2-Phenylquinazoline

Alkylquinazolines are catalytically reduced to the corresponding 3,4-dihydro derivatives/ The only example of a 4-substituted quin-azoline which was reduced to its 3,4-dihydro derivative is 2-chloro-4-phenylquinazoline which gave 4-phenyl-3,4-dihydroquinazoline/ 4-Methylquinazolines are susceptible to oxidation, as is shown by the attempted nitration of 2,4-diraethylquinazoline which causes the removal of the methyl group with formation of 4-hydroxy-2-methyl-6-nitroquinazoline/ When the 4-substituent is —C(Et) (C02Et)2 recrystallization of the picrate from ethanol is sufficient to convert it to 4-hydroxyquinazoline/ Similar hydrolyses occur in acid solution and the mechanism undoubtedly involves a hydrated intermediate/... 

When o-aminobenzophenone is heated with formamide in the presence of formic acid at 150°C for 20 min, a quantitative yield of 4-phenylquinazoline is obtained. In the absence of formic acid longer heating is necessary. Although this reaction does not proceed with o-acylamidobenzophenones, its extension to other o-acylanilines with aliphatic amides may prove fruitful. 

Ninety-eight grams of 6-chloro-2-chloromethyl-4-phenylquinazoline 3-oxide hydrochloride were introduced into 600 cc of ice cold 25% methanolic methylamine. The mixture was initially cooled to about 30°C and then stirred at room temperature. After 15 hours the reaction product which precipitated was filtered off. The mother liquor was concentrated in vacuo to dryness. The residue was dissolved in methylene chloride, washed with water and dried with sodium sulfate. The methylene chloride solution was concentrated in vacuo and the crystalline residue was boiled with a small amount of acetone to dissolve the more soluble impurities. The mixture was then cooled at 5°C for 10 hours and filtered. The crystalline product, 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine 4-oxide, was recrystallized from ethanol forming light yellow plates, MP 236° to 236.5°C. 

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]. 

It has been established that the conversion of 2-chloro-4-phenylquinazo-line into 2-amino-4-phenylquinazoline by treatment with potassium amide/liquid ammonia also occurs with ring opening (74RTC227).This was proved by the experimental result that in the 2-amino compound obtained from 2-chloro-4-phenyl[3- N]quinazoline, about 70% of the label is present in the amino group, i.e., formation of 2-[ N-amino]-4-phenylquina-zoline (83) see Scheme 11.36. 

Comparison of the percentage Sn(ANRORC) participation of 2-chloro-4-phenylquinazoline (70%) with that of 2-chloro-4,6-diphenylpyrimidine (70%) shows that the reactivity of C-4 in the quinazoline ring is somewhat higher than at C-4,6 in the pyrimidine ring, taking into account that the probability for attack at C-4 in 2-chloro-4-phenylquinazoline is only half of that at C-4,6 in 2-chloro-4,6-diphenylpyrimidine. 

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

Quite similarly, the reaction product obtained from 2-benzylthio-3-phenylquinazolin-4(3H)-thione and hydrazine should be assigned the structure 2-anilino-3-aminoquinazoline-4(3//)-hydrazone instead of the reported 2-hydrazino-3-phenyl quinazoline-4(3//)hydrazone (Scheme III.23) (70IJC1055). 

Attempts to convert 4(3//)-quinazolinone 118 to 4-bromoquinazoline with triphenylphosphine and iV-bromosucci-nimide were not very successful, although 2-bromo-4-phenylquinazoline 121 was formed from the 2-quinazolinone 120 in 49% yield under the same conditions <2001HCA1112>. 

Fluoro-2-phenylquinazoline has been prepared by fluoride displacement of chlorine from 4-chloro-2-phenylqui-nazoline <2002JOC8991>. 

Aldehydes have also been condensed with 2-aminobenzophenone oximes 811, but in this case an added oxidant is not needed, as loss of water from the iV-oxide intermediate 812 provides 2-substituted -phenylquinazolines 813 directly <2004AP239>. 

Quinazolines take part in the same types of reactions as pyrimidines, but because of their additional benzene ring, the products of these reactions may have the added feature of hindered rotation. An example of this is the synthesis of 2-phenyl-Quinazolinap by Guiry and co-workers <99TA2797>. Suzuki coupling of 4-chloro-2-phenylquinazoline (115) with boronic acids 116 led to 117 (R = OMe). These intermediates were parlayed into phosphinamines 117 (R = PPh2) and then subjected to chiral resolution to produce new chiral phosphinamine ligands for asymmetric catalysis. 

Indolo[2,l-b]quinazoline-12-thione (69) was obtained by cyclodehy-drohalogenation of 2-bromomethyl-3-phenylquinazoline-4(3//)-thione (68) with liquid ammonia (73IJC500) the expected amination product was not isolated. 

Photolytic molecular rearrangement of the 4-(l,2,3-benzotriazol-l-yl)-2-phenylquinazoline (182) gave (183) (74JHC737). 

The title compounds were synthesized from quinazoline precursors as exemplified by the dehydrative cyclization of the diformyl derivatives (456), obtained from 2-methyl-3-phenylquinazoline (455), with phosphoric acid to give the 6-formylquino[2,1 -b]quinazolin-12-one 457 (73IJC532). 

Cyclization of quinazolin-4(3//)-one with an excess of methyl isocyanate gave the 1,3,5-triazino[ 1,2-u]quinazoline-1,3,6-trione (643) (84H501). A one-pot synthesis of 1,3,5-triazino[ 1,2-u ]quinazolines (645) was carried out by reacting 2-amino-4-phenylquinazolines (644) with chlorocarbonyl isocyanate (85S892). 

ChIoro-5a-cholestane, 332 3/3-Chlorocholest-5-ene, 453 4-Chlorocyclohexanone, 72 3 /3-Chloro-5,6a-difluoro-5a-cholestane, 453 4-Chloro-17a-hydroxy-5/3-pregnane-3,11, 20-trione, 86 Chloroiridic acid, 101 4-Chloro-2-phenylquinazoline, 450 Choice of protecting groups, 375 A/B-cfs-cholanic acid, 228 Cholan-12-one, 36 Cholesta-3,5-diene, 207, 331, 336... 

Cyclization of 1 -(4-chlorobutyryl)-l, 2-dihydro-4-phenylquinazoline-2-carbonitrile (242) in dimethylformamide in the presence of sodium hydride (80%) overnight gave 4a-cyano-6-phenyl-2,3,4,4a-tetrahydro-l//-pyrido[l,2- ]quinazolin-l-one (243) [86JCS(P1)2295]. Treatment of l-(2,6-dioxopiperidino)-2-azidomethylbenzene with triphenylphosphine in xylene at ambient temperature followed by heating to reflux for 2 h gave 2,3,4,6-tetrahydro-l//-pyrido[l,2-c]quinazolin-l-one in 92% yield [89JCS(CC)602]. 

Ring expansion has also been observed in the transformation of certain 1-cyano- and 1-phenylisoquinoline 2-oxides to the corresponding benz[/]-l,3-oxazepines,163 of phenyl-substituted quinoxaline 1-oxides to the substituted benz[d]-l,3,6-oxadiazepines,161 164 and of 4-phenylquinazoline 3-oxide (190) to 2-phenylbenz[/]-l,3,5-oxadiazepine (191).165... 

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