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Imveliso eyongezelelweyo iyayitshintsha indlela abaphandi kunye nosomashishini abayila kwaye benze izixhobo zekhemikhali ukuhlangabezana neemfuno zabo ezithile.Kweli phepha, sichaza umzekelo wokuqala we-reactor flow reactor eyenziwe yi-ultrasonic additive production (UAM) i-lamination yeshiti eliqinileyo lesinyithi kunye neengxenye ze-catalytic ezidibeneyo kunye nezinto zokuva.Itekhnoloji ye-UAM ayisoyisi nje kuphela imida emininzi ngoku enxulunyaniswa nokuveliswa okongeziweyo kweereactors zemichiza, kodwa ikwandisa kakhulu amandla ezixhobo ezinjalo.Inani lezinto eziphilayo ezibalulekileyo ze-1,4-disubstituted i-1,2,3-triazole i-compounds yenziwe ngempumelelo kwaye iphuculwe yi-Cu-mediated 1,3-dipolar Huisgen cycloaddition reaction usebenzisa i-UAM chemistry facility.Ukusebenzisa iipropathi ezizodwa ze-UAM kunye nokuqhubela phambili kokuhamba, isixhobo siyakwazi ukuvuselela ukuphendula okuqhubekayo kunye nokubonelela ngengxelo yexesha langempela ukubeka iliso kunye nokwandisa ukuphendula.
Ngenxa yeenzuzo zayo ezibalulekileyo ngaphezu komlingani wayo obuninzi, ikhemistri ejikelezayo ibalulekile kwaye ikhula intsimi kuzo zombini iimeko zemfundo kunye nezoshishino ngenxa yokukwazi ukunyusa ukukhethwa kunye nokusebenza kakuhle kwe-chemical synthesis.Oku kudlulela ekubunjweni kwee-molecule ezilula ze-organic1 ukuya kwi-pharmaceutical compounds2,3 kunye neemveliso zendalo4,5,6.Ngaphezulu kwe-50% yeempendulo kwimizi-mveliso emihle yeekhemikhali kunye neyoxubo-mayeza inokuxhamla ekuhambeni ngokuqhubekayo7.
Kwiminyaka yakutshanje, kuye kwakho umkhwa okhulayo wamaqela afuna ukubuyisela izixhobo zeglasi zesiqhelo okanye izixhobo zekhemistri eziguquguqukayo "zeeactor"8 zekhemikhali.Uyilo oluphinda-phindayo, ukuveliswa okukhawulezayo, kunye nesakhono se-3-dimensional (3D) yezi ndlela ziluncedo kwabo bafuna ukwenza izixhobo zabo ngokweseti ethile yokusabela, izixhobo, okanye iimeko.Ukuza kuthi ga ngoku, lo msebenzi ugxininise phantse ngokukodwa ekusebenziseni iindlela zoshicilelo ze-polymer-based 3D ezifana ne-stereolithography (SL) 9,10,11, i-Fused Deposition Modeling (FDM) 8,12,13,14 kunye ne-inkjet printing7,15., 16. Ukungabikho kokuthembeka kunye nokukwazi kwezixhobo ezinjalo ukwenza uluhlu olubanzi lwee-chemical reactions / analyses17, 18, 19, 20 yinkalo enkulu yokunciphisa ukusetyenziswa okubanzi kwe-AM kule ndawo17, 18, 19, 20.
Ngenxa yokwanda kokusetyenziswa kwekhemikhali yokuhamba kunye neempawu ezithandekayo ezinxulumene ne-AM, iindlela ezingcono zifuna ukuphononongwa eziya kuvumela abasebenzisi ukuba benze iinqanawa zokusabela ukuhamba ngekhemistri ephuculweyo kunye namandla okuhlalutya.Ezi ndlela kufuneka zivumele abasebenzisi ukuba bakhethe kuluhlu lwamandla aphezulu okanye izinto ezisebenzayo ezikwaziyo ukusebenza phantsi koluhlu olubanzi lweemeko zokusabela, kunye nokuququzelela iindlela ezahlukeneyo zemveliso yohlalutyo ukusuka kwisixhobo ukwenza ukubeka iliso kunye nokulawula ukusabela.
Enye inkqubo yokuvelisa ezongezelelweyo ezingasetyenziselwa ukuphuhlisa i-reactors yekhemikhali yesiko yi-Ultrasonic Additive Manufacturing (UAM).Le ndlela ye-slid-state sheet lamination method isebenzisa ii-vibrations ze-ultrasonic kwiifoil zetsimbi ezibhityileyo ukuze zibophelele kunye umaleko ngomaleko kunye nobushushu obuncinci be-volumetric kunye neqondo eliphezulu lokuhamba kweplastiki 21, 22, 23. Ngokungafaniyo nezinye iiteknoloji ze-AM, i-UAM inokudityaniswa ngokuthe ngqo kunye nemveliso ekhuphayo, eyaziwa ngokuba yinkqubo yokuvelisa i-hybrid, apho i-periodical in-situ in-situ inquma ulawulo lwe-milling2 ye-laser okanye i-bonded milling ye-laser. 25. Oku kuthetha ukuba umsebenzisi akaphelelanga kwiingxaki ezinxulumene nokususwa kwezinto ezishiyekileyo zokwakha ezivela kumajelo amancinci amancinci, ahlala ekho kwi-powder kunye ne-liquid systems AM26,27,28.Le nkululeko yoyilo iphinda ifikelele ekukhethweni kwezinto ezikhoyo - i-UAM inokudibanisa imidibaniso ye-thermal efanayo kunye nezinto ezingafaniyo kwisinyathelo esisodwa senkqubo.Ukukhethwa kwezinto ezidityanisiweyo ngaphaya kwenkqubo yokunyibilika kuthetha ukuba iimfuno zoomatshini kunye neekhemikhali zezicelo ezithile zinokufezekiswa ngcono.Ukongeza kwi-bonding eqinile, enye into eyenzekayo kunye ne-ultrasonic bonding yi-fluidity ephezulu yezinto zeplastiki kumaqondo okushisa aphantsi kakhulu29,30,31,32,33.Olu phawu lukhethekileyo lwe-UAM luvumela izinto zomatshini / ezishushu ukuba zibekwe phakathi kweengqimba zetsimbi ngaphandle komonakalo.Ii-sensor ze-UAM ezifakwe ngaphakathi zinokuququzelela ukuhanjiswa kolwazi lwexesha langempela ukusuka kwisixhobo ukuya kumsebenzisi ngokusebenzisa uhlalutyo oludibeneyo.
Umsebenzi wangaphambili ngababhali32 ubonise ukukwazi kwenkqubo ye-UAM ukwenza i-metallic 3D izakhiwo ze-microfluidic ezinesakhono sokuvalelwa.Esi sixhobo senzelwe iinjongo zokubeka iliso kuphela.Eli nqaku libonisa umzekelo wokuqala we-microfluidic chemical reactor eyenziwa yi-UAM, isixhobo esisebenzayo esingalawuli nje kuphela kodwa sikhuthaza ukuhlanganiswa kweekhemikhali kunye nezinto ezidityanisiweyo ze-catalytic.Isixhobo sidibanisa iingenelo ezininzi ezinxulumene neteknoloji ye-UAM ekwenzeni izixhobo zeekhemikhali ze-3D, ezifana: ukukwazi ukuguqula uyilo olupheleleyo lwe-3D ngokuthe ngqo kwimodeli ye-computer-aid (CAD) kwimveliso;Ukwenziwa kwezinto ezininzi zokudityaniswa komgangatho ophezulu we-thermal conductivity kunye nezixhobo ze-catalytic, kunye ne-thermal sensors ezifakwe ngokuthe ngqo phakathi kwemijelo ye-reactant yokulawula okuchanekileyo kunye nokulawulwa kobushushu bokusabela.Ukubonisa ukusebenza kwe-reactor, ilayibrari ye-pharmaceutically ebalulekileyo ye-1,4-disubstituted 1,2,3-triazole compounds yenziwe nge-copper-catalyzed 1,3-dipolar Huisgen cycloaddition.Lo msebenzi ubalaselisa indlela ukusetyenziswa kwezinto zesayensi kunye noyilo oluncediswa yikhompyuter kunokuvula amathuba amatsha kunye namathuba ekhemistri ngophando lwezifundo ezahlukeneyo.
Zonke i-solvents kunye ne-reagents zathengwa kwi-Sigma-Aldrich, i-Alfa Aesar, i-TCI, okanye i-Fischer Scientific kwaye isetyenziswe ngaphandle kokuhlanjululwa kwangaphambili.I-1H kunye ne-13C i-spectra ye-NMR erekhodwe kwi-400 kunye ne-100 MHz, ngokulandelanayo, ifunyenwe kwi-JEOL ECS-400 400 MHz spectrometer okanye i-Bruker Avance II 400 MHz spectrometer ene-CDCl3 okanye (CD3) 2SO njenge-solvent.Zonke iimpendulo zenziwa kusetyenziswa iqonga lekhemistri equkuqelayo ye-Uniqsis FlowSyn.
I-UAM yasetyenziselwa ukwenza zonke izixhobo kolu phononongo.Ithekhnoloji yasungulwa kwi-1999 kunye neenkcukacha zayo zobugcisa, iiparameters zokusebenza kunye nophuhliso ukususela ekubeni ukuveliswa kwayo kunokufundwa ngokusetyenziswa kwezinto ezipapashiweyo ezilandelayo34,35,36,37.Isixhobo (umzobo 1) siphunyezwe kusetyenziswa umsebenzi onzima we-9 kW SonicLayer 4000® UAM inkqubo (Fabrisonic, Ohio, USA).Izinto ezikhethiweyo zesixhobo sokuhamba zaziyi-Cu-110 kunye ne-Al 6061. I-Cu-110 inomxholo ophezulu wobhedu (ubuncinci be-99.9% yobhedu), okwenza ukuba ibe ngumviwa olungileyo kwiimpendulo ze-catalyzed zethusi kwaye ngoko isetyenziswe "njengomaleko osebenzayo ngaphakathi kwe-microreactor.I-Al 6061 O isetyenziswa njenge "bulk" imathiriyeli., kunye ne-intercalation layer esetyenziselwa uhlalutyo;ukudityaniswa kwamacandelo e-alloy ancedisayo kunye ne-annealed state ngokudibanisa ne-Cu-110 layer.kufunyaniswe ukuba zizinzile ngokwekhemikhali kunye nee-reagents ezisetyenziswa kulo msebenzi.I-Al 6061 O ngokudibanisa ne-Cu-110 nayo ithathwa njengendibaniselwano yezinto ezihambelanayo ze-UAM kwaye ngoko yinto efanelekileyo yolu cwaningo38,42.Ezi zixhobo zidweliswe kwiThebhile 1 ngezantsi.
Amanyathelo okwenziwa kwe-reactor (1) 6061 i-aluminium alloy substrate (2) Ukwenziwa komjelo osezantsi ukusuka kwifoyile yobhedu (3) Ukufakwa kwe-thermocouples phakathi kwamaleko (4) Umjelo oPhezulu (5) I-Inlet kunye ne-outlet (6) i-Monolithic reactor.
Ifilosofi yoyilo lomjelo we-fluid kukusebenzisa indlela eyingozi yokwandisa umgama ohanjwa lulwelo olungaphakathi kwitshiphu ngelixa ugcina ubungakanani obulawulekayo betshiphu.Oku kunyuka komgama kuyanqweneleka ukwandisa ixesha loqhagamshelwano le-catalyst-reactant kunye nokubonelela ngemveliso egqwesileyo yemveliso.Iitshiphusi zisebenzisa i-90 ° ukugoba ekupheleni kwendlela ethe tye ukuze kubangele ukuxubana kwesiphithiphithi ngaphakathi kwesixhobo44 kunye nokwandisa ixesha loqhagamshelwano lolwelo kunye nomphezulu (i-catalyst).Ukuphucula ngakumbi ukuxuba okunokuthi kuphunyezwe, uyilo lwe-reactor lubandakanya i-reactant inlets ezimbini ezidibeneyo kwi-Y-connection ngaphambi kokungena kwicandelo le-coil yokuxuba.Umnyango wesithathu, owela isiqingatha sokungena kwindawo yawo yokuhlala, ubandakanyiwe kwisicwangciso sexesha elizayo leempendulo zokudityaniswa kwamanqanaba amaninzi.
Zonke iitshaneli zineprofayili yesikweri (akukho taper angles), esisisiphumo se-periodic CNC milling esetyenziselwa ukudala ijiyometri yetshaneli.Imilinganiselo yejelo ikhethwa ukubonelela ngemveliso ephezulu (ye-microreactor) yevolumetric, kodwa incinci ngokwaneleyo ukuququzelela intsebenziswano kunye nomphezulu (i-catalysts) kuninzi lolwelo oluquletheyo.Ubungakanani obufanelekileyo busekelwe kumava adlulileyo ababhali kunye nezixhobo zokusabela kwesinyithi-ulwelo.Imilinganiselo yangaphakathi yomjelo wokugqibela ibiyi-750 µm x 750 µm kwaye umthamo wereactor uwonke ube yi-1 ml.Isidibanisi esakhelwe ngaphakathi (i-1/4 "-28 intambo ye-UNF) ifakwe kwi-design ukuvumela ukudibanisa okulula kwesixhobo kunye nezixhobo ze-chemistry flow flow.Ubungakanani bomjelo bukhawulelwe ngobunzima bezinto ze-foil, iipropathi zayo zomatshini, kunye neeparitha zokudibanisa ezisetyenziswa kunye ne-ultrasonics.Kububanzi obuthile bezinto ezinikeziweyo, izinto ziya "kuntywila" kumjelo owenziweyo.Okwangoku akukho modeli ithile yolu balo, ngoko ke obona bubanzi bobubanzi betshaneli besixhobo esinikiweyo kunye noyilo bumiselwa ngokomfuniselo, kwimeko apho ububanzi be-750 µm bungayi kubangela i-sag.
Ubume (isikwere) somjelo sinqunywe ngokusebenzisa i-square cutter.Ubume kunye nobukhulu bamashaneli bunokutshintshwa kumatshini we-CNC usebenzisa izixhobo zokusika ezahlukeneyo ukuze ufumane amazinga okuhamba kunye neempawu ezahlukeneyo.Umzekelo wokudala itshaneli egobileyo ngesixhobo se-125 µm unokufumaneka kwi-Monaghan45.Xa umgca we-foil usetyenziswe ngokucokisekileyo, ukusetyenziswa kwezinto eziphathekayo kwiitshaneli kuya kuba ne-flat (isikwere).Kulo msebenzi, i-square contour yayisetyenziselwa ukugcina i-symmetry yeshaneli.
Ngethuba lekhefu elicwangcisiweyo kwimveliso, i-thermocouple sensors yeqondo lokushisa (uhlobo K) lwakhiwe ngokuthe ngqo kwisixhobo phakathi kwamaqela angaphezulu nangaphantsi (umzobo 1 - isigaba sesi-3).Ezi thermocouples zinokulawula utshintsho lobushushu ukusuka ku -200 ukuya ku 1350 °C.
Inkqubo yokubeka isinyithi iqhutywe ngophondo lwe-UAM usebenzisa i-foil yensimbi 25.4 mm ububanzi kunye ne-150 microns ubukhulu.Ezi zingqimba ze-foil zidibaniswe kwimicu edibeneyo yokugubungela yonke indawo yokwakha;ubungakanani bemathiriyeli egciniweyo inkulu kunemveliso yokugqibela njengoko inkqubo yokuthabatha idala ukumila kokugqibela okucocekileyo.Umatshini we-CNC usetyenziselwa ukutshiza iikhonto zangaphandle kunye nezangaphakathi zesixhobo, okukhokelela ekugqityweni komphezulu wesixhobo kunye nemijelo ehambelana nesixhobo esikhethiweyo kunye neeparamitha zenkqubo ye-CNC (kulo mzekelo, malunga ne-1.6 µm Ra).Ukuqhubeka, okuqhubekayo, okuqhubekayo kwe-ultrasonic imathiriyeli yokutshiza kunye nemijikelo yomatshini isetyenziswa kuyo yonke inkqubo yokwenziwa kwesixhobo ukuqinisekisa ukuchaneka komgangatho kugcinwa kwaye inxalenye egqityiweyo idibana namanqanaba achanekileyo okugaya i-CNC.Ububanzi bomjelo osetyenzisiweyo kwesi sixhobo buncinci ngokwaneleyo ukuqinisekisa ukuba izinto ze-foil "azigugi" kumjelo wamanzi, ngoko ke umjelo unecandelo lomnqamlezo wesikwere.Izikhewu ezinokwenzeka kwizinto zefoil kunye neeparameters zenkqubo ye-UAM zichongwe ngokuvavanywa ngumlingane wokuvelisa (Fabrisonic LLC, USA).
Uphononongo lubonise ukuba kwi-interface ye-46, i-47 ye-compound ye-UAM kukho ukusabalalisa okuncinci kwezinto ngaphandle kwonyango olongezelelweyo lobushushu, ngoko ke izixhobo kulo msebenzi i-Cu-110 layer ihlala ihluke kwi-Al 6061 layer kwaye itshintsha ngokuphawulekayo.
Faka i-pre-calibrated back pressure regulator (BPR) kwi-250 psi (1724 kPa) ezantsi kwe-reactor kunye nokumpompa amanzi nge-reactor kwizinga le-0.1 ukuya kwi-1 ml min-1.Uxinzelelo lwe-reactor lubekwe esweni kusetyenziswa i-FlowSyn yoxinzelelo lwe-transducer eyakhelwe kwinkqubo yokuqinisekisa ukuba inkqubo inokugcina uxinzelelo oluqhubekayo.Iqondo lokushisa elinokubakho kwi-reactor flow reactor yavavanywa ngokujonga nawuphi na umahluko phakathi kwe-thermocouples eyakhelwe kwi-reactor kunye ne-thermocouples eyakhelwe kwi-plate yokufudumeza ye-chip ye-FlowSyn.Oku kuphunyezwa ngokutshintsha iqondo lobushushu elicwangcisiweyo phakathi kwe-100 ne-150 °C kwi-25 °C yonyuso kunye nokubeka esweni nawuphi na umahluko phakathi kwamaqondo obushushu acwangcisiweyo kunye namaqondo arekhodiweyo.Oku kwaphunyezwa kusetyenziswa i-tc-08 data logger (PicoTech, Cambridge, UK) kunye ne-software ye-PicoLog ehamba nayo.
Iimeko ze-cycloaddition reaction ye-phenylacetylene kunye ne-iodoethane ziphuculwe (I-Scheme 1-Cycloaddition ye-phenylacetylene kunye ne-iodoethane, i-Scheme 1-Cycloaddition ye-phenylacetylene kunye ne-iodoethane).Olu lungelelwaniso lwenziwe kusetyenziswa indlela epheleleyo yoyilo lwe-factorial yovavanyo (DOE), usebenzisa ubushushu kunye nexesha lokuhlala njengezinto eziguquguqukayo ngelixa ulungisa umlinganiselo we-alkyne: azide kwi-1: 2.
Izisombululo ezihlukeneyo ze-sodium azide (0.25 M, 4: 1 DMF: H2O), iodoethane (0.25 M, DMF), kunye ne-phenylacetylene (0.125 M, DMF) zalungiswa.I-aliquot ye-1.5 ml yesisombululo ngasinye yaxutywa kwaye yampontshwa nge-reactor kwinqanaba lokuhamba kunye nobushushu obufunwayo.Impendulo yemodeli ithathwe njengomlinganiselo wencopho yendawo yemveliso ye-triazole kwizinto zokuqala ze-phenylacetylene kwaye yamiselwa kusetyenziswa i-chromatography yolwelo ephezulu (HPLC).Ukuhambelana kohlalutyo, zonke iimpendulo zathathwa ngokukhawuleza emva kokuba umxube wokusabela ushiye i-reactor.Uluhlu lweparameter ekhethiweyo ukwenzela ukusebenzela luboniswe kwiThebhile yesi-2.
Zonke iisampulu zahlalutywa kusetyenziswa inkqubo yeChromaster HPLC (VWR, PA, USA) equka impompo ye-quaternary, i-oven yekholomu, i-variable wavelength UV detector kunye ne-autosampler.Ikholamu yayi-Equivalence 5 C18 (VWR, PA, USA), 4.6 x 100 mm, 5 µm ubungakanani besuntswana, igcinwe kwi-40 ° C.I-solvent yayiyi-isocratic methanol: amanzi 50:50 kwinqanaba lokuhamba kwe-1.5 ml · min-1.Umthamo wenaliti wawuyi-5 μl kunye ne-detector wavelength yayiyi-254 nm.Ummandla we-% wencopho yesampulu ye-DOE ibalwe kwiindawo eziphakamileyo zentsalela ye-alkyne kunye neemveliso ze-triazole kuphela.Ukuqaliswa kwezinto zokuqala kwenza kube lula ukuchonga iincopho ezihambelanayo.
Ukudibanisa iziphumo zohlalutyo lwe-reactor kunye nesoftware ye-MODDE DOE (i-Umetrics, i-Malmö, e-Sweden) ivumele uhlalutyo olucokisekileyo lweziphumo kunye nokumiselwa kweemeko zokusabela ezizezona zilungileyo kule cycloaddition.Ukuqhuba i-optimizer eyakhelwe-ngaphakathi kunye nokukhetha yonke imigaqo ebalulekileyo yemodeli yenza iseti yeemeko zokusabela ezenzelwe ukwandisa indawo ephezulu yemveliso ngelixa unciphisa indawo ephezulu ye-acetylene feedstock.
I-Oxidation yobhedu yobhedu kwigumbi lokuphendula i-catalytic yaphunyezwa ngokusebenzisa isisombululo se-hydrogen peroxide (36%) egeleza kwigumbi lokuphendula (izinga lokuhamba = 0.4 ml min-1, ixesha lokuhlala = 2.5 min) ngaphambi kokuhlanganiswa kwekhompawundi nganye ye-triazole.ithala leencwadi.
Emva kokuba isethi efanelekileyo yeemeko inqunywe, isetyenziswe kuluhlu lwe-acetylene kunye ne-haloalkane derivatives ukuvumela ukuqulunqwa kwelayibrari encinci ye-synthesis, ngaloo ndlela kusekwa ithuba lokusebenzisa le miqathango kuluhlu olubanzi lwee-reagents ezinokubakho (Umfanekiso 1).2).
Lungiselela izisombululo ezahlukeneyo ze-sodium azide (0.25 M, 4: 1 DMF: H2O), haloalkanes (0.25 M, DMF), kunye ne-alkynes (0.125 M, DMF).I-Aliquots ye-3 ml yesisombululo ngasinye yaxutywa kwaye yampontshelwa kwi-reactor kwireyithi ye-75 µl/min kunye nobushushu be-150 °C.Umthamo wonke uqokelelwe kwi-vial kwaye uhlanjululwe nge-10 ml ye-ethyl acetate.Isisombululo sesampuli sihlanjwe nge-3 x 10 ml yamanzi.Iingqimba ezinamanzi zidibene kwaye zikhutshwe nge-10 ml ethyl acetate, emva koko i-organic layers idibaniswe, ihlanjwe nge-3 × 10 ml ye-brine, yomiswe phezu kwe-MgSO 4 kwaye ihluzwe, ngoko i-solvent isuswe kwi-vacuo.Iisampulu zahlanjululwa nge-silica gel ikholamu yechromatography usebenzisa i-ethyl acetate ngaphambi kokuhlalutya ngokudibanisa i-HPLC, i-1H ​​NMR, i-13C NMR kunye ne-high resolution mass spectrometry (HR-MS).
Zonke ii-spectra zifunyenwe kusetyenziswa i-Thermofischer Precision Orbitrap mass spectrometer ene-ESI njengomthombo we-ionization.Zonke iisampuli zalungiswa kusetyenziswa i-acetonitrile njenge-solvent.
Uhlalutyo lwe-TLC lwenziwa kwiipleyiti ze-silica kunye ne-aluminium substrate.Amacwecwe aye abonwa ngokukhanya kwe-UV (254 nm) okanye i-vanillin staining kunye nokufudumeza.
Zonke iisampulu zahlalutywa kusetyenziswa inkqubo ye-VWR Chromaster (VWR International Ltd., Leighton Buzzard, UK) exhotywe nge-autosampler, ipompo yebhinari ene-oven yekholomu kunye ne-wavelength detector enye.Ikholamu ye-ACE Equivalence 5 C18 column (150 x 4.6 mm, Advanced Chromatography Technologies Ltd., Aberdeen, Scotland) yasetyenziswa.
Izitofu (5 µl) zenziwe ngokuthe ngqo kumxube oxutyiweyo wempendulo ekrwada (1:10 dilution) kwaye zahlalutywa ngamanzi:imethanol (50:50 okanye 70:30), ngaphandle kweesampulu ezithile zisebenzisa inkqubo yokunyibilikisa eyi-70:30 (echazwa njengenani lenkwenkwezi) kumyinge wokuqukuqela we-1.5 ml/min.Uluhlu lwalugcinwe kuma-40°C.Ubude be-detector bungama-254 nm.
Indawo ye-% yencopho yesampulu yabalwa ukusuka kwindawo ephezulu ye-alkyne eshiyekileyo, imveliso ye-triazole kuphela, kunye nokuqaliswa kwezinto zokuqala kwenze ukuba kube lula ukuchonga iincopho ezihambelanayo.
Zonke iisampuli zahlalutywa kusetyenziswa i-Thermo iCAP 6000 ICP-OES.Yonke imigangatho yokulinganisa yalungiswa ngokusebenzisa isisombululo esiqhelekileyo se-1000 ppm Cu kwi-2% ye-nitric acid (SPEX Certi Prep).Yonke imigangatho yalungiswa kwisisombululo se-5% DMF kunye ne-2% ye-HNO3, kwaye zonke iisampuli zahlanjululwa ngamaxesha angama-20 ngesisombululo sesampula se-DMF-HNO3.
I-UAM isebenzisa i-ultrasonic metal welding njengendlela yokudibanisa i-foil yensimbi esetyenziselwa ukudala indibano yokugqibela.I-ultrasonic metal welding isebenzisa isixhobo sesinyithi esishukumisayo (esibizwa ngokuba luphondo okanye uphondo lwe-ultrasonic) ukufaka uxinzelelo kwi-foil / umaleko odityanisiweyo ngaphambili ukuba udibaniswe / udityaniswe ngaphambili ngokuxubha izinto.Ukusebenza ngokuqhubekayo, i-sonotrode inesimo se-cylindrical kwaye ijikeleza phezu kwendawo yezinto eziphathekayo, idibanisa yonke indawo.Xa uxinzelelo kunye nokungcangcazela kusetyenziswe, i-oxides ebusweni bezinto eziphathekayo zinokuqhekeka.Uxinzelelo oluqhubekayo kunye nokunyakaza kunokukhokelela ekutshatyalalisweni kobunzima bezinto eziphathekayo ze-36.Uqhagamshelwano olusondeleyo kunye nobushushu bendawo kunye noxinzelelo emva koko kukhokelela kwibhondi yesigaba esiluqilima kwi-interfaces eziphathekayo;inokukhuthaza ukubambisana ngokutshintsha amandla angaphezulu48.Ubume bomatshini bokudibanisa boyisa uninzi lweengxaki ezinxulumene nobushushu obuguquguqukayo bokunyibilika kunye neziphumo zobushushu obuphezulu obukhankanywe kobunye ubugcisa bokwenza okongeziweyo.Oku kuvumela uxhulumaniso oluthe ngqo (okt ngaphandle kokuguqulwa komphezulu, iifayili okanye i-adhesives) yeeleya ezininzi zezinto ezahlukeneyo kwisakhiwo esisodwa esidityanisiweyo.
Inqaku lesibini elincomekayo leCAM liqondo eliphezulu lokuhamba kweplastiki kwimathiriyeli yesinyithi nakumaqondo obushushu aphantsi, oko kukuthi, ngaphantsi kwendawo yokunyibilika yemathiriyeli yesinyithi.Ukudibanisa kwee-vibrations ze-ultrasonic kunye noxinzelelo lubangela umgangatho ophezulu wokufuduka komda wengqolowa wendawo kunye nokuhlaziywa kwakhona ngaphandle kokunyuka okukhulu kweqondo lokushisa ngokwesiko elihambelana nezinto ezininzi.Ngethuba lokudalwa kwendibano yokugqibela, le nto ingasetyenziselwa ukubethelela amacandelo asebenzayo kunye ne-passive phakathi kweengqimba ze-foil yensimbi, i-layer by layer.Izinto ezifana ne-fiber optical 49, ukuqinisa i-46, i-electronics 50 kunye ne-thermocouples (lo msebenzi) zihlanganiswe ngempumelelo kwizakhiwo ze-UAM ukudala iindibano ezidibeneyo ezisebenzayo kunye ne-passive.
Kulo msebenzi, zombini izakhono zokubopha izinto ezahlukeneyo kunye ne-UAM intercalation capabilities zisetyenzisiwe ukudala i-microreactor efanelekileyo yokulawula ubushushu.
Xa kuthelekiswa palladium (Pd) kunye nezinye ezisetyenziswa ngokuqhelekileyo metal catalysts, Cu catalysis iingenelo eziliqela: (i) Ngokoqoqosho, Cu zitshiphu ngaphezu kwezinye iintsimbi ezininzi ezisetyenziswa catalysis kwaye ngoko ke ukhetho enomtsalane kushishino imichiza (ii) uluhlu Cu-catalyzed reactions cross-ukudibanisa iyakhula kwaye kubonakala ukuba ngandlel ithile Pd2,5caary-5caary-3 culogiment-3,5caary-3,5caary-3 ukuphendulwa kwetalyzed kusebenza kakuhle xa kungekho ezinye iiligands.Ezi ligand zihlala zilula kwaye azibizi kakhulu.ukuba unqwenela, kanti ezo zisetyenziswa kwi-Pd chemistry zihlala zintsonkothile, zibiza kakhulu, kwaye zinobuntununtunu emoyeni (iv) Cu, eyaziwa kakhulu ngokukwazi ukubopha i-alkynes kwi-synthesis, njenge-Sonogashira's bimetallic catalyzed coupling kunye ne-cycloaddition kunye ne-azides (cofa i-chemistry) (v) I-Cu inokukhuthaza i-arylation ye-nucleotype ethile ye-nucleotype reaction.
Kutshanje, imizekelo ye-heterogenization yazo zonke ezi mpendulo phambi kweCu (0) ibonakalisiwe.Oku kubangelwa ubukhulu becala kwishishini lamachiza kunye nokugxila okukhulayo ekubuyiseleni nasekusebenziseni kwakhona i-catalysts yesinyithi55,56.
I-1,3-dipolar cycloaddition reaction phakathi kwe-acetylene kunye ne-azide kwi-1,2,3-triazole, yokuqala ecetywayo ngu-Huisgen kwi-1960s57, ithathwa njengempendulo yokubonisa i-synergistic.Iziphumo ze-1,2,3 ze-triazole fragments zinomdla ngokukodwa njenge-pharmacophore ekufumaneni iziyobisi ngenxa yezicelo zabo ze-biological kunye nokusetyenziswa kwii-agent ezahlukeneyo zonyango 58.
Oku kusabela kufumene ingqalelo ehlaziyiweyo xa uSharpless kunye nabanye bezisa ingqikelelo "cofa ichemistry"59.Igama elithi "cofa kwikhemistri" lisetyenziselwa ukuchaza isethi eyomeleleyo kunye nekhethiweyo yeempendulo zokwenziwa ngokukhawuleza kweekhompawundi ezintsha kunye namathala eencwadi adibeneyo asebenzisa i-heteroatomic bonding (CXC)60.Isibheno sokwenziwa kwezi mpendulo kungenxa yezivuno eziphezulu ezinxulumene nazo.iimeko zilula, ukuchasana ne-oksijini kunye namanzi, kunye nokwahlukana kwemveliso kulula61.
I-classical 1,3-dipole Huisgen cycloaddition ayiweleli kwinqanaba elithi "cofa chemistry".Nangona kunjalo, i-Medal kunye ne-Sharpless ibonise ukuba lo mcimbi wokudibanisa i-azide-alkyne uhamba nge-107-108 phambi kweCu (I) xa kuthelekiswa nokunyuka okuphawulekayo kwinqanaba le-non-catalytic 1,3-dipolar cycloaddition 62,63.Le ndlela yokusabela ephezulu ayifuni amaqela akhuselayo okanye iimeko zokusabela ezinzima kwaye inika ukuguqulwa okupheleleyo kunye nokukhetha kwi-1,4-disubstituted 1,2,3-triazoles (anti-1,2,3-triazoles) ngokuhamba kwexesha (Umfanekiso 3).
Iziphumo ze-Isometric ze-Huisgen cycloadditions eziqhelekileyo kunye ne-copper-catalyzed.Cu (I) -catalyzed Huisgen cycloadditions ukunika kuphela 1,4-disubstituted 1,2,3-triazoles, ngelixa thermally induced Huisgen cycloadditions ngokuqhelekileyo ukunika 1,4- kunye 1,5-triazoles 1:1 umxube azole stereoisomers.
Uninzi lweeprotocol lubandakanya ukunciphisa imithombo ezinzileyo ye-Cu (II), njengokunciphisa i-CuSO4 okanye i-Cu (II) / Cu (0) inhlanganisela kunye neetyuwa ze-sodium.Xa kuthelekiswa nezinye metal catalyzed reactions, ukusetyenziswa Cu (I) ineengenelo eziphambili ezingabizi kwaye kulula ukuyiphatha.
Izifundo zeKinetic kunye ne-isotopic nguWorrell et al.I-65 ibonise ukuba kwimeko ye-alkynes ye-terminal, ezimbini ezilinganayo zethusi zibandakanyeka ekusebenziseni i-reactivity ye-molecule nganye ngokubhekiselele kwi-azide.Umatshini ocetywayo uqhubela phambili ngekhonkco lentsimbi enamalungu amathandathu eyenziwe ngolungelelwaniso lwe-azide ukuya kwi-σ-bond acetylide yethusi kunye ne-π-bond copper njenge-ligand yomxhasi ozinzile.I-Copper triazolyl derivatives yenziwa ngenxa ye-ring contraction elandelwa kukubola kweproton ukwenza iimveliso ze-triazole kunye nokuvala umjikelo we-catalytic.
Ngelixa izibonelelo zezixhobo zekhemistri ezijikelezayo zibhalwe kakuhle, kuye kwakho umnqweno wokudibanisa izixhobo zokuhlalutya kwezi nkqubo zokujonga inkqubo yexesha langempela kwi-situ66,67.I-UAM ibonakalise ukuba yindlela efanelekileyo yokuyila kunye nokuvelisa i-3D flow reactors enzima kakhulu ukusuka kwi-catalytically active, i-thermal conductive materials kunye nezinto zokuva ezifakwe ngokuthe ngqo (umzobo 4).
I-aluminium-copper flow reactor eyenziwe yi-ultrasonic additive production (UAM) kunye nesakhiwo esiyinkimbinkimbi sangaphakathi seshaneli, i-thermocouples eyakhelweyo kunye negumbi lokuphendula i-catalytic.Ukujonga iindlela zolwelo lwangaphakathi, iprototype ecacileyo eyenziwe kusetyenziswa i-stereolithography nayo ibonisiwe.
Ukuqinisekisa ukuba ii-reactors zenzelwe ukwenzeka kwezinto eziphilayo kwixesha elizayo, izinyibilikisi kufuneka zitshiswe ngokukhuselekileyo ngaphezu kwendawo yazo yokubilisa;zivavanyiwe uxinzelelo kunye nobushushu.Uvavanyo loxinzelelo lubonise ukuba inkqubo igcina uxinzelelo oluzinzileyo kunye noluqhubekayo nangona uxinzelelo oluphezulu kwinkqubo (1.7 MPa).Uvavanyo lweHydrostatic lwenziwa kwiqondo lobushushu begumbi kusetyenziswa i-H2O njengolwelo.
Ukudibanisa i-built-in (Umfanekiso 1) i-thermocouple kwi-logger yedatha yeqondo lokushisa ibonise ukuba ubushushu be-thermocouple yi-6 °C (± 1 °C) ngaphantsi kweqondo lokushisa elicwangcisiweyo kwinkqubo ye-FlowSyn.Ngokuqhelekileyo, ukunyuka kweqondo lobushushu nge-10°C kuliphinda kabini ireyithi yokusabela, ngoko ke umahluko wobushushu weedigri ezimbalwa unokutshintsha umlinganiselo wokusabela kakhulu.Lo mahluko ubangelwa yilahleko yobushushu kuyo yonke i-RPV ngenxa ye-thermal diffusivity ephezulu yezinto ezisetyenziswa kwinkqubo yokuvelisa.Le drift thermal isoloko kwaye ngoko ke inokuthathelwa ingqalelo xa useka izixhobo zokuqinisekisa ukuba amaqondo obushushu achanekileyo afikeleleke kwaye alinganiswe ngexesha lokusabela.Ke, esi sixhobo sokubeka iliso kwi-intanethi siququzelela ulawulo oluluqilima lobushushu bokusabela kwaye sibe negalelo kwinkqubo echanekileyo yokuphucula kunye nophuhliso lweemeko ezifanelekileyo.Ezi zivamvo zinokusetyenziselwa ukubona iintshukumo eziphumayo kwaye zithintele ukusabela okubalekayo kwiinkqubo zesikali esikhulu.
I-reactor evezwe kweli phepha ngumzekelo wokuqala wokusetyenziswa kweteknoloji ye-UAM ekwenzeni i-reactors yamakhemikhali kunye needilesi zokunciphisa ezininzi eziphambili ngoku ezinxulumene ne-AM / 3D yoshicilelo lwezi zixhobo, ezifana: (i) Ukoyisa iingxaki eziphawulweyo ezinxulumene nokucutshungulwa kobhedu okanye i-aluminium alloy (ii) ukuphuculwa kwesisombululo sombhobho wangaphakathi xa kuthelekiswa nomgubo webhedi enyibilikayo (PBive6M)2 iindlela zokunyibilikisa ibhedi (PBive6M)2 izixhobo zokunyibilikisa i-laser (PBF6)2. 26 (iii) iqondo lokushisa elisezantsi, eliququzelela i-sensor ezidibanisa ngokuthe ngqo, ezingenakwenzeka kwi-teknoloji ye-powder bed, (v) ukoyisa iipropati ezimbi zemishini kunye novakalelo lwamacandelo asekelwe kwi-polymer kwiintlobo ezahlukeneyo ze-solvents eziqhelekileyo eziphilayo17,19.
Ukusebenza kwe-reactor kubonakaliswe ngoluhlu lwee-alkinazide ze-alkinazide cycloaddition reactions phantsi kweemeko ezihamba ngokuqhubekayo (umzobo 2).I-reactor yobhedu eprintiweyo ye-ultrasonic eboniswe kumkhiwane.I-4 idityaniswe nenkqubo yokuhamba kwezorhwebo kwaye isetyenziselwa ukudibanisa ilayibrari ye-azide ye-1,4-disubstituted 1,2,3-triazoles esebenzisa i-reaction control control control of acetylene kunye ne-alkyl group halides phambi kwe-sodium chloride (Fig. 3).Ukusetyenziswa kwendlela yokuhamba ngokuqhubekayo kunciphisa imiba yokhuseleko enokuthi ivele kwiinkqubo ze-batch, ekubeni le mpendulo ivelisa i-aside intermediates esebenzayo kakhulu kwaye enobungozi [317], [318].Ekuqaleni, ukusabela kwakulungiselelwe i-cycloaddition ye-phenylacetylene kunye ne-iodoethane (iSikimu 1 - i-Cycloaddition ye-phenylacetylene kunye ne-iodoethane) (jonga i-Fig. 5).
(Upper ekhohlo) Isikimu sokuseta esetyenziselwa ukubandakanya i-reactor ye-3DP kwinkqubo yokuhamba (phezulu ekunene) efunyenwe kwisikimu esiphuculweyo (esisezantsi) seskimu se-Huisgen 57 ye-cycloaddition phakathi kwe-phenylacetylene kunye ne-iodoethane yokuphucula kunye nokubonisa imilinganiselo yokuguqulwa kwemilinganiselo ephuculweyo yokusabela.
Ngokulawula ixesha lokuhlala le-reactants kwicandelo le-catalytic ye-reactor kunye nokubeka iliso ngokucokisekileyo ubushushu bokusabela kunye ne-sensor edibeneyo ye-thermocouple, iimeko zokuphendula zinokukhawuleza kwaye zichaneke ziphuculwe kunye nobuncinci bexesha kunye nezinto eziphathekayo.Kwakhawuleza kwafunyaniswa ukuba uguqulo oluphezulu luphunyeziwe kusetyenziswa ixesha lokuhlala lemizuzu eyi-15 kunye nobushushu bokusabela kwi-150 ° C.Inokubonwa kwi-coefficient ye-software ye-MODDE ukuba zombini ixesha lokuhlala kunye nobushushu bokusabela zibhekwa njengeemeko ezibalulekileyo zemodeli.Ukuqhuba isilungisi esakhelwe ngaphakathi usebenzisa ezi meko zikhethiweyo kudala iseti yeemeko zokusabela eziyilelwe ukunyusa imveliso kwiindawo eziphezulu ngelixa kucuthwa iindawo zokuqala zemathiriyeli.Oku kulungiswa kuvelise i-53% yoguqulo lwemveliso ye-triazole, ehambelana ncakasana noqikelelo lwemodeli lwama-54%.