DK154079B - PROCEDURE FOR PREPARING 4-HALOGEN-2H-PYRANE-3 (6H) -ON COMPOUNDS - Google Patents
PROCEDURE FOR PREPARING 4-HALOGEN-2H-PYRANE-3 (6H) -ON COMPOUNDS Download PDFInfo
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- 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
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- 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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Description
iin
DK 154079 BDK 154079 B
Opfindelsen angår en særlig fremgangsmåde til fremstilling af kendte og hidtil ukendte 4-halogen-2H-pyran-3 (6H)-on-forbindelser med den i krav l's indledning angivne almene formel (II), der er nyttige som mellemprodukter ved fremstilling af^-pyroner.The invention relates to a particular process for the preparation of known and novel 4-halo-2H-pyran-3 (6H) -one compounds of the general formula (II) set forth in claim 1, which are useful as intermediates in the preparation of -pyroner.
De forbindelser, der anvendes som udgangsmaterialer ved fremgangsmåden ifølge opfindelsen, d.v.s. forbindelser med den nedenfor angivne formel (IV), kan opnås ved en række forskellige fremgangsmåder. Når R' er hydrogen, er en særlig hensigtsmæssig fremgangsmåde oxidationen af en passende substitueret furfurylalkohol med i det væsentlige ét molært ækvivalent af en halogenholdig oxidant, som angivet i det følgende og i dansk patentansøgning nr. 2761/77; en anden fremgangsmåde er den ét-trins oxidation, som er angivet af Lefebvre et al., J.Med.Chem., vol.16,side 1084 (1973); se også US patentskrift nr.The compounds used as starting materials in the process of the invention, i.e. compounds of the formula (IV) listed below can be obtained by a variety of methods. When R 'is hydrogen, a particularly convenient process is the oxidation of a suitably substituted furfuryl alcohol with substantially one molar equivalent of a halogen-containing oxidant, as set forth herein and in Danish Patent Application No. 2761/77; another method is the one-stage oxidation disclosed by Lefebvre et al., J.Med.Chem., Vol.16, page 1084 (1973); see also U.S. Pat.
3 751 434.3 751 434.
Når R1 er en alkylgruppe, som danner en ether, kan forbindelserne med formlen (IV) opnås ud fra de tilsvarende forbindelser, hvori R' er hydrogen, ved den fremgangsmåde, som er beskrevet af Shono et al., Tetrahedron Letters, side 1363 - 1364 (1976), eller mere hensigtsmæssigt ud fra en passende substitueret furfurylalkohol via den totrins fremgangsmåde, som er beskrevet i dansk påtentskrift nr. 148 020.When R 1 is an alkyl group which forms an ether, the compounds of formula (IV) can be obtained from the corresponding compounds wherein R 1 is hydrogen by the method described by Shono et al., Tetrahedron Letters, pages 1363 - 1364 (1976), or more conveniently from an appropriately substituted furfuryl alcohol via the two-step process described in Danish Patent Specification No. 148,020.
Shono et al. og dansk patentskrift nr. 148 020 beskriver uafhængigt opfundne fremgangsmåder til omdannelse af forbindelser med formlen (IV), hvor R' er alkyl, til epoxider af typenShono et al. and Danish Patent No. 148,020 disclose independently invented methods for converting compounds of formula (IV) wherein R 1 is alkyl into epoxides of the type
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2 °\ .o CH30/ xCH3 som derpå i vandig syre omdannes direkte til maltol eller en analog forbindelse.2 ° / o CH30 / xCH3 which is then converted into aqueous acid directly into maltol or an analogous compound.
Paulsen et al., Tetrahedron Letters, side 4377 - 4380 (1974), har beskrevet sukkerafledte optisk aktive varianter af forbindelsernePaulsen et al., Tetrahedron Letters, pages 4377-4380 (1974), have described sugar-derived optically active variants of the compounds.
Xa >γ° CHjO^'NK r3 g g hvori X betyder chlor eller brom, og R betyder hydrogen eller methyl, men det blev ikke erkendt der, at disse forbindelser er af værdi som forstadier til pyromechonsyre og maltol.Xa> γ ° CH 2 O 2 NK r 3 g g wherein X means chlorine or bromine and R is hydrogen or methyl, but it was not recognized there that these compounds are of value as precursors to pyromechonic acid and maltol.
Dansk patentansøgning nr. 2761/77 angiver en fremgangsmåde til fremstilling afy-pyroner med formlen:Danish Patent Application No. 2761/77 discloses a process for preparing epipyrons of the formula:
OISLAND
11 XXr {i) R'f'1 .11 XXr {i) R'f'1.
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3 hvori R betyder hydrogen, alkyl med 1-4 carbonatomer, phenyl eller benzyl, og R''' betyder hydrogen eller alkyl med 1-4 carbonatomer, som er ejendommelig ved, at en _4-halogendihydro-pyran med formlen (II) eller en 6,61-oxybis- !4-halogen-2H-pyran-3(6H)-onj med formlen (V):3 wherein R is hydrogen, alkyl of 1-4 carbon atoms, phenyl or benzyl, and R '' 'means hydrogen or alkyl of 1-4 carbon atoms, which is characterized in that a 4-halo dihydropyran of formula (II) or a 6,61-oxybis-4-halo-2H-pyran-3 (6H) -one of formula (V):
x XXx XX
R'^J 1 Till (ID (V) hvori R og R'11 har den ovenstående betydning, R’ betyder hydrogen, alkyl med 1-4 carbonatomer eller -COR", hvor R" betyder methyl, ethyl eller phenyl, og X betyder chlor eller brom, opvarmes i sur vandig opløsning, indtil hydrolysen er i det væsentlige fuldført.R 1 is (Till (ID)) wherein R and R 11 are as defined above, R 1 is hydrogen, alkyl of 1-4 carbon atoms or -COR "where R" is methyl, ethyl or phenyl, and X means chlorine or bromine, heated in acidic aqueous solution until the hydrolysis is substantially complete.
Den syre, som kræves til hydrolysen, kan tilsættes reaktionsblandingen, f.eks. ved opløsning af mellemproduktet med formlen (II) eller formlen (V) i en vandig uorganisk el£ér organisk syre før opvarmningen, eller alternativt kan syren dannes in situ under fremstillingen af mellemprodukterne som beskrevet i det følgende.The acid required for the hydrolysis can be added to the reaction mixture, e.g. by dissolving the intermediate of formula (II) or formula (V) in an aqueous inorganic or organic acid before heating, or alternatively, the acid may be formed in situ during the preparation of the intermediates as described below.
4-Halogendihydropyran-me11emprodukterne med formlen (II) kan fremstilles ved fremgangsmåden ifølge opfindelsen, som er ejendommelig ved, at en forbindelse med formlen:The 4-halo dihydropyran intermediates of formula (II) can be prepared by the process of the invention, characterized in that a compound of formula:
“"sOT"" Sot
R,0</^0'x^V'RR, 0 </ ^ ^ 0'x V'R
44
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hvori R, R' og R'11 har den ovenstående betydning, omsættes med mindst ét ækvivalent af en halogenholdig oxidant, valgt blandt chlor, brom, bromchlorid, hypochlorsyrling, hypobromsyrling og . blandinger deraf, i et opløsningsmiddel ved en temperatur på fra -50 til 50°C, fortrinsvis ved stuetemperatur, indtil reaktionen er i det væsentlige fuldført.wherein R, R 'and R'11 have the above meaning, are reacted with at least one equivalent of a halogen-containing oxidant selected from chlorine, bromine, bromine chloride, hypochlorous acid, hypobromoric acid and. mixtures thereof, in a solvent at a temperature of from -50 to 50 ° C, preferably at room temperature, until the reaction is substantially complete.
Eksempler på egnede opløsningsmidler til denne reaktion er vand, en alkanol eller -diol med 1-4 carbonatomer, fortrinsvis methanol, en ether med 2-10 carbonatomer, fortrinsvis tetra-hydrofuran eller isopropylether, en lavmolekylær keton, fortrinsvis acetone, et lavmolekylært nitril, en lavmolekylær ester eller et lavmolekylært amid.Examples of suitable solvents for this reaction are water, an alkanol or diol of 1-4 carbon atoms, preferably methanol, an ether of 2-10 carbon atoms, preferably tetrahydrofuran or isopropyl ether, a low molecular ketone, preferably acetone, a low molecular nitrile, a low molecular weight ester or a low molecular weight amide.
Visse af 4-halogendihydropyran-forbindelserne med den almene formel (II) er hidtil ukendte, nemlig 6-hydroxy-forbindelserne med den almene formel R·"! ] («')Certain of the 4-halo dihydropyran compounds of general formula (II) are novel, namely, the 6-hydroxy compounds of general formula R
og 6-alkoxy- og acyloxy-2-ethyl-forbindelserne med den almene formel Xand the 6-alkoxy and acyloxy-2-ethyl compounds of general formula X
R'Vj 1 (VI) R4tf^O/^C2H5 4 hvori R, R'1' og X har den ovenstående betydning, og R be-R'Vj 1 (VI) R4tf ^ O / ^ C2H5 4 wherein R, R'1 'and X are as defined above and R is
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5 tyder alkyl med 1-4 carbonatomer eller -COR", hvor R" betyder methyl, ethyl eller phenyl.5 is alkyl of 1-4 carbon atoms or -COR ", where R" is methyl, ethyl or phenyl.
De forbindelser med formlen (II), h\/ori R er hydrogen eller methyl, R' er methyl, R'1' er hydrogen, og X har den ovenstående betydning, må betragtes som kendte fra Paulsen et al., ovenfor, hvor de opnås i lavt udbytte ud fra sukkerstoffer.The compounds of formula (II) wherein h 1 / ori R is hydrogen or methyl, R 1 is methyl, R 1 is hydrogen, and X has the above meaning must be considered as known from Paulsen et al., Above, where they are obtained in low yield from sugars.
Den foreliggende opfindelse tilvejebringer således en overraskende simpel og effektiv fremgangsmåde til fremstilling af nyttige mellemproduktforbindelser med formlen (II) ud fra mellemprodukter med formlen (IV), som på deres side kan fremstilles meget simpelt ud fra lettilgængelige udgangsmaterialer. Det kunne ikke f0r denne opfindelse forudses, at behandling af en forbindelse med formlen (IV) med en af de førnævnte halogenholdige oxidanter ville resultere i en simpel substitution med halogen i 4-stil-ling til dannelse af en forbindelse med formlen (II), som let kan omdannes til en nyttig ^»-pyron med formlen (I) ved sur hydrolyse under eliminering af HX og andre omlejrings- og elimineringsreaktioner.Thus, the present invention provides a surprisingly simple and effective process for preparing useful intermediate compounds of formula (II) from intermediates of formula (IV), which in turn can be prepared very simply from readily available starting materials. It was not foreseen for this invention that treatment of a compound of formula (IV) with one of the aforementioned halogen-containing oxidants would result in a simple substitution with halo in 4-position to form a compound of formula (II), which can be readily converted into a useful ^ - pyrone of formula (I) by acid hydrolysis, eliminating HX and other rearrangement and elimination reactions.
Udgangsmaterialerne med den ovenstående formel (IV), hvori R' er hydrogen, kan fremstilles ved omsætning af furfurylalkohol med formlen r —<(0Η di« hvori R og R1'1 har den i krav 1 angivne betydning, i en vandig opløsning med mindst ét ækvivalent af en halogenholdig oxidant, valgt blandt chlor, brom, bromchlorid, hypochlorsyrling, hypo-The starting materials of the above formula (IV) wherein R 'is hydrogen can be prepared by reacting furfuryl alcohol of formula r - <(0Η di' wherein R and R1'1 have the meaning of claim 1, in an aqueous solution of at least one equivalent of a halogen-containing oxidant selected from chlorine, bromine, bromine chloride, hypochlorous acid,
. DK 154079B. DK 154079B
6 bromsyrling og blandinger deraf ved en temperatur på mellem -50 og +50°C, fortrinsvis ved stuetemperatur, indtil reaktionen er i det væsentlige fuldført. Reaktionen kan gennemføres i nærvær af et hjælpeopløsningsmiddel, som passende kan være et af de opløsningsmidler, som er nævnt ovenfor til fremstilling af mellemproduktet med formlen (II).6 bromine acid and mixtures thereof at a temperature between -50 and + 50 ° C, preferably at room temperature until the reaction is substantially complete. The reaction may be carried out in the presence of an auxiliary solvent which may conveniently be one of the solvents mentioned above for the preparation of the intermediate of formula (II).
Ved hver af de ovenfor beskrevne reaktioner er den foretrukne halogenholdige oxidant chlor eller bromchlorid.In each of the reactions described above, the preferred halogen-containing oxidant is chlorine or bromine chloride.
Den halogenholdige oxidant vælges som nævnt blandt chlor, brom,bromchlorid, hypochlorsyrling, hypobromsyrling og blandinger deraf. Bromchlorid er en kommercielt tilgængelig gas. Den kan fremstilles in situ ved tilsætning af chlor til en opløsning af natrium- eller kaliumbromid eller ved tilsætning af brom til en opløsning af natrium- eller kaliumchlorid. Hypochlorsyrling og hypobromsyrling kan hensigtsmæssigt dannes in situ ved tilsætning af vandig syre (HC1, H2S04 eller HBr) til en opløsning af et alkalimetal- eller jordalkalimetalhypohalogenit, f.eks.As mentioned, the halogen-containing oxidant is selected from chlorine, bromine, bromine chloride, hypochlorous acid, hypobromoric acid and mixtures thereof. Bromine chloride is a commercially available gas. It can be prepared in situ by adding chlorine to a solution of sodium or potassium bromide or by adding bromine to a solution of sodium or potassium chloride. Hypochlorous acid and hypobromous acid may conveniently be formed in situ by the addition of aqueous acid (HCl, H2SO4 or HBr) to a solution of an alkali metal or alkaline earth metal hypohalogenite, e.g.
NaOCl, KOCl eller Ca(0Cl)2. De foretrukne halogenholdige oxi-danter ud fra omkostningshensyn er chlor og bromchlorid, fremstillet in situ.NaOCl, KOCl or Ca (OCl) 2. The preferred halogen-containing oxides for cost reasons are chlorine and bromine chloride produced in situ.
6-Alkoxy-2H-pyran-3(6H)-oner med den ovenstående formel (IV), hvori R' er alkyl, kan som tidligere nævnt fremstilles ved den metode, som er beskrevet af Shono et al. i Tetrahedron Letters No. 17, 1363 - 1364 (1976). En tilsvarende furfuryl-alkohol alkoxyleres anodisk til 2-(l-hydroxyalkyl)-2,5-dial-koxy-dihydrofuranen, og behandling af denne med en stærk organisk syre giver den ønskede 6-alkoxyforbindelse. En anden metode går ud på at behandle en passende substitueret fur-furylalkohol med en i hovedsagen vandfri syre med pKg 4 eller derunder som beskrevet i dansk patentskrift nr. 148 020.6-Alkoxy-2H-pyran-3 (6H) -ones of the above formula (IV) wherein R 1 is alkyl can, as previously mentioned, be prepared by the method described by Shono et al. in Tetrahedron Letters No. 17, 1363 - 1364 (1976). A corresponding furfuryl alcohol is anodically alkoxylated to the 2- (1-hydroxyalkyl) -2,5-dialkoxy dihydrofuran, and treatment thereof with a strong organic acid gives the desired 6-alkoxy compound. Another method is to treat a suitably substituted furfuryl alcohol with a substantially anhydrous acid of pKg 4 or less as described in Danish Patent No. 148,020.
En 6-acyloxyforbindelse kan fremstilles ved konventionel be-A 6-acyloxy compound can be prepared by conventional treatment.
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7 handling af 6-hydroxyforbindelsen med det tilsvarende syreanhydrid i nærvær af pyridin.7 action of the 6-hydroxy compound with the corresponding acid anhydride in the presence of pyridine.
I en udførelsesform af fremgangsmåden ifølge opfindelsen opløses en 6-acyl®xy- eller 6-alkoxy-2H-pyran-3(6H)-on i et opløsningsmiddel valgt blandt vand, ethesre, alkanoler eller -dioler med 1-4 carbonatomer ellaer lav-molekylære ketoner, nitriler, estere eller amidærr.. Det foretrukne opløsningsmiddel er methanol. Der tilssættes et ækvivalent af en af de ovennævnte halogenholxEige oxidanter valgt blandt chlor, brom, bromchlorid., "hypo-chlersyrling, hypobromsyrling eller blandinger iteraf, og ihalogeneringen gennemføres ved en temperatur fpS fra -20 til 20°C, fortrinsvis 5-10°C, i nærvær af en iorga-nisk base, såsom trietHnylamin. Efter omkring 30’minutter får reaktionsblandingerm lov at opvarmes til stueSaempera-tur, filtreres for at fjerne triethylamin-hydrolhsalogenid, og opløsningsmidlet fjernes under vakuum til opnåelse af 4-halogen-dihydropyranen.In one embodiment of the process of the invention, a 6-acyl®xy or 6-alkoxy-2H-pyran-3 (6H) -one is dissolved in a solvent selected from water, ethers, alkanols or diols of 1-4 carbon atoms or low Molecular ketones, nitriles, esters or amides. The preferred solvent is methanol. An equivalent of one of the above halogenoholic oxidants selected from chlorine, bromine, bromochloride, hypochlorous acid, hypobromoric acid or mixtures iterate is added and the halogenation is carried out at a temperature fpS of -20 to 20 ° C, preferably 5-10 °. C, in the presence of an organic base such as triethylamine. After about 30 minutes, the reaction mixture is allowed to warm to room temperature, filtered to remove triethylamine hydrolyzalide and the solvent removed in vacuo to give the 4-halo dihydropyran. .
De ved fremgangsmåden ifølge opfindelsen fremstnlllLede 4-halogen-2H-pyran-3(6iHO- on _ forbindelser hydrolyser es let til γ-pyroner ved opvarmning i omkring 1 time i vandig opløsning, om ømsket efter tilsætning af -syre, fortrinsvis ved en temperatur i området 70-160°(C., mest foretrukkent 100-110°C.The 4-halo-2H-pyran-3 (6HHO-1) compounds prepared by the process of the invention are readily hydrolyzed to γ-pyrones by heating for about 1 hour in aqueous solution, if softened after addition of acid, preferably at a temperature. in the range of 70-160 ° C, most preferably 100-110 ° C.
Forbindelserne med formlenThe compounds of the formula
XX
r^V°r ^ V °
HQ^ 0 . RHQ ^ 0. R
hvori R og X har den ovenstående betydning, kam også først dehydratiseres ved opvarmning under vakuum til dannelse af 6,61-oxybis-[4-halogen-2H-pyran-3-(6H)-on] -forbindelserne med formlen (V) og disse derpå hydrolyseres til y-pyronerne enm rt^n/nh m/finf nrwherein R and X have the above meaning, comb first is also dehydrated by heating under vacuum to give the 6,61-oxybis [4-halogen-2H-pyran-3- (6H) -one] compounds of formula (V) and these are then hydrolyzed to the γ-pyrones enm rt ^ n / nh m / finf no
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88
De følgende eksempler 1-4 tjener til nærmere belysning af fremgangsmåden ifølge opfindelsen, mens eksempel 5 belyser omdannelsen af den i eksempel 1 fremstillede fø’rbindelse til maltol i godt udbytte.The following Examples 1-4 illustrate the process of the invention, while Example 5 illustrates the conversion of the compound of Example 1 into maltol in good yield.
EKSEMPEL 1EXAMPLE 1
Til em opløsning af 6-methoxy-2-methyl-2H-pyran-3-(6H)-on (0,05 mol) i 70 ml diehlormethan ved -10°0 sattes chlor (0,05 mol) via et gasindførselsrør. Efter denne tilsætning tilsattes langsomt triethylamin (0,05 mol), medens temperaturen holdtes ved -10°C. Efter 30 minutters omrøring fik reaktionsblandingen lov at opvarmes til stuetemperatur, hvorpå den hlev filtreret for at fjerne triethylamin-hydrochlorid, og opløsningsmidlet blev fjernet under vakuum. Genopløsning af det rå produkt i ether/benzen og filtrering fjernede de sidste spor af triethylamin-hydrochlorid. Fjernelse af opløsningsmidlet gav 4-chlor-6-methoxy-2-methyl- 2H-pyran-3(6H)-on (udbytte 99%). NMR-analyse af signalerne ved 5,05 -5,25 viste klart to dubletter i et forhold på 3:1 svarende til protonen ved C-6 af de to mulige isomere af forbindelsen. Begge optiske former af trans-isomeren var blevet syntetiseret fra et carbonhydrat-forstadium af Paulsen, Eberstein and Koebemick, Tetrahedron Letters 4377 (1974).To a solution of 6-methoxy-2-methyl-2H-pyran-3- (6H) -one (0.05 mole) in 70 ml of dichloromethane at -10 ° 0 was added chlorine (0.05 mole) via a gas feed tube. After this addition, triethylamine (0.05 mole) was slowly added while maintaining the temperature at -10 ° C. After 30 minutes of stirring, the reaction mixture was allowed to warm to room temperature, then filtered to remove triethylamine hydrochloride and the solvent removed in vacuo. Redissolving the crude product in ether / benzene and filtration removed the last traces of triethylamine hydrochloride. Removal of the solvent gave 4-chloro-6-methoxy-2-methyl-2H-pyran-3 (6H) -one (yield 99%). NMR analysis of the signals at 5.05 -5.25 clearly showed two doublets in a ratio of 3: 1 corresponding to the proton at C-6 of the two possible isomers of the compound. Both optical forms of the trans isomer had been synthesized from a carbohydrate precursor by Paulsen, Eberstein and Koebemick, Tetrahedron Letters 4377 (1974).
EKSEMPEL 2 4zbrom-6-methoxyz£i52iliZiz£5l2HBBz2i§52z2£EXAMPLE 2 4-Bromo-6-methoxy-2-yl 2
Proceduren fra eksempel 1 blev gentaget under erstatning af chlor med brom til opnåelse af 4-brom-6-methoxy-2-methyl-2H-pyran-3(6H)-on i 93 # udbytte. De to optiske former af trans-isomeren var blevet syntetiseret af Paulsen og medarbejdere, Tetrahedron Letters 4377 (1974).The procedure of Example 1 was repeated replacing chlorine with bromine to give 4-bromo-6-methoxy-2-methyl-2H-pyran-3 (6H) -one in 93% yield. The two optical forms of the trans isomer had been synthesized by Paulsen and co-workers, Tetrahedron Letters 4377 (1974).
99
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ElKSEMPEL 3 4-bro®-6-acetoxy-2H-pyram-3(6H)-onEXAMPLE 3 4-Bridge®-6-acetoxy-2H-pyram-3 (6H) -one
En opløsning i dichlo.rmettian af 6-acetoxy-2H-pyran~3(6H)-on, fremstillet ved den metode, som er beskrevet i Tetrahedron 27, 1973 (1971), blev bromeret ved proceduren fra eksempel 2 til opnåelse af 4-brom-6-acetoxy-2H-pyran-3(6H)-on., ;smp.: 78 - 80°C, Forbindelsens massespektrum viste de fomvæntede stam-maksima ved 234 og 236 masseenheder.A solution in dichloromethane of 6-acetoxy-2H-pyran-3 (6H) -one, prepared by the method described in Tetrahedron 27, 1973 (1971), was brominated by the procedure of Example 2 to give 4 -bromo-6-acetoxy-2H-pyran-3 (6H) -one., mp: 78-80 ° C. The mass spectrum of the compound showed the expected strain maxima at 234 and 236 mass units.
EKSEMPEL 4 4-brom-6-acetoxy-2-methyl-2H-pyran-3(6H)-onEXAMPLE 4 4-Bromo-6-acetoxy-2-methyl-2H-pyran-3 (6H) -one
Proceduren fra eksempel 3 iblev gentaget med 6-aceto«X;,y--2-methyl-2H-pyran-3(6H)-on, fremstillet ved den samme metode, til opnåelse af 4-brom-6-acetoxy-2-methyl-2H-pyran—3(t6H)-on, som viste stam-masser på 249,96 og 247,96 ved massespskitnoskopi og det følgende NMR-spektnum: fc, CDCl-j) : 7,3 (IH, d) 6.4 (IH,d af d) 4,7 (IH, q) 2,2 (3H, s) 1.4 (3H, s).The procedure of Example 3 was repeated with 6-aceto [X], γ-2-methyl-2H-pyran-3 (6H) -one, prepared by the same method, to give 4-bromo-6-acetoxy-2 -methyl-2H-pyran-3 (t6H) -one, which showed stock masses of 249.96 and 247.96 by mass spectroscopy and the following NMR spectrum: fc, CDCl-j): 7.3 (1H, d ) 6.4 (1H, d of d) 4.7 (1H, q) 2.2 (3H, s) 1.4 (3H, s).
EKSEMPEL 5 I en rundbundet kolbe forsynet med omrøringsstav og 'tilbagesvaler fyldtes 4-chlor-6-«ethoxy-2-methyl-2H-pyran-3(6H)-on og eddikesyre, og reaktionsblandingen blev opvarmet 'til tilbagesvaling i en time. Maltol (65 pct.) blev opnået ved afkøling-EXAMPLE 5 In a round bottom flask equipped with stirring bar and reflux, 4-chloro-6-ethoxy-2-methyl-2H-pyran-3 (6H) -one and acetic acid were charged and the reaction mixture heated to reflux for one hour. Maltol (65 per cent) was obtained by cooling
Claims (3)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71090176A | 1976-08-02 | 1976-08-02 | |
| US71090176 | 1976-08-02 | ||
| US05/721,885 US4082717A (en) | 1976-08-02 | 1976-09-09 | Preparation of gamma-pyrones |
| US72188576 | 1976-09-09 | ||
| DK276177A DK153483C (en) | 1976-08-02 | 1977-06-22 | PROCEDURE FOR MANUFACTURING GAMMA PYRONS |
| DK276177 | 1977-06-22 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| DK326186D0 DK326186D0 (en) | 1986-07-09 |
| DK326186A DK326186A (en) | 1986-07-09 |
| DK154079B true DK154079B (en) | 1988-10-10 |
| DK154079C DK154079C (en) | 1989-02-27 |
Family
ID=27108548
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK276177A DK153483C (en) | 1976-08-02 | 1977-06-22 | PROCEDURE FOR MANUFACTURING GAMMA PYRONS |
| DK326186A DK154079C (en) | 1976-08-02 | 1986-07-09 | METHOD OF PREPARING 4-HALOGEN-2H-PYRANE-3 (6H) -ON COMPOUNDS |
| DK326086A DK153401C (en) | 1976-08-02 | 1986-07-09 | 4-HALOGEN-6-HYDROXY-2H-PYRANE-3 (6H) -ON COMPOUNDS FOR USE AS INTERMEDIATES IN THE PRODUCTION OF GAMMA PYRONS AND PROCEDURES FOR THE PRODUCTION OF INTERMEDIATE PRODUCTS |
| DK325986A DK153484C (en) | 1976-08-02 | 1986-07-09 | PROCEDURE FOR MANUFACTURING GAMMA PYRONS |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK276177A DK153483C (en) | 1976-08-02 | 1977-06-22 | PROCEDURE FOR MANUFACTURING GAMMA PYRONS |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK326086A DK153401C (en) | 1976-08-02 | 1986-07-09 | 4-HALOGEN-6-HYDROXY-2H-PYRANE-3 (6H) -ON COMPOUNDS FOR USE AS INTERMEDIATES IN THE PRODUCTION OF GAMMA PYRONS AND PROCEDURES FOR THE PRODUCTION OF INTERMEDIATE PRODUCTS |
| DK325986A DK153484C (en) | 1976-08-02 | 1986-07-09 | PROCEDURE FOR MANUFACTURING GAMMA PYRONS |
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| JP (7) | JPS5318578A (en) |
| AR (1) | AR216080A1 (en) |
| AT (3) | AT362790B (en) |
| BE (1) | BE855965A (en) |
| BG (4) | BG28989A4 (en) |
| BR (1) | BR7703970A (en) |
| CA (3) | CA1095921A (en) |
| CH (4) | CH625798A5 (en) |
| CS (3) | CS203921B2 (en) |
| DD (1) | DD132494A5 (en) |
| DE (3) | DE2760221C2 (en) |
| DK (4) | DK153483C (en) |
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| HK (5) | HK30681A (en) |
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| MY (3) | MY8100262A (en) |
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| PT (1) | PT66694B (en) |
| RO (4) | RO74367A (en) |
| SE (6) | SE433079B (en) |
| SU (2) | SU955859A3 (en) |
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| 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 |
| NZ579928A (en) | 2007-03-28 | 2012-09-28 | Apotex Technologies Inc | Fluorinated derivatives of deferiprone |
| PT2268282E (en) | 2008-04-25 | 2015-02-05 | Apotex Technologies Inc | Liquid formulation for deferiprone with palatable taste |
| PL2448922T3 (en) | 2009-07-03 | 2015-02-27 | Apotex Tech Inc | 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 |
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| 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 |
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1977
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1979
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1980
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1983
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1986
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