JPH06748B2 - Process for producing pyridine methanol - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing pyridinemethanol or a salt thereof from cyanopyridine. More specifically, it relates to a method for producing 2- or 4-cyanopyridine methanol or a salt thereof by subjecting 2- or 4-cyanopyridine to catalytic hydrogen reduction in an acidic aqueous solution in the presence of a noble metal hydrogenation catalyst.

[Problems to be Solved by Prior Art and Invention] Pyridinemethanol is useful because it is used as a pharmaceutical intermediate. Heretofore, a method of hydrolyzing α-acetoxymethylpyridine has been known as a production method thereof. (O. Bu
llitt, J. Am.chem. Soc. 76 1370 (1954)).

This uses α-picoline as a starting material, makes it into 2-picoline-N-oxide with hydrogen peroxide, and then reacts with acetic anhydride to give 2- (α-acetoxymethyl) pyridine,
The production of 2-pyridinemethanol by hydrolysis requires a long process, which is not an industrially advantageous production method.

[Means for Solving Problems] As a result of intensive studies conducted by the present inventors in view of the above-mentioned circumstances, as a result, 2- or 4-cyanopyridine was subjected to catalytic hydrogenation in an acidic aqueous solution in the presence of a precious metal hydrogenation catalyst. By reducing, 2- or 4-pyridinemethanol (hereinafter referred to as pyridinemethanol) or a salt thereof can be easily and easily carried out in a short step.
We have found a method for producing the product in good yield. Moreover, 2- or 4-cyanopyridine (hereinafter referred to as cyanopyridine) is easily obtained by ammoxidation of α- or γ-picoline.

[Examples] Examples of the noble metal hydrogenation catalyst used in the present invention include commonly used noble metal hydrogenation catalysts. Specific examples thereof include alumina, diatomaceous earth, clay and activated carbon, and a palladium content of 0.2 to 20. Examples include a palladium catalyst in which palladium is supported so that the content of the catalyst is% (% by weight, the same applies below).

The amount of the noble metal hydrogenation catalyst used is preferably in the range of 0.1 to 20% with respect to cyanopyridine, from the viewpoint of reaction efficiency, catalyst efficiency and the like.

Examples of the acidic aqueous solution used in the present invention include, but are not limited to, those obtained by diluting hydrochloric acid, sulfuric acid and the like with water. The amount of acid used as the acidic aqueous solution is
The range of 1 to 10 times the molar amount of cyanopyridine is preferable, and the amount of water used is preferably the range of 0.5 to 10 times by weight the acid. If the amount of the acid used as the acidic aqueous solution is less than 1-fold mole, hydrogen reduction is difficult to proceed and the yield tends to be poor. The amount of the neutralizing agent used for the separation is increased, and a large amount of an inorganic salt is generated by the neutralization, which makes the separation process of pyridinemethanol complicated, which is not preferable.

In the present invention, cyanopyridine is catalytically hydrogen-reduced in an acidic aqueous solution, but as the reaction temperature, cyanopyridine is not hydrolyzed in an acidic aqueous solution, and the productivity is good, that is, 100 ° C or lower is preferable. More preferably, it is 40 to 70 ° C., and the reaction pressure may be atmospheric pressure or higher, but the hydrogen partial pressure is preferably in the range of atmospheric pressure to 100 atm in view of reaction rate and ease of operation. Under such reaction conditions, the reaction is usually completed in 1 to 5 hours.

After removing the hydrogenation catalyst from the reaction solution containing the reaction product, a pyridinemethanolic acid addition salt, by filtration, the filtrate is adjusted to about pH 2 with alkali, water is distilled off, and the mixture is extracted with a suitable organic solvent. When the extract is concentrated and cooled, pyridine methanol salt is obtained. Alternatively, the filtrate may be made alkaline and then extracted with an organic solvent, and the obtained oil amount may be distilled to obtain pyridinemethanol.

According to the production method of the present invention, cyanopyridine can be easily obtained in a short process in a short process using cyanopyridine as a starting material.

Next, the production method of the present invention will be explained based on examples, but the present invention is not limited thereto.

Example 1 A magnetic stirring type autoclave having a volume of 3 was charged with 312 g of 2-cyanopyridine, 450 g of concentrated sulfuric acid, 630 g of water and 3 g of 5% Pd-carbon catalyst, and hydrogen was introduced thereinto and reacted at 5 atm and 30 ° C. As the hydrogen pressure decreased as the reaction proceeded, hydrogen was added successively. After reacting for 2 hours, the absorption of hydrogen disappeared and the reaction was completed.

The obtained reaction product was filtered to remove the catalyst by filtration, the filtrate was neutralized with caustic soda, and then extracted with butanol. After that, the obtained oil layer was distilled to collect a fraction of bp165 ° C. (100 mmHg), and 284 g of 2-pyridinemethanol having a GC purity of 99.8% (yield 86.9%) was obtained. In addition, 24.3 g of 2-aminomethylpyridine (yield 7.5%) was obtained as a by-product.

Example 2 A magnetic stirring type autoclave having a volume of 3 was charged with 390 g of 4-cyanopyridine, 564 g of concentrated sulfuric acid, 846 g of water and 31.2 g of 5% Pd-carbon catalyst, and hydrogen was introduced thereinto at 2 atm and 60 atm.
The reaction was carried out at ° C. As the hydrogen pressure decreased as the reaction proceeded, hydrogen was added successively. After reacting for 6.5 hours, the absorption of hydrogen disappeared and the reaction was completed. Then, the same treatment as in Example 1 was carried out. 4-pyridinemethanol 36
9 g (yield 90.3%) and 4-aminomethylpyridine 26.0
g (yield 6.4%) was obtained.

Example 3 A magnetic stirring autoclave having a volume of 3 was charged with 312 g of 4-cyanopyridine, 450 g of concentrated sulfuric acid, 1000 g of water and 3 g of 5% Pd-carbon catalyst, and hydrogen was introduced into the autoclave at 5 atm.
The reaction was carried out at ° C. As the hydrogen pressure decreased as the reaction proceeded, hydrogen was added successively. After reacting for 3 hours, the absorption of hydrogen disappeared and the reaction was completed. Hereinafter, Example 1
When treated in the same manner as in 4-pyridinemethanol 276
g (yield 84.4%) and 4-aminomethylpyridine 18 g
(Yield 5.6%) was obtained.

Example 4 A magnetic stirring autoclave having a volume of 3 was charged with 312 g of 2-cyanopyridine, 450 g of concentrated sulfuric acid, 1000 g of water and 3 g of 5% Pd-carbon catalyst, and hydrogen was introduced into the autoclave and reacted at 2 atm and 60 ° C. As the hydrogen pressure decreased as the reaction proceeded, hydrogen was added successively. After reacting for 2 hours, the absorption of hydrogen disappeared and the reaction was completed. Thereafter, the same treatment as in Example 1 was carried out and 292 g of 2-pyridinemethanol
(Yield 89.3%) and 2-aminomethylpyridine 18g (yield 5.5%) were obtained.

[Effect of the Invention] According to the production method of the present invention, cyanopyridine can be easily obtained in a short process in a short process using cyanopyridine as a starting material.

Claims (3)

[Claims] 1. A process for producing 2- or 4-pyridinemethanol or a salt thereof, which comprises catalytically reducing 2- or 4-cyanopyridine in an acidic aqueous solution in the presence of a precious metal hydrogenation catalyst. 2. The production method according to claim 1, wherein the reaction temperature is 40 to 70 ° C. 3. The method according to claim 1, wherein the noble metal hydrogen catalyst is a palladium catalyst.