Quaternization of heterocyclic compounds

Quaternization of Heterocyclic Compounds E. Balta, Stud. Cercet. Chim., 1972, 20, 957-979. 

The mesomeric effect of the C=S linkage is very pronounced and is responsible for the facile quaternization of heterocyclic N-alkylated thiones (159) this effect is operative even when such a shift does not increase the aromaticity of the ring. Thione derivatives of pyridazine, benzothiazole, quinazoline, 1,3-thiazine, triazole,and isoindole are examples of compounds which readily form quaternary salts. 

The third volume of this series covers three specific groups of compounds the carbolines (reviewed by R. A. Abramovitch and I. D. Spenser), the thiatriazoles (K. A. Jensen and C. Pedersen), and the pentazoles (I. Ugi). The remaining four chapters deal with topics of general chemical interest from the heterocyclic viewpoint the quaternization of heterocyclics (G. F. Duffin), carbene reactions (C. W. Rees and C. E. Smithen), applications of the Hammett equation (H. H. Jaffe and H. Lloyd Jones), and some aspects of the nucleophilic substitution of heterocyclic azines (G. Rluminati). 

Our review focuses on important developments dealing with quaternization of annular nitrogen atoms of heterocyclic compounds. Only six-and five-membered heteroaromatic rings are included. The organization comprises two main parts. Part I is a comprehensive narrative describing the main electronic and steric factors of heteroaromatic... 

An intriguing question then arises. Can evidence of the effects of pair-pair interactions be found in the solution chemistry of heterocyclic compounds in which electron transfer is not involved Although some unusual reactivity patterns have been observed in quaternization reactions, it is not obvious that the explanation lies with pair-pair interactions. 

Quaternization of Heteroaromatic Compounds Quantitative Aspects J. A. Zoltewicz and L. W. Deady, Adv. Heterocycl. Chem., 1978, 22, 71-121. 

Zoltewicz J. A, Deady L. W, "Quaternization of Heteroaromatic Compounds Quantitative Aspects", Advances in Heterocyclic Chemistry, Elsevier 1978. p. 71-121. DOI 10.1016/S0065-2725(08)60103-8... 

In spite of the fact that the vast majority of quaternizations of amino-heterocyclic compounds are reported as occurring on the ring nitrogen atom only, it seems quite likely that salt formation may also take place on the exocyclic nitrogen in other cases but that it has been overlooked in the absence of a test such as was available for 4. 

Solvent effects also depend on the ground-state structure of the substrate and on the transition-state structure, as is shown below. Here let us merely note that A-heterocyclic compounds tend to form a hydrogen bond with hydroxylic solvents even in the ground state. Hydrogen-bond formation in this case is a change in the direction of quaternization of the aza group, as demonstrated by spectral evidence. Therefore, it is undoubtedly a rate-enhancing interaction. 

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