EP0000343B1 - Process for the preparation of quinoline derivatives - Google Patents
Process for the preparation of quinoline derivatives Download PDFInfo
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- EP0000343B1 EP0000343B1 EP78100240A EP78100240A EP0000343B1 EP 0000343 B1 EP0000343 B1 EP 0000343B1 EP 78100240 A EP78100240 A EP 78100240A EP 78100240 A EP78100240 A EP 78100240A EP 0000343 B1 EP0000343 B1 EP 0000343B1
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- alkyl
- dichloromethyl
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- halogen
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- 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
- C07D215/04—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
-
- 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
- C07D215/20—Oxygen atoms
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- 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
- C07D215/36—Sulfur atoms
-
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/02—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with only hydrogen, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
Definitions
- the invention relates to a new process for the production of quinolines, preferably 3-hydroxyquinolines.
- Suitable alkyl radicals have 1-4 C atoms and can be substituted, for example, by halogen, CN, C 1 -C 4 alkoxy.
- the methyl radical is preferred.
- Suitable aryl radicals are phenyl radicals, which can be substituted by halogen, N0 2 , C 1 -C 4 alkyl or C 1 -C 4 alkoxy.
- Suitable alkylene radicals have at least 3 carbon atoms, such as - (CH 2 ) - 3 and - (CH 2 ) - 4 '
- halogen is understood to mean F, Br and especially CI.
- n is preferably the number 1.
- the procedure is expediently such that the dichloromethyl isocyanate is used in an aqueous medium which can contain an indifferent organic solvent and, if appropriate, an indifferent surfactant, at temperatures of -5 to 50 ° C., preferably 5 to 35 ° C., with vigorous stirring (15-90, preferably 30-45 minutes), treated with alkali, preferably an alkaline earth metal hydroxide, until isocyanate can no longer be detected in a sample (for example by IR spectroscopy), then - preferably after cooling to 0-5 ° C and addition of a defoaming agent by adding a mineral acid to a pH of 4-7, preferably 5-6, and after completion of the CO 2 development, the reaction mixture in a conventional manner under alkaline conditions with an ⁇ - Reacts methylene-active carbonyl compound to the corresponding quinoline (duration 1-6, preferably 2-4 hours). which can be isolated in the usual way after neutralization.
- an indifferent organic solvent preferably 5 to 35 °
- Suitable dichloromethyl isocyanates for carrying out the process according to the invention are those of the formula II where X and n have the meaning given above.
- Suitable organic solvents are chemically indifferent to the isocyanate and have good dissolving power both with respect to the isocyanate and to the carbonyl compound.
- Examples include: benzene, toluene, chlorobenzene or xylene.
- Suitable alkaline earth metal hydroxides are magnesium, calcium, strontium and above all barium hydroxide, which are used in solution or dispersion.
- Hydrochloric acid is particularly suitable as a mineral acid for adjusting the pH value of 4-7.
- Suitable carbonyl compounds correspond to the formula wherein Y 'is Y or halogen (preferably CI and Br), the halogen being converted into OH in the course of the condensation, and Z has the meaning given above.
- Examples include: acetaldehyde, acetone, chloroacetone and bromoacetone, ⁇ -chloroacetophenone, cyclohexanone, phloroglucinol, acetylacetone, barbituric acid, cyanoacetone, acetone sulfonic acid or acetoacetic acid ester.
- reaction with these compounds to form the quinolines can be catalyzed by adding customary alkalis (such as NaOH, KOH, Na 2 CO 3 or Ca (OH) 2 ).
- customary alkalis such as NaOH, KOH, Na 2 CO 3 or Ca (OH) 2 .
- reaction mixture which is necessary to achieve optimal yields, can e.g. with the help of a current breaker and an impeller stirrer.
- the alkaline earth chloride contained in the final mother liquor can be recovered by adding alkali hydroxide in the form of the less soluble alkaline earth hydroxide.
- the compounds of the formula are versatile.
- these compounds can be converted by reaction with isocyanates or phosphoric acid ester chlorides into the corresponding carbamates or phosphoric acid esters, which have insecticidal properties.
- reaction mixture is made alkaline with 4 ml of 50% NaOH, and after removing the external cooling bath, 25 g (0.25 mol) of acetylacetone are added dropwise within 15-30 minutes and 4- Stir for 6 hours at room temperature.
- the product is then filtered off with suction and the filter residue is taken up in methanol and heated to 40 ° C.
- the undissolved barium salt is filtered off with suction and the filtrate is evaporated.
- 33 g (94% of theory) 3-Acetyl-3-hydroxyquininaldine with a melting point of 54-56 ° C.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Gegenstand der Erfindung ist ein neues Verfahren zur Herstellung von Chinolinen, vorzugsweise 3-Hydroxychinolinen.The invention relates to a new process for the production of quinolines, preferably 3-hydroxyquinolines.
Unter den zahlreichen bekannten Chinolinsynthesen ist die Methode von Friedländer, bei welcher aromatische o-Aminocarbonylverbindungen mit methylenaktiven Carbonylverbindungen alkalisch kondensiert werden, wegen ihrer universellen Anwendbarkeit eine der gebräuchlichsten.Among the numerous known quinoline syntheses, Friedländer's method, in which aromatic o-aminocarbonyl compounds are alkaline condensed with methylene-active carbonyl compounds, is one of the most common because of its universal applicability.
Andererseits hat sich dieses Syntheseprinzip wegen der Schwerzugänglichkeit und der geringen Stabilität der dabei benötigten o-Amino-benzaldehyde in der Technik nicht durchsetzen können, sondern ist bisher in der Regel auf den Labormaßstab beschränkt geblieben (vgl. dazu "Heterocyclic Compounds" Bd. 4, S, 46 von R. C. Elderfield).On the other hand, this synthetic principle has not been able to assert itself in technology because of the difficult accessibility and the low stability of the o-amino-benzaldehydes required, but has hitherto generally been limited to the laboratory scale (cf. "Heterocyclic Compounds" Vol. 4, S, 46 from RC Elderfield).
Es wurde nun gefunden, dass man Chinoline in vergleichsweise hohen Ausbeuten und auch im technischen Maßstab unter Anwendung des Friedländer'schen Prinzips - jedenfalls im weitesten Sinne - erhält, wenn man die verhältnismässig beständigen und gut handhabbaren aromatischen ortho-Dichloromethylisocyanate durch Hydrolyse und Decarboxylierung in die entsprechenden ortho-Aminoaldehyde überführt und diese mit a-methylenaktiven Carbonylverbindungen kondensiert.It has now been found that quinolines can be obtained in comparatively high yields and also on an industrial scale using the Friedländer principle - at least in the broadest sense - if the relatively stable and easy-to-use aromatic ortho-dichloromethyl isocyanates are obtained by hydrolysis and decarboxylation in the corresponding ortho-amino aldehydes converted and these condensed with a-methylene-active carbonyl compounds.
Das neue Verfahren eignet sich besonders zur Herstellung von Chinolinen der Formel I
- X für Halogen, Nitro oder CF3,
- Z für Wasserstoff, Alkyl oder Aryl,
- Y für Wasserstoff, OH, CN, COR oder S03H
- R für Alkyl, Alkoxy oder Aryl und
- n für eine ganze Zahl von 0 bis 4 stehen,
wobei die Alkyl-, Alkoxy- und Arylreste gegebenenfalls substituiert sind und Z und Y gemeinsam eine Alkylenkette oder den Rest
- X for halogen, nitro or CF 3 ,
- Z represents hydrogen, alkyl or aryl,
- Y for hydrogen, OH, CN, COR or S0 3 H
- R represents alkyl, alkoxy or aryl and
- n stands for an integer from 0 to 4,
wherein the alkyl, alkoxy and aryl radicals are optionally substituted and Z and Y together represent an alkylene chain or the rest
Geeignete Alkylrest weisen 1-4 C-Atome auf und können z.B. durch Halogen, CN, C1-C4-Alkoxy substituiert sein. Bevorzugt ist der Methylrest. Geeignete Arylreste sind Phenylreste, die durch Halogen, N02, Cl-C4-Alkyl oder Cl-C4-Alkoxy substituiert sein können.Suitable alkyl radicals have 1-4 C atoms and can be substituted, for example, by halogen, CN, C 1 -C 4 alkoxy. The methyl radical is preferred. Suitable aryl radicals are phenyl radicals, which can be substituted by halogen, N0 2 , C 1 -C 4 alkyl or C 1 -C 4 alkoxy.
Geeignete Alkylenreste weisen mindestens 3 C-Atome auf, wie z.B. -(CH2)-3 und -(CH2)-4' Suitable alkylene radicals have at least 3 carbon atoms, such as - (CH 2 ) - 3 and - (CH 2 ) - 4 '
Unter "Halogen" wird im Rahmen dieser Erfindung F, Br und vor allem CI verstanden.In the context of this invention, “halogen” is understood to mean F, Br and especially CI.
Falls X die Nitrogruppe bedeutet, steht n vorzugsweise für die Zahl 1.If X is the nitro group, n is preferably the number 1.
Bevorzugt herzustellende Verbindungen entsprechen der oben genannten Formel I, worin
- X für Chlor,
- Z für C1-C4-Alkyl, vorzugsweise Methyl,
- Y für OH oder -CO-Ci-C4-Alkyl, vorzugsweise Acetyl; COOCH3, COOC2H5'
- n für 0 bis 4, vorzugsweise 0-2, stehen.
- X for chlorine,
- Z is C 1 -C 4 -alkyl, preferably methyl,
- Y represents OH or -CO-C i -C 4 alkyl, preferably acetyl; COOCH 3 , COOC 2 H 5 '
- n stands for 0 to 4, preferably 0-2.
Bei der praktischen Durchführung des erfindungsgemässen Verfahrens geht man zweckmässigerweise so vor, dass man das Dichlormethylisocyanat in einem wäßrigen Medium, welches als Lösungsvermittler ein indifferentes organisches Lösungsmittel und ggf, ein indifferentes Tensid enthalten kann, bei Temperaturen von -5 bis 50°C, vorzugsweise 5 bis 35°C, unter starkem Rühren solange (15-90, vorzugsweise 30-45 Minuten) mit Alkali, vorzugsweise einem Erdalkalihydroxid, behandelt, bis in einer Probe kein Isocyanat mehr nachweisbar ist (z.B. IR-spektroskopisch), anschliessend - vorzugsweise nach Abkühlen auf 0-5°C und Zusatz eines Entschäumungsmittels durch Zugabe einer Mineralsäure einen pH-Wert von 4-7, vorzugsweise 5-6, einstellt und nach Beendigung der CO2- entwicklung das Reaktionsgemisch in an sich bekannter Weise unter alkalischen Bedingungen mit einer α-methylenaktiven Carbonylverbindung zu dem entsprechenden Chinolin umsetzt (Dauer 1-6, vorzuasweise 2-4 Stunden). weiches nach dem Neutralstellen in üblicher Weise isoliert wprden kann.In the practical implementation of the process according to the invention, the procedure is expediently such that the dichloromethyl isocyanate is used in an aqueous medium which can contain an indifferent organic solvent and, if appropriate, an indifferent surfactant, at temperatures of -5 to 50 ° C., preferably 5 to 35 ° C., with vigorous stirring (15-90, preferably 30-45 minutes), treated with alkali, preferably an alkaline earth metal hydroxide, until isocyanate can no longer be detected in a sample (for example by IR spectroscopy), then - preferably after cooling to 0-5 ° C and addition of a defoaming agent by adding a mineral acid to a pH of 4-7, preferably 5-6, and after completion of the CO 2 development, the reaction mixture in a conventional manner under alkaline conditions with an α - Reacts methylene-active carbonyl compound to the corresponding quinoline (duration 1-6, preferably 2-4 hours). which can be isolated in the usual way after neutralization.
Geeignete Dichlormethylisocyanate zur Durchführung des erfindungsgemässen Verfahrens sind solche der Formel II
Beispielhaft seien genannt:
- 2-Dichlormethyl-phenylisocyanat
- 3-Chlor-2-dichlormethyl-phenylisocyanat
- 4-Chlor-2-dichlormethyl-phenylisocyanat
- 4-Brom-2-dichlormethyl-phenylisocyanat
- 5-Chlor-2-dichlormethyl-ßhenylisocyanat
- 6-Chlor-2-dichlormethyl-phenylisocyanat
- 4,6-Dichlor-2-dichlormethyl-phenylisocyanat
- 3,4,6-Trichlor-2-dichlormethyl-phenylisocyanat
- Tetrachlor-2-dichlormethyl-phenylisocyanat
- 5-Fluor-2-dichlormethyl-phenylisocyanat
- 3,4-Dichlor-2-dichlormethyl-phenylisocyanat
- 5-Trifluormethyl-2-dichlormethyl-phenylisocyanat
- 4-Nitro-2-dichlormethyl-phenylisocyanat.
- 2-dichloromethyl phenyl isocyanate
- 3-chloro-2-dichloromethyl phenyl isocyanate
- 4-chloro-2-dichloromethyl phenyl isocyanate
- 4-bromo-2-dichloromethyl phenyl isocyanate
- 5-chloro-2-dichloromethyl-phenyl isocyanate
- 6-chloro-2-dichloromethyl phenyl isocyanate
- 4,6-dichloro-2-dichloromethyl phenyl isocyanate
- 3,4,6-trichloro-2-dichloromethyl phenyl isocyanate
- Tetrachloro-2-dichloromethyl phenyl isocyanate
- 5-fluoro-2-dichloromethyl phenyl isocyanate
- 3,4-dichloro-2-dichloromethyl phenyl isocyanate
- 5-trifluoromethyl-2-dichloromethyl-phenyl isocyanate
- 4-nitro-2-dichloromethyl phenyl isocyanate.
Geeignete organische Lösungsmittel sind gegenüber dem Isocyanat chemisch indifferent und besitzen sowohl gegenüber dem Isocyanat als auch gegenüber der Carbonylverbindung ein gutes Lösungsvermögen.Suitable organic solvents are chemically indifferent to the isocyanate and have good dissolving power both with respect to the isocyanate and to the carbonyl compound.
Beispielhaft seien genannt: Benzol, Toluol, Chlorbenzol oder Xylol.Examples include: benzene, toluene, chlorobenzene or xylene.
Geeignete Erdalkalihydroxide sind Magnesium-, Calcium, Strontium- und vor allem Bariumhydroxid, die in Lösung bzw. Dispersion eingesetzt werden.Suitable alkaline earth metal hydroxides are magnesium, calcium, strontium and above all barium hydroxide, which are used in solution or dispersion.
Als Mineralsäure zur Einstellung des pH-Wertes von 4-7 kommt vor allem Salzsäure in Betracht.Hydrochloric acid is particularly suitable as a mineral acid for adjusting the pH value of 4-7.
Geeignete Carbonylverbindungen entsprechen der Formel
Beispielhaft seien genannt: Acetaldehyd, Aceton, Chlor- und Bromaceton, ω-Chloracetophenon, Cyclohexanon, Phloroglucin, Acetylaceton, Barbitursäure, Cyanaceton, Acetonsulfonsäure oder Acetessigester..Examples include: acetaldehyde, acetone, chloroacetone and bromoacetone, ω-chloroacetophenone, cyclohexanone, phloroglucinol, acetylacetone, barbituric acid, cyanoacetone, acetone sulfonic acid or acetoacetic acid ester.
Die Umsetzung mit diesen Verbindungen zu den Chinolinen kann durch Zusatz üblicher Alkalien (wie NaOH, KOH, Na2C03 oder Ca(OH)2 katalysiert werden.The reaction with these compounds to form the quinolines can be catalyzed by adding customary alkalis (such as NaOH, KOH, Na 2 CO 3 or Ca (OH) 2 ).
Die starke Durchmischung des Reaktionsgemisches, welche zur Erzielung optimaler Ausbeuten erforderlich ist, kann z.B. mit Hilfe eines Strombrechers und eines Impeller-Rührers erfolgen.The thorough mixing of the reaction mixture, which is necessary to achieve optimal yields, can e.g. with the help of a current breaker and an impeller stirrer.
Vor der Neutralstellung des Reaktionsgemisches am Ende der Umsetzung empfiehlt es sich, ungelöstes Erdalkalihydroxid abzufiltrieren.Before neutralizing the reaction mixture at the end of the reaction, it is advisable to filter off undissolved alkaline earth metal hydroxide.
Das in der Endmutterlauge enthaltene Erdalkalichlorid (falls mit HCI neutralgestellt) kann durch Zusatz von Alkalihydroxid in Form des schwerer löslichen Erdalkalihydroxids wiedergewonnen werden.The alkaline earth chloride contained in the final mother liquor (if neutralized with HCI) can be recovered by adding alkali hydroxide in the form of the less soluble alkaline earth hydroxide.
Die Verbindungen der Formel sind vielseitig anwendbar.The compounds of the formula are versatile.
Beispielsweise sind Verbindungen der angegebenen Formel, worin Z für Methyl steht, Ausgangsmaterialien zum Aufbau von wertvollen Chinophthalonfarbstoffen.For example, compounds of the formula given, in which Z represents methyl, are starting materials for building up valuable quinophthalone dyes.
Verbindungen der Formel I mit Y=OH eignen sich als Kupplungskomponenten zur Herstellung von Azofarbstoffen.Compounds of formula I with Y = OH are suitable as coupling components for the production of azo dyes.
Darüber hinaus können diese Verbindungen durch Umsetzung mit Isocyanaten oder Phosphorsäureesterchloriden in die entsprechenden Carbamate bzw. Phosphorsäureester umgewandelt werden, welche insektizide Eigenschaften besitzen.In addition, these compounds can be converted by reaction with isocyanates or phosphoric acid ester chlorides into the corresponding carbamates or phosphoric acid esters, which have insecticidal properties.
Verbindungen der Formel I mit Y=Acetyl sind z.T. wertvolle Analgetika.Compounds of formula I with Y = acetyl are partly valuable analgesics.
Zu einer Aufchlämmung von Bariumhydroxid [hergestellt durch Zusatz von 80 g (1 Mol) 50%iger NaOH zu einer Lösung von 125 g (0,53 Mol) Bariumchlorid] in 650 ml Wasser läßt man bei 15-18°C unter kräftigem Rühren (mit Hilfe eines Strombrechers und eines Impellerrührers) 48 g (0,24 Mol) 2-Dichlormethylphenylisocyanat zulaufen. Man rührt 30-40 Minuten bei dieser Temperatur nach und tropft bei 3-5°C ca. 100 ml 10%ige Salzsäure bis pH 5-6 in das Reaktionsgemisch, wobei C02 entwickelt wird. Um ein Uberschäumen zu vermeiden, empfiehlt es sich gelegentlich ein paar Tropfen eines handelsüblichen Silikonentschäumers zuzusetzen. Nach Abklingen der CO2-Entwicklung wird das Reaktionsgemisch mit ca. 120 ml 30%iger, NaOH alkalisch gestellt, wobei die Temperatur auf 8―10°C ansteigt. Nach Entfernung des äußeren Kühlbades fügt man dann 24,4 g (0,264 Mol) Chloraceton hinzu und läßt 2-4 Stunden bei Raumtemperatur nachrühren. Anschließend wird abgesaugt, der Filterrückstand mit wenig verdünnter NaOH gewaschen und das Filtrat mit ca. 130 ml 20%iger HCI auf pH 7 eingestellt. Das dabei ausfallende 3-Hydroxychinaldin wird abgesaugt, mit Wasser gewaschen und bei 70-90°C getrocknet. Ausbeute: 34,2 g (90%). Der Schmelzpunkt liegt bei 259=63°C.To a slurry of barium hydroxide [prepared by adding 80 g (1 mol) of 50% NaOH to a solution of 125 g (0.53 mol) barium chloride] in 650 ml of water is allowed to stir at 15-18 ° C with vigorous stirring ( with the help of a flow breaker and an impeller stirrer) 48 g (0.24 mol) of 2-dichloromethylphenyl isocyanate. The mixture is stirred for 30-40 minutes at this temperature and about 100 ml of 10% hydrochloric acid to pH 5-6 are added dropwise at 3-5 ° C., with CO 2 being removed is wrapped. In order to avoid over-foaming, it is advisable to occasionally add a few drops of a commercially available silicone defoamer. After the CO 2 evolution has subsided, the reaction mixture is made alkaline with about 120 ml of 30% NaOH, the temperature rising to 8-10 ° C. After removing the outer cooling bath, 24.4 g (0.264 mol) of chloroacetone are then added and the mixture is stirred for 2-4 hours at room temperature. It is then suctioned off, the filter residue is washed with a little dilute NaOH and the filtrate is adjusted to pH 7 with about 130 ml of 20% HCl. The resulting 3-hydroxyquinoline is suction filtered, washed with water and dried at 70-90 ° C. Yield: 34.2 g (90%). The melting point is 259 = 63 ° C.
Verfährt man wie vorstehend angegeben, arbeitet jedoch unter den in nachstehender Tabelle aufgeführten Bedingungen, so erhält man ebenfalls entsprechende Chinolinderivate in etwa gleich guten Ausbeuten:
Verfährt man wie in Beispiel 1, setzt jedoch die nachstehend aufgeführten Ausgangsmaterialien ein, so erhält man folgende Chinolinderivate.
60 g (0,19 Mol) Ba(OH)2 x 8H2O und 14,3 g (0,042 Mol) Tetrachlor-2-dichlormethyl-phenylisocyanat werden gut vermischt und in 450 ml Wasser unter Zusatz von 1 ml Toluol eingetragen. Man läßt bei 20-25°C unter kräftigem Rühren (mit Hilfe eines Strombrechers und eines lmpellerrührers) 6-8 Stunden rühren, anschließend wird unter Zugabe von 89 ml 10%iger Salzsäure bei 0-5°C ein pH-Wert von 2-3 eingestellt. Nach Beendigung der CO2-Entwicklung werden 30 ml konz. NaOH zugetropft, wobei die Temperatur auf 12°C steigt. Innerhalb von 15 Minuten läßt man dann 6.5 g (0,07 Mol) Chloraceton zutropfen, wobei die Temperatur langsam auf 50°C erhöht wird. Nach 3stündigem Rühren bei 50°C wird die Reaktionsmischung bei 20-25°C mit 75 ml 20%iger Salzsäure auf pH 2 gestellt, der Rückstand abgesaugt, gewaschen und getrocknet. Umkristallisation aus o-Dichlorbenzol führt zum 5,6,7,8-Tetrachlor-3-hydroxychinaldin mit einem Zersetzungspunkt bei 270°C. Die Ausbeute liegt mit 10,5 g bei 85% d.Th.60 g (0.19 mol) of Ba (OH) 2 x 8H 2 O and 14.3 g (0.042 mol) of tetrachloro-2-dichloromethylphenyl isocyanate are mixed well and introduced into 450 ml of water with the addition of 1 ml of toluene. The mixture is stirred at 20-25 ° C. with vigorous stirring (using a flow breaker and an impeller stirrer) for 6-8 hours, then a pH of 2- is added at 0-5 ° C. with the addition of 89 ml of 10% hydrochloric acid. 3 set. After completion of the CO 2 development, 30 ml of conc. NaOH added dropwise, the temperature rising to 12 ° C. 6.5 g (0.07 mol) of chloroacetone are then added dropwise in the course of 15 minutes, the temperature being slowly increased to 50.degree. After stirring for 3 hours at 50 ° C., the reaction mixture is adjusted to pH 2 with 75 ml of 20% hydrochloric acid at 20-25 ° C., the residue is filtered off with suction, washed and dried. Recrystallization from o-dichlorobenzene leads to 5,6,7,8-tetrachloro-3-hydroxyquininaldine with a decomposition point at 270 ° C. The yield of 10.5 g is 85% of theory
Zu einer Aufschlämmung von 135 g (0,43 Möl) Ba(OH)2 x 8H20 in 500 ml Wasser läßt man bei 15-18°C unter kräftigem Rühren (mit Hilfe eines Strombrechers und eines Impellerrührers (38,4 g (0,19 Mol) 2-Dichlormethyl-phenylisocyanat zulaufen. Man rührt 30-40 Minuten bei dieser Temperatur nach und tropft bei 3-5°C ca. 95 ml 10%ige Salzsäure bis pH-5-6 in das Reaktionsgemisch, wobei C02 entsteht. Nach Abklingen der CO2-Entwicklung wird das Reaktionsgemisch mit 4 ml 50%iger NaOH alkalisch gestellt. Nach Entfernung des äußeren Kühlbades läßt man dann innerhalb von 15-30 Minuten 25 g (0,25 Mol) Acetylaceton zutropfen und 4-6 Stunden bei Raumtemperatur nachrühren. Anschließend wird abgesaugt und der Filterrückstand in Methanol aufgenommen und auf 40°C erwärmt. Nach dem Abkühlen wird vom ungelösten Bariumsalz abgesaugt und das Filtrat eingedampft. Nach dem Trocknen im Exisikkator werden 33 g (94% d.Th.) 3-Acetyl-3-hydroxychinaldin vom Schmelzpunkt 54-56°C erhalten.To a slurry of 135 g (0.43 Möl) Ba (OH) 2 x 8H 2 0 in 500 ml of water is allowed to stir at 15-18 ° C with vigorous stirring (using a flow breaker and an impeller stirrer (38.4 g ( 0.19 mol) of 2-dichloromethyl-phenyl isocyanate, stirring is continued for 30-40 minutes at this temperature and about 95 ml of 10% hydrochloric acid to pH 5-6 are added dropwise to the reaction mixture at 3-5 ° C., C0 2. After the CO 2 evolution has subsided, the reaction mixture is made alkaline with 4 ml of 50% NaOH, and after removing the external cooling bath, 25 g (0.25 mol) of acetylacetone are added dropwise within 15-30 minutes and 4- Stir for 6 hours at room temperature. The product is then filtered off with suction and the filter residue is taken up in methanol and heated to 40 ° C. After cooling, the undissolved barium salt is filtered off with suction and the filtrate is evaporated. After drying in the desiccator, 33 g (94% of theory) ) 3-Acetyl-3-hydroxyquininaldine with a melting point of 54-56 ° C.
Verfährt man wie in Beispiel 18, setzt, jedoch die nachstehend aufgeführten Ausgangsmaterialien ein, so erhält man folgende Chinolinderivate:
Claims (5)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19772730061 DE2730061A1 (en) | 1977-07-02 | 1977-07-02 | PROCESS FOR THE PRODUCTION OF QUINOLINE DERIVATIVES |
| DE2730061 | 1977-07-02 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| EP0000343A2 EP0000343A2 (en) | 1979-01-24 |
| EP0000343A3 EP0000343A3 (en) | 1979-04-04 |
| EP0000343B1 true EP0000343B1 (en) | 1981-09-02 |
Family
ID=6013071
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP78100240A Expired EP0000343B1 (en) | 1977-07-02 | 1978-06-26 | Process for the preparation of quinoline derivatives |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US4220779A (en) |
| EP (1) | EP0000343B1 (en) |
| JP (1) | JPS5414977A (en) |
| DE (2) | DE2730061A1 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2509728A1 (en) * | 1981-07-17 | 1983-01-21 | Roussel Uclaf | NOVEL QUINOLINE DERIVATIVES, THEIR SALTS, PREPARATION METHOD, MEDICAMENT APPLICATION AND COMPOSITIONS COMPRISING THE SAME |
| US4472407A (en) * | 1983-03-17 | 1984-09-18 | Riker Laboratories, Inc. | Antimicrobial 8-alkoxy-6,7-dihydro-5-methyl-9-fluoro-1-oxo-1H,5H-benzo[ij]qu |
| DE3412292A1 (en) * | 1984-04-03 | 1985-10-03 | Basf Ag, 6700 Ludwigshafen | Process for the preparation of quinolines |
| DE3620856A1 (en) * | 1986-06-21 | 1987-12-23 | Basf Ag | 3-CYANCHINOLINE DERIVATIVES |
| JPS6399305A (en) * | 1986-10-09 | 1988-04-30 | 鶴巻 成男 | Punch parmanent hair style creation method in wig |
| CN104170824B (en) | 2010-01-04 | 2017-06-30 | 日本曹达株式会社 | Nitrogen-containing heterocycle compound and agricultural or horticultural use bactericide |
| AR086411A1 (en) | 2011-05-20 | 2013-12-11 | Nippon Soda Co | HETEROCICLIC COMPOUND CONTAINING NITROGEN AND FUNGICIDE FOR USE IN AGRICULTURE AND GARDENING |
| JP5946540B2 (en) * | 2012-10-22 | 2016-07-06 | 日本曹達株式会社 | Novel synthesis of 3-hydroxyquinoline derivatives |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3907808A (en) * | 1971-05-17 | 1975-09-23 | Sterling Drug Inc | 1,4-Dihydro-4-oxo-7-pyridyl-3-quinolinecarboxylic acid derivatives |
| US4139533A (en) * | 1976-08-19 | 1979-02-13 | Bristol-Myers Company | Bicyclo[2,2,1]heptane-2,3-diendo carboxylic acid imide esters of quinoline carboxylic acid |
-
1977
- 1977-07-02 DE DE19772730061 patent/DE2730061A1/en not_active Withdrawn
-
1978
- 1978-06-26 EP EP78100240A patent/EP0000343B1/en not_active Expired
- 1978-06-26 DE DE7878100240T patent/DE2860996D1/en not_active Expired
- 1978-06-30 US US05/920,778 patent/US4220779A/en not_active Expired - Lifetime
- 1978-06-30 JP JP7881478A patent/JPS5414977A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP0000343A2 (en) | 1979-01-24 |
| EP0000343A3 (en) | 1979-04-04 |
| DE2860996D1 (en) | 1981-11-26 |
| JPS5414977A (en) | 1979-02-03 |
| DE2730061A1 (en) | 1979-01-18 |
| US4220779A (en) | 1980-09-02 |
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