NO148487B - PROCEDURE FOR SULFUR ACID PREPARATION - Google Patents
PROCEDURE FOR SULFUR ACID PREPARATIONInfo
- Publication number
- NO148487B NO148487B NO761532A NO761532A NO148487B NO 148487 B NO148487 B NO 148487B NO 761532 A NO761532 A NO 761532A NO 761532 A NO761532 A NO 761532A NO 148487 B NO148487 B NO 148487B
- Authority
- NO
- Norway
- Prior art keywords
- carboxyphenyl
- acid
- dimethylphenyl
- anthranilic acid
- compound
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims description 13
- 238000000034 method Methods 0.000 title claims description 10
- 238000002360 preparation method Methods 0.000 title claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 title 1
- 229910052717 sulfur Inorganic materials 0.000 title 1
- 239000011593 sulfur Substances 0.000 title 1
- GTGJIXJUDNDAHV-UHFFFAOYSA-N C(=O)(O)C1=C(C=CC=C1)N=C1C(C(CCC1)C)C Chemical compound C(=O)(O)C1=C(C=CC=C1)N=C1C(C(CCC1)C)C GTGJIXJUDNDAHV-UHFFFAOYSA-N 0.000 claims description 15
- 239000003054 catalyst Substances 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 14
- 238000005984 hydrogenation reaction Methods 0.000 claims description 13
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 11
- -1 benzene compound Chemical class 0.000 claims description 3
- 229910000510 noble metal Inorganic materials 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000000370 acceptor Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 6
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 150000002430 hydrocarbons Chemical class 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 150000002828 nitro derivatives Chemical class 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- OZCVOEUWYVVVME-UHFFFAOYSA-N 2,3-dimethylcyclohexan-1-one Chemical compound CC1CCCC(=O)C1C OZCVOEUWYVVVME-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 2
- PLAZTCDQAHEYBI-UHFFFAOYSA-N 2-nitrotoluene Chemical compound CC1=CC=CC=C1[N+]([O-])=O PLAZTCDQAHEYBI-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000006286 aqueous extract Substances 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- FVHAWXWFPBPFOS-UHFFFAOYSA-N 1,2-dimethyl-3-nitrobenzene Chemical group CC1=CC=CC([N+]([O-])=O)=C1C FVHAWXWFPBPFOS-UHFFFAOYSA-N 0.000 description 1
- HFZKOYWDLDYELC-UHFFFAOYSA-N 1,2-dimethyl-4-nitrobenzene Chemical group CC1=CC=C([N+]([O-])=O)C=C1C HFZKOYWDLDYELC-UHFFFAOYSA-N 0.000 description 1
- SCEKDQTVGHRSNS-UHFFFAOYSA-N 1,3,5-trimethyl-2-nitrobenzene Chemical compound CC1=CC(C)=C([N+]([O-])=O)C(C)=C1 SCEKDQTVGHRSNS-UHFFFAOYSA-N 0.000 description 1
- HDFQKJQEWGVKCQ-UHFFFAOYSA-N 1,3-dimethyl-2-nitrobenzene Chemical group CC1=CC=CC(C)=C1[N+]([O-])=O HDFQKJQEWGVKCQ-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-UHFFFAOYSA-N 0.000 description 1
- VUZPGEIXNYGDJN-UHFFFAOYSA-N 1-nitroethanol Chemical compound CC(O)[N+]([O-])=O VUZPGEIXNYGDJN-UHFFFAOYSA-N 0.000 description 1
- BVALZCVRLDMXOQ-UHFFFAOYSA-N 1-nitropentane Chemical compound CCCCC[N+]([O-])=O BVALZCVRLDMXOQ-UHFFFAOYSA-N 0.000 description 1
- BBUPBICWUURTNP-UHFFFAOYSA-N 2,4-dimethyl-1-nitrobenzene Chemical group CC1=CC=C([N+]([O-])=O)C(C)=C1 BBUPBICWUURTNP-UHFFFAOYSA-N 0.000 description 1
- OAYXUHPQHDHDDZ-UHFFFAOYSA-N 2-(2-butoxyethoxy)ethanol Chemical compound CCCCOCCOCCO OAYXUHPQHDHDDZ-UHFFFAOYSA-N 0.000 description 1
- ZPTVNYMJQHSSEA-UHFFFAOYSA-N 4-nitrotoluene Chemical compound CC1=CC=C([N+]([O-])=O)C=C1 ZPTVNYMJQHSSEA-UHFFFAOYSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 229940019778 diethylene glycol diethyl ether Drugs 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- RTAYVMMFHJMXQP-UHFFFAOYSA-N n,n-dimethyl-2-(methylamino)benzamide Chemical compound CNC1=CC=CC=C1C(=O)N(C)C RTAYVMMFHJMXQP-UHFFFAOYSA-N 0.000 description 1
- 125000004971 nitroalkyl group Chemical group 0.000 description 1
- 150000005181 nitrobenzenes Chemical class 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229910003445 palladium oxide Inorganic materials 0.000 description 1
- JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B17/00—Sulfur; Compounds thereof
- C01B17/69—Sulfur trioxide; Sulfuric acid
- C01B17/74—Preparation
- C01B17/76—Preparation by contact processes
- C01B17/765—Multi-stage SO3-conversion
- C01B17/7655—Multi-stage SO3-conversion with intermediate absorption
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Treating Waste Gases (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Gas Separation By Absorption (AREA)
Description
Fremgangsmåte til fremstilling av den terapeutisk virksomme forbindelse N-(2,3-dimethylfenyl)-anthranilsyre og salter av denne syre. Process for the preparation of the therapeutically active compound N-(2,3-dimethylphenyl)-anthranilic acid and salts of this acid.
Foreliggende oppfinnelse angår en The present invention relates to a
fremgangsmåte til fremstilling av den terapeutisk virksomme forbindelse N-(2,3-dimethylfenyl)-anthranilsyre og salter av process for the preparation of the therapeutically active compound N-(2,3-dimethylphenyl)-anthranilic acid and salts of
denne syre med formelen: this acid with the formula:
N- (2,3-dimethylfenyl) -anthranilsyre oppviser antiinflammatorisk virkning i lavere doser enn lignende forbindelser som er kjent på området. Således oppviser N-(2,3-dimethylfenyl) -anthranilsyre anti-in-flammatorisk virkning i doser betydelig lavere enn 12 mg/kg ved standardmetoden for bestemmelse av beskyttelsen av mar-svin mot ultrafiolett bestråling, mens f. eks. den beslektede forbindelse N-methyl-anthranilsyre-dimethylamid, som er be-skrevet i tysk patentskrift 1 091 120, ved samme standardmetode er uvirksom i doser på 200 mg/kg. Det karakteristiske hovedtrekk ved oppfinnelsen er at man oppvarmer N-(o-carboxyfenyl)-2,3-dimethylcyklohexan-imin som i dets ikke cykliske form tilsva-rer strukturf ormelen: N-(2,3-dimethylphenyl)-anthranilic acid exhibits anti-inflammatory action in lower doses than similar compounds known in the field. Thus, N-(2,3-dimethylphenyl)-anthranilic acid exhibits anti-inflammatory action in doses significantly lower than 12 mg/kg by the standard method for determining the protection of guinea pigs against ultraviolet irradiation, while e.g. the related compound N-methyl-anthranilic acid-dimethylamide, which is described in German patent document 1 091 120, is ineffective by the same standard method in doses of 200 mg/kg. The characteristic main feature of the invention is that N-(o-carboxyphenyl)-2,3-dimethylcyclohexane imine is heated, which in its non-cyclic form corresponds to the structural formula:
eller et salt av denne forbindelse med en or a salt of this compound with a
hydrogeneringskatalysator og en hydrogenakseptor. hydrogenation catalyst and a hydrogen acceptor.
Som hydrogeneringskatalysatorer er edelmetallhydrogeneringskatalysatorer som palladiumoxyd, palladium på kull, platina-oxyd og platina på kull såvel som Raney-nikkel særlig egnet for anvendelse i fremgangsmåten ifølge oppfinnelsen. Den mengde hydrogeneringskatalysatorer som anvendes, er ikke kritisk og den anvendte mengde er i alminnelighet omtrent den samme eller noe mer enn den mengde som anvendes i katalytiske hydrogeneringer. As hydrogenation catalysts, noble metal hydrogenation catalysts such as palladium oxide, palladium on charcoal, platinum oxide and platinum on charcoal as well as Raney nickel are particularly suitable for use in the method according to the invention. The amount of hydrogenation catalysts used is not critical and the amount used is generally about the same or somewhat more than the amount used in catalytic hydrogenations.
Den hydrogenakseptor som anvendes ifølge fremgangsmåten, er et organisk stoff som lett hydrogeneres av det hydrogen som frigjøres under reaksjonens forløp. De foretrukne hydrogenakseptorer er organiske nitroforbindelser samt benzenforbindelser inneholdende minst én aromatisk nitro-gruppe, nitroalkaner, nitroalkanoler eller lignende organiske nitroforbindelser som ikke inaktiverer hydrogeneringskatalysatoren. Som noen spesielle eksempler på slike stoffer nevnes nitrobenzen, o-nitrotoluen, p-nitrotoluen, 3-nitro-l,2-xylen, 4-nitro-1,2-xylen, 2-nitro-l,3-xylen, 4-nitro-l,3-xylen, 2-nitro-l,3,5-trimethylbenzen, ni-troethanol og 1-nitropentan. Den relative mengde hydrogenakseptor som anvendes, er ikke særlig kritisk, men der bør anvendes en mengde som er tilstrekkelig til å reagere med de to molekyler hydrogen som frigjøres ved hvert molekyl av N-(o-carboxyfenyl)-2,3-dimethyl-cyklohexanimin-forbindelsen. Når man således anvender en organisk nitroforbindelse som hydrogenakseptor, bør der anvendes minst to tredjedels molekyler pr. molekyl N-(o-carboxyfenyl)-2,3-dimethylcyklohexan-imin-forbindelse. I praksis foretrekkes det å anvende et overskudd av hydrogenakseptoren og, om så ønskes, kan der anvendes en mengde som er tilstrekkelig til at hydrogenakseptoren kan tjene til oppløs-ningsmiddel for reaksjonskomponenten. The hydrogen acceptor used according to the method is an organic substance that is easily hydrogenated by the hydrogen that is released during the course of the reaction. The preferred hydrogen acceptors are organic nitro compounds as well as benzene compounds containing at least one aromatic nitro group, nitroalkanes, nitroalkanols or similar organic nitro compounds which do not inactivate the hydrogenation catalyst. As some special examples of such substances, nitrobenzene, o-nitrotoluene, p-nitrotoluene, 3-nitro-1,2-xylene, 4-nitro-1,2-xylene, 2-nitro-1,3-xylene, 4- nitro-1,3-xylene, 2-nitro-1,3,5-trimethylbenzene, nitroethanol and 1-nitropentane. The relative amount of hydrogen acceptor used is not particularly critical, but an amount sufficient to react with the two molecules of hydrogen released by each molecule of N-(o-carboxyphenyl)-2,3-dimethyl-cyclohexanimine should be used. - the connection. When an organic nitro compound is thus used as a hydrogen acceptor, at least two-thirds of the molecules should be used per molecule N-(o-carboxyphenyl)-2,3-dimethylcyclohexane-imine compound. In practice, it is preferred to use an excess of the hydrogen acceptor and, if desired, an amount sufficient for the hydrogen acceptor to serve as a solvent for the reaction component can be used.
Reaksjonen utføres fortrinnsvis ved en temperatur på 100° C eller høyere. I alminnelighet er der intet formål ved å anvende temperaturer over 175° C, følgelig er det vanlig anvendte temperaturområde fra 100 til 175° C. Den temperatur som fortrinnsvis anvendes i reaksjonen, er ca. 110 til 125° C. The reaction is preferably carried out at a temperature of 100° C or higher. In general, there is no purpose in using temperatures above 175° C, consequently the commonly used temperature range is from 100 to 175° C. The temperature that is preferably used in the reaction is approx. 110 to 125°C.
Reaksjonstiden kan også varieres betydelig. I alminnelighet kan der anvendes en reaksjonstid fra 10 til 100 timer. The reaction time can also be varied considerably. In general, a reaction time of 10 to 100 hours can be used.
Det er ikke nødvendig å fjerne det vann som dannes under reaksjonens forløp, fra reaksjonsblandingen, men det er for-delaktig å gjøre dette. Når der anvendes et med vann ikke blandbart oppløsnings-middel, kan det dannede vann oppsamles, om så ønskes, og den dannede vannmengde anvendes som middel til å følge reaksjonens forløp og til å fastslå reaksjonens fullstendighet. It is not necessary to remove the water formed during the course of the reaction from the reaction mixture, but it is advantageous to do so. When a water-immiscible solvent is used, the water formed can be collected, if desired, and the amount of water formed is used as a means to follow the progress of the reaction and to determine the completeness of the reaction.
Fremgangsmåten utføres fortrinnsvis i et organisk oppløsningsmiddel. Som oven-for nevnt, kan hydrogenakseptoren, særlig organiske nitroforbindelser, anvendes som oppløsningsmiddel. Der kan også anvendes hydrocarboner som benzen, xylen, toluen, nafthaien, mineralolje og petrole-umfraksjoner som koker ved 100° C eller høyere, en ether av en polyalkylenglycol som diethylenglycol-butylether, triethylen-glycol-dimethylether og diethylenglycol-diethylether; amider som dimethylformamid, ethere som dioxan og dibutylether, alkoholer som butanol og amylalkohol, og glycoler som ethylenglycol. De foretrukne oppløsningsmidler er når N-(o-carboxyfenyl) -2,3-dimethyl-cyklohexaniminet anvendes i form av den fri syre sem utgangsmateriale, hydrocarboner og andre ikke polare oppløsningsmidler, mens de foretrukne oppløsningsmidler når der anvendes et salt av cyklohexanimin-forbindelse er polare oppløsningsmidler. I sistnevnte tilfelle kan vann tilsettes til det organiske oppløsningsmiddel for å øke saltets opp-løselighet. Når der anvendes polare opp-løsningsmidler, foretrekkes det å bruke edelmetall-hydrogenerings-katalysatorer. The method is preferably carried out in an organic solvent. As mentioned above, the hydrogen acceptor, especially organic nitro compounds, can be used as a solvent. Hydrocarbons such as benzene, xylene, toluene, naphtha, mineral oil and petroleum fractions which boil at 100° C or higher can also be used, an ether of a polyalkylene glycol such as diethylene glycol butyl ether, triethylene glycol dimethyl ether and diethylene glycol diethyl ether; amides such as dimethylformamide, ethers such as dioxane and dibutyl ether, alcohols such as butanol and amyl alcohol, and glycols such as ethylene glycol. The preferred solvents are when the N-(o-carboxyphenyl)-2,3-dimethyl-cyclohexanimine is used in the form of the free acid starting material, hydrocarbons and other non-polar solvents, while the preferred solvents are when a salt of the cyclohexanimine compound is used are polar solvents. In the latter case, water can be added to the organic solvent to increase the solubility of the salt. When polar solvents are used, it is preferred to use noble metal hydrogenation catalysts.
Reaksjonen utføres fortrinnsvis under anvendelse av N-(o-carboxyfenyl)-2,3-cyklohexaniminet i form av den fri syre. The reaction is preferably carried out using N-(o-carboxyphenyl)-2,3-cyclohexanimine in the form of the free acid.
Når den fri syre anvendes som utgangsmateriale, kan N-(2,3-dimethylfenyl)-anthranilsyren overføres til et salt ved behandling med en anorganisk eller organisk base som natriumbicarbonat, ka-liumcarbonat, kalsiumhydroxyd, ammoni-akk, diethylamin eller lignende. Når der anvendes et salt av N-(o-carboxyfenyl) - 2,3-dimethylcyklohexaniminet som utgangsmateriale, er N-(2,3-dimethylfenyl)-antranilsyren tilstede i reaksjonsblandingen i form av et salt. Syren kan isoleres i form av dette salt, men det foretrekkes å isolere den som den fri syre efter behandling med en syre. When the free acid is used as starting material, the N-(2,3-dimethylphenyl)-anthranilic acid can be transferred to a salt by treatment with an inorganic or organic base such as sodium bicarbonate, potassium carbonate, calcium hydroxide, ammonia, diethylamine or the like. When a salt of the N-(o-carboxyphenyl)-2,3-dimethylcyclohexanimine is used as starting material, the N-(2,3-dimethylphenyl)-anthranilic acid is present in the reaction mixture in the form of a salt. The acid can be isolated in the form of this salt, but it is preferred to isolate it as the free acid after treatment with an acid.
N- (o-carboxyfenyl) -2,3-dimethyl-cyklohexaniminet og salter av denne forbindelse som anvendes som utgangsmateriale, behøver ikke å være i ren tilstand. I mange tilfelle foretrekkes det å anvende utgangsmaterialet i uren tilstand for å spare omkostningene ved isolering og rensning, fordi N-(2,3-dimethylfenyl)-anthra-nilsyren lett kan renses ved å oppløses i alkalier og felning påny med en syre, kry-stallisasjon og annen konvensjonell rens-ningsteknikk. The N-(o-carboxyphenyl)-2,3-dimethyl-cyclohexanimine and salts of this compound used as starting material need not be in a pure state. In many cases it is preferred to use the starting material in an impure state to save the costs of isolation and purification, because the N-(2,3-dimethylphenyl)-anthranilic acid can be easily purified by dissolving in alkalis and reprecipitating with an acid, cry -stallisation and other conventional cleaning techniques.
Ifølge en foretrukken utførelsesform for oppfinnelsen fremstiller man det som utgangsmateriale anvendte N- (o-carboxyfenyl) -2,3-dimethylcyklohexanimin ved omsetning av anthranilsyre med 2,3-dimethylcyklohexanon i et inert hydrocarbon som benzen, xylen eller toluen, hvorpå man anvender den herved erholdte oppløsning som inneholder N-(o-carboxyfenyl)-2,3-dimethylcyklohexaniminet, uten isolering eller rensning av denne forbindelse i hy-drogeneringsprosessen, ved simpelt hen å tilsette hydrogeneringskatalysatoren og hydrogenakseptoren til denne oppløsning. According to a preferred embodiment of the invention, the N-(o-carboxyphenyl)-2,3-dimethylcyclohexanimine used as starting material is prepared by reacting anthranilic acid with 2,3-dimethylcyclohexanone in an inert hydrocarbon such as benzene, xylene or toluene, after which it is used thereby obtained solution containing the N-(o-carboxyphenyl)-2,3-dimethylcyclohexanimine, without isolation or purification of this compound in the hydrogenation process, by simply adding the hydrogenation catalyst and the hydrogen acceptor to this solution.
N- (2,3-dimethylf enyl) -anthranilsy-ren og dens i formasøytisk henseende ak-septable salter er av verdi i medisinen til N-(2,3-dimethylphenyl)-anthranilic acid and its pharmaceutically acceptable salts are of value in the medicine of
lindring av smerter og til å nedsette de symptomer som er forbundet med reuma- relief of pain and to reduce the symptoms associated with rheumatism
tiske og arthritiske lidelser samt andre in-flammatoriske tilstander. Disse stoffer er effektive ved oral anvendelse. tic and arthritic disorders as well as other inflammatory conditions. These substances are effective when used orally.
I det følgende beskrives som eksempler noen utførelsesformer for oppfinnelsen. In the following, some embodiments of the invention are described as examples.
Eksempel 1 Example 1
En oppløsning av 10 g anthranilsyre og 9,3 g 2,3-dimethylcyklohexanon i 25 ml toluen oppvarmes under tilbakeløpskjøling i 3 timer, hvorved det vann som frigjøres ved reaksjonen, oppsamles i en oppfang-ningsanordning for vann. Den erholdte oppløsning som inneholder N-(o-carboxyfenyl)-2,3-dimethylcyklohexanimin avkjø-les og tilsettes 100 ml xylen, 2 g palladium-på-kull-hydrogeneringskatalysator med 10 pst. palladium samt 10 ml nitrobenzen. Reaksjonsblandingen oppvarmes så under til-bakeløpskjøling i 72 timer idet det dannede vann oppsamles i en oppfangningsanord-ning for vann. Derpå filtreres blandingen i varm tilstand for å fjerne katalysatoren og avkjøles. Derefter ekstraheres det organiske filtrat med 1 N vandig natriumhy-droxydoppløsning. Det vandige ekstrakt surgjøres med fortynnet saltsyre og N-(2,3-dimethylfenyl)-anthranilsyren som herved skiller seg ut, oppsamles og omkrystalliseres fra ethanol. Forbindelsens smeltepunkt er 229—230° C (brusning). A solution of 10 g of anthranilic acid and 9.3 g of 2,3-dimethylcyclohexanone in 25 ml of toluene is heated under reflux for 3 hours, whereby the water released by the reaction is collected in a water collection device. The resulting solution containing N-(o-carboxyphenyl)-2,3-dimethylcyclohexanimine is cooled and 100 ml of xylene, 2 g of palladium-on-charcoal hydrogenation catalyst with 10% palladium and 10 ml of nitrobenzene are added. The reaction mixture is then heated under reflux for 72 hours while the water formed is collected in a water collection device. The mixture is then filtered while hot to remove the catalyst and cooled. The organic filtrate is then extracted with 1 N aqueous sodium hydroxide solution. The aqueous extract is acidified with dilute hydrochloric acid and the N-(2,3-dimethylphenyl)-anthranilic acid which thereby separates, is collected and recrystallized from ethanol. The compound's melting point is 229-230° C (effervescent).
Eksempel 2 10 g N-(o-carboxyfenyl)-2,3-dimethyl-cyklohexanimin og 10 ml o-nitrotoluen oppløses i 100 ml toluen. Den erholdte opp-løsning tilsettes 2 g platina-på-kull-hydrogeneringskatalysator med 10 pst. platina og blandingen oppvarmes under til-bakeløpskjøling i 48 timer. Derpå fraskil-les katalysatoren ved filtrering og filtratet ekstraheres med et overskudd av 1 N vandig natriumhydroxydoppløsning. Det vandige ekstrakt surgjøres med fortynnet saltsyre og N-(2,3-dimethylfenyl)-anthranil-syren som herved utfelles, oppsamles og omkrystalliseres fra ethanol. Produktets smeltepunkt er 299—230° C (brusning). Example 2 10 g of N-(o-carboxyphenyl)-2,3-dimethyl-cyclohexanimine and 10 ml of o-nitrotoluene are dissolved in 100 ml of toluene. 2 g of platinum-on-charcoal hydrogenation catalyst with 10% platinum is added to the resulting solution and the mixture is heated under reflux for 48 hours. The catalyst is then separated by filtration and the filtrate is extracted with an excess of 1 N aqueous sodium hydroxide solution. The aqueous extract is acidified with dilute hydrochloric acid and the N-(2,3-dimethylphenyl)-anthranilic acid which is thereby precipitated, collected and recrystallized from ethanol. The product's melting point is 299-230° C (effervescent).
Eksempel 3 Example 3
10 g av natriumsaltet av N-(o-carboxyfenyl) -2,3-dimethylcyklohexanimin tilsettes til 125 ml dimethylformamid og den erholdte blanding oppvarmes til 75° C. Den tilsettes så 10 ml nitrobenzen og 2 g palladium-på-kull-hydrogeneringskata- 10 g of the sodium salt of N-(o-carboxyphenyl)-2,3-dimethylcyclohexanimine is added to 125 ml of dimethylformamide and the resulting mixture is heated to 75° C. It is then added to 10 ml of nitrobenzene and 2 g of palladium-on-charcoal hydrogenation catalyst.
lysator med 10 pst. palladium. Den erholdte blanding oppvarmes under tilbake-løpskjøling og omrøring i 48 timer, hvorpå katalysatoren fjernes ved filtrering. Filtratet fortynnes med 300 ml vann, ekstraheres med flere porsjoner ether og ether-ekstraktene kastes vekk. Den vandige opp-løsning surgjøres med fortynnet saltsyre. Den uoppløselige N-(2,3-dimethylfenyl)-anthranilsyre som herved skiller seg ut, oppsamles og renses ved omkrystallisasjon fra ethanol. Produktets smeltepunkt er 229—230° C (brusning). lysator with 10 percent palladium. The resulting mixture is heated under reflux and stirring for 48 hours, after which the catalyst is removed by filtration. The filtrate is diluted with 300 ml of water, extracted with several portions of ether and the ether extracts are discarded. The aqueous solution is acidified with dilute hydrochloric acid. The insoluble N-(2,3-dimethylphenyl)-anthranilic acid that separates out is collected and purified by recrystallization from ethanol. The product's melting point is 229-230° C (effervescent).
N-(o-carboxyfenyl)-2,3-dimethyl-cyklohexaniminet som anvendes som utgangsmateriale i fremgangsmåten ifølge oppfinnelsen, er en ny forbindelse som kan fremstilles ved å oppvarme anthranilsyre med 2,3-dimethylcyklohexanon i et oppløs-ningsmiddel bestående av et hydrocarbon som benzen, toluen eller xylen. Efter at reaksjonen er fullstendig, kan N-(o-carboxyfenyl ) -2,3 -dimethylcyklohexanimi-net isoleres ved å fordampe oppløsnings-midlet i vakuum. The N-(o-carboxyphenyl)-2,3-dimethyl-cyclohexanimine used as starting material in the process according to the invention is a new compound that can be prepared by heating anthranilic acid with 2,3-dimethylcyclohexanone in a solvent consisting of a hydrocarbon such as benzene, toluene or xylene. After the reaction is complete, the N-(o-carboxyphenyl)-2,3-dimethylcyclohexanimine can be isolated by evaporating the solvent in vacuo.
Saltene av N-(o-carboxyfenyl)-2,3-di-methylcyklohexaniminet kan fremstilles ved å oppløse den fri syre i en alkohol som ethanol og tilsette den erholdte oppløsning en ekvivalent mengde av et metallalkoho-lat eller -hydroxyd med påfølgende for-dampning av oppløsningsmidlet i vakuum. The salts of N-(o-carboxyphenyl)-2,3-dimethylcyclohexanimine can be prepared by dissolving the free acid in an alcohol such as ethanol and adding to the resulting solution an equivalent amount of a metal alcohol or hydroxide with subsequent for- evaporation of the solvent in vacuo.
Claims (2)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2529708A DE2529708C2 (en) | 1975-07-03 | 1975-07-03 | Process for the production of sulfuric acid |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO761532L NO761532L (en) | 1977-01-04 |
| NO148487B true NO148487B (en) | 1983-07-11 |
| NO148487C NO148487C (en) | 1983-10-19 |
Family
ID=5950589
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO761532A NO148487C (en) | 1975-07-03 | 1976-05-04 | PROCEDURE FOR SULFUR ACID PREPARATION |
Country Status (16)
| Country | Link |
|---|---|
| JP (1) | JPS5943402B2 (en) |
| AU (1) | AU502664B2 (en) |
| BE (1) | BE843771A (en) |
| BR (1) | BR7604368A (en) |
| DE (1) | DE2529708C2 (en) |
| ES (1) | ES448719A1 (en) |
| FI (1) | FI761917A (en) |
| FR (1) | FR2316186A1 (en) |
| GB (1) | GB1554764A (en) |
| IN (1) | IN146041B (en) |
| IT (1) | IT1063613B (en) |
| NL (1) | NL182468C (en) |
| NO (1) | NO148487C (en) |
| SE (1) | SE417948B (en) |
| YU (1) | YU117776A (en) |
| ZA (1) | ZA763524B (en) |
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| DE2905083A1 (en) * | 1979-02-10 | 1980-08-28 | Metallgesellschaft Ag | METHOD FOR THE PRODUCTION OF SULFURIC ACID |
| CA1146722A (en) * | 1981-04-10 | 1983-05-24 | Gordon M. Cameron | Energy recovery method and system for combined sulphuric and phosphoric acid manufacturing plant |
| DE3232446A1 (en) * | 1982-08-12 | 1984-02-16 | Metallgesellschaft Ag, 6000 Frankfurt | METHOD FOR PRODUCING SULFURIC ACID |
| DE3303287A1 (en) * | 1983-02-01 | 1984-08-02 | Bayer Ag, 5090 Leverkusen | METHOD FOR PRODUCING SULFURIC ACID |
| US4670242A (en) * | 1984-11-09 | 1987-06-02 | Monsanto Company | Heat recovery from concentrated sulfuric acid |
| JP2015054805A (en) * | 2013-09-13 | 2015-03-23 | 住友金属鉱山株式会社 | Method of drying sulfuric acid raw material gas |
| CN110642230A (en) * | 2019-10-31 | 2020-01-03 | 攀钢集团攀枝花钢铁研究院有限公司 | Method for improving concentration of titanium white waste acid |
| CN112875653B (en) * | 2021-02-06 | 2022-06-24 | 易门铜业有限公司 | Acid temperature and acid concentration balancing system and method for high-concentration flue gas acid making |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1567403B2 (en) * | 1965-12-14 | 1972-05-18 | Chemiebau Dr A Zieren GmbH & Co KG, 5000 Köln | PROCESS FOR THE MANUFACTURING OF SULFUR ACID |
| BE788625A (en) * | 1971-09-11 | 1973-01-02 | Metallgesellschaft Ag | PROCESS FOR THE REMOVAL OF SULFURIC ANHYDRIDE AND SULFURIC ACID MIST CONTAINED IN GASES |
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1975
- 1975-07-03 DE DE2529708A patent/DE2529708C2/en not_active Expired
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1976
- 1976-05-03 NL NLAANVRAGE7604675,A patent/NL182468C/en not_active IP Right Cessation
- 1976-05-04 NO NO761532A patent/NO148487C/en unknown
- 1976-05-11 YU YU01177/76A patent/YU117776A/en unknown
- 1976-05-18 IN IN864/CAL/76A patent/IN146041B/en unknown
- 1976-05-25 AU AU14257/76A patent/AU502664B2/en not_active Expired
- 1976-06-10 ES ES448719A patent/ES448719A1/en not_active Expired
- 1976-06-14 ZA ZA763524A patent/ZA763524B/en unknown
- 1976-06-23 FR FR7619142A patent/FR2316186A1/en active Granted
- 1976-06-25 JP JP51075949A patent/JPS5943402B2/en not_active Expired
- 1976-06-25 IT IT24700/76A patent/IT1063613B/en active
- 1976-06-29 GB GB27105/76A patent/GB1554764A/en not_active Expired
- 1976-07-01 FI FI761917A patent/FI761917A/fi not_active Application Discontinuation
- 1976-07-02 SE SE7607632A patent/SE417948B/en unknown
- 1976-07-02 BR BR7604368A patent/BR7604368A/en unknown
- 1976-07-02 BE BE6045581A patent/BE843771A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DE2529708A1 (en) | 1977-01-20 |
| ZA763524B (en) | 1977-05-25 |
| NL7604675A (en) | 1977-01-05 |
| NL182468B (en) | 1987-10-16 |
| JPS5235792A (en) | 1977-03-18 |
| DE2529708C2 (en) | 1982-09-02 |
| SE417948B (en) | 1981-04-27 |
| IT1063613B (en) | 1985-02-11 |
| FR2316186B1 (en) | 1981-05-22 |
| AU1425776A (en) | 1977-12-01 |
| NO761532L (en) | 1977-01-04 |
| AU502664B2 (en) | 1979-08-02 |
| BE843771A (en) | 1977-01-03 |
| NO148487C (en) | 1983-10-19 |
| JPS5943402B2 (en) | 1984-10-22 |
| IN146041B (en) | 1979-02-10 |
| SE7607632L (en) | 1977-01-04 |
| YU117776A (en) | 1982-10-31 |
| GB1554764A (en) | 1979-10-31 |
| BR7604368A (en) | 1977-07-26 |
| FI761917A (en) | 1977-01-04 |
| FR2316186A1 (en) | 1977-01-28 |
| NL182468C (en) | 1988-03-16 |
| ES448719A1 (en) | 1977-07-01 |
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