Solvent free preparation of n-substituted maleanilic acid

Article abstract of DOI:10.4314/bcse.v27i1.15

Six N-maleanilic acids namely N-(4-carboxy)maleanilic acid (CAMAA), N-(4- bromo)maleanilic acid (BMAA), N-(4-hydroxy)maleanilic acid (HMAA), N-(3-hydroxy)maleanilic acid (mHMAA), N-(4-chloro)maleanilic acid (CMAA) and N-(4-methyl)maleanilic acid (MMAA) we

Full text of DOI:10.4314/bcse.v27i1.15

Bull. Chem. Soc. Ethiop. 2013, 27(1), 137-141.
Printed in Ethiopia
DOI: http://dx.doi.org/10.4314/bcse.v27i1.15
ISSN 1011-3924
 2013 Chemical Society of Ethiopia
SHORT COMMUNICATION
SOLVENT FREE PREPARATION OF N-SUBSTITUTED MALEANILIC ACID
Habib Saedi*
Polymer Research Unit, College of Science, Al Mustansiriya University, Baghdad, Iraq
(Received May 10, 2011; revised November 28, 2012)
ABSTRACT. Six N-maleanilic acids namely N-(4-carboxy)maleanilic acid (CAMAA), N-(4-
bromo)maleanilic acid (BMAA), N-(4-hydroxy)maleanilic acid (HMAA), N-(3-hydroxy)maleanilic
acid (mHMAA), N-(4-chloro)maleanilic acid (CMAA) and N-(4-methyl)maleanilic acid (MMAA)
were prepared by solvent free reaction between maleic anhydride and a 4-carboxy, 4-bromo, 4-
hydroxy, 3-hydroxy, 4-chloro and 4-methyl aniline derivatives in good to excellent yield. FT-IR,
1H-NMR and 13C-NMR spectra revealed the confirmation of these compounds in good agreement.
KEYWORDS: Solvent free, Maleanilic acids, Maleic anhydride, Aniline derivatives
INTRODUCTION
The reaction of aniline or its derivatives with maleic anhydride is well-known, because the
product maleanilic acid or N-substituted maleanilic acid can be used to prepare the maleimides
which are an important class of substrates for biological as chemical probes of protein structure
[1], as a protective and curative fungicide [2] and in polymer chemistry as photoinitiators for
free-radical polymerization [3, 4] and monomers in polymaleimides or their copolymers
synthesis.
The literature contains a large number of publications regarding to the synthesis of
maleanilic acids mostly consisting of the reaction of equimolar of aniline or its derivatives with
maleic anhydride in the presence of a solvent. Different solvents can be used, ether [5], acetic
acid [6], acetone [7], nitrobenzene [8], chloroform [9] or mixed solvents such as equal volume
of ethyl alcohol and water [10]. The reactions were carried out at 0-5 oC [11], room temperature
[12, 13] or at 70-75 oC [14].
Also, it may be noted that the amount of used solvent is a large one for any of these
preparations. For example; to obtain about ninety grams of N-(p-chloro)maleanilic acid more
than half liter of methylene chloride had been used [15, 16].
In this article, six N-maleanilic acids CMAA, BMAA, HMAA, MMAA, mHMAA and
CAMAA were prepared by solvent free reaction between maleic anhydride and a 4-chloro, 4-
bromo, 4-hydroxy, 4-methyl, 3-hydroxy and 4-carboxy aniline derivatives at room temperature.
EXPERIMENTAL
Materials. All chemicals were purchased from Merck Chemical Co. (Germany). 4-
Chloroaniline, 4-bromoaniline, 4-aminophenol, 3-aminophenol, and 4-aminobenzoic acid were
used as received. Maleic anhydride was recrystallized from acetone.
Instrumental analysis. The IR spectra were recorded on a Shimadzu FTIR 8300 series
1
spectrometer using KBr pellets. The H and 13C NMR spectra were recorded on Bruker 500
__________
*Corresponding author. E-mail: habibmahtook@yahoo.com

138
Habib Saedi
MHz spectrometer in solutions of CDCl3 or DMSO-d6. The elemental analysis was taken by a
Carlo Erba Model NA 500 series analyzer. The melting points were determined by Stuart
(SMP3) Melting Point Apparatus.
N-(Substituted) maleanilic acids preparation. p-Chloroaniline 12.75 g (0.1 mol) was mixed and
ground at room temperature with maleic anhydride 9.8 g (0.1 mol) in an agate mortar. As a
crunching preceeded a nice greenish-yellow color appeared. The grinding was continued for 30
more min. The crude product was crystallized from ethanol and the collected greenish-yellow
crystals were dried. Melting point: 197-199 oC, yield 92%. The other five N-substituted
maleanilic acids were prepared on the same procedure. Time of grinding, melting point and
elemental analysis of the prepared N-(substituted) maleanilic acids are listed in Tables 1. Pure
1
and dry samples of prepared N-maleanilic acids were characterized by FT-IR (Table 2), H-
NMR (Table 3) and 13C-NMR (Table 4).
RESULTS AND DISCUSSION
A series of N-substituted maleanilic acids (MAA) have been prepared using a solid phase (new
approach) reaction between solid maleic anhydride and various solid N-substituted anilines at
room temperature. The prepared maleanilic acids are depicted in Scheme 1. The synthetic
method used to prepare the series is simple, clean, economic and nearly quantitative or high
yields (Table 1).
The FT-IR spectra of the compound CMAA exhibited no anhydride C=O stretching band at
1870-1725 cm-1 region indicating that the maleanilic acids have been successfully prepared. The
FT-IR spectrum showed several characterization bands. The broad -OH stretching band
associated with the carboxylic group between 3275-2877 cm-1, the weak –NH amide stretching
band at 3198 cm-1 and the C-H aromatic stretching absorption band at 3076 cm-1 have generally
been seen. The band at 1701 cm-1 are due to the carboxylic C=O stretching band expected to α-
β-unsaturated system for the dimers [15]. The absorption band at 1630 cm-1 is assigned to amide
I. The band at 1545 cm-1 are due to the interaction of the N-H bending and C-N stretching
vibration, also referred to as the amide II bands and are characterized to primary and secondary
amide [16]. The bands at 1392 cm-1 are assigned to the O-H bending of the carboxylic acid. The
CO stretching at 1317 cm-1 are those associated with the OC-OH carboxylic group. The
stretching absorption at 1088 cm-1 has been assigned to the aromatic C-Cl band. The structures
of the other prepared compounds have been confirmed by FT-IR (Table 2).
COOH
NH
2
O
+
R
NH
O
O
O
R
MAA
MA
where R = 4-Cl (CMAA) R = 4-Br (BMAA) R = 4-OH (HMAA) R = 4-CH3 (MMAA) R = 3-
OH (mHMAA) R = 4-COOH (CAMAA)
Scheme 1. Preparation of N-Substituted maleanilic acids.
Bull. Chem. Soc. Ethiop. 2013, 27(1)

Short Communication
139
Table 1. Mixing time, melting point, yield% and elemental analysis of prepared N-substituted maleanilic
acids.
Compound
Name of Mixing
compound
m.p.
(ºC)
Formula
Yield (M.Wt.)
(%)
Elemental Analysis
H %
time
(min)
C %
N %
Found Cal. Found Cal. Found Cal.
N-(-4-chloro)
maleanilic
acid
CMMA
30
197-199, Lit.
195-198 [9]
92.0 C10H8NO3Cl 53.28 53.25 3.51 3.55 6.24 6.21
(225.55)
N-(-4-bromo)
maleanilic
acid
BMAA
HMAA
MMAA
40
30
40
187-190, Lit.
192-193.5 [10]
90.3 C10H8NO3Br 44.50 44.48 2.95 2.96 5.24 5.19
(270.00)
N-(-4-hydro-
xy) male-
anilic acid
N-(-4-
207-208
195-197
Lit. 201-202 [11] 94.1 C11H11NO3 64.45 64.41 5.33 5.36 6.79 6.83
92.4 C10H9NO4 58.01 57.99 4.37 4.35 6.81 6.76
(207.10)
methyl) male
anilic acid
Lit. 174-175 [12]
Lit. 186-188 [9]
(205.11)
N-(-3-
HMAA
hydroxy)mal
eanilic acid
N-(-4-
30
30
186-189
91.0 C10H9NO4 57.98 57.99 4.39 4.35 6.73 6.76
(207.10)
219-221
Lit. 225-226 [13] 86.7 C11H9NO5 56.15 56.19 3.81 3.83 5,97 5.95
Lit. 222 [14] (235.11)
CAMAA
carboxy)mal
eanilic acid
The 1H-NMR data of compound CMAA, HMAA and mHMAA are shown in Table 3,
exhibit signals at 13.2 ppm and 10.44 ppm attributed to the carboxylic acid –OH and H-(NCO)
1
amide protons. The expanded H-NMR of the compound CMAA shows distinguished doublets
due to aromatic protons ; protons that are ortho to amide group show a doublet signal 7.65-7.67
ppm and that are ortho to chloride appear at 7.36-7.38 ppm . These two doublet signals have the
same coupling constant (J) and the same integrated area, indicating the presence of four protons
with two couples that are chemically but not magnetically equivalent [15]. The vinylic protons
resonate at 6.47-6.50 ppm as doublet. The integrated area of the aromatic region to that of
vinylic region in the 1H-NMR spectrum of the compound CMAA, indicated that aromatic
protons to vinylic protons are in the ratio of 3.893:2, which is in the region of theoretical value
1
4:2. The H-NMR spectra for the other maleanilic acids show typical signals which confirm
their structures (Table 3).
13C-NMR has also been useful to confirming some of the N-maleanilic acids, 13C-NMR
spectrum of compound CMAA exhibits two peaks at 167.54 ppm and 164.28 ppm for
carboxylic and amide carbons. The two vinylic carbons, adjacent to the carboxylic and amide
groups resonate at 131.11 and 128.44 ppm, respectively. The aromatic carbon signals appeared
as four different peaks; the carbon that is substituted with amide group resonates at 138.35 ppm
and that is substituted with chloride resonates at 132.76 ppm. The two carbon atoms ortho to
amide group resonate at 122.02 ppm and that which is ortho to chloride group resonates at
129.53 ppm. The other compounds show their own signals which are confirmed there chemical
structures (Table 4).
Bull. Chem. Soc. Ethiop. 2013, 27(1)

140
Habib Saedi
Table 2. FT-IR measurements of the prepared N-substituted maleanilic acids.
Comp-
ound
Structure
Band frequencies*
νCOO- νNH3 νar.C-H νC=O νC=O νsy.-
σ O-H
Others
νC-O
H
(amide
)
(C=C- (amide I) NHCO-
OOH) N-C=O (amide II)
COOH
CAMAA
3500- 3307
2500
3034
1699
1626
1545
1415 1298
σC-H
846
COOH
O
NH
Cl
CMAA
BMAA
HMAA
3275- 3198
2877
3076
3074
3072
1701
1706
1697
1630
1628
1625
1545
1546
1541
1392 1317
1394 1321
1412 1329
νar.C-Cl
1088
COOH
COOH
COOH
O
NH
NH
Br
3271- 3193
2870
νar.C-Br
1076
O
OH
3292- 3126
2821
νar.C-O
(pphenol)
1229,
O
NH
1246
CH3
MMAA
3277- 3205
2837
3078
3078
1699
1699
1633
1616
1531
1568
1398 1309
1407 1302
COOH
O
NH
mHMA
A
3336- 3282
2696
νar.C-O
(phenol)
1356,
COOH
O
NH
OH
1261
(*) ν = stretching band, σ = bending band, sy. = symmetric vibration mode.
Table 3. 1H-NMR measurements for some prepared n-substituted maleanilic acids.
Comp-
ound
Structure
Chemical shifts (σ/ppm) relative to TMS*
O-H N-H Ha Hb Hc Hd He Hf
Others
H
e
CMAA
13.20 10.43 6.47- 6.30- 7.65- 7.36- 7.36- 7.65-
6.50 6.34 7.67 7.38 7.38 7.67
f
H
Cl
COOH
O
(s)
(s)
(d)
(d)
(d)
(d)
(d)
(d)
a
H
NH
H d
H
b
H
H
c
e
HMAA
13.20 10.43 6.47- 6.26- 7.42- 6.74- 6.74- 7.42- 6.62-6.63
6.50 6.29 7.43 6.75 6.75 7.43 H-(ar.OH)
f
H
OH
H d
COOH
O
(s)
(s)
(d)
(d)
(d)
(d)
(d)
(d)
a
H
NH
H
b
H
c
H
e
mHMAA
13.20 10.30 6.46- 6.28- 7.25 6.52 7.09- 6.99- H-(ar.OH)
6.31 6.31
(d) (d)
f
H
H d
7.12 7.00
(d) (d)
9.44
broad
COOH
O
(s)
(s)
(s)
(d)
a
H
NH
OH
H
b
H c
(*)Multiplicity: s = singlet; m = multiplet; t = triplet; d = doublet.
Bull. Chem. Soc. Ethiop. 2013, 27(1)

Short Communication
141
Table 4. Spectral 13C-NMR data of some prepared n-substituted maleanilic acids.
Compound
CMAA
Structure
Chemical shifts (σ/ppm) relative to TMS
Cn Ce Cf Cg Ch Ci
Ca
Cb
Ck
Cm
k
131.11 128.44 167.54 164.28 138.35 122.02 129.35 132.76 129.35 122.02
C
Cl
i
C
m
n
COOH
O
C
a
C
C
b
C
e
C
f
C
h
NH
C
g
k
C
HMAA
132.96 132.36 166.96 163.23 130.49 122.58 116.14 155.80 116.14 122.58
-
116.67
OH
i
C
m
n
COOH
O
C
-
166.67
a
C
C
b
C
e
C
f
C
h
NH
C
g
k
C
mHMAA
132.83 131.37 167.55 164.10 140.25 107.77 158.50 113.37 130.33 112.10
i
C
m
n
COOH
O
C
h
a
C
C
b
C
e
C
f
C
NH
C
g
OH
CONCLUSIONS
This work involved preparation of six N-maleanilic acids CMAA, BMAA, HMAA, MMAA,
mHMAA and CAMAA by solvent free reaction between maleic anhydride and a 4-chloro, 4-
bromo, 4-hydroxy, 4-methyl, 3-hydroxy and 4-carboxy aniline derivatives at room temperature.
This new approach, solvent free preparation method is simple, clean, economic and nearly
quantitative or high yields.
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