DE1620535A1 - Process for the preparation of 2-methyl-3-hydroxypyridines - Google Patents

Description

Process for the preparation of 2-methyl-3-hydroxypyridines The invention relates to a process for the preparation of 2-diethyl-3-hydroxypyridines of the formula wherein R4 is hydroxymethyl, alkoxymethyl or halomethyl.

The process is characterized in that compounds of the formula where R1 is amino or hydroxyl, R2 is hydroxymethyl, alkoxymethyl, aminomethyl or halomethyl and R3 is aminomethyl or hydroxymethyl, with nitrosyl compounds of the formula III) NO - R where R is -O-SO3H or wCl at, whereby the case is excluded, that R1 = hydroxyl, B2 = hydroxymethyl, alkoxymethyl or halomethyl and R3 = hydroxymethyl, is converted and the product obtained is hydrolyzed under acidic conditions.

The compounds prepared according to the invention are valuable Starting materials for the production of pyridoxine, which is known as vitamin B6.

The reduction of the amino group of pyridine derivatives has so far taken place on an industrial scale by diazotization with sodium nitrate and mineral acid, such as Sulfuric acid and hydrochloric acid, with subsequent hydrolysis of the formed Diazonium salt. However, this procedure is suitable for the industrial production of tyridine derivatives not satisfactory, since the aftertreatment is cumbersome and the yield of the desired compound of formula (I) is low. In these known methods evaluate inorganic salts, e.g. B. sodium chloride or sodium sulfate, in large quantities formed in addition to the desired 2-ethyl-3-hydroxypyridine. This requires a cumbersome purification of the desired compound (I), as both this compound as well as the formed salt are easily soluble in water.

It has been found that nitrosyl compounds of formula (III) for the diazotization of the compound (II) are suitable, and that / by using the Nitrosyl compounds with the compound (II) have the above-mentioned disadvantages the known method can turn off. The nitrosyl compounds (III) are thus advantageous for the industrial production of 2-methyl-3-hydroxypyridines (I).

The compound (II) used as a starting material can be used in free Form or in the form of the salt can be used.

In this formula, R1 is an amino group or hydroxyl group, and F is hydroxymethyl aminomethyl, alkoxymethyl, e.g. B. methoxymethyl, ethoxymethyl, Propoxymethyl and butosymethyl, or halomethyl, e.g. Chloromethyl and bromomethyl, and R3 is aminomethyl or hydroxymethyl. Excluded from the procedure according to Invention, however, is the ball that at the same time R1 for hydroxyl, R2 for hydroxymethyl, Alkoxy methyl or halomethyl and R3 represents hydroxymethyl.

To carry out this process, it is therefore necessary that at least one of the radicals R1, R2 and R3 contains an amino group.

Examples of the nitrosyl compound used as another starting material of formula (III) are nitrosyl chloride and itrosylsulfuric acid. The nitrosyl chloride can be used in gas form or in liquid form. The procedure according to Invention can be carried out by treating the starting materials in acidic State and then hydrolyzed the product formed. Appropriate the starting materials are reacted in acidic aqueous solution. The Mitrosyl Compound is based at least in an equimolar amount, preferably in an amount of 1-2 mol used on the amino group or groups of the compound (II). Is preferred a low acidity of the reaction medium. For this purpose are preferred Acids are used which are capable of forming salts with the desired compound (I). For example, the reaction is preferably carried out in aqueous hydrochloric acid solution, when the hydrochloride of the desired compound (I) is to be produced. the Subsequent hydrolysis of the compound formed is preferably carried out in the presence a relatively large amount of water carried out, e.g. B. in the presence of 100 times Amount of water, based on the compound formed.

Example 1 II: a solution of 25.4 g of 2-methyl-3-amino-4-hydroxymethyl 5-aminomethylpyridine hydrochloride in 2 l of water, 19.5 g of nitrosyl chloride are introduced, while the temperature is maintained by cooling at 0-5 ° C. is; completed addition the reaction mixture is kept at 85 ° C. for 15 minutes.

After the hydrolysis is finished we: the ge ical is cooled to 200C, whereupon is filtered in the presence of activated coke. The filtrate is consensated, whereby vei # es crystalline @ -Methyl-3-hyiroxy-4,5-dihyroxymeti, l @ riiinhydrochlorid obtained will. Pure crystals with a melting point of 205.5 ° C. are obtained by recrystallization from water obtain.

Example 2 In a solution of 2-Uethyl-3-ariino-4-chloromethyl-5-aminomethylpyridine hydrochloride In 5 1 what he introduced 26 g of nitrosyl chloride, while the temperature at 85-90 ° C is maintained. After the addition is complete, the mixture is heated for a further 30 minutes. To When the reaction has ended, the reaction mixture is changed to that described in Example 1 Way worked up, with 17,6g2-methyl-3-hydroxy-4,5-dihydroxymethylpyridine hydrochloride with a melting point of 2030C. Example 3 In a solution of 25.4 g of 2-methyl-3-amino-4-methoxymethyl-5-aminomethylpyridine hydrochloride in 3 1st water 39 g of Mitrosyl chloride are introduced, while the temperature is at 0-50C is maintained. After the addition, the reaction mixture is reduced to the in Example 1 described way worked up, with 24.8 g of 2-methyl-3-hydroxy-4-methoxy Methyi-5-hy droxymethylpyrid inhydrocklorid from Yc @ melting point 171 ° C can be obtained Example 4 In a solution, heated to 85 ° C., of 18.2 g of 2-methyl-3-hydroxy-4-methoxymethyl-5-aminomethylpyridine 26 g of hydrosyl chloride are introduced into 2 l of water. After the addition is complete stirred for another 30 minutes. When the reaction has ended, the reaction mixture increases worked up as described in Example 1, with 24.7 g of 2-methyl-3-, hydroxy-4-methoxymethyl-5-hydroxymethylpyridine hydrochloride with a melting point of 173 ° C.

Example 5 To a solution, cooled to 0-50C, of 25.4 g of 2-methyl-3-amino-4-methoxymethyl-5-aminomethylpyrid in hydrochloride in 2 l of water weigh 38 g. g mitrosyl sulfuric acid given. To done In addition, the reaction mixture is kept at 850 ° C. for 15 minutes; After the hydrolysis has ended the mixture is cooled to 200 ° C. and filtered in the presence of 1 g of activated charcoal. The filtrate is adsorbed on a cation exchange resin and washed with 5% aqueous Hydrochloric acid solution eluted. The eluate is condensed, with 20.5 g of 2-methyl-3-hydroxy-4-methoxymethyl-5-hydroxymethylpyridine hydrochloride can be obtained.

Example 6 Nitrosyl chloride is converted into a solution of 20 g at 80.degree 2-methyl-3-hydroxy-4-aminomethyl-5-hydroxymethyl hydrochloride in 1 liter of 0.19N hydrochloric acid solution introduced within 2 hours. After the addition is complete, the mixture is heated for a further 2 hours. After the reaction has ended, the reaction mixture is condensed, whereby 16.7 g of 2-methyl-3-hydroxy-4,5-dihydroxymethylpyridine hydrochloride can be obtained. The yield is 98.2%.

Example 7 Mitrosyl chloride is obtained at 850C within 2.5 hours to a solution of 22.8 g of 2-methyl-3-hydroxy-4,5-dinminomethylpyridine hydrochloride given in 1 1 0, 028N hydrochloric acid discharge. When the addition is complete, it becomes a high of 3 hours heated.

When the reaction has ended, the reaction mixture is condensed and mixed with 100 ml of water. The aqueous solution is in the presence of activated charcoal filtered. The filtrate is condensed, yielding 16.2 g of 2-methyl-3-hydroxy-4,5-dihydroxymethylpyridine hydrochloride can be obtained. The yield is 95.1.

Example 8 To a solution of 20 g of 2-methyl-3-hydroxy-4-aminomethyl-5-hydroxymethylpyridine hydrochloride 1 liter of 0.2N hydrochloric acid solution is added at 8000 t3 g of nitrosyl chloride. After adding of the nitrosyl chloride is heated for 3 hours. After finished The reaction is condensed and dried in the reaction mixture, whereby 2-methyl-3-hydroxy-4,5-dihydroxymethylpyridine hydrochloride is obtained.

Claims (2)

Patent claims 1) Process for the preparation of 2-fdethyl-3-hydroxypyridines of the general formula I. in which R4 denotes a hydroxymethyl, alkoxymethyl or halomethyl group, characterized in that compounds of the general formula II in which R1 is an amino or hydroxyl, R2 is a hydroxymethyl, Alkoxyme thyl, Ami nomethyl! or halomethyl group and R is an aminomethyl or hydroxymethyl group, but at least one of the radicals R1, R2 or R @ is or contains an amino group, with nitrosyl compounds of the general formula III NO - R, in which R is the group -O-SO3H or chlorine atom mean, and the product obtained is hydrolyzed under acidic conditions. 2) Method according to claim 1, characterized in that as Compound of the general formula III nitrosyl chloride is used. n) procedure according to Claim 1, characterized in that the compound of the general formula III uses flitrosylsulfuric acid.