Synthesis and Biological Evaluation of Some Heterocyclic Compounds from Salicylic Acid Hydrazide

Article abstract of DOI:10.1002/jhet.2516

Different heterocyclic compounds were prepared starting from 2-hydroxy benzohydrazide; for example, cyclization of hydrazide hydrazone 3 derived from 2-hydroxybenzohydrazide 2 with acetic anhydride or concentrated sulfuric acid gave 1,3,4-oxadiazole derivatives 4–5. On the other hand, direct cyclization of 2-hydroxy benzohydrazide 2 with one carbon cyclizing agent gave a new derivative of 1,3,4-oxadiazole 7, 8, 9, 10, 11. Heating of hydrazide hydrazone 3 with thioglycolic acid in pyridine gave thiazolidinone 12. When 2-hydroxy benzohydrazide 2 reacted with aliphatic carboxylic acids such as formic acid or acetic acid, it gave the corresponding N-formyl or N-acetyl derivatives 6. Subsequent cyclization of 6 using phosphorous pentasulphide in pyridine gave 1,3,4-thiadiazoles 13. Cyclization of 2-hydroxy benzohydrazide with ethyl acetoacetate gives pyrazolone derivative 14. Finally, when an ethanolic solution of acid hydrazide 2 was treated with ammonium thiocyanate in 35% HCl, it gave the thiosemicarbazide 15. Subsequent treatment of 15 with concentrated sulfuric acid or 10% sodium hydroxide gave 5-amino-1,3,4-thiadiazole 16 and 1,2,4-triazole 17, respectively. The structures of all newly isolated compounds were confirmed using¹H NMR, IR spectra, and elemental analyses. The antimicrobial activities for all isolated compounds were examined against different microorganisms.

Full text of DOI:10.1002/jhet.2516

Month 2015
Synthesis and Biological Evaluation of Some Heterocyclic Compounds
from Salicylic Acid Hydrazide[1]
a
b
b
a
*
E. M. Sarshira, N. M. Hamada, Y. M. Moghazi, and M. M. Abdelrahman
aDepartment of Chemistry, Faculty of Science, Alexandria University, Alexandria 21321, Egypt
bDepartment of Chemistry, Faculty of Education, Alexandria University, Alexandria 21526, Egypt
*
E-mail: nagwahamada2002@yahoo.com
Received December 7, 2014
DOI 10.1002/jhet.2516
Published online in 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
Different heterocyclic compounds were prepared starting from 2-hydroxy benzohydrazide; for example,
cyclization of hydrazide hydrazone 3 derived from 2-hydroxybenzohydrazide 2 with acetic anhydride or
concentrated sulfuric acid gave 1,3,4-oxadiazole derivatives 4–5. On the other hand, direct cyclization of
2-hydroxy benzohydrazide 2 with one carbon cyclizing agent gave a new derivative of 1,3,4-oxadiazole
7–11. Heating of hydrazide hydrazone 3 with thioglycolic acid in pyridine gave thiazolidinone 12. When
2-hydroxy benzohydrazide 2 reacted with aliphatic carboxylic acids such as formic acid or acetic acid, it
gave the corresponding N-formyl or N-acetyl derivatives 6. Subsequent cyclization of 6 using phosphorous
pentasulphide in pyridine gave 1,3,4-thiadiazoles 13. Cyclization of 2-hydroxy benzohydrazide with ethyl
acetoacetate gives pyrazolone derivative 14. Finally, when an ethanolic solution of acid hydrazide 2 was
treated with ammonium thiocyanate in 35% HCl, it gave the thiosemicarbazide 15. Subsequent treatment
of 15 with concentrated sulfuric acid or 10% sodium hydroxide gave 5-amino-1,3,4-thiadiazole 16 and
1
1,2,4-triazole 17, respectively. The structures of all newly isolated compounds were confirmed using H
NMR, IR spectra, and elemental analyses. The antimicrobial activities for all isolated compounds were ex-
amined against different microorganisms.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
a highly privileged structure, the derivatives of which ex-
hibit a wide range of biological activities including antibac-
terial [28], antitubercular [29], vasodialatory [30], antifungal
[31], cytotoxic [32–34], hypolipidemic [35], anticancer [36],
and ulcerogenic [37] activities. 1, 3, 4-Oxadiazole deriva-
tives have been found to possess broad spectrum antimicro-
bial activity and therefore are useful substructures for further
molecular exploration [38].
Hydrazides and related compounds have been described
as useful building blocks for the assembly of various het-
erocyclic rings [2,3]. A large number of aliphatic, alicyclic,
aromatic, and heterocyclic carbohydrazides are reported to
present a plethora of biological activities [4–17]. In recent
years, Hydrazides have received much attention because of
their biological activities as tuberculostatic [18], antibacte-
rial agent [19], antitumor agent [20], and anticancer agent
[21]. In view of their high reactivity, hydrazides are also
important starting materials and intermediates in the
synthesis of hydrazones and heterocyclic compounds
[22–26]. Oxadiazole moiety and its various derivatives
were studied frequently in the past few decades and found
to be potent in various pharmacological and pathological
conditions [27]. Literature reveals that 1,3,4-oxadiazole is
RESULTS AND DISCUSSION
2-Hydroxybenzohydrazide 2 was prepared in good yield
for heterocyclic compounds synthesis by heating methyl
salicylate with hydrazine hydrate in 95% ethanol [39,40].
The synthetic routes to our prepared compounds 2–17 are
shown in Schemes 1, 2, and 3.
© 2015 HeteroCorporation

E. M. Sarshira, N. M. Hamada, Y. M. Moghazi, and M. M. Abdelrahman
Vol 000
Synthesis of 1,3,4-oxadiazole derivatives. In this work,
oxadiazole ring annulations were performed by two different
routes. The first route required cyclization of hydrazide
hydrazone 3 derived from 2-hydroxybenzohydrazide 2 using
either acetic anhydride or concentrated sulfuric acid
(Scheme 1).
such as aliphatic carboxylic acids, aromatic carboxylic acids,
ethyl chloroformate, chloroacetic acid, and carbon di-
sulphide (Scheme 2).
Synthesis of 1, 3, 4-oxadiazoles from hydrazide
hydrazones. Hydrazide hydrazones 3a-k were prepared
in good yields by acid catalyzed condensation of 2-
hydroxybenzohydrazide
2
with the appropriate
The second one required cyclization of 2-
hydroxybenzohydrazide 2 with one carbon cyclizing agent
benzaldehyde or acetophenone derivatives (Scheme 1).
Scheme 1
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Synthesis and Biological Evaluation of Some Heterocyclic Compounds from
Salicylic Acid Hydrazide
Scheme 3
The structures of the isolated compounds were supported
by spectral methods. The IR of benzaldehyde hydrazones
(R = H) 3a-f and acetophenone hydrazones (R=CH3) 3g-k
showed the characteristic bands for C¼C at 1528–1579,
C¼N at 1600–1620, C¼O at 1630–1642, secondary amine
acetic anhydride at the azomethine carbon of the
carbazone moiety followed by tautomerization, subsequent
nucleophilic attack by the unshared electron over the
oxygen atom of the hydroxyl group at the benzylic carbon,
and loss of acetic acid afford the desired products.
(NH) at 3196–3280, and phenolic OH at 3310–3467cmꢀ1
,
1
respectively. The H NMR spectra of 3a-k showed the
presence of two exchangeable singlets characteristic for
NH and phenolic OH protons. The aromatic protons of
3a-k appeared as a multiplet at δ = 6.88–8.28 ppm
characteristic for the aromatic protons. The azomethine proton
(CH¼N) of 3a-f appeared as a singlet at 8.39–8.65 ppm.
In the case of acetophenone hydrazones 3g-k, the 1H
NMR spectra revealed the presence of a singlet equivalent
to three protons intensity for methyl group attached to the
azomethine group (CH3–C¼N) at 2.26–2.34 ppm. The
cyclization reaction of the hydrazide hydrazone with
acetic anhydride to N-acetyl oxadiazole has been well
discussed [41–44]. Herein in the same context, treatment
of 3a-k with acetic anhydride produced N-acetyl
oxadiazole derivatives 4a-k in good yields (Mechanism 1).
The reaction would be initiated by nucleophilic addition of
The structures of 4a-k were supported by spectral
methods. The IR spectra revealed the absence of OH and
NH bands characteristic for the starting hydrazide
hydrazones, and instead they showed the characteristic bands
for amide carbonyl and ester carbonyl groups at 1656–1670
and 1733–1776cmꢀ1, respectively. The 1H NMR spectra of
Journal of Heterocyclic Chemistry
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E. M. Sarshira, N. M. Hamada, Y. M. Moghazi, and M. M. Abdelrahman
Vol 000
4a-k revealed the following signals: a singlet at δ=2.12–
2.88ppm characteristic for the N–COCH3 protons, another
singlet at δ =2.28–2.97ppm characteristic for the O-acetyl
protons attached to phenyl group (Ph–O–COCH3), and a
multiplet at δ =6.97–8.23 ppm characteristic for the aromatic
protons. In the case of 4a-f, C2-H of the 1,3,4-oxadiazole ring
appeared as a singlet at the deshielding area δ=6.87–
7.12ppm, while the methyl protons attached to C2 of the
1,3,4-oxadiazole ring for 4g-k appeared as a singlet at
δ=2.22–2.56ppm. On the other hand, when benzaldehyde
hydrazone derivatives (R = H) 3a-f were stirred for 2 days
with concentrated sulfuric acid [45] at room temperature, they
underwent cyclization reaction to give 2,3-dihydro-5-(2-
hydroxyphenyl)-2-aryl-1,3,4-oxadiazoles 5a-f (Scheme 1). It
is noteworthy that treatment of acetophenone hydrazone de-
rivatives (R= CH3) 3g-k with concentrated sulfuric acid
and subsequent neutralization using 10% Na2CO3 resulted
in formation of the starting 2-hydroxybenzohydrazide 2 and
acetophenone derivatives. The structure of 2,3-dihydro-
oxadiazole 5a-f was supported by spectral methods. The IR
spectra of 5a-f revealed the characteristic bands for C¼C at
1537–1602, C¼N at 1606–1625, NH at 3250–3380, and phe-
nolic OH at 3440–3480cmꢀ1. The 1H NMR spectra showed
the presence of two exchangeable singlet at δ=8.66–
11.79ppm and at δ=8.72–11.89 ppm characteristic for the
NH and OH protons, respectively. The C2-H of the 2,3-
dihydro-oxadiazole 5a-f appeared as a singlet and the aro-
intensity due to incorporation of acetyl group (COCH3).
On the other hand, the IR spectra of the 1,3,4-oxadiazoles
7a-b indicated the presence of stretching vibration bands
for C–O–C at 1265–1288, C¼C at 1503–1568, C¼N at
1609–1640, and OH at 3411–3439cmꢀ1. The IR spectra
of 7a-b lacked the presence of primary and secondary
amine stretching vibration bands characteristic of the
starting 2-hydroxybenzohydrazide 2. The 1H NMR
spectra of 7a-b showed an exchangeable singlet of one
proton intensity at 10.36–10.88 ppm for the phenolic OH
group and a multiplet of four protons intensity at 6.91–
7.93 ppm for the hydroxyphenyl aromatic protons. The
oxadiazole C5-H of 7a appeared as a singlet at 6.71ppm,
while the methyl protons attached to position five at the
oxadiazole ring in 7b appeared as a singlet of three
protons intensity at 2.83ppm. One pot cyclization reaction
to 1,3,4-oxadiazole derivative was performed by refluxing
acid hydrazide, aromatic carboxylic acid, and
phosphorous oxychloride [50]. Therefore, when a mixture
of 2-hydroxybenzohydrazide 2, p-substituted benzoic acid
and phosphorous oxychloride was heated under reflux, it
gave 2-(2-hydroxyphenyl)-5-aryl-1,3,4-oxadiazole 8a-b.
According to mechanism 2, the intermediate diaroyl
hydrazine (II) will be formed through the reaction of acid
chloride (I) with acid hydrazide 2. The reaction proceeds
through an ordinary nucleophilic substitution by the
electron pair of N-2 atom of the hydrazide to the acid
chloride carbonyl group. Finally, cyclodehydration
process of the intermediate (II) will take place by its
reaction with phosphorous oxychloride, which acts as a
chlorinating and dehydrating agent to give oxadiazole 8.
matic protons appeared as a multiplet at δ=6.94–8.62ppm.
Synthesis of 1,3,4-oxadiazoles from 2-hydroxybenzohydrazide.
Through previous studies, it has been reported that
treatment of some hydrazides with formic acid [46,47]
gave 1-formyl-2-acyl hydrazine, the synthesized 1-formyl
derivatives were converted to 2-substituted-1,3,4-
oxadiazoles by their reaction with phosphorous
oxychloride. Likewise, our study showed that the reaction
of 2-hydroxybenzohydrazide 2 with either formic acid or
acetic acid gave N-formyl or N-acetyl derivative 6a-b
(Scheme 2) and that subsequent dehydrative cyclization of
6a-b using phosphorous oxychloride gave 7a-b. The IR
spectra of 6a-b showed the characteristic bands for C¼C
at 1578–1609, NH–CO–Ph at 1634–1649, NH–CO–R
(R = H, CH3) at 1671–1684, and OH stretching vibration
band at 3304–3415 cmꢀ1, while the 1H NMR spectra
showed three exchangeable hydrogens at 10.15–
10.34 ppm, 10.50–10.59 ppm and 11.79–11.88 ppm
characteristic for NHCOR, o–OH–Ph–CO–NH and
phenolic OH, respectively. The aromatic ring protons of
6a-b appeared at 6.90–8.12 ppm. In the case of 6a, the
formyl proton (O¼C–H) appeared as a singlet at
8.13ppm. The high chemical shift value for the formyl
proton of 6a was attributed to strong deshielding effect by
the electronegative nitrogen atom and anisotropic effect of
carbonyl group [48,49]. The 1H NMR spectra of 6b
showed another singlet at δ= 1.94 ppm of three protons
The structure of 8a-b was confirmed by elemental anal-
yses and spectral methods. The IR spectra for 8a-b do not
reveal the characteristic stretching vibration bands of the
primary and secondary amine group at the starting hydra-
zide 2, but it reveals the OH stretching vibration band at
1
3133–3290cmꢀ1. The H NMR spectra of 8a-b showed a
broad exchangeable singlet at 10.38–12.07 ppm character-
istic for phenolic proton (OH), while the aromatic protons
appeared as a multiplet at 6.71–8.39 ppm.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Synthesis and Biological Evaluation of Some Heterocyclic Compounds from
Salicylic Acid Hydrazide
5-(2-Hydroxyphenyl)-1,3,4-oxadiazol-(3H)-2-one 9 was
synthesized through the reaction of the acid hydrazide 2
with ethyl chloroformate under reflux in n-butanol. The
IR spectrum of 9 showed absorption bands at 1562
(C¼C), 1608 (C¼N), 1640 (C¼O), 3094 (NH), and
band at 1630 cmꢀ1. A new strong band at 1699 cmꢀ1 in
the IR spectrum of 12 provided firm support for ring
closure. The most significant evidence for the reaction
was the presence of two doublets (dd, 2H, C5-H of
thiazolidine ring, J = 16 and 16 Hz) at δ = 3.79 ppm and
1
1
3448 cmꢀ1 (OH). The H NMR spectrum of 9 showed a
3.93 ppm in the H NMR spectrum of 12 [55]. Geminal
multiplet at δ= 6.92–7.89 ppm characteristic for four aro-
matic protons and two exchangeable singlets at
10.88 ppm and 11.80 ppm characteristic for NH and OH
protons, respectively. These data are in agreement with
the proposed structure for compound 9.
splitting was explained by the presence of chiral carbon
at C2 of the thiazolidine ring, which resulted in two
diastereotopic hydrogens at C5-H of the thiazolidine
ring. Moreover, the H NMR spectrum of 12 showed a
singlet at 6.03 ppm because of C2-H of the thiazolidine
1
5-Chloromethyl-2-(2-hydroxyphenyl)-1,3,4-oxadiazole
10 was prepared by condensation of acid hydrazide 2 with
chloroacetic acid using phosphorous oxychloride as
cyclising agent [51]. The most characteristic IR bands of
2-hydroxybenzohydrazide 2 appeared at 1597 for C¼C,
3270 cmꢀ1 for NH2 and NH, which disappeared in the
spectrum of compound 10 with new bands that appeared
at 1239 and 1626 cmꢀ1 because of C–O–C and C¼N
stretching vibrations, respectively. The 1H NMR spectrum
of compound 10 showed a singlet at δ =5.09 ppm because
of CH2–Cl protons, a multiplet at δ = 6.95–7.74 ppm be-
cause of aromatic protons, and an exchangeable singlet
equivalent to one proton intensity at δ= 10.35ppm because
of OH proton. These data confirmed the conversion of acid
hydrazide 2 to 1, 3, 4-oxadiazole derivative 10. When hy-
drazide 2 was reacted with carbon disulphide in ethanolic
KOH, it gave the corresponding 5-(2-hydroxyphenyl)-
1,3,4-oxadiazole-2(3H)-thione 11 in good yield. The ab-
sence of the characteristic weak SH stretching band at
2550–2600 cmꢀ1 and the appearance of strong C¼S
stretching band at 1180 cmꢀ1 in the IR spectrum of com-
pound 11 confirmed its thione form and excluded the
tautomeric thiol structure [52–54]. The IR spectrum of
11 showed also bands at 1266 cmꢀ1 (C–O–C stretching
of oxadiazole ring), 1576 cmꢀ1 (C¼C), 1613 cmꢀ1
ring.
When
N-formyl-
or
N-acetyl-2-
hydroxybenzohydrazide 6a-b was heated under reflux
with phosphorous pentasulphide in pyridine, it gave
1,3,4-thiadiazole derivative 13a-b. The structure of 13
was assigned on the basis of its IR, 1H NMR, and
elemental analysis. The IR spectra of 13 do not reveal
the presence of C¼O at the starting 6, but it showed
C¼N stretching vibration bands at 1624–1630 cmꢀ1
.
Furthermore, the IR spectra of 13 lacked the presence of
two stretching vibration bands for the two secondary
amino groups at the starting compound 6. The H NMR
1
spectra of 13a-b lacked the presence of two
exchangeable singlets characteristic for two amino
groups (2 NH) at the starting compound 6. The IR
spectrum of compound 15 revealed the appearance of a
new absorption band for C¼S. Stretching vibration at
1236 cmꢀ1 confirmed a thiosemicarbazide formation
[56]. The most significant evidence for the reaction was
the presence of four exchangeable singlets expressed
NH2 protons overlapped with aromatic hydrogens at
δ= 6.87–7.78 ppm, two NH protons at 9.40 ppm and
10.51 ppm, and OH proton at 11.85 ppm in the 1H
NMR spectrum of 15. The thiosemicarbazide 15 was
converted to 1,3,4-thiadiazole 16 and 1,2,4-triazole
17 by its reaction with concentrated sulfuric acid [57]
and 2 N sodium hydroxide [58] solution, respectively.
The structures of 1,3,4-thiadiazole 16 and 1,2,4-
triazole 17 were confirmed by spectral methods. The
IR spectra of 16 showed a new strong absorption
band at 1633 cmꢀ1 (C¼N), and it lacked the presence
of C¼S and C¼O stretching vibration bands in the
starting thiosemicarbazide 15.
1
(C¼N), 3204 cmꢀ1(NH), and 3333 cmꢀ1(OH). The H
NMR spectrum revealed the presence of the two ex-
changeable singlets at 10.43 ppm and 14.61 ppm char-
acteristic for the oxadiazolyl NH proton and phenolic
proton, respectively. The 1H NMR spectrum showed
also a multiplet at 6.93–7.62 ppm equivalent to four ar-
omatic protons.
1
The H NMR spectrum of 16 revealed the existence of
Synthesis of thiazolidinone, 1,3,4-thiadiazoles, pyrazole
and 1,2,4-triazole. In this part, we are interested in the
two exchangeable singlets at δ= 9.25 ppm (NH2) and
11.75 ppm (OH) instead of four exchangeable singlets
characteristic for the starting thiosemicarbazide 15. In the
case of 17, we have observed that extensive thiol–thione
synthesis of different types of heterocyclic compounds to
show the importance of 2-hydroxybenzohydrazide in
heterocyclic synthesis. The synthetic pathways for our
prepared compounds are outlined in Scheme 3. For
example, condensation of hydrazone 3a with thioglycolic
acid in dry pyridine gave thiazolidinone derivative 12.
The IR spectrum of 12 lacked the presence of C¼N
stretching vibration band at the starting hydrazone 3a. The
IR spectrum of the starting hydrazone 3a showed C¼O
1
tautomerism exists. In DMSO-d6 solution, the H NMR
spectrum of 17 showed an exchangeable singlet at
δ= 13.67 ppm, whereas IR (KBr) spectra of triazole 17 in
a solid state indicated a strong absorption band for C¼S
stretching vibration at 1242 cmꢀ1. It has been reported that
the crystal structures of 17-like compounds correspond to
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

E. M. Sarshira, N. M. Hamada, Y. M. Moghazi, and M. M. Abdelrahman
Vol 000
Table 1
Antimicrobial activities of all the synthesized compounds.
MIC in μg/mL and inhibition zone (A in mm) for different organisms
Compounds
numbers
Staphylococcus aureus
Candida albicans
MIC
Escherichia coli
MIC
A
8
MIC
—
A
13
15
15
15
13
13
15
15
13
15
13
25
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
18
15
15
15
15
15
27
30
15
15
15
15
15
20
15
23
30
13
A
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
16
10
10
10
10
10
10
10
10
10
26
10
3a
—
—
—
—
—
—
—
—
—
—
—
125
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
3b
3c
3d
3e
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
3f
3 g
3 h
3i
3j
3 k
4a
4b
4c
4d
4e
4f
4 g
4 h
4i
4j
4 k
5a
5b
5c
5d
5e
5f
6a
6b
7a
7b
8a
8b
9
10
11
12
13a
13b
14
15
16
17
Imipenem
DMF
8
—
20
11
8
8
8
62.50
31.25
—
—
—
—
—
62.50
—
62.50
—
62.5
62.5
—
—
—
—
—
31.5
—
62.5
—
62.5
—
—
—
—
—
—
—
—
—
—
—
8
8
15
8
15
30
8
—
—
MIC, minimum inhibitory concentration.
the thione form [59,60], but they showed thiol–thione tau-
tomerism in solution.
antimicrobial activity of various heterocyclic compounds
have been carried out. Prompted by these observations,
the antimicrobial activity of the synthesized compounds
was evaluated. All of our compounds were tested for
antimicrobial activity against three test organisms:
Staphylococcus aureus ATCC6538P, Escherichia coli
ATCC8739 and Candida albicans ATCC2091 using
Imipenem (10 μg/ disc) as standard drug. The agar well-
Antimicrobial activity. A drug is considered to have
bacteriostatic or fugistatic activity when it inhibits the
growth of bacteria or fungi, respectively, and bactericidal
or fungicidal when it kills the bacteria or fungi. Literature
survey reveals that the synthesis and evaluation of
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Synthesis and Biological Evaluation of Some Heterocyclic Compounds from
Salicylic Acid Hydrazide
diffusion method [61,62] was used for studying the
potential activities of these compounds. Minimum
inhibitory concentration (MIC) values for the individual
compounds that showed inhibition zones >10 were
determined by means of the agar well-diffusion method
in DMF. The results of antimicrobial activities of our
synthesized compounds against S. aureus and C. albicans
are shown in Table 1 as zone of inhibition (mm) and
minimum inhibitory concentration, MIC (μg/mL). The
investigation of antimicrobial screening revealed that
compound 9 showed significant activity against E. coli,
whereas the others had no remarkable activity on this
strain. Moreover, compound 9 was found to be more
active than the others against S. aureus and showed
moderate activity against C. albicans; on the other hand,
compound 10 was found to be more active than the
others against C. albicans, with low significant activity
against S. aureus. This depends on the different
substituents at C-5 position of the oxadiazole ring of both
The 1H-NMR spectra were measured in deuterated chloro-
form (CDCl3) or deuterated dimethylsulphoxide (DMSO-
d6) on a Jeol EAC 500MHz FT-NMR spectrophotometer
(Faculty of Science, Alexandria University, Egypt) and
on a Bruker AVANCE III Nano Bay 400 MHz FT-NMR
spectrophotometer (Faculty of Pharmacy, Cairo Univer-
sity, Egypt) and on a Varian Mercury VX-300 MHz spec-
trophotometer (Faculty of Science, Cairo University,
Egypt). Chemical shifts were recorded in δ as parts per
million (ppm) downfield from tetramethylsilane (TMS) as
internal standard. Reaction progresses were monitored by
thin layer chromatography (TLC) using Macherey-Nagel
Alugram Sil G/UV254 silica gel plates, and chloroform or
chloroform-ethanol (9:1) or (19:1) was used as an eluting
system to examine compound purity and reaction comple-
tion. The spots were visualized using Vilber Lourmet ultra-
violet lamp at 254= ג and 266 nm or using iodine vapor.
General procedure for preparation of 2-hydroxybenzo-
hydrazide (2). A mixture of methyl salicylate 1 (10 mM)
compounds
9,10
(ꢀC¼O,-CH2Cl),
respectively.
and hydrazine hydrate (20 mM) was heated under reflux
in 50mL of 95% ethanol for 15h, then the reaction
mixture was concentrated and poured onto crushed ice.
The separated crude solid was filtered off, washed
successively with water, dried and recrystallized from
ethanol to give 2 as colorless needles. The yield of 2 was
77%, m.p. 142–144°C and IR as reported previously in
literature [39,40].
General procedure for preparation of hydrazones (3a–k).
A mixture of the appropriate 2-hydroxybenzohydrazide 2
(10 mM), benzaldehyde, or acetophenone derivatives
(10 mM) in absolute ethanol (10 mL) and a few drops of
acetic acid was refluxed for 5–9 h, the reaction mixture
was left to attain room temperature, and the solid matter
that separated was filtered off and recrystallized from
ethanol to give hydrazones 3a-k.
Compounds 15,17 showed activity against S. aureus and
C. albicans. Compound 4a showed activity towards C.
albicans in the same range with compounds 9, 15, 17,
whereas it showed no activity against S. aureus.
From the aforementioned results, it can be concluded
that the trend of activity against S. aureus was observed
as follows: 9 >15¼17 >10, while 4a showed no activity,
and the trend of activity against C. albicans observed was
as follows: 10 > 9> 4a > 17 >15.
CONCLUSIONS
Many heterocyclic compounds were prepared starting
from 2-hydroxybenzohydrazide and its corresponding
hydrazide–hydrazones. The isolated compounds were ex-
amined against different microorganisms; structure–
activity relationship (SAR) plays an important role in the
study of the activities of synthesized compounds. The anti-
microbial activities for oxadiazoles depend on substituents
at C5 of the oxadiazole ring.
N-(Phenylmethylidene)-2-hydroxybenzohydrazide (3a).
Compound 3a was obtained in 88% yield as colorless
needles by recrystallization from ethanol, m.p. 244–
245°C; IR (KBr): (C¼C) 1564, (C¼N) 1620, (C¼O)
1
1630, (NH) 3237, (OH) 3450cmꢀ1; H NMR (DMSO-d6,
500MHz,) δ: 3.32 (s, 1H, NH), 6.94–6.99 (m, 2H, Ar-H),
7.43–7.49 (m, 4H, Ar-H), 7.75–7.77 (m, 2H, Ar-H),
7.88–7.91 (m, 1H, Ar-H), 8.47 (s, 1H, CH¼N), 11.85 (s,
1H, OH); Anal. calcd. For C14H12N2O2: C, 70.00; H,
5.00; N, 11.67. Found: C, 70.01; H, 4.96; N, 11.63.
EXPERIMENTAL
Melting points were taken in open capillary tubes using
an Electrothermal apparatus 9100 (Rochford, UK), and
they were uncorrected. Elemental microanalyses were per-
formed at the Regional Center for Mycology and Biotech-
nology, Al-Azhar University, Egypt, using an elemental
analyzer Euro EA 3000 (Italy). IR spectra were recorded
using potassium bromide disk on a Perkin Elmer Spectrum
RXI/FT-IR System (Faculty of Pharmacy, Alexandria Uni-
versity, Egypt) and on a Bruker FT-IR spectrometer
N-[(4-Chlorophenyl)methylidene]-2-hydroxybenzohydrazide
(3b). Compound 3b was isolated as colorless crystals in
83% yield by recrystallization from ethanol, m.p. 259–
261°C; IR (KBr) : (C¼C) 1528, (C¼N) 1606, (C¼O)
1
1632, (NH) 3280, (OH) 3452 cmꢀ1; H NMR (DMSO-d ,
500 MHz,) δ: 6.94–7.91 (m, 9H, Ar-H and NH), 8.47 (s,
1H, CH¼N), 11.86 (s, 1H, OH); Anal. calcd. For
C14H11N2O2Cl: C, 61.09; H, 4.00; N, 10.18; Cl, 13.09.
Found: C, 61.12; H, 3.97; N, 10.15; Cl, 13.13.
Model: Tensor 37 and expressed in wave number (υmax
)
cmꢀ1 (Faculty of Science, Alexandria University, Egypt).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

E. M. Sarshira, N. M. Hamada, Y. M. Moghazi, and M. M. Abdelrahman
Vol 000
N-[(4-Bromophenyl)methylidene]-2-hydroxybenzohydrazide
(3c). Compound 3c was obtained in a good yield (87%) as
colorless crystals by recrystallization from ethanol, m.p.
245–246°C; IR (KBr): (C¼C) 1557, (C¼N) 1604,
(C¼O) 1642, (NH) 3276, (OH) 3440cmꢀ1
;
1H NMR
(DMSO-d , 500MHz) δ: 2.29 (s, 3H, CH3–C¼N),
6.96–7.00 (m, 2H, Ar-H), 7.47–7.49 (m, 3H, Ar-H),
7.84–7.85 (m, 3H, Ar-H), 11.32 (s, 1H, NH, D2O
exch), 11.76 (s, 1H, OH, D2O exch); Anal. calcd. For
C15H13N2O2Cl: C, 62.28; H, 4.50; N, 9.69; Cl, 12.30.
Found: C, 62.31; H, 4.55; N, 9.65; Cl, 12.26.
N-[(4-Bromophenyl)ethylidene]-2-hydroxybenzohydrazide
(3i). Compound 3i was obtained as colorless crystals in 77%
243–244°C; IR (KBr): (C¼C) 1554, (C¼N) 1600, (C¼O)
1
1630, (NH) 3250, (OH) 3441cmꢀ1; H NMR (DMSO-d6,
500MHz) δ: 6.92–6.95 (m, 2H, Ar-H), 7.40 (m, 1H, Ar-
H), 7.62–7.67 (m, 4H, Ar-H), 7.83 (m, 1H, Ar-H), 8.39
(s, 1H, CH¼N), 11.85 (s, 2H, OH and NH, D2O exch);
Anal. calcd. For C14H11N2O2Br: C, 52.66; H, 3.45; N,
8.78; Br, 25.08. Found: C, 52.63; H, 3.44; N, 8.74; Br,
25.01.
yield by recrystallization from ethanol, m.p. 253–255°C; IR
(KBr): (C¼C) 1543, (C¼N) 1605, (C¼O) 1640, (NH) 3205,
(OH) 3310 cmꢀ1; 1H NMR (DMSO-d , 500MHz) δ: 2.26 (s,
3H CH3–C¼N), 6.94–7.00 (m, 2H, Ar-H), 7.37–7.96(m,
6H, Ar-H), 11.34 (s, 1H, NH, D2O exch), 11.88 (s, 1H, OH,
D2O exch); Anal. calcd. For C15H13N2O2Br: C, 54.05; H,
3.90; N, 8.41; Br, 24.02. Found: C, 54.01; H, 3.84; N, 8.44;
N-[(4-Nitrophenyl)methylidene]-2-hydroxybenzohydrazide
(3d). Compound 3d was obtained as colorless crystals
in 88% yield by recrystallization from ethanol, m.p.
278–279°C; IR (KBr) : (C¼C) 1550, (C¼N) 1620,
(C¼O) 1633, (NH) 3251, (OH) 3460 cmꢀ1
;
1H NMR
(DMSO-d , 500MHz) δ: 3.52 (s, 1H, NH, D2O exch),
6.93–6.97 (m, 2H, Ar-H), 7.82 (m, 1H, Ar-H), 7.96 (m,
1H, Ar-H), 7.97 (m, 2H, Ar-H), 8.26–8.28 (m, 2H, Ar-
H), 8.51 (s, 1H, CH¼N), 12.02 (s, 1H, OH, D2O exch);
Anal. calcd. For C14H11N3O4: C, 58.95; H, 3.86; N,
Br, 24.07.
N-[(4-Nitrophenyl)ethylidene]-2-hydroxybenzohydrazide
(3j). Compound 3j was obtained as colorless crystals in
a good yield (79%) by recrystallization from ethanol, m.p.
265–266°C; IR (KBr): (C¼C) 1553, (C¼N) 1606, (C¼O)
1638, (NH) 3270, (OH) 3460 cmꢀ1; 1H NMR (DMSO-d ,
500 MHz) δ: 2.34 (s, 3H, CH3–C¼N), 6.96–7.00 (m, 2H,
Ar-H), 7.40 (m, 1H, Ar-H), 8.05–8.07 (m, 3H, Ar-H),
8.23–8.25 (m, 2H, Ar-H), 11.08 (s, 1H, NH, D2O exch),
11.46 (s, 1H, OH, D2O exch); Anal. calcd. For
C15H13N3O4: C, 60.20; H, 4.35; N, 14.05. Found: C,
14.74. Found: C, 58.94; H, 3.88; N, 14.76.
N-[(4-Methoxyphenyl)methylidene]-2-hydroxybenzohydrazide
(3e). Compound 3e was isolated as colorless crystals in
86% yield by recrystallization from ethanol, m.p. 218–
220°C; IR (KBr) : (C¼C) 1549, (C¼N) 1609, (C¼O)
1633, (NH) 3251, (OH) 3441cmꢀ1; H NMR (DMSO-d6,
1
500MHz) δ: 2.26 (s, 3H, CH3), 3.52 (s, 1H, NH, D2O
exch), 6.93–6.96 (m, 2H, Ar-H), 7.41 (m, 1H, Ar-H),
7.95–7.97 (m, 3H, Ar-H), 8.26–8.28 (m, 2H, Ar-H), 8.51
(s, 1H, CH¼N), 12.03 (s,1H, OH, D2O exch); Anal.
calcd. For C15H14N2O3: C, 66.67; H, 5.19; N, 10.37
Found C, 66.63; H, 5.19; N, 10.36.
N-[(2-Hydroxyphenyl)methylidene]-2-hydroxybenzohydrazide
(3f). Compound 3f was obtained as colorless crystals in a
60.23; H, 4.37; N, 14.02.
N-[(4-Methylphenyl)ethylidene]-2-hydroxybenzohydrazide
(3k). Compound 3k was obtained as colorless crystals in
75% yield by recrystallization from ethanol, m.p. 231–
233°C; IR (KBr): (C¼C) 1579, (C¼N) 1606, (C¼O)
1
1636, (NH) 3275, (OH) 3467 cmꢀ1; H NMR (DMSO-d ,
500 MHz) δ: 2.28 (s, 6H, CH3–C¼N and CH3–Ph), 6.96–
7.99 (m, 8H, Ar-H), 11.27 (s, 1H, NH), 11.78 (s, 1H,
OH); Anal. calcd. For C16H16N2O2: C, 71.64; H, 5.97; N,
10.45. Found: C, 71.69; H, 5.97; N, 10.41.
good yield (89%) by recrystallization from ethanol m.p.
273–274°C; IR (KBr) : (C¼C) 1555, (C¼N) 1616, (C¼O)
1635, (NH) 3196, (OH) 3438 cmꢀ1; H NMR (DMSO-d ,
1
500MHz) δ: 3.51(s, 1H, NH), 6.88–7.86 (m, 8H, Ar-H),
8.65 (s, 1H, CH¼N), 11.22 (s, 1H, OH), 12.02 (s, 1H, OH);
Anal. calcd. For C14H12N2O3: C, 65.63; H, 4.69; N, 10.94.
Found: C, 65.61; H, 4.66; N, 10.91.
General procedure for the preparation of 3-N-acetyl-5-[2-
acetoxy-phenyl]-2-aryl-2,3-dihydro-1,3,4-oxadiazole derivatives
and 3-N-acetyl-5-[2-acetoxyphenyl]-2-methyl-2-aryl-2,3-dihydro-
1,3,4-oxadiazole derivatives (4a–k).
A
mixture of
N-(Phenylethylidene)-2-hydroxybenzohydrazide (3g).
Compound 3g was obtained as colorless crystals in 80%
yield by recrystallization from ethanol, m.p. 201–202°C;
IR (KBr): (C¼C) 1547, (C¼N) 1607, (C¼O) 1639, (NH)
hydrazone derivatives 3a-k (2 mM) and acetic anhydride
(10 mL) was heated under reflux for 7–9 h. After cooling,
the reaction mixture was poured onto crushed ice water
with vigorous stirring. The formed precipitate was
collected by filtration and recrystallized from ethanol to
give 4 as colorless needles.
1
3276, (OH) 3464 cmꢀ1; H NMR (DMSO-d , 400 MHz)
δ: 2.29 (s, 3H, CH3–C¼N), 6.96–7.03 (m, 2H, Ar-H),
7.40–7.44 (m, 4H, Ar-H), 7.84–8.00 (m, 3H, Ar-H),
11.11 (s, 1H, NH, D2O exch), 11.77 (s, 1H, OH, D2O
exch); Anal. calcd. For C15H14N2O2: C, 70.87; H, 5.51;
N, 11.02. Found: C, 70.99; H, 5.49; N, 11.14.
3-N-Acetyl-5-[2-acetoxyphenyl]-2-phenyl-2,3-dihydro-1,3,
4-oxadiazole (4a).
Oxadiazole 4a was obtained in 77%
yield, m.p. 112–114°C; IR (KBr): (C–O–C) 1202, (C¼C)
1530, (C¼N) 1620, (amide C¼O) 1661, (ester C¼O)
1
1760cmꢀ1; H NMR (CDCl3, 400MHz) δ: 2.12 (s, 3H, N–
N-[(4-Chlorophenyl)ethylidene]-2-hydroxybenzohydrazide
(3h). Compound 3h was isolated as colorless crystals
CO–CH3), 2.47 (s, 3H, O–CO–CH3), 7.02 (s, 1H, C2-H of
in 78% yield by recrystallization from ethanol, m.p.
oxadiazole), 7.25–7.61 (m, 6H, Ar-H), 8.10–8.14 (m, 3H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Synthesis and Biological Evaluation of Some Heterocyclic Compounds from
Salicylic Acid Hydrazide
Ar-H); Anal. calcd. For C18H16N2O4: C, 66.67; H, 4.94; N,
C19H18N2O4: C, 67.46; H, 5.33; N, 8.28. Found: C,
8.64. Found: C, 66.64; H, 4.96; N, 8.60.
3-N-Acetyl-5-[2-acetoxyphenyl]-2-(4-chlorophenyl)-2,3-dihydro-1,
3,4-oxadiazole (4b). Oxadiazole 4b was obtained in 79%
67.52; H, 5.37; N, 8.29.
3-N-Acetyl-5-[2-acetoxyphenyl]-2-methyl-2-(4-chlorophenyl)-2,3-
dihydro-1,3,4-oxadiazole (4h). Oxadiazole 4h was obtained
yield, m.p. 134–137°C; IR (KBr): (C–O–C) 1193, (C¼C)
in 89% yield, m.p. 139°C; IR (KBr): (C–O–C) 1188,
(C¼C) 1602, (C¼N) 1634, (amide C¼O) 1669, (ester
1557, (C¼N) 1626, (amide C¼O) 1661, (ester C¼O)
1
1760 cmꢀ1; H NMR (CDCl3, 400MHz) δ: 2.46 (s, 3H,
1
C¼O) 1776 cmꢀ1; H NMR (CDCl3, 500MHz) δ: 2.23
N–CO–CH3), 2.56 (s, 3H, O–CO–CH3), 7.12 (s, 1H, C2-
H of oxadiazole), 7.26–7.62 (m, 5H, Ar-H), 8.04–8.10
(m, 3H, Ar-H); Anal. calcd. For C18H15N2O4Cl: C,
60.17; H, 4.18; N, 7.80; Cl, 10.03. Found: C, 60.21; H,
(s, 3H, C2-CH3 of oxadiazole), 2.29 (s, 6H, N–CO–CH3
and O–CO–CH3), 7.14–7.47 (m, 7H, Ar-H), 7.49 (m, 1H,
Ar-H); Anal. calcd. For C19H17N2O4Cl: C, 61.13; H,
4.56; N, 7.51; Cl, 9.65. Found: C, 61.19; H, 4.60; N,
7.52; Cl, 9.71.
4.25; N, 7.88; Cl, 9.98.
3-N-Acetyl-5-[2-acetoxyphenyl]-2-(4-bromophenyl)-2,3-dihydro-
1,3,4-oxadiazole (4c). Oxadiazole 4c was obtained in 74%
3-N-Acetyl-5-[2-acetoxyphenyl]-2-methyl-2-(4-bromophenyl)-2
,3-dihydro-1,3,4-oxadiazole (4i).
Oxadiazole 4i was
yield, m.p. 133–135°C; IR (KBr): (C–O–C) 1192, (C¼C)
obtained in 92% yield, m.p. 115–117°C; IR (KBr): (C–
O–C) 1187, (C¼C) 1608, (C¼N) 1633, (amide C¼O)
1542, (C¼N) 1605, (amide C¼O) 1661, (ester C¼O)
1
1760 cmꢀ1; H NMR (CDCl3, 400MHz) δ: 2.29 (s, 3H,
1669, (ester C¼O) 1776 cmꢀ1
;
1H NMR (CDCl3,
N–CO–CH3), 2.32 (s, 3H, O–CO–CH3), 6.95 (s, 1H,
53.60; H, 3.72; N, 6.95; Br, 19.85. Found: C, 53.69; H,
3.68; N, 7.03; Br; 19.91.
3-N-Acetyl-5-[2-acetoxyphenyl]-2-(4-nitrophenyl)-2,3-dihydro-
1,3,4-oxadiazole (4d). Compound 4d was obtained in 89%
500 MHz) δ: 2.23 (s, 3H, C2-CH3 of oxadiazole), 2.29 (s,
6H, N–CO–CH3 and O–CO–CH3), 7.16–7.50 (m, 7H,
Ar-H), 7.51 (m, 1H, Ar-H); Anal. calcd. For
C19H17N2O4Br: C, 54.68; H, 4.08; N, 6.71; Br, 19.18.
Found: C, 54.66; H, 4.11; N, 6.73; Br, 19.21.
yield, m.p. 171–174°C; IR (KBr): (C–O–C) 1192, (C¼C)
3-N-Acetyl-5-[2-acetoxyphenyl]-2-methyl-2-(4-nitrophenyl)-2,3
-dihydro-1,3,4-oxadiazole (4j). Oxadiazole 4j was obtained
1542, (C¼N) 1599, (amide C¼O) 1656, (ester C¼O)
1
1766 cmꢀ1; H NMR (CDCl3, 500MHz) δ: 2.33 (s, 3H,
in 90% yield, m.p. 121–123°C; IR (KBr): (C–O–C)
1193, (C¼C) 1606, (C¼N) 1634, (amide C¼O) 1663,
N–CO–CH3), 2.35 (s, 3H, O–CO–CH3), 7.07 (s, 1H, C2-
H of oxadiazole), 7.17–8.34 (m, 8H, Ar-H); Anal. calcd.
For C18H15N3O6: C, 58.54; H, 4.07; N, 11.38. Found: C,
58.50; H, 4.12; N, 11.41.
3-N-Acetyl-5-[2-acetoxyphenyl]-2-(4-methoxyphenyl)-2,3-di-
hydro-1,3,4-oxadiazole (4e). Oxadiazole 4e was obtained in
1
(ester C¼O) 1770 cmꢀ1; H NMR (CDCl3, 500MHz) δ:
2.28 (s, 3H, C2-CH3 of oxadiazole), 2.29 (s, 3H, N–CO–
CH3), 2.30 (s, 3H, O–CO–CH3), 7.16–7.75 (m, 6H, Ar-
H), 8.22–8.23 (m, 2H, Ar-H); Anal. calcd. For
C19H17N3O6: C, 59.53; H, 4.44; N, 10.97. Found: C,
82% yield, m.p. 139–141°C; IR (KBr): (C–O–C) 1190,
(C¼C) 1514, (C¼N) 1613, (amide C¼O) 1664, (ester
59.57; H, 4.39; N, 10.94.
3-N-Acetyl-5-[2-acetoxyphenyl]-2-methyl-2-(4-methylphenyl)-
1
C¼O) 1765cmꢀ1; H NMR (CDCl3, 500MHz) δ: 2.46 (s,
2,3-dihydro-1,3,4-oxadiazole (4k).
Oxadiazole 4k was
3H,N–CO–CH3), 2.54 (s, 3H, O–CO–CH3), 3.88(s, 3H,
CH3), 6.87 (s, 1H, C2-H of oxadiazole), 7.02–7.57 (m, 5H,
Ar-H), 8.03–8.05 (m, 3H, Ar-H); Anal. calcd. For
C19H18N2O5: C, 64.41; H, 5.08; N, 7.91. Found: C, 64.45;
H, 5.11; N, 7.95.
obtained in 69% yield, m.p. 112–114°C; IR (KBr): (C–
O–C) 1188, (C¼C) 1591, (C¼N) 1633, (amide C¼O)
1670, (ester C¼O) 1775 cmꢀ1
;
1H NMR (CDCl3,
500 MHz) δ: 2.48 (s, 3H, CH3–Ph), 2.56 (s, 3H, C2–CH3
of oxadiazole), 2.88 (s, 3H, N–CO–CH3), 2.97 (s, 3H,
O–CO–CH3), 6.97 (m, 2H, Ar-H), 7.25 (m, 2H, Ar-H),
7.57 (m, 1H, Ar-H), 7.59 (m, 2H, Ar-H), 7.78–7.80 (m,
1H, Ar-H); Anal. calcd. For C20H20N2O4: C, 68.18; H,
5.68; N, 7.95. Found: C, 68.21; H, 5.71; N, 7.94.
3-N-Acetyl-5-[2-acetoxyphenyl]-2-(2-acetoxyphenyl)-2,3-dihydro-
1,3,4-oxadiazole (4f). Oxadiazole 4f was obtained in 89%
yield, m.p. 164°C; IR (KBr): (C–O–C) 1198, (C¼C)
1513, (C¼N) 1605, (amide C¼O) 1659, (ester C¼O)
1
1733 cmꢀ1; H NMR (CDCl3, 500MHz) δ: 2.14 (s, 3H,
General procedure for the synthesis of 2,3-dihydro-5-(2-
N–CO–CH3), 2.43 (s, 6H, O–CO–CH3), 7.10 (s, 1H, C2-
H of oxadiazole), 7.25–7.58 (m, 6H, Ar-H), 8.06–8.07
(m, 2H, Ar-H); Anal. calcd. For C20H18N2O6: C, 62.83;
H, 4.71; N, 7.33. Found: C, 62.86; H, 4.76; N, 7.36.
hydroxy-phenyl)-2-aryl-1,3,4-oxadiazoles (5a–f).
In
a
conical flask, a mixture of N-[phenylmethylidene]-2-
hydroxybenzohydrazide derivatives 3a-f (2 mM) and 10mL
of concentrated H2SO was stirred at room temperature for
2days. The formed mixture was treated with 50mL cold
H2O, and the formed solid matter was filtered off, washed
with 10% Na2CO (50mL), and recrystallized from
ethanol/chloroform to give 5 as yellow crystals.
3-N-Acetyl-5-[2-acetoxyphenyl]-2-methyl-2-phenyl-2, 3-dihydro-1,
3, 4-oxadiazole (4g). Compound 4g was obtained in 63%
yield, m.p. 126–128°C; IR (KBr): (C–O–C) 1188, (C¼C)
1600, (C¼N) 1634, (amide C¼O) 1670, (ester C¼O)
1
1776 cmꢀ1; H NMR (CDCl3, 500MHz) δ: 2.22–2.23 (s,
2,3-Dihydro-5-(2-hydroxyphenyl)-2-phenyl-1,3,4-oxadiazole
3H, C2-CH3 of oxadiazole), 2.28 (s, 6H, N–CO–CH3 and
(5a).
Compound 5a was obtained in 79% yield, m.p.
O–CO–CH3), 7.33–7.88 (m, 9H, Ar-H); Anal. calcd. For
203–204°C; IR (KBr): (C–O–C) 1215, (C¼C) 1537,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

E. M. Sarshira, N. M. Hamada, Y. M. Moghazi, and M. M. Abdelrahman
Vol 000
(C¼N) 1606, (NH) 3284, (OH) 3459 cmꢀ1
;
1H NMR
pressure. The formed solid matter was treated with 25 mL
cold water, filtered off, and recrystallized from ethanol to
give 6 as colorless needles.
(DMSO-d6, 500MHz) δ: 7.48–7.91 (m, 10 H, Ar-H and
C2-H of oxadiazole), 8.72 (s, 2H, OH, NH); Anal. calcd.
For C14H12N2O2: C, 70.00; H, 5.00; N, 11.67. Found: C,
70.06; H, 4.97; N, 11.64.
N-Formyl-2-hydroxybenzohydrazide (6a).
Compound
6a was obtained in 68% yield, m.p. 184–187°C; IR
(KBr): (C¼C) 1609, (NH–CO–Ar) 1649, (NH–COH)
2,3-Dihydro-5-(2-hydroxyphenyl)-2-(4-chlorophenyl)-1,3,4-oxa-
diazole (5b). Compound 5b was obtained in 68% yield, m.
1
1684, (NH) 3120, (NH) 3268, (OH) 3304 cmꢀ1; H NMR
p. 178–179°C; IR (KBr): (C–O–C) 1207, (C¼C) 1589,
(DMSO-d , 300MHz) δ: 6.91–7.01 (m, 2H, Ar-H), 7.41–
7.47 (m, 1H, Ar-H), 7.81–8.12 (m, 1H, Ar-H), 8.13 (s,
1H, H–C¼O), 10.34 (s, 1H, NH–CHO), 10.59 (s, 1H, o–
OH–Ph–CO–NH); 11.79 (s, 1H, OH); Anal. calcd. For
C8H8N2O3: C, 53.33; H, 4.44; N, 15.56. Found: C,
53.31; H, 4.42; N, 15.60.
(C¼N) 1622, (NH) 3255, (OH) 3480 cmꢀ1
;
1H NMR
(DMSO-d , 500MHz) δ: 6.94–8.46 (m, 9H, Ar-H and C2-H
of oxadiazole), 11.79 (s, 1H, NH), 11.89 (s, 1H, OH);
Anal. calcd. For C14H11N2O2Cl: C, 61.09; H, 4.00; N,
10.18; Cl, 13.09. Found: C, 61.11; H, 4.03; N, 10.21; Cl,
13.06.
N-Acetyl-2-hydroxybenzohydrazide (6b).
Compound
2,3-Dihydro-5-(2-hydroxyphenyl)-2-(4-bromophenyl)-1,3,4-oxa-
diazole (5c). Compound 5c was obtained in 77% yield, m.p.
6b was obtained in 73% yield, m.p. 175–176°C; IR
(KBr): (C¼C) 1578, (NH–CO–Ar) 1634, (NH–COCH3)
1
1671, (NH) 3198, (NH) 3320, (OH) 3415 cmꢀ1; H NMR
218–219°C; IR (KBr): (C–O–C) 1207, (C¼C) 1585, (C¼N)
1
1625, (NH) 3250, (OH) 3440 cmꢀ1; H NMR (DMSO-d ,
(DMSO-d , 300 MHz) δ: 1.94 (s, 3H, CH3–C¼O), 6.90–
6.97 (m, 2H, Ar-H), 7.40–7.46 (m, 1H, Ar-H), 7.86–7.89
(m, 1H, Ar-H), 10.15 (s, 1H, NH–COCH3, D2O exch),
10.50 (s, 1H, o–OH–Ph–CO–NH, D2O exch), 11.88 (s,
1H, OH, D2O exch); Anal. calcd. For C9H10N2O3: C,
55.67; H, 5.15; N, 14.43. Found: C, 55.69; H, 5.19; N,
14.47.
500MHz) δ: 7.38–7.80 (m, 9H, Ar-H and C2-H of
oxadiazole), 8.66 (s, 1H, NH, D2O exch), 9.95 (s, 1H, OH,
D2O exch); Anal. calcd. For C14H11N2O2Br: C, 52.66; H,
3.45; N, 8.78; Br, 25.08. Found: C, 52.66; H, 3.44; N, 8.74;
Br, 25.11.
2,3-Dihydro-5-(2-hydroxyphenyl)-2-(4-nitrophenyl)-1,3,4-oxa-
diazole (5d). Compound 5d was obtained in 69% yield, m.
General procedure for the preparation of 2-(2-
hydroxyphenyl)-1,3,4-oxadiazole and 2-(2-hydroxyphenyl)-5-
p. 210–212°C; IR (KBr): (C–O–C) 1207, (C¼C) 1572,
(C¼N) 1619, (NH) 3264, (OH) 3460cmꢀ1
;
1H NMR
methyl-1,3,4-oxadiazole (7a–b).
To a solution of N-
(DMSO-d , 500MHz) δ: 7.67–8.61 (m, 9H, Ar-H and C2-
H of oxadiazole), 9.80 (s, 1H, NH), 11.45 (s, 1H, OH);
Anal. calcd. For C14H11N3O4: C, 58.95; H, 3.86; N,
14.74. Found: C, 58.98; H, 3.89; N, 14.77.
formyl-2-hydroxybenzohydrazide 6a or N-acetyl-2-
hydroxybenzo-hydrazide 6b (10 mM) in xylene (150mL),
phosphorous oxychloride (10 mM) was added. The
mixture was heated under reflux for 16h, the solvent was
evaporated under reduced pressure, and the residue was
recrystallized form ethanol to give 7 as colorless needles.
2,3-Dihydro-5-(2-hydroxyphenyl)-2-(4-methoxyphenyl)-1,3,4-
oxadiazole (5e). Compound 5e was obtained in 83% yield,
m.p. 171–173°C; IR (KBr): (C–O–C) 1215, (C¼C) 1602,
2-(2-Hydroxyphenyl)-1,3,4-oxadiazole (7a).
Compound
(C¼N) 1623, (NH) 3345, (OH) 3462cmꢀ1
;
1H NMR
7a was obtained in 65% yield, m.p. 136–138°C; IR
(KBr) : (C–O–C) 1265, (C¼C) 1568, (C¼N) 1609, (OH)
(DMSO-d , 500MHz) δ: 3.84 (s, 3H, CH3), 6.94–8.62
(m, 9H, Ar-H and C2-H of oxadiazole), 10.08 (s, 1H,
NH), 11.78 (s, 1H, OH); Anal. calcd. For C15H14N2O3:
C, 66.67; H, 5.19; N, 10.37. Found: C, 66.63; H, 5.17; N,
10.34.
1
3411 cmꢀ1; H NMR (CDCl3, 400 MHz) δ: 6.71 (s, 1H,
C5-H of oxadiazole), 6.91–7.01 (m, 2H, Ar-H), 7.49–
7.54 (m, 1H, Ar-H), 7.91–7.93 (m, 1H, Ar-H), 10.36 (s,
1H, OH, D2O exch); Anal. calcd. For C8H6N2O2: C,
59.26; H, 3.70; N, 17.28. Found: C, 59.28; H, 3.66; N,
17.25.
2,3-Dihydro-5-(2-hydroxyphenyl)-2-(2-hydroxyphenyl)-1,3,4-
oxadiazole (5f). Compound 5f was obtained in 81% yield,
2-(2-Hydroxyphenyl)-5-methyl-1,3,4-oxadiazole (7b). Compound
7b was obtained in 61% yield, m.p. 120–123°C; IR (KBr):
(C–O–C) 1288, (C¼C) 1503, (C¼N) 1640, (OH)
m.p. 184–87°C; IR (KBr): (C–O–C) 1201, (C¼C) 1573,
(C¼N) 1624, (NH) 3380, (OH) 3465cmꢀ1
;
1H NMR
(CDCl3, 500MHz) δ: 6.96–7.34 (m, 9H, Ar-H and C2-H
of oxadiazole), 8.70 (s, 1H, NH, D2O exch), 11.40 (s,
1H, OH, D2O exch), 11.96 (s, 1H, OH, D2O exch); Anal.
calcd. For C14H12N2O3: C, 65.63; H, 4.69; N, 10.94.
Found: C, 65.62; H, 4.71; N, 10.91.
1
3439cmꢀ1; H NMR (CDCl3, 500MHz) δ: 2.83 (s, 3H,
CH3), 6.92–6.97 (m, 2H, Ar-H), 7.43 (m, 1H, Ar-H),
7.90–7.91 (m, 1H, Ar-H), 10.88 (s, 1H, OH, D2O exch);
Anal. calcd. For C9H8N2O2: C, 61.36; H, 4.55; N, 15.91.
Found: C, 61.34; H, 4.59; N, 15.96.
General procedure for preparation of N-formyl 2-hydroxybenzo-
hydrazide and N-acetyl-2-hydroxybenzohydrazide (6a–b).
A
General procedure for the preparation of 2-(2-hydro-
xyphenyl)-5-aryl-1,3,4-oxadiazole (8a–b). A mixture of 2-
hydroxybenzohydrazide 2 (10mM), aromatic acid (10 mM)
and phosphorous oxychloride (10mM) was heated under
mixture of 2-hydroxybenzohydrazide 2 (5mM) in 15mL
formic acid or acetic acid was heated under reflux for 25 h,
and the reaction mixture was evaporated under reduced
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Synthesis and Biological Evaluation of Some Heterocyclic Compounds from
Salicylic Acid Hydrazide
reflux for 18–22h; the reaction mixture was left to cool at
room temperature and then slowly poured onto crushed ice
(50g) and kept overnight. The separated solid mass was
filtered, dried, and purified by recrystallization from
ethanol to give 8 as colorless needles.
2-(2-Hydroxyphenyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole (8a).
(10 mL) in (50 mL) of 95% ethanol was heated under
reflux for 12h, and the formed mixture was concentrated
and cooled to attain room temperature then acidified with
dilute HCl (10 mL). The solid mass that separated out
was recrystallized from ethanol to give 11 as colorless
needles in 81% yield, m.p. 186–188°C; IR (KBr): (C¼S)
1180, (C–O–C) 1266, (C¼C) 1576, (C¼N) 1613, (NH)
Compound 8a was obtained in 75% yield, m.p. 163–165°C;
IR (KBr): (C–O–C) 1231, (C¼C) 1558, (C¼N) 1608, (OH)
1
3204, (OH) 3333cmꢀ1; H NMR (DMSO-d , 500MHz)
1
3133cmꢀ1; H NMR (CDCl3, 500MHz) δ: 6.71–6.72 (m,
δ: 6.9–7.02 (m, 2H, Ar-H), 7.40 (m, 1H, Ar-H), 7.61–
7.62 (m, 1H, Ar-H), 10.43 (s, 1H, NH, D2O exch), 14.61
(s, 1H, OH, D2O exch); Anal. calcd. For C8H6N2O2S: C,
49.48; H, 3.09; N, 14.43; S, 16.49. Found: C, 49.47; H,
2H, Ar-H), 6.90–6.91 (m, 2H, Ar-H), 6.93 (m, 2H, Ar-H),
7.52–7.53 (m, 1H, Ar-H), 7.85–8.27 (m, 1H, Ar-H), 12.08
(s, 1H, OH, D2O exch); Anal. calcd. For C14H9N2O2Cl:
C, 61.54; H, 3.97; N, 10.26; Cl, 13.19. Found: C, 61.65;
H, 4.03; N, 10.31.
2-(2-Hydroxyphenyl)-5-(4-nitrophenyl)-1,3,4-oxadiazole (8b).
3.11; N, 14.46; S, 16.52.
N-[2-Phenyl-4-oxo-1,3-thiazolidine-3-yl]-2-hydroxybenza-
mide (12).
A mixture of the appropriate N-(pheny-
Compound 8b was obtained in 74% yield, m.p. 215°C; IR
(KBr): (C–O–C) 1232, (C¼C) 1556, (C¼N) 1606, (OH)
lmethylidene)-2-hydroxybenzohydrazide 3a (10 mM) and
thioglycolic acid (10 mM) in dry pyridine (10 mL) was
heated under reflux for 16 h and left to attain room
temperature. The reaction mixture was poured onto cold
dilute HCl (15 mL), the residue that formed was filtered
off and recrystallized from ethanol to give 12 as
colorless needles, yield 92%, m.p. 165–167°C; IR
(KBr): (C¼C) 1600, (C¼O) 1646, (C¼O of thiazolidine
1
3290 cmꢀ1; H NMR (DMSO-d , 500 MHz) δ: 6.99–7.07
(m, 2H, Ar-H), 7.44 (m, 1H, Ar-H), 7.88 (m, 1H, Ar-H),
8.26–8.39 (m, 4H, Ar-H), 10.38 (s, 1H, OH, D2O exch);
Anal. calcd. For C14H9N3O4: C, 59.36; H, 3.18; N,
14.84. Found: C, 59.39; H, 3.21; N, 14.87.
5-(2-Hydroxyphenyl)-1,3,4-oxadiazol-(3H)-2-one (9).
A
ring) 1699, (NH) 3253, (OH) 3441 cmꢀ1 1H NMR
;
mixture of 2-hydroxybenzohydrazide 2 (5 mM), ethyl
chloroformate (5 mM), and n-butanol (20 mL) was heated
under reflux for 20 h, and the reaction mixture was kept
to cool at room temperature. The formed solid matter was
filtered, washed with water, dried, and recrystallized from
ethanol to give 9 as colorless needles in 75% yield, m.p.
303–305°C; IR (KBr): (C–O–C) 1249, (C¼C) 1562,
(CDCl3, 500 MHz) δ: 3.79 and 3.92 (dd, 2H, C5-H of
thiazolidine ring, J = 16 and 16 Hz), 6.03 (s, 1H, C2-H of
thiazolidin ring), 6.71–6.73 (m, 2H, Ar-H), 7.25–7.40
(m, 7H, Ar-H), 9.35 (s, 1H, NH), 11.15 (s, 1H, OH);
Anal. calcd. For C16H14N2O3S: C, 61.15; H, 4.46; N,
8.92; S, 10.19. Found: C, 61.13; H, 4.41; N, 8.89; S,
(C¼N) 1608, (C¼O) 1640, (NH) 3094, (OH) 3448cmꢀ1
;
10.22.
1H NMR (DMSO-d , 500 MHz) δ: 6.92–6.97 (m, 2H, Ar-
H), 7.42 (m, 1H, Ar-H), 7.88–7.89 (m, 1H, Ar-H), 10.88
(s, 1H, NH, D2O exch), 11.80 (s, 1H, OH, D2O exch);
Anal. calcd. For C8H6N2O3: C, 53.93; H, 3.37; N, 15.73.
General procedure for preparation of 2-(2-hydroxyphenyl)-
1,3,4 thiadiazole and 2-(2-hydroxyphenyl)-5-methyl-1,3,4-
thiadiazole (13a–b).
A
solution of N-formyl-2-
hydroxybenzohydrazide and N-acetyl-2-hydroxybenzo-
hydrazide 6a-b (10mM) in pyridine (20mL) was treated
with phosphorous pentasulphide (10mM). The mixture was
heated under reflux for about 20h, the solvent was
evaporated, and the residue that separated was washed
successively with water, dried, and recrystallized form
ethanol to give 13
Found: C, 53.91; H, 3.39; N, 15.77.
5-Chloromethyl-2-(2-hydroxyphenyl)-1,3,4-oxadiazole (10).
A
mixture of 2-hydroxybenzohydrazide
2
(5mM),
chloroacetic acid (5mM), and 10mL phosphorous
oxychloride was heated under reflux on a water bath for
10h. The reaction mixture was cooled and poured onto
crushed ice (50g) with continuous stirring. The solid mass
that separated was neutralized with (30mL) sodium
carbonate solution (10%), filtrated, washed well with water,
dried, and recrystallized from ethanol to give 10 as
colorless needles in 88% yield, m.p. 110°C; IR (KBr):
(C–O–C) 1239, (C¼C) 1589, (C¼N) 1626, (OH)
3458cmꢀ1; 1H NMR (DMSO-d6, 500MHz) δ: 5.09 (s, 2H,
CH2), 6.95–7.05 (m, 2H, Ar-H), 7.42 (m, 1H, Ar-H), 7.72–
7.74 (m, 1H, Ar-H), 10.35 (s, 1H, OH, D2O exch); Anal.
calcd. For C9H7N2O2Cl: C, 51.18; H, 3.32; N, 13.27; Cl,
2-(2-Hydroxyphenyl)-1,3,4-thiadiazole
(13a).
1,3,4-
Thiadiazole derivative 13a was obtained in good yield
(71%), m.p. 223–226°C; IR (KBr): (C¼C) 1594, (C¼N)
1
1624, (OH) 3463cmꢀ1; H NMR (CDCl3, 400MHz) δ:
6.73 (s, 1H, C5-H of thiadiazole), 6.93–6.95 (m, 2H, Ar-
H), 7.24–7.30 (m, 1H, Ar-H), 7.75–7.77 (m, 1H, Ar-H),
10.46 (s, 1H, OH, D2O exch); Anal. calcd. For
C8H6N2OS: C, 53.93; H, 3.37; N, 15.73; S, 17.98.
Found: C, 54.02; H, 3.35; N, 15.68; S, 18.04.
2-(2-Hydroxyphenyl)-5-methyl-1,3,4-thiadiazole (13b). 1,-3,4-
Thiadiazole derivative 13b was obtained in 70% yield, m.p.
188–189°C; IR (KBr): (C¼C) 1588, (C¼N) 1630, (OH)
17.06. Found: C, 51.18; H, 3.36; N, 13.29; Cl, 17.11.
5-(2-Hydroxyphenyl)-1,3,4-oxadiazole-2-(3H)-thione (11). A
1
3461cmꢀ1; H NMR (CDCl3, 500MHz) δ: 2.81–2.83 (s,
mixture of 2-hydroxybenzohydrazide
2
(10 mM),
3H, CH3), 6.92 (m, 1H, Ar-H), 7.08–7.10 (m, 1H, Ar-H),
potassium hydroxide (10 mM), and carbon disulphide
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

E. M. Sarshira, N. M. Hamada, Y. M. Moghazi, and M. M. Abdelrahman
Vol 000
7.43–7.44 (m, 2H, Ar-H), 10.94 (s, 1H, OH, D2O exch);
Anal. calcd. For C9H8N2OS: C, 56.25; H, 4.17; N, 14.58;
S, 16.67. Found: C, 56.23; H, 4.19; N, 14.55; S, 16.69.
1-(2-Hydroxybenzoyl)-3-methyl-1H-pyrazol-5(4H)-one (14).
NH, D2O exch), 13.19 (s, 1H, OH, D2O exch), 13.67 (s,
1H, SH, D2O exch); Anal. calcd. For C8H7N3OS: C,
49.74; H, 3.63; N, 21.76; S, 16.58. Found: C, 49.73; H,
3.60; N, 21.78; S, 16.52.
A mixture of 2-hydroxybenzohydrazide 2 (5 mM) and
ethyl acetoacetate (5 mM) was heated under reflux for
25 h. The formed mixture was left to cool at room
temperature; the solid that separated out was filtered off,
dried, and recrystallized from ethanol to give 14 as
colorless needles in 75% yield, m.p. 118–120°C, and IR
is identical to that published in literature [56].
Determination of antimicrobial activity.
Cultures of
three different microorganisms, namely E. coli, S. aureus,
and C. albicans, were used to investigate the
antimicrobial activities of all synthesized compounds.
The antimicrobial activities were assayed biologically
using diffusion plate technique. The experiments were
carried out by pouring spore suspension 106 colon-
forming units (CFU) per mL of the test strain to 75mL of
nutrient agar medium at 45°C, mixed well and then
poured into a 15cm sterile metallic Petri plate. The
medium was allowed to solidify, and 8mm wells were
dug with a sterile metallic borer, then a DMF solution of
the test sample (1 mL) at 1mg/mL was added to the
respective wells. DMF was served as negative control,
and the standard antimicrobial drug Imipenam is used as
positive control. The layer was allowed to set for 30min
and incubated at optimum incubation temperature 28 2°C.
Test organism growth may be affected by the inhibitory
action of the test compound, and so, a clear zone around
the disc appeared as an indication of the inhibition of the
test organism growth. The size of clearing zone is
proportional to the inhibitory action of the test compound.
Measurements were considered after 72h for fungi and
24h for bacteria.
1-(2-Hydroxybenzoyl)-3-thiosemicarbazide
(15).
A
mixture of 2-hydroxybenzohydrazide 2 (2 mM), excess
amount of ammonium thiocyanate (6 mM), hydrochloric
acid (8 mL, 35%) in absolute ethanol (50 mL) was heated
under reflux for 22 h. The formed mixture was evaporated
under reduced pressure, and the residue that separated out
was poured on crushed ice (20 g) with continuous
stirring. The solid that formed was filtered, dried, and
recrystallized from ethanol to give 15 as colorless needles
in 86% yield, m.p. 189–190°C; IR (KBr): (C¼S) 1236,
(C¼C) 1540, (C¼O) 1655, (NH2) 3199, (NH) 3304,
(OH) 3388 cmꢀ1 1H NMR (DMSO-d6, 500MHz) δ:
;
6.87–7.78 (m, 6H, Ar-H and NH2, D2O exch), 9.40 (s,
1H, NH, D2O exch), 10.51 (s, 1H, NH, D2O exch), 11.85
(s, 1H, OH, D2O exch); Anal. calcd. For C8H9N3O2S: C,
45.50; H, 4.27; N, 19.91; S, 15.17. Found: C, 45.49; H,
4.28; N, 19.88; S, 15.14.
5-Amino-2-(2-hydroxyphenyl)-1,3,4-thiadiazole (16).
A
mixture of 1-(2-hydroxybenzoyl)-3-thiosemicarbazide 15
(5 mM) was treated with concentrated sulfuric acid
(10 mL). The mixture was heated on a water bath at 90°C
with stirring for 2 h, cooled, then poured onto ice water
(30 g) and neutralized with cold concentrated ammonium
hydroxide solution (60 mL). The formed precipitate was
filtered, washed with cold water, dried, and recrystallized
from ethanol to give 16 as colorless needles. The yield of
16 was 81%, m.p. 118–119°C; IR (KBr): (C¼C) 1601,
Preparation of different concentrations for the tested
compounds.
All the synthesized compounds were
dissolved separately to prepare a stock solution containing
1000μg/mL of DMF, and so, 10mg of different
synthesized compounds was dissolved in 10mL of the
DMF; thus, 1mL of the resulted solution gives
1000μg/mL. Dilution was conducted by adding 1mL of
the aforementioned solution to 1mL of DMF to give half
concentration of the first solution. Successive
concentrations like 250, 125, and 62.5μg/mL were
prepared in a similar manner. The tubes were mixed well
after each addition, and all the tubes were inoculated with
one loopful of one test organism. The process was
repeated with a different test organism. Both a positive
control and a negative control were also prepared to
confirm the nutritive property and sterility, respectively, of
the prepared medium. The tubes were incubated at 25°C
for 48h, and the presence or absence of growth organisms
was observed after incubation.
(C¼N) 1633, (NH) 2918, (NH) 2957, (OH) 3433cmꢀ1
;
1H NMR (DMSO-d , 500 MHz) δ: 6.95–8.17 (m, 4H, Ar-
H), 9.25 (s, 2H, NH2, D2O exch), 11.75 (s, 1H, OH, D2O
exch); Anal. calcd. For C8H7N3OS: C, 49.74; H, 3.63; N,
21.76; S, 16.58. Found: C, 49.71; H, 3.61; N, 21.77; S,
16.62.
4H-5-(2-Hydroxyphenyl)-1,2,4-triazole-3-thiol (17).
A
mixture of 1-(2-hydroxybenzoyl)-3-thiosemicarbazide 15
(1 mM) and (10%) sodium hydroxide solution (15 mL)
was heated under reflux for 3 h. The formed mixture was
cooled acidified by 10% hydrochloric acid (8mL). The
formed solid matter was filtered and recrystallized from
ethanol to give 17 as colorless needles in 83% yield, m.p.
282–285°C; IR (KBr) : (C¼S) 1242, (C¼C) 1566,
REFERENCES AND NOTES
(C¼N) 1621, (NH) 3194, (OH) 3443 cmꢀ1
;
1H NMR
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Synthesis and Biological Evaluation of Some Heterocyclic Compounds from
Salicylic Acid Hydrazide
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet