Primidone(link:https://www.bloomtechz.com/synthetic-chemical/api-researching-only/primidone-powder-cas-125-33-7.html) yog ib qho tshuaj tiv thaiv kab mob uas muaj lub nplhaib isoprene thiab ob pawg carboxyl ua haujlwm hauv nws cov qauv. Cov txheej txheem hluavtaws ntawm Primidone yuav qhia hauv qab no.
1. Ethyl acetoacetate thiab urea txoj kev
Qhov no yog cov txheej txheem synthesis ntxov ntawm Primidone. Cov txheej txheem yog los ua Ethyl acetoacetate thiab urea los npaj Primidone, thiab cov kauj ruam yog raws li nram no:
(1) Thaum tshav kub kub Ethyl acetoacetate thiab urea nyob rau hauv kiag li ethanol thiab yaj nyob rau hauv stirring.
(2) Nyob rau hauv cov cua kub, ntxiv 0.5 moles ntawm txhuas acetate thiab poov tshuaj nitrate, thiab teb rau 24 teev.
(3) Acidification, distillation, extraction, txias, thiab sib cais ntawm Primidone crystals.
Txoj kev no muaj qee qhov zoo: cov khoom siv raw yog ib qho yooj yim kom tau, kev ua haujlwm yog yooj yim, tab sis lub sij hawm cov tshuaj tiv thaiv ntev thiab cov tawm los tsis siab.
2. -carbolinone txoj kev
Txoj kev no yog ib qho tseem ceeb tshaj plaws hluavtaws txoj kev ntawm Primidone, thiab cov kauj ruam yog raws li nram no:
2.1. Synthesis ntawm -carbolinone
Ua ntej ntawm tag nrho cov, nws yog ib qhov tsim nyog los ua ke -carbolinone, thiab nws txoj kev hluavtaws yog raws li nram no:
(1) Npaj oxane-2,5-dione (1,3-cyclohexanedione) los ntawm condensation cov tshuaj tiv thaiv ntawm benzaldehyde thiab acetone.
(2) React cyclohexanedione nrog acetic anhydride thiab sulfuric acid los ua 4-oxo-4-benzoylcyclohexane-1,3-dione (molecular formula C13H12O4), los yog hu ua {{8} }(benzoyl) -4-oxo-1, 3-cyclohexanedione los yog butyrolactone.
(3) Knoevenagel condensation cov tshuaj tiv thaiv ntawm butyrolactone nyob rau hauv catalysis ntawm poov tshuaj carbonate, cov tshuaj tiv thaiv nrog acetophenone los ua -benzylidene butyrolactic acid, thiab hydrogenation txo kom tau -benzylidene - -butyrolactic acid .
(4) Raws li Claisen condensation cov tshuaj tiv thaiv, -benzylidene- -butyrolactic acid thiab octyl acetate tau reacted los ntawm cua sov kom tau ethyl -(2-octyl acetate)carbazole-5-carboxylate (4,{ {7}} ethyl diphenyl-2, 3-carbazoledione-5-carboxylate).
(5) Thaum kawg, ethyl -(2-octyl acetate)carbazole-5-carboxylate tau hydrolyzed los ntawm lub hauv paus catalysis kom tau -carbolinone. Cov kauj ruam no yog kauj ruam tseem ceeb hauv kev sib txuas ntawm Primidone hauv txoj kev no.
2.2. Synthesis ntawm Primidone
Lub synthesis ntawm Primidone tuaj yeem ua tiav los ntawm cov kauj ruam hauv qab no:
(1) Ib qho nruab nrab yog tau los ntawm condensation cov tshuaj tiv thaiv ntawm -carbolinone thiab cymenophenone.
(2) Catalyzed los ntawm phosphorus pentachloride kom hnov mob nruab nrab nrog 1, 3-dioxane-2, 5-dione kom tau txais qhov nruab nrab tshiab.
(3) Thaum kawg, ib qho catalyst yog siv los catalyze qhov thib ob condensation los tsim Primidone.
Hauv cov kauj ruam saum toj no, thawj kauj ruam yog kom condense -carbolinone thiab cymenophenone kom tau txais ib qho nruab nrab. Sodium carbonate yuav tsum tau siv los ua catalyst hauv cov tshuaj tiv thaiv no, thiab cov tshuaj tiv thaiv yog nqa tawm hauv methanol. Hauv cov tshuaj tiv thaiv no, cov pab pawg carbonyl ntawm -carbolinone thiab cumenone hnov mob nrog sodium carbonate los ua cawv. Cov cawv no muaj ob lub nplhaib sib koom ua ke, uas yog ob lub nplhaib-carbolinone uas muaj nyob hauv Primidone molecule. Cov cawv tuaj yeem koom nrog hauv cov tshuaj tiv thaiv tom ntej raws li cov tshuaj reactant tshiab.
Qhov thib ob theem yog catalyzed los ntawm phosphorus pentachloride, thiaj li hais tias ib tug tshiab intermediate yog tsim. Nyob rau hauv cov qauv molecular ntawm qhov nruab nrab, cov pa atom sib koom ntawm lub nplhaib -carbolinone thiab pawg cumenone, tsim lub nplhaib. Lub nplhaib no yog qhov ua ntej rau cov tshuaj tiv thaiv hauv qib 3.
Qhov thib peb kauj ruam yog cov synthesis ntawm Primidone. Nyob rau hauv cov kauj ruam no, sodium hydroxide los yog poov tshuaj hydroxide yog siv los catalyze ib tug thib ob condensation cov tshuaj tiv thaiv rau tsim Primidone los ntawm cov saum toj no nruab nrab. Thaum lub sij hawm tus txheej txheem no, tus intermediate undergoes ib tug intracyclic condensation cov tshuaj tiv thaiv, yog li ua kom tiav cov synthesis ntawm Primidone.
Feem ntau, txoj kev -carbolinone synthesis yog ib qho kev sib xyaw ua ke ntawm Primidone, uas ua tiav siv ntau yam kev cuam tshuam xws li Claisen condensation, Knoevenagel cov tshuaj tiv thaiv thiab intracyclic condensation kom paub cov synthesis ntawm Primidone.
3. 2-methyl-2-butenoic acid methyl ester method
Txoj kev no yog los ntawm 2-methyl-2-butenoic acid methyl ester, npaj Primidone los ntawm cov tshuaj tiv thaiv, thiab cov kauj ruam yog raws li nram no:
(1) Thaum tshav kub kub 2-methyl{2}}butenoic acid methyl ester thiab urea nyob rau hauv kiag li ethanol los tsim Primidone intermediate.
(2) Ntxiv sodium hydroxide rau qhov tshwm sim nruab nrab thiab ua hydrolysis los tsim Primidone.
3.1. Txoj kev hluavtaws ntawm 2-methyl-2-butenoic acid methyl ester yog raws li nram no:
(1) Cov tshuaj tiv thaiv ntawm isoprene thiab formic acid kom tau txais 3-methylfuran-2-carboxylic acid.
(2) Cov tshuaj tiv thaiv ntawm isopentene 3-formate thiab trimethylalumina ntawm qhov kub thiab txias los tsim ua haujlwm hydroxypyridine (4-hydroxy-2-methylpyridine).
(3) Nyob rau hauv lub xub ntiag ntawm sodium hydroxide, ntxiv dimethyl phosphite (Diethyl phosphite) los ua haujlwm nrog hydroxypyridine nyob rau hauv lub catalysis ntawm polyamide los tsim 2-methyl-2-butenoic acid methyl ester (Ethyl {{3}) } methyl-2-butenoate).
Nyob rau hauv cov kauj ruam saum toj no, thawj kauj ruam yog ua ntej react isoprene nrog formic acid kom tau txais 3-isopentene formate, thiab tom qab ntawd los ntawm ob kauj ruam ntawm kev txo qis thiab acid catalysis thaum kawg tau txais ib qho kev ua haujlwm pyridine. Ntawm lawv, cov kauj ruam txo qis yuav hloov cov pab pawg carboxyl qhia rau hauv pawg cawv; cov kua qaub catalysis kauj ruam tuaj yeem ua rau pawg hydroxyl ntawm lub nplhaib dehydrate thiab tshem tawm thaum tsim cov pyridine compound. Kauj ruam 3 ces yog kauj ruam tseem ceeb ntawm reacting 2-methyl-2-butenoic acid methyl ester.
3. 2. Cov txheej txheem synthesis ntawm Primidone yog raws li nram no:
(1) Methyl 2-methyl-2-butenoate thiab benzaldehyde tau txais Claisen condensation cov tshuaj tiv thaiv los tsim -benzylidene- -butyrolactate.
(2) Nyob rau hauv lub xub ntiag ntawm sodium hydroxide, -benzylidene- -butyrolactate dhau los ua cov tshuaj tiv thaiv lactonization los tsim 4-benzoyloxy-4-benzylidenecyclohexanedione.
(3) React 4-benzoyloxy-4-benzylidenecyclohexanedione thiab isomenthylidene piperidine nyob rau hauv muaj phosphorus pentafluoride los tsim Primidone.
Hauv cov kauj ruam saum toj no, thawj kauj ruam yog los tsim -benzylidene- -butyrolactate los ntawm Claisen condensation cov tshuaj tiv thaiv ntawm 2-methyl-2-butenoic acid methyl ester thiab benzaldehyde. Cov tshuaj tiv thaiv no yuav tsum tau ua nyob rau hauv lub xub ntiag ntawm sodium hydroxide, thiab cov tshuaj tiv thaiv cov khoom yuav ua tau ntxiv lactonized.
Hauv qib thib ob, -benzylidene- -butyrolactate dhau los ua cov tshuaj tiv thaiv lactonization los tsim 4-benzoyloxy-4-benzylidenecyclohexanedione. Cov tshuaj tiv thaiv no tau ua tiav los ntawm kev tshem tawm cov dej cawv molecule, thiab lwm cov txiaj ntsig ntawm sodium hydroxide yog decarboxylate cov butyrolactic acid moiety hauv -benzylidene- -butyrolactate. Cov khoom kawg yog 4-benzoyloxy-4-benzylidenecyclohexanedione. Nws cov qauv muaj cov precursors ntawm ob-carbolinone rings.
Hauv kauj ruam 3, cov ntaub ntawv tseem ceeb ntawm Primidone: 4-benzoyloxy-4-benzylidenecyclohexanedione thiab isomenthylidenepiperidine yog reacted los ntawm catalysis ntawm phosphorus pentafluoride los tsim Primidone . Hauv cov txheej txheem tshuaj tiv thaiv no, isomengthylidene piperidine ua lub luag haujlwm tseem ceeb hauv kev txhawb nqa cov tshuaj tiv thaiv intracyclic condensation ntawm ob lub reactants. Primidone yog synthesized los ntawm cov kauj ruam no.
Feem ntau hais lus, cov txheej txheem hluavtaws ntawm 2-methyl-2-butenoic acid methyl ester yog ib qho ntawm cov txheej txheem hluavtaws tseem ceeb ntawm Primidone. Txoj kev paub txog kev sib txuas ntawm Primidone los ntawm ntau yam kev cuam tshuam xws li Claisen condensation, lactonization cov tshuaj tiv thaiv thiab phosphorus pentafluoride catalysis. Cov ntaub ntawv raw uas xav tau los ntawm txoj kev yog yooj yim kom tau thiab yooj yim rau kev khiav lag luam, thiab nws yog ib txoj hauv kev tseem ceeb rau kev lag luam loj loj ntawm Primidone.
4. Acid-catalyzed txoj kev:
Txoj kev yog nqa tawm cov kua qaub catalysis hauv -carbolinone thiab acetic acid kom tau txais Primidone. Ua raws li hauv qab no:
(1) Ntxiv -carbolinone rau hauv acetic acid, ntxiv acidic catalyst, thiab do kom txog thaum yaj tag.
(2) Ntxiv sodium carbonate rau cov tshuaj tiv thaiv kab mob thiab txuas ntxiv nplawm.
(3) Cov txheej txheem tshuaj tiv thaiv tau sib cais, cov khoom raug lim, thiab cov khoom siv lead ua Primidone tau muab rho tawm nrog ether.
Txoj kev no yooj yim rau kev khiav lag luam thiab tsis tas yuav siv sodium hydroxide hydrolysis, tab sis cov txiaj ntsig qis thiab nws tsis haum rau cov khoom loj.
Cov kauj ruam tshwj xeeb ntawm Primidone acid-catalyzed txoj kev yog raws li hauv qab no:
Thawj kauj ruam: npaj methyl 2-phenyl-2-butenoate.
Txoj kev hluavtaws ntawm 2-phenyl-2-butenoic acid methyl ester yog raws li nram no:
(1) Trans-pentadienoic acid thiab vinyl methyl ether undergo Claisen condensation cov tshuaj tiv thaiv los tsim 2-methyl-2-butenoic acid methyl ester.
(2) Nyob rau hauv lub xub ntiag ntawm sodium hydroxide, 2-methyl-2-butenoic acid methyl ester thiab benzaldehyde undergo Claisen condensation cov tshuaj tiv thaiv los tsim 2-phenyl-2-butenoic acid methyl ester.
Claisen condensation cov tshuaj tiv thaiv yog ib chav kawm ntawm cov tshuaj tiv thaiv uas txuas ob lub molecules uas muaj cov methylene active pawg los ntawm kev tsim cov carbon-carbon bonds. Cov tshuaj tiv thaiv no yog ib qho ntawm cov kauj ruam tseem ceeb hauv kev sib xyaw ntawm Primidone.
Qhov thib ob theem: synthesis ntawm Primidone.
Lub synthesis ntawm Primidone yuav tsum muaj ob qho kev ua kua qaub-catalyzed. Cov kauj ruam tshwj xeeb yog raws li hauv qab no:
(1) Ua ntej, nyob rau hauv ib puag ncig uas muaj cov catalyst (xws li tetrahydrofuran lossis ethanol), 2-phenyl-2-butenoic acid methyl ester thiab benzaldehyde raug rau cov tshuaj tiv thaiv acid-catalyzed los tsim {{4} }(4-benzoyloxy Benzyl)-2-butenoic acid methyl ester. Cov tshuaj tiv thaiv no ua rau cov kua qaub-catalyzed condensation ntawm carbonyl pawg ntawm benzaldehyde nrog hydroxyl pawg ntawm methyl 2-phenyl-2-butenoate los ua cov 4-benzoyloxybenzyl cawv moiety.
(2) Nyob rau hauv lub xub ntiag ntawm tib lub catalyst, ua cov tshuaj tiv thaiv acid-catalyzed ntawm cov tshuaj tiv thaiv cov khoom ntawm cov kauj ruam dhau los thiab dimethylformamide kom tau txais Primidone. Cov tshuaj tiv thaiv no yuav ua rau 4-benzoyloxybenzyl cawv ib feem hauv cov khoom siv tshuaj tiv thaiv ntawm cov kauj ruam dhau los ua ke nrog diformamide los tsim cov qauv ntawm ob-carbolinone rings.
Cov tshuaj tiv thaiv mechanism ntawm Primidone acid-catalyzed txoj kev yog raws li nram no:
Ua ntej, 2-phenyl{1}}butenoic acid methyl ester thiab benzaldehyde tau txais cov kua qaub-catalyzed Claisen condensation cov tshuaj tiv thaiv los tsim 2-(4-benzoyloxybenzyl)-2-butenoic acid methyl ester. Thaum lub sij hawm cov tshuaj tiv thaiv, cov carbonyl ib feem ntawm benzaldehyde thiab hydroxyl ib feem ntawm 2-phenyl-2-butenoic acid methyl ester tsim ib tug adduct nyob rau hauv tsib-membered nplhaib, thiab nyob rau tib lub sij hawm tsim 1,{{10 }} cov khoom ua kom lub cev qhuav dej, piv txwv li ketool.
Tom qab ntawd, 2-(4-benzoyloxybenzyl)-2-butenoic acid methyl ester thiab diformamide react nyob rau hauv acid catalysis los tsim Primidone. Cov kauj ruam ntawm kev sib xyaw ua ke yog raws li hauv qab no:
(1) Lub hydrogen atom ntawm ketone cawv tsim ib daim ntawv cog lus hydrogen nrog OH^- nyob rau hauv cov catalyst (xws li tetrahydrofuran los yog ethanol), kom cov carbonyl thiab lwm qhov chaw raug xa mus rau sab nraud, ua rau nws yog ib pab pawg tawm zoo.
(2) Raws li lub hauv paus no, ketone cawv yog condensed los ua ib lub nplhaib ob leeg, thiab tom qab ntawd cov tshuaj tiv thaiv nucleophilic ntxiv tshwm sim los tsim cov precursor ntawm Primidone 3-(4-benzoyloxybenzyl){{4} }hydroxy-2, 5 - Dimethyl- -carbolinone.
(3) Hauv cov kauj ruam kawg, lub nplhaib lub cev qhuav dej tshwm sim dua nyob rau hauv lub precursor molecule ntawm Primidone los tsim cov khoom kawg Primidone.
Zuag qhia tag nrho, nyob rau hauv cov kua qaub-catalyzed synthesis ntawm Primidone, ob Claisen condensations tau ua ib ntus, yog li sib txuas benzaldehyde thiab methyl 2-phenyl-2-butenoate los tsim cov molecular precursor ntawm Primidone. Cov txheej txheem no yuav tsum tau acid catalysis los txhawb cov tshuaj tiv thaiv. Los ntawm txoj kev no, Primidone tuaj yeem tau txais txiaj ntsig zoo thiab yooj yim, thiab nws yog txoj kev siv hluavtaws dav dav.
Nyob rau hauv luv luv, lub ntsiab txoj kev rau synthesizing Primidone yog -carbolinone txoj kev, 2-methyl-2-butenoic acid methyl ester txoj kev, acid-catalyzed txoj kev, thiab lwm yam, ntawm uas -carbolinone txoj kev yog qhov tseem ceeb tshaj plaws thiab feem ntau. siv. Nrog rau kev txhim kho thev naus laus zis, cov kws tshawb fawb tau tshawb nrhiav thiab txhim kho cov txheej txheem synthesis ntawm Primidone txhawm rau txhawm rau nce cov txiaj ntsig, txo tus nqi, thiab muab cov tshuaj zoo dua rau kev kho mob.