Palladium-catalyzed Hydrogen Transfer Reaction Selectively Synthesizes Quinazolinone Compounds

Quinoline,quinazolinone and its derivatives are a very important class of nitrogen-containing heterocyclic compounds,and their skeleton structures are widely present in alkaloids or pharmaceutically active molecules.Among them,2,3-dihydroquinazolin-4（1H）-one and quinazolin-4（3H）-one compounds are widely used for their excellent biological activity,pharmacological activity and application in clinical medicines.Quinazolinone is also an important intermediate for anticancer drugs.Through literature research,a process route for the selective synthesis of quinazolinone compounds by hydrogen transfer reaction was developed.Firstly,quinoline compounds were obtained from the aromatic amines starting from the Scrupp synthesis method.Then,through the nitration reaction,the Pd/C reduction reaction and the acylation reaction,seven 2-nitro-N-（quinolin-8-yl）benzamide compounds were obtained.Next,2-nitro-N-（quinolin-8-yl）benzamide（1.0 mmol）and benzyl alcohol（2.5mmol）were used as the reactants,Pd/C（2 mol%）as a catalyst,sodium hydroxide（1.0mmol）was reacted as an additive in DMSO（2 mL）at 80^oC for 2 hours.212-phenyl-3-（quinolin-8-yl）-2,3-dihydroquinazolin-4（1H）-one compounds were obtained.The same substrate,Pd/C（2 mol%）was used as a catalyst,and sodium hydroxide（5.0mmol）was used as an additive in DMSO（2 mL）at 80^oC for 4 hours.212-phenyl-3-（quinolin-8-yl）quinazolin-4（3H）-one compounds were obtained.The synthesized product was characterized by ¹H-NMR and ¹³C-NMR.Meanwhile,the mechanism of the reaction was speculated,and the reaction intermediate was captured,which proved the reaction mechanism of the cyclization reaction.Finally,the catalytic efficiency of the catalyst Pd/C of the hydrogen transfer reaction system was investigated.The results showed that the yield of the product did not change significantly after 6 cycles of use.