Quinazoline 3-oxide, reaction with active

A more detailed study of the reaction with malonitrile revealed that the yields are dependent of the molar ratio malonitrile/quinazoline. The yield increases from 29 (ratio 1.0) to 81% (ratio 2.0), suggesting that the mechanism of the ring transformation involves the contribution of 2 mol of malonitrile. Reaction of quinazoline 3-oxide with the above-mentioned active methylene compounds gives about the same results, although the yields are poor (Scheme 12) (73CPB1943, 75CPB746). 

Quinazoline 3-oxide differs markedly from the 1-oxide in its behavior towards anionic reagents. Whereas with quinazoline 1-oxide compounds a substituent is introduced into po.sition 2 or 4 (cf. p 104), in quinazoline 3-oxide ring fission occurs between C2 and N3 in the reaction with acetic anhydride, water, alkali hydroxide, and under the conditions of the Reissert reaction.2 -(Hydroxyiminomethyl)formanilide is also formed as a byproduct in the reaction of quinazoline 3-oxide with active methylene compounds. ... 

The reaction of quinazoline 3-oxide with active methylene compounds or ketones without a base catalyst similarly results in transformation into quinoline derivatives although in very poor yields (a few percent). ... 

A more highly oxidized derivative of quinazoline forms the heterocyclic moiety of a compound with CNS activity. Condensation of the aminopropylpiperazine 141 with isatoic anhydride gives the anthranilamide 142. Reaction of that amide with phosgene gives directly the heterocyclic ring. (The reaction may proceed by initial formation of the carbamoyl chloride ... 

Antibacterial activity has also been observed with a variety of sulphameth-oxypyridazine derivatives like the imine obtained upon reaction of (95, R1 = MeO R2 = H) with 5-nitrofurfural [312], 2-aryl-3-nitrofurylacrylamides (105) [313], quinazoline-2,4-diones (106) [314], thiazolin-4-ones of type (107) [315] and with aldol condensation products of the latter [316], Sulpnonylpyridazmones (108, R1, R3 = alkyl, Ph R2 = substituted NH2, HO, RO) [273,274], trichloromethylchloropyridazines (109) [317] and 3-mer-captopyridazine 2-oxide derivatives [318, 319] have been claimed as antibacterial agents. 

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... 

An efficient Cu(OTf)2-catalyzed synthesis of quinazolines from amidines and DMSO was reported by Xiong, Zhang, and coworkers. DMF, DMA, NMP (N-Methyl-2-pyrrolidone), or TMEDA (N,N,N, N -tetramethyl-ethane-l,2-diamine) was also a suitable carbon source for this transformation (Scheme 8.103). This process includes oxidative amination of N-H bonds and methyl C(sp )-H bonds of various carbon sources followed by intramolecular C-C bond formation with C(sp )-H bond activation. The quinazolines could be obtained with high selectivity and good yields via this domino reaction [177]. 

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