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Ukukhiqiza okungeziwe kushintsha indlela abacwaningi kanye nezimboni abaklama futhi bakhiqize ngayo amadivayisi amakhemikhali ukuze bahlangabezane nezidingo zabo ezithile. Kuleli phepha, sibika isibonelo sokuqala se-flow reactor esakhiwe yi-ultrasonic additive manufacturing (UAM) lamination yeshidi lensimbi eliqinile elinezingxenye ezihlanganisiwe eziqondile ze-catalytic kanye nezinto zokuzwa. Ubuchwepheshe be-UAM abugcini nje ngokunqoba imikhawulo eminingi ehlotshaniswa nokukhiqizwa okungeziwe kwama-chemical reactor, kodwa futhi bukhulisa kakhulu amakhono amadivayisi anjalo. Inani lamakhemikhali e-1,2,3-triazole abalulekile ngokwebhayoloji akhiwe futhi alungiselelwe ngempumelelo yi-Cu-mediated 1,3-dipolar Huisgen cycloaddition reaction esebenzisa isikhungo se-UAM chemistry. Sisebenzisa izakhiwo ezihlukile ze-UAM kanye nokucubungula okuqhubekayo kokugeleza, idivayisi iyakwazi ukuvuselela ukusabela okuqhubekayo kanye nokunikeza impendulo yesikhathi sangempela ukuqapha nokuthuthukisa ukusabela.
Ngenxa yezinzuzo zayo ezibalulekile kune-bulk counterpart yayo, i-flow chemistry iyinsimu ebalulekile nekhulayo kokubili ezindaweni zemfundo kanye nezimboni ngenxa yekhono layo lokukhulisa ukukhetha kanye nokusebenza kahle kokwenziwa kwamakhemikhali. Lokhu kusukela ekwakhekeni kwama-molecule alula e-organic1 kuya kuma-pharmaceutical compounds2,3 kanye nemikhiqizo yemvelo4,5,6. Ngaphezu kwama-50% okusabela embonini yamakhemikhali amahle kanye nemithi kungazuza ekugelezeni okuqhubekayo7.
Eminyakeni yamuva nje, kube nomkhuba okhulayo wamaqembu afuna ukufaka esikhundleni sezinto zokugqoka zeglasi noma imishini ye-flow chemistry “ama-reactor” amakhemikhali aguquguqukayo8. Umklamo ophindaphindayo, ukukhiqizwa okusheshayo, kanye namakhono amathathu-dimensional (3D) alezi zindlela awusizo kulabo abafuna ukwenza ngokwezifiso amadivayisi abo ukuze ahambisane nesethi ethile yokusabela, amadivayisi, noma izimo. Kuze kube manje, lo msebenzi ugxile kakhulu ekusetshenzisweni kwamasu okuphrinta e-3D asekelwe ku-polymer njenge-sterolithography (SL)9,10,11, i-Fused Deposition Modeling (FDM)8,12,13,14 kanye nokuphrinta kwe-inkjet7,15. , 16. Ukuntuleka kokuthembeka kanye nekhono lamadivayisi anjalo lokwenza uhla olubanzi lokusabela/ukuhlaziywa kwamakhemikhali17, 18, 19, 20 kuyisici esibalulekile sokunciphisa ukusetshenziswa kwe-AM kabanzi kulo mkhakha17, 18, 19, 20.
Ngenxa yokusetshenziswa okwandayo kwe-flow chemistry kanye nezakhiwo ezinhle ezihambisana ne-AM, kudingeka kuhlolwe amasu angcono azovumela abasebenzisi ukuthi bakhe imithambo yokusabela kokugeleza ngamakhemikhali athuthukisiwe kanye namakhono okuhlaziya. Lezi zindlela kufanele zivumele abasebenzisi ukuthi bakhethe ezintweni eziqinile noma ezisebenzayo ezikwazi ukusebenza ngaphansi kwezimo eziningi zokusabela, kanye nokwenza kube lula izinhlobo ezahlukene zokukhipha kokuhlaziya kudivayisi ukuze kuvunyelwe ukuqapha nokulawula ukusabela.
Inqubo eyodwa yokukhiqiza okungeziwe engasetshenziswa ukuthuthukisa ama-reactor amakhemikhali enziwe ngokwezifiso yi-Ultrasonic Additive Manufacturing (UAM). Le ndlela ye-solid-state sheet lamination isebenzisa ukudlidliza kwe-ultrasonic kuma-foil ensimbi amancane ukuze iwahlanganise ndawonye ungqimba ngengqimba ngokushisa okuncane kakhulu kanye nezinga eliphezulu lokugeleza kwepulasitiki 21, 22, 23. Ngokungafani nezinye ubuchwepheshe be-AM, i-UAM ingahlanganiswa ngqo nokukhiqizwa kokukhipha, okwaziwa ngokuthi inqubo yokukhiqiza ye-hybrid, lapho ukugaya kwe-periodic in-situ numeral control (CNC) noma ukucubungula nge-laser kunquma ukuma kwenetha kwengqimba yezinto eziboshiwe 24, 25. Lokhu kusho ukuthi umsebenzisi akakhawulelwe ezinkingeni ezihambisana nokususwa kwezinto zokwakha zangempela ezisele eziteshini ezincane zoketshezi, okuvame ukuba njalo ezinhlelweni zempuphu kanye noketshezi i-AM26,27,28. Le nkululeko yokuklama iphinde ifinyelele ekukhetheni izinto ezitholakalayo - i-UAM ingabopha inhlanganisela yezinto ezifanayo ngokushisa nezingafani ngesinyathelo senqubo eyodwa. Ukukhetha inhlanganisela yezinto ngale kwenqubo yokuncibilikisa kusho ukuthi izidingo zemishini nezamakhemikhali zezinhlelo ezithile zingahlangatshezwa kangcono. Ngaphezu kokubopha okuqinile, esinye isenzakalo esenzeka ngokubopha kwe-ultrasonic ukugeleza okuphezulu kwezinto zepulasitiki emazingeni okushisa aphansi kakhulu angu-29,30,31,32,33. Lesi sici esiyingqayizivele se-UAM sivumela izakhi zomshini/zokushisa ukuthi zibekwe phakathi kwezingqimba zensimbi ngaphandle komonakalo. Izinzwa ze-UAM ezifakiwe zingenza kube lula ukulethwa kolwazi lwesikhathi sangempela oluvela kudivayisi luye kumsebenzisi ngokusebenzisa ukuhlaziya okuhlanganisiwe.
Umsebenzi wangaphambilini wababhali32 ubonise ikhono lenqubo ye-UAM lokudala izakhiwo ze-microfluidic ze-3D zensimbi ezinamakhono okuzwa ahlanganisiwe. Le divayisi yenzelwe izinjongo zokuqapha kuphela. Lesi sihloko sinikeza isibonelo sokuqala se-reactor yamakhemikhali ye-microfluidic eyenziwe yi-UAM, idivayisi esebenzayo engalawuli nje kuphela kodwa futhi ekhuthaza ukuhlanganiswa kwamakhemikhali ngezinto zokwakha ezihlanganisiwe ngokwesakhiwo. Le divayisi ihlanganisa izinzuzo eziningana ezihambisana nobuchwepheshe be-UAM ekwenziweni kwamadivayisi amakhemikhali e-3D, njenge: ikhono lokuguqula umklamo ophelele we-3D ngqo kusuka kumodeli yomklamo osizwa yikhompyutha (CAD) ibe umkhiqizo; ukwenziwa kwezinto eziningi zokuhlanganiswa kokushisa okuphezulu kanye nezinto zokwakha, kanye nezinzwa zokushisa ezifakwe ngqo phakathi kwemifudlana ye-reactant ukuze kulawulwe kahle futhi kuphathwe izinga lokushisa lokusabela. Ukuze kuboniswe ukusebenza kwe-reactor, umtapo wezincwadi wamakhemikhali e-1,2,3-triazole abalulekile emithi akhiwe yi-cycloaddition ye-1,3-dipolar Huisgen efakwe ngethusi. Lo msebenzi uqokomisa indlela ukusetshenziswa kwesayensi yezinto zokwakha kanye nomklamo osizwa yikhompyutha okungavula ngayo amathuba amasha namathuba ekhemistri ngocwaningo oluhlanganisa imikhakha eyahlukene.
Zonke izinyibilikisi kanye nama-reagents athengwe kwa-Sigma-Aldrich, Alfa Aesar, TCI, noma Fischer Scientific futhi asetshenziswa ngaphandle kokuhlanzwa kwangaphambilini. Ama-spectra angu-1H kanye no-13C NMR aqoshwe ku-400 kanye no-100 MHz, ngokulandelana, atholakale ku-spectrometer ye-JEOL ECS-400 400 MHz noma ku-spectrometer ye-Bruker Avance II 400 MHz ene-CDCl3 noma (CD3)2SO njenge-solvent. Zonke izimpendulo zenziwe kusetshenziswa ipulatifomu ye-Uniqsis FlowSyn flow chemistry.
I-UAM yasetshenziswa ukwakha wonke amadivayisi kulolu cwaningo. Ubuchwepheshe basungulwa ngo-1999 futhi imininingwane yabo yobuchwepheshe, amapharamitha okusebenza kanye nentuthuko kusukela ekusungulweni kwayo kungafundwa kusetshenziswa izinto ezilandelayo ezishicilelwe34,35,36,37. Idivayisi (Umfanekiso 1) yasetshenziswa kusetshenziswa uhlelo olunzima lwe-9 kW SonicLayer 4000® UAM (Fabrisonic, Ohio, USA). Izinto ezikhethiwe zedivayisi yokugeleza kwakuyi-Cu-110 kanye ne-Al 6061. I-Cu-110 inokuqukethwe okuphezulu kwethusi (ubuncane bethusi obungu-99.9%), okwenza kube yinto enhle yokusabela okubangelwa yithusi ngakho-ke isetshenziswa njenge-"ungqimba olusebenzayo ngaphakathi kwe-microreactor. I-Al 6061 O isetshenziswa njengezinto "ezinobuningi". , kanye nengqimba yokuhlanganisa esetshenziselwa ukuhlaziya; ukuhlanganisa izingxenye ze-alloy ezisizayo kanye nesimo se-annealed kuhlanganiswe nengqimba ye-Cu-110. kutholakale ukuthi kuzinzile ngamakhemikhali nama-reagent asetshenziswe kulo msebenzi. I-Al 6061 O ehlanganiswe ne-Cu-110 nayo ibhekwa njengenhlanganisela yezinto ezihambisanayo ze-UAM futhi ngakho-ke iyinto efanelekile yalolu cwaningo38,42. Lawa madivayisi abhalwe kuThebula 1 ngezansi.
Izinyathelo zokwenziwa kwe-reactor (1) 6061 i-aluminium alloy substrate (2) Ukwenziwa kwesiteshi esingezansi kusuka ku-foil yethusi (3) Ukufakwa kwama-thermocouple phakathi kwezingqimba (4) Isiteshi esingaphezulu (5) Ukungena kanye nokuphuma (6) I-Monolithic reactor.
Ifilosofi yokuklama isiteshi soketshezi ukusebenzisa indlela egobile ukwandisa ibanga elihanjwa uketshezi ngaphakathi kwe-chip ngenkathi kugcinwa usayizi we-chip olawulekayo. Lokhu kwanda kwebanga kuyafiseleka ukwandisa isikhathi sokuxhumana kwe-catalyst-reactant futhi kunikeze isivuno esihle kakhulu somkhiqizo. Ama-chip asebenzisa ukugoba okungu-90° emaphethelweni endlela eqondile ukuze abangele ukuxubana okuguquguqukayo ngaphakathi kwedivayisi44 futhi andise isikhathi sokuxhumana koketshezi nomphezulu (i-catalyst). Ukuze kuthuthukiswe ukuxubana okungafinyelelwa, ukwakheka kwe-reactor kufaka phakathi ama-inlets amabili e-reactant ahlanganiswe ku-Y-connection ngaphambi kokungena esigabeni se-mixing coil. Umnyango wesithathu, owela ukugeleza phakathi nendawo yokuhlala kwawo, ufakiwe ohlelweni lokusabela kwe-multi-stage synthesis esikhathini esizayo.
Zonke iziteshi zinephrofayili yesikwele (awekho ama-engeli athambile), okuwumphumela wokugaya kwe-CNC okwenziwa ngezikhathi ezithile okusetshenziswa ukudala i-geometry yesiteshi. Ubukhulu besiteshi bukhethwa ukuze bunikeze isivuno esiphezulu (se-microreactor), kodwa buncane ngokwanele ukwenza kube lula ukusebenzisana nomphezulu (ama-catalyst) koketshezi oluningi oluqukethe. Usayizi ofanele usekelwe kokuhlangenwe nakho kwababhali kwangaphambilini ngamadivayisi okusabela kwensimbi-uketshezi. Ubukhulu bangaphakathi besiteshi sokugcina babungu-750 µm x 750 µm kanti ivolumu yenani le-reactor yayingu-1 ml. Isixhumi esakhelwe ngaphakathi (intambo ye-UNF engu-1/4″-28) sifakiwe ekwakhiweni ukuze kuvunyelwe ukuhlangana kalula kwedivayisi nemishini ye-chemistry yokugeleza kwezentengiselwano. Ubukhulu besiteshi bunqunyelwe ubukhulu bezinto ze-foil, izakhiwo zayo zemishini, kanye nemingcele yokubopha esetshenziswa ngama-ultrasonic. Ngobubanzi obuthile bezinto ezinikeziwe, izinto "zizogoba" esiteshini esidalwe. Okwamanje akukho modeli ethile yalokhu kubalwa, ngakho-ke ububanzi besiteshi esiphezulu sezinto ezinikeziwe kanye nomklamo bunqunywa ngokuhlola, lapho ububanzi obungu-750 µm bungeke bubangele ukugoba.
Ukuma (isikwele) sesiteshi kunqunywa kusetshenziswa umshini wokusika oyisikwele. Ukuma nosayizi weziteshi kungashintshwa emishinini ye-CNC kusetshenziswa amathuluzi okusika ahlukene ukuze kutholakale amazinga okugeleza ahlukene kanye nezici. Isibonelo sokudala isiteshi esigobile esinethuluzi elingu-125 µm singatholakala ku-Monaghan45. Lapho ungqimba lwe-foil lusetshenziswa luyisicaba, ukusetshenziswa kwezinto ze-foil eziteshini kuzoba nobuso obuyisicaba (isikwele). Kulo msebenzi, kwasetshenziswa ukwakheka kwesikwele ukuze kulondolozwe ukulingana kwesiteshi.
Ngesikhathi sokumisa okuhleliwe ekukhiqizeni, izinzwa zokushisa ze-thermocouple (uhlobo K) zakhiwa ngqo kudivayisi phakathi kwamaqembu eziteshi eziphezulu nezingezansi (Isithombe 1 - isigaba 3). Lawa ma-thermocouple angalawula izinguquko zokushisa kusukela ku--200 kuya ku-1350 °C.
Inqubo yokufaka insimbi yenziwa uphondo lwe-UAM kusetshenziswa i-foil yensimbi engu-25.4 mm ububanzi kanye nobukhulu obuyi-150 microns. Lezi zingqimba ze-foil zixhunywe ochungechungeni lwemichilo eseduze ukuze zimboze yonke indawo yokwakha; usayizi wezinto ezifakiwe mkhulu kunomkhiqizo wokugcina njengoba inqubo yokukhipha idala isimo sokugcina esihlanzekile. Umshini wokugaya we-CNC usetshenziselwa umshini wokulinganisa imingcele yangaphandle neyangaphakathi yemishini, okuholela ekuqedweni kobuso bemishini neziteshi ezihambisana nethuluzi elikhethiwe kanye nemingcele yenqubo ye-CNC (kulesi sibonelo, cishe i-1.6 µm Ra). Imijikelezo yokufafaza kanye nomshini wezinto ze-ultrasonic eqhubekayo, eqhubekayo isetshenziswa kuyo yonke inqubo yokukhiqiza yedivayisi ukuqinisekisa ukuthi ukunemba kobukhulu kuyagcinwa futhi ingxenye eqediwe ihlangabezana namazinga okunemba kokugaya okuhle kwe-CNC. Ububanzi besiteshi esisetshenziswe kule divayisi buncane ngokwanele ukuqinisekisa ukuthi izinto ze-foil "azigobi" esiteshini soketshezi, ngakho-ke isiteshi sinesigaba esiyisikwele. Izikhala ezingaba khona ezintweni ze-foil kanye nemingcele yenqubo ye-UAM zinqunywe ngokuhlola ngumlingani wokukhiqiza (Fabrisonic LLC, USA).
Izifundo zikhombisile ukuthi esibonakalayo 46, 47 se-UAM compound kukhona ukusabalala okuncane kwezinto ngaphandle kokwelashwa okwengeziwe kokushisa, ngakho-ke kumadivayisi akulo msebenzi ungqimba lwe-Cu-110 luhlala luhlukile kunengqimba ye-Al 6061 futhi lushintsha kakhulu.
Faka isilawuli sokucindezela emuva esilinganisiwe (i-BPR) ku-250 psi (1724 kPa) phansi kwe-reactor bese upompa amanzi nge-reactor ngesilinganiso esingu-0.1 kuya ku-1 ml min-1. Ingcindezi ye-reactor yaqashwa kusetshenziswa i-FlowSyn pressure transducer eyakhelwe ohlelweni ukuqinisekisa ukuthi uhlelo lungagcina ingcindezi engaguquki. Ukwehla kwezinga lokushisa okungenzeka ku-flow reactor kwahlolwa ngokubheka noma yimuphi umehluko phakathi kwama-thermocouple akhelwe ku-reactor kanye nama-thermocouple akhelwe epuletini lokushisa le-FlowSyn chip. Lokhu kufezwa ngokushintsha izinga lokushisa le-hotplate elihleliwe phakathi kuka-100 no-150 °C ngo-25 °C ukwanda kanye nokuqapha noma yimuphi umehluko phakathi kwamazinga okushisa ahleliwe narekhodiwe. Lokhu kufezwe kusetshenziswa i-tc-08 data logger (PicoTech, Cambridge, UK) kanye nesofthiwe ye-PicoLog ehambisanayo.
Izimo zokusabela kwe-cycloaddition kwe-phenylacetylene kanye ne-iodoethane zilungiselelwe (I-Scheme 1-Cycloaddition ye-phenylacetylene kanye ne-iodoethane, i-Scheme 1-Cycloaddition ye-phenylacetylene kanye ne-iodoethane). Lokhu kulungiswa kwenziwe kusetshenziswa indlela ephelele yokuklama izivivinyo (DOE), kusetshenziswa izinga lokushisa nesikhathi sokuhlala njengeziguquguquki ngenkathi kulungiswa isilinganiso se-alkyne:azide ku-1:2.
Izixazululo ezihlukene ze-sodium azide (0.25 M, 4:1 DMF:H2O), iodoethane (0.25 M, DMF), kanye ne-phenylacetylene (0.125 M, DMF) zalungiswa. I-aliquot engu-1.5 ml yesisombululo ngasinye yaxutshwa futhi yaphonswa nge-reactor ngesivinini sokugeleza kanye nokushisa okufiswayo. Impendulo yemodeli yathathwa njengesilinganiso sendawo ephezulu yomkhiqizo we-triazole nezinto zokuqala ze-phenylacetylene futhi yanqunywa kusetshenziswa i-high performance liquid chromatography (HPLC). Ukuze kuhlaziywe ukuhambisana, konke ukusabela kwathathwa ngokushesha ngemva kokuba ingxube yokusabela ishiye i-reactor. Ububanzi bepharamitha obukhethiwe bokwenza ngcono buboniswe kuThebula 2.
Zonke izibonelo zahlaziywa kusetshenziswa uhlelo lwe-Chromaster HPLC (VWR, PA, USA) oluqukethe ipompo ye-quaternary, i-column oven, i-variable wavelength UV detector kanye ne-autosampler. Ikholomu yayiyi-Equivalence 5 C18 (VWR, PA, USA), engu-4.6 x 100 mm, usayizi wezinhlayiya ezingu-5 µm, egcinwe ku-40°C. I-solvent yayiyi-isocratic methanol:water 50:50 ngesivinini sokugeleza esingu-1.5 ml·min-1. Umthamo womjovo wawungu-5 μl kanti ubude bomjovo babungu-254 nm. Indawo ye-% peak yesampula ye-DOE ibalwa kusukela ezindaweni ze-peak zemikhiqizo ye-alkyne ne-triazole esele kuphela. Ukwethulwa kwezinto zokuqala kwenza kube nokwenzeka ukuhlonza iziqongo ezifanele.
Ukuhlanganisa imiphumela yokuhlaziywa kwe-reactor nesofthiwe ye-MODDE DOE (Umetrics, Malmö, Sweden) kuvumele ukuhlaziywa okujulile kwemikhuba yemiphumela kanye nokunqunywa kwezimo zokusabela ezifanele kakhulu zalesi cycloaddition. Ukusebenzisa i-optimizer eyakhelwe ngaphakathi nokukhetha wonke amagama abalulekile emodeli kudala isethi yezimo zokusabela ezenzelwe ukukhulisa indawo ephezulu yomkhiqizo ngenkathi kunciphisa indawo ephezulu ye-acetylene feedstock.
Ukushiswa kobuso bethusi ekamelweni lokusabela kwe-catalytic kufezwe kusetshenziswa isisombululo se-hydrogen peroxide (36%) esigeleza ekamelweni lokusabela (isilinganiso sokugeleza = 0.4 ml min-1, isikhathi sokuhlala = 2.5 min) ngaphambi kokwenziwa komtapo wolwazi ngamunye we-triazole compound.
Uma isethi efanele yezimo isinqunyiwe, zafakwa kuhlu lwe-acetylene kanye ne-haloalkane derivatives ukuvumela ukuhlanganiswa komtapo wolwazi omncane wokwenziwa, ngaleyo ndlela kwamiswa ithuba lokusebenzisa lezi zimo kuhlu olubanzi lwe-reagents ezingaba khona (Isithombe 1). 2).
Lungisa izixazululo ezihlukene ze-sodium azide (0.25 M, 4:1 DMF:H2O), ama-haloalkanes (0.25 M, DMF), kanye nama-alkynes (0.125 M, DMF). Ama-aliquots angu-3 ml wesisombululo ngasinye axutshwe futhi adonswa nge-reactor ngesilinganiso esingu-75 µl/min kanye nokushisa okungu-150°C. Lonke ivolumu laqoqwa ebhodleleni futhi laxutshwa ne-10 ml ye-ethyl acetate. Isixazululo sesampula sagezwa nge-3 x 10 ml yamanzi. Izingqimba zamanzi zahlanganiswa futhi zakhishwa nge-10 ml ye-ethyl acetate, kwabe sekuhlanganiswa izingqimba eziphilayo, kwagezwa nge-3 × 10 ml ye-brine, komiswa phezu kwe-MgSO 4 futhi kwahlungwa, kwabe sekususwa i-solvent ku-vacuo. Amasampula ahlanzwa nge-silica gel column chromatography kusetshenziswa i-ethyl acetate ngaphambi kokuhlaziywa ngenhlanganisela ye-HPLC, 1H NMR, 13C NMR kanye ne-high resolution mass spectrometry (HR-MS).
Zonke izinhlayiya zitholakale kusetshenziswa i-Thermofischer Precision Orbitrap mass spectrometer ene-ESI njengomthombo we-ionization. Wonke amasampula alungiswa kusetshenziswa i-acetonitrile njenge-solvent.
Ukuhlaziywa kwe-TLC kwenziwe kumapuleti e-silica ane-substrate ye-aluminium. Amapuleti aboniswe ngokukhanya kwe-UV (254 nm) noma i-vanillin staining kanye nokushisa.
Wonke amasampula ahlaziywe kusetshenziswa uhlelo lwe-VWR Chromaster (VWR International Ltd., Leighton Buzzard, UK) oluhlonyiswe nge-autosampler, iphampu ye-binary ene-column oven kanye ne-single wavelength detector. Kusetshenziswe ikholomu ye-ACE Equivalence 5 C18 (150 x 4.6 mm, Advanced Chromatography Technologies Ltd., e-Aberdeen, eScotland).
Imijovo (5 µl) yenziwe ngqo kusuka engxubeni ye-crude reaction exutshwe (1:10 dilution) futhi yahlaziywa ngamanzi:methanol (50:50 noma 70:30), ngaphandle kwamanye amasampula asebenzisa uhlelo lwe-solvent lwe-70:30 (olukhonjiswe njengenombolo yenkanyezi ) ngesilinganiso sokugeleza esingu-1.5 ml/min. Ikholomu igcinwe ku-40°C. Ububanzi be-detector bungu-254 nm.
Indawo ephakeme engu-% yesampula ibalwa kusukela endaweni ephakeme ye-alkyne esele, umkhiqizo we-triazole kuphela, futhi ukwethulwa kwezinto zokuqala kwenza kwaba nokwenzeka ukuhlonza iziqongo ezifanele.
Zonke izibonelo zahlaziywa kusetshenziswa i-Thermo iCAP 6000 ICP-OES. Zonke izindinganiso zokulinganisa zalungiswa kusetshenziswa isisombululo esijwayelekile se-1000 ppm Cu ku-2% nitric acid (SPEX Certi Prep). Zonke izindinganiso zalungiswa kusisombululo se-5% DMF kanye ne-2% HNO3, futhi zonke izibonelo zahlanjululwa izikhathi ezingu-20 ngesisombululo sesampula se-DMF-HNO3.
I-UAM isebenzisa ukushisela kwensimbi ye-ultrasonic njengendlela yokuhlanganisa i-foil yensimbi esetshenziselwa ukudala ukuhlanganiswa kokugcina. Ukushisela kwensimbi ye-Ultrasonic kusebenzisa ithuluzi lensimbi elidlidlizayo (elibizwa ngokuthi uphondo noma uphondo lwe-ultrasonic) ukufaka ingcindezi ku-foil/ungqimba oluhlanganisiwe ngaphambilini ukuze luboshwe/luhlanganiswe ngaphambilini ngokudlidliza impahla. Ukuze kusebenze ngokuqhubekayo, i-sonotrode inesimo esiyindilinga futhi igoqa phezu kobuso bezinto, inamathisele yonke indawo. Lapho kusetshenziswa ingcindezi nokudlidliza, ama-oxide ebusweni bezinto angaqhekeka. Ingcindezi nokudlidliza okuqhubekayo kungaholela ekubhujisweni kobulukhuni bezinto 36. Ukuxhumana okuseduze nokushisa kwendawo kanye nengcindezi bese kuholela ekuboshweni kwesigaba esiqinile ezindaweni zokuhlangana kwezinto; kungakhuthaza futhi ukuhlangana ngokushintsha amandla obuso 48. Uhlobo lwendlela yokubopha lunqoba izinkinga eziningi ezihambisana nokushisa okuguquguqukayo okuncibilikayo kanye nemiphumela yokushisa ephezulu okukhulunywe ngayo kwezinye ubuchwepheshe bokukhiqiza okungeziwe. Lokhu kuvumela ukuxhumana okuqondile (okungukuthi ngaphandle kokuguqulwa kobuso, izigcwalisi noma izinamathiseli) zezingqimba eziningana zezinto ezahlukene zibe yisakhiwo esisodwa esihlanganisiwe.
Isici sesibili esihle se-CAM yizinga eliphezulu lokugeleza kwepulasitiki okubonwa ezintweni zensimbi ngisho nasemazingeni okushisa aphansi, okungukuthi ngaphansi kakhulu kwephuzu lokuncibilika kwezinto zensimbi. Ukuhlanganiswa kokudlidliza kwe-ultrasonic kanye nokucindezela kubangela izinga eliphezulu lokufuduka kwemingcele yendawo kanye nokuvuselelwa kabusha ngaphandle kokwanda okukhulu kokushisa okuhlotshaniswa ngokwesiko nezinto ezinkulu. Ngesikhathi sokudalwa kokuhlanganiswa kokugcina, lesi simo singasetshenziswa ukufaka izingxenye ezisebenzayo nezingasebenzi phakathi kwezingqimba ze-foil yensimbi, ungqimba ngengqimba. Izinto ezifana ne-optical fiber 49, i-reinforcement 46, i-electronics 50 kanye ne-thermocouples (lo msebenzi) zihlanganiswe ngempumelelo ezakhiweni ze-UAM ukudala izinhlangano ezisebenzayo nezingasebenzi.
Kulo msebenzi, kokubili amakhono okubopha izinto ahlukene kanye namakhono okuhlanganisa i-UAM asetshenziswe ukudala i-microreactor efanelekile yokulawula izinga lokushisa le-catalytic.
Uma kuqhathaniswa ne-palladium (Pd) nezinye izinto ezivame ukusetshenziswa njenge-metal catalyst, i-Cu catalysis inezinzuzo eziningana: (i) Ngokomnotho, i-Cu ishibhile kunezinye izinsimbi eziningi ezisetshenziswa ku-catalysis ngakho-ke iyindlela ekhangayo embonini yamakhemikhali (ii) ububanzi bezindlela zokuhlangana ezihlanganisiwe ze-Cu-catalyzed buyanda futhi bubonakala buhambisana kancane nezindlela ezisekelwe ku-Pd51, 52, 53 (iii) Izindlela zokusabela ezihlanganisiwe ze-Cu zisebenza kahle uma kungekho ezinye i-ligands. Lawa ma-ligands avame ukuba lula ngokwesakhiwo futhi angabizi. uma efunwa, kanti lawo asetshenziswa ku-Pd chemistry avame ukuba yinkimbinkimbi, ayabiza, futhi azwela emoyeni (iv) I-Cu, eyaziwa kakhulu ngekhono layo lokuhlanganisa ama-alkynes ekuhlanganiseni, njenge-Sonogashira's bimetallic catalyzed coupling kanye ne-cycloaddition ne-azides (click chemistry) (v) I-Cu ingakhuthaza futhi i-arylation yama-nucleophile athile ku-Ullmann-type reactions.
Muva nje, kuye kwaboniswa izibonelo zokwahlukahluka kwazo zonke lezi zindlela zokusabela lapho kukhona i-Cu(0). Lokhu kungenxa kakhulu yemboni yezokwelapha kanye nokugxila okukhulayo ekubuyiseleni nasekusebenziseni kabusha ama-catalyst ensimbi55,56.
Ukusabela kwe-cycloaddition okungu-1,3-dipolar phakathi kwe-acetylene ne-azide ku-1,2,3-triazole, okwaqala ukuphakanyiswa nguHuisgen ngawo-196057, kubhekwa njengokusabela kokubonisana okusebenzisanayo. Izingcezu ze-triazole ezingu-1,2,3 eziphumelayo zithakazelisa kakhulu njenge-pharmacophore ekutholakaleni kwemithi ngenxa yezicelo zazo zebhayoloji kanye nokusetshenziswa kwazo ekwelashweni okuhlukahlukene58.
Lokhu kusabela kwathola ukunakwa okusha lapho uSharpless nabanye bethula umqondo we-“click chemistry”59. Igama elithi “click chemistry” lisetshenziselwa ukuchaza isethi eqinile nekhethayo yezimpendulo zokwenziwa okusheshayo kwamakhemikhali amasha kanye nemitapo yolwazi ehlanganisiwe kusetshenziswa i-heteroatomic bonding (CXC)60. Ukukhanga kokwenziwa kwalezi zimpendulo kungenxa yesivuno esikhulu esihambisana nazo. izimo zilula, ukumelana nomoya-mpilo namanzi, futhi ukuhlukaniswa komkhiqizo kulula61.
I-cycloaddition yakudala ye-1,3-dipole Huisgen ayiweli esigabeni "se-click chemistry". Kodwa-ke, i-Medal kanye ne-Sharpless babonise ukuthi lesi sigameko sokuxhumanisa i-azide-alkyne sidlula ku-107-108 phambi kwe-Cu(I) uma kuqhathaniswa nokusheshisa okukhulu kwesilinganiso se-cycloaddition ye-1,3-dipolar 62,63 engeyona i-catalytic. Le ndlela yokusabela ethuthukisiwe ayidingi ukuvikela amaqembu noma izimo zokusabela ezinzima futhi inikeza ukuguqulwa okuphelele nokukhetha kuma-triazoles angu-1,2,3 ahlukaniswe yi-1,4 (anti-1,2,3-triazoles) ngokuhamba kwesikhathi (Umfanekiso 3).
Imiphumela ye-isometric ye-cycloadditions ye-Huisgen evamile ne-copper-catalyzed. I-Cu(I)-catalyzed Huisgen cycloadditions inikeza kuphela i-1,4-dissubstituted 1,2,3-triazoles, kuyilapho i-Huisgen cycloadditions ebangelwa ukushisa ngokuvamile inikeza i-1,4- kanye ne-1,5-triazoles ingxube ye-1:1 yama-stereoisomers e-azole.
Iningi lezinqubo zihilela ukunciphisa imithombo eqinile ye-Cu(II), njengokunciphisa i-CuSO4 noma i-Cu(II)/Cu(0) compound ngokuhlanganiswa nosawoti we-sodium. Uma kuqhathaniswa nezinye izimpendulo ezibangelwa yinsimbi, ukusetshenziswa kwe-Cu(I) kunezinzuzo eziyinhloko zokuthi ishibhile futhi kulula ukuyiphatha.
Izifundo ze-kinetic kanye ne-isotopic ezenziwe nguWorrell et al. 65 zibonise ukuthi endabeni yama-alkynes asemaphethelweni, izinto ezimbili ezifanayo zethusi zihilelekile ekusebenziseni ukusabela kwe-molecule ngayinye maqondana ne-azide. Indlela ehlongozwayo iqhubeka ngendandatho yensimbi yethusi enamalungu ayisithupha eyakhiwe ngokuhlanganiswa kwe-azide ne-acetylide yethusi ene-σ-bonded nethusi ene-π-bonded njenge-ligand ezinzile yomnikelo. Ama-derivatives e-triazolyl ethusi akhiwa ngenxa yokufinyela kwendandatho okulandelwa ukubola kwe-proton ukwakha imikhiqizo ye-triazole nokuvala umjikelezo we-catalytic.
Nakuba izinzuzo zamadivayisi e-flow chemistry zibhalwe kahle, kube nesifiso sokuhlanganisa amathuluzi okuhlaziya kulezi zinhlelo zokuqapha inqubo ngesikhathi sangempela ku-situ66,67. I-UAM ibonakalise iyindlela efanelekile yokuklama nokukhiqiza ama-reactor okugeleza kwe-3D ayinkimbinkimbi kakhulu ngezinto ezisebenzayo, eziqhuba ukushisa ezinezici zokuzwa ezifakwe ngqo (Isithombe 4).
I-reactor yokugeleza kwe-aluminium-copper eyenziwe yi-ultrasonic additive manufacturing (UAM) enesakhiwo sesiteshi sangaphakathi esiyinkimbinkimbi, ama-thermocouple akhelwe ngaphakathi kanye negumbi lokusabela elisebenzisa i-catalytic. Ukuze ubone ngeso lengqondo izindlela zangaphakathi zoketshezi, kuboniswe ne-prototype ecacile eyenziwe kusetshenziswa i-sterolithography.
Ukuqinisekisa ukuthi ama-reactor enzelwe ukusabela kwezinto eziphilayo esikhathini esizayo, ama-solvents kumele afudunyezwe ngokuphephile ngaphezu kwesilinganiso sawo sokubila; ayahlolwa ukucindezela kanye nokushisa. Ukuhlolwa kokucindezela kubonise ukuthi uhlelo lugcina ukucindezela okuzinzile nokungaguquguquki ngisho noma kucindezelwe okuphezulu ohlelweni (1.7 MPa). Ukuhlolwa kwe-hydrostatic kwenziwa ekushiseni kwegumbi kusetshenziswa i-H2O njengoketshezi.
Ukuxhuma i-thermocouple eyakhelwe ngaphakathi (Isithombe 1) ku-logger yedatha yokushisa kubonise ukuthi izinga lokushisa le-thermocouple lalingu-6 °C (± 1 °C) ngaphansi kwezinga lokushisa elihleliwe ohlelweni lwe-FlowSyn. Ngokuvamile, ukwanda kwezinga lokushisa okungu-10°C kuphinda kabili izinga lokusabela, ngakho-ke umehluko wokushisa wamadigri ambalwa nje ungashintsha izinga lokusabela kakhulu. Lo mehluko ubangelwa ukulahlekelwa izinga lokushisa kulo lonke i-RPV ngenxa yokwanda okukhulu kokushisa kwezinto ezisetshenziswa enkambisweni yokukhiqiza. Lokhu kuguquguquka kokushisa kuhlala njalo futhi ngakho-ke kungacatshangelwa lapho kusethwa imishini ukuqinisekisa ukuthi amazinga okushisa anembile ayafinyelelwa futhi alinganiswa ngesikhathi sokusabela. Ngakho-ke, leli thuluzi lokuqapha eliku-inthanethi lenza kube lula ukulawula izinga lokushisa lokusabela futhi lifaka isandla ekwenzeni ngcono inqubo kanye nokuthuthukiswa kwezimo ezifanele. Lezi zinzwa zingasetshenziswa futhi ukuthola ukusabela okungaphandle futhi kuvimbele ukusabela okubalekayo ezinhlelweni ezinkulu.
I-reactor eyethulwe kuleli phepha iyisibonelo sokuqala sokusetshenziswa kobuchwepheshe be-UAM ekwakhiweni kwama-reactor amakhemikhali futhi ibhekana nemikhawulo eminingana emikhulu ehlobene nokuphrinta kwe-AM/3D kwala madivayisi, njengokuthi: (i) Ukunqoba izinkinga eziphawuliwe ezihlobene nokucutshungulwa kwethusi noma i-aluminium alloy (ii) ukuxazululwa kwesiteshi sangaphakathi okuthuthukisiwe uma kuqhathaniswa nezindlela zokuncibilikisa umbhede wempuphu (PBF) njengokuncibilikisa i-laser ekhethiwe (SLM)25,69 Ukugeleza kwezinto ezingezinhle kanye nokuthungwa kwendawo okuqinile26 (iii) izinga lokushisa eliphansi lokucubungula, okusiza izinzwa zokuxhuma ngqo, okungenakwenzeka kubuchwepheshe be-powder bed, (v) ukunqoba izakhiwo ezimbi zemishini kanye nokuzwela kwezingxenye ezisekelwe ku-polymer ezixazululweni ezahlukahlukene eziphilayo ezivamile17,19.
Ukusebenza kwe-reactor kuboniswe uchungechunge lwe-alkinazide cycloaddition reactions eyenziwe ngethusi ngaphansi kwezimo zokugeleza okuqhubekayo (Isithombe 2). I-reactor yethusi ephrintiwe nge-ultrasonic eboniswe ku-Fig. 4 yahlanganiswa nesistimu yokugeleza kwezentengiselwano futhi yasetshenziswa ukuhlanganisa umtapo we-azide wezinhlobo ezahlukene ze-1,4-disubstituted 1,2,3-triazoles kusetshenziswa ukusabela okulawulwa ukushisa kwe-acetylene kanye ne-alkyl group halides lapho kukhona i-sodium chloride (Isithombe 3). Ukusetshenziswa kwendlela yokugeleza okuqhubekayo kunciphisa izinkinga zokuphepha ezingavela ezinqubweni ze-batch, njengoba lokhu kusabela kukhiqiza ama-intermediate e-azide asabela kakhulu futhi ayingozi [317], [318]. Ekuqaleni, ukusabela kwalungiselelwa i-cycloaddition ye-phenylacetylene kanye ne-iodoethane (Iskimu 1 - I-Cycloaddition ye-phenylacetylene kanye ne-iodoethane) (bheka Isithombe 5).
(Phezulu kwesobunxele) Isimiso sokusetha esisetshenziswe ukufaka i-reactor ye-3DP ohlelweni lokugeleza (phezulu kwesokudla) esitholwe kuhlelo olulungiselelwe (olungezansi) lwe-Huisgen 57 cycloaddition scheme phakathi kwe-phenylacetylene ne-iodoethane ukuze kulungiselelwe futhi kuboniswe amapharamitha esilinganiso sokuguqulwa okulungiselelwe kokusabela.
Ngokulawula isikhathi sokuhlala kwama-reactants esigabeni se-catalytic se-reactor nokuqapha ngokucophelela izinga lokushisa lokusabela nge-thermocouple sensor ehlanganiswe ngqo, izimo zokusabela zingalungiswa ngokushesha nangokunembile ngesikhathi esincane nezinto zokwakha. Kwatholakala ngokushesha ukuthi ukuguqulwa okuphezulu kakhulu kufezwe kusetshenziswa isikhathi sokuhlala semizuzu eyi-15 kanye nezinga lokushisa lokusabela elingu-150°C. Kungabonakala kusukela ku-coefficient plot yesofthiwe ye-MODDE ukuthi kokubili isikhathi sokuhlala kanye nezinga lokushisa lokusabela kubhekwa njengezimo ezibalulekile zemodeli. Ukusebenzisa i-optimizer eyakhelwe ngaphakathi kusetshenziswa lezi zimo ezikhethiwe kudala isethi yezimo zokusabela ezenzelwe ukukhulisa izindawo eziphakeme zomkhiqizo ngenkathi kunciphisa izindawo eziphezulu zezinto zokuqala. Lokhu kulungiswa kuveze ukuguqulwa okungu-53% komkhiqizo we-triazole, okuhambisana ncamashi nokubikezela kwemodeli okungu-54%.