Substituent effect on the formation of helical to layered hydrogen bond networks in hydroxyl and carboxyl substituted 1-aryl-1H-1,2,3-triazoles

Article abstract of DOI:10.1039/c4ce00738g

Six structurally related 1-aryl-1H-1,2,3-triazoles substituted with hydroxyl and carboxyl groups have been studied by single crystal X-ray crystallography. O-H...N and O-H...O hydrogen bond synthons play a predominant role in the crystal engineering of th

Full text of DOI:10.1039/c4ce00738g

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Substituent effect on the formation of helical to
layered hydrogen bond networks in hydroxyl and
carboxyl substituted 1-aryl-1H-1,2,3-triazoles†
Cite this: CrystEngComm, 2014, 16,
6098
*
Bemineni Sureshbabu, Ramkumar Venkatachalam and Sethuraman Sankararaman
Six structurally related 1-aryl-1H-1,2,3-triazoles substituted with hydroxyl and carboxyl groups have been
studied by single crystal X-ray crystallography. O–H⋯N and O–H⋯O hydrogen bond synthons play a
predominant role in the crystal engineering of these derivatives. The positions of the hydroxyl and
carboxyl groups are important and have an effect on the dihedral angle of the twisted conformations of
these molecules in the solid state which in turn dictates the formation of helical or layered hydrogen
bond motifs and the chirality of the crystals.
Received 8th April 2014,
Accepted 5th May 2014
DOI: 10.1039/c4ce00738g
www.rsc.org/crystengcomm
achiral 2-aminothiazole derivatives.26 Herein, we report a
systematic investigation of the effect of a molecular twist on
Introduction
Chirality is a fascinating and ever-green topic in chemistry.1,2
Molecules that are inherently achiral in the solution phase
can crystallize in specific conformations that are chiral in the
solid state.3–6 While doing so they can crystallize either as a
racemic modification (racemic conglomerate) consisting of
only one enantiomeric form in the crystal lattice or as a race-
mic compound consisting of a 1 : 1 mixture of both the
enantiomeric forms in the crystal lattice. The former leads to
the formation of chiral crystals. Chiral crystals are important
and they are useful in enantioselective catalysis, sensing and
chromatography as mentioned in a recent article by Avnir.7
In addition to molecular chirality of small achiral molecules
in the solid state, chiral supramolecular structures can be
formed by supramolecular assembly, typically through hydro-
gen bonds and other weak intermolecular interactions.8–12
One such supramolecular system is the formation of a hydro-
gen bonded helical assembly. Hydrogen bonded supramolec-
ular helical assembly is common in biological molecules
such as peptides and oligonucleotides and occurs in both
solution phase and solid state. Solid state supramolecular
chemistry is a contemporary topic and studies on organic
solid state supramolecular structures are actively pursued.13–20
Formation of an enantiopure helical supramolecular solid
state structure from a small achiral molecule is a very intrigu-
ing phenomenon. Formation of chiral crystals from small
achiral organic molecules is a challenge in crystal engineer-
ing and the outcome is still often unpredictable.21–25 Recently
Hu and Cao have reported generation of chiral crystals from
the molecular chirality in the solid state of otherwise achiral
1-aryl-1H-1,2,3-triazoles, the effect of hydroxyl and carboxyl
groups on the helical hydrogen bond synthon to form a
supramolecular hydrogen bond network and, finally, the role
of the position of hydroxyl and carboxyl groups in the forma-
tion of chiral or racemic crystals. An attempt is made to
correlate the structural features of six 1-aryl-1H-1,2,3-triazoles
to the chirality of the crystals and the formation of either
enantiopure or racemic helical hydrogen bonded networks.
Results and discussion
The structures of the triazole derivatives, namely
2-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)benzoic acid (1),
2-(4-phenyl-1H-1,2,3-triazol-1-yl)benzoic
acid
(2),
1-(2-carboxyphenyl)-1H-1,2,3-triazole-4-carboxylic acid (3),
1-(2-hydroxyphenyl)-1H-1,2,3-triazole-4-carboxylic acid (4),
2-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)phenol
(5)
and
4-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)benzoic acid (6),
along with their structures in the crystals with contact points
for non-covalent interactions, are shown in Fig. 1.
There are several reasons why these 1-aryltriazole derivatives
(1–6) (Fig. 1) are chosen for this study. These are as follows: (a)
the triazole ring is endowed with a hydrogen bond donor
(acidic C–H bond) and hydrogen bond acceptors (N atoms) that
can promote
a hydrogen bond network, (b) the ortho
substituted aryl ring and the triazole ring are expected to be
twisted that would render chirality in the solid state, (c) the
carboxylic acid and hydroxyl groups endow the structures with
multiple hydrogen bond contacts and hence would enable an
extended hydrogen bond network facilitating the formation of
supramolecular structures in the solid state. Derivatives 1, 2
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036,
India. E-mail: sanka@iitm.ac.in; Fax: +91 44 2257 0545; Tel: +91 44 2257 4210
† CCDC 924856–924858, 936289–936290, 936843. For crystallographic data in
CIF or other electronic format see DOI: 10.1039/c4ce00738g
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Scheme
1
Synthesis of phenyltriazole derivatives 1–6. Reaction
conditions: (A) toluene, 90 °C, 12 h; (B) CuSO4·5H2O, sodium ascorbate,
t-BuOH/H2O (1 : 1, v/v), rt, 48 h; (C) CuI, DMSO/H2O (9 : 1, v/v), rt, 24 h;
(D) CuSO4·5H2O, sodium ascorbate, PEG-600, rt, 48 h.
observed in the chiral crystals of organic molecules.27 The
dihedral angle between the N-aryl plane and the triazole
plane is 72.75°. The carboxyl acid group of one molecule is
doubly hydrogen bonded (O1 and O2 and H10) to the
triazole nitrogen and the hydroxyl group (N3, O3 and H20) of
another molecule that is related through 21 screw translation
parallel to the b-axis (Fig. 1A). Such extensive intermolecular
hydrogen bonding among molecules that are related through
21 screw translation parallel to the b-axis forms a helical
hydrogen bond synthon with the pitch of the helix as the
b-axis (9.6714 Å) itself (Fig. 2B and C). The bond lengths and
angles are O1–O3 = 2.830 Å, O1–H20 = 1.958 Å, O1–H20–O3 =
176.60°, O2–N3 = 2.659 Å, N3–H10 = 1.791 Å, O2–H10–N3 =
169.50°. In addition, there are C–H⋯O (H2 and O3, O3–C2 =
3.387 Å, O3–H2 = 2.511 Å, C2–H2–O3 = 157.14°) hydrogen
bonds between molecules that are related through 21 screw
axis parallel to the b-axis and C–H⋯N (H8 and N2, N2–C8 =
3.432 Å, N2–H8 = 2.603 Å, C8–H8–N2 = 148.76°) hydrogen
bonds between molecules that are related through 21 screw
axis parallel to the c-axis. These intermolecular hydrogen
bonding interactions are shown in Fig. 2A. Although absolute
configuration of the HTA molecule in the crystal is not deter-
mined, all of the four molecules in the unit cell have the
same absolute configuration. Hence, the crystal is chiral.
Fig. 1 Chemical structures of 1-aryl-1H-triazole derivatives (1–6) (left)
and their structures in the crystal (right) with multiple contact points
for non-covalent interactions in red.
and 3 were synthesized by the cycloaddition reaction of
2-azidobenzoic acid to propargyl alcohol, phenylacetylene and
propiolic acid, respectively. Derivatives 4 and 5 were synthesized
by the cycloaddition reaction of 2-azidophenol to propargyl alco-
hol and propiolic acid, respectively. Derivative 6 was synthesized
by the cycloaddition of 4-azidobenzoic acid with propargyl
alcohol (Scheme 1).
All of these derivatives were thoroughly characterized by
spectroscopic methods. First, we briefly describe the crystal
structure of each of the derivatives and then discuss the crystal
engineering aspects, namely, the effect of twisted conformation,
position and orientation of the hydrogen bond donor/acceptor
groups on the formation of hydrogen bond synthons leading to
chiral crystals or otherwise.
Structure of 2
Carboxylic acid 2 also crystallized in the orthorhombic sys-
tem with the P212121 space group forming chiral crystals. The
dihedral angle between the N-aryl plane and the triazole
plane is 78.14°. The C-phenyl and the triazole rings are nearly
coplanar with a dihedral angle of only 7.8°. The carboxylic
acid and the triazole nitrogen are hydrogen bonded (O1, H10
and N1, O1–N1 = 2.732 Å, H10–N1 = 1.725 Å and O1–H10N1 =
165.36°) resulting in a helical hydrogen bond network propa-
gating along the b axis with the pitch of the helix as the b axis
(11.9294 Å) itself (Fig. 3A and B). In addition, adjacent helices
Structure of 1
Hydroxy acid 1 crystallized in the orthorhombic system with
the P212121 space group, the most common space group
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Fig. 2 (A) Hydrogen bonding among the molecules in the unit cell, (B)
the helical hydrogen bond synthon (view along c axis), (C) the helical
hydrogen bond synthon (view along b axis).
are connected through C–H⋯π interactions (C3–H8 = 2.815 Å,
C6–H13 = 2.86 Å, C10–H4 = 2.862 Å) (Fig. 3A and C). All of the
four molecules in the unit cell have the same absolute config-
uration. Hence, the crystal is chiral.
Fig. 3 (A) Hydrogen bonding among the molecules in the unit cell, (B)
the helical hydrogen bond network, (C) the inter helical C–H⋯π
network (view along a axis).
The O–H⋯N (N3, H10, O1) hydrogen bond is between the
carboxylic acid of the phenyl group (O1, H10) and the nitro-
gen (N3) of the triazole ring (N3–O1 = 2.781 Å, N3–H10 =
1.803 Å, O1–H10–N3 = 177.12°) (Fig. 4A). Molecules that are
inversion equivalents also form a O–H⋯N hydrogen bonded
helix of opposite handedness (say right-handed helix). These
two untwined helices of opposite chirality are connected to
each other at every turn (pitch of the helix) by centrosymmet-
ric dimeric O–H⋯O (O4, H20, O3) hydrogen bonds between
the carboxylic acid groups of the triazole rings (O3–O4 =
2.684 Å, O3–H20 = 1.671 Å, O4–H20–O3 = 173.48°) forming a
very interesting supramolecular 3D hydrogen bond network
(Fig. 4B and C).
Structure of 3
Diacid derivative 3 crystallized in the monoclinic system with
the P21/n space group. The dihedral angle between the aryl
plane and the triazole plane is 85.75°, the highest among
derivatives 1–6. The unit cell contained four molecules,
which are two pairs of enantiomers with respect to the inver-
sion center. Both the carboxylic acid groups in the molecule
have a syn orientation, and the dihedral angle between the
planes containing the carboxylic acid groups is 81.36°. The
molecules related through 21 screw translation parallel to
b-axis form a hydrogen bonded helix (say left-handed helix)
with the pitch of the helix as b-axis (9.3768 Å) itself (Fig. 4A).
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Fig. 5 (A) Helical hydrogen bond network in 4, (B) bridging through
the centrosymmetric hydrogen bonded dimer of adjacent helices (both
views along b-axis).
Structure of 5
Dihydroxy derivative (5) crystallized in the triclinic system
¯
with the P1 space group. The dihedral angle between the aryl
plane and the triazole plane is only 20.79°, the smallest
among the ortho substituted derivatives 1–5. Considering that
the phenolic hydroxyl group in 5 is smaller in size compared
to the carboxylic acid group in 1, 2 and 3, a smaller dihedral
angle might be justified for this derivative. However, in 4
which also contains an ortho hydroxy group, the dihedral
angle is 70.4°. This large difference in the dihedral angles
between 4 and 5 might be due to the differences in the
hydrogen bond mode. Formation of the centrosymmetric
hydrogen bond between the two hydroxyl groups in 5 might
be responsible for the relatively planar structure in
5
compared to the twisted structure in 4. The molecule and
its inversion equivalent are doubly hydrogen bonded through
O–H⋯O (O2 and H1, O1–O2 = 2.687 Å, O2–H1 = 1.869 Å,
O1–H1–O2 = 175.45°) bonds forming a centrosymmetric
dimeric structure (Fig. 6A). The bc diagonal translation equiv-
alents of the pair in the dimer are further doubly bonded
through O–H⋯N (N3 and H2A, N3–O2 = 2.836 Å, N3–H2A =
2.206 Å, N3–H2A–O2 = 168.97°) bonds resulting in a one
dimensional ribbon (Fig. 6C). The ribbons are further linked
through weak C–H⋯N (N2 and H5, N5–H5 = 2.705 Å) interac-
tions leading to a 3D hydrogen bond network (Fig. 6B). The
ribbons are also further networked by C–H⋯π (C4 and H8,
C4–H8 = 2.871 Å) interactions through the triazole ring hydro-
gen and π–π (C1 and C3) interactions through the phenyl rings
(Fig. 6A and D). The π–π interactions are through slipped
π stacking of the phenyl rings, and the vertical inter-planar
distance is 3.358 Å.
Fig. 4 (A) Helical hydrogen bonded network in 3, (B) centrosymmetric
bridging of two helices of opposite chirality through hydrogen
bonding between COOH groups of the triazole ring (view along a axis),
(C) centrosymmetric hydrogen bonding (bridging units of the helices)
of molecules in the asymmetric unit (view along a axis).
Structure of 4
Phenolic acid 4 crystallized in the monoclinic system with
the P21/c space group. The phenyl and triazole rings are twisted
with an angle of 70.4° and the carboxylic acid group, and the
triazole ring are nearly coplanar. The unit cell contained four
molecules, which are two pairs of enantiomers with respect to
the inversion center as in the case of 3. The carboxylic acid
group in the molecule has a syn orientation. In this case, molecules
that are related through the glide plane form a hydrogen
bonded helix along the c-axis (glide component 0, 0, 1/2) with
the pitch of the helix as c-axis itself (Fig. 5A). The hydrogen bond
is between the phenolic OH and the triazole nitrogen (O1, H10
and N3, O1–N3 = 2.804 Å, H10–N3 = 1.912 Å, O1–H10–N3 =
176.3°). The carboxylic acid group connects molecules related
through the inversion center to the adjacent helices of opposite
Structure of 6
¯
Hydroxyacid 6 crystallized in the triclinic system with the P1
space group. In 6 the carboxylic acid group is present at the
para position of the phenyl ring. As a result, the phenyl ring,
the triazole ring and the carboxylic acid groups are nearly
chirality by
a centrosymmetric hydrogen bonded dimer
(Fig. 5B) as in the case of 3.
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Fig. 7 (A) Centrosymmetric hydrogen bond network in 6, (B) the
hydrogen bond mediated layered structure of 6 in the crystal.
(x, y, z) is centrosymmetrically hydrogen bonded through
O–H⋯O bonds to its neighbor (−x, 1 − y, 1 − z), through
O–H⋯N bonds to another neighbor (−x, 2 − y, −z) and
through C–H⋯O bonds to yet another neighbor (1 − x, 1 − y, −z)
(Fig. 7A). The hydrogen bond distances are O1–H2 = 1.808 Å,
O1–O2 = 2.62 Å, N3–H10 = 1.778 Å, and O3–H8 = 2.261 Å and
the angle is O1–H2–O2 = 170.55°, which are well within the
range. The inter layer distance is 3.357 Å, which is well within
the π stacking distance (Fig. 7B).
Correlation of crystal structures to the conformation of 1–6 in
the solid state
The crystallographic data of compounds 1–6 are presented in
Table 1. From the analysis of the crystal structures of 1–6 the
following inferences can be clearly made. In all of the cases,
the triazole hydrogen acted as a hydrogen bond donor and
the triazole nitrogen acted as a hydrogen bond acceptor for
the formation of hydrogen bonds. The dihedral (twist) angle
between the N-phenyl and the triazole rings is crucial for the
formation of helical hydrogen bonded structures. Com-
pounds 1–4 with twist angles in the range of 70 to 85° formed
helical hydrogen bonded solid state supramolecular struc-
tures due to the relative orientation of the hydrogen bond
donor group (COOH or phenolic OH) and the hydrogen bond
acceptor (triazole nitrogen). In the case of derivatives 5 and 6
the twist angles were only 20.79° and 6.27°, respectively,
which were not sufficient for the formation of a helical
hydrogen bond network. They are sufficiently planar to form
only layered structures and hence they both formed only
hydrogen bonded layered structures in the crystal. In both
cases, the layers were within the π stacking distance (3.35 Å).
In derivative 6 the bulky COOH group is deliberately placed
at the para position to test the hypothesis that the
phenyltriazoles must have a twisted conformation to exhibit
helical hydrogen bonded structures. Comparison of struc-
tures of 1 and 6 (ortho vs. para) clearly reveals that indeed it
is the COOH group placed at the ortho position of the phenyl
ring on 1 that results in twisted conformation. The twisted
Fig. 6 (A) Various non-covalent intermolecular interactions in 5 in the
crystal forming a hydrogen bond network, (B) formation of a 1D ribbon
like structure through O–H⋯O and C–H⋯N hydrogen bond synthons,
(C) formation of a 1D ribbon like structure through O–H⋯O and
O–H⋯N hydrogen bond synthons, (D) inter linking of the ribbons
through π–π and C–H⋯N interactions to a 3D hydrogen bonded network.
coplanar. The twist between the phenyl ring and the triazole
ring is only 6.27°, the lowest among derivatives 1–6. The unit
cell contained two molecules that are related through an
inversion center. In this structure, one molecule is
centrosymmetrically doubly hydrogen bonded with each of
its neighbours (Fig. 7A) forming an interesting hydrogen
bonded supramolecular stepped-layered network. A molecule
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Table 1 Crystallographic data, data collection and refinement for 1–6
Parameter
1
2
3
4
5
6
Formula
Formula weight
Radiation
Wavelength
Crystal system
Space group
a/Å
b/Å
C10H9N3O3
219.20
Mo Kα
0.71073 Å
Orthorhombic
P212121
5.2611 (2)
9.6714 (4)
19.3615 (8)
90
C15H11N3O2
265.27
C10H7N3O4
233.19
Mo Kα
0.71073 Å
Monoclinic
P21/n
5.0172 (11)
9.3768 (19)
21.357 (4)
90
96.602 (10)
90
C9H7N3O3
205.18
Mo Kα
0.71073 Å
Monoclinic
P21/c
14.5117 (7)
5.1416 (2)
12.3092 (6)
90
107.607 (2)
90
C9H9N3O2
191.19
Mo Kα
C10H9N3O3
219.20
Mo Kα
Mo Kα
0.71073 Å
Orthorhombic
P212121
5.7364 (2)
11.9294 (5)
18.4660 (9)
90
0.71073 Å
Triclinic
0.71073 Å
Triclinic
¯
¯
P1
P1
6.9540 (3)
7.6099 (3)
8.6454 (3)
106.098 (2)
101.881 (2)
93.586 (2)
426.66 (3)
298 (2)
5.5178 (8)
6.7350 (10)
13.337 (2)
87.308 (6)
82.823 (6)
74.791 (6)
c/Å
α/°
β/°
90
90
90
90
γ/°
V/Å3
985.16 (7)
298 (2)
4
1263.66 (9)
298 (2)
4
998.1 (4)
298 (2)
4
875.41 (7)
298 (2)
4
T/K
Z
298 (2)
2
2
Reflections/unique
Rint
3807/1871
0.0146
0.112
5076/2639
0.0240
0.096
6029/1729
0.0382
0.124
5304/1521
0.0170
0.121
5888/2247
0.0184
0.109
4813/1568
0.0359
0.117
μ/mm−1
F(000)
456
552
480
424
200
228
θ range
2.10–28.40
1.067
0.0295
0.0745
0.0316
0.0767
2.03–27.28
1.043
0.0476
0.0852
0.0765
1.92–25.00
1.074
0.0546
0.1173
0.0316
2.95–25.00
0.907
0.0323
0.1036
0.0395
2.52–33.88
1.603
0.0401
0.1273
0.0316
3.08–25.00
1.178
0.0591
0.1584
0.0839
0.1933
Goodness of fit on F2
R1 and wR2
[I > 2σ(I)]
R1 and wR2 (all data)
0.0973
0.0767
0.1186
0.0767
conformation in turn results in the chirality of 1 in the solid
state. Indeed, it is the twisted conformation of the otherwise
achiral compounds 1–4 that makes them chiral in the solid
state. Another interesting observation is the role of the
carboxylic acid group when placed on the triazole ring to
form a centrosymmetric hydrogen bonded dimer. In all of
the examples (1–4 and 6) the COOH group is in the syn con-
formation. In both 3 and 4 the acid group on the triazole ring
is engaged in the formation of a centrosymmetric hydrogen
bonded dimer through O–H⋯O homosynthons. As a result of
the centrosymmetric hydrogen bonded dimer formation,
these derivatives crystallized as only racemic compounds in
spite of the fact that a helical hydrogen bonding motif is
present in these structures. In triazoles containing COOH
and OH groups, both homo and hetero hydrogen bond
synthons can be involved in the formation of the solid state
supramolecular structures. The interplay of homo and hetero
hydrogen bond synthons is clearly evident from the observed
solid state supramolecular hydrogen bond networks in 1–6.
The heterosynthon, namely O–H⋯N, is predominant in all of
the structures and is responsible for the supramolecular heli-
cal hydrogen bond network in the case of 1–4. In the case of
5 both the O–H⋯O homosynthon involving both the OH
groups and the O–H⋯N heterosynthon involving one of the
hydroxyl groups and the triazole nitrogen are involved in the
formation of two distinct centrosymmetric supramolecular
hydrogen bond networks. In the present investigation, all of
the helical motifs in the supramolecular structures of 1–4 are
due to the heterosynthon, namely the O–H⋯N hydrogen
bond, whereas the centrosymmetric motifs are due to both
homo- and hetero hydrogen bond synthons. The inferences
discussed above are pictorially depicted in Fig. 8.
Experimental
2-(4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl)benzoic acid (1)
Method A. 2-Azidobenzoic acid (360 mg, 2.20 mmol) and
propargyl alcohol (1.23 g, 22.0 mmol) were dissolved in
10 mL of toluene. The reaction mixture was stirred at room
temperature for 10 minutes and then heated at 90 °C for
12 h to give a white precipitate. The precipitate was filtered
and washed with water and
a dichloromethane–hexane
mixture (1 : 1 v/v). The product HTA was obtained as a white
powder. Recrystallization from a mixture of acetonitrile and
methanol (1 : 1 v/v) afforded colorless crystals of 1. Yield:
68%. mp 177 °C, IR (KBr)/cm−1 3420 (broad), 3135, 2958, 1675,
1603, 1470, 1356, 1301, 1018; 1H NMR δH (400 MHz, DMSO-d6)
8.33 (1H, s), 7.90 (1H, d, J = 8 Hz ), 7.74 (1H, t, J = 8 Hz),
Fig. 8 Correlation of structural features of the triazole derivatives to
the observed hydrogen bonded supramolecular structures in the
crystals.
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7.65 (1H, t, J = 8 Hz), 7.58 (1H, d, J = 8 Hz), 5.32 (1H, broad, s),
4.60 (2H, s); 13C NMR δC (100 MHz, DMSO-d6) 166.6, 147.9,
135.2, 132.2, 130.2, 129.6, 128.6, 126.1, 123.9, 54.8; HRMS
calcd. for C10H10N3O3 (M + H)+ 220.0722, found 220.0712.
(2H, s), 4.50 (broad, 1H, OH); 13C NMR δC (100 MHz, DMSO-d6)
165.5, 149.6, 144.0, 139.7, 131.7, 121.2, 119.9, 55.0; HRMS
calcd. for C10H10N3O3 (M + H)+ 220.0722, found 220.0716.
1-(2-Carboxyphenyl)-1H-1,2,3-triazole-4-carboxylic acid (3)
2-(4-Phenyl-1H-1,2,3-triazol-1-yl)benzoic acid (2)
Method C. Propiolic acid (170 mg, 2.44 mmol) was added
to a stirred mixture of copper iodide (23 mg, 0.122 mmol)
and 2-azidobenzoic acid (200 mg, 1.22 mmol) in DMSO : H2O
(4.5 mL : 0.5 mL). The reaction mixture was stirred at room
temperature for 24 h, during which the progress of the reac-
tion was monitored by TLC. The reaction mixture was poured
into 50 mL of water. The aqueous layer was extracted with
ethyl acetate (3 × 50 mL) and dried over anhydrous Na2SO4.
Solvent was removed under reduced pressure. The crude
product was washed with dichloromethane : hexane (1 : 1) to
remove the unreacted starting materials. Compound 3 was
obtained as a white powder. Recrystallization from a mixture
of benzene : methanol (1 : 4, v/v) afforded colorless crystals.
Yield: 71%. mp 178–180 °C, IR (KBr)/cm−1 3142, 2922, 1725,
1693, 1604, 1555, 1252, 1064; 1H NMR δH (400 MHz, DMSO-d6)
9.1 (1H, s), 7.99 (1H, d, J = 7.2 Hz), 7.65–7.81 (3H, m); 13C NMR
δC (100 MHz, DMSO-d6) 165.9, 161.6, 139.6, 135.0, 132.7, 130.7,
130.6, 130.4, 128.3, 127.1. HRMS calcd. for C10H8N3O4 (M + H)+
234.0515, found: 220.0506.
Method B. Phenylacetylene (624 mg, 6.12 mmol) was
added to a stirred mixture of copper sulphate (30 mg,
0.122 mmol), sodium ascorbate (60 mg, 0.306 mmol) and
2-azidobenzoic acid (500 mg, 3.06 mmol) in t-BuOH : H2O
(10 mL : 10 mL). The reaction mixture was stirred at room
temperature for 48 h, during which the progress of the reac-
tion was monitored by TLC. The reaction mixture was poured
into 50 mL of cold water upon which the product precipi-
tated. The precipitate was washed with water and hexane.
Phenyltriazole (2) was obtained as a pale yellow powder.
Recrystallization from dichloromethane : acetonitrile (1 : 1 v/v)
afforded colorless crystals. Yield: 80%. mp 216 °C, IR (KBr)/cm−1
3150, 3090, 1628, 1550, 1408, 1290, 1013; 1H NMR δH (400 MHz,
DMSO-d6) 8.81 (1H, s), 7.92 (3H, m), 7.62–7.74 (3H, m), 7.43
(2H, t, J = 8 Hz), 7.32 (1H, t, J = 8 Hz), 4.50 (broad, 1H, OH),
13C NMR δC (100 MHz, DMSO-d6) 165.9, 146.4, 135.5, 132.2,
130.6, 130.3, 128.7, 127.8, 126.3, 125.2, 122.6; HRMS calcd.
for C15H12N3O2 (M + H)+ 266.093, found 266.0941.
1-(2-Hydroxyphenyl)-1H-1,2,3-triazole-4-carboxylic acid (4)
2-(4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl)phenol (5)
Compound 4 was prepared by following method B as described
above for 2. Propiolic acid (338 mg, 4.83 mmol) was added to a
stirred mixture of copper sulphate (30 mg, 0.120 mmol),
sodium ascorbate (79 mg, 0.402 mmol) and 2-azidophenol
(544 mg, 4.029 mmol) in t-BuOH : H2O (10 mL : 10 mL). The
reaction mixture was stirred at room temperature for 48 h to
give 4 as a brown crystalline powder. Recrystallization from
acetone : dichloromethane: methanol (1 : 1 : 1, v/v) afforded
pale brown crystals. Yield: 75%. mp 169 °C, IR (KBr)/cm−1
3380 (broad), 3090, 1660, 1450, 1385, 1089; 1H NMR δH
(400 MHz, DMSO-d6) 10.76 (1H, broad, s), 8.93 (1H, s), 7.61
(1H, d, J = 8 Hz), 7.37 (1H, t, J = 8 Hz), 7.12 (1H, d, J = 8 Hz),
7.0 (1H, t, J = 8 Hz), 3.49 (1H, broad, s, OH); 13C NMR δC
(100 MHz, DMSO-d6) 161.7, 150.0, 139.5, 130.7, 130.2, 125.4,
124.0, 119.5, 117.0; HRMS calcd. for C9H8N3O3 (M + H)+
206.0566, found 206.0561.
Method D. A solution of 2-azidophenol (594 mg, 4.4 mmol)
in PEG-600 (10 mL) was degassed with nitrogen. Copper
sulphate (11 mg, 0.044 mmol) dissolved in 1 ml of water and
sodium ascorbate (87 mg, 0.44 mmol) dissolved in 1 ml of
water were added to the reaction mixture. Under a nitrogen
atmosphere, propargyl alcohol (492 mg, 8.8 mmol) was added
dropwise to the reaction mixture. The reaction mixture was
stirred at room temperature for 48 h and then it was poured
into 100 mL of water. The aqueous layer was extracted with
ethyl acetate (3 × 50 mL) and dried over anhydrous Na2SO4.
Solvent was removed under reduced pressure. The crude
product was washed with ethyl acetate and hexane (1 : 9, v/v)
to remove the unreacted starting materials. Triazole 5 was
obtained as a brown solid. Recrystallization from a mixture of
ethyl acetate : methanol (1 : 1, v/v) afforded pale brown crystals.
Yield: 65%. mp 140 °C, IR (KBr)/cm−1 3169 (broad), 3110
1
(broad), 2950, 1601, 1515, 1474, 1371, 1230, 1008; H NMR δH
4-(4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl)benzoic acid (6)
(400 MHz, DMSO-d6) 10.24 (1H, broad, s), 8.30 (1H, s), 7.67
(1H, s), 7.26 (1H, s), 7.11 (1H, s), 6.95 (1H, s), 5.20 (1H, broad s),
4.75 (2H, s); 13C NMR δC (100 MHz, DMSO-d6) 148.1, 128.4,
123.6, 123.2, 118.5, 116.2, 54.6. HRMS calcd. for C9H10N3O2
(M + H)+ 192.0773, found: 192.0771.
Compound 6 was prepared by following method B as described
above for 2. Propargyl alcohol (355 mg, 6.13 mmol) was added
to a stirred mixture of copper sulphate (15 mg, 0.06 mmol),
sodium ascorbate (60 mg, 0.306 mmol) and 4-azidobenzoic
acid (500 mg, 3.06 mmol) in t-BuOH : H2O (10 mL: 10 mL). The
reaction mixture was stirred at room temperature for 48 h to Crystallographic data collection and
give
6 as a pale yellow powder. Recrystallization from
refinement
dichloromethane: acetonitrile : methanol (1: 1 : 1, v/v) afforded
colorless crystals. Yield: 85%. mp 252 °C, IR (KBr)/cm−1 3400,
3100, 2890, 2960, 1680, 1506, 1306, 1012; 1H NMR δH (400 MHz,
DMSO-d6) 8.73 (1H, s), 8.06 (4H, AB quartet, J = 7 Hz), 4.63
All crystals were stable at room temperature and data were
obtained at 298 K. The intensity data were collected using a
Bruker AXS (Kappa Apex II) diffractometer equipped with
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graphite monochromated Mo Kα radiation. The data were
collected for θ up to 25° for Mo Kα radiation, and ω and φ
scans were employed for data collection. The frame width for
ω was set to 0.5° for data collection. The frames were inte-
grated and data were reduced for Lorentz and polarization
correction using SAINT-NT Plus.28 The multi-scan absorption
correction29 was applied to the data. All structures were
solved using SIR-92 (ref. 30) and refined using SHELXL-97.31
The molecular and packing diagrams were drawn using
ORTEP-32 (ref. 32) and Mercury 2.4.33 The non-hydrogen
atoms were refined with anisotropic displacement parameters.
All hydrogens could be located in the difference Fourier map.
However, hydrogen atoms bonded to carbons were fixed at
chemically meaningful positions and were allowed to ride
with the parent atom during the refinement. All hydrogen
bond donor acceptor distances are well within the hydrogen
bonding interaction range.
Notes and references
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Conclusions
The crystal structures of six structurally related phenyltriazoles
endowed with hydrogen bond donor and acceptor groups have
been analyzed for the formation of a hydrogen bonded supra-
molecular network in the solid state. The triazole derivatives
are achiral in nature. The twisted molecular conformation of
derivatives 1–4 makes them chiral in the solid state, and the
relative orientation of the hydrogen bond donor and acceptor
groups enables the formation of a helical hydrogen bond
network. Whether they would form chiral crystals or not is
decided by the presence or absence of a carboxylic acid group
on the triazole ring. The carboxylic acid group in derivatives
3 and 4 showed preponderance in forming centrosymmetric
hydrogen bonded dimers which resulted in the formation
of achiral (racemic compound) crystals, whereas derivatives
1 and 2 formed chiral (racemic conglomerate) crystals.
Derivatives with a smaller twist between the phenyl and the
triazole rings did not form
a
helical hydrogen bond
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para position had the lowest dihedral angle (6.27°), and
the structure of this derivative in comparison with that of
1 supports our hypothesis that twisted chiral conformation is
essential for the formation of a helical hydrogen bond
network and a chiral crystal.
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Acknowledgements
We thank the Department of Chemistry, IIT Madras, for the
infrastructure and Dr. Babu Varghese for useful discussions.
Financial support from CSIR, New Delhi (fellowship to BS
and research grant to SS), and DST, New Delhi (research
grant to SS), is gratefully acknowledged.
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6106 | CrystEngComm, 2014, 16, 6098–6106
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