Commonly Encountered Pyridine Derivatives

The chemical behaviour of many substituents attached to the pyridine ring is similar to that of the corresponding groups in benzene, with the proviso that resonance with, and the inductive influence of, the ring nitrogen atom may significantly modify some reactions. 

These have the trivial generic name picolines on oxidation they give the appropriate acids pyridine-2- and -4-carboxylic acids are called 2- and 

4-picolinic acids, respectively (see Box 2.1). Pyridine-3-carboxylic acid is better known as nicotinic acid (reflecting its relationship to the alkaloid nicotine, see Section 1.3). 

Deprotonation of 3-picoline is more difficult (the anion cannot achieve stability through resonance, as happens with the others) and a much stronger base, LDA [lithium diisopropylamide (lithium propan-2-ylamide)], is needed. Once achieved, however, the conjugate anion behaves as a nucleophile and undergoes typical carbanion reactions (indeed, it is more reactive than its counterparts, since reactivity is most often the opposite of stability ). 

The tautorrehc preferences observed for hydroxy and amino heterocycles is a complex subject arid not always easily explained. -  

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For commonly encountered heterocycles, the chemical shifts of trifluo-romethyl substituents will depend somewhat upon where in the heterocycle they are located. Examples of trifluoromethyl derivatives for a number of common heterocycles, including pyridines, quinolines, pyrroles, indoles, thiophenes, benzothiophenes, furans, benzofurans, imidazoles, and uracils are given below. 

The commonly encountered compounds in this class are the formyl, acetyl and benzoyl derivatives. The formation of the N-formyl compound is readily accomplished by heating the amino compound with formic acid in the presence of acetic anhydride.223 Alternatively, formic acid in the presence of dicyclohexl-carbodiimide (DCC) in pyridine solution is a suitable method for the protection of amino acid esters.224... 

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