Synthesis And Analysis Of Diethylaminoethyl P-Nitrobenzoate As Medical Intermediate

Diethylaminoethyl p-nitrobenzoate is the key intermediate for preparation of Procaine, a local anesthetics. At present, there are two primary methods to produce Diethylaminoethyl p-nitrobenzoate:direct esterification and transesterification. Transesterification has more manufacture steps and is more difficult to treat the product. Direct esterification will take long reaction time with low yield. So it has strong realistic meaning to improve the manufacture technics.This paper studied the preparation of diethylaminoethyl p-nitrobenzoate by direct esterification using p-nitrobenzoic acid and diethylaminoethanol in xylene with catalysts. The effect of different catalysts on esterification yield was studied including tetrabutyl titanate ,solid super acid, Fe2(SO4)3·xH2O/ H2SO4,p-toluene sulfonic acid, tartaric acid, citric acid,and cation exchange resin. The result indicated that:Tetrabutyl titanate had the highest catalytic activity among all the catalysts used. The yield of esterification was incriseasd 11.8% comparing to that without catalyst.Compared with the acid catalysts,tetrabutyl titanate had less causticity and Contamination.There was no tetrabutyl titanate remained in the solution after washed. The purity of the product was high.Automatic electric potential titation(AEPT) has some advantages:simple management,low maintenance cost and high precision. This paper applid AEPT to determine diethylaminoethyl p-nitrobenzoate and p-nitrobenzoic acid. The result indicated that:(1) The analytic result of diethylaminoethyl p-nitrobenzoate by AEPT was comparable with those by diazotization.(2) AEPT could be used to determine p-nitrobenzoic acid either in synthetic solution or as starting material. The method had high accuracy and precision.The recovery of p-nitrobenzoic acid and xylene after the esterification catalyzed by tetrabutyl titanate was studied too. The result indicated that:The yield of diethylaminoethyl p-nitrobenzoate was decreased less than 2.6% using the p-nitrobenzoic acid of the third time recovery.Although the xylene recovered by hydrochloride acid extraction was colored, the yield of diethylaminoethyl p-nitrobenzoate had not been influenced using this xylene as solvent.AEPT was used to determinate diethylaminoethanol . The result indicated that:The analysis result of diethylaminoethanol by AEPT was comparable with those by manual titation.The relative standard deviation of 8 repeated measurements was 0.81%. It was indicated that AEPT has high precision.