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Synthesis and Characterization of Hetrocyclic Compounds Derived from

ethyl-4-aminobenzoate

Article · June 2018

DOI: 10.22401/JNUS.21.2.09

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Journal of Al-Nahrain University Vol.21 (2), June, 2018, pp.57-63 Science

Synthesis and Characterization of Hetrocyclic Compounds

Derived from ethyl-4-aminobenzoate
Hiba H. Ibraheem*, Khalida. F. Suhail and Shaymaa S. Hasan
Department of applied science, Chemistry division, University of Technology, Baghdad-Iraq.
*
Corresponding Author: [email protected].

Abstract
New series of Schiff Bases were synthesized by many steps starting from treatment of ethyl-4-
aminobenzoate with hydrazine hydrate to yield 4-aminobenzohydrazide (1) which was reacted with
ethyl acetoacetate in ethanol to form pyrazole derivative (2) and this reacted with salicylaldehyde to
yield azo compound (3). The azo compound condensation with appropriate amines (ethyl-4-
aminobenzoate and 3-nitroaniline) to give new Schiff bases (4,5). The synthesized compounds were
characterized by melting points, FTIR and 1HNMR. [DOI: 10.22401/JNUS.21.2.09]

Keywords: acid hydrazide, pyrazole, heterocyclic compounds, Schiff bases.

Introduction amines [6]. The general formula of these

Heterocyclic compounds chemistry are a Schiffs bases (R-N=CRIRII) and their
wide and developing area of chemistry nomenclature depend on the nature of the
because of the clear applications of organic groups R, RI, R.II. Schiff’s bases, which are
compounds derived by heterocyclic rings by derived from ketones, are known as ketemines,
pharmacy and medicine, agriculture and else while those derived from aldehydes known as
fields. The organic chemistry of heterocyclic aldimines [7,8]. Schiff bases form a significant
compounds was as pertinent as that of alicyclic class of the most vastly used organic
and aromatic compounds. Heterocyclic compounds and was been a vast variety of
organic compounds applied as applications in numerous fields, (biological,
pharmaceuticals, agrochemicals and veterinary inorganic and analytical chemistry). Several of
yields, applied as optical brightening agents, them were the basic units in certain dyes and
like antioxidants, like corrosion inhibitors and were also applied as liquid crystals [9]. Schiff
like additives with a variety of else functions base are classes of important compounds in the
[1]. Also, numerous dyestuffs and pigments pharmaceutical field [10]. They show
were heterocyclic structures [2]. biological activities, including antibacterial,
Pyrazole is an organic compound with the antifungal, and anticancer [11]. This
formula C3H3N2H. It is a heterocycle investigation demonstrated synthesis of new
characterized by a 5-membered ring of three Schiff's bases compounds derived from
carbon atoms and two adjacent nitrogen atoms. pyrazole with fully characterization, and
Pyrazoles are also a class of compounds that aiming to further biochemical studies.
have the ring C3N2 with adjacent nitrogen
atoms. Notable drugs containing a pyrazole
ring are celecoxib (Celebrex) and the anabolic
steroid stanozolol.
The pyrazole ring is found within a variety
of pesticides as fungicides, insecticides and
herbicides, including chlorfenapyr,
fenpyroximate, fipronil, tebufenpyrad,
tolfenpyrad, and tralopyril [3-5].
Schiff's bases are compounds which
contain an isomethine group (N=C), they are
named after Schiff who prepared a number of
these bases via condensation of aliphatic and
aromatic aldehyes and ketones with primary

57
 Hiba H. Ibraheem

H2 N C OC 2 H5

NH2NH2.H2O

H2 N C NHNH 2

(1)
EAA

H2 N C N N

O CH 3
(2)
CHO
/NaNO2,HCl
OH
O

CHO
N N C N N

O
H 3C
(3) OH
NH2

R = p-COOC2H5 ,
m-NO2 R
R
O
H
C N
N N C N N

O
H 3C
OH
(4,5) R = p-COOC2H5 ,
m-NO2
Scheme (1): Synthesis scheme of compounds.

Materials and Methods Spectrometer, d6-DMSO was use as a solvent

The melting points were determined in in1H-NMR Spectra.
open capillary tubes on a Gallen Kamp
melting point apparatus and are uncorrected. Synthesis of 4-aminobenzohydrazide (1)
The FT.IR Spectra of prepared derivatives [12]
were taken on Shimadzu-2N, FTIR-8400S,1H- A solution of 4-aminobenzoate (1.65 g.,
NMR Spectra of some prepared derivatives 0.01 mole) in ethanol (25mL.), hydrazine
were recorded on a Varian-Mercury 300MHZ hydrate (80%) (0.5g.,0.01 mole) was added

58
Journal of Al-Nahrain University Vol.21 (2), June, 2018, pp.57-63 Science

drop wise with stirring. The mixture has been 2330C, Yields: 78%. The FTIR spectral data
refluxed for 12 hrs. After cooling the product showed absorption in at (3200cm-1, for OH),
formed, filtered off, and recrystallize by (1726cm-1, for C=O, pyrazole), (1701cm-1,
ethanol: water (1:1). Melting point:217-2190C, for C=O,aldehyde), (1685cm-1, for C=O),
Yields: 90%. The FTIR spectral data showed (1604cm-1, for C=N), and (1577cm-1, for
absorption at (1629cm-1 for C=O), (1562cm-1 N=N). The 1H-NMR spectrum of compound
for C=C, Ar.), (3034cm-1, for C-H, (3) showed the following data: 2.00 ppm(s,
Aromatic) and (3429-3234 cm-1 for NHNH2). 3H, CH3 of pyrazole ring), 2.30 ppm (s,2H,
The ¹HNMR spectrum from compound [1] CH2 of pyrazole ring), 7.1-8.3 ppm (m,7H, Ar-
show the data: (DMSO,): 4.5ppm(s,due to 2H H ), 9.88 ppm (s, 1H,CHO) and 11.40 ppm
of – NH2), 5.5pmm(s,due to 2H of Ar– NH2), (s, 1H , for OH).
6.7-7.5 (m, 4H, due to 4H of Benzene ring,),
8.9(S,due to 1H of –NH). General procedure to synthesis of Schiff’s
basses compounds (4,5)
Synthesis of 1-(4-aminobenzoyl)-3-methyl- A solution of 2-hydroxy-5-((4-(3-methyl-
1H-pyrazol-5(4H)-one (2) 5-oxo-4,5-dihydro-1H-pyrazole-1-carbonyl)
A solution of 4-aminobenzohydrazide (1) phenyl)diazenyl)benzaldehyde (3) (0.35 g.,
(1.5g.,0.01mole) and ethyl acetoacetate 0.001mole) in absolute ethanol (10ml), and
(1.3g.,0.015mole) were taken in absolute appropriate aromatic amine (ethyl 4-
ethanol (25 ml.). The solution was refluxed for aminobenzoate and 3-nitroaniline)
4 hrs. The solution was cooled to give the (0.001mole) was refluxed for 4-6 hrs. in the
precipitate [13] and recrystallized by ethanol. presence of few drops of glacial acetic acid.
Melting point: 240-242 0C, Yields: 75%. The After cooling the product, a solid formed,
FTIR spectral data showed absorption at filtered off, dried and purified by
(3213cm-1, for -NH2), (3082cm-1, for C-H, recrystallization from ethanol.
Ar.), (2962,2920cm-1, for CH, aliphatic),
(1750cm-1, for C=O, pyrazole), (1697cm-1, Synthesis of 1-(4-((4-hydroxy-3-((4-
for C=O), (1604cm-1, for C=N), and propionylphenylimino)methyl)phenyl)
(1444cm-1, for C=C, Ar.). The 1H-NMR diazenyl)benzoyl)-3-methyl-1H-pyrazol-
spectrum of 1-(4-aminobenzoyl)-3-methyl-1H- 5(4H)-one (4)
pyrazol-5-(4H)-one (2) show the absorotion Melting point: 198-2000C, Yields: 82%.
bands at: 2.00 ppm(s, 3H, CH3 of pyrazole The FTIR spectral data showed absorption at
ring), 2.23 ppm (s,2H, CH2 of pyrazole ring), 5 (2923,2845cm-1, for CH, aliphatic),
(s,due to 2H of –NH2), and 6.1-7.6 ppm (1732cm , for C=O pyrazole), (1712cm-1, for
-1

(m,4H, Ar-H) . C=O, ester), (1698cm-1, for C=O, amide),

(1616cm-1, for C=N). The 1H-NMR spectrum
Synthesis of 2-hydroxy-5-((4-(3-methyl-5- of compound (4) showed the following data
oxo-4,5-dihydro-1H-pyrazole-1- :1.6 ppm(t, 3H,CH3), 2.00 ppm(s, 3H, CH3 of
carbonyl)phenyl)diazenyl)benzaldehyde (3) pyrazole ring), 2.30 ppm (s,2H, CH2 of
Compound (2) (2g.,0.01mole) was pyrazole ring), 3.1 ppm (q,2H, -CH2-), 7.2-9
dissolved in distilled water (4 mL) and conc. ppm (m,10H, Aromatic-H) ,8.4 ppm (s,1H for
HCl (2.25 ml). The mixture was stirring for 15 N=C-H) ) and 11.2 ppm (s,1H for OH).
min at 00C. A mixture of NaNO2 (0.69g.,0.01
mole) in water (2.55 mL) was added gradually. Synthesis of 1-(4-((4-hydroxy-3-((3-
After stirring for 15 min., the mixture of nitrophenylimino)methyl)phenyl)
diazonium salt has been added gradually to a diazenyl)benzoyl)-3-methyl-1H-pyrazol-
solution of salicylaldehyde (1.22g., 0.01 mole) 5(4H)-one (5)
in ethanol and 10% NaOH (10mL.) at (0-5)0C Melting point: 125-1270C, Yields: 80%.
and pH=6. The solution is stirring for 20 min. The FTIR spectral data showed absorption at
then is left for 1.5 hr. The solid has been (1730cm-1, for C=O pyrazole), (1707cm-1, for
filtered off, dry the precipitation and C=O, amide), (1618cm-1, for C=N). The 1H-
recrystallize by ethanol. Melting point: 231- NMR spectrum to 1-(4-((4-hydroxy-3-((3-
59
 Hiba H. Ibraheem

nitrophenylimino)methyl)phenyl)diazenyl)ben aminobenzohydrazide (1) show the data:

zoyl)-3-methyl-1H-pyrazol-5(4H)-one (5) (DMSO,): 4.5 ppm(s,due to 2H of – NH2),
show the data in at: 2.3 ppm(s, 3H, CH3 of 5.5 ppm (s,due to 2H of Ar– NH2), 6.7-
pyrazole ring), 2.5 ppm (s,2H, CH2 of pyrazole 7.5 ppm (m, 4H, due to 4H of Benzene ring,),
ring), 6.1 – 8.9 ppm (m, 10H, Aromatic-H) 8.4 8.9 ppm (s,due to 1H of –NH).
ppm (s,1H for N=C-H) and 10.5 ppm (s,1H , The pyrazole derivative is prepared
for OH). through the reaction of hydrazide derivative
(1) and ethyl acetoacetate to give compound
Result and Discussion (2). The FTIR spectrum of 1-(4-
The 4-aminobenzohydrazide (1) is aminobenzoyl)-3-methyl-1H-pyrazol-5(4H)-
prepared by substitution reaction between 4- one (2) showed new band at (1570) cm-1
aminobenzoate and hydrazine hydrate (80%) which belong to stretching absorbtion of C=N
in the presence of ethanol as a solvent. The of pyrazole, and the disappearance of the
reaction proceeds by nucleophilic substitution bands at (3419-3200) for NH2 Its worth to
of hydrazine hydrate to the ester carbonyl mention, that pyrazole (2) has other important
group in 4-aminobenzoate followed by losing bands at (1750) cm-1 for carbonyl in pyrazole
of CH3CH2OH molecule. The FTIR spectrum ring. The 1H-NMR spectrum of 1-(4-
for hydrazide derivative (1) shows the aminobenzoyl)-3-methyl-1H-pyrazol-5(4H)-
stretching vibration at regions(3419-3200)cm-1 one (2) showed the appearance 2 ppm (s,3H
for asymmetric and symmetric (NH-NH2), and for CH3).
disappearance band at (1685) cm-1 which
belong to stretching vibration of carbonyl
group of ester. The ¹HNMR spectrum of 4-
O O
H2N C N N H2N C N N
enol

O CH3 HO CH3

The synthesis of an azo dye requires two aminobenzoate and 3-nitroaniline) at absolute
molecules a diazonium salt and a coupling ethanol like a solvent. The reaction proceeds
component. The diazonium salt reacts an via nucleophilic attack of the amine on the
electrophile reaction for an electron-rich carbonyl carbon of the aldehyde with the loss
coupling component, such as a phenol of a water molecule. The FTIR spectrum of
derivative over an electrophilic aromatic compound (4) show the new band at (1610)
substitution mechanism. The -OH group like cm-1 which could be attributed to C=N, and the
salicylaldehyde direct the aryl diazonium ion disappearance of absorption band at (1685)
to the para position exceot if that position is cm-1 for (C=O) of aldehyde.
occupied, in which condition the ion link ortho
[14]. The FTIR spectrum 2-hydroxy-5-((4-(3-
methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-
carbonyl)phenyl)diazenyl) benzaldehyde (3)
showed an absorption band at (3200 cm-1)
because of stretching vibration for hydroxyl
group, band at (1685 cm-1) because of
stretching vibration at C=O of aldehyde, band
at (1510 cm-1) indicating the ( N=N).
The Schiff bases (4,5) were synthesized
through the condensation of 2-hydroxy-5-((4-
(3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-
carbonyl) phenyl)diazenyl)benzaldehyde (3)
for appropriate aromatic amine (ethyl-4-

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Journal of Al-Nahrain University Vol.21 (2), June, 2018, pp.57-63 Science

Table (1)
The physical properties for the yields.

Comp. Molecular
Nomenclature Structural formula Color
No. formula
O
4-
(1) H2N C NHNH 2 C9H11NO2 White
aminobenzohydrazide
O
1- (4-aminobenzoyl)-3-
H2N C N N White-
(2) methyl-1H-pyrazol- C7H9N3O
Milky
5(4H) -one CH 3
O

2-hydroxy-5-((4-(3- O

methyl-5-oxo-4,5- N N C N N
CHO

(3) dihydro-1H-pyrazole- C11H11N3O2 Red

1-carbonyl) phenyl) H3C
O

diazenyl) benzaldehyde OH

1-(4-((4-hydroxy-3- O
((4- H
C N COOC2H5
propionylphenylimino) N N C N N
(4) C24H18N6O5 Yellow
methyl)phenyl)diazeny
l)benzoyl) -3-methyl- O
H3C
1H-pyrazol-5(4H)-one OH

1-(4-((4-hydroxy-3- NO 2

((3-nitrophenylimino) O
H
(5) methyl)phenyl)diazeny N N C N N
C N
C24H18N6O5 Orange
l)benzoyl)-3-methyl- O
H3C
1H-pyrazol-5(4H)-one OH

Conclusion
The acid hydrazide (1) derivative can be
synthesized through the reaction of 4-
aminobenzoate for hydrazine hydrate. The
obtained yields of final product when ethanol
was used as solvent. In this study synthesized
pyrazole derivative using simple and
inexpensive method using ethyl acetoacetate to
cyclization compound. A series of Schiff bases
derivatives were successfully synthesized
using glacial acetic acid as catalysts. The
newly synthesized compounds were
characterized by using melting points and
spectroscopic methods (FTIR and 1H NMR).

61
 Hiba H. Ibraheem

Fig.(1): 1H NMR Spectrum of Compound (2).

Fig.(2): 1H NMR Spectrum of Compound (5).

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