Tetramisole Hydrochlorideyog ib qho dawb crystalline hmoov uas yog khoom ntawm chav tsev kub (piv txwv li 25 degree). Nws cov txheeb ze molecular hnyav yog 240.75g / mol thiab nws qhov ceev yog 1.17g / cm3.Tetramisole HclNws yooj yim soluble hauv dej thiab ethanol, tab sis tsis yooj yim soluble hauv acetone thiab ether. Nws solubility hauv dej yog 46.6g / L ntawm 25 degree. Nyob rau hauv qhov kev txiav txim ntawm lub teeb, Tetramisole Hydrochloride yuav oxidize, tab sis thaum raug rau hauv chav tsev kub, nws muaj peev xwm stably tuav nws cov khoom. Nws yog ib qho dav-spectrum antihelminth tshuaj uas nquag siv los kho cov kab mob cab hauv tib neeg thiab tsiaj txhu.
Thawj txoj kev: cov tshuaj tiv thaiv ntawm methyl imidazole acetate thiab 2-chloropropionyl chloride, txoj kev no yog ib txoj hauv kev siv ntau tshaj plaws hauv TH synthesis.
Cov txheej txheem tshwj xeeb yog raws li hauv qab no:
Methyl imidazole acetate thiab 2-chloropropionyl chloride yog cov khoom siv tseem ceeb rau kev sib txuas ntawm Tetramisole Hydrochloride. Methyl imidazole acetate yog hmoov dawb,
Synthesis ntawm Tetramisole Hydrochloride cov kauj ruam:
Thawj kauj ruam: methyl imidazole acetate thiab 2-chloropropionyl chloride cov tshuaj tiv thaiv:
Sib tov imidazole methyl acetate thiab 2-chloropropionyl chloride ntawm qhov sib piv ntawm 4: 1, thiab tom qab ntawd ntxiv qhov tsim nyog ntawm triethylamine (TEA) catalyst. Lub sijhawm no, cov tshuaj tiv thaiv yuav tsim cov gel zoo li precipitate, thiab tom qab ntawd cov khoom sib cais thiab huv si los ntawm kev pom, txias, ntxuav thiab lwm txoj kev.
Cov kauj ruam thib ob: hnov mob nrog phenylsulfuric acid:
Cov khoom tau txais nyob rau hauv thawj kauj ruam yog reacted nrog phenylsulfuric acid, thiab cov tshuaj tiv thaiv kub yog nqa tawm ntawm 10-15 degree . Nyob rau lub sijhawm no, cov khoom yuav dhau los ua cov kua dej dawb, uas tuaj yeem lim, ntxuav thiab ziab kom tau yooj yim 2-imidazolylvaleric acid.
Kauj ruam 3: Cov tshuaj tiv thaiv nrog tert-butylaluminum fluoride:
Cov khoom tau txais nyob rau hauv lub kauj ruam thib ob yog reacted nrog tert-butylaluminum fluoride, thiab cov tshuaj tiv thaiv yog nqa tawm nrog ib tug inert hnyav tetrahydrofuran (THF). Nyob rau lub sijhawm no, cov tshuaj tiv thaiv ua rau cov hmoov av dawb, thiab tom qab ntawd cov khoom sib cais thiab huv si los ntawm kev pom, ntxuav, ziab thiab lwm yam.
Kauj Ruam 4: Cov tshuaj tiv thaiv nrog 2, 3-dichloro-5, 6-dicyano-1, 4-benzenedione:
Sib tov cov khoom tau txais hauv qib peb nrog 2, 3-dichloro-5, 6-dicyano-1, 4-benzenedione hauv qhov sib piv ntawm 1: 1, thiab Cov khoom tau txais yuav dhau los ua cov hmoov dawb, thiab tuaj yeem Soluble hauv dej lossis ethanol, thaum tsim cov tshuaj pharmacological.
Kauj ruam tsib: teb nrog HCl:
Dissolve cov khoom uas tau txais nyob rau hauv lub thib plaub kauj ruam nyob rau hauv sodium hydroxide (NaOH), thiab ces ntxiv ib tug tsim nyog tus nqi ntawm hydrochloric acid (HCl) rau neutralize cov tshuaj tiv thaiv. Lub sijhawm no, Tetramisole Hydrochloride yog tsim, thiab nws tseem tuaj yeem ua kom huv los ntawm kev pom, ntxuav, ziab thiab lwm txoj kev.
Los ntawm reacting methyl imidazole acetate nrog 2-chloropropionyl chloride, reacting nrog phenylsulfuric acid, reacting nrog tert-butylaluminum fluoride, reacting nrog 2, 3-dichloro-5, 6-dicyano{{ 6}},4-benzenedi Tetramisole Hydrochloride tau ua tiav zoo los ntawm cov kauj ruam ntawm ketone cov tshuaj tiv thaiv thiab cov tshuaj tiv thaiv nrog HCl.
Qhov tsis zoo: Txoj kev no yuav tsum muaj cov tshuaj tiv thaiv hnyav thiab yuav tsum muaj cov kuab tshuaj organic ntau ntau.
Qhov thib ob txoj kev: reacting nrog imidazole acetone thiab crotonic acid:
Cov kauj ruam tseem ceeb ntawm txoj kev yog kev npaj ntawm 2-amino-2-methyl-1-propanol (AMP) precursor los ntawm kev txo cov tshuaj tiv thaiv nyob rau hauv muaj imidazole acetone thiab crotonic acid; Tom qab ntawd, sulfonylation ntawm AMP Reaction, tau TH. Cov kauj ruam tshwj xeeb yog raws li hauv qab no:
Thawj kauj ruam: kev npaj ntawm imidazole acetone:
Hauv 250 ml peb-caj dab, ntxiv 50 ml ntawm acetone thiab 1.75 g ntawm sodium pyruvate. Nws tau nplawm zoo, thiab 8 ml ntawm acetaldehyde tau maj mam ntxiv dropwise thereto. Tom qab ntawd, 10 mL ntawm methyl tert-butyl ether catalyst tau ntxiv, thiab cov tshuaj tiv thaiv sib xyaw yog nplawm. Lub vial raug muab tso rau hauv chav sov li 15 feeb kom txog thaum cov tshuaj tiv thaiv tiav. Thaum kawg, 100 mL ntawm cov dej deionized tau ntxiv, cov tshuaj tiv thaiv sib xyaw tau lim, thiab cov kua lim tau sau.
Kauj Ruam 2: Kev Npaj Tetramisole Hydrochloride:
Hauv 250 ml peb-caj dab dej, ntxiv 25 g ntawm crotonic acid thiab 50 ml ntawm 00 qib ethanol, thiab do nws tusyees. Txuas ntxiv mus, thiab maj mam ntxiv cov tshuaj imidazole acetone uas tau npaj ua ntej mus rau crotonic acid thiab 00 qib ethanol sib tov. Thaum ntxiv cov tshuaj imidazolium acetone, ib qho nyiaj ntawm 1M hydrochloric acid tau ntxiv los kho tus nqi pH, thiab cov tshuaj tiv thaiv sib xyaw tau txuas ntxiv rau 30 feeb. Tom qab ntawd cov sib tov tau muab rho tawm los ntawm kev ntxiv 20 ml ntawm glacial acetic acid thiab 50 ml ntawm n-hexane. Cov extract muaj Tetramisole Hydrochloride, thiab los ntawm cov concentration kom tshem tawm n-hexane thiab glacial acetic acid, cov khoom seem yog Tetramisole Hydrochloride.
Txoj kev npaj muaj cov tshuaj tiv thaiv nrog imidazolium acetone thiab crotonic acid, los ntawm kev kho pH, rho tawm thiab ua kom pom tseeb, thiab thaum kawg tau txais Tetramisole Hydrochloride ua tshuaj anthelmintic.
Qhov zoo: Cov kev mob tshwm sim yog qhov yooj yim thiab tsawg dua cov kuab tshuaj organic yuav tsum tau.
Disadvantage: tus nqi ntau lawm.
Qhov thib peb txoj kev: react imidazole acetone thiab N, N-dimethyl-N'-nitrohydrazine:
Nyob rau hauv txoj kev no, tus precursor ntawm TH yog N-(imidazolyl)-N, N-dimethyl-N'-nitrohydrazine (IDI). IDI tau txais kev txo qis kom tau txais TH. Cov kauj ruam ntxaws ntxaws yog raws li hauv qab no:
Kauj Ruam 1: Npaj imidazole acetone:
Ua ntej, peb yuav tsum npaj imidazole acetone. Lub npe tshuaj ntawm imidazole acetone yog 2,3,5,6-tetrahydro-6-phenylimidazo(2,1-b)thiazole, uas feem ntau siv rau hauv kev tsim tshuaj, tshuaj zawv plaub hau thiab tshuaj tua kab. . Imidazoleacetone tuaj yeem tau los ntawm kev ua haujlwm 3-phenyl-2, 3-dihydrothiazolone nrog tert-butylamine nyob rau hauv muaj sodium hydroxide.
Kauj Ruam 2: Npaj N, N-Dimethyl-N'-nitrohydrazine:
N, N-Dimethyl-N'-nitrohydrazine (DMNG) yog ib qho organic compound nrog cov tshuaj formula C6H14N4O4, uas yuav siv tau raws li ib tug muaj zog oxidant, catalyst thiab roj additive. DMNG tuaj yeem tau txais los ntawm kev ntxiv nitric acid thiab sulfuric acid rau dimethylformamide, ua raws li kev pom thiab ziab.
Kauj Ruam 3: Cov tshuaj tiv thaiv ntawm imidazole acetone thiab DMNG:
DMNG thiab imidazolium acetone tau ntxiv rau cyclohexane, ua raws li phosgene. Phosgene yog tau los ntawm reacting ammonia thiab chlorine nyob rau hauv lub teeb. Tom qab cov tshuaj tiv thaiv, cov reactant sib tov yog distilled nyob rau hauv lub siab txo kom tau ib tug roj. Tom qab ntawd, hydrochloric acid tau ntxiv, thiab nws tau txias rau 0 degree . Nyob rau hauv qhov xwm txheej ntawm kev nplawm tas li, ntxiv 10 feem pua los ntawm qhov hnyav tshaj cov kua dej ntawm acetic anhydride, txuas ntxiv stirring rau 20 feeb, thiab cov tshuaj tiv thaiv tiav. Thaum kawg, 25 feem pua ntawm qhov hnyav tshaj sodium hydroxide aqueous tov tau maj mam ntxiv dropwise hauv dej khov dej kom txog rau thaum cov xim tig daj, thiab tau txais los nag.
Kauj Ruam 4: Kev Npaj Tetramisole HCL:
Tetramisole HCL tuaj yeem tau los ntawm reacting DMNG intermediate tau nyob rau hauv cov kauj ruam dhau los nrog cawv thiab hydrochloric acid, thiab cov tshuaj tiv thaiv tsim los ntawm cov khoom methyl-(1-benzyl-2,3-dihydroimidazole{ {5}},5,6-trimethylpyridinium) chloride, los ntawm Kev Tswj cov pH kom tau cov purity ntawm Tetramisole HCL. Tom qab cov tshuaj tiv thaiv, cov khoom siv Tetramisole HCL tau txais los ntawm kev pom thiab ziab.
Qhov zoo: TH tuaj yeem tsim tau zoo thiab siv rau kev sib txuas ntawm qee cov tshuaj tua kab thiab tshuaj tshiab.
Disadvantages: Lub sij hawm cov tshuaj tiv thaiv ntev dua, ua rau qis qis thiab cov dej khib nyiab ntau.
Hauv cov ntsiab lus, muaj ntau txoj hauv kev sib txawv rau kev sib xyaw ntawm Tetramisole Hydrochloride. Txawm hais tias txhua txoj kev muaj nws qhov tshwj xeeb zoo thiab qhov tsis zoo, txoj kev tsim nyog tuaj yeem xaiv tsim nyog rau kev tsim khoom raws li qhov xav tau tiag tiag thiab cov xwm txheej tsim khoom. Cov saum toj no yog cov kauj ruam npaj ntawm Tetramisole Hydrochloride, qee cov tshuaj yuav tsum tau siv kom zoo. Nws yuav tsum raug sau tseg tias cov cai tswj kev nyab xeeb yuav tsum tau ua raws thiab cov cuab yeej tiv thaiv yuav tsum hnav kom raug thaum lub sijhawm sim.