DE707266C - Process for the extraction of connections with the action of the urine - Google Patents
Process for the extraction of connections with the action of the urineInfo
- Publication number
- DE707266C DE707266C DEM144408D DEM0144408D DE707266C DE 707266 C DE707266 C DE 707266C DE M144408 D DEM144408 D DE M144408D DE M0144408 D DEM0144408 D DE M0144408D DE 707266 C DE707266 C DE 707266C
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- Germany
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- solution
- amino
- methyl
- cyano
- methoxymethyl
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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
- C07D213/60—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 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
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
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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
- C07D213/60—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 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
- C07D213/66—One oxygen atom attached in position 3 or 5 having in position 3 an oxygen atom and in each of the positions 4 and 5 a carbon atom bound to an oxygen, sulphur, or nitrogen atom, e.g. pyridoxal
- C07D213/67—2-Methyl-3-hydroxy-4,5-bis(hydroxy-methyl)pyridine, i.e. pyridoxine
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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
- C07D213/60—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 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon 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
- C07D213/60—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 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
- C07D213/85—Nitriles in position 3
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Description
Verfähren zur Gewinnung von Verbindungen mit der Wirkung des Adermins Es sind bisher noch keine synthetisch gewonnenen Substanzen bekanntgeworden, die im biologischen Versuch die Wirkungen des Adermins (Vitamin B6) zeigen. Das Adermin selbst ist eine aus natürlichem Material auf sehr umständlichem Wege in nur geringen Mengen herstellbare Substanz, für die vor kurzem Kuhn eine wahrscheinliche Konstitutionsformel aufgestellt hat (Berichte der deutschen Chemischen Gesellschaft, Bd. 72 [I939], S. 31o). Es konnte bisher noch nicht synthetisch gewonnen werden.Process for the production of connections with the effect of the urine So far, no synthetically obtained substances have become known that show the effects of adermine (vitamin B6) in a biological test. The Adermin itself is one made of natural material in a very cumbersome way in only minor Substance that can be produced in quantities, for which Kuhn recently developed a probable constitutional formula (Reports of the German Chemical Society, Vol. 72 [1939], P. 31o). It has not yet been possible to obtain it synthetically.
Nach der Erfindung lassen sich Verbindungen mit der Wirkung des Adermins
herstellen, ausgehend von 2-Methyl-3-nitro-5-cyan-6-chlor-(oder-6-brom)-pyridinen,
die in Stellungq. den Rest CH2R (R=Wasserstoff, Hydroxyl oder eine in OH überführbare
Gruppe) tragen. Diese Substanzen sind sehr leicht herstellbar aus Acetylaceton bzw.
seinen Abkömmlingen der Formel -CH3--CO-CH2-CO-CH.R (R=OH oder ein in O H überführbarer
Rest), Ammoniak und einem zum Pyridinringschluß geeigneten Derivat der Malonsäure
oder der Cyanessigsäure (z. B. Malonsäureamid mit nachträglicher Überführung der
Säureamid- in die Nitrilgruppe oder Cyanessigsäureester bzw. ihr Amid, entsprechend
bekannten Synthesen des Pyridinringes, vgl. z. B. Chem. Zentralblatt 1899, 1, 289,
und 193o, 1, a31). Die genannten Reaktionspartner kann man gleichzeitig aufeinander
einwirken lassen, oder man stellt erst aus Acetylaceton (bzw. seinen Abkömmlingen)
und Ammoniak das Monoimin dieser Verbindungen her und setzt dies mit dem Malon-
Säurederivat
um. Man erhält so in guter Ausbeute Verbindungen der Formel ; 1 i, die sich durch
Nitrieren und Chlorieren (oder
Diese Substanz läßt sich null überraschenderweise in einem Arbeitsgang katalytisch zum 2, 4-Dimethyl-3-amiilo-5-aininonietliylpyridin reduzieren. (Die katalytische Reduktion einer Cvangruppe ist bisher in der Pyridinchemie überhaupt noch nicht durchgeführt worden; man hat die Reduktion immer auf sehr umständliche Weise mit reduzierend wirkenden Chemikalien durchgeführt und dabei oft nur schlechte Ergebnisse erzielen können.) Schließlich lassen sich auch die aliphatisch gebundene und die am Pyridinkern gebundene Aminogruppe in einem einzigen Arbeitsgang durch Diazotieren und Verkochen in saurer Lösung in Hydroxy-I-gruppen überführen.Surprisingly, this substance can be zero in one operation reduce catalytically to 2,4-dimethyl-3-amiilo-5-aininonietliylpyridine. (The catalytic reduction of a Cvan group has hitherto been used in pyridine chemistry at all not yet carried out; one always has the reduction to very cumbersome Wise done with reducing chemicals and often only bad ones Can achieve results.) Finally, the aliphatically bound and the amino group attached to the pyridine core in a single operation Diazotize and boil in acidic solution to convert into hydroxy-I groups.
Das erhaltene 2. 4-Diinetliyl-3-oxy-5-oxymethylpyridin vom Schmelzpunkt 25.I° zeigt überraschenderweise die biologische Wirkung des Adermitis (Vitamin B6). Bromieren) in das gewünschte Ausgangsmaterial von der Formel (II) überführen lassen: eignet ist. In der so erhaltenen Verbindung der Formel (III ) sollen sodann die beiden Aminogruppen durch Hydroxylgruppen ersetzt werden, was nach dem üblichen Verfahren durch Diazotieren und Verkochen geschehen kann. Beispiele 1. 5-Cyan-2, 4-dimethyl-(roxypyridin (vgl.The obtained 2,4-diinethyl-3-oxy-5-oxymethylpyridine of melting point 25.I ° surprisingly shows the biological effect of the adermitis (vitamin B6). Bromination) can be converted into the desired starting material of the formula (II): is suitable. In the compound of the formula (III) thus obtained, the both amino groups are replaced by hydroxyl groups, what after the usual Process can be done by diazotizing and boiling. Examples 1. 5-Cyan-2, 4-dimethyl- (roxypyridine (cf.
G u a r e s c h i, Chemisches Zentralblatt 1899, I, 289) wird zum 5-Cyan-3-nitro-2, 4-diinethyl-6-oxypyridin mit konzentrierter Salpetersäure und konzentrierter Schwefelsäure nitriert. Das erhaltene 3-Nitroderivat wird mit einem Gemisch von P O Cl, und P CIS chloriert. Man erhält 5-Cyan-3-nitro-6-chlor-2, 4-diniethylpyridin vom Schmelzpunkt 112'.G u a r e s c h i, Chemisches Zentralblatt 1899, I, 289) becomes 5-cyano-3-nitro-2, 4-diinethyl-6-oxypyridine with concentrated nitric acid and concentrated sulfuric acid nitrated. The 3-nitro derivative obtained is with a Mixture of P O Cl, and P CIS chlorinated. 5-cyano-3-nitro-6-chloro-2,4-diniethylpyridine is obtained of melting point 112 '.
j,1 g 6-Chlor-3-rlitro-5-cyan-2, 4-dimethylpyridin werden in 200 ccm 'Methanol unter Zusatz von 15,6 ccm 2 n-H Cl in Gegenwart von 5 g Pd-Kohle bei Raumtemperatur mit Hz geschüttelt. Nach 4o Stunden sind 6 Mol H= aufgenommen, und die Hydrierung kommt zum Stillstand. Nach Abfiltrieren des Katalysators wird das Lösungsmittel verdampft und der Rückstand aus Methanol -1- Äther umkristallisiert. Das entstandene 3-Amino-5-aminomethyl-2, 4-dimethylpyridin kristallisiert in Form seines Dichlorhydrates in weißen, glänzenden Blättchen vom Zersetzungspunkt 3 i o°. Ausbeute 95()/o der Theorie. Durch Extraktion einer konzentrierten alkalischen Lösung mit Chloroform läßt sich die freie Base isolieren, die nach Umkristallisiereii aus Methanol -Äther bei 136° schmilzt.j, 1 g of 6-chloro-3-rlitro-5-cyano-2, 4-dimethylpyridine are in 200 ccm 'Methanol with the addition of 15.6 ccm 2 n-H Cl in the presence of 5 g Pd-charcoal at room temperature shaken with Hz. After 40 hours, 6 moles of H = have been taken up, and the hydrogenation comes to a standstill. After filtering off the catalyst, the solvent becomes evaporated and the residue recrystallized from methanol -1- ether. The resulting 3-Amino-5-aminomethyl-2,4-dimethylpyridine crystallizes in the form of its dichlorohydrate in white, shiny leaflets with a decomposition point of 3 10 °. Yield 95 () / o der Theory. By extracting a concentrated alkaline solution with chloroform the free base can be isolated, which after recrystallization from methanol ether melts at 136 °.
2,24 g 3 -Amino - 5 -aniinoniethyl - 2, 4- diniethylpyridindichlorhydrat werden in i o ccm Wasser gelöst und mit einer Lösung von 1,5 g Natriumnitrit in i o ccm Wasser versetzt. Dazu läßt man unter Rühren i 5 ccm i n-Salzsäure zufließen. plan hält die Reaktionslösung ungefähr i Stunde bei 6o°, bis sich mit jodkalistärkepapier kein Nitrit mehr nachweisen läßt. Dann wird die Lösung im Vakuum eingedampft und der gut getrocknete Rückstand mit absolutem Alkohol mehrmals extrahiert. Der nach dem Abdampfen. des Alkohols verbleibende Rückstand wird aus Methanol + Äther umkristallisiert, wobei das 3-Oxy-5-oxymethyl-2, 4-dimethylpyridin vom Schmelzpunkt 254° als salzsaures Salz auskristallisiert. 2.24 g of 3-amino-5-aniinoniethyl-2,4-diniethylpyridinedichlorohydrate are dissolved in 10 cc of water and a solution of 1.5 g of sodium nitrite in 10 cc of water is added. For this purpose, i 5 cc of iN hydrochloric acid are allowed to flow in with stirring. The reaction solution is kept flat for about an hour at 60 ° until no more nitrite can be detected with iodine starch paper. The solution is then evaporated in vacuo and the well-dried residue is extracted several times with absolute alcohol. The one after the evaporation. the residue remaining from the alcohol is recrystallized from methanol + ether, the 3-oxy-5-oxymethyl-2,4-dimethylpyridine having a melting point of 254 ° crystallizing out as a hydrochloric acid salt.
Im Adermintest als Wuchsstoff für Milchsäurebakterien nach M ö 11 e r (Zeitschrift für physiologische Chemie 1938, Bd. 254, S.285) zeigt diese Substanz einwandfrei positive Wirkung, wobei die optimale Konzentration bei einigen y/ccm liegt. Bisher kannte man außen dem natürlichen Vitamin B6 noch keine in diesem Test wirksame Substanz.In the vein test as a growth substance for lactic acid bacteria according to M ö 11 e r (magazine for physiological chemistry 1938, vol. 254, p.285) shows this substance perfectly positive effect, with the optimal concentration at a few y / ccm lies. So far, the outside of the natural vitamin B6 was not yet known in this test effective substance.
2. 2 - Methyl - 3 - nitro - 4. - methoxymethyl -5-cyan-6-chlorpyridin wird wie folgt hergestellt: Durch Kondensation von Methoxyacetylaceton mit Cyanessigester in 25%igem Ammoniak bei 6o° erhält man 2-Methyl-4-methoxymethyl-5-cyan-6-oxypyridin. Diese Verbindung wird zunächst mittels 86%iger Salpetersäure in Essigsäureanhydrid bei nicht mehr als 6o° C nitriert und hierauf mit Phosphorpentachlorid und Phosphoroxychlorid durch Erhitzen am Rückfluß chloriert.2.2 - methyl - 3 - nitro - 4. - methoxymethyl -5-cyano-6-chloropyridine is produced as follows: By condensation of methoxyacetylacetone with cyanoacetic ester in 25% ammonia at 60 °, 2-methyl-4-methoxymethyl-5-cyano-6-oxypyridine is obtained. This compound is first made using 86% nitric acid in acetic anhydride nitrated at no more than 60 ° C and then with phosphorus pentachloride and phosphorus oxychloride chlorinated by refluxing.
15 g 2-Methyl-3-nitro-4-methoxymethyl-5-cyan-6-chlorpyridin werden in - 6oo ccm Methanol unter Zugabe von 31,5 ccm 2 n-Salzsäure in Gegenwart von io g io%iger Palladiumkohle mit Wasserstoff bei Zimmertemperatur geschüttelt. Die Aufnahme von 3M01 Wasserstoff verläuft sehr rasch und unter Wärmeentwicklung. Nach 15 Stunden kommt die Hydrierung zum Stillstand,. nachdem insgesamt 6 Mol Wasserstoff aufgenommen worden sind. Man filtriert vom Katalysator, destilliert das Lösungsmittel weitgehend ab und gibt Äther zu, wobei das entstandene 2-Methyl-3-amino-4-methoxymethyl-5-aminomethylpyridin als Dichlorhydrat in weißen Nadeln ausfällt. Nach Umlösen aus Methanol schmilzt es bei 236°. Die Ausbeute beträgt 9o % der Theorie.15 g of 2-methyl-3-nitro-4-methoxymethyl-5-cyano-6-chloropyridine become in - 6oo ccm of methanol with the addition of 31.5 ccm of 2N hydrochloric acid in the presence of io g io% palladium carbon shaken with hydrogen at room temperature. The recording of 3M01 hydrogen runs very quickly and generates heat. After 15 hours the hydrogenation comes to a standstill. after taking up a total of 6 moles of hydrogen have been. The catalyst is filtered off and most of the solvent is distilled from and ether is added, the resulting 2-methyl-3-amino-4-methoxymethyl-5-aminomethylpyridine as dichlorohydrate precipitates in white needles. Melts after dissolving from methanol it at 236 °. The yield is 90% of theory.
In eine Lösung von 7,3 g 2-Methyl-3-amino-4- methoxymethyl -5 - aminomethylpyridin - dichlorhydrat in 5o ccm Wasser wird bei Zimmertemperatur eine Lösung von 4,4 g Natriumnitrit in 5o ccm Wasser und 29 ccm 2 n-Salzsäure unter Rühren eingetropft. Die Lösung wird noch 30 Minuten auf 6o bis 7o° gehalten und anschließend im Vakuum bei 4o° zur Trockne verdampft. Durch Extrahieren des gut getrockneten Rückstandes mit absolutem Alkohol wird vom Kochsalz abgetrennt und die erhaltene Lösung im Vakuum eingedampft. Der Rückstand läßt sich aus absolutem Alkohol und Aceton umlösen. Man erhält so 2-Methyl-3-oxy-4-methoxymethyl-5-oxymethylpyridin als Monochlorhydrat vom F. 182'. Ausbeute 5 g. In a solution of 7.3 g of 2-methyl-3-amino-4-methoxymethyl -5 - aminomethylpyridine - dichlorohydrate in 5o ccm of water, a solution of 4.4 g of sodium nitrite in 5o ccm of water and 29 ccm of 2 n- Hydrochloric acid was added dropwise with stirring. The solution is kept at 6o to 7o ° for a further 30 minutes and then evaporated to dryness in vacuo at 40 °. By extracting the well-dried residue with absolute alcohol, the sodium chloride is separated off and the resulting solution is evaporated in vacuo. The residue can be redissolved from absolute alcohol and acetone. This gives 2-methyl-3-oxy-4-methoxymethyl-5-oxymethylpyridine as a monochlorohydrate of F. 182 '. Yield 5g.
Die- 4-Methoxymethylgruppe dieser Verbindung läßt sich leicht durch Kochen mit 66%iger Bromwasserstoffsäure in die Brommethylgruppe verwandeln. Da die Bromwasserstoffsäure das aliphatische Hydroxyl angreift, entsteht zunächst das 2-Methyl-3-oxy-4, 5-di-(brommethyl)-pyridin, das durch Kochen in Wasser und Behandlung mit Silberchlorid in 2-Methyl-3-oxy-4, 5-di-(oxymethyl)-pyridin übergeführt werden kann.The 4-methoxymethyl group of this compound is easily passed through Convert to the bromomethyl group by boiling with 66% hydrobromic acid. Since the Hydrobromic acid attacks the aliphatic hydroxyl, 2-methyl-3-oxy-4 is formed first, 5-di- (bromomethyl) pyridine, which is obtained by boiling in water and treating with silver chloride can be converted into 2-methyl-3-oxy-4,5-di (oxymethyl) pyridine.
3. 2,2 g-2-Methyl-3-nitro-4-methoxymethyl-5-cyan-6-brompyridin (hergestellt durch Behandeln der entsprechenden, in Beispiel?, beschriebenen 6-Chlorverbindung mit Bromwasserstoffsäure in Essigsäureanhydrid; aus Isopropylalkohol umkristallisiert, Nadeln vom Schmelzpunkt 88°) werden in i oo ccm Methanol gelöst und unter Zugabe. von 4 ccm 2 n-Salzsäure in Gegenwart von 2 g io%iger Palladiumkohle mit Wasserstoff geschüttelt. Nach mehreren Stunden kommt die Wasserstoffaufnahme zum Stillstand, wobei genau 6 Mol Wasserstoff adsorbiert sind. Die vom Katalysator befreite Lösung wird abgedampft, der Rückstand in Wasser aufgenommen, mit frisch gefälltem Silberchlorid behandelt und nochmals abgedampft. Durch Umkristallisieren aus Methanol und Äther erhält man das 2-Methyl-3-amino-4-methoxymethyl-5 - ,aminomethylpyridindichlorhydrat vom Schmelzpunkt 236°. Ausbeute i ,8 g = 89 % der Theorie. Diese Verbindung wird nach Beispiel 2 weiterverarbeitet.3. 2.2 g-2-methyl-3-nitro-4-methoxymethyl-5-cyano-6-bromopyridine (prepared by treating the corresponding 6-chloro compound described in Example? with hydrobromic acid in acetic anhydride; recrystallized from isopropyl alcohol, Needles with a melting point of 88 °) are dissolved in 100 ccm of methanol and added. of 4 ccm of 2N hydrochloric acid in the presence of 2 g of 10% palladium carbon with hydrogen shaken. After several hours, the hydrogen uptake comes to a standstill, where exactly 6 moles of hydrogen are adsorbed. The solution freed from the catalyst is evaporated, the residue taken up in water, with freshly precipitated silver chloride treated and evaporated again. By recrystallization from methanol and ether the 2-methyl-3-amino-4-methoxymethyl-5 -, aminomethylpyridinedichlorohydrate is obtained with a melting point of 236 °. Yield 1.8 g = 89% of theory. This connection will processed according to example 2.
4. i g 2-Methyl-3-nitro-4-anethoxymethyl-5-cyan-6-chlorpyridin (vgl. Beispiele) trägt man in 2,8 g Zinnch.lorür (2 aq) und 3, g konzentrierte Salzsäure (d = i,19) so ein, daß die Temperatur q.o° C nicht übersteigt. Danach erwärmt man noch 2 Stunden auf 35 bis 4o° C, kühlt mit Eis und macht mit Natronlauge alkalisch. Man äthert wiederholt aus, trocknet den Ätherextrakt mit Pottasche, entfärbt mit Tierkohle und engt ein. Beim Versetzen mit leicht siedendem Petroläther kristallisieren o,6 g 2-Methyl-3-amino-4-methoxymethyl-5-cyan-6-chlorpyridin in gelbweißen Kristallen aus. Schmelzpunkt 117 bis ii8° C. Ausbeute 68% der Theorie. Aus der Mutterlauge erhält man noch 0,04 g eines etwas unreinen Produktes.4. i g of 2-methyl-3-nitro-4-anethoxymethyl-5-cyano-6-chloropyridine (cf. Examples) are carried in 2.8 g of tin chloride (2 aq) and 3. g of concentrated hydrochloric acid (d = i, 19) so that the temperature does not exceed q.o ° C. Then you warm up 2 hours to 35 to 40 ° C, cool with ice and make alkaline with sodium hydroxide solution. Ethers are repeatedly extracted, the ether extract is dried with potash and decolorized with Animal charcoal and constricts. Crystallize when mixed with slightly boiling petroleum ether 0.6 g of 2-methyl-3-amino-4-methoxymethyl-5-cyano-6-chloropyridine in yellow-white crystals the end. Melting point 117 to 18 ° C. Yield 68% of theory. From the mother liquor 0.04 g of a somewhat impure product is obtained.
0,4 g 2-Methyl-3-amino-4-methoxymethyl-5-cyan-6-chlorpyridin werden in 5o ccm Methanol unter Zusatz von i ccm 2 n-H Cl in Gegenwart von i g 1oo/oiger Palladiumkohle bei Raumtemperatur mit Wasserstoffgas geschüttelt. Nach 9 Stunden kommt die Hydrierung zum Stillstand. Der Katalysator wird abfiltriert, die methanolische Lösung. weitgehend eingeengt und mit reichlich Äther" versetzt. Dabei fällt das Hydrierungsprodukt kristallin aus. Nach Umlösen aus Methanol/Äther schmilzt das Dichlorhydrat des 2-Methyl-3-amino -4-methoxymethyl -5-aminomethylpyridins bei 236° C. Ausbeute :15o mg t= 94% der Theorie). Diese Verbindung wird nach Beispiel 2 weiterverarbeitet.0.4 g of 2-methyl-3-amino-4-methoxymethyl-5-cyano-6-chloropyridine become in 50 cc of methanol with the addition of 1 cc of 2 n-H Cl in presence shaken from i g of 100% palladium carbon at room temperature with hydrogen gas. The hydrogenation comes to a standstill after 9 hours. The catalyst is filtered off, the methanolic solution. largely narrowed and mixed with plenty of ether ". The hydrogenation product precipitates in crystalline form. After dissolving from methanol / ether the dichlorohydrate of 2-methyl-3-amino -4-methoxymethyl -5-aminomethylpyridine melts at 236 ° C. Yield: 150 mg t = 94% of theory). This connection is according to example 2 further processed.
5.25 g 2, 4-Dimethyl-3-nitro-5-cy an-6-chlorpyridin (Herstellung vgl. Beispiel i) werden in Zoo ccm Alkohol unter Zusatz von 50o ccm verdünnter Schwefelsäure am Rückfluß auf dem Dampfbad erhitzt. In die Lösung wird im Verlauf von 2 Tagen portionsweise Zinkstaub eingetragen, bis die Lösung farblos geworden ist. Nachdem vom überschüssigen Zink abfiltriert ist, wird die Lösung stark alkalisch gemacht und ausgeäthert. Nach Trocknen des Äthers mit Natriumsulfat und Abdestillieren hinterbleibt 2, 4-Dimethyl-3-amino-5-cyanpyridin als kristalliner Rückstand. Nach Umkristallisieren aus 96%igem Alkohol schmilzt das Produkt bei 195o. Ausbeute 15 g.5.25 g of 2,4-dimethyl-3-nitro-5-cy an-6-chloropyridine (preparation cf. Example i) are in zoo cc alcohol with the addition of 50o cc dilute sulfuric acid heated to reflux on the steam bath. In the solution is over the course of 2 days Zinc dust added in portions until the solution has become colorless. After this the excess zinc is filtered off, the solution is made strongly alkaline and etherified. After drying the ether with sodium sulfate and distilling off remains 2,4-Dimethyl-3-amino-5-cyanopyridine as a crystalline residue. After recrystallization from 96% alcohol, the product melts at 195o. Yield 15g.
Durch Einleiten von Salzsäuregas in eine alkoholische Lösung des 2, 4-Dimethyl-3-amino-5-cyanpyridins läßt es sich in ein Chlorhydrat vom F.275° überführen.By introducing hydrochloric acid gas into an alcoholic solution of the 2nd 4-Dimethyl-3-amino-5-cyanopyridine can be converted into a chlorohydrate with a temperature of 275 °.
69 2, 4-Dimethyl-3-amino-5-cyanpyridin werden in Feinsprit gelöst und am Rührwerk mit der aus ioo g Kaliumbichromat (durch Reduktion mit Zink und Salzsäure und anschließende Fällung mit Natriumacetat) erhaltenen Menge Chromoacetat behandelt, wobei man im Verlaufe einer Stunde eine Lösung von 30 g Kaliumhydroxyd in wenig Wasser und Feinsprit zutropfen läßt. Man hält die Reaktionsmischung dann 4. Stunden in schwachem Sieden. Während der ganzen Zeit wird ein Wasserstoffstrom durch die Apparatur geleitet. Nach dem Erkalten wird vom ausgeschiedenen Chromhydroxyd abfiltriert, die filtrierte Lösung stark alkalisch gemacht und wiederholt mit Chloroform extrahiert. Nach Trocknen mit Natriumsulfat und Abdestillieren des Chloroforms erhält man das 2, 4-Dimethyl-3-amino-5-aminomethylpyridin in Kristallen, die, aus Feinsprit umkristallisiert, bei i36° schmelzen. Ausbeute 2 g. 69 2,4-Dimethyl-3-amino-5-cyanopyridine are dissolved in fine spirits and treated with the stirrer with the amount of chromoacetate obtained from 100 g of potassium dichromate (by reduction with zinc and hydrochloric acid and subsequent precipitation with sodium acetate) A solution of 30 g of potassium hydroxide in a little water and fine spirits can be added dropwise for an hour. The reaction mixture is then kept at a gentle boil for 4 hours. During the whole time a stream of hydrogen is passed through the apparatus. After cooling, the precipitated chromium hydroxide is filtered off, the filtered solution is made strongly alkaline and extracted repeatedly with chloroform. After drying with sodium sulfate and distilling off the chloroform, the 2,4-dimethyl-3-amino-5-aminomethylpyridine is obtained in crystals which, recrystallized from fine spirits, melt at i36 °. Yield 2g.
Durch Behandeln einer alkoholischen Lösung des 2, 4-Dimethyl-3-amino-5-aminomethylpyridins mit Salzsäure erhält man das entsprechende Dichlorhydrat, das bei 3109 unter Zersetzung schmilzt. Die Diazotierung und Verkochung dieser Verbindung erfolgt nach der in Beispiel i angegebenen Vorschrift.Treatment of an alcoholic solution of 2,4-dimethyl-3-amino-5-aminomethylpyridine with hydrochloric acid gives the corresponding dichlorohydrate, which melts at 3109 with decomposition. The diazotization and boiling of this compound is carried out according to the instructions given in Example i.
Claims (1)
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DEM144408D DE707266C (en) | 1939-02-28 | 1939-02-28 | Process for the extraction of connections with the action of the urine |
DK58703D DK58703C (en) | 1939-02-28 | 1939-10-16 | Process for the Preparation of Aminomethyl Derivatives of Pyridine. |
BE436830D BE436830A (en) | 1939-02-28 | 1939-10-26 |
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DEM144408D DE707266C (en) | 1939-02-28 | 1939-02-28 | Process for the extraction of connections with the action of the urine |
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DE707266C true DE707266C (en) | 1941-06-18 |
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DEM144408D Expired DE707266C (en) | 1939-02-28 | 1939-02-28 | Process for the extraction of connections with the action of the urine |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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DE1003210B (en) * | 1939-09-01 | 1957-02-28 | Merck & Co Inc | Process for the synthetic production of vitamin B. |
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1939
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- 1939-10-16 DK DK58703D patent/DK58703C/en active
- 1939-10-26 BE BE436830D patent/BE436830A/xx unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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DE1003210B (en) * | 1939-09-01 | 1957-02-28 | Merck & Co Inc | Process for the synthetic production of vitamin B. |
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DK58703C (en) | 1941-05-26 |
BE436830A (en) | 1939-11-30 |
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