JPH05125070A - New method for producing 4-aryl-2(5h)-furanone - Google Patents

Abstract

PURPOSE:To obtain the subject compound useful as an intermediate for synthesizing medicines, perfumes or insect pheromones by reacting a 3-arylcrotonic acid ester with selenium dioxide in the presence of glacial acetic acid and perchloric acid. CONSTITUTION:A compound of formula I (Ar is aryl; M is methyl or ethyl) is allowed to react with selenium dioxide in the presence of glacial acetic acid and perchloric acid at 0-120 deg.C to obtain a compound of formula II. 1-4Mol of selenium dioxide, 0.01-1mol of perchloric acid and 10-50mol of glacial acetic acid are used per mol of the compound of formula I, respectively. The starting compound of formula I is readily obtained by the Wittig-Horner reaction of acetophenone with diethyl phosphonoacetic acid ester.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to 4-aryl-2.
It relates to a novel method for producing (5H) -furanone.

[0002]

2. Description of the Related Art As a method for synthesizing 4-aryl-2 (5H) -furanone, generally known is the Reformatsky reaction of acetoxyacetophenone and ethyl bromoacetate. For example, Japanese Examined Patent Publication No. 27027/1969 describes a method for producing a γ-butyrolactone derivative having a hypnotic action. In addition, recently, a method using phosphorus ylide or a palladium acetate catalyst has been reported (Reference J. Org. Chem., Vol. 5).
4, No. 22, (1989), J. Am. Am. Che
m. Soc. , 83, 1733 (1966), Tetr
ahedron, 22, 3189 (1966), etc.).

[0003]

The present application provides a novel method for producing 4-aryl-2 (5H) -furanone which is useful as an intermediate for the production of pharmaceuticals / fragrances or sex pheromones of insects.

4-aryl-2 represented by the following formula (I)
The (5H) -furanone has the formula:

[Chemical 3] In the formula, Ar represents an optionally substituted aryl group,

The method of the present invention, the formula:

[Chemical 4] In the formula, Ar is the same as above, and M is a methyl group or an ethyl group, and a selenium dioxide is allowed to act on a 3-aryl crotonic acid ester represented by the presence of glacial acetic acid and perchloric acid. It can be manufactured by

According to the manufacturing method of the present invention, the conventional method,
For example, it has the following advantages as compared with the method of reacting α-acetoxyacetophenone with ethyl bromoacetate. The reaction is one step and the yield is good. Since the reaction conditions are mild and the reaction operation is simple, it is not necessary to set special equipment or strict temperature conditions. Moreover, the reaction time and the time required for the purification operation are short. The starting material, 3-aryl crotonic acid ester, can be synthesized relatively easily. 4-aryl-2 (5 produced by the present invention
Some H) -furanones have a pharmacological effect, an aroma, and an insect sex pheromone activity. It is also useful as an intermediate for producing pharmaceuticals (Reference Tetrahedron 19
78, 34, 1949. Tetrahedron 1
982, 38, 2377. J. Heterocycle
e. Chem. 1984, 21, 237).

In the above manufacturing method, as a raw material, for example, 3
When-(4-chlorophenyl) crotonic acid methyl ester is used, it is represented by the following reaction formula.

[Chemical 5]

In the compounds of formula (I), Ar is preferably an optionally substituted phenyl group, an optionally substituted 1-naphthyl group, an optionally substituted 2 -A naphthyl group or an optionally substituted 2-thienyl group is shown. The type, number, position, etc. of the substituent of Ar are not particularly limited, but the electron-donating substituent has a higher yield than the electron-withdrawing substituent.
Further, the yield is better when there is a substituent at another position than the ortho position. Examples of the substituent of Ar include nitro, cyano, halogen (fluorine, chlorine, bromine, iodine), lower alkyl (methyl, ethyl, propyl, isopropyl, n-).
(Sec-, tert-) butyl, etc.), lower haloalkyl (methyl, ethyl, propyl, isopropyl, substituted with fluorine, chlorine, bromine, iodine, n- (sec
-, Tert-) butyl, etc.), lower alkoxy (methoxy, ethoxy, propoxy, n- (sec-, tert-
-) Butoxy etc.), phenoxy (which may be substituted with halogen, lower alkyl, lower alkoxy) and the like. In the compound of formula (I):
M preferably represents methyl.

In the starting compound of the formula (II), Ar
Has the same meaning as above, preferably the same meaning as the above-mentioned preferred definition. The compound of formula (II) is a Wittig-Horner of acetophenone and diethylphosphonoacetic acid ester.
It can be easily synthesized by a reaction (Wittig-Horner reaction), and specific examples thereof include the following compounds. Methyl 3-phenylcrotonate, or ethyl ester, methyl 3- (4-methylphenyl) crotonate, or ethyl ester, methyl 3- (4-chlorophenyl) crotonate, or ethyl ester, 3- (4-nitrophenyl) Methyl crotonate, or ethyl ester, methyl 3- (4-methoxyphenyl) crotonate,
Or ethyl ester, methyl 3- (4-phenoxyphenyl) crotonate, or ethyl ester, 3-
[4- (2,4-Dichlorophenoxy) phenyl] crotonic acid methyl or ethyl ester, 3- (3,4-
Dimethoxyphenyl) crotonate methyl or ethyl ester, 3- (1-naphthyl) crotonate methyl or ethyl ester, 3- (2-naphthyl) crotonate methyl or ethyl ester, or 3- (2-thienyl) Crotonic acid methyl or ethyl ester etc.

The process of the present invention can be carried out within a substantially wide temperature range. Generally, about 0 to about 1
It can be carried out at 20 ° C, preferably between about 20 and about 120 ° C. Further, the reaction is preferably carried out under normal pressure, but it can be operated under increased pressure or reduced pressure. The present invention can be carried out in a substantially wide molar ratio, but generally, 1 mol of selenium dioxide to 1 mol of 3-arylcrotonic acid ester is used.
4 molar amount, preferably 1 molar amount to 2 molar amount, glacial acetic acid, 10 molar amount to 50 molar amount, preferably 10 molar amount to 20 molar amount, and perchloric acid, 3-aryl crotonic acid It is used in an amount of 0.01 to 1 mol, preferably 0.01 to 0.1 mol, based on 1 mol of the ester. The content of the present invention will be specifically described below with reference to Examples, but the present invention should not be limited thereto.

[0011]

【Example】

 Synthesis example 1

[Chemical 6] 1.76 g of methyl 3-phenylcrotonate and 1.11.
g of selenium dioxide was suspended in glacial acetic acid (4.4 g), and perchloric acid acetic acid solution (0.1 mol / l., 0.1 mol / l) was added to the suspension, which was then heated under reflux at 125 ° C. for 5 hours and a half. did. After cooling down,
Precipitated selenium was filtered off and the filtrate was diluted with toluene.
The organic layer was washed successively with water, saturated aqueous sodium hydrogen carbonate solution, 1N aqueous hydrochloric acid solution and water, and dried over anhydrous sodium sulfate. Toluene was distilled off and the residue was recrystallized from ether to give 4-phenyl-2 (5H) -furanone (1.
12 g) are obtained. Melting point 87 ° C

Synthesis Example 2

[Chemical 7] 1.90 g of methyl 3- (4-methylphenyl) crotonate and 1.11 g of selenium dioxide were added to glacial acetic acid (4.80).
g), and add to this perchloric acid acetic acid solution (0.1 mol /
(0.1 mol / l) was added, and the mixture was heated under reflux at 100 ° C. for 4 hours. After allowing to cool, ether (30 ml) was added and the mixture was filtered to remove precipitated selenium. The filtrate was evaporated, benzene (40 ml) was added to the residue, the mixture was washed with 5% aqueous sodium hydrogen carbonate solution (2 x 20 ml) and water (2 x 20 ml), and dried over anhydrous sodium sulfate. Benzene was distilled off and the residue was recrystallized from ether / hexane (1: 2) to give 4-
(4-Methylphenyl) -2 (5H) -furanone (1.
25 g) are obtained. Melting point 117 ° C

Synthesis Example 3

[Chemical 8] 2.21 g of methyl 3- (4-nitrophenyl) crotonate and 1.11 g of selenium dioxide were added to glacial acetic acid (4.80).
g), and add to this perchloric acid acetic acid solution (0.1 mol /
(0.1 mol / l) was added, and the mixture was heated under reflux at 100 ° C. for 12 hours. After cooling, the precipitated selenium was removed, and water (40 ml) was added to the filtrate. The precipitated crude product was collected by filtration and recrystallized from acetic acid to give 4- (4-nitrophenyl) -2 (5
H) -Furanone (0.78 g) is obtained.
A compound synthesized in the same manner as in Synthesis Example 1, 2 or 3 above is shown in Table 1 below.

[0014]

[Table 1]

Synthesis Example of Intermediate Reference Synthesis Example 1

[Chemical 9] Methyl diethylphosphonoacetate (105 g) was added to a solution of sodium methanolate (27 g) in methanol (5
00 ml) and stirred for 5 minutes. Β-Acetylnaphthalene (42.5 g) was added thereto, and the mixture was stirred at room temperature for 1 hour and then heated under reflux for 10 hours. After evaporating most of the solvent under reduced pressure, the residue was diluted with 200 ml of water and extracted with benzene. (50 ml x 2). The benzene layer was washed with water and then dried. By distilling off benzene, methyl 3- (β-naphthyl) crotonate is obtained. Boiling point 168-173 ℃ (0.1mmHg)

[0016]

INDUSTRIAL APPLICABILITY The 4-aryl-2 (5H) -furanone derivative can be easily produced with high yield by the production method of the present invention.

Claims (2)

[Claims] 1. The formula: In the formula, Ar represents an optionally substituted aryl group, and M represents a methyl group or an ethyl group, in the presence of glacial acetic acid and perchloric acid. And is treated with selenium dioxide in the formula: In the formula, Ar is the same as above, 4-aryl-2
Method for producing (5H) -furanone. 2. Ar is an optionally substituted phenyl group, an optionally substituted naphthyl group, or an optionally substituted thienyl group, and M is a methyl group. The synthetic method according to claim 1, wherein