Reactions heterocyclic nitrogen atoms

A true intramolecular proton transfer in the second step of an azo coupling reaction was found by Snyckers and Zollinger (1970a, 1970b) in the reaction of the 8-(2 -pyridyl)-2-naphthoxide ion (with the transition state 12.151). This compound shows neither a kinetic deuterium isotope effect nor general base catalysis, in contrast to the sterically similar 8-phenyl-2-naphthoxide ion. Obviously the heterocyclic nitrogen atom is the proton acceptor. 

Generation and Reactions of sp -Carbanionic Centers in the Vicinity of Heterocyclic Nitrogen Atoms... 

In summary, the cycloaddition reactions of 1,2-dihydropyridines have proven to be very useful in the total synthesis of natural products. The primary reasons for their utility are that they have electron-rich reactive 7r-systems, they contain a heterocyclic nitrogen atom for alkaloid synthesis, and the stereochemistry is controlled in their cycloaddition reactions. 

Rewcastle, G. W., Katritzky, A. R., Generation and Reactions of sp2-Carbanionic Centers in the Vicinity of Heterocyclic Nitrogen Atoms, 56, 155. 

ITie above synthetic routes may be accompanied by side reactions, such as, for example, nitrosation or P-methylation of the heterocyclic nitrogen atom. - Similarly, the Mannich reaction on 2-amino-ethancthiol (Fig. 50), in the presence of phosphorous acid, produces the quaternary ammonium salt 147 ... 

The reaction of l-mcthylindolc (6) with dimethyl acetylenedicarboxylate in acetonitrile under reflux gives, as the major product, dimethyl l-mcthylbcnzfne icpinc-3,4-dicarboxylate (8) as the major product. Evidently the heterocyclic nitrogen atom and the 2,3-double bond function as an cnaminc system, and the reaction involves a cyclo-butenc (7) as an intermediate. 

Unstable azido compounds which have been obtained by addition of hydrazoic acid to enamines such as 181 are also thought to arise from an Adf processAlthough catalysis of an Adj reaction by protonation of the heterocyclic nitrogen atom in 181 is possible, and in fact the salt (182) was isolated from the reaction, the position of the azido group in the products (183-185) indicates that an electrophilic addition on the unprotonated enamine is the rate-limiting step. Conjugation of the nitrogen lone-pair with the diene chain could provide sufficient activation for such an addition. 

Not all reactions can be carried out in basic solution so we also need a method for adding electrophiles to heterocyclic nitrogen atoms in acidic solution. This is an important problem in nucleoside synthesis,... 

Oxidative Coupling of Heterocyclic Hydrazones. This method has opened the way to the preparation of azo derivatives of diazo compounds unobtainable by other means, ie, heterocyclic compounds in which the diazotizable amino group is conjugated with the heterocyclic nitrogen atom as in 2- and 4-aminopyridine, compounds which do not normally yield stable diazonium salts (38). The reaction occurs as illustrated by equation 7 for the interaction of (IV-methylcarbostyryl)hydrazone [28219-37-6] and dimethylaniline the overall process is oxidation. 

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