Tetramisole hclyog dawb crystalline hmoov, uas yog ib hom imidazole compound. Nws muaj ntau yam tshuaj muaj txiaj ntsig, suav nrog tshuaj tiv thaiv, tshuaj tua kab mob, hypoglycemic thiab immunomodulatory teebmeem hauv vivo. 2-Chloropropionyl chloride yog cov kua tsis muaj xim thiab cov organic compound uas feem ntau siv rau hauv kev sib txuas ntawm ntau yam tshuaj tua kab, tshuaj thiab tshuaj pleev xim.
Thawj txoj kev: Condensation ntawm chloroacetate nrog imidazole thiab formaldehyde siv txoj kev siab:
Cov txheej txheem tau txais kev kub ntxhov siab (80-100 MPa) los npaj qhov nruab nrab los ntawm cov tshuaj tiv thaiv condensation ntawm chloroacetate, imidazole thiab formaldehyde, thiab tom qab ntawd ntxiv tetrabutylammonium bromide nyob rau hauv muaj hydrochloric acid thaum kawg tau txais cov khoom tetramisole hcl.
Cov kauj ruam tshuaj tiv thaiv yog raws li nram no:
1) Kev npaj ntawm chloroacetate:
Ua ntej, ntxiv chloroacetic acid thiab tshaj formaldehyde rau hauv cov kuab tshuaj organic, xws li methanol lossis ethanol, thiab do hauv chav sov. NaOH tau ntxiv kom coj pH ntawm cov tshuaj tiv thaiv ze rau 7.
Tom qab ntawd, siv lub tshuab hluav taws xob siab, cov tshuaj tiv thaiv tau ua nyob rau hauv cov tshuaj tiv thaiv ntawm 160 degree. Cov khoom kawg yog chloroacetic formaldehyde carboxylate nrog cov qauv OHC (CH2)2Cl.
2) Kev npaj ntawm imidazole:
Hauv cov tshuaj tiv thaiv kab mob, yaj methyl ethyl ketone hauv dej cawv, ntxiv chloroformamide thiab tooj liab chloride, thiab do hauv chav sov. Tom qab ntawd acetylimidazole tau ntxiv rau cov tshuaj tiv thaiv sib xyaw thiab ua rau lub zog thaum cua sov rau 70 degree. Cov tshuaj tiv thaiv tuaj yeem tshwm sim ntawm qhov kub ntawm 90 degree C., thiab lub sijhawm tshuaj tiv thaiv yog li 24 teev. Cov khoom kawg tau txais yog ib qho imidazole compound nrog cov qauv ntawm isoimidazolone, uas yog 2-(1H-imidazol-1-yl)acetophenone.
3) Condensation cov tshuaj tiv thaiv ntawm imidazole thiab chloroacetic acid formaldehyde carboxylate:
Imidazole tau yaj hauv methanol, thiab chloroacetic formaldehyde carboxylate tau ntxiv rau qhov sib xyaw. Cov reactants yog reacted ntawm qhov kub thiab txias ntawm 160 degree thiab pressurized nyob rau hauv lub reactor kom paub meej tias tag nrho cov reactants. Lub sijhawm tshuaj tiv thaiv yog 2 teev. Cov khoom tsim los ntawm condensation cov tshuaj tiv thaiv yog N-(2-oxo-5,5-dimethyl-1,3,2-imidazolyl)-chloroacetic acid formaldehyde amide nrog Molecular formula C13H16N3O3Cl.
Qhov nruab nrab no tseem xav tau hydrochlorination los ua tetramisole hcl. Qhov nruab nrab hais saum toj no yog kho nrog cov kua qaub uas muaj chloride ions, thiab tetrabutylammonium bromide yog ntxiv rau high-pressure hydrochlorination thaum kawg tau txais cov khoom Tetramisole Hcl.
Kev npaj ntawm Tetramisole Hcl intermediate yuav tsum tau siv cov tshuab hluav taws xob siab, thiab cov tshuaj tiv thaiv muaj kev kub ntxhov thiab kub siab. Ua tib zoo thiab meej tswj ntawm cov tshuaj tiv thaiv kab mob yuav tsum tau ua kom tiav cov tshuaj tiv thaiv ntawm cov reactants. Nyob rau hauv ib tug series ntawm cov txheej txheem tshuaj complex, tus intermediate N-(2-oxo-5,5-dimethyl-1,3,2-}}imidazolyl)-chloroacetic acid formaldehyde amide yog qhov tseem ceeb hauv kev npaj ntawm Tetramisole Hcl cov kauj ruam tseem ceeb.
Qhov zoo: yooj yim sib cais thiab purification ntawm cov tshuaj tiv thaiv cov khoom, siab yield.
Qhov tsis zoo: Txoj kev no yuav tsum muaj kev kub ntxhov ib puag ncig, thiab kev ua haujlwm yog qhov txaus ntshai dua.
Txoj kev thib ob: cov tshuaj tiv thaiv ntawm imidazole acetone, benzoic acid thiab carboxylic acid derivatives:
Cov kauj ruam tseem ceeb ntawm txoj kev yog kom hnov mob imidazole acetone, benzoic acid thiab carboxylic acid derivatives los ua plaub-tus tswv cuab heterocycle. Tom qab ntawd, kev txo qis ntawm plaub-tus tswv cuab heterocycle them TH.
Tetramisole hcl Inclusions yog cov tshuaj tua kab uas siv dav rau cov tsiaj nyeg thiab nws kuj tau siv hauv kev kho mob. Imidazole acetone, benzoic acid thiab carboxylic acid yog derivatives ntawm Tetramisole Hcl, uas yog tag nrho cov organic tebchaw. Cov tshuaj tiv thaiv thiab cov txheej txheem ntxaws ntxaws ntawm imidazole acetone, benzoic acid thiab carboxylic acid derivatives ntawm Tetramisole Hcl derivatives tau piav qhia hauv qab no.
1. Cov tshuaj tiv thaiv ntawm imidazole acetone derivatives:
Imidazole acetone derivatives yog cov tsis muaj zog hauv cov tebchaw uas tuaj yeem ua rau cov kua qaub los tsim cov ntsev. Hauv qab no yog cov tshuaj tiv thaiv thiab cov kauj ruam ntxaws ntawm imidazole acetone derivatives:
1.1 React nrog sulfuric acid:
Imidazole acetone derivatives tuaj yeem hnov mob nrog sulfuric acid los ua cov ntsev, thiab cov tshuaj tiv thaiv no feem ntau yog siv rau hauv kev npaj ntawm Tetramisole Hcl derivatives. Qhov sib npaug ntawm cov tshuaj tiv thaiv yog raws li nram no:
R-CH=N-CH3ntxiv H2YOG4→ R-CH=N-CH3·H2YOG4
Ntawm lawv, R-CH=N-CH3sawv cev rau imidazole acetone derivatives.
Cov kauj ruam tshuaj tiv thaiv yog raws li nram no:
1) Sib tov cov imidazole acetone derivative thiab concentrated sulfuric acid.
2) Do cov sib tov kom nws sib npaug.
3) Tom qab cov tshuaj tiv thaiv, yaug nrog dej khov thiab lim cov khoom kom tau txais imidazole acetone sulfate.
1.2 Cov tshuaj tiv thaiv nrog aldehydes:
Imidazoleacetone derivatives tuaj yeem cuam tshuam nrog aldehydes los tsim imidazoleacetone aldimines. Qhov sib npaug ntawm cov tshuaj tiv thaiv yog raws li nram no:
R-CH=N-CH3 plus R'CHO → R-CH=N-CH3CHO
Ntawm lawv, R-CH=N-CH3sawv cev rau imidazole acetone derivative, R'CHO sawv cev rau aldehyde.
Cov kauj ruam tshuaj tiv thaiv yog raws li nram no:
1) Sib tov imidazole acetone derivative thiab aldehyde.
2) Nyob rau hauv lub xub ntiag ntawm ethanol thiab anhydrous sodium hydroxide tov, cov tshuaj tiv thaiv yog catalyzed.
3) Tom qab cov tshuaj tiv thaiv, yaug nrog dej khov thiab lim cov khoom kom tau txais imidazole acetone aldimine.
2. Benzoic acid derivative cov tshuaj tiv thaiv:
Benzoic acid derivatives yog cov tshuaj tsis ruaj khov uas tuaj yeem tsim cov tshuaj ruaj khov dua los ntawm ntau yam kev cuam tshuam. Hauv qab no yog cov tshuaj tiv thaiv thiab cov kauj ruam ntxaws ntawm benzoic acid derivative:
2.1 Elemental analysis:
Benzoic acid derivatives tuaj yeem kuaj pom los ntawm kev txheeb xyuas cov ntsiab lus. Cov tshuaj ntsuam xyuas yuav hnov mob nrog cov tshuaj reagents los tsim cov pa roj, thiab tom qab ntawd cov roj yuav nkag mus rau hauv cov khoom siv tshuaj ntsuam xyuas kom pom. Qhov sib npaug ntawm cov tshuaj tiv thaiv yog raws li nram no:
C7H7O2plus O2→ CO2ntxiv H2O
Cov kauj ruam nrhiav tau yog raws li nram no:
1) Muab cov benzoic acid derivative rau hauv lub khob ntim ua ntej qhov hnyav.
2) Ntxiv cov khoom oxidizer (xws li tooj liab oxide) thiab sib tov zoo.
3) Siv lub teeb los hlawv cov pa oxygen-absorbing paj rwb nyob rau hauv qab ntawm lub raj mis thiab ignite cov tshuaj tiv thaiv sib tov.
4) Muab cov roj tso rau hauv lub ntsuas hluav taws xob txhawm rau kuaj pom.
2.2 Cov tshuaj tiv thaiv nrog sodium nitrite:
Benzoic acid derivatives tuaj yeem hnov mob nrog sodium nitrite los tsim benzimidazoles. Qhov sib npaug ntawm cov tshuaj tiv thaiv yog raws li nram no:
C7H7O2 plus NaNO2HCl → C11H8N2NaCl plus 2H2O
Ntawm lawv, C7H7O2sawv cev rau benzoic acid derivative, thiab C11H8N2sawv cev rau benzimidazole.
Cov kauj ruam tshuaj tiv thaiv yog raws li nram no:
1) Dissolve benzoic acid derivative nyob rau hauv concentrated hydrochloric acid.
2) Ntxiv sodium nitrite tov thiab do kom sib tov.
3) React ntawm chav tsev kub rau 6-8 teev.
4) Tom qab cov tshuaj tiv thaiv, ntxiv sodium hydroxide tov los kho tus nqi pH rau 7.
5) Ntxuav nrog ethanol, lim cov khoom kom tau txais benzimidazole.
3. Cov tshuaj tiv thaiv carboxylic acid derivatives:
Carboxylic acid derivatives yog ib chav kawm ntawm cov khoom siv dav siv uas tuaj yeem tsim lwm cov organic tebchaw los ntawm ntau yam kev cuam tshuam. Cov hauv qab no yog cov tshuaj tiv thaiv thiab cov kauj ruam ntxaws ntawm carboxylic acid derivatives:
3.1 Ntxiv cov tshuaj tiv thaiv:
Carboxylic acid derivatives tuaj yeem raug ntxiv cov tshuaj tiv thaiv nrog ob daim ntawv cog lus los tsim cov allyl carboxylic acid derivatives. Qhov sib npaug ntawm cov tshuaj tiv thaiv yog raws li nram no:
R-COOH plus H2C=CH-CN → R-COOCH=CHCH2CN
Ntawm lawv, R-COOH sawv cev rau carboxylic acid derivative, thiab H2C=CH-CN sawv cev rau ob daim ntawv cog lus.
Cov kauj ruam tshuaj tiv thaiv yog raws li nram no:
1) Sib tov carboxylic acid derivative thiab ob daim ntawv cog lus.
2) Ntxiv cov catalyst (xws li txhuas trichloride) thiab sib tov zoo.
3) Npuas nitrogen thiab do cov sib tov.
4) React rau ob peb teev ntawm chav tsev kub.
5) Tom qab cov tshuaj tiv thaiv, yaug nrog dej txias thiab lim cov khoom kom tau txais allyl carboxylic acid derivatives.
3.2 Carbonylation cov tshuaj tiv thaiv:
Carboxylic acid derivatives tuaj yeem tsim cov tshuaj carbonyl los ntawm cov tshuaj tiv thaiv carbonylation. Qhov sib npaug ntawm cov tshuaj tiv thaiv yog raws li nram no:
R-COOH plus (COCl)2→ R-COCl plus CO2plus HCl
Ntawm lawv, R-COOH sawv cev rau carboxylic acid derivative, thiab (COCl)2sawv cev rau carbonyl chloride.
Cov kauj ruam tshuaj tiv thaiv yog raws li nram no:
1) Carboxylic acid derivative thiab carbonyl chloride yog sib xyaw.
2) Ntxiv cocatalyst (xws li dichloromethane) thiab sib tov zoo.
3) React rau ob peb teev ntawm qhov kub thiab txias.
4) Tom qab cov tshuaj tiv thaiv dhau lawm, ntxiv cov reactant rau hauv dej khov, do thiab txias, thiab ntxiv sodium hydroxide tov rau neutralize.
5) Ntxuav nrog ether thiab lim cov khoom kom tau txais carbonyl compound.
Hauv cov ntsiab lus, imidazolactone, benzoic acid, thiab carboxylic acid derivatives ntawm Tetramisole Hcl yog cov organic tebchaw uas txhua tus tuaj yeem tsim lwm cov organic tebchaw los ntawm ntau yam kev cuam tshuam. Cov tshuaj sib txawv yuav tsum muaj cov kauj ruam sib txawv kom tau txais cov khoom xav tau.
Qhov zoo: cov nqi tsim khoom qis thiab yooj yim purification ntawm cov khoom siv tshuaj tiv thaiv.
Disadvantages: Cov tshuaj tiv thaiv tej yam kev mob hnyav thiab tawm los yog tsawg.