NO881936L - PROCEDURE FOR THE PREPARATION OF L-ASCORBIC ACID DERIVATIVES. - Google Patents
PROCEDURE FOR THE PREPARATION OF L-ASCORBIC ACID DERIVATIVES. Download PDFInfo
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- NO881936L NO881936L NO881936A NO881936A NO881936L NO 881936 L NO881936 L NO 881936L NO 881936 A NO881936 A NO 881936A NO 881936 A NO881936 A NO 881936A NO 881936 L NO881936 L NO 881936L
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- Prior art keywords
- ascorbic acid
- stated
- tertiary amine
- acid
- protected
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 16
- 150000000996 L-ascorbic acids Chemical class 0.000 title description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 23
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- 229960005070 ascorbic acid Drugs 0.000 claims description 12
- 150000003512 tertiary amines Chemical class 0.000 claims description 12
- 239000002211 L-ascorbic acid Substances 0.000 claims description 10
- 235000000069 L-ascorbic acid Nutrition 0.000 claims description 10
- HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 6
- XDBMXUKHMOFBPJ-ZAFYKAAXSA-N L-ascorbic acid 2-sulfate Chemical compound OC[C@H](O)[C@H]1OC(=O)C(OS(O)(=O)=O)=C1O XDBMXUKHMOFBPJ-ZAFYKAAXSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- POXUQBFHDHCZAD-MHTLYPKNSA-N (2r)-2-[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]-3,4-dihydroxy-2h-furan-5-one Chemical compound O1C(C)(C)OC[C@H]1[C@@H]1C(O)=C(O)C(=O)O1 POXUQBFHDHCZAD-MHTLYPKNSA-N 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000005270 trialkylamine group Chemical group 0.000 claims description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Inorganic materials O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
- KAQHZJVQFBJKCK-UHFFFAOYSA-L potassium pyrosulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OS([O-])(=O)=O KAQHZJVQFBJKCK-UHFFFAOYSA-L 0.000 description 2
- 229910021653 sulphate ion Inorganic materials 0.000 description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- BXVMXUPHPZDIMH-YCWPWOODSA-L [K+].[K+].OC[C@H](O)[C@H]1OC(=O)C(OS([O-])(=O)=O)=C1[O-] Chemical compound [K+].[K+].OC[C@H](O)[C@H]1OC(=O)C(OS([O-])(=O)=O)=C1[O-] BXVMXUPHPZDIMH-YCWPWOODSA-L 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- -1 alkaline earth metal salts Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 159000000009 barium salts Chemical class 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical class [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical compound [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052920 inorganic sulfate Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 235000012976 tarts Nutrition 0.000 description 1
- RKBCYCFRFCNLTO-UHFFFAOYSA-N triisopropylamine Chemical compound CC(C)N(C(C)C)C(C)C RKBCYCFRFCNLTO-UHFFFAOYSA-N 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical group CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical group CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/62—Three oxygen atoms, e.g. ascorbic acid
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Catalysts (AREA)
Description
Oppfinnelsen vedrører en fremgangsmåte ved fremstilling av L-askorbinsyrederivater, især L-askorbinsyre-2-sulfat og saltene derav. The invention relates to a method for the production of L-ascorbic acid derivatives, in particular L-ascorbic acid-2-sulphate and its salts.
Fremgangsmåten erkarakterisert vedat man behandler en L-askorbinsyre med beskyttet 5,6-stilling med et salt av et tert. amin med pyrosvovelsyre eller rykende svovelsyre og avspalter derefter beskyttelsesgruppen og overfører eventuelt det erholdte L-askorbinsyre-2-sulfat i et salt. The method is characterized by treating an L-ascorbic acid with a protected 5,6 position with a salt of a tart. amine with pyrosulphuric acid or fuming sulfuric acid and then cleaves off the protecting group and optionally transfers the obtained L-ascorbic acid-2-sulphate in a salt.
På egnet måte fremstiller man saltet av det tertiære amin med pyrosvovelsyre eller rykende svovelsyre in situ, dvs. man omsetter den beskyttede L-askorbinsyre med et alkali-eller jordalkalipyrosulfat i nærvær av det tertiære amin, hhv. at man omsetter den beskyttede L-askorbinsyre med rykende svovelsyre i nærvær av det tertiære amin. Alternativt kan imidlertid saltet fremstilles på forhånd, hensiktsmessig ved tilsetning av rykende svovelsyre til aminet i et oppløsningsmiddel såsom metylenklorid. The salt of the tertiary amine is suitably prepared with pyrosulphuric acid or fuming sulfuric acid in situ, i.e. the protected L-ascorbic acid is reacted with an alkali or alkaline earth pyrosulphate in the presence of the tertiary amine, or that the protected L-ascorbic acid is reacted with fuming sulfuric acid in the presence of the tertiary amine. Alternatively, however, the salt may be prepared in advance, conveniently by adding fuming sulfuric acid to the amine in a solvent such as methylene chloride.
Som beskyttelsesgrupper for 5,6-stillingen av L-askorbinsyren fungerer hensiktsmessig: Ketaler av lavere alifatiske eller cykloalifatiske ketoner som f.eks. av aceton, dietylketon, etylmetylketon eller cykloheksanon, acetaler av aldehyder som f.eks. benzalde-hyd eller propionaldehyd. Suitable protecting groups for the 5,6-position of L-ascorbic acid are: Ketals of lower aliphatic or cycloaliphatic ketones such as e.g. of acetone, diethyl ketone, ethyl methyl ketone or cyclohexanone, acetals of aldehydes such as benzaldehyde or propionaldehyde.
Den foretrukkede L-askorbinsyre med beskyttet 5,6-stilling er 5,6-isopropyliden-L-askorbinsyren. The preferred 5,6-protected L-ascorbic acid is 5,6-isopropylidene-L-ascorbic acid.
Egnede tertiære aminer er tri alkylaminer såsom tri-lavere-alkylaminer, f.eks. trimetyl-, trietyl-, tri-n-propyl- og tri-isopropylamin; eller aromatiske aminer, f.eks. pyridin og picolin. Suitable tertiary amines are tri alkylamines such as tri-lower alkylamines, e.g. trimethyl, triethyl, tri-n-propyl and tri-isopropylamine; or aromatic amines, e.g. pyridine and picoline.
Som alkalisalter av pyrosvovelsyren fungerer de vanlige respektive salter, nemlig litium-, natrium-, kalium- eller sesiumsaltet, som jordalkalimetallsalt magnesium-, kalsium-, strontium- eller bariumsaltet. As alkali salts of the pyrosulphuric acid, the usual respective salts, namely the lithium, sodium, potassium or cesium salt, act as alkaline earth metal salts the magnesium, calcium, strontium or barium salt.
Det frie SO^-innhold i den rykende svovelsyre (oleum) kan variere i et stort område, f.eks. 2-80 vekts%, spesielt ca. 55-70 vekts%. Det trengs 1 mol fritt SO^pr. mol av den beskyttede askorbinsyre. The free SO^ content in the fuming sulfuric acid (oleum) can vary over a large range, e.g. 2-80% by weight, especially approx. 55-70% by weight. 1 mole of free SO^per is needed. moles of the protected ascorbic acid.
Fremgangsmåten ifølge oppfinnelsen gjennomføres hensiktsmessig i et vannfritt aprotisk, basisk oppløsningsmiddel. Egnede slike oppløsningsmidler er f.eks. dimetylformamid, hhv. det ovennevnte tertiære amin. The method according to the invention is conveniently carried out in an anhydrous aprotic, basic solvent. Suitable such solvents are e.g. dimethylformamide, respectively the above tertiary amine.
Det molare forhold av tertiært amin til pyrosvovelsyre hhv. rykende svovelsyre kan variere i et stort område, f.eks. ca. 1-10:1. I en egnet utførelsesform fungerer det tertiære amin som oppløsningsmiddel. The molar ratio of tertiary amine to pyrosulphuric acid or fuming sulfuric acid can vary over a large area, e.g. about. 1-10:1. In a suitable embodiment, the tertiary amine acts as a solvent.
Det arbeides hensiktsmessig ved romtemperatur eller ved lett øket temperatur, dvs. ved temperaturer på ca. 20 - 50°C. It is appropriate to work at room temperature or at a slightly increased temperature, i.e. at temperatures of approx. 20 - 50°C.
Opparbeidelsen av det primære reaksjonsprodukt, dvs. L-askorbinsyre-2-sulfatet med beskyttet 5,6-stilling, omfatter hensiktsmessig følgende trinn: Fjerning av uor-ganiske sulfater, f.eks. ved utfelling med kalsiumhydroksyd, behandling med en sterkt sur ioneutbytter for av-spaltning av beskyttelsesgruppen, og til slutt behandling med en uorganisk base, dvs. et alkalimetall- eller jord-alkalimetallhydroksyd for fremstilling av alkalimetall-hhv. jordalkalisulfatet som er av spesiell interesse. The processing of the primary reaction product, i.e. the L-ascorbic acid 2-sulphate with a protected 5,6-position, suitably comprises the following steps: Removal of inorganic sulphates, e.g. by precipitation with calcium hydroxide, treatment with a strongly acidic ion exchanger to remove the protective group, and finally treatment with an inorganic base, i.e. an alkali metal or alkaline earth metal hydroxide to produce alkali metal or the alkaline earth sulfate which is of particular interest.
Fra US-patent nr. 3 954 809 er det kjent en fremgangsmåte til sulfatering av L-askorbinsyre til det tilsvarende 2-sulfat under anvendelse av et preformert amin-svovel trioksyd-kompleks som sulfateringsmiddel.Imidlertid er fremstillingen av dette amin-svoveltrioksyd-kompleks be-lastet med temmelig store ubehageligheter, fordi man tvangsmessig må arbeide med fritt SO^. Disse ubehageligheter bortfaller i det foreliggende tilfellet: Idet oleum i svovelsyre-fremstillingen dannes i lukket kretsløp, kreves det ved fremstillingen av amin-svoveltrioksyd-komplekset sikkerhetsforanstaltninger over gjennomsnittet ved håndteringen av fritt svoveltrioksyd. From US patent no. 3,954,809, a method is known for sulphating L-ascorbic acid to the corresponding 2-sulphate using a preformed amine-sulfur trioxide complex as a sulphating agent. However, the production of this amine-sulfur trioxide complex is burdened with rather great unpleasantness, because one has to compulsorily work with free SO^. These inconveniences disappear in the present case: As oleum in the sulfuric acid production is formed in a closed circuit, above-average safety measures are required in the production of the amine-sulphur trioxide complex when handling free sulfur trioxide.
Fremgangsmåten ifølge oppfinnelsen skal forklares nærmere ved hjelp av de følgende eksempler: The method according to the invention shall be explained in more detail by means of the following examples:
EKSEMPEL 1EXAMPLE 1
I en 3 1 firehalset rundkolbe med rører, termometer og inertbegassing anbringes 216 g (1,00 mol) 216 g (1.00 mol) are placed in a 3 1 four-neck round-bottomed flask with stirrer, thermometer and inert gas
5,6-isopropyliden-L-askorbinsyre, 600 ml pyridin, 356 g (1,40 mol) kaliumdisulfat (kaliumpyrosulfat ) , 400 ml glasskuler (ø3 mm) og røres i 16 timer ved romtemperatur. Glasskulene separeres og eftervaskes med 500 ml vann. Suspensjonen avfiltreres. Filtratet oppvarmes i en 3 1 sulfoneringskolbe med rører og termometer til 50°C. Til dette tilsettes en suspensjon av 104 g kalisumhydroksyd (96% =1,4 mol) i 500 ml vann. Efter 1 times omrøring ved romtemperatur avfiltreres det utfelte kalsiumsulfat og eftervaskes med 2 x 250 ml vann. Filtratet inndampes i en rotavapor i vannstrålevakuum til ca. 700 ml. Produktopp-løsningen filtreres gjennom en ioneutbytter, nemlig 1,5 kg Dowex 50W X8 16-40 mesh. Ioneutbytteren eftervaskes med 1,6 1 vann. Eluatet fanges opp og henstår ved romtemperatur inntil fullstendig hydrolyse av isopropyliden-beskyttelsesgruppen. Oppløsningen innstilles med 184 ml 10N kalium-hydroksyd til pH 8,0 + 0,5 og inndampes i rotavaporen i vannstrålevakuum til ca. 750 ml. I en 2 1 rundkolbe tilsettes til denne oppløsning dråpevis under omrøring 850 ml metanol. Det utfelte produkt avfiltreres og filtratkaken 5,6-isopropylidene-L-ascorbic acid, 600 ml pyridine, 356 g (1.40 mol) potassium disulfate (potassium pyrosulfate), 400 ml glass balls (ø3 mm) and stirred for 16 hours at room temperature. The glass beads are separated and washed with 500 ml of water. The suspension is filtered off. The filtrate is heated in a 3 1 sulphonation flask with stirrer and thermometer to 50°C. To this is added a suspension of 104 g of potassium hydroxide (96% = 1.4 mol) in 500 ml of water. After stirring for 1 hour at room temperature, the precipitated calcium sulphate is filtered off and washed with 2 x 250 ml water. The filtrate is evaporated in a rotavapor in a water jet vacuum to approx. 700 ml. The product solution is filtered through an ion exchanger, namely 1.5 kg Dowex 50W X8 16-40 mesh. The ion exchanger is then washed with 1.6 1 water. The eluate is collected and left at room temperature until complete hydrolysis of the isopropylidene protecting group. The solution is adjusted with 184 ml of 10N potassium hydroxide to pH 8.0 + 0.5 and evaporated in the rotavapor in a water jet vacuum to approx. 750 ml. In a 2 1 round-bottomed flask, 850 ml of methanol are added dropwise to this solution while stirring. The precipitated product is filtered off and the filtrate cake
eftervaskes med en blanding, av 400 ml metanol/vann (55:45 G/G). Filtratkaken tørkes i vannstrålevakuum. Man oppnår: 273,7 g dikalium-L-askorbat-2-sulfat . 2 H^O, innhold: washed with a mixture of 400 ml methanol/water (55:45 G/G). The filtrate cake is dried in a water jet vacuum. One obtains: 273.7 g of dipotassium L-ascorbate-2-sulphate. 2 H^O, content:
96% (ifølge HPLC).96% (according to HPLC).
EKSEMPEL 2EXAMPLE 2
I en 3 1 firehalset rundkolbe med rører og termometer anbringes under nitrogenatmosfaere 216 g (1,00 mol) 5,6-isopropylidenaskorbinsyre, 600 ml pyridin og 280 g (= 1,10 mol fritt SO^) pyridinpolysulfat og røres i 18 timer ved romtemperatur. ["Pyridinpolysulfatet" fremstilles ved tilsetning av 100 ml rykende svovelsyre (oleum 60%) til 240 ml pyridin (Py) ill metylenklorid. Det resulterende "pyridinpolysulfat" (378,4 g) har sammensetningen<Py>2<H>2S2°7"0,84<p>yS03^-Til den nesten 216 g (1.00 mol) of 5,6-isopropylidene ascorbic acid, 600 ml of pyridine and 280 g (= 1.10 mol of free SO^) of pyridine polysulphate are placed under a nitrogen atmosphere in a 3 l four-necked round flask with stirrer and thermometer and stirred for 18 hours at room temperature. [The "pyridine polysulphate" is prepared by adding 100 ml of fuming sulfuric acid (oleum 60%) to 240 ml of pyridine (Py) in methylene chloride. The resulting "pyridine polysulfate" (378.4 g) has the composition<Py>2<H>2S2°7"0.84<p>yS03^-To the almost
fullstendig oppløste blanding tilsettes 600 ml vann. Oppløsningen oppvarmes til 50°C. Til dette tilsettes en suspensjon av 136 g (96 % = 1,84 mol) kalsiumhydroksyd og 500 ml vann i løpet av 30 minutter. Suspensjonen røres i 1 time ved romtemperatur og det utfelte kalsiumsulfat avfiltreres og utpresses kraftig. Filtratkaken løses i 200 ml vann og eftervaskes. Filtratet inndampes på vannstrålevakuum til ca. 500 ml. Suspensjonen avfiltreres og resten eftervaskes med 300 ml vann. Filtratet filtreres gjennom en sterkt sur ioneutbytter, dvs. 1,58 kg Dowex 50 W X8. Det eftervaskes med 1,6 1 vann og eluatet fanges opp og henstår ved romtemperatur inntil isopropylidenbeskyttelsesgruppens fullstendige hydrolyse. Den sterkt sure oppløsning completely dissolved mixture is added to 600 ml of water. The solution is heated to 50°C. To this is added a suspension of 136 g (96% = 1.84 mol) of calcium hydroxide and 500 ml of water over the course of 30 minutes. The suspension is stirred for 1 hour at room temperature and the precipitated calcium sulphate is filtered off and squeezed out vigorously. The filtrate cake is dissolved in 200 ml of water and then washed. The filtrate is evaporated on a water jet vacuum to approx. 500 ml. The suspension is filtered off and the residue is washed with 300 ml of water. The filtrate is filtered through a strongly acidic ion exchanger, i.e. 1.58 kg Dowex 50 W X8. It is then washed with 1.6 1 water and the eluate is collected and left at room temperature until the complete hydrolysis of the isopropylidene protecting group. The strongly acidic solution
innstilles med 214 ml 10N KOH til pH 8,0 + 0,5 og inndampes i vannstrålevakuum til ca. 750 ml. Til produktoppløsningen tilsettes dråpevis under omrøring i en 2 1 rundkolbe 850 ml metanol. Det utfelte produkt avfiltreres og filtratkaken adjusted with 214 ml 10N KOH to pH 8.0 + 0.5 and evaporated in a water jet vacuum to approx. 750 ml. 850 ml methanol is added dropwise to the product solution while stirring in a 2 l round bottom flask. The precipitated product is filtered off and the filtrate cake
eftervaskes med en blanding av 400 ml metanol/vann 55:45 G/G. Produktet tørkes i 18 timer i vannstrålevakuum ved 45°C. Man oppnår 290,5 g dikaliumaskorbat-2-sulfat . 2 H20, innhold 92 %. washed with a mixture of 400 ml methanol/water 55:45 G/G. The product is dried for 18 hours in a water jet vacuum at 45°C. 290.5 g of dipotassium ascorbate-2-sulphate is obtained. 2 H20, content 92%.
Claims (10)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH167687 | 1987-05-04 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO881936D0 NO881936D0 (en) | 1988-05-03 |
| NO881936L true NO881936L (en) | 1988-11-07 |
Family
ID=4215991
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO881936A NO881936L (en) | 1987-05-04 | 1988-05-03 | PROCEDURE FOR THE PREPARATION OF L-ASCORBIC ACID DERIVATIVES. |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0289894A1 (en) |
| JP (1) | JPS63297375A (en) |
| KR (1) | KR880013913A (en) |
| CN (1) | CN88102718A (en) |
| DK (1) | DK227188A (en) |
| NO (1) | NO881936L (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991013068A1 (en) * | 1990-03-01 | 1991-09-05 | Enco Engineering Chur Ag | Process for the production of dipostassium ascorbate-2-sulphate |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US278831A (en) * | 1883-06-05 | Car-signal | ||
| US3954809A (en) * | 1973-01-22 | 1976-05-04 | Kansas State University Research Foundation | Preparation of l-ascorbate 2-sulfate from l-ascorbic acid |
| US4071534A (en) * | 1973-11-07 | 1978-01-31 | Kumiai Chemical Industry Co., Ltd. | Process for producing l-ascorbic acid-2-sulfate |
-
1988
- 1988-04-23 EP EP88106550A patent/EP0289894A1/en not_active Withdrawn
- 1988-04-26 DK DK227188A patent/DK227188A/en not_active Application Discontinuation
- 1988-05-02 JP JP63107721A patent/JPS63297375A/en active Pending
- 1988-05-03 NO NO881936A patent/NO881936L/en unknown
- 1988-05-03 KR KR1019880005133A patent/KR880013913A/en not_active Application Discontinuation
- 1988-05-03 CN CN198888102718A patent/CN88102718A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN88102718A (en) | 1988-11-16 |
| DK227188A (en) | 1988-11-05 |
| NO881936D0 (en) | 1988-05-03 |
| JPS63297375A (en) | 1988-12-05 |
| DK227188D0 (en) | 1988-04-26 |
| KR880013913A (en) | 1988-12-22 |
| EP0289894A1 (en) | 1988-11-09 |
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