DE102009012954A1 - Preparation of beta-hydroxy-gamma-butyrolactone, useful as a starting material or intermediates for preparing functional materials, medicines and agrochemicals, comprises reducing tetronic acid - Google Patents

Abstract

Preparation of beta -hydroxy-gamma -butyrolactone (I) comprises reducing tetronic acid.

Description

Background of the invention

1. Field of the invention

The The present invention relates to a method of manufacture of β-hydroxy-γ-butyrolactone, which is used as starting material for functional materials, pharmaceutical preparations (Drugs) and agrochemicals is useful.

2. Description of the state of the technique

There are several known processes for the preparation of hydroxylactones such as 4-hydroxy-dihydrofuran-2-one. Typically disclosed U.S. Patent No. 4,968,817 (Patent Document 1) A process for producing 4-hydroxy-dihydrofuran-2-one by reacting glycidol with carbon monoxide in the presence of a noble metal catalyst. However, this method is industrially disadvantageous because the reaction should be carried out at a high pressure of about 3 MPa or higher using poisonous carbon monoxide.

Angew. Chem. Int. Ed., Eng., 5 (1966), 994 (Non-Patent Document 1) discloses a process for producing 4-hydroxy-dihydrofuran-2-one by treating 3-butenoic acid with hydrogen peroxide and formic acid coexisting and further treating the product with hydrochloric acid. PCT International Publication No. WO 98/04543 (Patent Document 2) discloses a process for producing 4-hydroxy-dihydrofuran-2-one by treating a carbohydrate such as lactose with an aqueous hydrogen peroxide under basic conditions, and then carrying out acidification with an acid; and another process for producing 4-hydroxydihydrofuran-2-one by converting 3,4-dihydroxybutanoic acid formed as a result of acidification by the action of acetone in an acetonide (ketal) and treating the ketal with hydrochloric acid.

European patent application with publication no. EP 761663 (A1) (Patent Document 3) discloses a process for producing 4-hydroxy-dihydrofuran-2-one by treating ethyl 4-chloro-3-hydroxybutanoate with hydrochloric acid and neutralizing the product with sodium hydroxide. The international PCT publication WO 99/33817 (Patent Document 4) discloses a process for producing 4-hydroxy-dihydrofuran-2-one by cyanating glycidol, hydrolysis and subsequent lactonization.

These However, processes are all industrially disadvantageous because they are water use as a solvent and distilling off Water takes a lot of time and heat energy and acids or bases used in these processes should be neutralized. It may be possible to use 4-hydroxy-dihydrofuran-2-one extract with an organic solvent. 4-hydroxy-dihydro-furan-2-one However, it is easily soluble in water and this is difficult an efficient extraction with such an organic acid. Accordingly, those in Non-Patent Document 1 and the patent documents 1-3, methods disclosed the target compound not efficiently. In addition, careful handling of the peroxides, those disclosed in Non-Patent Document 1 and Patent Document 1 Processes used and the cyano compounds used in the required in Patent Document 3 are required.

Synlett, 1997, 71 (Non-Patent Document 2) discloses a process for producing 4-hydroxy-dihydrofuran-2-one by thermally treating carnitine. However, this process should use a high boiling solvent such as dimethyl sulfoxide and this hinders isolation of the product.

Japanese Unexamined Patent Application ( JP-A) with the publication no. 2001-302653 (Patent Document 4) discloses a process for producing 4-hydroxy-dihydrofuran-2-one from an epoxy-carboxylic acid or a derivative thereof. The process efficiently synthesizes the target lactone, but the industrial production of the starting material 3,4-epoxybutanoic acid ester has not yet been established. Accordingly, there is a need to provide a process for the preparation of 4-hydroxy-dihydrofuran-2-one using a starting material that is more readily available industrially.

Tetrahedron Letters, 30 (1989), 2513 (Non-Patent Document 3) discloses a process for producing 4-hydroxy-5-ethyldihydrofuran-2-one by treating a 4,4-dimethyl-3,4-epoxypentanoic acid ester with hydrochloric acid. When a 3,4-epoxypentanoic acid ester having no substituent in the 4-position, is used as the starting material, but this process does not give the target lactone, but a 3-hydroxy-4-chlorpentansäureester.

Tetrahedron, 47 (1991) 7171 (Non-Patent Document 4) discloses a process for producing 4-hydroxy-5-ethyldihydrofuran-2-one by treating a 4-ethyl-3,4-epoxypentanoic acid ester with 3% aqueous sulfuric acid solution. However, this method does not give 4-acyloxy-dihydrofuran-2-one which has no substituent at the 5-position because the starting material epoxy-pentanoic acid ester has an epoxy group substituted with an ethyl group. In addition, this method uses a 3% sulfuric acid aqueous solution so that the produced target compound should be extracted from an aqueous layer. However, the target compound is easily soluble in water and thus difficult to extract from such an aqueous layer.

Summary of the invention

Under In these circumstances, it is an object of the present invention, a process for producing β-hydroxy-γ-butyrolactones and in particular, a β-hydroxy-γ-butyrolactone in which the carbon atom attached to the oxygen atom bound to the endocyclic ester group (such as the carbon atom in the 5-position of dihydrofuran-2-one) is unsubstituted.

A Another object of the present invention is to provide a method for to efficiently produce a lactone from tetronic acid.

Yet Another object of the present invention is a method for producing a lactone using such a reducing agent which are separated from the product efficiently can.

Yet Another object of the present invention is a method to provide a lactone in which a catalyst, if used, can be separated from the product efficiently.

To have intensive investigations to solve the tasks the inventors of the present invention found that β-hydroxy-γ-butyrolactone (4-hydroxydihydrofuran-2-one) by the reduction of tetronic acid can be produced. The present invention is based These findings and further investigations have been brought about.

More specifically, according to one embodiment of the present invention, there is provided a process for producing β-hydroxy-γ-butyrolactone (4-hydroxy-dihydrofuran-2-one) represented by the following formula (2):

The method includes the step of reducing tetronic acid represented by the following formula (1):

According to this Process can be β-hydroxy-γ-butyrolactone (4-hydroxy-dihydrofuran-2-one) easily prepared using tetronic acid, which is produced industrially and typically as a commercial one Product is readily available. The product β-hydroxy-γ-butyrolactone (4-Hydroxy-dihydrofuran-2-one) is very useful as it is a lactone is that in which the oxygen atom of the endocyclic Ester group in the lactone ring bonded carbon atom unsubstituted is.

In In a preferred embodiment, hydrogen is used as Reducing agent used. According to this embodiment may be β-hydroxy-γ-butyrolactone (4-hydroxy-dihydrofuran-2-one) be easily isolated.

In a further preferred embodiment, the reduction is carried out in the presence of a cata- tors. In a more preferred embodiment, the catalyst is a solid catalyst. Such a solid catalyst, if used in the reaction, can be easily removed after the reaction and this helps to more efficiently isolate the product β-hydroxy-γ-butyrolactone (4-hydroxy-dihydrofuran-2-one).

These and other objects, features and advantages of the present invention will become apparent from the following detailed description of preferred embodiments emerge clearer. From All numbers in this application are believed to be correct the term "about" is modified.

Description of the preferred embodiments

[Tetronic]

According to one Embodiment of the present invention may be β-hydroxy-γ-butyrolactone (4-hydroxy-dihydrofuran-2-one) by the reduction of tetronic acid getting produced. Tetronic acid is commonly referred to as tautomers before, d. H. the ketone form (1a) and enol form (1b) of the following Formula (1-1). As the term is used herein, "tetronic acid" refers to any of the ketone form (1a), the enol form (1b) and a mixture of these.

[Reducing agent]

Any known or customary reducing agents may be used arbitrarily in the reduction. Exemplary reducing agents include hydrogen (H ₂ ) and sodium borohydride (NaBH ₄ ). Of these, hydrogen is preferably used. The use of hydrogen as the reducing agent enables easy separation of the target compound β-hydroxy-γ-butyrolactone from the residual reducing agent and an oxidized form of the reducing agent after completion of the reaction.

The Amount of reducing agents is not particularly limited and can be selected within commonly used areas become. A reaction can be when using hydrogen as a reducing agent, in an atmosphere from hydrogen gas or in an atmosphere of a mixture of hydrogen gas with an inert gas such as helium or nitrogen gas be performed.

[Catalyst]

In In a preferred embodiment, the reduction takes place of tetronic acid in the presence of one or more catalysts, to produce β-hydroxy-γ-butyrolactone even more efficiently.

The Catalysts can be any of various catalysts which accelerate the reduction of tetronic acid. Exemplary catalysts include noble metal catalysts, which include precious metals such as Pd, Pt, Rh and Ru, and Compounds containing such noble metal elements; and non-noble metal catalysts, which include non-noble metals such as Ni, Fe and Cu, and Compounds containing such metals. Each of these different Catalysts can be used alone or in combination. Of these, catalysts are one or more of Rh, Pd and Ni and metal compounds containing one or more of these Contain metals, preferably. As the term used here "Metal compounds" include oxides and complexes of any kind.

The Reduction can be done in a homogeneous system or in one heterogeneous system using a solid catalyst become. Exemplary solid catalysts include solid ones Noble metal catalysts containing one or more noble metal catalysts on a suitable support such as silica gel, alumina or activated carbon applied; and solid non-noble metal catalysts Non-noble metal catalysts with a higher reduction activity typically as a result of an improvement in shape, such as nickel sponge, and non-noble metal catalysts containing a or more non-noble metals (such as nickel) on a suitable one Carrier applied.

firm Catalysts are preferably used here as catalysts, since such solid catalysts are easily removed from the reaction after the reaction Reaction mixture can be separated, typically through filtration, and this improves the work efficiency.

The Amount of a catalyst is z. For example 0.000001 to 100 parts by weight, preferably about 0.0001 to 10 parts by weight, more preferably about 0.005 to 0.5 parts by weight, and more preferably about 0.001 to 0.5 parts by weight, based on 1 part by weight of tetronic acid. The amount of a catalyst when acting as one on a carrier applied catalyst (a support containing a catalyst carries) refers to the weight which by subtracting the weight of the carrier from the Total weight of the carrier and the applied thereto Catalyst receives.

A Reaction temperature can typically be in accordance with the rate of formation of target lactone and stability of the starting material tetronic acid and of the product (β-hydroxy-γ-butyrolactone) be set appropriately. typically, the reaction temperature can be in the range of -30 ° C to 150 ° C, preferably from -10 ° C to 100 ° C, and more preferably from 15 ° C to 40 ° C be fixed.

The Reaction becomes generally below normal atmospheric pressure or under a pressure (under a load) (eg at a Pressure of about 0.1 to 50 MPa and preferably at a pressure of about 0.1 to 10 MPa). The reaction can also be carried out for a more comfortable handling be carried out reduced pressure.

The Reaction can be in the presence or absence of a solvent be performed, but it is generally in the presence carried out by one or more solvents. Exemplary solvents include ether solvents such as diethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, Dioxane and 1,2-dimethoxyethane; Nitriles such as acetonitrile and benzonitrile; Sulfoxide solvents such as dimethylsulfoxide; Sulfolane like sulfolane; Ester solvents such as methyl acetate, ethyl acetate and butyl acetate; Lactones such as γ-butyrolactone; amide solvent such as dimethylformamide; Alcohol solvents such as methanol, Ethanol, propanol, isopropanol, n-butanol, s-butanol and t-butanol; saturated or unsaturated hydrocarbon solvents such as pentane, hexane, heptane, octane and petroleum ether; halogenated Hydrocarbon solvents such as methylene chloride, chloroform, 1,2-dichloroethane, chlorobenzene and bromobenzene; and high boiling solvents such as polyethylene glycols and silicone oils. Of such solvents become ester solvents, such as acetic acid esters preferably used. Each of these different solvents can be used alone or in combination.

The Amount of solvents is not particularly limited as long as it is such an amount that reaction components soluble or dispersible therein and the cost efficiency and other factors will not be affected. The amount of solvents may, for. For example, about 1 to 100,000 Parts by weight, and preferably about 1 to 10,000 parts by weight, to 100 parts by weight of tetronic acid, the reaction system is supplied.

The Reaction can be according to any system like a discontinuous system, a semi-continuous system or a continuous system. If necessary, the product can be β-hydroxy-γ-butyrolactone by a usual separation and purification process such as separation by neutralization, extraction, distillation, Rectification, molecular distillation, crystallization, recrystallization or column chromatography or any combination be cleaned of these.

The resulting β-hydroxy-γ-butyrolactone can be used as Intermediate in the production of functional materials, pharmaceutical preparations (medicines) and agrochemicals be used. Among the β-hydroxy-γ-butyrolactones becomes β-hydroxy-γ-butyrolactone (4-hydroxy-dihydrofuran-2-one) classified as a lactone in which the to the oxygen atom the endocyclic ester group bonded carbon atom (such as the carbon atom at the 5-position of dihydrofuran-2-one) is unsubstituted is. Accordingly, this compound is as a starting material for the production of highly functional materials as linear polymers without side chain useful.

Examples

The present invention will be explained in more detail below with reference to several examples. It should be noted, however, that these are illustrated by way of example only and never should be construed as limiting the scope of the present invention.

The NMR spectra of the compounds prepared according to the Examples were measured at 500 MHz using a ¹ H NMR system (Bruker Corporation, "AVANCE 500") with tetramethylsilane (TMS) as the internal standard.

Example 1: Preparation of β-hydroxy-γ-butyrolactone by catalysis with a rhodium-alumina catalyst.

In A 50 ml two-necked flask was 0.05 g of a rhodium / alumina catalyst (N.E. Chemcat Corporation, trade name "5% Rh / Alumina"), 9.06 g of ethyl acetate (Wako Pure Chemical Industries, Ltd.) and 1 g Tetronic acid (Tokyo Chemical Industry Co., Ltd.). After purging with nitrogen, it became a hydrogen balloon attached to the flask to a hydrogen atmosphere in the system. After 7.5 hours stirring the mixture at room temperature, the reaction was stopped and the reaction mixture was filtered. The filtrate was concentrated at 40 ° C under reduced pressure Concentrated pressure, thereby yielding 0.83 g of crude 4-hydroxy-dihydrofuran-2-one (the compound of formula (2)) as a liquid.

The ¹ H-NMR spectrum of the crude 4-hydroxy-dihydrofuran-2-one was measured and resulted in the following result.

The target compound 4-hydroxy-dihydrofuran-2-one was obtained in a yield of 72 mol%, with dihydrofuran-2-one (in a yield of 12 mol%) as the major by-product.
¹ H-NMR spectrum of 4-hydroxy-dihydro-furan-2-one (CDCl _3): δ 2.53 (td, J = 1.0, 17.9 Hz, 1H), 2.76 (dd, J = 17.9, 6.1 Hz, 1H), 4.30 (d, J = 10.3 Hz, 1H), 4.42 (dd, J = 10.3, 4.5 Hz, 1H), 4, 6-4.7 (m, 1H).

Example 2: Preparation of β-hydroxy-γ-butyrolactone by catalysis with a palladium-carbon catalyst

raw 4-hydroxy-dihydrofuran-2-one (the compound of formula (2)) as a mixture with tetronic acid by the method of Example 1, except that instead of the rhodium / alumina catalyst 0.105 g of a 10% palladium / carbon catalyst (N.E. Chemcat Corporation, trade name "PE, 50% water content" ("PE, 50% water content ")) was used.

The Yield of 4-hydroxy-dihydrofuran-2-one was 2.1 mol%.

Example 3: Preparation of β-hydroxy-γ-butyrolactone by catalysis with a nickel catalyst

raw 4-hydroxy-dihydrofuran-2-one (the compound of formula (2)) as a mixture with tetronic acid by the method of Example 1, except that instead of the rhodium / alumina catalyst 0.12 g of a nickel sponge catalyst (Kawaken Fine Chemicals Co., Ltd., trade name "NDHT 90-M").

The Yield of 4-hydroxy-dihydrofuran-2-one was 0.40 mol%.

Example 4: Preparation of β-hydroxy-γ-butyrolactone by catalysis with a nickel catalyst

One Nickel catalyst was prepared by introducing 20 ml of water and 4.5 g sodium hydroxide in a 100 ml Erlenmeyer flask, add of 1.00 g of a nickel-aluminum alloy (Kawaken Fine Chemicals Co., Ltd .; ND type), developing the mixture on a hot water bath at 100 ° C for 45 minutes and rinse the reaction mixture five times with water and once with Tetrahydrofuran (THF).

Of the prepared nickel catalyst was combined with THF, wherein 1.2 g of a slurry and the slurry was further combined with 100 mg tetronic acid and 2.0 ml THF, followed by reaction at 80 ° C in a hydrogen atmosphere with 5 MPa for 5 hours. The system was then on Room temperature and normal atmospheric pressure, the reaction mixture was filtered, concentrated and thereby yielded crude 4-hydroxy-dihydrofuran-2-one (the compound of formula (2)) with a conversion of tetronic acid of 90% and one Reaction selectivity of 90%.

Example 5: Preparation of β-hydroxy-γ-butyrolactone by catalysis with a palladium / carbon catalyst

A Mixture of 50 mg tetronic acid and 50 mg of a palladium / carbon catalyst (N. E. Chemcat Corporation) in 2.0 ml of tetrahydrofuran (THF) 5 hours at 50 ° C in a hydrogen atmosphere implemented with 5 MPa. The system was then brought to room temperature and brought to normal atmospheric pressure, the reaction mixture was filtered, concentrated, thereby giving crude 4-hydroxy-dihydrofuran-2-one (the compound of formula (2)) with a conversion of tetronic acid of 50% and a reaction selectivity of 90%.

Although the above description is the preferred embodiments of the present invention should be noted Be that different modifications, modifications and variations possible, without depending on the scope and importance of to deviate from the following claims.

QUOTES INCLUDE IN THE DESCRIPTION

This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.

Cited patent literature

• US 4968817 [0002]
• WO 98/04543 [0003]
• EP 761663 (A1) [0004]
• WO 99/33817 [0004]
• JP 2001-302653 A [0007]

Cited non-patent literature

• - Angew. Chem. Int. Ed., Eng., 5 (1966), 994 [0003]
• - Synlett, 1997, 71 [0006]
• Tetrahedron Letters, 30 (1989), 2513 [0008]
• Tetrahedron, 47 (1991) 7171 [0009]

Claims (4)

A process for producing β-hydroxy-γ-butyrolactone represented by the following formula (2):

the process comprising the step of reducing tetronic acid represented by the following formula (1):

The method of claim 1, wherein the reduction is under Use of hydrogen as a reducing agent becomes. Method according to one of claims 1 and 2, wherein the reduction is carried out in the presence of a catalyst becomes. The method of claim 3, wherein a solid catalyst as the catalyst is used.