7-ADCA反應(yīng)結(jié)晶過程研究.pdf

1、天津大學(xué)博士學(xué)位論文7ADCA反應(yīng)結(jié)晶過程研究姓名：劉越申請(qǐng)學(xué)位級(jí)別：博士專業(yè)：化學(xué)工程指導(dǎo)教師：王靜康20030301ABSTRACT7amino一3一desacetoxycephalosporanicacid(7ADCA)isoneofthemostimportantinterrnediateinthemanufactureofantibioticsWiththeincreasingdemandforcephalosporinsin

2、recentyearstherequirementof7ADCAwasincreasedcofrespondinglyInordertoimprovethequailtyandincreasetheyieldof7ADCAproductssemi，batchreactivecrystallizationof7一ADCAWaSstudiedsystematicallybothinexperimentandtheorySynthesispr

3、ocessesof7ADCAfromCephalosporinGconsistsoffollowingsteps：dissolutionofCephalosporinG，hydrolyzatienbyenzyme，extraction，decolorationandreactivecrystallizationToimprovethequalityofproductandlowerthecost，theoptimaloperationc

4、onditionsofaboveprocesseswereexperimentalstudiedindetmlByindexingthe7一ADCApowderX—raydi仃ractiondatathecrystalMillerindicesandcrystalsystemweredeterminedThecrystalspaceIa／riceof7一ADCAwascalculatedbSurmingPolymorphincommer

5、ciaI：softwareCeriusjtthasbeenprovedthatthcpr9ducts。whichwereproducedfromdifferentreactivecrystallizationmanners，belonginthesarflecrystalsystembutdifferenthabit，basedonthemeasureddatawithIRspectraDSCandpowderXRDinstrument

6、sThetheoreticalcrystalhabitof7一ADCAwaspredictedbvBFDHandAEmodeJrespectivelyTheresultofAEmodelresemblestheobservedmorphologyWhencrystallizingfromtheacidmannercertainfaceswerestuntedbyH’SOthatthosefacesCanbeohservedinfinal

7、crystalserystalyieldisdecidedbycrystallizationthermodynamics：Thesolubilityof7ADCA泌purewatetunderdilyerentItemperatureandpHweremeasuredThesolubilityof％卿CAit)purewaterincreaseswithtemperature、11leeffectsbfimpurity。wereobse

8、rvedManysalts，suchasNH4ClandPAA，don’thaveimpactonthesolubilityof7ADCAwiththeexceptionofCefGAsakindofzwitter7一ADCAexistsinsolutionasthreeforms：anions，cationsandneutraldipolarspeciesSolutionchemistryplaysanimportantrolewit

9、hrespecttopHeffeCtonsolubilityWhenpHiSlowerorhi吐erthanisoelectricpoint，thesolubilityof7一ADCAincreasesdramaticallyTheeffectofseedingandsulfa倫acid／ammoniaaddingrateoa7一ADCAmetastablezoilewidthweremeasuredTheresultsshowthat

10、metastablezonewidthisn’tinfluencedbyseedingwhencrystallizingbytheacidmannerOthorbasicphysicochemicaldataofsolution，suchasviscosity，densityof7一ADCAsolutionanddissociationconstants，werealsomeasuredwhichareusefulinformation

11、fordesignandcontrolofcrystallizationprocessReactivecrystallizationconsistsofthreesteps：mixing，reactionandcrystallization，Asfor7ADCA，mixingandreactionisrapid，thatistosaycrystallizationisthecontrolstepofthewholeprocessIn7A