Study On The Oxidative Chlorination Of Aminopyridine

Chloropyridine compounds are important intermediates to produce medicines,pesticides and veterinary medicines.At present,chloropyridine bases are mainly synthesized by direct chlorination of chlorine,in which there are many problems,such as safety,environmental protection and so on.Therefore,it is greatly significant to develop new chlorination method for the green synthesis of chloropyridines.In this paper,the oxidative chlorination of aminopyridines were studied by use of sodium hypochlorite aqueous and hydrochloric acid as chlorinating agent.Finally,new synthesis methods of 2-amino-5-chloropyridine and 3-chloro-2-aminopyridine were respectively proposed by the optimization of synthetic route and reaction conditions.At first,the oxidative chlorination reactivity and the chlorinated products were investigated by use of 2-aminopyridine as raw material.The results indicated that2-aminopyridine can be chlorinated with sodium hypochlorite aqueous and hydrochloric acid as chlorinating agent to produce 2-amino-5-chloropyridine as major product.Further,the optimized reaction conditions were also obtained as follows,n（2-aminopyridine）:n（Na Cl O）:n（HCl）is 1:1.5:5,sodium hypochlorite aqueous and hydrochloric acid were added in turn under 10℃,subsequently the reaction lasts4 hours at 25^oC.Under optimized conditions,2-aminopyridine can be completely reacted,and the yield of the target product is up to 91.25%.Secondly,3-aminopyridine was used as raw material to investigate its oxidative chlorination reactivity in the system of sodium hypochlorite aqueous and hydrochloric acid.The results indicated that 3-aminopyridine has lower chlorinating reactivity than2-aminopyridine.The major chlorinating products of 3-aminopyridine is2-chloro-3-aminopyrodine.The synethic conditions of 2-chloro-3-aminopydrine were optimized as follows,n（3-amin pyridine）:n（Na Cl O）:n（HCl）is 1:1.5:6,hydrochloric acid and sodium hypochlorite aqueous were added in turn under 10℃,then the reaction lasts 5 hours at 25 ^oC.The oxidative chlorination of 3-aminopyridine show high selectivity of product,and the yield of the target product is up to 33.46%.In addition,the oxidative chlorination reactivity of pyridine was also explored with hydrochloric acid as the resource of chlorine and Na Cl O,H₂O₂as oxidant.The results show that only a little of 2-chloropyridine was observed in the system of sodium hypochlorite aqueous and hydrochloric acid.