Synthesis, crystal structure and biological activity of novel N-2-chlorophenyl-N′-2-[3-phenoxymethyl-4-phenyl-[1,2,4]triazole-5-thio]acetyl Hydrazone

Article abstract of DOI:10.14233/ajchem.2015.18778

N-2-Chlorophenyl-N′-2-[3-phenoxymethyl-4-phenyl[1,2,4]triazole-5-thio]acetyl hydrazone was synthesized by condensation reaction of 2-[3-phenoxymethyl-4-phenyl[1,2,4]triazole-5-thio]acethydrazide with 2-chlorobenzaldehyde under the conditions of microwave

Full text of DOI:10.14233/ajchem.2015.18778

Asian Journal of Chemistry; Vol. 27, No. 6 (2015), 2303-2306
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2015.18778
Synthesis, Crystal Structure and Biological Activity of Novel
N-2-Chlorophenyl-N'-2-[3-phenoxymethyl-4-phenyl-[1,2,4]triazole-5-thio]acetyl Hydrazone
2
2
2,*
BING HU1,2,*, XIAO-LI DU , YOU-MING ZHANG and TAI-BAO WEI
1College of Science, Gansu Agricultural University, Lanzhou 730070, Gansu Province, P.R. China
2College of Chemistry and Chemical Engineering, Key Laboratory of Polymer Materials of Gansu Province, Northwest Normal University,
Lanzhou 730070, Gansu Province, P.R. China
*Corresponding authors: E-mail: bb810410@aliyun.com, weitaibao@126.com
Received: 24 September 2014;
Accepted: 5 December 2014;
Published online: 17 March 2015;
AJC-17015
N-2-Chlorophenyl-N'-2-[3-phenoxymethyl-4-phenyl[1,2,4]triazole-5-thio]acetyl hydrazone was synthesized by condensation reaction
of 2-[3-phenoxymethyl-4-phenyl[1,2,4]triazole-5-thio]acethydrazide with 2-chlorobenzaldehyde under the conditions of microwave
irradiation. The structure of the title compound was conformed by IR, 1H NMR, 13C NMR, elemental analysis and single crystal X-ray
diffraction. In the crystal, the compound was assembled to one-dimensional chain-like supramolecular by three intermolecular hydrogen
bonds. The promoting effects of the compound on rape growth was also tested preliminarily.
Keywords: Microwave synthesis, Hydrazone, Crystal structure, Biological activity.
digital FTS-3000 infrared spectrometer (KBr pellet). 1H NMR
INTRODUCTION
and 13C NMR spectra were determined as DMSO-d6 solutions
In recent years, a number of hydrazone derivatives having
using a varian mercury plus-400 MHz spectrometer. Elemental
been claimed to possess a wide range of biological activities,
analyses were determined using PE-2400 C H N elemental
such as antibacterial1, antifungal2, antimalarial3 and antitumor4.
analyzer. Microwave irradiations were carried out in a Galanz
In addition, owning to the strong coordination ability, hydrazone
domestic microwave oven in which a hole was made in the
derivatives are extensively utilized as the collector for some
roof of the oven to permit a condenser to be fitted to the flask
transition metals5. Recently, these compounds have attracted
undergoing irradiation. In periods of irradiation, precautions
considerable attention for their potential uses as in supramole-
were taken to avoid exposure to experimentalists.
cular chemistry because of their characteristic behaviours based
All commercially available products were used without
on strong hydrogen-bond donors. In fact, the biological activity
and the coordination ability of these kinds of compounds are
closed related to their structure. Moreover, it has become an
important means to study the supramolecular compounds from
further purification; Phenoxyacetyl hydrazine (2), 1-phenoxy-
acetyl-4-phenylamino thiocarbamide (3) and 2-[3-phenoxy-
methyl-4-phenyl-1,2,4-triazole]-5-thione (4) were prepared
according to literature procedures10-13
.
the crystallography view6-8. In view of this and as a part of our
research, we synthesized N-2-chloro-phenyl-N'-2-[3-phenoxy-
methyl-4-phenyl[1,2,4]triazole-5-thio]acetyl hydrazone and
studied the crystal structure which indicated that the compound
was assembled to one-dimensional chain-like supramolecular.
In addition, the preliminary biological activity tests showed
that the title compound remarkably enhanced the root elongation
of rape seedings, moreover, it possesed antibacterial activity
against bacillus subtilis.
2-[3-Phenoxymethyl-4-phenyl[1,2,4]triazole-5-thio]-
ethyl acetate (5): A mixture of the 2-[3-phenoxymethyl-4-
phenyl-1,2,4-triazole]-5-thione (20 mmol), ethyl chloroacetate
(22 mmol) and anhydrous potassium carbonate (25 mmol) in
acetone was mixtured, The solution was heated under reflux on
a oil-bath for 8 h. Then the mixture was filtered off, the filtrate
was evaporated and recrystallized from EtOH-H2O.
2-[3-Phenoxymethyl-4-phenyl-[1,2,4]-triazole-5-thio]-
acethydrazide (6): 2-[3-Phenoxymethyl-4-phenyl-1,2,4-
triazole-5-thio]ethyl acetate (5) (20 mmol) was added to a solution
of ethanol (30 mL) and in 85 % hydrazine hydrate (20 mmol),
The solution was heated under reflux on a oil-bath for 10 h. The
mixture was filtered off and recrystallized from EtOH-DMF-H2O.
EXPERIMENTAL
Melting points were recorded using a digital model X-4
apparatus and are uncorrected. IR spectra were recorded on a

2304 Hu et al.
Asian J. Chem.
N-2-chlorophenyl-N'-2-[3-phenoxymethyl-4-phenyl-
selected and mounted on the top of a glass fiber in a random
orientation. All X-ray crystallographic data were collected on
a Bruker SMARTAPEX II CCD diffractometer equipped with
a graphite-monochromatized MoKα radiation (λ = 0.71073
Å) radiation using ϕ/ω scan technique at 293 K. The structures
were solved by a direct method and refined by a full-matrix
least-squares procedure based on F2 using the SHELXTL
program package.The molecular structure of compound 7 is
shown in Fig. 1 and a summary of the crystallographic data
and refinement parameters are given in Table-1.
Bioactivity assay: The title compound was investigated
for plant growth regulation activity. Method of plate culture
was adopted and the compound solutions were prepared in
the concentration of 100, 10, 1, 0.1, 0.01 and 0.001 ppm,
whereafter, rape seeds were cultured in a 10 cm petri dish
with 10 mL of different solution and a circular fiter paper.
Then, the roots were allowed to grow at room temperature, the
roots length was gained after 4 days, the percentage plant growth
activity was calculated according to the following equation:
[1,2,4]triazole-5-thio]acetyl hydrazone (7): 2-[3-Phenoxy-
methyl-4-phenyl-1,2,4-triazole-5-thio]acethydrazide (7)(2 mmol),
2-chlorobenzaldehyde and DMF (6 mL) were placed in a dried
round-bottomed flask and the reaction mixture was subjected to
microwave irradiation (230 W) for 1 min periods up to a total of
5 min irradiation (400 W) again. The mixture was cooled to
room temperature and then recrystallization from EtOH-DMF.
The structure of the title compound has been elucidated by
spectral (IR, 1H NMR, 13C NMR) and elemental analysis data.
Compound 7: Yield: 70 %, m.p. 175-177 ºC. IR (KBr,
ν
max, cm-1): ν = 3228 (N-H), 3066 (Ar-H), 1699 (C=O), 1597
(C=N), 1494 (C=N-N), 1214 (C-O-C), 690 (C-S-C). 1H NMR
(DMSO-d6): δH = 12.01 (s, 1H, NH), 11.85 (s, 1H, NH), 8.39
(s, 1H, N=CH), 8.59 (s, 1H, N=CH), 4.09 (s, 2H, SCH2C=O),
4.51 (s, 2H, SCH2C=O), 5.07 (s, 2H, OCH2), 6.84-7.95 (m,
14H, Ar-H); 13C NMR (DMSO-d6): δC = 34.6, 59.8, 115.0,
122.0, 124.5, 124.8, 127.8, 128.4, 128.6, 129.4, 129.9, 130.6,
130.8, 132.7, 132.8, 133.7, 133.9, 139.5, 142.8, 148.5, 152.6,
154.7, 157.1, 163.2, 168.4. Anal. Calcd for C24H20N5O2SCl:
C: 60.31, H: 4.22, N: 14.65; found: C: 60.33, H: 4.20, N: 14.63.
From the data shown above, the spectroscopic data was in
agreement with the crystal structure. In the 1H NMR spectra, it
was found out that the N-H proton peak of the title compound
appeared in 12.01 and 11.85 ppm and the N-H proton peak shifted
to low field, which was in accord with the strong hydrogen bond,
N-H…N. Morever, the IR spectra exhibited the N-H stretching
vibration absorption at 3228 cm-1, which was also in accord with
the intermolecular hydrogen bond N-H…N.
(N − N1)
Plant growth activity (%) =
×100
N1
where N is the root length cultured in compound solution and
N1 is the length cultured in the distilled water under the same
condition.
RESULTS AND DISCUSSION
The general synthesis routes of these compounds followed
as (Scheme-I). The crystal structure of title compound atom-
labelling scheme was shown in Fig. 1. The crystal data and
structure refinement details for title compound was summa-
rized in Table-1, selected bond distances and angles is listed
in Table-2.
Crystal structure of 7: The single-crystal was obtained
from the slow evaporation of EtOH solution of compound 7
at room temperature for one month. A suitable crystal was
O
N
N
N
N
EtO CCH2Cl
O
O
N
S CH2COOEt
N
SH
CH3CCH3,
K2CO3, reflux , 8h
O
5
4
Cl
N
N
CHO
O
O
NH2NH2 H2O, 85%, EtOH
reflux ,10 h
N
S
CH2CNHNH2
MW, 6min
6
N
N
O
O
N
S
CH2CNHN=CH
Cl
7
Scheme-I

Vol. 27, No. 6 (2015)
Synthesis of N-2-Chlorophenyl-N'-2-[3-phenoxymethyl-4-phenyl-[1,2,4]triazole-5-thio]acetyl Hydrazone 2305
Fig. 1. Molecular structure of the title compound 7
TABLE-1
Fig. 2. C-H…O, N-H…C and N-H…N which link the supramolecule of
the title compound with one-dimenisional chain superamolecule
CRYSTAL DATA AND STRUCTURE
REFINEMENT DETAILS FOR COMPOUND 7
m.f.
C96H80N20O8S4Cl4
Formula weigh
Crystal group
Space group
a (Å)
1911.84
Triclnic
P21/c
1.6858(3)
b (Å)
9.988(2)
c (Å)
14.406(3)
90.00
α (°)
112.61(9)
β (°)
90.00
223.92 (8)
γ (°)
V (Å3)
Z
1
Dcalcd (Mg m-3)
Absorption correction
F (000)
1.418
Empirical
992
Limiting indices
Reflections collected
Independent reflections
Date/restraints/parameters
Final R indices[I > 2σ(I)]
R indices (all data)
Refinement method
Goodness of fit on F2
Crystal chromatography data
deposited accession number
-22 ≤ h ≤ 22, -12 ≤ k ≤ 13, -17 ≤ l ≤ 19
3321
5383 [Rint = 0.0304]
5383/0/298
R1 = 0.0416, wR2 = 0.0673
R1 = 0.0792, wR2 = 0.0723
SHELXL
1.564
CCDC 739430
Fig. 3. Paking dingram of title compound
crystal of the compound. However, the distance between the
centers of two parallel phenyl rings is 39.32 nm, which is out
of the accepted range of the intermolecular π-π interaction9.
There are three types hydrogen bonds in the crystal struchure
as shown in Fig. 2. The first one is N(5C)-H(5AC)…N(3A),
the other is O(2C)-H(23D)…C(23D) and the last one is N(3A)-
As shown in Fig. 2, the title compound contains a triazole
ring and three benzene rings. Just as anticipation, the triazole
ring is in one plane and the mean deviation from the best plane
of the five non-H atoms is 0.0005 Å. In addition, from Fig. 3
we can find the parallel packing of the phenyl rings in the
TABLE-2
SELECTED BOND LENGTHS (Å) AND BOND ANGLES (°) FOR COMPOUND 7
C1-C15
O1-C18
N1-C14
N2-C14
N4-C12
C7-S1-C21
C7-N2-C14
C7-N3-N1
N3-C7-N2
C17-C8-N2
O2-C13-N5
1.7284(18)
1.3735(19)
1.3033(19)
1.3722(19)
1.2789(18)
99.07(8)
104.6(13)
106.7(13)
110.5(15)
119.2(14)
120.6(17)
S1-C7
O1-C20
N1-N3
N2-C8
N4-N5
C18-O1-C20
C7-N2-C8
C12-N4-N5
N3-C7-S1
C10-C8-N2
N1-C14-N2
1.7407(18)
1.4209(18)
1.3997(18)
1.4468(18)
1.3745(16)
118.65(12)
126.94(14)
115.36(14)
127.11(13)
119.62(14)
110.66(15)
S1-C21
O2-C13
N2-C7
N3-C7
N5-C13
C14-N1-N3
C14-N2-C8
C13-N5-N4
N2-C7-S1
N4-C12-C9
N2-C14-C20
1.7958(16)
1.2135(17)
1.3657(19)
1.3176(18)
1.3552(19)
107.37(13)
128.26(14)
122.07(14)
122.31(12)
120.73(16)
124.59(15)

2306 Hu et al.
Asian J. Chem.
TABLE-3
DATA OF HYDROGEN BOND FOR 3
D-H…A
D-H (nm)
0.086
0.093
H…A (nm)
0.2388
0.2464
D…A (nm)
0.3236
0.1214
D-H…A (°)
168.78
154.7
Symmetry code
-X, -Y, -Z
N(5C)-H(5AC)…N(3A)
O(2C)-H(23D)…C(23D)
N(3A)-H(17D)…C(17D)
-
-
0.093
0.2598
0.1318
166.9
TABLE-4
PLANT GROWTH REGULATING ACTIVITY DATA
% Plant growth activitya
Compound
100 (ppm)
10 (ppm)
-40.9
-95.5
1 (ppm)
15.5
0.1 (ppm)
22.1
0.01 (ppm)
0.001 (ppm)
49.3
-100
-100
30.7
-46.1
7
Heteroauxing
-88.9
-47.6
-10.7
aSolution was prepared in the proportion of H2O:DMF = 99.5:0.5, and 0.1 g Tween-100 was added to promote the compound to dissolved
H(17D)…C(17D). From Table-3, it is noted that the hydrogen
bond N(5C)-H(5AC)…N(3A) is stronger than O(2C)-
H(23D)…C(23D) and N(3A)-H(17D)…C(17D), because the
hydrogen bond length of N(5C)---H(5AC)…N(3A) is shorter
than the later two, respectively. Morever, it can also be seen
that the crystals were linked to one-dimenisional chain-like
superamolecule through three intermolecular hydrogen bonds,
which form a nine-membered ring with C17D, C23D, H23D,
O2C, C13C, N5C, H5AC, N3A, H17D. From Fig. 3, it can be
seen that the supramolecular are connected by intermolecular
hydrogen bond of O(2C)- H(23D)…C(23D) along the oc-axis
direction and parallel packing along the ob-axis direction.
From the results summarized in Table-4, it is apparent
that the title compound exhibit inhibition activity at high
concentration of 100 and 10 ppm, while displayed enhancing
root elongation activity at the low concentration. Also, com-
pared with the hetero-auxing of isoconcentration, compound
7 remarkablely showed enhancement activity in low condition.
ACKNOWLEDGEMENTS
This work was supported by the National Natural Science
Foundation of china (NSFC) (Nos. 21064006, 21161018 and
21262032), the Natural Science Foundation of Gansu Province
(1010RJZA018) and the Program for Changjiang Scholars and
innovative Research Team in University of Ministry of Educa-
tion of China (IRT1177).
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Conclusion
The synthesis and 1 D chain supramolecular structure of
the title compound has been reported. The compound 7 is
synthesized with the method of microwave-induced synthesis
and this method has the advantages of mild conditions, simple
operation, short reaction times and high yield. Interesting, there
is an unusual NMR shift of the N-H is found. Finally, in the
crystal of compound 7, there are there types of hydrogen bonds
in the crystal structure; and, with the help of them, the com-
pound was assembled to 1 D chain supramolecular structure
by these three types of intramolecular hydrogen bonds.
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