Quinazoline oxides 1,2-dihydro- from

Dihydroquinazolines are normally stable compounds but they deteriorate on long standing. Some examples are known to oxidize to the corresponding 4(3H)quinazolinones. 3-Methyl-3,4-dihydroquin-azoline is converted to the 4-oxo compound after three recrystallizations from light petroleum. The most remarkable example is 3,4-dihydro-6-fluoro-3(p-fluorophenyl)quinazoline [(44), R = F] which oxidizes at its melting point (137°-I38°C), Other halogenated derivatives of (44) are more stable. ... 

Introduction of carbofunctional groups into positions 2 and 4 of quinazolines is usually a twO Step process whereby the corresponding dihydroquinazoline which results from addition of a C-nucleophile in the first step (cf p 165) is isolated and subsequently oxidized to give 2-or 4-substituted quinazolines (cf. p 86). Here, only reactions in which carbofunctional substituents are introduced into positions 2 and/or 4 without isolation of the dihydro intermediate are mentioned. 

Sternbach and coworkers pointed out that the reactions of the 6-chloro-2-chloromethyl-l,2-dihydro-4-phenylquinazoline 3-oxides 11 with a base gives either the 1,3-dihydro-2//-azirino[ 1,2-fl]quinazoline 4-oxides 13 or the 3H-1,4-benzodiazepine 4-oxide 15. In the first step of the reaction the anion 12 is formed by abstraction of a proton from the 1-nitrogen. The intermediate anion 12 can rearrange to the ring-chain tautomer 14. The relative stabilities of the two anions 12 and 14 are assumed to determine whether product 13 or 15 is formed. Thus when R is hydrogen or chloromethyl, the anion 12 is relatively sufficiently stable to allow the formation of the azirino-quinazoline 13. If, however, R is the electron-releasing methyl group, the anion 12 is destabilized and is converted to anion 14, which leads to benzodiazepine 15. The solvent polarity also influences the stability of the anions 12 and 14. In a nonpolar solvent (ether), the 5//-benzodiazepine 16 (R = Me) was obtained, which can be derived from anion 12 (R = Me) via the azirinoquinazoline 13 (R = Me). In a polar solvent (aqueous ethanol), however, the 3H-benzodiazepine 15 derived from anion 14 (R = Me) was the major product. As bases, potassium /er/-butoxide and sodium hydride were used. ... 

A general synthesis of quinazoline 1,3-dioxides and their 1,2-dihydro derivatives was devised by Taylor and Bartulin. In this synthesis o-hydroxyl-aminobenzaldehyde oxime condensed with aldehydes and ketones to yield 2,2-disubstituted 1,2-dihydro-l-hydroxyquinazoline 3-oxides (63). When the dihydro compounds (63 = H) derived from aldehydes or from formalde-... 

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