JPH0326190B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula () The present invention relates to α-hydroxycarboxylic acids and derivatives thereof. In the above formula, R ¹ represents a hydrogen atom or a lower alkyl group such as a methyl group, ethyl group, propyl group, butyl group. R ² and R ³ are the same or different and each represents a hydrogen atom; a lower alkyl group such as a methyl group, an ethyl group, a propyl group, or a butyl group; or a lower alkoxy group such as a methoxy group, an ethoxy group, a propoxy group, or a butoxy group; Or ^R2 and ^R3 together form a -CH=CH-CH=CH- group.
R ⁴ represents a hydrogen atom. n means an integer from 0 to 2. Further, derivatives of α-hydroxycarboxylic acid represented by the general formula () include alkyl esters such as methyl ester, ethyl ester, propyl ester, butyl ester, octyl ester, tetradecyl ester, and stearyl ester; lithium salt, Alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as magnesium salts and calcium salts; lower salts such as ammonium salts, methylammonium salts, ethylammonium salts, trimethylammonium salts, tetramethylammonium salts, and tetraethylammonium salts It is an ammonium salt that may be substituted with an alkyl group. The α-hydroxycarboxylic acid represented by the general formula () and its derivatives provided by the present invention are:
This is a new compound that has not been described in any known literature. These α
-Hydroxycarboxylic acids and their derivatives have excellent antioxidant effects and are useful as antioxidants for oxygen-sensitive organic materials, such as oils and fats, rubber products, plastics, and processed foods. Salts of α-hydroxycarboxylic acids represented by the general formula () are particularly suitable for use as antioxidants in processed foods, taking advantage of their water-soluble properties. Further, when R ⁴ in the general formula () is a protecting group, the compound having the above-mentioned antioxidant effect can be obtained by replacing this protecting group with a hydrogen atom by a conventional method. α given by the general formula ()
-Since salts of hydroxycarboxylic acids are highly water-soluble, it is easy to separate these salts from removable impurities mixed in during production, and the salts from which fat-soluble impurities have been removed are neutralized using conventional methods. By this, highly pure α-hydroxycarboxylic acid can be obtained, and by further subjecting this α-hydroxycarboxylic acid to a normal esterification reaction, highly pure α-hydroxycarboxylic acid can be obtained.
-Hydroxycarboxylic acid ester. 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 found that α-hydroxycarboxylic acid and its derivatives represented by the general formula () have a superior antioxidant effect than vitamin E. The present inventors have discovered that these α-hydroxycarboxylic acids and derivatives thereof can be easily produced, and have thus arrived at the present invention. According to the invention, the general formula () [In the formula, R ¹ , R ² R ³ and n have the same meanings as in the general formula (), and R represents a hydrogen atom. ] By reacting the aldehyde represented by the cyanide compound with the general formula () [In the formula, R ¹ , R ² , R ³ , R and n have the same meanings as in the general formula (). ] The α-hydroxycarboxylic acid represented by the general formula () can be produced by obtaining the α-hydroxynitrile represented by the following and then hydrolyzing the a-hydroxynitrile. Here, the cyanide compounds include hydrogen cyanide; alkali metal cyanides such as sodium cyanide and potassium cyanide; organic aluminum cyanides such as dimethylaluminum cyanide and diethylaluminum cyanide; trimethylsilylanide and dimethyl-t-butylsilylanide. Examples include organic silicon cyanide such as. The reaction between the aldehyde represented by the general formula () and the cyanide compound can be carried out under conventionally known general cyanhydrination reaction conditions. Representative examples of the cyanohydrination reaction are shown below. (Reaction example a) Reaction between aldehyde and hydrogen cyanide The aldehyde represented by the general formula () and about 1 to 10 times the mole of the aldehyde, preferably about 1 to 3 times the mole of the aldehyde
twice the molar amount of hydrogen cyanide, preferably in the presence of a catalytic amount of an alkali metal cyanide such as sodium cyanide or potassium cyanide, in an inert solvent such as diethyl ether, methanol, ethanol, benzene, toluene, dichloroethane, or chloroform, or an inert solvent such as α represented by the general formula () by reacting under cooling or pressure in the presence of
- Obtain hydroxynitrile. (Reaction example 2) Reaction between aldehyde and alkali metal cyanide. First, the aldehyde represented by the general formula () is mixed with an alkali metal bisulfite such as potassium bisulfite or sodium bisulfite in an amount of about 1 to 2 times the mole of the aldehyde. For example, in a mixed solvent of water and ethanol,
By reacting at about 0 to 50°C, an alkali metal bisulfite salt adduct of the aldehyde is produced, and then to this, about 1 to 2 times the mole of alkali metal cyanide to the aldehyde is reacted at about 0 to 5°C. By doing so, α-hydroxynitrile represented by the general formula () is obtained. (Reaction Example C) Reaction between aldehyde and organic aluminum cyanide or organic silicon cyanide The aldehyde represented by the general formula () and about 1 to 3 times the mole of the aldehyde, preferably about 1 to 2 times the mole of the aldehyde.
Double the molar amount of organic aluminum cyanide or organic silicon cyanide and methylene chloride, dichloroethane,
α-Hydroxynitrile represented by the general formula () is obtained by reacting in an inert solvent such as carbon tetrachloride, tetrahydrofuran, benzene, toluene, etc. at about -50°C to 50°C, preferably at about -20°C to room temperature. . The α-hydroxycarboxylic acid represented by the general formula () can be produced by hydrolyzing the α-hydroxynitrile represented by the general formula () obtained by the above-mentioned cyanohydrination reaction in accordance with a conventional method. This hydrolysis reaction can be carried out using mineral acids such as hydrochloric acid and sulfuric acid, or potassium hydroxide,
The reaction can be carried out in the presence of an alkali metal hydroxide such as sodium hydroxide, and if necessary in the presence of a high-boiling alcohol such as glycerin, ethylene glycol or methyl cellosolve, at room temperature or under heating. By subjecting the α-hydroxycarboxylic acid represented by the general formula () to a conventionally known general esterification reaction or salt formation reaction, the general formula ()
It is possible to obtain an ester or salt of α-hydroxycarboxylic acid represented by For example, an α-hydroxycarboxylic acid represented by the general formula () and an alkyl alcohol such as methyl alcohol, ethyl alcohol, butyl alcohol, octyl alcohol, or stearyl alcohol in an equimolar or large excess amount are combined with p-toluenesulfonic acid, sulfuric acid, or a strong acid. The reaction is carried out in the presence of an acid catalyst such as a neutral ion exchange resin, in an inert solvent such as benzene, toluene, dichloroethane, etc., or in the absence of a solvent at room temperature or under heated reflux, and preferably the water produced is removed from the system. By removing, the corresponding α-hydroxycarboxylic acid ester is obtained. Also, alkaline metal hydroxides such as potassium hydroxide and sodium hydroxide in an equimolar amount to the α-hydroxycarboxylic acid represented by the general formula (); ammonia, methylamine, dimethylamine, trimethylamine, triethylamine, tetramethyl hydroxide The corresponding α-hydroxycarboxylic acid salt can be obtained by reacting an amine such as ammonium in the presence of water and/or a lower alcohol such as methyl alcohol, ethyl alcohol, or propyl alcohol. The alkali metal salt of α-hydroxycarboxylic acid thus obtained and an alkaline earth metal halide such as calcium chloride, magnesium chloride, and magnesium bromide are mixed in water and/or a lower alcohol such as methyl alcohol or ethyl alcohol. An alkaline earth metal salt of α-hydroxycarboxylic acid can be obtained by reacting in the presence of α-hydroxycarboxylic acid. The α-hydroxycarboxylic acid represented by the general formula () and its ester obtained by the above method can be separated and recovered by a conventional method. For example, water is added to the reaction mixture, and if necessary, an acid such as hydrochloric acid or sulfuric acid is added to make it weakly acidic, followed by extraction with diethyl ether or the like. After washing the extract with water and drying, the solvent is distilled off, and the residue is recrystallized or purified by column chromatography to obtain α-hydroxycarboxylic acid or its ester represented by the general formula (). Obtainable. Further, in order to separate and recover the α-hydroxycarboxylic acid salts represented by the general formula () from the reaction mixture, the reaction mixture may be concentrated to dryness by a conventional method. As mentioned above, the salts of α-hydroxycarboxylic acid represented by the general formula () are highly water-soluble, so it is easy to separate these salts from fat-soluble impurities that are mixed in during production. By neutralizing the removed salts with an acid such as hydrochloric acid or sulfuric acid, highly pure α-hydroxycarboxylic acid can be obtained.
Furthermore, by subjecting this α-hydroxycarboxylic acid to the above-mentioned esterification reaction, a highly purified α-hydroxycarboxylic acid ester can be obtained. The aldehyde represented by the general formula () used as a raw material is a known compound represented by the following general formula ()
It can be easily obtained by oxidizing the alcohol represented by, for example, with chromic anhydride in the presence of pyridine [Helvetica Chimica Acta Vol. 61, 837-
See page 843 (1978)]. The present invention will be specifically described below with reference to Examples and Test Examples. Example 1 Add sodium bisulfite to a solution of 1.18 g of 2-(6-benzyloxy-3,4-dihydro-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)acetaldehyde and 13 ml of ethanol.
2 ml of an aqueous solution of 0.73 g was added dropwise. After the sodium bisulfite adduct precipitates, an aqueous solution of 0.34 g of sodium cyanide is added to the reaction mixture with vigorous stirring.
1.5 ml was added dropwise. After the dropwise addition, the mixture was stirred at room temperature for 4 hours, water was added to the reaction mixture, and the mixture was extracted with diethyl ether. After washing the extract with water, low-boiling substances were distilled off. 20 ml of concentrated hydrochloric acid was added to the obtained crude cyanohydrin, and the mixture was heated under reflux for 1 hour. After cooling,
Water was added to the reaction mixture, and the mixture was extracted with diethyl ether. The extract was washed with water and dried over anhydrous magnesium sulfate, and then low-boiling substances were distilled off under reduced pressure. By dissolving the obtained concentrate in diethyl ether and reprecipitating it by adding n-hexane, 2-hydroxy-3-[2-(3,4
-dihydro-6-hydroxy-2,5,7,8-
Tetramethyl-2H-benzopyran-2-yl)]
0.84 g of propionic acid was obtained (yield 81.9%). FD mass spectrum [M] ⁺ 294 NMR spectrum (90MHz) δ ^HMS _CDCl3 : 1.28 (s, 3H); 1.7-2.3 (m, 13H); 2.57
(t, J=7Hz, 2H); 4.33~4.57 (m,
1H); 6.3 (br, s, 3H) Example 2 In Example 1, 2-(6-benzyloxy-
2-(6-acetoxy-3,
4-dihydro-2,5,7,8-tetramethyl-
2-Hydroxy-3-[2-(3,4-dihydro-6-hydroxy) 0.89 g of -2,5,7,8-tetramethyl-2H-benzopyran-2-yl)propionic acid was obtained (yield 86.7%). Examples 3-4 In Example 1, 2-(6-benzyloxy-
2-(6-benzyloxy-3,4-dihydro-2,5,7 , 8-tetramethyl-2H-benzopyran-2-yl)carbaldehyde 1.13 g, 3-(6-benzyloxy-3,
4-dihydro-2,5,7,8-tetramethyl-
By carrying out the reaction and separation and recovery in the same manner as in Example 1 except for using 1.23 g of 2H-benzopyran-2-yl)propionaldehyde, the corresponding 2-hydroxy-2-[2-(3,4-dihydro -6-hydroxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)acetic acid and 2-hydroxy-4-[2-(3,4-dihydro-6-hydroxy-2,5, 7,8-tetramethyl-2H-benzopyran-2-yl)butyric acid was obtained.
The results are shown in Table 1.

[Table] Examples 5-6 In Example 1, 2-(6-benzyloxy-
3,4-dihydro-2,5,7,8-tetramethyl-2H-benzopyranyl)acetaldehyde
2-(6-benzyloxy-3,
1.29 g of 4-dihydro-7,8-dimethoxy-2,5-dimethyl-2H-benzopyran-2-yl)acetaldehyde, 2-(6-benzyloxy-
By carrying out the reaction and separation and recovery in the same manner as in Example 1, except that 1.26 g of 3,4-dihydro-2,5-dimethyl-2H-naphtho[1,2-b]pyran-2-yl)acetaldehyde was used. , respectively the corresponding 2-hydroxy-3-[2-(3,4-dihydro-7,8-dimethoxy-2,5-dimethyl-6-hydroxy-2H-benzopyran-2-yl)propionic acid and 2-hydroxy -3-[2
-{3,4-dihydro-6-hydroxy-2,5
-dimethyl-2H-naphtho(1,2-b)pyran-2-yl}]propionic acid was obtained. The results are shown in Table 2.

[Table] Test Examples 1 to 12 The test compounds shown in Table 3 were added to ethyl linoleate at 0.020 g per 100 g of the ethyl linoleate.
g was added and mixed to prepare a sample. These samples were tested using AOM (Antioxygen method) test equipment.
The material was abused under AOM conditions (97.8°C, aeration 2.33cc/sec), and the time required for POV (peroxide value) to reach 100meq/Kg was measured. The results are shown in Table 3.

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【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, a hydrogen atom,
Represents a lower alkyl group or a lower alkoxy group, or R ² and R ³ together represent -CH=CH-CH
Forms a =CH- group. R ⁴ represents a hydrogen atom.
n represents an integer from 0 to 2. ) α-Hydroxycarboxylic acids represented by the following, and their esters and salts.