Quinazolines quaternization

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. 

Quinazoline. As with cinnoline, quinazoline (56) preferentially undergoes quaternization at the isoquinoline nitrogen atom. The N-... 

The nitrogen atom of 3-pyridyl and 5-pyrimidinyl moieties in the N-substituted 8-carboxamide group of 2,3-dimethyl-ll-oxo-ll//-pyrido-[2,l-b]quinazoline-8-carboxamides was quaternized by methyl iodide (88JMC466). 

Whereas older reports suggest on the basis of chemical evidence, that the quaternization of quinazoline with iodomethane gives exclusively 3-methylquinazolin-3-ium iodide,it has been demonstrated, by H NMR spectroscopy, that quaternization of quinazoline with methyl iodide produces both 1-methylquinazolin-l-ium and 3-methylquinazolin-3-ium iodide in the ratio of 1 5 in favor of the latter isomer. Quinazolines 3 are generally reported to give only products 4 quaternized at N3. When quinazolin-3-ium quaternary salts are recrystallized from alcohols or when alcohol is used as a solvent for the reaction, the corresponding 3,4-adducts are obtained(cf. p 161). 

Introduction of a substituent at position 4 of the quinazoline nucleus produces a shift of the quaternary center from N3 to 4-Substituted quinazolines 5 arc claimed to quaternize... 

Aryl-4-(allylsulfanyl)quinazolines and 2-aryl-4-(prop-2-ynylsulfanyl)quinazolines 7 undergo quaternization at N3 and cyclization on reaction with bromine in glacial acetic acid to give... 

Quaternization of the pyrimidine ring of quinazolines enhances its reactivity toward nucleophiles. This reactivity has been used to advantage for preparing 1,2,3,4-tetrahydro derivatives. Methylation of 4-phenylquinazoline occurred at N-1 and N-3 (7 1) and was the first example in which it was shown that alkylating at two different sites in quinazolines was possible. The l-methyl(and 3-methyl)quinazolinium salt that was formed was reduced with sodium borohydride to l-methyl(and 3-methyl)-4-phenyl-l,2,3,4-tetra-hydroquinazoline. Potassium permanganate oxidized the latter compound to l-methyl-4-phenylquinazolin-2(lH)-one. 

Quaternary salts, isolation of, 10 Quaternization, by alkyl halides, 2-7 by aryl halides, 7-9 on carbon, 53 definition of, 2 by dimethyl sulfate, 9 electronic effects in, 11 in JV-heterocycles, 16, 38 by heterocyclyl halides, 7—9 isotope effect on, 55 mechanism of, 53-56 by methyl euyl-sulfonates, 9, 10 on oxygen, 52 rates of, 55 reagents for, 2-10 by self-condensation, 8 solvent effect on, 10, 55 solvents for, 10 steric effects on, 12, 13 substituents, influence on, 11, 19, 23 on sulfur, 51 Quinaldine, 4-amino-, 4 Quinazolines, 2-alkyl-, salt formation of, 6... 

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