NL8301175A - PROCESS FOR THE PREPARATION OF 2- (E) -PENYLMETHYLENE CYCLOHEPTAN-1-ON- (E) -OXIM. - Google Patents
PROCESS FOR THE PREPARATION OF 2- (E) -PENYLMETHYLENE CYCLOHEPTAN-1-ON- (E) -OXIM. Download PDFInfo
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- NL8301175A NL8301175A NL8301175A NL8301175A NL8301175A NL 8301175 A NL8301175 A NL 8301175A NL 8301175 A NL8301175 A NL 8301175A NL 8301175 A NL8301175 A NL 8301175A NL 8301175 A NL8301175 A NL 8301175A
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- Prior art keywords
- reaction
- cycloheptan
- water
- alcohol
- phenylmethylene
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- 238000000034 method Methods 0.000 title claims description 12
- 238000002360 preparation method Methods 0.000 title claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 29
- 238000006243 chemical reaction Methods 0.000 claims description 16
- BQCRDGOBIZRDJH-ACCUITESSA-N (2e)-2-benzylidenecycloheptan-1-one Chemical compound O=C1CCCCC\C1=C/C1=CC=CC=C1 BQCRDGOBIZRDJH-ACCUITESSA-N 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 9
- 239000011541 reaction mixture Substances 0.000 claims description 9
- 150000002443 hydroxylamines Chemical class 0.000 claims description 5
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 4
- 238000011065 in-situ storage Methods 0.000 claims description 4
- 239000012429 reaction media Substances 0.000 claims description 3
- 125000001931 aliphatic group Chemical group 0.000 claims 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 238000009835 boiling Methods 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 2
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- -1 aliphatic alcohols Chemical class 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- QUXBXCLXGZYNFP-UHFFFAOYSA-N 2-methylidenecycloheptan-1-one Chemical compound C=C1CCCCCC1=O QUXBXCLXGZYNFP-UHFFFAOYSA-N 0.000 description 1
- DCDAOVIVXGHHHU-UHFFFAOYSA-N 3-benzyl-3-azabicyclo[3.2.1]octan-8-one Chemical compound O=C1C(C2)CCC1CN2CC1=CC=CC=C1 DCDAOVIVXGHHHU-UHFFFAOYSA-N 0.000 description 1
- ZNBNBTIDJSKEAM-UHFFFAOYSA-N 4-[7-hydroxy-2-[5-[5-[6-hydroxy-6-(hydroxymethyl)-3,5-dimethyloxan-2-yl]-3-methyloxolan-2-yl]-5-methyloxolan-2-yl]-2,8-dimethyl-1,10-dioxaspiro[4.5]decan-9-yl]-2-methyl-3-propanoyloxypentanoic acid Chemical compound C1C(O)C(C)C(C(C)C(OC(=O)CC)C(C)C(O)=O)OC11OC(C)(C2OC(C)(CC2)C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CC1 ZNBNBTIDJSKEAM-UHFFFAOYSA-N 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229910000378 hydroxylammonium sulfate Inorganic materials 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000010583 slow cooling Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 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
- 238000004857 zone melting Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
- C07C249/08—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reaction of hydroxylamines with carbonyl compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/15—Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C251/44—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups being part of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
, N/3l.378-Kp/Pf-vdM , ..... ; - 1 -, N / 31778-Kp / Pf-vdM, .....; - 1 -
Werkwijze voor de bereiding van 2—(E)-fenylmethyleencyclo-heptan-1-on-(E)-oxim-Process for the preparation of 2— (E) -phenylmethylene-cyclo-heptan-1-one- (E) -oxime-
De uitvinding heeft betrekking op een werkwijze voor de bereiding van 2-(E)-fenylmethyleencycloheptan-l-on- (E)-oxim met de formule I van het formuleblad, vrij van andere isomeren. De verbinding met formule I dient als tussenprodukt 5 dat bruikbaar is bij de synthese van derivaten met waardevolle farmaceutische eigenschappen, bijv. bij de synthese van de verbindingen beschreven in het Hongaarse octrooischrift 169.289.The invention relates to a process for the preparation of 2- (E) -phenylmethylene-cycloheptan-1-one- (E) -oxime of the formula I of the formula sheet, free from other isomers. The compound of formula I serves as an intermediate 5 which is useful in the synthesis of derivatives of valuable pharmaceutical properties, e.g. in the synthesis of the compounds described in Hungarian patent 169,289.
Tot dusver werd in de literatuur geen methode beschreven voor de bereiding van de verbinding met formule I.To date, no method has been described in the literature for the preparation of the compound of formula I.
10 - Het is bekend dat ketonen een interactie ver tonen met hydroxylamine dat in situ is verkregen uit een hydroxylaminezout in aanwezigheid van een base. De reactie leidt tot een oxim. De structurele eigenschappen van het uit-gangsketon in aanmerking genomen kunnen twee isomeren worden 15 gevormd in de reactie. In meer eenvoudige gevallen worden deze ,rsynH resp. 11 anti" genoemd, terwijl in het geval van verbindingen met een meer gecompliceerde structuur de aanduidingen "Z" resp. "E" worden gebruikt.10 - Ketones are known to interact with hydroxylamine obtained in situ from a hydroxylamine salt in the presence of a base. The reaction results in an oxime. Considering the structural properties of the starting ketone, two isomers can be formed in the reaction. In simpler cases these, rsynH resp. 11 are called anti ", while in the case of compounds of a more complicated structure, the designations" Z "and" E "are used.
Het is bekend dat de verschillende isomeren 20 verschillende biologische eigenschappen bezitten. Dat is de reden waarom in veel gevallen het noodzakelijk is deze in zuivere vorm te bereiden, hetgeen slechts uit tussenprodukten die vrij van isomeren zijn, kan worden bereikt.The different isomers are known to have different biological properties. That is why in many cases it is necessary to prepare them in pure form, which can only be achieved from isomer-free intermediates.
Het doel van onze onderzoekingen was een werk-25 wijze uit te werken die geschikt is voor de bereiding van het 2-(E)-fenylmethyleencycloheptan-l-on-(E)-oxim, dat vrij is van andere isomeren.The purpose of our studies was to devise a process suitable for the preparation of the 2- (E) -phenylmethylene-cycloheptan-1-one (E) -oxime, which is free from other isomers.
Gevonden werd dat wanneer het 2-(E)-fenyl-methyleencycloheptan-l-on met formule II van het formuleblad 30 tot reactie wordt gebracht met hydroxylamine dat in situ is verkregen uit een hydroxylaminezout in aanwezigheid van een base, in water en/of in een lagere, met water onbeperkt mengbare alifatische alcohol en het alcoholgehalte van het reac-tiemedium tot 40-60 %, bij voorkeur tot 50 %, wordt bijgesteld, 35 vrijwel uitsluitend het gewenste (E,E)-isomeer wordt verkregen.It was found that when the 2- (E) -phenyl-methylene-cycloheptan-1-one of formula II of formula sheet 30 is reacted with hydroxylamine obtained in situ from a hydroxylamine salt in the presence of a base, in water and / or in a lower water-unlimited miscible aliphatic alcohol and the alcohol content of the reaction medium is adjusted to 40-60%, preferably up to 50%, almost exclusively the desired (E, E) isomer is obtained.
Het produkt bevat ten hoogste 5 % aan andere isomeren, die 8301175 - 2 - desgewenst langs bekende wegen verwijderd kunnen worden.The product contains at most 5% of other isomers, which can be removed if desired by known routes.
De uitgangsverbinding met formule II is bekend en kan worden bereid volgens in de literatuur beschreven werkwijzen /bijv.: Gazz. Chim. Ital. '91, 326-48 (1961/7· De 5 hydroxylaminezouten (sulfaat, hydrochloride) zijn commercieel verkri j gbare produkten.The starting compound of formula II is known and can be prepared according to methods described in the literature / e.g. Gazz. Chim. Ital. 91, 326-48 (1961/7) The 5 hydroxylamine salts (sulfate, hydrochloride) are commercially available products.
De reactie van het 2-(E)-fenylmethyleencyclo-heptan-l-on met het hydroxylamine dat in situ wordt verkregen uit een hydroxylaminezout (bij voorkeur sulfaat of hydrochlo-10 ride) wordt in water en/of in een waterige alcohol als medium uitgevoerd. Hiertoe kunnen rechte of vertakte, met water onbeperkt mengbare alifatische alcoholen worden gebruikt, zoals methanol, ethanol, n-propanol, isopropanol, enz. De reactie wordt bij voorkeur uitgevoerd in het mengsel van een alcohol 15 en water, bij voorkeur in een (50-98) : (2-50)-mengsel van deze oplosmiddelen. Wanneer de reactie is afgelopen wordt de alcoholconcentratie bijgesteld tot 40-60, bij voorkeur tot ca. 50 %, door de toevoeging van water (ijs) of alcohol.The reaction of the 2- (E) -phenylmethylene-cyclo-heptan-1-one with the hydroxylamine obtained in situ from a hydroxylamine salt (preferably sulfate or hydrochloride) is in water and / or in an aqueous alcohol as medium executed. To this end, straight or branched water-unlimited miscible aliphatic alcohols such as methanol, ethanol, n-propanol, isopropanol, etc. can be used. The reaction is preferably carried out in the mixture of an alcohol and water, preferably in a (50 -98): (2-50) mixture of these solvents. When the reaction is complete, the alcohol concentration is adjusted to 40-60, preferably to about 50%, by the addition of water (ice) or alcohol.
De reactie wordt uitgevoerd in aanwezigheid van 20 een base. Hiertoe kunnen organische basen (pyridine of pyri-dinebasen, d.w.z. het mengsel van 2-, 3- en 4-picoline en lutidine) of anorganische basen (alkalihydroxiden, -carbonaten of -waterstofcarbonaten) worden gebruikt.The reaction is carried out in the presence of a base. For this purpose, organic bases (pyridine or pyridine bases, i.e. the mixture of 2-, 3- and 4-picoline and lutidine) or inorganic bases (alkali hydroxides, carbonates or hydrogen carbonates) can be used.
De reactietemperatuur beïnvloedt de opbrengst 25 niet in wezenlijke mate en kan binnen een wijd gebied worden gevariëerd. Men werkt in het algemeen tussen 20°C en 90°C,,bij voorkeur tussen 75°C en 85°C.The reaction temperature does not substantially affect the yield 25 and can be varied over a wide range. Generally it is operated between 20 ° C and 90 ° C, preferably between 75 ° C and 85 ° C.
De stereochemische zuiverheid van het zo verkregen 2-(E)-fenylmethyleencycloheptan-l-on-(E)-oxim hangt af 30 van die van het voor de reactie gebruikte 2-(E)-fenylmethyleencycloheptan-l-on. Indien deze laatste verbinding namelijk verontreinigd is met een tamelijk grote hoeveelheid van zijn 2—(Z)-isomeer, neemt het aantal van de mogelijke isomeerver-ontreinigingen tweevoudig toe en kan de onzuiverheid van het 35 zo verkregen produkt de boven gegeven limiet overschrijden.The stereochemical purity of the 2- (E) -phenylmethylene-cycloheptan-1-one (E) -oxime thus obtained depends on that of the 2- (E) -phenylmethylene cycloheptan-1-one used for the reaction. Namely, if the latter compound is contaminated with a fairly large amount of its 2- (Z) -isomer, the number of possible isomer impurities increases two-fold and the impurity of the product thus obtained may exceed the above-given limit.
Indien een bijzonder zuiver produkt noodzakelijk is, kan het in de reactie verkregen ruwe produkt langs op zich bekende wegen worden gezuiverd (bijv. kolomchromatografie, 8301175 Ί» - 3 - destillatie, zonesmelting, kristallisatie uit petroleumether of uit ethanol).If a particularly pure product is necessary, the crude product obtained in the reaction can be purified by means known per se (eg column chromatography, 8301175 - 3 - distillation, zone melting, crystallization from petroleum ether or from ethanol).
De uitvinding wordt toegelicht aan de hand van de volgende niet beperkende voorbeelden.The invention is illustrated by the following non-limiting examples.
5 VOORBEELD IEXAMPLE I
33
In 100 cm 96 % ethanol worden 20 g (0,1 mol) 2-(E)-fenylmethyleencycloheptan-l-on en 7,65 g (0,11 mol) hydroxylaminehydrochloride opgelost en onder roeren wordt 5,94 g (0,056 mol) natriumcarbonaat aan het reactiemengsel 10 toegevoegd. Daarop wordt het verhit tot aan koken en bij deze temperatuur gehouden totdat de gasvorming (kooldioxide) ophoudt. Daarna wordt 98 g vergruisd ijs toegevoegd aan het reactiemengsel en wordt het in de vorm van kristallen afgescheiden 2-(E)-fenylmethyleencycloheptan-l-on-(E)-oxim afge-15 filtreerd.20 g (0.1 mol) of 2- (E) -phenylmethylene cycloheptan-1-one and 7.65 g (0.11 mol) of hydroxylamine hydrochloride are dissolved in 100 cm of 96% ethanol and 5.94 g (0.056 mol) is stirred ) sodium carbonate was added to the reaction mixture 10. It is then heated to boiling and kept at this temperature until gas formation (carbon dioxide) ceases. 98 g of crushed ice are then added to the reaction mixture and the 2- (E) -phenylmethylene-cycloheptan-1-one (E) -oxime separated in the form of crystals is filtered off.
Opbrengst: 19,8 g (92 %) witte kristallen. Smp.: 67°C.Yield: 19.8 g (92%) of white crystals. Mp .: 67 ° C.
Analyse: C-^H^NO (215,29).Analysis: C-H-NO (215.29).
Berekend: C: 78,1 % H: 7,96 % N: 6,5 % gevonden: C: 78,0 % H: 8,0 % N: 6,5 % 20 NMR (CDC13): 6,95 ppm 6,55 ppm 2,5 ppm UV: Xmax: 258 nm; E** (258) = 740,23Calculated: C: 78.1% H: 7.96% N: 6.5% found: C: 78.0% H: 8.0% N: 6.5% 20 NMR (CDCl3): 6.95 ppm 6.55 ppm 2.5 ppm UV: Xmax: 258 nm; E ** (258) = 740.23
VOORBEELD IIEXAMPLE II
25 ...........25 ...........
Aan een oplossing van 20 g (0,1 mol) 2-(E)- 3 fenylmethyleencycloheptan-l-on in 100 cm methanol worden 7,64 g (0,11 mol) hydroxylaminehydrochloride en 8,7 g (0,11 mol) pyridine toegevoegd. Het reactiemengsel wordt gedurende .2 h bij kamertemperatuur geroerd en 100 g vergruisd ijs wordt 30 toegevoegd. De gewenste verbinding scheidt zich af in de vorm van witte kristallen.To a solution of 20 g (0.1 mol) of 2- (E) - 3 phenylmethylene cycloheptan-1-one in 100 cm of methanol are added 7.64 g (0.11 mol) of hydroxylamine hydrochloride and 8.7 g (0.11 mol) pyridine added. The reaction mixture is stirred at room temperature for 2 h and 100 g of crushed ice are added. The desired compound separates in the form of white crystals.
Opbrengst: 16,55 g (76,97 %). Smp.: 66-67°C.Yield: 16.55 g (76.97%). M.p .: 66-67 ° C.
Analyse: de gegevens zijn identiek aan die welke in voorbeeld I werden gegeven.Analysis: The data is identical to that given in Example I.
35 VOORBEELD IIIEXAMPLE III
33
In 200 cm van een 1 : 1-mengsel van ethanol en water laat men 20 g (0,1 mol) 2-(E)-fenylmethyleencycloheptan- l-on, 7,64 g (0,11 mol) hydroxylaminehydrochloride en 5,83 g 830117520 g (0.1 mol) of 2- (E) -phenylmethylene-cycloheptan-1-one, 7.64 g (0.11 mol) of hydroxylamine hydrochloride and 5 ml of a 1: 1 mixture of ethanol and water are placed in 200 cm 83 g 8301175
^ * 'C^ * 'C
- 4 - (0,055 mol) natriumcarbonaat reageren bij het kookpunt van het reactiemengsel, waarop het wordt gekoeld tot een temperatuur tussen 5°C en 10°C onder heftig roeren. Het kristallijne 2-(E)-fenylmethyleencycloheptan-l-on-(E)-oxim wordt door filtra-5 tie uit het reactiemengsel geïsoleerd.4 (0.055 mol) sodium carbonate react at the boiling point of the reaction mixture, at which point it is cooled to a temperature between 5 ° C and 10 ° C with vigorous stirring. The crystalline 2- (E) -phenylmethylene-cycloheptan-1-one- (E) -oxime is isolated from the reaction mixture by filtration.
Opbrengst: 17,65 g (82 %). Smp.: 66-67°C.Yield: 17.65 g (82%). M.p .: 66-67 ° C.
VOORBEELD IVEXAMPLE IV
Gedurende enkele uren worden 20 g (0,1 mol) 3 2-(E)-fenylmethyleencycloheptan-l-on, 100 cm water, 8,7 g 10 (0,11 mol) pyridine en 7,64 g (0,11 mol) hydroxylaminehydro-chloride heftig geroerd bij 80°C, waarna 100 cm^ ethanol wordt toegevoegd aan het reactiemengsel en het laatste onder langzame koeling geroerd wordt totdat kristallisatie heeft plaatsgevonden .For several hours, 20 g (0.1 mol) of 3 2- (E) -phenylmethylene cycloheptan-1-one, 100 cm of water, 8.7 g of 10 (0.11 mol) pyridine and 7.64 g (0.11 mol) hydroxylamine hydrochloride stirred vigorously at 80 ° C, after which 100 ml of ethanol is added to the reaction mixture and the latter is stirred under slow cooling until crystallization has taken place.
15 Opbrengst: 15,7 g (72,92 %) wit, kristallijn 2-(E)-fenyl-Yield: 15.7 g (72.92%) white, crystalline 2- (E) -phenyl-
methyleencycloheptan-l-on-(E)-oxim. Smp.: 66-67°C. VOOKBEELD Vmethylene cycloheptan-1-one (E) -oxime. M.p .: 66-67 ° C. FOREVIEW V
3 33 3
Aan een mengsel van 95 cm propanol en 5 cm water worden 20 g (0,1 mol) 2-(E)—fenylmethyleencycloheptan- 20 l-on en 21,49 g (0,11 mol) hydroxylaminesulfaat toegevoegd.20 g (0.1 mol) of 2- (E) -phenylmethylene cycloheptan-1-one and 21.49 g (0.11 mol) of hydroxylamine sulfate are added to a mixture of 95 cm of propanol and 5 cm of water.
Daarop wordt 10,94 g (0,056 mol) kaliumcarbonaat onder roeren toegevoegd. Na koken van het mengsel gedurende enkele uren10.94 g (0.056 mol) of potassium carbonate are then added with stirring. After boiling the mixture for several hours
is de reactie voltooid. Daarop wordt het mengsel tot ca. 50°Cthe reaction is complete. The mixture is then heated to about 50 ° C
gekoeld, wordt 100 g vergruisd ijs toegevoegd en worden de 25 kristallen afgefiltreerd en gedroogd.cooled, 100 g of crushed ice are added and the crystals are filtered and dried.
Opbrengst: 18,48 g (87,5 %) witte kristallen, welke tenminste 95 % 2-(E)-fenylmethyleencycloheptan-l-on-(E)-oxim bevatten. Smp.: 6 7 °C.Yield: 18.48 g (87.5%) of white crystals containing at least 95% 2- (E) -phenylmethylene-cycloheptan-1-one- (E) -oxime. Mp .: 6 7 ° C.
Analyse: Cl4H17NO (215,29) 3Q Berekend: C: 78,1 % H: 7,96 % N: 6,5 % gevonden: C: 77,91 % H: 7,8 % N: 6,47 %.Analysis: Cl4H17NO (215.29) 3Q Calculated: C: 78.1% H: 7.96% N: 6.5% Found: C: 77.91% H: 7.8% N: 6.47%.
VOORBEELD VIEXAMPLE VI
Onder heftig roeren werden 20 g (0,1 mol) 2-(E)-fenylmethyleencycloheptan-l-on en 7,65 g (0,11 mol) 35 hydroxylaminehydrochloride in 100 cm ethanol tot koken verhit en een oplossing van 6,17 g (0,11 mol) kaliumhydroxide in 3 100 cm water werd bij het reactiemengsel gedruppeld. Daarop liet men de reactie voortgaan gedurende een half uur, werd 8301175 "ΊWith vigorous stirring, 20 g (0.1 mole) of 2- (E) -phenylmethylene cycloheptan-1-one and 7.65 g (0.11 mole) of hydroxylamine hydrochloride in 100 cm of ethanol were heated to boiling and a solution of 6.17 g (0.11 mol) of potassium hydroxide in 3 100 cm of water were added dropwise to the reaction mixture. The reaction was then allowed to proceed for half an hour, 8301175 Ί
* -7 - V* -7 - V.
- 5 - langzaam gekoeld en werd het afgescheiden 2- (E) -fenylmethyleenr· cycloheptan-l-on-(E)-oxim afgefiltreerd.- cooled slowly and the separated 2- (E) -phenylmethylene-cycloheptan-1-one (E) -oxime was filtered off.
Opbrengst: 20,3 g (94,3 %). Smp.: 67°C.Yield: 20.3 g (94.3%). Mp .: 67 ° C.
VOORBEELD VIIEXAMPLE VII
5 Onder roeren werden 20 g (0,1 mol) 2-(E)- fenylmethyleencycloheptan-l-on, 7,65 g (0,11 mol) hydroxyl- 3 3 aminehydrochloride, 90 cm ethanol, 10 cm water en 9,24 g (0,11 mol) natriumwaterstofcarbonaat gedurende 3 h tot koken verhit. Daarop werd 80 g vergruisd ijs aan het reactiemengsel 10 toegevoegd en werd het in de vorm van witte kristallen afgescheiden 2-(E)-fenylmethyleencycloheptan-l-on-(E)-oxim afgefiltreerd en gedroogd.5 While stirring, 20 g (0.1 mole) of 2- (E) -phenylmethylene cycloheptan-1-one, 7.65 g (0.11 mole) of hydroxyl-3 amine hydrochloride, 90 cm of ethanol, 10 cm of water and 9, 24 g (0.11 mol) of sodium hydrogen carbonate heated to boiling for 3 h. 80 g of crushed ice were then added to the reaction mixture and the 2- (E) -phenylmethylene cycloheptan-1-one (E) -oxime separated as white crystals was filtered off and dried.
Opbrengst: 20,2 g (93,8 %). Smp. 67°C.Yield: 20.2 g (93.8%). Mp. 67 ° C.
Analyse: C14Hl7NO (215,29).Analysis: C14H17NO (215.29).
15 Berekend: C: 78,1 % H: 7,96 % N: 6,5 % gevonden: C: 78,23 % H: 7,72 % N: 6,53 %.Calculated: C: 78.1% H: 7.96% N: 6.5%. Found: C: 78.23% H: 7.72% N: 6.53%.
20 830 1 1 7 520 830 1 1 7 5
Claims (7)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU99782 | 1982-04-01 | ||
| HU82997A HU185518B (en) | 1982-04-01 | 1982-04-01 | Process for preparing 2-/e/-phenyl-methylene-cycloheptan-1-one-/e/-oxime |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL8301175A true NL8301175A (en) | 1983-11-01 |
Family
ID=10952372
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8301175A NL8301175A (en) | 1982-04-01 | 1983-04-01 | PROCESS FOR THE PREPARATION OF 2- (E) -PENYLMETHYLENE CYCLOHEPTAN-1-ON- (E) -OXIM. |
Country Status (18)
| Country | Link |
|---|---|
| JP (1) | JPS58208262A (en) |
| AT (1) | AT384423B (en) |
| BE (1) | BE896279A (en) |
| CA (1) | CA1210027A (en) |
| CH (1) | CH656121B (en) |
| DD (1) | DD209619A5 (en) |
| DE (1) | DE3311895A1 (en) |
| DK (1) | DK148783A (en) |
| ES (1) | ES521096A0 (en) |
| FI (1) | FI831087L (en) |
| FR (1) | FR2524464B1 (en) |
| GB (1) | GB2117773B (en) |
| HU (1) | HU185518B (en) |
| IL (1) | IL68079A (en) |
| IT (1) | IT1194184B (en) |
| NL (1) | NL8301175A (en) |
| SE (1) | SE8301817L (en) |
| YU (1) | YU77683A (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4083978A (en) * | 1976-01-27 | 1978-04-11 | Egyt Gyogyszervegyeszeti Gyar | Oxime ethers |
-
1982
- 1982-04-01 HU HU82997A patent/HU185518B/en not_active IP Right Cessation
-
1983
- 1983-03-07 IL IL68079A patent/IL68079A/en unknown
- 1983-03-28 BE BE1/10748A patent/BE896279A/en not_active IP Right Cessation
- 1983-03-29 ES ES521096A patent/ES521096A0/en active Granted
- 1983-03-30 FI FI831087A patent/FI831087L/en not_active Application Discontinuation
- 1983-03-30 SE SE8301817A patent/SE8301817L/en not_active Application Discontinuation
- 1983-03-30 DK DK148783A patent/DK148783A/en not_active IP Right Cessation
- 1983-03-31 FR FR8305314A patent/FR2524464B1/en not_active Expired
- 1983-03-31 JP JP58056809A patent/JPS58208262A/en active Pending
- 1983-03-31 DE DE19833311895 patent/DE3311895A1/en not_active Withdrawn
- 1983-03-31 CH CH179183A patent/CH656121B/de unknown
- 1983-03-31 GB GB08308956A patent/GB2117773B/en not_active Expired
- 1983-03-31 CA CA000425105A patent/CA1210027A/en not_active Expired
- 1983-04-01 AT AT0116983A patent/AT384423B/en not_active IP Right Cessation
- 1983-04-01 IT IT20428/83A patent/IT1194184B/en active
- 1983-04-01 NL NL8301175A patent/NL8301175A/en not_active Application Discontinuation
- 1983-04-01 YU YU00776/83A patent/YU77683A/en unknown
- 1983-04-04 DD DD83249465A patent/DD209619A5/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK148783A (en) | 1983-10-02 |
| DD209619A5 (en) | 1984-05-16 |
| CH656121B (en) | 1986-06-13 |
| IL68079A (en) | 1986-10-31 |
| SE8301817D0 (en) | 1983-03-30 |
| IL68079A0 (en) | 1983-06-15 |
| GB8308956D0 (en) | 1983-05-11 |
| FI831087A0 (en) | 1983-03-30 |
| ATA116983A (en) | 1987-04-15 |
| IT1194184B (en) | 1988-09-14 |
| DK148783D0 (en) | 1983-03-30 |
| BE896279A (en) | 1983-09-28 |
| JPS58208262A (en) | 1983-12-03 |
| HU185518B (en) | 1985-02-28 |
| AT384423B (en) | 1987-11-10 |
| SE8301817L (en) | 1983-10-02 |
| GB2117773A (en) | 1983-10-19 |
| FI831087L (en) | 1983-10-02 |
| ES8405366A1 (en) | 1984-06-01 |
| DE3311895A1 (en) | 1983-10-06 |
| FR2524464B1 (en) | 1986-05-30 |
| GB2117773B (en) | 1985-08-29 |
| IT8320428A0 (en) | 1983-04-01 |
| ES521096A0 (en) | 1984-06-01 |
| IT8320428A1 (en) | 1984-10-01 |
| FR2524464A1 (en) | 1983-10-07 |
| YU77683A (en) | 1985-12-31 |
| CA1210027A (en) | 1986-08-19 |
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| A85 | Still pending on 85-01-01 | ||
| BT | A notification was added to the application dossier and made available to the public | ||
| BV | The patent application has lapsed |