JPH0649020A - Production of 2-hydroxy-4-methylthiobutanoic acid - Google Patents

Abstract

PURPOSE:To efficiently produce 2-hydroxy-4-methylthiobutanoic acid without generating a large amount of wastes at a low cost. CONSTITUTION:2-Hydroxy-4-methylthiobutyronitrile is converted through hydration to 2-hydroxy-4-methylthiobutanamide and methyl formate is reacted therewith to obtain methyl 2-hydroxy-4-methylthiobutanoate and formamide. The above-mentioned methyl 2-hydroxy-4-methylthiobutanoate is hydrolyzed to produce 2-hydroxy-4-methylthiobutanoic acid and methanol. Since sulfuric acid is not used as a reactant, a large amount of ammonium sulfate is not discharged. Each of formaldehyde and methanol as the by-products can be used as the raw material.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing 2-hydroxy-4-methylthiobutanoic acid which is useful as a feed additive and the like.

[0002]

2. Prior Art and Problems to be Solved by the Invention 2-
As a method for producing hydroxy-4-methylthiobutanoic acid,
2 from acrolein, methanethiol and hydrogen cyanide
It is known to prepare -hydroxy-4-methylthiobutyronitrile and obtain it by hydrating this 2-hydroxy-4-methylthiobutyronitrile in the presence of excess sulfuric acid. This method is industrially used because the reaction is relatively easy and the yield is high.

However, in the above method, a large amount of waste sulfuric acid and ammonium sulfate are discharged in the reaction step. Therefore, these treatment steps are required, and a lot of energy is required, which increases the production cost of 2-hydroxy-4-methylthiobutanoic acid. Further, it is not preferable to discharge a large amount of ammonium sulfate and other sulfates to the natural world from the viewpoint of environmental protection.

Therefore, it is an object of the present invention to provide an efficient and inexpensive method for producing 2-hydroxy-4-methylthiobutanoic acid without enormous waste.

The following techniques are known as techniques relevant to the present invention. That is, Japanese Patent Publication No. 46-79
No. 25 publication discloses that 2-acrolein cyanhydrin
A method of making hydroxy-4-methylthiobutyronitrile is disclosed. JP-B-62-28943 discloses a method for producing a carboxylic acid ester by reacting a formic acid ester with a carboxylic acid amide.
Further, Japanese Patent Application Laid-Open No. 1-290653 discloses a method for producing methyl methacrylate using acetone and methyl formate as raw materials. Furthermore, JP-A-2-2358
Japanese Patent Publication No. 46 discloses a method for producing hydrogen formate by dehydrogenating methanol. However, in these documents, 2-hydroxy-4-methylthiobutyronitrile is hydrated to give 2-hydroxy-4-methylthiobutanamide, and then methyl formate is allowed to act thereon to give 2-hydroxy-4-methylthiobutanoic acid. There is no description of a method for producing 2-hydroxy-4-methylthiobutanoic acid by converting it to methyl and further hydrolyzing it.

[0006]

In order to achieve the above-mentioned object, the present inventor has
As a result of diligent study, 2-hydroxy-4-methylthiobutyronitrile was hydrated to give 2-hydroxy-4-methylthiobutanamide, which was then reacted with methyl formate to give 2
By using methyl 4-hydroxy-4-methylthiobutanoate and subjecting it to a hydrolysis reaction, by-products can be reused and substantially no sulfuric acid is used, so that a large amount of waste is not generated and extremely efficient. It was found that 2-hydroxy-4-methylthiobutanoic acid was obtained in
The present invention has been completed.

That is, the present invention provides (1) a first step of hydrating 2-hydroxy-4-methylthiobutyronitrile to produce 2-hydroxy-4-methylthiobutanamide, (2) the first step 2-hydroxy-obtained in the step of
A second step of producing methyl 2-hydroxy-4-methylthiobutanoate and formamide from 4-methylthiobutanamide and methyl formate, and (3) 2-hydroxy-4-methylthiobutanoic acid obtained in the second step Provided is a method for producing 2-hydroxy-4-methylthiobutanoic acid, which comprises a third step of hydrolyzing methyl to produce 2-hydroxy-4-methylthiobutanoic acid and methanol.

The reaction process formula in the method of the present invention is shown, for example, as follows.

[0009]

[Chemical 1] 2-Hydroxy-4-methylthiobutyronitrile used as a raw material in the first step of the above reaction scheme can be produced from hydrogen cyanide, acrolein and methanethiol by a conventional method.

For example, acrolein and methanethiol are reacted in the presence of a catalyst to give 3-methylthiopropionaldehyde. Examples of the catalyst include alkali metal alkoxides such as sodium methoxide; copper acetate,
Acetic acid salts such as cobalt acetate; organic bases such as pyridine, piperidine, triethylamine and the like.

Then, the obtained 3-methylthiopropionaldehyde is treated with hydrogen cyanide in the presence of a catalyst to easily and highly yield 2-hydroxy-.
4-Methylthiobutyronitrile can be obtained. As a catalyst, an alkali metal hydroxide such as sodium hydroxide; an alkali metal carbonate such as sodium carbonate; an alkali metal hydrogen carbonate such as sodium hydrogen carbonate; an alkali metal sulfite such as sodium sulfite; sodium hydrogen sulfite. Examples thereof include bisulfites of alkali metals; organic bases such as pyridine and triethylamine.

Alternatively, 2-hydroxy-4-methylthiobutyronitrile can be obtained by reacting acrolein with hydrogen cyanide to give acrolein cyanohydrin and then reacting with methanethiol. Furthermore, hydrogen cyanide, acrolein and methanethiol can be reacted in the presence of a catalyst such as ammonium carbonate to produce the 2-hydroxy-4-methylthiobutyronitrile in one step.

The hydration reaction in the first step is 2-
It can be carried out by reacting hydroxy-4-methylthiobutyronitrile with water in the presence of a catalyst.

As the catalyst, a catalyst effective for hydration of nitriles, for example, strong acid such as sulfuric acid; weakly basic substance such as alkali metal salt or alkaline earth metal salt of weak acid; manganese, copper, nickel, etc. And the oxides of these metals. Examples of the weakly basic substance include alkali metal salts of boric acid such as sodium tetraborate, potassium tetraborate, sodium metaborate and potassium metaborate; alkaline earth metal salts of boric acid such as magnesium orthoborate; Alkali metal salts of phosphoric acid such as lithium phosphate, sodium phosphate and potassium phosphate; alkaline earth metal salts of phosphoric acid such as magnesium phosphate and calcium phosphate; alkali metal salts of silicic acid such as sodium silicate; silicic acid Examples thereof include alkaline earth metal salts of silicic acid such as calcium; alkali metal salts of carbonic acid such as sodium carbonate, potassium carbonate and sodium hydrogen carbonate; alkaline earth metal salts of carbonic acid such as magnesium carbonate and calcium carbonate. Among these, weakly basic substances such as alkali metal salts of boric acid such as sodium tetraborate and metal oxides such as manganese oxide are preferably used. Also, even if sulfuric acid is used, the amount used may be extremely small,
Since ammonium sulfate is not substantially formed, it is extremely advantageous industrially.

In the hydration reaction, the amount of water used is not particularly limited, but is usually 0.1 to 300 mol, relative to 1 mol of 2-hydroxy-4-methylthiobutyronitrile.
It is preferably about 1 to 150 mol. Further, in order to allow the reaction to proceed smoothly, a water-soluble organic solvent such as acetone or methanol can be added to the system.

The reaction temperature is usually 20 to 150 ° C, preferably 40 to 120 ° C. The reaction time varies depending on the catalyst used and the reaction temperature, but is usually about 0.4 to 12 hours. If the reaction temperature is too high or the reaction time is too long, a part of the produced 2-hydroxy-4-methylthiobutanamide further reacts with water to give 2-hydroxy-4.
-Methylthiobutanoic acid is changed, or a polymer is by-produced, and the yield is apt to decrease.

The reaction mixture may be used as it is in the second step, or if necessary, it may be subjected to a commonly used separation means to give the product 2-hydroxy-.
4-methylthiobutanamide can also be separated and recovered. The obtained 2-hydroxy-4-methylthiobutanamide is subjected to the second step.

2-hydroxy-4- in the second step
The reaction of methylthiobutanamide and methyl formate may be carried out without a catalyst, for example, by heating at about 100 to 300 ° C., but it is usually carried out in the presence of a catalyst.

Examples of the catalyst include mineral acids such as hydrochloric acid, sulfuric acid and nitric acid; alkalis such as sodium hydroxide; metal salts such as copper acetate, manganese naphthenate, aluminum chloride, lead nitrate and iron acetylacetonate; sodium methoxide. ,
Examples include metal alkoxides such as sodium ethoxide, sodium butoxide, titanium tetraisopropoxide, titanium tetrabutoxide, and aluminum tetraisopropoxide; solid acids such as silica, zeolite, and solid phosphoric acid. Of these, metal salts such as copper acetate and metal alkoxides such as sodium methoxide are frequently used.

Since the reaction between the 2-hydroxy-4-methylthiobutanamide and methyl formate is an equilibrium reaction,
In order to obtain methyl 2-hydroxy-4-methylthiobutanoate in a high yield, it is preferable to use methyl formate in a theoretical amount or more, particularly 1 to 20 times the theoretical amount, and particularly about 1 to 8 times the theoretical amount. Methyl formate may be used as a solvent.

The above reaction may be carried out without a solvent, but it is preferably carried out in the presence of a solvent in order to allow the reaction to proceed smoothly. The solvent is not particularly limited as long as it is inert to the reaction, and examples thereof include aromatic hydrocarbons such as benzene, toluene, xylene, and ethylbenzene; aliphatic hydrocarbons such as pentane, hexane, heptane, and octane. Alicyclic hydrocarbons such as cyclohexane and methylcyclohexane; acetone, methanol and the like can be used. Of these, solvents that readily dissolve the reaction components, such as methanol and acetone, especially methanol, are often used.

The reaction temperature varies depending on the kind and amount of the catalyst used, but it is usually 0 to 250 ° C., preferably 20 to
It is about 100 ° C. The reaction time can be appropriately selected depending on the reaction rate, but is usually about 0.1 to 6 hours.

By subjecting the reaction mixture to a commonly used separation means, the product methyl 2-hydroxy-4-methylthiobutanoate, formamide and unreacted starting materials can be separated and recovered. Normal,
It is possible to separate and collect by simple separation means such as distillation.

The methyl 2-hydroxy-4-methylthiobutanoate is subjected to the next third step, and unreacted methyl formate or the like can be recycled as a raw material for the second step.

In a preferred embodiment of the present invention, formamide by-produced in the second step is dehydrated and converted into hydrogen cyanide, which is used as a raw material for producing 2-hydroxy-4-methylthiobutyronitrile used in the first step. .

The formamide dehydration reaction is carried out by a dehydration catalyst such as alumina, silica-alumina, iron-silica,
It can be carried out by a gas phase catalytic reaction in the presence of a conventional solid catalyst such as iron phosphate and aluminum phosphate. The reaction temperature is usually 200 to 600 ° C., preferably 300 to 5
It is about 50 ° C. The reaction proceeds almost quantitatively.

2-Hydroxy-in the third step
The hydrolysis reaction of methyl 4-methylthiobutanoate can be carried out by an alkali hydrolysis method, but is preferably carried out by an acid hydrolysis method using an acidic catalyst. According to the acid hydrolysis method, not only is waste such as salt hardly discharged, but side reactions such as polymerization and dehydration reaction are significantly suppressed.

Examples of the acidic catalyst include mineral acids such as sulfuric acid and hydrochloric acid; sulfonic acids such as benzenesulfonic acid, p-toluenesulfonic acid and naphthalenesulfonic acid; and cation exchange resins. Among these, a cation exchange resin, particularly a strongly acidic cation exchange resin, particularly a porous strongly acidic cation exchange resin, which facilitates separation and recovery of the catalyst, is preferably used. As the porous strong acid cation exchange resin, Amberlyst 15, Amberlite 200 (above, manufactured by Rohm and Haas), Diaion HP
K [manufactured by Mitsubishi Kasei Co., Ltd.] and the like.

Since the above hydrolysis reaction is an equilibrium reaction,
In order to obtain 2-hydroxy-4-methylthiobutanoic acid in a high yield, the amount of water used is not less than the theoretical amount, particularly 1 to 1
It is preferably about 00 times.

The reaction temperature varies depending on the kind and amount of the catalyst used, but is usually 0 to 100 ° C., preferably 20 to 10
The temperature is 0 ° C, more preferably about 50 to 100 ° C.
The reaction time can be appropriately selected according to the reaction rate, but is usually about 0.5 to 12 hours. The reaction proceeds almost quantitatively.

After the completion of the reaction, the reaction mixture is subjected to a commonly used separation means, if necessary, to separate and collect the target compound, 2-hydroxy-4-methylthiobutanoic acid.

In a preferred embodiment of the present invention, methanol produced as a by-product in the third step is converted to methyl formate by a dehydrogenation reaction or a carbonylation reaction with carbon monoxide, and used as a raw material component in the second step. To do.

The methanol dehydrogenation reaction can be carried out by a gas phase catalytic reaction in the presence of a dehydrogenation catalyst, for example, a solid catalyst such as copper oxide-zinc oxide-aluminum oxide or copper chromite. The reaction temperature is usually 100 to 5
The temperature is 00 ° C, preferably about 100 to 400 ° C.

The carbonylation reaction of methanol is preferably carried out in the presence of a catalyst such as a metal alkoxide.

As described above, in the method of the present invention, since sulfuric acid is not used as a reaction component, a large amount of waste sulfuric acid or ammonium sulfate is not discharged, and these treatment steps are unnecessary.
Formamide produced as a by-product in the second step of the present invention is used as a raw material for producing 2-hydroxy-4-methylthiobutyronitrile used in the first step, and methanol produced as a by-product in the third step is Since it can be used as a raw material for producing methyl formate used in the second step, carbon and nitrogen yields are high, and 2-hydroxy-4-methylthiobutanoic acid as a target compound can be produced very efficiently.

[0036]

According to the method of the present invention, since sulfuric acid is not used as a reaction component, a large amount of ammonium sulfate is not produced as a by-product. In addition, the by-product generated in each step can be used as a reaction raw material, so that the target compound is extremely efficiently used.
Hydroxy-4-methylthiobutanoic acid can be prepared.

[0037]

The present invention will be described in more detail based on the following examples, but the invention is not intended to be limited by these examples.

Example [Production of 2-hydroxy-4-methylthiobutyronitrile] A flask having an internal volume of 2 liter equipped with a stirrer and a thermometer was charged with 280 g of acrolein, 1 g of hydroquinone and 2.2 g of copper acetate and reacted. While maintaining the temperature at 20 ° C., 280 g of methanethiol was added dropwise over 1 hour with stirring. After continuing stirring for further 1 hour, unreacted methanethiol was distilled out of the system under reduced pressure to obtain 464 g of 3-methylthiopropionaldehyde (yield 88.5).
%).

Then, a 2-liter flask having an internal volume equipped with a stirrer, a thermometer and a dropping funnel was charged with 208 g of 3-methylthiopropionaldehyde obtained in the above reaction, 800 g of methanol and 0.05 g of sodium hydroxide, and the reaction was carried out. While maintaining the temperature at 20 ° C., 59.5 g of hydrogen cyanide was added dropwise over 20 minutes with stirring. Furthermore, 2
After continuing stirring at 0 ° C. for 2 hours, a 50% sulfuric acid aqueous solution was added to the reaction mixture to adjust the pH to 3. Unreacted hydrogen cyanide was distilled off under reduced pressure to obtain 255 g of 2-hydroxy-4-methylthiobutyronitrile (yield 96.1%).

[Production of 2-hydroxy-4-methylthiobutanamide (first step) (1)] Stirrer, thermometer,
In a flask with an internal volume of 2 liter equipped with a reflux condenser, 197 g of 2-hydroxy-4-methylthiobutyronitrile obtained in the above step, 450 g of water, 150 g of acetone
And 65 g of manganese dioxide were charged, and the mixture was kept at 60 ° C. for 6 hours,
The reaction was carried out with stirring.

After cooling the reaction mixture, the catalyst was separated off by suction filtration. The filtrate was concentrated under reduced pressure and recrystallized from acetone to obtain 199 g of 2-hydroxy-4-methylthiobutanamide (yield 89.0%).
Melting point: 98 ° C.

[Production of 2-hydroxy-4-methylthiobutanamide (first step) (2)] Stirrer, thermometer,
A flask having an internal volume of 2 liter equipped with a reflux condenser was charged with 49.3 g of 2-hydroxy-4-methylthiobutyronitrile obtained in the above step, 750 g of water and 15 g of sodium tetraborate, and 2 The reaction was allowed to stir for hours. The reaction mixture was concentrated under reduced pressure and recrystallized from acetone to obtain 44.2 g of 2-hydroxy-4-methylthiobutanamide (yield 79.2%). Melting point: 98.5 ° C.

[Production of methyl 2-hydroxy-4-methylthiobutanoate (second step)] In an autoclave equipped with a stirrer, 224 g of 2-hydroxy-4-methylthiobutanamide obtained in the previous step and 450 g of methyl formate were added. , 240 g of methanol and 1.2 g of sodium methoxide were charged and reacted at 60 ° C. for 2 hours with stirring.

As a result of analyzing the reaction mixture, the conversion rate of 2-hydroxy-4-methylthiobutanamide was 64%, and methyl 2-hydroxy-4-methylthiobutanoate based on 2-hydroxy-4-methylthiobutanamide. Selectivity of 91.5%, formamide selectivity of 86.4%
Met.

After neutralizing sodium methoxide in the reaction mixture with hydrochloric acid, it was distilled by a conventional method to give 2-hydroxy-
141 g of methyl 4-methylthiobutanoate and 35.3 g of formamide were obtained.

[Production of 2-hydroxy-4-methylthiobutanoic acid (third step)] A 2-liter flask equipped with a stirrer, a thermometer and a distilling tube was charged with 2-hydroxy-obtained in the previous step. 131 g of methyl 4-methylthiobutanoate, 432 g of water and 8 g of Amberlyst 15 (manufactured by Rohm and Haas Co.) were charged and reacted at a reaction temperature of 95 ° C. for 5 hours while distilling off by-produced methanol. The amount of methanol distilled off was 30.2 g.

As a result of analyzing the reaction mixture and the distillate,
The conversion rate of methyl 2-hydroxy-4-methylthiobutanoate is 98.8%, and the selectivities of 2-hydroxy-4-methylthiobutanoic acid and methanol are each 97.1.
% And 98.8%.

After the catalyst was filtered off from the reaction mixture, the filtrate was concentrated under reduced pressure to obtain 127 g of 88% by weight aqueous solution of 2-hydroxy-4-methylthiobutanoic acid (112 g).

[Production of hydrogen cyanide by dehydration of formamide] Reaction tube made of stainless steel (inner diameter 28 mm, length 3)
0 cm), alumina catalyst (N-612, manufactured by JGC Chemicals)
50 g was charged, and at a reaction temperature of 500 ° C., formamide by-produced in the process for producing methyl 2-hydroxy-4-methylthiobutanoate and nitrogen for dilution were each added at 0.67
It was fed at a rate of 50 g / min. The reaction product gas was bubbled through water to absorb hydrogen cyanide.

As a result of analyzing the absorption liquid, the conversion of formamide was 97.4% and the selectivity of hydrogen cyanide was 93.3%.
Met.

Hydrogen cyanide was separated and recovered from this absorbing solution by a conventional method and used for the production of 2-hydroxy-4-methylthiobutyronitrile.

[Production of methyl formate from methanol] 210 g of copper nitrate was dissolved in 400 g of water and heated to 70 ° C. Separately, dissolve 23 g of ammonium chromate in 100 g of water and
The solution was heated to 0 ° C., and the copper nitrate aqueous solution was added while stirring. Furthermore, an aqueous ammonia solution is added to this mixed solution,
The pH was adjusted to 9.5. The formed precipitate was filtered, washed thoroughly with water, dried at 90 ° C. for 24 hours, then 450
Baked at ° C. The obtained powder is 3 mm in diameter x 3 mm in length
Was molded into a cylindrical shape to prepare a catalyst.

50 ml of the above catalyst was filled in a stainless steel reaction tube (inner diameter 28 mm, length 30 cm) and the temperature was adjusted to 200
Hydrogen gas was supplied at a space velocity of 5000 / hour at 0 ° C., and reduction treatment was performed for 8 hours.

After reducing the catalyst, the methanol obtained in the step of producing 2-hydroxy-4-methylthiobutanoic acid was supplied at a temperature of 180 ° C. and a space velocity of 2500 / hour.

As a result of analyzing the reaction product gas, the conversion of methanol was 36.4% and the selectivity of methyl formate was 91.0.
%Met.

Methyl formate was separated and recovered by a conventional method, and
It was used as a raw material for the production of methyl hydroxy-4-methylthiobutanoate.

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Claims (3)

[Claims] 1. A first step of hydrating 2-hydroxy-4-methylthiobutyronitrile to produce 2-hydroxy-4-methylthiobutanamide, (2) the first step
The second step of producing methyl 2-hydroxy-4-methylthiobutanoate and formamide from 2-hydroxy-4-methylthiobutanamide and methyl formate obtained in the step of (3), and (3) obtained in the second step Hydrolyze methyl 2-hydroxy-4-methylthiobutanoate to give 2
-A method for producing 2-hydroxy-4-methylthiobutanoic acid, which comprises a third step of producing hydroxy-4-methylthiobutanoic acid and methanol. 2. Use of hydrogen cyanide, acrolein and methanethiol as reaction components in the first step 2-
2-Hydroxy-4-hydroxy-4 according to claim 1, comprising a step of producing hydroxy-4-methylthiobutyronitrile, wherein hydrogen cyanide produced by a dehydration reaction of formamide obtained in the second step is used as said hydrogen cyanide.
Method for producing methylthiobutanoic acid. 3. The production of 2-hydroxy-4-methylthiobutanoic acid according to claim 1, wherein the methanol obtained in the third step is converted into methyl formate and the obtained methyl formate is used in the second step. Law.