3-氟-4-碘苯甲醚的合成

Synthesis of 3-Fluoro-4-iodoanisole

以间氨基苯甲醚为原料,在浓HCl、NaNO2作用下,反应温度5℃以下,加入40%的氟硼酸,加热,经Schiemann反应生成间氟苯甲醚,产率36.6%.然后在60℃水浴中缓慢滴加65%～68%的发烟硝酸、冰乙酸和醋酐的混合液（间氟苯甲醚与浓硝酸的摩尔比为0.0624：0.0721、冰乙酸与醋酐的体积比为10.6：7.6）,苯环上4-位硝化1 h后得3-氟-4-硝基苯甲醚,产率48.7%,沸点151.2℃.在ZnCl2和浓HCl作用下反应12 h,再还原成3-氟-4-氨基苯甲醚,产率84.1%,熔点240～241℃.加入NaNO2、浓H2SO4和KI,在5℃下重氮化,经Sandmeyer反应碘代合成3-氟-4-碘苯甲醚,产率72.0%,熔点123～123.5℃.通过沸点、熔点、IR、1H NMR、MS和元素分析对产物进行了表征.

3-aminoanisole was diazotized with conc. HCl and NANO2 below 5 ℃ and treated with fluoroboric acid 4% （Sehiemann reaction）to give 3-fluoroanisole in 36.6 % yield. Then, the mixture of 65 % -68 % nitric acid, glacial acetic acid and acetic anhydride was dropped slowly to 3-fluoroanisole at 60℃ for lh （3-fluoroanisole and nitric acid molar ratio 0.0624：0.0721,glacial acetic acid and acetic anhydride volume ratio 10.6：7.6） on water bath to produce 3-fluoro-4- nitroanisole in 48.7% yield（bp 151.2 ℃）.3-Fluoro-4-nitroanisole was reduced by ZnC12 and HCl for 12h to form 3- fluoro-4-aminoanisole in 84.1% yield（rap 240- 241 ℃ . Finally,3-fluoro-4-iodoanisole was 0btainde in 72.0% yield （mp 123 - 123.5 ℃）by diazotization of 3-fluoro-4-aminoanisole at 5 ℃ in NaNO2 and H2SO4 and addition of KI （Sandmeyer reaction）. The product was characterized by boiling point , melting point, melting point IR, ^1H NMR, MS and elemental analysis.