3- Phenylquinazolin-4-one

Dihydroquinazolines have been formed by the acid- or base-catalyzed disproportionation of 4-alkoxy(or hydroxy)-3-phenyl-3,4-dihydroquinazo-line-2(l//)-thiones(or -ones). These gave a mixture of 3-phenylquinazolin-4-one-2(liJ)-thione(or -one) and 3-phenyl-3,4-dihydroquinazoline-2(lf/)-thione(or -one). The disproportionation is akin to a Cannizzaro reaction. ... 

In the absence of 7r-deficiency, conditions are milder. 2-Acetamidobenzoic acid and sodium acetate, refluxed for 1 hr in acetic anhydride, gave an excellent yield of 2-methyl-3-phenylquinazolin-4-one.214... 

N-Methylformamide converted 2-aminopyridine-3-carboxylic acid to 3-methylpyrido[2,3-d]pyrimidin-4-one (5 hr at 180°C) in good yield.290 The same reagent also made 3-methyl-6-nitroquinazolin-4-one from 2-amino-5-nitrobenzoic acid in excellent yield some slowly reacting 2-aminobenzoic acids were assisted with phosphoryl chloride.291 A moderate yield of 3-phenylquinazolin-4-one was obtained from the action of formani-lide on 2-aminobenzoic acid (90 min at 140°C).282... 

Phenyl isocyanate boiled with 2-methylaminobenzoic acid gave 1-methyl-3-phenylquinazoline-2,4-dione, but methyl isocyanate did not react. On the other hand, methyl isothiocyanate at 145°C (sealed vessel) produced 1,2-dimethyl-2-thioxoquinazolin-4-one, whereas phenyl isothiocyanate gave poor results (yields not stated).314 Anthranilic acid heated with amyl isocyanate gave the ureide, which could be cyclized with acid or base315 however, potassium anthranilate, set aside overnight in ethanolic phenyl isocyanate, gave a moderate yield of 2-thioxo-3-phenylquinazolin-4-one directly.316... 

Most of the work described here has been done with guanidine. In one of the few amidine examples, methyl anthranilate and N,jV -diphenylformami-dine gave 3-phenylquinazolin-4-one in excellent yield when heated at 155°C for 45 min. The authors state that the initial attack is on the amino group.282... 

A series of novel l-substituted-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-ones 1 were synthesized by the cyclization of 2-hydrazino-3-phenyl-quinazolin-4(3H) 2 with various one carbon donors. The starting material 2-hydrazino-3-phenylquinazolin-4(3H)-one 2, was synthesized from aniline 7 by a novel innovative route. When tested for their in vivo Hi-antihistaminic activity on conscious guinea pigs all the test compounds protected the animals from histamine-induced bronchospasm significantly, whereas the compound l-methyl-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-one lb (percentage protection 70.7%) was found to be equipotent with the reference standard chlorpheniramine maleate (percentage protection 71%). These compounds show negligible sedation (5%) when compared to the reference standard (26%). Hence they could serve as prototype molecules for future development [1,4,5]. 

Degenerate rearrangements have also been found during hydrazinolysis of 2-thioalkyl-3-phenylquinazolin-4(3//)-one (42). The product obtained is... 

Path A involves N-formylation of anthranilic acid, condensation of the resultant 2-formaminobenzoic acid with the amine followed by intramolecular amidation of the intermediate amidine to form the product. On the other hand, the amine instead of anthranalic acid may be formylated and go through the known Niementowski reaction (path B). When the reaction of 2-formamidobenzoic acid with aniline and the condensation of formanilide with anthralic acid were conducted under microwave irradiation, the desired 3-phenylquinazolin-4(3 JT)-one was obtained in both cases in a few minutes in 68-87% yield. 

The unexpected reducing power of formamide was discovered when 2-aminobenzoic acid and that amide were refluxed for 4 hr, giving 2,3-dihydro- l-phenylquinazolin-4-one (m/e 224) instead of 164. The latter was dihydrogenated when boiled with formamide.292 The presence of an isolated double bond in 164 and the severe conditions should explain the result. 

Nitriles and imidates have found little use, so far. Heating propionitrile and 2-aminobenzoic acid at 210°C in a closed vessel gave only a low yield of 2-methylquinazolin-4-one.297 Anthranilic add and 10 of its C-substituted derivatives were refluxed (5-50 hr) with ethyl acetimidate and benzimidate in methanol to give 2-methyl- and 2-phenylquinazolin-4-ones, respectively, in moderate yields three aminopyridine carboxylic acids behaved similarly.298 JV-Phenylbenzimidoyl chloride [PhC(NPh)Cl] and ammonium 2-aminobenzoate, in cold acetone, produced 2,3-diphenylquinazolin-4-one in good yield.299... 

Thiazolo[3,2-a]quinazolines.—[C3NS-C4N2-C6]. A number of thiazolo-[3,2-a]quinazolones have been obtained by the application of conventional cyclization reactions. Thus, the condensation of 2-mercapto-3-phenylquinazolin-4(3/f)-one (301) and phenacyl bromide yields the S -alkylated derivatives (302) which are reduced by sodium borohydride tol,2-dihydro-2-(a-hydroxyphenethyl)mercapto-3-phenylquinazolin-4(3/f)-one (303). Cyclodehydration by acetic anhydride or toluene-p-sulphonic... 

The crystal and molecular structure of quinazoline was solved in 1976 by X-ray diffraction. Bond lengths and interbond angles of quinazoline (1) [with two crystallographically independent molecules (A and B) in the unit cell], 2-methylquinazolin-4(3/f)-one (2a), ° 2-phenylquinazolin-4(32f)-one (2b)," 2-acetylquinazolin-4(3//)-one (2c), " quinazoline-2,4-diamine monohydrate (3), 5-chloroquinazoline-2,4,6-triamine (4), 2-phenylquinazoline 1,3-dioxide (S). and ( )- , 2-bis(2-methylquinazolin-4-yl)ethene (6) obtained by X-ray crystallography are collected in Table 1. 

Irradiation of cither A -benzoyl-7V-tosylbenzimidamide in dichloromethane or 4,6-diphenyl-2,2-dioxo-1,2,3,5-oxathiadiazine in dichloromethane containing 5% by volume of ethanol or 2-methylpropan-2-ol at / > 290 nm produces 2-phenylquinazolin-4(3//)-one in 40-71% yields. 

Carbonylation of a complex obtained from A -phenylbenziinidamide and lithium tetra-chloropalladate(II) (LijPdClJ with carbon monoxide affords 2-phenylquinazolin-4(3//)-one in 97% yield. ... 

Acetamido-7-chloro-5-phenyl-3//-1,4-benzodiazepin-3-one (3) undergoes ring contraction and hydrolysis in cold dilute alkali to form 6-chloro-4-phenylquinazoline-2-carboxylic acid (4). In refluxing ethanolic hydrogen chloride, 3 affords the ethyl ester of 4. When heated with acetic acid, rearrangement and ring contraction of 3 to the isomeric A -acetyl-6-chloro-4-phenylquin-azoline-2-carboxamide take place. ... 

Chloro-2,5-epoxy-2-methyl-5-phenyl-l,2,4,5-tetrahydro-3//-l,4-benzodiazepin-3-one undergoes ring contraction to afford 2-acetyl-6-chloro-4-phenylquinazoline on treatment with ethanolic hydrogen chloride. ... 

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