Mahalo no kou kipa ʻana iā Nature.com. ʻO ka polokalamu kele pūnaewele āu e hoʻohana nei he kākoʻo CSS kaupalena. No ka ʻike maikaʻi loa, manaʻo mākou e hoʻohana i kahi polokalamu kele pūnaewele hou (a i ʻole e hoʻopau i ke ʻano Compatibility Mode ma Internet Explorer). I kēia manawa, e hōʻoia i ke kākoʻo mau ʻana, e hāʻawi mākou i ka pūnaewele me ka ʻole o nā ʻano a me JavaScript.
He carousel e hōʻike ana i ʻekolu paheʻe i ka manawa like. E hoʻohana i nā pihi Mua a me Next no ka neʻe ʻana i ʻekolu paheʻe i ka manawa, a i ʻole e hoʻohana i nā pihi paheʻe ma ka hopena e neʻe i ʻekolu mau paheʻe i ka manawa.
Ke hoʻololi nei ka hana additive i ke ʻano o ka hoʻolālā ʻana a me ka hana ʻana o nā mea noiʻi a me nā mea hana ʻenehana i nā mea kemika e hoʻokō i kā lākou mau pono kikoʻī. Ma kēia pepa, hōʻike mākou i ka hiʻohiʻona mua o kahi reactor kahe i hana ʻia e ka ultrasonic additive manufacturing (UAM) lamination o kahi ʻāpana metala paʻa me nā ʻāpana catalytic i hoʻohui pono ʻia a me nā mea ʻike. ʻAʻole lanakila ka ʻenehana UAM i nā palena he nui i kēia manawa me ka hana hoʻohui ʻana o nā reactors kemika, akā hoʻonui nui i nā hiki o ia mau mea hana. Ua hoʻohui maikaʻi ʻia kekahi mau pūhui 1,4-disubstituted 1,2,3-triazole koʻikoʻi koʻikoʻi a hoʻopaʻa ʻia e ka hopena cycloaddition Huisgen 1,3-dipolar Cu-mediated me ka hoʻohana ʻana i ka hale kemika UAM. Ke hoʻohana nei i nā waiwai kūʻokoʻa o ka UAM a me ka hoʻoheheʻe ʻana i ka kahe mau, hiki i ka mea hana ke hoʻoikaika i nā hopena e hoʻomau ʻia a hāʻawi pū i ka manaʻo manawa maoli e nānā a hoʻopaʻa i nā hopena.
Ma muli o kāna mau pōmaikaʻi nui ma luna o kāna hui nui, ʻo ka flow chemistry kahi kahua koʻikoʻi a ulu nui i ka hoʻonaʻauao a me nā ʻoihana ʻoihana ma muli o kona hiki ke hoʻonui i ka koho a me ka pono o ka synthesis kemika. Hoʻonui kēia mai ka hoʻokumu ʻana i nā molekala organik maʻalahi1 i nā pūhui lāʻau lapaʻau2,3 a me nā huahana kūlohelohe4,5,6. Ma luna o 50% o nā hopena i loko o nā ʻoihana kemika maikaʻi a me nā ʻoihana lāʻau hiki ke pōmaikaʻi mai ke kahe mau ʻana7.
I kēia mau makahiki i hala iho nei, ua ulu nui nā pūʻulu e ʻimi nei e pani i nā mea aniani kahiko a i ʻole nā ​​​​mea hana kemika kahe me nā "reactors" kemika hiki ke hoʻololi. ʻO ka hoʻolālā iterative, ka hana wikiwiki, a me nā mana ʻekolu-dimensional (3D) o kēia mau ʻano he mea pono no ka poʻe makemake e hoʻopilikino i kā lākou mau mea hana no kahi hoʻonohonoho o nā hopena, nā mea hana, a i ʻole nā ​​kūlana. I kēia lā, ʻaneʻane pili wale kēia hana i ka hoʻohana ʻana i nā ʻenehana paʻi 3D polymer e like me stereolithography (SL)9,10,11, Fused Deposition Modeling (FDM)8,12,13,14 a me ka paʻi inkjet7,15. , 16. ʻO ka nele o ka hilinaʻi a me ka hiki ʻana o ia mau mea hana ke hana i kahi ākea o nā hopena kemika17, 18, 19, 20 kahi kumu palena nui no ka hoʻohana ākea ʻana o AM ma kēia kahua17, 18, 19, 20.
Ma muli o ka hoʻohana nui ʻana o ka kemika kahe a me nā waiwai maikaʻi e pili ana me AM, pono e ʻimi ʻia nā ʻenehana ʻoi aku ka maikaʻi e hiki ai i nā mea hoʻohana ke hana i nā moku hoʻoheheʻe kahe me ka maikaʻi o ka kemika a me ka hiki ke nānā. Pono kēia mau ala e ʻae i nā mea hoʻohana e koho mai kahi ʻano o ka ikaika kiʻekiʻe a i ʻole nā ​​​​mea hana i hiki ke hana ma lalo o kahi ākea o nā kūlana pane, a me ka hoʻomaʻamaʻa ʻana i nā ʻano like ʻole o ka hoʻopuka analytical mai ka hāmeʻa e hiki ai ke nānā a mālama i ka hopena.
Hoʻokahi kaʻina hana hoʻohui i hiki ke hoʻohana ʻia no ka hoʻomohala ʻana i nā reactors kemika maʻamau ʻo Ultrasonic Additive Manufacturing (UAM). Hoʻohana kēia ʻano lamination sheet solid-state i nā haʻalulu kani ultrasonic i nā ʻāpana metala lahilahi e hoʻopaʻa iā lākou i ka papa ma ka papa me ka hoʻomehana volumetric liʻiliʻi a me kahi kiʻekiʻe o ka kahe plastik 21, 22, 23. ʻAʻole like me ka hapa nui o nā ʻenehana AM, hiki ke hoʻohui pono ʻia ʻo UAM me ka hana subtractive, i ʻike ʻia he kaʻina hana hybrid, kahi e hoʻoholo ai i ka papa helu helu a i ʻole ka hoʻoponopono laser (CNC2) mi. 25. 'O ia ho'i, 'a'ole i kaupalena 'ia ka mea ho'ohana i nā pilikia e pili ana i ka wehe 'ana i ke koena o ka hale kūkulu kumu mai nā kahawai wai li'ili'i. Hoʻopili pū ʻia kēia kūʻokoʻa hoʻolālā i ke koho ʻana i nā mea i loaʻa - hiki iā UAM ke hoʻopaʻa i nā hui pū ʻana o nā mea thermally like ʻole a me nā mea like ʻole i kahi kaʻina hana hoʻokahi. ʻO ke koho ʻana i nā hui pū ʻana ma mua o ke kaʻina hoʻoheheʻe, ʻo ia ka mea e hiki ke hoʻokō maikaʻi ʻia nā koi mechanical a me nā kemika o nā noi kikoʻī. Ma waho aʻe o ka hoʻopaʻa paʻa paʻa, ʻo kekahi mea ʻē aʻe e kū nei me ka hoʻopaʻa ʻana ultrasonic ʻo ia ka wai kiʻekiʻe o nā mea plastik ma nā haʻahaʻa haʻahaʻa29,30,31,32,33. ʻO kēia hiʻohiʻona kūʻokoʻa o UAM hiki ke hoʻokomo i nā mea mechanical/thermal ma waena o nā papa metala me ka ʻole o ka pōʻino. Hiki i nā mea ʻike UAM i hoʻokomo ʻia ke hoʻomaʻamaʻa i ka hāʻawi ʻana i ka ʻike manawa maoli mai ka mea hoʻohana i ka mea hoʻohana ma o ka hoʻopili ʻana.
ʻO ka hana mua a nā mea kākau32 i hōʻike i ka hiki o ke kaʻina UAM e hana i nā ʻōnaehana microfluidic 3D metala me nā mana ʻike i hoʻokomo ʻia. No ka nānā wale ʻana kēia mea hana. Hōʻike kēia ʻatikala i ka laʻana mua o ka microfluidic chemical reactor i hana ʻia e UAM, kahi mea hana ʻaʻole e hoʻomalu wale akā hoʻoulu pū i ka synthesis kemika me nā mea catalytic i hoʻohui ʻia. Hoʻohui ka mea hana i kekahi mau mea maikaʻi e pili ana i ka ʻenehana UAM i ka hana ʻana i nā mea kemika 3D, e like me: ka hiki ke hoʻololi pololei i kahi hoʻolālā 3D piha mai kahi hoʻolālā kōkua kamepiula (CAD) i kahi huahana; hana nui-mea no ka hui pu ana o ka wela wela a me na mea catalytic, a me na mea ike wela i hookomo pono ia mawaena o na kahawai reactant no ka hoomalu pono a me ka hooponopono ana i ka wela o ka hopena. E hōʻike i ka functionality o ka reactor, ua synthesized he waihona o pharmaceutically koʻikoʻi 1,4-disubstituted 1,2,3-triazole pūhui e ke keleawe-catalyzed 1,3-dipolar Huisgen cycloaddition. Hōʻike kēia hana i ke ʻano o ka hoʻohana ʻana i ka ʻepekema waiwai a me ka hoʻolālā kōkua kamepiula e hiki ai ke wehe i nā mea hou a me nā manawa no ke kemika ma o ka noiʻi interdisciplinary.
Ua kūʻai ʻia nā solvents a me nā reagents a pau mai Sigma-Aldrich, Alfa Aesar, TCI, a i ʻole Fischer Scientific a hoʻohana ʻia me ka hoʻomaʻemaʻe mua ʻole. ʻO 1H a me 13C NMR spectra i hoʻopaʻa ʻia ma 400 a me 100 MHz, i loaʻa ma kahi JEOL ECS-400 400 MHz spectrometer a i ʻole Bruker Avance II 400 MHz spectrometer me CDCl3 a i ʻole (CD3)2SO ma ke ʻano he solvent. Hoʻohana ʻia nā hopena a pau me ka Uniqsis FlowSyn flow chemistry platform.
Ua hoʻohana ʻia ʻo UAM e hana i nā mea hana a pau i kēia noiʻi. Ua hoʻokumu ʻia ka ʻenehana i ka makahiki 1999 a me kāna mau kikoʻī ʻenehana, nā ʻāpana hana a me nā hoʻomohala ʻana mai ka wā i hiki ke aʻo ʻia kāna mea i hana ai me ka hoʻohana ʻana i nā mea i paʻi ʻia ma lalo nei34,35,36,37. Ua hoʻokō ʻia ka hāmeʻa (Fig. 1) me ka hoʻohana ʻana i kahi ʻōnaehana koʻikoʻi 9 kW SonicLayer 4000® UAM (Fabrisonic, Ohio, USA). ʻO nā mea i koho ʻia no ka mīkini kahe ʻo Cu-110 a me Al 6061. ʻO Cu-110 kahi mea keleawe kiʻekiʻe (99.9% copper ka liʻiliʻi), e lilo ia i moho maikaʻi no ka copper catalyzed reactions a no laila ua hoʻohana ʻia ma ke ʻano he "papa hana i loko o ka microreactor. Hoʻohana ʻia ʻo Al 6061 O ma ke ʻano he "bulk" mea; ʻO ke kūlana i hui pū ʻia me ka papa Cu-110 i ʻike ʻia he paʻa kemika me nā reagents i hoʻohana ʻia ma kēia hana ʻo Al 6061 O i hui pū ʻia me Cu-110 i manaʻo ʻia he hui kūpono no kēia study38,42.
Nā ʻanuʻu hana Reactor (1) 6061 Aluminum Aluminum substrate (2) Ka hana ʻana i ke kahawai haʻahaʻa mai ka pahu keleawe (3) Hoʻokomo ʻia nā thermocouples ma waena o nā papa (4) Kawa luna (5) Inlet a me waho (6) Monolithic reactor.
ʻO ka manaʻo hoʻolālā kaila wai ʻo ia ka hoʻohana ʻana i kahi ala wili e hoʻonui ai i ka mamao i hele ʻia e ka wai i loko o ka chip me ka mālama ʻana i ka nui o ka chip. Makemake ʻia kēia hoʻonui i ka mamao e hoʻonui i ka manawa hoʻopili catalyst-reactant a hāʻawi i nā hua huahana maikaʻi loa. Hoʻohana nā ʻōpala i nā piko 90° ma nā wēlau o ke ala pololei e hoʻoulu i ka hui ʻana i loko o ka mīkini44 a hoʻonui i ka manawa pili o ka wai me ka ʻili (catalyst). No ka hoʻonui hou ʻana i ka hui ʻana i hiki ke hoʻokō ʻia, ʻo ka hoʻolālā ʻana o ka reactor e loaʻa i ʻelua inlets reactant i hui pū ʻia i kahi Y-connection ma mua o ke komo ʻana i ka ʻāpana hui hui. ʻO ke kolu o ka puka komo, e hele ana i ke kahe i ka hapalua o kona noho ʻana, ua hoʻokomo ʻia i loko o ka hoʻolālā no nā hopena synthesis multi-stage e hiki mai ana.
Loaʻa i nā kahawai āpau kahi ʻaoʻao huinahā (ʻaʻohe kihi taper), ʻo ia ka hopena o ka milling CNC i hoʻohana ʻia no ka hana ʻana i ka geometry channel. Koho ʻia nā ana o ke kahawai e hāʻawi i kahi hua volumetric kiʻekiʻe (no ka microreactor), akā liʻiliʻi naʻe e maʻalahi i ka launa pū ʻana me ka ʻili (catalysts) no ka hapa nui o nā wai i loko. Hoʻokumu ʻia ka nui kūpono i ka ʻike o nā mea kākau i hala me nā mea hana metala-wai. ʻO ka nui o loko o ke kahawai hope he 750 µm x 750 µm a ʻo ka nui o ka reactor volume he 1 ml. Hoʻokomo ʻia kahi mea hoʻohui i kūkulu ʻia (1/4″-28 UNF thread) i loko o ka hoʻolālā e ʻae i ka hoʻopili maʻalahi o ka hāmeʻa me nā lako kemika kahe kalepa. Ua kaupalena ʻia ka nui o ke kahawai e ka mānoanoa o ka mea foil, kona mau waiwai mechanical, a me nā ʻāpana hoʻopaʻa i hoʻohana ʻia me nā ultrasonic. Ma kahi ākea no nā mea i hāʻawi ʻia, e "kau" ka mea i loko o ke kahawai i hana ʻia. ʻAʻohe kumu hoʻohālike kikoʻī no kēia helu ʻana, no laila ua hoʻoholo ʻia ka laulā kiʻekiʻe o ke kahawai no kahi mea i hāʻawi ʻia a me ka hoʻolālā ʻana ma ka hoʻokolohua ʻana, inā ʻaʻole e hoʻoheheʻe ka laula o 750 µm.
Hoʻoholo ʻia ke ʻano (square) o ke kahawai me ka hoʻohana ʻana i kahi ʻoki ʻoki. Hiki ke hoʻololi i ke ʻano a me ka nui o nā kahawai ma nā mīkini CNC me ka hoʻohana ʻana i nā mea ʻoki ʻokoʻa e loaʻa ai nā kahe kahe ʻokoʻa a me nā ʻano. Hiki ke loaʻa ma Monaghan45 kahi laʻana o ka hana ʻana i kahi ala curved me kahi mea hana 125 µm. I ka hoʻopili ʻia ʻana o ka ʻili pepa palahalaha, ʻo ka hoʻohana ʻana i nā mea ʻala i nā kahawai e loaʻa kahi ʻili palahalaha (pāhālike). Ma kēia hana, ua hoʻohana ʻia kahi ʻāpana huinaha no ka mālama ʻana i ka symmetry channel.
I loko o kahi hoʻomaha i hoʻolālā ʻia i ka hana ʻana, kūkulu pololei ʻia nā mea ʻike wela thermocouple (ʻano K) i loko o ka hāmeʻa ma waena o nā pūʻulu o luna a me lalo (Fig. 1 - pae 3). Hiki i kēia mau thermocouple ke hoʻomalu i nā loli wela mai -200 a 1350 °C.
Lawe ʻia ke kaʻina hana hoʻoheheʻe metala e ka pu UAM me ka hoʻohana ʻana i ka pahu metala 25.4 mm ākea a me 150 microns mānoanoa. Hoʻopili ʻia kēia mau ʻāpana pepa i loko o ke ʻano o nā ʻāpana pili e uhi i ka wahi kūkulu holoʻokoʻa; ʻoi aku ka nui o ka mea i waiho ʻia ma mua o ka huahana hope e like me ke kaʻina hana unuhi i ke ʻano maʻemaʻe hope loa. Hoʻohana ʻia ka mīkini CNC e mīkini i nā contours waho a me loko o nā mea hana, e hopena i ka hoʻopau ʻana i ka ʻili o nā mea hana a me nā kahawai e pili ana i ka mea hana i koho ʻia a me nā ʻāpana kaʻina hana CNC (ma kēia hiʻohiʻona, ma kahi o 1.6 µm Ra). Hoʻohana ʻia ka hoʻomau ʻana o ka ultrasonic material spraying a me nā pōʻai mīkini i loko o ke kaʻina hana o ka mea hana e hōʻoia i ka mālama ʻana i ka pololei o ka dimensional a me ka ʻāpana i hoʻopau ʻia e hālāwai me nā pae kikoʻī milling CNC. ʻO ka laulā o ke kahawai i hoʻohana ʻia no kēia hāmeʻa he liʻiliʻi ia e hōʻoia i ka ʻole o ka "sag" o ka mea foil i loko o ke kahawai wai, no laila he ʻāpana keʻa huinahā. Ua hoʻoholo ʻia ma ka hoʻokolohua ʻana e ka hoa hana hana (Fabrisonic LLC, USA).
Ua hōʻike ʻia nā haʻawina ma ka interface 46, 47 o ka pūhui UAM he liʻiliʻi ka diffusion o nā mea me ka ʻole o ka mālama ʻana i ka wela, no laila no nā mea hana i kēia hana, ʻokoʻa ka papa Cu-110 mai ka papa Al 6061 a loli nui.
E hoʻouka i kahi mea hoʻoponopono kaomi hope (BPR) i hoʻopaʻa ʻia ma mua o 250 psi (1724 kPa) ma lalo o ke kahawai a paʻi i ka wai ma o ka reactor ma ka wikiwiki o 0.1 a 1 ml min-1. Ua nānā ʻia ke kaomi reactor me ka hoʻohana ʻana i ka transducer puʻe FlowSyn i kūkulu ʻia i loko o ka ʻōnaehana e hōʻoia i hiki i ka ʻōnaehana ke mālama i kahi kaomi mau. Ua hoʻāʻo ʻia nā ʻanuʻu wela kūpono i loko o ka reactor kahe ma ka ʻimi ʻana i nā ʻokoʻa ma waena o nā thermocouple i kūkulu ʻia i loko o ka reactor a me nā thermocouple i kūkulu ʻia i loko o ka pā wela o ka chip FlowSyn. Loaʻa kēia ma ka hoʻololi ʻana i ka wela wela wela ma waena o 100 a me 150 °C i nā hoʻonui 25 °C a me ka nānā ʻana i nā ʻokoʻa ma waena o nā mahana i hoʻopaʻa ʻia a i hoʻopaʻa ʻia. Ua hoʻokō ʻia kēia me ka hoʻohana ʻana i ka logger data tc-08 (PicoTech, Cambridge, UK) a me ka lako polokalamu PicoLog.
Hoʻoponopono ʻia nā kūlana no ka hopena cycloaddition o phenylacetylene a me iodoethane (Scheme 1-Cycloaddition of phenylacetylene and iodoethane, Scheme 1-Cycloaddition of phenylacetylene and iodoethane). Ua hana ʻia kēia loiloi me ka hoʻohana ʻana i ka hoʻolālā factorial piha o nā hoʻokolohua (DOE), me ka hoʻohana ʻana i ka mahana a me ka manawa noho ma ke ʻano he mau loli i ka wā e hoʻoponopono ai i ka ratio alkyne: azide ma 1:2.
Ua hoʻomākaukau ʻia nā hoʻonā kaʻawale o ka sodium azide (0.25 M, 4:1 DMF:H2O), iodoethane (0.25 M, DMF), a me phenylacetylene (0.125 M, DMF). He 1.5 ml aliquot o kēlā me kēia hoʻonā i hui ʻia a hoʻomoʻi ʻia ma o ka reactor i ka makemake kahe a me ka mahana. Ua lawe ʻia ka pane o ke kumu hoʻohālike e like me ka ratio o ka wahi kiʻekiʻe o ka huahana triazole i ka mea hoʻomaka o ka phenylacetylene a ua hoʻoholo ʻia me ka hoʻohana ʻana i ka high performance liquid chromatography (HPLC). No ka paʻa ʻana o ka loiloi, ua lawe koke ʻia nā hopena āpau ma hope koke o ka haʻalele ʻana o ka hui ʻana i ka reactor. Hōʻike ʻia nā pae ʻāpana i koho ʻia no ka loiloi ma ka Papa 2.
Ua kālailai ʻia nā laʻana a pau me ka hoʻohana ʻana i kahi ʻōnaehana Chromaster HPLC (VWR, PA, USA) i loaʻa i kahi pahu quaternary, umu kolamu, mea ʻike UV lōʻihi hawewe a me ka autosampler. ʻO ke kolamu he Equivalence 5 C18 (VWR, PA, USA), 4.6 x 100 mm, 5 µm nui ʻāpana, mālama ʻia ma 40°C. ʻO ka mea hoʻoheheʻe he methanol isocratic: wai 50:50 ma kahi kahe kahe o 1.5 ml·min-1. ʻO ka nui o ka injection he 5 μl a he 254 nm ka lōʻihi o ka hawewe. Ua helu ʻia ka % ʻāpana kiʻekiʻe no ka laʻana DOE mai nā wahi kiʻekiʻe o ke koena alkyne a me nā huahana triazole wale nō. ʻO ka hoʻokomo ʻana i ka mea hoʻomaka e hiki ke ʻike i nā piko pili.
ʻO ka hui pū ʻana i nā hopena o ka loiloi reactor me ka polokalamu MODDE DOE (Umetrics, Malmö, Suedena) i ʻae ʻia i ka nānā ʻana i nā hopena a me ka hoʻoholo ʻana i nā kūlana hopena maikaʻi loa no kēia cycloaddition. ʻO ka holo ʻana i ka optimizer i kūkulu ʻia a koho i nā huaʻōlelo koʻikoʻi āpau e hana i kahi hoʻonohonoho o nā kūlana hopena i hoʻolālā ʻia e hoʻonui i ka wahi kiʻekiʻe o ka huahana aʻo ka hoʻemi ʻana i ka wahi kiʻekiʻe no ka feedstock acetylene.
Ua hoʻokō ʻia ka oxidation o ka ʻili keleawe i loko o ke keʻena hopena catalytic me ka hoʻohana ʻana i ka solution hydrogen peroxide (36%) e kahe ana ma ke keʻena pane (ka kahe kahe = 0.4 ml min-1, noho manawa = 2.5 min) ma mua o ka synthesis o kēlā me kēia hui triazole. hale waihona puke.
I ka manawa i hoʻoholo ʻia ai ka hoʻonohonoho kūpono o nā kūlana, ua hoʻohana ʻia lākou i kahi ʻano o ka acetylene a me ka haloalkane derivatives e ʻae i ka hui ʻana o kahi waihona synthesis liʻiliʻi, a laila e hoʻokumu ai i ka hiki ke hoʻopili i kēia mau kūlana i kahi ākea ākea o nā reagents (Fig. 1). 2).
E hoʻomākaukau i nā haʻina kaʻawale o ka sodium azide (0.25 M, 4:1 DMF:H2O), nā haloalkanes (0.25 M, DMF), a me nā alkynes (0.125 M, DMF). Ua hui pū ʻia nā Aliquots o 3 ml o kēlā me kēia hoʻonā a hoʻomoʻi ʻia ma o ka reactor ma ka wikiwiki o 75 µl/min a me kahi mahana o 150°C. Ua hōʻiliʻili ʻia ka nui holoʻokoʻa i loko o kahi hue a hoʻoheheʻe ʻia me 10 ml o ka ethyl acetate. Ua holoi ʻia ka hāpana hāpana me 3 x 10 ml o ka wai. Hoʻohuiʻia nā papa wai a hoʻokuʻuʻia me ka 10 ml ethyl acetate, a laila ua hui pūʻia nā papa honua, holoiʻia me ka 3 × 10 ml brine, maloʻo ma luna o MgSO 4 a kānana, a laila ua weheʻia ka mea hoʻoheheʻe i ka vacuo. Hoʻomaʻemaʻe ʻia nā laʻana e ka silica gel column chromatography me ka hoʻohana ʻana i ka ethyl acetate ma mua o ka nānā ʻana e ka hui pū ʻana o HPLC, 1H NMR, 13C NMR a me ke kiʻekiʻe resolution mass spectrometry (HR-MS).
Loaʻa ʻia nā kikoʻī āpau me ka Thermofischer Precision Orbitrap mass spectrometer me ESI ke kumu ionization. Hoʻomākaukau ʻia nā laʻana a pau me ka hoʻohana ʻana i ka acetonitrile ma ke ʻano he solvent.
Ua lawe ʻia ka loiloi TLC ma nā papa silica me kahi substrate alumini. ʻIke ʻia nā papa me ka kukui UV (254 nm) a i ʻole ka hoʻopaʻa ʻana i ka vanillin a me ka hoʻomehana.
Ua kālailai ʻia nā laʻana a pau me ka hoʻohana ʻana i kahi ʻōnaehana VWR Chromaster (VWR International Ltd., Leighton Buzzard, UK) i hoʻolako ʻia me kahi autosampler, kahi paila binary me ka umu kolamu a me kahi mea ʻike hawewe lōʻihi. Ua hoʻohana ʻia kahi kolamu ACE Equivalence 5 C18 (150 x 4.6 mm, Advanced Chromatography Technologies Ltd., Aberdeen, Scotland).
Ua hana pololei ʻia nā injections (5 µl) mai loko mai o ka hui ʻana i hoʻoheheʻe ʻia (1:10 dilution) a nānā ʻia me ka wai: methanol (50:50 a i ʻole 70:30), koe wale no kekahi mau laʻana e hoʻohana ana i kahi ʻōnaehana solvent 70:30 (i hōʻike ʻia ʻo ka helu hōkū) ma ke kahe kahe o 1.5 ml/min. Ua mālama ʻia ke kolamu ma 40 ° C. ʻO 254 nm ka lōʻihi o ka nalu.
Ua helu ʻia ka % peak area o ka laʻana mai ka wahi kiʻekiʻe o ke koena alkyne, ka huahana triazole wale nō, a me ka hoʻokomo ʻana i ka mea hoʻomaka i hiki ke ʻike i nā piko pili.
Ua kālailai ʻia nā laʻana a pau me ka Thermo iCAP 6000 ICP-OES. Ua hoʻomākaukau ʻia nā kūlana calibration a pau me ka hoʻohana ʻana i kahi hopena maʻamau 1000 ppm Cu ma 2% nitric acid (SPEX Certi Prep). Ua hoʻomākaukauʻia nā kūlana a pau i ka hopena o 5% DMF a me 2% HNO3, a ua hoʻoheheʻeʻia nā mea hoʻohālike a pau i 20 mau manawa me kahi hāpana hāpana o DMF-HNO3.
Hoʻohana ʻo UAM i ka hoʻoheheʻe metala kani ultrasonic e like me ke ʻano o ka hui ʻana i ka pahu metala i hoʻohana ʻia e hana i ka hui hope. Hoʻohana ʻia ka mea hoʻoheheʻe metala kani i kahi mea metala vibrating (i kapa ʻia ʻo horn a i ʻole kani kani kani ultrasonic) e hoʻopili i ke kaomi i ka foil/papa i hoʻohui mua ʻia e hoʻopaʻa ʻia/hoʻohui mua ʻia e ka haʻalulu ʻana i ka mea. No ka hana mau, he cylindrical shape ka sonotrode a ʻōwili ma luna o ka ʻili o ka mea, gluing i ka wahi holoʻokoʻa. Ke hoʻohana ʻia ke kaomi a me ka haʻalulu, hiki i nā oxides ma luna o ka ʻili o ka mea ke pohā. Hiki i ke kaomi mau a me ka haʻalulu ke alakaʻi i ka luku ʻana i ke ʻano o ka mea 36. Hoʻopili pili me ka wela a me ke kaomi kūloko a laila alakaʻi i kahi paʻa paʻa paʻa ma nā pilina mea; Hiki iā ia ke hoʻoikaika i ka pilina ma o ka hoʻololi ʻana i ka ikehu ili48. ʻO ke ʻano o ka mīkini hoʻopaʻa paʻa e lanakila ai i nā pilikia he nui e pili ana i ka wela hoʻoheheʻe ʻana a me nā hopena wela kiʻekiʻe i ʻōlelo ʻia ma nā ʻenehana hana hoʻohui ʻē aʻe. ʻAe kēia i ka hoʻopili pololei ʻana (ʻo ia hoʻi me ka hoʻololi ʻole ʻana o ka ʻili, nā mea hoʻopihapiha a i ʻole nā ​​​​pilikia) o kekahi mau papa o nā mea like ʻole i loko o kahi hale hoʻokahi.
ʻO ka lua o ka mea maikaʻi no ka CAM ʻo ia ke kiʻekiʻe o ke kahe plastik i ʻike ʻia i loko o nā mea metala a me nā mahana haʻahaʻa, ʻo ia hoʻi ma lalo o ka helu heheʻe o nā mea metala. ʻO ka hui pū ʻana o nā haʻalulu kani ultrasonic a me ke kaomi ke kumu o ka neʻe ʻana o ka palena palaoa kūloko a me ka recrystallization me ka ʻole o ka piʻi nui ʻana o ka mahana e pili ana me nā mea nui. I ka wā o ka hana ʻana o ka hui hope, hiki ke hoʻohana ʻia kēia ʻano e hoʻokomo i nā mea hana a me nā mea passive ma waena o nā ʻāpana o ka pahu metala, ka papa ma ka papa. ʻO nā mea e like me ka fiber optical 49, reinforcement 46, electronics 50 a me nā thermocouple (kēia hana) ua hoʻohui maikaʻi ʻia i loko o nā hale UAM e hana i nā hui composite ikaika a passive.
Ma kēia hana, ua hoʻohana ʻia nā mana hoʻopaʻa mea like ʻole a me nā mana intercalation UAM e hana i kahi microreactor kūpono no ka mālama ʻana i ka wela catalytic.
Ke hoʻohālikelike ʻia me ka palladium (Pd) a me nā mea hoʻoheheʻe metala maʻamau i hoʻohana ʻia, he nui nā pōmaikaʻi o Cu catalysis: (i) Ma ke ʻano waiwai, ʻoi aku ka maikaʻi o Cu ma mua o nā metala ʻē aʻe i hoʻohana ʻia i ka catalysis a no laila he koho maikaʻi ia no ka ʻoihana kemika (ii) ke hoʻonui ʻia nei ka nui o nā hopena cross-coupling Cu-catalyzed a ʻike ʻia he ʻano hoʻohui 513-2, Hana maikaʻi nā hopena Cu-catalyzed me ka loaʻa ʻole o nā ligand ʻē aʻe. ʻO kēia mau ligands he mea maʻalahi a maʻalahi. inā makemake ʻia, ʻoiai ʻo nā mea i hoʻohana ʻia i loko o ka Pd chemistry he paʻakikī, pipiʻi, a me ka ea maʻamau (iv) Cu, ʻike nui ʻia no kona hiki ke hoʻopaʻa i nā alkynes i ka synthesis, e like me ka Sonogashira's bimetallic catalyzed coupling a me ka cycloaddition me azides (kaomi kemika) (v) Hiki nō hoʻi iā Cu ke hoʻoikaika i ka hopena o kekahi mau nucleophiles.
I kēia mau lā, ua hōʻike ʻia nā hiʻohiʻona o ka heterogenization o kēia mau hopena āpau i mua o Cu(0). ʻO ka hapa nui kēia ma muli o ka ʻoihana lāʻau lapaʻau a me ka ulu ʻana o ka manaʻo i ka hoʻihoʻi ʻana a me ka hoʻohana hou ʻana i nā catalysts metala55,56.
ʻO ka hopena cycloaddition 1,3-dipolar ma waena o ka acetylene a me ka azide i ka 1,2,3-triazole, i manaʻo mua ʻia e Huisgen i ka makahiki 1960s57, ua manaʻo ʻia he hopena hōʻike synergistic. ʻO ka hopena 1,2,3 mau ʻāpana triazole he mea hoihoi loa ia ma ke ʻano he pharmacophore i ka ʻike ʻana i ka lāʻau ma muli o kā lākou noi olaola a hoʻohana ʻia i nā ʻano lāʻau lapaʻau 58.
Ua loaʻa ka manaʻo hou i kēia pane i ka wā i hoʻokomo ai ʻo Sharpless a me nā mea ʻē aʻe i ka manaʻo o "click chemistry"59. Hoʻohana ʻia ka huaʻōlelo “click chemistry” no ka wehewehe ʻana i kahi pūʻulu ikaika a koho ʻia no ka hoʻopaʻa wikiwiki ʻana o nā pūhui hou a me nā hale waihona puke hui pū me ka hoʻohana ʻana i ka heteroatomic bonding (CXC)60. ʻO ka hoʻopiʻi synthetic o kēia mau hopena ma muli o nā hua kiʻekiʻe e pili ana iā lākou. maʻalahi nā kūlana, kū'ē i ka oxygen a me ka wai, a maʻalahi ka hoʻokaʻawale huahana61.
ʻAʻole hāʻule ka cycloaddition Huisgen 1,3-dipole maʻamau i loko o ka māhele "click chemistry". Eia naʻe, ua hōʻike ʻo Medal a me Sharpless i kēia hanana hui azide-alkyne i ka 107-108 ma ke alo o Cu (I) i hoʻohālikelike ʻia i kahi wikiwiki nui i ka helu o ka non-catalytic 1,3-dipolar cycloaddition 62,63. ʻAʻole pono kēia ʻano hana hoʻokō holomua i ka pale ʻana i nā hui a i ʻole nā ​​kūlana hoʻohālikelike paʻakikī a hāʻawi i ka hoʻololi piha ʻana a me ke koho ʻana i ka 1,4-disubstituted 1,2,3-triazoles (anti-1,2,3-triazoles) i ka manawa (Fig. 3).
Nā hualoaʻa isometric o nā hui huisgen cycloadditions maʻamau a me ke keleawe-catalyzed. Cu(I)-catalyzed Huisgen cycloadditions haawi wale 1,4-disubstituted 1,2,3-triazoles, oiai thermally induced Huisgen cycloadditions typically haawi 1,4- a me 1,5-triazoles he 1:1 hui o azole stereoisomers.
ʻO ka hapa nui o nā protocols e pili ana i ka hōʻemi ʻana i nā kumu paʻa o Cu (II), e like me ka hoʻemi ʻana o CuSO4 a i ʻole ka hui Cu (II)/Cu (0) i hui pū ʻia me nā paʻakai sodium. Ke hoʻohālikelike ʻia me nā mea ʻē aʻe metala catalyzed reactions, ʻo ka hoʻohana ʻana iā Cu (I) ka mea nui o ka maʻalahi a maʻalahi hoʻi e mālama.
Nā haʻawina kinetic a me isotopic e Worrell et al. Ua hōʻike ʻo 65 i ke ʻano o nā alkynes terminal, ʻelua mau mea like o ke keleawe i komo i ka hoʻoulu ʻana i ka reactivity o kēlā me kēia mole e pili ana i ka azide. Hoʻomaka ka mīkini i manaʻo ʻia ma o ke apo metala keleawe ʻeono lālā i hana ʻia e ka hui ʻana o azide i σ-paʻa keleawe acetylide me π-paʻa keleawe ma ke ʻano he ligand hāʻawi paʻa. Hoʻokumu ʻia nā derivatives copper triazolyl ma muli o ka hoʻopaʻa ʻana o ke apo i ukali ʻia e ka decomposition proton e hana i nā huahana triazole a pani i ka pōʻai catalytic.
ʻOiai ua kākau maikaʻi ʻia nā pōmaikaʻi o nā hāmeʻa kemika kahe, aia ka makemake e hoʻohui i nā mea hana analytical i loko o kēia mau ʻōnaehana no ka nānā ʻana i ke kaʻina hana maoli ma situ66,67. Ua hōʻike ʻia ʻo UAM he ala kūpono no ka hoʻolālā ʻana a me ka hana ʻana i nā reactors kahe 3D paʻakikī loa mai ka catalytically active, thermally conductive material me nā mea ʻike i hoʻokomo pono ʻia (Fig. 4).
Aluminum-keleawe kahe reactor i hana ʻia e ka ultrasonic additive manufacturing (UAM) me ka paʻakikī o loko o ke kahawai, nā thermocouples i kūkulu ʻia a me kahi keʻena catalytic reaction. No ka ʻike ʻana i nā ala wai i loko, hōʻike pū ʻia kahi prototype maopopo i hana ʻia me ka stereolithography.
No ka hōʻoia ʻana i ka hana ʻana o nā reactors no nā hopena kūlohelohe e hiki mai ana, pono e hoʻomehana ʻia nā mea hoʻoheheʻe ma luna o ko lākou wahi paila; ua hoʻāʻo ʻia ke kaomi a me ka mahana. Ua hōʻike ʻia ka hoʻāʻo ʻana e mālama ka ʻōnaehana i ka paʻa paʻa a me ke kaomi mau ʻana ma ke kaomi kiʻekiʻe o ka ʻōnaehana (1.7 MPa). Ua hana ʻia nā hoʻāʻo hydrostatic ma ka lumi wela me ka hoʻohana ʻana iā H2O ma ke ʻano he wai.
ʻO ka hoʻohui ʻana i ka thermocouple i kūkulu ʻia (Figure 1) i ka logger data wela ua hōʻike ʻia ʻo 6 °C (± 1 °C) ka mahana thermocouple ma lalo o ka mahana i hoʻonohonoho ʻia ma ka ʻōnaehana FlowSyn. ʻO ka mea maʻamau, ʻo ka piʻi ʻana o ka mahana he 10°C e pāpālua i ka wikiwiki o ka hopena, no laila hiki i ka ʻokoʻa wela o nā degere liʻiliʻi ke hoʻololi nui i ka helu pane. ʻO kēia ʻokoʻa ma muli o ka pau ʻana o ka mahana i loko o ka RPV ma muli o ke kiʻekiʻe thermal diffusivity o nā mea i hoʻohana ʻia i ke kaʻina hana. Paʻa mau kēia kahe wela a no laila hiki ke noʻonoʻo ʻia i ka wā e hoʻonohonoho ai i nā mea hana e hōʻoia i ka loaʻa ʻana o nā mahana kūpono a ana ʻia i ka wā o ka hopena. No laila, hoʻomaʻamaʻa kēia hāmeʻa mākaʻikaʻi pūnaewele i ka hoʻomalu paʻa ʻana i ka wela o ka hopena a hāʻawi i ka ʻoi aku ka pololei o ke kaʻina hana a me ka hoʻomohala ʻana i nā kūlana maikaʻi loa. Hiki ke hoʻohana ʻia kēia mau mea ʻike no ka ʻike ʻana i nā hopena exothermic a pale i nā hopena holo i nā ʻōnaehana nui.
ʻO ka reactor i hōʻike ʻia ma kēia pepa ʻo ia ka laʻana mua o ka hoʻohana ʻana i ka ʻenehana UAM i ka hana ʻana i nā reactors kemika a kamaʻilio i kekahi mau palena nui e pili ana i kēia manawa me ka paʻi AM/3D o kēia mau mea, e like me: (i) Ke lanakila ʻana i nā pilikia i ʻike ʻia e pili ana i ka hana ʻana o ke keleawe a i ʻole ka alumini alumini (ii) hoʻomaikaʻi ʻia ka hoʻonā ʻana o ke kahawai kūloko i hoʻohālikelike ʻia me ka hoʻoheheʻe ʻana i ka lepo (PBF) a me nā ʻano melting melting (PBF9) a me nā mea melting (PBF) a me nā ʻano melting powder bed (PBF). ili kino texture26 (iii) haʻahaʻa hana wela, ka mea maʻalahi i ka hoʻopili pololei 'ana i nā mea ike, i hiki ole i ka pauda moe enehana, (v) lanakila ana i ka ilihune mechanical waiwai a me ka sensitivity o polymer-e pili ana i nā mea like ole organik solvents17,19.
Ua hōʻike ʻia ka hana o ka reactor e ke ʻano o ka copper-catalyzed alkinazide cycloaddition reactions ma lalo o nā kūlana kahe mau (Fig. 2). ʻO ka ultrasonic paʻi keleawe reactor i hōʻike ʻia ma ka fig. Ua hoʻohuiʻiaʻo 4 me kahi'ōnaehana kahe kālepa a hoʻohanaʻia e synthesize i kahi waihona azide o nāʻano 1,4-disubstituted 1,2,3-triazoles me ka hoʻohanaʻana i ka hopena wela o ka acetylene a me ka hui alkyl halides i mua o ka sodium chloride (Fig. 3). ʻO ka hoʻohana ʻana i ke ala kahe mau e hōʻemi i nā pilikia palekana e hiki ke ala mai i nā kaʻina hana pūʻulu, no ka mea, hoʻopuka kēia hopena i nā azide intermediates nui loa a weliweli [317], [318]. I ka hoʻomaka ʻana, ua ʻoi aku ka maikaʻi o ka hopena no ka cycloaddition o phenylacetylene a me iodoethane (Scheme 1 – Cyclloaddition of phenylacetylene and iodoethane) (e nānā i ke kiʻi 5).
(Ma ka hema hema) Hoʻolālā o ka hoʻonohonoho hoʻonohonoho i hoʻohana ʻia e hoʻokomo i kahi reactor 3DP i loko o kahi ʻōnaehana kahe (luna ʻākau) i loaʻa mai ka hoʻolālā i hoʻopaʻa ʻia (lalo) o ka hui cycloaddition Huisgen 57 ma waena o ka phenylacetylene a me ka iodoethane no ka hoʻonui ʻana a me ka hōʻike ʻana i nā palena o ka hoʻololi ʻana o ka hopena.
Ma ka mālama ʻana i ka manawa noho o nā mea hoʻopiʻi ma ka ʻāpana catalytic o ka reactor a me ka nānā pono ʻana i ka wela o ka hopena me kahi sensor thermocouple i hoʻohui pono ʻia, hiki ke hoʻopaʻa ʻia nā kūlana hopena me ka liʻiliʻi o ka manawa a me nā mea. Ua ʻike koke ʻia ua hoʻokō ʻia ka hoʻololi kiʻekiʻe me ka hoʻohana ʻana i ka manawa noho o 15 mau minuke a me kahi mahana hopena o 150 ° C. Hiki ke ʻike ʻia mai ka ʻāpana coefficient o ka polokalamu MODDE e manaʻo ʻia ka manawa noho a me ka wela o ka hopena i nā kūlana koʻikoʻi o ke kumu hoʻohālike. ʻO ka holo ʻana i ka mea hoʻonui i kūkulu ʻia me ka hoʻohana ʻana i kēia mau kūlana i koho ʻia e hana i kahi hoʻonohonoho o nā kūlana hopena i hoʻolālā ʻia e hoʻonui i nā wahi kiʻekiʻe o ka huahana i ka wā e hoʻemi ana i nā wahi kiʻekiʻe o nā mea. Ua hāʻawi kēia hoʻonui i ka 53% o ka hoʻololi ʻana o ka huahana triazole, i kūlike loa me ka wānana o ke kumu hoʻohālike o 54%.