Kinetics of Electrophilic Alkylations of Barbiturate and Thiobarbiturate Anions

• Published in: Journal of organic chemistry 2017-08, Vol.82 (16), p.8476-8488
• Main Authors: Schade, Alexander, Tchernook, Ivan, Bauer, Mirko, Oehlke, Alexander, Breugst, Martin, Friedrich, Joachim, Spange, Stefan
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.7b01223

Second-order rate constants (k 2) of the reactions of various barbiturate anions such as the parent barbiturate, 1,3-dimethylbarbiturate, 2-thiobarbiturate, and 1,3-diethyl-2-thiobarbiturate with diarylcarbenium ions and Michael acceptors have been determined in dimethyl sulfoxide solution at 20 °C. The reactivity parameters N and s N of the barbiturate anions were derived from the linear plots of log k 2 versus the electrophilicity parameters E of these reference electrophiles, according to the linear-free-energy relationship log k 2 (20 °C) = s N (E + N). Several reactions of these nucleophiles with benzylidenemalononitriles and quinone methides proceeded with reversible formation of the new C–C-bond followed by rate-determining proton shift. No evidence for initial attack of the electrophiles at the enolate oxygens of these nucleophiles was found by the kinetic measurements, in line with quantum chemical DFT calculations, which showed that in all cases C-attack is kinetically and thermodynamically preferred over O-attack. The nucleophilic reactivities of barbiturate anions were compared with those of structurally related carbanions, e.g., Meldrum’s acid and dimedone anions.