Pyridines protonation, regioselectivity

More vigorous conditions are required for the amination of 2- or 4-alkyl-pyridines, since proton abstraction from the side-chain (cf. 8.10) by the amide occurs first, and ring attack must therefore involve a dianionic intermediate. Amination of 3-alkyl-pyridines is regioselective for the 2-position. ... 

Due to the low solubility of the concave pyridines 3 in diethyl ether, the corresponding pyridine buffers could not be compared with the experiments of Table 4. But when the protonations were carried out in other solvents, no influences of the acids (including the acids of Table 4) on the regioselectivity could be found. The exchange of diethyl ether by other solvents caused a color change of the allyl anion solution which indicated different structures for the anions in diethyl ether and in other, more polar solvents [44],... 

Radical alkylations of pyridines and quinolines preferentially occur at positions 2 and 4. Protonation of the ring nitrogen influences the regioselectivity by favoring C-4 substitution. 

In 2004, excellent yields of hydroperoxides 91 and 92 were obtained (>95%) in the photooxidation of racemic acid 90 (Scheme 11.17) [96]. The diastereoselectivity of the photooxidation favored the trans-configured products due to the anti-directing effect of the protonated carboxylic acid group. Regioselectivity favored the formation of 92 over 91. Pyridine helped to accelerate the deprotonation of the CH next to COOH of 90, affording 92, and also suppressed the formation of aromatic compounds which otherwise would take place in the absence of pyridine. A great many studies of ene reactions have been conducted in organic solvents [97-101] or aqueous media [102-106] one such report appeared which used a fluorous biphasic solution [107]. 

The regioselectivity of the reaction is dependent on the hydrofluorinating reagent used. Pyridine-(HF) is highly acidic and the reaction proceeds by protonation of the ring oxygen, followed by fluoride ion attack on the carbon atom upon which the developing... 

Electrophilic nitration and bromination of pyridine iV-oxides can be controlled to give 4-substituted products by way of attack on the free A-oxide. ° Under conditions where the A-oxide is 0-protonated, substitution follows the typical pyridine/pyridinium reactivity pattern thus, in fuming sulfuric acid, bromination shows P-regioselectivity. Mercuration takes place at the a-position, however mercuric-catalysed sulfonation produces the 3-sulfonic acid. ... 

Tsuji and coworkers have developed diisobutylaluminum phenoxide-pyridine as an effective aldol condensation catalyst and applied it to the macrocyclization of 2,15-hexadecanedione (equation 132). Addition of the diketone at high dilution to a solution of the catalyst in hexane provides a mixture of cis and trans isomers of the and A enones. Catalytic hydrogenation of the mixture affords ( )-muscone. The authors explain the regioselectivity of the process by assuming that the aluminum phenoxide functions as a Lewis acid, coordinating to the carbonyl group. Pyridine functions as a base to remove a proton from the less hindered methyl group. 

The reaction of nucleophilic radicals, under acidic conditions, with heterocycles containing an imine unit is by far the most important and synthetically useful radical substitution of heterocyclic compounds. Pyridines, quinolines, diazines, imidazoles, benzothiazoles, and purines are amongst the systems which have been shown to react with a wide range of nucleophilic radicals, selectively at positions a and 7 to the nitrogen, with replacement of hydrogen. Acidic conditions are essential because N-protonation of the heterocycle both greatly increases its reactivity and promotes regioselectivity towards a nucleophilic radical, most of which hardly react at all with... 

The radical alkylation of protonated heteroaromatic compounds-the so-called Minisci reaction-has been intensively investigated [2e, g, 111]. Protonated hetero-arenes are electron-deficient substrates, which react with nucleophilic radicals with high regioselectivity to yield the corresponding homolytic aromahc substitution products. For para-substituted pyridine derivatives the reaction occurs with complete regioselectivity at the 2-position, whereas for nonprotonated pyridines, arylations occur with low regioselectivity and in low yields. 

Regioselective alkyne cycloaddition to the azacyclobutadiene 115 affords the 1-aza-Dewar-pyridine 116. Photochemical ring-closure converts 116 to the azaprismane 117, which on heating or proton-catalyzed isomerizes to the sterically crowded pyridine... 

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