《制藥工程》PPT電子課件
《制藥工程》PPT電子課件,制藥工程,制藥,工程,PPT,電子,課件
第二章、藥物化學(xué)合成工藝第二章、藥物化學(xué)合成工藝與化學(xué)制藥反應(yīng)器與化學(xué)制藥反應(yīng)器Chapter2Pharmaceuticalchemicalsynthesisprocessandchemicalandpharmaceuticalreactor如何建立化學(xué)合成藥生產(chǎn)車間如何建立化學(xué)合成藥生產(chǎn)車間國內(nèi):國內(nèi):浙江、江蘇,中間體生產(chǎn)廠浙江、江蘇,中間體生產(chǎn)廠制藥廠的現(xiàn)狀制藥廠的現(xiàn)狀,制劑為主,原料為輔制劑為主,原料為輔國際上:美國等外包業(yè)務(wù)國際上:美國等外包業(yè)務(wù)印度的合成能力印度的合成能力HowtocreateachemicalsyntheticdrugproductionworkshopDomestic:Domestic:Zhejiang,Jiangshu:intermediatemanufacturingplantZhejiang,Jiangshu:intermediatemanufacturingplantStatusofpharmaceuticalproductplant:mainlyproduceStatusofpharmaceuticalproductplant:mainlyproduceformulations,secondlyproducerawmaterialsformulations,secondlyproducerawmaterialsInternationally:UnitedStates,outsourcingbusinessInternationally:UnitedStates,outsourcingbusinessIndiasabilitytosynthesizeIndiasabilitytosynthesize第一節(jié)、藥物化學(xué)合成工藝第一節(jié)、藥物化學(xué)合成工藝SectionIMedicinalchemistrysynthesisprocess2.1.1、工藝路線的設(shè)計(jì)、工藝路線的設(shè)計(jì)(1)、)、利用類型反應(yīng)法利用類型反應(yīng)法根據(jù)藥物或它們的關(guān)鍵中間分子的化學(xué)根據(jù)藥物或它們的關(guān)鍵中間分子的化學(xué)結(jié)構(gòu)類型及功能基團(tuán)情況,采用類型法結(jié)構(gòu)類型及功能基團(tuán)情況,采用類型法進(jìn)行設(shè)計(jì)。進(jìn)行設(shè)計(jì)。所謂所謂類型反應(yīng)類型反應(yīng)一般系指功能基形成的一般系指功能基形成的單單元反應(yīng)和特殊反應(yīng)元反應(yīng)和特殊反應(yīng),以及各類物質(zhì)的通,以及各類物質(zhì)的通用合成方法等。用合成方法等。2.1.1、Thedesignofprocessroute(1)UsetypereactionUsetypereactionAccordingtothechemicalstructureofthedrugortheirAccordingtothechemicalstructureofthedrugortheirkeyintermediatemoleculetypeandfunctionalgroups,keyintermediatemoleculetypeandfunctionalgroups,usethetypemethodtodesign.usethetypemethodtodesign.Theso-calledtypereactiongenerallyreferstounitTheso-calledtypereactiongenerallyreferstounitreactionandspecialreactionformedbyfunctionalreactionandspecialreactionformedbyfunctionalgroups,aswellasotherkindsofgeneralsyntheticgroups,aswellasotherkindsofgeneralsyntheticmethodofdifferentsubstances.methodofdifferentsubstances.。(2 2)、利用倒推法)、利用倒推法所謂所謂倒推法倒推法就是從最終產(chǎn)品的就是從最終產(chǎn)品的化學(xué)結(jié)構(gòu)化學(xué)結(jié)構(gòu)出發(fā),將其合成過程一步一步地往前推出發(fā),將其合成過程一步一步地往前推導(dǎo)和演繹,即首先以藥物的最后一個結(jié)導(dǎo)和演繹,即首先以藥物的最后一個結(jié)合點(diǎn)考慮前一步的合點(diǎn)考慮前一步的中間體中間體是什么,并經(jīng)是什么,并經(jīng)過什么過什么反應(yīng)反應(yīng)得到最終產(chǎn)物,接著再從該得到最終產(chǎn)物,接著再從該中間體的中間體的結(jié)合點(diǎn)結(jié)合點(diǎn)考慮其前一步的考慮其前一步的中間體中間體是什么和利用什么是什么和利用什么反應(yīng)反應(yīng)得到的。得到的。(2 2)Backwardinferencemethod BackwardinferencemethodisfromthechemicalBackwardinferencemethodisfromthechemicalstructureofthefinalproducts,toderivatethestructureofthefinalproducts,toderivatethesynthesisprocessstepbystep.Thatis,firstly,startsynthesisprocessstepbystep.Thatis,firstly,startfromthelastpointtoconsiderwhatisthepreviousfromthelastpointtoconsiderwhatisthepreviousintermediateandhowtogetthefinalproduction.intermediateandhowtogetthefinalproduction.Afterthat,fromthebindingpointofthisAfterthat,fromthebindingpointofthisintermediatetoconsiderwhatisthepreviousintermediatetoconsiderwhatisthepreviousintermediateandhowtogetthisintermediateviaintermediateandhowtogetthisintermediateviathereactionthereaction(3)、利用逐步綜合法A、基本骨架的構(gòu)成基本骨架的構(gòu)成B、功能基的生成與轉(zhuǎn)化功能基的生成與轉(zhuǎn)化功能基的定位功能基的定位功能基的活化功能基的活化功能基的保護(hù)功能基的保護(hù)多個功能基的引入多個功能基的引入功能基的轉(zhuǎn)化功能基的轉(zhuǎn)化(3)GradualconsolidationmethodA.ThebasicskeletonB.GenerationandtransformationoffunctionalgroupsPositioningfunctionalgroupsActivationoffunctionalgroupsProtectiongroupsIntroductionofmultiplefunctionalgroupsFunctionalgrouptransformation(4)、仿照類似化合物的合成當(dāng)文獻(xiàn)資料中無現(xiàn)成的合成方法,可仿當(dāng)文獻(xiàn)資料中無現(xiàn)成的合成方法,可仿照類似化合物的合成方法進(jìn)行工藝路線照類似化合物的合成方法進(jìn)行工藝路線設(shè)計(jì)。設(shè)計(jì)。(4)Imitatingsynthesisofanalogouscompounds WhennoexistingliteratureshowssynthesisWhennoexistingliteratureshowssynthesismethod,designthesynthesismethodaccordingmethod,designthesynthesismethodaccordingtosynthesisofanalogouscompounds.tosynthesisofanalogouscompounds.2.1.2、立體化學(xué)控制與不對稱合成手性藥物在藥物中占的比重手性藥物在藥物中占的比重手性藥物災(zāi)難?手性藥物災(zāi)難?2.1.2StereochemicalcontrolandasymmetricsynthesisTheproportionofchiraldrugsinthetotaldrugChiralDrugsdisaster?(1)、)、光學(xué)異構(gòu)體的拆分光學(xué)異構(gòu)體的拆分a.非對映異構(gòu)體結(jié)晶拆分法非對映異構(gòu)體結(jié)晶拆分法利用消旋體的化學(xué)性質(zhì)使其與某一利用消旋體的化學(xué)性質(zhì)使其與某一光學(xué)光學(xué)活性試劑活性試劑(即光學(xué)拆分劑)作用以生成(即光學(xué)拆分劑)作用以生成兩種非對映的異構(gòu)體,然后利用這兩種兩種非對映的異構(gòu)體,然后利用這兩種物質(zhì)的非對映性所產(chǎn)生的物質(zhì)的非對映性所產(chǎn)生的某些理化性質(zhì)某些理化性質(zhì)的差異,將其分離,再脫去拆分劑,便的差異,將其分離,再脫去拆分劑,便可得到左旋體和右旋體。可得到左旋體和右旋體。(1 1)ResolutionofopticalisomersResolutionofopticalisomersa.diastereomericcrystalresolutionmethoda.diastereomericcrystalresolutionmethodusingthechemicalnatureofracemate,actwithanusingthechemicalnatureofracemate,actwithanopticallyactivereagent(i.e.,theopticalresolutionopticallyactivereagent(i.e.,theopticalresolutionagent)togeneratetwodiastereomericisomers.Thenagent)togeneratetwodiastereomericisomers.Thenusethedifferencesofphysicalandchemicalpropertiesusethedifferencesofphysicalandchemicalpropertiesbetweenthetowsubstancestoseparatethem.Finally,betweenthetowsubstancestoseparatethem.Finally,getridofresolvingagent,youcangetlevoanddextral.getridofresolvingagent,youcangetlevoanddextral.b.誘導(dǎo)結(jié)晶拆分法此法系在消旋體過飽和溶液中加入其中此法系在消旋體過飽和溶液中加入其中一種(左旋或右旋)純的單旋體結(jié)晶作一種(左旋或右旋)純的單旋體結(jié)晶作為為晶種晶種,則晶體成長并先析出同種旋光,則晶體成長并先析出同種旋光體的結(jié)晶,迅速過濾,再加入一定量的體的結(jié)晶,迅速過濾,再加入一定量的消旋體,則溶液中的另一種對映體達(dá)到消旋體,則溶液中的另一種對映體達(dá)到飽和,冷卻,該單旋體便結(jié)晶析出。飽和,冷卻,該單旋體便結(jié)晶析出。b.Inducedcrystallizationresolutionmethod Thismethodistoadda(LorD)puresinglespinThismethodistoadda(LorD)puresinglespincrystalasaseed.Thecrystalsgrowandcrystalasaseed.Thecrystalsgrowandprecipitationofthesamekindsofopticallyactiveprecipitationofthesamekindsofopticallyactivecrystalsprecipitate.Rapidlyfiltered,andthenaddcrystalsprecipitate.Rapidlyfiltered,andthenaddacertainamountofracemate,anotherenantiomeracertainamountofracemate,anotherenantiomerinthesolutionsaturates.Aftercooling,thesingleinthesolutionsaturates.Aftercooling,thesinglespincrystalisobtained.spincrystalisobtained.(2)、不對稱轉(zhuǎn)化)、不對稱轉(zhuǎn)化不對稱轉(zhuǎn)化是指光學(xué)不穩(wěn)定的一對消旋不對稱轉(zhuǎn)化是指光學(xué)不穩(wěn)定的一對消旋體,在某種手性的影響下,受到體,在某種手性的影響下,受到立體化立體化學(xué)學(xué)的不均一作用,在這兩種光學(xué)異構(gòu)體的不均一作用,在這兩種光學(xué)異構(gòu)體的立體構(gòu)型達(dá)到平衡以前,發(fā)生了的立體構(gòu)型達(dá)到平衡以前,發(fā)生了向一向一方轉(zhuǎn)化方轉(zhuǎn)化的變化現(xiàn)象。這種不對稱轉(zhuǎn)化可的變化現(xiàn)象。這種不對稱轉(zhuǎn)化可以認(rèn)為是與差向異構(gòu)體相同的構(gòu)型變化以認(rèn)為是與差向異構(gòu)體相同的構(gòu)型變化現(xiàn)象?,F(xiàn)象。(2)Asymmetrictransformation AsymmetrictransformationreferstoapairofAsymmetrictransformationreferstoapairofopticalinstabilityracemates,undersomechiralopticalinstabilityracemates,undersomechiralinfluence,affectedbytheuneveneffectofinfluence,affectedbytheuneveneffectofstereochemistry,conversetoonesidepriortostereochemistry,conversetoonesidepriortoequilibriumofthethree-dimensionalequilibriumofthethree-dimensionalconfigurationofthetwoopticalisomers.Thisconfigurationofthetwoopticalisomers.Thisasymmetrictransformationcanbeconsideredasymmetrictransformationcanbeconsideredidenticalwiththephenomenonofepimericidenticalwiththephenomenonofepimericconfigurationchange.configurationchange.(3)、不對稱誘導(dǎo))、不對稱誘導(dǎo)發(fā)生不對稱誘導(dǎo)的因素有物理的和化學(xué)發(fā)生不對稱誘導(dǎo)的因素有物理的和化學(xué)的兩種。的兩種。物理因素:利用物理因素:利用圓偏光圓偏光等手性物理力的等手性物理力的作用。作用?;瘜W(xué)因素:反應(yīng)物本身、手性催化劑、化學(xué)因素:反應(yīng)物本身、手性催化劑、手性試劑、手性溶劑。手性試劑、手性溶劑。(3)Asymmetricinduction AsymmetricinductionoccursundertheAsymmetricinductionoccursunderthephysicalandchemistryfactors.physicalandchemistryfactors.Physicalfactors:theuseofcircularlypolarizedPhysicalfactors:theuseofcircularlypolarizedlight,suchaschiralphysicalforce.light,suchaschiralphysicalforce.Chemicalfactors:thereactionitself,chiralChemicalfactors:thereactionitself,chiralcatalysts,chiralreagents,chiralsolventcatalysts,chiralreagents,chiralsolvent(4)、不對稱合成)、不對稱合成不對稱合成系指手性分子或前手性分子不對稱合成系指手性分子或前手性分子在形成新的手性中心的反應(yīng)過程中,占在形成新的手性中心的反應(yīng)過程中,占優(yōu)勢的生成某一優(yōu)勢的生成某一立體構(gòu)型立體構(gòu)型產(chǎn)物,而其非產(chǎn)物,而其非對映異構(gòu)體的生成量卻很少。對映異構(gòu)體的生成量卻很少。a.利用手性試劑利用手性試劑b.利用微生物的手性合成利用微生物的手性合成c.利用手性催化劑利用手性催化劑(4)Asymmetricsynthesis AsymmetricsynthesisreferstochiralorAsymmetricsynthesisreferstochiralorprochiralmoleculesformeddominantlyaprochiralmoleculesformeddominantlyastereochemistryproductduringthereactionofstereochemistryproductduringthereactionofnewchiralcenter,butlessitsisomersgeneratenewchiralcenter,butlessitsisomersgeneratea.useofchiralreagentsa.useofchiralreagentsb.useofchiralsynthesisofmicroorganismsb.useofchiralsynthesisofmicroorganismsc.usingachiralcatalystc.usingachiralcatalyst2.1.3、工藝路線的選擇、工藝路線的選擇要考慮的因素要考慮的因素(1)原輔材料供應(yīng)原輔材料供應(yīng)(2)合成步驟、操作方法與收率合成步驟、操作方法與收率(3)單元反應(yīng)的次序安排單元反應(yīng)的次序安排(4)技術(shù)條件與設(shè)備要求技術(shù)條件與設(shè)備要求(5)安全生產(chǎn)與環(huán)境保護(hù)安全生產(chǎn)與環(huán)境保護(hù)2.1.3、ProcessrouteselectionFactorstobeconsideredFactorstobeconsidered(1)rawmaterialsupply(1)rawmaterialsupply(2)synthesisstep,methodsofoperationandthe(2)synthesisstep,methodsofoperationandtheyieldyield(3)arrangementofthereactionunit(3)arrangementofthereactionunit(4)technicalconditionsandequipment(4)technicalconditionsandequipmentrequirementsrequirements(5)safetyandenvironmentalprotection(5)safetyandenvironmentalprotection2.1.42.1.4、工藝路線的改革和新反應(yīng)、工藝路線的改革和新反應(yīng)(1 1)、相轉(zhuǎn)移催化反應(yīng))、相轉(zhuǎn)移催化反應(yīng))、相轉(zhuǎn)移催化反應(yīng))、相轉(zhuǎn)移催化反應(yīng) 過程:過程:過程:過程:七十年代以來,發(fā)展了一種新的有機(jī)試劑,在七十年代以來,發(fā)展了一種新的有機(jī)試劑,在七十年代以來,發(fā)展了一種新的有機(jī)試劑,在七十年代以來,發(fā)展了一種新的有機(jī)試劑,在均勻相反應(yīng)中,它能使均勻相反應(yīng)中,它能使均勻相反應(yīng)中,它能使均勻相反應(yīng)中,它能使水相水相水相水相中的反應(yīng)物順利轉(zhuǎn)中的反應(yīng)物順利轉(zhuǎn)中的反應(yīng)物順利轉(zhuǎn)中的反應(yīng)物順利轉(zhuǎn)入入入入有機(jī)相有機(jī)相有機(jī)相有機(jī)相。效果:效果:效果:效果:改變了離子的改變了離子的改變了離子的改變了離子的溶劑化程度溶劑化程度溶劑化程度溶劑化程度,增大離子,增大離子,增大離子,增大離子反反反反應(yīng)應(yīng)應(yīng)應(yīng)活性,加快反應(yīng)速度,簡化處理手續(xù)?;钚?,加快反應(yīng)速度,簡化處理手續(xù)。活性,加快反應(yīng)速度,簡化處理手續(xù)。活性,加快反應(yīng)速度,簡化處理手續(xù)。這種試劑稱為相轉(zhuǎn)移催化劑。這類新的合成方這種試劑稱為相轉(zhuǎn)移催化劑。這類新的合成方這種試劑稱為相轉(zhuǎn)移催化劑。這類新的合成方這種試劑稱為相轉(zhuǎn)移催化劑。這類新的合成方法稱為相轉(zhuǎn)移催化反應(yīng)。法稱為相轉(zhuǎn)移催化反應(yīng)。法稱為相轉(zhuǎn)移催化反應(yīng)。法稱為相轉(zhuǎn)移催化反應(yīng)。常用的催化劑有常用的催化劑有常用的催化劑有常用的催化劑有鎓鹽和大環(huán)多醚鎓鹽和大環(huán)多醚鎓鹽和大環(huán)多醚鎓鹽和大環(huán)多醚兩大類。兩大類。兩大類。兩大類。2.1.42.1.4ReformofprocessrouteandthenewReformofprocessrouteandthenewreactionreaction(1 1)PhasetransfercatalysisPhasetransfercatalysisProcess:Process:Sincethe1970s,anovelorganicreagentwasdeveloped.InaSincethe1970s,anovelorganicreagentwasdeveloped.Inahomogeneousphasereaction,itenablestheaqueousphasetohomogeneousphasereaction,itenablestheaqueousphasetosmoothlygointotheorganicphasereaction.smoothlygointotheorganicphasereaction.Effects:changethesolvationdegreeofions,increasingtheionEffects:changethesolvationdegreeofions,increasingtheionreactivity,speeduptheresponse,simplifyprocedures.reactivity,speeduptheresponse,simplifyprocedures.Thisreagentiscalledaphasetransfercatalyst.SuchnewsyntheticThisreagentiscalledaphasetransfercatalyst.Suchnewsyntheticmethodiscalledphasetransfercatalysis.methodiscalledphasetransfercatalysis.Catalystscommonlyusedarethetwocategories,catalystssaltandCatalystscommonlyusedarethetwocategories,catalystssaltandmacrocyclicpolyether.macrocyclicpolyether.(2 2)微生物催化(酶催化)反應(yīng))微生物催化(酶催化)反應(yīng)a.酶催化反應(yīng)的特點(diǎn)酶催化反應(yīng)的特點(diǎn)酶具有高度的催化活性酶具有高度的催化活性酶催化作用具有高度的專一性酶催化作用具有高度的專一性催化反應(yīng)條件溫和催化反應(yīng)條件溫和(2)Microbialcatalysis(enzymatic)reactionsa.Charactersofenzyme-catalyzedreactionsEnzymeswithhighcatalyticactivityEnzymecatalysiswithhighspecificityCatalyticreactionundermildconditionsb.酶催化反應(yīng)的影響因素溫度溫度pH抑制劑和激活劑抑制劑和激活劑其它因素:其它因素:X射線、紫外線照射射線、紫外線照射b.Factorsaffectingtheenzyme-catalyzedreactionsTemperaturepHInhibitorsandinducersOtherfactors:Xray、UVc.c.微生物(酶)的固定化微生物(酶)的固定化固定化酶仍具有高度的專一性、高效、反應(yīng)條固定化酶仍具有高度的專一性、高效、反應(yīng)條固定化酶仍具有高度的專一性、高效、反應(yīng)條固定化酶仍具有高度的專一性、高效、反應(yīng)條件溫和的特點(diǎn),還可連續(xù)化生產(chǎn),產(chǎn)物容易分件溫和的特點(diǎn),還可連續(xù)化生產(chǎn),產(chǎn)物容易分件溫和的特點(diǎn),還可連續(xù)化生產(chǎn),產(chǎn)物容易分件溫和的特點(diǎn),還可連續(xù)化生產(chǎn),產(chǎn)物容易分離,收率高,使用批次多,貯藏時(shí)間長。離,收率高,使用批次多,貯藏時(shí)間長。離,收率高,使用批次多,貯藏時(shí)間長。離,收率高,使用批次多,貯藏時(shí)間長。如何制備固定化酶如何制備固定化酶如何制備固定化酶如何制備固定化酶?固定化酶的制備固定化酶的制備吸附法吸附法載體偶聯(lián)法載體偶聯(lián)法交聯(lián)法交聯(lián)法包埋法包埋法c.c.Microorganisms(enzymes)immobilizationFeaturesofimmobilizedenzyme:ahighdegreeofFeaturesofimmobilizedenzyme:ahighdegreeofspecificity,efficiency,mildreactionconditions,specificity,efficiency,mildreactionconditions,continuousproduction,theproductiseasytoseparate,continuousproduction,theproductiseasytoseparate,highyield,multi-usebatch,longstoragetime.highyield,multi-usebatch,longstoragetime.Howtopreparetheimmobilizedenzyme?Howtopreparetheimmobilizedenzyme?PreparationoftheimmobilizedenzymeAdsorptionVectorcouplingmethodCrosslinkingmethodEmbedding最新進(jìn)展最新進(jìn)展微波合成微波合成離子液體離子液體作業(yè):作業(yè):離子液體的機(jī)制及進(jìn)展(離子液體的機(jī)制及進(jìn)展(10003000字)字)ThelasteddevelopmentsMicrowaveSynthesisIonicliquidsHomework:MechanismandProgressofionicliquids(1000-3000words)離子液體離子液體定義定義定義定義:離子液體是一批在室溫下完全由離子組成的有機(jī)液體物質(zhì):離子液體是一批在室溫下完全由離子組成的有機(jī)液體物質(zhì):離子液體是一批在室溫下完全由離子組成的有機(jī)液體物質(zhì):離子液體是一批在室溫下完全由離子組成的有機(jī)液體物質(zhì)特性:特性:特性:特性:無蒸氣壓、可取代揮發(fā)性有機(jī)溶劑、可循環(huán)使用無蒸氣壓、可取代揮發(fā)性有機(jī)溶劑、可循環(huán)使用無蒸氣壓、可取代揮發(fā)性有機(jī)溶劑、可循環(huán)使用無蒸氣壓、可取代揮發(fā)性有機(jī)溶劑、可循環(huán)使用應(yīng)用領(lǐng)域:應(yīng)用領(lǐng)域:應(yīng)用領(lǐng)域:應(yīng)用領(lǐng)域:分離工程分離工程分離工程分離工程:氣體吸收劑和液體萃取劑;:氣體吸收劑和液體萃取劑;:氣體吸收劑和液體萃取劑;:氣體吸收劑和液體萃取劑;反應(yīng)反應(yīng)反應(yīng)反應(yīng):在化學(xué)反應(yīng)中作反應(yīng)介質(zhì)或作為催化劑;:在化學(xué)反應(yīng)中作反應(yīng)介質(zhì)或作為催化劑;:在化學(xué)反應(yīng)中作反應(yīng)介質(zhì)或作為催化劑;:在化學(xué)反應(yīng)中作反應(yīng)介質(zhì)或作為催化劑;電化學(xué)電化學(xué)電化學(xué)電化學(xué):作電解質(zhì)等。:作電解質(zhì)等。:作電解質(zhì)等。:作電解質(zhì)等。離子液體符合綠色化學(xué)的原則,因而被稱為綠色溶劑。離子液體符合綠色化學(xué)的原則,因而被稱為綠色溶劑。離子液體符合綠色化學(xué)的原則,因而被稱為綠色溶劑。離子液體符合綠色化學(xué)的原則,因而被稱為綠色溶劑。IonicliqiudsDefinition:Definition:IonicliquidsareagroupoforganicliquidsubstanceIonicliquidsareagroupoforganicliquidsubstanceconsistedentirelyofionsatroomtemperatureconsistedentirelyofionsatroomtemperatureFeatures:Features:novaporpressure,canreplaceavolatileorganicsolvent,novaporpressure,canreplaceavolatileorganicsolvent,canberecycledcanberecycledApplicationareas:Applicationareas:SeparationEngineering:gasabsorbentandliquidextractionagent;SeparationEngineering:gasabsorbentandliquidextractionagent;Reaction:asareactionmediumoracatalystinachemicalreaction;Reaction:asareactionmediumoracatalystinachemicalreaction;Electrochemistry:aselectrolytes.Electrochemistry:aselectrolytes.Ionicliquidsconformtotheprinciplesofgreenchemistry,whichisIonicliquidsconformtotheprinciplesofgreenchemistry,whichiscalledgreensolvents.calledgreensolvents.第二節(jié)、化學(xué)制藥反應(yīng)器結(jié)構(gòu)、第二節(jié)、化學(xué)制藥反應(yīng)器結(jié)構(gòu)、性能及傳遞參數(shù)性能及傳遞參數(shù)SectionIIChemicalandpharmaceuticalreactorconfiguration,performance,andpassingparameters制藥工業(yè)中反應(yīng)器是反應(yīng)合成過程的核制藥工業(yè)中反應(yīng)器是反應(yīng)合成過程的核心設(shè)備,其性能由以下方面決定:心設(shè)備,其性能由以下方面決定:(1)反應(yīng)器的傳遞特性)反應(yīng)器的傳遞特性(2)反應(yīng)器的設(shè)計(jì)與放大)反應(yīng)器的設(shè)計(jì)與放大(3)反應(yīng)器的優(yōu)化與控制)反應(yīng)器的優(yōu)化與控制反應(yīng)器主要包括攪拌釜式反應(yīng)器、固定反應(yīng)器主要包括攪拌釜式反應(yīng)器、固定床式反應(yīng)器等。床式反應(yīng)器等。IntheInthepharmaceuticalindustry,thesynthesispharmaceuticalindustry,thesynthesisreactorisareactorisacorecoredevicedeviceinreactionprocess.Theinreactionprocess.Theperformanceperformanceisdeterminedbythefollowingisdeterminedbythefollowingaspects:aspects:(1)Transfer(1)Transfercharacteristicscharacteristicsoftheofthereactorreactor(2)Reactordesignandamplification(2)Reactordesignandamplification(3)(3)ReactorReactoroptimizationandcontroloptimizationandcontrolThereactorincludesastirredtankreactors,Thereactorincludesastirredtankreactors,fixedbedfixedbedreactorsandsoon.reactorsandsoon.2.2.12.2.1、攪拌釜式反應(yīng)器、攪拌釜式反應(yīng)器2.2.1.1、常用攪拌器、常用攪拌器低黏度流體的攪拌器:漿式、渦輪式、低黏度流體的攪拌器:漿式、渦輪式、三葉后掠式、布魯馬金式等。三葉后掠式、布魯馬金式等。高黏度流體的攪拌器:錨式、門式、鏍高黏度流體的攪拌器:錨式、門式、鏍帶式等。帶式等。2.2.1Stirredtankreactor2.2.1.1、CommonstirrerLowviscosityfluidagitator:paddle,turbine,swept-backclover,Burumagoldtypeandsoon.High-viscosityfluidmixer:anchor,gantry,screwtapeandsoon.2.2.1.22.2.1.2、評價(jià)攪拌操作特性的參數(shù)、評價(jià)攪拌操作特性的參數(shù)性能參數(shù)性能參數(shù)性能參數(shù)性能參數(shù):攪拌雷諾數(shù)攪拌雷諾數(shù)攪拌雷諾數(shù)攪拌雷諾數(shù)ReRe排量排量排量排量QQd d循環(huán)流量循環(huán)流量循環(huán)流量循環(huán)流量QcQc排量數(shù)排量數(shù)排量數(shù)排量數(shù)NqdNqd循環(huán)量數(shù)循環(huán)量數(shù)循環(huán)量數(shù)循環(huán)量數(shù)NqeNqe翻轉(zhuǎn)次數(shù)翻轉(zhuǎn)次數(shù)翻轉(zhuǎn)次數(shù)翻轉(zhuǎn)次數(shù)NtNt循環(huán)次數(shù)循環(huán)次數(shù)循環(huán)次數(shù)循環(huán)次數(shù)NcNc剪切數(shù)剪切數(shù)剪切數(shù)剪切數(shù)NsNs單位體積攪拌功率單位體積攪拌功率單位體積攪拌功率單位體積攪拌功率PvPv功率數(shù)功率數(shù)功率數(shù)功率數(shù)NpNp混合時(shí)間數(shù)混合時(shí)間數(shù)混合時(shí)間數(shù)混合時(shí)間數(shù)TmTm混合效率數(shù)混合效率數(shù)混合效率數(shù)混合效率數(shù)CeCe漿端線速度漿端線速度漿端線速度漿端線速度U Ui i2.2.1.2、ParametersforevaluationofstirredoperatingcharacteristicsPerformanceparameters:Performanceparameters:StirringReynoldsnumberStirringReynoldsnumberRe,DisplacementRe,DisplacementQdQdDisplacementDisplacementofcirculationofcirculationflowflowQc,DisplacementnumberQc,DisplacementnumberNqdNqdCirculatingvolumenumberCirculatingvolumenumberNqeTheNqeThenumbernumberofturnsNtofturnsNtCyclesNcTheCyclesNcThenumbernumberofcutNsofcutNsStirringpowerperunitvolumePvStirringpowerperunitvolumePvPowernumberNpPowernumberNpMixingMixingtimeTmtimeTmTheThen numberumberofmixingefficiencyofmixingefficiency CeCeSpeedofpulpSpeedofpulpendlineendlineUiUi問題問題:誘導(dǎo)流量誘導(dǎo)流量Qi與排量有什么區(qū)別與排量有什么區(qū)別?Tm表示達(dá)到規(guī)定的混合均勻度攪拌器需要表示達(dá)到規(guī)定的混合均勻度攪拌器需要旋轉(zhuǎn)的圈數(shù)旋轉(zhuǎn)的圈數(shù).Tm大好還是小好大好還是小好?Tm在什么條件下是常數(shù)在什么條件下是常數(shù)?Ce是能耗是能耗Wv和和(m/)之積之積,大好還是小好大好還是小好?Questions:WhatWhatistheisthedifferencebetweeninducedflowdifferencebetweeninducedflowQiQiandanddisplacement?displacement?TmrepresentsthenumberTmrepresentsthenumberofturnsofofturnsofrotationrotationinordertoinordertoachieveachievetherequireddegreeofhomogeneity.therequireddegreeofhomogeneity.TmTmgreatorgreatorsmall,whichissmall,whichisgood?good?TmisconstantTmisconstantunderunderwhatconditions?whatconditions?CeisCeistheprductofthetheprductoftheenergyWvandenergyWvand(mm/),),greatorgreatorsmall,whichsmall,whichisgoodisgood?CeCe是能耗是能耗是能耗是能耗WWv v和和和和(mm/)之積之積之積之積,大好還是小好大好還是小好大好還是小好大好還是小好?2.2.1.32.2.1.3、攪拌器的混合性能攪拌器的混合性能宏觀混合宏觀混合:機(jī)械攪拌機(jī)械攪拌微觀混合微觀混合:分子擴(kuò)散分子擴(kuò)散對低粘度流體和高粘度流體二者之間的對低粘度流體和高粘度流體二者之間的相互作用是什么相互作用是什么?2.2.1.3、MixingperformanceofstirrerMacromixingMacromixing:mechanicalagitation:mechanicalagitation Micromixing:moleculardiffusionMicromixing:moleculardiffusionWhatistheinteractionbetweenthelowWhatistheinteractionbetweenthelowviscosityviscosityfluidsfluidsandhighviscosityandhighviscosityfluids?fluids?2.2.1.42.2.1.4、攪拌器的功率消耗、攪拌器的功率消耗攪拌功率是軸功率,主要有以下攪拌功率是軸功率,主要有以下4種影響因素:種影響因素:(1)與葉輪與有關(guān)的因素,如葉輪直徑、葉寬、)與葉輪與有關(guān)的因素,如葉輪直徑、葉寬、傾角、轉(zhuǎn)速傾角、轉(zhuǎn)速(2)與攪拌槽有關(guān)的因素,如槽形、槽徑、液)與攪拌槽有關(guān)的因素,如槽形、槽徑、液深、擋板數(shù)、擋板寬深、擋板數(shù)、擋板寬(3)被攪拌液體的性質(zhì),密度、黏度)被攪拌液體的性質(zhì),密度、黏度(4)重力加速度)重力加速度攪拌功率與什么有關(guān)系攪拌功率與什么有關(guān)系?2.2.1.42.2.1.4、ThepowerconsumptionofthestirrerThepowerconsumptionofthestirrerStirringpowerStirringpowerisisshaftpower.Therearemainlyfourshaftpower.Therearemainlyfour kindsofkindsoffactorsaffectingthepower:factorsaffectingthepower:(1)(1)Factorsrelatedtotheimpeller-,Factorsrelatedtotheimpeller-,suchastheimpellersuchastheimpellerdiameter,leafwidth,diameter,leafwidth,angleandangleandspeedspeed(2)(2)FactorsFactorsrelatedtothemixingtank,suchasthegroove,therelatedtothemixingtank,suchasthegroove,thegroovediameter,liquiddepth,numberofbaffles,bafflewidthgroovediameter,liquiddepth,numberofbaffles,bafflewidth(3)(3)Thecharacteristic,densityandviscosityofThecharacteristic,densityandviscosityoftheliquidbeingtheliquidbeingstirredstirred(4)thegravitationalacceleration4)thegravitationalaccelerationWhattherelationshipiswithmixingpower?Whattherelationshipiswithmixingpower?攪拌功率可按下式計(jì)算:攪拌功率可按下式計(jì)算:P=N3d5NpN轉(zhuǎn)速轉(zhuǎn)速Np與葉輪及攪拌釜的尺寸及幾何形狀有關(guān)與葉輪及攪拌釜的尺寸及幾何形狀有關(guān)Stirringpowercanbecalculatedusingthisequation:P=N3d5NpNSpeedNpisrelatedtothesizeandgeometricshapeofstirredtank2.2.1.52.2.1.5、攪拌釜式反應(yīng)器的傳熱、攪拌釜式反應(yīng)器的傳熱攪拌釜包括夾套、內(nèi)構(gòu)件等傳熱元件。攪拌釜包括夾套、內(nèi)構(gòu)件等傳熱元件。夾套包括環(huán)形、帶擾流噴嘴的環(huán)形夾套、夾套包括環(huán)形、帶擾流噴嘴的環(huán)形夾套、螺旋擋板夾套、半管螺旋夾套。螺旋擋板夾套、半管螺旋夾套。同樣的體積,夾套傳熱面積與釜徑的關(guān)系同樣的體積,夾套傳熱面積與釜徑的關(guān)系?2.2.1.5、HeattransferofstirredtankreactorStirredStirredtankincludessheathtankincludessheath,theinnermembertheinnermemberandsoon.andsoon.SheathSheathincludesincludesringsheath,sheathwithringsheath,sheathwithspoilerspoilernozzle,spiralbafflenozzle,spiralbafflesheath,sheath,half-pipespiralhalf-pipespiralsheath.sheath.Thesamevolume,Thesamevolume,whatiswhatistherelationshiptherelationshipbetweenthebetweentheheattransferareaofsheathandheattransferareaofsheathanddiameter?diameter?內(nèi)構(gòu)件盤管和直管是最常用的。盤管和直管是最常用的。D擋板、發(fā)夾形管和板式管組也屬直管型擋板、發(fā)夾形管和板式管組也屬直管型傳熱內(nèi)構(gòu)件傳熱內(nèi)構(gòu)件InnermembersThecoilandstraightpipesarecommonlyused.Dbaffleplate,hairpin-shapedtubeandpipegroupalsofallswithinthestraighttube-type,heattransfermember.HowtocalculatetheheatflowrateLearnedfromPrinciplesLearnedfromPrinciplesofChemicalofChemicalEngineeringEngineeringProblem:Problem:Howtochoosethematerialofthereactor?Howtochoosethematerialofthereactor?Stainlesssteel(304,acid:316L)Stainlesssteel(304,acid:316L)Glass-linedGlass-linedPleasecheckoutPleasecheckoutwhatmaterialsarethewhatmaterialsarethefluoride-fluoride-resistantresistantmaterials?materials?制藥合成過程中的反應(yīng)有哪些特點(diǎn)?制藥合成過程中的反應(yīng)有哪些特點(diǎn)?你知道的高壓反應(yīng)有哪些?你知道的高壓反應(yīng)有哪些?Whatarethefeaturesinpharmaceuticalsynthesisreaction?Whichhigh-pressurereactionsyouknow?壓力容器分類標(biāo)準(zhǔn)壓力容器分類標(biāo)準(zhǔn)壓力容器是內(nèi)部或外部承受氣體或液體壓力、壓力容器是內(nèi)部或外部承受氣體或液體壓力、并對安全性有較高要求的密封容器。并對安全性有較高要求的密封容器。壓力容器主要為圓柱形,少數(shù)為球形或其他形壓力容器主要為圓柱形,少數(shù)為球形或其他形狀。狀。圓柱形壓力容器通常由筒體、封頭、接管、法圓柱形壓力容器通常由筒體、封頭、接管、法蘭等零件和部件組成,壓力容器工作壓力越高,蘭等零件和部件組成,壓力容器工作壓力越高,筒體的壁就應(yīng)越厚。筒體的壁就應(yīng)越厚。壓力容器分類標(biāo)準(zhǔn)壓力容器分類標(biāo)準(zhǔn)(四類四類):PressurevesselclassificationcriteriaThepressurevesselThepressurevesselisasealingcontainerwhichisisasealingcontainerwhichisexposedexposedtoagasorliquidundertoagasorliquidunderpressureinsidepressureinsideoroutsideoroutsidewithhighwithhighsafetysafetyrequirements.requirements.TheThemainpressuremainpressurevesselsarevesselsarecylindrical,cylindrical,fewaresphericalfewaresphericalorotherorothershape.shape.AAcylindricalpressurevesselcylindricalpressurevesselusuallyusuallyconsistsofconsistsofcylindercylinder,head,receivership,flangesandotherpartsandhead,receivership,flangesandotherpartsandcomponents.Thecomponents.Thehigherworkingpressureofthepressurehigherworkingpressureofthepressurevessel,vessel,thethickercylinderthethickercylinderwallsshouldwallsshouldbe.be.Pressurevesselclassificationcriteria(fourPressurevesselclassificationcriteria(four):):1、按容器的壓力等級分類、按容器的壓力等級分類 壓力容器可分為內(nèi)壓容器與外壓容器。壓力容器可分為內(nèi)壓容器與外壓容器。壓力容器可分為內(nèi)壓容器與外壓容器。壓力容器可分為內(nèi)壓容器與外壓容器。內(nèi)壓容器又可按設(shè)計(jì)壓力(內(nèi)壓容器又可按設(shè)計(jì)壓力(內(nèi)壓容器又可按設(shè)計(jì)壓力(內(nèi)壓容器又可按設(shè)計(jì)壓力(p p p p)大小分為四個)大小分為四個)大小分為四個)大小分為四個壓力等級,具體劃分如下:壓力等級,具體劃分如下:壓力等級,具體劃分如下:壓力等級,具體劃分如下:低壓低壓低壓低壓(代號代號代號代號L)L)L)L)容器容器容器容器 0.1 MPa p 1.6 MPa;0.1 MPa p 1.6 MPa;0.1 MPa p 1.6 MPa;0.1 MPa p 1.6 MPa;中壓中壓中壓中壓(代號代號代號代號M)M)M)M)容器容器容器容器 1.6 MPa p 10.0 MPa;1.6 MPa p 10.0 MPa;1.6 MPa p 10.0 MPa;1.6 MPa p 10.0 MPa;高壓高壓高壓高壓(代號代號代號代號H)H)H)H)容器容器容器容器 10.0MPa p 100 MPa;
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