PURIFICATION OF LACTIDES BY MELTCRYSTALLIZATION熔融结晶制备丙交酯Word文档格式.docx
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13.09.1994
(51)Int.Cl.
C07D319/12
(21)Applicationnumber:
06-020338
(71)Applicant:
EIDUPONTDENEMOURS&
CO
(22)Dateoffiling:
17.02.1994
(72)Inventor:
O'
BRIENWILLIAMG
SLOANGILBERTJ
(30)Priority
Prioritynumber:
9328773
Prioritydate:
17.02.1993
Prioritycountry:
US
(54)PURIFICATIONOFLACTIDESBYMELT-CRYSTALLIZATION
(57)Abstract:
PURPOSE:
Toprovideamethodforpurifyingalactidebymelt-crystallization.
CONSTITUTION:
Themethodforpurifyingalactidecomprises
(1)coolingamoltenmixtureofalactideandimpuritiestothesolidifyingpointofthelactideortoatemp.slightlybelowthanthesolidifyingpointofthelactide,then
(2)partiallycrystallizingthemoltenmixturetoformasolidphasehavingimpuritycontentslowerthanthoseofthemoltenmixtureandtoformaliquidphasehavingimpuritycontentshigherthanthoseofthemoltenmixtureand(3)separatingthesolidphasefromtheliquidphase.
CLAIMS
[Claim(s)]
[Claim1]
(1)Amoltenmixtureoflactideandanimpurityiscooleddownwardmoreslightlythanacoagulatingpointoflactide,oracoagulatingpointoflactide,
(2)Arefiningmethodoflactidewhichconsistsofmakingsolidphaseofanimpuritycontentlowerthanamoltenmixture,andtheliquidphaseofanimpuritycontenthigherthanamoltenmixtureform,andmakingsolidphasewhichseparated(3)solidphasebydissociatingfromtheliquidphaseformbycrystallizingsomemoltenmixtures.
[Claim2]Amethodaccordingtoclaim1ofconsistingofL-lactidewithmoremoltenmixturesthan80%,orD-lactide.
[Claim3]Awayaccordingtoclaim1amoltenmixtureconsistsof20to80%ofL-lactide,and20to80%ofD-lactide.
[Claim4]Awayaccordingtoclaim1,2,or3amoltenmixtureison1-5**fromacoagulatingpointoflactide.
[Claim5]Amethodaccordingtoclaim1,2,3,or4ofconsistingofastagewhichmakesanadditionalmoltenmixtureformandrepeats(5)stage
(1)-(3)aboutanadditionalmoltenmixturebyfusingsolidphasewhichfurthermorecarriedout(4)separation.
[Claim6]Amethodaccordingtoclaim1,2,3,or4ofconsistingofmakingthesecondliquidphaseform,andthissecondliquidphaseconsistingofsomeremainingimpuritiesatleast,andremovingthe(5)secondliquidphasebywarminggraduallysolidphasewhichfurthermorecarriedout(4)separationafterastage(3)toatemperaturelowerthanthatmeltingpoint.
[Claim7]Amethodaccordingtoclaim1,2,3,4,or6ofconsistingofmakingamoltenmixturerecyclethe(6)secondliquidphaseafterastage(5)furthermore.
[Claim8]
(1)Arefiningmethodoflactidewhichconsistsofcarryingawayanimpurityinazone-of-meltingregionbymakingazone-of-meltingregioninsaidsolids-mixingthing,andmoving
(2)zone-of-meltingregionstoasolidzonebyheatinganarrowzoneofasolids-mixingthingoflactideandanimpurity.
[Claim9]Amethodaccordingtoclaim8ofconsistingofL-lactidewithmoremoltenmixturesthan80%,orD-lactide.
[Claim10]Awayaccordingtoclaim8amoltenmixtureconsistsof20to80%ofL-lactide,and20to80%ofD-lactide
DETAILEDDESCRIPTION
[DetailedDescriptionoftheInvention]
[0001]
[FieldoftheInvention]Thisinventionaboutmeltingcrystallizationrefiningoflactideincludingtheopticalactivitygestalt,Lactideisthoroughlyseparatedfromotherimpuritiesliketheimpuritycontainingahydroxylimpurity,forexample,water,themonomerusuallygeneratedbetweenthatmanufacturetogetherwithlactide,andoligomerichydroxycarboxylicacid,asolvent,andacatalystbythismethod.Furthermore,onethisinventionrelatestotheseparationandrefiningoflactidewhichexistwithmanyisomergestalten.Itisobtainedsimplyandpromptly,withoutusingotherpubliclyknownphysicalmeansinthestateofthepurityadjustedbysuchrefiningand/orlactidewashighbyfractionationcrystallizationfromanalternativesolventandasolvent,distillation,orthistechnicalfield.
[0002]
[Explanationofrelatedart]Lactide(1,4-dioxane3,5-dimethyl-2,5-dione),Sincetheby-productwhichisdecomposedbyhydrolysisandisphysiologicallypermittedfromenvironmentmaybeproducedbiologically,itisanintermediateofthepolymerspolylacticacidinwhichtheusefulthingbecameclearforabiomedicineandotheruses.Itisbecauseitisrequiredforlactidenottocontainahydroxyl(hydroxylcarboxylisincluded)impurityinrealizingtheamountofpolymersrequiredforsuchausesubstantially,becauseitbarsthatsuchanimpurityreachesadesiredmolecularweight.Asfortheacidcontentoflactide,itispreferredthatitislower,forexamplethan10milliequivalent(meq/kg)perkgandmuchmorepreferablylowerthan5meq/kg.
[0003]Otherimportantfactorsarethestereoisomerismgestaltenoflactide.WhilelacticacidexistswithbothDandLstereoisomerismgestalt,lactidehasmesoformvoicefurther.SimilarlytheracemicmixtureofimportantDandLlactideispointedoutcommercially,andDLlactideiscalled.Suchisomerlactidehasdifferentstability,andsincepolymerwithsubstantiallydifferentcharacterisproduced,fortheuseofacertainkindofpolymer,itisnecessarytoadjusttheratioofeachisomergestaltinafinalproduct.Theseratioscanbeadjustedusingthemethodofmakingonlyasingleisomer,orbyrefiningthemixtureofanisomer.Sinceanisomerhasanapproximatephysicalproperty,therefiningmethodpubliclyknownatthistechnicalfieldisextremelytroublesomelydifficult.
[0004]Lactidepolymerizescorrespondinglacticacidinthepolylacticacidoflowmolecularweight(oligomer)comparatively,Subsequently,oligomerisheatedunderexistenceofthecatalystwhichthistechnicalfieldmaygenerallybesufficientas,andwasknown,itisdepolymerizedinlactide,anditismadewiththemostsufficientconveniencebysubsequentlycollectingtheseasaningredientoftheflowofsteamyoutput.Gruteretc.,U.S.Pat.No.1,095,205(1914);
Lowe,U.S.Pat.No.2,668,162(1954);
Bhatia,U.S.Pat.No.4,835,293(1989);
DeVries,U.S.Pat.No.4,797,468(1989);
.AndpleaserefertoMullerandU.S.Pat.No.5,053,522(1991).Thesepatentsareincludedinthisspecificationbyreference.
[0005]ThesethissteamyproductstreamnotonlyincludinglactidebutincludingavolatilehydroxylimpurityalwaysWater,Sinceitismuchmorevolatilemonomerlacticacidandapolymerizationchainterminatorinwhichtheseallbarthearrivaltoadesiredmolecularweightincludingoligomeroflacticacidofahighboilingpointoftenmore,itisnotmoredesirablethanlactide.Theymayincludeasmallamountofthesolventsorcatalystswhichremainfromaformerprocessingstage.Typically,asteamyproductstreamcontainsmorelactidethan90%andimpuritiesfewerthan10%containingarbitraryisomers.
[0006]Thetypicaltechnicalprocedureofseparationofthelactidefromasteamyproductstreamandrecoveryincludescrystallizationfromscrubbingorasolventwhichgenerallyusesasolvent.However,ahydroxylimpurityespeciallywater,andlacticacidhavethecapabilitytostarttheringopeningreactionoflactide,undersuchconditions,and,asaresult,reductionoftheamountoflactideacquisitionandtheincreaseintheacidityofoutputareproduced.Suchareactionmuchmoresuchislikelytooccurthatthetemperatureoftherecoveryprocesstobeusedishigh.Inordertocollectcyclicester,thatitismoreoverdependentonasolventasteamyproductstreambycarryingoutscrubbingThat,orthethingforwhichrecrystallizationrefinesit--be--asolventisstored,itisused,itisrefined,theequipmentforpreventingitbeingemittedandpollutingenvironmentisneeded,andtheseallaredisadvantageousthingsfrombecomingtheloadtotheinvestmentinaprocess,andoperationexpenseremarkably.
[0007]Refiningandrecoveryoflactidebythedistillationandcondensationwhichareoptionsfallintothefaultthatthelossofaremarkableoutputoftenarises,easily,andthisdependsthemonareactionwiththelactideofthewateratdistillationtemperature,andotherhydroxyacidimpuritiesclearly.Inanelevatedtemperature,ametalionmayariseasaresultofthecorrosionbytheacidicenvironmentofadistillationapparatus,and,subsequentlythismaycarryoutthecatalysisofaprematurelactidepolymerizationintothedeviceitself.Separationofthelactidewhichexistswithmoreisomergestaltenthanonekindisstillmuchmorecomplicated,andoftenneedsthecombinationofmuchsolventrecrystallizationandfractionationdistillation.
[0008]Themeltingcrystallizingmethodwasoftenusedforrefiningofanorganiccompoundofacertainkind.However,itcannotpredictfeasibility[ofthismethod]easily.Itdependsforthestructureofthecrystalbywhethertheoutput,eutecticmixture,orsolidsolutionwhichitshouldrefinethatitisdependentonthecoagulatingpointofadesiredoutput,itsimpurity,andamixturewiththoseoutput,i.e.,animpurity,isformedformed,thereforeanimpurityalsoonthetendencywhichcarriesoutocclusion.Moreover,itdependsforthesizeandproductivityofacrystallizingdeviceonthespeedwhichcanformasuitablecrystalintoacrystalstructurewithouttheocclusionofanimpurityhappening.Thelatesttotaltheoryofthisart[Wynn,"
separationoftheorganicsubstancebymeltingcrystallization(SeparateOrganicsbyMeltCrystallization)"
itisstatedtoChemicalEngineeringProgress(March,1992)and52-60pages]--as--