Solvent-free synthesis of azomethines, spectral correlations and antimicrobial activities of some E-benzylidene-4-chlorobenzenamines

Article abstract of DOI:10.4314/bcse.v29i2.10

Some azomethines including substituted benzylidene-4-chlorobenzenamines (E-imines) have been synthesized by fly-ash: PTS catalyzed microwave assisted condensation of 4-chloroaniline and substituted benzaldehydes under solvent-free conditions. The yield of the imines has been found to be more than 85%. The purity of all imines has been checked using their physical constants and UV, IR and NMR spectral data. These spectral data have been correlated with Hammett substituent constants and F and R parameters using single and multi-linear regression analysis. From the results of statistical analysis, the effect of substituents on the above spectral data has been studied. The antimicrobial activities of all imines have been studied using standard methods.

Full text of DOI:10.4314/bcse.v29i2.10

Bull. Chem. Soc. Ethiop. 2015, 29(2), 275-290.
Printed in Ethiopia
DOI: http://dx.doi.org/10.4314/bcse.v29i2.10
ISSN 1011-3924
 2015 Chemical Society of Ethiopia
SOLVENT-FREE SYNTHESIS OF AZOMETHINES, SPECTRAL CORRELATIONS
AND ANTIMICROBIAL ACTIVITIES OF SOME E-BENZYLIDENE-4-
CHLOROBENZENAMINES
R. Suresh1, S.P. Sakthinathan1, D. Kamalakkannan1, K. Ranganathan1, K. Sathiyamoorthi1,
V. Mala1, R. Arulkumaran1, S. Vijayakumar1, R. Sundararajan1, G. Vanangamudi1,
M. Subramanian1,*, G. Thirunarayanan2, G. Vanaja3 and P. Kanagambal3
1PG & Research Department of Chemistry, Government Arts College, C-Mutlur, Chidambaram-
608102, India
2Department of Chemistry, Annamalai University, Annamalainagar-608002, India
3Department of Chemistry, Dhanalakshmi Arts and Science College for Women, Perambalur-
621212, India
(Received April 3, 2013; revised February 20, 2015)
ABSTRACT. Some azomethines including substituted benzylidene-4-chlorobenzenamines (E-imines) have been
synthesized by fly-ash: PTS catalyzed microwave assisted condensation of 4-chloroaniline and substituted
benzaldehydes under solvent-free conditions. The yield of the imines has been found to be more than 85%. The
purity of all imines has been checked using their physical constants and UV, IR and NMR spectral data. These
spectral data have been correlated with Hammett substituent constants and F and R parameters using single and
multi-linear regression analysis. From the results of statistical analysis, the effect of substituents on the above
spectral data has been studied. The antimicrobial activities of all imines have been studied using standard
methods.
KEY WORDS: Solvent-free synthesis, Fly-ash: PTS, Aryl imines, Spectral correlations, Antimicrobial activities
INTRODUCTION
Azomethines are the imine compounds, which contain –C=N– group. These compounds are also
known as imines but most commonly, they are known as Schiff bases to honor Hugo Schiff,
who synthesized these compounds first [1]. Schiff bases can be hemiaminal which followed by a
dehydration to generate imines. Schiff bases are synthesized from aromatic amines and carbonyl
compound by nucleophilic condensation forming important class of organic compounds,
especially in the medicinal and pharmaceutical fields. Now-a-days the development and
synthesis of novel Schiff’s base derivatives as potential chemotherapeutics still attract the
attention of organic and medicinal chemists [2, 3]. Many studies reported the biological
activities of Schiff’s bases, including their anticancer, antibacterial, antifungal, and herbicidal
activities [4]. Spectroscopic data is very useful for studying the ground state equilibrium of
organic molecules through linear relationships [5]. The infrared and NMR spectroscopic data
determines the structure of unsaturated systems, such as E- or Z, s-cis and s-trans conformers of
styrenes, enones, unsaturated acid chlorides, acyl chlorides and their esters [6, 7]. Recently,
Suresh et al. [8] have synthesized some aryl E-imines and studied the UV, IR and NMR spectral
liner correlation analysis through Hammett equation. In their investigations they observed
satisfactory and good correlations for the above spectroscopic data with Hammett substituent
constants and Swain Luptons’ [9] parameters.
It is well known that microwave (MW) irradiation can accelerate a great number of chemical
processes and in particular, the reaction time and energy input are supposed to be mostly
reduced in the reactions that are run for a long time at high temperatures under conventional
conditions [10]. The most successful applications of microwave irradiation are found to be
__________
*Corresponding author. E-mail: drmsgacplcmcdm@gmail.com

276
R. Suresh et al.
related to the use of solvent-free systems, in which microwaves interact directly with reagents.
Therefore, it can more efficiently accelerate chemical reactions. In classical organic synthesis of
Schiff bases, the common problems are removal of solvents from the reaction mixture, solvent
extraction especially in the case of aprotic dipolar solvents with high boiling point and product
isolation through solvent-solvent extraction. The absence of solvent reduces the risk of
hazardous explosions when the reaction takes place in a closed vessel or a microwave oven [11].
Local overheating, which can lead to product, substrate and reagent degradation is avoided in
microwave-assisted synthesis [12]. The solvent-free organic synthesis mediated by microwave
irradiation offers several advantages such as they involve shorter duration, operational
simplicity, easy workup procedure, less hazardousness to humans and environment and better
yields. Therefore the authors have taken efforts to synthesis imines from substituted
benzaldehydes and 4-chloroaniline using fly-ash: PTS catalyst with microwave irradiation under
solvent-free conditions. The spectral data of these imines have been utilized for studying the
quantitative structure-activity relationships through Hammett correlations. The biological
activities of these imine derivatives have been studied using standardmethod [13].
EXPERIMENTAL
General
All the chemicals involved in the present investigation, have been procured from Sigma-Aldrich
and E-Merck chemical companies. Melting points of all imines have been determined in open
glass capillaries on SUNTEX melting point apparatus and are uncorrected. The UV spectra of
all the imines, synthesized, have been recorded with ELICO-BL222 spectrophotometer (max
,
nm) in spectral grade methanol solvent. Infrared spectra (KBr, 4000-400 cm-1) have been
recorded on SHIMADZU-2010 Fourier transform spectrophotometer. Bruker AV400 NMR
1
spectrometer has been utilized for recording H NMR, operating at 400 MHz spectra and 100
MHz for 13C spectra in CDCl3 solvent using TMS as internal standard. Electron impact (EI) (70
eV) and chemical ionization mode FAB+ mass spectra have been recorded with a JEOL
JMS600H spectrometer.
Synthesis of catalyst
The fly-ash:PTS catalyst has been prepared following the procedure published in literature [14].
In a 50 mL Borosil beaker, 1 g of fly-ash and 0.8 mL (0.5 mol) of PTS have been taken and
mixed thoroughly with glass rod. This mixture has been heated on a hot air oven at 85 oC for 1
h, cooled to room temperature, stored in a borosil bottle and tightly capped.
Synthesis of imines
An appropriate equimolar quantity of aryl amines (2 mmol), substituted benzaldehydes (2
mmol) and fly-ash:PTS (0.5 g) have been taken in borosil tube and tightly capped. The mixture
was subjected to microwave irradiation for 6-12 min in a microwave oven at 650W (Scheme 1)
(Samsung GW73BD Grill Model microwave Oven, 100-750 W, 230 V - 50 Hz, 2450 MHz) and
then cooled to room temperature. After separating the organic layer with dichloromethane the
solid product has been obtained on evaporation. The solid, on recrystallization with benzene-
hexane mixture afforded glittering product. The insoluble catalyst has been recycled by washing
with ethyl acetate (8 mL) followed by drying in an oven at 100 oC for 1 h and reused for further
reactions.
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Solvent-free synthesis of azomethines
277
O
fly-ash:PTS
MW, 650W
N
Ar'
H
Ar'
Ar
NH2
Ar
H
(1-36)
Entry 30: Ar= 4-ClPh
Ar'=Ph
Scheme 1. Synthesis of substituted benzylidene-4-chloroanilines in presence of fly-ash:PTS
catalyst under microwave irradiation.
RESULTS AND DISCUSSION
Fly-ash has been converted into useful catalyst fly-ash:PTS by mixing fly-ash and PTS. The
PTS and other chemical species present in the fly-ash have enhanced the catalytic activity [7, 8,
10, 14, 15]. During the course of the reactions these species are responsible for promoting
condensation between the aryl amines and aryl aldehydic groups leading to the formation of
imines. In these experiments the products were isolated and the catalyst was washed with ethyl
o
acetate, heated to 100 C then reused for further five run reactions. In this protocol the reaction
gave better yields of the imines during the condensation without any environmental discharge.
We have investigated the catalytic effect of fly-ash: PTS on the synthesis of benzylidene-4-
chloroaniline (entry 30, Table 2) by varying the catalyst quantity from 0.1 g to 1 g. As the
catalyst quantity was increased from 0.1 g to 1 g, the percentage of yield of product was
increased from 85 to 92%. The effect of catalyst loading was shown in Figure 1. The proposed
mechanism for the condensation of the amine and aldehydes is shown in Scheme 2. Further
increase the catalyst amount there was no significant increasing of the percentage of product.
The optimum quantity of catalyst loading was found to be 0.4 g. The reusability of catalyst on
condensation of 4-chloroaniline and substituted benzaldehyde are studied. First two runs gave
92% product. The third, fourth and fifth runs of reactions gave the yields 91.5, 91.5 and 91% of
imines. The reusability of the catalyst on the yields of the imines is presented in Table 1. There
was no appreciable loss in its effect of catalytic activity was observed up to fifth run. The
analytical and mass spectral data were presented in Table 2. The complete UV, IR and NMR
spectral data of all imines were presented Table 3. The IR and NMR spectra of selective
compounds are provided in supplementary data.
Bull. Chem. Soc. Ethiop. 2015, 29(2)

278
R. Suresh et al.
O
H
Acidic site of
OH
C
OH2
C
Fly-ash:PTS
Ar
NH2
N
H
Ar'
N
H
Ar'
H
Ar'
Ar
Ar
MW
H
H
OH2
C
N
Ar'
N
H
Ar'
Acidic site of
Fly-ash:PTS
Ar
C
H
-H2O
Acidic site of
Fly-ash:PTS
Ar
H
30: Ar=4-ClPh
Ar'=Ph
Scheme 2. The proposed mechanism for the synthesis of E- imines in presence of fly-ash:PTS
catalyst under microwave irradiation.
Figure 1. The effect of loading of catalyst on synthesis of substituted benzylidene-4-
chloroanilines in presence of fly-ash: PTS catalyst under microwave irradiation (entry
30).
Table 1. Reusability of catalyst on condensation of 4-methoxy aniline (2 mmol) and benzaldehydes (2
mmol) (entry 30) under microwave irradiation.
Run
1
2
3
4
5
Yield
92
92
91.5
91.5
91
Table 2. Analytical and mass spectral data of aryl imines synthesized by aryl amines and substituted
benzaldehydes reaction of the type Ar-NH2 + Ar’-CHO → Ar-N=CH-Ar’ under microwave
irradiation.
Entry Ar
Ar’
Product
M.W. Yield M.p.
(%) (oC)
Mass (m/z)
---
C6H5
C6H5
C6H5N=CHC6H5
181
87
52-53
(50-52)
[8]
1
C6H5
C6H5
4-ClC6H4
C6H5N=CHC6H4Cl(4)
215
211
85
87
61 (60- ---
62) [8]
2
3
4-CH3O-C6H4 C6H5N=CHC6H4OCH3(4)
56
-57 ---
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Solvent-free synthesis of azomethines
279
(54-56)
[8]
C6H5
C6H5
4-CH3C6H4
4-NO2C6H4
C6H5
C6H5N=CHC6H4CH3(4)
C6H5N=CHC6H4NO2(4)
C10H7N=CHC6H5
195
226
231
265
261
245
276
295
306
260
85
86
88
85
87
88
85
85
85
89
36-37
(35-37)
[8]
88-90
(87-89)
[8]
120-121 ---
(118-
120) [8]
94-95
(90-93)
[8]
85-86
(84-86)
[8]
---
---
4
5
6
4-ClC6H4
C10H7N=CHC6H4Cl(4)
---
---
7
4-CH3O-C6H4 C10H7N=CHC6H4OCH3(4)
8
4-CH3C6H4
4-NO2C6H4
4-Cl C6H4
3-NO2C6H4
C6H5
C10H7N=CHC6H4CH3(4)
C10H7N=CHC6H4NO2(4)
71 (68- ---
70) [8]
9
156-158 ---
(153-
155) [8]
83-84
(78-82)
[8]
77-78
(72-76)
[8]
10
11
12
13
2-Cl, 4-NO2C6H3
2-Cl,4-NO2C6H3
2-Cl,4-
NO2C6H3N=CHC6H4Cl(4)
---
---
2-Cl,4-
NO2C6H3N=CHC6H4NO2(3)
NO2SC6H6 N=CHC6H5
171-181 ---
(170-
180) [8]
H2NO2
H2NO2
H2NO2
S
S
S
3-NO2-C6H4
NO2SC6H6 N=CH
C6H4NO2(3)
306
251
85
86
182-183 ---
(180-
182) [8]
14
15
NO2SC6H6N=CHC4H4O
4-CH3C6H4N=CHC6H5
192-193 ---
(190-
192) [8]
O
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
3-CH3OC6H4
4-CH3OC6H4
4-BrC6H4
C6H5
195
226
241
211
228
260
90
92
85
86
88
85
114-115 ---
(112-
115) [8]
95-96
(93-95)
[8]
125-126 ---
(121-
125) [8]
156-157 ---
(154-
157) [8]
221-22 ---
(215-
16
17
18
19
20
21
4-CH3OC6H4 4-
CH3C6H4N=CHC6H4OCH3(4
---
)
4-
4- NO2C6H4
C6H5
CH3C6H4N=CHC6H4NO2(4)
3-CH3OC6H4N=CHC6H5
4-OH C6H4
C6H5
4-
CH3OC6H4N=CHC6H4OH(4)
220) [8]
62-63
4-BrC6H4N=CHC6H5
---
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280
R. Suresh et al.
(61-62)
[8]
4-NO2C6H4
C6H5
4-NO2C6H4N=CHC6H5
226
272
88
85
85
88
85
85
87
140-141 ---
(138-
140) [8]
182-183 ---
(178-
182) [8]
135-36 ---
(135) [8]
22
4-NO2C6H4
4-NO2C6H4
4-
23
24
25
26
27
28
NO2C6H4N=CHC6H4NO2(4)
4-IC6H4
4-OH,
OCH3,
5-NO2C6H2
C6H5
3- 4-IC6H4N=CHC6H2 4-OH,3- 398
OCH3,5-NO2
2-Cl-4-CH3- C6H3
2-Cl-4-CH3- C6H3
2-Cl-4-CH3- C6H3
2-Cl-4-CH3- C6H3
2-Cl-4-CH3-
C6H3N=CHC6H5
228
261
247
243
120-121 ---
119-120
[16]
2-Cl C6H4
2-FC6H4
2-Cl-4-CH3-
C6H3N=CHC6H4Cl(2)
65-66
64-65
[16]
61
---
2-Cl-4-CH3-
C6H3N=CHC6H4F(2)
---
60-61
[16]
61
4-CH3C6H4
2-Cl-4-CH3-
C6H3N=CHC6H4CH3(4)
60-61
[16]
4-OCH3C6H4
4-ClC6H4
C6H5
C6H5
(4)H3COC6H4N=CHC6H5
4-ClC6H4N=CHC6H5
177
215
90
92
50-51 [8] ---
29
30
56
215[M+],
217[M2+], 180,
138, 111, 104,
77
31
4-ClC6H4
4-BrC6H4
4-ClC6H4N=CHC6H5-Br(4) 295
86
117
(119-
295[M+],
297[M2+],
120) [17] 299[M4+], 258,
182, 155, 138,
111
4-ClC6H4
4-ClC6H4
2-ClC6H4
4-ClC6H4
4-ClC6H4N=CHC6H5-Cl(2) 249
4-ClC6H4N=CHC6H5-Cl(4) 249
85
87
58-59
249[M+],
32
33
251[M2+],
253[M4+], 214,
138, 111
106
249[M+], 251
[M2+],
(110-
111)[17] 253[M4+],
214, 138, 111
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-FC6H4
4-ClC6H4N=CHC6H5-F(4)
233
86
92
91
87
86
66-67
64[18]
233[M+],
34
35
36
37
38
235[M2+], 198,
138, 122, 111,
95
4-OCH3C6H4 4-ClC6H4N=CHC6H5-OCH3 245
(4)
92(90-
245[M+],
94)[19] 247[M2+], 210,
138, 134, 111,
107
4-CH3C6H4
2-NO2C6H4
3-NO2C6H4
4-ClC6H4N=CHC6H5- CH3 229
(4)
102-103 229[M+],
231[M2+], 194,
138, 122, 118,
111
4-ClC6H4N=CHC6H5-NO2
(2)
261
261
98-99
261[M+],
263[M2+], 225,
149, 138, 122,
111
4-ClC6H4N=CHC6H5-NO2
(3)
104-105 261[M+],
263[M2+], 225,
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Solvent-free synthesis of azomethines
281
149, 138, 122,
111
4-ClC6H4
4-NO2C6H4
4-ClC6H4N=CHC6H5-NO2
(4)
261
88
113-114 261[M+],
(110-
39
263[M2+], 225,
113)[19] 149, 138, 122,
111
UV spectral study
In the present study the spectral linearity of synthesized imines (entries 30-39) has been studied
by evaluating the substituent effects. The spectral data observed for the imines, UV (λmax, nm),
infrared νC=N, the proton chemical shifts δ (ppm), of C-H and carbon chemical shifts of C=N
are correlated with various substituent constants. The measured absorption maxima (λmax, nm) of
synthesized imines are presented in Table 3. These values have been correlated with Hammett
substituent constants and F and R parameters using single and multi-linear regression analysis
[5-8, 14, 15] Hammett equation employed, for the correlation analysis, involving the absorption
maxima is as shown below in equation (1).
λ = ρσ + λo
(1)
where λo is the frequency for the parent member of the series.
The results of statistical analysis [5-8, 14, 15, 20] of these values with Hammett substituent
constants are presented in Table 4. From Table 4, it is evident that Hammett σ and σ+ constants
and R parameters give satisfactory correlations with λmax. The σI, σR and F values give poor
correlations. All constants give negative ρ values. This is due to the fact that the polar,
resonance, filed and inductive effects of the substituents are sufficiently weaker for predicting
the reactivity on the absorption through conjugation. This is attributed to the resonance
conjugative structure shown in Figure 2. The multi regression analysis of these UV spectral data
of all imines with inductive, resonance and Swain-Lupton’s [9] constants produce satisfactory
correlations as shown in equations 2 and 3.
λmax (nm) = 263.345(±11.926) - 39.007(±15.523) σI + 38.677 (±10.729) σR
(R = 0.970, n = 10, p > 95%)
(2)
(3)
λmax (nm) = 269.501(±13.210) - 10.646 (±4.952) F – 40.724 (±24.589) R
(R = 0.955, n = 10, p > 95%)
Table 3. The ultraviolet absorption maxima (λmax, nm), infrared absorptions (ν, cm-1) and NMR chemical
shifts (δ, ppm) imines (entries 30-39).
1H
13C
max (cm-1)
Ent- X
ry
λmax
(nm)
CN
X
CH Ar-H
8.48 7.196-7.982
(m, 9H)
8.38 7.093- 7.799
(m, 8H)
8.95 7.168- 8.320
(m, 8H)
8.41 7.127- 8.226
(m, 8H)
Bull. Chem. Soc. Ethiop. 2015, 29(2)
X
---
C=N Ar-C
X
H
262.5 1622.13 ---
160.72 122.04-150.42 ---
159.27 119.683-150.562 ---
158.56 122.330-150.355 ---
159.12 122.205-150.113 ---
30
31
32
33
7
4-Br 273.0 1626.57 ---
2-Cl 266.2 1614.42 ---
4-Cl 270.5 1624.06 ---
---
---
---
4
2
6

282
R. Suresh et al.
4-F 269.0 1625.99 ---
8.41 7.160- 7.934
(m, 8H)
8.42 7.160- 7.820
(m, 8H)
---
159.10 122.179-150.289 ---
34
35
36
6
4- 269.5 1614.42 ---
CH3
4- 317.5 1608.26 1236.8 8.37 7.002- 7.820
2.410 160.68 122.270-150.723 21.67 (CH3)
(s, 3H)
3.780 160.99 122.183-159.048 55.43 (OCH3)
8
OC
H3
9
(m, 8H)
(s, 3H)
37 2- 237.5 1620.62 ---
8.88 7.501- 8.372
(m, 8H)
8.55 7.210- 8.362
(m, 8H)
8.55 7.103-8.360
(m, 8H)
---
---
---
160.84 122-85-155.536 ---
159.6 122.337-150.432 ---
157.65 122.336-149.433 --
NO2
9
3- 259.0 1602.72 ---
NO2
4- 289.5 1589.34 ---
NO2
38
39
6
9
Table 4. Results of statistical analysis of UV λmax (nm), νC=N (cm-1) IR, NMR δ1H (ppm) CH=N and δ13C
(ppm) C=N of substituted benzylidene-4-chlorobenzamines (entries 30-39) with Hammett
substituent constants σ, σ+, σI, σR, F and R parameters.
Frequency Constants
r
I
ρ
s
n
7
Correlated derivatives
λmax (nm)
σ
σ+
σI
σR
F
0.951
278.39
-27.67
18.91
H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
3-NO2
H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
3-NO2
0.961
0.819
0.748
0.718
0.952
0.838
0.821
0.723
0.843
0.809
0.826
0.752
0.758
0.832
0.832
0.722
0.741
0.941
0.951
276.50
277.91
266.37
277.39
264.81
1617.83
1615.99
1619.69
1612.30
1618.59
1612.05
8.48
-25.23
-15.76
-44.29
-13.94
-41.56
-11.83
-5.67
-11.76
-22.41
-8.73
-17.60
0.26
17.33
21.59
19.19
21.66
18.60
11.67
12.25
12.21
11.38
12.38
11.60
0.19
7
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
7
R
H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
3-NO2,
νC=N
σ
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
σ+
σI
σR
F
R
δCH=N
σ
σ+
σI
σR
F
8.50
0.24
0.18
8.42
0.30
0.20
8.58
0.31
0.21
8.45
0.21
0.21
R
8.60
0.32
0.20
δC=N
σ
159.95
159.88
-1.18
-1.42
1.09
8
H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 4-NO2
H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
σ+
1.02
8
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Solvent-free synthesis of azomethines
4-OCH3, 4-NO2
283
σI
σR
F
0.957
0.704
0.905
0.811
160.68
159.62
160.63
159.58
-2.51
-0.24
-2.30
-0.43
0.97
1.19
1.00
1.18
7
H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-NO2
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
7
H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-NO2
R
10 H, 4-Br, 2-Cl, 4-Cl, 4-F, 4-CH3,
4-OCH3, 2-NO2, 3-NO2,4-NO2
r = correlation co-efficient; ρ = slope; I = intercept; s = standard deviation; n = number of substituents.
Figure 2. The resonance-conjugative structure.
IR spectral study
The infrared νC=N stretching frequencies (cm-1) of the synthesized imines (entries 30-39) have
been recorded and presented in Table 3. These data are correlated [5-8, 14, 15, 20] with
Hammett substituent constants and Swain-Lupton’s [9] parameters. In this correlation the
structure parameter relation equation employed is as shown in equation (4).
ν = ρσ + νo
(4)
where νo is the frequency for the parent member of the series.
The observed νC=N stretching frequencies (cm-1) are correlated with various Hammett
substituent constants and F and R parameters through single and multi-regression analyses
including Swain-Lupton’s [9] parameters. The results of statistical analysis of single parameter
correlation are shown in Table 4. The correlation of νC=N (cm-1) frequencies of imines with all
the Hammett substituent constants and F and R parameters fail to give a satisfactory correlation,
All correlations give negative ρ value. This is due to the absence of polar, field and inductive
effects of the substituents and hence they are unable to predict the reactivity on C=N stretches.
This is associated with the conjugative structure shown in Figure 2. In short all the single
parameter correlations of νC=N (cm-1) frequencies with Hammett substituent constants fail in
correlation. So, the authors think that it is worthwhile to seek the multi regression analysis
which may produce a satisfactory correlation with Resonance, Field and Swain-Lupton’s [9]
constants. This is shown in the following equations 5 and 6.
νC=N (cm-1) = 1618.593(±9.264) – 2.943 (±1.054) σI – 7.640 (±3.875) σR
(R = 0.972, n = 10, p > 95%)
(5)
(6)
νC=N(cm-1) = 1615.292 (±8.216) – 7.352 (±1.510) F – 17.013(±1.284) R
(R = 0.945, n = 10, p > 95%)
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R. Suresh et al.
1H NMR spectral study
1
The H NMR spectra of the imine derivatives (entries 30-39) under investigation have been
recorded in deuteriochloroform solution employing tetramethylsilane (TMS) as internal
standard. The signals of the imine protons have been assigned and are presented in Table 3. In
1
nuclear magnetic resonance spectra, the H or the 13C chemical shifts (δ, ppm) depends on the
electronic environment of the nuclei concerned. These chemical shifts have been correlated with
reactivity parameters. Thus the Hammett equation has been used in the form as shown in (7).
log δ = log δ0 + ρσ
(7)
where δ0 is the chemical shift of the corresponding parent compound.
The assigned proton chemical shifts (ppm) of imines have been correlated [5-8, 14, 15, 20]
with various Hammett sigma constants, F and R parameters. The results of statistical analysis
are presented in Table 3. These proton chemical shifts (ppm) fail in correlation with Hammett
substituent constants and F and R parameters. All correlations give positive ρ values. This
shows that the normal substituent effect operates in all systems. The failure in correlation is
attributed to the conjugative structure shown in Figure 2. In view of the inability of the Hammett
σ constants to produce individually satisfactory correlations with the imine proton chemical
shifts, the authors think that, it is worthwhile to seek multiple correlations involving either σI
and σR constants or Swain-Lupton’s [9] F and R parameters. This is shown in the following
equations (8) and (9) for protons:
δCH(ppm) = 8.470(±0.144) + 0.253 (±0.028) σI + 0.244(±0.031) σR
(R = 0.945, n = 10, p > 95%)
(8)
(9)
δCH(ppm) = 8.515 (±0.140) + 0.187 (±0.026) F + 0.309(±0.025) R
(R = 0.948, n = 10, p > 95%)
13C spectral study
The chemical shifts (ppm) of imine C=N carbon, have been assigned and are presented in Table
2. Attempts have been made to correlate the δC=N chemical shifts (ppm) with Hammett
substituent constants, field and resonance parameters, with the help of single and multi-
regression analyses to study the reactivity through the effect of substituents. The chemical shifts
(ppm) observed for the δC=N has been correlated [5-8, 14, 15, 20] with Hammett constants and
the results of statistical analysis are presented in Table 4. The δC=N chemical shifts (ppm) give
satisfactory correlation with Hammett σ, σ+ and σI, constants and F parameter. The remaining
Hammett σR, constant and R parameter are found to fail in correlation. This is due to the reason
stated earlier with resonance conjugative structure shown in Figure 2. In view of inability of
some of the σ constants to produce individually satisfactory correlation, the authors think that it
is worthwhile to seek multiple correlation involving σI, σR, F and R parameters. This is given in
the following correlation equations (10) and (11).
δC=N (ppm) = 160.776(±0.716) - 2.606(±1.388) σI + 0.439 (±0.054) σR
(R = 0.958, n = 10, p > 95%)
(10)
(11)
δC=N (ppm) = 160.587(±0.719) – 2.288(±1.059) F -0.254(±0.033) R
(R = 0.954, n = 10, p > 95%)
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Solvent-free synthesis of azomethines
285
Antibacterial activity
Antibacterial sensitivity assay has been performed by using [13] disc diffusion technique. In
each Petri plate about 0.5 mL of the test bacterial sample has been spread uniformly over the
solidified Mueller Hinton agar using sterile glass spreader. Then the discs with 5 mm diameter
made up of Whatmann No. 1 filter paper, impregnated with the solution of the compound have
been placed on the medium using sterile forceps. The plates have been incubated for 24 hours at
o
37 C by keeping the plates upside down to prevent the collection of water droplets over the
medium. After 24 hours, the plates have been visually examined and the diameter values of the
zone of inhibition were measured. Triplicate results have been recorded by repeating the same
procedure.
The antibacterial screening effect of synthesized Schiff bases (entries 30-39) is shown in
(Figure 3) (Plates 1-10). The antibacterial activities of all the synthesized imines have been
studied against three gram positive pathogenic strains Micrococcus luteus, Bacillus substilis,
Staphylococcus aureus and two gram negative strains Escherichia coli and Pseudomonas
species. The disc diffusion technique was followed, at a concentration of 250 μg/mL with
ampicillin taken as the standard drug. The zone of inhibition is compared using Table 5 and the
corresponding clustered column chart is shown in (Figure 4). A good antibacterial activity has
been possessed by all substituents on the microorganisms in general. The substituents H,
4-OCH3 and 3-NO2 have shown very good activity against Micrococcus luteus. The substituents
4-Br, 4-Cl, 4-CH3 and 4-OCH3 have improved antibacterial activity against E. coli species. The
substituent 4-CH3 has very good activity against Pseudomonas and Bacillus subtilis. The
substituents H, 4-Cl, 4-OCH3, 3-NO2 have good antibacterial activity against Staphylococcus
aureus.
Table 5. Antibacterial activity of substituted benzylidene-4-chloroanilines
Entry
X
Zone of inhibition (mm)
Gram positive bacteria Gram negative bacteria
B. subtilis
M. luteus
S. aureus
E. coli
P. aeruginosa
H
4-Br
2-Cl
7
9
9
12
8
9
10
7
7
7
11
8
8
7
8
30
31
32
33
34
4-Cl
4-F
8
9
8
8
9
8
10
9
7
8
4-CH3
4-OCH3
2-NO2
3-NO2
4-NO2
AMPICILLIN
DMSO
10
7
8
9
7
8
12
7
11
7
17
-
7
9
8
9
7
15
-
11
10
8
9
7
10
8
9
7
8
35
36
37
38
39
Standard
Control
13
-
15
-
13
-
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286
R. Suresh et al.
PLATE I
PLATE II
PLATE III
PLATE IV
PLATE V
PLATE VI
PLATE VII
PLATE VIII
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Solvent-free synthesis of azomethines
287
PLATE IX
PLATE X
Figure 3. Antibacterial activity of substituted benzylidene-4-chloroanilines-petri dishes (30-39).
Figure 4. The antibacterial activities of substituted benzylidene-4-chloroanilines-clustered
column chart (30-39).
Antifungal activities
Antifungal sensitivity assay has been performed using [13] disc diffusion technique. PDA
medium was prepared and sterilized as above. It has been poured (ear bearing heating condition)
in the Petri-plate which has been already filled with 1 mL of the fungal species. The plates have
been rotated clockwise and counter clock-wise for uniform spreading of the species. The discs
have been impregnated with the test solution. The test solution has been prepared by dissolving
15 mg of the Schiff bases in 1 mL of DMSO solvent. The medium have been allowed to solidify
and kept for 24 hours. Then the plates have been visually examined and the diameter values of
zone of inhibition have been measured. Triplicate results have been recorded by repeating the
same procedure. The antifungal activities of substituted imines (entries 30-39) have been studied
and are shown in (Figure 5) for Plates (1-4) and the zone of inhibition values of the effect is
given in Table 6. The clustered column chart, shown in (Figure 6) reveals that all the
compounds have moderate antifungal activity against both the fungal species namely A. niger
and Penicilium scup.
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288
R. Suresh et al.
Table 6. Antifungal activity of substituted benzylidene-4-chloroanilines
Entry
Zone of inhibition (mm)
X
A. niger
P. scup
H
4-Br
2-Cl
4-Cl
8
6
7
-
7
7
-
6
6
6
7
-
-
-
12
-
30
31
32
33
34
35
36
37
38
39
Standard
Control
4-F
-
4-CH3
4-OCH3
2-NO2
3-NO2
4-NO2
Miconazole
DMSO
8
7
7
7
6
13
-
PLATE I
PLATE II
PLATE III
PLATE IV
Figure 5. Antifungal activity of substituted benzylidene-4-chloroanilines-petri dishes (entries 30-
39).
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Solvent-free synthesis of azomethines
289
Figure 6. Antifungal activity of substituted benzylidene-4-chloroaniline-clustered column chart
(entries 30-39).
CONCLUSIONS
A series of some 2E-imines including substituted benzylidene-4-chloroanilines have been
synthesized by condensation of 4-chloroaniline and substituted benzaldehydes using microwave
irradiation in the presence of fly-ash:PTS under solvent-free conditions. This reaction protocol
offers a simple, eco-friendly; nonhazardous, easier work-up procedure and good yields. These
imines are characterized by their physical constants, spectral data. The UV, IR, NMR spectral
data of these imines has been correlated with Hammett substituent constants, F and R
parameters. From the results of statistical analyses the effects of substituent on the spectral data
have been studied. The antimicrobial activities of all synthesized imines have been studied using
Bauer-Kirby method.
ACKNOWLEDGEMENT
The authors thank DST-NMR Facility, Department of Chemistry, Annamalai University,
Annamalainagar-608002, India, for recording NMR spectra of compounds.
REFERENCES
1. Schiff, H.J. Lieb. Ann. Chem. 1864, 131, 118.
2. (a) Bharti, S.K.; Nath, G.; Tilak, R.; Singh, S.K. Eur. J. Med. Chem. 2010, 45, 651. (b)
Shabani, F.; Saghatforoush, L.A.; Ghammamy, S. Bull. Chem. Soc. Ethiop. 2010, 24, 193.
3. Rosu, T.; Pahontu, E.; Maxim, C.; Georgescu, R.; Stanica, N.; Gulea, A. Polyhedron 2011,
30, 154.
4. Gudipati, R.; Anreddy, R.N.; Manda, S. Saudi Pharm. J. 2011, 19, 153.
5. Thirunarayanan, G.; Vanangamudi, G. Spectrochim. Acta 2011, 81A, 390.
6. Thirunarayanan, G.; Ananthakrishna Nadar, P. Indian J. Chem. Soc. 2006, 83, 1107.
7. Thirunarayanan, G.; Vanangamudi, G.; Sathiyendiran, V.; Ravi, K. Indian J. Chem. 2011,
50B, 593.
8. Suresh, R.; Kamalakkannan, D.; Ranganathan, K.; Arulkumaran, R.; Sundararajan, R.;
Sakthinathan, S.P.; Vijayakumar, S.; Sathiyamoorthi, K; Mala, V.; Vanangamudi, G.;
Thirumurthy, K.; Mayavel, P.; Thirunarayanan, G. Spectrochim. Acta 2013, 101A, 239.
9. Swain, C.G.; Lupton, E.C., Jr. J. Am. Chem. Soc. 1968, 90, 4328.
Bull. Chem. Soc. Ethiop. 2015, 29(2)

290
R. Suresh et al.
10. Thirunarayanan, G.; Vanangamudi, G. IUP. J. Chem. 2011, 1, 54.
11. Yang, H.J.; Sun, W.H.; Li, Z.L.; Ma, Z. Chin. Chem. Lett. 2002, 13, 3.
12. Lidstorm, P.; Tierney, J.; Wathey, B.; Westman, J. Tetrahedron 2001, 57, 9225.
13. Bauer, A.W.; Kirby, W.M.M.; Sherris, J.C.; Truck, M. Am. J. Clin. Pathol. 1966, 45, 493.
14. Arulkumaran, R.; Vijayakumar, S.; Sakthinathan, S.P.; Kamalakkannan, D.; Ranganathan,
K.; Suresh, R.; Sundararajan, R.; Vanangamudi, G.; Thirunarayanan, G. J. Chil. Chem. Soc.
2013, 58, 1684.
15. Thirunarayanan, G.; Mayavel, P.; Thirumurthy, K. Spectrochim. Acta 2012, 91A, 18.
16. Vananja, G.; Kanagambal, P.; Thirunarayanan, G. National Conference on Exploring
Excellence in Chemistry, NCEEC-12, December 21, 2012, Department of Chemistry,
Dhanalakshmi Srinivasan College of Arts and Science for Women, Perambalur-621 212,
India; 2012.
17. Neuvonen, H.; Neuvonen, K.; Koch, A.; Kleinpeter, E. J. Mol. Struct. 2007, 815, 95.
18. Karki, S.S.; Butle, S.R.; Shaikh, R.M.; Zubaidha, P.K.; Pedgaonkar, G.S.; Shendarkar, G.S.;
Chitra G.R. Res. J. Pharm. Biol. Chem. Sci. 2010, 1, 707.
19. Patil, S.; Jadhav, S.D.; Shinde, S.K. Org. Chem. Int. 2012, 2012, 1-5; Article ID 153159,
http://dx.doi.org/10.1155/2012/153159.
20. Sakthinathan, S.P.; Suresh, R.; Mala, V.; Sathiyamoorthi, K.; Kamalakkannan, D.;
Ranganathan, K.; Arulkumaran, R.; Vijayakumar, S.; Sundararajan, R.; Vanangamudi,
G.; Thirunarayanan, G. Int. Lett. Chem. Phys. Astro. 2013, 6, 77.
Bull. Chem. Soc. Ethiop. 2015, 29(2)