Methyl picolinate

Table 4-2. Computed and experimental primary 12C/13C and secondary 14N/15N kinetic isotope effects for the decarboxylation of N-methyl picolinate at 25 °C in water...

Results. The experimental 15N isotope effect at N1 for the decarboxylation of OMP in ODCase (Scheme 1) was measured by Cleland et al. to be 1.0068.66 Comparison of this normal isotope effect with IEs measured for the model compounds picolinic acid (17) and A-methyl picolinic acid (18) led Cleland and coworkers to conclude that the normal IE observed for OMP decarboxylation is indicative of the lack of a bond order change at Nl. This conclusion was based on the following reasoning. The IE for the decarboxylation of picolinic acid (17) is 0.9955 this inverse value is due to the change in bond order incurred when the proton shifts from the carboxylate group to the N in order to effect decarboxylation (equation 2) the N is ternary in the reactant, but becomes quaternary in the intermediate, which results in the inverse IE. The decarboxylation of A-methyl picolinic acid (18) involves no such bond order change (equation 3), and the observed normal IE of 1.0053 reflects this. 

Phillips and Lee calculated the 15N isotope effect for the decarboxylation of 1-methyl orotate (lb) via 2-protonation (4b) and via 4-protonation (6b). They found that in both cases, the calculated isotope effect is normal 1.0043 for 2-protonation, and 1.0054 for 4-protonation. An examination of the optimized structures showed clearly that very little bond order change occurs at Nl, regardless of which oxygen is protonated. Phillips and Lee also benchmarked their calculations by computing the IEs for protonation of pyridine and for decarboxylation of picolinic acid (17) and A-methyl picolinic acid (18) the results of these calculations are in agreement with the experimental values mentioned above. Therefore, Philips and Lee asserted that... 

Sodio-2-methylpyrazine with methyl picolinate afforded a mixture containing 2-(pyridin-2 -ylcarbonylmethyl)pyrazine (42.6%) (24) and 2-pyridinylbis(pyrazinyl-methyl)carbinol (22.8%), and with ethyl formate gave only bis(pyrazinylmethyl> carbinol (642). 

The situation is simplified if the substituent is at a para position to the reaction site since in this case there are no conditions for realizing the indirect resonance effect. The substituent and the reaction site cannot be simultaneously directly conjugated with the nitrogen heteroatom of the azine ring and, as a rule, the reactivity parameters correlate well with the Hammett ffp values. Examples include (1) the ionization constants of 5-substituted picolinic (57) and 6-substituted nicotinic acids (59) (59NKZ1293) (2) the rates of alkaline hydrolysis of 5-substituted methyl picolinates (58) (70JCS(B) 1063) ... 

Caerulomycin E (18b) was isolated from cultures of Streptomyces caeruleus. Its structure was determined by MS and by comparison of its and 13c NMR spectra with those of the previously isolated caerulomycin A (18a) and similar compounds [112]. Caerulomycin A (and its Z-isomer) have been synthesized from methyl picolinate and 3,5-dimethyloxazole [113]. 

A great variety of pyridines (currently 341) has been identified in tobacco and tobacco smoke. As a class, there are more pyridines in smoke than any other heterocycle. Vohl and Eulenberg (4064) were the first to isolate and identify pyridine in tobacco smoke in 1871. Since that time a wide variety of substituted (methyl- [picolines], dimethyl- [lutidines]. 

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