N-酰基苯并三唑的高效合成

EfficientSynthesis of N-acylbenzotriazoles

N-酰基苯并三唑是媲美酰氯的良好的N-、O-、S-、C-酰化剂,可以用于许多有机转化。在1, 2-二氯乙烷中加入苯并三唑(BtH)和氯化亚砜(SOCl2),待苯并三唑溶解后加入羧酸,加热回流,即可便捷地合成各种N-酰基苯并三唑。以月桂酸为例,考察了合成N-酰基苯并三唑的反应影响因素,得到了最优反应条件:羧酸(1.0 eq.)、 BtH(1.2 eq.)、 SOCl2(1.2 eq.)、 1, 2-二氯乙烷为溶剂,120℃油浴加热下回流6 h,产率94.5%。接着拓展底物,在该反应条件下合成了35种N-酰基苯并三唑化合物,羧酸包括脂肪族羧酸、脂肪族二酸、取代芳香酸和芳香族二酸等,产率基本在80%以上。同时探究了芳香取代基种类和取代位置、脂肪链长短等因素对产率的影响,产物结构都经1H NMR和13C NMR确证。在该反应体系下将投料放大10倍,同样很平稳、顺利和方便地以高产率得到了所需产物。本文主要通过改变溶剂和提高反应温度的方法使反应顺利进行,尤其是对溶解度低的羧酸和二元酸的产率大幅度提高,并且原料苯并三唑的使用量减少了2~3倍。最后还优化了部分产物的提纯方法,使得提纯更简单方便,为长链脂肪族酰基苯并三唑的提纯提供了一种新方法,使得成本更低,更适合工业化生产。

N-acylbenzotriazole is a good N-,O-,S-,C-acylation agent comparable to acyl chloride,which can be used for many organic transformations.Benzotriazole(BtH)and thionyl chloride(SOCl_(2))were added to 1,2-dichloroethane.After the benzotriazole was dissolved,carboxylic acid was added and heated to reflux to synthesize various N-acylbenzotriazoles.Taking lauric acid as an example,the reaction factors affecting the synthesis of N-acylbenzotriazole were investigated,and the optimal reaction conditions were obtained:carboxylic acid(1.0 eq.),BtH(1.2 eq.),SOCl_(2)(1.2 eq.),1,2-dichloroethane as solvent,120℃oil bath heating and refluxing for 6 h,the yield is 94.5%.Then,the substrate was expanded,and 35 N-acylbenzotriazole compounds were synthesized under the reaction conditions.The carboxylic acids included aliphatic carboxylic acids,aliphatic diacids,substituted aromatic acids and aromatic diacids,and the yield was basically over 80%.At the same time,the effects of the type and position of aromatic substituents and the length of aliphatic chain on the yield were investigated.The structures of the products were confirmed by^(1)H NMR and^(13)C NMR.Under this reaction system,the feed was amplified by 10 times,and the desired product was obtained in a stable,smooth and convenient manner with high yield.In this paper,the reaction was carried out smoothly by changing the solvent and increasing the reaction temperature.In particular,the yield of carboxylic acid and dicarboxylic acid with low solubility was greatly improved,and the amount of benzotriazole was reduced by 2~3 times.Finally,the purification method of some products was optimized,which made the purification simpler and more convenient.It provided a new method for the purification of long-chain aliphatic acylbenzotriazole,which made the cost lower and more suitable for industrial production.