JP2009256316A - METHOD FOR PRODUCING beta-HYDROXY-gamma-BUTYROLACTONE - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for easily, efficiently and economically producing a lactone wherein the carbon atom bonding to an oxygen atom in the ring ester group (e.g. the 5-position carbon atom of dihydrofuran-2-one) in the lactone ring is unsubstituted, and useful as a raw material for e.g. an intermediate of functional materials, pharmaceuticals and agrochemicals. <P>SOLUTION: The β-hydroxy-γ-butyrolactone (4-hydroxy-dihydrofuran-2-one) is produced by reducing tetronic acid according to the chemical formula (A). Hydrogen can be used as a preferable reducing agent, and the reaction is preferably carried out in the presence of a reduction catalyst such as a solid catalyst. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a method for producing β-hydroxy-γ-butyrolactone, which is useful as a raw material for functional materials, pharmaceuticals or agrochemical intermediates.

  Various methods are known as a method for producing hydroxylactone (such as 4-hydroxy-dihydrofuran-2-one). For example, US Pat. No. 4,968,817 discloses a method 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 it is necessary to react with carbon monoxide, which is a toxic gas, under high pressure (about 3 MPa or more).

  In addition, (Angevante Chemy International Edition English (Angew. Chem. Int. Ed., Eng.), 5, 994 (1966) (Non-patent Document 1) includes coexistence of hydrogen peroxide and formic acid. A method of producing 4-hydroxy-dihydrofuran-2-one by treating 3-butenoic acid with a system and further reacting with hydrochloric acid is disclosed, and WO 98/04543 (Patent Document 2) discloses lactose. And the like, and a method for producing 4-hydroxy-dihydrofuran-2-one by treating with a hydrogen peroxide solution under basic conditions followed by acid treatment, and 3,4-obtained by the acid treatment. By converting dihydroxybutanoic acid into acetonide with acetone and treating the ketal with hydrochloric acid, 4-hydroxyl - process for preparing dihydrofuran-2-one is disclosed.

  In EP 761663 (Patent Document 3), 4-hydroxy-3-dihydrofuran-2-one is produced by treating ethyl 4-chloro-3-hydroxybutanoate with hydrochloric acid and neutralizing with sodium hydroxide. A method is disclosed, and WO99 / 33817 (Patent Document 4) discloses a method for producing 4-hydroxy-dihydrofuran-2-one by cyanating glycidol, hydrolyzing and then lactonizing. Yes.

  However, since these methods all use water as a solvent, they require time and heat energy for the distillation, and are industrially disadvantageous. In addition, it is necessary to neutralize the acid or base used to form a salt. Furthermore, it is conceivable to extract 4-hydroxy-dihydrofuran-2-one with an organic solvent, but 4-hydroxy-dihydrofuran-2-one is poor in extraction efficiency because of its high water solubility. Therefore, the target compound cannot be produced efficiently by the methods of Non-Patent Document 1 and Patent Documents 1 to 3. Further, in the methods of Non-Patent Document 1 and Patent Document 1, a peroxide is used, and in the method of Patent Document 3, a cyano compound is used.

  Synlett, page 71 (1997) (Non-Patent Document 2) describes a method for producing 4-hydroxy-dihydrofuran-2-one by heat-treating carnitine. However, this method requires the use of a high boiling point solvent such as dimethyl sulfoxide, making it difficult to isolate the product.

  JP 2001-302653 A (Patent Document 4) describes a method for producing 4-hydroxy-dihydrofuran-2-one from an epoxycarboxylic acid or a derivative thereof. In this method, the target lactone can be efficiently synthesized, but 3,4-epoxybutanoic acid ester as a starting material has not been established industrially, and is a raw material that is more easily available industrially. It is desirable to establish a method for producing 4-hydroxy-dihydrofuran-2-one using

  Tetrahedron Letters, 30, 2513 (1989) (Non-Patent Document 3) discloses that 4-hydroxy-5 is obtained by treating 4,4-dimethyl-3,4-epoxypentanoic acid ester with hydrochloric acid. A process for producing ethyldihydrofuran-2-one is described. However, in this method, when 3,4-epoxypentanoic acid ester having no substitution at the 4-position is used as a raw material, 3-hydroxy-4-chloropentanoic acid ester is produced and lactone cannot be obtained.

  In Tetrahedron, 47, 7171 (1991) (Non-patent Document 4), 4-hydroxy-3,4-epoxypentanoic acid ester is treated with 3% aqueous sulfuric acid to give 4-hydroxy- A process for producing 5-ethyldihydrofuran-2-one is described. However, this method cannot obtain 4-acyloxydihydrofuran-2-one having no substituent at the 5-position because the epoxy group of the raw material, epoxypentanoic acid ester, is substituted with an ethyl group. Further, since 3% sulfuric acid water is used, it is necessary to extract the target product from the aqueous layer, but the target product is highly water-soluble, so that extraction is difficult.

US Pat. No. 4,968,817 WO 98/04543 EP761663 publication WO99 / 33817

Angewante Chemie International Edition English (Angew. Chem. Int. Ed., Eng.), 5, 994 (1966) Synlett, 71 (1997) Tetrahedron Letters, 30, 2513 (1989) Tetrahedron, 47, 7171 (1991)

  The object of the present invention is to provide an unsubstituted carbon atom (for example, carbon atom at the 5-position of dihydrofuran-2-one) that is bonded to the oxygen atom of the endocyclic ester group among the β-hydroxy-γ-butyrolactone. It is to provide a method for producing a certain lactone.

  Another object of the present invention is to provide a method capable of efficiently producing a lactone from tetronic acid.

Another object of the present invention is to provide a process for producing a lactone using a reducing agent that can be efficiently separated from a product.
Still another object of the present invention is to provide a process for producing a lactone that can efficiently separate a catalyst even if a catalyst is used.

  As a result of intensive studies to solve the above problems, the present inventors have found that β-hydroxy-γ-butyrolactone (4-hydroxy-dihydrofuran-2-one) can be produced by reduction of tetronic acid. Was completed.

を還元することにより下記式（２）

で表されるβ−ヒドロキシ−γ−ブチロラクトン（４−ヒドロキシ−ジヒドロフラン−２−オン）を得る、β−ヒドロキシ−γ−ブチロラクトン（４−ヒドロキシ−ジヒドロフラン−２−オン）の製造方法を提供する。 That is, the present invention provides a tetronic acid represented by the following formula (1):

To reduce the following formula (2)

[Beta] -hydroxy- [gamma] -butyrolactone (4-hydroxy-dihydrofuran-2-one) represented by the formula [beta] -hydroxy- [gamma] -butyrolactone (4-hydroxy-dihydrofuran-2-one) is provided To do.

  As the reducing agent, hydrogen can be preferably used.

  The reduction is preferably performed in the presence of a catalyst, and a solid catalyst can be preferably used as the catalyst.

  According to the present invention, a carbon atom bonded to an oxygen atom of an endoester group of a lactone ring, which has high utility value, is produced and sold industrially and easily available, and is unsubstituted. Lactone, β-hydroxy-γ-butyrolactone (4-hydroxy-dihydrofuran-2-one) can be easily produced. Further, when hydrogen is used as a reducing agent, β-hydroxy-γ-butyrolactone (4-hydroxy-dihydrofuran-2-one) can be easily isolated. In particular, when the reaction is carried out in the presence of a solid catalyst, the catalyst can be easily removed, and β-hydroxy-γ-butyrolactone (4-hydroxy-dihydrofuran-2-one) can be isolated efficiently.

[Tetronic acid]
According to the present invention, β-hydroxy-γ-butyrolactone (4-hydroxy-dihydrofuran-2-one) can be produced by reducing tetronic acid. Here, tetronic acid usually exists as a tautomer of keto type (1a) and enol type (1b) as shown in the following formula (1-1). The keto type shown by (1a), the enol type shown by (1b), or a mixture of both may be sufficient.

[Reducing agent]
In the reduction, any commonly used known reducing agent can be used, and is not particularly limited. Examples thereof include hydrogen (H ₂ ) and sodium borohydride (NaBH ₄ ). Of these, hydrogen can be most preferably used. By using hydrogen as the reducing agent, after the reaction is completed, excess reducing agent and oxidized oxidant of the reducing agent can be easily separated from the target product, β-hydroxy-γ-butyrolactone.

  The amount of the reducing agent used can be selected from the range usually used and is not particularly limited. When hydrogen is used as the reducing agent, the reaction may be performed in a hydrogen atmosphere or a mixed gas atmosphere of hydrogen and a gas inert to the reaction such as helium or nitrogen.

[catalyst]
By reducing tetronic acid in the presence of a catalyst, β-hydroxy-γ-butyrolactone can be produced more efficiently.

  As the catalyst, any of various catalysts that promote the reduction of tetronic acid can be used and is not particularly limited. For example, a noble metal catalyst such as a noble metal such as Pd, Pt, Rh, Ru or a compound containing these noble metal elements; a base metal catalyst containing a metal such as Ni, Fe, Cu, or these metal compounds may be used. These catalysts can be used alone or in admixture of two or more. Among these, a catalyst containing Rh, Pd, Ni or these metals is preferable. The metal compound includes oxides and various complexes.

  The reduction may be performed in a homogeneous system or in a heterogeneous system using a solid catalyst. For the solid catalyst, a noble metal-based catalyst supported on an appropriate carrier such as silica gel, alumina, activated carbon, or the like; for example, by modifying the shape of a base metal catalyst such as sponge nickel A base metal solid catalyst in which a base metal such as Ni or the like is supported on an appropriate support is included.

  As the catalyst, it is preferable to use a solid catalyst because the catalyst can be easily removed from the reaction solution by filtration or the like after the reaction and work efficiency can be improved.

  The amount of the catalyst used is, for example, about 0.000001 to 100 parts by weight, preferably about 0.0001 to 10 parts by weight, more preferably 0.005 to 0.5 parts by weight (particularly with respect to 1 part by weight of tetronic acid. 0.001 to 0.5 parts by weight). In addition, when using a supported catalyst as a catalyst, the usage-amount of the said catalyst is the weight remove | excluding the weight of the support body from the weight of the supported catalyst.

  The reaction temperature can be appropriately selected according to the production rate of the lactone, the stability of the raw material tetronic acid and the product (β-hydroxy-γ-butyrolactone), and the like. For example, it can be selected from the range of -30 to 150 ° C, preferably -10 to 100 ° C, particularly preferably 15 to 40 ° C.

  The reaction is often carried out under normal pressure or under pressure (for example, about 0.1 to 50 MPa, preferably about 0.1 to 10 MPa). Alternatively, the reaction may be performed under reduced pressure for operational reasons.

  The reaction can be carried out in the presence or absence of a solvent, but is usually carried out in the presence of a solvent. Examples of the solvent include ether solvents such as diethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane, and 1,2-dimethoxyethane; nitriles such as acetonitrile and benzonitrile; and sulfoxide solvents such as dimethyl sulfoxide. Sulfolanes such as sulfolane; ester solvents such as methyl acetate, ethyl acetate and butyl acetate; lactones such as γ-butyrolactone; amide solvents such as dimethylformamide; methanol, ethanol, propanol, isopropanol, n-butanol, s -Alcohol solvents such as butanol and t-butanol; saturated or unsaturated hydrocarbon solvents such as pentane, hexane, heptane, octane and petroleum ether; methylene chloride, chloroform , 1,2-dichloroethane, chlorobenzene, a halogenated hydrocarbon solvent such as bromobenzene, polyethylene glycol, a high boiling solvent, such as silicone oil can be used. Of these, ester solvents such as acetates can be particularly preferably used. A solvent can be used individually or in mixture of 2 or more types.

  The amount of the solvent used is not particularly limited as long as it can dissolve or disperse the reaction components and does not impair the economy. For example, it can be selected from a range of about 1 to 100,000 parts by weight, preferably about 1 to 10,000 parts by weight with respect to 100 parts by weight of tetronic acid supplied to the reaction system.

  The reaction may be carried out by any of batch, semi-batch and continuous methods. The produced β-hydroxy-γ-butyrolactone can be separated by conventional separation and purification means (neutralization, extraction, distillation, rectification, molecular distillation, crystallization, recrystallization, separation using column chromatography, etc.) as necessary. It may be purified.

  The β-hydroxy-γ-butyrolactone thus obtained can be used as a functional material or a production intermediate for pharmaceuticals or agricultural chemicals. In particular, among β-hydroxy-γ-butyrolactones, the carbon atom bonded to the oxygen atom of the endocyclic ester group (such as the 5-position carbon atom of dihydrofuran-2-one) is unsubstituted, so that it has high functionality. It is useful as a raw material for materials (such as linear polymers having no side chain).

Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.
In addition, the NMR spectrum of the compound obtained in the Example was measured using a 500 MHz, ¹ H-NMR spectrum measuring apparatus (“AVANCE 500” manufactured by Bruker) using tetramethylsilane (TMS) as an internal standard. It was measured.

Example 1 (Production of β-hydroxy-γ-butyrolactone with rhodium alumina catalyst)
A 50 ml two-necked flask is charged with 0.05 g of rhodium alumina catalyst (manufactured by NE Chemcat; trade name “5% Rh alumina”), 9.06 g of ethyl acetate (manufactured by Wako Pure Chemical Industries), and 1 g of tetronic acid (manufactured by Tokyo Chemical Industry). After purging with nitrogen, a hydrogen balloon was attached to bring the system into a hydrogen atmosphere. After stirring for 7.5 hours at room temperature, the reaction was stopped and the reaction mixture was filtered. The obtained filtrate was concentrated at 40 ° C. under reduced pressure to obtain 0.83 g of crude 4-hydroxy-dihydrofuran-2-one (compound represented by formula (2)) as a liquid.
When the ¹ H-NMR analysis of the crude 4-hydroxy-dihydrofuran-2- ^one was performed, the following results were obtained.
The yield of 4-hydroxy-dihydrofuran-2-one was 72 mol%, and the main by-product was dihydrofuran-2-one (yield 12 mol%).
¹ H-NMR spectrum (CDCl ₃ ) of 4-hydroxy-dihydrofuran-2- ^one : 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 (Production of β-hydroxy-γ-butyrolactone with palladium carbon catalyst)
In place of the rhodium alumina catalyst, the same operation as in Example 1 was carried out except that 0.105 g of a 10% palladium carbon catalyst (manufactured by NE Chemcat; trade name “PE, 50% water-containing product”) was used. Hydroxy-dihydrofuran-2-one (compound represented by formula (2)) was obtained as a mixture with tetronic acid.
The yield of 4-hydroxy-dihydrofuran-2-one was 2.1 mol%.

Example 3 (Production of β-hydroxy-γ-butyrolactone with nickel catalyst)
A crude 4-hydroxy-dihydrofuran was prepared in the same manner as in Example 1 except that 0.12 g of a sponge nickel catalyst (manufactured by Kawaken Fine Chemicals; trade name “NDHT90-M”) was used instead of the rhodium alumina catalyst. 2-one (compound represented by formula (2)) was obtained as a mixture with tetronic acid.
The yield of 4-hydroxy-dihydrofuran-2-one was 0.40 mol%.

Example 4 (Production of β-hydroxy-γ-butyrolactone with nickel catalyst)
Add 20 ml of water and 4.5 g of sodium hydroxide to an Erlenmeyer flask with a capacity of 100 ml, add 1.00 g of Ni / Al alloy (manufactured by Kawaken Fine Chemicals; ND type), and then in a 100 ° C. hot water bath for 45 minutes. Expanded. Thereafter, it was washed 5 times with water and once with tetrahydrofuran (THF).
THF was added to the nickel catalyst thus prepared to make a total slurry of 1.2 g, 100 mg of tetronic acid and 2.0 ml of THF were further added, and the reaction was carried out at 80 ° C. for 5 hours under 5 MPa hydrogen. Thereafter, the system was returned to room temperature and normal pressure, filtered and concentrated to obtain crude 4-hydroxy-dihydrofuran-2-one (compound represented by formula (2)). Tetronic acid conversion was 90% and reaction selectivity was 90%.

Example 5 (Production of β-hydroxy-γ-butyrolactone with palladium carbon catalyst)
Tetronic acid 50 mg, palladium carbon catalyst (manufactured by NE Chemcat) 50 mg, and tetrahydrofuran (THF) 2.0 ml were reacted at 50 ° C. for 5 hours under 5 MPa hydrogen. Thereafter, the system was returned to room temperature and normal pressure, filtered and concentrated to obtain crude 4-hydroxy-dihydrofuran-2-one (compound represented by formula (2)). Tetronic acid conversion was 50% and reaction selectivity was 90%.

Claims (4)

Tetronic acid represented by the following formula (1)

By reducing the following formula (2)

The manufacturing method of (beta) -hydroxy-gamma-butyrolactone which obtains (beta) -hydroxy-gamma-butyrolactone represented by these.   The method for producing β-hydroxy-γ-butyrolactone according to claim 1, wherein hydrogen is used as a reducing agent.   The method for producing β-hydroxy-γ-butyrolactone according to claim 1 or 2, wherein the reduction is performed in the presence of a catalyst.   The method for producing β-hydroxy-γ-butyrolactone according to claim 3, wherein the catalyst is a solid catalyst.