Synthesis and Determination of pKa Values of Some New 3,4-Disubstituted-4,5-Dihydro-1H-1,2,4-triazol-5-one Derivatives in Non-aqueous Solvents

Haydar Yüksek,Mustafa Özdemir,Muzaffer Alkan,Sule Bahçeci,Zafer Ocak

doi:10.3390/90400232

Haydar Yüksek, Mustafa Özdemir + Show 3 more

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https://doi.org/10.3390/90400232

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Abstract

3-Alkyl(Aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (2) reacted with 2-furoyl chloride and thiophene-2-carbonyl chloride to afford the corresponding 3- alkyl(aryl)-4-(2-furoylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3) and 3-alkyl(aryl)- 4-(2-thienylcarbonylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (4), respectively. The new compounds synthesized were characterized by using IR, 1H-NMR, 13C-NMR and UV spectral data together with elemental analysis. In addition, to investigate the effects of solvents and molecular structure upon acidity, compounds 3 and 4 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents (isopropyl alcohol, tert-butyl alcohol, N,N-dimethylformamide and acetonitrile). The half-neutralization potential values and the corresponding pKa values were determined for all cases.

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 such as antifungal, antimicrobial, hypoglycemic, antihypertensive, analgesic, antiparasitic, hypocholesteremic, antiviral, anti-inflammatory, antitumor and anti-HIV properties [1,2,3,4,5,6,7,8,9,10,11,12,13,14]
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 nonaqueous medium [21, 22], where we determined the pKa values of these compounds for each nonaqueous solvent
For each new compound synthesized, the halfneutralization potential (HNP) and the corresponding pKa value were determined in the four mentioned non-aqueous solvents

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 such as antifungal, antimicrobial, hypoglycemic, antihypertensive, analgesic, antiparasitic, hypocholesteremic, antiviral, anti-inflammatory, antitumor and anti-HIV properties [1,2,3,4,5,6,7,8,9,10,11,12,13,14]. These observations prompted us to synthesize some new 4,5-dihydro-1H-1,2,4triazol-5-one derivatives with potential biological activity. Determination of pKa values of active constituents of certain pharmaceutical preparations is important, because their distribution, transport behavior, bonding to receptors, and contributions to metabolic behavior depend on the ionization constant [23]

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