NO145788B - QUINOLINE DERIVATIVES FOR USE AS INTERMEDIATES IN THE PREPARATION OF 6,7-DIALCOXY-4-OXY-QUINOLIN-3-CARBOXYL ACID ESTERS - Google Patents
QUINOLINE DERIVATIVES FOR USE AS INTERMEDIATES IN THE PREPARATION OF 6,7-DIALCOXY-4-OXY-QUINOLIN-3-CARBOXYL ACID ESTERS Download PDFInfo
- Publication number
- NO145788B NO145788B NO743064A NO743064A NO145788B NO 145788 B NO145788 B NO 145788B NO 743064 A NO743064 A NO 743064A NO 743064 A NO743064 A NO 743064A NO 145788 B NO145788 B NO 145788B
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- Prior art keywords
- quinoline
- ethoxy
- compounds
- hydroxy
- carbon atoms
- Prior art date
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- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title claims description 3
- 239000002253 acid Substances 0.000 title description 4
- 150000002148 esters Chemical class 0.000 title description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title 1
- 239000000543 intermediate Substances 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- -1 6-acetoxy-7-ethoxy-4-oxo-quinoline-3-carboxylic acid ethyl ester Chemical group 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 150000003248 quinolines Chemical class 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- HLASKCWWYKMAFY-UHFFFAOYSA-N ethyl 7-ethoxy-6-hydroxy-4-oxo-3h-quinoline-3-carboxylate Chemical group CCOC1=C(O)C=C2C(=O)C(C(=O)OCC)C=NC2=C1 HLASKCWWYKMAFY-UHFFFAOYSA-N 0.000 claims description 3
- WZZXNOPGKYPHRW-UHFFFAOYSA-N benzyl 7-ethoxy-6-hydroxy-4-oxo-3H-quinoline-3-carboxylate Chemical group C(C1=CC=CC=C1)OC(=O)C1C=NC2=CC(=C(C=C2C1=O)O)OCC WZZXNOPGKYPHRW-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000001589 carboacyl group Chemical group 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 31
- 239000000047 product Substances 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000000155 melt Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 125000002252 acyl group Chemical group 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 238000007363 ring formation reaction Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- GAKQMSVBEZWYGU-UHFFFAOYSA-N C(C)(=O)OC1=C(C=C(N)C=C1)OCC Chemical compound C(C)(=O)OC1=C(C=C(N)C=C1)OCC GAKQMSVBEZWYGU-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- CAWVNWVFAVJLIL-UHFFFAOYSA-N dibenzyl 2-(ethoxymethylidene)propanedioate Chemical compound C=1C=CC=CC=1COC(=O)C(=COCC)C(=O)OCC1=CC=CC=C1 CAWVNWVFAVJLIL-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000006798 ring closing metathesis reaction Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- VCYQNCHWCSKOTO-UHFFFAOYSA-N 4-amino-2-ethoxyphenol Chemical compound CCOC1=CC(N)=CC=C1O VCYQNCHWCSKOTO-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 238000003723 Smelting Methods 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 2
- AZCOMUGSJJOYHH-UHFFFAOYSA-N diethyl 2-[(3-ethoxy-4-hydroxyanilino)methylidene]propanedioate Chemical compound CCOC(=O)C(=CNC1=CC(OCC)=C(O)C=C1)C(=O)OCC AZCOMUGSJJOYHH-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YIFCWYUSYGFFMH-UHFFFAOYSA-N 2-(ethoxymethylidene)propanedioic acid Chemical compound CCOC=C(C(O)=O)C(O)=O YIFCWYUSYGFFMH-UHFFFAOYSA-N 0.000 description 1
- GIHYKBDWFSOKNN-UHFFFAOYSA-N 2-ethoxy-4-nitrophenol Chemical compound CCOC1=CC([N+]([O-])=O)=CC=C1O GIHYKBDWFSOKNN-UHFFFAOYSA-N 0.000 description 1
- MHYNVHMGKMPURK-UHFFFAOYSA-N 3-ethoxy-2-ethoxycarbonylprop-2-enoic acid Chemical compound CCOC=C(C(O)=O)C(=O)OCC MHYNVHMGKMPURK-UHFFFAOYSA-N 0.000 description 1
- 150000004333 6-hydroxyquinolines Chemical class 0.000 description 1
- FKHZSVWGOFCGCJ-UHFFFAOYSA-N C(C)(=O)OC1=C(C=C(C=C1)[N+](=O)[O-])OCC Chemical compound C(C)(=O)OC1=C(C=C(C=C1)[N+](=O)[O-])OCC FKHZSVWGOFCGCJ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- GHKISGDRQRSCII-UHFFFAOYSA-N chelidonine Natural products C1=C2C3N(C)CC4=C(OCO5)C5=CC=C4C3C(O)CC2=CC2=C1OCO2 GHKISGDRQRSCII-UHFFFAOYSA-N 0.000 description 1
- 230000002192 coccidiostatic effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 229960002819 diprophylline Drugs 0.000 description 1
- KSCFJBIXMNOVSH-UHFFFAOYSA-N dyphylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1N(CC(O)CO)C=N2 KSCFJBIXMNOVSH-UHFFFAOYSA-N 0.000 description 1
- 125000002587 enol group Chemical group 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- KTMGNAIGXYODKQ-UHFFFAOYSA-N ethyl 2-cyano-3-ethoxyprop-2-enoate Chemical compound CCOC=C(C#N)C(=O)OCC KTMGNAIGXYODKQ-UHFFFAOYSA-N 0.000 description 1
- OGFGOEBARPUXOW-UHFFFAOYSA-N ethyl 6-acetyloxy-7-ethoxy-4-oxo-1H-quinoline-3-carboxylate Chemical compound C(C)(=O)OC=1C=C2C(=C(C=NC2=CC1OCC)C(=O)OCC)O OGFGOEBARPUXOW-UHFFFAOYSA-N 0.000 description 1
- GLUQMYQDGHKVIX-UHFFFAOYSA-N ethyl 7-ethoxy-6-hydroxy-4-oxo-1h-quinoline-3-carboxylate Chemical compound CCOC1=C(O)C=C2C(=O)C(C(=O)OCC)=CNC2=C1 GLUQMYQDGHKVIX-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Description
Foreliggende oppfinnelse angår nye kinolinderivater med formel I som angitt i karakteristikken til kravene, og som er' anvendbare som mellomprodukter ved fremstilling av de kjente coccidiostatica, 6,7-dialkoxy-kinolin-carboxylsyreestere ved fremgangsmåten beskrevet i norsk patentansøkning 74 3063. I den generelle formel: The present invention relates to new quinoline derivatives of formula I as stated in the characteristics of the claims, and which can be used as intermediate products in the production of the known coccidiostatics, 6,7-dialkoxy-quinoline-carboxylic acid esters by the method described in Norwegian patent application 74 3063. In the general formula:
er R alkyl med 1-4 carbonatomer, R 3alkyl med 1-4 carbonatomer eller benzyl, og R 4 er hydrogen eller alkanoyl med 1-4 carbonatomer. is R alkyl of 1-4 carbon atoms, R 3 alkyl of 1-4 carbon atoms or benzyl, and R 4 is hydrogen or alkanoyl of 1-4 carbon atoms.
Forbindelsene med formel I kan foreligge i begge tauto-mere former, keto- og enolformen. The compounds of formula I can exist in both tautomeric forms, the keto and enol forms.
Til fremstilling av 6,7-dialkoxy-kinolin-carboxylsyreestere er kjent forskjellige metoder, som har det til felles at der som utgangsmateriale i hvert tilfelle anvendes 6,7-dialkoxy-derivater, som f.eks. ved fremgangsmåten ifølge de nederlandske patentansøkninger nr. 6 508 117 og 6 600 447, såvel som britisk patentskrift nr. 1 172 841. Ved alle fremgangsmåter fåes 6,7-dialkoxy-4-oxy-kinolinene fra 6,7-dialkoxy-4-acyloxy-kinolin-derivatene. For the production of 6,7-dialkoxy-quinoline-carboxylic acid esters, various methods are known, which have in common that 6,7-dialkoxy derivatives are used as starting material in each case, such as e.g. by the process according to Dutch Patent Applications No. 6,508,117 and 6,600,447, as well as British Patent Specification No. 1,172,841. In all processes, the 6,7-dialkyloxy-4-oxy-quinolines are obtained from 6,7-dialkyloxy-4- the acyloxy-quinoline derivs.
6,7-dialkoxy-4-acyloxy-kinolinene kan dessuten fremstilles ved termisk ringslutning, hvorunder forbindelsene ved høy temperatur kommer i berøring med spaltningsprodukter som senere neppe er fjernbare. Rensingen av slike produkter er overordentlig vanskelig, da de er uoppløselige, hvilket innskrenker muligheten for omkrystallisasjon sterkt. The 6,7-dialkoxy-4-acyloxy-quinolines can also be prepared by thermal cyclization, during which the compounds at high temperature come into contact with cleavage products which are hardly removable later. The purification of such products is exceedingly difficult, as they are insoluble, which greatly limits the possibility of recrystallization.
Disse ulemper kan overkommes ved foreliggende oppfinnelse. 6-acyloxy-derivatene ifølge oppfinnelsen kan overraskende fåes med meget godt utbytte ved termisk ringslutning og kan renses These disadvantages can be overcome by the present invention. The 6-acyloxy derivatives according to the invention can surprisingly be obtained in very good yield by thermal cyclization and can be purified
uten vanskelighet og omsettes til de rene 6-hydroxy-derivater, without difficulty and is converted into the pure 6-hydroxy derivatives,
som er egnet for videre reaksjoner. which are suitable for further reactions.
I fransk patentskrift nr. 1 531 495 er beskrevet 6-alkoxy-7-acyloxy-4-oxy-kinolin-3-carboxylsyre-derivater som kan betraktes som strukturisomerer av forbindelsene ifølge foreliggende oppfinnelse. 6-Alkoxy-7-acyloxy-4-oxy-quinoline-3-carboxylic acid derivatives which can be regarded as structural isomers of the compounds according to the present invention are described in French patent document No. 1 531 495.
Fra fransk patentskrift nr. 2 013 519 er 6-hydroxy-kinolin-derivater kjent, ved hvilke kinolinringen har en cyclo-alkylgruppe i 7,8-stillingen. 6-hydroxy-quinoline derivatives are known from French patent document no. 2,013,519, in which the quinoline ring has a cycloalkyl group in the 7,8-position.
Ved én- utførelsesform av.fremgangsmåten ifølge oppfinnelsen fremstilles de nye forbindelser med den generelle formel I, ved at forbindelser med formelen: In one embodiment of the method according to the invention, the new compounds with the general formula I are prepared, in that compounds with the formula:
hvor R^- og R<4> er som ovenfor angitt, reduseres til forbindelser med den generelle formel: _ 4 hvor Ri og R er som ovenfor angitt, og de erholdte forbindelser omsettes med ethoxy-methylen-malonsyre-dialkylestere med den generelle formel: hvor R 3 er som ovenfor angitt, og de erholdte forbindelser med den generelle formel: where R^- and R<4> are as indicated above, are reduced to compounds of the general formula: _ 4 where Ri and R are as indicated above, and the compounds obtained are reacted with ethoxy-methylene-malonic acid dialkyl esters of the general formula : where R 3 is as indicated above, and the obtained compounds with the general formula:
1 3 A1 3 A
hvor R , R og R er som ovenfor angitt, underkastes en ringslut-ningsreaksjon. where R , R and R are as indicated above, is subjected to a ring closure reaction.
I den generelle formel I er R"<*>" en rettkjedet eller forgrenet alkylgruppe med 1-4 carbonatomer, fortrinnsvis ethyl. ;R^ er éh rettkjedet eller forgrenet alkylgruppe med 1-4 carbonatomer, fortrinnsvis ethyl t eller benzyl; ;4 ;R er hydrogen eller alkanoyl med 1-4 carbonatomer. ;Forbindelsene med formel II hvor R <4>er hydrogen, kan fremstilles ved den av D. F. Page og 0. Clinton i Org. Chem. 27, 218 (1962) beskrevne måte. Forbindelsene med formel II hvor R<4 >er alkanoyl, kan fåes ved acylering av hydroxyderivatet. ;Reduksjonen av forbindelsene med formel II utføres i 9, nærvær av en katalysator, fortrinnsvis i nærvær av palladium-aktivt kull ved atmosfæretrykk eller forhøyet trykk. ;Ved reduksjonen av alkanoylderivatet arbeides i et opp-løsningsmiddel, fortrinnsvis eddiksyreethylester. ;Reduksjonen av fenolene med formel II utføres ;med fordel i vandig saltsyre eller i en blanding av vandige opp-løsninger av saltsyre og eddiksyre. ;Kondensasjonen av den reduserte forbindelse med formel III med forbindelsen med formel IV blir, når R 4er alkanoyl, fortrinnsvis utført i et oppløsningsmiddel, f.eks. i eddiksyreethylester, under kokning. ;Når forbindelsen med formel III er en hydroxylforbindelse, kondenseres den likeledes i et oppløsningsmiddel under oppvarming med forbindelsen med formel IV. Som oppløsningsmiddel anvendes fortrinnsvis bensin som imidlertid heller virker som fortynningsmiddel. Reaksjonen kan like godt utføres uten fortynningsmiddel i smeiten. ;Utføres reaksjonen av hydroxyforbindelsen med formel III med malonsyrederivatet uten oppløsningsmiddel i smeiten, behøver ikke forbindelsen med formel V å isoleres, men reaksjonsblandingen kan umiddelbart underkastes ringslutningsreaksjonen i "Difyl" ;ved 250°C. ;Ved en annen utførelsesform av fremgangsmåten foretaes ringslutningsreaksjonen av forbindelsene med formel V, hvor R 4 er hydrogen, i et oppløsningsmiddelmedium av svovelsyre og eddiksyreanhydrid. I dette tilfelle blir den kondenserte forbindelse opp-løst i eddiksyreanhydrid og svovelsyren tilsettes dråpevis til oppløsningen. Under idryppingen av svovelsyre oppvarmer reaksjonsblandingen seg til 60°C, og ved denne temperatur omrøres blandingen i 10 minutter. Derpå helles reaksjonsblandingen i vann, hvorved produktet utfelles. ;i 3 4 Forbindelsene med formel I, hvor Rx, R og R er som ovenfor angitt* kan fremstilles ved en annen utførelsesform av foreliggende fremgangsmåte, idet de nye forbindelser med den generelle formel:.. In the general formula I, R"<*>" is a straight-chain or branched alkyl group with 1-4 carbon atoms, preferably ethyl. R^ is a straight-chain or branched alkyl group with 1-4 carbon atoms, preferably ethyl or benzyl; ;4 ;R is hydrogen or alkanoyl with 1-4 carbon atoms. The compounds of formula II where R <4> is hydrogen can be prepared by that of D. F. Page and O. Clinton in Org. Chem. 27, 218 (1962) described manner. The compounds of formula II where R<4 >is alkanoyl can be obtained by acylation of the hydroxy derivative. The reduction of the compounds of formula II is carried out in 9, in the presence of a catalyst, preferably in the presence of palladium-activated carbon at atmospheric pressure or elevated pressure. In the reduction of the alkanoyl derivative, work is carried out in a solvent, preferably acetic acid ethyl ester. The reduction of the phenols of formula II is advantageously carried out in aqueous hydrochloric acid or in a mixture of aqueous solutions of hydrochloric acid and acetic acid. The condensation of the reduced compound of formula III with the compound of formula IV is, when R 4 is alkanoyl, preferably carried out in a solvent, e.g. in ethyl acetate, while boiling. When the compound of formula III is a hydroxyl compound, it is likewise condensed in a solvent under heating with the compound of formula IV. Petrol is preferably used as a solvent, which, however, acts rather as a diluent. The reaction can just as easily be carried out without a diluent in the smelting. If the reaction of the hydroxy compound of formula III with the malonic acid derivative is carried out without a solvent in the smelting, the compound of formula V does not need to be isolated, but the reaction mixture can be immediately subjected to the cyclization reaction in "Difyl" at 250°C. In another embodiment of the method, the cyclization reaction of the compounds of formula V, where R 4 is hydrogen, is carried out in a solvent medium of sulfuric acid and acetic anhydride. In this case, the condensed compound is dissolved in acetic anhydride and the sulfuric acid is added dropwise to the solution. During the instillation of sulfuric acid, the reaction mixture heats up to 60°C, and at this temperature the mixture is stirred for 10 minutes. The reaction mixture is then poured into water, whereby the product is precipitated. ;i 3 4 The compounds of formula I, where Rx, R and R are as indicated above* can be prepared by another embodiment of the present method, as the new compounds with the general formula:..
hvor R og R<4> er som ovenfor angitt, omsettes med orthomaursyre-ester og alkylmalonat, og den erholdte forbindelse med formel V underkastes ringslutning. Metodene for ringslutning er de samme som beskrevet ovenfor. De nye forbindelser med formel VI kan fremstilles på den av CC. Price u.a. i J. Am. Chem. 68, 1251 beskrevne måte. where R and R<4> are as indicated above, is reacted with orthoformic acid ester and alkyl malonate, and the resulting compound of formula V is subjected to ring closure. The methods for ring closure are the same as described above. The new compounds of formula VI can be prepared on that of CC. Price u.a. in J. Am. Chem. 68, 1251 described manner.
Forbindelsene med formel I, hvor R 4 er hydrogen, altså forbindelsene med den generelle formel: The compounds with formula I, where R 4 is hydrogen, i.e. the compounds with the general formula:
kan dessuten fåes med følgende metoder, og med spesiell renhet: can also be obtained by the following methods, and with particular purity:
en forbindelse med den generelle formel I, hvor R<4> er alkanoyl med 1-4 carbonatomer, underkastes en selektiv acylspaltning. Acylspaltningen foretas i et svakt alkalisk medium, fortrinnsvis a compound of the general formula I, where R<4> is alkanoyl with 1-4 carbon atoms, is subjected to a selective acyl cleavage. The acyl cleavage is carried out in a weakly alkaline medium, preferably
i nærvær av kaliumhydrogencarbonat i en. vann-alkohol-blanding, in the presence of potassium bicarbonate in a. water-alcohol mixture,
ved blandingens kokepunkt. Under disse betingelser forblir estergruppen uforandret. at the boiling point of the mixture. Under these conditions, the ester group remains unchanged.
Ved en annen utførelsesform av foreliggende fremgangsmåte kan 6-hydroxy-forbindelsene fremstilles ved at forbindelser med den generelle formel III, hvor R<4> er hydrogen, omsettes med ethyl-a-cyano-3-ethoxy-acrylat, og den erholdte forbindelse med den generelle formel: hvor R er som ovenfor angitt, underkastes en ringslutning, og.de. erholdte nye forbindelser med den generelle formel: In another embodiment of the present method, the 6-hydroxy compounds can be prepared by reacting compounds of the general formula III, where R<4> is hydrogen, with ethyl-α-cyano-3-ethoxy-acrylate, and the compound obtained with the general formula: where R is as indicated above, subject to a circular conclusion, and.de. obtained new compounds with the general formula:
hvor R?~ er som ovenfor angitt, underkastes en sur eller alkalisk hydrolyse, og forestres derpå, eller nitrilet med den generelle formel VIII omsettes umiddelbart med alkoholen i et surt medium. where R?~ is as indicated above, is subjected to an acid or alkaline hydrolysis, and then esterified, or the nitrile of the general formula VIII is immediately reacted with the alcohol in an acidic medium.
Forbindelsene med den generelle formel I, hvor R 4 er The compounds of the general formula I, where R 4 is
hydrogen, kan ved hydrolyse omsettes til de tilsvarende syrer, fra hvilke en annen ester kan dannes ved tilsetning av en alkohol. De erholdte forbindelser kan overføres til sine salter eller frigjøres fra sine salter. Esterne danner f.eks. hydroklorider og hydrobro-mider. hydrogen, can by hydrolysis be converted into the corresponding acids, from which another ester can be formed by the addition of an alcohol. The obtained compounds can be transferred to their salts or liberated from their salts. The esters form e.g. hydrochlorides and hydrobromides.
Eksempel 1 Example 1
Fremstilling av utgangsmateriale Production of starting material
Trinn a: 22,52 g (0,1 mol) 4-acetoxy-3-ethoxy-nitrobenzen oppløses i 225 ml eddiksyreethylester, og hydreres ved 5-10 atm i nærvær av 5 g palladium-aktivt kull. Etter opptagelse av den beregnede mengde hydrogen frafiltreres katalysatoren og reaksjonsblandingen inndampes til tørrhet.. Ved avkjøling krystalliserer 4-acetoxy-3-ethoxy-anilinet, og vaskes på nutschen med kald alkohol. Der fåes Step a: 22.52 g (0.1 mol) of 4-acetoxy-3-ethoxy-nitrobenzene are dissolved in 225 ml of acetic acid ethyl ester, and hydrated at 5-10 atm in the presence of 5 g of palladium activated carbon. After absorption of the calculated amount of hydrogen, the catalyst is filtered off and the reaction mixture is evaporated to dryness. On cooling, the 4-acetoxy-3-ethoxy-aniline crystallizes and is washed on the nut with cold alcohol. There are available
i 86 %-ig utbytte et hvitt og krystallinsk produkt med smeltepunkt 96° C. in 86% yield a white and crystalline product with melting point 96° C.
Beregnet: C 61,53 %, H 6,71 %, N 7,17 % Calculated: C 61.53%, H 6.71%, N 7.17%
Funnet : C 61,30 %, H 6,40 %, N 6,81 % Found : C 61.30%, H 6.40%, N 6.81%
Trinn b: Step b:
25,4' g (0,13 mol) 4-acetoxy-3-ethoxy-anilin oppløses i 250 ml ethylacetat og oppløsningen tilsettes 32,4 g (0,15 mol) ethoxymethylen-malonsyre-diethylester. Reaksjonsblandingen kokes i 3 timer og inndampes så til tørrhet. Residuet bringes ved avkjø-ling til krystallisasjon. Krystallene vaskes på en nusch med kold alkohol. Den hvite, 4-acetoxy-3-ethoxy-anilino-methylenmalonsyre-ethylester som smelter ved 102°C, fåes i 91%-ig utbytte. 25.4 g (0.13 mol) of 4-acetoxy-3-ethoxy-aniline are dissolved in 250 ml of ethyl acetate and 32.4 g (0.15 mol) of ethoxymethylene malonic acid diethyl ester are added to the solution. The reaction mixture is boiled for 3 hours and then evaporated to dryness. The residue is brought to crystallization by cooling. The crystals are washed on a nusch with cold alcohol. The white, 4-acetoxy-3-ethoxy-anilino-methylenemalonic acid ethyl ester which melts at 102°C is obtained in 91% yield.
Beregnet: C 59,17 %, H 6,34 %, N 3,83 % Calculated: C 59.17%, H 6.34%, N 3.83%
Funnet :C59,3%, H 6,50%, N 3,91% Found :C59.3%, H 6.50%, N 3.91%
Fremstilling av produkt Manufacturing of product
35,45 g (0,1 mol) 4-acetoxy-3-ethoxy-anilino-methylen-malonsyrediethylester kokes i 365 ml difyl i 60 minutter. Produktet utskilles langsomt fra oppløsningen. Suspensjonen avkjøles, fortyn-nes med 350 ml bensin og filtreres derpå. Produktet settes under bensin på nutschen. Man får den ved 300° C under spaltning smelt-ende , sandfarvede 6-acetoxy-7-ethoxy-4-hydroxy-kinolin-3-carboxy.l-syreethylester i 95 %-ig utbytte. Etter omkrystallisasjon fra dimethylsulfoxyd er smeltepunktet 310° C. 35.45 g (0.1 mol) of 4-acetoxy-3-ethoxy-anilino-methylene-malonic acid diethyl ester is boiled in 365 ml diphyllo for 60 minutes. The product slowly separates from the solution. The suspension is cooled, diluted with 350 ml of petrol and then filtered. The product is placed under petrol on the nut. It is obtained at 300° C. under cleavage melting, sand-colored 6-acetoxy-7-ethoxy-4-hydroxy-quinoline-3-carboxyl-acid ethyl ester in 95% yield. After recrystallization from dimethylsulfoxide, the melting point is 310° C.
Beregnet: C 60,18 %, H 5,36 %, N 4,38 % Calculated: C 60.18%, H 5.36%, N 4.38%
Funnet : C 60,20 %, H 5,16 %, N 4,32 %. Found: C 60.20%, H 5.16%, N 4.32%.
Eksempel 2 Example 2
På lignende måte som ovenfor beskrevet får man ved iste-denfor ethoxy-methylen-malonsyreethylester å anvende ethoxy-methylen-malonsyredibenzylester, den tilsvarende benzylesterforbin-delse. 4-acetoxy-3-ethoxy-anilin omsettes, i eddiksyreethylester med ethoxy-methylen-malonsyre-dibenzylester, og den erholdte for---bindelse blir etter inndampning av reaksjonsblandingen uten iso-lering straks underkastet ringslutningsreaksjonen i"Difyl". Den erholdte 6-acetoxy-7-ethoxy-4-oxo-kinolin-3-carboxylsyre-benzyl-ester er et sandfarvet stoff, som smelter ved 260° C under spaltning. Etter omkrystallisasjon fra dimethylsulfoxyd får man et hvitt produkt som smelter ved 265° C under spaltning. In a similar way as described above, by using ethoxy-methylene-malonic acid dibenzyl ester instead of ethoxy-methylene-malonic acid ethyl ester, the corresponding benzyl ester compound is used. 4-acetoxy-3-ethoxy-aniline is reacted, in acetic acid ethyl ester with ethoxy-methylene-malonic acid-dibenzyl ester, and the compound obtained is, after evaporation of the reaction mixture without isolation, immediately subjected to the ring closure reaction in "Difyl". The 6-acetoxy-7-ethoxy-4-oxo-quinoline-3-carboxylic acid benzyl ester obtained is a sand-coloured substance, which melts at 260° C during decomposition. After recrystallization from dimethylsulfoxide, a white product is obtained which melts at 265° C during cleavage.
Beregnet: C 66,14 %, H 5,02 %, N 3,67 % Calculated: C 66.14%, H 5.02%, N 3.67%
Funnet : C 65,80 %, H 5,27 %, N 3,78 % Found : C 65.80%, H 5.27%, N 3.78%
Eksempel 3 Example 3
Fremstilling av utgangsmateriale Production of starting material
Trinn a: 18,31 g (Q,l mol) 2-ethoxy-4-nitrofenol reduseres i en blanding av 180 ml vann, 10 ml konsentrert saltsyre og 50 ml eddiksyre i nærvær av en palladium-kull-katalysator. Etter frafiltrering av katalysatoren innstilles reaksjonsblandingens pH på 6 med 10 %-ig natriumcarbonatoppløsning. Det utskilte materiale frasuges, vaskes med vann og settes derpå under aceton. Man får 13,6 g (89 %) sandfarvet 2-ethoxy-4-aminofenol. Step a: 18.31 g (Q.1 mol) of 2-ethoxy-4-nitrophenol is reduced in a mixture of 180 ml of water, 10 ml of concentrated hydrochloric acid and 50 ml of acetic acid in the presence of a palladium-charcoal catalyst. After filtering off the catalyst, the pH of the reaction mixture is adjusted to 6 with a 10% sodium carbonate solution. The separated material is suctioned off, washed with water and then placed under acetone. 13.6 g (89%) of sand-colored 2-ethoxy-4-aminophenol is obtained.
Analyse:. Analysis:.
Beregnet: C 63,73 %, H 7,23 %, N 9,14 % Calculated: C 63.73%, H 7.23%, N 9.14%
Funnet : C 62,22 %, H 7,18 %, N 9,08 % Found : C 62.22%, H 7.18%, N 9.08%
Trinn b: 15,31 g (0,1 mol) 2-ethoxy-4-aminofenol og 26,0 g Step b: 15.31 g (0.1 mol) 2-ethoxy-4-aminophenol and 26.0 g
(0,12 mol) ethoxy-methylen-malonsyrediethylester oppvarmes i (0.12 mole) of ethoxy-methylene-malonic acid diethyl ester is heated in
2 timer på vannbad. Til den seige reaksjonsblanding tilsettes så 2 hours in a water bath. To the viscous reaction mixture is then added
30 ml bensin og blandingen kokes i 2 timer under tilbakeløp. Ved avkjøling utskilles der fra tofaseblandingen et fast stoff, som frafiltreres og settes under bensin. Man får 27,87 g sandfarvet 4-hydroxy-3-ethoxy-anilino-methylen-malonsyrediethylester, som smelter ved 80°C. Utbyttet utgjør 86%. 30 ml of petrol and the mixture is boiled for 2 hours under reflux. During cooling, a solid substance separates from the two-phase mixture, which is filtered off and placed under petrol. 27.87 g of sand-colored 4-hydroxy-3-ethoxy-anilino-methylene-malonic acid diethyl ester is obtained, which melts at 80°C. The yield amounts to 86%.
Analyse: Analysis:
Beregnet: C 59,43 %, H 6,54 %, N 4,33 % Calculated: C 59.43%, H 6.54%, N 4.33%
Funnet : C 59,57 %, H 6,61 %, N 4,30 % Found : C 59.57%, H 6.61%, N 4.30%
Fremstilling av sluttprodukt Production of final product
19,35 g (0,06 mol) 4-hydroxy-3-ethoxy-anilino-methylen-malonsyrediethylester holdes ved 250° C i 30 minutter i 190 ml"Difyl". Reaksjonsblandingen avkjøles og det ved ringslutningen dannede pro-du]ct felles ved tilsetning av 190 ml bensin. Produktet vaskes på filteret med bensin. Man får 14,8 g sandfarvet 6-hydroxy-7-ethoxy-4-oxo-kinolin-3-carboxylsyre-ethylester, som smelter ved 266° C. Utbyttet utgjør 89,3 %. Det fra dimethylformamid omkrystalliserte produkt smelter ved 270 - 272° C. 19.35 g (0.06 mol) of 4-hydroxy-3-ethoxy-anilino-methylene-malonic acid diethyl ester is kept at 250° C. for 30 minutes in 190 ml of "Difyl". The reaction mixture is cooled and the product formed during the ring closure is combined by adding 190 ml of petrol. The product is washed on the filter with petrol. 14.8 g of sand-coloured 6-hydroxy-7-ethoxy-4-oxo-quinoline-3-carboxylic acid ethyl ester is obtained, which melts at 266° C. The yield is 89.3%. The product recrystallized from dimethylformamide melts at 270 - 272°C.
Analyse: Analysis:
Beregnet: C 60,64 %, H 5,45 %, N 5,05 % Calculated: C 60.64%, H 5.45%, N 5.05%
Funnet : C 60,24 %, H 5,55 %, N 5,04 % Found : C 60.24%, H 5.55%, N 5.04%
Eksempel 4 Example 4
4,59 g (0,03 mol) 2-eth.oxy-4-aminof enol og 10,52 g (0,031 mol) ethoxy-methylen-malonsyredibenzylester holdes ved 100° C på vannbad i 4 timer. Derpå tilsettes reaksjonsblandingen 50 ml difyl og kokes i 60 minutter ved 250° C. Blandingen avkjøles, tilsettes 50 ml bensin, det utskilte produkt frafUtreres og vaskes med alkohol. Man får 3,4 g brun 6-hydroxy-7-ethoxy-4-oxo-kinolin-3-carboxylsyre-benzylester som smelter ved 256° C. Utbyttet utgjør 50,2 %. 4.59 g (0.03 mol) of 2-eth.oxy-4-aminophenol and 10.52 g (0.031 mol) of ethoxy-methylene-malonic acid dibenzyl ester are kept at 100° C. in a water bath for 4 hours. The reaction mixture is then added with 50 ml of diphylline and boiled for 60 minutes at 250° C. The mixture is cooled, 50 ml of petrol is added, the separated product is filtered off and washed with alcohol. 3.4 g of brown 6-hydroxy-7-ethoxy-4-oxo-quinoline-3-carboxylic acid benzyl ester is obtained which melts at 256° C. The yield is 50.2%.
Analyse: Analysis:
Beregnet: C 67,25 %, H 5,05 %, N 4,13 % Calculated: C 67.25%, H 5.05%, N 4.13%
Funnet : C 66,76 %, H 4,88 %, N 4,37 % Found : C 66.76%, H 4.88%, N 4.37%
Eksempel 5 Example 5
En blanding av 25,52 g (0,08 mol) 6-acetoxy-7-ethoxy-4-hydroxy-kinolin-3-carboxylsyre-ethylester, 2000 ml alkohol, 200 ml vann og 240,28 g (2,4 mol) kaliumhydrogencarbonat kokes i 1 time. Derpå avtrekkes alkoholen i vakuum og den gjenblivende tykke suspen-sjon blandes med 2000 ml vann. Det uoppløste materiale frafiltreres og suspenderes i nutsch-fuktig tilstand i 200 ml vann. Suspensjo-nens pH-verdi innstilles med 5 %-ig saltsyre på 3. Det uoppløste materiale frafiltreres, vaskes med vann og settes under alkoholen. Man får 16,87 g sandfarvet 6-hydroxy-7-ethoxy-4-hydroxy-kinolin-3-carboxylsyre-ethylester, som smelter ved 268 - 270° C. Utbyttet ut-gjør 76,0 %. Smeltepunktet av det fra dimethylformamid omkrystalliserte produkt ligger ved 272° C. A mixture of 25.52 g (0.08 mol) 6-acetoxy-7-ethoxy-4-hydroxy-quinoline-3-carboxylic acid ethyl ester, 2000 ml alcohol, 200 ml water and 240.28 g (2.4 mol ) potassium bicarbonate is boiled for 1 hour. The alcohol is then drawn off under vacuum and the remaining thick suspension is mixed with 2000 ml of water. The undissolved material is filtered off and suspended in a Nutsch-moist state in 200 ml of water. The suspension's pH value is set to 3 with 5% hydrochloric acid. The undissolved material is filtered off, washed with water and placed under the alcohol. 16.87 g of sand-colored 6-hydroxy-7-ethoxy-4-hydroxy-quinoline-3-carboxylic acid ethyl ester is obtained, which melts at 268 - 270° C. The yield is 76.0%. The melting point of the product recrystallized from dimethylformamide is 272°C.
Eksempel 6 Example 6
En blanding av 5,54 g (0,02 mol) 6-hydroxy-7-ethoxy-4-oxo-kinolin-3-carboxylsyre-ethylester og 110 ml 10 %-ig natrium-hydroxydoppløsning kokes i 3 timer. Den ved avslutning av reaksjonen erholdte oppløsning avsuges skarpt og filtratet innstilles på pH 2 med 1:1 fortynnet saltsyre. Det utskilte faste materiale fra- > suges og vaskes med vann. Man får 4,85 g (97,5 % av det teoretiske) hvitt 6-hydroxy-7-ethoxy-4-oxo-kinolin-3-carboxylsyre, som smelter ved 278° C. Etter omkrystallisasjon fra dimethylformamid ligger smeltepunktet ved 285 - 287° C. A mixture of 5.54 g (0.02 mol) 6-hydroxy-7-ethoxy-4-oxo-quinoline-3-carboxylic acid ethyl ester and 110 ml of 10% sodium hydroxide solution is boiled for 3 hours. The solution obtained at the end of the reaction is sucked off sharply and the filtrate is adjusted to pH 2 with 1:1 diluted hydrochloric acid. The separated solid material is > suctioned off and washed with water. 4.85 g (97.5% of the theoretical) of white 6-hydroxy-7-ethoxy-4-oxo-quinoline-3-carboxylic acid is obtained, which melts at 278° C. After recrystallization from dimethylformamide, the melting point is at 285 - 287°C.
Analyse: Beregnet: C 57,83 %, H 4,45 %, N 5,62 % Analysis: Calculated: C 57.83%, H 4.45%, N 5.62%
Funnet : C 57,76 %, H 4,52 %, N 5,66 % Found : C 57.76%, H 4.52%, N 5.66%
Claims (4)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HUCI001403 HU167572B (en) | 1973-08-28 | 1973-08-28 | |
| HUCI001404 HU167573B (en) | 1973-08-28 | 1973-08-28 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO743064L NO743064L (en) | 1975-03-24 |
| NO145788B true NO145788B (en) | 1982-02-22 |
| NO145788C NO145788C (en) | 1982-06-02 |
Family
ID=26318396
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO743064A NO145788C (en) | 1973-08-28 | 1974-08-27 | QUINOLINE DERIVATIVES FOR USE AS INTERMEDIATES IN THE PREPARATION OF 6,7-DIALCOXY-4-OXY-QUINOLIN-3-CARBOXYL ACID ESTERS |
Country Status (13)
| Country | Link |
|---|---|
| JP (1) | JPS5082077A (en) |
| AT (1) | AT338789B (en) |
| CA (1) | CA1044239A (en) |
| CH (1) | CH615917A5 (en) |
| DD (1) | DD114077A1 (en) |
| DK (1) | DK141167B (en) |
| GB (1) | GB1467225A (en) |
| IN (1) | IN140826B (en) |
| NL (1) | NL7411324A (en) |
| NO (1) | NO145788C (en) |
| PL (1) | PL92578B1 (en) |
| SE (1) | SE406911B (en) |
| SU (1) | SU567402A3 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4014171A1 (en) * | 1990-05-03 | 1991-11-07 | Basf Ag | cyanoquinoline |
-
1974
- 1974-08-23 SE SE7410745A patent/SE406911B/en unknown
- 1974-08-26 NL NL7411324A patent/NL7411324A/en not_active Application Discontinuation
- 1974-08-26 AT AT688374A patent/AT338789B/en not_active IP Right Cessation
- 1974-08-26 PL PL1974187261A patent/PL92578B1/pl unknown
- 1974-08-27 CA CA207,894A patent/CA1044239A/en not_active Expired
- 1974-08-27 DK DK454774AA patent/DK141167B/en not_active IP Right Cessation
- 1974-08-27 JP JP49098309A patent/JPS5082077A/ja active Pending
- 1974-08-27 SU SU7402057994A patent/SU567402A3/en active
- 1974-08-27 NO NO743064A patent/NO145788C/en unknown
- 1974-08-27 GB GB3745174A patent/GB1467225A/en not_active Expired
- 1974-08-27 CH CH1168574A patent/CH615917A5/en not_active IP Right Cessation
- 1974-08-28 IN IN1940/CAL/1974A patent/IN140826B/en unknown
- 1974-08-28 DD DD180757A patent/DD114077A1/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AT338789B (en) | 1977-09-12 |
| DD114077A1 (en) | 1975-07-12 |
| SE7410745L (en) | 1975-03-03 |
| ATA688374A (en) | 1977-01-15 |
| PL92578B1 (en) | 1977-04-30 |
| SU567402A3 (en) | 1977-07-30 |
| GB1467225A (en) | 1977-03-16 |
| CH615917A5 (en) | 1980-02-29 |
| NO743064L (en) | 1975-03-24 |
| DK141167C (en) | 1980-06-23 |
| SE406911B (en) | 1979-03-05 |
| DK454774A (en) | 1975-04-28 |
| NO145788C (en) | 1982-06-02 |
| NL7411324A (en) | 1975-03-04 |
| JPS5082077A (en) | 1975-07-03 |
| CA1044239A (en) | 1978-12-12 |
| IN140826B (en) | 1976-12-25 |
| DK141167B (en) | 1980-01-28 |
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