Improvement On The Synthesis Of 2-Amino-5-Fluoropyridine

2-amino-5-fluoropyridine is an important pharmaceutical intermediate containing fluori-ne, in this thesis, its synthesis process was improved based on the literature:2-amino-5-fluor-opyridine was prepared from 2-aminopyridine by acylation. nitration, reduction, diazotization. schiemann reaction and hydrolysis. The main factors influence on the each reaction were discussed base on the reaction mechanism, the process conditions were obtained from optimization of the various factors on unit reaction, thus, the yield and purity of the final product was increased.The experiment results showed that the optimal conditions of acylation were obtained as follows:2-aminopyridine 9.9g, acetic anhydride 21mL, reacting at 45℃for 2.5h. the yield was 96.26%. Optimal conditions of nitration were obtained as follows:2-acetylamino pyridine 13.6g. concentrated sulfuric acid 113mL, fuming nitric acid 14.6mL. reacting at 60℃for 2h, the yield was 88.40%.Optimal conditions of reduction were obtained as follows:2-acetylamin-o-5-nitropyridine 4.53g. anhydrous ethanol 40mL. hydrazine hydrate 2.94g. Pd/C catalyst 0.6g. reacting at 80℃for 3.5h. the yield was 93.26%. Optimal conditions of diazotization were obtained as follows:2-acetylamino-5-aminopyridine 3.8g. ethanol 15.8mL. fluoroborate 11.1mL. sodium nitrite 3.28g, reacting at 25℃for 1.5h, the yield was 87.22%. Optimal conditions of schiemann reaction were obtained as follows:2-acetylamino-5-pyridine tetrafl-uoroborate diazonium salt decomposed in toluene, decomposition temperature 110℃. charg-ing several batches, the yield was 64.94%. Optimal conditions of hydrolysis were obtained as follows:2-acetylamino-5-fluoropyridine 6g, NaOH 5g (20% aqueous solution), reaction at 80℃for 2h, the yield was 95.25%. Total yield was 42.81%.The final product was characterized by MS.1H NMR. and IR.