Ua tsaug rau koj tuaj xyuas Nature.com. Lub browser version uas koj siv muaj kev txhawb nqa CSS tsawg. Rau qhov kev paub zoo tshaj plaws, peb xav kom koj siv lub browser hloov tshiab (lossis kaw Compatibility Mode hauv Internet Explorer). Lub sijhawm no, kom ntseeg tau tias muaj kev txhawb nqa txuas ntxiv, peb yuav ua rau lub xaib tsis muaj cov qauv thiab JavaScript.
Ib lub carousel uas qhia peb daim slides tib lub sijhawm. Siv cov nyees khawm Yav dhau los thiab Tom ntej kom txav mus los ntawm peb daim slides ib zaug, lossis siv cov nyees khawm slider thaum kawg kom txav mus los ntawm peb daim slides ib zaug.
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 tsab ntawv no, peb tshaj tawm thawj qhov piv txwv ntawm lub tshuab ua kua dej uas tsim los ntawm kev tsim khoom ntxiv ultrasonic (UAM) lamination ntawm daim ntawv hlau khov kho nrog cov khoom catalytic ncaj qha thiab cov khoom siv sensing. UAM thev naus laus zis tsis yog tsuas yog kov yeej ntau qhov kev txwv tam sim no cuam tshuam nrog kev tsim khoom ntxiv ntawm cov tshuaj reactors, tab sis kuj nthuav dav lub peev xwm ntawm cov khoom siv no. Ib qho ntawm cov tshuaj lom neeg tseem ceeb 1,4-disubstituted 1,2,3-triazole tau ua tiav synthesized thiab optimized los ntawm Cu-mediated 1,3-dipolar Huisgen cycloaddition reaction siv UAM chemistry chaw. Siv cov khoom tshwj xeeb ntawm UAM thiab kev ua tiav ntawm kev ntws tas mus li, lub cuab yeej muaj peev xwm ua rau cov tshuaj tiv thaiv tas mus li thiab muab cov lus teb tiag tiag los saib xyuas thiab ua kom zoo dua cov tshuaj tiv thaiv.
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 molecules 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 zoo thiab tshuaj tuaj yeem tau txais txiaj ntsig los ntawm kev ntws tas mus li7.
Nyob rau xyoo tas los no, muaj kev sib txawv 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 tshuaj "reactors" uas hloov tau yooj yim8. Kev tsim qauv rov ua dua, kev tsim khoom sai, thiab peb-seem (3D) muaj peev xwm ntawm cov txheej txheem no yog qhov muaj txiaj ntsig zoo rau cov neeg uas xav kho lawv cov khoom siv rau ib pawg 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 printing7,15., 16. Qhov tsis muaj kev ntseeg siab 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 rau kev siv dav dua ntawm AM hauv daim teb no17, 18, 19, 20.
Vim muaj kev siv cov tshuaj lom neeg ntau ntxiv thiab cov khoom zoo uas cuam tshuam nrog AM, yuav tsum tshawb nrhiav cov txheej txheem zoo dua uas yuav ua rau cov neeg siv tsim cov hlab ntsha uas muaj cov tshuaj lom neeg zoo dua thiab muaj peev xwm txheeb xyuas tau zoo dua. Cov txheej txheem no yuav tsum tso cai rau cov neeg siv xaiv los ntawm ntau yam khoom siv muaj zog lossis ua haujlwm tau zoo uas muaj peev xwm ua haujlwm nyob rau hauv ntau yam kev mob ntawm cov tshuaj lom neeg, nrog rau kev pab txhawb ntau hom kev tso zis los ntawm lub cuab yeej kom ua rau kev saib xyuas thiab tswj tau cov tshuaj lom neeg.
Ib qho txheej txheem tsim khoom ntxiv uas siv tau los tsim cov tshuaj reactors tshwj xeeb yog Ultrasonic Additive Manufacturing (UAM). Txoj kev lamination ntawm daim ntawv khov kho no siv cov ultrasonic vibrations rau cov ntawv ci hlau nyias nyias kom txuas lawv ua ke txheej los ntawm txheej nrog qhov cua sov volumetric 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 kev tswj hwm tus lej hauv-situ (CNC) milling lossis laser ua tiav txiav txim siab qhov zoo ntawm cov txheej ntawm cov khoom sib txuas 24, 25. Qhov no txhais tau tias tus neeg siv tsis txwv rau cov teeb meem cuam tshuam nrog kev tshem tawm cov khoom siv tsev qub qub los ntawm cov kua me me, uas feem ntau yog qhov teeb meem hauv cov hmoov thiab kua AM26,27,28. Kev ywj pheej tsim qauv no kuj nthuav dav mus rau kev xaiv cov ntaub ntawv muaj - UAM tuaj yeem sib txuas cov khoom sib xyaw ua ke ntawm cov khoom siv thermally zoo sib xws thiab sib txawv hauv ib kauj ruam txheej txheem. Kev xaiv cov khoom sib xyaw ua ke 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 rau qhov kev sib txuas khov kho, lwm qhov xwm txheej uas tshwm sim nrog kev sib txuas ultrasonic yog qhov muaj zog ntawm cov khoom siv yas ntawm qhov kub qis qis 29, 30, 31, 32, 33. Qhov tshwj xeeb no ntawm UAM tso cai rau cov khoom siv kho tshuab / thermal kom muab tso rau ntawm cov txheej hlau yam tsis muaj kev puas tsuaj. Embedded UAM 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 haujlwm yav dhau los los ntawm cov kws sau ntawv32 tau qhia txog lub peev xwm ntawm cov txheej txheem UAM los tsim cov qauv hlau 3D microfluidic nrog cov peev xwm sensing embedded. Lub cuab yeej no tsuas yog rau kev saib xyuas lub hom phiaj xwb. Tsab xov xwm no nthuav qhia thawj qhov piv txwv ntawm lub microfluidic tshuaj reactor tsim los ntawm UAM, ib lub cuab yeej ua haujlwm uas tsis tsuas yog tswj hwm tab sis kuj ua rau muaj kev sib xyaw tshuaj nrog cov khoom siv catalytic sib xyaw ua ke. Lub cuab yeej ua ke ntau qhov zoo cuam tshuam nrog UAM thev naus laus zis hauv kev tsim cov khoom siv tshuaj 3D, xws li: lub peev xwm los hloov pauv tag nrho 3D tsim ncaj qha los ntawm lub khoos phis tawj-pab tsim qauv (CAD) qauv mus rau hauv cov khoom; ntau yam khoom siv rau kev sib xyaw ua ke ntawm cov thermal conductivity siab thiab cov ntaub ntawv catalytic, nrog rau cov sensors thermal embedded ncaj qha ntawm cov kwj dej reactant rau kev tswj hwm thiab kev tswj hwm 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 1,3-dipolar Huisgen cycloaddition. Daim ntawv no qhia txog kev siv cov ntaub ntawv tshawb fawb thiab kev tsim qauv siv computer pab tau li cas qhib tau cov cib fim tshiab 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 siv yam tsis tau ntxuav ua ntej. 1H thiab 13C NMR spectra kaw ntawm 400 thiab 100 MHz, raws li, tau txais ntawm JEOL ECS-400 400 MHz spectrometer lossis Bruker Avance II 400 MHz spectrometer nrog CDCl3 lossis (CD3) 2SO ua kuab tshuaj. Tag nrho cov tshuaj tiv thaiv tau ua tiav 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 tawm tuaj yeem kawm tau siv 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 hnyav 9 kW SonicLayer 4000® UAM system (Fabrisonic, Ohio, USA). Cov ntaub ntawv xaiv rau lub cuab yeej 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 6061O yog siv ua cov khoom "ntau". , nrog rau txheej intercalation siv rau kev tshuaj xyuas; intercalation ntawm cov khoom siv alloy thiab annealed xeev ua ke nrog Cu-110 txheej. pom tias muaj kev ruaj khov tshuaj nrog cov reagents siv hauv txoj haujlwm no. Al 6061O ua ke nrog Cu-110 kuj suav hais tias yog cov khoom sib xws ua ke rau UAM thiab yog li ntawd yog cov khoom siv tsim nyog rau kev tshawb fawb no 38,42. Cov khoom siv no tau teev nyob rau hauv Rooj 1 hauv qab no.
Cov kauj ruam tsim lub tshuab hluav taws xob (1) 6061 txhuas alloy substrate (2) Kev tsim cov channel qis dua los ntawm cov ntawv ci tooj liab (3) Kev ntxig 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 cov kua dej yog siv txoj kev tortuous kom nce qhov deb uas cov kua dej mus ncig hauv lub chip thaum tswj hwm qhov loj me ntawm lub chip uas tswj tau. Qhov kev nce qhov deb no yog qhov xav tau los ua kom lub sijhawm sib cuag catalyst-reactant nce ntxiv 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 nce lub sijhawm sib cuag ntawm cov kua dej nrog qhov chaw (catalyst). Txhawm rau txhim kho qhov kev sib tov uas tuaj yeem ua tiav, kev tsim qauv ntawm lub reactor suav nrog ob lub reactant inlets ua ke hauv Y-kev sib txuas ua ntej nkag mus rau hauv qhov sib xyaw coil. Qhov nkag thib peb, uas hla qhov ntws ib nrab ntawm nws qhov chaw nyob, suav nrog hauv txoj kev npaj rau yav tom ntej ntau theem synthesis reactions.
Txhua txoj kab muaj ib daim duab plaub fab (tsis muaj lub kaum sab xis), uas yog qhov tshwm sim ntawm kev siv CNC milling los tsim cov duab geometry ntawm txoj kab. Qhov ntev ntawm txoj kab raug xaiv los muab qhov siab (rau lub microreactor) volumetric yield, tseem me txaus los pab txhawb kev sib cuam tshuam nrog qhov chaw (catalysts) rau feem ntau ntawm cov kua uas nws muaj. Qhov loj me tsim nyog yog raws li cov kws sau ntawv qhov kev paub dhau los nrog cov khoom siv hlau-kua. 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 ua ke (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 ntaub ntawv ntawv ci, nws cov khoom siv kho tshuab, thiab cov kev sib txuas siv nrog ultrasonics. Ntawm qhov dav rau cov khoom siv, cov khoom siv yuav "sag" rau hauv txoj kab tsim. Tam sim no tsis muaj tus qauv tshwj xeeb rau qhov kev xam no, yog li qhov dav tshaj plaws ntawm cov channel rau ib yam khoom thiab kev tsim qauv tau txiav txim siab los ntawm kev sim, uas yog qhov dav ntawm 750 µm yuav tsis ua rau sag.
Lub duab (square) ntawm cov channel yog txiav txim siab siv lub tshuab txiav plaub fab. Lub duab thiab qhov loj ntawm cov channel tuaj yeem hloov pauv 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 nkhaus nrog lub cuab yeej 125 µm tuaj yeem pom hauv Monaghan45. Thaum cov txheej ntawv ci raug siv tiaj tus, daim ntawv thov ntawm cov khoom ntawv ci rau cov channel yuav muaj qhov chaw tiaj tus (square). Hauv txoj haujlwm no, ib qho contour plaub fab tau siv los khaws cia qhov sib xws ntawm cov channel.
Thaum lub sijhawm ncua sijhawm tsim khoom, cov ntsuas kub thermocouple (hom K) tau tsim ncaj qha rau hauv lub cuab yeej ntawm cov pab pawg sab saud thiab sab qis (Daim Duab 1 - theem 3). Cov thermocouples no tuaj yeem tswj kev hloov pauv kub ntawm -200 txog 1350 °C.
Cov txheej txheem tso hlau yog ua los ntawm UAM horn siv cov ntawv ci hlau dav 25.4 hli thiab tuab 150 microns. Cov txheej ntawm ntawv ci no txuas nrog ua ke 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 huv kawg. CNC machining yog siv los tshuab cov duab sab nraud thiab sab hauv ntawm cov khoom siv, ua rau qhov chaw tiav ntawm cov khoom siv thiab cov channel sib raug rau cov cuab yeej xaiv thiab CNC txheej txheem cov txheej txheem (hauv qhov piv txwv no, kwv yees li 1.6 µm Ra). Kev txau cov khoom siv ultrasonic tas mus li thiab cov voj voog machining tas mus li siv thoob plaws hauv cov txheej txheem tsim khoom ntawm lub cuab yeej kom ntseeg tau tias qhov tseeb ntawm qhov ntev yog khaws cia thiab qhov tiav tiav ua tau raws li CNC zoo milling precision theem. Qhov dav ntawm cov channel siv rau lub cuab yeej no yog me me txaus kom ntseeg tau tias cov khoom siv ntawv ci tsis "sag" hauv cov kua dej, yog li cov channel muaj ib qho square cross section. Cov qhov sib txawv hauv cov khoom siv ntawv ci thiab cov kev cai ntawm cov txheej txheem UAM tau txiav txim siab los ntawm kev sim los ntawm tus khub tsim khoom (Fabrisonic LLC, USA).
Cov kev tshawb fawb tau qhia tias ntawm qhov interface 46, 47 ntawm UAM compound muaj me ntsis diffusion ntawm cov ntsiab lus yam tsis muaj kev kho cua sov ntxiv, yog li rau cov khoom siv hauv txoj haujlwm no Cu-110 txheej tseem txawv ntawm Al 6061 txheej thiab hloov pauv dramatically.
Nruab ib lub tshuab tswj qhov siab rov qab (BPR) uas tau teeb tsa ua ntej ntawm 250 psi (1724 kPa) hauv qab ntawm lub reactor thiab tso 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 pressure transducer uas ua rau hauv lub system kom ntseeg tau tias lub system tuaj yeem tswj tau qhov siab tas li. Qhov kub thiab txias uas yuav tshwm sim hauv lub flow reactor tau raug kuaj los ntawm kev nrhiav qhov sib txawv ntawm cov thermocouples uas ua rau hauv lub reactor thiab cov thermocouples uas ua rau hauv lub phaj cua sov ntawm FlowSyn chip. Qhov no ua tiav los ntawm kev hloov qhov kub ntawm lub hotplate uas tau teeb tsa ntawm 100 thiab 150 °C hauv 25 °C nce ntxiv thiab saib xyuas qhov sib txawv ntawm qhov kub thiab txias uas tau teeb tsa thiab sau tseg. Qhov no tau ua tiav siv lub tc-08 data logger (PicoTech, Cambridge, UK) thiab cov software PicoLog uas nrog nws.
Cov xwm txheej rau qhov kev sib xyaw ua ke 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 siv txoj hauv kev tsim qauv ntawm kev sim (DOE), siv qhov kub thiab lub sijhawm nyob ua cov 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. Ib qho 1.5 ml aliquot ntawm txhua cov tshuaj tau sib xyaw thiab pumped los ntawm lub reactor ntawm qhov ntws thiab kub xav tau. Cov lus teb ntawm tus qauv tau coj los ua qhov piv ntawm thaj chaw siab tshaj plaws ntawm cov khoom triazole rau cov khoom pib ntawm phenylacetylene thiab tau txiav txim siab siv cov kua chromatography ua haujlwm siab (HPLC). Rau kev sib xws ntawm kev tshuaj xyuas, txhua qhov kev cuam tshuam tau coj tam sim ntawd tom qab cov tshuaj sib xyaw tawm hauv 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 x 100 mm, qhov loj me ntawm 5 µm, khaws cia ntawm 40°C. Cov kuab tshuaj yog isocratic methanol:dej 50:50 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 DOE qauv tau suav los ntawm cov cheeb tsam ncov ntawm cov khoom seem alkyne thiab triazole xwb. Kev qhia txog cov khoom pib ua rau nws muaj peev xwm txheeb xyuas cov ncov sib xws.
Kev sib xyaw ua ke cov txiaj ntsig ntawm kev tshuaj xyuas reactor nrog MODDE DOE software (Umetrics, Malmö, Sweden) tau tso cai rau kev tshuaj xyuas qhov sib txawv ntawm cov txiaj ntsig 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 tsim ib pawg ntawm cov xwm txheej tshuaj tiv thaiv uas tsim los ua kom thaj chaw siab tshaj plaws ntawm cov khoom thaum txo qis thaj chaw siab tshaj plaws rau cov khoom noj acetylene.
Kev oxidation ntawm qhov chaw tooj liab 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 cov tshuaj triazole.
Thaum cov txheej txheem zoo tshaj plaws tau txiav txim siab lawm, lawv tau siv rau ntau yam acetylene thiab haloalkane derivatives kom tso cai rau kev 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). Cov khoom sib xyaw ntawm 3 ml ntawm txhua cov tshuaj tau sib xyaw thiab pumped los ntawm lub reactor ntawm tus nqi ntawm 75 µl/min thiab qhov kub ntawm 150°C. Tag nrho cov ntim tau sau rau hauv lub raj mis thiab diluted nrog 10 ml ntawm ethyl acetate. Cov tshuaj qauv tau ntxuav nrog 3 x 10 ml dej. Cov txheej aqueous tau sib xyaw thiab rho tawm nrog 10 ml ethyl acetate, tom qab ntawd cov txheej organic tau sib xyaw, ntxuav nrog 3 × 10 ml brine, ziab hla MgSO4 thiab lim, tom qab ntawd cov kuab tshuaj tau tshem tawm hauv vacuo. Cov qauv tau purified los ntawm silica gel column chromatography 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 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 nrog cov khoom siv txhuas. Cov phaj tau pom nrog lub teeb UV (254 nm) lossis vanillin staining thiab cua sov.
Tag nrho cov qauv kuaj tau raug tshuaj xyuas siv lub tshuab VWR Chromaster (VWR International Ltd., Leighton Buzzard, UK) uas muaj lub tshuab kuaj autosampler, lub twj tso kua mis binary nrog lub qhov cub kem thiab lub tshuab ntes wavelength ib leeg. Lub kem ACE Equivalence 5 C18 (150 x 4.6 mm, Advanced Chromatography Technologies Ltd., Aberdeen, Scotland) tau siv.
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 lub kaw lus solvent 70:30 (qhia ua tus lej hnub qub) ntawm tus nqi ntws ntawm 1.5 ml / min. Lub kem tau khaws cia ntawm 40 ° C. Lub wavelength ntawm lub detector yog 254 nm.
Qhov % qhov siab tshaj plaws ntawm cov qauv tau suav los ntawm qhov siab tshaj plaws ntawm cov alkyne seem, cov khoom triazole xwb, thiab kev qhia txog cov khoom pib ua rau nws muaj peev xwm txheeb xyuas cov ncov sib xws.
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 cov kua ntawm 5% DMF thiab 2% HNO3, thiab tag nrho cov qauv tau diluted 20 zaug nrog cov kua qauv ntawm DMF-HNO3.
UAM siv ultrasonic hlau vuam ua ib txoj kev koom nrog cov ntawv ci hlau 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 siab rau cov ntawv ci / txheej ua ntej sib sau ua ke kom sib txuas / ua ntej sib sau ua ke los ntawm kev co cov khoom siv. Rau kev ua haujlwm tas mus li, sonotrode muaj lub puab tsaig thiab dov hla qhov chaw ntawm cov khoom siv, nplaum tag nrho thaj chaw. Thaum siab thiab kev co siv, cov oxides ntawm qhov chaw ntawm cov khoom siv tuaj yeem tawg. Lub siab tas li thiab kev co tuaj yeem ua rau kev puas tsuaj ntawm qhov roughness ntawm cov khoom siv 36. Kev sib cuag ze nrog cov cua sov thiab siab hauv zos ces ua rau muaj kev sib txuas ruaj khov ntawm cov khoom siv interfaces; nws kuj tseem tuaj yeem txhawb kev sib koom ua ke los ntawm kev hloov pauv lub zog ntawm qhov chaw 48. Qhov xwm txheej ntawm cov txheej txheem sib txuas kov yeej ntau yam teeb meem cuam tshuam nrog qhov kub thiab txias hloov pauv thiab cov teebmeem kub siab uas tau hais hauv lwm cov thev naus laus zis tsim khoom ntxiv. Qhov no tso cai rau kev sib txuas ncaj qha (piv txwv li tsis muaj kev hloov kho 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.
Qhov thib ob zoo rau CAM 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 vibrations thiab siab ua rau muaj qib siab ntawm kev tsiv teb tsaws chaw hauv zos thiab recrystallization yam tsis muaj qhov kub nce ntxiv uas ib txwm muaj feem cuam tshuam nrog cov khoom siv loj. Thaum lub sijhawm tsim cov rooj sib txoos kawg, qhov xwm txheej no tuaj yeem siv los embed cov khoom siv nquag thiab passive ntawm cov khaubncaws sab nraud povtseg ntawm cov ntawv ci hlau, txheej los ntawm txheej. Cov ntsiab lus xws li optical fiber 49, reinforcement 46, electronics 50 thiab thermocouples (cov haujlwm no) tau ua tiav kev koom ua ke rau hauv UAM cov qauv los tsim cov khoom sib xyaw ua ke nquag thiab passive.
Hauv txoj haujlwm no, ob qho tib si sib txawv ntawm cov khoom siv sib txuas thiab UAM intercalation peev xwm tau siv los tsim ib qho microreactor zoo tagnrho rau kev tswj qhov kub catalytic.
Piv rau 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 tshuaj lom neeg (ii) ntau yam ntawm Cu-catalyzed cross-coupling reactions tab tom nthuav dav thiab zoo li yog qee yam sib txuas rau Pd51, 52, 53-raws li cov txheej txheem (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 neeg siv hauv Pd chemistry feem ntau nyuaj, kim, thiab huab cua rhiab heev (iv) Cu, tshwj xeeb tshaj yog paub txog nws lub peev xwm los khi alkynes hauv kev sib xyaw, xws li Sonogashira's bimetallic catalyzed coupling thiab cycloaddition nrog azides (nias chemistry) (v) Cu kuj tseem tuaj yeem txhawb nqa arylation ntawm qee cov nucleophiles hauv Ullmann-hom reactions.
Tsis ntev los no, cov piv txwv ntawm heterogenization ntawm tag nrho cov kev tshuaj tiv thaiv no nyob rau hauv qhov muaj Cu (0) tau pom tseeb. Qhov no feem ntau yog vim kev lag luam tshuaj thiab kev tsom mus rau kev rov qab thiab rov siv cov hlau catalysts55,56.
Qhov kev sib xyaw ua ke ntawm 1,3-dipolar cycloaddition ntawm acetylene thiab azide rau 1,2,3-triazole, thawj zaug tau hais los ntawm Huisgen hauv xyoo 1960s57, yog suav hais tias yog kev sib xyaw ua ke. Cov khoom seem 1,2,3 triazole uas tshwm sim yog qhov tshwj xeeb tshaj yog ua ib qho pharmacophore hauv kev tshawb pom tshuaj vim lawv cov kev siv tshuaj lom neeg thiab kev siv hauv ntau yam tshuaj kho mob 58.
Cov tshuaj tiv thaiv no tau txais kev saib xyuas 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 thiab xaiv tau rau kev sib xyaw ua ke sai ntawm cov tshuaj tshiab thiab cov tsev qiv ntawv sib xyaw ua ke siv heteroatomic bonding (CXC)60. Qhov kev thov ntawm cov tshuaj tiv thaiv no yog vim muaj cov txiaj ntsig siab uas cuam tshuam nrog lawv. tej yam kev mob yooj yim, tiv taus oxygen thiab dej, thiab kev sib cais khoom yooj yim61.
Cov qauv 1,3-dipole Huisgen cycloaddition tsis poob rau hauv qeb "click chemistry". Txawm li cas los xij, Medal thiab Sharpless tau qhia tias qhov kev sib txuas azide-alkyne no dhau los ntawm 107–108 nyob rau hauv qhov muaj Cu (I) piv rau qhov kev nrawm dua hauv tus nqi ntawm cov tsis yog catalytic 1,3-dipolar cycloaddition 62,63. Cov txheej txheem tshuaj tiv thaiv siab heev no tsis tas yuav tiv thaiv cov pab pawg lossis cov xwm txheej tshuaj tiv thaiv hnyav thiab muab kev hloov pauv thiab kev xaiv yuav luag tiav rau 1,4-disubstituted 1,2,3-triazoles (anti-1,2,3-triazoles) dhau sijhawm (Daim duab 3).
Cov txiaj ntsig isometric ntawm cov tshuaj Huisgen cycloadditions ib txwm muaj thiab cov tshuaj tooj liab uas ua rau muaj zog. Cu(I)-catalyzed Huisgen cycloadditions tsuas yog muab 1,4-disubstituted 1,2,3-triazoles xwb, thaum cov tshuaj Huisgen cycloadditions uas ua rau muaj zog los ntawm cua sov feem ntau muab 1,4- thiab 1,5-triazoles sib xyaw ua ke 1:1 ntawm azole stereoisomers.
Feem ntau cov txheej txheem cuam tshuam nrog kev txo cov peev txheej ruaj khov ntawm Cu(II), xws li kev txo qis ntawm CuSO4 lossis Cu(II)/Cu(0) compound ua ke nrog cov ntsev sodium. Piv rau lwm cov tshuaj catalyzed hlau, kev siv Cu(I) muaj cov txiaj ntsig tseem ceeb ntawm kev pheej yig thiab yooj yim rau kev tuav.
Kev tshawb fawb Kinetic thiab isotopic los ntawm Worrell et al. 65 tau qhia tias nyob rau hauv cov ntaub ntawv ntawm cov terminal alkynes, ob qho sib npaug ntawm tooj liab koom nrog hauv kev ua kom muaj kev cuam tshuam ntawm txhua lub molecule nrog 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. Cov tooj liab triazolyl derivatives raug tsim los ntawm qhov tshwm sim ntawm lub nplhaib contraction ua raws li proton decomposition los tsim 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 cov txheej txheem tiag tiag hauv situ66,67. UAM tau ua pov thawj tias yog ib txoj hauv kev tsim nyog rau kev tsim thiab tsim cov reactors 3D ntws nyuaj heev los ntawm cov khoom siv catalytic, cov khoom siv thermally conductive nrog cov ntsiab lus sensing ncaj qha (Daim duab 4).
Lub tshuab hluav taws xob aluminium-tooj ​​liab uas tsim los ntawm kev tsim khoom siv ultrasonic additive manufacturing (UAM) nrog cov qauv channel sab hauv uas nyuaj, cov thermocouples uas ua rau hauv thiab lub chamber catalytic reaction. Txhawm rau kom pom cov kev ntws hauv cov kua dej, ib daim qauv pob tshab uas ua los ntawm kev siv stereolithography kuj tau qhia.
Yuav kom ntseeg tau tias cov reactors tau ua rau cov tshuaj tiv thaiv organic yav tom ntej, cov kuab tshuaj yuav tsum tau ua kom sov siab tshaj qhov kub ntawm lawv lub qhov kub npau; lawv raug kuaj xyuas qhov siab thiab qhov kub. Kev kuaj xyuas qhov siab qhia tau tias lub kaw lus tswj tau qhov siab ruaj khov thiab tas li txawm tias muaj qhov siab siab hauv lub kaw lus (1.7 MPa). Kev kuaj hydrostatic tau ua tiav ntawm chav tsev kub siv H2O ua kua.
Txuas lub thermocouple uas twb muaj lawm (Daim Duab 1) rau lub tshuab ntsuas kub qhia tau tias qhov kub ntawm thermocouple yog 6 °C (± 1 °C) qis dua qhov kub uas tau teeb tsa hauv FlowSyn system. Feem ntau, qhov kub nce 10 °C ua rau qhov kub nce ob npaug, yog li qhov sib txawv ntawm qhov kub tsuas yog ob peb degrees tuaj yeem hloov qhov kub ntawm qhov sib txawv. Qhov sib txawv no yog vim qhov kub poob thoob plaws RPV vim yog qhov kub ntawm cov ntaub ntawv siv hauv cov txheej txheem tsim khoom. Qhov kev hloov pauv thermal no yog qhov tsis tu ncua thiab yog li ntawd tuaj yeem coj mus rau hauv tus account thaum teeb tsa cov khoom siv kom ntseeg tau tias qhov kub raug ncav cuag thiab ntsuas thaum lub sijhawm sib xyaw. Yog li, lub cuab yeej saib xyuas online no pab tswj hwm qhov kub ntawm qhov sib xyaw thiab pab txhawb rau kev ua kom zoo dua qub thiab kev txhim kho cov xwm txheej zoo tshaj plaws. Cov sensors no kuj tseem siv tau los ntes cov tshuaj tiv thaiv exothermic 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 thev naus laus zis UAM 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) Kev kov yeej cov teeb meem sau tseg cuam tshuam nrog kev ua cov tooj liab lossis txhuas alloy (ii) kev daws teeb meem sab hauv channel zoo dua piv rau cov hmoov txaj yaj (PBF) txoj kev xws li kev xaiv laser yaj (SLM)25,69 Cov khoom siv tsis zoo thiab cov qauv ntxhib26 (iii) qhov kub ua haujlwm qis dua, uas ua rau cov sensors txuas ncaj qha, uas tsis tuaj yeem ua tau hauv cov hmoov txaj thev naus laus zis, (v) kev kov yeej cov khoom siv tsis zoo thiab kev nkag siab ntawm cov khoom polymer-raws li ntau yam organic solvents17,19.
Qhov ua haujlwm ntawm lub reactor tau pom los ntawm ntau yam kev cuam tshuam ntawm cov tooj liab-catalyzed alkinazide cycloaddition nyob rau hauv cov xwm txheej ntws tas mus li (Daim duab 2). Lub tshuab hluav taws xob luam tawm ultrasonic uas pom hauv daim duab 4 tau koom ua ke nrog lub kaw lus ntws lag luam thiab siv los tsim cov tsev qiv ntawv azide ntawm ntau yam 1,4-disubstituted 1,2,3-triazoles siv cov tshuaj tiv thaiv kub 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 cov teeb meem kev nyab xeeb uas tuaj yeem tshwm sim hauv cov txheej txheem batch, vim tias qhov kev cuam tshuam no tsim cov tshuaj tiv thaiv azide intermediates thiab txaus ntshai heev [317], [318]. Thaum pib, qhov kev cuam tshuam tau ua kom 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 lub kaw lus ntws (sab xis saum toj) tau los ntawm qhov kev tsim kho zoo tshaj plaws (qis dua) ntawm Huisgen 57 cycloaddition txoj kev npaj ntawm phenylacetylene thiab iodoethane rau kev ua kom zoo tshaj plaws thiab qhia cov kev hloov pauv zoo tshaj plaws ntawm cov tshuaj tiv thaiv.
Los ntawm kev tswj lub sijhawm nyob ntawm cov tshuaj reactants hauv seem catalytic ntawm lub reactor thiab ua tib zoo saib xyuas qhov kub ntawm cov tshuaj reaction nrog lub thermocouple sensor ncaj qha, cov xwm txheej ntawm cov tshuaj reaction tuaj yeem ua kom sai thiab raug nrog lub sijhawm thiab cov khoom siv tsawg kawg nkaus. Nws tau pom sai sai tias qhov kev hloov pauv siab tshaj plaws tau ua tiav siv lub sijhawm nyob ntawm 15 feeb thiab qhov kub ntawm cov tshuaj reaction ntawm 150 ° C. Nws tuaj yeem pom los ntawm daim duab coefficient ntawm MODDE software tias ob qho tib si lub sijhawm nyob thiab qhov kub ntawm cov tshuaj reaction yog suav tias yog cov xwm txheej tseem ceeb ntawm tus qauv. Kev khiav lub optimizer uas tau tsim los ntawm kev siv cov xwm txheej xaiv no tsim cov txheej txheem ntawm cov xwm txheej tshuaj reaction tsim los ua kom cov khoom siab tshaj plaws thaum txo cov khoom pib cov khoom siv siab tshaj plaws. Qhov kev ua kom zoo no tau ua rau muaj kev hloov pauv 53% ntawm cov khoom triazole, uas phim tus qauv qhov kev kwv yees ntawm 54%.