Synthesis Of Adrenaline

Allergic diseases have become an epidemic in the new century.Anaphylactic shock is a type of immediate allergic reaction,it has a systemic,multi-system characteristics.In the world,extremely serious allergic reactions induced by food,drugs and other allergens are increasing.Since the incidence of anaphylactic shock in the general population is unknown,and most people neglect or understand the symptoms,some patients die because they have not received timely and correct treatment.Facing this severe situation,it is of great significance to develop and study anti-anaphylactic shock drugs.Adrenaline,chemicalname(R)-1-(3’,4’-dihydroxyphenyl)-2-methylamino-ethanol,developed by the United States Forest Labs company and listed in 1951.There are two enantiomers,R-(-)-adrenaline and S-(+)-adrenaline in the adrenaline,and R-(-)-adrenaline has physiological activity.Adrenaline mentioned herein refers to R-adrenaline.Adrenaline has a significant agonistic effect on the adrenalineαandβreceptors.Adrenaline is clinically used for the rescue of cardiac arrest and anaphylactic shock.It can also be used for the treatment of other allergic diseases such as bronchial asthma and urticaria.This thesis mainly studied the synthesis of adrenaline and its technological conditions.Through literature review and comprehensive analysis,it was found that thepreparationofadrenalinewasmainlyreductionreactionof3’,4’-dihydroxy-2-(methylamino)acetophenone hydrochloride andresolution reaction ofRS-(±)-1-(3’,4’-dihydroxyphenyl)-2-methylaminoethanol.Based on the reported literature,this article had improved and perfected the synthesis route and process,and obtained a process route of simple synthetic synthesis of adrenaline with simple and mild conditions.In this route,catechol is used as the starting material.After acylation with chloroacetic acid,3’,4’-dihydroxy-2-chloroacetophenone(2)is formed.2 amination with methylamine and salt with hydrochloric acid,then formed into 3’,4’-dihydroxy-2-(methylamino)acetophenone hydrochloride(3).Under atmospheric pressure,3hydrogenation with hydrogen over palladium carbon catalysis to produce RS-(±)-1-(3’,4’-hydroxyphenyl)-2-methylaminoethanol(4),4 and L-tartaric acid are separated to give the target product R-adrenaline(1).In the reaction to form 4,using normal pressure catalytic hydrogenation and extend the reaction time,higher yields can be obtained.In the reaction for forming the target 1,the crystals are crystallized by a gradient cooling and diastereomeric salt crystallizing method,and the resulting S-(+)-adrenaline is racemized and recovered for resolution.The raw material of the process is cheap and easy to obtain,the process conditions are mild,and the total yield can reach 27.6%.The chemical structures of the target products and important intermediates were characterized by MS and ~1H-NMR.