5-Cyanoindoleyog ib qho tseem ceeb organic compound dav siv nyob rau hauv kev tshawb fawb ntawm bioactive molecules nyob rau hauv cov tshuaj. Hauv qab no peb yuav qhia ob peb txoj kev hluavtaws ntawm 5-Cyanoindole.
Qhov txuas ntawm 5-Cyanoindole:
1. Bergman tshuaj tiv thaiv txoj kev:
Cov tshuaj tiv thaiv ntawm txoj kev yog siv alkynes ua raw cov ntaub ntawv los tsim cov nplhaib sib txuas los ntawm dehydrogenation cov tshuaj tiv thaiv. 5-Cyanoindole tuaj yeem ua ke raws li qhov no. Cov khoom siv raw siv hauv cov tshuaj tiv thaiv yog diethyl terephthalate thiab 2-phenylacetylene. Tom qab ob lub tebchaw saum toj no yog irradiated los ntawm ultraviolet lub teeb, intermediates yog tsim, thiab thaum kawg 5-Cyanoindole yog generated los ntawm ib tug cyclization cov tshuaj tiv thaiv. Qhov kom zoo dua ntawm txoj kev no yog tias cov kev mob tshwm sim kuj yog me me thiab cov synthesis efficiency siab, tab sis cov ntaub ntawv raw yog kim thiab tus nqi siab.
Cov kauj ruam ntawm Bergman cov tshuaj tiv thaiv:
Kauj Ruam 1: Kev npaj ntawm 5-cyanndole thiab nyiaj trifluoroacetate:
Hauv kev kuaj mob, {{0}}cyanndole thiab silver trifluoroacetate sib xyaw, feem ntau yog nyob ntawm qhov kev txiav txim ntawm 0.1 mmol. Maj mam ntxiv dimethyl sulfoxide (DMSO) tov nyob rau hauv lub evaporator teb thiab do kom sib tov, ua kom sov li 60 degree kom txog thaum tag nrho cov substrates yog yaj. Ob npaug ntau nyiaj trifluoroacetate tau ntxiv dua li substrate.
Kauj Ruam 2: Reflux Reaction:
Cov tshuaj tiv thaiv sib tov tau rhaub rau 1 h thiab refluxed kom qhov kub thiab txias ntawm 60 degree.
Kauj Ruam 3: Hydrolysis:
Tom qab cov tshuaj tiv thaiv, cov tshuaj tov tau txias rau hauv chav tsev kub, thiab cov dej tsim nyog tau maj mam ntxiv rau kev sib xyaw, thiab cov khoom raug muab rho tawm nrog cov tshuaj sib xws (xws li acetone). Nyob rau hauv cov txheej txheem no, vim lub polarity ntawm ob daim ntawv cog lus tus yam ntxwv nyob rau hauv lub 5-cyanndole skeleton, lub extraction ntawm cov khoom yuav ua teeb meem ntau.
Kauj Ruam 4: Ua kom pom tseeb:
Tsom ntsoov rau cov khoom muab rho tawm los ntawm kev txo qis, ntxuav cov khoom ntau zaus nrog lub lim thiab dej ntshiab, thiab evaporate thiab qhuav.
Bergman cov tshuaj tiv thaiv yog ib qho tseem ceeb intramolecular cyclization cov tshuaj tiv thaiv, thiab nws cov tshuaj tiv thaiv mechanism muaj ob txoj hauv qab no:
Mechanism 1: Prominent hydrogen / oxygen oxidation cov tshuaj tiv thaiv:
Lub tshuab ntawm Bergman cov tshuaj tiv thaiv cuam tshuam nrog hydrogen / oxygen oxidation cov tshuaj tiv thaiv, thiab nws nyuaj rau teeb tsa cov pa roj carbon-carbon cov tshuaj tiv thaiv hauv hom intramolecular no. Ntawm lawv, lub xeev rho tawm ntawm carbon-hydrogen hauv 5-cyanindole ua rau nws dav dav thiab yooj yim rau kev cuam tshuam rau cyclization cov tshuaj tiv thaiv. Hauv cov tshuaj tiv thaiv no, cov ntaub ntawv xov xwm nuclear sib nqus resonance (NMR) tau lees paub qhov hloov pauv oxidative ntawm N-cyanonitrogen hauv 5-cyanindole rau N-subvalent nitrogen atom (oN≡C). Lub generated nitrogen oxides (oN≡C) tuaj yeem raug txo rau cov carboxylic acids thiab amines los ntawm lwm cov homogeneous thiab heterogeneous reagents. Hauv cov txheej txheem no, heterogeneous chemical catalyst (Acid / base) kuj ua lub luag haujlwm tseem ceeb.
Mechanism 2: Prominent hydrogen/nitrogen oxidation cov tshuaj tiv thaiv:
Cov tshuaj tiv thaiv Bergman kuj tuaj yeem piav qhia los ntawm hydrogen / nitrogen oxidation cov tshuaj tiv thaiv. Hauv cov tshuaj tiv thaiv no, qhov txo qis ntawm cov pa roj carbon-hydrogen hauv 5-cyanindole kuj reacts zoo. N-cyano nitrogen tuaj yeem oxidize carbon-hydrogen bonds uas nyob ib sab. Cov oxidized intermediates no yog tsim los ntawm lwm cov tshuaj tiv thaiv (xws li hydrogen oxidation, nitration, thiab lwm yam). Cov tshuaj tiv thaiv ntawm Mo(CO)6 ntawm Cp2Fe thiab cov khoom tsim nitrogen oxide intermediates kuj tseem tuaj yeem muab cov neeg ua haujlwm txo qis zog. Cov kev hloov pauv hluav taws xob sib txuas tuaj yeem ua lub luag haujlwm tseem ceeb.
2. Suzuki coupling tshuaj tiv thaiv txoj kev:
Suzuki coupling cov tshuaj tiv thaiv txoj kev yog dav siv cov tshuaj tiv thaiv tseem ceeb, uas tuaj yeem siv los tsim cov pob txha ntawm cov nplhaib sib txuas. 5-Cyanoindole kuj tseem tuaj yeem ua ke los ntawm cov tshuaj tiv thaiv no. Qhov kom zoo dua ntawm txoj kev no yog cov khoom siv raw khoom pheej yig thiab cov tshuaj tiv thaiv yog yooj yim los tswj, tab sis yuav tsum muaj cov kuab tshuaj organic.
(1) Ua ntej, cov ntaub ntawv yuav tsum tau npaj, suav nrog 5-Bromoindole, 5-Cyano-1, 3-dimethylpyrimidine-2, 4-dione, Palladium acetate (Pd (OAc)2), Phosphine ligands (xws li Phosphine los yog Phosphite), alkali (xws li sodium benzoate los yog sodium carbonate), Organic solvents (xws li dimethyl sulfoxide chloride, acetonitrile, los yog dichloromethane) thiab dej.
(2) Dissolve 5-Bromoindole, 5-Cyano-1, 3-dimethylpyrimidine-2, 4-dione thiab Phosphine ligands hauv cov organic hnyav xws li dimethyl sulfoxide chloride, acetonitrile los yog dichloromethane, thiab ntxiv alkali nyob rau hauv cryogenic tej yam kev mob. Piv txwv li, yaj 5-Bromoindole (0.5mmol), {{10}}Cyano-1,3-dimethylpyrimidine-2,{ {14}}dione (0.6mmol), Phosphine ligands (xws li TRIPHOS, {{20}}}.9mol feem pua) thiab sodium carbonate (2.0eq) hauv CH3CN, nplawm kom txog thaum yaj tag , ces ntxiv sodium carbonate (2.0 eq) ntawm -78 degree .
(3) Ntxiv Palladium acetate (Pd(OAc)2) rau hauv cov tshuaj tiv thaiv kab mob thiab do kom sib tov. Piv txwv li, ntxiv Palladium acetate (1.0 mol feem pua) mus rau qhov sib tov saum toj no thiab do cov tshuaj tiv thaiv ntawm -78 degree .
(4) Cov tshuaj tiv thaiv sib tov yuav muab rhaub rau hauv chav sov lossis 70 degree nyob rau hauv lub ntsuas kub, thiab hnov mob rau 1-2 teev. Tom qab cov tshuaj tiv thaiv tiav lawm, cov tshuaj tiv thaiv sib tov yog lim, thiab cov tshuaj tiv thaiv sib tov yog sib cais thiab muab rho tawm nrog dej thiab cov kuab tshuaj organic.
(5) Extract thiab purify lub hom phiaj cov khoom 5-Cyanoindole los ntawm inorganic ntsev thiab lwm yam impurities los ntawm kem chromatography los yog lwm yam kev sib cais. Piv txwv li, los ntawm kev siv silica gel kem chromatography, lub hom phiaj cov khoom yog muab rho tawm los ntawm impurities nyob rau hauv kem chromatography, thiab characterized los ntawm txhais tau tias xws li NMR.
Hauv kev xaus, cov kauj ruam rau kev sib txuas ntawm 5-Cyanoindole los ntawm Suzuki coupling cov tshuaj tiv thaiv yog qhov yooj yim heev, tab sis yuav tsum tau them nyiaj rau kev xaiv cov tshuaj tiv thaiv thiab cov ntaub ntawv.
3. Friedel-Crafts tshuaj tiv thaiv txoj kev:
Friedel-Crafts cov tshuaj tiv thaiv (Fujiwara-Moritani cov tshuaj tiv thaiv) yog ib qho kev sib txuas ntawm cov organic rau kev sib txuas ntawm cov tshuaj tsw qab los ntawm kev sib pauv cov tshuaj tiv thaiv ntawm imines thiab aryl sulfides. Nws yog cov tshuaj tiv thaiv cyclization uas txuas lub nplhaib imidazole los yog pyrrole nrog lub nplhaib aldehyde los yog ketone los tsim ib qho aromatic amine uas muaj heterocycle. 5-Cyanoindole yog ib qho amide compound nrog nitrogen heterocycle, uas tuaj yeem ua ke los ntawm Friedel-Crafts cov tshuaj tiv thaiv. Qhov kom zoo dua ntawm txoj kev no yog tias cov khoom siv tshuaj lom neeg ntawm cov khoom siv raw yog qhov ruaj khov, thiab cov qauv ntawm cov khoom tshwm sim yog qhov ruaj khov. Txawm li cas los xij, nws yuav tsum tau them sai sai rau kev xaiv cov tshuaj tiv thaiv thaum lub sijhawm ua haujlwm.
Cov kauj ruam ntxaws ntxaws ntawm Friedel-Crafts cov txheej txheem tshuaj tiv thaiv yog raws li hauv qab no:
(1.) Reactant npaj: Ntxiv 5-Cyanoindole thiab cov kuab tshuaj organic uas muaj formaldehyde rau hauv lub khob peb-caj dab huv si thiab qhuav. Nyob rau hauv tas li ntawd, cov organic hnyav yuav ua tau anhydrous organic solvents xws li nitriles, ethers, esters, thiab lwm yam, tab sis yuav tsum tau saib xyuas kom xaiv lub polarity ntawm cov kuab tshuaj thiab cov compatibility ntawm cov reactants.
(2.) Cov tshuaj tiv thaiv cua sov: Muab lub raj mis peb-caj dab rau hauv cov roj kub da dej, ua ntej ua kom sov cov reactant sib tov nrog qhov kub thiab txias, thiab tom qab ntawd maj mam ua kom sov rau qhov kub thiab txias. Lub sijhawm tshuaj tiv thaiv feem ntau yog 15-60 feeb. Qhov ntsuas kub zoo tshaj plaws rau cov tshuaj tiv thaiv no feem ntau yog nyob nruab nrab ntawm 100-140 degree, uas tuaj yeem hloov kho rau cov reactants sib txawv.
(3.) Kev sib cais ntawm cov khoom siv tshuaj tiv thaiv: Tom qab cov tshuaj tiv thaiv tiav, txias cov tshuaj tiv thaiv sib tov rau hauv chav sov, ntxiv cov dej ntau thiab cov xim organic, thiab tom qab ntawd kho cov pH kom nruab nrab nrog cov kua qaub lossis hydrochloric acid aqueous tov. Cov theem ntawm cov organic thiab cov theem aqueous tau sib cais, thiab cov theem ntawm cov organic tau qhuav dhau anhydrous sodium sulfate thiab tom qab ntawd concentrated kom qhuav. Cov khoom tuaj yeem sib cais thiab ua kom huv los ntawm txoj kab ke chromatography thiab lwm yam.
Hauv cov ntsiab lus, Friedel-Crafts cov tshuaj tiv thaiv yog ib qho tseem ceeb hluavtaws txoj kev, uas yog tsim rau cov synthesis ntawm aromatic amines los ntawm heterocyclic compounds. Rau cov tebchaw nrog nitrogen heterocyclic amides xws li 5-Cyanoindole, cov tshuaj tiv thaiv no muaj zog siv tau thiab tuaj yeem paub txog cyclization synthesis, uas muaj qee qhov txiaj ntsig rau kev tshawb fawb hauv daim teb no.
4. Linearization tshuaj tiv thaiv txoj kev:
Cov txheej txheem linearization cov tshuaj tiv thaiv yog ib txoj hauv kev los hloov cov nucleic acid molecules rau hauv linearized DNA lossis RNA, uas 5-Cyanoindole yog ib qho kev siv tshuaj reagent. Cov khoom siv raw siv hauv cov tshuaj tiv thaiv yog benzyl cawv thiab sodium cyanohydroxide, thiab 5-Cyanoindole yog txuas ntxiv los ntawm cov tshuaj tiv thaiv cyclization. Qhov kom zoo dua ntawm txoj kev no yog cov khoom siv raw khoom yooj yim kom tau txais thiab tus nqi qis, thiab nws tsim nyog rau ntau yam nucleic acid tsom xam thiab kev tshawb fawb teb. Txawm li cas los xij, nws yuav tsum tau ua tib zoo saib xyuas cov xwm txheej cyclization thaum siv cov txheej txheem kom pom seb cov khoom lag luam puas tuaj yeem tsim tau.
Txoj kev tawm tsam linearization ntawm 5-Cyanoindole thiab nws cov kauj ruam ntxaws.
(1) Ntxiv lub hom phiaj DNA lossis RNA rau qhov tsis muaj 5-Cyanoindole, feem ntau yog siv Tris tsis nrog pH 8.5. 5-Cyanoindole yog ib qho muaj zog photochemical cross-linking reagent, uas tuaj yeem tsim ib txoj hauv kev nrog NC khi nrog nucleic acid hauv paus, ua rau kev sib txuas ntawm nucleic acid strands.
(2) Tshaj tawm cov tshuaj tiv thaiv sib xyaw rau 365 nm ultraviolet lub teeb, thiab dhau los ntawm kev ua ntawm ultraviolet lub teeb, 5-Cyanoindole tsim cov kab txuas txuas nrog lub hauv paus hauv DNA lossis RNA, yog li ua tiav linearization.
(3) Ntxiv gel loading tsis, them cov tshuaj tiv thaiv cov khoom thiab khiav nws mus rau hauv agarose gel rau electrophoresis sib cais. Vim hais tias linearized DNA los yog RNA tsim ib lub band nyob rau hauv cov gel, nws muaj peev xwm cais linear fragments ntawm DNA los yog RNA los ntawm electrophoretic sib cais.
Feem ntau, cov hau kev saum toj no txhua tus siv los ua ke 5-Cyanoindole, thiab lawv muaj lawv tus kheej qhov zoo thiab qhov tsis zoo. Hauv kev siv tswv yim, nws yog ib qho tsim nyog los xaiv txoj kev tsim nyog tshaj plaws raws li cov khoom xav tau tiag tiag.