Investigation On The Synthesis Of 4,5-Disubstituted Pyrimidine Derivatives And Highly Substituted Oxatriazepines

Heterocyclic compounds are a class of very important organic compounds. According to statistics, about one-third of organic compounds are heterocycles. Within this context, the nitrogen-containing heterocyclic compounds are widely found in products, drugs, pesticides, organic functional materials and other fields because of their unique biological and chemical properties. Therefore, developing a new method to construct nitrogen-containing heterocyclic compounds has always been a hot topic in the field of organic chemistry. This article briefly reviews the history of pyrimidines and azepines and focuses on the development of new strategy for the synthesis of 4-substituted or 4,5-disubstituted pyrimidines catalyzed by small organic molecules and the assembly of highly substituted oxatriazepine derivatives. The main contents divided into the following three parts.(1) A new method of the synthesis of prymidines via 1,3,5-triazine and acetophenone catalyzed by morpholine has been developed. In this method, the organocatalyst morphline reacts with acetophenone and formes the enamine in situ, then the enamine (electron-rich dienophile) reacts with 1,3,5-triazine (electron-deficient diene) through inverse electron demand Diels-Alder reaction and gives the 4-substituted or 4,5-disubstituted pyrimidine in a good yield. In addition, we not only have develope a new method on the synthesis of 4-substituted or 4,5-disubstituted pyrimidines, but also proposed possible reaction mechanism for it.(2) A new method of construction of 4,5-disubstituted pyrimidines in one step via inverse electron demand Diels-Alder reaction of α,β-unsaturated ketone benzylidene acetone with 1,3,5-triazine catalyzed by morpholine has been developed. In this method, the organocatalyst morphline reacts with unsaturated ketone to generate the imine intermediate in situ firstly, then the imine intermediate continuously reacts with 1,3,5-triazine via [4+2] cycloaddition reaction to access the 4,5-disubstituted pyrimidine directly. On the other hand, this method not only provides a new synthetic stratege for pyrimidine synthesis and also proposes a possible mechanism.(3) An unprecedented [4+3] cycloaddition of in site generated azoalkene with nitrone promoted by base has been developed. This method constructs new and highly substituted oxatriazepine quickly and efficently promoted by inorganic base K2CO3. In addition, it well enriches the method of the construction of azepine skeleton which has unique biological activity and completes the building of new highly subsituted seven-membered nitrogen-containing heterocyclic compound skeleton.Finally, a short summary and outlook based on the organocatalytic synthesis of pyrimidine derivatives and seven-mumbered nitrogen-containing heterocycles are made.