Simple Substituted Quinazolin-4-ones

THE ALKALOIDS, VOL. 29 Copyrighi 1986 by Academic Press. Inc. All right.s of reproduction in any form reserved. 

On the basis of a critical study of the UV and the IR absorption spectra of 1, dihydroarborine, and some other quinazoline derivatives of unambigous structure, Chakravarti 16) has shown that arborine is 2-benzyl-1-methyl-quinazol-4-one (1) and not the tautomer, 2-benzylidene-l,2,3,4-tetrahydro-l-meth-yl-quinazolin-4-one, postulated by Chatterjee and Majumdar 13). Also, the absence of a vinyl proton in the -H-NMR spectrum of arborine is unequivocal evidence against the benzylidene structure. 

Mass spectral studies on 1 have been carried out by Pakrashi et al. (17). The formation of benzaldehyde by oxidative degradation can be explained by the formation of a small portion of the highly reactive tautomeric form (see above), which undergoes rapid oxidative fission there are many well-known analogies 

Arboricine was shown to be l,2-dihydro-4-hydroxy-l-methyl-2-oxo-3-phe-nylquinoline (10) or its diketo tautomer. It was synthesized by condensation of ethyl phenylmalonate with A-methylaniline (9). The formation of 10 during the alkaline hydrolysis of 1 probably takes place through the intermediate A -meth-yl-A -phenylacetylanthranilamide with loss of ammonia. 

Mohrle and Seidel (25) realized the synthesis of 1 by the intramolecular Mannich reaction of A-methylanthranilamide with phenylacetaldehyde and dehydrogenation of the resulting tetrahydroquinazoline with mercuric EDTA. 

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In practically all theories of the biosynthesis of quinazolines, anthranilic acid or an equivalent is regarded as one of the building blocks. Robinson 158) postulated that anthranilic acid (N-methylated where necessary), ammonia or amine, and formic acid or phenylacetic acid derived from phenylalanine units or their equivalents build up the simple substituted quinazoline derivatives. Thus vasicine (28) may be derived from anthranilic acid and proline, or closely related metabolites. Febrifugine (9) possibly could be formed from anthranilic acid, formic acid, ammonia, a Cj-unit, and lysine or equivalent compounds. For... 

A -Aryl-A -(ethoxyearbonyl)iinidamides and 2-alkyl-l-aryl-3-(ethoxycarbonyl)isothioureas 12 cyclize thermally to yield 2-substituted quinazolin-4(3//)-ones 13. When an A-aryl-A -(ethoxy-carbonyl)imidamide is boiled briefly in quinoline, ethanol is evolved and the corresponding 2-arylquinazolin-4(3//)-one is formed in 49-88% yield. Presumably elimination of ethanol yields an imidoyl isocyanate which undergoes cyclization to form the 2-arylquinazolin-4(3//)-one. These cyclizations are most likely simple thermal processes, since they proceed equally well when diphenyl ether is used instead of quinoline or when the imidamide is heated at 50-70 C above its melting point in the absence of a solvent.This reaction is also suitable for the synthesis of benzo-fused quinazolin-4(3//)-ones. °... 

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