Synthesis ntawm Hydroxypropyl Methyl Cellulose Acetate thiab Propionate

Siv hydroxypropyl methylcellulose (HPMC) ua raw khoom, acetic anhydride thiab propionic anhydride ua esterification agents, cov tshuaj esterification hauv pyridine npaj hydroxypropyl methylcellulose acetate thiab hydroxypropyl methylcellulose Cellulose propionate. Los ntawm kev hloov tus nqi ntawm cov kuab tshuaj siv nyob rau hauv lub system, ib yam khoom uas muaj cov khoom zoo dua qub thiab hloov cov degree tau txais. Kev hloov pauv qib tau txiav txim siab los ntawm txoj kev titration, thiab cov khoom tau raug tus cwj pwm thiab sim rau kev ua haujlwm. Cov txiaj ntsig tau pom tias cov tshuaj tiv thaiv kab mob tau tshwm sim ntawm 110°C rau 1-2.5 h, thiab cov dej deionized tau siv los ua tus neeg sawv cev ua ntej tom qab cov tshuaj tiv thaiv, thiab cov khoom siv hmoov uas muaj kev hloov pauv ntau dua 1 (theoretical degree ntawm kev hloov pauv yog 2) tuaj yeem tau. Nws muaj zoo solubility nyob rau hauv ntau yam organic solvents xws li ethyl ester, acetone, acetone / dej, thiab lwm yam.

Lo lus tseem ceeb: hydroxypropyl methylcellulose; hydroxypropyl methylcellulose acetate; Hydroxypropyl methylcellulose propionate hmoov

Hydroxypropylmethylcellulose (HPMC) yog non-ionic polymer compound thiab cellulose ether nrog ntau yam kev siv. Raws li ib qho tshuaj ntxiv zoo heev, HPMC feem ntau siv rau hauv ntau qhov chaw thiab hu ua "kev lag luam monosodium glutamate". Hydroxypropyl methylcellulose (HPMC) tsis tsuas yog muaj emulsifying zoo, thickening, thiab binding zog, tab sis kuj siv tau los tswj cov dej noo thiab tiv thaiv colloids. Nws yog dav siv nyob rau hauv ntau lub teb xws li zaub mov, tshuaj, txheej, textiles, thiab kev ua liaj ua teb. . Kev hloov kho ntawm hydroxypropyl methylcellulose tuaj yeem hloov qee yam ntawm nws cov khoom, kom nws tuaj yeem siv tau zoo dua hauv qee qhov chaw. Cov mis mos molecular ntawm nws cov monomer yog C10H18O6.

Nyob rau hauv xyoo tas los no, kev tshawb fawb ntawm hydroxypropyl methylcellulose derivatives tau maj mam dhau los ua qhov chaw kub. Los ntawm kev hloov kho hydroxypropyl methylcellulose, ntau yam derivative tebchaw nrog cov khoom sib txawv tuaj yeem tau txais. Piv txwv li, kev qhia txog cov pab pawg acetyl tuaj yeem hloov tau yooj yim ntawm cov txheej txheem kho mob.

Kev hloov kho ntawm hydroxypropyl methylcellulose feem ntau yog ua los ntawm cov kua qaub catalyst xws li concentrated sulfuric acid. Qhov kev sim no feem ntau siv acetic acid ua cov kuab tshuaj. Cov tshuaj tiv thaiv tej yam kev mob yog cumbersome thiab lub sij hawm-siv, thiab cov resulting khoom muaj ib tug tsawg degree ntawm kev hloov. (tsawg dua 1).

Hauv daim ntawv no, acetic anhydride thiab propionic anhydride tau siv los ua cov tshuaj esterification los hloov hydroxypropyl methylcellulose los npaj hydroxypropyl methylcellulose acetate thiab hydroxypropyl methylcellulose propionate. Los ntawm kev tshawb xyuas cov xwm txheej xws li kev xaiv cov kuab tshuaj (pyridine), hnyav npaum li cas, thiab lwm yam, nws cia siab tias cov khoom lag luam nrog cov khoom zoo dua thiab kev hloov pauv tuaj yeem tau txais los ntawm txoj kev yooj yim. Nyob rau hauv daim ntawv no, los ntawm kev soj ntsuam kev tshawb fawb, lub hom phiaj cov khoom uas muaj ib tug hmoov precipitate thiab ib tug degree ntawm kev hloov ntau dua 1 tau, uas muab ib co theoretical kev taw qhia rau zus tau tej cov hydroxypropyl methylcellulose acetate thiab hydroxypropyl methylcellulose propionate.

1. Kev sim ib feem

1.1 Cov ntaub ntawv thiab cov tshuaj reagents

Pharmaceutical qib hydroxypropyl methylcellulose (KIMA CHEMICAL CO., LTD, 60HD100, methoxyl pawg feem 28%-30%, hydroxypropoxyl pawg feem 7%-12%); acetic anhydride, AR, Sinopharm Group Chemical Reagent Co., Ltd.; Propionic Anhydride, AR, West Asia Reagent; Pyridine, AR, Tianjin Kemiou Chemical Reagent Co., Ltd.; methanol, ethanol, ether, ethyl acetate, acetone, NaOH thiab HCl yog cov khoom lag luam muaj kev tshuaj ntsuam xyuas ntshiab.

KDM thermostat hluav taws xob cua sov mantle, JJ-1A ceev ntsuas cov zaub hluav taws xob stirrer, NEXUS 670 Fourier hloov infrared spectrometer.

1.2 Kev npaj ntawm hydroxypropyl methylcellulose acetate

Ib qho nyiaj ntawm pyridine tau ntxiv rau hauv peb-caj dab, thiab tom qab ntawd 2.5 g ntawm hydroxypropyl methylcellulose tau ntxiv rau ntawd, cov reactants tau nplawm tusyees, thiab qhov kub tau nce mus rau 110.°C. Ntxiv 4 mL ntawm acetic anhydride, react ntawm 110°C rau 1 h, nres cua sov, txias rau hauv chav tsev kub, ntxiv ib tug loj npaum li cas ntawm deionized dej los precipitate cov khoom, lim nrog suction, ntxuav nrog deionized dej rau ob peb zaug kom txog thaum lub eluate yog nruab nrab, thiab qhuav cov khoom txuag.

1.3 Kev npaj ntawm hydroxypropyl methylcellulose propionate

Ib qho nyiaj ntawm pyridine tau ntxiv rau hauv lub khob peb-caj dab, thiab tom qab ntawd 0.5 g ntawm hydroxypropyl methylcellulose tau ntxiv rau ntawd, cov reactants tau nplawm tusyees, thiab qhov kub tau nce mus rau 110.°C. Ntxiv 1.1 mL ntawm propionic anhydride, react ntawm 110°C rau 2.5 h, nres cua sov, txias rau hauv chav tsev kub, ntxiv ib tug loj npaum li cas ntawm deionized dej los precipitate cov khoom, lim nrog suction, ntxuav nrog deionized dej rau ob peb zaug kom txog thaum lub eluate yog nruab nrab khoom, khaws cov khoom qhuav.

1.4 Kev txiav txim siab ntawm infrared spectroscopy

Cov hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate, hydroxypropyl methylcellulose propionate thiab KBr tau tov thiab hauv av feem, thiab tom qab ntawd nias rau hauv cov ntsiav tshuaj los txiav txim siab qhov infrared spectrum.

1.5 Kev txiav txim siab ntawm kev hloov pauv

Npaj NaOH thiab HCl cov kev daws teeb meem nrog rau qhov concentration ntawm 0.5 mol / L, thiab ua tiav kev ntsuas kom txiav txim siab qhov tseeb; hnyav 0.5 g ntawm hydroxypropylmethylcellulose acetate (hydroxypropylmethylcellulose propionic acid ester) nyob rau hauv 250 mL Erlenmeyer lub hwj, ntxiv 25 mL ntawm acetone thiab 3 tee ntawm phenolphthalein qhia, sib tov zoo, ces ntxiv 25 mL ntawm NaOH electromagnetic tov rau ntawm ib tug stirr thiab 2 h;ua. titrate nrog HCI kom txog thaum cov xim liab ntawm cov tshuaj ploj, sau cov ntim V1 (V2) ntawm hydrochloric acid noj; siv tib txoj kev los ntsuas qhov ntim V0 ntawm hydrochloric acid noj los ntawm hydroxypropyl methylcellulose, thiab xam qhov degree ntawm kev hloov.

1.6 Kev sim Solubility

Noj cov khoom uas tsim nyog ntawm cov khoom siv hluavtaws, ntxiv rau cov organic hnyav, co me ntsis, thiab saib xyuas cov khoom tawg.

2. Cov txiaj ntsig thiab kev sib tham

2.1 Cov txiaj ntsig ntawm cov nyiaj pyridine (cov kuab tshuaj)

Kev cuam tshuam ntawm ntau qhov sib txawv ntawm pyridine ntawm morphology ntawm hydroxypropylmethylcellulose acetate thiab hydroxypropylmethylcellulose propionate. Thaum cov kuab tshuaj tsawg dua, nws yuav txo qhov extensibility ntawm macromolecular saw thiab viscosity ntawm lub cev, kom cov degree ntawm esterification ntawm cov tshuaj tiv thaiv yuav raug txo, thiab cov khoom yuav raug precipitated raws li ib tug loj pawg. Thiab thaum tus nqi ntawm cov kuab tshuaj tsawg dhau lawm, cov reactant yog ib qho yooj yim rau condense rau hauv ib lub pob thiab ua raws li lub thawv ntim phab ntsa, uas tsis yog tsuas yog tsis zoo rau kev nqa tawm ntawm cov tshuaj tiv thaiv, tab sis kuj ua rau muaj kev tsis txaus siab rau kev kho mob tom qab cov tshuaj tiv thaiv. . Hauv kev sib xyaw ntawm hydroxypropyl methylcellulose acetate, tus nqi ntawm cov kuab tshuaj siv tau raug xaiv raws li 150 mL / 2 g; Rau kev sib txuas ntawm hydroxypropyl methylcellulose propionate, nws tuaj yeem raug xaiv raws li 80 mL / 0.5 g.

2.2 Infrared spectrum tsom xam

Infrared sib piv daim duab ntawm hydroxypropyl methylcellulose thiab hydroxypropyl methylcellulose acetate. Piv nrog rau cov khoom siv raw, qhov infrared spectrogram ntawm cov khoom hydroxypropyl methylcellulose acetate muaj kev hloov pauv ntau dua. Nyob rau hauv lub infrared spectrum ntawm cov khoom, ib tug muaj zog ncov tshwm sim ntawm 1740cm-1, qhia tau hais tias ib tug carbonyl pawg tau tsim; Tsis tas li ntawd, qhov kev siv zog ntawm qhov stretching vibration ncov ntawm OH ntawm 3500cm-1 yog qis dua li ntawm cov khoom siv raw, uas kuj tau qhia tias -OH Muaj cov tshuaj tiv thaiv.

Lub infrared spectrogram ntawm cov khoom hydroxypropyl methylcellulose propionate kuj tau hloov pauv loj piv nrog cov khoom siv raw. Nyob rau hauv infrared spectrum ntawm cov khoom, ib tug muaj zog ncov tshwm sim ntawm 1740 cm-1, qhia tau hais tias ib tug carbonyl pawg tau tsim; Tsis tas li ntawd, OH stretching vibration peak siv ntawm 3500 cm-1 yog qis dua li ntawm cov khoom siv raw, uas kuj tau qhia tias OH reacted.

2.3 Kev txiav txim siab ntawm kev hloov pauv

2.3.1 Kev txiav txim siab ntawm kev hloov qib ntawm hydroxypropyl methylcellulose acetate

Txij li thaum hydroxypropyl methylcellulose muaj ob OH nyob rau hauv txhua chav tsev, thiab cellulose acetate yog cov khoom tau los ntawm kev hloov ib COCH3 rau H hauv ib OH, qhov theoretical siab tshaj plaws ntawm kev hloov pauv (Ds) yog 2.

2.3.2 Kev txiav txim siab ntawm kev hloov pauv ntawm hydroxypropyl methylcellulose propionate

2.4 Solubility ntawm cov khoom

Ob yam khoom sib xyaw ua ke muaj cov yam ntxwv zoo sib xws, thiab hydroxypropyl methylcellulose acetate yog me ntsis soluble dua li hydroxypropyl methylcellulose propionate. Cov khoom siv hluavtaws tuaj yeem yaj hauv acetone, ethyl acetate, acetone / dej sib xyaw hnyav, thiab muaj kev xaiv ntau dua. Tsis tas li ntawd, cov dej noo uas muaj nyob hauv acetone / dej sib xyaw hnyav tuaj yeem ua rau cov cellulose derivatives muaj kev nyab xeeb dua thiab zoo ib puag ncig thaum siv los ua cov ntaub ntawv txheej.

3. Cov lus xaus

(1) Lub synthesis tej yam kev mob ntawm hydroxypropyl methylcellulose acetate yog raws li nram no: 2.5 g ntawm hydroxypropyl methylcellulose, acetic anhydride li esterification tus neeg sawv cev, 150 mL ntawm pyridine raws li hnyav, cov tshuaj tiv thaiv kub ntawm 110° C, thiab lub sijhawm tshuaj tiv thaiv 1 h.

(2) Lub synthesis tej yam kev mob ntawm hydroxypropyl methylcellulose acetate yog: 0.5 g ntawm hydroxypropyl methylcellulose, propionic anhydride li esterification tus neeg saib xyuas, 80 mL ntawm pyridine li hnyav, tshuaj tiv thaiv kub ntawm 110°C, thiab cov tshuaj tiv thaiv lub sij hawm ntawm 2.5 h.

(3) Cov cellulose derivatives synthesized nyob rau hauv cov mob no yog ncaj qha nyob rau hauv daim ntawv ntawm cov hmoov zoo nrog ib tug zoo degree ntawm kev hloov, thiab ob cellulose derivatives yuav yaj nyob rau hauv ntau yam organic solvents xws li ethyl acetate, acetone, thiab acetone / dej.