2，3-二氯苯基哌嗪合成方法的改进

第34卷第4期2007正北京化工大JOURNALOFBEIJINGUNIVERSITY学学报OFCHEMICAITECHN0L0GYVo1．34．No．42007Processdevelopmentofthesynthesisof2，3-dichl0r0phenylpiperazineHIJIMorrisFrankZHENGGuoJunYUANQiPeng(CollegeofLifeScienceandTechnology，BeijingUniversityofChemicalTechnology，Beijing100029，China)Abstract：Thenewpathwayforthesynthesisof2，3-dichlorophenylpiperazinefromcheaprawmaterial，2，3-dichloroanilineispresented．Thehydrogensulphatesaltof2，3-dichloroanilinewasconvertedtothecorrespondingAry1Iodideingoodyieldof81％byreactingwithconc．H2SO4andNaNOztoformintermediatediazoniumsalt，whichwasfurtherdisplacedbyKI．ThedesiredproductwasobtainedbyreactingArylIodideandpiperazineinthepresenceofCuIascatalyst，prolineaslig—and，K2CO3asbaseanddimethylsulfoxideassolventwithyieldof20％．Themethodissimple，utilizescheapcatalystandligand，insensitivetomoisture；itiseasytoseparatetheproduct，andcanundergolarge-scaleproduction．Keywords：2。3-dichlorophenylpiperazine；2，3-dichloroaniline；diazoniumsalt；1，2-dichloro-3一iodobenzeneChinaclassificationNo．：R971．41Introduction2，3一dichlorophenylpiperazineisapotentialpre—cursorinsynthesizingpotentdrugsthattargetdopamineandserotoninreceptor，suchasaripipra—z0le[11．NGB284912_3]andNGB290412_3]．Particu1ar—ly，bybeingkeyintermediateinsynthesisofaripipra—zole．thelatestschizophreniadrug[，一]whichpossesbothpostsynapticdopaminereceptorandpre—synapticauto—receptor，attractsspecialattentioninitssynthe—sis．Thecurrentmethodofpreparing2，3一dichl—orophenylpiperazineinvolvesreactionbetween1，2一dichloro-3一iodobenzeneandpiperazineinthepresenceofPd(Palladium)catalyst，S-Binapasligand，baseandsolventliketoluene[7_8]．Thismethodwhichfol—lowedabreakthroughindevelopmentofC—NbondusingpalladiumcatalystreportedbyBuchawald[]in1997．hasayieldbetween50％一60％．Theindustri—aluseofthismethodishinderedbyhighcostofPdcatalystandrelativeligandsaswellasairandmois—Reeeived：2007—03—22Firstwriter：male，bornin1976，postgraduatestudent*CorrespondingauthorE—mail：yuanqF}@mail．buct．edu．cnturesensitivity[．Contaminationoftheproductisanothercrucialp