Crystal and molecular structures of two triazole derivatives: 4-Cyclopropyl-4,5-dihydro-1H-1,2,3-triazole and Methyl 1-benzyl-1H-1,2,3- triazole-4-carboxylate

Article abstract of DOI:10.1007/s10870-010-9809-4

The molecule in 4-cyclopropyl-4,5-dihydro-1H-1,2,3-triazole (I) is disposed about a mirror plane with the triazole ring lying in the plane and being orthogonal to the cyclopropyl ring. Considerable delocalization of π-electron density within the triazole

Full text of DOI:10.1007/s10870-010-9809-4

J Chem Crystallogr (2010) 40:1137–1141
DOI 10.1007/s10870-010-9809-4
ORIGINAL PAPER
Crystal and Molecular Structures of Two Triazole Derivatives:
4
1
-Cyclopropyl-4,5-dihydro-1H-1,2,3-triazole and Methyl 1-benzyl-
H-1,2,3-triazole-4-carboxylate
N u´ bia Boechat
Ane L. S. Camilo
Edward R. T. Tiekink
•
Maria de L. G. Ferreira
•
•
Monica M. Bastos
James L. Wardell
•
Solange M. S. V. Wardell
•
•
Received: 4 December 2009 / Accepted: 20 May 2010 / Published online: 5 June 2010
Ó Springer Science+Business Media, LLC 2010
Abstract The molecule in 4-cyclopropyl-4,5-dihydro-
H-1,2,3-triazole (I) is disposed about a mirror plane with
crystallizes in the orthorhombic space group Pnma with
˚
˚
a = 5.6470(2) A, b = 7.3359(4) A, c = 13.4404(7) A, and
˚
1
the triazole ring lying in the plane and being orthogonal to
the cyclopropyl ring. Considerable delocalization of
p-electron density within the triazole ring is indicated by
the pattern of bond distances in (I). The molecule of methyl
Z = 4. Compound (II) crystallizes in the monoclinic space
˚
group P2 /c with a = 12.1314(5) A, b = 5.5951(2) A,
˚
1
˚
c = 16.4339(7) A, b = 111.269(2)°, and Z = 4.
1-benzyl-1H-1,2,3-triazole-4-carboxylate (II) adopts a
curved shape with the dihedral angle formed between the
Keywords Triazole Á Hydrogen bonding Á Conformation
triazole and benzene rings being 63.23(8)°. By contrast to
I), localization of p-electron density within the triazole
(
Introduction
ring in (II) is indicated. Both (I), via N–HÁÁÁN hydrogen
bonding, and (II), via C–HÁÁÁO and C–HÁÁÁN interactions,
associate in the solid state to form supramolecular chains.
In (I), the chain is a zigzag with a flat topology, whereas in
The azide-alkyne Huisgen cycloaddition is a 1,3-dipolar
cycloaddition between an azide and a terminal or internal
alkyne to give a 1,2,3-triazole [1]. Exploiting the so-called
‘‘Click chemistry’’, the Cu(I)-catalyzed [3 ? 2] cycload-
dition of terminal alkynes and azides forming 1,2,3-tria-
zoles, has proven to be an efficient and innovative route to
bioactive compounds as it is selective and devoid of side
reactions, for examples see references [2–6]. Our interests
in 1,2,3-triazoles and their biological activities, particularly
as anti-leishmanial agents [7] and tuberculosis inhibitors
(
II) the linear chain has a curved topology. Compound (I)
N. Boechat Á M. de L. G. Ferreira Á M. M. Bastos Á
A. L. S. Camilo
Departamento de Pesquisa e Desenvolvimento de F a´ rmacos,
Instituto de Tecnologia em F a´ rmacos, Farmanguinhos/
FIOCRUZ, Rua Sizenando Nabuco, 100, Manguinhos,
Rio de Janeiro 21041-250, Brazil
[
8] has led to the synthesis of the title compounds
4
1
-cyclopropyl-4,5-dihydro-1H-1,2,3-triazole (I) and methyl
-benzyl-1H-1,2,3-triazole-4-carboxylate (II); see Scheme 1
S. M. S. V. Wardell
CHEMSOL, 1 Harcourt Road, Aberdeen AB15 5NY,
Scotland, UK
e-mail: solangewardell@yahoo.co.uk
for chemical structures. Herein, their full and unambiguous
characterization by X-ray crystallography are reported
and their structures compared with related 1,2,3-triazole
derivatives.
J. L. Wardell
Centro de Desenvolvimento Tecnol o´ gico em Sa u´ de,
(
CDTS), Funda c¸ a˜ o Oswaldo, Cruz (FIOCRUZ),
Casa Amarela, Campus de Manguinhos, Av. Brasil 4365,
Rio de Janeiro 21040-900, Brazil
Experimental
E. R. T. Tiekink (&)
Reagents were commercial compounds and were used as
received. Melting points were determined on a Buchi
apparatus and are uncorrected. NMR spectra were recorded
Department of Chemistry, University of Malaya,
Kuala Lumpur 50603, Malaysia
e-mail: Edward.Tiekink@gmail.com
123

1
138
J Chem Crystallogr (2010) 40:1137–1141
1
3
N
N
C NMR (100.0 MHz, DMSO-d ): d 160.5 (CO), 138.6
6
(
Cquart, triazole), 135.3, 129.1, 128.7, 128.2 (all phenyl),
HN
1
27.9 (CH, triazole), 53.0(CH ), 51.6 (Me) ppm.
2
The sample used in the crystallography study was grown
(
I)
from EtOH solution.
X-Ray Crystallography
N
N
O
Intensity data for colorless blocks were collected at 120 K
on a Enraf–Nonius KappaCCD area detector fitted with Mo
N
Ka radiation generated by a FR591 rotating anode
(k = 0.71073 A). The data sets were reduced using stan-
dard methods [12]. The structures were solved by direct
O
(II)
˚
Scheme 1 Chemical structures for 4-cyclopropyl-4,5-dihydro-1H-
,2,3-triazole (I) and methyl 1-benzyl-1H-1,2,3-triazole-4-carboxyl-
ate (II)
1
methods with SHELXS97 [13] and refined by a full-matrix
2
least-squares procedure on F using SHELXL97 [13] with
anisotropic displacement parameters for non-hydrogen
on Bruker Avance 400 spectrometer with Me Si as the
4
atoms and a weighting scheme of the form w = 1/
2
reference.
2
2
2
2
[
r (F ) ? (aP) ? bP] where P = (F ? 2F )/3. All
o
o
c
hydrogen atoms were located in a difference Fourier map,
including the N–H hydrogen atom in (I), but were included
in the final refinement in their calculated positions. A
rotating group model was used for the methyl groups.
Crystal data and refinement details are given in Table 1.
All figures were drawn with DIAMOND [14]. Data
manipulation and interpretation were accomplished using
WinGX [15] and PLATON [16].
Synthesis
4
-Cyclopropyl-4,5-dihydro-1H-1,2,3-triazole (I)
A mixture of 1-benzyl-4-cyclopropyl-4,5-dihydro-1H-1,2,3-
triazole (3.51 g, 18.6 mmol), palladium hydroxide on acti-
vated charcoal (14.2 mmol) and aqueous MeOH (1:1,
1
00 mL) was hydrogenated at room temperature for 72 h
under 3 bar hydrogen pressure. The reaction mixture was
filtered using Celite, and extracted with CHCl . The chlo-
3
Results and Discussion
roform extract was washed with water, dried over sodium
sulfate and rotary evaporated to leave a solid residue. The
solid was recrystallised from EtOH, m.p. 54.8–55.2 °C,
Compound II was prepared by a slight modification to the
1
3
method previously published [11]. Only the C NMR
1
spectrum of II is reported herein, as the H NMR spectrum
yield 76%.
1
H NMR (400.00 MHz, DMSO-d ): d 14.63 (s, 1H,
has been previously published [11]. Compound I, obtained
by the dehydrogenation of 1-benzyl-4-cyclopropyl-4,5-dihy-
dro-1H-1,2,3-triazole using palladium hydroxide catalysis, is
6
NH), 7.55 (s, 1H, CH, triazole), 1.98–1.92 (m, 1H, CH,
cyclopropyl), 0.91–0.90 (m, 2H) and 0.74–0.67 (m, 2H,
1
13
CH , cyclopropyl] ppm.
2
a new compound. Both the H and C NMR spectra of I
are reported. The different signals arising from the CH2
groups of the cyclopropyl substituent in the NMR spectra
of I suggests that rotation of the cyclopropyl group is
hindered about the attached triazole ring in DMSO solu-
tion. Significant differences are observed in the NMR
chemical shift values of the Cquart and CH atoms of the
triazole unit in the two compounds, I and II. This must
arise from differences in the electronic delocalisation
within the triazole ring and thus parallels the crystallo-
graphic findings, discussed below.
13
C NMR (100.0 MHz, DMSO-d ): d 149.1 (Cquart, tri-
6
azole), 130.3 (CH, cyclopropyl), 128.6 (CH, triazole), 7.79
(
CH , cyclopropyl), 6.31 (CH , cyclopropyl) ppm.
2
2
Methyl 1-benzyl-1H-1,2,3-triazole-4-carboxylate (II)
A reaction mixture of benzyl azide (2.71 g, 22.5 mmol),
prepared from benzyl chloride and sodium azide in MeCN/
DMF [9], and MeO CC:CH (2.80 g, 33.7 mmol), sodium
2
ascorbate (3.50 g, 2.25 mmol) and copper(II) sulfate
(
4.5 g, 0.225 mmol) in aqueous tert-butanol (1:1, 40 mL)
was stirred at room temperature for 24 h [10]. After addi-
tion of water (50 mL), the reaction mixture was cooled to
The molecular structure of 4-cyclopropyl-4,5-dihydro-
1H-1,2,3-triazole, (I), is illustrated in Fig. 1 and selected
geometric parameters are collected in Table 2. The mole-
cule has crystallographically imposed mirror symmetry
such that the triazole ring and cyclopropyl-C3 atom lie in
the plane with the wing-C4 atoms of the cyclopropyl group
0
1
°C and the precipitate was collected, yield 86%, m.p.
1
04.1–106.6 °C, lit. m.p 104–7 °C [11]. The H NMR
spectrum has been reported previously [11].
1
23

J Chem Crystallogr (2010) 40:1137–1141
1139
Table 1 Crystal data and refinement details for (I) and (II)
(
I)
(II)
Empirical formula
Formula weight
Crystal habit, color
Crystal system
C
5
H
7
N
3
11 11 3 2
C H N O
109.14
217.23
Block, colorless
Orthorhombic
Pnma
Block, colorless
Monoclinic
Space Group
1
P2 /c
˚
a (A)
5.6470(2)
7.3359(4)
13.4404(7)
90
12.1314(5)
5.5951(2)
16.4339(7)
111.269(2)
1039.50(7)
4
˚
b (A)
Fig. 1 Molecular structure of 4-cyclopropyl-4,5-dihydro-1H-1,2,3-
triazole (I). Displacement ellipsoids are drawn at the 50% probability
level. The molecule has crystallographic mirror symmetry with
symmetry operation i: x, 1/2 - y, z
˚
c (A)
b (°)
Volume (A )
3
˚
556.78(5)
4
Z
Density (calculated,
g cm
1.302
1.388
˚
Table 2 Selected bond distances and angles (A, °) within the triazole
ring in (I) and (II)
-3
)
Absorption coefficient 0.087
-
0.099
456
1
)
Parameter
(I)
1.333(3)
(II)
(
mm
F(000)
232
N1–N2
N2–N3
N1–C
1.3548(16)
1.3119(16)
1.3429(17)
1.3626(17)
1.3731(19)
107.24(11)
111.06(11)
108.44(11)
Crystal size (mm)
0.04 9 0.16 9 0.24 0.10 9 0.12 9 0.42
1.329(2)
1.343(3)
h range for data
collection (°)
Reflections collected
3.2–27.5
3.6–27.5
N3–C
1.360(3)
8466
11646
2383
0.050
1906
C–C
1.379(3)
Independent reflections 684
N1–N2–N3
N2–N1–C
N2–N3–C
108.91(18)
109.95(18)
107.29(18)
R
int
0.075
593
Reflections with
I C 2r(I)
Number of parameters 46
2
147
Goodness-of-fit on F
1.12
1.05
of the geometric parameters within the triazole ring in each
of these structures shows a clear disparity in the N–N bond
distances, indicating a diminished level of delocalization of
p-electron density in these rings compared to the situation in
a, b for weighting
scheme
0.053, 0.404
0.041, 0.341
Final R indices
[
R1 = 0.054,
wR2 = 0.132
R1 = 0.042,
wR2 = 0.094
I C 2r(I)]
(
I). Notably, in each of the literature structures, there is a
R indices [all data]
R1 = 0.062,
wR2 = 0.137
R1 = 0.056,
wR2 = 0.102
formal double bond connected to the a-carbon atom of the
C1-substituent suggesting that electronic effects are
responsible for the observed differences.
Largest difference peak 0.33, -0.30
-
0.20, -0.24
3
)
˚
and hole (A
CCDC deposition no.
756636
756637
The crystal structure is dominated by N–HÁÁÁN hydrogen
bonds, Table 3, that lead to the formation of a supramo-
lecular 1-D chain along the a-axis through a sequence of
{N–HÁÁÁN} interactions. These interactions involve the N2
atom which is directly adjacent to the amine-N1 so that the
topology of the chain is a zigzag, Fig. 2; overall, the chain
is flat as the majority of the atoms lie on the mirror plane.
Within the chain, C–HÁÁÁN interactions, Table 3, involving
the N3 atom, otherwise not engaged in hydrogen bonding,
provide additional stability to the chain and closes nine-
related to each other across the mirror. This arrangement
ensures that the five- and three-membered rings are orthog-
onal. The cyclopropyl group occupies a position syn to the
formal azo, N2 = N3, bond. The pattern of N–N bond dis-
tances within the triazole ring, i.e. the experimental equiv-
alence of the N1–N2 and N2–N3 bond distances, indicate
significant delocalization of p-electron density over these
atoms. The remaining distances within the ring suggest that
the delocalization extends throughout the entire ring,
Table 1. There are only two other crystal structures in the
crystallographic literature [17] featuring the basic frame-
work of (I), namely methyl 1H-1,2,3-triazole-4-carboxylate
membered {ÁÁÁHNCHÁÁÁN ÁÁÁHNNÁÁÁ} synthons.
2
The molecular structure of methyl 1-benzyl-1H-1,2,3-
triazole-4-carboxylate, (II), is shown in Fig. 3 and selected
geometric parameters are included in Table 2. Although
not crystallographically imposed, the five atoms compris-
ing the triazole ring are co-planar with maximum devia-
[
18] and 4,4,5,5-tetramethyl-2-(1H-1,2,3-triazol-4-yl)-4,5-
˚
tions of ?0.004(1) and -0.004(1) A for the N1 and N2
dihydro-1H-imidazole-3-oxide-1-oxyl [19]. An evaluation
123

1
140
J Chem Crystallogr (2010) 40:1137–1141
Symmetry operation
˚
Table 3 Hydrogen bonding parameters (A–HÁÁÁB; A, °) for (I) and (II)
A
H
B
HÁÁÁB
AÁÁÁB
A–HÁÁÁB
(I)
N1
C2
H1n
H2
N2
N3
2.00
2.55
2.871(3)
3.427(3)
173
153
-1/2 ? x, 1/2 - y, 1 1/2 - z
-1 ? x, y, z
(II)
C1
C4
C5
C5
C10
H1b
H4
O1
2.47
2.60
2.53
2.67
2.97
3.281(2)
3.3969(16)
3.519(2)
140
141
175
128
132
x, 1 ? y, z
N3
x, -1 ? y, z
H5b
H5b
H10
N2
x, -1 ? y, z
N2
3.3617(19)
3.6752(17)
1 - x, 2 - y, -z
2 - x, -1/2 ? y, 1/2 - z
a
Cg(1)
a
Cg(1) is the ring centroid of five-membered ring: N1–N3, C3, C4
Fig. 3 Molecular structure of methyl 1-benzyl-1H-1,2,3-triazole-4-
carboxylate (II). Displacement ellipsoids are drawn at the 50%
probability level
˚
Table 2, match those in the literature with N1–C (1.344 A)
˚
being systematically shorter than N3–C (1.364 A).
Fig. 2 Detail of the supramolecular association mediated by N–HÁÁÁN
hydrogen bonding (blue dashed lines) reinforced by C–HÁÁÁN contacts
In the absence of formal hydrogen atom donors and
acceptors, the crystal packing in (II) is dominated by non-
traditional contacts involving C–H as the donor [20, 21].
The presence of C–HÁÁÁO contacts, reinforced by C–HÁÁÁN
contacts, lead to the formation of supramolecular chains
along the b-axis, Fig. 4 and Table 3. Owing to the curved
conformation of (II), the overall topology of the linear one-
dimensional chain, whereby the molecules are related by
(
green dashed lines) in the crystal structure of (I). The topology of the
resulting 1-D zigzag chain along the a-axis is planar. (Color figure
online)
atoms, respectively. However, the ester group is not
co-planar with this ring as quantified in the N3–C3–C2–O1
torsion angle of 168.48(13)°. The dihedral angle formed
between the triazole and benzene rings is 63.23(8)°, and
twisting between these groups is indicated by the N2–N1–
C5–C6 and N1–C5–C6–C7 torsion angles of 63.96(16) and
-
75.80(16)°, respectively. Globally, the molecule has a
distinctive curved conformation. The substitution of the
N1–H atom for a carbon has a profound influence upon the
geometric parameters within the triazole ring, Table 2. By
contrast to the situation operating in (I), the N2–N3 bond is
significantly shorter than the N1–N2 bond in (II). Notably,
the N–C and C–C bonds within the ring have not altered
significantly compared to (I). A search of the literature [17]
reveals 119 structures containing the substitution pattern
observed for the triazole framework in (II). The average
Fig. 4 Detail of the supramolecular association mediated by C–HÁÁÁO
(
orange dashed lines) and C–HÁÁÁN (blue dashed lines) contacts in the
˚
N1–N2 and N3–N3 bond distances are 1.353 and 1.310 A,
crystal structure of (II). The topology of the resulting linear 1-D chain
along the b-axis is curved. (Color figure online)
respectively. Similar trends in the N–C bond distances,
1
23

J Chem Crystallogr (2010) 40:1137–1141
1141
Acknowledgements The use of the EPSRC X-ray crystallographic
service at the University of Southampton, England and the valuable
assistance of the staff there is gratefully acknowledged. JLW
acknowledges support from CAPES (Brazil). NB acknowledges
support from FAPERJ (Brazil).
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123