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Kupanga zinthu zowonjezera kukusintha momwe ofufuza ndi akatswiri opanga mafakitale amapangira ndi kupanga zida zamankhwala kuti akwaniritse zosowa zawo. Mu ntchito iyi, tikupereka chitsanzo choyamba cha reactor yoyenda yomwe imapangidwa ndi njira yolimba yachitsulo yopangira ma Ultrasonic Additive Manufacturing (UAM) yokhala ndi zida zolumikizirana mwachindunji ndi zinthu zowunikira. Sikuti ukadaulo wa UAM umangogonjetsa zoletsa zambiri zomwe zimagwirizana ndi kupanga zinthu zowonjezera za ma reactor a mankhwala, komanso umawonjezera kwambiri mphamvu za zida zotere. Mndandanda wa mankhwala ofunikira a 1,4-dissubstituted 1,2,3-triazole adapangidwa bwino ndikukonzedwa bwino ndi Huisgen 1,3-dipolar cycloaddition reaction pogwiritsa ntchito njira ya UAM chemistry. Pogwiritsa ntchito mawonekedwe apadera a UAM ndi njira yoyendetsera kayendedwe ka kayendedwe ka madzi mosalekeza, chipangizochi chimatha kuyambitsa zochitika zomwe zikuchitika komanso kupereka ndemanga yeniyeni yowunikira ndi kukonza momwe zinthu zimachitikira.
Chifukwa cha ubwino wake waukulu kuposa wofanana nawo, mayendedwe amadzimadzi ndi gawo lofunika komanso lokulirakulira m'masukulu ndi m'mafakitale chifukwa cha kuthekera kwake kowonjezera kusankha ndi kugwira ntchito bwino kwa kapangidwe ka mankhwala. Izi zimayambira pakupanga mamolekyulu osavuta achilengedwe1 mpaka mankhwala ophatikizika2,3 ndi zinthu zachilengedwe4,5,6. Zoposa 50% za machitidwe m'mafakitale abwino a mankhwala ndi mankhwala zimatha kupindula ndi kugwiritsa ntchito njira yopititsira patsogolo kayendedwe ka madzi7.
M'zaka zaposachedwapa, pakhala chizolowezi chowonjezeka cha magulu omwe akufuna kusintha magalasi achikhalidwe kapena zida zamagetsi zoyendera ndi "zotengera zoyeserera" zomwe zimasinthidwa kukhala zowonjezeredwa (AM) chemistry 8. Kapangidwe kake, kupanga mwachangu, ndi kuthekera kwa 3-dimensional (3D) kwa njirazi ndizothandiza kwa iwo omwe akufuna kusintha zida zawo kuti zigwirizane ndi machitidwe, zida, kapena mikhalidwe inayake. Mpaka pano, ntchitoyi yayang'ana kwambiri kugwiritsa ntchito njira zosindikizira za 3D zochokera ku polymer monga stereolithography (SL)9,10,11, fused deposition modeling (FDM)8,12,13,14 ndi inkjet printing 7, 15, 16. Kusowa kwa kulimba ndi kuthekera kwa zida zotere kuchita zinthu zosiyanasiyana zokhudzana ndi mankhwala17, 18, 19, 20 ndi chinthu chachikulu chomwe chimalepheretsa kukhazikitsa AM m'munda uno17, 18, 19, 20.
Chifukwa cha kuchuluka kwa kugwiritsa ntchito mankhwala oyendera ndi makhalidwe abwino okhudzana ndi AM, pakufunika kufufuza njira zamakono zomwe zimathandiza ogwiritsa ntchito kupanga zombo zoyendera ndi mphamvu zowonjezera za mankhwala ndi kusanthula. Njirazi ziyenera kulola ogwiritsa ntchito kusankha kuchokera ku zipangizo zosiyanasiyana zolimba kwambiri kapena zogwira ntchito zomwe zingathe kuthana ndi mitundu yosiyanasiyana ya machitidwe, komanso kuthandizira mitundu yosiyanasiyana ya zotsatira zowunikira kuchokera ku chipangizocho kuti zilole kuwunika ndi kuwongolera machitidwe.
Njira imodzi yopangira zowonjezera zomwe zingathe kupanga ma reactor a mankhwala apadera ndi Ultrasonic Additive Manufacturing (UAM). Njira yopangira solid-state sheet lamination iyi imagwiritsa ntchito ma ultrasonic oscillations ku ma foil owonda achitsulo kuti awalumikize pamodzi wosanjikiza ndi wosanjikiza ndi kutentha kochepa komanso kuchuluka kwa pulasitiki 21, 22, 23. Mosiyana ndi ukadaulo wina wa AM, UAM ikhoza kuphatikizidwa mwachindunji ndi kupanga kochotsa, komwe kumadziwika kuti njira yopangira yosakanikirana, momwe kugayira kwa in-situ periodic computer numerical control (CNC) kapena laser machining kumatanthauzira mawonekedwe a net a wosanjikiza wa zinthu zomangiriridwa 24, 25. Izi zikutanthauza kuti wogwiritsa ntchito salepheretsedwa ndi mavuto okhudzana ndi kuchotsa zinthu zotsalira kuchokera ku njira zazing'ono zamadzimadzi, zomwe nthawi zambiri zimakhala ndi ufa ndi madzi AM systems26, 27, 28. Ufulu wa kapangidwe kameneka umafalikiranso ku zisankho zazinthu zomwe zilipo - UAM imatha kulumikiza zinthu zofanana ndi kutentha komanso zosiyana mu sitepe imodzi yopangira. Kusankha kuphatikiza zinthu kupitirira njira yosungunula kumatanthauza kuti zofunikira zamakina ndi mankhwala za ntchito zinazake zitha kukwaniritsidwa bwino. Kuphatikiza pa mgwirizano wolimba, wina Chomwe chimakumana nacho panthawi yolumikizana ndi ma ultrasound ndi kuchuluka kwa zinthu zapulasitiki pa kutentha kochepa 29,30,31,32,33. Mbali yapadera ya UAM iyi ingathandize kuyika zinthu zamakanika/zotentha pakati pa zigawo zachitsulo popanda kuwonongeka. Masensa ophatikizidwa ndi UAM angathandize kufalitsa chidziwitso cha nthawi yeniyeni kuchokera ku chipangizocho kupita kwa wogwiritsa ntchito kudzera mu kusanthula kophatikizidwa.
Ntchito zakale za olemba32 zinasonyeza kuthekera kwa njira ya UAM kupanga mapangidwe achitsulo a 3D microfluidic okhala ndi mphamvu zolumikizirana. Ichi ndi chipangizo chowunikira chokha. Pepala ili likuwonetsa chitsanzo choyamba cha reactor ya microfluidic chemical yopangidwa ndi UAM; chipangizo chogwira ntchito chomwe sichimangoyang'anira komanso chimayambitsa kupanga mankhwala kudzera muzinthu zolumikizirana. Chipangizochi chimaphatikiza zabwino zingapo zokhudzana ndi ukadaulo wa UAM popanga zida zamakemikolo a 3D, monga: kuthekera kosintha mapangidwe athunthu a 3D mwachindunji kuchokera ku mitundu yopangidwa ndi makompyuta (CAD) kukhala zinthu; kupanga zinthu zambiri kuphatikiza kutentha kwambiri ndi zinthu zolumikizirana; ndi kuyika masensa otentha mwachindunji pakati pa mitsinje ya reagent kuti azitha kuyang'anira kutentha ndikuwongolera momwe zinthu zilili. Pofuna kuwonetsa momwe reactor imagwirira ntchito, laibulale ya mankhwala ofunikira a 1,4-dissubstituted 1,2,3-triazole opangidwa ndi mankhwala adapangidwa ndi Huisgen 1,3-dipolar cycloaddition yokhala ndi mkuwa. Ntchitoyi ikuwonetsa momwe kugwiritsa ntchito sayansi ya zinthu ndi kapangidwe kothandizidwa ndi makompyuta kungatsegule mwayi watsopano ndi mwayi wa chemistry kudzera mu kafukufuku wamitundu yambiri.
Zosungunulira zonse ndi ma reagents zinagulidwa kuchokera ku Sigma-Aldrich, Alfa Aesar, TCI kapena Fischer Scientific ndipo zinagwiritsidwa ntchito popanda kuyeretsa kale. 1H ndi 13C NMR spectra zomwe zinalembedwa pa 400 MHz ndi 100 MHz, motsatana, zinapezeka pogwiritsa ntchito JEOL ECS-400 400 MHz spectrometer kapena Bruker Avance II 400 MHz spectrometer ndi CDCl3 kapena (CD3)2SO ngati zosungunulira. Ma reaction onse adachitika pogwiritsa ntchito nsanja ya Uniqsis FlowSyn flow chemistry.
UAM idagwiritsidwa ntchito popanga zipangizo zonse mu kafukufukuyu. Ukadaulowu unapangidwa mu 1999, ndipo tsatanetsatane wake waukadaulo, magawo ogwirira ntchito, ndi chitukuko kuyambira pomwe idapangidwa zitha kuphunziridwa kudzera muzinthu zotsatirazi zofalitsidwa34,35,36,37. Chipangizochi (Chithunzi 1) chidagwiritsidwa ntchito pogwiritsa ntchito mphamvu yayikulu kwambiri, 9kW SonicLayer 4000® UAM system (Fabrisonic, OH, USA). Zipangizo zomwe zidasankhidwa popanga chipangizo choyendera zinali Cu-110 ndi Al 6061. Cu-110 ili ndi mkuwa wambiri (wochepera 99.9% mkuwa), zomwe zimapangitsa kuti ikhale yoyenera kuchitapo kanthu pogwiritsa ntchito mkuwa, ndipo chifukwa chake imagwiritsidwa ntchito ngati "gawo logwira ntchito mkati mwa microreactor. Al 6061 O imagwiritsidwa ntchito ngati "gulu", komanso gawo loyika lomwe limagwiritsidwa ntchito pofufuza; Kuyika gawo lothandizira la alloy ndi mkhalidwe wophatikizidwa ndi gawo la Cu-110. Al 6061 O ndi chinthu chomwe chawonetsedwa kuti chikugwirizana kwambiri ndi njira za UAM38, 39, 40, 41 ndipo yayesedwa ndikupezeka kuti ndi yokhazikika ndi ma reagents omwe agwiritsidwa ntchito pantchitoyi. Kuphatikiza kwa Al 6061 O ndi Cu-110 kumaonedwanso ngati kuphatikiza kwa zinthu zogwirizana ndi UAM ndipo chifukwa chake ndi chinthu choyenera pa kafukufukuyu. 38,42 Zipangizozi zalembedwa mu Table 1 pansipa.
Magawo opangira ma reactor (1) Al 6061 substrate (2) Kupanga njira yoyambira pansi yolumikizidwa ku foil yamkuwa (3) Kuyika ma thermocouple pakati pa zigawo (4) Njira yapamwamba (5) Kulowa ndi kutuluka (6) Reactor ya monolithic.
Malingaliro a kapangidwe ka njira yamadzimadzi ndikugwiritsa ntchito njira yozungulira kuti muwonjezere mtunda womwe madzi amayenda mkati mwa chip, pomwe chipyo ikusunga kukula koyenera. Kuwonjezeka kwa mtunda kumeneku ndikofunikira kuti muwonjezere nthawi yolumikizirana ndi catalyst/reagent ndikupereka zokolola zabwino kwambiri. Ma chips amagwiritsa ntchito ma bend a 90° kumapeto kwa njira yowongoka kuti apangitse kusakanikirana kosasunthika mkati mwa chipangizocho44 ndikuwonjezera nthawi yolumikizirana yamadzimadzi ndi pamwamba (catalyst). Kuti muwonjezere kusakaniza komwe kungatheke, kapangidwe ka reactor kali ndi ma inlet awiri a reagent ophatikizidwa pa Y-junction asanalowe mu gawo losakaniza la serpentine. Inlet yachitatu, yomwe imadutsa mtsinje pakati pa residence yake, ikuphatikizidwa mu kapangidwe ka multistep reaction syntheses yamtsogolo.
Ma channel onse ali ndi mawonekedwe a sikweya (opanda ma angles odulira), zomwe zimachitika chifukwa cha CNC milling yomwe imagwiritsidwa ntchito popanga mawonekedwe a channel. Miyeso ya channel imasankhidwa kuti iwonetsetse kuti voliyumu yatuluka (ya microreactor), pomwe imakhala yaying'ono mokwanira kuti ithandizire kuyanjana kwa pamwamba (ma catalysts) amadzimadzi ambiri omwe alimo. Kukula koyenera kumadalira zomwe olemba adakumana nazo kale ndi zida zachitsulo-madzimadzi kuti zichitike. Miyeso yamkati ya channel yomaliza inali 750 µm x 750 µm ndipo voliyumu yonse ya reactor inali 1 ml. Cholumikizira cholumikizidwa (1/4″—28 UNF thread) chimaphatikizidwa mu kapangidwe kake kuti chilolere kulumikizana kosavuta kwa chipangizocho ndi zida zamakemikolo oyenda. Kukula kwa channel kumachepetsedwa ndi makulidwe a foil, mawonekedwe ake amakaniko, ndi magawo omangirira omwe amagwiritsidwa ntchito ndi ma ultrasonic. Pa mulifupi winawake wa chinthu choperekedwa, chinthucho "chidzagwera" mu channel yopangidwa. Pakadali pano palibe chitsanzo chenicheni cha kuwerengera uku, kotero mulifupi waukulu kwambiri wa channel wa chinthu choperekedwa ndi kapangidwe kake umatsimikiziridwa mwa kuyesa; Pankhaniyi, m'lifupi mwa 750 μm sizingachititse kuti ming'alu igwe.
Mawonekedwe (sikweya) a njirayo amatsimikiziridwa pogwiritsa ntchito chodulira sikweya. Mawonekedwe ndi kukula kwa njirayo zitha kusinthidwa ndi makina a CNC pogwiritsa ntchito zida zosiyanasiyana zodulira kuti apeze kuchuluka kwa kayendedwe ndi mawonekedwe osiyanasiyana. Chitsanzo chopangira njira yokhotakhota pogwiritsa ntchito chida cha 125 μm chingapezeke mu ntchito ya Monaghan45. Pamene gawo la foil liyikidwa munjira yolinganizika, pamwamba pa zinthu za foil pamwamba pa njirayo padzakhala ndi mapeto athyathyathya (sikweya). Mu ntchitoyi, kuti pakhale kulinganiza kwa njirayo, mawonekedwe a sikweya adagwiritsidwa ntchito.
Pa nthawi yopuma yokonzedwa kale popanga, ma probe a kutentha kwa thermocouple (Mtundu K) amaikidwa mwachindunji mkati mwa chipangizocho pakati pa magulu apamwamba ndi otsika a njira (Chithunzi 1 - Gawo 3). Ma thermocouple awa amatha kuyang'anira kusintha kwa kutentha kuyambira -200 mpaka 1350 °C.
Njira yoyika zitsulo imachitidwa ndi nyanga ya UAM pogwiritsa ntchito pepala lachitsulo la 25.4 mm mulifupi, 150 micron wandiweyani. Zigawo za pepalali zimalumikizidwa mu mndandanda wa mizere yoyandikana kuti ziphimbe malo onse omangira; kukula kwa zinthu zomwe zasungidwa kumakhala kwakukulu kuposa chinthu chomaliza chifukwa njira yochotsera imapanga mawonekedwe omaliza a ukonde. Makina a CNC amagwiritsidwa ntchito popanga mawonekedwe akunja ndi amkati a zida, zomwe zimapangitsa kuti zida ndi njira ziwonekere mofanana ndi zida zosankhidwa ndi magawo a njira ya CNC (pafupifupi 1.6 μm Ra mu chitsanzo ichi). Kuyika zinthu kosalekeza komanso kosalekeza kwa ma ultrasonic ndi makina opangidwa ndi ma ultrasonic kumagwiritsidwa ntchito panthawi yonse yopanga zida kuti zitsimikizire kuti kulondola kwa miyeso kukusungidwa ndipo gawo lomalizidwa lidzakwaniritsa mulingo wolondola wa CNC. Kukula kwa njira yomwe imagwiritsidwa ntchito pa chipangizochi ndi kochepa mokwanira kuti zitsimikizire kuti zinthu za pepalali "sizikugwa" mu njira yamadzimadzi, kotero njirayo imasunga gawo lalikulu. Mipata yomwe ingakhalepo muzinthu za pepalali ndi magawo a njira ya UAM idatsimikiziridwa mwa kuyesa ndi mnzake wopanga (Fabrisonic LLC, USA).
Kafukufuku wasonyeza kuti kufalikira pang'ono kwa elemental kumachitika pa UAM bonding interface 46, 47 popanda chithandizo chowonjezera cha kutentha, kotero pazida zomwe zili mu ntchitoyi, gawo la Cu-110 limakhala losiyana ndi gawo la Al 6061 ndipo limasintha mwadzidzidzi.
Ikani chowongolera kuthamanga kwa mpweya cha 250 psi (1724 kPa) chowongolera kuthamanga kwa mpweya (BPR) chomwe chili kale pamalo otulukira riyakitala ndikupopera madzi kudzera mu riyakitala pa liwiro la 0.1 mpaka 1 mL min-1. Kuthamanga kwa riyakitala kunayang'aniridwa pogwiritsa ntchito sensa ya kuthamanga kwa mpweya ya FlowSyn yomangidwa mkati kuti atsimikizire kuti riyakitala ikhoza kusunga kuthamanga kokhazikika. Kuchuluka kwa kutentha komwe kungachitike kudutsa riyakitala yoyenda kunayesedwa pozindikira kusiyana kulikonse pakati pa ma thermocouple omwe ali mkati mwa riyakitala ndi omwe ali mkati mwa mbale yotenthetsera ya FlowSyn chip. Izi zimachitika mwa kusintha kutentha kwa hotplate komwe kungakonzedwe pakati pa 100 ndi 150 °C mu 25 °C increments ndikuwona kusiyana kulikonse pakati pa kutentha komwe kwakonzedwa ndi komwe kwalembedwa. Izi zidachitika pogwiritsa ntchito tc-08 data logger (PicoTech, Cambridge, UK) ndi pulogalamu ya PicoLog yotsagana nayo.
Mikhalidwe ya cycloaddition reaction ya phenylacetylene ndi iodoethane idakonzedwa bwino (Chiwembu 1- Cycloaddition ya phenylacetylene ndi iodoethane Chiwembu 1- Cycloaddition ya phenylacetylene ndi iodoethane). Kukonza kumeneku kunachitika pogwiritsa ntchito njira yonse yopangira zoyeserera (DOE), pogwiritsa ntchito kutentha ndi nthawi yokhazikika ngati magawo osinthika, pomwe akukonza chiŵerengero cha alkyne:azide pa 1:2.
Mayankho osiyana a sodium azide (0.25 M, 4:1 DMF:H2O), iodoethane (0.25 M, DMF), ndi phenylacetylene (0.125 M, DMF) adakonzedwa. Aliquot ya 1.5 mL ya yankho lililonse idasakanizidwa ndikupopedwa kudzera mu reactor pamlingo wofunikira wa flow ndi kutentha. Yankho la chitsanzo lidatengedwa ngati chiŵerengero cha dera lapamwamba la triazole product ku phenylacetylene starting material ndipo lidatsimikiziridwa ndi high performance liquid chromatography (HPLC). Kuti kusanthula kukhale kofanana, mayankho onse adatengedwa atangomaliza kusakaniza kwa reaction kuchoka mu reactor. Ma parameter ranges omwe adasankhidwa kuti akonzedwe akuwonetsedwa mu Table 2.
Zitsanzo zonse zinasanthulidwa pogwiritsa ntchito njira ya Chromaster HPLC (VWR, PA, USA) yokhala ndi pampu ya quaternary, uvuni wa column, chowunikira cha UV chosinthasintha komanso chowunikira chodziyimira pawokha. Column inali Equivalence 5 C18 (VWR, PA, USA), kukula kwa 4.6 × 100 mm, kukula kwa tinthu ta 5 µm, yosungidwa pa 40 °C. Chosungunuliracho chinali isocratic 50:50 methanol:madzi pamlingo woyenda wa 1.5 mL.min-1. Kuchuluka kwa jakisoni kunali 5 µL ndipo kutalika kwa jakisoni kunali 254 nm. Malo okwana % peak a chitsanzo cha DOE adawerengedwa kuchokera kumadera okwana peak a zinthu zotsalira za alkyne ndi triazole zokha. Kulowetsa zinthu zoyambira kumalola kuzindikira peaks zoyenera.
Kuphatikiza zotsatira za kusanthula kwa reactor ku pulogalamu ya MODDE DOE (Umetrics, Malmö, Sweden) kunalola kusanthula bwino momwe zotsatira zikuyendera komanso kudziwa momwe zinthu zilili bwino pa cycloaddition iyi. Kuyendetsa chowongolera chomangidwa mkati ndikusankha mawu onse ofunikira a chitsanzo kumabweretsa mikhalidwe yochitapo kanthu yomwe idapangidwa kuti iwonjezere malo oyambira azinthuzo pomwe ikuchepetsa malo oyambira a acetylene.
Kuchuluka kwa okosijeni wa mkuwa pamwamba pa nthaka mkati mwa chipinda chothandizira kuchitapo kanthu kunapezeka pogwiritsa ntchito yankho la hydrogen peroxide (36%) lomwe limayenda m'chipinda chothandizira (kuchuluka kwa madzi = 0.4 mL min-1, nthawi yokhazikika = mphindi 2.5) lisanapangidwe laibulale iliyonse ya triazole compound.
Pamene mikhalidwe yabwino kwambiri yapezeka, idagwiritsidwa ntchito pamitundu yosiyanasiyana ya acetylene ndi haloalkane derivatives kuti ilole kupangidwa kwa kapangidwe kakang'ono ka laibulale, motero kukhazikitsa kuthekera kogwiritsa ntchito mikhalidwe iyi pamitundu yambiri ya ma reagents (Chithunzi 1).2).
Konzani njira zosiyana za sodium azide (0.25 M, 4:1 DMF:H2O), haloalkanes (0.25 M, DMF) ndi alkynes (0.125 M, DMF). Ma aliquots atatu a yankho lililonse adasakanizidwa ndikupopedwa kudzera mu reactor pa 75 µL.min-1 ndi 150 °C. Kuchuluka konse kunasonkhanitsidwa mu vial ndikuchepetsedwa ndi 10 mL ya ethyl acetate. Njira yoyezera idatsukidwa ndi 3 × 10 mL ya madzi. Zigawo zamadzi zidaphatikizidwa ndikuchotsedwa ndi 10 mL ya ethyl acetate; zigawo za organic kenako zidaphatikizidwa, kutsukidwa ndi 3 x 10 mL ya brine, kuumitsidwa pa MgSO4 ndikusefedwa, kenako solvent idachotsedwa mu vacuo. Zitsanzozo zidayeretsedwa ndi column chromatography pa silica gel pogwiritsa ntchito ethyl acetate musanayesedwe ndi kuphatikiza HPLC, 1H NMR, 13C NMR ndi high resolution mass spectrometry (HR-MS).
Ma spectra onse adapezeka pogwiritsa ntchito Thermofischer precision Orbitrap resolution mass spectrometer yokhala ndi ESI ngati gwero la ionization. Zitsanzo zonse zidakonzedwa pogwiritsa ntchito acetonitrile ngati solvent.
Kusanthula kwa TLC kunachitika pa mbale za silica zothandizidwa ndi aluminiyamu. Ma mbalewo anawonetsedwa ndi kuwala kwa UV (254 nm) kapena utoto wa vanillin ndi kutentha.
Zitsanzo zonse zinafufuzidwa pogwiritsa ntchito makina a VWR Chromaster (VWR International Ltd., Leighton Buzzard, UK) okhala ndi autosampler, column oven binary pump ndi single wavelength detector. Column yomwe inagwiritsidwa ntchito inali ACE Equivalence 5 C18 (150 × 4.6 mm, Advanced Chromatography Technologies Ltd., Aberdeen, Scotland).
Majakisoni (5 µL) anapangidwa mwachindunji kuchokera ku chisakanizo cha crude reaction chochepetsedwa (1:10 dilution) ndipo anawunikidwa ndi madzi:methanol (50:50 kapena 70:30), kupatula zitsanzo zina pogwiritsa ntchito njira yosungunulira ya 70:30 (yomwe imatchedwa nambala ya nyenyezi) pamlingo woyenda wa 1.5 mL/min. Mzatiwo unasungidwa pa 40 °C. Kutalika kwa nthawi yowunikira ndi 254 nm.
Malo okwana % ya chiŵerengero cha chitsanzocho anawerengedwa kuchokera ku malo okwana 100 a alkyne yotsala, chinthu cha triazole chokha, ndipo kubayidwa kwa zinthu zoyambira kunathandiza kuzindikira 100 omwe ali oyenera.
Zitsanzo zonse zinasanthulidwa pogwiritsa ntchito Thermo iCAP 6000 ICP-OES. Miyezo yonse yoyezera inakonzedwa pogwiritsa ntchito yankho la 1000 ppm Cu mu 2% nitric acid (SPEX Certi Prep). Miyezo yonse inakonzedwa mu yankho la 5% DMF ndi 2% HNO3, ndipo zitsanzo zonse zinachepetsedwa ka 20-fold mu yankho la chitsanzo la DMF-HNO3.
UAM imagwiritsa ntchito njira yolumikizira zitsulo pogwiritsa ntchito ultrasonic metal foil yomwe imagwiritsidwa ntchito popanga chomangira chomaliza. Kulumikiza zitsulo pogwiritsa ntchito ultrasonic metal horn (yotchedwa nyanga kapena ultrasound horn) kuti igwiritse ntchito mphamvu pa chomangira cha foil/chomangira chomwe chinali cholumikizidwa kale kuti chigwirizane pamene chikugwedeza zinthuzo. Kuti chigwire ntchito mosalekeza, sonotrode imakhala yozungulira ndipo imazungulira pamwamba pa zinthuzo, ndikulumikiza dera lonselo. Pamene kupanikizika ndi kugwedezeka zimagwiritsidwa ntchito, ma oxide omwe ali pamwamba pa zinthuzo amatha kusweka. Kupanikizika ndi kugwedezeka kopitilira kungayambitse kusokonekera kwa zinthuzo. Kukhudzana kwapafupi ndi kutentha ndi kupanikizika komwe kumachitika m'deralo kumabweretsa mgwirizano wolimba pamalo olumikizirana; kungathandizenso kumamatira kudzera mu kusintha kwa mphamvu ya pamwamba48. Mtundu wa njira yolumikizira umathetsa mavuto ambiri okhudzana ndi kutentha kosinthasintha komanso zotsatira za kutentha kwambiri zomwe zatchulidwa mu njira zina zopangira zowonjezera. Izi zimalola kugwirizana mwachindunji (monga, popanda kusintha pamwamba, zodzaza kapena zomatira) za zigawo zingapo za zinthu zosiyanasiyana kukhala kapangidwe kamodzi kogwirizana.
Chinthu china chabwino cha UAM ndi kuchuluka kwa pulasitiki komwe kumapezeka muzinthu zachitsulo, ngakhale kutentha kochepa, mwachitsanzo pansi pa malo osungunuka azinthu zachitsulo. Kuphatikiza kwa kugwedezeka kwa ultrasonic ndi kupanikizika kumayambitsa kuchuluka kwa kusamuka kwa tirigu m'deralo ndi kubwezeretsanso popanda kutentha kwakukulu komwe kumagwirizanitsidwa ndi zinthu zambiri. Pakumanga msonkhano womaliza, chodabwitsachi chingagwiritsidwe ntchito poyika zinthu zogwira ntchito komanso zosagwira ntchito pakati pa zigawo za zojambulazo zachitsulo, gawo ndi gawo. Zinthu monga ulusi wa kuwala 49, zolimbikitsira 46, zamagetsi 50, ndi ma thermocouples (ntchitoyi) zonse zalowetsedwa bwino mu kapangidwe ka UAM kuti apange magulu ogwirira ntchito komanso osagwira ntchito.
Mu ntchito iyi, njira zosiyanasiyana zolumikizira zinthu ndi zolumikizirana za UAM zagwiritsidwa ntchito popanga microreactor yowunikira kutentha kwa catalytic.
Poyerekeza ndi palladium (Pd) ndi zinthu zina zogwiritsidwa ntchito kwambiri zachitsulo, Cu catalysis ili ndi zabwino zingapo: (i) Pazachuma, Cu ndi yotsika mtengo kuposa zitsulo zina zambiri zomwe zimagwiritsidwa ntchito mu catalysis ndipo motero ndi njira yokongola kwa makampani opanga mankhwala (ii) Mitundu ya Cu-catalyzed cross-coupling reactions ikuwonjezeka ndipo ikuwoneka kuti ikugwirizana pang'ono ndi njira zozikidwa pa Pd51,52,53 (iii) Cu-catalyzed reactions imagwira ntchito bwino popanda ma ligand ena. Ma ligand awa nthawi zambiri amakhala osavuta kupanga komanso otsika mtengo ngati mukufuna, pomwe omwe amagwiritsidwa ntchito mu Pd chemistry nthawi zambiri amakhala ovuta, okwera mtengo, komanso ogwirizana ndi mpweya (iv) Cu, yomwe imadziwika bwino chifukwa cha kuthekera kwake kogwirizanitsa alkynes mu synthesis, Mwachitsanzo, bimetallic-catalyzed Sonogashira coupling ndi cycloaddition ndi azides (click chemistry) (v)Cu imathanso kulimbikitsa arylation ya ma nucleophiles angapo mu Ullmann-type reactions.
Zitsanzo za kusintha kwa zinthu zonsezi zawonetsedwa posachedwapa pamaso pa Cu(0). Izi makamaka chifukwa cha makampani opanga mankhwala komanso kuyang'ana kwambiri pakubwezeretsa ndi kugwiritsanso ntchito zitsulo55,56.
Yoyambitsidwa ndi Huisgen m'zaka za m'ma 1960, 1,3-dipolar cycloaddition reaction pakati pa acetylene ndi azide ku 1,2,3-triazole imaonedwa ngati synergistic demonstration reaction. Zotsatira za 1,2,3 triazole ndi zofunika kwambiri ngati pharmacophore pankhani yopeza mankhwala chifukwa cha ntchito zawo zamoyo komanso kugwiritsa ntchito mankhwala osiyanasiyana 58.
Kachitidwe kameneka kanayambanso kugwiritsidwa ntchito pamene Sharpless ndi ena adayambitsa lingaliro la "click chemistry"59. Mawu akuti "click chemistry" amagwiritsidwa ntchito pofotokoza gulu lamphamvu, lodalirika komanso losankha la kachitidwe ka kupanga mwachangu mankhwala atsopano ndi malaibulale ophatikizana kudzera mu heteroatom linkage (CXC)60. Kukongola kwa kachitidwe kameneka kumachokera ku zokolola zambiri zomwe zimagwirizana nazo, momwe zimachitikira ndi zosavuta, kukana mpweya ndi madzi, komanso kulekanitsidwa kwa zinthu ndikosavuta61.
Kachitidwe ka Huisgen 1,3-dipole cycloaddition si ka gulu la "click chemistry". Komabe, Medal ndi Sharpless adawonetsa kuti chochitika ichi cholumikizira azide-alkyne chimadutsa 107 mpaka 108 pamaso pa Cu(I) poyerekeza ndi 1,3-dipolar cycloaddition 62,63 significant rate acceleration. Njira yowongolerayi siyifuna kuteteza magulu kapena mikhalidwe yovuta ya reaction ndipo imapereka kutembenuka kwathunthu ndi kusankha ku 1,4-dissubstituted 1,2,3-triazoles (anti-1,2,3-triazole) pamlingo wa nthawi (Chithunzi 3).
Zotsatira za isometric za Huisgen cycloadditions zachikhalidwe komanso zamkuwa. Cu(I)-catalyzed Huisgen cycloadditions zimapanga 1,4-dissubstituted 1,2,3-triazoles zokha, pomwe Huisgen cycloadditions zomwe zimayambitsidwa ndi kutentha nthawi zambiri zimapanga 1,4- ndi 1,5-triazoles 1:1 osakaniza stereoisomers a azoles.
Ma protocol ambiri amakhudza kuchepetsa magwero okhazikika a Cu(II), monga kuchepetsa mitundu ya CuSO4 kapena Cu(II)/Cu(0) kuphatikiza ndi mchere wa sodium. Poyerekeza ndi machitidwe ena opangidwa ndi zitsulo, kugwiritsa ntchito Cu(I) kuli ndi ubwino waukulu wokhala wotsika mtengo komanso wosavuta kugwiritsa ntchito.
Kafukufuku wa Kinetic ndi isotopic wolemba Worrell et al. 65 adawonetsa kuti, pankhani ya ma terminal alkynes, ma equivalents awiri a mkuwa amakhudzidwa pakuyambitsa reactivity ya molekyulu iliyonse kupita ku azide. Njira yomwe ikuperekedwayi imapitilira kudzera mu mphete yachitsulo yamkuwa yokhala ndi ziwalo zisanu ndi chimodzi yopangidwa ndi mgwirizano wa azide ndi acetylide yamkuwa yokhala ndi σ-bonded ndi mkuwa wokhala ndi π ngati ligand yokhazikika ya donor. Zotumphukira zamkuwa za Triazolyl zimapangidwa ndi ring shrinkage, kutsatiridwa ndi kuwonongeka kwa proton kuti apereke zinthu za triazole ndikutseka catalytic cycle.
Ngakhale ubwino wa zipangizo zamagetsi zoyendera madzi zalembedwa bwino, pakhala chikhumbo chophatikiza zida zowunikira mu machitidwe awa kuti zigwiritsidwe ntchito pa intaneti, mkati, poyang'anira njira66,67. UAM yakhala njira yoyenera yopangira ndi kupanga ma reactor ovuta kwambiri a 3D flow opangidwa ndi zinthu zoyendetsera kutentha zomwe zimagwira ntchito molimbika, zomwe zimakhala ndi zinthu zowunikira zomwe zimayikidwa mwachindunji (Chithunzi 4).
Choyezera madzi cha aluminiyamu-mkuwa chopangidwa ndi ultrasonic additive manufacturing (UAM) chokhala ndi kapangidwe ka njira zamkati zovuta, ma thermocouple ophatikizidwa ndi chipinda chothandizira. Kuti muwone njira zamkati zamadzimadzi, chitsanzo chowonekera chopangidwa pogwiritsa ntchito stereolithography chikuwonetsedwanso.
Kuti zitsimikizidwe kuti ma reactor apangidwa kuti agwiritsidwe ntchito mtsogolo, zosungunulira ziyenera kutenthedwa bwino pamwamba pa kutentha; zimayesedwa ndi kupanikizika ndi kutentha. Kuyesa kwa kupanikizika kunasonyeza kuti makinawo amakhala ndi kupanikizika kokhazikika komanso kosalekeza ngakhale atakhala ndi kupanikizika kowonjezereka kwa makina (1.7 MPa). Kuyesa kwa hydrostatic kunachitika kutentha kwa chipinda pogwiritsa ntchito H2O ngati madzi.
Kulumikiza thermocouple yomwe ili mkati (Chithunzi 1) ku deta yowunikira kutentha kunawonetsa kuti thermocouple inali yozizira ndi 6 °C (± 1 °C) kuposa kutentha komwe kunakonzedwa pa dongosolo la FlowSyn. Kawirikawiri, kuwonjezeka kwa kutentha ndi 10 °C kumapangitsa kuti liwiro la reaction liwonjezeke kawiri, kotero kusiyana kwa kutentha kwa madigiri ochepa chabe kungasinthe kwambiri liwiro la reaction. Kusiyana kumeneku kumachitika chifukwa cha kutayika kwa kutentha m'thupi lonse la reactor chifukwa cha kutentha kwakukulu kwa zinthu zomwe zimagwiritsidwa ntchito popanga. Kuthamanga kwa kutentha kumeneku kumakhala kofanana ndipo chifukwa chake kumatha kuwerengedwa mu makina okhazikitsa kuti zitsimikizire kuti kutentha kolondola kumafikiridwa ndikuyesedwa panthawi ya reaction. Chifukwa chake, chida ichi chowunikira pa intaneti chimapangitsa kuti kutentha kwa reaction kuyende bwino komanso kumathandiza kukonza bwino njira ndikukula kwa mikhalidwe yabwino. Masensawa angagwiritsidwenso ntchito kuzindikira ma exotherms a reaction ndikuletsa ma reaction othawa m'makina akuluakulu.
Reactor yomwe yaperekedwa mu ntchitoyi ndi chitsanzo choyamba cha kugwiritsa ntchito ukadaulo wa UAM popanga ma reactor a mankhwala ndipo imayang'ana zoletsa zazikulu zingapo zomwe zikugwirizana ndi kusindikiza kwa AM/3D kwa zida izi, monga: (i) kuthana ndi mavuto omwe anenedwa okhudzana ndi kukonza mkuwa kapena aluminiyamu (ii) kukonza bwino njira zamkati poyerekeza ndi njira zolumikizira ufa (PBF) monga kusungunuka kwa laser (SLM)25,69 Kuyenda bwino kwa zinthu ndi kapangidwe koyipa ka pamwamba26 (iii) Kutsika kwa kutentha kwa processing, komwe kumathandiza kulumikizana mwachindunji kwa masensa, komwe sikungatheke muukadaulo wa ufa, (v) kuthana ndi zovuta zamakaniko komanso kukhudzidwa kwa zigawo zozikidwa pa polima ku mitundu yosiyanasiyana ya zosungunulira zachilengedwe17,19.
Kugwira ntchito kwa reactor kunawonetsedwa ndi mndandanda wa machitidwe a alkyne azide cycloaddition omwe amathandizidwa ndi mkuwa pansi pa mikhalidwe yopitilira ya kuyenda (Chithunzi 2). Reactor ya mkuwa yosindikizidwa ndi ultrasonic yomwe yafotokozedwa mu Chithunzi 4 idalumikizidwa ndi njira yogulitsira ndipo idagwiritsidwa ntchito popanga azide za library za 1,4-dissubstituted 1,2,3-triazoles zosiyanasiyana kudzera mu kutentha komwe kumayendetsedwa ndi acetylene ndi alkyl groups halides pamaso pa sodium chloride (Chithunzi 3). Kugwiritsa ntchito njira yopitilira ya kuyenda kumachepetsa nkhawa zachitetezo zomwe zingabuke mu njira zamagulu, chifukwa izi zimapangitsa kuti azide izikhala yogwira ntchito komanso yoopsa [317], [318]. Poyamba, reaction idakonzedwa kuti igwirizane ndi phenylacetylene ndi iodoethane (Chiwembu 1 - Cycloaddition ya phenylacetylene ndi iodoethane) (onani Chithunzi 5).
(Pamwamba kumanzere) Chithunzi cha momwe zinthu zimakhalira zomwe zimagwiritsidwa ntchito pophatikiza 3DP reactor mu flow system (pamwamba kumanja) zomwe zapezeka mu optimized (pansi) scheme ya Huisgen cycloaddition 57 scheme pakati pa phenylacetylene ndi iodoethane kuti zitheke bwino komanso kuwonetsa kuchuluka kwa kusintha kwa reaction parameters.
Mwa kuwongolera nthawi yokhalamo ya ma reagents mu gawo lothandizira la reactor ndikuyang'anira kutentha kwa reaction pogwiritsa ntchito thermocouple probe yolumikizidwa mwachindunji, momwe zinthu zimachitikira zimatha kukonzedwa mwachangu komanso molondola ndi nthawi yochepa komanso kugwiritsa ntchito zinthu. Zinadziwika mwachangu kuti kusintha kwakukulu kunapezeka pamene nthawi yokhalamo ya mphindi 15 ndi kutentha kwa reaction ya 150 °C zinagwiritsidwa ntchito. Kuchokera ku coefficient plot ya pulogalamu ya MODDE, zitha kuwoneka kuti nthawi yokhalamo ndi kutentha kwa reaction zimaonedwa kuti ndizofunikira kwambiri. Kuyendetsa optimizer yomangidwa mkati pogwiritsa ntchito mawu osankhidwawa kumapanga mikhalidwe yochitira yomwe idapangidwa kuti iwonjezere madera okhala ndi zinthu pomwe ikuchepetsa madera okhala ndi zinthu zoyambira. Kukonza kumeneku kunapereka kusintha kwa 53% kwa chinthu cha triazole, chomwe chinafanana kwambiri ndi kulosera kwa chitsanzo cha 54%.
Kutengera ndi mabuku omwe akusonyeza kuti copper(I) oxide (Cu2O) imatha kugwira ntchito ngati mtundu wothandiza kwambiri wa catalytic pamwamba pa mkuwa wa zero-valent m'machitidwe awa, kuthekera koyambitsa oxidize pamwamba pa reactor asanayambe kuchita zomwe zikuchitika mu kayendedwe ka madzi kunafufuzidwa70,71. Kenako yankho pakati pa phenylacetylene ndi iodoethane linachitidwanso pansi pa mikhalidwe yabwino ndipo zokolola zinayerekezeredwa. Zinaonedwa kuti kukonzekera kumeneku kunapangitsa kuti zinthu zoyambira ziwonjezeke kwambiri, zomwe zinawerengedwa kuti zinali >99%. Komabe, kuyang'aniridwa ndi HPLC kunawonetsa kuti kusinthaku kunachepetsa kwambiri nthawi yayitali yochitira mpaka pafupifupi mphindi 90, pomwe ntchitoyi inkaoneka kuti ikufanana ndikufika "mkhalidwe wokhazikika". Izi zikusonyeza kuti gwero la ntchito yothandiza limapezeka kuchokera ku copper oxide pamwamba osati kuchokera ku zero-valent copper substrate. Cu chitsulo chimasungunuka mosavuta kutentha kwa chipinda kuti chipange CuO ndi Cu2O zomwe sizili zigawo zodziteteza. Izi zimachotsa kufunikira kowonjezera gwero lothandizira la mkuwa (II) la co-composition71.