PURIFICATION OF LACTIDES BY MELTCRYSTALLIZATION熔融结晶制备丙交酯Word文档格式.docx

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--