Solvent-Free Synthesis and Assessment of Substituent Effects from IR &amp;amp; NMR Spectra of some Substituted Benzylidene-5-Ethyl-1,3,4-Thiadiazole-2-Amines

<jats:p>A series containing ten titled compounds were synthesized by SiO2:H3PO4 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<jats:sup>-1</jats:sup>) 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.</jats:p>

section_content: The five membered rings containing one sulphor atom, two nitrogen atoms vicinal pattern b with two double thiadiazoles. known are onds as were thiadiazoles These 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-and methods free solvent assisted were methods 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]. 

Spectroscopic data are most useful for predicting the ground state equilibration of alkenes [20], alkynes [21], chalcones [22], Troger bases [23], bis-imines [24], sulfonamides [25], thienyl-3-carboxamides [26], acyl halides and its esters [27]. The spectral data like UV absorption (λmax, nm), IR stretches ν (cm -1 ) and NMR proton and carbon chemical shifts (δ, ppm) were used for the study of effect of substituent on the spectral group frequencies of organic substrates [28, 29]. 

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 and synthesis 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.
section_name: INTRODUCTION

section_name: EXPERIMENTAL

section_content: 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 as internal using solvent standard. TMS all of spectra synthesised Mass thiadiazoles-2-amines were recorded on SHIMADZU mass spectrometer using chemical ionization technique.
section_name: 1. General

section_content: An equi-molar quantities of 2-amino-5-ethyl-1,3,4-thiadiazole (1 mmol), substituted benzaldehydes (1 mmol) and SiO 2 :H 3 PO 4 (0. 4 g) were taken in a 50 mL borosil beaker and closed with watch glass. These contents were subjected to microwave irradiation for 2-5 minutes at 650 W (Scheme 1) (Samsung, Microwave Oven, 100-700 W). After completion of the reaction, dichloromethane (20 mL) was added, followed by simple filtration. 

The solution was concentrated and purified by re-crystallization. The synthesized thiadiazoles-2-amines were characterized by their physical constants, IR, 1 H and 13 C NMR and Mass spectral data. The analytical, physical constants and mass fragments (m/z) data are presented in Table 1.
section_name: General procedure for synthesis of substituted benzylidene-5-ethyl-1,3,4-thiadiazole-2-amines

section_content: Scheme 1. Solvent-free synthesis of substituted benzylidene-5-ethyl-1,3,4-thiadiazole-2-amines.
section_name: ILCPA Volume 24

section_content: 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.
section_name: RESULTS AND DISCUSSION

section_content: 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, ν = ρσ + ν o. . . (1) 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).
section_name: 1. IR spectral study

section_name: 2. NMR Spectral study

section_content: 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.
section_name: 2. 1. 1 H NMR spectra

section_content: The 13 C NMR chemical shift (δ, ppm) of CH=N carbon of all substituted benzylidene-5-ethyl-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. The results of statistical analysis was presented in Table 3. From Table 3, The Hammett Hammett σ, σ + substituent constants have shown satisfactory r values(σ: r = 0. 932, σ + : r = 0. 921). The Hammett σ I, σ R, F and R parameters correlated satisfactorily (σ I : r = 0. 937, σ R : r = 904, F: r = 0. 910, R = 0. 900) 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. Similarly the multi-regression analysis of the NMR chemical shifts (δ, ppm) of CH=N proton and carbon of all substituted benzylidene-5-ethyl-1,3,4-thiadiazole-2-amines were satisfactorily correlated with σ I and σ R or F and R parameters [34]. The generated multiregression analysis equations are given in (9) (10) (11) (12).
section_name: 2. 2. 13 C NMR spectra

section_content: 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.
section_name: CONCLUSIONS

section_name: ACKNOWLEDGEMENT

section_content: The author thank DST-NMR facility, Department of Chemistry, Annamalai University, Annamalainagar -608002 for recording NMR spectra.
section_name: ACKNOWLEDGEMENT