3-氟苯甲酸的合成工艺
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摘要
[目的]改进含氟中间体3-氟苯甲酸的合成方法。[方法]以3-氨基苯甲酸为起始原料,在氟化氢吡啶试剂中进行重氮化和氟化反应合成3-氟苯甲酸,并经正交试验优化得到最佳条件。[结果]氟化氢吡啶试剂浓度为70%,3-氨基苯甲酸、NaNO_2和氟化氢吡啶投料摩尔比为1∶1∶50,收率为96.90%,纯度为99.09%。[结论]利用氟化氢吡啶试剂合成3-氟苯甲酸具有反应条件温和、收率高、后处理方便等优点,实用性强。
[Aims] Improvement of the synthesis of fluorine-contained intermediate 3-fluorobenzoic acid. [Methods] 3-Fluorobenzoic acid was synthesized from 3-aminobenzoic acid by diazotization and fluorination in the reagent of hydrogen fluoride-pyridine. An optimized reaction condition wasobtained through orthogonalexperiment. [Results]With 70% hydrogen fluoride-pyridine reagent and a mole ratio of 3-aminobenzoic acid, NaNO_2 to HF as 1 ∶1 ∶50, the 3-fluorobenzoic acid was yield in 96.90% with purity of 99.09%. [Conclusions] The synthesis of 3-fluorobenzoic acid using hydrogen fluoride-pyridine is a practical method with advantages of mild reaction conditions, high yield and convenient post-treatment.
[Aims] Improvement of the synthesis of fluorine-contained intermediate 3-fluorobenzoic acid. [Methods] 3-Fluorobenzoic acid was synthesized from 3-aminobenzoic acid by diazotization and fluorination in the reagent of hydrogen fluoride-pyridine. An optimized reaction condition wasobtained through orthogonalexperiment. [Results]With 70% hydrogen fluoride-pyridine reagent and a mole ratio of 3-aminobenzoic acid, NaNO_2 to HF as 1 ∶1 ∶50, the 3-fluorobenzoic acid was yield in 96.90% with purity of 99.09%. [Conclusions] The synthesis of 3-fluorobenzoic acid using hydrogen fluoride-pyridine is a practical method with advantages of mild reaction conditions, high yield and convenient post-treatment.
引文
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[2]陈德化,黄建华.含氟芳香、杂环化合物的开发与进展[J].有机氟工业,1995(1):12-17.
[3]韩俭,杨小荣,赵素英,等.含氟药物的研究进展[J].中国药房,2011,22(1):67-70.
[4]陈卫东,钱旭红,宋恭华.相转移催化在芳香氟化反应中的应用[J].化工生产与技术,2003,10(2):1-4.
[5]MILNER D J.Fluoroaromatics from Arylamines,a Convenient One-pot Conversion using Nitrosonium Tetrafluoroborate[J].Syn Commun,1992,22(1):73-82.
[6]徐杰,张伟.芳香族含氟化合物的合成及应用[J].精细化工原料及中间体,2005(11):3-7.
[7]OLAH G A,WELCH J T,VANKAR Y D,et al.Pyridinium Poly(Hydrogen Fluoride)(30%Pyridine-70%Hydrogen Fluoride):a Convenient Reagent Fororganic Fluorination Reactions[J].J Org Chem.,1979,44(22):3872-3881.
[8]OLAH G A,NOJIMA M,KEREKES I.Hydrofluorination of Alkenes,Cyclopropane and Alkynes with Poly-hydrogen Fluoride/Pyridine(Trialkylamine)Reagents[J].Synth,1973(12):779-780.
[9]杨柳,毛淑芬,覃兆海.新氟化试剂氟化氢络合液[J].化学试剂,2003,25(6):341-342.
[10]FUKUHARA T,YONEDA N,SAWADA T,et al.An Improved Procedure for Diazotization Fluoro-dediazoniation of Anilines using Organic Base-HF Agents[J].Synth Commun,1987,17(6):685-692.
[11]FUKUHARA T,YONEDA N,TAKAMURA K,et al.The Preparation of p-Fluorophenols from p-Aminophenols:Diazotization and Fluorodediazoniation in Pyridine-HF[J].J F Chem,1991,22(51):299-304.