Synthesis and biological assessment of novel cyanopyridine derivatives

Article abstract of DOI:10.1080/00397911.2019.1616096

New pyridine derivatives bearing p-dimethyl amino phenyl and p-bromophenyl moieties at position-4 and 6 have been prepared. The behavior of pyridone derivative 2 toward ethyl chloroacetate followed by hydrazine hydrate gave pyridinyl acetohydrazide derivative 7, and its behavior toward carbon electrophiles has been investigated by its reaction with aromatic aldehydes, ethyl acetoacetate, acetyl acetone, cyclohexanone, phthalic anhydride, maleic anhydride, and isatin affording the pyridine derivatives 8a–e to 16, respectively. Treatment of compound 2 with acrylonitrile in Et₃N, yielded the N- alkylated derivative 17. Some pyrazole derivatives have been synthesized by interaction of the chalcone 1 with hydrazine hydrate afforded pyrazole derivative 18. Treatment of compound 18 with benzoyl chloride and or acetic anhydride resulted in the formation of the acylated compounds 19 and 20. Elemental and spectroscopic pieces of evidence characterized all the newly synthesized compounds. Some of the synthesized compounds were tested for their antibacterial activities against Gram-positive and Gram-negative bacteria.

Full text of DOI:10.1080/00397911.2019.1616096

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Synthesis and biological assessment of novel
cyanopyridine derivatives
Maher A. EL-Hashash & Safaa S. Shaban
To cite this article: Maher A. EL-Hashash & Safaa S. Shaban (2019): Synthesis and
biological assessment of novel cyanopyridine derivatives, Synthetic Communications, DOI:
10.1080/00397911.2019.1616096
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https://doi.org/10.1080/00397911.2019.1616096
Synthesis and biological assessment of novel cyanopyridine
derivatives
Maher A. EL-Hashash and Safaa S. Shaban
Faculty of Science, Department of Chemistry, Ain Shams University, Cairo, Egypt
ABSTRACT
ARTICLE HISTORY
New pyridine derivatives bearing p-dimethyl amino phenyl and p-bro-
mophenyl moieties at position-4 and 6 have been prepared. The
behavior of pyridone derivative 2 toward ethyl chloroacetate followed
by hydrazine hydrate gave pyridinyl acetohydrazide derivative 7, and
its behavior toward carbon electrophiles has been investigated by its
reaction with aromatic aldehydes, ethyl acetoacetate, acetyl acetone,
cyclohexanone, phthalic anhydride, maleic anhydride, and isatin
affording the pyridine derivatives 8a–e to 16, respectively. Treatment
Received 22 February 2019
KEYWORDS
Antibacterial activities;
chalcone; pyrazole; pyridine
3
of compound 2 with acrylonitrile in Et N, yielded the N- alkylated
derivative 17. Some pyrazole derivatives have been synthesized by
interaction of the chalcone 1 with hydrazine hydrate afforded pyra-
zole derivative 18. Treatment of compound 18 with benzoyl chloride
and or acetic anhydride resulted in the formation of the acylated com-
pounds 19 and 20. Elemental and spectroscopic pieces of evidence
characterized all the newly synthesized compounds. Some of the syn-
thesized compounds were tested for their antibacterial activities
against Gram-positive and Gram-negative bacteria.
GRAPHICAL ABSTRACT
CONTACT Safaa S. Shaban
safashaban@ymail.com, shaban@sci.asu.edu.eg
Faculty of Science, Department of
Chemistry, Ain Shams University, Khalifa El-Maamon st., Abbasiya sq., Cairo 11566, Egypt.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

2
M. A. EL-HASHASH AND S. S. SHABAN
Introduction
Pyridine nucleus is an essential component in natural products like Nudifluorine and
Ricinine. Also, different Pyridine derivatives and fused pyridines have remarkable pharma-
[
1–3]
ceutical importance because of their pronounced activities as antimicrobial,
antiviral
[
4–8]
[9]
[10]
[11]
agents,
nootropic or antiepileptic activity,
mediate in the bacterial metabolism. A survey of literature in the recent past reveals that
anticancer,
anti-inflammatory agents,
antihelminthic,
psychotropic,
antimycotic, vasodilating agents, and as inter-
[
12–14]
[15]
[16]
[
17]
,[18]
[19]
[20]
some pyrazole derivatives have antimicrobial
anti-cyclooxygenase,
anticonvulsing,
[
21]
[22]
[23]
[24]
[25]
antitubercular,
antitumor,
anti-inflammatory,
In the view of the aforementioned facts and our continuing
directed toward the synthesis of new heterocyclic compounds with anticipated
analgesic,
antidiabetic,
and
[
26]
antifungal effects.
[
27–29]
efforts
biological activities, we report in this study the synthesis of new pyridone and pyrazole
derivatives for the sake of their biological activity.
Result and discussion
[
30–34]
The enone (1-(4-bromophenyl)-3-(4-(dimethyl amino) phenyl) prop-2-en-1-one (1)
was a starting material for the synthesis of 6-(4-bromophenyl)-4-(4-(dimethylamino) phe-
[
35]
nyl)-2-oxo-1, 2-dihydropyridine-3-carbonitrile (2)
through the reaction of enone 1 with
ethyl cyanoacetate in the presence of ammonium acetate. The carbanion generated from
ethyl cyanoacetate using ammonium acetate undergoes Michael addition to the b-position
(
CH -carbon) of the chalcone to yield the enol which undergoes nucleophilic displacement
b
of –OH group by ammonia (generated from ammonium acetate) to yield the conform-
ational intermediates A/B. In the Neumann projection A, the carboethoxy group lies in
between hydrogen and nitrile groups. Both these groups being smaller in molecular size and
structure brings the amino and carboethoxy functional groups in close vicinity leading to
nucleophilic substitution to finally yield (2). On the contrary, in the projection B, the nitrile
lies in between hydrogen and bulky carboethoxy groups, which makes the nucleophilic add-
ition of amine with the nitrile group difficult due to steric hindrance thus not leading to the
formation of (5) as depicted in Scheme 1.
The structure of compound 2 was elucidated from its spectral data, where its IR spec-
ꢀ
1
trum revealed bands at 3279, 2216, and 1657 cm corresponding to NH, CN, and CO
1
groups, respectively. While. The H-NMR spectrum exhibited a singlet at d 4.32 and
12.52 ppm, attributed to NH and OH proton, respectively. The aforementioned spectral
data revealed the existence of lactam–lactim Tautomerism. When compound 2 was
[
36]
reacted with ethyl chloroacetate in anhydrous K CO /dry acetone,
it gave 4. The
2
3
structure of compound 4 was confirmed by IR spectrum which showed a strong absorp-
–1
1
tion band at 1734 cm (CO ester). The H NMR spectrum showed signals at 4.13, 1.21,
and 5.11 ppm as a quartet, triplet, and singlet, respectively, attributable to (OCH CH )
2
3
and (OCH CO) protons.
2
[
37]
It was reported that
4,6-dimethyl-2-oxo-1,2-dihydro pyridine-3-carbonitrile has
been reacted with ethyl chloroacetate in the presence of sodium ethoxide and yielded
the furopyridine derivative 5.
In the present work when the pyridone derivative 2 was subjected to react with ethyl
chloroacetate in the presence of sodium ethoxide it yielded the corresponding ester 4

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Scheme 1. Formation of compound 2.
and no ring closure takes place to yield the furo derivative 6. Here, the lone pair of
0
N,N -dimethyl amino group of 4 is delocalized in the aromatic ring thus making the
pyridyl group electron rich and the nitrile group less electrophilic. Thus, the carbanion
generated in the presence of sodium ethoxide does not cyclize with the nitrile group of
4
to yield the furyl derivative 6.
Moreover, compound 4 was treated with hydrazine hydrate in ethanol, which gave
the pyridinyl acetohydrazide derivative 7. The structure of compound 7 was elucidated
from its elemental analyses and spectral data. The IR spectrum displayed the following

4
M. A. EL-HASHASH AND S. S. SHABAN
–
1
absorption bands 3325, 3309, and 1617 cm corresponding to NH , NH, and CO
2
1
groups, respectively. While H-NMR exhibited three singlet signals at 9, 9.2, and
9
.5 ppm attributed to NH and NH protons, respectively.
2
The behavior of pyridinyl acetohydrazide derivative 7 towards carbon electrophiles
has been investigated by its reaction with differently substituted benzaldehydes, ethyl
acetoacetate, acetyl acetone, cyclohexanone, phthalic anhydride, maleic anhydride and
isatin with a view to obtain some interesting new pyridine derivatives.
[
38]
Interaction of acetohydrazide derivative 7 with aromatic aldehydes,
namely benzal-
dehyde, P-dimethylaminobenzaldehyde, P-nitrobenzaldehyde, P-methoxy benzaldehyde,
and P-chloro-benzaldehyde, afforded the condensation products 8a–e, respectively. The
1
structures of compounds 8a–e were confirmed by their spectral data. The H NMR
spectrum of compound 8b (as an example) showed the presence of two singlet signals
at 2.98 and 5.4 ppm, corresponding to 2 (–N(CH ) ) and –OCH protons, respectively.
3
2
2
In addition to the appearance of two singlet signals at 8.4 and 11.22 ppm attributed to
N ¼ C–H and NH protons, respectively. Also, its IR spectrum showed bands at 3421,
–1
2
216, 1656 cm for NH, CN, and CO groups, respectively.
[
38]
Reaction of ethyl acetoacetate with compound 7 in boiling butanol,
afforded
mixture of the corresponding ethyl 3-(2-(2-(6-(4-bromophenyl)-3-cyano-4-(4-(dimethy-
lamino) phenyl) pyridin-2- yloxy)acetyl) hydrazono)butanoate (9) and 6-(4-bromo-
phenyl)-4-(4-(dimethylamino) phenyl)-2-(2-(3-methyl-5-oxo-4,5-dihydropyrazol-1-yl)-2-
[
39,40]
oxoethoxy) nicotinonitrile (10).
The IR spectrum of compound 9 displayed absorp-
–
1
tion bands at 3356, 1731 cm attributed to NH, CO ester, respectively. While the
1
H-NMR spectrum exhibited the OCH2CH protons as quartet and triplet at d 4.15,
3
1
.12, in addition to singlet signal at 10.79 ppm attributed to NH with D O exchangeable.
2
1
Similarly, the H-NMR spectrum of 10 was in agreement with the predicted structure as

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it showed singlet signals at 2.93 and 4.84 corresponding to CH of pyrazolone ring and
2
OCH CO protons. The IR spectrum showed the disappearance of NH and NH bands.
2
2
[
38,41,42]
Condensation of compound 7 with acetyl acetone,
1. The IR spectrum of compound 11 displayed bands at 2218 and 1648 cm corre-
sponding to CN and CO groups, respectively. The H-NMR spectrum of compound 11
showed the presence of three singlet signals at d 2.35, 2.65, and 6.11 ppm, corresponding
to pyrazole –CH and CH, respectively. Also, signals of NH, NH protons were not
gave the pyrazole derivative
ꢀ
1
1
1
3
2
1
seen in the H-NMR spectrum, proving that they were involved in the cyclization.
[
36]
Moreover, when compound 7 reacted with cyclohexanone, it gave 12.
The IR spec-
trum of compound 12 show no absorption bands for NH but absorption bands appear
2
ꢀ
1
1
at 3324 cm for NH. H-NMR showed signals at 1.58, 2.28, and 10.5 ppm attributed to
cyclohexylidene protons (3CH þ 2CH –C¼N–) and NH group, respectively. Scheme 2.
2
2
The reaction of phthalic anhydride with compound 7 afforded the pyridine deriva-
tives 13, 14 and the phthalazinone derivative 13a-was not obtained. The IR spectrum of
ꢀ
1
compound 13 displayed bands at 1740 and 1652 cm corresponding to 2CO of imide
1
and amide groups, respectively. While the H-NMR spectrum showed singlet signals at
d 10.88 attributed to NH proton (D O exchangeable).
2
1
Similarly, Elemental analyses, IR, H-NMR, and mass spectra supported the structure
–1
of compound 14. IR spectrum of 14 revealed band at 1692 cm and sub maxima
–1
between 2500–3300 cm account for CO acid, OH, and NH groups, respectively. The
1
H-NMR showed signals at 9.98–10.17 and at 13.8 ppm, attributed to 2NH and acidic
OH with D O exchangeable. Also, the structure of compound 14 was confirmed by
2
mass-spectrum which showed the molecular ion peak corresponding to its molecu-
lar weight.
Scheme 2. Formation of compounds 9-12.

6
M. A. EL-HASHASH AND S. S. SHABAN
The overall ease of ring closure may be derived from two factors: a monotonous
decrease in the ease of having the ends of the ring meet and a strain factor, which
becomes more favorable to closure as the ring size increases from three- to six-mem-
bered. The ease of formation of six-membered ring is less than for a five-membered
one because the slight improvement in the strain factor is outweighed by a deterioration
[
43]
in the distance factor.
This compound (13) was isolated as a sole product because its formation is kinetically
favored than the phthalazinone derivative (13a). Also, it is thermodynamically stable
through intramolecular H-bonding.
On the other hand, when compound 7 reacted with maleic anhydride in DMF, gave
1
5 as the sole product. Scheme 3. Compound 15 gets support from its spectral data,
–1
where its IR spectrum displayed bands at 3409, 2927, and 1722 cm attributed to che-
lated OH group or NH, (C–H) aliphatic, and CO acid. At the same time, the H-NMR
1
revealed peaks at 6.41, from 10.20–12.5, and at 15.98 ppm, attributed to olefinic protons,
2NH, OH, respectively.
Isatin derivatives are reported to show a wide variety of important biological activities
[
44]
[45]
[46]
[47]
like antibacterial,
antifungal,
antiviral,
and anti-inflammatory.
In view of
these facts, novel isatin derivative 16 has been synthesized through the interaction of
[
44,48]
compound 7 with isatin in ethanol and drops of acetic acid
The structure of com-
pound 16 was approved by its elemental and spectral data, where the IR spectrum
–1
exhibited bands at 3381, 1647 cm corresponding to NH and C¼N groups, respectively.
Scheme 3. Formation of compounds 13-16.

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Scheme 4. Formation of componds 18-20.
1
The H-NMR showed signals at 11.22, 12.52 ppm corresponding to 2NH protons
exchangeable with D O.
2
Usually, Compounds with activated double bond react with 2- pyridone derivatives
and afford the N- alkylated derivatives. Thus the dihydropyridine 2 reacted with acrylo-
[
38]
nitrile in the presence of triethylamine,
giving the N-propionitrile derivative 17 as a
Michael type product, the lone pair of N,N-dimethyl amino group of 2 is delocalized in
the pyridyl ring making the pyridyl nitrogen more nucleophilic, thus facilitating the
Michael addition of 2 with acrylonitrile to yield 17. The IR spectrum of compound 17
–1
revealed the existence of bands at 2248, 2213, and 1642 cm corresponding to 2CN and
CO groups, respectively. Also, the NH group is devoid of any absorption. Similarly,
1
the H-NMR spectrum was devoid of any signal for NH group (cf. the
Experimental section).
Chalcones possess high reactivity because of the presence of the carbonyl group con-
jugated with the double bond. Nucleophiles can react with chalcones at both the car-
bonyl group and the double bond. The author investigated the reaction of chalcone 1
[
29]
with hydrazine hydrate (as binucleophile),
and suggested the formation of some
novel pyrazole derivatives 18–20. Scheme 4, evaluate their antibacterial activity. The
reaction takes place through aza-Michael 1,4-addition followed by heterocyclization of
the polarized system leading to the desired pyrazole derivative 18. The polar factor of
4-(N,N)-dimethyl amino moiety has no significant role in the course of the reaction. It
decreases the reactivity but not opposed the mode of addition. The structure of 18 was
–1
confirmed by IR spectrum which revealed bands at 3339 and 1607 cm corresponding
1
to NH and C¼N groups, and H-NMR showed signal at 10.22 ppm corresponding to
NH proton, exchangeable with D O.
2
Furthermore, the reaction of Pyrazole derivative 18 with benzoyl chloride and/or
[
49]
acetic anhydride
resulted in the formation of the acylated compounds 19 and 20.
1
The IR and the H-NMR spectra of 1-benzoyl-pyrazole derivative 19 and 1-acetyl-
pyrazole derivative 20 revealed the existence of bands at 1636, 1645 cm corresponding
–1

8
M. A. EL-HASHASH AND S. S. SHABAN
1
to 2CO groups, and devoid of any absorption for NH group. The H-NMR spectrum of
0 revealed singlet signal at 2.52 ppm corresponding to COCH protons.
2
3
The following mechanism was suggested for the formation of compound 18
Antibacterial activity
[
50]
Antibacterial activity of some of the synthesized compounds has been evaluated.
results are depicted in Table 1.
The
Conclusion
Our results as given in Table 1 showed that compounds 4, 7 exhibited the highest activ-
ity against Gram-negative bacteria Escherichia coli. Compounds 2, 8a, 8b, 8e, 9, 13, 17
showed moderate activity. Meanwhile compounds 8d, 11, 18, 19, 20 demonstrated weak
activity. Compounds 8c, 12 were inactive against Escherichia coli.

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Table 1. Response of various microorganisms to some selected synthesized compounds in
in vitro culture.
Escherichia Coli
Gm(ꢀ) bacteria
Staphylococcus aureus
Gm(þ) bacteria
Diameter of inhibition
Diameter of inhibition
No.
Compound
zone (mm)
% Activity index
zone (mm)
% Activity index
1
2
3
4
5
6
7
8
9
2
4
7
14
16
1.5
10
10
NA
8
13
11
8
NA
10
11
8
5
7
56.0
64.0
60.0
40.0
40.0
0.00
32.0
52.0
44.0
32.0
0.00
40.0
44.0
32.0
20.0
28.0
100
10
16
NA
10
14
10
9
11
13
12
10
11
NA
20
15
21
25
40.0
64.0
0.00
40.0
56.0
40.0
36.0
44.0
52.0
48.0
40.0
44.0
0.00
80.0
60.0
84.0
100
8a
8b
8c
8d
8e
9
11
12
13
17
18
19
20
10
11
12
13
14
15
16
Cefoxitin
25
NA: No activity.
Compounds 4, 18, 19, 20 showed strong activity against Gram-positive bacteria
Staphylococcus aureus). Also, compound 20 has the maximum activity, while com-
(
pounds 2, 8a, 8b, 8c, 8e, 9, 11, 12, 13 have moderate activity. compound 8d showed
weak activity. The remaining compounds 7, 17 were inactive against
Staphylococcus aureus.
Experimental
All melting points were uncorrected and recorded on a Gallen Kamp electric melting
point apparatus (Shimadzu, Japan). The infrared spectra were recorded using potassium
bromide disks on a PyeUnicamSP-3-300 infrared spectrophotometer (Thermo Scientific,
1
Waltham, MA, USA), H NMR spectra were run at 300 MHz, on a Varian Mercury
VX-300 NMR spectrophotometer (Billerica, Massachusetts, USA) and Brukeravance III
400 MHz (Billerica, Massachusetts, USA) using TMS as an internal standard in deuter-
ated dimethyl sulphoxide. Chemical shifts – are quoted in ppm. The mass spectra were
recorded on Shimadzu GCMS-QP-1000EX mass spectrophotometer at 70 ev. All the
spectral measurements were carried out at the NMR laboratory of Cairo University,
Egypt, at the NMR laboratory of Faculty of Pharmacy, Ain Shams University, Egypt, the
Microanalytical data were measured in Central Lab of Cairo University, Egypt, and the
Ministry of Defence Chemical Laboratories, Egypt, and at the Micro Analytical Center
of Ain Shams University, Egypt, All the chemical reactions were monitored by TLC on
silica gel coated aluminum sheets (Silica Gel 60 F254, Merck).
Starting materials
The chemicals used in this study were commercially available.

1
0
M. A. EL-HASHASH AND S. S. SHABAN
Synthesis of 1-(4-bromophenyl)-3-(4-(dimethyl amino) phenyl) prop-2-en-1-one (1)
The mixture of (1.99 g, 0.01 mol) of 4-bromo acetophenone and (1.49 g, 0.01 mol) 4-
dimethylamino benzaldehyde was dissolved in 30 mL ethanol and 10 mL of 5% KOH
was added portion wise then stirred in an ice bath for 1 h. The separated solid was fil-
tered, washed with water, dried, crystallized from ethanol, yellow crystals, yield 98%,
ꢁ
ꢀ1
1
mp 120–122 C. IR (KBr, ꢀ/cm ):1649, 1584 (C¼O, C¼C). H NMR (DMSO-d ), d,
6
ppm: 2.98 (s, 6H, –N(CH ) ), 6.77 (d, 2H, ortho-N(CH ) ), 7.56 (d, 1H, CH ¼), 7.8 (d,
3
2
3 2
a
2
(
H, ortho bromophenyl moiety), 7.5–8.02 (m, 4H, Ar–H), 8.12 (d, 1H, ¼CH ). MS m/z
b
þ
%): 330 [M] (16). Found, %: C 61.97, H 4.70, Br 24.08, N 3.98 for C H BrNO
17
16
(330).Calculated,%: C 61.83, H 4.88, Br 24.20, N 4.24.
Synthesis of 6-(4-bromophenyl)-4-(4-(dimethylamino) phenyl)-2-oxo-1,2-
dihydropyridine-3-carbonitrile (2)
The mixture of compound 1 (3.3 g, 0.01 mol), ethyl cyanoacetate (0.01 mol), and ammo-
nium acetate (0.08 mol) in ethanol (40 mL) was refluxed 3 h, an orange precipitate
formed while hot was filtered off, dried, and recrystallized from glacial acetic acid,
ꢁ
ꢀ1
orange crystals, yield 68%, mp 310–312 C. IR (KBr, ꢀ/cm ): 3279, 2216, 1657 (NH,
1
CN, C¼O); H NMR (DMSO-d ), d, ppm: 2.99 (s, 6H, –N(CH ) ), 4.32 (s, 1H, NH
6
3 2
D O exchangeable), 6.68 (d, 2H, ortho-N(CH ) ), 7.8 (m, 5H, Ar–H þ pyridine–H5),
2
3 2
8
.12 (d, 2H, ortho bromophenyl moiety), 12.52 (s, 1H, OH, D O exchangeable). MS m/
2
.
þ
z (%): 394 [M] (2), 377 (4.2), 351 (100), 156 (13.09), 158 (11.07), 75 (50). Found, %:
C 61.12, H 3.89, Br 20.21, N 10.79 for C H BrN O (394). Calculated, %: C 60.93, H
2
0
16
3
4.09, Br 20.27, N 10.66.
Synthesis of ethyl 2-(6-(4-bromophenyl)-3-cyano-4-(4-(dimethylamino) phenyl)
pyridin-2-yloxy) acetate (4): Method A
The mixture of compound 2 (3.94 g, 0.01 mol), ethyl chloroacetate (4.4 g, 0.04 mol), and
anhydrous potassium carbonate (5.5 g, 0.04 mol) in dry acetone (30 mL) was refluxed
for 10 h. The excess solvent was evaporated, and the solid obtained was diluted with
H O to remove excess K CO then filtered off, dried, and recrystallized from ethanol,
2
2
3
ꢁ
yellow crystals, yield 96%, mp 179–180 C.
Synthesis of 2-((6-(4-bromophenyl)-3-cyano-4-(4-(dimethylamino) phenyl) pyridin-
2
-yl) oxy) acetohydrazide (7)
A solution of compound 4 (4.80 g, 0.01 mol) in EtOH (50 mL) and hydrazine hydrate
(
0.02 mol, 99%) was refluxed for 6 h. After cooling, the separated solid was collected
ꢁ
and recrystallized from butanol, yellow powder, and yield 88%, mp 208–210 C. IR
(
ppm: 3.3 (s, 6H, (–N(CH ) ), 5.3 (s, 2H, –OCH –CO), 6.67 (d, 2H, ortho (–N(CH ) ),
ꢀ
1
1
KBr, ꢀ/cm ): 3400–3309, 2216, 1617 (NH , NH, CN, C¼O); H NMR (DMSO-d ), d,
2
6
3
2
2
3 2
7
.65 (m, 5H, Ar–H þ pyridine–H5), 8.23 (d, 2H, ortho bromophenyl moiety), 9–9.2
(2H, NH , D O exchangeable), 9.5 (1H, NH, D O exchangeable). MS m/z (%): 466 [M]
2
2
2
.
þ
.þ
(
21.4), 468 [M þ 2] (25.3), 378 (12.2), 316 (8.1), 279 (100), 91(10),77(7); Found,%: C

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11
5
4
6.73, H 4.19, Br 17.02, N 15.00 for C H BrN O (466). Calculated, %: C 56.66, H
22 20 5 2
.32, Br 17.13, N 15.02.
Synthesis of hydrazone derivatives 8a–e
General method
A solution of the hydrazide compound 7 (4.66 g 0.01 mol) in butanol (40 mL) and
0.01 mol) of aromatic aldehydes namely, benzaldehyde, P-dimethylaminobenzaldehyde,
(
P-nitrobenzaldehyde, P-methoxy benzaldehyde, and P-chlorobenzaldehyde, respectively
was refluxed for 10 h. Then the excess solvent was evaporated under reduced pressure
and the residue was recrystallized from the appropriate solvent to give com-
pounds 8a–e.
Acknowledgment
The authors would like to extend their sincere appreciation to, Ain Shams University, and Egypt
Microanalysis Armed Force for their cooperation in this research.
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[
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