NO150560B - 6,6`-OXYBIS HALOGEN-SUBSTITUTED PYRON DERIVATIVES AND PROCEDURES FOR PREPARING THEREOF - Google Patents
6,6`-OXYBIS HALOGEN-SUBSTITUTED PYRON DERIVATIVES AND PROCEDURES FOR PREPARING THEREOF Download PDFInfo
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- NO150560B NO150560B NO821851A NO821851A NO150560B NO 150560 B NO150560 B NO 150560B NO 821851 A NO821851 A NO 821851A NO 821851 A NO821851 A NO 821851A NO 150560 B NO150560 B NO 150560B
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- halogen
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- 238000000034 method Methods 0.000 title claims description 7
- NQBKFULMFQMZBE-UHFFFAOYSA-N n-bz-3-benzanthronylpyrazolanthron Chemical class C12=CC=CC(C(=O)C=3C4=CC=CC=3)=C2C4=NN1C1=CC=C2C3=C1C1=CC=CC=C1C(=O)C3=CC=C2 NQBKFULMFQMZBE-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Chemical group 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 230000018044 dehydration Effects 0.000 claims description 2
- 238000006297 dehydration reaction Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- XPCTZQVDEJYUGT-UHFFFAOYSA-N 3-hydroxy-2-methyl-4-pyrone Chemical compound CC=1OC=CC(=O)C=1O XPCTZQVDEJYUGT-UHFFFAOYSA-N 0.000 description 16
- HYMLWHLQFGRFIY-UHFFFAOYSA-N Maltol Natural products CC1OC=CC(=O)C1=O HYMLWHLQFGRFIY-UHFFFAOYSA-N 0.000 description 7
- 229940043353 maltol Drugs 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- XPFVYQJUAUNWIW-UHFFFAOYSA-N furfuryl alcohol Chemical compound OCC1=CC=CO1 XPFVYQJUAUNWIW-UHFFFAOYSA-N 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000013067 intermediate product Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- UABXUIWIFUZYQK-UHFFFAOYSA-N 1-(furan-2-yl)ethanol Chemical compound CC(O)C1=CC=CO1 UABXUIWIFUZYQK-UHFFFAOYSA-N 0.000 description 2
- VEYIMQVTPXPUHA-UHFFFAOYSA-N 3-hydroxypyran-4-one Chemical compound OC1=COC=CC1=O VEYIMQVTPXPUHA-UHFFFAOYSA-N 0.000 description 2
- DSEPAHSEUBGYDG-UHFFFAOYSA-N 4-bromo-2-hydroxy-6-methyl-2h-pyran-5-one Chemical compound CC1OC(O)C=C(Br)C1=O DSEPAHSEUBGYDG-UHFFFAOYSA-N 0.000 description 2
- YIKYNHJUKRTCJL-UHFFFAOYSA-N Ethyl maltol Chemical compound CCC=1OC=CC(=O)C=1O YIKYNHJUKRTCJL-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CVQUWLDCFXOXEN-UHFFFAOYSA-N Pyran-4-one Chemical compound O=C1C=COC=C1 CVQUWLDCFXOXEN-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 229940093503 ethyl maltol Drugs 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 239000002304 perfume Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YQIUCEVQCDXCBS-UHFFFAOYSA-N 4-bromo-2-[(4-bromo-6-methyl-5-oxo-2h-pyran-2-yl)oxy]-6-methyl-2h-pyran-5-one Chemical compound C1=C(Br)C(=O)C(C)OC1OC1C=C(Br)C(=O)C(C)O1 YQIUCEVQCDXCBS-UHFFFAOYSA-N 0.000 description 1
- -1 6-methyl-2-ethyl-3-hydroxy-4H-pyran- Chemical compound 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241000723343 Cichorium Species 0.000 description 1
- 235000007542 Cichorium intybus Nutrition 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000218652 Larix Species 0.000 description 1
- 235000005590 Larix decidua Nutrition 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical compound BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 description 1
- 150000001719 carbohydrate derivatives Chemical class 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 239000000686 essence Substances 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000197 pyrolysis Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical class CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/32—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/34—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D309/36—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
- C07D309/40—Oxygen atoms attached in positions 3 and 4, e.g. maltol
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrane Compounds (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Cosmetics (AREA)
- Plural Heterocyclic Compounds (AREA)
- Furan Compounds (AREA)
- Saccharide Compounds (AREA)
- Transforming Electric Information Into Light Information (AREA)
- Picture Signal Circuits (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Processing Of Color Television Signals (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Seasonings (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Control Of El Displays (AREA)
Abstract
6,6'-oksybis-halogensubstituert-pyron-derivater . og fremgangsmåte for fremstilling derav.6,6'-oxybis-halogen-substituted-pyrone derivatives. and method of making the same.
Description
Foreliggende oppfinnelse gjelder nye 6,6 '-oksybis-halogensubstituert-pyron-derivater egnet for anvendelse som mellomprodukter ved fremstilling av gamma-pyroner, samt en fremgangsmåte for fremstilling derav. The present invention relates to new 6,6'-oxybis-halogen-substituted-pyrone derivatives suitable for use as intermediates in the production of gamma-pyrones, as well as a method for their production.
Fremstilling av gamma-pyroner ved hydrolyse av mellomproduktene ifølge oppfinnelsen er beskrevet i patentsøknad 77.2193. Production of gamma-pyrones by hydrolysis of the intermediate products according to the invention is described in patent application 77.2193.
Maltol (2-metyl-3-hydroksy-4H-pyran-4-on) er en naturlig forekommende substans funnet i barken hos unge lerketrær, furu-nåler og sikori. Tidlig kommersiell produksjon foregikk ved destruktiv destillasjon av ved. Syntesen av maltol fra 3- hydroksy-2-(1-piperidylmetyl)-1,4-pyron ble omtalt av Spielman og Freifelder i J. Am. Chem. Soc, 69, 2908 (1947). Schenck og J. Am. Chem. Soc, 67, 2267 (1945) oppnådde maltol Maltol (2-methyl-3-hydroxy-4H-pyran-4-one) is a naturally occurring substance found in the bark of young larch trees, pine needles and chicory. Early commercial production took place by destructive distillation of wood. The synthesis of maltol from 3-hydroxy-2-(1-piperidylmethyl)-1,4-pyrone was discussed by Spielman and Freifelder in J. Am. Chem. Soc, 69, 2908 (1947). Schenck and J. Am. Chem. Soc, 67, 2267 (1945) obtained maltol
ved alkalisk hydrolyse av streptomycinsalter. Chawla og McGonigal, J. Org. Chem., 39, 3281 (1974) og Lichtenthaler by alkaline hydrolysis of streptomycin salts. Chawla and McGonigal, J. Org. Chem., 39, 3281 (1974) and Lichtenthaler
og Heidel, Angew. Chem., 81, 998 (1969), omtalte syntese av maltol fra beskyttende karbohydrat-derivater. Shono og Matsumura, Tetrahedron Letters nr. 17, 1363 (1976), beskrev and Heidel, Angew. Chem., 81, 998 (1969), discussed the synthesis of maltol from protective carbohydrate derivatives. Shono and Matsumura, Tetrahedron Letters No. 17, 1363 (1976), described
en fem trinns syntese av maltol utgående fra metylfurfurylalkohol. a five-step synthesis of maltol starting from methylfurfuryl alcohol.
Isoleringen av 6-metyl-2-etyl-3-hydroksy-4H-pyran- The isolation of 6-methyl-2-ethyl-3-hydroxy-4H-pyran-
4- on som en av de karakteristiske søt-aromabestanddelene i raffinert, ferdig melasse bie omtalt av Hiroshi Ito i Agr. 4- on as one of the characteristic sweet aroma constituents in refined, finished molasses bee discussed by Hiroshi Ito in Agr.
Biol. Chem., 40 (5), 827-832 (1976). Denne forbindelse ble tidligere syntetisert ved hjelp av den fremgangsmåte som er beskrevet i US-patent 3.468.915. Biol. Chem., 40 (5), 827-832 (1976). This compound was previously synthesized using the method described in US patent 3,468,915.
Synteser av gamma-pyroner som f.eks. pyromekonsyre, Syntheses of gamma pyrones such as pyromeconic acid,
maltol, etylmaltol og andre 2-substituerte 3-hydroksy-gamma-pyroner er beskrevet i US-patenter 3.130.204, 3.133.089, maltol, ethyl maltol and other 2-substituted 3-hydroxy-gamma-pyrones are described in US patents 3,130,204, 3,133,089,
3.140.239, 3.159.652, 3.365.469, 3.376.317, 3.440.183, 3,140,239, 3,159,652, 3,365,469, 3,376,317, 3,440,183,
3.446.629 og 3.468.915. 3,446,629 and 3,468,915.
Maltol og etylmaltol øker smak og aroma for for- Maltol and ethyl maltol increase taste and aroma for
skjellige næringsmidler. I tillegg brukes disse forbindelser som ingredienser i parfymer og essenser. De 2-alkenylpyromekon-syrer som er beskrevet i US-patent 3.64 4.6 35 og de 2-arylmetyl-pyromekonsyrer som er beskrevet i US-patent 3.365.469 hindrer vekst av bakterier og sopper og er anvendbare som smaks- og aromaøkende midler i næringsmidler og drikker og aromaøkende midler i parfymer. different foodstuffs. In addition, these compounds are used as ingredients in perfumes and essences. The 2-alkenylpyromeconic acids described in US patent 3.64 4.6 35 and the 2-arylmethylpyromeconic acids described in US patent 3,365,469 prevent the growth of bacteria and fungi and are usable as flavor and aroma enhancers in foodstuffs and beverages and aroma enhancers in perfumes.
Patentsøknad 77..2193 beskriver en fremgangsmåte for fremstilling av et gamma-pyron med formelen Patent application 77..2193 describes a method for producing a gamma pyrone with the formula
som omfatter oppvarmning i sur, vandig løsning, fortrinnsvis ved en temperatur i området 70 til 160°C, inntil hydrolysen er i hovedsak fullstendig, av bl.a. et 6,6'-oksybis[4-halogen-2H-pyran-3(6H)-on] med formel (V): which comprises heating in acidic, aqueous solution, preferably at a temperature in the range of 70 to 160°C, until the hydrolysis is essentially complete, of i.a. a 6,6'-oxybis[4-halo-2H-pyran-3(6H)-one] of formula (V):
hvor R bl.a. er hydrogen eller alkyl med 1 til 4 karbonatomer, R''<*> bl.a. er hydrogen og X er klor eller brom. where R i.a. is hydrogen or alkyl with 1 to 4 carbon atoms, R''<*> i.a. is hydrogen and X is chlorine or bromine.
Den syre som kreves for hydrolysen kan tilsettes til reaksjonsblandingen, f.eks. ved å oppløse mellomproduktet med formel (V) i en vandig, uorganisk eller organisk syre før oppvarmningen; eller alternativt kan syren genereres in situ under fremstillingen av mellomproduktene som beskrevet senere. The acid required for the hydrolysis can be added to the reaction mixture, e.g. by dissolving the intermediate of formula (V) in an aqueous, inorganic or organic acid prior to heating; or alternatively the acid can be generated in situ during the preparation of the intermediates as described later.
Noen av forbindelsene med formel (V) er nye, og ifølge oppfinnelsen tilveiebringes forbindelser med formel Some of the compounds of formula (V) are new, and according to the invention compounds of formula are provided
(V): (V):
hvor R er hydrogen.eller alkyl med 1 til 4 karbonatomer, og X er klor eller brom. where R is hydrogen or alkyl of 1 to 4 carbon atoms, and X is chlorine or bromine.
Ifølge oppfinnelsen fremstilles det nye mellomprodukt med formel (V) ved å dehydratisere en forbindelse med formelen: According to the invention, the new intermediate product with formula (V) is produced by dehydrating a compound with the formula:
hvor R og X er som ovenfor angitt, ved 40°C. where R and X are as above, at 40°C.
Dehydratiseringen utføres fortrinnsvis ved oppvarmning av forbindelsen med formel II" ved en temperatur på 40°C i 16 timer. The dehydration is preferably carried out by heating the compound of formula II" at a temperature of 40°C for 16 hours.
Som beskrevet i patentsøknad 77.219 3 kan utgangs-forbindelsen med formel (II") fremstilles ved omsetning av en furfurylalkohol i vandig løsning sammen med et eventuelt ko-løsningsmiddel ved -10 til 10°C med to ekvivalenter av et halogenholdig oksydasjonsmiddel. Det foretrukne halogen-holdige oksydasjonsmiddel er klor eller bromklorid. Efter omrøring ved romtemperatur i 30 minutter reguleres reaksjons-blandingens pH-verdi til 2 med en sterk base, og reaksjonsblandingen ekstraheres med et løsningsmiddel så som etylacetat. Fjernelse av løsningsmidlet gir 4-halogen-6-hydroksy-2H-pyran-3(6H)-on-forbindelsen med formel (II") som kan dehydratiseres ved oppvarmning under vakuum for å gi 6,6'-oksybis-[4-halogen-2H-pyran-3(6H)-on]-forbindelsen. As described in patent application 77,219 3, the starting compound of formula (II") can be prepared by reacting a furfuryl alcohol in aqueous solution together with an optional co-solvent at -10 to 10°C with two equivalents of a halogen-containing oxidizing agent. The preferred halogen -containing oxidizing agents are chlorine or bromine chloride. After stirring at room temperature for 30 minutes, the pH value of the reaction mixture is adjusted to 2 with a strong base, and the reaction mixture is extracted with a solvent such as ethyl acetate. Removal of the solvent gives 4-halo-6-hydroxy The -2H-pyran-3(6H)-one compound of formula (II") which can be dehydrated by heating under vacuum to give 6,6'-oxybis-[4-halo-2H-pyran-3(6H)- on] connection.
Følgende eksempler illustrerer fremstillingen av de nye mellomproduktene ved fremgangsmåten ifølge oppfinnelsen. The following examples illustrate the preparation of the new intermediate products by the method according to the invention.
I spektraldataene angitt i eksempel l(a) er kjemiske NMR-skift-data angitt ved hjelp av konvensjonell litteratur-symbolisme, og alle skift er uttrykt som 6-enheter fra tetrametylsilan: In the spectral data given in Example 1(a), NMR chemical shift data are given using conventional literature symbolism, and all shifts are expressed as 6-units from tetramethylsilane:
d = dublett d = duplicate
q = kvartett q = quartet
m = multiplett m = multiplet
Eksempel 1 Example 1
a) Fremstilling av 4- brom- 6- hydroksy- 2- metyl- 2H- pyran-3( 6H)- on ( utgangsmateriale) a) Preparation of 4-bromo-6-hydroxy-2-methyl-2H-pyran-3(6H)-one (starting material)
Til en løsning av 25 g 1-(2-furyl)-1-etanol i 125 ml tetrahydrofuran og 125 ml vann ved 0 til 5°C ble tilsatt dråpevis 2,2 ekvivalenter brom. Under tilsetningen ble temperaturen holdt ved 5 til 10°C. Efter bromtilsetningen ble løsningen om-rørt ved romtemperatur i 30 minutter og pH justert til 2,1 med 2N NaOH-løsning. Reaksjonsblandingen ble ekstrahert med etylacetat (3 x 100 ml). Etylacetatekstraktene ble kombinert, tørket over MgSO^, filtrert og inndampet til tørrhet. Residuet ble kromatografert på silikagel og eluert med klorofqrm-etylacetat (95:5). Produktet var en oransje olje som ble om-kromatografert på silikagel og eluert med klorofprm-etylacetat (95:5) . To a solution of 25 g of 1-(2-furyl)-1-ethanol in 125 ml of tetrahydrofuran and 125 ml of water at 0 to 5°C was added dropwise 2.2 equivalents of bromine. During the addition, the temperature was maintained at 5 to 10°C. After the addition of bromine, the solution was stirred at room temperature for 30 minutes and the pH adjusted to 2.1 with 2N NaOH solution. The reaction mixture was extracted with ethyl acetate (3 x 100 mL). The ethyl acetate extracts were combined, dried over MgSO 4 , filtered and evaporated to dryness. The residue was chromatographed on silica gel and eluted with chloroform-ethyl acetate (95:5). The product was an orange oil which was re-chromatographed on silica gel and eluted with chloroform-ethyl acetate (95:5).
NMR (CDC13, 6) 7,3 (1H, d); 5,6 (1H, d); 4,7-5,0 (1H, q); 1,1-1,5 (3H, m). NMR (CDCl 3 , δ) 7.3 (1H, d); 5.6 (1H, d); 4.7-5.0 (1H, q); 1.1-1.5 (3H, m).
b) Fremstilling av sluttprodukt b) Production of final product
4-brom-6-hydroksy-2-metyl-2H-pyran-3(6H)-on ble 4-bromo-6-hydroxy-2-methyl-2H-pyran-3(6H)-one was
oppvarmet under vakuum i 16 timer ved 40°C. Det resulterende oljeaktige faste stoff ble krystallisert fra isopropylalkohol for å gi 6,6'-oksybis[4-brom-2-metyl-2H-pyran-3(6H)-on], heated under vacuum for 16 hours at 40°C. The resulting oily solid was crystallized from isopropyl alcohol to give 6,6'-oxybis[4-bromo-2-methyl-2H-pyran-3(6H)-one],
sm.p. 125°C. sm.p. 125°C.
Eksempel 2 Example 2
Fremgangsmåten fra eksempel 1 ble gjentatt ved å gå ut fra en forbindelse med formelen: hvor R er metyl eller etyl, for å gi en forbindelse med formelen: The procedure from example 1 was repeated starting from a compound of the formula: where R is methyl or ethyl, to give a compound of the formula:
Claims (3)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71090176A | 1976-08-02 | 1976-08-02 | |
| US05/721,885 US4082717A (en) | 1976-08-02 | 1976-09-09 | Preparation of gamma-pyrones |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO821851L NO821851L (en) | 1978-02-03 |
| NO150560B true NO150560B (en) | 1984-07-30 |
| NO150560C NO150560C (en) | 1984-11-07 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO772193A NO150561C (en) | 1976-08-02 | 1977-06-22 | PROCEDURE FOR MANUFACTURING GAMMA PYRONS |
| NO821849A NO150559C (en) | 1976-08-02 | 1982-06-03 | 4-HALOGEN-DIHYDROPYRANE COMPOUNDS AND PROCEDURES FOR PREPARING THEREOF |
| NO821851A NO150560C (en) | 1976-08-02 | 1982-06-03 | 6,6`-OXYBIS HALOGEN-SUBSTITUTED PYRON DERIVATIVES AND PROCEDURES FOR PREPARING THEREOF |
| NO821848A NO150043C (en) | 1976-08-02 | 1982-06-03 | PROCEDURE FOR MANUFACTURING GAMMA PYRONS |
| NO821850A NO821850L (en) | 1976-08-02 | 1982-06-03 | PROCEDURE FOR THE PREPARATION OF 4-HALOGEN-DIHYDROPYRANE DERIVATIVES |
| NO821847A NO150042C (en) | 1976-08-02 | 1982-06-03 | PROCEDURE FOR MANUFACTURING GAMMA PYRONS |
| NO834236A NO151365C (en) | 1976-08-02 | 1983-11-18 | PROCEDURE FOR THE PREPARATION OF 4-HALOGEN-DIHYDROPYRANE DERIVATIVES. |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO772193A NO150561C (en) | 1976-08-02 | 1977-06-22 | PROCEDURE FOR MANUFACTURING GAMMA PYRONS |
| NO821849A NO150559C (en) | 1976-08-02 | 1982-06-03 | 4-HALOGEN-DIHYDROPYRANE COMPOUNDS AND PROCEDURES FOR PREPARING THEREOF |
Family Applications After (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO821848A NO150043C (en) | 1976-08-02 | 1982-06-03 | PROCEDURE FOR MANUFACTURING GAMMA PYRONS |
| NO821850A NO821850L (en) | 1976-08-02 | 1982-06-03 | PROCEDURE FOR THE PREPARATION OF 4-HALOGEN-DIHYDROPYRANE DERIVATIVES |
| NO821847A NO150042C (en) | 1976-08-02 | 1982-06-03 | PROCEDURE FOR MANUFACTURING GAMMA PYRONS |
| NO834236A NO151365C (en) | 1976-08-02 | 1983-11-18 | PROCEDURE FOR THE PREPARATION OF 4-HALOGEN-DIHYDROPYRANE DERIVATIVES. |
Country Status (36)
| Country | Link |
|---|---|
| JP (7) | JPS5318578A (en) |
| AR (1) | AR216080A1 (en) |
| AT (3) | AT362790B (en) |
| BE (1) | BE855965A (en) |
| BG (4) | BG28849A3 (en) |
| BR (1) | BR7703970A (en) |
| CA (3) | CA1095921A (en) |
| CH (4) | CH625798A5 (en) |
| CS (3) | CS203921B2 (en) |
| DD (1) | DD132494A5 (en) |
| DE (3) | DE2728499C2 (en) |
| DK (4) | DK153483C (en) |
| EG (1) | EG13080A (en) |
| ES (5) | ES459994A1 (en) |
| FI (6) | FI72722C (en) |
| FR (1) | FR2372821A1 (en) |
| GB (5) | GB1538371A (en) |
| GR (1) | GR68938B (en) |
| HK (5) | HK30381A (en) |
| HU (4) | HU186026B (en) |
| IE (5) | IE45645B1 (en) |
| IT (1) | IT1106258B (en) |
| LU (1) | LU77600A1 (en) |
| MX (1) | MX4597E (en) |
| MY (3) | MY8100287A (en) |
| NL (5) | NL170955C (en) |
| NO (7) | NO150561C (en) |
| NZ (1) | NZ184342A (en) |
| PH (5) | PH13557A (en) |
| PL (4) | PL115496B1 (en) |
| PT (1) | PT66694B (en) |
| RO (4) | RO78951A2 (en) |
| SE (6) | SE433079B (en) |
| SU (2) | SU955859A3 (en) |
| TR (1) | TR19652A (en) |
| YU (4) | YU40166B (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1095921A (en) | 1976-08-02 | 1981-02-17 | Thomas M. Brennan | Preparation of gamma-pyrones |
| FR2402654A1 (en) * | 1977-09-12 | 1979-04-06 | Shinetsu Chemical Co | Tetra:hydro-pyranone derivs. - useful as intermediates for cpds. used as food flavours |
| JPS5444675A (en) * | 1977-09-12 | 1979-04-09 | Shin Etsu Chem Co Ltd | Production of 3-hydroxy-4-pyrone analog |
| JPS5741226U (en) * | 1980-08-20 | 1982-03-05 | ||
| JPS59135008U (en) * | 1983-02-28 | 1984-09-10 | 松下電工株式会社 | Distribution board device |
| JPS6050245A (en) * | 1983-08-29 | 1985-03-19 | Nissan Motor Co Ltd | Fuel injection device in internal-combustion engine |
| JPH0226945Y2 (en) * | 1985-09-11 | 1990-07-20 | ||
| JP2586607B2 (en) * | 1987-10-30 | 1997-03-05 | 日産化学工業株式会社 | Production method of optically active alcohol |
| TWI404533B (en) * | 2007-03-28 | 2013-08-11 | Apotex Technologies Inc | Fluorinated derivatives of deferiprone |
| UA102254C2 (en) | 2008-04-25 | 2013-06-25 | Апотекс Технолоджис Инк. | Normal;heading 1;heading 2;heading 3;LIQUID FORMULATION FOR DEFERIPRONE WITH PALATABLE TASTE |
| CN102712591B (en) | 2009-07-03 | 2014-06-25 | 阿普泰克斯科技公司 | Fluorinated derivatives of 3-hydroxypyridin-4-ones |
| WO2017168309A1 (en) * | 2016-03-29 | 2017-10-05 | Dr. Reddy’S Laboratories Limited | Process for preparation of eribulin and intermediates thereof |
| CN108609456B (en) * | 2016-12-13 | 2021-03-12 | 奥的斯电梯公司 | Openable expansion panel and elevator suspended ceiling, elevator car and elevator system with same |
| CN111606879A (en) * | 2020-05-25 | 2020-09-01 | 安徽金禾实业股份有限公司 | Method for preparing 2-hydroxymethyl-3-alkoxy-4H-pyran-4-ketone by one-pot method |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3491122A (en) * | 1966-09-14 | 1970-01-20 | Monsanto Co | Synthesis of 4-pyrones |
| US3547912A (en) * | 1968-07-29 | 1970-12-15 | American Home Prod | Derivatives of 2h-pyran-3(6h)-ones and preparation thereof |
| JPS5145565B1 (en) * | 1968-10-12 | 1976-12-04 | ||
| US3621063A (en) * | 1968-12-24 | 1971-11-16 | Monsanto Co | Unsaturated acyclic ketones |
| US3832357A (en) * | 1971-05-26 | 1974-08-27 | Daicel Ltd | Process for preparation of 3-hydroxy-2-alkyl-4-pyrone |
| JPS5212166A (en) * | 1975-07-17 | 1977-01-29 | Tatsuya Shono | Process for preparation of 4-pyron derivatives |
| IE42789B1 (en) * | 1975-08-28 | 1980-10-22 | Pfizer | Preparation of gamma-pyrones |
| CA1095921A (en) * | 1976-08-02 | 1981-02-17 | Thomas M. Brennan | Preparation of gamma-pyrones |
-
1977
- 1977-06-06 CA CA279,922A patent/CA1095921A/en not_active Expired
- 1977-06-08 NZ NZ184342A patent/NZ184342A/en unknown
- 1977-06-09 GR GR53666A patent/GR68938B/el unknown
- 1977-06-13 YU YU1469/77A patent/YU40166B/en unknown
- 1977-06-15 MX MX775807U patent/MX4597E/en unknown
- 1977-06-16 SE SE7707035A patent/SE433079B/en not_active IP Right Cessation
- 1977-06-16 JP JP7157277A patent/JPS5318578A/en active Granted
- 1977-06-17 PH PH19887A patent/PH13557A/en unknown
- 1977-06-20 BR BR7703970A patent/BR7703970A/en unknown
- 1977-06-21 FI FI771934A patent/FI72722C/en not_active IP Right Cessation
- 1977-06-21 NL NLAANVRAGE7706811,A patent/NL170955C/en not_active IP Right Cessation
- 1977-06-21 BE BE1008209A patent/BE855965A/en not_active IP Right Cessation
- 1977-06-22 PT PT66694A patent/PT66694B/en unknown
- 1977-06-22 DE DE2728499A patent/DE2728499C2/en not_active Expired
- 1977-06-22 DE DE2760221A patent/DE2760221C2/de not_active Expired
- 1977-06-22 LU LU77600A patent/LU77600A1/xx unknown
- 1977-06-22 NO NO772193A patent/NO150561C/en unknown
- 1977-06-22 EG EG371/77A patent/EG13080A/en active
- 1977-06-22 DE DE2760220A patent/DE2760220C2/de not_active Expired
- 1977-06-22 DK DK276177A patent/DK153483C/en active
- 1977-06-22 CH CH765877A patent/CH625798A5/en not_active IP Right Cessation
- 1977-06-22 ES ES459994A patent/ES459994A1/en not_active Expired
- 1977-06-22 AT AT0440477A patent/AT362790B/en not_active IP Right Cessation
- 1977-06-22 TR TR19652A patent/TR19652A/en unknown
- 1977-06-23 DD DD7700199657A patent/DD132494A5/en not_active IP Right Cessation
- 1977-06-23 AR AR268164A patent/AR216080A1/en active
- 1977-06-23 FR FR7719250A patent/FR2372821A1/en active Granted
- 1977-06-23 IT IT49950/77A patent/IT1106258B/en active
- 1977-07-14 BG BG036892A patent/BG28849A3/en unknown
- 1977-07-14 CS CS774705A patent/CS203921B2/en unknown
- 1977-07-14 BG BG042608A patent/BG29136A3/en unknown
- 1977-07-14 BG BG7942607A patent/BG28989A4/en unknown
- 1977-07-14 BG BG7742606A patent/BG28988A4/en unknown
- 1977-07-20 RO RO7799825A patent/RO78951A2/en unknown
- 1977-07-20 RO RO7799826A patent/RO78952A/en unknown
- 1977-07-20 RO RO7799830A patent/RO78953A/en unknown
- 1977-07-20 RO RO7791106A patent/RO74367A/en unknown
- 1977-07-21 SU SU772508256A patent/SU955859A3/en active
- 1977-07-21 GB GB30759/77A patent/GB1538371A/en not_active Expired
- 1977-07-21 HU HU82156A patent/HU186026B/en unknown
- 1977-07-21 HU HU82157A patent/HU185687B/en unknown
- 1977-07-21 HU HU82155A patent/HU185686B/en unknown
- 1977-07-21 PL PL1977215007A patent/PL115496B1/en unknown
- 1977-07-21 PL PL21500877A patent/PL215008A1/en unknown
- 1977-07-21 GB GB4242/78A patent/GB1538374A/en not_active Expired
- 1977-07-21 PL PL1977199798A patent/PL115586B1/en unknown
- 1977-07-21 PL PL1977215006A patent/PL115497B1/en unknown
- 1977-07-21 GB GB4243/78A patent/GB1538375A/en not_active Expired
- 1977-07-21 GB GB4240/78A patent/GB1538372A/en not_active Expired
- 1977-07-21 GB GB4241/78A patent/GB1538373A/en not_active Expired
- 1977-07-21 HU HU77PI584A patent/HU180040B/en unknown
- 1977-07-29 IE IE587/79A patent/IE45645B1/en not_active IP Right Cessation
- 1977-07-29 IE IE1587/77A patent/IE45641B1/en not_active IP Right Cessation
- 1977-07-29 IE IE584/79A patent/IE45642B1/en not_active IP Right Cessation
- 1977-07-29 IE IE585/79A patent/IE45643B1/en not_active IP Right Cessation
- 1977-07-29 IE IE586/79A patent/IE45644B1/en not_active IP Right Cessation
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1978
- 1978-02-03 PH PH20746A patent/PH13926A/en unknown
- 1978-02-03 PH PH20745A patent/PH15185A/en unknown
- 1978-05-25 JP JP6281778A patent/JPS5436266A/en active Pending
- 1978-05-25 JP JP6281978A patent/JPS5436268A/en active Pending
- 1978-05-25 JP JP6282178A patent/JPS5436270A/en active Granted
- 1978-05-25 JP JP53062820A patent/JPS5814433B2/en not_active Expired
- 1978-05-25 JP JP6282278A patent/JPS5436271A/en active Granted
- 1978-05-25 JP JP6281878A patent/JPS5436267A/en active Granted
- 1978-06-07 CS CS783706A patent/CS203923B2/en unknown
- 1978-06-07 CS CS783705A patent/CS203922B2/en unknown
- 1978-06-13 ES ES470743A patent/ES470743A1/en not_active Expired
- 1978-06-13 ES ES470746A patent/ES470746A1/en not_active Expired
- 1978-06-13 ES ES470745A patent/ES470745A1/en not_active Expired
- 1978-06-13 ES ES470744A patent/ES470744A1/en not_active Expired
- 1978-07-05 SU SU782631651A patent/SU1015826A3/en active
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1979
- 1979-02-01 PH PH22150A patent/PH13874A/en unknown
- 1979-02-01 PH PH22149A patent/PH14625A/en unknown
-
1980
- 1980-03-06 AT AT0124380A patent/AT364356B/en not_active IP Right Cessation
- 1980-03-06 AT AT0124480A patent/AT363470B/en not_active IP Right Cessation
- 1980-10-24 CA CA363,273A patent/CA1110254A/en not_active Expired
- 1980-10-24 CA CA000363274A patent/CA1117541A/en not_active Expired
- 1980-10-30 CH CH808580A patent/CH625235A5/en not_active IP Right Cessation
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1981
- 1981-02-20 CH CH116181A patent/CH626358A5/en not_active IP Right Cessation
- 1981-02-20 CH CH116081A patent/CH626357A5/en not_active IP Right Cessation
- 1981-07-02 HK HK303/81A patent/HK30381A/en unknown
- 1981-07-02 HK HK305/81A patent/HK30581A/en unknown
- 1981-07-02 HK HK307/81A patent/HK30781A/en unknown
- 1981-07-02 HK HK304/81A patent/HK30481A/en unknown
- 1981-07-02 HK HK306/81A patent/HK30681A/en unknown
- 1981-12-09 NL NLAANVRAGE8105537,A patent/NL182476C/en not_active IP Right Cessation
- 1981-12-09 NL NLAANVRAGE8105538,A patent/NL182477C/en not_active IP Right Cessation
- 1981-12-09 NL NLAANVRAGE8105540,A patent/NL182805C/en not_active IP Right Cessation
- 1981-12-09 NL NLAANVRAGE8105539,A patent/NL182478C/en not_active IP Right Cessation
- 1981-12-30 MY MY287/81A patent/MY8100287A/en unknown
- 1981-12-30 MY MY267/81A patent/MY8100267A/en unknown
- 1981-12-30 MY MY262/81A patent/MY8100262A/en unknown
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1982
- 1982-01-29 SE SE8200519A patent/SE445042B/en not_active IP Right Cessation
- 1982-01-29 SE SE8200521A patent/SE452616B/en not_active IP Right Cessation
- 1982-01-29 SE SE8200520A patent/SE444564B/en not_active IP Right Cessation
- 1982-01-29 SE SE8200518A patent/SE445041B/en not_active IP Right Cessation
- 1982-01-29 SE SE8200522A patent/SE444565B/en not_active IP Right Cessation
- 1982-06-03 NO NO821849A patent/NO150559C/en unknown
- 1982-06-03 NO NO821851A patent/NO150560C/en unknown
- 1982-06-03 NO NO821848A patent/NO150043C/en unknown
- 1982-06-03 NO NO821850A patent/NO821850L/en unknown
- 1982-06-03 NO NO821847A patent/NO150042C/en unknown
- 1982-12-07 YU YU02703/82A patent/YU270382A/en unknown
- 1982-12-13 YU YU2747/82A patent/YU42613B/en unknown
-
1983
- 1983-05-16 FI FI831702A patent/FI72720C/en not_active IP Right Cessation
- 1983-05-16 FI FI831700A patent/FI72119C/en not_active IP Right Cessation
- 1983-05-16 FI FI831703A patent/FI73424C/en not_active IP Right Cessation
- 1983-05-16 FI FI831704A patent/FI72721C/en not_active IP Right Cessation
- 1983-05-16 FI FI831701A patent/FI72723C/en not_active IP Right Cessation
- 1983-08-08 YU YU1663/83A patent/YU43190B/en unknown
- 1983-11-18 NO NO834236A patent/NO151365C/en unknown
-
1986
- 1986-07-09 DK DK326186A patent/DK154079C/en active
- 1986-07-09 DK DK326086A patent/DK153401C/en not_active IP Right Cessation
- 1986-07-09 DK DK325986A patent/DK153484C/en active
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