Oxygen, quaternization

The other known case, a more general one, of attack at an oxygen atom is the formation of N-alkoxy-quaternary salts by quaternization of the N-oxides and is illustrated by Eq. (5). 

Alkylation of hydroxyazines where reaction does not lead to quaternization is not considered. Molecules such as 4-pyridone usually exist largely as the carbonyl, but not as the 4-hydroxypyridine, tautomer in polar solvents8 [Eq. (1)]. Monoalkylation of the neutral species of such molecules can take place preferentially at either the annular nitrogen atom of the OH form or the oxygen atom of the N—H form in each case subsequent proton loss yields a neutral product. Dialkylation then gives rise to a cationic product, the second alkyl group being introduced at the other site. 

Other solvents also are not inert to the alkylating agent. For example, DMSO and Mel react, first (reversibly) at oxygen and then at sulfur.45 This side-reaction becomes important only in quaternization studies involving poorly nucleophilic heteroaromatic substrates.41... 

Many heterocyclic bases having a cyclopentadiene structure are sensitive to oxydation they form dimers110,113 or cyclopentadienones51,1 25,132 in the presence of atmospheric oxygen. Therefore, the quaternization should be performed under an inert atmosphere. Further difficulties arise from the tautomerism of some heterocyclic bases (Scheme 5). This can lead to the... 

Using an oxaziridinium salt derived from dihydroisoquinoline, Lusinchi was able to transfer the oxygen atom to several simple alkenes in good yield (Scheme 5.2) [5,6]. Following this work, the first enantiomerically pure oxaziridinium salt was prepared [7]. Quaternization of chiral oxaziridine (1), derived from (lS,2R)-(+)-norephedrine, produced the oxaziridinium salt (2) (Scheme 5.3). 

Cinnolines ° (see Sections V,B,3, D, and E). The greater reactivity of N-2 of cinnoline (26) can be reduced by introducing an alkyl group at the 3-position.More product resulting from quaternization of N-1 then results. A preference for alkylation at N-2 of the anion of 4(l.ff)-cinnolone (52) is also noted betaine 53 is favored 3 1 over cinnolone 54. Alkylation at oxygen is not observed. Again, the presence of a substituent at position 3 forces more reaction to occur at N-1. ... 

Numerous creative solutions for asymmetric bond installation have been unveiled as a result of experimental efforts directed toward quaternization of oxindole C3. Examples in this section have been broadly categorized on the basis of the nature of the functionality that has been installed at C3 (i.e., C3-carbon, C3-oxygen, or C3-nitrogen bond construction). 

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