Preparation, GIAO NMR calculations and acidic properties of some novel 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives with their antioxidant activities.

Haydar Yüksek,Mustafa Calapoğlu,Mahfuz Elmastaş,Muzaffer Alkan,Ali Kolomuç,Havva Aksu,Zafer Ocak,Ismail Cakmak,Şule Bahçeci

doi:10.3390/ijms9010012

Abstract

Six novel 3-alkyl(aryl)-4-(p-nitrobenzoylamino)-4,5-dihydro-1H-1,2,4-triazol-5- ones (2a-f) were synthesized by the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H- 1,2,4-triazol-5-ones (1a-f) with p-nitrobenzoyl chloride and characterized by elemental analyses and IR, (1)H-NMR, (13)C-NMR and UV spectral data. The newly synthesized compounds 2 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents such as acetone, isopropyl alcohol, tert-butyl alcohol and N,N-dimethylformamide, and the half-neutralization potential values and the corresponding pK(a) values were determined for all cases. Thus, the effects of solvents and molecular structure upon acidity were investigated. In addition, isotropic (1)H and (13)C nuclear magnetic shielding constants of compounds 2 were obtained by the gauge-including-atomic-orbital (GIAO) method at the B3LYP density functional level. The geometry of each compound has been optimized using the 6-311G basis set. Theoretical values were compared to the experimental data. Furthermore, these new compounds and five recently reported 3-alkyl-4-(2-furoylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3a-c,e,f) were screened for their antioxidant activities.

Highlights

1,2,4-Triazole and 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives are reported to show a broad spectrum of biological activities [1,2,3,4,5,6], and several papers have devoted with the synthesis of acyl derivatives of 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives [2,4,7,8,9,10,11,12]
The newly synthesized compounds 2 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents such as acetone, isopropyl alcohol, tert-butyl alcohol and N,Ndimethylformamide, and the half-neutralization potential values and the corresponding pKa values were determined for all cases
We examined the potentiometric titrations of the synthesized type 2 compounds with tetrabutylammonium hydroxide (TBAH) in four non-aqueous solvents to determine the corresponding half-neutralization potentials (HNP) and the corresponding pKa values

Summary

Introduction

1,2,4-Triazole and 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives are reported to show a broad spectrum of biological activities [1,2,3,4,5,6], and several papers have devoted with the synthesis of acyl derivatives of 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives [2,4,7,8,9,10,11,12]. It is known that 1,2,4-triazole and 4,5-dihydro-1H-1,2,4-triazol-5-one rings have weak acidic properties, so that some 1,2,4-triazole and 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives were titrated potentiometrically with tetrabutylammonium hydroxide in non-aqueous solvents, and the pKa values of the compounds were determined [2,13,14]. We have previously described the synthesis and potentiometric titrations of some new 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives in different non-aqueous medium [9,10,11,12,15,16,17,18], where we determined the pKa values of these compounds for each non-aqueous solvent. We examined the potentiometric titrations of the synthesized type 2 compounds with tetrabutylammonium hydroxide (TBAH) in four non-aqueous solvents (acetone, isopropyl alcohol, tert-butyl alcohol and N,N-dimethylformamide) to determine the corresponding half-neutralization potentials (HNP) and the corresponding pKa values. The data obtained from the potentiometric titrations was interpreted, and the effect of the C-3 substituent in 4,5-dihydro-1H-1,2,4triazol-5-one ring as well as solvent effects were determined to previous studies [9,10,11,12,13,14,15,16,17,18]

Methods

Results

Conclusion