Microwave Assisted Green Synthesis of Pyrazole, 1, 2, 3- Triazole Based Novel Benzohydrazones and Their Antibacterial Activities

Article abstract of DOI:10.1002/jhet.3073

A series of novel pyrazole, triazole based benzohydrazones (7a-l) were synthesized via conventional and microwave methods in the presence of acetic acid catalyst. Microwave method provided green and economical approach towards the synthesis of novel Schif

Full text of DOI:10.1002/jhet.3073

Month 2017 Microwave Assisted Green Synthesis of Pyrazole, 1, 2, 3- Triazole Based
Novel Benzohydrazones and Their Antibacterial Activities
a
b
a
Sravanthi K, Snehalatha P, and Subhashini NJP *
a
Department of Chemistry, University College of Science, Osmania University, Hyderabad, India
b
Department of Pharmacy, University College of Technology, Osmania University, Hyderabad, India
*
E-mail: njsubhashini@yahoo.co.in
Received August 31, 2017
DOI 10.1002/jhet.3073
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel pyrazole, triazole based benzohydrazones (7a-l) were synthesized via conventional and
microwave methods in the presence of acetic acid catalyst. Microwave method provided green and econom-
ical approach towards the synthesis of novel Schiff bases (7a-l). Some intermediates and all the final
compounds were characterized by NMR, mass, and elemental analysis. The compounds were screened for
their in vitro antibacterial activity against Gram-negative bacteria (Escherichia coli and Pseudomonas
aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus). Compounds 7e and
7
g showed good antibacterial activity.
J. Heterocyclic Chem., 00, 00 (2017).
INTRODUCTION
esterification [23], cycloaddition [24], epoxidation [25],
reduction [26], condensation [27], and cyclization [28]
reactions.
The hydrazones constitute an important class of
biologically active molecules, which have attracted
attention of medicinal chemists due to their wide ranging
pharmacological properties. They act as intermediate for
synthesis of various heterocyclic compounds such as 1, 3,
In continuation of our work on pyrazole aldehydes
towards the synthesis of biologically potent 1, 2, 3-
triazoles [29], here we report a very simple and
highly efficient protocol for the synthesis of new
pyrazolyl substituted 1,2,3-triazole-benzohydrazones using
4
-oxadiazolines, 1, 3, 4-oxadiazines, 1, 2, 4-triazines,
0
pyrazoles [1], and 1, 3, 4-oxadiazolines, azetidinones,
thiazolidinones [2,3]. They are reported to show wide
variety of biological properties such as anti-convulsant
4], anti-HIV, anticancer [5,6], antitubercular [7],
antioxidant [8], antimicrobial [9], and antimalarial activity
10]. On the other hand, benzohydrazone derivatives have
microwave irradiation technique. (E)-N -((1,3-diaryl-1H-
pyrazol-4-yl)methylene)-3-(4-phenyl-1H-1,2,3-triazol-1-yl)
benzohydrazides (7a-l) were obtained by the condensation
of pyrazole aldehydes 1(a-l) with 3-(4-Phenyl-1H-1,2,3-
triazol-1-yl)benzohydrazide (6). All the newly synthesized
compounds were stable at room temperature and were
characterized by IR, NMR, MASS, and elemental analysis.
[
[
also received much attention especially for their structures
and biological aspects, such as antiinflammatory activity
[
11], antimicrobial activity [12], antioxidant activity [13],
MATERIALS AND METHODS
and antimutagenicity activity [14].
Microwave heating has much superiority over the
classical ones with respect to its provision of higher
efficiency, purity of products, and reduced reaction time.
Over the years, chemists have successfully conducted a
large range of organic reactions under microwave
irradiation, including the Diels–Alder reaction [15], Ene
reaction [16], Heck reaction [17], Suzuki reaction [18],
Mannich reaction [19], as well as hydrogenation of
lactam [20], hydrolysis [21], dehydration [22],
All the solvents and chemicals used were of analytical
reagent grade. All chemicals were of the lab research
grade and were purchased from Avra, Sigma-Aldrich, and
Merck. Thin-layer chromatography (TLC) was run on
silica gel GF-254 sheet (Merck) and monitored under UV
light visualization. The compounds were purified by
column chromatography (silica gel 60–120 mesh).
Melting points were recorded on a Mettler Toledo
melting point apparatus (Mettler Toledo India Private
©
2017 Wiley Periodicals, Inc.

S. K, S. P, and S. NJP
Vol 000
1
Limited, Mumbai, India). H NMR (DMSO/CDCl3,
4
MgSO and was found to be pure. 3-Azidobenzoic acid (3)
4
1
3
00 MHz) and C NMR (DMSO, 100 MHz) spectra
were recorded on a Bruker Biospin Avance-III spectrometer
Switzerland). The chemical shifts were reported in δ/ppm
relative to tetramethylsilane (TMS). Mass spectra were
measured on a QSTAR XL Hybrid LC/MS/MS quadrupole
electro spray ionization time-of-flight mass spectrometer
(3.5 gm, 21.5 mmol) and phenyl acetylene (2.2 mL,
21.5 mmol) were suspended in a 1:1 mixture of water and
dimethylformamide (40 mL). Sodium ascorbate (6 mL of
freshly prepared 1 M solution in water) was added,
followed by copper (II) sulfate pentahydrate (5 mmol, in
2 mL of water). The heterogeneous mixture was stirred
vigorously for 12 h, and TLC analysis indicated complete
consumption of the reactants. The reaction mixture was
diluted with ice cold water (100 mL), and the solid was
collected by filtration. After washing the precipitate with
cold water (2 × 25 mL), it was dried under vacuum to
afford 3-(4-phenyl-1H-1,2,3-triazol-1-yl)benzoic acid (4).
Yield (%): 65. 3-(4-Phenyl-1H-1,2,3-triazol-1-yl)benzoic
acid (4) (4 gm, 15.1 mmol) was dissolved in 20 mL of
ethanol taken in a round bottomed flask, and 1 mL of conc.
(
(
Bruker India Scientific Pvt. Ltd., Bangalore, India).
EXPERIMENTAL
General experimental procedure for synthesis of 1,3-
Diphenyl-1H-pyrazole-4-carbaldehyde (1a-l).
of 1,3-Diphenyl-1H-pyrazole-4-carbaldehyde (1a-l) was
discussed in our earlier reports [29].
Synthesis
General experimental procedure for synthesis of 3-(4-phenyl-
H SO was added. The reaction flask was attached to a
2 4
1
H-1,2,3-triazol-1-yl)benzohydrazide (6): Scheme 1. Twenty
reflux water condenser and stirred at 80°C for 2 h. The
reaction was monitored by TLC, and after completion of
reaction, ethanol was evaporated under reduced pressure.
The contents of the flask were poured in crushed ice and
stirred well. After 2 h, the solid separated was filtered and
washed several times thoroughly with distilled water.
Precipitate was collected and dried. The crude product was
purified using column chromatography (60–120 mesh silica
gel) with ethyl acetate and pet ether (3:1) to give ethyl 3-(4-
phenyl-1H-1,2,3-triazol-1-yl)benzoate (5) in pure form.
Ethyl 3-(4-phenyl-1H-1,2,3-triazol-1-yl)benzoate (5) (3 gm,
10.2 mmol) was taken in a round bottomed flask. To this,
10 mL of ethanol was added and stirred well at room
temperature for 5 min. Then, hydrazine hydrate (0.40 mL,
12.28 mmol) was added to the reaction mixture and the
flask was attached to reflux water condenser and stirred at
80°C for 3 h. The reaction was monitored by TLC, and
milliliters of dilute HCl was taken in a round bottomed
flask and cooled it to 0°C. To this 3-amino benzoic acid (2)
(4 gm, 29.2 mmol) was slowly added with stirring for
5
min at 0°C and cold NaNO (2.42 gm, 35.0 mmol)
2
solution was added to the flask slowly with continuous
stirring at 0°C for 10 min, then stirred at room temperature
for 1 h. Then, the contents of the flask were again cooled to
0
°C and a cold aqueous NaN3 (2.41 gm, 35.0 mmol)
solution was slowly added to the flask and stirred under
cooling for another 10 min, then stirred at room temperature
for another 4 h. The reaction was monitored by TLC. After
completion of the reaction, the contents of the flask were
poured into 25 mL of ice cold water, extracted with
dichloro methane thrice. The extractions were collected in a
round bottomed flask and concentrated under reduced
pressure. The obtained 3-azidobenzoic acid (3) was dried on
Scheme 1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis of Novel Benzohydrazones and Their Antibacterial Activities
after completion of reaction, ethanol was evaporated under
reduced pressure. The contents of the flask were poured on
to 25 gm of crushed ice and stirred well. After 2 h, the
solid separated was filtered and washed several times
thoroughly with distilled water. Precipitate was collected
and dried. The product 3-(4-phenyl-1H-1,2,3-triazol-1-yl)
benzohydrazide (6) obtained was found to be pure. Yield
5 min and the yield increased from 65–80% to 88–98%.
Hence, the microwave irradiation method I proved to be
environmentally benign reaction medium, providing
easy isolation of products, shorter reaction times with
good yields.
(
%): 80. mp 250–253°C; IR (potassium bromide): 3282
SPECTRAL DATA
ꢀ
1 1
(NH ), 3024 (NH), 1625 (CO) cm ; H NMR (dimethyl
2
0
sulfoxide d ): δ 4.65 (broad singlet, 2H, NH ), 7.40 (t, 1H,
6
2
(E)-N -((1,3-Diphenyl-1H-pyrazol-4-yl)methylene)-3-(4-phenyl-
Ar-H), 7.52 (t, 2H, Ar-H), 7.73 (m, 1H, Ar-H), 7.96 (m,
H, Ar-H), 8.12 (m, 1H, Ar-H), 8.40 (m, 1H, Ar-H), 9.39
s, 1H, NH), 10.00 (s, 1H, triazole-H); MS: m/z 280 (M + H).
1H-1,2,3-triazol-1-yl)benzohydrazide 7(a).
205–207°C; IR (potassium bromide): 3055, 3024 (NH),
White solid, mp
3
(
ꢀ
1
1
2306 (C=N), 1739 (ꢀNH-C=O), 1660 (CO) cm
; H
NMR (dimethyl sulfoxide d ): δ 7.42 (m, 2H, Ar-H), 7.55
6
General experimental procedure for synthesis of new (E)-
0
(m, 7H, Ar-H), 7.74 (d, 2H, Ar-H, J = 7.36 Hz), 7.82 (t,
1H, Ar-H), 8.01 (d, 2H, Ar-H, J = 7.52 Hz), 8.06 (d, 3H,
Ar-H, J = 7.36 Hz), 8.22 (d, 1H, Ar-H, J = 8.03 Hz), 8.50
N -((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-3-(4-phenyl-
H-1,2,3-triazol-1-yl)benzohydrazide (7a) under conventional
and microwave irradiation methods: Scheme 1.
Conventional method.
1
A mixture of 1,3-diphenyl-1H-
pyrazole-4-carbaldehyde (1a) (0.2 mmol) and 3-(4-
phenyl-1H-1,2,3-triazol-1-yl)benzohydrazide (6)
0.2 mmol) were taken in a round bottomed flask
(s, 1H, triazole-H), 8.65 (s, 1H, pyrazole-H), 9.06 (s, 1H,
13
ꢀ
CH=N–), 9.45 (s, 1H, Ar-H), 11.99 (s, 1H, N-H);
C
NMR (dimethyl sulfoxide d ): δ 119.8, 122.8, 125.3,
6
(
126.9, 127.6, 128.4, 128.7, 129.0, 129.6, 130.1, 130.2,
containing 4 mL of ethanol. The reaction mixture was
stirred well for 5 min. Then, a catalytic amount of glacial
acetic acid was added to the reaction vessel, which was
then attached to reflux water condenser and stirred at 80–
1
31.9, 135.4, 136.7, 139.0, 141.5, 147.4, 151.9, 161.7; MS:
m/z 510 (M + H). Anal. Calcd for C H N O (%): C,
31 23 7
73.07; H, 4.55. Found (%): C, 73.09; H, 4.56.
0
(
E)-3-(4-Phenyl-1H-1,2,3-triazol-1-yl)-N -((1-phenyl-3-(p-tolyl)-
1
00°C for 1–2 h. The reaction was monitored by TLC,
1
H–pyrazol-4-yl)methylene)benzohydrazide 7(b).
White
and ethanol was evaporated. Twenty millimeters of ice
cold water was added to the contents of the flask and
stirred at room temperature for 10 min. Then, the solid
separated was filtered and washed thoroughly with
distilled water and dried. The crude product was purified
solid, mp 200–203°C; IR (potassium bromide): 3028
(
(
NH), 2306 (C=N), 1736 (ꢀNH-C=O), 1663 (CO), 1226
ꢀ1 1
C-N) cm ; H NMR (dimethyl sulfoxide d ): δ 2.09 (s,
6
3
H, CH ), 7.34 (m, 4H, Ar-H), 7.52 (m, 4H, Ar-H), 7.89
3
(m, 3H, Ar-H), 7.91 (d, 2H, Ar-H, J = 7.78 Hz), 8.06 (d,
0
on silica using hexane/ethyl acetate (1:3) to afford (E)-N -
3
8
1
H, Ar-H, J = 8.24 Hz), 8.20 (d, 1H, Ar-H, J = 8.28 Hz),
.51 (s, 1H, triazole-H), 8.63 (s, 1H, pyrazole-H), 9.06 (s,
H, ꢀCH = N–), 9.51 (s, 1H, Ar-H), 11.99 (s, 1H, N-H);
((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-3-(4-phenyl-
1H-1,2,3-triazol-1-yl)benzohydrazide (7a). Yield (%): 75;
mp 205–207°C.
By employing the same procedure, remaining
compounds (7b-l) were prepared.
13
C NMR (dimethyl sulfoxide d ): δ 30.6, 118.9, 119.8,
6
1
1
22.9, 125.3, 127.0, 127.5, 127.6, 128.3, 129.0, 129.6,
30.1, 130.2, 130.6, 130.7, 135.2, 136.7, 138.9, 141.4,
Microwave irradiation method.
A suspension of 1,3-
Diphenyl-1H-pyrazole-4-carbaldehyde (1a) (50 mg,
.2 mmol) and 3-(4-Phenyl-1H-1,2,3-triazol-1-yl)
147.5, 150.9, 161.5; MS: m/z 524 (M + H). Anal. Calcd
for C H N O (%): C, 73.41; H, 4.81. Found (%): C,
32 25 7
0
73.43; H, 4.82.
benzohydrazide (6) (56 mg, 0.2 mmol) in 2 mL of ethanol
and two drops of glacial acetic acid were irradiated at 300
watts for 4 min with an interval of 30 s. Progress of the
reaction was monitored by TLC. After completion of the
reaction, chilled water was added to the reaction mixture.
The precipitate formed was filtered, washed with water,
and subjected to column chromatography on silica gel
0
(
E)-N -((3-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)
methylene)-3-(4-phenyl-1H-1,2,3-triazol-1-yl)benzohydrazide
7(c). White solid, mp 243–245°C; IR (potassium bromide):
3138 (NH), 2312 (C=N), 1728 (ꢀNH-C = O), 1662 (CO)
ꢀ
1
1
cm ; H NMR (dimethyl sulfoxide d ): δ 3.93 (s, 3H,
6
ꢀOCH
), 7.12 (m, 1H, Ar-H), 7.31 (m, 1H, Ar-H), 7.40
3
(m, 3H, Ar-H), 7.60 (m, 5H, Ar-H), 7.83 (m, 1H, Ar-H),
8.02 (d, 2H, Ar-H, J = 7.53 Hz), 8.14 (d, 3H, Ar-H,
J = 8.17 Hz), 8.17 (d, 1H, Ar-H, J = 8.51 Hz), 8.50 (s,
1H, triazole-H), 8.71 (s, 1H, pyrazole-H), 9.02 (s, 1H,
0
using hexane/ethyl acetate (1:3) to afford (E)-N -((1,3-
diphenyl-1H-pyrazol-4-yl)methylene)-3-(4-phenyl-1H-
1
,2,3-triazol-1-yl)benzohydrazide (7a).
13
By employing the same procedure, remaining compounds
ꢀCH=N–), 9.50 (s, 1H, Ar-H), 11.95 (s, 1H, N-H);
C
(
7b-l) were prepared.
NMR (dimethyl sulfoxide d ): δ 55.6, 111.7, 111.9, 116.6,
6
From the comparison of the results cited in Table 1, it is
clear that the reaction time is reduced from 1–3 h to 2–
119.8, 121.0, 122.9, 124.5, 125.3, 126.9, 127.2, 127.6,
128.3, 129.0, 129.5, 130.1, 130.2, 135.3, 136.7, 139.0,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. K, S. P, and S. NJP
Vol 000
Table 1
Comparison of yields of compounds 7(a-l) under conventional and microwave irradiation methods
Conventional Heating
Time (h) Yield (%)
Microwave Irradiation
Time (min) Yield (%)
Compound
M.F. (M.Wt.)
C
31
H
23
25
25
N
N
N
7
7
7
O
O
O
1
75
75
74
70
76
2
95
97
95
90
97
(
509)
32
C H
1
3
3
5
4
(
523)
C
32
H
2
1
2
1
.5
(
539)
C
31
H22FN
7
O
(
527)
C
31
H22ClN
7
O
(
543)
(
Continues)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis of Novel Benzohydrazones and Their Antibacterial Activities
Table 1
(Continued)
Conventional Heating
Time (h) Yield (%)
Microwave Irradiation
Time (min) Yield (%)
Compound
M.F. (M.Wt.)
C
31
H
22BrN
7
O
2
65
68
72
80
68
5
92
(
587)
C
31
H
22
21
23
23
N
8
N
7
N
7
N
7
O
3
1
2
1
1
.5
5
5
3
4
90
90
98
95
(
554)
C
29
H
OS
(
515)
C
31
H
O
2
(
525)
C
31
H
O
3
(
541)
(
Continues)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. K, S. P, and S. NJP
Vol 000
Table 1
(Continued)
Conventional Heating
Time (h) Yield (%)
Microwave Irradiation
Time (min) Yield (%)
Compound
M.F. (M.Wt.)
33 27 7 3
C H N O
2
70
5
90
(
569)
35 25 7
C H N O
2
65
5
88
(
559)
141.9, 147.5, 148.8, 149.3, 152.0, 161.6; MS: m/z 540
NMR (dimethyl sulfoxide d ): δ 116.9, 118.9, 119.1, 119.8,
6
(
4
M + H). Anal. Calcd for C H N O (%): C, 71.23; H,
122.9, 127.1, 127.8, 128.3, 128.7, 129.0, 129.6, 130.1,
130.2, 130.8, 133.4, 135.1, 136.7, 138.9, 141.3, 147.5,
150.6, 161.6; MS: m/z 544 (M + H). Anal. Calcd for
C H ClN O (%): C, 68.44; H, 4.08. Found (%): C, 68.43;
32 25 7 2
.67. Found (%): C, 71.24; H, 4.67.
0
(
E)-N -((3-(4-Fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-
3
-(4-phenyl-1H-1,2,3-ctriazol-1-yl)benzohydrazide 7(d).
Light
31
22
7
gray solid, mp 190–192°C; IR (potassium bromide): 3132
H, 4.10.
ꢀ
1
(NH), 2312 (C=N), 1737 (ꢀNH-C=O), 1670 (CO) cm ;
0
(E)-N -((3-(4-Bromophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-
1
H NMR (dimethyl sulfoxide d ): δ 7.39 (m, 4H, Ar-H),
3-(4-phenyl-1H-1,2,3-triazol-1-yl)benzohydrazide 7(f). White
6
7
.52 (m, 4H, Ar-H), 7.84 (m, 3H, Ar-H), 7.98 (d, 2H,
Ar-H, J = 7.57 Hz), 8.06 (d, 3H, Ar-H, J = 7.78 Hz), 8.22
d, 1H, Ar-H, J = 7.78 Hz), 8.51 (s, 1H, triazole-H), 8.59
solid, mp 210–213°C; IR (potassium bromide): 3129 (NH),
ꢀ
1
1
2322 (C=N), 1745 (ꢀNH-C=O), 1663 (CO) cm ; H
(
NMR (dimethyl sulfoxide d ): δ 7.40 (m, 2H, Ar-H), 7.54
6
(
s, 1H, pyrazole-H), 9.10 (s, 1H, ꢀCH=N–), 9.46 (s, 1H,
(m, 4H, Ar-H), 7.63 (d, 2H, Ar-H), 7.82 (m, 3H, Ar-H),
7.97 (d, 2H, Ar-H, J = 7.03 Hz), 8.09 (d, 3H, Ar-H,
J = 7.78 Hz), 8.25 (d, 1H, Ar-H, J = 9.26 Hz), 8.50 (s, 1H,
triazole-H), 8.63 (s, 1H, pyrazole-H), 9.08 (s, 1H,
13
Ar-H), 11.99 (s, 1H, N-H); C NMR (dimethyl sulfoxide
d6): δ 115.5, 115.7, 116.7, 118.8, 119.0, 119.8, 122.9,
125.3, 127.0, 127.6, 128.3, 129.0, 129.6, 130.1, 130.2,
130.6, 130.7, 135.2, 136.7, 138.9, 141.4, 147.5, 150.9,
161.6, 163.6; MS: m/z 528 (M + H). Anal. Calcd for
13
ꢀCH=N–),9.46 (s, 1H, Ar-H), 12.01 (s, 1H, N-H); C
NMR (dimethyl sulfoxide d ): δ 116.9, 118.9, 119.1,
6
C H FN O (%): C, 70.58; H, 4.20. Found (%): C, 70.57;
119.8, 122.9, 125.3, 127.1, 127.6, 127.7, 128.3, 128.7,
31
22
7
H, 4.20.
129.0, 129.6, 130.1, 130.2, 130.8, 133.4, 135.3, 136.7,
0
1
38.9, 141.3, 147.5, 150.6, 161.7; MS: m/z 588 (M + H).
(
E)-N -((3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-
3-(4-phenyl-1H-1,2,3-triazol-1-yl)benzohydrazide 7(e). Wheatish
Anal. Calcd for C H BrN O (%): C, 63.27; H, 3.77.
31
22
7
solid, mp 212–215°C; IR (potassium bromide): 3126 (NH),
Found (%): C, 63.29; H, 3.79.
ꢀ
1
1
0
2319 (C=N), 1742 (ꢀNH-C=O), 1666 (CO) cm ;
H
(E)-N -((3-(4-Nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-
NMR (dimethyl sulfoxide d ): δ 7.40 (m, 2H, Ar-H), 7.58
3-(4-phenyl-1H-1,2,3-triazol-1-yl)benzohydrazide 7(g).
Pale
6
(
7
m, 4H, Ar-H), 7.66 (m, 2H, Ar-H), 7.79 (m, 3H, Ar-H),
.97 (d, 2H, Ar-H, J = 7.28 Hz), 8.09 (d, 3H, Ar-H,
yellow solid, mp 252–255°C; IR (potassium bromide):
3133 (NH), 2320 (C=N), 1741 (ꢀNH-C=O), 1659 (CO)
ꢀ
1 1
J = 7.78 Hz), 8.18 (d, 1H, Ar-H, J = 9.28 Hz), 8.55 (s, 1H,
cm ; H NMR (dimethyl sulfoxide d ): δ 7.42 (m, 2H,
6
triazole-H), 8.59 (s, 1H, pyrazole-H), 9.16 (s, 1H,
Ar-H), 7.56 (m, 4H, Ar-H), 7.84 (t, 1H, Ar-H), 7.99 (d,
2H, Ar-H, J = 8.13 Hz), 8.07 (d, 3H, Ar-H, J = 8.34 Hz),
13
ꢀ
CH=N–), 9.46 (s, 1H, Ar-H), 11.98 (s, 1H, N-H); C
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis of Novel Benzohydrazones and Their Antibacterial Activities
1
3
8
.20 (m, 3H, Ar-H), 8.39 (d, 2H, Ar-H, J = 8.14 Hz), 8.51
1H, Ar-H), 11.89 (s, 1H, N-H); C NMR (dimethyl
(
ꢀ
s, 1H, triazole-H), 8.65 (s, 1H, pyrazole-H), 9.13 (s, 1H,
sulfoxide d ): δ 102.7, 106.8, 109.9, 117.9, 118.5,
6
13
CH=N–), 9.49 (s, 1H, Ar-H), 12.07 (s, 1H, N-H);
C
119.0, 119.8, 122.8, 125.3, 125.5, 126.6, 127.6, 128.3,
129.0, 129.5, 130.1, 130.2, 131.6, 135.2, 136.6, 139.1,
143.4, 147.4, 151.2, 156.2, 159.2, 161.5; MS: m/z 542
(M + H). Anal. Calcd for C H N O (%): C, 68.75;
NMR (dimethyl sulfoxide d ): δ 117.5, 119.0, 119.8,
6
1
1
1
23.0, 123.8, 125.3, 127.4, 127.6, 128.3, 128.8, 129.0,
29.5, 129.7, 130.0, 130.3, 135.0, 136.7, 138.4, 138.7,
40.9, 147.5, 149.3, 161.7; MS: m/z 555 (M + H). Anal.
3
1
23
7 3
H, 4.28. Found (%): C, 68.76; H, 4.26.
Calcd for C H N O (%): C, 67.14; H, 4.00. Found (%):
C, 67.16; H, 4.02.
0
31
22
8
3
(E)-N -((3-(3,4-Dimethoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)
methylene)-3-(4-phenyl-1H-1,2,3-triazol-1-yl)benzohydrazide
0
7(k).
White solid, mp 253–256°C; IR (potassium
(
E)-3-(4-Phenyl-1H-1,2,3-triazol-1-yl)-N -((1-phenyl-3-(thiophen-
-yl)-1H-pyrazol-4-yl)methylene)benzohydrazide 7(h). White
solid, mp 220–222°C; IR (potassium bromide): 3145 (NH),
2
bromide): 3134 (NH), 1743 (ꢀNH-C=O), 1670 (CO)
ꢀ
1 1
cm ; H NMR (dimethyl sulfoxide d ): δ 3.83 (s, 3H,
6
ꢀ
1
1
ꢀ
OCH ), 3.93 (s, 3H, ꢀOCH ), 7.19 (m, 1H, Ar-H),
2
332 (C=N), 1746 (ꢀNH-C=O), 1661 (CO) cm ; H
3
3
NMR (dimethyl sulfoxide d ): δ 7.24 (m, 1H, Ar-H),
7.31 (m, 1H, Ar-H), 7.38 (m, 3H, Ar-H), 7.62 (m, 5H,
Ar-H), 8.01 (d, 2H, Ar-H), 8.08 (d, 3H, Ar-H), 8.20 (d,
6
7
.41 (m, 2H, Ar-H), 7.55 (m, 4H, Ar-H), 7.69 (d, 1H, Ar-
H, J = 8.03 Hz), 7.85 (t, 1H, Ar-H), 7.99 (m, 4H, Ar-H),
.04 (d, 1H, Ar-H, J = 7.98 Hz), 8.09 (d, 1H, Ar-H,
J = 8.30 Hz), 8.22 (d, 1H, Ar-H, J = 8.05 Hz), 8.53 (s, 1H,
triazole-H), 8.74 (s, 1H, pyrazole-H), 9.08 (s, 1H,
CH = N-), 9.48 (s, 1H, Ar-H), 12.07 (s, 1H, N-H);
NMR (dimethyl sulfoxide d ): δ 116.3, 118.7, 119.1,
19.8, 122.9, 125.3, 127.1, 127.6, 127.9, 128.0, 128.3,
28.9, 129.0, 129.6, 130.1, 130.3, 134.1, 135.2, 136.7,
1
H, Ar-H), 8.42 (s, 1H, triazole-H), 8.79 (s, 1H,
8
pyrazole-H), 9.44 (s, 1H, ꢀCH=N–), 9.70 (s, 1H, Ar-H),
1
3
11.98 (s, 1H, N-H); C NMR (dimethyl sulfoxide d
): δ
6
5
5.6, 111.7, 111.9, 116.6, 119.8, 121.0, 122.9, 124.5,
13
ꢀ
C
125.3, 126.9, 127.2, 127.6, 128.3, 129.0, 129.5, 130.1,
130.2, 135.3, 136.7, 139.0, 141.9, 147.5, 148.8, 149.3,
6
1
52.0, 161.6; MS: m/z 570 (M + H). Anal. Calcd for
C H N O (%): C, 69.58; H, 4.78. Found (%): C,
33 27 7 3
1
1
1
38.7, 141.0, 145.8, 147.5, 161.7; MS: m/z 516 (M + H).
Anal. Calcd for C H N OS (%): C, 67.56; H, 4.11.
69.59; H, 4.77.
0
2
9 21 7
(E)-N -((3-(Naphthalen-1-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)-
Found (%): C, 67.52; H, 4.12.
3-(4-phenyl-1H-1,2,3-triazol-1-yl)benzohydrazide 7(l). White
0
solid, mp 158–161°C; IR (potassium bromide): 1736
(
E)-N -((3-(3-Hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)
ꢀ
1
1
methylene)-3-(4-phenyl-1H-1,2,3-triazol-1-yl)benzohydrazide
(i).
(ꢀNH-C=O), 1660 (CO) cm
;
H NMR (dimethyl
7
White solid, mp 215–218°C; IR (potassium
sulfoxide d ): δ 7.40 (m, 5H, Ar-H), 7.66 (m, 4H, Ar-H),
6
bromide): 3123 (NH), 2321 (C=N), 1745 (ꢀNH-C=O),
7.79 (m, 4H, Ar-H), 8.42 (m, 3H, Ar-H), 8.54 (s, 1H,
triazole-H), 8.55(s, 1H, pyrazole-H), 8.76 (s, 1H,
ꢀCH = N–), 9.13 (s, 1H, Ar-H), 9.43 (m, 4H, Ar-H),
ꢀ
1
1
1
660 (CO) cm
δ 6.90 (d, 1H, Ar-H, J = 7.02 Hz), 7.14 (m, 2H, Ar-H),
.37 (m, 3H, Ar-H), 7.54 (m, 4H, Ar-H), 7.81 (t, 1H,
Ar-H, J = 8.03 Hz), 7.99 (d, 2H, Ar-H, J = 8.28 Hz),
; H NMR (dimethyl sulfoxide d ):
6
13
7
12.06 (s, 1H, N-H); C NMR (dimethyl sulfoxide d ): δ
6
108.3, 112.1, 117.0, 117.8, 118.9, 119.1, 119.8, 122.5,
125.3, 126.1, 126.5, 127.0, 127.5, 127.6, 127.7, 127.8,
128.2, 128.3, 128.4, 129.0, 129.4, 130.0, 130.1, 135.8,
136.5, 147.4, 151.7, 162.1; MS: m/z 560 (M + H). Anal.
Calcd for C H N O (%): C, 75.12; H, 4.50. Found (%):
8
8
1
.05 (m, 3H, Ar-H), 8.20 (d, 1H, Ar-H, J = 8.03 Hz),
.50 (s, 1H, Ar-H), 8.62 (s, 1H, triazole-H), 9.03 (s,
H, pyrazole-H), 9.45 (s, 1H, ꢀCH=N–), 9.69 (s, 1H,
1
3
Ar-H), 11.99 (s, 1H, N-H);
C NMR (dimethyl
35 25 7
sulfoxide d ): δ 115.1, 115.7, 116.7, 118.8, 119.0,
C, 75.19; H, 4.47.
6
119.2, 119.8, 123.0, 125.4, 126.9, 127.0, 127.6, 128.4,
129.0, 129.6, 129.9, 130.0, 130.3, 133.0, 135.1, 136.7,
139.5, 147.5, 152.2, 157.6, 160.9; MS: m/z 526
ANTIBACTERIAL ACTIVITY STUDIES
(
M + H). Anal. Calcd for C H N O (%): C, 70.84;
31 23 7 2
H, 4.41. Found (%): C, 70.83; H, 4.42.
Antibacterial assay. The synthesized novel compounds
7a–j were screened for their antibacterial activity against
different types of bacterial strains, viz. Gram-positive
bacterial strains Bacillus B. cereus and Staphylococcus
aureus; Gram-negative bacterial strains Escherichia coli
and Pseudomonas aeruginosa at a concentration of
10 μg/mL and 20 μg/mL. The cultures were diluted with
5% saline autoclaved, and the final volume was made
with concentration approximately 105–106 CFU/mL. The
synthesized compounds were diluted in DMSO for
antibacterial biological assays using agar well diffusion
0
(
E)-N -((3-(2,4-Dihydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)
methylene)-3-(4-phenyl-1H-1,2,3-triazol-1-yl)benzohydrazide
(j).
7
White solid, mp 202–204 °C; IR (potassium
bromide): 3123 (NH), 1732 (ꢀNH-C=O), 1663 (CO)
ꢀ
1 1
cm ; H NMR (dimethyl sulfoxide d ): δ 6.39 (d, 1H,
6
Ar-H), 6.48 (s, 1H, Ar-H), 7.23 (d, 1H, Ar-H), 7.40
(
7
m, 2H, Ar-H), 7.52 (m, 4H, Ar-H), 7.80 (t, 1H, Ar-H),
.99 (m, 5H, Ar-H), 8.18 (d, 1H, Ar-H), 8.36 (s, 1H,
Ar-H), 8.49 (s, 1H, Ar-H), 8.95 (s, 1H, triazole-H), 9.44
s, 1H, pyrazole-H), 9.59 (s, 1H, ꢀCH=N–), 9.70 (s,
(
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. K, S. P, and S. NJP
Vol 000
Table 2
Antibacterial activity (MICs in μM) of newly synthesized compounds 7a-l
MIC80 (μg/mL)
Compound
R
S. aureus
B. cereus
E. coli
P. aeruginosa
7
7
7
7
7
7
7
7
7
7
7
7
a
b
c
d
e
f
g
h
i
H
4-CH
4-OCH
4-F
4-Cl
4-Br
4-NO
2-thiophene
3-OH
2,4-DiOH
16 ± 2.4
16 ± 2.4
32 ± 6.4
64 ± 9.6
16 ± 2.0
128 ± 15.6
8 ± 1.6
16 ± 3.6
256 ± 0.0
128 ± 14.2
32 ± 6.4
512 ± 38.4
4 ± 1.2
32 ± 6.4
256 ± 28.4
128 ± 15.2
64 ± 6.4
4 ± 0.0
32 ± 2.4
2 ± 0.8
128 ± 12.6
32 ± 6.4
256 ± 20.0
128 ± 05.0
256 ± 0.0
2 ± 0.0
8 ± 0.0
128 ± 25.6
16 ± 2.4
128 ± 19.6
4 ± 1.2
32 ± 8.2
256 ± 28.4
128 ± 0.0
64 ± 3.6
8 ± 1.6
64 ± 0.0
3
3
16 ± 8.4
8 ± 0.0
2
4 ± 2.4
128 ± 12.6
64 ± 9.6
256 ± 31.4
512 ± 10.0
128 ± 9.6
2 ± 0.8
256 ± 20.4
128 ± 15.6
16 ± 0.0
256 ± 12.0
128 ± 11.6
4 ± 0.0
j
k
l
3,4-DiOCH
1-Napthyl
3
Ciprofloxacin
MIC, minimum inhibitory concentration.
method [30]. Simultaneously, the standard antibiotic
ciprofloxacin is tested against the pathogens. The tested
compounds and reference drug were prepared in nutrient
broth by twofold serial dilution to obtain the required
concentrations of 512, 256, 128, 64, 32, 16, 8, 4, 2, 1,
expressed as minimum inhibitory concentration (MIC).
The lowest concentration that inhibited visible growth of
the tested organisms was recorded as MIC, and the
results are presented in Table 2.
Investigation of the antibacterial efficiency results revealed
that most of the tested compounds displayed variable
inhibitory effects on the growth of the tested Gram-positive
and Gram-negative bacterial strains. It is evident from
Table 2, among synthesized compounds, the inhibitory
efficiency of compound 7e and 7g exhibited broad
spectrum of antibacterial activity as the observed MIC
values against all the tested strains were less and all other
compounds showed higher MIC values. The antibacterial
activity study results revealed that compounds with Chloro
and Nitro substitutions showed promising antibacterial
activity compared with other substituted compounds (Fig. 1).
0
.5 μg/mL. For agar disc diffusion method, the liquid
form of test compound was soaked on to the disc and
then allowed to air dry, such that the disc gets completely
saturated with test compound. The saturated chemical
discs were introduced onto the upper layer of the medium
evenly floated with the bacteria. The discs were dipped in
different chemical samples, were placed over the evenly
spread bacterial nutrient media, and incubated at 37°C for
48 h for better inhibition of bacteria. The zones of
inhibition were measured after 48 h. All the experiments
were carried out in triplicates, and the results were
Figure 1. Graphical representation of antibacterial activity of compounds 7a-l in MICs using Ciprofloxacin as standard drug. MIC, minimum inhibitory
concentration. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis of Novel Benzohydrazones and Their Antibacterial Activities
CONCLUSION
[8] Hruskova, K.; Kovarikova, P.; Bendova, P.; Haskova, P.;
Mackova, E.; Stariat, J.; Vavrova, A.; Vavrova, K.; Simunek, T. Chem
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0
We have successfully synthesized new series of (E)-N -
(1,3-diphenyl-1H-pyrazol-4-yl)methylene)-3-(4-phenyl-
H-1,2,3-triazol-1-yl)benzohydrazide derivatives 7(a-l)
under conventional and microwave irradiation methods.
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facile and environmentally benign synthesis in which the
reaction time is reduced with better yields. This method
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divergent synthetic protocol for the
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Acknowledgments. The authors are thankful to the Head,
Department of Chemistry, Osmania University for providing
laboratory facilities. One of the authors (N. J. P. S.) is thankful
to UGC, New Delhi for financial support (MRP-F no. 39-772/
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[
Osmania University, Hyderabad, for providing elemental and
spectral analysis facilities.
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Additional Supporting Information may be found online
in the supporting information tab for this article.
[
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet