Quinazolin-4-ones, from isatoic anhydride

Azole approach. Quinazolines can be prepared from isatoic anhydride and an amide. When the amide function is part of a cyclic structure such as in a 3-isoxazolidinone, the 2,3-dihydro-9//-isoxazolo[3,2-h]quinazolin-9-one (84) is formed (77AF766). 

A study of all the stages in the synthesis of 4-aminoquinazolines from isatoic anhydride, via anthranilamide and o-aminobenzonitrile, made possible the preparation of these compounds by a one-pot synthesis. The anhydride was treated with ammonia in dimethylformamide, nitrogen was then bubbled through the solution to remove excess of ammonia, phosphoryl chloride was added and heated at 40°-60°C for conversion into the nitrile, and finally the respective amine was added to yield the 4-(substituted-amino)-quinazolines in 44-79% yields. ... 

In the synthesis of 2-alkylthio-3-quinazolin-4-ones 76 reported by Powers, treatment of isatoic anhydride (74), derived from anthranilic acid, with aminoacetonitrile followed by reaction with thiophosgene provided the quinazolinone 75 <01JHC419>. Alkylation of 75 led to the thioethers 76 in good to excellent yields. A very similar compound, quinazolin-2.4-dione 78, was synthesized from 77 and aminoacetonitrile bisulfate <01JOC4723>. 

The mono- and disubstituted quinazolin-4(3/7)-one derivatives were firstly synthesized under solvent-free conditions by one-pot three-component reaction of isatoic anhydride, ortho ester, and anunonium acetate or an aliphatic and aromatic primary amine in the presence of SSA (Salehi et al., 2005) (Scheme 5.8). After completion of the reaction, the crude mass was diluted with hot ethanol and filtered. The filtrate was concentrated and products were purified by recrystallization from ethanol. Solvent-free... 

To conclude this section and to provide a bridge to the next, the work of Pal s group on novel phosphodiesterase 4 (PDE4) inhibitors will be discussed [40]. In their paper from 2012, a new multicomponent strategy was described that unites isatoic anhydride 149, aryl hydrazines 150, and 2-iodobenzaldehyde 151. This palladium-catalyzed MCR gratifyingly generates quinazolin-4-ones in acetonitrile under air atmosphere in 24 h at reflux temperatures (Scheme 14.19). 

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