Benzaldehyde reaction with 4-methylpyridine

A 2-Methylpyridine can be deprotonated by a base such as sodium methoxide and the resultant anion can be reacted with ben-zaldehyde to form a hydroxylated adduct (Scheme 2.21). This product can then be dehydrated by acid, or base, to form the conjugated compound stilbazole. Alternatively 2-methylpyridine can be A -acetylated by reaction with acetic anhydride and the initial product deprotonated to give an A -acetylenamine intermediate that traps benzaldehyde, A similar reaction to that of the first procedure occurs, but under the reaction conditions the zwitterionic (dipolar) product eventually loses acetic acid, perhaps by an interna shift of an acetyl group from nitrogen to oxygen. 

The reaction of 6-methylpyridine-3-carboxylic acid methyl ester with N,0-dimethylhydroxylamine and isopropyl-magnesium chloride in toluene gives the N-methoxyamide derivative (x), which is reduced with diisobutyl aluminium hydride (DIBAL) to afford 6-methylpyridine-3-carbaldehyde (xi). The reaction of the aldehyde (xi) with a phosphite provides the diphenyl phosphonate derivative, which is condensed with 4-(methylsulfonyl)benzaldehyde in the presence of potassium fe/f-butoxide in HF to yield the enimine (xii). Finally, this compound is hydrolyzed with HCI to yield the ketosulfone (ix). 

Methylpyridine reacts with benzaldehyde (CeHsCHO) in the presence of base to form A. (a) Draw a stepwise mechanism for this reaction, (b) Would you expect 2-methylpyridine or 3-methylpyridine to undergo a similar type of condensation reaction Explain why or why not. 

Carboxylation of the potassium salt of 3-hydroxy-6-methylpyridine (145) gave the picolinic acid 146(84MI16). The Hammick condensation reaction of picolinic acid with benzaldehyde has been studied with regard to the effect of solvent, temperature, and molar ratio of reactants (85MI5). Benzoyl chloride, or benzaldehyde, and l-benzyl-4,6-diphenylpyridinium-2-carboxylate afford 2-benzoyl-4,6-diphenylpyridine (85JCS(P1)2167). Sulfur and 1,4,6-triaryl-pyridinium-2-carboxylates 147 in xylene at 140°C give the corresponding pyridine-2-thiones 148(838149). 

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