JP2003146979A - Method for producing lactone - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a lactone in high yield under mild conditions in reducing an acid anhydride raw material compound having a specific structure. SOLUTION: This method for producing the lactone comprises adding a primary alcohol and/or a secondary alcohol to the reaction system in reducing the acid anhydride derived from a norbornenecarboxylic acid derivative with the specific structure.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention reduces a specific acid anhydride raw material compound with a reducing agent such as sodium borohydride,
It relates to a method for producing a compound having a corresponding lactone structure.

[0002]

The lactone compound obtained by the present invention is widely used as a raw material for functional chemicals such as medicines and agricultural chemicals. In particular, the compound obtained in the present invention is
It has a carbon double bond to which a polymerizable carboxylic acid such as (meth) acrylic acid can be added. The resist material obtained by using a polymer compound containing a lactone structure-containing (meth) acrylic acid ester as a monomer in this way is sensitive to high-energy rays and has excellent sensitivity, resolution, and etching resistance. Therefore, it is useful for fine processing with electron beams or deep ultraviolet rays. In particular, since the absorption at the exposure wavelength of ArF excimer laser and KrF excimer laser is small, it has a feature that a fine pattern can be easily formed perpendicular to the substrate. Further, ring-opening polymerization or vinyl polymerization is carried out using the active double bond of the lactone compound obtained in the present invention to obtain a resin in which the lactone is pendantly bonded to the main chain. Although these resins are polyolefins, they are useful as resins that are useful in various fields as new resins that also have the properties of polar functional groups.

As a reducing agent for reducing an acid anhydride having a carbon-carbon double bond in the same molecule to selectively reduce only the acid anhydride while leaving the double bond, thereby leading to a lactone. , Sodium borohydride / dimethylformamide (DMF) system and lithium aluminum hydride are known (MMKayser et al., Canadian Journal
of Chemistry, 56, p. 1524 (1978); EM Mangnus et al., S
ynthetic Communications, 22, p.783 (1992); J. Haslo
uin et al., Tetrahedron Letters, p. 4651 (1976)).
In these reaction systems, the yield of the target compound is 80% or higher, which is relatively high. However, in the former reaction system, DMF is used as a solvent, so that the product can be efficiently isolated. It requires complicated operations. Further, in the latter reaction system, a severe reaction condition of -78 ° C must be selected, which is a disadvantageous technique for industrial implementation.

On the other hand, tetrahydrofuran (THF), ethanol and the like are known as general solvents when sodium borohydride is used as a reducing agent in the same reaction. In the former THF solvent, the yield of the target product is as low as about 50% as shown in the comparative example of the present invention. In addition, the latter ethanol solvent system, Tetrahedron Letters,
Vol.35, No.8, pp. 1165-1168 (1994), the reducing agent undergoes solvolysis relatively quickly, so an excessive amount of reducing agent is required. Not suitable for practical implementation.

[0005]

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and an acid anhydride raw material compound having a specific structure, which has not been disclosed in the prior art, is added under mild reaction conditions.
It is an object of the present invention to provide a method capable of producing a desired lactone compound in a high yield with a reasonable amount of a reducing agent.

[0006]

The present inventors have added a specific alcohol to a reaction system when reducing an acid anhydride raw material compound having a specific structure of the present invention.
The present inventors have found that the desired lactone compound can be produced in a high yield with a reasonable amount of a reducing agent under mild reaction conditions, and have arrived at the present invention.

That is, the gist of the present invention is to provide the following reaction formula (1)
Of the starting compound (A) and / or the starting compound (B) of the reaction formula (2) in the presence of a reducing agent, and then (a1) and / or (a2) of the reaction formula (1), or the reaction (B in equation (2)
1) and / or a method for producing a lactone represented by (b2), which comprises adding a primary alcohol and / or a secondary alcohol to the reaction system, Exist.

[0008]

[Chemical 2]

(In the reaction formulas (1) and (2), R ^{1 to} R ¹
Each ⁸ independently represents a hydrogen atom or an optionally substituted linear, branched or alicyclic alkyl group having 1 to 8 carbon atoms. )

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION (Acid Anhydride Raw Material Compound) The raw material compound used in the present invention is an acid anhydride derived from a norbornenecarboxylic acid derivative represented by the following general formula (A) and / or (B).

[0011]

[Chemical 3]

R ^{1 to} R ⁶ in the general formula (A) and R ^{1 to} R ⁸ in the general formula (B) are a hydrogen atom, a linear, branched or alicyclic alkyl group having 1 to 8 carbon atoms. A group selected from the group. Among them, in the reaction formula (1), it is preferable that R ^{1 to} R ³ are hydrogen atoms and R ^{4 to} R ⁶ are hydrogen atoms or a methyl group, and particularly, all of R ^{1 to} R ⁶ are hydrogen. It is preferably an atom. In reaction formula (2), R ¹
It is preferred that all of R ⁸ are hydrogen atoms. The alkyl group of R ^{1 to} R ⁶ in these reaction formulas (1) or (2) may be further substituted, and as the substituent, a phenyl group,
An aryl group such as a toluyl group; an alkoxyl group such as a hydroxyl group, a methoxy group and an ethoxy group, and a carboalkoxyl group such as a methoxycarbonyl group and an ethoxycarbonyl group. Specifically, 5-norbornene-2,3
-Dicarboxylic acid anhydride, 2-methylnorbornene-2,
Examples thereof include 3-dicarboxylic anhydride, Diels-Alder adduct of cyclopentadiene and itaconic anhydride, and the like.

The concentration (weight percentage) of the raw material compound is 1 to 70% by weight, preferably 3 to 50% by weight, and more preferably 5 to 40% by weight based on the reaction liquid at the end of dropping.
Is the range. (Primary or Secondary Alcohol) Examples of the primary or secondary alcohol that can be used in the present invention include linear or branched aliphatic or alicyclic primary or C1-8 or Secondary alcohols are preferably used. Specifically, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, secondary butanol, n-amyl alcohol, isoamyl alcohol, n
-Hexanol, cyclohexanol, n-heptanol, n-octanol, 2-ethylhexanol and the like. Among them, alcohols having 1 to 4 carbon atoms selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, and 1-methylpropanol are preferable, and particularly alcohols selected from methanol, ethanol or isopropanol. Is preferred. Particularly, primary alcohol is preferable.

The preferred amount of alcohol used varies depending on the type of alcohol used, but generally, the molar ratio to the reducing agent is 0.01 to 50, preferably 0.1 to 50.
20 and more preferably 0.5 to 10. (Solvent) The solvent used for the reduction reaction is preferably an aprotic solvent that dissolves the starting compound. For example, aliphatic or aromatic hydrocarbons such as hexane and benzene, ethers such as diethyl ether, THF and dioxane, esters such as methyl acetate and ethyl acetate, lactones such as γ-butyrolactone and δ-valerolactone. It can be preferably used. (Reducing agent) As the reducing agent, known reducing agents such as alkali metal borohydride and lithium aluminum hydride can be used. Among them, alkali metal borohydride is preferable, and examples of the alkali metal include lithium and sodium. Further, sodium borohydride is particularly preferable.

The amount of the reducing agent used is in the range of 0.5 to 4, preferably 0.7 to 3, and more preferably 1 to 2 in terms of molar ratio with respect to the raw material compound. (Reaction Method) In the present invention, it is preferable to bring the acid anhydride raw material compound into contact with the reducing agent and alcohol by a method in which the reducing agent and alcohol are not brought into contact with each other before the reduction reaction starts. For example, a method of preparing a mixed solution of the primary and / or secondary alcohol and the starting compound (A) and / or (B) in advance and mixing the mixed solution with a liquid containing a reducing agent is adopted. Is good.

Generally, a suspension containing a reducing agent is charged into a reactor, and the acid anhydride raw material compound dissolved in the same solvent as the solvent charged in the reactor is continuously or intermittently added dropwise thereto. To drive the reaction. At this time, it is easy to make a preset amount of alcohol coexist in the raw material solution, but alcohol may be dropped separately if necessary. Further, the raw material and the alcohol solution may be charged into a reactor and the reducing agent or its suspension may be dropped. (Reaction conditions) The reaction temperature varies depending on the dropping rate and concentration of the raw material solution, but the optimum temperature is generally -50 to 100.
℃, preferably -40 to 70 ℃, more preferably -3
It is in the range of 0 to 50 ° C. The reaction time is the same as the dropping rate and is 0.1 to 30 hours, preferably 0.2 to 2
It is 0 hour, more preferably 0.5 to 10 hours. If necessary, an aging time of 20 hours or less can be set after the dropping. The reaction is carried out while avoiding contamination with water as much as possible. For that purpose, it is preferable to keep the reactor and the receiver of the raw material solution in an inert gas atmosphere.
Any inert gas may be used as long as it does not hinder the smooth progress of the reaction, and hydrogen, helium, nitrogen, argon, methane and the like can be exemplified. (Isolation and purification of product) After completion of the reaction, the reaction product solution is acidified with a suitable acid such as hydrochloric acid, extracted with an organic solvent such as toluene, and then the target product is obtained by a method such as distillation, recrystallization and chromatography. Although it can be purified, in general, a sufficiently high purity product can be obtained by concentrating the extract. (Production of (meth) acrylic acid ester) The lactone compound of the present invention thus synthesized has a polymerizable carboxylic acid such as (meth) acrylic acid at its carbon-carbon double bond portion and an acid catalyst such as sulfuric acid. In the presence of, by a conventional method, a carboxylic acid ester having a lactone structure,
In particular, (meth) acrylic acid esters can be produced.

[0017]

EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to the following examples as long as the gist thereof is not exceeded. (Example 1) A four-necked round-bottomed flask (reactor) with a capacity of 200 L, equipped with a dropping funnel with a side tube, a thermometer, and a backflow condenser was equipped with a magnetic stirrer and heated and dried while flowing nitrogen gas. . To this, 350 ml of THF and 18.15 g (0.48 mol) of sodium borohydride were sequentially charged. 5-Norbornene-2,3-dicarboxylic acid anhydride prepared by adding 15.38 g (0.48 mol) of methanol to the dropping funnel (compound (A)
In the above, a solution of 78.80 g (0.48 mol) of THF (250 ml) corresponding to a compound in which R1 to R6 are all hydrogen atoms was charged.
The reactor was cooled to −10 ° C. in an ice / salt bath, and a solution containing the acid anhydride raw material compound was added dropwise from a dropping funnel over 1 hour while stirring. During that time, the temperature of the reaction solution was kept at 8 ° C or lower.

After completion of the dropping, 2N hydrochloric acid aqueous solution (280 m
When l) was added carefully, it became a colorless and transparent two-layer solution. This was separated to obtain a THF layer and an aqueous layer (1).
The solvent of the THF layer was distilled off under reduced pressure, 200 ml of toluene was added, and after sufficient stirring, the insoluble matter was removed by filtration, and a two-layer solution of the toluene layer and the aqueous layer was obtained. The two layers were separated, the aqueous layer was extracted with toluene (100 ml), and separated into a toluene layer and an aqueous layer (2), and the toluene layer was combined with the above toluene layer. The aqueous layers (1) and (2) were combined, extracted with toluene (300 ml), and the extract was combined with the above toluene layer. The combined toluene layers were washed 4 times with 50 ml of saturated sodium hydrogen carbonate and then 3 times with 50 ml of pure water. After drying over anhydrous magnesium sulfate, toluene was distilled off under reduced pressure to yield 62.47 g (0.416 mol) of white crystals.
was gotten. This crystal was analyzed by NMR and gas chromatography, and as a result, 3-oxo-4-oxatricyclo [5.2.1.0 ^2,6 ] decene-8 (in formula (a1), R 1 to R 6 are all hydrogen). Corresponding to a compound that is an atom). The yield based on the starting material, 5-norbornene-2,3-dicarboxylic acid anhydride, was 8
It was 6.7%. (Example 2) In Example 1, instead of 5-norbornene-2,3-dicarboxylic acid anhydride as a raw material, 5-norbornene-2,2-dicarboxylic acid anhydride (compound (B)) was used.
In (corresponding to a compound in which R1 to R8 are all hydrogen atoms), the same reaction operation and post-treatment operation as in Example 1 were performed. As a result, the desired product bicyclo [2.2.1] heptane-2-ene-6-spiro (2 '
63.86 g (0.389 mol) of -oxo-3'-oxa) cyclopentane (corresponding to the compound in which R1 to R6 in the formula (b1) are all hydrogen atoms) was obtained as white crystals. The yield based on the starting material 5-norbornene-2,2-dicarboxylic acid anhydride was 81.0%. Comparative Example 1 The same reaction operation and post-treatment operation as in Example 1 were carried out except that methanol was not used in Example 1. As a result, the desired product 3-oxo-4-oxatricyclo [5.2.1.0 ^2,6 ] decene-8 (formula (a
The yield of 1) was 40.35 g (0.269 mol), which corresponds to a compound in which R1 to R6 are all hydrogen atoms). Raw material 5-
The yield based on norbornene-2,2-dicarboxylic anhydride was 56.0%. (Example 3) 3-oxo-4-oxatricyclo [5.
2.1.0 ^2,6 ] Decan-8-ylmethacrylate and 5-oxo-4-oxatricyclo [5.2.1.0]
Preparation of ^2,6 ] decane-8-yl methacrylate; 100
3 ml obtained in Example 1 above in a ml eggplant-shaped flask
-Oxo-4-oxatricyclo [5.2.1.
0 ^2,6 ] decane-8-ene 13.12 g (87.4 mm
ol) and 30 mg of 4-methoxyphenol were dissolved in 30.09 g (350 mmol) of methacrylic acid.
To this was added 3.62 g (35 mmol) of 95% concentrated sulfuric acid, and the contents were heated on an oil bath at 120 ° C. for 3 hours while stirring. After cooling to room temperature, 4 g of sodium carbonate was added to 100 parts of water.
The reaction product solution obtained above was carefully added to an aqueous solution dissolved in ml and stirred at room temperature for 30 minutes. Toluene 100
After adding ml, the aqueous layer was separated and concentrated under reduced pressure on a water bath at 70 ° C. until the content weight became 22.5 g. Toluene (100 ml) was added thereto, washed with 50 ml of a saturated aqueous sodium hydrogencarbonate solution four times, and the produced brown solid was removed by filtration, and then washed with 50 ml of pure water three times. By drying over anhydrous magnesium sulfate and distilling off toluene under reduced pressure, 17.31 g
Viscous product was obtained. This was subjected to silica gel column chromatography (eluent: ethyl acetate: toluene = 1: 1).
Volume ratio), and with a purity of 99% or higher, 3-oxo-4-
Oxatricyclo [5.2.1.0 ^2,6 ] decane-8-
15.69 g (66.4 mmol) of a mixture of ilmethacrylate and 5-oxo-4-oxatricyclo [5.2.1.0 ^2,6 ] decan-8-ylmethacrylate was obtained. The yield based on the raw material 3-oxo-4-oxatricyclo [5.2.1.0 ^2,6 ] decane-8-ene was 76%. Example 4 Bicyclo [2.2.1] heptane-spiro- (2'-oxo-3'-oxa) cyclopentane-2
Preparation of -ylmethacrylate and bicyclo [2.2.1] heptane-spiro- (2'-oxo-3'-oxa) cyclopentan-3-ylmethacrylate; 100 ml.
In a round bottom flask, the bicyclo [2.2.1] heptane-2-ene-spiro- (2′-obtained in Example 2 was obtained.
Oxo-3'-oxa) cyclopentane 12.15g (74.0mmo
l), methacrylic acid 25.50 g (296.2 mmol), and 4-methoxyphenol 14.6 mg were mixed to form a uniform solution. To this was added 1.943 g (18.8 mmol) of 95% concentrated sulfuric acid, and the mixture was heated with stirring on an oil bath at 120 ° C. for 2 hours while stirring. After cooling the reaction solution to room temperature, an aqueous solution (20 ml) of sodium carbonate 2.02 g (19.06 mmol) was added, and after stirring and standing, the aqueous layer was separated, and the obtained toluene solution was heated under reduced pressure of 70 ° C / 10 mmHg. 1
After treatment for a time, toluene and methacrylic acid were distilled off.
Wash 4 times with 20 ml of saturated aqueous sodium hydrogen carbonate solution,
Furthermore, the organic layer was washed 4 times with 10 ml of pure water each time. After drying over anhydrous magnesium sulfate, 30 ml of toluene and silica gel for chromatography were added, and this suspension was stirred at room temperature for 1 hour,
The silica gel was filtered off and washed with toluene, and the filtrate and the washing solution were combined. When the solvent was distilled off from this, 15.60 g of an oily yellow transparent product was obtained. Most of the product crystallized when left at room temperature. Expanded by capillary chromatography, it was found to consist of at least 8 compounds with similar retention times. The yield was 84.2%.

[0019]

Industrial Applicability According to the method of the present invention, it is possible to produce a lactone compound, which is a raw material for medicines, agricultural chemicals and functional resins, under mild conditions and in high yield.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Takako Takahashi             1000 Kamoshida-cho, Aoba-ku, Yokohama-shi, Kanagawa             Mitsubishi Chemical Corporation Yokohama Research Institute (72) Inventor Taketoshi Naito             1000 Kamoshida-cho, Aoba-ku, Yokohama-shi, Kanagawa             Mitsubishi Chemical Corporation Yokohama Research Institute F-term (reference) 4C037 UA03 UA05 WA10

Claims (11)

[Claims] 1. A starting compound (A) of the following reaction formula (1) and / or a starting compound (B) of the reaction formula (2) is reduced in the presence of a reducing agent to give (a1) of the reaction formula (1). ) And / or (a
2), or (b1) and / or (b2) of reaction formula (2)
In the method for producing a lactone represented by, a primary alcohol and / or a secondary alcohol is added to the reaction system. [Chemical 1] (In the reaction formulas (1) and (2), R ^{1 to} R ⁸ each independently represent a hydrogen atom, or an optionally substituted linear, branched or alicyclic alkyl group having 1 to 8 carbon atoms. Point) 2. The method for producing a lactone according to claim 1, wherein the reducing agent is an alkali metal borohydride. 3. The method for producing a lactone according to claim 1, wherein the reducing agent and the alcohol are not brought into contact with each other before the reduction reaction is started. 4. A mixed solution of a primary and / or secondary alcohol and a starting compound (A) and / or (B) is prepared in advance, and this mixed solution is mixed with a liquid containing a reducing agent. The method for producing a lactone according to claim 3, wherein a reduction reaction is performed. 5. R ^{1 to} R ⁸ in the reaction formulas (1) and (2) are each independently selected from the group consisting of a hydrogen atom, a methyl group and an ethyl group. The method for producing a lactone according to 1. 6. The primary and / or secondary alcohol is
The method for producing a lactone according to any one of claims 1 to 5, which is an alcohol having 1 to 8 carbon atoms. 7. The lactone according to claim 1, wherein R ^{1 to} R ³ in the reaction formula (1) are hydrogen atoms, and R ^{4 to} R ⁶ are hydrogen atoms or methyl groups. Production method. 8. The method for producing a lactone according to claim 1, wherein R ^{1 to} R ⁸ in the reaction formula (2) are hydrogen atoms. 9. The method for producing a lactone according to claim 1, wherein the alcohol is selected from methanol, ethanol or isopropanol. 10. The molar ratio of the alcohol to be added to the raw material compound is in the range of 0.1 to 10.
The method for producing a lactone according to any one of 1. 11. A method for producing a (meth) acrylic acid ester by reacting a lactone obtained by the method according to claim 1 with a (meth) acrylic acid.