DE1301310B - Process for the preparation of pyridoxine - Google Patents
Process for the preparation of pyridoxineInfo
- Publication number
- DE1301310B DE1301310B DE1965M0063890 DEM0063890A DE1301310B DE 1301310 B DE1301310 B DE 1301310B DE 1965M0063890 DE1965M0063890 DE 1965M0063890 DE M0063890 A DEM0063890 A DE M0063890A DE 1301310 B DE1301310 B DE 1301310B
- Authority
- DE
- Germany
- Prior art keywords
- pyridoxine
- aluminum
- acid
- boral
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
-
- D—TEXTILES; PAPER
- D02—YARNS; MECHANICAL FINISHING OF YARNS OR ROPES; WARPING OR BEAMING
- D02G—CRIMPING OR CURLING FIBRES, FILAMENTS, THREADS, OR YARNS; YARNS OR THREADS
- D02G1/00—Producing crimped or curled fibres, filaments, yarns, or threads, giving them latent characteristics
- D02G1/02—Producing crimped or curled fibres, filaments, yarns, or threads, giving them latent characteristics by twisting, fixing the twist and backtwisting, i.e. by imparting false twist
- D02G1/04—Devices for imparting false twist
- D02G1/06—Spindles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Mechanical Engineering (AREA)
- Textile Engineering (AREA)
- Pyridine Compounds (AREA)
Description
;0 —I; 0 -I
— C- C
— C- C
;O;O
X den, doch wird Boranaluminiumisopropylat, Boran-X den, but borane aluminum isopropylate, borane
in der X Die Reduktion des 2-Methyl-3-hydroxy-4,5-di-in the X The reduction of 2-methyl-3-hydroxy-4,5-di-
carboxypyridins und der oben beschrieben verwand-carboxypyridins and the related
H2 ten Verbindungen kann zweckmäßigerweise in Lö-H 2 th compounds can expediently in Lö-
sungsmitteln erfolgen, die nicht mit den Reduktionsmitteln reagieren, wie beispielsweise Hexan, Cyclohexan, Benzol, Dimethoxyäthan und Tetrahydrofuran. Kombinationen von Lösungsmitteln können ebenfalls verwendet werden. Vorzugsweise wird diesolvents that do not react with the reducing agents, such as hexane, cyclohexane, Benzene, dimethoxyethane and tetrahydrofuran. Combinations of solvents can can also be used. Preferably the
O — C' 25 Reduktion unter einer inerten Atmosphäre durchO - C '25 reduction under an inert atmosphere
geführt.guided.
O Das Anfangsprodukt der Reduktion ist ein KomO The initial product of the reduction is a com
plex vom Alkoholattyp, dessen genaue Struktur noch nicht bekannt ist. Diese Alkoholatkomplexeplex of the alcoholate type, the exact structure of which is not yet known. These alcoholate complexes
— COOR 30 können mit Wasser oder einem niedrigen aliphati-- COOR 30 can be mixed with water or a low aliphatic
— COOR' sehen Alkohol, wie beispielsweise Methanol oder- COOR 'see alcohol, such as methanol or
Äthanol, hydrolysiert werden. Die Hydrolyse wird vorzugsweise in einem sauren Medium durchgeführtEthanol, to be hydrolyzed. The hydrolysis is preferably carried out in an acidic medium
bedeutet, R und R' Wasserstoffatome oder niedrig- und das Pyridoxin als Säureadditionssalz isoliert, molekulare Alkylreste bedeuten, mit einem Boran- 35 Es kann zwar jede beliebige Säure verwendet werden, aluminiumalkylat der allgemeinen Formel II doch wird vorzugsweise eine starke Mineralsäure,means, R and R 'hydrogen atoms or low and the pyridoxine is isolated as an acid addition salt, denote molecular alkyl radicals, with a borane 35 Although any acid can be used, aluminum alkoxide of the general formula II but preferably a strong mineral acid,
wie beispielsweise eine Halogenwasserstoffsäure, ver-such as a hydrohalic acid,
AlH3(BH:)):i3Al(OR2):i (II) wendet. Das als Säureadditionssalz isolierte PyridAlH 3 (BH :)): i3Al (OR 2 ): i (II) turns. The pyrid isolated as an acid addition salt
oxin kann aus der Hydrolyselösung ausgefällt undoxine can be precipitated from the hydrolysis solution and
in der R2 einen Alkyl-, Cycloalkyl- oder Aralkylrest 40 abfiltriert und leicht nach an sich bekannten Methomit 1 bis 10 Kohlenstoffatomen bedeutet, umsetzt den in die freie Base zurückgeführt werden, und den gebildeten Komplex zu Pyridoxin hydroly- Gemäß einer besonderen Ausführungsweise derin which R 2 an alkyl, cycloalkyl or aralkyl radical 40 is filtered off and means slightly according to the known metho having 1 to 10 carbon atoms, converts which are returned to the free base, and hydrolyzate the complex formed to pyridoxine
siert. Das erfindungsgemäße Verfahren geht also von Erfindung wird somit Äthyl-2-methyl-3-hydroxy-2
- Methyl - 3 - hydroxy - 4,5 - dicarboxypyridin, das 4,5-pyridindicarboxylat mit Boranaluminiumisoproüblicherweise
als Ichibasäure bezeichnet wird, den 45 pylat in einem Gemisch von Dimethoxyäthan und
Alkylestern der Ichibasäure, dem Ichibasäureanhy- Benzol in innigen Kontakt gebracht und der so erdrid
und Lactonen von 4-Pyridoxinsäure und
5-Pyridoxinsäure aus.sated. The process according to the invention is thus based on the invention is ethyl 2-methyl-3-hydroxy-2-methyl-3-hydroxy-4,5-dicarboxypyridine, 4,5-pyridinedicarboxylate with borane aluminum isopropyl alcohol is commonly referred to as ichibic acid, the 45 pylate in a mixture of dimethoxyethane and alkyl esters of ichibic acid, the Ichibasäureanhy- benzene brought into intimate contact and the so erdrid and lactones of 4-pyridoxic acid and
5-pyridoxinic acid.
Es wurden schon verschiedene Methoden zur Herstellung von Pyridoxin durch Reduktion von 2-Methyl-3-hydroxy-pyridin-4,5-dicarbonsäure oder derenThere have been various methods for the preparation of pyridoxine by reducing 2-methyl-3-hydroxypyridine-4,5-dicarboxylic acid or their
Derivaten vorgeschlagen. So werden nach dem Verfahren der USA.-PatentscHrift 2 590 841 Lithiumaluminiumhydrid, nach demjenigen der USA.-Patentschrift 2 744 114 Lithiumborhydrid, nach demjenigen der britischen Patentschrift 804 236 Dialkylaluminiumhydrid und nach dem in der britischen Patentschrift 839 583 und in J. Amer. Chem. Soc, 80 (1958), S. 6244 bis 6249, beschriebenen VerfahrenDerivatives proposed. Thus, according to the procedure of the USA patent specification 2,590,841 lithium aluminum hydride, after that of U.S. Patent 2,744,114 lithium borohydride, after that British Patent 804,236 dialkyl aluminum hydride and after that in British Patent 839 583 and in J. Amer. Chem. Soc, 80, pp. 6244 to 6249 (1958)
haltene Komplex durch Zugabe von methanolischem Chlorwasserstoff unter Bildung von Pyridoxinhydrochlorid hydrolysiert.held complex by adding methanolic hydrogen chloride with formation of pyridoxine hydrochloride hydrolyzed.
Die folgenden Beispiele, die verschiedene Methoden zur Herstellung von Pyridoxin gemäß der Erfindung zeigen, erläutern die Erfindung.The following examples illustrate various methods for making pyridoxine according to the invention show, explain the invention.
Zu einer Lösung von 2,35 g Äthyl-2-methyl-3-hydroxy-4,5-pyridindicarboxylat in 30 ml Dimethoxyäthan wird eine Lösung von 6,0 g Boranaluminiumisopropylat in 20 ml Benzol zugegeben, und das Gemisch wird 2 Stunden unter einer Stickstoff-Natriumborhydrid zusammen mit Aluminiumchlorid 60 atmosphäre bei 70 bis 75 C erhitzt. 100 ml methaverwendet. Gegenüber diesen bekannten Verfahren nolische 25"/uige Salzsäure wird vorsichtig zugegeben, bietet das erfindungsgemäße Verfahren Vorteile. und das gebildete Methylborat-Methanol-Gemisch Einer dieser Vorteile ist die Tatsache, daß Bor- wird dann durch eine Vigreux-Kolonne destilliert, aluminiumalkylate der erfindungsgemäß verwendeten Ein gleiches Volumen Methanol wird kontinuierlich Art in technischen Anlagen leichter verwendet werden f>5 zu dem Reaktionsgemisch durch einen Tropftrichter können als die bekannten Reduktionsmittel. Ein zugegeben, um das abdestillierte zu ersetzen. Nach anderer Vorteil ist die Möglichkeit, das Pyridoxin Kühlen der Lösung scheiden sich glänzende, farblose unmittelbar aus dem Reaktionsgemisch zu isolieren. Kristalle des Produkts ab, die abfiltriert werden.To a solution of 2.35 g of ethyl 2-methyl-3-hydroxy-4,5-pyridinedicarboxylate in 30 ml of dimethoxyethane, a solution of 6.0 g of boranaluminum isopropylate in 20 ml of benzene is added, and that The mixture is heated under a nitrogen-sodium borohydride together with aluminum chloride 60 atmospheres at 70 to 75 ° C. for 2 hours. 100 ml metha used. Compared to this known process, 25 ″ hydrochloric acid is carefully added, the method according to the invention offers advantages. and the methyl borate-methanol mixture formed One of these advantages is the fact that boron is then distilled through a Vigreux column, aluminum alkoxides of the inventively used. An equal volume of methanol becomes continuous Kind to be used more easily in technical plants f> 5 to the reaction mixture through a dropping funnel can be used as the known reducing agents. One added to replace that which was distilled off. To Another advantage is the possibility of the pyridoxine cooling the solution excreted shiny, colorless to isolate immediately from the reaction mixture. Crystals of the product from which are filtered off.
Diese Kristalle sind reines Pyridoxinhydrochlorid vom Schmelzpunkt 206 bis 2070C; EJ* = 426 bis 282 ηΐμ.These crystals are pure pyridoxine hydrochloride with a melting point of 206 to 207 ° C .; EJ * = 426 to 282 ηΐμ.
Die erste Mutterlaugenfraktion wird im Vakuum zur Trockne eingedampft und der Rückstand in 30 ml 5 2,5 η-Salzsäure gelöst. Die Lösung wird dann mit gasförmigem Chlorwasserstoff bei 00C gesättigt. Das gebildete Aluminiumchloridhydrat wird abfiltriert und das Filtrat zur Trockne eingedampft. Der verbleibende kristalline Rückstand wird mit 4 ml heißem absolutem Äthanol verrieben, abgekühlt und abfiltriert, wobei man farbloses kristallines Pyridoxinhydrochlorid erhält. Diese zweite Fraktion von Pyridoxinhydrochlorid hat einen Schmelzpunkt von 205 C; Ei* = 426 bis 292 ηΐμ.The first mother liquor fraction is evaporated to dryness in vacuo and the residue is dissolved in 30 ml of 5 2.5 η hydrochloric acid. The solution is then saturated with gaseous hydrogen chloride at 0 ° C. The aluminum chloride hydrate formed is filtered off and the filtrate is evaporated to dryness. The remaining crystalline residue is triturated with 4 ml of hot absolute ethanol, cooled and filtered off, giving colorless crystalline pyridoxine hydrochloride. This second fraction of pyridoxine hydrochloride has a melting point of 205 ° C; Ei * = 426 to 292 ηΐμ.
Nach der Arbeitsweise vom Beispiel 1 wird 2-Methyl-3-hydroxy-4,5-dicarboxypyridin, 2-Methyl-3-hydroxy-4,5-pyridindicarboxyanhydrid oder eines der Lactone von 4-Pyridoxinsäure oder 5-Pyridoxinsäure reduziert und hydrolysiert, um Pyridoxinhydrochlorid zu erhalten.Following the procedure of Example 1, 2-methyl-3-hydroxy-4,5-dicarboxypyridine, 2-methyl-3-hydroxy-4,5-pyridinedicarboxy anhydride or one of the lactones of 4-pyridoxinic acid or 5-pyridoxinic acid reduced and hydrolyzed to give pyridoxine hydrochloride.
Nach der Arbeitsweise vom Beispiel 1 wird Äthyl- - methyl - 3 - hydroxy - 4,5 - pyridindicarboxylat mit einer äquivalenten Menge Boranaluminiumcyclohexylat oder Borarialuminiumbenzylat reduziert und dann hydrolysiert, um Pyridinhydrochlorid zu erhalten. Following the procedure of Example 1, ethyl - methyl - 3 - hydroxy - 4,5 - pyridinedicarboxylate is used an equivalent amount of Boraluminiumcyclohexylat or Borarialuminiumbenzylat reduced and then hydrolyzed to obtain pyridine hydrochloride.
Verwendet man in einem der obigen Beispiele eine starke Mineralsäure, wie beispielsweise Schwefelsäure oder Phosphorsäure, an Stelle von Salzsäure, so erhält man das entsprechende Säureadditionssalz, wie beispielsweise das Pyridoxinsulfat oder Pyridoxinphosphat. Use a strong mineral acid such as sulfuric acid in any of the above examples or phosphoric acid, instead of hydrochloric acid, the corresponding acid addition salt is obtained, such as for example pyridoxine sulfate or pyridoxine phosphate.
Claims (6)
H2 - C
H 2
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34711264A | 1964-02-25 | 1964-02-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1301310B true DE1301310B (en) | 1969-08-21 |
Family
ID=23362374
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE1965M0063890 Pending DE1301310B (en) | 1964-02-25 | 1965-01-22 | Process for the preparation of pyridoxine |
Country Status (3)
| Country | Link |
|---|---|
| CH (1) | CH451937A (en) |
| DE (1) | DE1301310B (en) |
| GB (1) | GB1075191A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2590841A (en) * | 1952-04-01 | Manufacture of fykidoxin | ||
| US2744114A (en) * | 1952-05-21 | 1956-05-01 | Lilly Co Eli | Pyridoxine synthesis |
| GB804236A (en) * | 1956-04-07 | 1958-11-12 | Philips Nv | Improvements in or relating to methods of producing adermin (vitamin b) |
| GB839583A (en) * | 1956-12-31 | 1960-06-29 | Pfizer & Co C | Process for preparing a pyridoxine |
-
1965
- 1965-01-22 DE DE1965M0063890 patent/DE1301310B/en active Pending
- 1965-02-08 GB GB536565A patent/GB1075191A/en not_active Expired
- 1965-02-18 CH CH223065A patent/CH451937A/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2590841A (en) * | 1952-04-01 | Manufacture of fykidoxin | ||
| US2744114A (en) * | 1952-05-21 | 1956-05-01 | Lilly Co Eli | Pyridoxine synthesis |
| GB804236A (en) * | 1956-04-07 | 1958-11-12 | Philips Nv | Improvements in or relating to methods of producing adermin (vitamin b) |
| GB839583A (en) * | 1956-12-31 | 1960-06-29 | Pfizer & Co C | Process for preparing a pyridoxine |
Also Published As
| Publication number | Publication date |
|---|---|
| CH451937A (en) | 1968-05-15 |
| GB1075191A (en) | 1967-07-12 |
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