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Ukwenziwa kwezinto ezongezelelekileyo kutshintsha indlela abaphandi kunye nabasebenzi bemizi-mveliso abayila kwaye benze ngayo izixhobo zeekhemikhali ukuhlangabezana neemfuno zabo ezithile. Kulo msebenzi, sixela umzekelo wokuqala we-flow reactor eyenziwe yindlela ye-solid-state metal sheet lamination technique Ultrasonic Additive Manufacturing (UAM) eneendawo ezidityanisiweyo ngokuthe ngqo kunye nezinto zokuva. Itekhnoloji ye-UAM ayipheleli nje ekunqobeni uninzi lwemida enxulumene nokuveliswa kwezinto ezongezelelekileyo zee-chemical reactors, kodwa ikwanyusa kakhulu amandla ezixhobo ezinjalo. Uthotho lwee-compounds ze-1,2,3-triazole ezibalulekileyo ngokwebhayoloji zenziwe ngempumelelo kwaye zalungiswa yi-Cu-mediated Huisgen 1,3-dipolar cycloaddition reaction kusetyenziswa i-UAM chemistry set-up. Ngokusebenzisa iipropati ezizodwa ze-UAM kunye nokuqhubekeka kokucubungula ukuhamba, isixhobo siyakwazi ukuququzelela iimpendulo eziqhubekayo ngelixa sikwabonelela ngempendulo yexesha langempela yokujonga kunye nokwenza ngcono impendulo.
Ngenxa yeenzuzo zayo ezibalulekileyo kune-bulk counterpart yayo, i-flow chemistry yintsimi ebalulekileyo nekhulayo kwiindawo zemfundo nakwimizi-mveliso ngenxa yokukwazi kwayo ukwandisa ukukhetha nokusebenza kakuhle kokwenziwa kweekhemikhali. Oku kususela ekubunjweni okulula kweemolekyuli ze-organic1 ukuya kwiikhompawundi zamayeza2,3 kunye neemveliso zendalo4,5,6. Ngaphezulu kwe-50% yeempendulo kwimizi-mveliso yeekhemikhali ezintle kunye namayeza zinokungenelwa kukusetyenziswa kokucubungula ukuhamba okuqhubekayo7.
Kwiminyaka yakutshanje, bekukho umkhwa okhulayo wamaqela afuna ukutshintsha izixhobo zeglasi zemveli okanye izixhobo zekhemistri yokuhamba ngezixhobo zekhemistri ezinokwenziwa ngokwezifiso (AM) zekhemistri "iinqanawa zempendulo"8. Uyilo oluphindaphindayo, imveliso ekhawulezayo, kunye nobuchule be-3-dimensional (3D) bezi ndlela ziluncedo kwabo bafuna ukwenza ngokwezifiso izixhobo zabo kwiseti ethile yeempendulo, izixhobo, okanye iimeko. Ukuza kuthi ga ngoku, lo msebenzi ugxile kakhulu ekusebenziseni iindlela zokuprinta ze-3D ezisekelwe kwi-polymer ezifana ne-sterolithography (SL)9,10,11, i-fused deposition modeling (FDM)8,12,13,14 kunye ne-inkjet printing 7, 15, 16. Ukungabikho kokuqina kunye nokukwazi kwezixhobo ezinjalo ukwenza uluhlu olubanzi lweempendulo/uhlalutyo lweekhemikhali17, 18, 19, 20 yinto ebalulekileyo ethintela ukuphunyezwa okubanzi kwe-AM kweli candelo17, 18, 19, 20.
Ngenxa yokusetyenziswa okwandayo kwekhemistri yokuhamba kunye neempawu ezilungileyo ezinxulumene ne-AM, kukho imfuneko yokuphonononga iindlela eziphucukileyo ezivumela abasebenzisi ukuba benze imithambo yokusabela ukuhamba ngezixhobo eziphuculiweyo zamakhemikhali kunye nohlalutyo. Ezi ndlela kufuneka zivumele abasebenzisi ukuba bakhethe kuluhlu lwezinto eziqinileyo okanye ezisebenzayo ezikwaziyo ukusingatha uluhlu olubanzi lweemeko zokusabela, ngelixa zikwanceda iindlela ezahlukeneyo zokukhupha uhlalutyo kwisixhobo ukuvumela ukujonga nokulawula ukusabela.
Enye inkqubo yokwenziwa kwezinto ezongeziweyo enokukwazi ukuphuhlisa ii-reactors zeekhemikhali ezenziwe ngokwezifiso yi-Ultrasonic Additive Manufacturing (UAM). Le ndlela yokubeka i-solid-state sheet lamination isebenzisa ii-ultrasonic oscillations kwiifoyile zesinyithi ezibhityileyo ukuze zihlanganiswe kunye umaleko ngomaleko kunye nobushushu obuncinci kunye nenqanaba eliphezulu lokuhamba kweplastiki 21, 22, 23. Ngokungafaniyo nezinye iiteknoloji ze-AM, i-UAM inokudityaniswa ngokuthe ngqo nokuveliswa kwezinto ezingaphantsi, okwaziwa njengenkqubo yokwenziwa kwe-hybrid, apho i-in-situ periodic computer numerical control (CNC) milling okanye i-laser machining ichaza imo yenethi yomaleko wezinto ezibotshelelweyo 24, 25. Oku kuthetha ukuba umsebenzisi akathintelwa ziingxaki ezinxulumene nokususa izinto zokwakha eziluhlaza ezisele kwiitshaneli ezincinci zolwelo, okuhlala kunjalo kwiinkqubo ze-powder kunye ne-AM ezingamanzi 26, 27, 28. Le nkululeko yoyilo ikwafikelela kwiindlela zokukhetha izinto ezikhoyo - i-UAM inokudibanisa iindibaniselwano zezinto ezifanayo ngobushushu kunye nezingafaniyo kwinqanaba lenkqubo enye. Ukukhetha indibaniselwano yezinto ngaphaya kwenkqubo yokunyibilika kuthetha ukuba iimfuno zoomatshini kunye neekhemikhali zezicelo ezithile zinokuhlangatyezwa ngcono. Ukongeza kwi-solid state bonding, enye Into eyenzeka ngexesha lokubopha nge-ultrasonic kukuhamba okuphezulu kwezinto zeplastiki kumaqondo obushushu aphantsi kakhulu. Olu phawu lukhethekileyo lwe-UAM lunokwenza kube lula ukufakwa kwezinto zoomatshini/zobushushu phakathi kweengqimba zesinyithi ngaphandle komonakalo. Iisensa ezifakwe kwi-UAM zinokwenza kube lula ukuhanjiswa kolwazi lwexesha langempela oluvela kwisixhobo ukuya kumsebenzisi ngokusebenzisa uhlalutyo oludibeneyo.
Umsebenzi wababhali odlulileyo32 ubonise amandla enkqubo ye-UAM okudala izakhiwo ze-metallic 3D microfluidic ezinezakhono zokuva ezidityanisiweyo. Esi sisixhobo sokujonga kuphela. Eli phepha libonisa umzekelo wokuqala we-microfluidic chemical reactor eyenziwe yi-UAM; isixhobo esisebenzayo esingagcini nje ngokujonga kodwa sikwakhuthaza ukwenziwa kweekhemikhali ngokusebenzisa izixhobo ze-catalyst ezidityanisiweyo ngokwesakhiwo. Esi sixhobo sidibanisa izibonelelo ezininzi ezinxulumene netekhnoloji ye-UAM ekwenzeni izixhobo zeekhemikhali ze-3D, ezinje: ukukwazi ukuguqula uyilo olupheleleyo lwe-3D ngokuthe ngqo kwiimodeli zoyilo oluncediswa yikhompyutha (CAD) zibe ziimveliso; ukwenziwa kwezinto ezininzi ukudibanisa ukuhanjiswa kobushushu obuphezulu kunye nezinto ze-catalytic; kunye nokufaka izinzwa zobushushu ngokuthe ngqo phakathi kwemithombo ye-reagent ukuze kujongwe kwaye kulawulwe ubushushu bempendulo ngokuchanekileyo. Ukubonisa ukusebenza kwe-reactor, ithala leencwadi leekhompawundi ze-1,2,3-triazole ezibalulekileyo kwi-1,4-dissubtituted pharmacologically zenziwe yi-Huisgen 1,3-dipolar cycloaddition ebangelwa yikopolo. Lo msebenzi ugxininisa indlela ukusetyenziswa kwesayensi yezinto kunye noyilo oluncediswa yikhompyutha olunokuvula ngayo amathuba amatsha kunye namathuba ekhemistri ngophando oluhlukeneyo.
Zonke izinyibilikisi kunye nee-reagents zithengwe kwiSigma-Aldrich, Alfa Aesar, TCI okanye Fischer Scientific kwaye zisetyenziswe ngaphandle kokucocwa kwangaphambili. I-1H kunye ne-13C NMR spectra ezirekhodwe kwi-400 MHz kunye ne-100 MHz, ngokulandelanayo, zifunyenwe kusetyenziswa i-JEOL ECS-400 400 MHz spectrometer okanye i-Bruker Avance II 400 MHz spectrometer kunye ne-CDCl3 okanye (CD3)2SO njenge-solvent. Zonke ii-reactions zenziwe kusetyenziswa iqonga le-Uniqsis FlowSyn flow chemistry.
I-UAM yasetyenziswa ukwenza zonke izixhobo kolu phononongo. Le teknoloji yasungulwa ngo-1999, kwaye iinkcukacha zayo zobugcisa, iiparameter zokusebenza kunye nophuhliso ukusukela oko yasungulwa zinokufundwa ngezi zinto zilandelayo zipapashiweyo34,35,36,37. Esi sixhobo (Umfanekiso 1) sasetyenziswa kusetyenziswa amandla aphezulu kakhulu, inkqubo ye-9kW SonicLayer 4000® UAM (Fabrisonic, OH, USA). Izinto ezikhethiweyo zokwenza isixhobo sokuhamba yayiyi-Cu-110 kunye ne-Al 6061. I-Cu-110 inomxholo ophezulu wekopolo (ubuncinci be-99.9% yekopolo), nto leyo eyenza ukuba ibe ngumviwa olungileyo weempendulo zekopolo-catalyzed, kwaye ke ngoko isetyenziswa "njengomaleko osebenzayo ngaphakathi kwe-microreactor. I-Al 6061 O isetyenziswa njengesixhobo "esininzi", kunye nomaleko wokushumeka osetyenziselwa uhlalutyo; Ukushumeka kwe-alloy assistant component kunye nemeko yokushumeka edityaniswe nomaleko we-Cu-110. I-Al 6061 O sisixhobo esibonakaliswe ukuba sihambelana kakhulu neenkqubo ze-UAM38, 39, 40, 41 kwaye ivavanyiwe yaza yafunyanwa izinzile ngokweekhemikhali kunye nee-reagents ezisetyenzisiweyo kulo msebenzi. Udibaniso lwe-Al 6061 O kunye ne-Cu-110 lukwathathwa njengodibaniso lwezinto ezihambelanayo ze-UAM kwaye ke ngoko luyinto efanelekileyo kolu phononongo. 38,42 Ezi zixhobo zidweliswe kwiTheyibhile 1 ngezantsi.
Amanqanaba okwenziwa kwe-Reactor (1) I-Al 6061 substrate (2) Ukwenziwa kwetshaneli esezantsi ebekwe kwi-copper foil (3) Ukufakwa kwee-thermocouples phakathi kweeleya (4) Itshaneli ephezulu (5) Ukungena kunye nokuphuma (6) I-Monolithic reactor.
Ifilosofi yoyilo lwendlela yolwelo kukusebenzisa indlela edibeneyo ukwandisa umgama ohanjwa lulwelo ngaphakathi kwetship, ngelixa igcina itship ikwisayizi elawulekayo. Olu nyuko lomgama lufanelekile ukwandisa ixesha lokusebenzisana kwe-catalyst/reagent kunye nokubonelela ngemveliso emihle kakhulu. Iitships zisebenzisa ii-90° bends eziphelweni zendlela ethe tye ukuze zibangele ukuxubana okuguquguqukayo ngaphakathi kwesixhobo44 kunye nokwandisa ixesha lokudibana kolwelo nomphezulu (i-catalyst). Ukwandisa ukuxubana okunokufezekiswa, uyilo lwe-reactor luneendawo ezimbini zokungena ze-reagent ezidityaniswe kwi-Y-junction ngaphambi kokungena kwicandelo lokuxuba le-serpentine. Ukungena kwesithathu, okudibana nomlambo phakathi kwendawo yokuhlala kwawo, kuqukwe kuyilo lwe-multistep reaction syntheses yexesha elizayo.
Zonke iitshaneli zineprofayili yesikwere (akukho zi-engile zedrafti), isiphumo se-CNC milling esetyenziswa rhoqo ukwenza i-geometry yetshaneli. Ubukhulu betshaneli bukhethwa ukuqinisekisa ukuphuma komthamo ophezulu (we-microreactor), ngelixa buncinci ngokwaneleyo ukwenza lula ukusebenzisana komphezulu (ii-catalysts) uninzi lweziselo eziqulethweyo. Ubungakanani obufanelekileyo busekelwe kumava angaphambili ababhali ngezixhobo zesinyithi-ulwelo kwimpendulo. Ubukhulu bangaphakathi betshaneli yokugqibela babuyi-750 µm x 750 µm kwaye umthamo we-reactor iyonke yayiyi-1 ml. Isixhumi esidibeneyo (1/4″—28 UNF thread) sifakiwe kuyilo ukuvumela ukudibana okulula kwesixhobo nezixhobo zekhemistri yokuhamba korhwebo. Ubungakanani betshaneli bunqunyelwe bubukhulu bezinto zefoyile, iimpawu zayo zoomatshini, kunye neeparamitha zokubopha ezisetyenziswa nge-ultrasonics. Kububanzi obuthile bezinto ezinikiweyo, izinto ziya "kugoba" kwitshaneli eyenziweyo. Okwangoku akukho modeli ithile yolu balo, ngoko ke ububanzi betshaneli obuphezulu bezinto ezinikiweyo kunye noyilo bumiselwa ngovavanyo; Kule meko, ububanzi obuyi-750 μm abuyi kubangela ukuwohloka.
Ubume (isikwere) setshaneli bumiselwa ngokusebenzisa isixhobo sokusika isikwere. Ubume kunye nobukhulu betshaneli bunokutshintshwa ngoomatshini be-CNC abasebenzisa izixhobo zokusika ezahlukeneyo ukuze bafumane amazinga okuhamba kunye neempawu ezahlukeneyo. Umzekelo wokudala itshaneli yemilo egobileyo usebenzisa isixhobo se-125 μm unokufumaneka kumsebenzi weMonaghan45. Xa umaleko wefoyile ubekwe ngendlela ecwangcisiweyo, ukugqunywa kwezinto zefoyile phezu kwetshaneli kuya kuba nokugqitywa okuthe tyaba (isikwere). Kulo msebenzi, ukuze kugcinwe ulungelelwaniso lwetshaneli, kusetyenziswe umzobo wesikwere.
Ngexesha lokuma okucwangcisiweyo kwangaphambili kokwenziwa, ii-thermocouple temperature probes (Type K) zifakwa ngqo ngaphakathi kwesixhobo phakathi kwamaqela etshaneli ephezulu nesezantsi (Umfanekiso 1 - Inqanaba lesi-3). Ezi thermocouples zinokujonga utshintsho lobushushu ukusuka kwi-−200 ukuya kwi-1350 °C.
Inkqubo yokufaka isinyithi yenziwa luphondo lwe-UAM kusetyenziswa i-foil yesinyithi engama-25.4 mm ububanzi, ubukhulu be-150 micron. Ezi layers zefoil zidityaniswe zibe luluhlu lwemigca ekufutshane ukuze zigubungele yonke indawo yokwakha; ubungakanani bezinto ezifakweyo bukhulu kunemveliso yokugqibela njengoko inkqubo yokukhupha ivelisa imo yokugqibela yenethi. Umatshini wokugaya we-CNC usetyenziselwa umatshini wokulinganisa i-contours yangaphandle neyangaphakathi yesixhobo, nto leyo ebangela ukugqitywa komphezulu wesixhobo kunye nemijelo elingana ne-parameters yesixhobo esikhethiweyo kunye ne-CNC process (malunga ne-1.6 μm Ra kulo mzekelo). Umjikelo wokufaka kunye nomatshini we-ultrasonic oqhubekayo, oqhubekayo usetyenziswa kuyo yonke inkqubo yokwenza isixhobo ukuqinisekisa ukuchaneka kobukhulu kuyagcinwa kwaye inxalenye egqityiweyo iya kuhlangabezana namanqanaba okuchaneka kokugqiba kwe-CNC. Ububanzi betshaneli esetyenziselwa esi sixhobo buncinci ngokwaneleyo ukuqinisekisa ukuba izinto zefoil "azigobi" kwitshaneli yolwelo, ngoko ke itshaneli igcina icandelo elinqamlezileyo lesikwere. Izikhewu ezinokwenzeka kwizinto zefoil kunye neeparameter zenkqubo ye-UAM zichongiwe ngovavanyo liqabane lokuvelisa (Fabrisonic LLC, e-USA).
Izifundo zibonise ukuba akukho kukhanya kuncinci okwenzekayo kwi-UAM bonding interface 46, 47 ngaphandle konyango olongezelelweyo lobushushu, ngoko ke kwizixhobo ezikulo msebenzi, umaleko weCu-110 uhlala wahlukile kumaleko we-Al 6061 kwaye utshintsha ngequbuliso.
Faka i-pre-calibrated 250 psi (1724 kPa) back pressure regulator (BPR) kwindawo yokuphuma kwe-reactor uze upompe amanzi nge-reactor ngesantya se-0.1 ukuya kwi-1 mL min-1. Uxinzelelo lwe-reactor lujongwe kusetyenziswa i-FlowSyn built-in system pressure sensor ukuqinisekisa ukuba inkqubo inokugcina uxinzelelo oluzinzileyo. Ii-gradients zobushushu ezinokubakho kwi-flow reactor zivavanyiwe ngokuchonga nawuphi na umahluko phakathi kwe-thermocouples ezifakwe kwi-reactor kunye nezo zifakwe kwi-FlowSyn chip heating plate. Oku kufezekiswa ngokutshintsha ubushushu be-hotplate obucwangcisiweyo phakathi kwe-100 kunye ne-150 °C kwii-25 °C increments kunye nokuphawula nawuphi na umahluko phakathi kobushushu obucwangcisiweyo kunye nobo burekhodiweyo. Oku kufezekisiwe kusetyenziswa i-tc-08 data logger (PicoTech, Cambridge, UK) kunye nesoftware yePicoLog ehamba nayo.
Iimeko zempendulo ye-cycloaddition ye-phenylacetylene kunye ne-iodoethane zenziwe ngcono (Iskimu 1- Iskimu 1- Iskimu 1- Iskimu 1- Iskimu 2- Iskimu 2). Olu phuculo lwenziwe ngendlela yoyilo olupheleleyo lwe-factorial of experiments (DOE), kusetyenziswa ubushushu kunye nexesha lokuhlala njengeeparameter eziguquguqukayo, ngelixa kulungiswa umlinganiselo we-alkyne:azide kwi-1:2.
Izisombululo ezahlukeneyo 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 yaza yapontshwa kwi-reactor ngesantya sokuhamba kunye nobushushu obufunekayo. Impendulo yemodeli yathathwa njengomlinganiselo wendawo yencopho yemveliso ye-triazole kwizinto zokuqala ze-phenylacetylene kwaye yamiselwa yi-high performance liquid chromatography (HPLC). Ukuze kuhambelane nohlalutyo, zonke iimpendulo zathathwa iisampulu emva kokuba umxube wempendulo ushiye i-reactor. Uluhlu lweeparameter ezikhethiweyo zokwenziwa ngcono ziboniswe kwiTheyibhile 2.
Zonke iisampulu zihlalutywe kusetyenziswa inkqubo yeChromaster HPLC (VWR, PA, USA) equlathe ipompo ye-quaternary, i-oven yekholamu, isixhobo sokubona ubunzulu be-UV esiguquguqukayo kunye nesampulu ye-autosampler. Ikholamu yayiyi-Equivalence 5 C18 (VWR, PA, USA), ubukhulu be-4.6 × 100 mm, ubungakanani be-particle ye-5 µm, igcinwe kwi-40 °C. Isisombululo sasiyi-isocratic 50:50 methanol:water kwisantya sokuhamba se-1.5 mL.min-1. Umthamo wenaliti yayiyi-5 µL kwaye ubude be-detector yayiyi-254 nm. Indawo ye-peak yesampuli ye-DOE ibalwe kwiindawo ze-peak zeemveliso ze-alkyne kunye ne-triazole ezisele kuphela. Ukufakwa kwezinto zokuqala kuvumela ukuchongwa kwee-peaks ezifanelekileyo.
Ukudibanisa imveliso yohlalutyo lwe-reactor kwisoftware ye-MODDE DOE (Umetrics, Malmö, Sweden) kuvumele uhlalutyo olupheleleyo lweendlela zeziphumo kunye nokumisela iimeko ezifanelekileyo zokuphendula kule cycloaddition. Ukusebenzisa i-optimizer eyakhelwe ngaphakathi kunye nokukhetha onke amagama abalulekileyo emodeli kuvelisa iseti yeemeko zokuphendula ezenzelwe ukwandisa indawo yencochoyi yemveliso ngelixa kunciphisa indawo yencochoyi yezinto zokuqala ze-acetylene.
Ukucolwa kobhedu olungaphezulu ngaphakathi kwigumbi le-catalytic reaction kufezekiswe kusetyenziswa isisombululo se-hydrogen peroxide (36%) esihamba kwigumbi le-reaction (isantya sokuhamba = 0.4 mL min-1, ixesha lokuhlala = 2.5 min) ngaphambi kokwenziwa kwethala leencwadi ngalinye le-triazole compound.
Nje ukuba kuchongwe iseti efanelekileyo yeemeko, zisetyenziswe kuluhlu lwee-acetylene kunye ne-haloalkane derivatives ukuvumela ukuhlanganiswa kwe-synthesis encinci yelayibrari, ngaloo ndlela kumiselwa amandla okusebenzisa ezi meko kuluhlu olubanzi lwee-reagents ezinokubakho (Umfanekiso 1).2).
Lungisa izisombululo ezahlukeneyo ze-sodium azide (0.25 M, 4:1 DMF:H2O), ii-haloalkanes (0.25 M, DMF) kunye nee-alkynes (0.125 M, DMF). Ii-aliquots ze-3 mL zesisombululo ngasinye zixutywe zaza zapontshwa kwi-reactor kwi-75 µL. min-1 kunye ne-150 °C. Umthamo uwonke waqokelelwa kwi-vial kwaye waxutywa ne-10 mL ye-ethyl acetate. Isisombululo sesampuli sahlanjwa nge-3 × 10 mL yamanzi. Iileya zamanzi zadityaniswa zaza zakhutshwa nge-10 mL ye-ethyl acetate; iileya ze-organic zadityaniswa, zahlanjwa nge-3 x 10 mL ye-brine, zomiswa phezu kwe-MgSO4 zaza zahluzwa, emva koko i-solvent yasuswa kwi-vacuo. Iisampulu zacocwa yi-column chromatography kwi-silica gel kusetyenziswa i-ethyl acetate ngaphambi kohlalutyo ngokudibanisa i-HPLC, 1H NMR, 13C NMR kunye ne-high resolution mass spectrometry (HR-MS).
Zonke ii-spectra zifunyenwe kusetyenziswa i-Thermofischer precision Orbitrap resolution mass spectrometer ene-ESI njengomthombo we-ionization. Zonke iisampulu zilungiselelwe kusetyenziswa i-acetonitrile njenge-solvent.
Uhlalutyo lwe-TLC lwenziwe kwiipleyiti ze-silica ezixhaswe yi-aluminium. Iipleyiti zibonwe ngokukhanya kwe-UV (254 nm) okanye i-vanillin staining kunye nokufudumeza.
Zonke iisampulu zihlalutywe kusetyenziswa inkqubo yeVWR Chromaster (VWR International Ltd., Leighton Buzzard, UK) exhotyiswe nge-autosampler, i-column oven binary pump kunye ne-single wavelength detector. Ikholamu esetyenzisiweyo yayiyi-ACE Equivalence 5 C18 (150 × 4.6 mm, Advanced Chromatography Technologies Ltd., e-Aberdeen, eScotland).
Iinaliti (5 µL) zenziwe ngokuthe ngqo ngomxube we-diluted crude reaction mix (1:10 dilution) zaza zahlalutywa ngamanzi:methanol (50:50 okanye 70:30), ngaphandle kwezinye iisampuli ezisebenzisa inkqubo ye-solvent ye-70:30 (ebizwa ngokuba yinombolo yenkwenkwezi) kwisantya sokuhamba se-1.5 mL/min. Ikholamu igcinwe kwi-40 °C. Ububanzi be-detector yi-254 nm.
Indawo yencochoyi yesampuli ibalwa ukusuka kwindawo yencochoyi ye-alkyne eseleyo, kuphela yimveliso ye-triazole, kwaye ukufakwa kwezinto zokuqala kuvumela ukuchongwa kweencochoyi ezifanelekileyo.
Zonke iisampulu zihlalutywe kusetyenziswa iThermo iCAP 6000 ICP-OES. Zonke imigangatho yokulinganisa ilungiselelwe kusetyenziswa isisombululo esiqhelekileyo se-1000 ppm Cu kwi-2% nitric acid (SPEX Certi Prep). Zonke imigangatho ilungiselelwe kwisisombululo se-5% DMF kunye ne-2% HNO3, kwaye zonke iisampulu zixutywe kangangama-20 kwisisombululo sesampulu se-DMF-HNO3.
I-UAM isebenzisa i-ultrasonic metal welding njengendlela yokubopha izinto ze-metal foil ezisetyenziselwa ukwakha indibano yokugqibela. I-Ultrasonic metal welding isebenzisa isixhobo sesinyithi esingcangcazelayo (esibizwa ngokuba yi-horn okanye i-ultrasonic horn) ukufaka uxinzelelo kumaleko we-foil/umaleko odibeneyo ngaphambili ukuze ubotshelelwe ngelixa ungcangcazela izinto. Ukuze kuqhubeke ukusebenza, i-sonotrode iyi-cylindrical kwaye iqengqeleka phezu komphezulu wezinto, ibotshelelwe yonke indawo. Xa kusetyenziswa uxinzelelo kunye nokungcangcazela, ii-oxides kumphezulu wezinto zinokuqhekeka. Uxinzelelo oluqhubekayo kunye nokungcangcazela kunokubangela ukuba izinto ziqhekeke 36. Ukudibana okusondeleyo nobushushu kunye noxinzelelo olubangelwa kwindawo ethile kukhokelela ekubambeni okuqinileyo kwiindawo ezibonakalayo; inokunceda nokunamathela ngotshintsho kumandla omphezulu 48. Uhlobo lwendlela yokubopha luyoyisa iingxaki ezininzi ezinxulumene nobushushu obuguquguqukayo bokunyibilika kunye neziphumo zobushushu obuphezulu ezikhankanyiweyo kwezinye iindlela zokwenza izinto ezongezelelweyo. Oku kuvumela ukubotshelelwa ngokuthe ngqo (oko kukuthi, ngaphandle kokuguqulwa komphezulu, izizalisi okanye izincamathelisi) zeeleya ezininzi zezinto ezahlukeneyo kwisakhiwo esinye esidibeneyo.
Into yesibini eluncedo kwi-UAM kukunyuka kokuhamba kweplastiki okubonwa kwizinto zesinyithi, nokuba kubushushu obuphantsi, oko kukuthi, ngaphantsi kakhulu kwinqanaba lokunyibilika kwezinto zesinyithi. Ukudibana kwe-ultrasonic oscillation kunye noxinzelelo kubangela amanqanaba aphezulu okufuduka kwemida yengqolowa yendawo kunye nokuphinda kusetyenziswe ngaphandle kokunyuka okukhulu kobushushu okuqhele ukunxulunyaniswa nezinto ezininzi. Ngexesha lokwakhiwa kwendibano yokugqibela, le nto ingasetyenziswa ukufaka izinto ezisebenzayo nezingasebenziyo phakathi kweengqimba zefoyile yesinyithi, umaleko ngomaleko. Izinto ezifana neefayibha ze-optical 49, ukuqinisa 46, i-electronics 50, kunye ne-thermocouples (lo msebenzi) zonke zifakwe ngempumelelo kwizakhiwo ze-UAM ukwenza iindibano ezisebenzayo nezingasebenziyo.
Kulo msebenzi, zombini iindlela ezahlukeneyo zokubopha izinto kunye namathuba okudibanisa i-UAM asetyenzisiwe ukudala i-microreactor yokugqibela yokujonga ubushushu be-catalytic.
Xa kuthelekiswa ne-palladium (Pd) kunye nezinye ii-catalysts zesinyithi ezisetyenziswa rhoqo, i-Cu catalysis ineengenelo ezininzi: (i) Ngokwezoqoqosho, i-Cu ibiza kancinci kunezinye iintsimbi ezininzi ezisetyenziswa kwi-catalysis kwaye ke ngoko lukhetho olunomtsalane kushishino lokucubungula iikhemikhali (ii) Uluhlu lwee-Cu-catalyzed cross-coupling reactions luyanda kwaye lubonakala luhambelana neendlela ezisekwe kwi-Pd51,52,53 (iii) Ii-Cu-catalyzed reactions zisebenza kakuhle xa kungekho ezinye ii-ligands, Ezi ligands zihlala zilula ngokwesakhiwo kwaye azibizi kakhulu ukuba ziyafunwa, ngelixa ezo zisetyenziswa kwi-Pd chemistry zihlala ziyinkimbinkimbi, zibiza kakhulu, kwaye zinomoya obuthathaka (iv) I-Cu, eyaziwa kakhulu ngokukwazi kwayo ukubopha ii-alkynes kwi-synthesis, Umzekelo, i-bimetallic-catalyzed Sonogashira coupling kunye ne-cycloaddition ene-azides (click chemistry) (v)I-Cu ikwakwazi ukukhuthaza i-arylation yee-nucleophiles ezininzi kwi-Ullmann-type reactions.
Imizekelo yokwahlukahlukana kwazo zonke ezi mpendulo ibonakaliswe kutshanje xa kukho i-Cu(0). Oku kungenxa kakhulu kushishino lwamayeza kunye nokugxila okukhulayo ekubuyiselweni nasekusetyenzisweni kwakhona kwe-metal catalyst55,56.
Yaqalwa nguHuisgen ngeminyaka yoo-1960, i-1,3-dipolar cycloaddition reaction phakathi kwe-acetylene kunye ne-azide kwi-1,2,3-triazole ithathwa njenge-synergistic demonstration reaction. I-1,2,3 triazole moieties eziphumayo zinomdla kakhulu njenge-pharmacophore kwicandelo lokufunyanwa kwamayeza ngenxa yezicelo zawo zebhayoloji kunye nokusetyenziswa kwazo kwiiarhente ezahlukeneyo zonyango 58.
Le mpendulo yaqala ukujongwa kwakhona xa uSharpless nabanye bazisa ingcamango "yekhemistri yokucofa"59. Igama elithi "ikhemistri yokucofa" lisetyenziselwa ukuchaza iseti eqinileyo, ethembekileyo nekhethiweyo yeempendulo zokwenziwa ngokukhawuleza kweekhompawundi ezintsha kunye neelayibrari ezidibeneyo nge-heteroatom linkage (CXC)60. Ukutsala okwenziwa kwezi mpendulo kuvela kwimveliso yazo ephezulu ehambelana nazo, iimeko zokuphendula zilula, ukumelana neoksijini namanzi, kwaye ukwahlukana kwemveliso kulula61.
I-Huisgen 1,3-dipole cycloaddition yakudala ayiyonxalenye yoluhlu lwe-"click chemistry". Nangona kunjalo, iMedal kunye neSharpless zibonise ukuba esi siganeko sokudibanisa i-azide-alkyne sidlula kwi-107 ukuya kwi-108 phambi kwe-Cu(I) xa kuthelekiswa ne-1,3-dipolar cycloaddition 62,63 significant rate acceleration. Le ndlela yokusabela ephuculweyo ayifuni ukukhusela amaqela okanye iimeko zokusabela ezinzima kwaye ivelisa ukuguquka okupheleleyo kunye nokukhetha kwi-1,4-dissubstituted 1,2,3-triazoles (anti-1,2,3-triazole) ngexesha elithile (Umfanekiso 3).
Iziphumo ze-Isometric ze-Huisgen cycloadditions zesiqhelo kunye ne-copper-catalyzed. I-Huisgen cycloadditions ezi-Cu(I)-catalyzed zivelisa kuphela i-1,4-dissubstituted 1,2,3-triazoles, ngelixa i-Huisgen cycloadditions ezibangelwa ngubushushu zihlala zivelisa umxube we-1,4- kunye ne-1,5-triazoles 1:1 we-stereoisomers ze-azoles.
Uninzi lweenkqubo zibandakanya ukunciphisa imithombo yeCu(II) ezinzileyo, njengokunciphisa iintlobo zeCuSO4 okanye Cu(II)/Cu(0) kunye netyuwa yesodium. Xa kuthelekiswa nezinye ii-reactions ezibangelwa yimetal, ukusetyenziswa kweCu(I) kuneenzuzo ezinkulu zokuba akubizi kakhulu kwaye kulula ukuyiphatha.
Izifundo ze-Kinetic kunye ne-isotopic labeling ezenziwe nguWorrell et al. 65 zibonise ukuba, kwimeko ye-terminal alkynes, ii-equivalents ezimbini ze-copper zibandakanyeka ekuvuseleleni i-reactivity ye-molecule nganye kwi-azide. Le ndlela icetywayo iqhubeka ngendandatho yesinyithi yobhedu enamalungu amathandathu eyenziwe ngokudityaniswa kwe-azide kwi-acetylide yobhedu ene-σ-bonded kunye ne-π-bonded copper njenge-ligand ezinzileyo yomnikelo. Ii-triazolyl copper derivatives zenziwa ngokuncitshiswa kwendandatho, kulandele ukubola kweproton ukubonelela ngeemveliso ze-triazole kunye nokuvala umjikelo we-catalytic.
Nangona iingenelo zezixhobo zekhemistri yokuhamba zibhalwe kakuhle, bekukho umnqweno wokudibanisa izixhobo zohlalutyo kwezi nkqubo zokubeka esweni inkqubo ngaphakathi, ngaphakathi, 66,67. I-UAM ibonakalise ukuba yindlela efanelekileyo yokuyila nokuvelisa ii-reactors ze-3D flow ezintsonkothileyo ezenziwe ngezinto ezisebenzayo neziqhuba ubushushu ezinee-elements ezifakwe ngqo (Umfanekiso 4).
I-aluminiyam-copper flow reactor eyenziwe yi-ultrasonic additive manufacturing (UAM) enesakhiwo esintsonkothileyo se-internal channel, ii-thermocouples ezifakwe ngaphakathi kunye ne-catalytic reaction chamber. Ukuze ubone iindlela zangaphakathi zolwelo, i-prototype ebonakalayo eyenziwe kusetyenziswa i-stereolithography nayo iyaboniswa.
Ukuqinisekisa ukuba ii-reactors zenzelwe ii-organic reactions zexesha elizayo, izinyibilikisi kufuneka zifudunyezwe ngokukhuselekileyo ngaphezu kweqondo lokubila; ziyavavanywa uxinzelelo kunye nobushushu. Uvavanyo loxinzelelo lubonise ukuba inkqubo igcina uxinzelelo oluzinzileyo noluqhubekayo nokuba uxinzelelo lwenkqubo luphezulu (1.7 MPa). Uvavanyo lwe-hydrostatic lwenziwe kubushushu begumbi kusetyenziswa i-H2O njengolwelo.
Ukuqhagamshela i-thermocouple efakwe kwi-(Figure 1) kwi-data logger yobushushu kubonise ukuba i-thermocouple yayipholile nge-6 °C (± 1 °C) kunobushushu obucwangcisiweyo kwinkqubo ye-FlowSyn. Ngokwesiqhelo, ukunyuka kwe-10 °C kubushushu kubangela ukuphindaphindeka kwesantya sokusabela, ngoko ke umahluko wobushushu we-degrees ezimbalwa nje unokutshintsha kakhulu izinga lokusabela. Lo mahluko ubangelwa kukulahleka kobushushu kuwo wonke umzimba we-reactor ngenxa yokwanda kobushushu okuphezulu kwezinto ezisetyenziswa kwinkqubo yokuvelisa. Olu tshintsho lobushushu luhlala luhleli kwaye ke ngoko lunokubalwa kwisetingi yezixhobo ukuqinisekisa ukuba amaqondo obushushu achanekileyo ayafikelelwa kwaye alinganiswe ngexesha lokusabela. Ke ngoko, esi sixhobo sokujonga kwi-intanethi senza kube lula ukulawula ubushushu bokusabela kwaye senza kube lula ukwenza ngcono inkqubo kunye nophuhliso lweemeko ezifanelekileyo. Ezi sensors zinokusetyenziswa ukuchonga ii-exotherms zokusabela kunye nokuthintela iimpendulo ezibalekayo kwiinkqubo ezinkulu.
I-reactor evezwe kulo msebenzi ngumzekelo wokuqala wokusetyenziswa kwetekhnoloji ye-UAM ekwenziweni kwee-reactors zeekhemikhali kwaye ijongana nemida emininzi emikhulu enxulumene nokuprintwa kwe-AM/3D kwezi zixhobo, ezinje: (i) ukoyisa iingxaki ezixeliweyo ezinxulumene nokucubungula i-copper okanye i-aluminium alloy (ii) ukuphuculwa kwesisombululo setshaneli yangaphakathi xa kuthelekiswa neendlela ze-powder bed fusion (PBF) ezifana nokunyibilika kwe-laser ekhethiweyo (SLM)25,69 Ukuhamba kakubi kwezinto kunye nokuthungwa komphezulu orhabaxa26 (iii) Ubushushu obuphantsi bokucubungula, obunceda ukubopha ngokuthe ngqo kwee-sensors, okungenakwenzeka kwitekhnoloji ye-powder bed, (v) ukoyisa iipropati ezimbi zoomatshini kunye novakalelo lwezinto ezisekwe kwi-polymer kwiintlobo ngeentlobo ze-organic solvents17,19.
Ukusebenza kwe-reactor kuboniswe luluhlu lwee-alkyne azide cycloaddition reactions ze-copper-catalyzed phantsi kweemeko zokuhamba okuqhubekayo (Umzobo 2). I-reactor ye-copper eprintiweyo nge-ultrasonic echazwe kuMfanekiso 4 yadibaniswa nenkqubo yokuhamba kwemali kwaye yasetyenziselwa ukwenza ii-azide zelayibrari ze-1,4-dissubstituted 1,2,3-triazoles nge-reaction elawulwa bubushushu ye-acetylene kunye ne-alkyl groups halides phambi kwe-sodium chloride (Umfanekiso 3). Ukusetyenziswa kwendlela yokuhamba rhoqo kunciphisa iingxaki zokhuseleko ezinokuvela kwiinkqubo ze-batch, njengoko le reaction ivelisa i-azide intermediates esabela kakhulu kwaye inobungozi [317], [318]. Ekuqaleni, i-reaction yalungiselelwa i-cycloaddition ye-phenylacetylene kunye ne-iodoethane (Iskimu 1 - I-Cycloaddition ye-phenylacetylene kunye ne-iodoethane) (jonga uMfanekiso 5).
(Phezulu ekhohlo) Isicwangciso sokuseta esisetyenzisiweyo ukufaka i-reactor ye-3DP kwinkqubo yokuhamba (phezulu ekunene) esifunyenwe kwisicwangciso esilungiselelweyo (ezantsi) se-Huisgen cycloaddition 57 scheme phakathi kwe-phenylacetylene kunye ne-iodoethane ukuze kuphuculwe kwaye kuboniswe izinga lokuguqulwa kwempendulo yeeparameter ezilungiselelweyo.
Ngokulawula ixesha lokuhlala kwee-reagents kwicandelo le-catalytic le-reactor kunye nokujonga ngokusondeleyo ubushushu bokusabela nge-probe ye-thermocouple edityaniswe ngqo, iimeko zokusabela zinokulungiswa ngokukhawuleza nangokuchanekileyo ngexesha elincinci kunye nokusetyenziswa kwezinto. Kwagqitywa ngokukhawuleza ukuba ukuguqulwa okuphezulu kufunyenwe xa ixesha lokuhlala lemizuzu eli-15 kunye nobushushu bokusabela obuyi-150 °C kusetyenziswa. Ukusuka kwi-coefficient plot yesoftware ye-MODDE, kunokubonwa ukuba zombini ixesha lokuhlala kunye nobushushu bokusabela zithathwa njengeemodeli ezibalulekileyo. Ukusebenzisa i-optimizer eyakhelwe ngaphakathi usebenzisa la magama akhethiweyo kuvelisa iseti yeemeko zokusabela ezenzelwe ukwandisa iindawo zencochoyi yemveliso ngelixa kunciphisa iindawo zencochoyi yezixhobo zokuqala. Olu phuculo luvelise ukuguqulwa kwemveliso ye-triazole engama-53%, ehambelana kakhulu noqikelelo lwemodeli lwama-54%.
Ngokusekelwe kuncwadi olubonisa ukuba i-copper(I) oxide (Cu2O) inokusebenza njenge-catalytic species esebenzayo kwiindawo ze-copper zero-valent kwezi mpendulo, ubuchule boku-oxidize umphezulu we-reactor ngaphambi kokuba kwenziwe impendulo ekuhambeni kwamanzi buphandwe70,71. Impendulo phakathi kwe-phenylacetylene kunye ne-iodoethane yenziwa kwakhona phantsi kweemeko ezifanelekileyo kwaye isivuno sathelekiswa. Kwabonwa ukuba olu lungiselelo lubangele ukwanda okukhulu ekuguqulweni kwezinto zokuqala, okwabalwa ukuba yi>99%. Nangona kunjalo, ukubekwa esweni yi-HPLC kubonise ukuba olu tshintsho lunciphise kakhulu ixesha elide kakhulu lokuphendula kude kube malunga nemizuzu engama-90, apho umsebenzi ubonakala ngathi ulingana kwaye ufikelela "kwimeko ezinzileyo". Olu phononongo lubonisa ukuba umthombo womsebenzi we-catalytic ufunyanwa kwi-copper oxide yomphezulu endaweni ye-zero-valent copper substrate. I-Cu metal i-oxidized ngokulula kubushushu begumbi ukuze yenze i-CuO kunye ne-Cu2O ezingezizo iileya ezizikhuselayo. Oku kususa isidingo sokongeza umthombo we-copper(II) oncedisayo wokudibanisa izinto71.