Synthesis of 2-amino-6-bromopyridine
|School||Nanjing University of Technology and Engineering|
|Keywords||2 - Amino-6 - methylpyridine Australia on behalf of Oxidation Acidification Hoffman hydrolysis 2 - Amino-6 - bromopyridine|
2 - amino - 6 - bromopyridine is an important pharmaceutical synthesis intermediates for the synthesis of novel treatment of inflammation, diabetes, high blood pressure , nerve damage , HIV virus infection , and hyperplasia disease drugs . 2 - amino-6 - the bromopyridine the synthesis method are generally the cyclization method ammonation hydrolysis method . Cyclization method based on epichlorohydrin , with the the KCN role of open-loop , and then cyclization obtained in HBr , the high yield of the method , serious pollution ; the ammoniated method based on 2,6 - Dibromo -3 - dimethylamino pyridine as the raw material, obtained by the reaction with potassium amide in liquid ammonia , the method many side reactions , the yield is very low ; hydrolysis method is 2 - methyl - pyridine N-oxide as a starting material , by nitration , obtained after oxidation , Curtius rearrangement, hydrolysis , alkalinization , and the process flow , the low yield. I designed on the basis of analysis of 2 - amino - 6 - methyl - pyridin- synthesis method , the new synthetic preparation means . 2 - amino-6 - methyl pyridine as raw material , the bromo , KMnO4 oxidation , acylation Hoffman after hydrolysis obtained the target product 2 - amino-6 - bromopyridine , infrared spectroscopy and nuclear magnetic resonance spectroscopy on intermediates and products were characterized . The experiment has been preferred synthesis condition of the intermediates and of the target product : 2 - bromo - 6 - methyl - pyridine in the n (Br2) : N ( 2 - Amino-6 - methyl- pyridyl) = 3:1 , -15 ~ -10 ℃ , the yield was 87.1% ; 2 - carboxy - 6 - bromopyridine n (KMnO4): n (2 - bromo-6 - methyl pyridine ) = 3:1 , water as solvent , 80 ℃ condition next , the yield was 44.1%; 6 - bromo - 2 - pyridinecarbonyl chloride in n - (2 - carboxy-6 - bromo- pyridine ) : n ( SOCl2) = 1:5 , DMF, as a catalyst , a reflux condition , yield 92.4%; 6 - bromopyridine-2 - carboxamide in the N (6 - bromopyridin-2 - carbonyl chloride ): n ( ammonia) = 1:6 ; 6 - bromo - pyridin-2 - methyl chloride was added aqueous ammonia , - under the conditions of 10 ° C , yield 83.6% ; 2 - amino - 6 - bromopyridine- N ( 6 - bromopyridin-2 - carboxamide ) : n (Br2 ) = 1:1.2, the NaOH concentration of the solution 10 % , 70 ° C conditions, the yield was 81.0% ; target product, 2 - amino-6 - bromopyridine in total yield of 24.0% . Experimental results show that this synthetic route is feasible , simple operation , less waste emissions , and provide the basis for amplification test and industrial production .