Preparation of 5‐substituted benzylbarburituric acids and investigation of the effect of the benzyl and substituted benzyl groups on the acidity of barbituric acid

Abstract

The acidity of 5‐benzylbarbituric acid and a series of 5‐substituted benzylbarbituric acids has been determined in 50% ethanol/water and they were found to be more acidic than barbituric acid. The pKas of these derivatives obey Hammett's equation indicating that their acidity is affected by substituents in the same manner as the benzoic acid ionization constants. A synthesis of these acids is described.

Curtailing the Hydroxylaminobarbituric Acid–Hydantoin Rearrangement To Favor HNO Generation

“…As expected, substituents on the benzyl moiety affect the acidity of the barbituric acid; electron-withdrawing groups increase acidity and electron-donating groups decrease acidity. These substituent effects have been previously demonstrated to obey the Hammett equation on a series of 5-substituted benzyl 1,3-unsubstituted barbituric acid derivatives …”

“…These substituent effects have been previously demonstrated to obey the Hammett equation on a series of 5-substituted benzyl 1,3-unsubstituted barbituric acid derivatives. 21 The rates of decomposition of the benzyl derivatives, HABA-3, HABA-4, and HABA-5, correlate with the pK a values of their respective BA byproducts. As the stability of the resultant carbanion increases, so too does the rate of HNO evolution.…”

Two-Component Gelators and Nucleating Agents for Polypropylene Based upon Supramolecular Assembly

“…5-(4-Methylbenzyl)barbituric Acid (MeBz-BA). According to the procedure described by Tate 0.2 mol of barbituric acid in 500 mL of water reacted within 3 days at 20 °C with 0.1 mol of 1-(bromomethyl)-4-methylbenzene using 0.1 mol triethanolamine as base. Yield: 65%.…”

A Concise Sar-Analysis of Antimicrobial Cationic Amphipathic Barbiturates for an Improved Activity-Toxicity Profile

“…Weak electrophiles, such as alkyl halides posed an inherent problem. Harsher conditions were needed, which inevitably led to additional N-alkylation due to the acidity of the N-H protons (pK a = 7-9 [35,36] compared to the pK a (H-C5) = 3-4 [36,37]).…”

“…To obtain unsymmetrically 5,5-dialkylated barbituric acids 3k-q a different approach was needed, since mono-alkylation enhances the nucleophilicity of the barbiturate C-5 carbon leading to inevitable dialkylation [37]. We investigated several reported methods for selective monoalkylation and in situ reductions [37][38][39], which did not work well in our hands. We therefore decided to use a stepwise approach as shown in Scheme 1-II.…”