HU185518B - Process for preparing 2-/e/-phenyl-methylene-cycloheptan-1-one-/e/-oxime - Google Patents
Process for preparing 2-/e/-phenyl-methylene-cycloheptan-1-one-/e/-oxime Download PDFInfo
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- HU185518B HU185518B HU82997A HU99782A HU185518B HU 185518 B HU185518 B HU 185518B HU 82997 A HU82997 A HU 82997A HU 99782 A HU99782 A HU 99782A HU 185518 B HU185518 B HU 185518B
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- cycloheptan
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- phenylmethylene
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- 238000004519 manufacturing process Methods 0.000 title abstract description 4
- 238000000034 method Methods 0.000 claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000002443 hydroxylamines Chemical class 0.000 claims abstract description 6
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims abstract description 5
- 230000001476 alcoholic effect Effects 0.000 claims abstract description 5
- 238000011065 in-situ storage Methods 0.000 claims abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 23
- 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 20
- 239000000203 mixture Substances 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000001931 aliphatic group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 239000000047 product Substances 0.000 abstract description 4
- MBPFOTDJJDXNEW-HSPBJUNWSA-N C[C@@H](CCC[C@@H](C)CCC/C(=C/CC1(CCCCCC1=O)C)/C)CCCC(C)C Chemical compound C[C@@H](CCC[C@@H](C)CCC/C(=C/CC1(CCCCCC1=O)C)/C)CCCC(C)C MBPFOTDJJDXNEW-HSPBJUNWSA-N 0.000 abstract 1
- 239000012450 pharmaceutical intermediate Substances 0.000 abstract 1
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 12
- 235000019441 ethanol Nutrition 0.000 description 10
- 239000011541 reaction mixture Substances 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 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000002585 base 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
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-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
- 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
- 238000009835 boiling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000010583 slow cooling Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 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
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical class CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- -1 aliphatic alcohols Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 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
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229910000378 hydroxylammonium sulfate Inorganic materials 0.000 description 1
- 150000007529 inorganic bases 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
- 239000002244 precipitate Substances 0.000 description 1
- KIDBBTHHMJOMAU-UHFFFAOYSA-N propan-1-ol;hydrate Chemical compound O.CCCO KIDBBTHHMJOMAU-UHFFFAOYSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 238000003786 synthesis reaction Methods 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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- 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)
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- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
DIE ERFINDUNG BETRIFFT EIN VERFAHREN ZUR HERSTELLUNG VON 2-(E)-PHENYLMETHYLEN-CYCLOHEPTAN-I-ON-(E)-OXIM DER FORMEL (I) IN VON ANDEREN ISOMEREN FREIEM ZUSTAND DURCH UMSETZUNG VON 2-(E)-PHENYLMETHYLEN-CYCLOHEPTAN-I-ON DER FORMEL (II) MIT AUS EINEM HYDROXYLAMINSALZ IN GEGENWART EINER BASE "IN SITU" GEBILDETEM HYDROXYLAMIN, DAS DADURCH GEKENNZEICHNET IST, DASS MAN DIE UMSETZUNG IN EINEM WAESSRIGEN UND/ODER MIT WASSER UNBEGRENZT VERMISCHBAREN NIEDEREN ALIPHATISCHEN ALKOHOLISCHEN MEDIUM DURCHFUEHRT UND NACH ABLAUF DER REAKTION DEN ALKOHOLGEHALT DES MEDIUMS AUF 40 BIS 60 % EINSTELLT UND DAS 2-(E)-PHENYLMETHYLEN-CYCLOHEPTAN-I-ON-(E)-OXIN IN AN SICH BEKANNTER WEISE ISOLIERT. DER VORTEIL DES VERFAHRENS LIEGT DARIN, DASS DIE GEWUENSCHTE VERBINDUNG DER FORMEL I IN ISOMERFREIEM ZUSTAND UND MIT SEHR GUTER AUSBEUTE HERSTELLBAR IST. DIE VERBINDUNG DER FORMEL I IST EIN BEKANNTES UNDWERTVOLLES PHARMAZEUTISCHES ZWISCHENPRODUKT.The invention relates to a method for producing 2- (E) -phenyl-methylene-cyclophosphatan-1-one (E) -oxime of the formula (I) in other free state by reaction of 2- (E) -phytyl-methylcycloheptane -I-ON THE FORMULA (II) WITH A HYDROXYLAMINE SALT IN THE PRESENCE OF A BASE "IN SITU" HYDROXYLAMINE DESIGNATED THAT MANUFACTURING AND IMMEDIATELY IMPLEMENTING IN A WAESSED AND / OR WATER UNMISTAKED MIXABLE LOW ALIPHATIC ALCOHOLIC MEDIUM PROCEDURE OF THE RESPONSE SET THE ALCOHOLIC STRENGTH OF THE MEDIUM AT 40 TO 60% AND ISOLATING THE 2- (E) -PHENYLMETHYLENE CYCLOHEPTAN-I-ON- (E) -OXIN IN A KNOWN WAY. THE ADVANTAGE OF THE PROCEDURE IS THAT THE DESIRED CONNECTION OF FORMULA I IS MANUFACTURABLE IN ISOMER-FREE CONDITION AND WITH VERY GOOD PROFIT. THE CONNECTION OF FORMULA I IS A KNOWN AND VALUABLE PHARMACEUTICAL INTERMEDIATE PRODUCT.
Description
A találmány tárgya eljárás az (I) képletü 2-(E)-fenilmetilén-cikloheptán-l-on-(E)-oxim egyéb izomerektől mentes formában történő előállítására. Az (I) képletü vegyület értékes gyógyászati hatású származékok intermedierje, felhasználható többek között a 169 289 lsz. magyar szabadalomból ismert vegyületek szintéziséhez.The present invention relates to a process for the preparation of the 2- (E) -phenylmethylene-cycloheptan-1-one (E) -oxime of formula (I) in the free form from other isomers. The compound of formula (I) is an intermediate of valuable pharmaceutically active derivatives, which may be used, inter alia, in U.S. Pat. for the synthesis of compounds known from the Hungarian patent.
Az (I) képletü vegyület előállítására az irodalomban nem közöltek eljárást.No process for the preparation of the compound of formula (I) has been reported in the literature.
Ismeretes, hogy valamely keton egy hidroxilamin-sóból bázis jelenlétében ,,in situ” keletkező hidroxilaminnal reakcióba lép és oximot eredményez. A kiindulási keton szerkezeti sajátosságait figyelembe véve a reakció során két izomer keletkezhet. Megkülönböztetésükre egyszerűbb esetben a szín-, illetve anti-, bonyolultabb szerkezetű vegyületeknél a Z, illetve E megjelölést használjuk.It is known that a ketone reacts with hydroxylamine "in situ" formed from a hydroxylamine salt in the presence of a base to produce an oxime. Depending on the structural properties of the starting ketone, two isomers may be formed during the reaction. In their simplest case, the compounds of color and anti-complex structures are designated by the designation Z or E, respectively.
A különböző izomerek biológiai hatása tudvalevőleg különbözik egymástól, ezért van szükség ezek tisztán történő előállítására, ami csupán izomermentes intermedierekből oldható meg.The biological activity of the various isomers is known to differ from each other and it is therefore necessary to prepare them purely, which can only be solved from intermediates without isomers.
Kutatásaink során célul tűztük ki egy olyan eljárás kidolgozását, amely alkalmas a 2-(E)-fenilmetilén-cikloheptán-l-on-(E)-oxim egyéb izomerektől mentes formában történő előállítására.It has been the object of our research to develop a process for the preparation of 2- (E) -phenylmethylene-cycloheptan-1-one (E) -oxime in a form free from other isomers.
Azt tapasztaltuk, hogy ha a (II) képletü 2-(E)-fenilmetilén-cikloheptán-l-ont és/vagy vízzel korlátlanul elegyedő rövid szénláncú alifás alkoholos közegben reagáltatjuk valamilyen hidroxilamin-sóból bázis jelenlétében ,,in situ” keletkező hidroxilaminnal, majd a rekacióközeg alkoholtartalmát 40—60%-osra — előnyösen 50%-osra — állítjuk be, gyakorlatilag a kívánt (E, E)-ízomer különíthető el a reakcióelegyből. A termék legfeljebb 5%-bán tartalmaz egyéb izomereket amiktől kívánt esetben önmagukban ismert módszerekkel megtisztítható.It has been found that by reacting 2- (E) -phenylmethylene-cycloheptan-1-one of the formula (II) and / or a water-miscible lower aliphatic alcoholic medium with hydroxylamine formed in situ from a hydroxylamine salt in the presence of a base, the alcohol content of the reaction medium is adjusted to 40-60%, preferably 50%, practically the desired (E, E) isomer can be isolated from the reaction mixture. The product contains up to 5% of other isomers which may be purified by methods known per se, if desired.
A (II) képletü kiindulási vegyület ismert, és az irodalomban leírt eljárásokkal (pl. Gazz. Chim. ital. 91, 326—48 (1961) állítható elő. Hidroxilamin-sók (szulfát, hidroklorid) a kereskedelemből beszerezhetők.The starting compound of formula (II) is known and can be prepared by methods described in the literature (e.g., Gazz. Chim. Ital., 91, 326-48 (1961).) Hydroxylamine salts (sulfate, hydrochloride) are commercially available.
A 2-(E)-fenilmetilén-cikloheptán-l-on reagáltatását a hidroxilamin-sóból (célszerűen szulfátból vagy hidrokloridból) ,,in situ” keletkező hidroxilaminnal vizes és/vagy vizes alkoholos közegben végezzük. Erre a célra olyan, egyenes vagy elágazó láncú alifás alkoholok alkalmazhatók, amelyek vízzel korlátlanul elegyednek. Ilyenek pl. a metil-alkohol, etil-alkohol, n-propil-alkohol, izopropil-alkohol. Előnyösen alkohol és víz elegyében játszatjuk le a reakciót, célszerűen ezek (50—98): (2—50) részarányú elegyét alkalmazzuk. A reakció lejátszódása után víz (jég) vagy alkohol hozzáadásával állítjuk be az alkoholkoncentrációt 40—60%-ra, előnyösen kb. 50%-ra.The reaction of 2- (E) -phenylmethylene-cycloheptan-1-one with hydroxylamine "in situ" from the hydroxylamine salt (preferably sulphate or hydrochloride) is carried out in aqueous and / or aqueous alcoholic media. For this purpose, straight or branched aliphatic alcohols which are miscible with water can be used. For example, methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol. Preferably, the reaction is carried out in a mixture of alcohol and water, preferably a mixture of (50-98): (2-50). After completion of the reaction, the alcohol concentration is adjusted to 40-60%, preferably ca. To 50%.
A reakciót bázis jelenlétében hajtjuk végre. Erre a célra szerves bázisok (piridin vagy piridin-bázisok, azaz 2,3- és 4-pikolinok keveréke, illetve lutidin) vagy szervetlen bázisok (alkálifém-hidroxidok, -karbonátok vagy -hidrogén-karbonátok) alkalmazhatók.The reaction is carried out in the presence of a base. Organic bases (pyridine or a mixture of pyridine bases, i.e. 2,3- and 4-picolines, and lutidine) or inorganic bases (alkali metal hydroxides, carbonates or bicarbonates) can be used for this purpose.
A reakcióhőmérsékletet tág intervallumban változtathatjuk anélkül, hogy ez a termelést számottevően befolyásolná. Általában 20 és 90 °C között, előnyösen 75— 85 °C között dolgozunk.The reaction temperature can be varied over a wide range without significantly affecting production. Generally, temperatures of from 20 to 90 ° C, preferably from 75 to 85 ° C, are employed.
Az előállított 2-(E)-fenilmetilén-cikloheptán-l-on (E)-oxim sztereokémiái tisztasága függ az alkalmazott 2-(E)fenilmetilén-cikloheptán-l-on sztereokémiái tisztaságától. Ha ugyanis ez utóbbi vegyületet nagyobb mennyiségű 2-(Z)-izomerje szennyezi, a lehetséges izomer-szeny2 nyezések száma megkétszereződik, és a kapott termék szennyezettsége az általunk megadott limitetet meghaladhatja.The stereochemical purity of the prepared 2- (E) -phenylmethylene-cycloheptan-1-one (E) -oxime depends on the stereochemical purity of the 2- (E) -phenylmethylene-cycloheptan-1-one used. In fact, if the latter compound is contaminated with a greater amount of its 2- (Z) -isomer, the number of possible isomeric impurities is doubled, and the impurity of the resulting product may exceed the limit given by us.
Amennyiben különlegesen tiszta termékre van szükség, akkor a reakció során keletkező nyers terméket önmagukban ismert módszerekkel (pl. oszlopkromatografálás, desztillálás, zónás olvasztás, kristályosítás petroléterből vagy etanolból) tisztíthatjuk.If a particularly pure product is required, the crude product of the reaction can be purified by methods known per se (e.g., column chromatography, distillation, zone melting, crystallization from petroleum ether or ethanol).
A találmány szerinti eljárást az alábbi példákkal szemléltetjük anélkül, hogy találmányunkat a példákra korlátoznánk:The invention is illustrated by the following non-limiting examples.
1. példa g (0,1 mól) 2-(E)-fenilmetilén-cikloheptán-l-on-t ésExample 1 g (0.1 mol) of 2- (E) -phenylmethylene-cycloheptan-1-one and
7,65 g (0,11 mól) hidroxilamin-hidrokloridot 100 cm3 96%-os etil-alkoholban oldunk, és keverés közben 5,94 g (0,056 mól) nátrium-karbonátot adagolunk a reakcióelegyhez. Ezután forráspontig melegítjük, és a széndioxid gázfejlődés befejeztéig ezen a hőmérsékleten tartjuk. Ezt követően 98 g apróra tört jeget adagolunk a reakcióelegyhez, majd a kristályosán kiváló 2-(E)-fenilmetilén-cikloheptán-on-l-(E)-oximot szűréssel elkülönítjük.7.65 g (0.11 mol) of hydroxylamine hydrochloride are dissolved in 100 cm 3 of 96% ethyl alcohol and 5.94 g (0.056 mol) of sodium carbonate are added to the reaction mixture. It is then heated to reflux and maintained at this temperature until the evolution of carbon dioxide gas has ceased. 98 g of crushed ice are then added to the reaction mixture, and the crystalline 2- (E) -phenylmethylene-cycloheptanone-1- (E) -oxime is isolated by filtration.
Nyeredék: 19,8 g (92%) fehér, kristályok. O.p.: 67 °CYield: 19.8 g (92%) white, crystals. Mp: 67 ° C
Analízis a Ci4H17NO (215,29) képlet alapján:Calculated for C 4 H 17 NO (215.29) Analysis:
Számított: C: 78,1% H: 7,96% N: 6,5%Calculated: C, 78.1; H, 7.96; N, 6.5%.
Mért: C: 78,0% H: 8,0 % N: 6,5%Found: C: 78.0% H: 8.0% N: 6.5%
NMR (CDC13): 6,95 ppmNMR (CDCl 3 ): 6.95 ppm
6,55 ppm6.55 ppm
2,5 ppm2.5 ppm
U.V. λ^: 258 nm; (258) = 740,23U.V. λmax: 258 nm; (258) = 740.23
2. példa:Example 2:
g (0.1 mól) 2-(E)-fenilmetilén-cikloheptán-l-on 100 cm3 metil-alkohollal készült oldatához 7,64 g (0,11 mól) hidroxilamin-hidrokloridot, valamint 8,7 g (0,11 mól) piridint mérünk be. A rekacióelegyet 2 órán át szobahőmérsékleten kevertetjük, majd 100 g apróra tört jeget adagolunk hozzá. Fehér kristályos formában kiválik ag (0.1 mol) of 2- (E) -phenylmethylenecycloheptan-l-one in 100 cm 3 of methyl alcohol was added (0.11 mole) of hydroxylamine hydrochloride, 7.64 g and 8.7 g (0.11 mole ) pyridine was weighed. The reaction mixture was stirred for 2 hours at room temperature and then 100 g of crushed ice was added. White crystalline form precipitates
2-(E)-fenilmetilén-cikloheptán-l-on-(E)-oxim.2- (E) -phenylmethylenecycloheptan-l-one- (E) -oxime.
Nyeredék: 16,55 g (76,97%) O.p.: 66-67 °CYield: 16.55 g (76.97%) Mp: 66-67 ° C
Analízis-adati azonosak az 1. példdánál megadottakkal.The analytical data are the same as in Example 1.
3. példa g (0,1 mól) 2-(E)-fenilmetilén-cikloheptán-l-on-t,Example 3 g (0.1 mol) of 2- (E) -phenylmethylene-cycloheptan-1-one,
7,64 g (0,11 mól) hidroxilamin-hidrokloridot és 5,83 g (0,055 mól) nátrium-karbonátot 200 cm3 etil-alkohol — víz (1/1) elegyében reagáltatunk a rekacióelegy forráspontján, majd az elegyet intenzív keverék közben 5—10 °C közötti hőmérsékletre hűtjük. A kristályos 2-(E)fenilmetilén-cikloheptán-l-on-(E)-oximot szűréssel különítjük el a reakcióelegyből.7.64 g (0.11 mol) of hydroxylamine hydrochloride and 5.83 g (0.055 mol) of sodium carbonate are reacted in 200 cm 3 of ethanol-water (1/1) at the boiling point of the reaction mixture and the mixture is then stirred vigorously. Cool to 5-10 ° C. Crystalline 2- (E) phenylmethylene-cycloheptan-1-one (E) -oxime is isolated from the reaction mixture by filtration.
Nyeredék: 17,65 g (82%) O.p.: 66—67 °CYield: 17.65 g (82%) Mp: 66-67 ° C
4. példa g (0,1 mól) 2-(E)-fenilmetilén-cikloheptán-l-on-t, 100 cm3 vizet, 8,7 g (0,11 mól) piridint és 7,64 g (0,11 mól) hidroxilamin-hidrokloridot intenzív keverés közben 80 °Con néhány órán át kevertetjük, majd 100 cm3 etil-alkoholt adunk a reakcióelegyhez és kristályosodásig keveijük, lassú hűtés közben.Example 4 g (0.1 mol) of 2- (E) -phenylmethylene-cycloheptan-1-one, 100 cm 3 of water, 8.7 g (0.11 mol) of pyridine and 7.64 g of (O) Hydroxylamine hydrochloride (11 mol) was stirred at 80 ° C for several hours with vigorous stirring, then ethyl alcohol (100 cm 3 ) was added to the reaction mixture and stirred until crystallized under slow cooling.
Nyeredék: 15,7 g (72,92%) fehér, kristályos 2-(E)fenilmetilén-cikloheptán-l-on-(E)-oxim. O.p.: 66—67 °C.Yield: 15.7 g (72.92%) of white crystalline 2- (E) phenylmethylene-cycloheptan-1-one (E) -oxime. Mp: 66-67 ° C.
-2185 518-2185 518
5. példa g (0,1 mól) 2-(E)-fenilmetilén-cikloheptán-l-on-t ésExample 5 g (0.1 mol) of 2- (E) -phenylmethylene-cycloheptan-1-one and
21,49 g (0,11 mól) hidroxilamin-szulfátot 95 cm3 propilalkohol és 5 cm3 víz elegyébe mérünk, és keverés közbenHydroxylamine sulfate, 21.49 g (0.11 mole) of 95 cm 3 and 5 cm 3 propanol-water mixture, and stirring
10,94 g (0,056 mól) kálium-karbonátot adagolunk hozzá, g Néhány óra forralás után a reakció teljes. Ekkor mintegy 50 °C-ra hűtjük a rekacióelegyet, és 100 g apróra tört jeget adagolunk hozzá, majd a kristályokat szűréssel különítjük és szárítjuk.10.94 g (0.056 mol) of potassium carbonate are added, g After a few hours of reflux, the reaction is complete. The reaction mixture is cooled to about 50 ° C and 100 g of crushed ice are added, and the crystals are filtered off and dried.
Nyeredék: 18,48 g (87,5%) fehér kristályos anyag, amely -|θ minimálisan 95%-bán 2-(E)-fenilmetilén-cikloheptán-l-on-(E)-oxim. O.p.: 67 °CYield: 18.48 g (87.5%) of a white crystalline solid which has a minimum of 95% 2- (E) -phenylmethylene-cycloheptan-1-one (E) -oxime. Mp: 67 ° C
Analízis a C14H17NO (215,29) képlet alapján:Calc'd for C 14 H 17 NO (215.29) Analysis:
Számított: C: 78,1 % H: 7,96% N: 6,5 % 15Calculated: C, 78.1; H, 7.96; N, 6.5;
Mért: C: 77,91% H: 7,8 % N: 6,47%Found: C, 77.91; H, 7.8; N, 6.47.
6. példa g (0,1 mól) 2-(E)-fenilmetilén-cikloheptán-l-on-t és 7,65 g (0,11 mól) hidroxilamin-hidrokloridot 100 cm3 20 etil-alkoholban intenzív keverés közben forráspontig melegítjünk és 6,17 g (0,11 mól) kálium-hidroxid 100 cm3 vízzel készült oldatát csepegtetjük a rekacióelegyhez. Fél óra utóreagáltatás után lassú hűtéssel kristályosítjuk a 2-(E)-fenilmetilén-cikloheptán-l-on-(E)- 25 -oximot.Example 6 g (0.1 mol) of 2- (E) -phenylmethylene-cycloheptan-1-one and 7.65 g (0.11 mol) of hydroxylamine hydrochloride in 100 cm 3 of ethyl alcohol with vigorous stirring to boiling point heat and a solution of 6.17 g (0.11 mol) of potassium hydroxide in 100 cm 3 of water is added dropwise to the reaction mixture. After half an hour of reaction, 2- (E) -phenylmethylene-cycloheptan-1-one (E) -25-oxime is crystallized by slow cooling.
Nyeredék: 20,3 g (94,3%) O.p.: 67 °C.Yield: 20.3 g (94.3%) Mp 67 ° C.
7. példa g (0,1 mól) 2-(E)-fenilmetilén-cikloheptán-l-on-t, 30Example 7 g (0.1 mol) of 2- (E) -phenylmethylene-cycloheptan-1-one, m.p.
7,65 g (0,11 mól) hidroxilamin-hidrokloridot, 90 cm3 etil-alkoholt, 10 cm3 vizet és 9,24 g (0,11 mól) nátrium-hidrogén-karbonátot 3 órán át keverés közben forralunk, majd 80 g apróra tört jeget adagolunk a reakcióelegyhez, végül a fehér, kristályos 2-(E)-fenilmetilén- 35 cikloheptán-l-on-(E)-oximot szűrjük, szárítjuk.Of hydroxylamine hydrochloride, 90 cm 3 of ethanol, 10 cm 3 of water and sodium hydrogen carbonate, 9.24 g (0.11 mol) 7.65 g (0.11 mole) are refluxed with stirring for 3 hours, and then 80 g of crushed ice was added to the reaction mixture, and the white crystalline 2- (E) -phenylmethylene-cycloheptan-1-one (E) -oxime was filtered off and dried.
Nyeredék: 20,2 g (93,8%) O.p.: 67 °C.Yield: 20.2 g (93.8%) Mp 67 ° C.
Analízis a C14H17NO (215,29) képlet alapján:Calc'd for C 14 H 17 NO (215.29) Analysis:
Számított: C: 78,1 % H: 7,96% N: 6,5 % 40Calculated: C, 78.1; H, 7.96; N, 6.5;
Mért: C: 78,23% H: 7,72% N: 6,53%Found: C, 78.23; H, 7.72; N, 6.53.
Claims (6)
Priority Applications (18)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU82997A HU185518B (en) | 1982-04-01 | 1982-04-01 | Process for preparing 2-/e/-phenyl-methylene-cycloheptan-1-one-/e/-oxime |
| IL68079A IL68079A (en) | 1982-04-01 | 1983-03-07 | Preparation of 2-(e)-phenyl-methylenecycloheptan-1-one-(e)-oxime |
| BE1/10748A BE896279A (en) | 1982-04-01 | 1983-03-28 | PROCESS FOR THE PREPARATION OF 2- (E) -PHENYLMETHYLENE-CYCLOHEPTAN-1-ONE- (E) -OXIME |
| ES521096A ES521096A0 (en) | 1982-04-01 | 1983-03-29 | PREPARATION PROCEDURE OF 2- (E) -PHENYL METHYLENE CYCLOHEPTAN-1-ONA- (E) -OXIME. |
| DK148783A DK148783A (en) | 1982-04-01 | 1983-03-30 | METHOD FOR PREPARING 2- (E) -PHENYLMETHYLENCYCLOHEPTAN-1-ON- (E) -OXIM |
| FI831087A FI831087L (en) | 1982-04-01 | 1983-03-30 | PROCEDURE FOR FRAMSTATION OF AV 2- (E) -PHENYLMETHYLENCYCLOHEPTAN-1-ON- (E) -OXIM |
| SE8301817A SE8301817L (en) | 1982-04-01 | 1983-03-30 | PROCEDURE FOR THE PREPARATION OF 2- (E) -PHENYLMethylcycloOHEPTAN-1-ON- (E) -OXIM |
| CA000425105A CA1210027A (en) | 1982-04-01 | 1983-03-31 | Process for the preparation of 2-/e/phenyl- methylenecycloheptan-1-one-/e/-oxime |
| GB08308956A GB2117773B (en) | 1982-04-01 | 1983-03-31 | Process for the preparation of 2-/e/-phenylmethylene-cycloheptan-1-one-/e/-oxime |
| DE19833311895 DE3311895A1 (en) | 1982-04-01 | 1983-03-31 | 2- (E) - (BENZAL) -CYCLOHEPTAN-1 - ((E) -OXIM), METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCT CONTAINING THE SAME |
| JP58056809A JPS58208262A (en) | 1982-04-01 | 1983-03-31 | Manufacture of 2-(e)-phenylmethylenecycloheptan- 1-one-(e)-oxime |
| CH179183A CH656121B (en) | 1982-04-01 | 1983-03-31 | |
| FR8305314A FR2524464B1 (en) | 1982-04-01 | 1983-03-31 | PROCESS FOR THE PREPARATION OF 2- (E) -PHEPHENYLMETHYLENE-CYCLOHEPTAN-1-ONE- (E) -OXIME |
| IT20428/83A IT1194184B (en) | 1982-04-01 | 1983-04-01 | PROCEDURE FOR THE PREPARATION OF 2- (E) -PHENYLMETHYL-CICLOEPTAN-1-ONE- (E) -OXY |
| AT0116983A AT384423B (en) | 1982-04-01 | 1983-04-01 | METHOD FOR PRODUCING 2- (E) -PHENYLMETHYLENE-CYCLOHEPTAN-1-ON- (E) -OXIM |
| NL8301175A NL8301175A (en) | 1982-04-01 | 1983-04-01 | PROCESS FOR THE PREPARATION OF 2- (E) -PENYLMETHYLENE CYCLOHEPTAN-1-ON- (E) -OXIM. |
| YU00776/83A YU77683A (en) | 1982-04-01 | 1983-04-01 | Process for obtaining 2-(e-)-phenylmethlyene-cycloheptne-1-one-(e)-oxime |
| DD83249465A DD209619A5 (en) | 1982-04-01 | 1983-04-04 | PROCESS FOR THE PREPARATION OF 2- (E) -PHENYLMETHYLENE-CYCLOHEPTAN-1-ON- (E) -OXIM |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| 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 |
|---|---|
| HU185518B true HU185518B (en) | 1985-02-28 |
Family
ID=10952372
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU82997A HU185518B (en) | 1982-04-01 | 1982-04-01 | Process for preparing 2-/e/-phenyl-methylene-cycloheptan-1-one-/e/-oxime |
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 SE SE8301817A patent/SE8301817L/en not_active Application Discontinuation
- 1983-03-30 DK DK148783A patent/DK148783A/en not_active IP Right Cessation
- 1983-03-30 FI FI831087A patent/FI831087L/en not_active Application Discontinuation
- 1983-03-31 CA CA000425105A patent/CA1210027A/en not_active Expired
- 1983-03-31 JP JP58056809A patent/JPS58208262A/en active Pending
- 1983-03-31 GB GB08308956A patent/GB2117773B/en not_active Expired
- 1983-03-31 CH CH179183A patent/CH656121B/de unknown
- 1983-03-31 DE DE19833311895 patent/DE3311895A1/en not_active Withdrawn
- 1983-03-31 FR FR8305314A patent/FR2524464B1/en not_active Expired
- 1983-04-01 IT IT20428/83A patent/IT1194184B/en active
- 1983-04-01 YU YU00776/83A patent/YU77683A/en unknown
- 1983-04-01 NL NL8301175A patent/NL8301175A/en not_active Application Discontinuation
- 1983-04-01 AT AT0116983A patent/AT384423B/en not_active IP Right Cessation
- 1983-04-04 DD DD83249465A patent/DD209619A5/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| YU77683A (en) | 1985-12-31 |
| ES8405366A1 (en) | 1984-06-01 |
| NL8301175A (en) | 1983-11-01 |
| CH656121B (en) | 1986-06-13 |
| FR2524464B1 (en) | 1986-05-30 |
| IT8320428A1 (en) | 1984-10-01 |
| DK148783D0 (en) | 1983-03-30 |
| JPS58208262A (en) | 1983-12-03 |
| IT8320428A0 (en) | 1983-04-01 |
| ATA116983A (en) | 1987-04-15 |
| ES521096A0 (en) | 1984-06-01 |
| IL68079A0 (en) | 1983-06-15 |
| DK148783A (en) | 1983-10-02 |
| FI831087A0 (en) | 1983-03-30 |
| DD209619A5 (en) | 1984-05-16 |
| AT384423B (en) | 1987-11-10 |
| GB8308956D0 (en) | 1983-05-11 |
| FI831087L (en) | 1983-10-02 |
| IL68079A (en) | 1986-10-31 |
| DE3311895A1 (en) | 1983-10-06 |
| GB2117773B (en) | 1985-08-29 |
| GB2117773A (en) | 1983-10-19 |
| SE8301817L (en) | 1983-10-02 |
| SE8301817D0 (en) | 1983-03-30 |
| BE896279A (en) | 1983-09-28 |
| FR2524464A1 (en) | 1983-10-07 |
| CA1210027A (en) | 1986-08-19 |
| IT1194184B (en) | 1988-09-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HU90 | Patent valid on 900628 | ||
| HMM4 | Cancellation of final prot. due to non-payment of fee |