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World Scientific News

8 (2015) 176-191 EISSN 2392-2192

Synthesis, Assessment of substituent effect and Antimicrobial activities of some substituted (E)-N-

benzylidene-4H-1,2,4-triazol-4-amines

R. Senbagam1, M. Rajarajan1, R. Vijayakumar1, V. Manikandan1, S. Balaji1,

G. Vanangamudi1, G. Thirunarayanan2,*

1PG & Research Department of Chemistry, Government Arts College, C-Mutlur, Chidambaram - 608 102, India

2Department of Chemistry, Annamalai University, Annamalainagar - 608 002, India

*E-mail address: [email protected]

ABSTRACT

A series of heterocyclic Schiff base compounds have been synthesized from 4H-1,2,4-triazol-4-

amine with various substituted benzaldehydes and were refluxed for 3h with 20 mL of absolute

ethanol. The purity of all the Schiff base compounds has been checked using their physical constants

and spectral data. The UV λmax (nm), IR νC=N (cm-1), NMR δ (ppm) of CH=N and C=N spectral data

have been correlated with Hammett substituent constants and Swain-Lupton’s 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 single parameter correlation with few Hammett

constants and Swain-Lupton’s parameters gave satisfactory correlation coefficients whereas all

multiple correlations gave satisfactory correlation coefficients with Inductive, Resonance, Field and

Swain-Lupton’s parameters. The antimicrobial activities of all the Schiff bases have been studied

using standard methods.

Keywords: synthesis, heterocyclic Schiff bases, UV, IR and NMR spectra, QSAR study, antimicrobial

study

1. INTRODUCTION

Schiff bases are prepared by condensation of primary amine with a compound

containing an active carbonyl group [1]. They are also known as ‘azomethines’, ‘anils’ or

‘imines’. Among the large number of synthetic and naturally occurring nitrogen donor

molecules, schiff bases are of the greatest interest. In general, Schiff bases are represented by

the general formula RCH=NR’ where >C=N is the azomethine group. The colour of the schiff

World Scientific News 8 (2015) 176-191

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bases is due to the presence of this azomethine (>C=N) linkage and can vary by introducing

other auxochromic groups. Schiff basess are characterized by the –N=CH– group and this

finds importance in elucidating the mechanism of transamination and racemization reactions

in biological systems [2, 3]. They have been used in the study of asymmetric catalysis [4],

magnetic properties [5], dyes and photographic chemicals [6], corrosion inhibitors [7, 8] and

in the preparation of polymers [9].

Schiff’s bases have attracted considerable attention of organic chemists due to their

significant biological activities like anticancer [10], antitumor [11], anti-inflammatory agents

[12], insecticidal [13], antituberculosis [14], antimicrobial [15], anticonvulsant [16] activity.

In the present day the correlation analysis of Schiff base compounds has become one of

the important studies for researchers to study their substituent effect. Recently, the correlation

analysis of Schiff base compounds have been reported [17-19]. The author also synthesized

ten number of heterocyclic Schiff base compounds from 4H-1,2,4-triazol-4-amine and

substituted benzaldehydes and studied their substituent effects using single and multi-linear

regression analysis. The biological activities of these Schiff base derivatives have been studied.

2. EXPERIMENTAL

2. 1. General

All the chemicals used have been purchased from Sigma–Aldrich and E-Merck

chemical companies. Melting points of all of substituted (E)-N-benzylidene-4H-1,2,4-triazol-

4-amine compounds have been determined in open glass capillaries on a Mettler FP51

melting point apparatus and are uncorrected. The UV spectra of all synthesized (E)-N-

benzylidene-4H-1,2,4-triazol-4-amine compounds have been recorded using SHIMADZU-

1650 SPECTROMETER in spectral grade methanol. IR spectra (KBr, 4000-400 cm-1) have

been recorded on AVATAR-300 Fourier transform spectrophotometer. The NMR spectra of

all the substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds have been

recorded in BRUKER 400 spectrometer operating at 400 MHz for 1H NMR spectra and 100

MHz for 13C NMR spectra in CDCl3 solvent using TMS as internal standard.

2. 2. Synthesis of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds

An appropriate mixture of equimolar quantities of 4H-1,2,4-triazol-4-amine (0.01 mol),

substituted benzaldehyde (0.01 mol) and 0.5ml acetic acid were refluxed for 3h with 20 mL of

absolute ethanol [17].

Scheme 1. X = H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH3, 4-OCH3, 3-NO2, 4-NO2


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The completion of the reaction was monitored by TLC continuously. The resultant

mixture was cooled at room temperature. Then the precipitate obtained, was filtered at the

filter pump and washed several times with cold water. A pale yellow solid was obtained as the

final product. This crude product was recrystallized from ethanol to get glittering colorless

solid, and their melting points have been noted. The general reaction is shown in Scheme 1.

Table 1. The UV, IR and NMR spectroscopic data of substituted

(E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds.

Entry X M.F. M. W. M. p.

(°C)

λmax (nm)

ν C=N

(cm-1)

δ1H

CH=N

(ppm)

δ13C

C=N

(ppm)

1 H C9H10N4 174 134-135 275.20 1602.99 8.644 156.82

2 3-Br C9H7BrN4 251 113-114 273.00 1619.03 8.620 167.71

3 4-Br C9H7BrN4 251 174-175 284.00 1588.11 8.573 158.62

4 3-Cl C9H7ClN4 206 107-108 272.80 1620.19 8.301 155.44

5 4-Cl C9H7ClN4 206 150-151 282.00 1593.23 8.654 155.39

6 4-F C9H7FN4 190 120-121 277.20 1602.40 8.649 153.77

7 4-CH3 C10H10N4 18 128-129 283.00 1607.74 8.647 157.17

8 4-OCH3 C10H10N4O 202 87-88 305.40 1604.76 8.598 163.43

9 3-NO2 C9H7N5O2 217 108-109 259.60 1578.31 8.730 155.34

10 4-NO2 C9H7N5O2 217 228-229 295.40 1592.32 8.684 154.65

3. RESULTS AND DISCUSSION

All the compounds synthesized in the present investigation have been confirmed by

their physical constants and UV, IR and NMR spectral data as shown in Table 1. The spectral

data of all the synthesized substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine

compounds have been correlated with Hammett substituent constants and F and R parameter

and are shown in Table-2.

3. 1. UV-visble spectral correlations of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-

amine compounds

The assigned UV absorption maximum λmax (nm) values of all the substituted (E)-N-

benzylidene-4H-1,2,4-triazol-4-amine compounds are presented in Table 1. These UV

absorption maximum values are correlated with different Hammett substituent constants and

F and R parameters using single and multi-linear regression analyses [17-21]. Hammett

equation employed, for the correlation analysis, involving the UV absorption maximum is

shown in equation (1).

λ = ρ σ + λ0 … (1)

where λ0 is the absorption maximum of the parent member of this series.

The results of statistical analysis [17-21] are shown in Table 2. The assigned UV

absorption maximum λmax (nm) values of all the substituted (E)-N-benzylidene-4H-1,2,4-

triazol-4-amine compounds, except that with 4-NO2 substituent have shown satisfactory


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12

3

4

5

6

7

8

9

10

250,00

260,00

270,00

280,00

290,00

300,00

310,00

-1 -0,5 0 0,5 1

λmax

(n

m)

σ+

correlation with Hammett substituent constants σ+ (r = 0.902) only. All the compounds

except those with H, 4-CH3 and 4-NO2 substituents have shown satisfactory correlation with

Hammett constant σI (r = 0.952) only.

In addition, all the substituents except those with 4-F and 4-NO2 substituents have

shown satisfactory correlation with R parameter (r = 0.905). When those substituents that

have been exception are included in regression they reduce the correlations considerably. The

single linear plot of UV absorption maximum λmax (nm) values against Hammett constant σ+ is shown in the following Fig. 1.

Fig. 1. Single linear plot of λmax (nm) values of substituted

(E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds Vs σ+

Table 2. Results of statistical analysis of UV λmax (nm), IR νC=N (cm-1), NMR δ1H (ppm) CH=N and

δ13C (ppm) C= N of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds with

Hammett substituent constants σ, σ+, σI, σR and F and R parameters.

Frequency Constants r I ρ s n Correlated derivatives

λmax (nm) σ 0.846 284.20 -14.704 12.31 10

H, 3-Br, 4-Br, 3-Cl,

4-Cl, 4-F, 4-CH3, 4-OCH3,

3-NO2, 4-NO2

σ+ 0.915 283.05 -13.637 11.54 9 H, 3-Br, 4-Br, 3-Cl, 4-Cl,

4-F, 4-CH3, 4-OCH3, 3-NO2

σI 0.952 284.31 -9.053 13.27 7 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F,

4-OCH3, 3-NO2,

σR 0.833 277.92 -20.664 12.69 10

H, 3-Br, 4-Br, 3-Cl, 4-Cl,

4-F, 4-CH3, 4-OCH3, 3-NO2,

4-NO2

11. H

12. 3-Br

13. 4-Br

14. 3-Cl

15. 4-Cl

16. 4-F

17. 4-CH3

18. 4-OCH3

19. 3-NO2

20. 4-NO2

1. H

2. 3-Br

3. 4-Br

4. 3-Cl

5. 4-Cl

6. 4-F

7. 4-CH3

8. 4-OCH3

9. 3-NO2

10. 4-NO2

1. H 2. 3-Br 3. 4-Br 4. 3-Cl 5. 4-Cl 6. 4-F 7. 4-CH3 8. 4-OCH3 9. 3-NO2 10. 4-NO2


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r = correlation coefficient, I = intercept, ρ = slope, s = standard deviation, n = number of correlated derivatives

F 0.875 284.02 -8.002 13.31 10

H, 3-Br, 4-Br, 3-Cl, 4-Cl,

4-F, 4-CH3, 4-OCH3, 3-NO2,

4-NO2

R 0.905 277.06 -19.426 12.48 8 H, 3-Br, 4-Br, 3-Cl, 4-Cl,

4-CH3, 4-OCH3, 3-NO2

νC=N(cm-1) σ 0.937 1604.24 -14.261 12.99 8 H, 4-Br, 4-Cl, 4-F, 4-CH3,

4-OCH3, 3-NO2, 4-NO2

σ+ 0.934 1602.47 -9.347 13.20 8 H, 4-Br, 4-Cl, 4-F, 4-CH3,

4-OCH3, 3-NO2, 4-NO2

σI 0.903 1608.93 -20.425 13.01 8 H, 4-Br, 4-Cl, 4-F, 4-CH3,

4-OCH3, 3-NO2, 4-NO2

σR 0.843 1597.12 -27.591 12.66 10

H, 3-Br, 4-Br, 3-Cl, 4-Cl,

4-F, 4-CH3, 4-OCH3, 3-NO2,

4-NO2

F 0.835 1608.57 -18.794 13.11 10

H, 3-Br, 4-Br, 3-Cl, 4-Cl,

4-F, 4-CH3, 4-OCH3, 3-NO2,

4-NO2

R 0.839 1596.84 -21.380 12.87 10

H, 3-Br, 4-Br, 3-Cl, 4-Cl,

4-F, 4-CH3, 4-OCH3, 3-NO2,

4-NO2

δCH=N(ppm) σ 0.909 8.60 0.032 0.123 9 H,3-Br, 4-Br, 4-Cl, 4-F,

4-CH3, 4-OCH3, 3-NO2, 4-NO2

σ+ 0.902 8.61 0.005 0.123 9 H,3-Br, 4-Br, 4-Cl, 4-F,4-CH3,

4-OCH3, 3-NO2, 4-NO2

σI 0.893 8.60 0.014 0.124 10 H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F,

4-CH3, 4-OCH3, 3-NO2, 4-NO2

σR 0.928 8.63 0.163 0.118 9 H,3-Br, 4-Br, 4-Cl, 4-F,4-CH3,

4-OCH3, 3-NO2, 4-NO2

F 0.913 8.59 0.049 0.123 9 H,3-Br, 4-Br, 4-Cl, 4-F,4-CH3,

4-OCH3, 3-NO2, 4-NO2

R 0.922 8.63 0.106 0.121 9 H,3-Br, 4-Br, 4-Cl, 4-F,4-CH3,

4-OCH3, 3-NO2, 4-NO2

δC=N(ppm) σ 0.901 158.55 -3.073 4.54 8 H, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH3,

3-NO2, 4-NO2

σ+ 0.902 158.24 -2.455 4.51 8 H, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH3,

3-NO2, 4-NO2

σI 0.816 158.99 -2.938 4.62 10 H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F,

4-CH3, 4-OCH3, 3-NO2, 4-NO2

σR 0.823 157.15 -4.939 4.56 10 H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F,

4-CH3, 4-OCH3, 3-NO2, 4-NO2

F 0.826 159.49 -4.063 4.56 10 H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F,

4-CH3, 4-OCH3, 3-NO2, 4-NO2

R 0.927 156.88 -5.002 4.50 8 H, 4-Br, 3-Cl, 4-Cl, 4-CH3,

4-OCH3, 3-NO2, 4-NO2


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However, UV absorption maximum λmax (nm) values of all the substituted (E)-N-

benzylidene-4H-1,2,4-triazol-4-amine compounds have shown poor correlations (r < 0.900)

with the remaining Hammett constant σR and F parameter.

The poor in correlation is attributed to weak resonance and field effect of the

substituents for predicting the reactivity through resonance as per the resonance conjugative

structure shown in Fig. 2.

Fig. 2. The resonance-conjugative structure.

All the correlations with Hammett constants and F and R parameters have shown

negative ρ values. This indicates the operation of reverse substituent effect with respect to UV

absorption maximum λmax (nm) values of all the substituted (E)-N-benzylidene-4H-1,2,4-

triazol-4-amine compounds.

Since, some of the single regression analyses have shown poor correlation with few

Hammett constants and F and R parameters. Hence, the authors think that worthwhile to seek

the multi regression analysis of the UV absorption maximum λmax (nm) values of all the

substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds with inductive, resonance

and swain-Lupton’s[15] parameters produces satisfactory correlations as shown in equations

(2) and (3).

λmax (nm) = 280.780 (±9.272) - 6.89 (± 2.584) σI - 19.618 (±3.809) σ R … (2)

(R = 0.900, n = 10, P > 90%)

λmax (nm) = 280.574 (± 8.772) - 8.751 (±2.378) F - 19.778 (±2.726) R … (3)

(R = 0.900, n = 10, P > 90%)

3. 2. IR Spectral correlations of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine

compounds

The assigned infrared stretching frequency νC=N (cm-1) values of all the substituted

(E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds are presented in Table 1.

These infrared stretching frequency values are correlated [17-21] using single and

multi-linear regression analyses. The structure parameter correlation involving group

frequencies, the employed Hammett equation is shown in equation (4).

ν = ρ σ + ν0 … (4)

where ν0 is the frequency of the parent member of this series.


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1

2

3

4

5

6

78

9

10

1575,00

1580,00

1585,00

1590,00

1595,00

1600,00

1605,00

1610,00

1615,00

1620,00

1625,00

-0,4 -0,2 0 0,2 0,4 0,6 0,8 1

νC=N

(cm

-1)

σ

The results of the statistical analysis [17-21] are presented in Table-2, it is evident that

the infrared that the infrared stretching frequency νC=N (cm-1) values of all the substituted

(E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds, except those with 3-Br and 3-Cl

substituents have shown satisfactory correlations with Hammett constants σ (r = 0.937), σ+ (r

= 0.934) and σI (r = 0.903). When these substituents that have been given exception are

included in regression they reduce the correlations considerably. The single linear plot of IR

frequency νC=N (cm-1) values against Hammett constant σ is shown in the following Fig. 3. However the infrared stretching frequency νC=N (cm-1) values of all the substituted

(E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds, have shown poor correlations (r <

0.900) with the Hammett constant σR and F & R parameters. This is attributed to weak

resonance and field effect of the substituents to predict the reactivity on frequency through

resonance as per conjugative structure shown in Fig. 2.

Fig. 3. Single linear plot of IR frequency νC=N (cm-1)values of

substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds Vs σ

All the correlations have shown negative ρ values. This indicates the operation of

reverse substituent effect with respect to infrared stretching frequency νC=N (cm-1) values of

all the substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amines.

Since some of the single regression analyses, have shown poor correlations with

Hammett constant and F and R parameters. It is decided to go for multi regression analysis.

The multi regression analysis of the stretching frequency νC=N(cm-1) values of all Schiff base

compounds with inductive, resonance and Swain-Lupton’s [22] parameters produce

satisfactory correlations as shown in equations (5) and (6).

νC=N (cm-1) = 1604.44 (±8.721) - 17.679 (±5.82) σI - 24.908 (±4.151) σR… (5)

(R = 0.999, n = 10, P > 95%)

νC= N (cm-1) = 8.608 (± 0.085) + 0.084 (± 0.021) F + 0.108 (± 0.051) R … .(6)

(R = 0.999, n = 10, P > 95%)

31. H

32. 3-Br

33. 4-Br

34. 3-Cl

35. 4-Cl

36. 4-F

37. 4-CH3

38. 4-OCH3

39. 3-NO2

40. 4-NO2

21. H

22. 3-Br

23. 4-Br

24. 3-Cl

25. 4-Cl

26. 4-F

27. 4-CH3

28. 4-OCH3

29. 3-NO2

30. 4-NO2 1. H 2. 3-Br 3. 4-Br 4. 3-Cl 5. 4-Cl 6. 4-F 7. 4-CH3 8. 4-OCH3 9. 3-NO2 10. 4-NO2


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12

3

4

5678

9

10

8,250

8,300

8,350

8,400

8,450

8,500

8,550

8,600

8,650

8,700

8,750

8,800

-0,4 -0,2 0 0,2 0,4 0,6 0,8 1

δC

H=

N(p

pm

)

σ

3. 3. NMR spectral correlations of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-

amine compounds

The observed chemical shift values (ppm) of all the substituted (E)-N-benzylidene-4H-

1,2,4-triazol-4-amine compounds are presented in Table 1. These chemical shift values (ppm)

are correlated with different Hammett substituent constants and F and R parameters using

single and multi-linear regression analyses [17-21]. In this correlation, the structure-parameter

equation employed is shown in equation (7).

δ = ρσ + δ0 … (7)

where δ0 is the chemical shift of the corresponding parent compound.

3. 3. 1. 1 H NMR spectral correlation:

From Table 2, it is evident that the 1H NMR chemical shift δCH=N (ppm) values of all

the substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds except that with 3-Cl

substituent have shown satisfactory correlations with σ(r = 0.909), σ+(r = 0.902), σR (r =

0.928), F (r = 0.913) and R (r = 0.922) parameters.

The single linear plot of 1H NMR chemical shift δCH=N (ppm) values against Hammett

constant σ is shown in the following Fig. 4.

Fig. 4. Single linear plot of 1H NMR chemical shift δCH=N (ppm) values of

substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds Vs σ

The remaining Hammett constant σI has shown poor correlation (r < 0.900) with all the

substituents. The failure in correlation is due to the reason that has been stated earlier with

resonance conjugative structure as shown in Fig. 2.

All the correlations with Hammett substituent constants F and R parameters have

shown positive ρ values. It indicates the operation of normal substituent effect with respect to 1H NMR spectral data of all the compounds. While seeking the multi–correlation collectively

the inductive, resonance and field effects [22] have shown satisfactory correlation as shown in

the equations (8) and (9).



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1

2

3

45

6

7

8

9

10

152,00

154,00

156,00

158,00

160,00

162,00

164,00

166,00

168,00

170,00

-0,4 -0,2 0 0,2 0,4 0,6 0,8 1

δC

=N

(pp

m)

σ

δC= N (ppm) = 8.633 (±0.087) - 0.0933 (±0.022) σI + 0.1639 (±0.05)σR … (8)

(R = 0.999, n = 10, P > 95%)

δC= N (ppm) = 8.608 (±0.085) + 0.054 (± 0.002) F + 0.108 (± 0.051) R … (9)

(R = 0.999, n = 10, P > 95%)

3. 3. 2. 13C NMR spectral correlation

The results of the statistical analysis [17-21] are presented in Table-2. It is evident that

the 13 CNMR chemical shift δ C=N (ppm) values of all the substituted (E)-N-benzylidene-4H-

1,2,4-triazol-4-amine compounds except 3-Br and 4-OCH3 substituents have shown

satisfactory correlations with Hammett constants σ (r = 0.901) and σ+(r = 0.902). All the

compounds except 3-Br and 4-F have also shown satisfactory correlation with R (r = 0.927)

parameter.

The single linear plot of 13C NMR chemical shift δC=N (ppm) values against Hammett

constant σ is shown in the following Fig. 5.

Fig. 5. Single linear plot of 13C NMR chemical shift δC=N (ppm) values of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds Vs σ

The remaining Hammett constants σI, σR and F parameter have shown poor correlations

(r < 0.900). The failure in correlation is due to the reason that has been stated earlier with

resonance conjugative structure as shown in Fig. 2. All the Hammett constants F and R

parameters have shown positive ρ values. This shows that the normal substituent effect

operates in all systems. While seeking the multi-correlation, collectively with inductive,

resonance and field effects [22] satisfactory correlation as shown in equations (10) and (11).

δC = N(ppm) = 158.16(±3.329) - 2.434(±0.41)σI - 4.578(±1.52) σR …(10) (R = 0.904, n = 10, P > 95%)

δC= N(ppm) = 158.59(±3.11) – 4.259(±1.52)F - 5.17(±1.72) R …(11)

(R = 0.904, n = 10, P > 95%)

1. H 2. 3-Br 3. 4-Br 4. 3-Cl 5. 4-Cl 6. 4-F 7. 4-CH3 8. 4-OCH3 9. 3-NO2

10. 4-NO2


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3. 4. Antimicrobial activities of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine

compounds

3. 4. 1. Antibacterial activity

Antibacterial sensitivity assay has been performed by using [23] 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 5mm 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 37 ºC 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 all the synthesized substituted (E)-N-benzylidene-

4H-1,2,4-triazol-4-amine compounds is shown in (Fig. 6) (Plates 1-10). The antibacterial

activities have been studied against three gram positive pathogenic strains Bacillus substilis,

Micrococcus luteus, Staphylococcus aureus and two gram negative strains Escherichia coli

and Pseudomonas aurogenosa. The disc diffusion technique was followed, at a concentration

of 250μg/mL with ciprofloxacin taken as the standard drug. The zone of inhibition is

compared using Table 3 and the corresponding clustered column chart is shown in (Fig. 7). A

good antibacterial activity has been possessed by all substituents on the microorganisms in

general. The substituents 3-Cl, 4-F, 3-NO2 and 4-NO2 have shown very good antibacterial

activity against Bacillus subtilis. The substituents 4-Br and 4-NO2 have shown very good

activity against Micrococcus luteus. The substituent 4-CH3 has shown very good activity

against Staphylococcus aureus. The substituents 3-Cl, 4-F, 4-CH3, and 4-NO2 have shown

very good antibacterial activity against E.coli. The substituents 3-Cl, 4-Cl, 4-F, 4-CH3, 3-NO2

and 4-NO2 have shown very good antibacterial activity against Pseudomonas.

Table 3. Antibacterial activity of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds.

S.No. Substituents

Zone of inhibition (mm)

Gram positive Bacteria Gram negative Bacteria

B. subtilis M. luteus S. aureus E. coli P. aeruginosa

1 H 7 7 6 7 6

2 3-Br 6 9 6 10 7

3 4-Br 7 11 6 8 7

4 3-Cl 10 7 9 10 9

5 4-Cl 6 8 6 7 8

6 4-F 10 9 6 11 9

7 4-CH3 8 7 12 10 8

8 4-OCH3 7 8 7 9 7

9 3-NO2 13 9 9 9 9

10 4-NO2 12 11 8 11 8

Standard Ciprofloxacin 9 9 10 8 7

Control DMSO 0 0 0 0 0


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Plate-1 Plate-2

Plate-3 Plate-4

Plate-5 Plate-6

Plate-7 Plate-8

Plate-9 Plate-10

Fig. 6. Antibacterial activity of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine

compounds -petri dishes.


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0

2

4

6

8

10

12

14

Zon

e of

inh

ibit

ion

(m

m)

substituents

Antibacterial Activity

Bacillus

M. luteus

S. aureus

E. coli

P. aurogenosa

Fig. 7. The antibacterial activities of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine

compounds -clustered column chart.

3. 4. 2. Antifungal activities

The antifungal activities of all the synthesized heterocyclic Schiff base compounds have

been studied against Aspergillus niger, Mucour species and Tricoderma viride using [23] 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 15mg of the Schiff base compounds in 1ml 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 Schiff base have been studied and are shown in

(Fig. 8 for Plates (1-4) and the zone of inhibition values of the effect is given in Table 4. The

clustered column chart, shown in (Fig. 9). A good antifungal activity has been possessed by

all substituents on the microorganisms in general. The substituents 4-F, 3-NO2 and 4-NO2

have shown very good fungal activity against A. niger. All the compounds have shown

moderate antifungal activity against the fungal species Peniciliumscup.



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sTable 4. Antifungal activity of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds.

S.No. Substituents Zone of inhibition(mm)

A. niger M. species T. species

1 H 5 8 6

2 3-Br 6 8 7

3 4-Br 7 5 8

4 3-Cl 6 6 7

5 4-Cl 6 5 6

6 4-F 9 8 7

7 4-CH3 6 9 7

8 4-OCH3 8 8 6

9 3-NO2 12 9 9

10 4-NO2 10 7 5

Standard Ciprofloxacin 8 10 6

Control DMSO 0 0 0

Fig. 8. Antifungal activity of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine

compounds -petri dishes.

Plate-1 Plate-2

Plate-3 Plate-4

Plate-5 Plate-6


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0

2

4

6

8

10

12

14

Zon

e o

f in

hib

itio

n (

mm

)

substituents

Antifungal Activity A. niger

M. species

T. viride

Fig. 9. Antifungal activity of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds -clustered column chart.

4. CONCLUSIONS

A series of ten number of heterocyclic Schiff base compounds viz., substituted (E)-N-

benzylidene-4H-1,2,4-triazol-4-amine compounds have been synthesized by condensation

method. These compounds were confirmed by their physical constants and spectral data.

The spectral data of these compounds have been correlated with Hammett sigma

constants and F and R parameters using single and multi-linear regression analysis. From the

results of statistical analysis, most of the correlations were found to be satisfactory. The

antimicrobial activities of these heterocyclic Schiff base compounds were found to be

moderate to good activity.

ACKNOWLEDGEMENT

The authors thank DST NMR Facility, Department of Chemistry, Annamalai University, Annamalainagar - 608

002, for recording NMR spectra of all compounds.

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( Received 10 April 2015; accepted 22 April 2015 )

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