Heteroaromatic compounds quaternization

Solvent effects on relative rate constants are also usually small. When a heteroaromatic compound quaternizes at more than one site, for example, the product ratio can be insensitive to solvent variations. A constant isomer ratio is recorded for methylation (Mel) of 3-/erf-butyl-6-dimethylaminopyridazine (10), in hexane, benzene, carbon tetrachloride, acetone, and acetonitrile, but not in dimethoxyethane or tetrahydrofuran. The suggestion was made that Mel may have reacted with the last two ether solvents to give an oxonium ion. Since the identity of the quaternizing agent changes, the product ratio varies as well.13... 

The entire area of the reversible quaternization of heteroaromatic compounds is undeveloped very little quantitative information is available. The following provides an enticing introduction to the type of information that can result from quantitative work. 

Quaternization of Heteroaromatic Compounds Quantitative Aspects John A. Zoltewicz and Leslie W. Deady PartI. Discussion... 

Quaternization of Heteroaromatic Compounds Quantitative Aspects, 22,71. Zappala, M., see Chimirri, A., 63, 61. 

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... 

Zoltewicz, J. A., Deady, L. W., Quaternization cf Heteroaromatic Compounds Quantitative Aspects, 22, 71. 

Quantitative aspects of the quaternization of heteroaromatic compounds have been the subject of a review. ... 

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... 

Amino-1,2,4-triazoles (50) or their derivatives are usually starting material for the synthesis. They are readily available and already contain the exocyclic N-N bond required for heteroaromatic A-imines. 4-Amino-1,2,4-triazoles can be quaternized by alkyl halides or tosylates at the N-l atom to give the salt 52.79-82 (Scheme 5) The orientation of quatemization is proved by the reactions in Scheme 6 for the example of the quaternary acylamino salts 52. Quaternary salts of the type 52 can also be prepared by reaction of 1,3,4-oxadiazolium salts (51)83 with aryl hydrazines84 and from aryl hydrazine hydrohalides and orthoesters.86 With alkali, the 1-alkyl-s-triazole-4-imines8(7-82 86 can be obtained in the normal manner from these salts (Scheme 5). The free A-imines are all stable except the A-unsubstituted compound itself.87 Recently, other structures were tentatively reported 88 for the deprotonation products of analogous quaternary salts (52) with hydrazine. 

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