CS225512B1 - Process for preparing 2-hydroxyethylester of methacrylic acid - Google Patents
Process for preparing 2-hydroxyethylester of methacrylic acid Download PDFInfo
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- CS225512B1 CS225512B1 CS566982A CS566982A CS225512B1 CS 225512 B1 CS225512 B1 CS 225512B1 CS 566982 A CS566982 A CS 566982A CS 566982 A CS566982 A CS 566982A CS 225512 B1 CS225512 B1 CS 225512B1
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- Czechoslovakia
- Prior art keywords
- methacrylic acid
- mol
- ester
- hydroxyethylester
- preparing
- Prior art date
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- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 title claims description 4
- 238000004519 manufacturing process Methods 0.000 title 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- ZACNFVFUIHISPI-UHFFFAOYSA-N OC(=O)C(C)=CCCOCCO Chemical compound OC(=O)C(C)=CCCOCCO ZACNFVFUIHISPI-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- -1 ethyl methacrylic ester Chemical compound 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 6
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 6
- 239000000243 solution Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 3
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 229950000688 phenothiazine Drugs 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 2
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 229960003280 cupric chloride Drugs 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 2
- 229940073455 tetraethylammonium hydroxide Drugs 0.000 description 2
- LRGJRHZIDJQFCL-UHFFFAOYSA-M tetraethylazanium;hydroxide Chemical compound [OH-].CC[N+](CC)(CC)CC LRGJRHZIDJQFCL-UHFFFAOYSA-M 0.000 description 2
- NYKNKJCCLKRCKJ-UHFFFAOYSA-N 2-(2-hydroperoxyethoxy)ethanol Chemical compound OCCOCCOO NYKNKJCCLKRCKJ-UHFFFAOYSA-N 0.000 description 1
- OLQFXOWPTQTLDP-UHFFFAOYSA-N 2-(2-hydroxyethoxy)ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCOCCO OLQFXOWPTQTLDP-UHFFFAOYSA-N 0.000 description 1
- JJYWRQLLQAKNAD-UHFFFAOYSA-N 2-methylpent-2-enoic acid Chemical compound CCC=C(C)C(O)=O JJYWRQLLQAKNAD-UHFFFAOYSA-N 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M acrylate group Chemical group C(C=C)(=O)[O-] NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000009477 glass transition Effects 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000005397 methacrylic acid ester group Chemical group 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- LMHHRCOWPQNFTF-UHFFFAOYSA-N s-propan-2-yl azepane-1-carbothioate Chemical compound CC(C)SC(=O)N1CCCCCC1 LMHHRCOWPQNFTF-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Vynález se týká způsobu přípravy 2-hydroxyethoxyethyl esteru kyseliny methakrylové vzorceThe invention relates to a process for the preparation of a methacrylic acid 2-hydroxyethoxyethyl ester of the formula
ch2 = c . cooch2ch2och2ch2oh dále nazývaného diglykolmethakrylát, základního monomeru, který se polymeraci převádí na hydrofilní polymer, uplatňující se v řadě průmyslových odvětví, zejména v oblasti léčebné protetiky a farmacie, kde slouží k přípravě látek používaných k regulaci uvolňování účinných látek z lékových forem.ch 2 = c. cooch 2 ch 2 and 2 ch 2 oh hereafter called diglycol methacrylate, the basic monomer that converts polymerisation into hydrophilic polymer, used in a number of industries, especially in the field of therapeutic orthotics and pharmacy, where it serves to prepare substances used to control the release of active substances from dosage forms.
Diglykolmethakrylát se připravuje průmyslově reesterifikací esterů kyseliny methakrylové, například methyl- nebo ethylesteru, 2-/2-hydr’oxyethoxy/ethanolem(diethylenglykolemj, za katalýzy alkoholáty alkalických kovů, například methylátu,isopropylátu atd. Tato metoda poskytuje žádaný produkt v čistotě přijatelné pro technické účely. Při studiu čistoty látky určené pro medicínskou aplikaci bylo shledáno, že je nedostatečná a že je tedy nutné diglykolmethakrylát čistit dosti složitými postupy, neboť bylo prokázáno, že při popsaném provedení reesterifikace dochází současně, a to nikoliv v míře zanedbatelné, k adici alkoxidového iontu na dvoj nou vazbu akrylátového fragmentu za vzniku 1 až 5 % hmot. látek, které již dvojnou vazbu nemají. Tyto látky působí mj.bě225 512 hem polymerace jako inertní rozpouštědlo, což má za následek snížení hodnoty Tg /teplota skelného přechodu polymeru/. V praxi je tím zhoršena možnost mechanického opracování blokového polymeru. Také pro přípravu polymerů používaných ve farmacii k regulaci uvolňování účinných složek z farmaceutických lékových forem je nutno používat výchozího monomeru vysoké čistoty.Diglycol methacrylate is prepared industrially by esterification of methacrylic acid esters, for example methyl or ethyl ester, with 2- (2-hydroxyoxyethoxy) ethanol (diethylene glycol) under catalysis of alkali metal alcoholates such as methylate, isopropylate etc. This method yields the desired product in purity acceptable for technical In studying the purity of a substance intended for medical application, it has been found to be inadequate and therefore diglycol methacrylate needs to be purified by quite complex procedures, since it has been shown that the addition of alkoxide ion occurs simultaneously, and not negligibly to the double bond of the acrylate fragment to form 1 to 5% by weight of the non-double bonded materials, which, among other things, act as an inert solvent during the polymerization, resulting in a decrease in the Tg (glass transition temperature of the polymer). practice is thereby impaired Also for the preparation of polymers used in pharmacy to control the release of active ingredients from pharmaceutical dosage forms, it is necessary to use a high purity starting monomer.
Získání vysoce čisté látky pro uvedené účely umožnilo vypracování způsobu přípravy 2-hydroxyethoxyethylesteru kyseliny methakrylové reesterifikací methyl- nebo ethylesteru kyseliny methakrylové 2-/2-hydroxyethoxy/ethanolem podle vynálezu, jehož podstata spočívá v tom, že se reesterifikace provádí za přítomnosti katalyzátoru, kterým je kvarterní amoniová bázi obecného vzorceObtaining a high purity substance for this purpose has enabled the preparation of a process for the preparation of 2-hydroxyethoxyethyl methacrylic acid ester by reesterification of methyl or ethyl methacrylic acid ester with 2- (2-hydroxyethoxy) ethanol according to the invention. a quaternary ammonium base of the general formula
ve kterém fíj značí alkyl s 1 až 4 atomy uhlíku a Rg alkyl s 1 až 4 atomy uhlíku nebo benzyl, v množství 0,005 až 0,1 mol, vztaženo na 1 mol výchozího esteru kyseliny methakrylové jako katalyzátoru.in which F11 denotes alkyl of 1 to 4 carbon atoms and R g is alkyl of 1 to 4 carbon atoms or benzyl, in an amount of 0.005 to 0.1 mol, based on 1 mol of the methacrylic acid starting ester catalyst.
Provedení reesterifikace způsobem podle vynálezu je technicky velmi jednoduché a současně splňuje provozně význam né podmínky bezpečné práce. Jako katalyzátory je možno používat všechny běžně dostupné a cenově přijatelné kvartérní amoniové báze. Jako nejvýhodnější se jeví například tetramethylamoniumhydroxid, tetraethylamoniumhydroxid, trimethylbenzylamoniumhydroxid apod.The reesterification by the method according to the invention is technically very simple and at the same time fulfills the operationally important conditions of safe work. All commercially available and affordable quaternary ammonium bases can be used as catalysts. Tetramethylammonium hydroxide, tetraethylammonium hydroxide, trimethylbenzylammonium hydroxide and the like seem to be most preferred.
Provedení reesterifikace způsobem podle vynálezu nevybočuje nikterak z norem obvyklé metodiky a poskytuje žádanou látku o obsahu 99,9 % hmot. v dobrých výtěžcích.Carrying out the reesterification by the method according to the invention does not depart from the standards of the usual methodology and gives the desired substance with a content of 99.9% by weight. in good yields.
225 512225 512
Bližší podrobnosti způsobu podle vynálezu jsou patrné z následujících příkladů provedení, které tento způsob pouze ilustrují, ale nijak neomezují.Further details of the process according to the invention can be seen from the following examples, which are illustrative but not limiting.
Příklad 1Example 1
Suroviny / v kg/ :Raw materials (in kg):
methylester kyseliny methakrylové /1 mol/ 10,000 diethylenglykol /1,27 mol/ 12,700 fenothiazin 0,005 petrolether 13,000 chlorid sodný 8,000 ethylether 22,000 chlorid měůný 0,012 tetramethylamoniumhydroxid /0,01 mol/ 0>450 /ve formě 2C0i» methanolického roztoku/Methacrylic acid methyl ester (1 mol) 10,000 diethylene glycol (1.27 mol) 12,700 phenothiazine 0.005 petroleum ether 13.000 sodium chloride 8.000 ethyl ether 22.000 cupric chloride 0.012 tetramethylammonium hydroxide (0.01 mol / 0> 450) in the form of a 2C0 »methanol solution /
Postup:Method:
Do osmdesátilitrového skleněného kotlíku se umístí suroviny v tomto pořadí: diethylenglykol, methylester kyseliny methakrylové, kvartérní báze a fenothiazin a reakční směs se zvolna za míchání vyhřeje na vnitřní teplotu 5G^C. Po vyčistění roztoku se zvýší teplota na 60 až 65 °C a udržuje seIn an 80-liter glass kettle, the raw materials are placed in the following order: diethylene glycol, methacrylic acid methyl ester, quaternary bases, and phenothiazine, and the reaction mixture is slowly warmed to an internal temperature of 5 ° C under stirring. After cleaning the solution, the temperature is raised to 60-65 ° C and maintained
h. Pak se ochladl na teplotu 20 °C, zředí se 10 litry vody a nechá stát 2 h v klidu. Horní vrstva, která obsahuje ne zreagovaný výchozí ester, se oddělí a dá stranou k případné regeneraci, vodná vrstva se zředí dalšími 30 litry vody a vy extrahuje důkladně nejméně 3 dávkami petroletheru. Vodný podíl se nasytí chloridem sodným a vyextrahuje opět nejméně dávkami ethyletheru. Ke spojeným etherickým extraktům se přidá chlorid mě3ný a ethylether se oddestiluje. Odparek surového diglykolmethakrylátu se čistí destilací za sníženého tlaku. Teplota varu 70 až 80^C/67 až 70 Pa. Výtěžek 8 kg.h. Then cool to 20 ° C, dilute with 10 liters of water and allow to stand for 2 h. The upper layer, which contains the unreacted starting ester, is separated and set aside for possible regeneration, the aqueous layer is diluted with an additional 30 liters of water and extracted thoroughly with at least 3 portions of petroleum ether. The aqueous portion was saturated with sodium chloride and extracted again with at least portions of ethyl ether. Copper (II) chloride was added to the combined ether extracts and the ethyl ether was distilled off. The crude diglycol methacrylate residue is purified by distillation under reduced pressure. Boiling point 70-80 ° C. Yield 8 kg.
Příklad 2Example 2
225 512225 512
Postup zůstává stejný jako v přikladu 1, bylo však použito ethylesteru kyseliny methakrylové.The procedure remains the same as in Example 1, but ethyl methacrylate was used.
Suroviny / v kg/:Raw materials (in kg):
ethylester kyseliny methakrylové /1 mol/ 11,400 diethylenglykol /1,27 mol/ 12,700 fenothiazin 0,005 petrolether 13,000 chlorid sodný 8,000 ethylether 22,000 chlorid měáný 0,012 tetramethylamoniumhydroxid /0,01 mol/ 0,450 / ve formě 20% methanolického roztoku/methacrylic acid ethyl ester (1 mol) 11,400 diethylene glycol (1.27 mol) 12,700 phenothiazine 0.005 petroleum ether 13.000 sodium chloride 8.000 ethyl ether 22.000 cupric chloride 0.012 tetramethylammonium hydroxide (0.01 mol (0.450) as a 20% methanolic solution)
Výtěžek 8,2 kg /t,v. 70 až 8Í°C / 65 až 70/Pa.Yield 8.2 kg / t, v. 70-8 ° C / 65-70 / Pa.
Příklad 3Example 3
Postup i násady surovin zůstávají stejné jako v příkladu 1, jako katalyzátor byl použit tetraethylamoniumhydroxid nebo tetrabutylamoniumhydroxid v množství 0,005 mol na 1 mol výchozího methylesteru kyseliny methakrylové, ve formě 20^ roztoku v toluenu. Výtěžek 9 kg /t.v. 72 až 77 °C/67 Pa/.The process and the feedstocks remain the same as in Example 1, with the catalyst being tetraethylammonium hydroxide or tetrabutylammonium hydroxide in an amount of 0.005 mol per 1 mol of the starting methacrylic acid methyl ester, as a 20% solution in toluene. Yield 9 kg / t. 72-77 ° C (67 Pa).
Příklad 4Example 4
Postup i násady surovin zůstávají stejné jako v příkladu 1, jako katalyzátor byl použit trimethylbenzylamoniumhydroxid v množství 0,1 mol na 1 mol výchozího methylesteru kyseliny methakrylové, ve formě 4(L.% vodného roztoku. VýtěžekThe procedure and the feedstocks remain the same as in Example 1, using as the catalyst the trimethylbenzylammonium hydroxide in an amount of 0.1 mol per 1 mol of the methacrylic acid starting methyl ester, as Form 4 (L.% aqueous solution).
8,2 kg /t.v. 80 °C/65 Pa/.8.2 kg / t. 80 DEG C. (65 Pa).
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS566982A CS225512B1 (en) | 1982-07-27 | 1982-07-27 | Process for preparing 2-hydroxyethylester of methacrylic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS566982A CS225512B1 (en) | 1982-07-27 | 1982-07-27 | Process for preparing 2-hydroxyethylester of methacrylic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS225512B1 true CS225512B1 (en) | 1984-02-13 |
Family
ID=5401970
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS566982A CS225512B1 (en) | 1982-07-27 | 1982-07-27 | Process for preparing 2-hydroxyethylester of methacrylic acid |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS225512B1 (en) |
-
1982
- 1982-07-27 CS CS566982A patent/CS225512B1/en unknown
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