HCCP-Mediated Direct Formation Of Thioethers And Ethers From Quinazolin-4(3H)-Ones

Quinazoline derivatives widely exist in animals,plants and microorganisms.They have attracted interest over the past years because of their varied biological activities such as,hypnotic,sedative,analgesic,antibacterial,antiviral,anti-inflammatory and anticancer.Generally,quinazoline(thio)ethers are obtained through SNAr substitution of 4-chloroquinazolines with the appropriate thiophenols or phenols in the presence of base.The common method for preparation of 4-chloroquinazolines is the chlorination of corresponding quinazolin-4(3H)-ones.In conditional chlorination reaction,SOCl2,POCl3,and PC15,were used as chlorination reagent.These chlorination reagents are not environmentally benign,and some drawbacks,such as low selectity and low yields,exsit in the chlorination reaction.In order to overcome these disadvantages,in-situ C-OH bond activation of quinazolin-4(3H)-ones by hexachlorocyclotriphosphazene(HCCP)for C-S and C-O cross-coupling to obain quinazoline(thio)ethers were studied in this dissertation.HCCP was used as the activating reagent to in situ active C-OH bond of quinazolin-4(3H)-ones.N,N-Diisopropylethylamine was selected as the base,acetonitrile was selected as the solvent,and the reaction conditions were optimized in the model reaction of quinazolin-4(3H)-one and thiophenol.Under the optimal reaction conditions,the coupling reaction to form C-S bond between quinazolin-4(3H)-ones and thiophenols were performed.Most of the reaction could be completed in the mild conditions,and gave the desired 4-arylthioquinazolines.The expeimantal results were satisfactory.In addition,phenols and sodium alkoxides were utilized as the nucleophiles.The coupling reaction to form C-O bond between quinazolin-4(3H)-ones and phenols or sodium alkoxides were performed,and a variety of 4-aryloxyquinazolines and 4-alkoxyquinazolines were synthesized.