Na gode don ziyartar Nature.com. Sigar burauzar da kuke amfani da ita tana da iyakataccen tallafi ga CSS. Don mafi kyawun ƙwarewa, muna ba da shawarar ku yi amfani da sabunta burauza (ko kashe yanayin dacewa a cikin Internet Explorer) A halin yanzu, don tabbatar da ci gaba da tallafi, za mu nuna rukunin yanar gizon ba tare da salo da JavaScript ba.
Ƙarin masana'antu yana canza hanyar masu bincike da masana'antun masana'antu suna tsarawa da kera na'urorin sinadarai don saduwa da takamaiman bukatunsu.A cikin wannan aikin, mun bayar da rahoton misali na farko na kwararar reactor kafa ta hanyar m-jihar karfe takardar lamination dabara Ultrasonic Additive Manufacturing (UAM) tare da kai tsaye hadedde catalytic sassa da kuma ji element.Ba kawai UAM fasahar shawo kan da yawa daga cikin gazawar a halin yanzu hade da ƙari iyawar, amma kuma muhimmanci biochemical na'urorin. 1,4-disubstituted 1,2,3-triazole mahadi da aka samu nasarar hada da kuma inganta ta wani Cu-mediated Huisgen 1,3-dipolar cycloaddition dauki ta amfani da UAM chemistry saitin-up.By leveraging na musamman Properties na UAM da ci gaba da kwarara aiki, da na'urar ne iya catalyze ci gaba da martani da kuma samar da realtime amsawa.
Saboda da gagarumin abũbuwan amfãni a kan girma takwaransa, ya kwarara sunadarai ne mai muhimmanci da kuma girma filin a duka ilimi da kuma masana'antu saituna saboda ta ikon ƙara selectivity da kuma yadda ya dace da sinadaran synthesis.This kara daga sauki kwayoyin kwayoyin formation1 zuwa Pharmaceutical mahadi2,3 da na halitta kayayyakin4,5,6.Fiye da kashi 50% na halayen da ke cikin sinadarai masu kyau da masana'antun harhada magunguna na iya amfana daga amfani da ci gaba da sarrafa kwarara7.
A cikin 'yan shekarun nan, akwai wani girma Trend na kungiyoyin neman maye gurbin gargajiya gilashin ko kwarara ilmin sunadarai kayan aiki tare da customizable ƙari masana'antu (AM) sunadarai "reaction tasoshin"8.The iterative zane, m samar, da 3-dimensional (3D) capabilities na wadannan dabaru ne m ga waɗanda suke so su siffanta su na'urorin zuwa wani takamaiman sa na halayen, na'urorin, ko da fasaha da aka mayar da hankali a kan 3 na'urorin da wannan fasahar da aka mayar da hankali a kan na'urorin, kwanan wata, ko yanayin aiki. irin su stereolithography (SL) 9,10,11, fused deposition modeling (FDM) 8,12,13,14 da inkjet bugu 7, 15, 16. Rashin ƙarfi da ikon irin waɗannan na'urori don yin nau'i mai yawa na halayen sinadaran / nazari17, 18, 19, 19 AM, 1 mafi girma a cikin wannan filin yana da iyakacin iyaka. 20 .
Saboda karuwar amfani da sinadarai masu gudana da kyawawan kaddarorin da ke da alaƙa da AM, akwai buƙatar bincika ƙarin dabarun haɓakawa waɗanda ke ba masu amfani damar ƙirƙira tasoshin ruwa tare da ingantattun sinadarai da ƙarfin nazari.Waɗannan fasahohin yakamata su ba masu amfani damar zaɓar daga kewayon kayan aiki masu ƙarfi ko kayan aiki waɗanda ke iya ɗaukar yanayi da yawa na yanayin amsawa, yayin da kuma sauƙaƙe nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan na'urar don ba da damar sarrafa na'urar.
Daya ƙari masana'antu tsari da cewa yana da yuwuwar samar da al'ada sinadaran reactors ne Ultrasonic Additive Manufacturing (UAM) .This m-jihar takardar lamination dabara shafi ultrasonic oscillations zuwa bakin ciki karfe foils domin ya shiga su tare Layer da Layer da kadan girma dumama da kuma wani babban mataki na filastik kwarara 21 , 22 , 23 .Ba kamar sauran masana'antun da aka sani kai tsaye a cikin masana'antu na AM, ba kamar sauran masana'antu na zamani ba, kamar yadda aka sani da sauran fasahohin da aka sani da AMbrid, kamar sauran masana'antun masana'antu, Um kamar sauran fasahohin da aka fi sani da su. situ periodic kwamfuta lamba iko (CNC) milling ko Laser machining ma'anar da net siffar wani Layer na bonded abu 24, 25.Wannan yana nufin cewa mai amfani ba a iyakance ta da matsaloli hade da cire saura raw gina jiki daga kananan ruwa tashoshi, wanda shi ne sau da yawa yanayin tare da foda da ruwa AM Systems26,27,28.Wannan zane 'yancin kuma ya mika zuwa ga guda abu hade da zabin UAM. zabi na abu haduwa bayan narke tsari yana nufin cewa inji da sinadaran bukatar takamaiman aikace-aikace za a iya mafi alhẽri met.In Bugu da kari ga m jihar bonding, wani sabon abu ci karo a lokacin ultrasonic bonding shi ne babban ya kwarara na filastik kayan a in mun gwada da low yanayin zafi29,30,31,32,33.This na musamman alama na UAM iya sauƙaƙe saka na inji / thermal abubuwa a tsakanin karfe yadudduka da na'urar haska, ta hanyar mai amfani da hadi da yadudduka ba tare da lalacewa ta hanyar UAM. tics.
Ayyukan marubutan da suka gabata32 sun nuna ikon tsarin UAM don ƙirƙirar sifofin microfluidic na ƙarfe na 3D tare da haɗaɗɗun damar haɓaka.Wannan na'ura ce kawai saka idanu.Wannan takarda ta gabatar da misali na farko na injin sarrafa sinadarai na microfluidic wanda UAM ya ƙirƙira;na'ura mai aiki wanda ba kawai saka idanu ba amma har ma yana haifar da haɗakar sinadarai ta hanyar kayan aikin haɓakaccen tsari.Na'urar ta haɗu da fa'idodi da yawa da ke da alaƙa da fasahar UAM a cikin kera na'urorin sinadarai na 3D, kamar: ikon juyar da cikakkun ƙirar 3D kai tsaye daga ƙirar kayan aikin kwamfuta (CAD) zuwa samfuran;Ƙirƙirar abubuwa masu yawa don haɗawa da haɓakaccen haɓakaccen zafi da kayan haɓakawa;da kuma saka thermal na'urori masu auna firikwensin kai tsaye tsakanin reagent rafuffuka domin daidai dauki zafin jiki saka idanu da kuma iko.To nuna ayyuka na reactor, a library na pharmaceutically muhimmanci 1,4-disubstituted 1,2,3-triazole mahadi da aka hada da jan karfe-catalyzed Huisgen 1,3-dipolar cyclosdition da za a iya bude sabon cycloadization kimiyya da kwamfuta. ssibilities ga sunadarai ta hanyar multidisciplinary bincike.
An siyo duk abubuwan kaushi da reagents daga Sigma-Aldrich, Alfa Aesar, TCI ko Fischer Scientific kuma an yi amfani da su ba tare da tsarkakewa ba. (CD3)2SO a matsayin sauran ƙarfi.An yi duk halayen ta hanyar amfani da dandalin Uniqsis FlowSyn.
An yi amfani da UAM don ƙirƙira duk na'urori a cikin wannan binciken. An ƙirƙira fasahar fasaha a cikin 1999, kuma cikakkun bayanai na fasaha, sigogin aiki da abubuwan haɓakawa tun lokacin da aka ƙirƙira ta ana iya yin nazarin ta ta hanyar abubuwan da aka buga ta gaba34,35,36,37. An aiwatar da na'urar (Hoto 1) ta amfani da babban ƙarfi mai ƙarfi, 9kW SonicLayer 4000s ® USA ya kasance tsarin masana'anta na CuAM, tsarin na'urar OAM. 110 da Al 6061.Cu-110 yana da babban abun ciki na jan karfe (mafi ƙarancin 99.9% jan ƙarfe), yana mai da shi ɗan takara mai kyau don halayen jan ƙarfe-catalyzed, don haka ana amfani dashi azaman "launi mai aiki a cikin microreactor.Al 6061 O ana amfani da shi azaman “kauri” abu, da kuma saka Layer amfani da bincike;Haɗin kayan haɗin gwal da yanayin da aka haɗa tare da Layer Cu-110.Al 6061 O abu ne wanda aka nuna ya dace sosai tare da hanyoyin UAM38, 39, 40, 41 kuma an gwada shi kuma an same shi da kwanciyar hankali tare da reagents da aka yi amfani da su a cikin wannan aikin.Haɗin Al 6061 O tare da Cu-110 kuma ana ɗaukarsa azaman haɗin kayan haɗin gwiwa don UAM kuma saboda haka abu ne mai dacewa don wannan binciken.38,42 Waɗannan na'urori an jera su a cikin Tebur na 1 a ƙasa.
Matakan ƙirƙira reactor (1) Al 6061 substrate (2) Ƙirƙirar tashar ƙasa da aka saita zuwa foil na jan karfe (3) Haɗewar ma'aunin zafi da sanyio tsakanin yadudduka (4) Babban tashar (5) Mai shiga da fitarwa (6) Monolithic reactor.
The zane falsafar hanyar ruwa hanya ne don amfani da convoluted hanya don ƙara nisa ruwa tafiya a cikin guntu, yayin da ajiye guntu a wani m size.Wannan karuwa a nesa yana da kyawawa don ƙara mai kara kuzari / reagent hulda lokaci da kuma samar da kyakkyawan samfurin da ake samu.The kwakwalwan kwamfuta amfani da 90 ° lankwasa a ƙarshen madaidaicin hanya don haifar da tashin hankali 44 na'ura da kara hadawa a cikin na'urar da kara hadewa da ruwa lokaci (Don ƙara ƙararrawa na'urar) da kuma ƙara lokacin haxawa da ruwa. wanda za a iya cimma, da reactor zane siffofi biyu reagent inlets hade a Y-junction kafin shigar da serpentine hadawa sashe. Na uku mashiga, wanda intersects rafi rabin ta wurin zama, an haɗa a cikin zane na gaba multistep dauki kira.
Dukkan tashoshi suna da bayanan murabba'i (babu daftarin kusurwoyi), sakamakon milling na CNC na lokaci-lokaci da aka yi amfani da shi don ƙirƙirar geometry ta tashar.An zaɓi ma'aunin tashoshi don tabbatar da babban fitarwa (don microreactor) girma, yayin da yake ƙarami don sauƙaƙe hulɗar saman (masu haɓakawa) don yawancin abubuwan da ke ƙunshe. Girman da ya dace ya dogara ne akan ƙwarewar marubutan da suka gabata tare da na'urorin ƙarfe-fluidic na x5. µm kuma jimlar reactor ya kasance 1 ml. An haɗa haɗin haɗin haɗin gwiwa (1/4″—28 UNF zaren) a cikin ƙira don ba da damar hulɗar sauƙi na na'urar tare da kayan aikin sinadarai na kasuwanci.Girman tashar yana iyakance ta kauri na kayan ɓoye, kayan aikin injin sa, da sigogin haɗin kai da aka yi amfani da su tare da ultrasonics.A wani nisa na musamman don kayan da aka ba, kayan za su "sag" a cikin tashar da aka halicce.A halin yanzu babu takamaiman samfuri don wannan lissafin, don haka matsakaicin nisa na tashar don kayan da aka ba da ƙira an ƙaddara ta gwaji;A wannan yanayin, nisa na 750 μm ba zai haifar da sag ba.
An ƙayyade siffar (square) na tashar ta hanyar yin amfani da maƙalar murabba'i. Za'a iya canza siffar da girman tashoshi ta hanyar na'urorin CNC ta yin amfani da kayan aikin yankan daban-daban don samun nau'o'in nau'i daban-daban da halaye.Misalin ƙirƙirar tashar tashar mai lankwasa ta amfani da kayan aiki na 125 μm za a iya samuwa a cikin aikin Monaghan45.Lokacin da aka ajiye Layer Layer a cikin wani tsari na kayan aiki, za a yi amfani da kayan aiki a kan tashar kayan aiki. don kula da ma'auni na tashar, an yi amfani da ƙayyadaddun murabba'i.
A lokacin da aka riga aka shirya dakata a cikin masana'anta, ana shigar da gwaje-gwajen zafin jiki na thermocouple (Nau'in K) kai tsaye a cikin na'urar tsakanin ƙungiyoyin tashoshi na sama da na ƙasa (Hoto 1 - Mataki na 3).Wadannan thermocouples na iya lura da canjin yanayin zafi daga -200 zuwa 1350 ° C.
Ana yin aikin ƙaddamar da ƙarfe ta ƙaho na UAM ta amfani da 25.4 mm fadi, 150 micron lokacin farin ciki na karfe.Girman kayan da aka ajiye ya fi girma fiye da samfurin ƙarshe kamar yadda tsarin subtractive ya haifar da siffar net na ƙarshe.CNC machining ana amfani dashi don inji na waje da na ciki contours na kayan aiki, sakamakon da surface gama na kayan aiki da kuma tashoshi daidai da zaba kayan aiki da CNC tsari sigogi (kimanin 1.6 μm Ramin a cikin wannan misali).Ci gaba, da ci gaba da yin amfani da machining na'urar a ko'ina cikin girma na'urorin da ake amfani da machining na'urar da ake ci gaba da yin amfani da machining na'urar. gama sashi zai sadu da CNC gama milling daidaito matakan.The tashar nisa amfani da wannan na'urar ne kananan isa don tabbatar da cewa tsare abu ba ya "sag" a cikin ruwa tashar, don haka tashar kula da wani square giciye-section. Yiwuwar gizagizai a tsare abu da UAM tsari sigogi da aka ƙaddara experimentally da masana'antu abokin tarayya (Fabrisonic LLC, Amurka).
Nazarin ya nuna cewa ɗan ƙaramin yaduwa yana faruwa a UAM bonding interface 46, 47 ba tare da ƙarin jiyya na thermal ba, don haka ga na'urorin da ke cikin wannan aikin, Layer Cu-110 ya bambanta da Layer Al 6061 kuma yana canzawa ba zato ba tsammani.
Shigar da pre-calibrated 250 psi (1724 kPa) baya matsa lamba regulator (BPR) zuwa kanti na reactor da kuma famfo ruwa ta cikin reactor a wani kudi na 0.1 zuwa 1 mL min-1.The reactor matsa lamba da aka saka idanu ta amfani da FlowSyn gina-in tsarin matsa lamba firikwensin don tabbatar da cewa tsarin zai iya kula da wani m bambance-bambancen da matsa lamba steactor steta. The thermocouples saka a cikin reactor da waɗanda aka saka a cikin FlowSyn guntu dumama farantin.Wannan yana samuwa ta hanyar sãɓãwa da programmable hotplate zafin jiki tsakanin 100 da 150 ° C a 25 ° C increments da kuma lura da wani bambance-bambance tsakanin shirye-shirye da kuma rikodi yanayin zafi.An samu wannan ta amfani da tc-08 data, Cambridge data Logger da kuma UKPccoicog.
An inganta yanayin halayen cycloaddition na phenylacetylene da iodoethane (Tsarin 1- Cycloaddition na phenylacetylene da iodoethane Scheme 1- Cycloaddition na phenylacetylene da iodoethane) .Wannan haɓakawa an yi shi ta hanyar cikakken tsari na ƙira na gwaje-gwaje (DOE) lokacin daidaitawa a matsayin ma'auni na ma'auni na gwaje-gwaje (DOE) lokacin da ake yin amfani da ma'auni na al'ada. .
Rarrabe mafita na sodium azide (0.25 M, 4: 1 DMF: H2O), iodoethane (0.25 M, DMF), da kuma phenylacetylene (0.125 M, DMF) da aka shirya.A 1.5 mL aliquot kowane bayani da aka gauraye da pumped ta hanyar reactor a so samfurin ya kwarara rabo da kuma zafin jiki triazole. kuma an ƙaddara ta babban aikin ruwa chromatography (HPLC) .Domin daidaito na bincike, duk halayen da aka samo su ne kawai bayan cakudaccen abu ya bar reactor. Matsalolin da aka zaɓa don ingantawa an nuna su a cikin Table 2.
All samfurori da aka bincikar ta amfani da wani Chromaster HPLC tsarin (VWR, PA, USA) kunsha wani quaternary famfo, shafi tanda, m zangon UV ganowa da autosampler.The shafi ya wani Daidaita 5 C18 (VWR, PA, USA), 4.6 × 100 mm a size, 5 µm .0 mm a size, 5 µm . ol: ruwa a cikin adadin 1.5 mL.min-1. Ƙarfin allurar ya kasance 5 µL kuma tsawon ma'aunin ma'aunin ya kasance 254 nm. An ƙididdige yanki mafi girma na% na samfurin DOE daga wurare mafi girma na ragowar alkyne da samfurori na triazole kawai. Injection na farawa kayan yana ba da damar gano kololuwar dacewa.
Haɗa kayan aikin bincike na reactor zuwa software na MODDE DOE (Umetrics, Malmö, Sweden) ya ba da izinin cikakken bincike game da yanayin sakamako da ƙudurin yanayin haɓaka mafi kyau ga wannan cycloaddition.Gudanar da ginanniyar haɓakawa da zaɓin duk mahimman sharuɗɗan ƙirar ƙira suna haifar da saitin yanayin amsawa wanda aka tsara don haɓaka yanki mafi girman samfurin yayin rage yankin farawa ga acety.
An sami iskar oxygenation na jan ƙarfe na saman a cikin ɗakin ɗaukar hoto ta hanyar amfani da maganin hydrogen peroxide (36%) yana gudana ta cikin ɗakin amsawa (yawan kwarara = 0.4 mL min-1, lokacin zama = 2.5 min) kafin haɗin kowane ɗakin karatu na fili na triazole.
Da zarar an gano mafi kyawun saiti na yanayi, an yi amfani da su zuwa kewayon acetylene da abubuwan haloalkane don ba da damar haɗar ƙaramin haɗin ɗakin karatu, ta haka ne ke tabbatar da ikon yin amfani da waɗannan sharuɗɗan zuwa faɗuwar kewayon yuwuwar reagents (Figure 1).2).
Shirya daban-daban mafita na sodium azide (0.25 M, 4: 1 DMF: H2O), haloalkanes (0.25 M, DMF) da kuma alkynes (0.125 M, DMF) .3 mL aliquots na kowane bayani da aka gauraye da pumped ta hanyar reactor a 75 µL.min-1 da kuma 150 ° C da aka tattara a cikin wani totaled vial da 150 ° C. acetate. An wanke samfurin samfurin tare da 3 × 10 mL na ruwa. An haɗu da yadudduka masu ruwa da ruwa kuma an fitar da su tare da 10 ml na ethyl acetate;Sannan an haɗa nau'ikan kwayoyin halitta, an wanke su da 3 x 10 ml na brine, bushe a kan MgSO4 kuma an tace su, sa'an nan kuma an cire sauran ƙarfi a cikin vacuo. An tsarkake samfurori ta hanyar chromatography na shafi akan gel silica ta amfani da ethyl acetate kafin bincike ta hanyar haɗin HPLC, 1H NMR, 13C NMR da babban ƙuduri na HR-MSrometry).
An samo duk nau'ikan bakan ta amfani da ma'aunin ma'aunin ƙuduri na Thermofischer daidaitaccen Orbitrap tare da ESI a matsayin tushen ionization.Duk samfuran an shirya su ta amfani da acetonitrile azaman sauran ƙarfi.
An gudanar da bincike na TLC akan faranti na silica masu goyon bayan aluminum. An hango faranti ta hanyar hasken UV (254 nm) ko vanillin tabo da dumama.
An bincika dukkan samfurori ta amfani da tsarin VWR Chromaster (VWR International Ltd., Leighton Buzzard, UK) wanda aka sanye shi da autosampler, famfo tanda na binaryar famfo da kuma mai gano tsawon tsayi guda ɗaya. Rukunin da aka yi amfani da shi shine ACE Equivalence 5 C18 (150 × 4.6 mm, Advanced Chromatography Technologies Ltd., Aberdeen, Scotland).
Injections (5 µL) da aka sanya kai tsaye daga diluted danyen dauki cakuda (1:10 dilution) da kuma bincikar ruwa: methanol (50:50 ko 70:30), sai dai wasu samfurori ta amfani da 70:30 sauran ƙarfi tsarin (laƙanta a matsayin tauraro lambar) a kwarara kudi na 1.5 mL / min. The shafi na 4.5 mL / min.
An ƙididdige yanki mafi girman % na samfurin daga mafi girman yanki na ragowar alkyne, samfurin triazole kawai, da allurar kayan farawa sun ba da izinin gano kololuwar da suka dace.
An yi nazarin duk samfurori ta amfani da Thermo iCAP 6000 ICP-OES. An shirya duk matakan daidaitawa ta amfani da 1000 ppm Cu daidaitaccen bayani a cikin 2% nitric acid (SPEX Certi Prep) . An shirya duk matakan a cikin 5% DMF da 2% HNO3 bayani, kuma duk samfurori an diluted 20.
UAM utilizes ultrasonic karfe waldi a matsayin bonding dabara ga karfe tsare abu amfani da gina karshe taro.Ultrasonic karfe waldi utilizes wani vibrating karfe kayan aiki (wanda ake kira ƙaho ko ultrasonic ƙaho) don amfani da matsa lamba ga tsare Layer / baya ƙarfafa Layer da za a bonded yayin da vibrating da material.Don ci gaba da aiki, da sonotrode da vibring ne surface na cylin amfani da surface yankin. , oxides a saman kayan zai iya fashewa. Ci gaba da matsa lamba da rawar jiki na iya haifar da asperities na kayan don rushewa 36. Mutuncin da ke haifar da zafi da matsa lamba na gida sannan ya haifar da haɗin kai mai ƙarfi a cikin musaya na kayan aiki;shi kuma iya taimaka mannewa ta hanyar canje-canje a surface energy48.The yanayin da bonding inji shawo kan da yawa daga cikin matsalolin da alaka da m narkewa zafin jiki da kuma high zafin jiki bayan-sakamakon da aka ambata a cikin sauran ƙari masana'antu dabaru.This damar domin kai tsaye bonding (watau, ba tare da surface gyare-gyare, fillers ko adhesives) na mahara yadudduka na daban-daban kayan a cikin guda consolidated tsarin.
Na biyu m factor for UAM ne babban mataki na filastik kwarara lura a karfe kayan, ko da a low yanayin zafi, watau da kyau a kasa da narkewa batu na karfe kayan.The hade da ultrasonic oscillation da matsa lamba induces high matakan na gida hatsi iyaka hijirarsa da recrystallization ba tare da babban yawan zafin jiki karuwa bisa ga al'ada hade da girma kayan, ko da a low yanayin zafi, watau da kyau a kasa da narkewa batu na karfe material.The hade da ultrasonic oscillation da matsa lamba induces high matakan na gida hatsi iyaka hijirarsa da recrystallization ba tare da babban yawan zafin jiki karuwa bisa ga al'ada hade da girma kayan.During da gina na karshe taron, wannan phenomened karfe Layer iya wuce gona da iri. Abubuwan da suka haɗa da fiber na gani 49, ƙarfafawa 46, kayan lantarki 50, da thermocouples (wannan aikin) duk an samu nasarar shigar da su cikin sifofin UAM don ƙirƙirar taruka masu haɗaka masu aiki da masu wucewa.
A cikin wannan aikin, duka biyun nau'ikan haɗin kayan abu daban-daban da damar haɗin kai na UAM an yi amfani da su don ƙirƙirar microreactor na saka idanu na zafin jiki na ƙarshe.
Idan aka kwatanta da palladium (Pd) da sauran abubuwan karafa na ƙarfe da aka saba amfani da su, Cu catalysis yana da fa'idodi da yawa: (i) Tattalin arziki, Cu ba shi da tsada fiye da sauran karafa da ake amfani da su a cikin catalysis don haka zaɓi ne mai ban sha'awa ga masana'antar sarrafa sinadarai (ii) Kewayon halayen haɗin giciye na Cu-catalyzed yana ƙaruwa kuma ya bayyana ya zama ɗan dacewa ga Pd5-based. da kyau in babu sauran ligands, Wadannan ligands sau da yawa structurally sauki da kuma m idan ana so, yayin da waɗanda aka yi amfani da Pd sunadarai sau da yawa hadaddun, tsada, da kuma iska-m (iv) Cu, musamman da aka sani da ikon daure alkynes a cikin kira, Misali, bimetallic-catalyzed Sonogashira coupling da amistryuclidition (Cu) yana haɓaka haɓakar haɓakawa da haɓakawa na nucleophiles da yawa a cikin halayen Ullmann.
Misalai na heterogenization na duk waɗannan halayen kwanan nan an nuna su a gaban Cu (0) .Wannan ya fi girma saboda masana'antun harhada magunguna da kuma ci gaba da mayar da hankali ga farfadowa na karafa na karfe da sake amfani da su55,56.
Majagaba da Huisgen a cikin 1960s57, da 1,3-dipolar cycloaddition dauki tsakanin acetylene da azide zuwa 1,2,3-triazole an dauke a synergistic reaction.Sakamakon 1,2,3 triazole moieties ne na musamman sha'awa a matsayin pharmacophore a cikin filin na daban-daban aikace-aikace na kwayoyi da kuma amfani da 8.
Wannan dauki ya zo cikin mayar da hankali sake lokacin da Sharpless da sauransu suka gabatar da manufar "danna sunadarai"59. Kalmar "danna sunadarai" Ana amfani da kalmar "danna sunadarai" da ake amfani da su bayyana wani robust, abin dogara da kuma zabar sa na halayen ga m kira na sabon mahadi da combinatorial dakunan karatu via heteroatom linkage (CXC) 60 The roba roko na wadannan halayen ruwa ne mai sauki juriya, da oxygen da ake samu daga wadannan yanayi da ake samu daga ruwa mai tushe. 1.
Huisgen 1,3-dipole cycloaddition na gargajiya ba ya cikin nau'in "click chemistry" . Duk da haka, Medal da Sharpless sun nuna cewa wannan taron haɗin gwiwar azide-alkyne yana fuskantar 107 zuwa 108 a gaban Cu (I) idan aka kwatanta da uncatalyzed 1,3-dipolar 6 cycloadlementation system, ba ya buƙatar haɓaka haɓakar cycloadition. ko matsananciyar halayen halayen da haɓakawa kusa da cikakkiyar juzu'i da zaɓin zaɓi zuwa 1,4-rasuwar 1,2,3-triazoles (anti- 1,2,3-triazole) akan sikelin lokaci (Hoto 3).
Sakamakon isometric na al'ada da tagulla-catalyzed Huisgen cycloadditions.Cu (I) - catalyzed Huisgen cycloadditions yana samar da 1,4-diubstituted 1,2,3-triazoles kawai, yayin da Huisgen cycloadditions da aka haifar da thermally ya haifar da 1,4- da 1,5: 1 isomers na 1,5-triazoles na 1.
Yawancin ka'idoji sun haɗa da rage barga tushen Cu(II), kamar rage CuSO4 ko Cu(II)/Cu(0) nau'in haɗin gwiwa tare da sodium salts. Idan aka kwatanta da sauran halayen ƙarfe-catalyzed, amfani da Cu (I) yana da manyan abũbuwan amfãni na kasancewa maras tsada da sauƙin rikewa.
Kinetic da nazarin alamar isotopic ta Worrell et al.65 ya nuna cewa, a cikin yanayin tashar alkynes, nau'i biyu na jan karfe suna da hannu wajen kunna reactivity na kowane kwayoyin halitta zuwa azide. Tsarin da aka tsara yana samuwa ta hanyar zoben ƙarfe na ƙarfe mai mambobi shida da aka kafa ta hanyar daidaitawa na azide zuwa σ-bonded jan acetylide tare da π-bonded jan karfe da π-bonded tagulla a matsayin barga da aka samu ta hanyar zoben jan ƙarfe na ƙarfe na ƙarfe. bazuwar proton don samar da samfuran triazole da rufe zagayowar catalytic.
Duk da yake amfanin ya kwarara sunadarai na'urorin da aka rubuce da kyau rubuce, akwai sha'awar hade Analytical kayayyakin aiki, a cikin wadannan tsarin for in-line, a-wuri, tsari monitoring66,67.UAM tabbatar da zama dace hanya don zayyana da kuma samar da sosai hadaddun 3D kwarara reactors Ya sanya daga catalytically aiki, thermally conductive kayan tare da kai tsaye saka ji abubuwa 4 (Figure).
Aluminum-Copper kwarara reactor ƙirƙira ta ultrasonic ƙari masana'antu (UAM) tare da hadaddun ciki tashar tsarin, saka thermocouples da catalytic dauki chamber.To visualize ciki ruwa hanyoyin, m samfur ƙirƙira ta amfani da stereolithography kuma an nuna.
Don tabbatar da reactors an ƙirƙira don halayen kwayoyin halitta na gaba, masu kaushi suna buƙatar mai zafi sama da wurin tafasa;sun kasance matsa lamba da zafin jiki da aka gwada. Gwajin gwajin ya nuna cewa tsarin yana kula da kwanciyar hankali da matsa lamba har ma da karuwar tsarin tsarin (1.7 MPa) . An yi gwajin gwajin hydrostatic a dakin da zafin jiki ta amfani da H2O a matsayin ruwa.
Haɗin da aka saka (Hoto 1) thermocouple zuwa ma'aunin bayanan zafin jiki ya nuna cewa thermocouple ya kasance 6 ° C (± 1 ° C) mai sanyaya fiye da yanayin da aka tsara akan tsarin FlowSyn. Yawanci, haɓakar 10 ° C a cikin yanayin zafi a cikin sau biyu na ƙimar amsawa, don haka bambancin zafin jiki na kawai 'yan digiri na iya bambanta da yawan zafin jiki a duk lokacin da yawan zafin jiki ya canza zuwa yanayin zafi. usivity na kayan amfani a cikin masana'antu process.This thermal gantali ne m kuma saboda haka za a iya lissafta a cikin kayan saitin don tabbatar da daidai yanayin zafi da aka kai da kuma auna a lokacin reaction.Saboda haka, wannan online monitoring kayan aiki facilitates m iko da dauki zafin jiki da kuma facilitates mafi daidai aiwatar ingantawa da kuma ci gaban da mafi kyau duka yanayi.These na'urori masu auna sigina kuma za a iya amfani da su gane dauki exotherms da tsarin a cikin manyan-Trunaway dauki.
The reactor gabatar a cikin wannan aikin shi ne na farko misali na aikace-aikace na UAM fasahar zuwa ƙirƙira na sinadaran reactors da kuma magance da dama manyan gazawar a halin yanzu hade da AM / 3D bugu na wadannan na'urorin, kamar: (i) shawo kan da rahoton matsalolin da suka shafi jan karfe ko aluminum gami aiki (ii) inganta ciki tashar ƙuduri idan aka kwatanta da foda gado Fusion (PBF) dabaru irin su zažužžukan Laser kwarara 5 (SLM 9) kayan aiki narkar da (PBF) da fasaha na 6 (SLM9) narkar da kayan aiki kamar 6. duced aiki zafin jiki, wanda facilitates kai tsaye bonding na na'urori masu auna sigina, wanda ba zai yiwu a foda gado fasaha, (v) shawo kan matalauta inji Properties da ji na ƙwarai na polymer-tushen aka gyara zuwa wani iri-iri na kowa Organic solvents17,19.
Ayyukan reactor da aka nuna ta hanyar sycodor na jan ƙarfe na alkyneyzed alycodple na coatyne a karkashin tsarin kwarara na kasuwanci da aka yi amfani da shi da tsarin amfani da na kasuwanci da kuma alylyled dauki na Acetylene da Alkyl Combarin Helko da offise Laide a gaban sodium chloride (Hoto na 3). Yin amfani da ci gaba da keke na yau da kullun da na iya motsawa mai haɗari da iodoethane. Ethane) (duba Hoto na 5).
(Hagu na sama) Tsarin saitin da aka yi amfani da shi don haɗa reactor na 3DP a cikin tsarin kwarara (a saman dama) da aka samu a cikin ingantacciyar (ƙasa) makirci na Huisgen cycloaddition 57 makirci tsakanin phenylacetylene da iodoethane don haɓakawa da nuna ingantattun sigogin amsa ƙimar amsawa.
Ta hanyar sarrafa lokacin zama na reagents a cikin ɓangaren catalytic na reactor da kuma kula da yanayin zafin jiki tare da bincike na thermocouple kai tsaye, ana iya inganta yanayin amsawa cikin sauri da daidai tare da ƙarancin lokaci da kayan amfani.An ƙaddara da sauri cewa an sami mafi girman juzu'i lokacin da lokacin zama na mintuna 15 da zafin jiki na 150 ° C ana amfani da shi azaman yanayin zafin jiki na 150 ° C, ana iya amfani da madaidaicin lokaci na software. .Gudanar da ginanniyar haɓakawa ta amfani da waɗannan sharuɗɗan da aka zaɓa yana haifar da saiti na yanayin amsawa da aka tsara don haɓaka wuraren kololuwar samfur yayin da rage farawar wuraren kololuwar kayan aiki.Wannan haɓakawa ya haifar da juzu'in 53% na samfurin triazole, wanda ya dace da tsinkayar samfurin 54%.
Dangane da wallafe-wallafen da ke nuna cewa jan karfe (I) oxide (Cu2O) na iya aiki azaman ingantacciyar nau'in nau'in haɓakar kuzari akan sifili-valent jan karfe saman a cikin waɗannan halayen, ikon pre-oxidize da reactor surface kafin aiwatar da dauki a cikin kwarara da aka bincika70,71.A dauki tsakanin phenylacetylene da iodoethane da aka sa'an nan yi sake a karkashin mafi kyau duka yanayi da aka lura da sakamakon da aka yi a cikin mafi kyaun yanayi. abu, wanda aka lasafta su zama> 99%.Duk da haka, sa idanu ta HPLC ya nuna cewa wannan jujjuya muhimmanci rage wuce kima tsawaita dauki lokaci har zuwa kamar 90 minutes, sa'ilin da aiki ya bayyana zuwa matakin kashe da kuma kai wani "kwayayyen jihar" .Wannan lura da nuna cewa tushen catalytic aiki da aka samu daga surface jan karfe oxide maimakon sifi-valent jan karfe substrate da sifili-valent tagulla substrate da oxide da kai Layer zuwa Cucunity Layer da sauƙi a cikin daki. .Wannan yana kawar da buƙatar ƙara tushen tagulla (II) don haɗin gwiwa71.