JPH037673B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula The present invention relates to a dicarboxylic acid monoester represented by the following formula and a method for producing the same. In the above formula, R ¹ represents a hydrogen atom or a lower alkyl group such as a methyl group, ethyl group, propyl group, or butyl group. R ² and R ³ are the same or different; each is a hydrogen atom; a lower alkyl group such as a methyl group, an ethyl group, a propyl group, a butyl group; or a lower alkoxy group such as a methoxy group, an ethoxy group, a propoxy group, a butoxy group, etc. represent or
R ² and R ³ are together −CH=CH−CH=CH−
form a group. R ⁴ is a hydrogen atom, an acyl group, a methyl group, a t-butyl group, a triphenylmethyl group,
Represents a benzyl group or a trimethylsilyl group. Examples of the acyl group include an acetyl group, a propionyl group, a butyryl group, and a benzoyl group. The above-mentioned acyl group, methyl group, t-butyl group, triphenylmethyl group, benzine group and trimethylsilyl group are protecting groups used for the purpose of protecting a hydroxyl group. R ⁵ , R ⁶ , R ⁷ and R ⁸ are the same or different and each represents a hydrogen atom or an alkyl group such as a methyl group, an ethyl group, a propyl group, a butyl group, or R ⁵ and R ⁶ or R ⁷ and R ⁸ are together CH ₂ =
To represent a group, R ⁵ and R ⁷ together represent a single bond, or R ⁶ and R ⁸ together represent -CH=CH-
CH=CH− group, −CH ₂ CH=CHCH ₂ − group,

【formula】

[Formula] -CH ₂ CH ₂ CH ₂ CH ₂ - group,

【formula】

[Formula] Group or

[Formula] represents a group, and X represents a halogen atom. n represents an integer of 0.1 or 2. The dicarboxylic acid monoester represented by the general formula provided by the present invention is a new compound that has not been described in any known literature. Among these dicarboxylic acid monoesters, those in which R ⁴ in the general formula is a hydrogen atom have an excellent antioxidant effect and are useful for oxygen-sensitive organic materials, such as oils and fats, rubber products, plastics, processed foods, etc. It is useful as an antioxidant. In addition, those in which R ⁴ in the general formula is an acyl group, methyl group, t-butyl group, triphenylmethyl group, benzyl group or trimethylsilyl group,
By replacing these groups with hydrogen atoms using conventional methods, compounds having the above-mentioned antioxidant action can be obtained. Recently, vitamin E has attracted attention as a highly safe antioxidant, but it has not yet become a general-purpose antioxidant because it is relatively expensive and is easily oxidized and colored. As a result of intensive research to develop a new antioxidant that surpasses vitamin E, the present inventors have found that the dicarboxylic acid monoester represented by the above general formula has an antioxidant effect superior to vitamin E, or It was discovered that these monoesters of dicarboxylic acids can be easily produced as precursors of compounds having the same action, and the present invention has been achieved. According to the invention, the general formula [In the formula, R ¹ , R ² and R ³ have the same meanings as in the general formula, and R is the same as or different from R ⁴ in the general formula, and R is a hydrogen atom, an acyl group, a methyl group, t-
Represents a butyl group, a triphenylmethyl group, a benzyl group or a trimethylsilyl group. ] 2-substituted ethyl alcohol and the general formula [In the formula, R ⁵ , R ⁶ , R ⁷ , R ⁸ and n have the same meanings as in the general formula. ] The dicarboxylic acid monoester represented by the above general formula can be produced by reacting with the dicarboxylic acid anhydride represented by the following. This reaction can be carried out under the same conditions as in the usual reaction between an alcohol and an acid anhydride. For example, a 2-substituted ethyl alcohol represented by the general formula and a dicarboxylic acid anhydride represented by the general formula in an approximately equimolar equivalent amount to the 2-substituted ethyl alcohol are mixed in an inert solvent such as benzene, toluene, chloroform, dichloroethane, etc. in the presence of a tertiary amine such as pyridine or triethylamine or an acid such as sulfuric acid or p-toluenesulfonic acid in an amount of 2 molar equivalents or less based on the 2-substituted ethyl alcohol. By reacting at room temperature or under heating, the desired dicarboxylic acid monoester represented by the general formula can be obtained. The dicarboxylic acid monoester represented by the general formula obtained by the above ester synthesis reaction can be separated and recovered by a conventional method. For example, water is added to the reaction mixture, then extracted with ether etc., the extract is washed with water and dried, the solvent is distilled off, and the residue is recrystallized or purified by column chromatography to obtain the general formula A dicarboxylic acid monoester represented by can be obtained. Most of the 2-substituted ethyl alcohols represented by the general formula used as raw materials are compounds known per se;
56-145282), according to the method previously discovered by the present inventors, the general formula [In the formula, R, R ¹ , R ² and R ³ have the same meanings as in the general formula. Hydroquinone or its derivative represented by 4-
It can be easily obtained by reacting methyl-5,6-dihydro-2H-bilane in the presence of a Lewis acid (see Japanese Patent Application No. 1983-83654). Examples of Lewis acids used in this condensation reaction include trifluoroboric acid. Ether complex, aluminum chloride, aluminum bromide, ferrous chloride, ferric chloride
Examples include iron, stannous chloride, stannic chloride, zinc chloride, sulfuric acid, p-toluenesulfonic acid, etc., but aluminum chloride, boron trifluoride, and ether complexes are preferable. The amount of Lewis acid used is 0.1 to 2 times the molar amount, preferably 0.5 to 2 times the amount of the hydroquinone or its derivative represented by the general formula.
1.0 times the molar amount. This condensation reaction is preferably carried out in a solvent. For example, 1,2-dichloroethane, dichloromethane, chloroform, 1,1,2
-Halogenated hydrocarbons such as trichloroethylene, carbon tetrachloride, and chlorobenzene; Hydrocarbons such as benzene, toluene, xylene, cyclohexane, n-hexane, and ligroin; = Nitrogen-containing compounds such as nitromethane, nitrobenzene, benzonitrile, and acetonitrile; Oxygen-containing compounds such as methyl ethyl ketone, ethyl acetate, butyl acetate, or mixtures thereof can be used as the solvent, and 1,2-dichloroethane is particularly preferred. The amount of the solvent used is about 2 to 100 times, preferably about 5 to 20 times the weight of hydroquinone or its derivative represented by the general formula. This condensation reaction is usually -
The reaction is carried out at a temperature of 40°C to 150°C, preferably 0°C to 100°C.
The 4-methyl-5,6-dihydro-2H-pyran used here is a large amount of by-product when producing isoprene from isopten and formalin. It can also be synthesized by reaction with a liquid, etc., and is easily and inexpensively available. The dicarboxylic anhydride represented by the general formula, which is one of the raw materials, is a known compound. The present invention will be specifically described below with reference to Examples and Test Examples. Example 1 3,4-dihydro-2-(hydroxyethyl-
2,5,7,8-tetramethyl-2H-benzopyran-6-ol 10g, succinic anhydride 4.0g, p-
A mixture consisting of 0.6 g of toluenesulfonic acid and 100 ml of toluene was stirred at room temperature overnight and then heated under reflux for 2 hours. The resulting reaction solution was poured into water and extracted with diethyl ether. An aqueous sodium bicarbonate solution was added to the extract, and the target product was extracted into the aqueous layer. The resulting aqueous layer was washed with diethyl ether, acidified with dilute hydrochloric acid, and extracted with diethyl ether. After washing the ether extract with water and drying over anhydrous magnesium sulfate, low-boiling substances were distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to produce succinic acid having the following physical properties. 7.8 g of mono[2-(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]ester
I got it. (yield 56%). FD mass spectrum: [M] ⁺ 350 NMR spectrum (90MHz) δ ^HMS _CDCl3 : 1.22 (s,
3H); 1.65-2.2 (m, 13H); 2.45-2.73
(m, 6H); 4.05-4.55 (m, 2H); 7.0-8.0
(br.s, 2H) Example 2 2.5 g of 3,4-dihydro-2-(2-hydroxyethyl-2,5,7,8-tetramethyl-2H-benzopyran-6-ol, 0.8 g of pyridine and 1 , 2-Dichloroethane (50 ml) was added with 1.0 g (100 mmol) of succinic anhydride, stirred overnight at room temperature, and then heated under reflux for 2 hours.The resulting reaction solution was poured into dilute hydrochloric acid and extracted with diethyl ether. After washing the extract with water, an aqueous solution of sodium hydrogen carbonate was added thereto, and the target product was extracted into the aqueous layer.
After washing the resulting aqueous layer with diethyl ether,
This was made acidic by adding dilute hydrochloric acid, and extracted with diethyl ether. After washing the extract with water and drying over anhydrous magnesium sulfate, low-boiling substances were distilled off under reduced pressure, and the resulting concentrate was purified by silica gel chromatography to obtain succinic acid mono[2-(3, 4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]
3.2g of ester was obtained (yield 91%). Examples 3 to 6 The corresponding dicarboxylic acid was obtained by carrying out the reaction and separation and recovery in the same manner as in Example 2, except that 10 mmol of the dicarboxylic acid anhydride shown in Table 1 was used instead of 10 mmol of succinic anhydride in Example 2. A monoester was obtained. The results are shown in Table 1.

[Table] Example 7 In Example 2, 3,4-dihydro-2-(2
-Hydroxyethyl-2.5,7,8-tetramethyl-2H-benzobilan-6-ol instead of 2.5 g
By carrying out the reaction and separation and recovery in the same manner as in Example 2 except for using 3.4 g of 2,5,7,8-tetramethyl-2H-benzopyran-2-yl) ethanol, succinic acid having the following physical properties was obtained. Mono[2-(6-benzyloxy-3,4-dihydro-
4.1 g of 2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]ester was obtained (yield 93%). FD mass spectrum: [M] ⁺ 440 NMR spectrum (90MHz) δ ^HMS _CDCl3 : 1.22 (s,
3H); 1.65-2.25 (m, 13H); 2.4-2.8 (m,
6H); 4.07-4.56 (m, 2H); 4.7 (s,
2H); 7.2-7.6 (m, 5H); 10.8 (br.s, 1H) Example 8 In Example 2, 3,4-dihydro-2-(2
-hydroxyethyl, 2-(6-acetoxy-3,4-dihydro-
The following FD was obtained by carrying out the reaction and separation and recovery in the same manner as in Example 2, except that 2.5 g of 2-methyl-2H-benzopyran-2-yl)ethenol was used.
Mass spectrum of succinic acid mono[2-(6
-acetoxy-3,4-dihydro-2-methyl-2H
-benzopyran-2-yl)ethyl]ester
3.1g was obtained (yield 86%). FD mass spectrum: [M] ⁺ 350 Examples 9 to 16 In Example 2, instead of 10 mmol of succinic anhydride, cyclohexane-1,2-dicarboxylic anhydride, 1-cyclohexene-1,2-dicarboxylic anhydride, 4-cyclohexene-1,2-dicarboxylic anhydride, norbornane-2,3-dicarboxylic anhydride, 5-norbornene-2,3-dicarboxylic anhydride, 4-methyl-4-cyclohexene-
1,2-dicarboxylic anhydride, 1,4,5,6,
7,7-hexachloro-5-norbornene-2,
The corresponding dicarboxylic acid monoesters were obtained by performing the reaction and separation and recovery in the same manner as in Example 2, except that 10 mmol of each of 3-dicarboxylic anhydride or citraconic acid anhydride was used. The results are shown in Table 2.

【table】

[Table] Examples 17 to 23 In Example 2, instead of 2.5 g of 3.4-dihydro-2-(2-hydroxyethyl-2,5,7,8-tetramethyl-2H-benzopyran-6-ol, Table 3) 10 mmol of 2-substituted ethyl alcohol shown in
The corresponding succinic acid monoesters were obtained by carrying out the reaction and separation and recovery in the same manner as in Example 2, except that the respective succinic acid monoesters were used. The results are shown in Table 3.

【table】

[Table] Test Examples 1 to 19 Add 0.020g of each of the test compounds shown in Table 4 to ethyl linoleate per 100g of the ethyl linoleate.
were added and mixed to create a sample solution. AOM 20ml of these samples
(AntiOxygenmethod) test equipment, AOM
Abused under conditions (97.8℃, ventilation 2.33cc/sec),
The time required for POV (peroxide value) to reach 100meq/Kg was measured. The results are shown in Table 4.

【table】

【table】

【table】

【table】

Claims (1)

[Claims] 1. General formula [In the formula, R ¹ represents a hydrogen atom or a lower alkyl group. R ² and R ³ are the same or different and each represents a hydrogen atom, a lower alkyl group, or a lower alkoxy group, or R ² and R ³ together represent -CH=
Forms a CH-CH=CH- group. R ⁴ is a hydrogen atom,
It represents an acyl group, methyl group, t-butyl group, triphenylmethyl group, benzyl group or trimethylsilyl group. R ⁵ R ⁶ , R ⁷ and R ⁸ are the same or different and each represents a hydrogen atom or an alkyl group, or R ⁵ and R ⁶ or R ⁷ and R ⁸ together represent CH ₂ =
R ⁵ and R ⁷ together represent a single bond, R ⁶ and R ⁸ together represent -CH=CH-
CH=CH− group, −CH ₂ CH=CHCH ₂ − group,
[Formula] [Formula] represents a -CH ₂ CH ₂ CH ₂ CH ₂ - group, [Formula] [Formula] group or [Formula] group, and X represents a halogen atom. n represents an integer from 0 to 2. ] A dicarboxylic acid monoester represented by 2 General formula (In the formula, R is a hydrogen atom, an acyl group, a methyl group,
It represents a t-butyl group, a triphenylmethyl group, a benzine group or a trimethylsilyl group, and R ¹ represents a hydrogen atom or a lower alkyl group. R ² and R ³ are the same or different and each represents a hydrogen atom, a lower alkyl group, or a lower alkoxy group, or R ²
and R ³ together form a -CH=CH-CH=CH- group. ) 2-substituted ethyl alcohol and general formula (In the formula, R ⁵ , R ⁶ , R ⁷ and R ⁸ are the same or different and each represents a hydrogen atom or an alkyl group,
Or R ⁵ and R ⁶ or R ⁷ and R ⁸ together are CH ₂
= group, or R ⁵ and R ⁷ together represent a single bond, or R ⁶ and R ⁸ together represent -CH=CH
-CH=CH- group, _CH2CH = _CHCH2- group,
[Formula] [Formula] represents a -CH ₂ CH ₂ CH ₂ CH ₂ - group, [Formula] [Formula] group or [Formula] group, and X represents a halogen atom. n represents an integer from 0 to 2. ] A general formula characterized by reacting with a dicarboxylic acid anhydride represented by (In the formula, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and n
has the same meaning as above, and R ⁴ is the same as or different from R and represents a hydrogen atom, an acyl group, a methyl group, a t-butyl group, a triphenylmethyl group, a benzyl group, or a trimethylsilyl group. A method for producing a dicarboxylic acid monoester represented by