World Scientific News

Transcription

1 Available online at World Scientific News 2 (2015) EISSN Synthesis, Assessment of substituent effect and Antimicrobial activities of some substituted (E)-Nbenzylidene-4H-1,2,4-triazol-4-amines R. Senbagam a, M. Rajarajan a, R. Vijayakumar a, V. Manikandan a, S. Balaji a, G. Vanangamudi a, G. Thirunarayanan b, * a PG & Research Department of Chemistry, Government Arts College, C-Mutlur, Chidambaram , India b Department of Chemistry, Annamalai University, Annamalainagar , India * address: drgtnarayanan@gmail.com 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 λ max (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 and 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 bases is due to the presence of this azomethine (>C=N) linkage and can vary by introducing

2 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 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)-Nbenzylidene-4H-1,2,4-triazol-4-amine compounds have been recorded using SHIMADZU SPECTROMETER in spectral grade methanol. IR spectra (KBr, 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 1 H NMR spectra and 100 MHz for 13 C NMR spectra in CDCl 3 solvent using TMS as internal standard 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 (0.01mol), substituted benzaldehyde (0.01mol) 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-CH 3, 4-OCH 3, 3-NO 2, 4-NO

3 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. Entry X M.F. M. W. Table 1. The UV, IR and NMR spectroscopic data of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds. M. p. ( C) λ max (nm) ν C=N (cm -1 ) δ 1 H CH=N (ppm) δ 13 C C=N (ppm) 1 H C 9 H 10 N Br C 9 H 7 BrN Br C 9 H 7 BrN Cl C 9 H 7 ClN Cl C 9 H 7 ClN F C 9 H 7 FN CH 3 C 10 H 10 N OCH 3 C 10 H 10 N 4 O NO 2 C 9 H 7 N 5 O NO 2 C 9 H 7 N 5 O 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 UV-visble spectral correlations of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4- amine compounds The assigned UV absorption maximum λ max (nm) values of all the substituted (E)-Nbenzylidene-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 + λ 0 (1) where λ 0 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 λ max (nm) values of all the substituted (E)-N-benzylidene-4H-1,2,4- triazol-4-amine compounds, except that with 4-NO 2 substituent have shown satisfactory -213-

4 λmax (nm) World Scientific News 2 (2015) correlation with Hammett substituent constants σ + (r = 0.902) only. All the compounds except those with H, 4-CH 3 and 4-NO 2 substituents have shown satisfactory correlation with Hammett constant σ I (r = 0.952) only. In addition, all the substituents except those with 4-F and 4-NO 2 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 λ max (nm) values against Hammett constant σ + is shown in the following Fig ,00 300,00 290,00 280,00 270,00 260, H 2. 3-Br 3. 4-Br 4. 3-Cl 5. 4-Cl 6. 4-F 7. 4-CH OCH NO NO 2 250, ,5 0 0,5 1 σ + Fig. 1. Single linear plot of λ max (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 λ max (nm), IR νc=n (cm -1 ), NMR δ 1 H(ppm) CH=N and δ 13 C (ppm) C= N of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds with Hammett substituent constants σ, σ +, σ I, σ R and F and R parameters. Frequency Constants r I ρ s n Correlated derivatives λ max(nm) σ σ σ I σ R H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH 3, 4-OCH 3, 3-NO 2 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F, 4-OCH 3, 3-NO 2, H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH 3, 4-OCH 3, 3-NO 2, 4-NO

5 F R νc=n(cm -1 ) σ σ σ I σ R F R δch=n(ppm) σ σ σ I σ R F R δc=n(ppm) σ σ σ I σ R F R H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-CH 3, 4-OCH 3, 3-NO 2 H, 4-Br, 4-Cl, 4-F, 4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H, 4-Br, 4-Cl, 4-F, 4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H, 4-Br, 4-Cl, 4-F, 4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H,3-Br, 4-Br, 4-Cl, 4-F, 4-CH3, 4-OCH 3, 3-NO 2, 4-NO 2 H,3-Br, 4-Br, 4-Cl, 4-F,4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H,3-Br, 4-Br, 4-Cl, 4-F,4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H,3-Br, 4-Br, 4-Cl, 4-F,4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H,3-Br, 4-Br, 4-Cl, 4-F,4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH 3, 3-NO 2, 4-NO 2 H, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH 3, 3-NO 2, 4-NO 2 H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H, 3-Br, 4-Br, 3-Cl, 4-Cl, 4-F, 4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 H, 4-Br, 3-Cl, 4-Cl, 4-CH 3, 4-OCH 3, 3-NO 2, 4-NO 2 r = correlation coefficient, I = intercept, ρ = slope, s = standard deviation, n = number of correlated derivatives -215-

6 However, UV absorption maximum λ max (nm) values of all the substituted (E)-Nbenzylidene-4H-1,2,4-triazol-4-amine compounds have shown poor correlations (r < 0.900) with the remaining Hammett constant σ R 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 λ max (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 λ max (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). λ max (nm) = (±9.272) (± 2.584) σ I (±3.809) σ R (2) (R = 0.900, n = 10, P > 90%) λ max (nm) = (± 8.772) (±2.378) F (±2.726) R (3) (R = 0.900, n = 10, P > 90%) 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 + ν 0 (4) where ν 0 is the frequency of the parent member of this series

7 νc=n (cm -1 ) World Scientific News 2 (2015) 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 σ I (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 σ R 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 , , , , , , , , , , ,00-0,4-0,2 0 0,2 0,4 0,6 0,8 1 σ 1. H 2. 3-Br 3. 4-Br 4. 3-Cl 5. 4-Cl 6. 4-F 7. 4-CH OCH NO NO 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 ) = (±8.721) (±5.82) σ I (±4.151) σ R (5) (R = 0.999, n = 10, P > 95%) νc= N (cm -1 ) = (± 0.085) (± 0.021) F (± 0.051) R.(6) (R = 0.999, n = 10, P > 95%) -217-

8 δch=n(ppm) World Scientific News 2 (2015) 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 structureparameter equation employed is shown in equation (7). δ = ρσ + δ 0 (7) where δ 0 is the chemical shift of the corresponding parent compound H NMR spectral correlation: From Table 2, it is evident that the 1 H 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), σ R (r = 0.928), F (r = 0.913) and R (r = 0.922) parameters. The single linear plot of 1 H NMR chemical shift δch=n (ppm) values against Hammett constant σ is shown in the following Fig. 4. 8,800 8, , , , ,550 8,500 8,450 8,400 8,350 8, ,250-0,4-0,2 0 0,2 0,4 0,6 0,8 1 σ 1. H 2. 3-Br 3. 4-Br 4. 3-Cl 5. 4-Cl 6. 4-F 7. 4-CH OCH NO NO 2 Fig. 4. Single linear plot of 1 H 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 σ I 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 1 H 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)

9 δc=n(ppm) World Scientific News 2 (2015) δc= N (ppm) = (±0.087) (±0.022) σ I (±0.05)σ R (8) (R = 0.999, n = 10, P > 95%) δc= N (ppm) = (±0.085) (± 0.002) F (± 0.051) R (9) (R = 0.999, n = 10, P > 95%) C 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-OCH 3 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 13 C NMR chemical shift δc=n (ppm) values against Hammett constant σ is shown in the following Fig ,00 168, ,00 164, ,00 160,00 158, , ,00 152,00-0,4-0,2 0 0,2 0,4 0,6 0,8 1 σ 1. H 2. 3-Br 3. 4-Br 4. 3-Cl 5. 4-Cl 6. 4-F 7. 4-CH OCH NO NO 2 Fig. 5. Single linear plot of 13 C 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 σ I, σ R 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) = (±3.329) (±0.41)σ I (±1.52) σ R (R = 0.904, n = 10, P > 95%) δc= N(ppm) = (±3.11) 4.259(±1.52)F (±1.72) R (R = 0.904, n = 10, P > 95%) (10) (11) -219-

10 3. 4. Antimicrobial activities of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds 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-NO 2 and 4-NO 2 have shown very good antibacterial activity against Bacillus subtilis. The substituents 4-Br and 4-NO 2 have shown very good activity against Micrococcus luteus. The substituent 4-CH 3 has shown very good activity against Staphylococcus aureus. The substituents 3-Cl, 4-F, 4-CH 3, and 4-NO 2 have shown very good antibacterial activity against E.coli. The substituents 3-Cl, 4-Cl, 4-F, 4-CH 3, 3-NO 2 and 4-NO 2 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. Zone of inhibition (mm) S.No. Substituents Gram positive Bacteria Gram negative Bacteria B.subtilis M.luteus S.aureus E.coli P.aeruginosa 1 H Br Br Cl Cl F CH OCH NO NO Standard Ciprofloxacin Control DMSO

11 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

12 zone of inhibition (mm) World Scientific News 2 (2015) Antibacterial Activity 1. H 2. 3-Br 3. 4-Br 4. 3-Cl 5. 4-Cl 6. 4-F 7. 4-CH OCH NO NO Bacillus 2 M. luteus S. aureus 0 E. coli P. aurogenosa substituents Fig. 7. The antibacterial activities of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds -clustered column chart 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-NO 2 and 4-NO 2 have shown very good fungal activity against A. niger. All the compounds have shown moderate antifungal activity against the fungal species Peniciliumscup

13 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 Br Br Cl Cl F CH OCH NO NO Standard Ciprofloxacin Control DMSO Plate-1 Plate-2 Plate-3 Plate-4 Plate-5 Plate-6 Fig. 8. Antifungal activity of substituted (E)-N-benzylidene-4H-1,2,4-triazol-4-amine compounds -petri dishes

14 Zone of inhibition (mm) World Scientific News 2 (2015) Antifungal Activity substituents 1. H 2. 3-Br 3. 4-Br 4. 3-Cl 5. 4-Cl 6. 4-F 7. 4-CH OCH NO NO 2 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)-Nbenzylidene-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 , for recording NMR spectra of all compounds. References [1] Schiff H., Justus Liebigs Annalen der Chemie. 131(1) (1864) [2] Lau K. Y., Mayr A., Cheung K. K., Inorgnic Chimica Acta. 285 (1999) [3] Shawali A. S., Harb N. M. S., Badahdah K. O., Journal of Heterocyclic Chemistry. 22 (1985) [4] Gupta K. C., Sutar A. K., Coordination Chemistry Review. 252 (2008)

15 [5] Yuan M., Zhao F., Zhang W., Wang Z. M., Gao S., Inorgnic Chemistry. 46 (2007) [6] Nakaic T., Meddu S., Kurahashi T., Japan Patent (1973); Chemical Abstracts. 81(1974) [7] Quraishi Harion M. A., Sharma K., Journal of Materials Chemistry and Physics. 78 (2002) [8] Ramesh S., Rajeshwari S., Elctrochimica Acta. 49 (2004) [9] Colter R. J., Matzner M., Ring terming poly, Part B-1, Heterocyclic Ring Academic, New Youk, (1972). [10] Popp. F. D., Journal of Organic Chemistry. 26 (1961) [11] Rao X., Huang X., He L., Song J., Song Z., Shang S., Combinatorial Chemistry & High Throughput Screening. 15 (2012) [12] Hadjipavlou-litina D. J., Geronikaki A. A., Letters in Drug Design & Discovery. 15 (1996) [13] Tiwary M., Naik S. N., Tiwari D. K., Mittal P. K., Yadav S., Journal of vector Brone Diseases. 44 (2007) [14] Solak N., Rollas S., Arkivoc. (2006) [15] Wadher S. J., Puranik M. P., Karande N. A., Yeole P. G., International Journal of Pharm Tech Research 1 (2009) [16] Cates A. L., Rasheed S. M., Pharmaceutical Research 6 (1984) [17] Sakthinathan S. P., Suresh R., Mala V., Sathiyamoorthi K., Kamalakkannan D., Ranganathan K., John Joseph S., Vanangamudi G., Thirunarayanan G., International Journal of Scientific Research and Knowledge, 1(11) (2013) 472. [18] Sakthinathan S. P., Suresh R., Mala V., Sathiyamoorthi K., Kamalakkannan D., Ranganathan K., Arulkumaran R., Vijayakumar S., Sundararajan R., Vanangamudi G., Thirunarayanan G., International Letters of Chemistry, Physics and Astronomy. 6 (2013) 77. [19] 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, 101A (2013) 239. [20] Arulkumaran R., Vijayakumar S., Sakthinathan S.P., Kamalakkannan D., Ranganathan K., Suresh R., Sundararajan R., Vanangamudi G., Thirunarayanan G., Journal of Chilean Chemical Society. 2 (2013) 58. [21] Thirunarayanan G., Gopalakrishnan M., Vanangamudi G., Spectrochemica Acta 67A (2007) [22] Swain C. G., Lupton E. C., Journal of American Chemical Society. 90 (1968)

16 [23] Bauer A. W., Kirby W. M. M., Sherris J. C., Truck M., American Journal of Clinical Pathology. 45 (1966) ( Received 10 April 2015; accepted 22 April 2015 ) -226-