DE676114C - Process for the introduction of organic residues into the side chains of pyridine or quinoline homologues - Google Patents

Process for the introduction of organic residues into the side chains of pyridine or quinoline homologues

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DE676114C
DE676114C DESCH108920D DESC108920D DE676114C DE 676114 C DE676114 C DE 676114C DE SCH108920 D DESCH108920 D DE SCH108920D DE SC108920 D DESC108920 D DE SC108920D DE 676114 C DE676114 C DE 676114C
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pyridine
quinoline
methylpyridine
homologues
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Alexei Tschitschibabin
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Bayer Pharma AG
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Schering AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/26—Radicals substituted by halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
    • C07D213/46—Oxygen atoms
    • C07D213/51—Acetal radicals
    • 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
    • C07D215/12—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 substituted hydrocarbon radicals attached to ring carbon atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Description

Verfahren zur Einführung von organischen Resten in die Seitenketten von Pyridin-bzw. Chinolinhomologen Es wurde gefunden, daß die Metallverbindungen von in 2- ioder q.-Stellung substituierten Pyridin- oder Chiinolinhom@ologen, die sich bei Einwirkung von Alkaliamiden bilden, sich mit organischen Halogenverbindungen, Schwefelsäure,estern, Sulfosäurcestern und anderen,. analog reagierenden Verbindungen umsetzen, wobei die Metallatome durch @organische Reste hersetzt werden. Zu diesem Zwecke kann man sowohl von den fertigen Mietallverbindung@ein .als auch von den Gemischen der Pyridin- oder Chinnolinbasen mit Alkaliamidein ausgehen. Das letztere Verfahre,n hat außer dem Vorteil der Einfachheit auch ;noch den Vorzug, daß ,nach ihm mit besonders guter Ausbeute die sonst schwer zugänglichen, durch organische Reste in 2-oder q.-Stellung substituierten Chiniolinverbindung,en erhalten werden können.Process for the introduction of organic residues into the side chains of pyridine or. Quinoline homologues It was found that the metal compounds of pyridine or quinoline homologues substituted in the 2- i or q-position, the form when exposed to alkali amides, form with organic halogen compounds, Sulfuric acid, esters, sulfonic acid esters and others. analogously reacting compounds convert, whereby the metal atoms are replaced by organic radicals. To this Purposes can be derived from the finished rental connection @ a. As well as from the Starting out mixtures of pyridine or chinnoline bases with alkali amidein. The latter Proceed, n has, besides the advantage of simplicity, also the advantage that, after with particularly good yield the otherwise difficult to access, organic ones Quinioline compounds substituted in the 2- or q-position are obtained can.

Die besten Ergebnisse werden bei Einhaltung von Bedingungen, bei denen die Bildung von quaternärein Pyridiniumsalzen zurückgedrängt ist, erzielt. Aus diesem Grunde @ergeben Chloride in vielen Fällen bessere Ausbeutein als Bromide und besonders als jodide, so daß man sich vorzugsweise dieser ersteren Verbindungen bedient.The best results are obtained when conditions are met where the formation of quaternary pyridinium salts is suppressed. For this Basically, chlorides give better yields than bromides and especially in many cases than iodide, so that these former compounds are preferably used.

In den Fällen, in denen das erste KohlenstotF-atom der Seitenkette zwei oder drei Wasserstoffatome enthält, besteht auch die Möglichkeit der Bildung höher substituierter Pyridin-bzw. Chiinolinbasien neben monosubstituierten Abkömmlingen, wie aus folgenden Gleichungen hervorgeht G, II;# N - C H.= Na + C,; H;, - C H., Cl --. Na Cl -f- C; H4 N - C H.= C" H (r) Die Verfahrensprodukte sollen zur Herstellung von 'Arzneimitteln sowie, da viele von ihnen einen sehr starken Blumengeruch besitzein, als Riechstoffe dienen. Beispiel i 2o Teile Natriumamid werden mit 2oTeilen 2-Methylpyridin übergossen und zu einem feinen Pulver zerrieben, wobei für Abwesenheit vorn Feuchtigkeit zu sorgen ist. Dann werden 2o Teile Benzylchlorid unter kräftigem Rühren in kleinen Anteilen im Laufevon 2 Taben zugesetzt. Das Gemisch Wir,c.-. noch i Tab stehengelassen. Während eTi.S Umsetzung entwickelt sich Ammoniak. N2.clt:@, beendeter Umsetzung wird das Gemisch mit Eiswasser zerlegt und mit Salzsäure angesäuert.In cases in which the first carbon atom of the side chain contains two or three hydrogen atoms, there is also the possibility of forming more highly substituted pyridine or pyridine atoms. Quinoline bases in addition to monosubstituted descendants, as can be seen from the following equations G, II; # N - C H. = Na + C ,; H ;, - C H., Cl -. Na Cl -f- C; H4 N - C H. = C "H (r) The products of the process are intended to be used for the production of pharmaceuticals and, since many of them have a very strong odor of flowers, as odoriferous substances. EXAMPLE I 20 parts of sodium amide are poured over 20 parts of 2-methylpyridine and ground to a fine powder, care being taken to ensure the absence of moisture. Then 20 parts of benzyl chloride are added in small portions over the course of 2 taps with vigorous stirring. The mixture we, c.-. still i tab left. Ammonia develops during eTi.S implementation. N2.clt: @, when the reaction is complete, the mixture is broken down with ice water and acidified with hydrochloric acid.

Nach dem Abtrennen des Neutralanteils, der hauptsächlich aus Stilben besteht, wird die saure Lösung mit Natriumcarbonat zersetzt.After removing the neutral part, which mainly consists of stilbene the acidic solution is decomposed with sodium carbonate.

Nach dem Lösen der basischen Anteile in Äther .oder Benzol und Trocknen der Lösung wird das Lösungsmittel abdestilliert und der Rückstand unter vermindertem Druck destilliert. Dabei werden außer dem unveränderten Methylpyridin 12,5 Teile 2-Phenyläthylpyridin als ein bei 155' unter i 7 mm Druck siedendes Öl (Schmelzpunkt des Pikrats 127°) und 5 Teile einer # höhersiedenden Fraktion .erhalten, welche durch Kristallisation des Pikrats aus Alkohol (Prismen vom Schmelzpunkt i36°) gereinigt werden kann.After dissolving the basic components in ether. Or benzene and drying the solution is distilled off the solvent and the residue under reduced Distilled pressure. In addition to the unchanged methylpyridine, 12.5 parts are added 2-Phenylethylpyridine as an oil boiling at 155 'under 7 mm pressure (melting point of the Picrat 127 °) and 5 parts of a higher boiling fraction Purified by crystallization of the picrate from alcohol (prisms with a melting point of i36 °) can be.

Beispiel 2 30 Teile 2, 6-Dixriethylpyridin und 2o Teile Natriumamid werden, wie in Beispiel i beschrieben, zerrieben. Dann gießt man 25,5 Teile Benzylchlorid auf einmal hinzu und läßt die Mischung unter Kühlung mit Wasser 5 Tage stehen. Die Aufarbeitung erfolgt wie im Beispiel i ; bei der Destillation unter vermindertem Druck werden außer dem -unveränderten 2, 6-Dimethylpyridin 12,1 Teile des bei i 6o bis 162° (16 mm Druck) siedenden 2-Methyl-6-phenyläthylpyridins, das mit Pikrinsäure Nadeln-oder Prismen vom Schmelzpunkt 125' ergibt, und 5,25 Teile einer höhersiedenden öligen Fraktion, die die Zusammensetzung des Dibenzyldimethylpyridins bat und wahrscheinlich ein Isomerengemisch darstellt, erhalten.Example 2 30 parts of 2,6-dixriethylpyridine and 20 parts of sodium amide are triturated as described in Example i. 25.5 parts of benzyl chloride are then poured in all at once and the mixture is left to stand for 5 days while cooling with water. Working up is carried out as in Example i; in the distillation under reduced pressure, in addition to the unchanged 2,6-dimethylpyridine, 12.1 parts of 2-methyl-6-phenylethylpyridine boiling at 160 ° to 162 ° (16 mm pressure), which with picric acid needles or prisms with a melting point 125 'results, and 5.25 parts of a higher-boiling oily fraction, which has the composition of the dibenzyldimethylpyridine and is probably a mixture of isomers, obtained.

Beispiel 3 3o Teile 4-Methylpyridin und 2o Teile gepulvertes Natriumamid werden, wie im Beispiel i beschrieben, zerrieben. Zum Gemisch werden i o Teile Äther und darauf eine Lösung von 16,5 Teilen Äthylbromid in Äther tropfenweise unter Kühlung und Rühren zugesetzt. Das Umstetzungsgut wird mit Eis zerlegt und mit Äther versetzt. Nach dem Trocknen der -ätherischen Lösung und Abdestillieren des Äthers wird der Rückstand destilliert. Es werden so 12,5 Teile 4-Propylpyridin vom Siedepunkt 184 bis i86" @erhalten. Beispiel 4 Zu 15 g 4-Methylpyridin werden tuiter Rühren 3,99 fein gepulvertes Natriumamid zugesetzt. Die eintretende Reaktion verläuft unter Selbsterwärmung und Ammoniakent-Wicklung. Nach seinem 1/2stündigen Rühren wird - das überschüssige Methylpyridin im Vakuum bei i2mm Druck abdestilliert und ;dez Rückstand unter gleichem Druck zu-'@ähst bei 6o° und dann bei i i o° getrocknet. ', '@@Das so erhaltene trockne Methylpyridiziüätrium wird mit trocknem Äther angefeuchtet und mit tropfenweise hinzugegebenen io,9g Athylbromid umgesetzt. Nachdem alles Äthylbromid zugegeben, wird das Umsetzungsprodukt wie im Beispiel 3 weiterverarbeitet. Es resultiert ein Gemisch von 4-Propylpyridili und Diäthyl-4-methylpyridin.Example 3 3o parts of 4-methylpyridine and 2o parts of powdered sodium amide are triturated as described in Example i. 10 parts of ether and then a solution of 16.5 parts of ethyl bromide in ether are added dropwise to the mixture with cooling and stirring. The reaction material is broken down with ice and ether is added. After the ethereal solution has dried and the ether has been distilled off, the residue is distilled. This gives 12.5 parts of 4-propylpyridine with a boiling point of 184 to 186 "@. EXAMPLE 4 3.99 finely powdered sodium amide is added to 15 g of 4-methylpyridine while stirring. The reaction that occurs takes place with self-heating and evolution of ammonia its 1/2 hour stirring - the excess methylpyridine is distilled off in vacuo at 12mm pressure and; the residue under the same pressure to - '@ at 6o ° and then dried at 100 °.', '@@ The dry methylpyridylation thus obtained is with moistened with dry ether and reacted with dropwise added 10.9 g of ethyl bromide.After all the ethyl bromide has been added, the reaction product is processed as in Example 3. A mixture of 4-propylpyridyl and diethyl-4-methylpyridine results.

Beispiel 5 Zu i 2, S Teilen Methylpyridin und i 2 Teilen Natriumamid wurden 13 Teile Äthylbromid tropfenweise unter Kühlung zugesetzt. Nach i Stunde werden noch weitere io Teile Natriumamid und in kleinen Anteilen 14 Teile Äthylbromid zugegeben. Dann läßt man däs Gemisch i Tag stehen. Es -werden 44 Teile des 4-Propylpyridins und 12 Teile des 4-(Diäthylmethyl)-pyridins, einer veilchenähnlich riechenden Flüssigkeit, de bei 26o bis 2o2° siedet, erhalten. Das Pih°rat schmilzt bei io5°. Beispiel 6 Auf .ähnliche Weise wie in Beispie13 werden aus 30 Teilen 4-Methylpyridin, 2o Teilen Natriumamid und i 9 Teilen Benzylchlorid 16,5 Teile 4-Plenyläthylpyridin vom Schmelzpunkt 65" und 5,7 Teile 4-Dibenzylmethylpyridin erhalten. Beispiel 7 Aus 30 Teilen .4-Methyl-3-.äthylpyridin, 2o Teilen Natriumamid und 9 Teilen Allylchlorid werden. unter Bedingungen, die im wesentlichen mit denen des Beispiels i übereinstimmen, außer nicht umgesetztem 4-Methyl-3-.ätliylpyridin und ziemlich viel höhersiedenden Basen io Teile des bei iio° (2omm) siedenden 4-BItenyl-3-äthylpyridins erhalten. - Beispiel 8 Aus 3o Teilern 4-Methylpyridin, 2o Teilen Natriumamid und 15 Teilen Chloracetäl wird 4-Pyridylpropionaldehydacetalerhalten, das eine bei i 5o bis 16o' (16 mm) siedende Flüs= sigkeit darstellt. EXAMPLE 5 13 parts of ethyl bromide were added dropwise with cooling to 1/2.5 parts of methylpyridine and 1/2 parts of sodium amide. After 1 hour, a further 10 parts of sodium amide and, in small portions, 14 parts of ethyl bromide are added. The mixture is then left to stand for a day. 44 parts of 4-propylpyridine and 12 parts of 4- (diethylmethyl) -pyridine, a violet-like smelling liquid that boils at 26o to 2o2 °, are obtained. The Pih ° rat melts at io5 °. Example 6 In .ähnliche manner as in Beispie13 obtained from 30 parts of 4-methylpyridine, 2o parts of sodium amide and 9 parts of benzyl chloride i 16.5 parts of 4-Plenyläthylpyridin of melting point 65 "and 5.7 parts of 4-Dibenzylmethylpyridin. Example 7 From 30 Parts of 4-methyl-3-ethylpyridine, 20 parts of sodium amide and 9 parts of allyl chloride are obtained under conditions which are essentially the same as those of Example i, except for unreacted 4-methyl-3-ethylpyridine and a good deal of higher-boiling bases Parts of 4-btenyl-3-ethylpyridine boiling at 100 ° (2omm) are obtained.- Example 8 From 3o parts of 4-methylpyridine, 20 parts of sodium amide and 15 parts of chloroacetal, 4-pyridylpropionaldehyde acetal is obtained, the one at 15o to 16o '(16 mm) represents a boiling liquid.

Beispiel 9 30 Teile 4-Methylpyridin, 25 Teile Kaliumamid und 15 Teile Äthylbromid liefern in gleicher Weise, wie in Beispiel4 beschrieben, 13 Teile 4-Propylpyridin. Beispiel 10 Auf ähnliche Weise wie im Beispie13 wird aus i i Teilen 4-Methylpyridin, 8 Teilen Natriumamid und io Teilen Isopropylchlorid in guter Ausbeute 4-Isobutylpyridin vom Kp. 195' erhalten; F. des Pikrats r22°.Example 9 30 parts of 4-methylpyridine, 25 parts of potassium amide and 15 parts of ethyl bromide give 13 parts of 4-propylpyridine in the same manner as described in Example 4. Example 10 In a manner similar to that in Example 13, 4-isobutylpyridine with a boiling point of 195 'is obtained in good yield from two parts of 4-methylpyridine, 8 parts of sodium amide and 10 parts of isopropyl chloride; F. of the picrat r22 °.

Beispiel il . Aus i o Teilen 4-Methylpyridin, 8 Teilen Natriumamid und 9 Teilen Isabutylchl:orid werden 6,5 Teile des bei 225 bis 227° siedenden 4-Isoamylpyridins (F. des Pikrats 112 bis 113°) und 3,8 Teile des Diisobutyl-4-methylpyridins vom Kp. 261° (F. des Pikrats 88°) erhalten.Example il. From 10 parts of 4-methylpyridine, 8 parts of sodium amide and 9 parts of isabutyl chloride are 6.5 parts of 4-isoamylpyridine, which boils at 225 to 227 ° (F. of the picrate 112 to 113 °) and 3.8 parts of diisobutyl-4-methylpyridine from Bp. 261 ° (F. of the Picrat 88 °) preserved.

Beispiel 12 Aus i o Teilen 4-Methylpyridin, 8 Teilen Natriumamid und 8 Teilen p-Toluolsulfonsäureisobutylester werden die gleichen Verbindungen erhalten wie im Beispiel io.Example 12 From 10 parts of 4-methylpyridine, 8 parts of sodium amide and 8 parts of isobutyl p-toluenesulfonate give the same compounds as in the example io.

Beispiel 13 Aus i o Teilen 4-Methylpyridin, 8 Teilen Natriumamid und 12 Teilen Äthylsulfat wird unter den Bedingungen des Beispiels 3 4-Propylpyridin erhalten.Example 13 From 10 parts of 4-methylpyridine, 8 parts of sodium amide and 12 parts of ethyl sulfate is under the conditions of Example 3 4-propylpyridine obtain.

Beispiel 14 Aus 8,9 Teilen 4-Äthylpyridin, io Teilen Natriumamid und io Teilen Äthylbromid loder 14 Teilen Äthylj,odid wird in guter Ausbeute das bei 197° siedende sekundäre 4-Butylpyridi,nerhalten; F. des Pikrats 142°.Example 14 From 8.9 parts of 4-ethylpyridine, 10 parts of sodium amide and 10 parts of ethyl bromide or 14 parts of ethyl, odid is the in good yield 197 ° boiling secondary 4-butylpyridines obtained; F. of the picrat 142 °.

Beispiel 15 Aus 31 Teilen 2-Methylpyridin, 2o Teilen Natriumamid und 18 Teilen Phenylätlrylchlflrid werden nach den Bedingungen des Beispiels i i i Teile 2-Plienylpropylpyridin, eine angenehm riechende Flüssigkeit vom KP-2" 14o° und 2-Di-(phenyläthyl)-methylpyridin vorn Kp. =,5 212° erhalten; die Pik-rate dieser Basen schmelzen bei io8,5" bzw. 102". Beispiel 16 i 9 Teile 2-Methylpyridin, i o Teile Natriumamid und 13 Teile Cyclopentylbromid werden 15 Stunden auf i i o° ierwärmt, die Masse nach Erkalten mit Eiswasser versetzt und, wie üblich, aufgearbeitet. Außer dem unveränderten Methylpyridin "verden 13,75 Teile des bei 117,5° unter 16mm Druck siedenden 2-Cyclopemtylmethylpyridins,einer angenehm riechenden Flüssigkeit, erhalten.EXAMPLE 15 From 31 parts of 2-methylpyridine, 20 parts of sodium amide and 18 parts of phenylethylchloride, parts of 2-plienylpropylpyridine, a pleasant-smelling liquid of KP-2 "140 ° and 2-di- (phenylethyl) -methylpyridine, are obtained according to the conditions of Example iii Bp = .5 212 °; the pic rate of these bases melt at 10 8.5 "and 102". EXAMPLE 16 9 parts of 2-methylpyridine, 10 parts of sodium amide and 13 parts of cyclopentyl bromide are heated to 10 for 15 hours, the mass is mixed with ice water after cooling and, as usual, worked up. In addition to the unchanged methylpyridine, 13.75 parts of 2-cyclopemtylmethylpyridine, a pleasant-smelling liquid, boiling at 117.5 ° under 16 mm pressure, are obtained.

Beispiel 17 Man setzt 2 Teilen 4-Methylpyridin und 7 Teilen Natriumamid tropfenweise 7 Teile Cyclohexylchlorid zu und läßt das Gemisch 5 Stunden. stehen. Es wird 4-Hexahydrobenzylpyrid'm in. guter Ausbeute verhalten, eine stark riechende Flüssigkeit, die bei 266" siedet. Pikrat, gelbe Nadeln vom F.172°. Chloroplatinat, sehr wenig in Wasser lösliche Kristalle, die sich frei 2q.3° zersetzen.Example 17 2 parts of 4-methylpyridine and 7 parts of sodium amide are used 7 parts of cyclohexyl chloride are added dropwise and the mixture is left for 5 hours. stand. 4-Hexahydrobenzylpyrid'm will behave in good yield, a strong-smelling one Liquid boiling at 266 ". Picrat, yellow needles of 172 ° F. Chloroplatinate, Very little water soluble crystals, which decompose freely 2q.3 °.

Beispiel 18 Aus 2-Methylpyridin, N,atriumamid und -Cycloh exylehlorid wird das bei 118° unter i2mm Druck sIedende 2-H,exahydrobienzylpyridin erhalten.Example 18 From 2-methylpyridine, N, atrium amide and cyclohexyl chloride the 2-H, exahydrobienzylpyridine which sIde at 118 ° under 12 mm pressure is obtained.

Beispiel i9 15 Teile 2-Methyl-5-äthylpyridin, 12 Teile Natriumamid und i 9 Teile Benzylchlorid werden 8 Stunden im Wasserbad am Rück= flußkühler erwärmt und dann bis zum beginnenden Sieden erhitzt. Nach der Weiter-Verarbeitung wie im Beispiel i werden 4,8 Teile 2-Phenyläthyl-5-äthylpyridin vom Kp. i85 bis 195° außer unverändertem Ausgangsstoff erhalten. Bei Anwendung von Kaliumamid verläuft die Umsetzung kräftiger und mit besserer Ausbeute.Example 19 15 parts of 2-methyl-5-ethylpyridine, 12 parts of sodium amide and i 9 parts of benzyl chloride are heated in a water bath on a reflux condenser for 8 hours and then heated until it begins to boil. After further processing as in Example i are 4.8 parts of 2-phenylethyl-5-ethylpyridine with a boiling point of 85 ° to 195 ° received unchanged starting material. When using potassium amide, the Implementation stronger and with better yield.

Beispiel 2o 9 Teile 2, 4, 6-Trimethylpyridin, io Teile Natriumamid und 6 Teile Isopropylchlorid werden zunächst in der Kälte gemischt und dann allmählich während 5 Stunden gelinde erwärmt. Man erhält ein bei 185 bis 200° siedendes Gemisch von in 2- und 4-Stellung substituierten Homiologen, hauptsächlich 2-Is,obuty1-q., 6-dimethylpyridin.Example 2o 9 parts of 2, 4, 6-trimethylpyridine, 10 parts of sodium amide and 6 parts of isopropyl chloride are mixed first in the cold and then gradually warmed gently for 5 hours. A mixture boiling at 185 to 200 ° is obtained of homiologues substituted in the 2- and 4-position, mainly 2-Is, obuty1-q., 6-dimethylpyridine.

Beispiel 21 3o Teile 2-Methylpyridin, 28 Teile Natriumamid und 22 Teile Diäthylaminoäthylchlorid geben in guter Ausbeute das bei 148° und 28 mm Druck siedende 2-Diniethylaminapr opylpyridin.Example 21 3o parts of 2-methylpyridine, 28 parts of sodium amide and 22 parts Parts of diethylaminoethyl chloride give this in good yield at 148 ° and 28 mm pressure boiling 2-diniethylamine propylpyridine.

Beispiel 22 i 9 Teilen 2-Methylpyridin und 12 Teilen Natriumamid, mit einem halben Raumteil wasserfreiem Äther versetzt, werden unter starkem Kühlen 2 Teile Trichloräthylen tropfenweise zugesetzt. Die Umsetzung ist sehr kräftig. Nach Zugabe von viel Äther wird das Gemisch unter guter Kühlung mit Eiswasser zersetzt. Die ätherische Schicht wird mehrmals mit Wasser gewaschen, dann mit hTatriumsulfat getrocknet und der Äther unter vermindertem Druck verdampft. Es bleibt eine scharf riechende Flüssigkeit zurück, das 2-Dichlorallylpyridin, welches sich beim Aufbewahren leicht polymerisiert.Example 22 i 9 parts of 2-methylpyridine and 12 parts of sodium amide, mixed with half a volume of anhydrous ether, are subjected to strong cooling 2 parts of trichlorethylene added dropwise. The implementation is very powerful. After adding a lot of ether, the mixture is decomposed with good cooling with ice water. The ethereal layer is washed several times with water, then with sodium sulfate dried and the ether evaporated under reduced pressure. It remains a sharp one smelling liquid back, the 2-dichloroallylpyridine, which is when stored easily polymerized.

Beispiel 23 2o Teile 2-Methylchiinolin werden in ätherischer Lösung mit 5 Teilen Natriumamid versetzt. Zur Mischung werden 12,5 Teile in Äther gelöstes Benzylchlorid tropfenweise zugesetzt. Nach Eingießen in Wasser, Abtrenxlen der ätherischen Schicht und Abdampfen des Athers wird der Rückstand unter vermindertem Druck destilliert. Die unter io_mm Druck bei 215 bis 22o° übergehende ridltZ tion stellt-das fast reine 2-Phenyläthylchi" dar, das nach Umlristallisieren aus bei 3o° schmilzt. Beispiel 24 Aus 11,2 Teilen 4-Methylchinolin, i o Teilen Natriumamid und i o Teilen Äthylbromid werden 8o% der Theorie an 4-Propylchinolin vom Kp. 28o bis 285° erhalten; F. des Pi- krats 2o4°. Beispiel 25 12 Teile 4-Methylchinolin, 9 Teile Natrium- amid und i o i Teile Diäthylaminoäthylchlorid ergeben in guter Ausbeute das bei 225 bis 230° und 2omm Druck siedende 4-Diäthyl- aminopropylchinolin. Beispiel 26 15 Teile 2-Methylchinolin, i vTeile iV,atriiun- amid und II Teile Benzylchlorid Bergreben mit güte-r Ausbeute das bei 30° schmelzende 2-Phenyläthylchinolin und außerdem Dibenzyl- methylchinolin. Example 23 5 parts of sodium amide are added to 20 parts of 2-methylquinoline in an ethereal solution. To the mixture, 12.5 parts of benzyl chloride dissolved in ether are added dropwise. After pouring into water, separating off the ethereal layer and evaporating the ether, the residue is distilled under reduced pressure. The under io_mm Pressure at 215 to 22o ° transient ridltZ tion provides - the almost pure 2-Phenyläthylchi " represents that after recrystallization melts at 30 °. Example 24 From 11.2 parts of 4-methylquinoline, 10 parts Sodium amide and 10 parts of ethyl bromide 8o% of theory of 4-propylquinoline obtained from b.p. 28o to 285 °; F. of the Pi- krats 2o4 °. Example 25 12 parts of 4-methylquinoline, 9 parts of sodium amide and ioi parts of diethylaminoethyl chloride result in a good yield at 225 bis 4-diethyl boiling at 230 ° and 2omm pressure aminopropylquinoline. Example 26 15 parts of 2-methylquinoline, i v parts iV, atriiun- amide and II parts of benzyl chloride mountain vines with Good yield that melting at 30 ° 2-phenylethylquinoline and also dibenzyl methylquinoline.

Claims (1)

PATENTANSPRÜCI3E: i. Verfahren zur Einführung von organischen Resten in die Seitenketten von Pyridin- bzw. Chinolinhomologen, da- durch gekenllzeichrnet, daß man Pyridin- bzw. Chinolinverbindungen, die in 2- oder 4-Stellung durch Metall substituierbare Kohlmlwasserstoffgruppen, wie C H3-, C H3- @oder CH-Gruppen, enthalten, in Gegenwart von Alkaliamiden mit torganischen Ver- bindungen umsetzt, die einen Substituan- tm tragen, der mit dem Metallatom der Metallverbindung der Pyridin- bzw. Chino- linhomologen zu reagieren vermag. 2. Ausführungsform des Verfahrens nach Anspruch i, dadurch gekennzeich- met, daß man die Pyridin- bzw. Chinolin- homologen mit organischen Halogenver- bindungen in Gegenwart eines Alkaliamids umsetzt.
PATENT CLAIMS: i. Procedure for introducing organic residues in the side chains of pyridine or quinoline homologues, since characterized by the fact that pyridine or quinoline compounds in 2- or 4-position substitutable by metal Hydrocarbon groups, such as C H3-, C H3- @or CH groups, included, in the present of alkali amides with inorganic converts bonds that have a substituent tm, the one with the metal atom of the Metal compound of the pyridine or quino- linhomologen able to react. 2nd embodiment of the method according to claim i, characterized met that the pyridine or quinoline homologues with organic halogen compounds bonds in the presence of an alkali amide implements.
DESCH108920D 1936-01-11 1936-01-11 Process for the introduction of organic residues into the side chains of pyridine or quinoline homologues Expired DE676114C (en)

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