2-(N,N-二甲胺基)丙酸十二醇酯的合成研究

以 2 氯丙酸、正十二醇为原料 ,氯化铁催化 ,甲苯共沸回流带水酯化 ;再与二甲胺在三乙胺的作用下胺化 ,合成了透皮吸收促进剂 2 (N ,N 二甲胺基 )丙酸十二醇酯 (DDAIP) ,合成总收率达 72 5 %。考察了催化剂的用量、物质的量比及反应时间对反应的影响 ,确定出反应的最佳工艺条件为 :n(正十二醇 )∶n (2 氯丙酸 )∶n(FeCl3 ·6H2 O)∶n(甲苯 ) =1∶1 4∶0 0 4 5∶9 4 ,回流反应 4 5h制得 2 氯丙酸十二醇酯 ,收率为 83 8% ;n(2 氯丙酸十二醇酯 )∶n(二甲胺 )∶n(三乙胺 )∶n(氯仿 ) =1∶ 4∶1 5∶11,室温反应 16h制得DDAIP ,收率为 86 5 %。

Synthesis of Dodecyl 2-(N,N-Dimethylamino)-propionate

The biodegradable transdermal penetration enhancer,dodecyl 2 ( N,N dimethylamino) propionate (DDAIP),was synthesized by reacting dodecyl 2 chloropropionate,obtained by esterification of n dodecanol with 2 chloropropionic acid under the catalysis of ferric chloride in toluene,with dimethylamine by the action of triethylamine.The total yield was 72 5%.The effect of amount of catalyst,molar ratio and reaction time was investigated.The optimal process conditions were as follows.In molar ratio n (n dodecanol)∶ n (2 chloropropionic acid)∶ n (FeCl 3·6H 2O)∶ n (toluene)= 1∶1 4∶0 045∶9 4 by refluxing for 4 5 h,dodecyl 2 chloropropionate was obtained in 83 8% yield. In molar ratio n (dodecyl 2 chloropropionate)∶ n (dimethylamine)∶ n (triethylamine)∶ n (chloroform)=1∶4∶1 5∶11 and reacting at room temperature for 16 h,DDAIP was obtained in 86 5% yield.