32967-14-9Relevant articles and documents
Selectivity under microwave irradiation. Benzylation of 2-pyridone: an experimental and theoretical study
de la Hoz, Antonio,Prieto, María Pilar,Rajzmann, Michel,de Cózar, Abel,Díaz-Ortiz, Angel,Moreno, Andrés,Cossío, Fernando P.
, p. 8169 - 8176 (2008/12/21)
The reaction of 2-pyridone with benzyl bromide in the absence of base and under solvent-free conditions has been studied experimentally and by computational methods. This reaction was one of the first reported examples in which modification of selectivity under microwave irradiation was observed. C- and/or N-alkylations were obtained depending on the benzyl halide and the heating system. N-Alkylation through mechanism A (SN2 mechanism) is kinetically favoured while C-alkylation through an SN1-type mechanism is thermodynamically favoured and is observed under microwave irradiation. Two SN1-type mechanisms (mechanisms B and C) have been calculated, mechanism C being a kind of SNi. The influence of the pyridone/benzyl bromide ratio was studied. A second molecule of pyridone stabilizes the transition state and assists the leaving of the bromide ion. The occurrence of C-alkylation under microwave irradiation is explained by the predominance of the thermodynamic control in these conditions. Under microwave irradiation N-alkylation through an SN1-type mechanism (mechanism C) can also occur. The dependence of the outcome of N-alkylation on the benzyl bromide ratio has been explained by a shift in the mechanism from SN2 to SN1 under microwave irradiation. Computational calculations have shown to be a useful tool for determination of the origin of the selectivity under microwave irradiation.
Some Benzyl-Substituted Imidazoles, Triazoles, Tetrazoles, Pyridinethiones, and Structural Relatives as Multisubstrate Inhibitors of Dopamine β-Hydroxylase. 4. Structure-Activity Relationships at the Copper Binding Site
Kruse, Lawrence I.,Kaiser, Carl,DeWolf, Walter E.,Finkelstein, Joseph A.,Frazee, James S.,et al.
, p. 781 - 789 (2007/10/02)
Structure-activity relationships (SAR) were determined for novel multisubstrate inhibitors of dopamine β-hydroxylase (DBH; EC 1.14.17.1) by examining the effects upon in vitro inhibitory potencies resulting from structural changes at the copper-binding region of inhibitor.Attempts were made to determine replacement groups for the thione sulfur atom of the prototypical inhibitor 1-(4-hydroxybenzyl)imidazole-2-thione described previously.The synthesis and evaluation of oxygen and nitrogen analogues of the soft thione group demonstrated the sulfur atom to be necessary for optimal activity.An additional series of imidazole-2-thione relatives was prepared in an effort to probe the relationship between the pKa of the ligand group and inhibitor potency.In vitro inhibitory potency was shown not to correlate with ligand pKa over a range of approximately 10 pKa units, and a rationale for this is advanced.Additional ligand modifications were prepared in order to explore bulk tolerance at the enzyme oxygen binding site and to determine the effects of substituting a six-membered ligand group for the five-membered imidazole-2-thione ligand.
