide (Fig. 1c) with
relevant hydrogen bonding distances and numbering
scheme are shown in Fig. 1.1. Hydrogen bonding
distances and angles are summarized in Table 2. In
Fig. 1 and Table 2, the D±H bonds have not been
extended to the typical neutron diffraction value of
3. Results and discussion
Ê
1.020 A, a practice often followed in rigorous crystal-
lographic studies [25]. Each molecule has 2-fold
symmetry that passes through N(1) and C(1) in pyri-
dine-2,6-dicarboxamide, C(1) and C(4) in 1,3-benze-
nedicarboxamide, and N(2) and C(5) in N,N0-
dimethyl-2,6-pyridinedicarboxamide (the 2-fold
symmetry is non-crystallographic in this case). The
crystal structure of pyridine-2,6-dicarboxamide
reveals that there are two long N±H´´´N intramole-
cular hydrogen bonds per molecule between the
pyridyl nitrogen N(1) and the carboxamide hydrogens
H(2A) and H(2A0) on either side of it (Fig. 1a). The
two intermolecular hydrogen bonds between (i) N(2)
and O(100) and (ii) N(2) and O(1000) form half of an
eight membered hydrogen bonding ring between four
individual molecules. This type of hydrogen bonding
motif in which an eight membered hydrogen bonding
ring forms between four individual molecules is
called an R24ꢀ8† set in graph-set nomenclature. In
this nomenclature, R42ꢀ8† describes a hydrogen
bonding pattern where R represents a ring, the
Pyridine-2,6-dicarboxamide can be readily recrys-
tallized (within minutes) from several solvents and
depending on the type of solvent used, it affords either
prisms or needles. Needles were grown from H2O or
DMSO/H2O, while prisms were obtained by recrys-
tallization from pyridine, ethanol, or nitromethane.
The structure of pyridine-2,6-dicarboxamide was
determined for both the needle and the prism
morphologies and it was found to be the same. The
crystal data for the prismatic form are listed in Table
1. X-ray quality blocks of 1,3-benzenedicarboxamide
were grown from H2O and were also obtained rapidly
(within less than an hour). N,N0-dimethyl-2,6-pyridi-
nedicarboxamide is much more soluble than pyridine-
2,6-dicarboxamide and readily dissolves in alcohols,
water, THF, methylene chloride and acetonitrile.
Crystallization of this compound was achieved by
slow evaporation of its solution in methylene chloride
or ethanol. Plates were obtained from both solvents. It
is interesting to note that although strongly hydrogen
bonding solvents such as H2O, DMSO and ethanol
were used to recrystalize the above compounds, in
no case did the solvent form part of the crystal
structure.
1
In two of the three molecules, the asymmetric unit is smaller
than one molecule due to point symmetry and hence the IUPAC
numbering scheme cannot be easily applied. For this reason, the
numbering scheme in Fig. 1 assigns atom numbers in a consecutive
fashion to the atoms of the asymmetric unit.
Views of pyridine-2,6-dicarboxamide (Fig. 1a),
1,3-benzenedicarboxamide (Fig. 1b), and N,N0-

216
D.S. Marlin et al. / Journal of Molecular Structure 554 (2000) 211±223
Fig. 2. A stereo view of pyridine-2,6-dicarboxamide that reveals the honeycomb-like pattern created by the R24ꢀ8† graph-sets. Intramolecular
hydrogen bonds omitted for clarity.
superscript and subscript are the number of hydrogen
bond acceptors and donors, respectively, and the
number in brackets refers to how many members
make up the ring [16]. The R24ꢀ8† graph-set pattern
is the basis of the extended structure for pyridine-
2,6-dicarboxamide. The amido groups are not in the
pyridyl plane, and this is what leads to the propagation
of the R24ꢀ8† hydrogen bonded rings in two directions
(Fig. 2). The propagation directions can be related to
the direction of the C(4)±O(1) lines. Within one mole-
cule, the dihedral angle between C(4)±O(1) and
C(40)±O(10) is 132.48. Also, the C(4)±O(1) line0 is
tipped 15.48 above the pyridyl plane while C(4 )±
O(10) is tipped 215.48 below it. The planes formed
by the repeating R24ꢀ8† sets give rise to a honeycomb-
like three-dimensional structure as shown in Fig. 2. In
this stereo view diagram, the repeating R24ꢀ8† sets that
form planes propagating in two directions are clearly
visible.
Using the graph-set formalism and representing the
individual molecules as dots and the intermolecular
hydrogen bonding between these molecules as lines,
the hydrogen bonding network around a central mole-
cule can be simpli®ed to the one shown in Fig. 3a. An
Fig. 3. (a) A graph-set drawing for pyridine-2,6-dicarboxamide.
Individual molecules are represented as dots and intermolecular
hydrogen bonds are shown as lines. (b) The graph-set in three
dimensions (vertical extension of the structure is omitted at several
points for clarity).
extension of the simpli®ed drawing of Fig. 3a is
shown in Fig. 3b. In the simpli®ed version, the

D.S. Marlin et al. / Journal of Molecular Structure 554 (2000) 211±223
217
Fig. 4. Stereo view of 1,3-benzenedicarboxamide showing a segment of the up/down±up/down R22ꢀ8†=R42ꢀ8† staircase-like motif.
R24ꢀ8† graph-sets can be clearly seen as four membered
rings arranged in a crinkled sheet-like fashion in two
directions. Each molecule sits at an intersection
between these sheets (Fig. 3b). It is also apparent
that from each molecule, four R24ꢀ8† graph-sets are
generated, three of these R24ꢀ8† sets share a common
molecule (in addition to the one from which they
stem) which gives rise to a paddle-wheel type motif
with three blades. The fourth R24ꢀ8† set connects this
paddle-wheel to two adjacent sheets (Fig. 3b). To the
best of our knowledge, this robust and elegant three-
dimensional array of R24ꢀ8† hydrogen bonding motifs
has not been shown or predicted yet for any other
hydrogen bonded lattice.
Replacement of the pyridine ring of pyridine-2,6-
dicarboxamide with the benzene ring in 1,3-benzene-
dicarboxamide (Fig. 1b) removes the intramolecular
hydrogen bonding. As a result of this alteration, the
amide hydrogens are not held in place and rotate. In
the solid state, the two amide groups are furthest apart
from each other (Fig. 1b). This has a profound effect
on the intermolecular hydrogen bonding scheme as
shown in Fig. 4. The extended structure for this mole-
cule comprises alternating R24ꢀ8† and R22ꢀ8† graph-set
motifs. This type of alternating R24ꢀ8†=R22ꢀ8† motif has
been demonstrated for other terminal amides [16]. A
stereo view of this molecule showing the three-dimen-
sional propagation of the R24ꢀ8† and R22ꢀ8† sheets rela-
tive to each other is shown in Fig. 4. The propagation
of the sheets in two directions for this molecule arises
from the angle of the two NH2 planes, which are tilted
61.28 with respect to each other. Each molecule sits at
the intersection of two sheets. This pattern is more
clearly demonstrated when the individual 1,3-benze-
nedicarboxamide molecules are shown as dots and the
hydrogen bonds as lines, as shown in the simpli®ed
graph-set pattern of Fig. 5a. Here the R22ꢀ8† graph-sets
are depicted as bowed lines between two molecules
(dots) and the R24ꢀ8† sets as four molecule rings with
straight lines connecting the two sets of bowed lines
together. The 618 angle between the two planes is
indicated. The way four such planes interact with
each other is depicted in Fig. 5b. In this drawing, it
is important to note that the repeating R22ꢀ8†=R42ꢀ8† sets
are not coplanar but form staircase-like patterns that
connect each other in an up/down±up/down fashion
(Fig. 4). Extension of the simpli®ed graph-set (Fig.
5b) in three dimensions yields a complex network,

218
D.S. Marlin et al. / Journal of Molecular Structure 554 (2000) 211±223
Fig. 5. (a) Graph-set representation of 1,3-benzenedicarboxamide indicating the sheets formed from the repeating R22ꢀ8†=R42ꢀ8† sets and the
angle between them. (b) Four repeating R22ꢀ8†=R42ꢀ8† sheets are connected to each other in an up/down±up/down fashion. (c) Extension of the
graph-set. Selected hydrogen bonds around molecules at the perimeter are omitted for clarity.
which is shown in Fig. 5c. Eight hydrogen bonds
originate from each molecule as shown for the central
molecules in Fig. 5c. Comparison of Fig. 3b and 5c
demonstrates that the presence or absence of intramo-
lecular hydrogen bonding plays a crucial role in
formation of the three-dimensional structures of
these two similar primary carboxamides, pyridine-
2,6-dicarboxamide and 1,3-benzenedicarboxamide.
The crystal structure of N,N0-dimethyl-2,6-pyri-
dinedicarboxamide is markedly different from that
of pyridine-2,6-dicarboxamide and 1,3-benzenedicar-
boxamide with regard to its extended hydrogen
bonding network. Although in the structures of all
three compounds a carbonyl oxygen is hydrogen
bonded to two NH hydrogens at one time, in the
case of the primary amides, the carbonyl oxygen
accepts one NH hydrogen from each of two individual
molecules (Fig. 1a,b), while in the secondary amide,
the carbonyl oxygen O(20) is bonded to both NH
hydrogens (H(1) and H(3)) from the same molecule
(Fig. 1c). There are also two long intramolecular
hydrogen bonds between the amide NHs (H(1) an0d
H(3)) and the pyridyl nitrogen N(2) in N,N -
dimethyl-2,6-pyridinedicarboxamide, which gives

D.S. Marlin et al. / Journal of Molecular Structure 554 (2000) 211±223
219
Fig. 6. Stereo view of N,N0-dimethyl-2,6-pyridinedicarboxamide showing the one-dimensional chains and their packing arrangement in the
crystal lattice. Intramolecular hydrogen bonds omitted for clarity.
rise to an internal diamond-like hydrogen bonding
network (Fig. 1c). These features allow for propaga-
tion of the extended structure in only one dimension
as shown in the stereo view of the extended structure
for N,N0-dimethyl -2,6-pyridinedicarboxamide (Fig.
6). From this perspective, the extension of the one-
dimensional chains throughout the lattice is demon-
strated as well as the way these chains interact with
one another.
Secondary carboxamides can have either a cis or a
trans geometry, which refers to the orientation of the
alkyl group on the nitrogen relative to the substituent
on the carbonyl carbon. In N,N0-dimethyl-2,6-pyridi-
nedicarboxamide, the two carboxamide groups exist
in trans con®guration most likely due to the intramo-
lecular hydrogen bonding just described (Fig. 1c). The
proximity of the two transamide NH donors is the key
factor that lends to the one-dimensional structure (Fig.
6) and such mode of hydrogen bonding of one
carbonyl oxygen from one molecule to two amide
hydrogens of the next molecule is quite unusual [16].
The trans amide hydrogen bonding motifs are espe-
cially important in biological systems that form the
common secondary structures of a-helices and b-
sheets, and also in synthetic ®bers [8]. Hydrogen
bonding in cis secondary amides usually results in
cyclic dimers ꢀR22ꢀ8†† or chains in which one carbonyl
oxygen accepts only one NH hydrogen (C(4)), where
C in the graph-set nomenclature refers to a chain [8].
In the chain motif, a helical two-fold screw axis
results due to the formation of a more preferable
CyO´´´H angle (this is also the case for trans amide
C(4) chains). The preference for the formation of
these secondary structures such as helices in the cis
and trans amide chains results from a preferred hybri-
dization angle of hydrogen bonding on the carbonyl
oxygen. Taylor et al. have examined the geometries
for intermolecular N±H´´´OyC hydrogen bonds of a
large number of compounds contained in the
Cambridge Structural Database [26,27]. They
concluded that on average, the carbonyl oxygens
that accept either one or two NH hydrogens form
hydrogen bonds in the direction of the oxygen sp2
lone pairs with an angle F of approximately
1308. All three compounds presented in this report
are of the type where the carbonyl oxygen accepts
two NH hydrogens. For pyridine-2,6-dicarboxa-
mide, the F(angles (are 126(4)8 and 140(4)8 and

1
Fig. 7. Variable-temperature H NMR spectra of pyridine-2,6-dicarboxamide in [D6]DMSO. Temperature and magni®cation are indicated for each spectrum.

D.S. Marlin et al. / Journal of Molecular Structure 554 (2000) 211±223
221
for 1,3-benzenedicarboxamide, the values are 118(5)8
and 144(5)8. It is evident that while pyridine-2,6-
dicarboxamide exhibits F values in the normal
range for primary amides, [26,27] a larger deviation
from 1308 is noted for 1,3-benzenedicarboxamide. In
the case of N,N0-dimethyl-2,6-pyridinedicarboxa-
mide, a secondary amide, the F angles are 104(4)8
and 144(4)8. The relatively large deviation from 1308
in this case is likely due to the strain arising from the
fact that both NH hydrogen donors come from the
same molecule (Fig. 1c). It is interesting to note that
the extent of hydrogen bonding in the three
compounds is diminished (Figs. 2, 4, and 6) as the
angle F deviates further from 1308.
information for studying hydrogen bonds in the
solid state. In the present study, the IR spectra of all
three compounds have been examined in KBr matrix.
The nCO for pyridine-2,6-dicarboxamide and 1,3-
benzenedicarboxamide appear as a single band at
1670 cm21 and 1659 cm21, respectively, while for
N,N0-dimethyl-2,6-pyridinedicarboxamide, the car-
bonyl stretch is split into two peaks with maxima at
1684 cm21 and 1661 cm21. The reason for this behavior
is evident in the crystal structures. In pyridine-2,6-dicar-
boxamide and 1,3-benzenedicarboxamide, all the
carbonyl groups are involved in similar hydrogen
bonding (Figs. 2 and 4) while in N,N0-dimethyl-2,6-
pyridinedicarboxamide, only one of two carbonyl
groups participates in hydrogen bonding (Fig. 6). The
Infrared (IR) spectroscopy provides additional
1
Fig. 8. Variable-temperature H NMR spectra of 1,3-benzenedicarboxamide in [D6]DMSO. Temperature and magni®cation are indicated for
each spectrum.

222
D.S. Marlin et al. / Journal of Molecular Structure 554 (2000) 211±223
NH2 groups of pyridine-2,6-dicarboxamide and 1,3-
benzenedicarboxamide exhibit two nNH peaks each
with maxima at 3406 cm21 and 3231 cm21 for the
former, and at 3367 cm21 and 3155 cm21 for the latter.
In summary, results of structural and spectroscopic
studies on the three amides in solid state clearly
demonstrate that the three-dimensional structure of
pyridine-2,6-dicarboxamide can be altered to the
completely different structure of 1,3-benzenedicar-
boxamide by removing the intramolecular hydrogen
bonds. The same structure collapses to the one-dimen-
sional structure of N,N0-dimethyl-2,6-pyridinedicar-
boxamide upon removal of two intermolecular
hydrogen bonds. Although the extended hydrogen
bonding motifs seen in crystalline pyridine-2,6-dicar-
boxamide (Fig. 3) and 1,3-benzenedicarboxamide
(Fig. 5) collapse in solution, the NMR data suggest
that both compounds maintain substantial hydrogen
bonding in DMSO. Further work is required to under-
stand the nature of hydrogen bonding for these mole-
cules in solution.
Much smaller splitting (3323 cm21 and 3294 cm21
)
is observed in case of N,N0-dimethyl-2,6-pyridine-
dicarboxamide.
With the structures of the title compounds in hand
we were curious to ®nd out whether the hydrogen
bonding pattern of pyridine-2,6-dicarboxamide and
1,3-benzenedicarboxamide, as noted in solid state,
are partially retained in solution. In order to study
such bonding in solution, the technique of variable-
1
temperature H NMR spectroscopy was employed for
both compounds in [D6]DMSO. At 258C in DMSO
solution, pyridine-2,6-dicarboxamide exhibits two
NH peaks of equal intensity at 8.88 and 7.69 ppm
(Fig. 7). Upon warming, the peaks begin to broaden
and ®nally coalesce into one broad peak at ,7:7 ppm
at 1508C (Fig. 7). The resistance to disruption of the
hydrogen bonding in DMSO solution up to tempera-
tures as high as 1508C implies a very strong hydrogen
bonding interaction. From this data, we estimated a
rate constant (kn) of 30.4 s21 and an activation energy
Acknowledgements
This research was supported by a grant from the
National Science Foundation (CHE-9818492). We
would like to thank Jim Loo for technical assistance.
³
(DG ) of 19.0 Kcal/mol for the chemical exchange at
the temperature of coalescence using standard proce-
dures [7,28].2 Similar measurement was also
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