Synthesis Of 2-amino-6-bromopyridine

2-amino-6-bromopyridine is a kind of important pharmaceutical intermediates which can be used to synthesize medicines against inflammation, diabetes, high blood pressure, nerve injury, HIV infection and proliferative.2-amino-6-bromopyridine was prepared by cyclization, amination and hydrolysis protocol in common. Cyclization method was started with epichlorohydrin as raw material, ring was opened with potassium cyanide, and then it was cyclized in the hydrobromic acid again. The yield was high with more pollution waste. In amination method, 2,6-dibromo-3-dimethylaminopyridine was selected as raw material, reaction was proceeded with amino-potassium in liquid ammonia with low-yield and much side effect. In hydrolysis method,2-amino-6-bromopyridine was synthesized from 2-methyl-pyridine N-oxide by nitration, oxidation, Curtius rearrangement, hydrolysis, alkalization, and the yield was low with complex process.On the basis that synthetic methods of 2-amino-6-bromopyridine were analyzed, a new synthetic method was designed.In the paper,2-amino-6-bromopyridine was synthesized from 2-amino-6-methylpyridine through brominating, oxidating, acylating, Hoffman hydrolysis reaction. Structures of the intermediates and target product were characterized by IR and 1H NMR.Optimum conditions of intermediates and target product were obtained as follows:with n (liquid bromine):n(2-amino-6-methylpyridine)=3:1 under-15～-10℃, the yield of 2-bromo-6-methylpyridine was 87.1%. With n(potassium permanganate): n(2-bromo-6-methylpyridine)=3:1 in water,6-bromopicolinic acid was prepared in 44.4% yield under 80℃. While DMF as the catalyst, n(6-bromopicolinic acid):n(thionyl chloride)=1:5,6-bromopyridine-2-carboxylicacid chloride came to the yield of 92.4%. When n(6-bromopyridine-2-carboxylicacid chloride):n(ammonia):=1:6 under-10℃, 6-bromopyridine-2-carboxylicacid chloride was mixed in ammonia, the yield of 6-bromopyridine-2-carboxamide was 83.6%. At 70℃n(6-bromopyridine-2-carboxamide):n(liquid bromine)=1:1.2, the yield of 2-amino-6-bromopyridine was 81.0% with w(NaOH)=10% sodium hydroxide solution. The overall yield of target product 2-amino-6-bromopyridine was 24.0%.The experimental result showed that our synthetic route was feasible with easy-operation and less pollution waste which could provide with basis for amplification and industrization.