含吡咯侧链的2-氟-6-甲氧基苯醚合成及其硝化产物表征

Synthesis and Characterization of Nitration Products of 2-Fluoro-6-methoxyphenyl Ethers Containing Pyrrole Side Chains

以2-氟-6-甲氧基苯酚(2)和1-(3-氯丙基)吡咯烷盐酸盐(3)为原料,经过羟烷基化反应得到1-[3-(2-氟-6-甲氧基苯氧基)丙基]吡咯烷盐酸盐(4),然后发生硝化反应得到1-[3-(2-氟-6-甲氧基-4-硝基苯氧基)丙基]吡咯烷盐酸盐(1a)和1-[3-(2-氟-6-甲氧基-3-硝基苯氧基)丙基]吡咯烷盐酸盐(1b),产物及中间体结构经1H NMR、1H-1H NOESY和ESI-MS表征。并研究了影响羟烷基化反应收率的重要因素,确定化合物4合成优化条件为:n(3)∶n(2)=1.2∶1,n(K_(2)CO_(3))∶n(2)=2.5∶1,乙腈为反应溶剂,回流反应2 h,在该条件下,化合物4收率为82.4%。

1-(3-(2-Fluoro-6-methoxyphenoxy)propyl)pyrrolidine hydrochloride(4)was synthesized from 2-fluoro-6-methoxyphenol(2)and 1-3-chloropropylpyrrolidine hydrochloride(3)via hydroxyalkylation,next the compounds of 1-(3-(2-fluoro-6-methoxy-4-nitrophenoxy)propyl)pyrrolidine hydrochloride(1 a)and 1-(3-(2-fluoro-6-methoxy-3-nitrophenoxy)propyl)pyrrolidine hydrochloride(1 b)were obtained by nitration.The structures of products and intermediates were characterized by 1H NMR,1H-1H NOESY and ESI-MS.The optimum conditions for the synthesis of compound 4 were determined as follows:n(3)∶n(2)is 1.2∶1,n(K_(2)CO_(3))∶n(2)is 2.5∶1;acetonitrile as reaction solvent,the reaction was refluxed for 2 h,under these conditions,the yield of compound 4 was up to 82.4%.