苯甲酸苄酯的电化学合成方法

Electrochemical synthesis of benzyl benzoate

羧酸普遍存在于天然产物中,如松香树脂酸、柠檬酸、琥珀酸、乙酸、苯甲酸。同时羧酸基团是有机合成中最具吸引力的官能团之一。其中,苯甲酸是天然羧酸中一种重要的芳香族酸,其天然存在于多种植物以及食品中,因其具有较高的生物活性和应用价值而备受关注,常被应用于香料、农药、染料、医药和食品等领域。笔者以苯甲酸和芳基丙酸为原料,在电化学条件下合成了17个苯甲酸苄酯类化合物。其中,改变苯甲酸含有基团,包括苯甲酸1-苯乙酯(3a)、对位或邻位含有不同取代基苯甲酸苄酯(3b~3e)以及1-苯乙基噻吩-2-羧酸酯(3f);芳基丙酸类合成对应化合物,包括苯甲酸苄酯(3g~3m)、苯甲酸苯基苄酯(3n)、苯甲酸1-苯基丙酯(3o)、药物分子布洛芬修饰后的1-(4-异丁基苯基)苯甲酸乙酯(3p)、9H-芴-9-基苯甲酸酯(3q)等。采用氢核磁共振(^(1)H NMR)对产物结构进行表征,确证了产物结构。电解质直接影响反应的导电能力,以2-苯基丙酸和苯甲酸为模板底物考察了电解质种类,同时也分析了电流和电压的大小等反应条件对产率的影响。得出最优的反应条件为:0.05 mol/L二氯甲烷为溶剂,在10 mA恒电流电解下,四正丁基高氯酸铵(nBu_(4)NClO_(4),0.9 mmol)和2,4,6-三甲基吡啶(0.45 mmol)室温反应6 h,反应结束后经柱层析分离纯化计算产率。在此条件下,产物3a的产率高达99%,此反应能够兼容于两原料含有各种取代基团,合成苯甲酸苄酯类化合物(3b~3q)的产率为56%~94%。

Carboxylic acids are ubiquitously present in natural products,such as rosin acid,citric acid,succinic acid,succinic acid,acetic acid,and benzoic acid.Carboxylic acid group is one of the most attractive functional groups in organic synthesis.Benzoic acid is an important aromatic acid among natural carboxylic acids,which naturally exists in various plants and foods.Due to its high biological activity and significant application value,it has garnered widespread attention and is commonly employed in various fields including fragrances,pesticides,dyes,pharmaceuticals,and food.17 benzyl benzoate compounds were synthesized by the electrochemical method from benzoic acid and aryl propionic acid.The altered benzoic acid contains groups,including benzoate 1-phenyl ethyl ester(3a),benzyl benzoate(3b-3e) with different substituents in para or ortho position and 1-phenylethylthiophene-2-carboxylate(3f).The corresponding compounds of aryl propionic acid were synthesized,including benzyl benzoate(3g-3m),phenyl benzyl benzoate(3n),benzoate 1-phenylpropyl benzoate(3o),1-(4-isobutylphenyl) ethyl benzoate derived from the drug molecule ibuprofen(3p),9H-fluorene-9-phenyl benzoate(3q).The structure of the product was confirmed by ~1H NMR.Using 2-phenylpropionic acid and benzoic acid as model substrates,the impact of various types of electrolytes on the yield was consecutively examined,as electrolytes play a direct role in determining the conductivity of the entire reaction system.Furthermore,this study delved into how varying dosages of the same electrolyte affect the yield.Electrode materials,serving as both positive and negative electrodes,were also identified as a crucial factor that influences reaction effectiveness.Additionally,this study considered the influence of different types of bases,including inorganic and organic alkalis,on the yield.Organic alkalis notably exhibited significantly better solubility compared to inorganic alkalis,and the quantity of base used also significantly impacts the yield.Furthermore,this study explored the effects of various solvents and solvent mixtures on the yield,noting that these solvents differed in their conductivity properties.Then,the impact of varying current and voltage levels on the yield was also investigated.Finally,the reaction was carried out under the condition of a constant current of 10 mA,with dichloromethane(DCM,0.05 mol/L) as the solvent.In the presence of tetrabutylammonium perchlorate(nBu_4NClO_4,0.9 mmol) and 2,4,6-trimethylpyridine(0.45 mmol),the reaction was carried out for 6 h.After the reaction was completed,the product was separated by column chromatography,and the yield of product 3a was calculated to be 99%.A variety of benzyl benzoate compounds using benzoic acid or phenylpropionic acid as raw material could be tolerated under the optimized reaction conditions and the yield of 3b-3q was between 56% and 94%.