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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 reactor wanda aka 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 sinadaran reactors yana ƙaruwa. Abubuwan da ke da mahimmanci na nazarin halittu 1,4-disubstituted 1,2,3-triazole mahadi an samu nasarar haɗa su kuma inganta su ta hanyar Cu-mediated Huisgen 1,3-dipolar cycloaddition reaction ta amfani da saitin sunadarai na UAM.
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 da 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 kuma 3-girma (3D) capabilities na wadannan dabaru ne da amfani ga wadanda suke so su siffanta na'urorin su zuwa wani takamaiman sa na halayen, na'urorin, ko da yanayin aiki da aka mayar da hankali a kan na'urorin, kwanan wata, ko yanayin aiki da aka mayar da hankali a kan wannan yanayin. Dabarun bugu na 3D 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 aiwatar da nau'ikan halayen halayen sinadarai / nazari17, 19, 01 mafi girma a cikin wannan babban fa'idar AM. filin17, 18, 19, 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 wani babban mataki na filastik ya kwarara 21 , 22 , 23 .Ba kamar sauran masana'antun da aka sani da subctive AM kai tsaye tare da fasaha na zamani, kamar sauran masana'antu AM, ba kamar sauran fasahohin masana'antu na AM, ba kamar sauran fasahohin masana'antu na AMbri. tsari, a cikin abin da in-situ lokaci-lokaci kwamfuta numerical 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 da matsalolin da ke hade da cire sauran albarkatun gina jiki daga kananan ruwa tashoshi, wanda shi ne sau da yawa yanayin tare da foda da ruwa AM Systems26,27,28 -Wannan zanen zabi na iya karawa da irin wannan 'yanci da kuma damar da za a iya karawa da irin wannan 'yanci na UAM. dissimilar abu haduwa a cikin guda tsari step.The zabi na abu haduwa bayan narke tsari yana nufin cewa inji da kuma sinadaran bukatun na 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.Wannan musamman alama na UAM / embed karfe abubuwa na inji na iya sauƙaƙe ba tare da lalacewa ba. zai iya sauƙaƙe isar da bayanai na ainihi daga na'urar zuwa mai amfani ta hanyar haɗaɗɗiyar nazari.
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 zazzabi saka idanu da kuma iko.To nuna da 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 cycloadition kayan aikin da kwamfuta iya bude cyclosditions da kwamfuta. samar da sabbin damammaki da yuwuwar ga ilimin sunadarai ta hanyar bincike da yawa.
An siyo duk kaushi da reagents daga Sigma-Aldrich, Alfa Aesar, TCI ko Fischer Scientific kuma an yi amfani da su ba tare da tsarkakewa ba. CDCl3 ko (CD3) 2SO a matsayin mai narkewa. Dukkan halayen an yi su ta amfani da dandalin Uniqsis FlowSyn na kemistry.
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 ci gaba tun lokacin da aka ƙirƙira ta za a iya yin nazari ta hanyar abubuwan da aka buga ta gaba34,35,36,37. An aiwatar da na'urar (Figure 1) ta amfani da babban ƙarfi mai ƙarfi, 9kW SonicLayer 4000s ® USA tsarin tsarin OAM, tsarin masana'anta na OAM. ya kwarara na'urar kasance Cu-110 da Al 6061.Cu-110 yana da wani babban jan karfe abun ciki (mafi ƙarancin 99.9% jan karfe), yin shi mai kyau dan takara ga jan karfe-catalyzed halayen, sabili da haka ana amfani da a matsayin "aiki Layer a cikin wani microreactor. Al 6061 O da ake amfani da matsayin" girma" abu, kuma Embedding Layer a hade tare da wani bangaren hadaddun hadaddun hadaddun da kuma anneili. Cu-110 Layer Al 6061 O wani abu ne wanda aka nuna ya dace sosai tare da matakan UAM38, 39, 40, 41 kuma an gwada shi kuma an sami kwanciyar hankali na Chemical tare da reagents da aka yi amfani da su a cikin wannan aikin kasa.
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.
Tsarin falsafar zane na hanyar ruwa shine yin amfani da hanya mai rikitarwa don ƙara yawan tafiyar ruwa mai nisa a cikin guntu, yayin da yake ajiye guntu a girman girman da za a iya sarrafawa.Wannan karuwa a nesa yana da kyawawa don ƙara yawan lokacin hulɗar mai kara kuzari / reagent da kuma samar da samfurori masu kyau. The kwakwalwan kwamfuta suna amfani da 90 ° lanƙwasa a ƙarshen madaidaiciyar hanya don haifar da rikice-rikice na na'ura na lokaci-lokaci da kuma ƙara yawan lokaci tare da ruwa. kara ƙara hadawa da za a iya samu, da reactor zane siffofi biyu reagent inlets hade a Y-junction kafin shigar da serpentine hadawa sashe. Na uku mashigai, 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 ƙarshe na tashar 7. x 750 µm kuma jimlar reactor ya kasance 1 ml. An haɗa haɗin haɗin haɗin gwiwa (1/4″ — zaren UNF 28) 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 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 tashar jiragen ruwa zai sami kayan da aka yi a kan zane-zane, za a yi amfani da kayan da aka yi a kan zane-zane. gamawa.A cikin wannan aikin, 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 ta ƙarshe.CNC machining ana amfani dashi don inji na waje da na ciki contours na kayan aiki, sakamakon wani surface gama na kayan aiki da tashoshi daidai da zaba kayan aiki da CNC tsari sigogi (kimanin 1.6 μm Ramin a cikin wannan misali) ci gaba, ci gaba da yin amfani da machining girma na na'urar a ko'ina cikin yanayin da ake iya yin amfani da na'ura na'urar da za a iya amfani da ultrasonic girma na'urar. ana kiyayewa kuma ɓangaren da ya ƙare zai hadu da CNC gama milling daidaito matakan.The tashar nisa amfani da wannan na'urar ne kananan isa don tabbatar da cewa tsare kayan ba ya "sag" a cikin ruwa tashar, don haka tashar kula da wani square giciye-section. Yiwuwar giciye a tsare kayan da UAM tsarin sigogi da aka ƙaddara experimentally ta wani 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 matsa lamba a fadin Potenta reactor. gano duk wani bambance-bambance tsakanin thermocouples saka a cikin reactor da waɗanda aka saka a cikin FlowSyn guntu dumama farantin.Wannan yana samuwa ta hanyar sãɓãwar launukansa 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 rikodin yanayin zafi.Wannan an samu ta amfani da wani loechgger, Cambridge data da kuma UKPccony data. PicoLog software.
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, daidaitaccen ma'auni na gwaje-gwajen (DOE) a matsayin ma'auni na al'ada. ku 1:2.
Rarrabe mafita na sodium azide (0.25 M, 4: 1 DMF: H2O), iodoethane (0.25 M, DMF), da phenylacetylene (0.125 M, DMF) da aka shirya.A 1.5 mL aliquot na kowane bayani da aka gauraye da pumped ta hanyar reactor a so samfurin ya kwarara kudi da kuma zafin jiki triazole. phenylacetylene farawa abu da ƙaddara ta high yi ruwa chromatography (HPLC) .Domin daidaito na bincike, duk halayen da aka sampled kawai bayan dauki cakuda bar reactor.The siga jeri zaba domin ingantawa da aka nuna a cikin Table 2.
All samfurori da aka bincikar ta amfani da Chromaster HPLC tsarin (VWR, PA, USA) kunsha wani quaternary famfo, shafi tanda, m raƙuman ruwa UV ganowa da autosampler.The shafi ya daidai 5 C18 (VWR, PA, USA), 4.6 × 100 mm a size, 5 µm isocrat size, 5 ° C 4.5 µm da aka warware a size. 50: 50 methanol: ruwa a kwararar ruwa na 1.5 ml.min-1. Ƙarfin allura ya kasance 5 µL kuma tsayin daka mai mahimmanci ya kasance 254 nm. An ƙididdige yankin % ganiya don samfurin DOE daga ƙananan yankunan alkyne na ragowar alkyne da samfurori na triazole kawai. allura na farawa kayan da ya dace yana ba da izinin ganewa.
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 yanayin yanayi, an yi amfani da su zuwa kewayon acetylene da abubuwan haloalkane don ba da damar haɗar ƙaramin haɗaɗɗiyar 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. mL na ethyl 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 5.5 mL / min. nm.
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 kuma cylin matsa lamba a kan surface yankin. kuma ana amfani da vibration, 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 .Tsarin hulɗa tare 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 cikin surface energy48.The yanayin da bonding inji shawo kan da yawa daga cikin matsalolin da ke hade 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 gyara, fillers ko adhesives) na mahara yadudduka na daban-daban kayan a cikin guda consolidated tsarin.
A karo 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 ultrasonic oscillation da matsa lamba induces high matakan na gida hatsi iyaka hijirarsa da recrystallization ba tare da babban yawan zafin jiki karuwa a al'ada hade da girma kayan.During gina na karshe taron, wannan phenomented Layer iya wuce haddi da aka gyara a cikin phenomented Layer. Karfe foil, Layer by Layer.Abubuwa kamar na gani zaruruwa 49, ƙarfafa 46, Electronics 50, da thermocouples (wannan aikin) duk an samu nasarar shigar a cikin UAM Tsarin don ƙirƙirar aiki da m hada taro.
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 karfe 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 aka yi 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. Cu-catalyzed halayen aiki da kyau in babu sauran ligands, Wadannan ligands sau da yawa structurally sauki da kuma m idan ana so, alhãli kuwa waɗanda aka yi amfani da Pd chemistry sau da yawa hadaddun, tsada, da kuma iska-sensitive (iv) Cu, musamman da aka sani da ikon ɗaure alkynes a cikin kira, misali, bimetallic-catalyzed Sonogazidklickups da kuma ashiraziklock. (v)Cu kuma yana iya haɓaka arylation 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" 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 daga cikin wadannan halayen ruwa ne mai sauki juriya, da oxygen da ake samu daga wadannan yanayi da ake samu daga ruwa mai tushe. rabuwa da sauki61.
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 rashin daidaituwa na 1,3-dipolar 62 cycloadition. baya buƙatar ƙungiyoyin karewa ko yanayin halayen halayen da ake samarwa kusa da cikakkiyar juzu'i da zaɓin zaɓi zuwa 1,4-disustituted 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 alkynes m, 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 jan karfe mai mambobi shida da aka kafa ta hanyar daidaitawa na azide zuwa σ-bonded jan acetylide tare da π-bonded jan ƙarfe a matsayin barga da aka kafa ta hanyar haɗin gwiwa na tagulla. raguwa, biye da 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 (Figure 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, karuwar 10 ° C a cikin zafin jiki yana haifar da sau biyu na yawan amsawa, don haka bambancin zafin jiki na kawai 'yan digiri na iya bambanta da yawan zafin jiki na jiki saboda yawan zafin jiki. thermal diffusivity na kayan da ake amfani da su 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 tsari ingantawa da kuma ci gaban da mafi kyau duka yanayi.These na'urori masu auna sigina kuma za a iya amfani da su gane a cikin manyan runaway tsarin 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 gudãna (PBF) da fasaha narkar da 6. (iii) Rage aiki zafin jiki, wanda sauƙaƙe 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 daga polymer-tushen aka gyara zuwa wani iri-iri na kowa Organic solvents17,19.
The ayyuka na reactor da aka nuna da jerin jan karfe-catalyzed alkyne azide cycloaddition halayen a karkashin m kwarara yanayi (Fig. 2) The ultrasonic-buga jan reactor daki-daki a cikin Figure 4 da aka hadedde tare da wani kasuwanci ya kwarara tsarin da kuma amfani da su hada azides library na daban-daban 1,4-disubstituted 1,2,3-rasasshen 1,2,3-lenetin da zafin jiki na aceyl-triazoles hali a cikin yanayin da zafin jiki iko da aceyl-triazoles a cikin hali na aceyltyazoles da kungiyoyin. kasancewar sodium chloride (Figure 3) .Yin amfani da ci gaba mai gudana yana rage damuwa da damuwa na tsaro wanda zai iya tasowa a cikin tsari na tsari, kamar yadda wannan amsa ya haifar da matsakaicin matsakaici na azide mai mahimmanci da haɗari [317], [318] . Da farko, an inganta yanayin don cycloaddition na phenylacetylene da iodoethylene phenylacetylene da iodoethylene -chylene phenylacetylene. iodoethane) (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 zazzabi na 150 ° C ana amfani da software na yanayin zafi da yanayin zafi na zamani. ana la'akari da mahimman sharuɗɗan ƙirar ƙira.Gudanar da ginanniyar haɓakawa ta amfani da waɗannan sharuɗɗan da aka zaɓa yana haifar da saitin yanayin halayen da aka tsara don haɓaka wuraren kololuwar samfur yayin da rage farawar wuraren kololuwar kayan aiki.Wannan haɓakawa ya haifar da jujjuyawar 53% na samfurin triazole, wanda ya dace da tsinkayar samfurin 54%.
Dangane da wallafe-wallafen nuna cewa tagulla (IO) Oxide (Cu2o) zai iya bincika yanayi mai kyau da kuma Idodoethane da aka bincika. haifar da mahimmanci a ciki da hira da farawa abu, wanda aka lasafta su zama> 99% .Duk da haka, sa idanu ta HPLC ya nuna cewa wannan juyi muhimmanci rage wuce kima tsawon dauki lokaci har zuwa kamar 90 minutes, sa'ilin da aiki ya bayyana zuwa matakin kashe da kuma kai wani "kwayayyen hali" .Wannan lura ya nuna cewa tushen catalytic aiki da aka samu daga surface jan karfe oxide maimakon da sifili-valentu karfe oxide da aka samar da tagulla Cucu, sauƙi a dakin da zazzabi Cucu. waɗanda ba masu kariya ba ne. Wannan yana kawar da buƙatar ƙara tushen tagulla (II) don haɗin gwiwa71.