Novel N-acyl/aroyl-2-(5-phenyl-2H-tetrazol-2-yl)acetohydrazides: Synthesis and characterization

Article abstract of DOI:10.3906/kim-1307-13

A number of novel N -acyl/aroyl-2-(5-phenyl-2H-tetrazol-2-yl) acetohydrazides (4a-j) of biological interest were efficiently synthesized by treating 2-(5-phenyl-2H-tetrazole-2-yl)acetohydrazide (3) with a variety of aroyl/heterocyclyl or alkanoyl chlorides. FTIR, ₁H NMR, ₁₃C NMR, GC-MS, and elemental analyses data confirmed the structures assigned to the newly synthesized compounds. TUeBITAK.

Full text of DOI:10.3906/kim-1307-13

Turk J Chem
Turkish Journal of Chemistry
(2014) 38: 436 – 442
¨
http://journals.tubitak.gov.tr/chem/
˙
c
⃝ TUBITAK
doi:10.3906/kim-1307-13
Research Article
Novel N -acyl/aroyl-2-(5-phenyl-2H -tetrazol-2-yl)acetohydrazides: synthesis and
characterization
Aamer SAEED∗, Majid HUSSAIN, Muhammad QASIM
Department of Chemistry, Quaid-I-Azam University, Islamabad, Pakistan
Received: 07.07.2013
•
Accepted: 26.10.2013
•
Published Online: 14.04.2014
•
Printed: 12.05.2014
Abstract: A number of novel N -acyl/aroyl-2-(5-phenyl-2H -tetrazol-2-yl)acetohydrazides (4a–j) of biological interest
were efficiently synthesized by treating 2-(5-phenyl-2H -tetrazole-2-yl)acetohydrazide (3) with a variety of aroyl/hetero-
cyclyl or alkanoyl chlorides. FTIR, 1 H NMR, 13 C NMR, GC-MS, and elemental analyses data confirmed the structures
assigned to the newly synthesized compounds.
Key words: Tetrazoles, hydrazides, acylation
1. Introduction
Heterocyclic compounds display a broad spectrum of biological activities. 5-Substituted 1,2,3,4-tetrazoles
are 5-member aromatic heterocyclic compounds containing 4 nitrogen atoms. The literature on this nu-
cleus is rapidly expanding. This heterocycle has gained significance not only in coordination chemistry as
a ligand1 but also in medicinal chemistry as a metabolically stable surrogate for a carboxylic acid group.2
5-Substituted 1,2,3,4-tetrazoles are reported to possess several biological activities including antibacterial,3
antifungal,4 antinoceceptive,5 analgesic,6 anti-inflammatory,7 anticonvulsant,8 hypoglycemic,9 and antihy-
pertensive activities.10
In conjunction with tetrazoles, hydrazide is another important functionality and a key precursor for the
synthesis of several bioactive scaffolds such as oxadiazoles, thiadiazoles, Schiff bases, pyrazoles, and triazoles.
The conversion of tetrazoles bearing hydrazide moiety into Schiff bases11 and triazoles12 has been reported.
In the light of these studies, concerning the individual importance of tetrazoles and hydrazides, the aim
of this work was to synthesize some new N -acyl/aroyl-2-(5-phenyl-2H -tetrazol-2-yl)acetohydrazides. Diversity
can be introduced by using a variety of aryl/heterocyclyl substituents leading to compounds with enhanced
biological activities. The tetrazole scaffold is especially a bioisostere for the carboxylate group and a novel
ligand for applications in coordination chemistry. Figure 1 illustrates the medicinally important tetrazole
derivatives like anticonvulsant8 (a), analgesic6 (b), antinoceceptive,5 (c), hypoglycemic,9 (d) antibacterial3
(e), and antifungal4 (f) reported in the literature.
∗Correspondence: aamersaeed@yahoo.com
436

SAEED et al./Turk J Chem
Figure 1. Some pharmacologically important tetrazole derivatives reported in the literature.
2. Experimental
Melting points were recorded using a digital Gallenkamp (SANYO, Loughborough, UK) model MPD BM 3.5
apparatus and are uncorrected. 1 H and 13 C NMR spectra were determined in CDCl3 at 300 and 75 MHz,
respectively, using a Bruker AM-300 spectrophotometer (Billerica, Middlesex, MA, USA). FT-IR spectra were
recorded using a Rad Excalibur FTS 3000 MX spectrophotometer (Madison, WI, USA). Mass spectra (EI, 70
eV) were recorded on a GC-MS instrument (Agilent Technologies 1200 series, Santa Clara, CA, USA), and
elemental analyses were carried out with a LECO-183 CHNS analyzer (LECO Corporation, St Joseph, MI,
USA). The Rf values are reported in n−hexane:ethyl acetate (1:1) as mobile phase.
Synthesis of 5-phenyl-2H -tetrazole (1)
5-Phenyl tetrazole was prepared according to the literature procedure.2 A mixture of sodium azide (3
mmol), benzonitrile (0.20 g, 2 mmol), and zinc(II) chloride (0.40 g, 3 mmol) was suspended in H2 O (16 mL)
and the reaction mixture was refluxed for 15 h. On completion (TLC control), the mixture was cooled to room
temperature and the solid obtained was filtered and then was washed with water. In continuation of the workup,
the solid residue was treated with 3 N HCl (4 mL) to afford the product as a white solid (2.1 g, yield 78%).
mp 216 ◦ C (lit.2 217 ◦ C). 1 H NMR (300 MHz, DMSO) δ (ppm): 7.59–7.62 (m, 3H, Ar–H), 8.02–8.06 (m, 2H,
Ar–H), 13 C NMR (75 MHz, DMSO) δ (ppm): 124.55 (1’C), 127.24 (2’C), 129.89 (3’C) 131.73 (4’C), 155.79
(tetrazole ring carbon).
Synthesis of methyl 2-(5-phenyl-2H -tetrazole-2-yl)acetate (2)
A mixture of 5-phenyltetrazole (0.438 g, 3 mmol), triethylamine (1.674 mL, 12 mmol), and acetonitrile
(25 mL) was added dropwise to a stirred solution of methyl chloroacetate (0.523 mL, 6 mmol) in 15 mL of
acetonitrile. The reaction mixture was heated on an oil bath for 2 h, keeping the temperature at 82 ◦ C. The
437

SAEED et al./Turk J Chem
progress of the reaction was monitored by TLC. Acetonitrile was removed under reduced pressure and the
product was recrystallized in n-hexane to get pure methyl 2-(5-phenyl-2H -tetrazole-2-yl)acetate as a white
crystalline solid, (1.85 g, yield 73%). mp 98–100 ◦ C. IR (Neat) cm−1 : 1281 (N=N–N), 1547 (Ar–C=C), 1606
(C=N), 1756 (C=O), 2854 (CH3), 3067 (Ar–C–H); 1 H NMR (300 MHz, DMSO) δ (ppm): 3.75 (s, 2H, CH3),
5.93 (s, 2H, CH2), 7.56–7.59 (m, 3H, Ar–H), δ 8.06–8.10 (m, 2H, Ar–H). 13 C NMR (75 MHz, DMSO) δ (ppm):
53.43, 53.83 (CH2 C=O, OCH3), 126.82 (1’C), 126.99 (2’C), 129.84 (3’C) 131.28 (4’C), 164.85 (tetrazole ring
carbon), 167.11 (C=O).
Synthesis of 2-(5-phenyl-2H -tetrazole-2-yl)acetohydrazide (3)
To a solution of tetrazole-ester (2) (0.218 g, 1.0 mmol) in 10 mL of dry distilled methanol was added
hydrazine hydrate (2 mmol).13 The reaction mixture was stirred at room temperature. The reaction was
monitored by TLC. The precipitates obtained were filtered and then washed with methanol to obtain tetrazole-
hydrazide (3). White crystalline solid, (0.35 g, yield 95%). mp 212 ◦ C. (lit.2 205 ◦ C). IR (Neat) cm−1 : 1280
(N=N–N), 1549 (Ar–C=C), 1608 (C=N), 1659 (C=O), 3057 (Ar–C–H), 3132 (N–H), 3307 (NH2); 1 H NMR
(300 MHz, DMSO) δ (ppm): 4.46 (s, 2H, NH2), 5.45 (s, 2H, CH2), 7.55–7.61 (m, 3H, Ar–H), 8.05–8.08 (m,
2H, Ar–H), 9.65 (s, 1H, NH), 13 C NMR (75 MHz, DMSO) δ (ppm): 54.14 (CH2 C=O), 124.89 (1’C), 126.24
(2’C), 130.09 (3’C) 131.93 (4’C), 163.99 (tetrazole ring carbon), 164.62 (C=O).
General procedure for the synthesis of N -acyl/aroyl-2-(5-phenyl-2H -tetrazol-2-yl)acetohyd-
razides (4a–j)
Different acyl/aroyl chlorides were synthesized by refluxing a variety of acids in thionyl chlorides for
25–30 min. The acid chlorides (0.1 mmol) were added slowly to a stirred solution of 2-(5-phenyl-2H -tetrazole-
2-yl)acetohydrazide (3) (0.1 mmol) in dry DMF at room temperature. The reaction mixture was stirred for
a further 30 min and the progress of the reaction was followed by TLC. On completion, the reaction mixture
was poured into an excess of cold water and the solid precipitated out, which was filtered and washed with
methanol. The solid was further recrystallized in ethanol/methanol to afford the pure products.
4-Nitro-N’-(2-(5-phenyl-2H -tetrazol-2-yl)acetyl)benzohydrazide (4a)
Light green solid (0.82 g, yield 95%). mp 245–247 ◦ C. IR (Neat) cm−1 : 1280 (N=N–N), 1549 (Ar–
C=C), 1564 (–NO2), 1608 (C=N), 1654, 1659 (C=O), 3057 (Ar–C–H), 3132, 3170 (N–H); 1 H NMR (300 MHz,
DMSO) δ (ppm): 5.75 (s, 2H, CH2), 7.57 (t, J = 3.6 Hz, 4’, 3’, 3H), 8.07 (d, J = 8.7 Hz, 2”, 2H), 8.33 (m,
2’, 2”, 4H), 10.88, 11.03 (s, 2H, –NH), 13 C NMR (75 MHz, DMSO) δ (ppm): 53.64 (CH2), 124.24 (1’C),
126.82 (2’C), 129.58 (3’, 2”C), 149.92 (nitro-C), 164.19 (tetrazole ring carbon), 164.30, 164.74 (C=O). Analysis
of C16 H13 N7 O4 (367.10). (% calcd./found): C: 52.32/52.02, H: 3.57/3.80, N: 26.69/26.08. MS, m/z(%): 367
·+
[M]
(67), 202 (100), 165 (25), 159 (45), 208 (37).
2-Chloro-N’-(2-(5-phenyl-2H -tetrazol-2-yl)acetyl)benzohydrazide (4b)
Yellowish solid (0.75 g, yield 82%). mp 230 ◦ C. IR (Neat) cm−1 : 1280 (N=N–N), 1553 (Ar–C=C), 780
(–C–Cl), 1608 (C=N), 1654, 1659 (C=O), 3060 (Ar–C–H), 3130, 3172 (N–H); 1 H NMR (300 MHz, DMSO) δ
(ppm): 5.71 (s, 2H, CH2), 7.41–8.11 (m, 9H, Ar–H), 10.74, 10.93 (s, 2H, –NH), 13 C NMR (75 MHz, DMSO)
δ (ppm): 53.80 (CH2), 126.82 (1’C), 127.01 (2’C), 128.84 (3’C) 133.28 (4’C), 138.80 (2”C), 163.59 (tetrazole
ring carbon), 164.72, 166.40 (C=O). Analysis of C16 H13 ClN6 O2 (356.08). (% calcd./found): C: 53.86/53.02,
·+
H: 3.67/3.80, N: 23.56/24.08. MS, m/z(%): 256 [M]
(70), 258 (25), 202 (100), 154 (45), 159 (55), 197 (37).
438

SAEED et al./Turk J Chem
2-Bromo-N’-(2-(5-phenyl-2H -tetrazol-2-yl)acetyl)benzohydrazide (4c)
Light brown solid (0.73 g, yield 90%). mp 257–260 ◦ C. IR (Neat) cm−1 : 1285 (N=N–N), 1540 (Ar–
C=C), 695 (–C–Br), 1608 (C=N), 1654, 1660 (C=O), 3057 (Ar–C–H), 3132, 3170 (N–H); 1 H NMR (300 MHz,
DMSO) δ (ppm): 5.73 (s, 2H, CH2), 7.42–7.47 (m, 7H, Ar–H), 8.22 (2’H), 10.62, 10.93 (s, 2H, –NH), 13 C
NMR (75 MHz, DMSO) δ (ppm): 53.78 (CH2), 118.8 (2”C) 126.82 (dd, J = 7.5, 1.8 Hz, 1’C), 126.99 (2’C),
129.84 (3’C) 131.28 (4’C), 163.59 (tetrazole ring carbon), 164.72, 166.40 (C=O). Analysis of C16 H13 BrN6 O2
(400.03). (% calcd./found): C: 47.90/40.98, H: 3.27/3.80, N: 20.95/20.80. MS, m/z(%): 400 [M]·+ (70), 402
(55), 240 (48), 202 (100), 197 (50) 159 (55).
2-Chloro-6-nitro-N’-(2-(5-phenyl-2H -tetrazol-2-yl)acetyl)benzohydrazide (4d)
Light yellowish solid (0.86 g, yield 80%). mp 275 ◦ C. IR (Neat) cm−1 : 1280 (N=N–N), 1549 (Ar–C=C),
782 (–C–Cl), 1560 (–NO2), 1608 (C=N), 1650, 1655 (C=O), 3057 (Ar–C–H), 3132, 3170 (N–H); 1 H NMR (300
MHz, DMSO) δ (ppm): 5.60 (s, 2H, CH2), 7.41–7.61 (m, 3’, 4’H, 3H) 7.71–8.31 (m, 5H, Ar–H), 10.88, 11.03 (s,
2H, –NH), 13 C NMR (75 MHz, DMSO) δ (ppm): 53.84 (CH2), 122.24 (1’C), 127.24 (2’C), 129.89 (3’C), 133.3
(chloro-C) 147.50 (nitro-C), 163.19 (tetrazole ring carbon), 164.30, 165.74 (C=O). Analysis of C16 H12 ClN7 O4
(401.06). (% calcd./found): C: 47.83/47.50, H: 3.01/3.70, N: 24.40/24.80. MS, m/z(%): 401 [M]·+ (75), 403
(45), 242 (60), 202 (100), 199 (55), 159 (55).
3,5-Dimethoxy-N’-(2-(5-phenyl-2H -tetrazol-2-yl)acetyl)benzohydrazide (4e)
White solid (0.58 g, yield 76%). mp 265 ◦ C. IR (Neat) cm−1 : 1280 (N=N–N), 1552 (Ar–C=C), 1220
(–C–O), 1608 (C=N), 1652, 1656 (C=O), 3055 (Ar–C–H), 3132, 3170 (N–H); 1 H NMR (300 MHz, DMSO) δ
(ppm): 3.84 (s, 6H, –OMe), 5.51 (s, 2H, CH2), 6.69–7.63 (m, 9H, Ar-H), 9.98, 10.03 (s, 2H, –NH), 13 C NMR
(75 MHz, DMSO) δ (ppm): 53.36 (CH2), 57.69 (–OMe), 126.97 (1’C), 127.24 (2’C), 129.89 (3’C), 131.73 (4’C),
161.70 (3”, 5”Cs), 164.57 (tetrazole ring carbon), 167.30, 168.75 (C=O). Analysis of C18 H18 N6 O4 (382.14).
(% calcd./found): C: 56.54/56.10, H: 4.74/5.04, N: 21.98/22.02. MS, m/z(%): 382 [M]·+ (70), 223 (69), 202
(100), 180 (63), 159 (55).
4-Bromo-3,5-dimethoxy-N’-(2-(5-phenyl-2H -tetrazol-2-yl)acetyl)benzohydrazide (4f)
Brown solid (0.85 g, yield 78%). mp 282 ◦ C. IR (Neat) cm−1 : 790 (–C–Br), 1280 (N=N–N), 1549
(Ar–C=C), 1608 (C=N), 1654, 1659 (C=O), 3057 (Ar–C–H), 3132, 3170 (N–H); 1 H NMR (300 MHz, DMSO)
δ (ppm): 3.94 (s, 6H, –OMe), 5.50 (s, 2H, CH2), 6.69–7.63 (m, 9H, Ar–H), 9.88, 10.03 (s, 2H, –NH), 13 C
NMR (75 MHz, DMSO) δ (ppm): 53.36 (CH2), 56.69 (–OMe), 126.97 (1’C), 127.24 (2’C), 129.89 (3’C), 131.73
(4’C), 158.70 (3”, 5”Cs), 164.57 (tetrazole ring carbon), 166.30, 168.25 (C=O). Analysis of C18 H17 BrN6 O4
(460.05). (% calcd./found): C: 46.87/46.90, H: 3.71/3.62, N: 18.22/18.85. MS, m/z(%): 460 [M]·+ (80), 462
(45), 301(65), 258 (40), 243 (63), 202 (100), 217 (57), 159 (55).
N’-(2-(5-Phenyl-2H -tetrazol-2-yl)acetyl)furan-2-carbohydrazide (4g)
White solid (0.79 g, yield 88%). mp 198–200 ◦ C. IR (Neat) cm−1 : 1280 (N=N–N), 1551 (Ar–C=C), 1608
(C=N), 1654, 1659 (C=O), 3072 (Ar–C–H), 3130, 3168 (N–H); 1 H NMR (300 MHz, DMSO) δ (ppm): 5.64 (s,
2H, CH2), 6.66–8.09 (m, 8H, Ar–H), 10.55, 10.65 (s, 2H, –NH), 13 C NMR (75 MHz, DMSO) δ (ppm): 54.02
(CH2), 126.97 (1’C), 127.24 (2’C), 129.89 (3’C), 149.08 (1”C), 164.20 (tetrazole ring carbon), 164.30, 164.74
(C=O). Analysis of C14 H12 N6 O3 (312.10). (% calcd./found): C: 53.85/53.40, H: 3.87/4.00, N: 26.91/27.05.
MS, m/z(%): 256 [M]·+ (70), 257 (10), 258 (25), 202 (100), 154 (45), 159 (55), 197 (37).
439

SAEED et al./Turk J Chem
2-Oxo-N’-(2-(5-phenyl-2H-tetrazol-2-yl)acetyl)-2H -chromene-3-carbohydrazide (4h)
Light yellowish solid (0.91 g, yield 90%). mp 253 ◦ C. IR (Neat) cm−1 : 1280 (N=N–N), 1608 (C=N),
1654, 1660 (C=O), 3132, 3170 (N–H), 3250 (H–C=C–); 1 H NMR (300 MHz, DMSO) δ (ppm): 5.73 (s, 2H,
CH2), 7.43–8.10 (m, 9H, Ar–H), 8.91 (s, H–C=C–), 10.75, 11.47 (s, 2H, –NH), 13 C NMR (75 MHz, DMSO)
δ (ppm): 53.64 (CH2), 120.20 (1’C), 127.24 (2’C), 129.89 (3’C), 131.73 (4’C), 153.0 (olefinic-C), 159.4 (C=O),
164.19 (tetrazole ring carbon), 164.30, 165.74 (C=O). Analysis of C19 H14 N6 O4 (390.11). (% calcd./found):
C: 58.46/58.40, H: 3.61/3.62, N: 21.53/21.56. MS, m/z(%): 390 [M]·+ (68), 231 (25), 245 (55), 202 (100), 188
(45), 159 (55), 145 (57).
(E)-3-(4-Methoxyphenyl)-N ’-(2-(5-phenyl-2H -tetrazol-2-yl)acetyl)acrylohydrazide (4i)
White solid (0.85 g, yield 83%). mp 162–164 ◦ C. IR (Neat) cm−1 : 1280 (N=N–N), 1608 (C=N), 1654,
1659 (C=O), 1675 (C=C), 3132, 3170 (N–H), 3255 (H–C=C–); 1 H NMR (300 MHz, DMSO) δ (ppm): 3.8 (s,
–OMe), 5.75 (s, 2H, CH2), 6.91–8.37 (m, 9H, Ar–H), 6.53 (d, J = 15.9, 1H), 7.86 (d, J = 15.9, 1H), 10.88,
11.03 (s, 2H, –NH), 13 C NMR (75 MHz, DMSO) δ (ppm): 53.64 (CH2), 55.8 (–OMe), 114.24, 126.97 (1’C),
127.24 (2’, 2”C), 129.89 (3’C), 131.73 (4’C, 4”C), 109.62 (α-C), 152.14 (β -C), 164.19 (tetrazole ring carbon),
164.30, 164.74 (C=O). Analysis of C19 H18 N6 O3 (378.18). (% calcd./found): C: 60.31/59.95, H: 4.79/5.02, N:
22.21/22.26. MS, m/z(%): 378 [M]·+ (70), 219 (65), 202 (100), 258 (58), 176 (68), 120 (45), 159 (55).
N’-(2-(5-Phenyl-2H -tetrazol-2-yl)acetyl)pivalohydrazide (4j)
Light greenish solid (0.92 g, yield 97%). mp 135–137 ◦ C. IR (Neat) cm−1 : 1280 (N=N–N), 1608 (C=N),
1654, 1659 (C=O), 3125, 3160 (N–H); 1 H NMR (300 MHz, DMSO) δ (ppm): 1.20 (s, 9H), 5.61 (s, 2H,
CH2), 7.56–8.08 (m, 5H, Ar–H), 9.74, 10.37 (s, 2H, –NH), 13 C NMR (75 MHz, DMSO) δ (ppm): 28.3 (3C),
41.4 (quaternary-C), 54.95 (CH2), 126.97 (1’C), 128.24 (2’C), 129.89 (3’C), 163.19 (tetrazole ring carbon),
165.30, 166.74 (C=O). Analysis of C14 H18 N6 O2 (302.15). (% calcd./found): C: 55.62/55.58, H: 6.00/6.02, N:
27.80/27.78. MS, m/z(%): 302 [M]·+ (74), 202 (100), 187 (44), 115 (65), 100 (48).
3. Results and discussion
The synthesis of the title compounds (4a–j) was carried out according to the synthetic route sketched in Figure
2. Accordingly the [3+2] cycloaddition of sodium azide and benzonitrile in the presence of zinc chloride in
aqueous medium led to the formation of 5-phenyl-2H -1,2,3,4-tetrazole (1), which is capable of existing in
solution as equilibrium mixtures of N1 and N2 tautomers.2
The next step was the base catalyzed abstraction of the acidic NH of the tetrazole ring followed by
treatment with methyl 2-chloroacetate to afford the ester (2). A study of the literature shows that N-(R-
aminoalkyl)tetrazoles exist in solution as equilibrium mixtures of N1 and N2 tautomers. The position of
equilibrium depends significantly on the polarity of the solvent and the substituents in the tetrazole ring.
Interconversion between individual tautomers is shown to proceed via tight ion-pair intermediates in which
intramolecular recombination is faster than the intermolecular crossover since the latter probably requires solvent
separation of ion-pair intermediates.14 Normally, such reactions have been carried out using potassium carbonate
in acetone, which leads to the formation of isomeric esters, which not only requires separation. However, the
use of triethylamine and acetonitrile followed by recrystallization from n-hexane led to the formation of pure
methyl 2-(5-phenyl-2H -tetrazol-2-yl)acetate as a single pure tautomer. In FTIR the presence of stretches at
1756 cm−1 corroborates the attachment of ester (1b) moiety. In 1 H NMR, the presence of 2 and 3 proton
440

SAEED et al./Turk J Chem
singlets at 5.94 and 3.75 ppm indicated the methylene and ester methyl groups respectively and in the 13 C
NMR spectrum the signal at 167.11 ppm was observed for ester carbonyl carbon.
Reaction of ester (2) with slight excess of hydrazine hydrate in dry methanol at 45–50 ◦ C afforded 2-
(5-phenyl-2H -tetrazol-2-yl)acetohydrazide (3). In FTIR the stretching at 3132 (–NH) and 3307 (–NH2) cm−1
confirmed the conversion of ester into hydrazide. In the 1 H NMR spectrum the singlet at 4.46 ppm was assigned
to the –NH2 and that at 9.65 ppm to the –NH proton. In the 13 C NMR spectrum the slight upfield shift of
the carbonyl signal from 167.11 to 164.62 ppm further confirmed the conversion of ester into hydrazide.15
Finally a number of acid chlorides were freshly prepared by refluxing the carboxylic acids with thionyl
chloride. The title N -acyl/aroyl-2-(5-phenyl-2H -tetrazol-2-yl)acetohydrazides (4a–j) were obtained by stir-
ring acid chlorides at room temperature with 2-(5-phenyl-1H -tetrazole-1-yl)acetohydrazide (3) in dry N, N -
dimethylformamide (DMF) (Figure 2).
A typical aryl derivative (4e) bearing a 3,5-dimethoxyphenyl group showed absorption at 1280 (N=N–N),
1552 (Ar–C=C), 1220 (–C–O), 1608 (C=N), 1652, 1656 (C=O), 3055 (Ar–C–H), 3132, and 3170 cm−1 (N–H)
in the FTIR spectrum. 1 H NMR singlets at 3.84, 5.51, 9.98, and 10.03 are assignable to CH2 , NHs, and OMe
besides the aromatic protons. 13 C NMR showed characteristic methylene signals at 53.36, methoxy at 57.69,
tetrazole ring carbon at 64.57, and carbonyl carbons at 167.30 and 168.75 ppm.
In the case of a typical heteroaryl compound (4h) bearing a 3-coumarinyl substituent, in the 1 H NMR
Figure 2. Synthesis of N -acyl/aroyl-2-(5-phenyl-2H -tetrazol-2-yl)acetohydrazides.
441

SAEED et al./Turk J Chem
spectrum singlets appeared at 5.73 10.75, and 11.47, for CH2 and NHs, and the doublet at 8.9 ppm indicated
the olefinic proton of the coumarin ring. The 13 C NMR spectrum showed the corresponding signals at 53.64
(CH2), 153.0 (olefin-C), 159.4 (lactonic C=O), 164.19 (tetrazole ring carbon), and 164.30 and 165.74 (C=O)
ppm, besides aromatic carbons in the range 120.2–131.1.
4. Conclusion
In the present study, different acyl/alkenyl or aroyl groups were attached to the tetrazole hydrazide nucleus via
–CONH–NH–CO– linkage to obtain new compounds with potentially improved biological activities and for use
as novel ligands in coordination chemistry.
References
1. Xue, X.; Wang, X.; Wang, L.; Xiong, R.; Abrahams, F.; You, X.; Xue, Z.; Che, C. Inorg. Chem. 2002, 41, 6544–
6546.
2. Demko, Z. P.; Sharpless, K. B. J. Org. Chem. 2001, 66, 7945–7950.
3. Varadaraji, D.; Suban, S. S.; Ramasamy, V. R.; Kubendiran, K.; Raguraman, J. S. K. G.; Nalilu, S. K.; Pati, H.
N. Org. Commun. 2010, 3, 45–56.
4. Malik, M. A.; Al-Thabaiti, S. A.; Malik, M. A. Int. J. Mol. Sci. 2012, 13, 10880–10898.
5. Maione, S.; Morera, E.; Marabese, I.; Ligresti, A.; Luongo, L.; Ortar G.; Marzo, V. D. Br. J. Pharmacol. 2008,
155, 775–782.
6. Rajasekaran, A.; Thampi, P. P. Eur. J. Med. Chem. 2004, 39, 273–279.
7. Bepary, S.; Das, B. K.; Bachar, S. C.; Kundu, J. K.; Rouf, A. S. S.; Datta, B. K. Pak. J. Pharm. Sci. 2008, 21,
295–298.
8. Sun, X.; Wei, C.; Deng, X.; Sun, Z. Pharma. Rep. 2010, 62, 273–277.
9. Gao, Y. L.; Zhao, G. L.; Liu, W.; Shao, H.; Wang, Y. L.; Xu, W. R.; Tang, L. D.; Wang, J. W. Indian. J. Chem.
2010, 49B, 1499–1508.
10. Rao, S. N.; Babu, K. S. Org. Commun. 2011, 4, 105–111.
11. Bhaskar, V. H.; Mohite, P. B. Digt. J. Nanomat. Biostruct. 2010, 5, 177–183.
12. Khanage, S. G.; Mohite, P. B.; Pandhare R. B.; Deshmukh, V. K.; Raju, S. A. Drug Invention Today 2010, 2,
240–243.
13. Bhaskar, V. H.; Mohite, P. B. Dig. J. Nanomater. Bios. 2010, 5, 177–183.
14. Katritzky, H. A. R.; El-Gendy B. E. M.; Draghici, B.; Dennis, C.; Steel, P. J. J. Org. Chem. 2010, 75, 6468–6476.
15. LaForge, R. A.; D’Adamo, A.; Cosgrove, C. E.; Jacobson, C. R. J. Org. Chem. 1956, 21, 767–771.
442

Copyright of Turkish Journal of Chemistry is the property of Scientific and Technical
Research Council of Turkey and its content may not be copied or emailed to multiple sites or
posted to a listserv without the copyright holder's express written permission. However, users
may print, download, or email articles for individual use.