JPH07578B2 - Method for producing 1,3-dihydroxyacetone - Google Patents

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing 1,3-dihydroxyacetone. More specifically, it relates to a method for producing 1,3-dihydroxyacetone from formaldehyde with good productivity.

1,3-Dihydroxyacetone is useful as a raw material for medicines and cosmetics, and as a method for producing it, there has been known a method in which formaldehyde is subjected to an addition reaction in an organic solvent using a thiazolium salt and a base as a catalyst ( Journal of the American Chemical Society
106, 1892 (1984)). There is also known a method in which formaldehyde is subjected to an addition reaction by using a base and a polymer catalyst in which a chlorinated ion of a quaternary thiazolium salt, which is a reaction product of a crosslinked chloromethyl polystyrene and a thiazole compound, is replaced with a cyanide ion. 64
-85944).

However, in the former method, it is extremely difficult to separate the reaction product from the thiazolium salt used as a catalyst. Further, it is extremely difficult to recover the separated thiazolium salt and reuse it, and it cannot be said that the method is suitable for industrial production. In the latter method, it is necessary to use an organic solvent having low solubility of formaldehyde, and the catalyst life cannot be said to be long. In both methods, the thiazole ring 2
It is necessary to generate an anion at the position, and therefore it is essential to use a tertiary amine which is a base. Although there is no description about the addition reaction of formaldehyde, there is also known a method of using a quaternary thiazolium salt as a catalyst for benzoin condensation in a mixed solvent of a phosphate buffer and dimethylsulfoxide (Bioorganic Chem. 12: 206). P. (1984)).

[0004]

DISCLOSURE OF INVENTION Problems to be Solved by the Invention The present inventors have conducted intensive research on a method for producing 1,3-dihydroxyacetone with high productivity by addition reaction of formaldehyde, except for the drawbacks of the above-mentioned production method. The quaternary thiazolium salt or the specific quaternary thiazolium salt bound to a styrene resin is used for addition reaction of formaldehyde hydrate (formalin or formaldehyde aqueous solution) in an alkaline buffer aqueous solution or a mixed solution of an alkaline buffer aqueous solution and an organic solvent. It was found that the desired 1,3-dihydroxyacetone exhibits extremely high selectivity and that the desired 1,3-dihydroxyacetone can be obtained with high productivity, and the application was previously filed as Japanese Patent Application No. 2-230402. However, this method showed very high activity in the initial stage of the reaction, but the activity decreased with time, and was not industrially sufficiently satisfactory.

It was noted that this decrease in activity may be due to the structural change of the thiazolium ring accompanying the exchange of the counter anion of the quaternary thiazolium salt with the so-called hard base anion. Therefore, when a salt having a so-called soft base as a counter anion was introduced into the reaction system, a decrease in catalytic activity was not seen, and extremely high selectivity was exhibited, and the desired 1,3-dihydroxyacetone was industrially produced. The present invention has been reached and the present invention has been reached. That is, an object of the present invention is to produce 1,3-dihydroxyacetone industrially advantageously with a decrease in the activity of the catalyst as small as possible and with a high selectivity.

[0006]

The present invention relates to a method for producing 1,3-dihydroxyacetone by subjecting formaldehyde to an addition reaction in an alkaline buffer to carry out the addition reaction at the 2-position of the thiazole ring bound to the resin. Provided is a method for producing 1,3-dihydroxyacetone, which is carried out in the presence of a quaternary thiazolium salt having no substituent and a salt having a soft base as a counter anion.

The catalyst used in the present invention is a quaternary thiazolium salt having no substituent at the 2-position of the thiazole ring bound to the resin. In the quaternary thiazolium salt catalyst bound to the resin, since the anion generated on the carbon at the 2-position of the thiazole ring catalyzes the addition reaction of formaldehyde, the 2-position of the thiazole ring is not substituted and must be hydrogen. I won't. The quaternary thiazolium salt having no substituent at the 2-position of the thiazole ring may have a substituent at a position other than the 2-position. The substituent on the nitrogen atom is preferably an alkyl group, an alkenyl group, an aralkyl group or the like, and the substituent at a position other than the 2-position is preferably an alkyl group or a hydroxyalkyl group. It may also be a benzothiazolium salt. Examples thereof include 3-ethyl-4-methyl-5- (2-hydroxyethyl) quaternary thiazolium salt and 3-ethylbenzo quaternary thiazolium salt. Preferable examples of the counter anion include chlorine ion, bromine ion, iodine ion, cyanide ion and the like.

The above quaternary thiazolium salt is used in a resin-bound form in order to remarkably enhance the activity of the reaction and facilitate the separation of the catalyst. As the resin used, polyvinyl chloride-based, polyvinyl chloride ether-based, polystyrene-based and the like are preferable in terms of the hydrolysis resistance of the resin, and among them polystyrene that may be crosslinked, polystyrene-based resin such as polymethylstyrene. preferable.

Two of the thiazole rings attached to these resins
A quaternary thiazolium salt having no substituent at the position (hereinafter also referred to as a resin-bonded quaternary thiazolium salt) can be obtained, for example, by reacting chloromethylpolystyrene with a thiazole compound. What was obtained may be obtained by any manufacturing method. The bonding ratio of the quaternary thiazolium salt to the resin is usually in the range of 0.1 to 90% by weight based on the resin. Resin-bound quaternary thiazolium salts are available in the Journal of the A
American Chemical Society, 160, 4829 (1
984), JP-A-64-85944, Journal of
Chinese Chemical Society, 30, 55-58 (1
983), which descriptions are incorporated herein by reference.

Formaldehyde is used by adjusting the concentration of ordinary formalin or paraformaldehyde dissolved in water. The alkaline buffer solution is prepared by dissolving inorganic salts in an aqueous formaldehyde solution or by dissolving inorganic salts in a mixed solution of an aqueous formaldehyde solution and an organic solvent. Prepare an alkaline buffer separately,
It may be mixed with an aqueous formaldehyde solution. Examples of the inorganic salts include phosphates, carbonates, borates, citrates and the like, and the pH values are adjusted by combining them in appropriate amounts.

When used in a mixed system with an organic solvent, examples of the organic solvent include methanol, ethanol, dioxane, tetrahydrofuran, dimethyl sulfoxide, N,
A polar organic solvent that is compatible with water, such as N-dimethylformamide, is preferred because of the relatively high solubility of formaldehyde. The organic solvent is used in a concentration of 0 to 90% by weight, more preferably 0 to 40% by weight, based on water. Regarding the pH value of the buffer solution, by-products such as polyoxymethylene are produced in the acidic region and the selectivity is lowered in the strongly alkaline region. Therefore, the pH is preferably 7.0 to 12.0, more preferably pH 7.0 to 8.0.

The method of the present invention is further characterized in that a salt having a soft base as a counter anion is present in the reaction system. The soft base, electronegativity is small, high polarizability, an easy base is oxidized, RGPearson, Science,
151,172 (1966), bases and trans-Pt.
The scale of the softness of the base obtained from the rate constant of the reaction with (C ₅ H ₅ N) ₂ Cl ₂ means one or more bases. Specifically, chlorine ion, bromine ion, iodine ion, SC
Anions such as N ⁻ , CN ⁻ , NO ₂ ⁻ , SO ₃ ⁻ , C ₆ H ₅ S ^{− and the} like can be mentioned. Preferred salts with these anions as counter anions include sodium chloride, potassium bromide, sodium thiocyanate and the like.

In the present invention, by using a salt having a soft base as a counter anion, the counter anion of the quaternary thiazolium salt is a hard base (base having a softness of base of less than 1) (eg, hydroxyl group). The deactivation of the catalytic activity due to the structural change of the thiazolium ring, which is exchanged by ions, phosphate ions, etc.) is prevented. That is, this has the effect of significantly reducing the decrease in catalyst activity.

The addition reaction of formaldehyde is carried out, for example, by preparing a buffer solution in which formaldehyde is dissolved in an inert gas, adding a resin-bound quaternary thiazolium salt as a catalyst to the buffer solution, and heating at 25 to 50 ° C. with stirring. . The concentration of formaldehyde in the reaction system is 10 to 50.
Weight percent is preferred. It is one of the advantages of the present invention that a concentrated aqueous formaldehyde solution can be used, which improves productivity. When a commonly used organic solvent such as dioxane or dimethyl sulfoxide is used, the formaldehyde concentration cannot be 1% by weight or more.

The addition reaction of formaldehyde can be carried out by adopting a continuous system in which a catalyst is packed in a column and an alkaline buffer solution in which formaldehyde is dissolved is continuously circulated at a predetermined temperature. The amount of the resin-bound quaternary thiazolium salt used is usually about 0.01 to 1 mol as the amount of thiazolium salt with respect to 1 mol of formaldehyde.

After the completion of the reaction, the dissolved inorganic salts are removed by a usual cation and anion exchange resin.
The resin-bound quaternary thiazolium salt can be easily separated by filtration. The solution obtained by separation is concentrated under reduced pressure and the solvent is distilled off to obtain 1,3-dihydroxyacetone. If necessary, it may be purified by recrystallization.

The present invention will be described in more detail based on the following examples. In the following examples,% means% by weight unless otherwise specified. Example 1 In 10 ml of commercially available formalin (formaldehyde content 3.7 g, 123 mmol), sodium dihydrogen phosphate (0.3 g) and disodium hydrogen phosphate (0.3 g) were dissolved, and phosphoric acid containing formaldehyde having a pH of 7.5 was dissolved. A buffer solution was prepared. In a 50 ml capacity reactor equipped with a thermometer, a reflux condenser and a nitrogen gas inlet tube, 0.35 g (0.6 mol) of sodium chloride and 4-methyl-5- (2- Hydroxyethyl) thiazolium chloride (0.3 g, as a thiazolium salt 0.64 mmol) was added, and the mixture was stirred with a magnetic stirrer in a nitrogen gas atmosphere at 75-8.
The reaction was carried out at 0 ° C for 10 hours. Formaldehyde 1 mol
On the other hand, the amount of thiazolium salt was 0.006 mol. After completion of the reaction, 4-methyl-5-bonded to polystyrene
(2-Hydroxyethyl) thiazolium chloride was removed by filtration, the reaction solution was passed through a cation and anion exchange resin to remove disodium hydrogen phosphate and sodium chloride, and then concentrated under reduced pressure to remove water. After vacuum-drying, 1,3-dihydroxyacetone was obtained in a yield of 95.0% (measured by GC chromatography).

Comparative Example 0.3 g of sodium dihydrogen phosphate and 0.3 g of disodium hydrogen phosphate were dissolved in 10 ml of commercially available formalin (formaldehyde content 3.7 g, 123 mmol), and phosphorus containing formaldehyde having a pH of 7.5 was dissolved. An acid buffer was prepared. In a reactor having a capacity of 50 ml equipped with a thermometer, a reflux condenser and a nitrogen gas introducing tube, 4-methyl-5- (2-hydroxyethyl) thiazolium chloride (0.3 g, bound to the above solution and polystyrene) was added. 0.5 mmol) as a thiazolium salt was added, and the mixture was stirred with a magnetic stirrer under a nitrogen gas atmosphere for 75-
The reaction was carried out at 80 ° C for 6 hours. Formaldehyde 1 mol
On the other hand, the ratio of thiazolium salt was 0.006 mol. Up to the reaction time of 4 hours, the yield of 1,3-dihydroxyacetone increased in proportion to the reaction time, but thereafter the yield was constant.

After completion of the reaction, 4-bonded to polystyrene
Methyl-5- (2-hydroxyethyl) thiazolium chloride was removed by filtration, sodium dihydrogen phosphate was removed from the reaction solution through a cation and anion exchange resin, and the mixture was concentrated under reduced pressure to remove water. After vacuum drying, the yield of 13.2% (measured by GC chromatography) 1,3-
Dihydroxyacetone was obtained.

Example 2 To 10 ml of commercially available formalin (formaldehyde content 3.7 g, 123 mmol), 0.006 g of sodium dihydrogen phosphate and 0.064 g of disodium hydrogen phosphate were added.
Were dissolved and a phosphate buffer containing formaldehyde having a pH of 7.7 was prepared. In a reactor of 50 ml capacity equipped with a stirrer, a thermometer, a reflux condenser and a nitrogen gas introduction tube, the above solution and sodium thiocyanate (0.04) were added.
1 g (0.005 mol) and 0.3 g of 4-methyl-5- (2-hydroxyethyl) thiazolium chloride bound to polystyrene (0.64 as thiazolium salt).
mmol) was added, and the mixture was reacted at 75 to 80 ° C. for 5 hours while stirring with a magnetic stirrer under a nitrogen gas atmosphere. The ratio of thiazolium salt to 0.001 mol of formaldehyde was 0.006 mol.

The activity of the catalyst did not decrease during the reaction, but the yield or conversion increased in proportion to the reaction time.
After completion of the reaction, 4-methyl-5-bonded to polystyrene
(2-Hydroxyethyl) thiazolium chloride was removed by filtration, and the reaction solution was passed through a cation and anion exchange resin to remove sodium dihydrogen phosphate, disodium hydrogen phosphate and sodium thiocyanate,
It was filtered under reduced pressure and the water was distilled off. Yield 92.3% after vacuum drying
1,3-dihydroxyacetone (measured by GC chromatography) was obtained.

Example 3 To 10 ml of commercially available formalin (formaldehyde content 3.7 g, 123 mmol), 0.006 g of sodium dihydrogen phosphate and 0.064 of disodium hydrogen phosphate were added.
g was dissolved and a phosphate buffer containing formaldehyde having a pH of 7.7 was prepared. In a reactor of 50 ml capacity equipped with a thermometer, a reflux condenser and a nitrogen gas introduction tube,
The above solution and sodium iodide 0.075 g (0.005 m
ol) and 4-methyl-5-bound to polystyrene
(2-Hydroxyethyl) thiazolium chloride (0.3 g, as a thiazolium salt, 0.64 mmol) was added, and the mixture was reacted at 75-80 ° C for 5 hours while stirring with a magnetic stirrer under a nitrogen gas atmosphere. The ratio of thiazolium salt to 0.001 mol of formaldehyde is 0.00
It was 6 mol. The activity of the catalyst did not decrease during the reaction, and the yield or conversion increased in proportion to the reaction time.

After completion of the reaction, 4-bonded to polystyrene
After removing methyl-5- (2-hydroxyethyl) thiazolium chloride by filtration and passing the reaction solution through a cation and anion exchange resin to remove sodium dihydrogen phosphate, disodium hydrogen phosphate and sodium iodide After concentration under reduced pressure, water was distilled off. Yield 8 after vacuum drying
7.5% (determined by GC) of 1,3-dihydroxyacetone were obtained.

Example 4 To 10 ml of commercially available formalin (formaldehyde content: 3.7 g, 123 mmol) was added sodium carbonate.
1 g and 0.1 g of potassium carbonate were dissolved to prepare a phosphate buffer containing formaldehyde having a pH of 8.0. In a reactor of 50 ml capacity equipped with a thermometer, a reflux condenser and a nitrogen gas introducing tube, 0.05 g (0.0009 mol) of sodium chloride and 4-methyl-5- (2-hydroxy) bonded to polystyrene were added. Ethyl) thiazolium chloride (0.3 g, as a thiazolium salt, 0.64 mmol) was added, and the mixture was reacted under a nitrogen gas atmosphere with a magnetic stirrer at 75 to 80 ° C. for 3 hours. The ratio of thiazolium salt to 0.001 mol of formaldehyde was 0.006 mol. The activity of the catalyst did not decrease during the reaction, and the yield or conversion increased in proportion to the reaction time.

After completion of the reaction, 4-bonded to polystyrene
Methyl-5- (2-hydroxyethyl) thiazolium chloride was removed by filtration, the reaction solution was passed through a cation and anion exchange resin to remove sodium carbonate, potassium carbonate and sodium chloride, and then concentrated under reduced pressure to remove water. I left. After vacuum drying, 1,3-dihydroxyacetone was obtained in a yield of 95.7% (determined by GC chromatography).

[0026]

INDUSTRIAL APPLICABILITY According to the present invention, there is provided a method for producing 1,3-dihydroxyacetone, which is capable of producing 1,3-dihydroxyacetone with water or an aqueous solvent with high selectivity. Further, according to the present invention, there is provided a method for producing 1,3-dihydroxyacetone capable of reacting formaldehyde at a high concentration. The present invention does not substantially lower the catalytic activity of the quaternary thiazolium salt 1,3
An industrially advantageous method for producing dihydroxyacetone is provided.

[Brief description of drawings]

FIG. 1 is a graph illustrating changes over time in reaction activity in Example 1 and Comparative Example 1. The horizontal axis represents reaction time and the vertical axis represents yield.

Claims (3)

[Claims] 1. A method for producing 1,3-dihydroxyacetone by subjecting formaldehyde to an addition reaction in an alkaline buffer to prepare a quaternary thiazolium having no substituent at the 2-position of the thiazole ring bonded to the resin. A method for producing 1,3-dihydroxyacetone, which is carried out in the presence of a salt and a salt having a soft base as a counter anion. 2. The pH of the alkaline buffer solution is about 7.0 to 8.0.
The method for producing 1,3-dihydroxyacetone according to claim 1, wherein 3. The method for producing 1,3-dihydroxyacetone according to claim 1, wherein the alkaline buffer solution is an aqueous solution or a mixed solution of an organic solvent and water.