NO129952B - - Google Patents
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- NO129952B NO129952B NO01507/70A NO150770A NO129952B NO 129952 B NO129952 B NO 129952B NO 01507/70 A NO01507/70 A NO 01507/70A NO 150770 A NO150770 A NO 150770A NO 129952 B NO129952 B NO 129952B
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- Norway
- Prior art keywords
- benzyl
- methylenedioxy
- salts
- formula
- lower alkyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 15
- 150000003839 salts Chemical group 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 150000002431 hydrogen Chemical group 0.000 claims description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 3
- 239000011574 phosphorus Substances 0.000 claims description 3
- 229910052698 phosphorus Inorganic materials 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical group 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 9
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 229920000137 polyphosphoric acid Polymers 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000002192 coccidiostatic effect Effects 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- -1 alkali metal salts Chemical class 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical group C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 1
- RSSAOYGNGJHIPY-UHFFFAOYSA-N 2-anilino-1,3-dioxane-4,6-dione Chemical class O1C(=O)CC(=O)OC1NC1=CC=CC=C1 RSSAOYGNGJHIPY-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000001165 anti-coccidial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Chemical group 0.000 description 1
- GPOGKMPXBDGPJH-UHFFFAOYSA-N butan-2-yl acetate hydrochloride Chemical compound Cl.CCC(C)OC(C)=O GPOGKMPXBDGPJH-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000006200 ethylation reaction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical group C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
- C07D317/66—Nitrogen atoms not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Fodder In General (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Analogifremgangsmåte ved fremstilling av nye, Analogy method in the production of new,
anticoccidialt og antiviralt aktive kinolinderivater. anticoccidially and antivirally active quinoline derivatives.
Det er kjent at de i 6- og 7-stillingen substituerte kinolin-3-carboxylsyrederivater har verdifull kjemoterapeutisk virkning. 1-ethyl-l,^-dihydro-6 ^-methylendioxy-^-oxo-kinolin-^-carboxylsyre er f.eks. et verdifullt bakterlDStaticum (US patentskrift 3.287.1+58). I henhold til dette US patentskrift fremstilles denne forbindelse ved opphetning i "Diphyl" av diethyl-[(3,^-methylendioxy-anilino)-methylen]-malonat og påfolgende hydrolyse av den således erholdte lf-hydroxy-6,7-methylendioxy-kinolin-3-carboxylsyreester og til slutt N-ethylering av det dannede produkt. Diethyl-[(3,^-methylendioxy-anilino)-methylen]-malonatet fremstilles ved omsetning av 3,^-methylen-dioxy-anilin med ethoxy-methylen-malonsyre-diethylester. It is known that the quinoline-3-carboxylic acid derivatives substituted in the 6- and 7-position have a valuable chemotherapeutic effect. 1-ethyl-1,^-dihydro-6^-methylenedioxy-^-oxo-quinoline-^-carboxylic acid is e.g. a valuable BacterilDSaticum (US Patent 3,287,1+58). According to this US patent, this compound is prepared by heating in "Diphyl" diethyl-[(3,^-methylenedioxy-anilino)-methylene]-malonate and subsequent hydrolysis of the thus obtained 1f-hydroxy-6,7-methylenedioxy- quinoline-3-carboxylic acid ester and finally N-ethylation of the product formed. The diethyl-[(3,^-methylenedioxy-anilino)-methylene]-malonate is prepared by reacting 3,^-methylene-dioxy-aniline with ethoxy-methylene-malonic acid diethyl ester.
Det er videre kjent at de i 7-stillingen med en alkyl-, fenyl-eller aralkylgruppe substituerte U-klor-kinolin-3-carboxylsyreestere kan fremstilles ved omsetning av de i 3-stillingen tilsvarende substituerte anilino-methylen-malonater med fosforoxyklorid. (Ungarsk patentskrift 155.0|?3). It is also known that the U-chloro-quinoline-3-carboxylic acid esters substituted in the 7-position with an alkyl, phenyl or aralkyl group can be prepared by reacting the correspondingly substituted anilino-methylene malonates in the 3-position with phosphorus oxychloride. (Hungarian patent document 155.0|?3).
Det har vist seg at de nye forbindelser med den generelle formel: It has been shown that the new compounds with the general formula:
og deres salter (hvor R er hydrogen, lavere alkyl eller benzyl, og X er halogen) har verdifull anticoccidial og antiviral aktivitet, og kan anvendes i terapien som coccidiostaticum. and their salts (where R is hydrogen, lower alkyl or benzyl, and X is halogen) have valuable anticoccidial and antiviral activity, and can be used in therapy as coccidiostatics.
Når R er lavere alkyl, er den en rettkjedet eller forgrenet mettet hydrocarbongruppe. When R is lower alkyl, it is a straight chain or branched saturated hydrocarbon group.
X er fortrinnsvis klor eller brom, spesielt klor. X is preferably chlorine or bromine, especially chlorine.
Saltene av forbindelsene med formel I hvor R er hydrogen, kan fortrinnsvis være alkalimetallsalter (f.eks. natrium- eller kalium-salter), jordalkalimetallsalter, magnesiumsalter eller ammoniumsalter. Saltene av alkyl- eller benzylesterne av forbindelsene med formel I kan være syreaddisjonssalter (f.eks. hydroklorid, sulfat, fosfat, acetat eller tartrat). The salts of the compounds of formula I where R is hydrogen can preferably be alkali metal salts (e.g. sodium or potassium salts), alkaline earth metal salts, magnesium salts or ammonium salts. The salts of the alkyl or benzyl esters of the compounds of formula I may be acid addition salts (eg hydrochloride, sulphate, phosphate, acetate or tartrate).
De nye forbindelser med formel I og deres salter fremstilles ifolge oppfinnelsen ved at en forbindelse med den generelle formel: The new compounds of formula I and their salts are prepared according to the invention by a compound of the general formula:
(hvor R er lavere alkyl eller benzyl) omsettes med et forforoxy-halogenid, og at om onskes den således erholdte forbindelse med formel I, hvor R er lavere alkyl eller benzyl overfores til den frie syre, hvor R er hydrogen, og at det således erholdte produkt eventuelt overfores i et salt, eller basen frigjores fra et salt. (where R is lower alkyl or benzyl) is reacted with a phoroxy halide, and that if desired the thus obtained compound of formula I, where R is lower alkyl or benzyl is transferred to the free acid, where R is hydrogen, and that thus the product obtained is possibly transferred into a salt, or the base is released from a salt.
Som utgangsmateriale kan man med fordel anvende en forbindelse A compound can advantageously be used as starting material
av formel II hvor R"<*>" er ethyl, n-butyl eller benzyl. Som fosforoxy-halogenid kan man med fordel anvende fosforoxyklorid. of formula II where R"<*>" is ethyl, n-butyl or benzyl. Phosphorus oxychloride can advantageously be used as phosphorus oxyhalide.
Ved.en fordelaktig utforelsesform av foreliggende fremgangsmåte anvendes fosforoxykloridet i overskudd, hvorved det tjener som reak-sjonskomponent såvel som reaksjonsmedium. Eventuelt kan man også anvende andre opplosningsmidler (f.eks. toluen eller xylen). Reaksjonen utfores fortrinnsvis ved forhoyet temperatur, særlig ved koke-punktet for reaksjonsblandingen. Det er fordelaktig å anvende en katalysator, og til dette formål kan man anvende f.eks. polyfosforsyre. In an advantageous embodiment of the present method, phosphorus oxychloride is used in excess, whereby it serves as a reaction component as well as a reaction medium. Optionally, other solvents can also be used (e.g. toluene or xylene). The reaction is preferably carried out at an elevated temperature, in particular at the boiling point of the reaction mixture. It is advantageous to use a catalyst, and for this purpose one can use e.g. polyphosphoric acid.
Reaksjonsblandingen kan opparbeides på i og for seg kjent vis. Man. kan også gå frem på den måte at man utskiller produktet med en alkanol, særlig med ethanol, hvorved man får et rent krystallinsk produkt. The reaction mixture can be worked up in a manner known per se. Mon. can also proceed in such a way that the product is separated with an alkanol, in particular with ethanol, whereby a pure crystalline product is obtained.
Ved omsetning av forbindelsene med formel II med et fosforoxy-halogenid dannes der en forbindelse av formel I hvor R er lavere alkyl eller benzyl. Den således erholdte ester kan om bnskes overfores i den tilsvarende syre hvor R er hydrogen. Hydrolysen kan utfores i et basisk medium, fortrinnsvis med et alkalimetallhydroxyd (f.eks. natriumhydroxyd eller kaliumhydroxyd). Reaksjonen kan utfores i vann eller i alkohol, fortrinnsvis under oppvarmning av reaksjonsblandingen. By reacting the compounds of formula II with a phosphorus oxyhalide, a compound of formula I is formed where R is lower alkyl or benzyl. The ester thus obtained can, if desired, be transferred into the corresponding acid where R is hydrogen. The hydrolysis can be carried out in a basic medium, preferably with an alkali metal hydroxide (eg sodium hydroxide or potassium hydroxide). The reaction can be carried out in water or in alcohol, preferably while heating the reaction mixture.
De således erholdte forbindelser med formel I kan overfores til saltene på i og for seg kjent vis. Forbindelsene med formel I og deres salter, har, som ovenfor nevnt, en verdifull coccidiostatisk virkning, og kan anvendes i farmasien i form av virkestoffet og prep-. arater inneholdende ikke-giftige fortynnings- eller bæremidler. Som fortynningsmiddel kan man f.eks. anvende kaolin, talkum, calcium-carbonat, fullerjord og lignende. The thus obtained compounds of formula I can be transferred to the salts in a manner known per se. The compounds of formula I and their salts have, as mentioned above, a valuable coccidiostatic effect, and can be used in pharmacy in the form of the active substance and prep-. arates containing non-toxic diluents or carriers. As a diluent, you can e.g. use kaolin, talc, calcium carbonate, fuller's earth and the like.
Preparatene kan med fordel lagres i form av forblandinger med hoy virkestoffkonsentrasjon [ca. 0,1-25 vekt$]. Forblandingen blir for anvendelse fortynnet til man får den i hvert tilfelle onskede virkestoffkonsentrasjon. Virkestoffkonsentrasjonen av de direkte anvendte preparater kan forandres innen vide grenser, i alminnelighet ligger de mellom 0,0001-0,1 vekt%. Doseringen av virkestoffet av-henger av de gitte betingelser og er vanligvis 1 g/dag. The preparations can advantageously be stored in the form of premixes with a high active ingredient concentration [approx. 0.1-25 wt$]. The premix is diluted for use until the desired active ingredient concentration is obtained in each case. The active substance concentration of the directly used preparations can be changed within wide limits, in general they are between 0.0001-0.1% by weight. The dosage of the active ingredient depends on the given conditions and is usually 1 g/day.
Eksempel 1 Example 1
30,73 g (0,1 mol) 3,^-methylendioxy-anilino-methylen-malonsyre-diethylester oppvarmes til kokning i h6, 0 g (0,3 mol) fosforoxyklorid i nærvær av 2 g polyfosforsyre, og oppvarmes så 1 time under tilbakelop. Reaksjonsblandingen avkjoles litt hvorpå 80 ml vannfri ethanol tildryppes. Krystalliseringen begynner allerede efter til-setning av noen dråper alkohol. Efter avkjoling avsuges de utskilte krystaller, dekkes med litt vannfri ethanol og torres. Man får 3-carbethoxy-^-klor-é^-methylendioxy-kinolin-hydroklorid med smeltepunkt 19^-].95°C- Utbytte: 31,5 g (praktisk talt kvantitativt). 30.73 g (0.1 mol) of 3,^-methylenedioxy-anilino-methylene-malonic acid diethyl ester is heated to boiling in h6, 0 g (0.3 mol) of phosphorus oxychloride in the presence of 2 g of polyphosphoric acid, and then heated for 1 hour during backflow. The reaction mixture is cooled slightly, after which 80 ml of anhydrous ethanol is added dropwise. Crystallization begins already after the addition of a few drops of alcohol. After cooling, the separated crystals are suctioned off, covered with a little anhydrous ethanol and dried. One obtains 3-carbethoxy-^-chloro-é^-methylenedioxy-quinoline hydrochloride with melting point 19^-].95°C- Yield: 31.5 g (practically speaking quantitatively).
Ovenstående reaksjon kan også utfores i fravær av katalysator-en, ved den angitte fremgangsmåte. Også i dette tilfelle får man produktet i godt utbytte. Hydrokloridet suspenderes-i vann o<v>g nøytra-liseres med 10^-ig natriumhydrocarbonatopplosning. Krystallene fra-filtreres i vakuum, dekkes med vann og torres. Smeltepunkt: 105-107°C. Ved orakrystallisas jon fra den tredobbelte mengde ethanol får man sne-hvitt krystallinsk 3-carbethoxy-Lf-klor-6,7-methylendioxy-kinolin med smeltepunkt 111-112°C. The above reaction can also be carried out in the absence of the catalyst, by the specified method. In this case too, you get the product at a good profit. The hydrochloride is suspended in water and neutralized with 10^-ig sodium bicarbonate solution. The crystals are filtered off in vacuo, covered with water and dried. Melting point: 105-107°C. By oracrystallization from three times the amount of ethanol, snow-white crystalline 3-carbethoxy-Lf-chloro-6,7-methylenedioxy-quinoline with a melting point of 111-112°C is obtained.
Dette produkt har en betydelig coccidiostatisk virkning. This product has a significant coccidiostatic effect.
Eksempel 2 Example 2
7,26 g (0,02 mol) 3,^-methylendioxy-anilino-methylen-malonsyre-dibutylester oppvarmes til kokning under omroring i ?>20 g (0,06 mol) fosforoxyklorid i nærvær av 0,5 g polyfosforsyre og' derpå kokes under tilbakelop i 90 minutter. Reaksjonsblandingen avkjoles litt og derpå tildryppes 25 ml butylalkohol for krystallisering. Efter avkjoling blir det utskilte produkt frasuget og dekket med ethanol. 7.26 g (0.02 mol) of 3,^-methylenedioxy-anilino-methylene-malonic acid dibutyl ester is heated to boiling with stirring in ?>20 g (0.06 mol) of phosphorus oxychloride in the presence of 0.5 g of polyphosphoric acid and' then boil under reflux for 90 minutes. The reaction mixture is cooled slightly and then 25 ml of butyl alcohol is added dropwise for crystallization. After cooling, the secreted product is sucked off and covered with ethanol.
Man får ^-klor-6,7-methylendioxy-3-kinolincarboxylsyre-butylester-hydroklorid. Smeltepunkt: 170-172°G. Utbytte: ^-,8 g (78$). ^-Chloro-6,7-methylenedioxy-3-quinolinecarboxylic acid butyl ester hydrochloride is obtained. Melting point: 170-172°G. Yield: ^-.8 g ($78).
Ovenstående reaksjon foregår også uten nærvær av katalysator. The above reaction also takes place without the presence of a catalyst.
Saltsyresaltet suspenderes 1 vann og nøytraliseres med 10#-ig natriumhydrocarbonatopplosning. Krystallene frafUtreres og dekkes med litt vann. Man får h, k3 g ( 73%) ^-klor-6,7-methylendioxy-3-kinolin-carboxylsyre-butylester med smeltepunkt 88-90°C. Omkrystalli-sert fra butylalkohol smelter produktet ved 90-92°C. The hydrochloric acid salt is suspended in 1 water and neutralized with 10% sodium bicarbonate solution. The crystals are filtered off and covered with a little water. One obtains h, k3 g (73%) ^-chloro-6,7-methylenedioxy-3-quinoline-carboxylic acid butyl ester with a melting point of 88-90°C. Recrystallized from butyl alcohol, the product melts at 90-92°C.
Eksempel 3 Example 3
8,62 g (0,02 mol) 3,^-methylendioxy-anilino-methylen-malonsyre-dibenzylester oppvarmes til kokning under omroring i 9)2 g (0,6 mol) fosforoxyklorid i nærvær av 0,5 g polyfosforsyre. Reaksjonsblandingen avkjoles litt og derpå tildryppes 15 ml vannfri ethanol for krystallisering. Efter avkjoling frasuges krystallene, dekkes med litt ethanol og torres. Man får 3,1 g ^--klor-6,7-methylendioxy-3-kinolin-carboxylsyre-benzylester-hydroklorid med smeltepunkt 166-168°C. 8.62 g (0.02 mol) of 3,^-methylenedioxy-anilino-methylene-malonic acid dibenzyl ester is heated to boiling with stirring in 9.2 g (0.6 mol) of phosphorus oxychloride in the presence of 0.5 g of polyphosphoric acid. The reaction mixture is cooled slightly and then 15 ml of anhydrous ethanol is added dropwise for crystallization. After cooling, the crystals are sucked off, covered with a little ethanol and dried. 3.1 g of β-chloro-6,7-methylenedioxy-3-quinoline-carboxylic acid benzyl ester hydrochloride with a melting point of 166-168°C is obtained.
Ovenstående reaksjon kan også utfores i fravær av katalysa-toren ved den angitte fremgangsmåte. Også i dette tilfelle får man produktet i godt utbytte. The above reaction can also be carried out in the absence of the catalyst by the specified method. In this case too, you get the product at a good profit.
HydroklDridet suspenderes i vann og nøytraliseres med 10%- lg natriumhydrocarbonatopplosning. Krystallene frasuges, dekkes med vann og torres. Som råprodukt får man 2 g ^--klor-6,7-methylendioxy-3-kinolin-carboxylsyre-benzylester med smeltepunkt 100-102°C. The hydrochloride is suspended in water and neutralized with 10% sodium bicarbonate solution. The crystals are sucked off, covered with water and dried. As crude product, 2 g of β-chloro-6,7-methylenedioxy-3-quinoline-carboxylic acid benzyl ester with a melting point of 100-102°C is obtained.
Eksempel k Example k
27,97 g (0,1 mol) 3-carbethoxy-lf-klor-6,7-methylendioxy-kinolln og 6,0 g (0,15 mol) natriumhydroxyd oppvarmes i en blanding av 200 ml vann og 30 ml 96#-ig alkohol i 1,5-2 timer. Reaksjonsblandingen filtreres og filtratet syres med fortynnet saltsyre. De utskilte krystaller frafUtreres og torres. Man får 16, k g 6,7-methylen-dioxy-^--klor-kinolin-3-carboxylsyre med smeltepunkt over 320°C. 27.97 g (0.1 mol) of 3-carbethoxy-1f-chloro-6,7-methylenedioxy-quinolin and 6.0 g (0.15 mol) of sodium hydroxide are heated in a mixture of 200 ml of water and 30 ml of 96# -ig alcohol for 1.5-2 hours. The reaction mixture is filtered and the filtrate acidified with dilute hydrochloric acid. The separated crystals are filtered off and dried. 16,000 g of 6,7-methylene-dioxy-3-chloro-quinoline-3-carboxylic acid with a melting point above 320°C is obtained.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HUCI000886 | 1969-04-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO129952B true NO129952B (en) | 1974-06-17 |
Family
ID=10994363
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO01507/70A NO129952B (en) | 1969-04-26 | 1970-04-21 |
Country Status (7)
| Country | Link |
|---|---|
| JP (1) | JPS4811119B1 (en) |
| AT (1) | AT296989B (en) |
| CH (1) | CH536315A (en) |
| DK (1) | DK125648B (en) |
| FI (1) | FI49826C (en) |
| NO (1) | NO129952B (en) |
| SE (2) | SE369601B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS51106368U (en) * | 1975-02-24 | 1976-08-25 |
-
1970
- 1970-04-21 NO NO01507/70A patent/NO129952B/no unknown
- 1970-04-21 SE SE05500/70A patent/SE369601B/xx unknown
- 1970-04-23 DK DK206270AA patent/DK125648B/en unknown
- 1970-04-24 AT AT375770A patent/AT296989B/en not_active IP Right Cessation
- 1970-04-24 FI FI701156A patent/FI49826C/en active
- 1970-04-27 JP JP45035483A patent/JPS4811119B1/ja active Pending
- 1970-08-21 CH CH595370A patent/CH536315A/en not_active IP Right Cessation
-
1974
- 1974-05-09 SE SE7406223A patent/SE407573B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SE369601B (en) | 1974-09-09 |
| DK125648B (en) | 1973-03-19 |
| JPS4811119B1 (en) | 1973-04-10 |
| FI49826C (en) | 1975-10-10 |
| AT296989B (en) | 1972-03-10 |
| SE407573B (en) | 1979-04-02 |
| CH536315A (en) | 1973-04-30 |
| FI49826B (en) | 1975-06-30 |
| SE7406223L (en) | 1974-05-09 |
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