Study On The Synthetic Process Of 2,5-dichloro-3-bromopyridine

5-chloro-2,3-difluoropyridine is a very important chemical intermediate for the preparation of the fluoro-containing herbicide chodinafop-propargyl.At the present time,there are mainly two methods being used according to the report in literature to synthesize 5-chloro-2,3-difluoropyridine.One way is utilizing 3-nitro-2,5-dichloropyri -dine as starting material,through the first hydrogenation reduction of nitro group in pyridine ring of the starting material in the presence of Raney nicknel catalyst,3-amino-2,5-dichloropyridine was formed;subsequent diazotization by the means of the addition of diazotising agent sodium nitrite solution and exchange of the diazo group in an excess of liquid hydrogen fluoride in a Monel autoclave,3-fluoro-2,5-dichloropyridine was produced and the last fluorine replacement reaction with potassium fluoride or cesium fluoride or the mixture of both the fluoride salts to introduce the fluorine atom in the 2-position of the pyridine ring to give 5-chloro-2,3-difluoropyridine finally.The other way is making 2-aminopyridine as starting material,through the first selective dichlorination in pyridine ring of the starting material in suitable acid medium,2-amino-3,5-dichloropyrine was formed;subsequent diazotization by the means of the addition of diazotising agent sodium nitrite solution and exchange of the diazo group in an excess of hydrochloric acid solvent,2,3,5-trichloropyridine was obtained and the last fluorine replacement reaction with adequate fluoride salts in additional presence of phase transfer catalyst to introduce both fluorine atoms in 2&3-positions in one step to give 5-chloro-2,3-difluoropyridine.In this paper,2-aminopyridine was used as starting material for the whole process,and the second method mentioned above to synthesize 5-chloro-2,3-difluoropyridine was explored in another new view.In addition a novel process for the preparation of 5-chloro-2,3-difluoropyridine different from references was disclosed at the same time.Furthermore,study on the preparation of 2,5-dichloro-3-bromopyridine as the precursory intermediate product of 5-chloro-2,3-difluoropyridine was emphasised on.Proportion between materials added,reaction time,reaction temperature,choice and application of solvent,choice and application of chlorination reagent and operation mode,treatment dependence of intermediate product in each steps etc.influence factors were studied in detail. In the synthesis process of the desired product 2,5-dichloro-3-bromopyridine in this paper,2-aminopyridine was firstly chloridized in the strongly sulfuric acid medium by a selective monochlorination to 2-amino-5-chloropyridine with a yield of 95%;secondly 2-amino-5-chloropyridine was bromized in the same acid solvent as the first chlorination step to 2-amino-3-bromo-5-chloropyridine with a yield of 97.8%;and then the diazotising agent sodium nitrite solution was added with the existence of aqueous hydrochloric acid to diazotize the 2-amino-3-bromo-5-chloropyridine,and after this diazotization step,3-bromo-5-chloropyridin-2-one was gotten;finally,the desired product 2,5-dichloro-3-bromopyridine with a total yield of 86.8%to the last two reaction steps was obtained through chloridization once again with the chlorination reagent thionyl chloride.Compared to known processes,the process according to this paper that 5-chloro-2,3-difluoropyridine was prepared through a total four reaction steps with 2-aminopyridine as starting material is absolutely novel and economically feasible.The research on the synthesis of 2,5-dichloro-3-bromopyridine requires only easily available and cheap resources,concise steps and convenient operation with a total yield of the desired product about 80.6%.