| 2,4,5-trifluorophenylacetic acid is an important intermediates for the synthesis of sitagliptin which is a hypoglycemic drug,and his market potential is tremendous.Afloqualone is a kind of muscle relaxant for central nervous,compared with the known muscle relaxant,his side effect and toxicity are minor,so it has good security.This dissertation consisted of two parts.The first one was focused on process improvement on the synthesis of 2,4,5-trifluorophenylacetic acid.The second one was focused on the synthesis of afloqualone.In chapter one,firstly,the processes for synthesis of sitagliptin and 2,4,5-trifluorophenylacetic acid in recent years were briefly reviewed,and then summarized synthetic methods of afloqualone with brief comments on the advantages and disadvantages of each route.In chapter two,on the basis of systematic analysis of the existing literatures,we design two routes for the synthesis of 1,2,4-trifluorobenzene: 1.1,2,4-trifluorobenzene was synthesized from m-dichlorobenzene via four steps including nitration,halogen exchange,reduction and Schiemann reaction.2.1,2,4-trifluorobenzene was synthesized from 2,4-dichlorofluorobenzene via four steps including nitration,halogen exchange,reduction and diazotization deamination.Considering the cost,environmental factors,we chose the second route.In addition,on the basis of systematic analysis of the existing literatures,we also design a route for synthesis of 2,4,5-trifluorophenylacetic acid starting from 1,2,4-trifluorobenzene via two steps including chloromethylation and Grignard reaction.Meanwhile,factors including temperature,solvent and catalyst were investigated.Compared with the reported methods,this new procedure has the advantages of safety,easy operation and low cost,and it has a good prospect for industrialization.In chapter three,firstly,there is a brief introduction of synthesis for afloqualone.Then we designed a scheme for the synthesis of afloqualone on the basis of the existing literatures.Afloqualone was synthesized from cheap isatoic anhydride via seven steps including nitration,reduction,protection,solasodamine,annulation,halogen exchange and deprotection.Meanwhile,all kinds of factors were investigated to get better reaction conditions,and the yield reached to 50%.This new procedure has the advantages of safety,easy operation and low cost,and it has a good prospect for industrialization. |
