Quinazoline 3-oxide, 2- cyclization

Oxidative cyclization of 1 -[(2 -aminocarbonyl)phenyl]piperidine and its 4 -substituted derivatives with Hg(OAc)2-EDTA reagent afforded 1,2,3,4-tet-rahydro-6//-pyrido[2,l-Z)]quinazolin-6-one and its 3-substituted derivatives in 36-82% yields (99ZN(B)1577). Similarly, ( )-2-(piperidin-2-yl)benzal-doximes gave 2,3,4,4u-tetrahydro-l//-pyrido[l,2-u]quinazolin-5-oxide and... 

Oxidative cyclization of 3-aryl-4-oxo-2-thioxo-tetrahydroquinazolines (278) with N-bromosuccinimide and sulfuric acid gave examples of the title compounds (e.g. 279) (87H2371, 87BSB797). Cyclocondensation of 2-thioxoquinazolines (280) with 2-chlorocyclohexanone (72IJC605) or 4-chloro-3,5-dinitrobenzotrifluoride (87AP569) also afforded benzothia-zolo[2,3- ]quinazolines (e.g. 281). 

Oxidative cyclization of the 4-(2-aminobenzyl)-l,4-oxazine (576) with manganese dioxide gave the 1,4-oxazino[3,4-6]quinazoline (577) through the formation of its pyrimidine ring [68JCS(C)1722]. Cyclocondensation of anthranilic acids with the thioimidate ester (578) gave 3,4-dihydro-l,4-oxazino[3,4-6]quinazolin-6(l/f)-ones (579) [791JC(B) 107]. 

In a similar fashion, 1-acetylisatin, when reacted with hydroxylamine hydrochloride furnishes quinazoline-3-oxide through cyclization of the intermediate hydroxamic acid234. This intermediate hydroxamic acid can be isolated by treatment of the quinazoline oxide with alkali235 (Scheme 54). 

Several oxidative catalytic systems utilizing elemental iodine as the catalyst have been developed. Wang and colleagues have reported several tandem oxidative cyclization reactions using I2 as a catalyst and 70% aqueous TBHP (Bu OOH) as a stoichiometric oxidant (Scheme 4.77) [119-122], Heteroaromatic compounds such as oxazoles 151, quinazolines 152 and pyridine derivatives 153 were synthesized in moderate to high yields under these catalytic conditions. The authors suggested that the h/l catalytic cycle might play an important role in the radical mechanism under these conditions [122]. 

In another approach, the pyrrole ring of the title compounds (e.g. 26) was formed by acid- or base-catalyzed cyclization of suitably functionalized quinazolin-2-yl derivatives (71JIC743 72JIC1185 73JMC633) such as 2-(2-cyanoethyl)quinazoline-3-oxide (25) (70USP3506663). When... 

Oxidation of the 1-aminoquinazolinones (44) with lead tetraacetate culminated in the intramolecular addition of the resulting N-nitrene intermediate to the triple bond to give the pyrrolo[2, l-b]quinazoline (45) [85CC544 86JCS(P1)1215]. The pyrrole ring of 47 was also formed by cyclization of 2-methyl-3-phenacylquinazolin-4-one (46) with dilute aqueous alkali followed by fusion (86T4481). 

The oxazolo[3,2-tf]quinazoline (200) was obtained by cyclization of 3-(2-chloroethyl)quinazoline-2,4-dioine (199) with potassium carbonate (60JCS3551). The same compound was also obtained when ethylene oxide reacted with 2-chloroquinazolin-4-one (201) in the presence of sodium hydroxide (60JCS3551). 3-Acylalkylquinazoline-2,4-diones (201) underwent intramolecular dehydrative cyclization upon heating with polypho-phoric acid to 203 [89IJC(B)274]. 

Oxidation of 3-amino-2-(2,5-dihydroxybenzyl)quinazolin-(3i/)-one (494) with acidic ferric chloride or aqueous sodium hydroxide gave a quinone that spontaneously cyclized to the quinazolino[3,2-fc]cinnoline-2,7(13//)-dione (495) [66JCS(C)2190]. 

Controlled potential electrolysis at a mercury pool cathode, carried out at the plateau of the first reduction wave of At-(2-nitrobenzoyl)acetamide, leads in practically quantitative yield to 2-methylquinazolin-4(3/f)-one 1-oxide (mp >260°C), resulting from a ring closure of the A-phenylhydroxylamine intermediate. 2-Methylquinazolin-4(3//)-one 1-oxide is further reduced in Sulfuric acid media to give 2-methylquinazolin-4(3//)-one. A -(2-Nitrobenzoyl)-succinimide and A-(2-nitrobenzoyl)phthalimide undergo similar electrochemical reduction and cyclization to quinazoline derivatives. ... 

Garcia et a/. cyclized the anti oxime 148 to the pyrrolo[l,2-a]quinoline 4-oxide 149 by use of one molar equivalent of bromine, and to the pyr-rolo[l,2-a]quinazoline 4-oxide 150 with formaldehyde in acetic acid. 

From the reaction of 2-chlorobenzoic acid and 2-amino-5-nitropyridine in the presence of potassium carbonate and copper powder or copper(II) oxide, Carboni and Pardi isolated the condensation product 210 (R = H, R -= 5-NO2), which was then cyclized with a strong concentrated acid to the pyrido[2,l-i)]quinazoline 211 (R= H, R = S-NOj). 

Methylquinazolin-4(3//)-one was obtained in over 62% yield by reacting the phosphorane (25) with sodium hydride in methyl cyanide. The phos-phorane was readily formed from anthranilamide and prop-2-ynyltriphenyl-phosphonium bromide. When anthranilamide was fused with benzoin and a trace of acid at 150°C, it gave 2-phenylquinazolin-4(3H)-one together with o-iV-(a-benzoyl benzyl)aminobenzamide. The latter was cyclized, with ethyl orthoformate, to l-(a-benzoylbenzyl)quinazolin-4-one. If anthranilamide and benzoin were boiled in benzene with azeotropic removal of water, then the Schiff base (26) was formed. This gave 2-phenylquinazolin-4(3Jf/)-one and benzoic acid on heating alone at 150°C or with ethyl orthoformate. The mechanism of this reaction is not clear unless a retro-benzoin condensation and oxidation are occurring. 

Lin and coworkers prepared 2-substituted quinazolines via a metal-free oxidative sp C—H/sp C—H cyclization of amidines (Scheme 23) (140L2822). Two methods were developed. Method A uses iodobenzene diacetate as a source of hypervalent iodine(lll) and a nonpolar solvent, toluene. In Method B potassium persulfate is used as the oxidant in the presence of a catalyst, TEMPO, and a polar solvent, acetonitrile. Both methods... 

Quinazolinones are an important class of fused heterocycles that have been reported with remarkable activities in biology and pharmacology such as anticancer, antiinflammatory, anticonvulsant, antibacterial, antidiabetic, hypolipidemic, and protein tyrosine kinase inhibitors. Alper and Zheng reported a palladium-catalyzed cyclocarbonylation of o-iodoanilines with imidoyl chlorides to produce quinazolin-4(3H)-ones in 2008. A wide variety of substituted quinazolin-4(3H)-ones were prepared in 63-91% yields (Scheme 3.27a). The reaction is believed to proceed via in situ formation of an amidine, followed by oxidative addition, CO insertion, and intramolecular cyclization to give the substituted quinazolin-4(3H)-ones. Later on, a procedure was established based on generating the amidine in situ by a copper-catalyzed reaction of terminal allq nes, sulfonyl azide and o-iodo-anilines. The desired quinazolinones can be produced by carbonylation with Pd(OAc)2-DPPB-NEt3-THF as the reaction system. In the same year, Alper s group developed a procedure for 2,3-dihydro-4(lH)-quinazolinone preparation. The reaction started with the reaction of 2-iodoanilines and N-toluenesulfonyl aldimines followed by palladium-catalyzed intramolecular... 

Wu and co-workers presented an efficient domino reaction for the rapid synthesis of 5-phenyl-[l,2,3]triazolo[l,5-c]quinazolines derivatives (80) from simple and readily available (E)-l-bromo-2-(2-nitrovinyl)benzenes 79, aldehydes, and sodium azide (Scheme 7.56) [124]. This reaction cascade comprised [3 + 2] cycloaddition, copper-catalyzed SnAt, reduction, cyclization, and oxidation. It is noteworthy that sodium azide is used as a dual nitrogen source in the construction of these fascinating fused A-heterocycles. 

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