JPH0643414B2 - Method for producing 2,2 dimethyl delta valerolactone - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing 2,2 dimethyl delta valerolactone, wherein 2,2 dimethyl delta valero lactone is a compound of-(CH ₂ ) ₃ C (CH ₃ ) ₂ Compounds with a COOH group, such as effective as antilipid hyperproteinemia drug (Lopid manufactured by Park Dehis Co., USA) and the like are useful as raw materials.

2. Description of the Related Art Conventionally, the following method has been known as a method for producing 2,2 dimethyl delta valerolactone.

1) A method in which 2,2 dimethylglutaric acid anhydride is reduced with metallic soda in anhydrous alcohol. (J.oc.vol.35, No.10
(1970) pp. 3574-3576).

2) A method of reacting 2,2 dimethyl vinyl butyrate with CO (CO) ₄ (Belgian Patent No. 616,141).

3) A method of producing lithium isopropyl amide from butyl lithium and isopropyl amine, reacting this with sodium isobutyrate, and then reacting with dibromopropane for alkali treatment (USP3674,836).

4) Method for transferring acetal of allyl alcohol of isobutyraldehyde (Synth. Commn 10 (4) 273 (1980).

5) A method of making acetal of ethylene glycol of acrolein, adding HBr to make a Grignard reagent, reacting with 2-bromoisobutyric acid, and then hydrolyzing and lactonizing.

However, the method 1) has a poor lactone yield due to intramolecular steric hindrance, and the method 2) uses a specific reagent such as cobalt carbonyl, which makes handling difficult and expensive.
Since the method 3) uses an expensive chemical such as butyllithium, the cost is high. The method (4) is costly because the reaction time of acetal transfer is long and the yield is poor. The method (5) has drawbacks such as high raw material cost and high cost.

OBJECT OF THE INVENTION The present invention has been made to solve the drawbacks in the conventional method, and its object is to use easily available raw materials without using a specific drug or an expensive drug, and easily and in good yield. Another object of the present invention is to provide a method for producing 2,2 dimethyl delta valerolactone at low cost.

As a result of earnest research to achieve the above-mentioned object, the present inventor has found that
Using 2 dimethyl 4 pentenoic acid as a raw material, and adding HBr with benzoyl peroxide as a catalyst to this to make 2,2 dimethyl 5 bromovaleric acid, and subjecting this to alkali treatment, 2,2 dimethyl was easily obtained in good yield. It was determined that δ valerolactone was obtained.

The reaction formula is shown below.

The present invention has been completed based on this finding.

The gist of the present invention is that 2,2 dimethyl 4 pentenoic acid is added with HBr using benzoyl peroxide as a catalyst to synthesize 2,2 dimethyl 5 bromovaleric acid, which is treated with an alkali. There is a method for producing δ-valerolactone.

The 2,2 dimethyl 4-pentenoic acid used in the method of the present invention can be easily obtained, for example, by transposing an allyl group of isobutyric acid allyl ester using sodium hydride. The reaction formula is as follows.

Alternatively, it can be easily obtained by a method in which an acetal form of isobutyraldehyde with allyl alcohol is subjected to acetal rearrangement and then subsequently oxidized.

The reaction of adding HBr to 2,2 dimethyl 4 pentenoic acid is to charge 2,2 dimethyl 4 pentenoic acid and benzoyl peroxide into a reaction vessel, and to add 1 to 1.5 moles of HBr to 2,2 dimethyl 4 pentenoic acid. Blow in gas for 1-5 hours. After the completion of blowing HBr gas, the reaction is completed by aging for 1 to 5 hours. Although the reaction temperature is -10 to 70 ° C, the reaction temperature is as low as possible in order to reduce side reactions, preferably -10 to 40 ° C. HBr
The addition reaction is preferably carried out in a homogeneous system using an organic solvent. As the organic solvent, any solvent such as an aliphatic hydrocarbon-based solvent, an aromatic hydrocarbon-based solvent, an ether-based solvent or a halogen-based solvent may be used as long as it dissolves 2,2 dimethyl 4-pentenoic acid and benzoyl peroxide and does not react with HBr. Examples include hexane, pentane, ether, toluene, carbon tetrachloride, benzene, dioxane, THF and acetic acid. The amount used is 1 to 20% by weight with respect to the acid.

Further, in the present invention, HBr needs to be radically added to 2,2 dimethyl 4 pentenoic acid. That is,
Bromine must be attached to the end (5-position). When bromine is added to the 4-position, a five-membered ring lactone is produced as a by-product when treated with alkali, which is not preferable. Therefore, it is necessary to use benzoyl peroxide as a catalyst to effect radical addition. The amount used is 0.05 to 5% by weight of 2,2 dimethyl 4-pentenoic acid, preferably 0.1.
1-2% by weight is good.

Next, the alkali treatment of 2,2 dimethyl 5 bromovaleric acid (hereinafter referred to as DPA-Br) obtained by adding HBr to obtain 2,2 dimethyl delta valerolactone is DP.
5) containing 1.0-3.0 times the molar amount of alkali with respect to A-Br
Add a 50% alkaline aqueous solution and react at a reaction temperature of 0-50 ° C
Stir for minutes to 3 hours. In this alkaline treatment, DPA-Br isolated from the reaction solution or the reaction solution as it is can be used. The alkali used in the ring-closing reaction is an alkali metal hydroxide or carbonate, such as NaOH, KOH, Na ₂ CO ₃ ,
Examples include K ₂ CO ₃ . In this reaction, the added bromine atom is for elimination as alkali bromide,
At least 1.0 mol of alkali is required with respect to DPA-Br. Usually, the amount used is 1.0 to 3.0 times mol with respect to DPA-Br.

After the reaction, the organic layer and the aqueous layer are separated, and 2,2 dimethyl delta valerolactone is obtained from the organic layer. The product obtained in this manner has a high degree of purity, but it is advisable to carry out distillation purification when a further higher purity is required.

Example 1. 4 equipped with stirrer, separatory funnel, thermometer, condenser
In a neck flask, 2,2 dimethyl 4 pentenoic acid 64
g, and 300 cc of CCl _{4 as} a solvent were charged and dissolved with stirring. To this, 56 g of anhydrous NaBr was added as a powder and suspended. Next, add 0.5 g of benzoyl peroxide and add H at room temperature while stirring.
27.5 g of ₂ SO ₄ was gradually added dropwise, and the reaction was continued for 2 hours after the completion of the addition. Dispersed in water, Na ₂ SO ₄ dissolves in the water layer and the reaction product moves to the solvent layer, so the solvent layer is separated, washed with water and dehydrated, and most of the CCl ₄ is collected and cooled by cooling. A bromine compound was obtained. This was washed with excess water and 10% soda ash was added. Then, the mixture was extracted with benzene, benzene was removed from the extract, and the mixture was fractionated under reduced pressure.

First distillation to 108/19 mm 7 g Main distillation 108 to 113/19 mm 43.7 g The yield was 67.9% (purity 97.1%).

Example 2. Into the flask of Example 1, 64 g of 2,2 dimethyl 4-pentenoic acid and 300 cc of solvent benzene were charged and dissolved with stirring.

To this, 0.5 g of benzoyl peroxide was added, and HBr gas was blown in at room temperature for 2 to 3 hours while stirring. After the completion of blowing, stirring was continued for 2 hours, and then the reaction product solution was washed with water to collect the solvent.
The recovered amount of benzene was 204 g, and the residual liquid was 106 g.

To this residual liquid, 10% NaOH was added to make it weakly alkaline, and 100 cc of benzene was added to this for extraction. Activated carbon was added to the aqueous layer, and after passing, HCl was added to adjust the pH to 4.0 and the mixture was extracted with benzene. Benzene was removed from this benzene solution and fractionally distilled under reduced pressure.

First distillation to 108/20 mm 9 g Main distillation 108 to 113/20 mm 42.9 g The yield was 66.7% (purity 97.2%).

Example 3. Instead of 10% NaOH in Example 2, 270 g of 10% Na ₂ CO ₃ water
Was carried out in the same manner as in Example 2.

The yield was 70.5% (purity 97.4%).

Example 4. 2,2 dimethyl 4-pentenoic acid 10g hexane 100c
Reaction was carried out in the same manner as in Example 2 using 7.15 g of dry HBr in the presence of 100 mg of benzoyl peroxide in c.

The yield was 86.4% (purity 98.0%).

Example 5. Instead of the 10% NaOH water in Example 2, 350% 10% K ₂ CO ₃ water.
The same procedure as in Example 2 was carried out using g.

The yield was 85.7% (purity 95.7%).

EFFECTS OF THE INVENTION According to the method of the present invention, a readily available raw material is used without using a specific drug or an expensive drug, and it is easily obtained in good yield. It has an excellent effect of obtaining lactone.

Claims (1)

[Claims] 1. A method of synthesizing 2,2 dimethyl 5 bromovaleric acid by adding hydrogen bromide to 2,2 dimethyl 4 pentenoic acid using benzoyl peroxide as a catalyst, and subjecting this to alkali treatment. 2 Method for producing dimethyl delta valerolactone.