Ua tsaug rau koj tuaj xyuas Nature.com. Lub browser version uas koj siv muaj kev txhawb nqa tsawg rau CSS. Rau qhov kev paub zoo tshaj plaws, peb xav kom koj siv lub browser hloov tshiab (lossis tua hom kev sib raug zoo hauv Internet Explorer). Lub sijhawm no, kom ntseeg tau tias muaj kev txhawb nqa txuas ntxiv, peb yuav tso saib lub xaib tsis muaj cov qauv thiab JavaScript.
Kev tsim khoom ntxiv tab tom hloov txoj kev uas cov kws tshawb fawb thiab cov neeg ua lag luam tsim thiab tsim cov khoom siv tshuaj kom tau raws li lawv cov kev xav tau tshwj xeeb. Hauv txoj haujlwm no, peb tshaj tawm thawj qhov piv txwv ntawm lub tshuab ua kom dej ntws los ntawm cov txheej txheem lamination hlau khov kho Ultrasonic Additive Manufacturing (UAM) nrog cov khoom catalytic ncaj qha thiab cov khoom siv sensing. Tsis yog tsuas yog UAM thev naus laus zis kov yeej ntau qhov kev txwv tam sim no cuam tshuam nrog kev tsim khoom ntxiv ntawm cov tshuaj reactors, tab sis nws kuj ua rau muaj peev xwm ntawm cov khoom siv zoo li no ntau dua. Ib qho ntawm cov khoom siv tseem ceeb ntawm 1,4-disubstituted 1,2,3-triazole tau ua tiav synthesized thiab optimized los ntawm Cu-mediated Huisgen 1,3-dipolar cycloaddition reaction siv UAM chemistry teeb tsa. Los ntawm kev siv cov khoom tshwj xeeb ntawm UAM thiab kev ua haujlwm ntws tas mus li, lub cuab yeej muaj peev xwm ua rau cov tshuaj tiv thaiv tas mus li thaum tseem muab cov lus teb tiag tiag rau kev saib xyuas thiab kev ua kom zoo dua.
Vim nws muaj qhov zoo dua li nws cov khoom loj, kev siv tshuaj lom neeg yog ib qho tseem ceeb thiab loj hlob hauv kev kawm thiab kev lag luam vim nws muaj peev xwm ua kom muaj kev xaiv thiab kev ua haujlwm ntawm kev tsim tshuaj lom neeg. Qhov no txuas ntxiv mus los ntawm kev tsim cov organic molecule yooj yim1 mus rau cov tshuaj sib xyaw2,3 thiab cov khoom ntuj4,5,6. Ntau tshaj 50% ntawm cov tshuaj tiv thaiv hauv kev lag luam tshuaj lom neeg thiab tshuaj zoo tuaj yeem tau txais txiaj ntsig los ntawm kev siv cov txheej txheem ntws tas mus li7.
Nyob rau xyoo tas los no, muaj kev loj hlob ntawm cov pab pawg uas tab tom nrhiav kev hloov cov khob iav ib txwm muaj lossis cov khoom siv tshuaj lom neeg nrog cov khoom siv tsim kho ntxiv (AM) chemistry "cov hlab ntsha tshuaj tiv thaiv"8. Kev tsim kho dua tshiab, kev tsim khoom sai, thiab 3-dimensional (3D) muaj peev xwm ntawm cov txheej txheem no yog qhov zoo rau cov neeg uas xav kho lawv cov khoom siv rau cov txheej txheem tshwj xeeb ntawm cov tshuaj tiv thaiv, cov khoom siv, lossis cov xwm txheej. Txog niaj hnub no, txoj haujlwm no tau tsom mus rau kev siv cov txheej txheem luam ntawv 3D raws li polymer xws li stereolithography (SL)9,10,11, fused deposition modeling (FDM)8,12,13,14 thiab inkjet luam ntawv 7, 15, 16. Qhov tsis muaj kev ruaj khov thiab muaj peev xwm ntawm cov khoom siv no los ua ntau yam tshuaj tiv thaiv / kev tshuaj xyuas17, 18, 19, 20 yog qhov tseem ceeb txwv rau kev siv dav dua ntawm AM hauv daim teb no17, 18, 19, 20.
Vim muaj kev siv tshuaj lom neeg ntau ntxiv thiab cov khoom zoo uas cuam tshuam nrog AM, muaj qhov xav tau los tshawb nrhiav cov txheej txheem siab dua uas ua rau cov neeg siv tsim cov hlab ntsha uas muaj peev xwm tshuaj lom neeg thiab kev txheeb xyuas zoo dua. Cov txheej txheem no yuav tsum ua rau cov neeg siv xaiv los ntawm ntau yam khoom siv uas muaj zog lossis ua haujlwm tau zoo uas muaj peev xwm tswj tau ntau yam kev mob ntawm cov tshuaj tiv thaiv, thaum tseem pab txhawb ntau hom kev tso zis los ntawm lub cuab yeej kom tso cai rau kev saib xyuas thiab tswj cov tshuaj tiv thaiv.
Ib qho txheej txheem tsim khoom ntxiv uas muaj peev xwm tsim cov tshuaj reactors tshwj xeeb yog Ultrasonic Additive Manufacturing (UAM). Cov txheej txheem lamination ntawm daim ntawv khov kho no siv cov oscillations ultrasonic rau cov ntawv ci hlau nyias kom koom ua ke txheej los ntawm txheej nrog qhov kub tsawg kawg nkaus thiab qib siab ntawm cov yas ntws 21, 22, 23. Tsis zoo li feem ntau lwm cov thev naus laus zis AM, UAM tuaj yeem koom ua ke ncaj qha nrog kev tsim khoom rho tawm, hu ua cov txheej txheem tsim khoom sib xyaw, uas nyob rau hauv-situ periodic computer numerical tswj (CNC) milling lossis laser machining txhais cov duab ntawm ib txheej ntawm cov khoom sib txuas 24, 25. Qhov no txhais tau tias tus neeg siv tsis txwv los ntawm cov teeb meem cuam tshuam nrog kev tshem tawm cov khoom siv raw seem los ntawm cov kua dej me me, uas feem ntau yog qhov teeb meem nrog hmoov thiab kua AM systems26,27,28. Qhov kev ywj pheej tsim no kuj nthuav dav mus rau cov kev xaiv khoom siv muaj - UAM tuaj yeem sib txuas cov khoom sib xyaw thermally zoo sib xws thiab sib txawv hauv ib kauj ruam txheej txheem. Kev xaiv cov khoom sib xyaw dhau ntawm cov txheej txheem yaj txhais tau tias cov kev xav tau kho tshuab thiab tshuaj lom neeg ntawm cov ntawv thov tshwj xeeb tuaj yeem ua tau zoo dua. Ntxiv nrog rau kev sib txuas khov kho, lwm qhov xwm txheej ntsib thaum lub sijhawm Kev sib txuas ultrasonic yog qhov ntws siab ntawm cov khoom siv yas ntawm qhov kub qis dua 29, 30, 31, 32, 33. Qhov tshwj xeeb no ntawm UAM tuaj yeem pab txhawb kev ntxig cov khoom siv kho tshuab / thermal ntawm cov txheej hlau yam tsis muaj kev puas tsuaj. UAM embedded sensors tuaj yeem pab txhawb kev xa cov ntaub ntawv tiag tiag los ntawm lub cuab yeej mus rau tus neeg siv los ntawm kev sib xyaw ua ke.
Cov kws sau ntawv txoj haujlwm yav dhau los 32 tau qhia txog lub peev xwm ntawm cov txheej txheem UAM los tsim cov qauv hlau 3D microfluidic nrog cov peev xwm sib xyaw ua ke. Qhov no yog ib qho cuab yeej saib xyuas xwb. Daim ntawv no nthuav qhia thawj qhov piv txwv ntawm lub tshuab hluav taws xob microfluidic uas tsim los ntawm UAM; ib lub cuab yeej ua haujlwm uas tsis yog tsuas yog saib xyuas tab sis kuj ua rau muaj kev sib xyaw ua ke ntawm cov tshuaj los ntawm cov khoom siv catalyst sib xyaw ua ke. Lub cuab yeej ua ke ntau qhov zoo cuam tshuam nrog thev naus laus zis UAM hauv kev tsim khoom siv tshuaj 3D, xws li: lub peev xwm los hloov cov qauv 3D tag nrho ncaj qha los ntawm cov qauv tsim computer-aided (CAD) mus rau hauv cov khoom; ntau yam khoom siv los ua ke cov khoom siv thermal conductivity siab thiab cov ntaub ntawv catalytic; thiab embedding thermal sensors ncaj qha ntawm cov kwj dej reagent rau kev saib xyuas thiab tswj qhov kub thiab txias. Txhawm rau qhia txog kev ua haujlwm ntawm lub reactor, lub tsev qiv ntawv ntawm cov tshuaj tseem ceeb 1,4-disubstituted 1,2,3-triazole compounds tau synthesized los ntawm tooj liab-catalyzed Huisgen 1,3-dipolar cycloaddition. Txoj haujlwm no qhia txog yuav ua li cas siv cov ntaub ntawv tshawb fawb thiab kev tsim qauv computer-aided tuaj yeem qhib cov cib fim tshiab thiab cov peev xwm rau chemistry los ntawm kev tshawb fawb ntau yam.
Tag nrho cov kuab tshuaj thiab cov tshuaj reagents tau yuav los ntawm Sigma-Aldrich, Alfa Aesar, TCI lossis Fischer Scientific thiab tau siv yam tsis tau ua kom huv ua ntej. 1H thiab 13C NMR spectra kaw ntawm 400 MHz thiab 100 MHz, raws li, tau txais los ntawm kev siv JEOL ECS-400 400 MHz spectrometer lossis Bruker Avance II 400 MHz spectrometer thiab CDCl3 lossis (CD3) 2SO ua cov kuab tshuaj. Tag nrho cov tshuaj tiv thaiv tau ua tiav los ntawm kev siv Uniqsis FlowSyn flow chemistry platform.
UAM tau siv los tsim txhua yam khoom siv hauv txoj kev tshawb fawb no. Cov thev naus laus zis tau tsim tawm xyoo 1999, thiab nws cov ntsiab lus kev siv tshuab, cov kev ua haujlwm thiab kev txhim kho txij li nws txoj kev tsim kho tuaj yeem kawm los ntawm cov ntaub ntawv luam tawm hauv qab no34,35,36,37. Lub cuab yeej (Daim Duab 1) tau siv los ntawm kev siv lub zog siab heev, 9kW SonicLayer 4000® UAM system (Fabrisonic, OH, USA). Cov ntaub ntawv xaiv rau kev tsim cov khoom siv ntws yog Cu-110 thiab Al 6061. Cu-110 muaj cov ntsiab lus tooj liab siab (tsawg kawg 99.9% tooj liab), ua rau nws yog tus neeg sib tw zoo rau cov tshuaj tiv thaiv tooj liab, thiab yog li ntawd siv ua "txheej txheem nquag hauv microreactor. Al 6061 O siv ua cov khoom siv "ntau", kuj yog txheej Embedding siv rau kev tshuaj xyuas; Alloy auxiliary component embedding thiab annealed mob ua ke nrog Cu-110 txheej. Al 6061 O yog cov khoom siv uas tau pom tias sib xws nrog UAM txheej38, 39, 40, 41 thiab tau raug sim thiab pom tias Chemically ruaj khov nrog cov reagents siv hauv txoj haujlwm no. Kev sib xyaw ua ke ntawm Al 6061 O nrog Cu-110 kuj suav hais tias yog kev sib xyaw ua ke ntawm cov khoom siv rau UAM thiab yog li ntawd yog cov khoom siv tsim nyog rau txoj kev tshawb fawb no. 38,42 Cov khoom siv no tau teev nyob rau hauv Rooj 1 hauv qab no.
Cov theem tsim cov reactor (1) Al 6061 substrate (2) Kev tsim cov channel hauv qab teeb tsa rau cov ntawv ci tooj liab (3) Kev muab cov thermocouples ntawm cov khaubncaws sab nraud povtseg (4) Cov channel sab saud (5) Qhov nkag thiab qhov tawm (6) Monolithic reactor.
Lub tswv yim tsim ntawm txoj kev kua dej yog siv txoj kev convoluted kom nce qhov deb ntawm cov kua dej mus ncig hauv lub chip, thaum khaws lub chip ntawm qhov loj me uas tswj tau. Qhov kev nce qhov deb no yog qhov xav tau los ua kom lub sijhawm sib cuam tshuam catalyst / reagent thiab muab cov khoom lag luam zoo heev. Cov chips siv 90 ° khoov ntawm qhov kawg ntawm txoj kev ncaj los ua kom muaj kev sib xyaw turbulent hauv lub cuab yeej44 thiab ua kom lub sijhawm sib cuag ntawm cov kua dej nrog qhov chaw (catalyst). Txhawm rau kom nce qhov kev sib xyaw uas tuaj yeem ua tiav, tus qauv tsim reactor muaj ob lub qhov nkag reagent ua ke ntawm Y-junction ua ntej nkag mus rau hauv qhov chaw sib xyaw serpentine. Qhov nkag thib peb, uas sib tshuam cov kwj dej ib nrab ntawm nws qhov chaw nyob, suav nrog hauv kev tsim ntawm cov tshuaj tiv thaiv ntau kauj ruam yav tom ntej.
Txhua txoj kab muaj ib daim duab plaub fab (tsis muaj lub kaum sab xis), qhov tshwm sim ntawm lub sijhawm CNC milling siv los tsim cov geometry ntawm txoj kab. Qhov ntev ntawm txoj kab raug xaiv los xyuas kom meej tias muaj qhov tso zis siab (rau lub microreactor), thaum me txaus los pab txhawb kev sib cuam tshuam ntawm qhov chaw (catalysts) rau feem ntau ntawm cov kua dej uas muaj. Qhov loj me tsim nyog yog raws li cov kws sau ntawv qhov kev paub dhau los nrog cov khoom siv hlau-fluidic rau cov tshuaj tiv thaiv. Qhov ntev sab hauv ntawm txoj kab kawg yog 750 µm x 750 µm thiab tag nrho cov reactor ntim yog 1 ml. Ib qho txuas sib xyaw (1/4″—28 UNF xov) suav nrog hauv kev tsim kom yooj yim sib txuas ntawm lub cuab yeej nrog cov khoom siv tshuaj lom neeg lag luam. Qhov loj ntawm txoj kab yog txwv los ntawm qhov tuab ntawm cov khoom siv ntawv ci, nws cov khoom siv kho tshuab, thiab cov kev sib txuas siv nrog ultrasonics. Ntawm qhov dav tshwj xeeb rau ib yam khoom siv, cov khoom siv yuav "sag" rau hauv txoj kab tsim. Tam sim no tsis muaj qauv tshwj xeeb rau qhov kev xam no, yog li qhov dav tshaj plaws ntawm txoj kab rau ib yam khoom siv thiab kev tsim qauv tau txiav txim siab sim; hauv qhov no, qhov dav ntawm 750 μm yuav tsis ua rau sag.
Lub duab (square) ntawm cov channel yog txiav txim siab los ntawm kev siv lub tshuab txiav plaub fab. Lub duab thiab qhov loj ntawm cov channel tuaj yeem hloov pauv los ntawm CNC tshuab siv cov cuab yeej txiav sib txawv kom tau txais cov nqi ntws sib txawv thiab cov yam ntxwv. Ib qho piv txwv ntawm kev tsim cov channel zoo li nkhaus siv cov cuab yeej 125 μm tuaj yeem pom hauv txoj haujlwm ntawm Monaghan45. Thaum cov txheej ntawv ci raug tso rau hauv ib qho planar fashion, qhov overlay ntawm cov khoom ntawv ci hla cov channel yuav muaj qhov tiaj tiaj (square) tiav. Hauv txoj haujlwm no, txhawm rau kom tswj tau qhov sib xws ntawm cov channel, ib daim duab plaub fab tau siv.
Thaum lub sijhawm ncua sijhawm ua ntej hauv kev tsim khoom, cov khoom ntsuas kub thermocouple (Hom K) tau muab tso rau hauv lub cuab yeej ntawm cov pab pawg sab saud thiab sab qis (Daim Duab 1 - Theem 3). Cov thermocouples no tuaj yeem saib xyuas qhov kub hloov pauv ntawm -200 txog 1350 °C.
Cov txheej txheem tso hlau yog ua los ntawm lub tshuab raj UAM siv cov ntawv ci hlau dav 25.4 hli, tuab 150 micron. Cov txheej ntawv ci no tau sib txuas ua ke rau hauv cov kab sib txuas kom npog tag nrho thaj chaw tsim kho; qhov loj ntawm cov khoom tso yog loj dua li cov khoom kawg raws li cov txheej txheem rho tawm tsim cov duab kawg. CNC machining yog siv los tshuab cov duab sab nraud thiab sab hauv ntawm cov khoom siv, ua rau qhov tiav ntawm cov khoom siv thiab cov channel sib npaug rau cov cuab yeej xaiv thiab CNC txheej txheem parameters (kwv yees li 1.6 μm Ra hauv qhov piv txwv no). Kev txuas ntxiv, txuas ntxiv ultrasonic khoom deposition thiab machining cycles yog siv thoob plaws hauv cov txheej txheem tsim khoom siv kom ntseeg tau tias qhov tseeb ntawm qhov ntev yog khaws cia thiab qhov tiav lawm yuav ua tau raws li CNC tiav milling qib raug. Qhov dav ntawm channel siv rau lub cuab yeej no yog me txaus kom ntseeg tau tias cov khoom siv ntawv ci tsis "sag" rau hauv cov kua channel, yog li cov channel tswj hwm ib qho square cross-section. Tej zaum qhov sib txawv hauv cov khoom siv ntawv ci thiab cov txheej txheem UAM parameters tau txiav txim siab los ntawm kev sim los ntawm tus khub tsim khoom (Fabrisonic LLC, USA).
Cov kev tshawb fawb tau qhia tias me ntsis kev sib kis ntawm cov khoom tshwm sim ntawm UAM bonding interface 46, 47 yam tsis muaj kev kho cua sov ntxiv, yog li rau cov khoom siv hauv txoj haujlwm no, Cu-110 txheej tseem sib txawv ntawm Al 6061 txheej thiab hloov pauv sai sai.
Nruab ib lub tshuab tswj qhov siab rov qab (BPR) uas tau teeb tsa ua ntej 250 psi (1724 kPa) rau ntawm qhov tawm ntawm lub reactor thiab twj dej los ntawm lub reactor ntawm tus nqi ntawm 0.1 txog 1 mL min-1. Lub zog ntawm lub reactor tau saib xyuas siv lub FlowSyn lub tshuab ntsuas siab uas ua rau lub kaw lus ua haujlwm kom paub tseeb tias lub kaw lus tuaj yeem tswj tau qhov siab tas li. Kev hloov pauv kub ntawm lub tshuab hluav taws xob tau raug sim los ntawm kev txheeb xyuas qhov sib txawv ntawm cov thermocouples uas nyob hauv lub reactor thiab cov uas nyob hauv lub FlowSyn chip heating plate. Qhov no yog ua tiav los ntawm kev hloov pauv qhov kub ntawm lub phaj kub uas tau teeb tsa ntawm 100 thiab 150 °C hauv 25 °C increments thiab sau tseg qhov sib txawv ntawm qhov kub uas tau teeb tsa thiab kaw cia. Qhov no tau ua tiav los ntawm kev siv lub tc-08 data logger (PicoTech, Cambridge, UK) thiab cov software PicoLog uas nrog nws.
Cov xwm txheej cycloaddition ntawm phenylacetylene thiab iodoethane tau raug kho kom zoo (Scheme 1- Cycloaddition ntawm phenylacetylene thiab iodoethane Scheme 1- Cycloaddition ntawm phenylacetylene thiab iodoethane). Qhov kev kho kom zoo no tau ua tiav los ntawm kev tsim qauv tag nrho ntawm kev sim (DOE), siv qhov kub thiab lub sijhawm nyob ua cov kev hloov pauv, thaum kho qhov piv ntawm alkyne:azide ntawm 1: 2.
Cov tshuaj sib cais ntawm sodium azide (0.25 M, 4:1 DMF:H2O), iodoethane (0.25 M, DMF), thiab phenylacetylene (0.125 M, DMF) tau npaj tseg. Ib qho 1.5 mL aliquot ntawm txhua cov tshuaj tau sib xyaw thiab pumped los ntawm lub reactor ntawm qhov nrawm thiab kub xav tau. Cov lus teb qauv tau coj los ua qhov piv ntawm thaj chaw siab tshaj plaws ntawm cov khoom triazole rau cov khoom pib phenylacetylene thiab txiav txim siab los ntawm cov kua ua haujlwm siab chromatography (HPLC). Rau kev sib xws ntawm kev tshuaj xyuas, tag nrho cov tshuaj tiv thaiv tau kuaj tom qab cov tshuaj tiv thaiv sib xyaw tawm ntawm lub reactor. Cov parameter ntau yam xaiv rau kev ua kom zoo dua tau qhia hauv Rooj 2.
Tag nrho cov qauv kuaj tau raug tshuaj xyuas siv lub tshuab Chromaster HPLC (VWR, PA, Tebchaws USA) uas muaj lub twj tso kua mis quaternary, lub qhov cub kem, lub tshuab ntes UV hloov pauv wavelength thiab lub tshuab kuaj autosampler. Lub kem yog Equivalence 5 C18 (VWR, PA, Tebchaws USA), 4.6 × 100 mm loj, 5 µm qhov loj ntawm cov khoom me me, khaws cia ntawm 40 °C. Cov kuab tshuaj yog isocratic 50:50 methanol:dej ntawm tus nqi ntws ntawm 1.5 mL.min-1. Lub ntim txhaj tshuaj yog 5 µL thiab lub tshuab ntes wavelength yog 254 nm. Lub cheeb tsam % ncov rau cov qauv DOE tau suav los ntawm cov cheeb tsam ncov ntawm cov khoom seem alkyne thiab triazole xwb. Kev txhaj tshuaj ntawm cov khoom pib tso cai rau kev txheeb xyuas cov ncov tseem ceeb.
Kev txuas cov zis ntawm cov tshuaj ntsuam xyuas reactor rau MODDE DOE software (Umetrics, Malmö, Sweden) tau tso cai rau kev tshuaj xyuas kom meej ntawm cov qauv tshwm sim thiab kev txiav txim siab ntawm cov xwm txheej zoo tshaj plaws rau qhov cycloaddition no. Kev khiav lub optimizer uas tau tsim thiab xaiv tag nrho cov lus tseem ceeb ntawm tus qauv ua rau muaj cov xwm txheej tshuaj ntsuam uas tsim los ua kom thaj chaw siab tshaj plaws ntawm cov khoom thaum txo thaj chaw siab tshaj plaws rau cov khoom pib acetylene.
Qhov oxidation ntawm tooj liab saum npoo av hauv lub chamber catalytic reaction tau ua tiav los ntawm kev siv cov tshuaj hydrogen peroxide (36%) ntws los ntawm lub chamber reaction (flow rate = 0.4 mL min-1, residence time = 2.5 min) ua ntej kev tsim txhua lub tsev qiv ntawv triazole compound.
Thaum twg tau txheeb xyuas cov xwm txheej zoo tshaj plaws, lawv tau siv rau ntau yam acetylene thiab haloalkane derivatives kom tso cai rau kev sib sau ua ke ntawm lub tsev qiv ntawv me me, yog li tsim kom muaj peev xwm siv cov xwm txheej no rau ntau yam tshuaj reagents (Daim Duab 1).2).
Npaj cov tshuaj sib cais ntawm sodium azide (0.25 M, 4:1 DMF:H2O), haloalkanes (0.25 M, DMF) thiab alkynes (0.125 M, DMF). 3 mL aliquots ntawm txhua cov tshuaj tau sib xyaw thiab pumped los ntawm lub reactor ntawm 75 µL.min-1 thiab 150 °C. Tag nrho cov ntim tau sau rau hauv lub vial thiab diluted nrog 10 mL ntawm ethyl acetate. Cov kua qauv tau ntxuav nrog 3 × 10 mL ntawm dej. Cov txheej aqueous tau sib xyaw thiab rho tawm nrog 10 mL ntawm ethyl acetate; cov txheej organic tau sib xyaw ua ke, ntxuav nrog 3 x 10 mL ntawm brine, ziab hla MgSO4 thiab lim, tom qab ntawd cov kuab tshuaj tau tshem tawm hauv vacuo. Cov qauv tau purified los ntawm kem chromatography ntawm silica gel siv ethyl acetate ua ntej kev tshuaj xyuas los ntawm kev sib xyaw ua ke ntawm HPLC, 1H NMR, 13C NMR thiab high resolution mass spectrometry (HR-MS).
Tag nrho cov spectra tau txais los ntawm kev siv Thermofischer precision Orbitrap resolution mass spectrometer nrog ESI ua qhov chaw ionization. Tag nrho cov qauv tau npaj siv acetonitrile ua cov kuab tshuaj.
Kev tshuaj xyuas TLC tau ua rau ntawm cov phaj silica uas muaj txhuas. Cov phaj tau pom los ntawm lub teeb UV (254 nm) lossis vanillin staining thiab cua sov.
Tag nrho cov qauv kuaj tau raug tshuaj xyuas siv lub VWR Chromaster (VWR International Ltd., Leighton Buzzard, UK) system uas muaj lub autosampler, lub twj tso kua mis binary ntawm lub qhov cub thiab lub tshuab ntes wavelength ib leeg. Lub kem siv yog ACE Equivalence 5 C18 (150 × 4.6 mm, Advanced Chromatography Technologies Ltd., Aberdeen, Scotland).
Cov tshuaj txhaj (5 µL) tau ua ncaj qha los ntawm cov tshuaj sib tov uas tau diluted (1:10 dilution) thiab tshuaj xyuas nrog dej:methanol (50:50 lossis 70:30), tshwj tsis yog qee cov qauv siv 70:30 solvent system (qhia ua tus lej hnub qub) ntawm tus nqi ntws ntawm 1.5 mL / feeb. Lub kem tau khaws cia ntawm 40 ° C. Lub wavelength ntawm lub tshuab ntes yog 254 nm.
Qhov % qhov siab tshaj plaws ntawm cov qauv tau suav los ntawm qhov siab tshaj plaws ntawm cov alkyne seem, tsuas yog cov khoom triazole, thiab kev txhaj tshuaj ntawm cov khoom pib tau tso cai rau kev txheeb xyuas cov ncov tseem ceeb.
Tag nrho cov qauv kuaj tau raug tshuaj xyuas siv Thermo iCAP 6000 ICP-OES. Tag nrho cov qauv calibration tau npaj siv 1000 ppm Cu cov kua txheem hauv 2% nitric acid (SPEX Certi Prep). Tag nrho cov qauv tau npaj hauv 5% DMF thiab 2% HNO3 kua, thiab tag nrho cov qauv tau diluted 20-npaug hauv cov qauv DMF-HNO3 kua.
UAM siv ultrasonic hlau vuam ua ib txoj kev sib txuas rau cov hlau ntawv ci siv los tsim qhov sib dhos kawg. Ultrasonic hlau vuam siv lub cuab yeej vibrating hlau (hu ua lub horn lossis ultrasonic horn) los siv lub zog rau cov ntawv ci txheej / cov txheej sib sau ua ke yav dhau los kom sib txuas thaum vibrating cov khoom. Rau kev ua haujlwm tas mus li, lub sonotrode yog cylindrical thiab dov hla qhov chaw ntawm cov khoom, sib txuas tag nrho thaj chaw. Thaum muaj kev siab thiab kev co, cov oxides ntawm qhov chaw ntawm cov khoom tuaj yeem tawg. Kev siab thiab kev co txuas ntxiv tuaj yeem ua rau cov khoom tsis zoo ntawm cov khoom tawg 36. Kev sib cuag nrog cov cua sov thiab siab hauv zos ces ua rau muaj kev sib txuas khov kho ntawm cov khoom sib txuas; nws kuj tseem tuaj yeem pab kev sib txuas los ntawm kev hloov pauv hauv lub zog nto 48. Qhov xwm txheej ntawm lub tshuab sib txuas kov yeej ntau yam teeb meem cuam tshuam nrog qhov kub thiab txias hloov pauv thiab qhov kub siab tom qab-cov teebmeem hais hauv lwm cov txheej txheem tsim khoom ntxiv. Qhov no tso cai rau kev sib txuas ncaj qha (piv txwv li, tsis muaj kev hloov pauv ntawm qhov chaw, cov khoom sau lossis cov nplaum) ntawm ntau txheej ntawm cov khoom sib txawv rau hauv ib qho kev sib koom ua ke.
Ib qho thib ob zoo rau UAM yog qib siab ntawm cov yas ntws pom hauv cov khoom siv hlau, txawm tias nyob rau qhov kub qis, piv txwv li qis dua qhov melting point ntawm cov khoom siv hlau. Kev sib xyaw ua ke ntawm ultrasonic oscillation thiab siab ua rau muaj qib siab ntawm kev tsiv teb tsaws chaw hauv zos thiab recrystallization yam tsis muaj qhov kub nce siab uas ib txwm muaj feem cuam tshuam nrog cov khoom siv loj. Thaum lub sijhawm tsim kho qhov kev sib dhos kawg, qhov xwm txheej no tuaj yeem siv los ntxig cov khoom siv nquag thiab tsis nquag ntawm cov khaubncaws sab nraud povtseg ntawm cov ntawv ci hlau, txheej los ntawm txheej. Cov ntsiab lus xws li cov fibers optical 49, reinforcements 46, electronics 50, thiab thermocouples (qhov haujlwm no) tau raug ntxig rau hauv UAM cov qauv los tsim cov khoom sib dhos ua ke thiab tsis nquag.
Hauv txoj haujlwm no, ob qho tib si qhov sib txawv ntawm cov khoom sib txuas thiab kev sib xyaw ua ke ntawm UAM tau siv los tsim qhov kawg catalytic kub saib xyuas microreactor.
Piv nrog palladium (Pd) thiab lwm yam hlau catalysts uas siv ntau, Cu catalysis muaj ntau qhov zoo: (i) Kev lag luam, Cu pheej yig dua li ntau lwm yam hlau siv hauv catalysis thiab yog li ntawd yog qhov kev xaiv zoo rau kev lag luam ua tshuaj lom neeg (ii) Qhov ntau ntawm Cu-catalyzed cross-coupling reactions tab tom nce ntxiv thiab zoo li yog qee yam sib txuas rau Pd-based methodologies51,52,53 (iii) Cu-catalyzed reactions ua haujlwm zoo thaum tsis muaj lwm yam ligands, Cov ligands no feem ntau yog cov qauv yooj yim thiab pheej yig yog tias xav tau, thaum cov uas siv hauv Pd chemistry feem ntau nyuaj, kim, thiab huab cua-sensitive (iv) Cu, tshwj xeeb tshaj yog paub txog nws lub peev xwm los khi alkynes hauv kev sib xyaw, Piv txwv li, bimetallic-catalyzed Sonogashira coupling thiab cycloaddition nrog azides (nias chemistry) (v) Cu kuj tseem tuaj yeem txhawb nqa arylation ntawm ntau lub nucleophiles hauv Ullmann-hom reactions.
Piv txwv ntawm heterogenization ntawm tag nrho cov kev tshuaj tiv thaiv no tau tsis ntev los no tau pom tseeb nyob rau hauv qhov muaj Cu (0). Qhov no feem ntau yog vim kev lag luam tshuaj thiab kev tsom mus rau kev rov qab los ntawm cov hlau catalyst thiab rov siv dua 55,56.
Ua thawj coj los ntawm Huisgen hauv xyoo 1960s57, 1,3-dipolar cycloaddition tshuaj tiv thaiv ntawm acetylene thiab azide rau 1,2,3-triazole yog suav hais tias yog ib qho kev ua haujlwm synergistic. Cov txiaj ntsig 1,2,3 triazole moieties yog qhov tshwj xeeb tshaj yog pharmacophore hauv kev tshawb pom tshuaj vim lawv cov ntawv thov biological thiab siv rau hauv ntau yam tshuaj kho mob 58.
Qhov kev tshuaj tiv thaiv no tau rov qab los ua qhov tseem ceeb dua thaum Sharpless thiab lwm tus tau qhia txog lub tswv yim ntawm "click chemistry"59. Lo lus "click chemistry" yog siv los piav qhia txog cov tshuaj tiv thaiv uas muaj zog, txhim khu kev qha thiab xaiv tau rau kev sib xyaw ua ke sai ntawm cov tshuaj tshiab thiab cov tsev qiv ntawv sib xyaw ua ke ntawm heteroatom linkage (CXC)60 Qhov kev thov ntawm cov tshuaj tiv thaiv no yog los ntawm lawv cov txiaj ntsig siab, cov xwm txheej tshuaj tiv thaiv yooj yim, oxygen thiab dej tsis kam, thiab kev sib cais khoom yooj yim61.
Cov Huisgen 1,3-dipole cycloaddition tsis yog pawg ntawm "click chemistry". Txawm li cas los xij, Medal thiab Sharpless tau qhia tias qhov kev sib txuas azide-alkyne no dhau los ntawm 107 txog 108 nyob rau hauv qhov muaj Cu (I) piv rau qhov tsis muaj catalyzed 1,3-dipolar cycloaddition 62,63 qhov kev nrawm nrawm tseem ceeb. Cov txheej txheem tshuaj tiv thaiv zoo dua no tsis tas yuav tiv thaiv cov pab pawg lossis cov xwm txheej tshuaj tiv thaiv hnyav thiab ua rau muaj kev hloov pauv thiab kev xaiv rau 1,4-disubstituted 1,2,3-triazoles (anti-1,2,3-triazole) ntawm lub sijhawm teev (Daim Duab 3).
Cov txiaj ntsig isometric ntawm cov tshuaj Huisgen cycloadditions ib txwm muaj thiab tooj liab-catalyzed.Cu(I)-catalyzed Huisgen cycloadditions tsuas yog tsim tau 1,4-disubstituted 1,2,3-triazoles, thaum cov cua sov ua rau Huisgen cycloadditions feem ntau tsim tau 1,4- thiab 1,5-triazoles 1:1 sib xyaw ntawm stereoisomers ntawm azoles.
Feem ntau cov txheej txheem cuam tshuam nrog kev txo cov peev txheej Cu(II) ruaj khov, xws li kev txo cov hom CuSO4 lossis Cu(II)/Cu(0) sib xyaw ua ke nrog cov ntsev sodium. Piv nrog rau lwm cov tshuaj tiv thaiv hlau, kev siv Cu(I) muaj qhov zoo tshaj plaws ntawm kev pheej yig thiab yooj yim rau kev tuav.
Kev tshawb fawb txog kinetic thiab isotopic labeling los ntawm Worrell et al. 65 qhia tau hais tias, nyob rau hauv cov ntaub ntawv ntawm terminal alkynes, ob qho sib npaug ntawm tooj liab koom nrog hauv kev ua kom muaj kev cuam tshuam ntawm txhua lub molecule rau azide. Lub tswv yim tau hais tseg ua mus los ntawm lub nplhaib hlau tooj liab rau tus tswv cuab uas tsim los ntawm kev sib koom tes ntawm azide rau σ-bonded tooj liab acetylide nrog π-bonded tooj liab ua tus neeg pub dawb ruaj khov. Triazolyl tooj liab derivatives yog tsim los ntawm lub nplhaib shrinkage, ua raws li proton decomposition los muab cov khoom triazole thiab kaw lub voj voog catalytic.
Txawm hais tias cov txiaj ntsig ntawm cov khoom siv tshuaj lom neeg tau sau tseg zoo, muaj kev xav kom koom ua ke cov cuab yeej tshuaj ntsuam xyuas rau hauv cov kab ke no rau kev saib xyuas hauv-kab, hauv-situ, cov txheej txheem 66,67.UAM tau ua pov thawj tias yog ib txoj hauv kev tsim nyog rau kev tsim thiab tsim cov tshuab ua haujlwm 3D uas nyuaj heev ua los ntawm cov khoom siv catalytic, cov khoom siv thermally conductive nrog cov khoom siv sensing ncaj qha (Daim Duab 4).
Lub tshuab hluav taws xob aluminium-tooj ​​liab uas tsim los ntawm kev tsim khoom siv ultrasonic additive (UAM) nrog cov qauv channel sab hauv uas nyuaj, cov thermocouples embedded thiab catalytic reaction chamber. Txhawm rau kom pom cov dej hauv cov kab ke, ib daim qauv pob tshab uas tsim los ntawm kev siv stereolithography kuj tau qhia.
Yuav kom ntseeg tau tias cov reactors tau tsim rau cov tshuaj tiv thaiv organic yav tom ntej, cov kuab tshuaj yuav tsum tau ua kom sov siab tshaj qhov kub npau; lawv raug kuaj xyuas qhov siab thiab kub. Qhov kev sim siab qhia tau tias lub kaw lus tswj tau qhov siab ruaj khov thiab tas li txawm tias muaj qhov siab ntawm lub kaw lus nce ntxiv (1.7 MPa). Qhov kev sim hydrostatic tau ua tiav ntawm qhov kub thiab txias hauv chav siv H2O ua kua.
Txuas lub thermocouple uas muab tso rau hauv (Daim Duab 1) rau lub tshuab ntsuas kub qhia tau tias lub thermocouple txias dua li qhov kub uas tau teeb tsa rau ntawm FlowSyn system 6 °C (± 1 °C). Feem ntau, qhov kub nce 10 °C ua rau qhov kev ua haujlwm ntawm cov tshuaj tiv thaiv nce ob npaug, yog li qhov sib txawv ntawm qhov kub tsuas yog ob peb degrees tuaj yeem hloov pauv qhov kev ua haujlwm ntawm cov tshuaj tiv thaiv. Qhov sib txawv no yog vim qhov kub poob thoob plaws lub cev reactor vim yog qhov kub ntawm cov ntaub ntawv siv hauv cov txheej txheem tsim khoom. Qhov kev hloov pauv thermal no yog qhov sib xws thiab yog li ntawd tuaj yeem suav nrog hauv kev teeb tsa khoom siv kom ntseeg tau tias qhov kub raug thiab ntsuas thaum lub sijhawm ua haujlwm. Yog li ntawd, lub cuab yeej saib xyuas online no pab tswj hwm qhov kub ntawm cov tshuaj tiv thaiv thiab pab txhawb kev ua kom zoo dua thiab kev txhim kho cov xwm txheej zoo tshaj plaws. Cov sensors no kuj tseem siv tau los txheeb xyuas cov tshuaj tiv thaiv exotherms thiab tiv thaiv cov tshuaj tiv thaiv khiav tawm hauv cov kab ke loj.
Lub reactor uas tau nthuav tawm hauv daim ntawv no yog thawj qhov piv txwv ntawm kev siv UAM thev naus laus zis rau kev tsim cov tshuaj reactors thiab hais txog ntau qhov kev txwv tseem ceeb uas tam sim no cuam tshuam nrog AM / 3D luam ntawv ntawm cov khoom siv no, xws li: (i) kov yeej cov teeb meem tau tshaj tawm cuam tshuam nrog tooj liab lossis txhuas alloy ua tiav (ii) txhim kho kev daws teeb meem sab hauv channel piv rau hmoov txaj fusion (PBF) cov txheej txheem xws li xaiv laser melting (SLM)25,69 Cov khoom siv tsis zoo thiab cov qauv ntxhib26 (iii) Txo qhov kub ua tiav, uas ua rau kev sib txuas ncaj qha ntawm cov sensors, uas tsis tuaj yeem ua tau hauv hmoov txaj technology, (v) kov yeej cov khoom siv tsis zoo thiab kev rhiab heev ntawm cov khoom polymer-raws li cov khoom sib txawv rau ntau yam organic solvents17,19.
Qhov kev ua haujlwm ntawm lub reactor tau pom los ntawm ntau yam kev cuam tshuam ntawm cov tooj liab-catalyzed alkyne azide cycloaddition nyob rau hauv cov xwm txheej ntws tas mus li (Daim duab 2). Lub tshuab hluav taws xob ultrasonic-luam tawm uas tau piav qhia hauv Daim Duab 4 tau koom ua ke nrog lub kaw lus ntws lag luam thiab siv los tsim cov tsev qiv ntawv azides ntawm ntau yam 1,4-disubstituted 1,2,3-triazoles ntawm qhov kub thiab txias tswj cov tshuaj tiv thaiv ntawm acetylene thiab alkyl pawg halides nyob rau hauv qhov muaj sodium chloride (Daim Duab 3). Kev siv txoj hauv kev ntws tas mus li txo qhov kev txhawj xeeb txog kev nyab xeeb uas tuaj yeem tshwm sim hauv cov txheej txheem batch, vim tias qhov tshuaj tiv thaiv no tsim cov tshuaj tiv thaiv thiab txaus ntshai azide intermediates [317], [318]. Thaum pib, qhov tshuaj tiv thaiv tau zoo rau cycloaddition ntawm phenylacetylene thiab iodoethane (Scheme 1 - Cycloaddition ntawm phenylacetylene thiab iodoethane) (saib Daim Duab 5).
(Sab laug saum toj) Daim duab qhia txog kev teeb tsa siv los koom ua ke 3DP reactor rau hauv qhov system ntws (sab xis saum toj) tau txais hauv qhov kev kho kom zoo (hauv qab) ntawm Huisgen cycloaddition 57 txoj kev npaj ntawm phenylacetylene thiab iodoethane rau kev kho kom zoo dua thiab qhia cov kev hloov pauv ntawm cov tshuaj tiv thaiv zoo dua.
Los ntawm kev tswj lub sijhawm nyob ntawm cov tshuaj reagents hauv qhov catalytic ntawm lub reactor thiab saib xyuas qhov kub ntawm cov tshuaj tiv thaiv nrog lub thermocouple probe ncaj qha, cov xwm txheej ntawm cov tshuaj tiv thaiv tuaj yeem ua kom zoo dua sai thiab raug nrog lub sijhawm tsawg kawg nkaus thiab kev siv khoom siv. Nws tau txiav txim siab sai sai tias qhov kev hloov pauv siab tshaj plaws tau txais thaum lub sijhawm nyob ntawm 15 feeb thiab qhov kub ntawm cov tshuaj tiv thaiv ntawm 150 ° C tau siv. Los ntawm cov duab kos ntawm MODDE software, nws tuaj yeem pom tias ob qho tib si lub sijhawm nyob thiab qhov kub ntawm cov tshuaj tiv thaiv yog suav tias yog cov qauv tseem ceeb. Kev khiav lub optimizer uas tau tsim los ntawm kev siv cov lus xaiv no tsim cov txheej txheem ntawm cov xwm txheej tshuaj tiv thaiv uas tsim los ua kom cov khoom siab tshaj plaws thaum txo cov khoom pib siab tshaj plaws. Qhov kev ua kom zoo no tau ua rau muaj kev hloov pauv 53% ntawm cov khoom triazole, uas phim cov qauv kwv yees ntawm 54%.
Raws li cov ntaub ntawv qhia tias tooj liab (I) oxide (Cu2O) tuaj yeem ua haujlwm ua cov tshuaj catalytic zoo ntawm cov nplaim tooj liab xoom hauv cov tshuaj tiv thaiv no, lub peev xwm los ua ntej oxidize lub reactor nto ua ntej ua qhov tshuaj tiv thaiv hauv kev ntws tau tshawb xyuas 70,71. Cov tshuaj tiv thaiv ntawm phenylacetylene thiab iodoethane tau ua dua hauv qab qhov zoo tshaj plaws thiab cov txiaj ntsig tau piv. Nws tau pom tias qhov kev npaj no ua rau muaj kev nce ntxiv ntawm kev hloov pauv ntawm cov khoom pib, uas tau suav tias yog > 99%. Txawm li cas los xij, kev saib xyuas los ntawm HPLC tau qhia tias qhov kev hloov pauv no tau txo qis lub sijhawm tshuaj tiv thaiv ntev dhau mus txog li 90 feeb, qhov twg qhov kev ua ub no zoo li yuav nce qib thiab mus txog "lub xeev ruaj khov". Qhov kev soj ntsuam no qhia tau hais tias qhov chaw ntawm kev ua ub no catalytic tau txais los ntawm qhov chaw tooj liab oxide es tsis yog qhov chaw tooj liab xoom. Cu hlau yooj yim oxidized ntawm chav tsev kub los tsim CuO thiab Cu2O uas tsis yog cov txheej txheem tiv thaiv tus kheej. Qhov no tshem tawm qhov xav tau ntxiv qhov chaw tooj liab (II) rau kev sib koom ua ke 71.