Tricllabendazice hmoovYog ib qho dawb lossis tawm dawb crystalline hmoov, CAS68786-}}} {662os, nrog molecular hnyav ntawm 359.66 g / mol. Tshaj tawm raws li ib tug dawb kom tawm dawb hmoov, tus xeeb ceem no muaj feem cuam tshuam nrog nws cov qauv siv lead. Lub conjugated system ntawm benzimidazole nplhaib thiab chlorinated phenoxy ua tau zoo nyob rau hauv nws thaj chaw pom kev, yog li nthuav tawm cov xim dawb. Cov xim dawb tuaj yeem pib los ntawm qhov sib txawv hauv microcrystalline loj los yog txwv tsis meej adsorbed rau saum npoo. Cov tshuaj muaj ntxhiab tsw me ntsis, uas yog cuam tshuam nrog Sulphur atom (- S-Ch3) hauv nws cov qauv molecular. Sulphur atoms yog ib qho ruam dhau los ntawm cov kab mob noo noo lossis cov pa oxygen rau saum huab cua, ua yeeb yaj kiab sulpur lossis sulfoxide sib txuas nrog cov tshuaj tsw qab.
Cov ntaub ntawv ntxiv ntawm kev sib txuas lus:
Peb Cov Khoom
Triclabendazole +. coa
Hom hluavtaws ib txwm muaj ntawmTricllabendazice hmoov
TriclabendazeSazole yog benzimidazole antiparasitic tshuaj tsuas yog siv los kho fascioliasis los ntawm kev sim siab. Cov txheej txheem synthesis cuam tshuam nrog ntau cov kauj ruam tseem ceeb, kev sib deev, methylation, thiab lwm yam rau synthesizing trichlorobakothole:
Txoj Kev 1: Txoj kev pib los ntawm 4-chloro-5- (2,3-dichlorophenoxy) -2-nitroaniline
Cov khoom siv raw: 4-chloro-5- (2,3-dichlorophenoxy) -2-nitroaniline.
Cov tshuaj tiv thaiv: hauv cov kuab tshuaj organic yog siv los ua cov tshuaj tiv thaiv kev txo qis kom tau txais cov tshuaj tiv thaiv kev txo qis kom tau cov tshuaj tiv thaiv kev txo qis kom tau txais cov tshuaj tiv thaiv dhau los tsis muaj kev sib cais.
Nta: Cov kauj ruam no txhim kho txoj kev txo qis, txo cov khoom siv, thiab yooj yim tshaj tawm {{0} {txheej txheej.
Cov khoom siv raw: thawj zaug nruab nrab hauv nruab nrab.
Cov tshuaj tiv thaiv: Muaj cov tshuaj pleev Hydroundium hydroxide, kev sib cav sib ceg los npaj cov pa nyem thib ob (5-dichlorophenoxy) -2-thiobenznidazole).
Nta: Los ntawm kev hloov ua ntu zus, tso tawm ntawm hydrogen sulfide yog tswj hwm, txo qhov cuam tshuam rau ib puag ncig.
Cov Khoom Siv Raw: Qib Thib Ob.
Cov tshuaj tiv thaiv: hauv qab catalysis ntawm DBU (1,8-diazabicyclo [5.4.0] underylage carbonate thaum kawg ua cov trichloropyrepyole.
Nta: Siv dimethil carbonate hloov chaw ntawm dimethyl sulfate lossis iodomethane ua tus neeg sawv cev methylating yog ib puag ncig ib puag ncig.
Tag nrho cov txiaj ntsig ntawm cov txheej txheem no tuaj yeem ncav cuag 55% rau 60%, thiab ntau yam ntsuas ntawm tau triclosan ua tau raws li cov qauv ntawm European pharapacoeia.
Cov txheej txheem tau txhim kho cov theem nitro, yooj yim cov txheej txheem ua haujlwm, thiab tau txais txiaj ntsig zoo, uas muaj kev lag luam zoo kawg.
Txoj Kev 2: Txoj Kev Synthesis pib los ntawm 3,4-dichloroaniline
Aclation txawv:
Raw khoom: 3,4-dichloroaniline.
Cov tshuaj tiv thaiv: kev sib tawm tau zoo tshwm sim nrog acetyl chloride lossis acetic anhydride hauv acetic acid los tsim 3,4-dichloroacetanilide.
Nitricification tiv thaiv:
Cov Khoom Siv Raw: 3,4-dichloroacetanilide.
Cov mob tshwm sim: nyob rau hauv muaj cov sulfuric acid, nitration cov tshuaj tiv thaiv tshwm sim nrog cov acid thiab acetic acid los tsim 4,5-dichloro-2-nitroacetanilide.
Hydrolysis tiv thaiv:
Cov Khoom Siv Raw: 4,5-Dichloro-2-Nitroacetanilide.
Cov kev tshwm sim: Kev tawm tsam hydrolysis tshwm sim nyob rau hauv lub xub ntiag ntawm potassium carbonate thiab dej los tsim 4,5-dichloro-2-nitroaniline.
Ethetification tiv thaiv:
Cov khoom siv raw: 4,5-dichloro-2-nitroaniline thiab 2,3-dichlorophenol.
Cov tshuaj tiv thaiv: Kev xaiv cov tshuaj tiv thaiv tshwm sim ntawm cov tshuaj tua hluav taws xob thiab theem hloov potassium thiab theem hloov pauv 4-chloro-5- dichlorophenoxy) -2-nitroaniline.
Tricllabendazice hmoov, raws li benzimidazole compound, muaj qhov cuam tshuam tseem ceeb rau cov yam ntxwv solubility hauv kev ua yeeb yam yeeb tshuaj kev txhim kho, kev sim kev sim, thiab cov ntawv thov kev lag luam. Lub solubility ntawm cov khoom no sib txawv hauv cov kuab tshuaj sib txawv, feem ntau cuam tshuam los ntawm cov qauv molecular, daws polarity, thiab kub.
Lub solubility ntawm Triclosan hauv cov kuab tshuaj organic thiab dej qhia tau tias muaj cov polarization tseem ceeb. Raws li cov ntaub ntawv cov ntaub ntawv thiab kev sim ua pov thawj, nws cov yam ntxwv solubility muaj raws li nram no:
(1) cov kuab tshuaj heev
Methanol: Ua ib lub zog polar organic, methanol tau zoo tshaj plaws sterubility rau trichhlorobakothole. Cov kev sim tau qhia tias Trichhlorobakothiazole tuaj yeem ua tag nrho cov tshuaj methhanol, ua cov tshuaj sib haum xeeb, thiab cov solubility tseem ceeb nrog kev nce qib. Cov xeeb ceem no ua rau nws nyiam cov kuab tshuaj rau kev sim synthesis, kev ua kom huv, thiab kev npaj ua tiav.
Acetone: acetone muaj solubility zoo ib yam li methanol rau trichlorobakothiazole thiab tuaj yeem yaj cov khoom ntawm chav tsev. Acetone yog feem ntau siv nyob rau hauv lub crystallization thiab purification txheej txheem ntawm trichlorobakothiazole hauv kev lag luam khoom lag luam yog npaj los ntawm kev kho cov qauv sib piv.
Dichhloromethane: Raws li ib tug qauv polruvetly, Dichhloromethane tau txo qis solubility rau cov khoom siv methanol thiab acetone, tab sis tseem tuaj yeem ntsib qee qhov kev tsim khoom.
Phau Ntawv Sau Txog Kev Cai
Nws qhov tsawg boiling taw qhia tus yam ntxwv (39.8 Degree) muab nws qhov txiaj ntsig zoo hauv cov kuab tshuaj rov qab los.
(2) QUB SOLUBILDY SELLENT
Dej: Trichloronazole muaj solubility tsis tshua muaj qis hauv dej, yuav luag Insoluble. Cov yam ntxwv no yog vim muaj cov qauv hydrophobic muaj zog, xws li cov qauv moleculs, uas ua rau nws nyuaj rau nws los ntawm hydrogen tsev lossis kev sib cuam tshuam dipole. Hauv cov tshuaj ua haujlwm, nws yog qhov tsim nyog los txhim kho lawv cov dej solubility los ntawm nanocrystal thev naus laus zis lossis surfactant solubilization.
Ethyl acetate: txawm tias kev ua kom pom tseeb yog ib qho kev siv hluav taws xob organic, nws solubility hauv trichlorobakothone muaj tsawg thiab tsuas yog yaj. Qhov tshwm sim no yuav cuam tshuam nrog tsis txaus ntseeg polarity txuam nrog cov kuab tshuaj, thiab cov kev sib cais los ntawm cov kuab tshuaj sib xyaw.
Tricholrethane: Zoo ib yam li Dichhloromethane, Trichloromethane muaj cov solubility thiab ntau dua kev lom zem thiab ntau dua rau hauv Trichlorobakothole, thiab tsis tshua siv nyob rau hauv cov ntawv thov kev siv.
Qhov sib txawv hauv solubility ntawm Trichhlorobakothiazole tuaj yeem piav qhia ntawm qib molecular:
Hydrophobic hydrophilic hydrohules muaj trichhlorophenyl (muaj methylthio (tsis muaj zog polar), nthuav qhia muaj zog hydrophobicity raws li tag nrho. Nyob rau hauv cov kuab tshuaj ncov qaumteb qab zib xws li Methanol, cov kuab tshuaj molecules tau encepsulate tshuaj molecules los ntawm kev sib cuam tshuam dipole, sib sau ua ke ruaj khov; Hauv tsis - polar cov kuab tshuaj xws li dej, cov teeb meem hydrophobic dominate, ua rau molecular sib sau ua ke thiab nag lossis daus.
Kev muaj peev xwm ua rau kev muaj peev xwm ua rau methanol thiab acetone yog qhov tsis muaj zog, uas muaj peev xwm tsis muaj zog ntawm cov tshuaj thiab txhawb kev sib cais; Lub hydrogen kev sib koom tes ntawm cov dej muaj cov nyhuv tseem ceeb ntawm hydrophobic molecules, ntxiv txo solubility.
Qhov kub nyhuv: solubility feem ntau nce nrog kev nce kub. Piv txwv li, cov solubility ntawm trichlorobakothiazole hauv methanol nce los ntawm ntau peb zaug ntawm 60 degree, uas muaj cov ntsiab lus tseem ceeb hauv kev muaj cov txheej txheem crystallization.
Tswv yim thov: cov tswv yim los daws cov sib txawv ntawm solubility
Drug formulation development: In response to the poor water solubility problem of triclosan, researchers have developed various techniques, such as co melting the drug with polyethylene glycol (PEG) to prepare solid dispersions, or improving bioavailability through liposome encapsulation.
Kev Tshawb Fawb: Hauv Vitro Kws Muag Tshuaj Techniments, Trichlorobakothiazole yuav tsum tau yaj nyob rau hauv cov organic cov kuab tshuaj xws li DMOPS, thiab tom qab ntawd diluted nrog kab lis kev cai rau cov phiaj xwm. Txij ntawm no, nws yog ib qho tsim nyog yuav tswj hwm cov txheej txheem sab nraud kom tsis txhob muaj kuab lom rau cov hlwb.
Kev tsim khoom lag luam: nyob rau hauv lub synthesis ntawm raw cov ntaub ntawv, methanol dej sib xyaw cov kuab tshuaj uas tau sib xyaw rau crystallization prystallization. Los ntawm kev kho cov solvent piv thiab ntsuas kub, kev sib cais ua tau zoo thiab huv ntawm Trichhlorobakothiazole tuaj yeem ua tiav.
Ntawj ntom:
Lub ntom ntawm Trichlorobakothiazole yog 1.59-1.6 g / cm ³ oms ntawm chlorine atoms nyob rau hauv nws molecule (35.5 g / mol) thiab nruj nreem ntim crystal qauv. Cov yam ntxwv ntom ntom ntom nti kom tau xim rau cov teeb meem sedimentation hauv kev tsim cov qauv kev pab, uas tuaj yeem hloov kho los ntawm kev ntxiv hydroxyprropyl cellulose.
Stacking txoj kev:
Nws cov siv lead ua rau lub kaw lus monoclin Cov txheej txheem no tau tshwm sim hauv cov hmoov tsis zoo flower thiab yooj yim agglomeration, cov uas yuav tsum tau tswj av (<60% RH) and the addition of anti caking agents (such as silica) during storage.
Cov yam ntxwv spectral
UV {- Vis:
Trichhloronazole cov khoom ua kom muaj kev haum siab muaj zog ntawm 254 nm, sib raug mus rau → → Kev hloov pauv ntawm Benzimidazole nplhaib; Nws tsis muaj zog nqus nqus ntawm 300-350 nm, thaum pib los ntawm n → au kev hloov ntawm chlorophenoxy pab pawg. Cov xeeb ceem no tuaj yeem siv rau nws cov tshuaj ntsuam xyuas ntau ntxiv (xws li HPLC Nrhiav tau).
Infrared spectral yam ntxwv:
3200 {- 3500 cm ⁻¹ 3500 cm ⁻¹ 35 Ncab kev co ntawm Benzimidazole nplhaib.
1600-1700 cm ⁻¹: Ncab xyab ntawm c=n ob daim ntawv cog lus.
Ncab kev co ntawm 1200 {- 1300 cm ⁻¹ 1300 cm ⁻¹: c {}} oc (phenoxy).
600 {{- 800 cm ⁻¹: Ncab Kev Cib Kev Cuv ntawm C-Pob Bond.
Txoj kev txhim kho ntawm Triclosan tuaj yeem raug rov qab mus rau nruab nrab thaum lig xyoo pua 20th. Nws cov kev tshawb fawb thiab kev txhim kho, kev thov, thiab txhim kho cov txheej txheem cuam tshuam nrog kev sib koom ua ke ntawm cov tshuaj lom neeg xws li thiab tswj cov kev xav tau. Cov hauv qab no yog cov lus qhia ntxaws ntxaws rau nws cov txheej txheem kev txhim kho:
Nyob rau hauv nruab nrab-20th caug xyoo, tshwm sim los ntawm kev loj hlob ntawm cov tsiaj txhu muaj kev loj hlob, thiab ploj mus rau hauv cov tsiaj uas tau ua rau tsiaj txhu loj, thiab ua rau cov tsiaj muaj sia nyob hauv ntiaj teb Nyob rau tib lub sijhawm, txawm hais tias muaj mob tib neeg nrog kev mob siab yog tsawg, kev kho mob tsis yooj yim, thiab siv tshuaj tsis yooj yim, thiab siv tau sai. Nyob rau lub sijhawm ntawd, cov tshuaj txag dej uas tso quav xws li Praziquantel thiab Albendazole tau ua hauj lwm zoo rau daim siab thiab muaj teeb meem tiv thaiv, cov kws tshawb fawb kev tshawb nrhiav tshiab.
1. CompoundCov tshuaj ntsuam thiab kev ua kom zoo
Xyoo 1970, cov neeg tshawb nrhiav pom los ntawm kev ntsuas siab heev ntawm kev ntsuas benzimidazole muaj peev xwm tiv thaiv flukes. Cov txheej txheem kev hloov kho ntxiv qhia tias kev qhia me me methylthio pab pawg (} txoj hauj lwm ntawm cov kab cenoxy ntawm txoj haujlwm 5 thiab 6 tuaj yeem txhim kho cov kev tua tsiaj 5 thiab 6 tuaj yeem txhim kho cov kev tua ntawm daim siab. Nyob rau xyoo 1980, Swiss tuam txhab Ciba Geiger (tam sim no Novartis)-angoroCal-6-
2. Kev tsom xam ntawm cov txheej txheem ntawm kev nqis tes ua
Kev tshawb fawb tau pom tias Triclosan exervts nws cov tshuaj tua kab mob los ntawm kev cuam tshuam nrog lub zog metabolism ntawm cov kab
Inhibiting cov kab ntawm cov kab bergberine reductase system, thaiv anaerobic glycolysis, coj mus rau lub zog (ATP) depetion;
Cuam tshuam nrog microlotuble qauv ntawm cov cab, inhibiting protein synthesis, thiab ua rau tuag tes tuag taw thiab kev tuag ntawm tus cab;
Nws muaj cov nyhuv muaj zog rau ob qho loj thiab cov neeg laus ntawm fasciola hepatica, thiab tus cab tau tshem tawm tom qab cov tshuaj, txo cov ntaub so ntswg puas tsuaj.
1. Wid thov thoob plaws hauv cov tsiaj tus txiv
Thaum xyoo 1980s, Triclosan tau pom zoo rau siv hauv cov tsiaj txhu ruminant xws li cov nyuj thiab yaj, ua cov tshuaj uas nyiam dua rau kev kho mob daim siab. Nws cov txiaj ntsig suav nrog:
Kev ua tau zoo: ib qho koob tshuaj (10-12 mg / kg) tuaj yeem ua tiav tus nqi txua ntawm ntau tshaj 95%;
Kev Nyab Xeeb: Tsawg toxicity rau tus tswv tsev, haum rau kev siv hauv ob qho kev xeeb tub thiab cov tsiaj me;
Kev yooj yim: Cov tshuaj muaj kev ruaj khov thiab tuaj yeem ua rau cov ntsiav tshuaj, granules, ua kom yooj yim los tswj hwm.
Nrog rau qhov loj - nplai kev txhim kho tsiaj ntawm cov tsiaj txiv, lub ntiaj teb xav kom loj hlob, nrog kev muag khoom txhua xyoo dhau ntau pua pua nyiaj.
2. Kev Siv Khoom Siv Hluav Taws Xob Hauv Tib Neeg Cov Tshuaj
Xyoo 1988, cov kws kho mob Askiv thawj zaug tau kho ob lub siab ntawm tib neeg lub siab mob cov neeg mob tus neeg mob tus neeg mob cov neeg mob Trichhlorofluazuron thiab ua tiav qhov kev cuam tshuam loj thiab ua tiav. Tomqab ntawd, cov tshuaj tau siv los kho cov kab mob xws li Paragonimiasis (Lung Fluke tus kab mob) thiab Paragonimiasis, tshwj xeeb yog rau cov neeg tiv thaiv mus rau Prazatantel. Lub Koom Haum Ntiaj Teb Kev Noj Qab Haus Huv (Leej twg tau teev nws raws li cov tshuaj uas pom zoo rau kev kho mob fasciola thiab txhawb nws cov kev siv hauv Africa thiab Asmeskas Qab Teb.
1.traditionch txoj kev
Cov txheej txheem thaum ntxov siv 4-chloro-5- (2,3-dichlorophenox, thiab npaj cov khoom siv roj ntsha Tab sis txoj kev no muaj cov teeb meem nram qab no:
Kev siv cov muaj txiaj ntsig zoo ntawm trichhlorosilane thiab carbon disulfide ua qhov kev nyab xeeb ntawm kev nyab xeeb;
Cov kauj ruam cyclization ua rau cov roj av roj av roj av roj av, uas yuav tsum muaj cov cuab yeej siv roj av nyuaj ntxiv;
Tus nqi ntawm methylation reagent reagent Detethyl carbonate yog qhov siab.
2.Green Synthesis Kev Siv Tshiab
Txij li 21st caug xyoo, cov kws tshawb nrhiav tau tsim cov kev phooj ywg zoo ib puag ncig los ntawm kev tsim qauv catalyst kev tsim kho, thiab lwm txoj kev
Nitro Txo: Siv cov hmoov av hlau / hydrochloric acid system lossis catalytic hydrogenation txoj kev los txo kev siv trichlorosilane;
Ntiv nplhaib tshuaj tiv thaiv: Hloov cov pa roj carbon disulfide nrog thaiacetamide kom tsis txhob tsim ntawm hydrogen sulfide;
Methylation Txheej txheem: Siv pheej yig Dovethyl sulethyl sulethyl sulethyl sulfate (xav tau cov khoom lag luam nruj me nyuam tab sis tus nqi siab (siab} nplai ntau lawm los ntawm cov nyom ntws nrad.
Piv txwv li, cov thev naus laus zis txo cov kev tso tawm ntawm hydrogen sulfide hauv kev ua ntu zus los ntawm kev pub mis ua ntu zus los ntawm kev pub mis rau 81.5% thiab ua tiav kev coj dawb huv tshaj 99%.
Cim npe nrov: Tricllabendazendazole Hmoov, Tuam Tshoj chaw tsim khoom, chaw tsim khoom, Hoobkas, lag luam Wholesale, yuav, nqe, loj, loj, rau muag