Solvent-free synthesis and assessment of substituent effects from IR & NMR spectra of some substituted benzylidene-5-ethyl-1,3,4-thiadiazole-2-amines

A series containing ten titled compounds were synthesized by SiO 2 :H 3 PO 4 catalyzed solvent-free condensation of substituted benzaldehydes and 2-amino-5-ethyl-1,3,4-thiadiazole under microwave irradiation. The yields of prepared amines are more than 90 %. The synthesized amines were characterized by their physical constants and spectroscopic data reported in literature earlier for known compounds. The assigned spectral group frequencies such as infrared νC=N, C-S-C, N-N (cm - 1 ) and NMR chemical shifts (δ, ppm) of CH, C=N have been correlated with Hammett substituent constants, F and R parameters using single and multi-linear regression analysis. From the results of statistical analyses, the effects of substituent on the above spectral data have been discussed.


INTRODUCTION
The five membered rings containing one sulphor atom, two nitrogen atoms vicinal pattern with two double bonds are known as thiadiazoles. These thiadiazoles were medicinally important due to the presence of C=N, C-S-C and N-N moieties in the five membered ring. Therefore chemists and researchers paid more attentions for synthesis of heterocyclic compounds by synthetic routes or naturally occurring methods [1]. Some of the important biological activities of these thiadiazoles are antitumor agent [2], potent inhibitors of 5-lipoxygenase and cyclooxygenase [3], antimicrobials [4], anti-tuberculosis [5,6], antiinflammatory [7], antidepressant and anxiolytics [8], anticancer [9,10], anthelmintic [11] and antimicrobial [1]. Numerous solvent-free methods and solvent assisted methods were reported for the synthesis of heterocyclics [1,[12][13][14]. Currently, organic chemists and researchers paid much more interest for solvent-free synthetic methods due to easy handling procedure, technique, non-hazardousness, pollution free environment, shorter reaction time and better yields [16][17][18][19].
Recently, Thirunarayanan and Sekar studied the effect of substituents on the pyrazoline derivatives using IR and NMR data [30]. Thirunarayanan have studied the solvent-free synthesis and spectral correlation of some six membered heterocyclic compounds [19]. Suresh et al., have studied the solvent-free synthesis and spectral correlations of some aryl E-imines [18].
Thirunarayanan et al. have studied the solvent-free synthesis and spectral linearity of some trifluoromethyl imines [31]. Sakthinathan et al., have studied the Spectral correlations and antimicrobial activities of some (E)-N-Benzylidenepyridin-2-amines [32] and aryl (E)-Nbenzylidene-3-nitrobenzenamines [33]. Within the above view, there is no report available for the solvent-free synthesis and the study of effect of substituents on the substituted benzylidene-5-ethyl-1,3,4-thiadiazole-2-amines in the past and present. Therefore, first time, the author wishes to report the solvent-free synthesis of some substituted benzylidene-5ethyl-1,3,4-thiadiazole-2-amines and recorded the IR and NMR spectra for studying the effect of substituents on the spectral frequencies.

1. General
Chemical used in this present study were procured from Sigma-Aldrich and E-Merck chemical companies. The melting point of all compounds were determined in in open glass capillaries on V-SCIENTIFIC MP-DS melting point apparatus and are uncorrected. The infrared spectra of all compounds were recorded in KBr discs on Thermo scientific Nicolet iS5, US made Fourier transform spectrophotometer.
The NMR spectra of selective compounds were recorded in BRUKER AV 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. Mass spectra of all synthesised thiadiazoles-2-amines were recorded on SHIMADZU mass spectrometer using chemical ionization technique.

RESULTS AND DISCUSSION
In the present investigation, the author have synthesized and recorded IR and NM spectra for studying the effect of substituents on the spectral frequencies of substituted benzylidene-5-ethyl-1,3,4-thiadiazole-2-amines by infrared and NMR spectra.

1. IR spectral study
The infrared spectra of all substituted benzylidene-5-ethyl-1,3,4-thiadiazole-2-amines were recorded in KBr discs. The characteristic stretches of the substituted benzylidene-5ethyl-1,3,4-thiadiazole-2-amines such as νC=N, C-S-C, N-N (cm -1 ) were assigned and tabulated in Table 2. These stretches were correlated with Hammett substituent constants, F and R parameters [34] using linear regression analysis. In this correlation, the Hammett equation is employed in the form as, where ν is the carbonyl frequencies of substituted system and ν o is the corresponding quantity of unsubstitued system, σ is a Hammett substituent constant, which in principle is characteristics of the substituent and ρ is a reaction constant which is depend upon the nature of the reaction. The results of statistical analyses [12,18,19,[22][23][24][27][28][29]32] was presented in Table 3. From the Table 3, The correlation of νC=N (cm -1 ) stretches with Hammett σ, σ + substituent constants have shown satisfactory r values (σ: r = 0.954, σ + : r = 0.951). The Hammett σ I , σ R , F and R parameters correlated satisfactorily (σ I : r = 0.904, σ R : r = 903, F: r = 0.904, R = 0.904) excluding H, 4-F and 4-CH 3 substituents. If these substituents were included in the correlation, they reduced the r values significantly. All correlations gave positive ρ values. This implies that the normal substituent effect operates in all system.
The νC-S-C (cm -1 ) and νN-N (cm -1 ) stretches of substituted benzylidene-5-ethyl-1,3,4thiadiazole-2-amines were fail in correlation with Hammett substituent constants, F and R parameters. All correlations gave positive ρ values. This implies that the normal substituent effect operates in all system. The failure in correlation is due to the inability of the effect of substituents on the group frequencies and associated with resonance conjugative structure as shown in Fig. 1. In infrared spectral correlation of substituted benzylidene-5-ethyl-1,3,4-thiadiazole-2amines, the correlation of νC-S-C (cm -1 ) and νN-N (cm -1 ) stretches with Hammett substituent constants, F and R parameters were fail in single parameter regression analysis. These data gave satisfactory correlations, when they worthful, while seeking in multi-regression analysis with σ I and σ R or F and R parameters [34]. The generated multi-regression analysis equations are given in (2-7).

2. 1. 1 H NMR spectra
The 1 H NMR chemical shift (δ, ppm) of CH=N proton of all substituted benzylidene-5ethyl-1,3,4-thiadiazole-2-amines were assigned and presented in Table 2. These chemical shifts are correlated [12,18,19,[22][23][24][27][28][29]32] with Hammett substituent constants, F and R parameters. In nuclear magnetic resonance spectra, the proton or the 13 C chemical shifts (δ) depends on the electronic environment of the nuclei concerned. The assigned vinyl proton chemical shifts (ppm) have been correlated with reactivity parameters using Hammett equation in the form of log δ = log δ o + ρσ … (8) where δ o is the chemical shift of unsubstitued ketones. σ is a Hammett substituent constant, which in principle is characteristics of the substituent and ρ is a reaction constant which is depend upon the nature of the reaction.
The results of statistical analysis were presented in Table 3. From Table 3, The Hammett σ, σ + substituent constants have shown satisfactory r values(σ: r = 0.951, σ + : r = 0.953). The Hammett σ I , σ R , F and R parameters correlated satisfactorily (σ I : r = 0.903, σ R : r = 904, F: r = 0.904, R = 0.904) excluding H, 4-F, 4-OH and 4-CH 3 substituents. If these substituents were included in the correlation, they reduced the r values significantly. All correlations gave positive ρ values. This implies that the normal substituent effect operates in all system.

CONCLUSIONS
Totally ten substituted benzylidene-5-ethyl-1,3,4-thiadiazole-2-amines were synthesized by SiO 2 :H 3 PO 4 catalyzed solvent-free condensation under microwave irradiation. The yields of prepared amines are more than 90 %. This synthetic methodology offers environmentally benign reaction, easy work-up procedure, technique, non-hazardousness, pollution free to environment, shorter reaction time and better yields. The synthesized amines were characterized by their physical constants and spectroscopic data reported in literature earlier for known compounds. The assigned spectral group frequencies such as infrared νC=N, C-S-C, N-N (cm -1 ) and NMR chemical shifts (δ, ppm) of CH, C=N have been correlated with Hammett substituent constants, F and R parameters using single and multilinear regression analysis. From the results of statistical analyses, infrared νC=N (cm -1 ) and NMR chemical shifts (δ, ppm) of CH, C=N have shown satisfactory correlations with single and multi-regression analysis.