JPH08134054A - Production of beta,gamma-butenolides - Google Patents

Abstract

PURPOSE: To obtain the subject compound useful as perfumes, pharmaceuticals and intermediates for organic syntheses from a γ-keto acid under a nearly neutral mild condition in high efficiency by using a specific haloiminium salt as a dehydrating agent. CONSTITUTION: The objective α,β-butenolide of formula III is produced by reacting (A) a γ-keto acid of formula I (R<3> is an organic group; R<4> is H or an organic group; R<3> and R<4> may together form a ring) with (B) a haloiminimum salt of formula II (R<1> and R<2> are each a lower alkyl; X is a halogen; (n) is 2 or 3) as a dehydrating agent. The haloiminium salt used as the component B can be produced by reacting an easily available compound of formula IV with a halogenation agent such as an oxalyl halogenide. Preferable example of the haloiminium salt is 2-chloro-1,3dimethylimidazolinium chloride. The reaction is preferably carried out at room temperature or thereabout by adding about 1mol of the component B and about 2mol of a base to 1mol of the component A.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing β, γ-butenolides, and more particularly to a method for producing β, γ-butenolides from γ-keto acids by using a special haloiminium salt.

[0002]

BACKGROUND OF THE INVENTION β, γ-Butenolides are useful as fragrances because they have a unique fragrance, and many compounds having physiological activities such as antihypertensive action are also useful as pharmaceuticals. Is. Furthermore, since it has a highly reactive methylene group in its structure and easily forms a dehydration condensation product with an aldehyde, it is also useful as an organic synthetic intermediate for various compounds.

Conventionally, several methods are known as a method for producing β, γ-butenolides, and one of them is known by a ring closure reaction of γ-keto acids. And, as this method, 1) a method of heating and refluxing in toluene using p-toluenesulfonic acid as a catalyst,
2) A method of heating and refluxing in acetic anhydride-acetic acid using concentrated sulfuric acid as a catalyst, 3) a method of heating and refluxing in acetic anhydride in the presence of sodium acetate, and a method of heating and refluxing in acetic anhydride are known. .

[0004]

However, 1) p
-The method of using toluenesulfonic acid or concentrated sulfuric acid of 2) as a catalyst cannot be applied to γ-keto acids having a functional group that is weak against acid because the reaction system becomes strongly acidic, or the yield decreases, and 3 ) And 4) using acetic anhydride requires a large amount of reagent because acetic anhydride is used as a solvent,
It has a drawback that it cannot be applied to heat-unstable γ-keto acids because of severe reaction conditions. Further, these methods also have a drawback that isomers of α, β-butenolides are produced as by-products together with β, γ-butenolides.

[0005]

Accordingly, the object of the present invention is to produce β, γ-butenolides from γ-keto acids industrially advantageously under mild conditions without being affected by the properties of raw materials. To provide a method.

[0006]

Under such circumstances, the present inventor has conducted diligent research to find out a new method for producing β, γ-butenolides, and as a result, has revealed that a haloiminium salt represented by the following general formula (1) It was found that β, γ-butenolides can be produced from γ-keto acids under mildly neutral conditions by using as a dehydrating agent, and the present invention has been completed.

The method of the present invention is shown by the following reaction formula.

[0008]

[Chemical 4]

[Wherein R ¹ and R ² are the same or different and each represents a lower alkyl group, and X represents a halogen atom,
n represents an integer of 2 or 3. R ³ represents an organic group, R ⁴ represents a hydrogen atom or an organic group, or R ³ and R ⁴ may combine to form a ring. B represents a base]

That is, in the present invention, γ-keto acids (2) are reacted with haloiminium salt (1) as a dehydrating agent to form β,
This is a method for producing γ-butenolides (3).

The haloiminium salt used in the present invention is represented by the general formula (1), and the lower alkyl group represented by R ¹ and R ² in the formula (1) includes a methyl group, an ethyl group and n-. Examples thereof include propyl group, isopropyl group, n-butyl group, isobutyl group and the like. Further, examples of the halogen atom represented by X include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and among them, a chlorine atom is particularly preferable. Specific preferred examples of the haloiminium salt (1) include 2-chloro-1,3-dimethylimidazolinium chloride, 2-chloro-1,3-dimethyl-3,
Examples include 4,5,6-tetrahydropyrimidinium chloride.

This haloiminium salt (1) can be obtained by, for example, adding an oxalyl halogenide, a phosphorus trihalide, a phosphorus pentahalide or an oxyhalogen to a compound represented by the general formula (5) which is known as an easily available solvent. It can be easily obtained by reacting a halogenating agent known per se such as phosphorus bromide, phosgene, trichloromethyl chloroformate and the like. In this reaction, either compound (5) or a halogenating agent is dissolved in a suitable solvent such as carbon tetrachloride,
The other is added little by little to this, and the reaction is further carried out at room temperature to 70 ° C. for several hours to several tens of hours. The haloiminium salt (1) thus obtained can be isolated, but the reaction solution can also be used in the reaction of the present invention without isolation.

Γ-Keto acids as raw material compounds of the present invention (2)
In the above, examples of the organic group of R ³ and R ⁴ include an alkyl group, an alkenyl group, an aromatic group, and a heterocyclic group which may have a substituent. Particularly, R ³ is preferably an aromatic group. The substituent may have a substituent containing an ether bond, an olefin bond, or the like.

Examples of the base represented by B include 2,6-lutidine, pyridine, triethylamine and tributylamine.

To carry out the method of the present invention, about 1 mol of the haloiminium salt (1) and about 2 mol of the base (4) are added to 1 mol of the γ-keto acids (2), and the mixture is allowed to react at room temperature. Good. Although a reaction solvent may not be used, a solvent that does not participate in the reaction, such as a halogenated hydrocarbon such as dichloromethane or dichloroethane, a hydrocarbon, an ether, an aromatic hydrocarbon, or the like can be used. Further, even when the reaction apparatus is carried out on an industrial scale, it is possible to use an ordinary stainless steel reaction kettle instead of a special reaction kettle such as glass lining. In the method of the present invention, the haloiminium salt (1) is changed to the water-soluble compound (5), so that separation and purification are easy.
Therefore, the desired β, γ-butenolides can be isolated from the reaction mixture simply by a conventional method such as distillation or recrystallization.

[0016]

According to the method of the present invention, only the β, γ-butenolides, which are useful as fragrances, pharmaceuticals, organic synthetic intermediates and the like, are converted from γ-keto acids under conventional neutral conditions under mild conditions. It can be efficiently produced without producing α, β-butenolides as a by-product.

[0017]

The present invention will be described in more detail below with reference to examples, but the present invention is not limited thereto.

Example 1 Preparation of 4- (4-methylphenyl) -3-butene-4-olide: 3.0 g (16 mmol) of 4- (4-methylphenyl) -4-oxobutanoic acid in 100 ml of methylene chloride and 3.2 g (19 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride was added, 3.8 g (38 mmol) of triethylamine was slowly added dropwise thereto, and after completion of the addition, the mixture was stirred at room temperature for 17.5 hours. Continued. Next, water was added to the reaction solution and the mixture was extracted with methylene chloride. The extract was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 3.9 g of a crystalline residue. The obtained residue was purified by silica gel column chromatography (solvent n-hexane / ethyl acetate) to give 1.5 g of the title compound.
(Yield 56%) was obtained. IR; ν _max ^KBr (cm ⁻¹ ) 1795.

Example 2 4- (2,3,4-trimethoxy) -3-butene-4-
Olide preparation: 4- (2,2) in 100 ml of methylene chloride.
3.0 g (11 mmol) of 3,4-trimethoxyphenyl) -4-oxobutanoic acid and 2.3 g (13 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride were added, and 2.7 g of triethylamine was added thereto ( 27 mmol)
Was slowly added dropwise, and after the addition was completed, stirring was continued at room temperature for 1 hour. Then, the same operation as in Example 1 was carried out to obtain 2.8 g (yield 100%) of the title compound. IR; ν _max ^neat (cm ^-1 ) 1795.

Example 3 4,5-Dihydronaphtho [1,2-b] furan-2 (3
Preparation of H) -one: 2.0 g (10 mmo) of 1-oxotetrahydronaphthalene-2-acetic acid in 50 ml of methylene chloride.
l) and 2.0 g (12 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride are dissolved therein, 2.4 g (24 mmol) of triethylamine is slowly added dropwise thereto, and after completion of the addition, 21 at room temperature. The stirring was continued for 5 hours. Then, the same operation as in Example 1 was carried out to obtain 1.4 g of the title compound (yield 78%). IR; ν _max ^KBr (cm ^-1 ) 1785.

Claims (1)

[Claims] 1. The following general formula (2):[In the formula, R³Has an organic group, R^FourIs a hydrogen atom or organic
Represents a group or R ³And R^FourTogether form a ring
Γ-keto acids represented by the general formula (1):[In the formula, R¹And R²Are the same or different and each is lower
Represents an alkyl group, X is a halogen atom, and n is 2 or 3
The haloiminium salt represented by
As represented by the general formula (3):[In the formula, R³And R^FourRepresents the same as above]
Of producing β, γ-butenolides.