JP4972343B2 - Method for producing amide compound - Google Patents

Description

  The present invention relates to an efficient method for producing an amide compound.

Conventionally, as a method for obtaining a 1,3-diamide derivative from a 1,3-dicarboxylic acid derivative, (1) a method of heating and dehydrating condensation of a 1,3-dicarboxylic acid derivative and an excess amount of amine, (2) It is known how to convert a 1,3-dicarboxylic acid derivative to a 1,3-diester derivative and then exchange it from diester to diamide by adding an excess amount of amine and heating in the presence of a catalyst such as alkali. It has been.
However, in these reactions, an intramolecular imidization reaction due to the formation of a 6-membered ring is likely to proceed even in the presence of a large excess of amine, and once formed, the intramolecular imide compound reacts in the presence of an excessive amount of amine. There is a problem that even if it continues, it does not disappear easily.
Further, as a method for producing a gelling agent for an oily substrate, a method for producing a triamide compound in which an alkanetricarboxylic acid is reacted with 3 to 10 mol of an excess amine compound with respect to 1 mol of the carboxylic acid (see Patent Document 1). ), A method for producing an N-acyl-L-aspartic acid diamide compound in which a fatty acid halide and L-aspartic acid are reacted and further reacted with an amine compound is known (see Patent Document 2).
In these production processes, an intramolecular imide compound is generated. When such an amide compound containing an intramolecular imide compound is used as a gelling agent for an oily substrate, there is a problem that the strength of the gel is lowered.

JP 2005-281292 A JP 2002-316971 A

  It is an object of the present invention to provide a method for producing an amide compound that reacts a carboxylic acid derivative with an amine, and that can reduce the production of by-product intramolecular imide compounds. .

When the present inventors produced an amide compound by reacting a carboxylic acid derivative with an amine, the by-product intramolecular imide compound was reacted at a temperature below the melting point of the carboxylic acid derivative and amine present in the system. It was found that by aging the mixture, it was quickly converted into the desired amide compound.
That is, the present invention is a method for producing an amide compound by reacting a carboxylic acid derivative represented by the following general formula (1) or general formula (2) with an amine represented by the following general formula (3). And the manufacturing method of the amide compound represented by following General formula (4) including the process of ageing | curing | ripening a reaction mixture at the temperature below melting | fusing point of this carboxylic acid derivative and this amine after reaction is provided.

[Wherein, X ¹ and X ² are each independently a halogen atom or —OR ⁵ (R ⁵ is a hydrogen atom, or a saturated or unsaturated straight chain having 1 to 5 carbon atoms which may have a substituent. Z ¹ , Z ² and Z ³ each independently represents an amide group, an ester group or a phenyl group, and m, n and p are each independently selected. Represents 0 or 1, and each of R ¹ , R ² and R ³ independently represents a hydrogen atom or a saturated or unsaturated linear or branched group having 1 to 20 carbon atoms which may have a substituent. A chain hydrocarbon group is shown. ]

(In the formula, Z ¹ , Z ² and Z ³ , m, n and p, and R ¹ , R ² and R ³ are the same as above.)

(In the formula, R ⁴ is a saturated or unsaturated linear chain having 1 to 24 carbon atoms, which may contain at least one selected from a hydroxyl group, an ether group, an ester group, an amino group, and an amide group. Or a branched hydrocarbon group.)

(Wherein Z ¹ , Z ² and Z ³ , m, n and p, and R ^{1 to} R ³ are the same as above, and R ⁴ is independently the same as above.)
Is to provide.

  The production of an intramolecular imide compound by-produced by the production method of the present invention can be reduced, and an amide compound can be obtained efficiently.

In general, there is a positive correlation between reaction temperature and reaction rate. Further, in the case of a compound that solidifies at a low temperature, once it is solidified, it becomes difficult to handle, and it takes a lot of labor and cost to redissolve. Also in the case of producing an amide compound, industrially, the target product is usually produced by carrying out the reaction and purification while keeping the liquid state at a temperature higher than the liquefaction temperature.
On the other hand, the present invention reacts a carboxylic acid derivative represented by the following general formula (1) or (2) with an amine represented by the following general formula (3) to carry out an amidation reaction. Thereafter, the reaction mixture is aged at a temperature below the melting point of the carboxylic acid derivative and the amine to produce an amide compound represented by the following general formula (4).

  Preferred examples of the amide compound produced by the method of the present invention include hexane-1,3,6-tricarboxylic acid tri (3′-octadecyloxypropyl) amide, hexane-1,3,6-tricarboxylic acid trioctadecylamide, Examples include hexane-1,3,6-tricarboxylic acid tri (2′-ethylhexyl) amide, hexane-1,3,6-tricarboxylic acid tridodecylamide, and the like. Among these, hexane-1,3,6-tricarboxylic acid tri (3'-octadecyloxypropyl) amide is particularly mentioned.

[Amidation reaction]
The carboxylic acid derivative used as a starting material in the present invention is represented by the general formula (1) or the general formula (2).
In the general formula (1), X ¹ and X ² each independently represent a halogen atom or —OR ⁵ .
The halogen atom is preferably a chlorine atom from the viewpoints of reactivity and economy.
R ⁵ represents a hydrogen atom or a saturated or unsaturated linear or branched hydrocarbon group having 1 to 5 carbon atoms which may have a substituent. R ⁵ is preferably a hydrogen atom or a saturated linear or branched hydrocarbon group having 1 to 3 carbon atoms which may have a substituent from the viewpoints of reactivity and economy. A hydrogen atom or a saturated hydrocarbon group having 1 to 2 carbon atoms is more preferable. Among these, a hydrogen atom or a methyl group is particularly preferable.

In the general formulas (1) and (2), Z ¹ , Z ² and Z ³ each independently represent a substituent selected from an amide group, an ester group and a phenyl group. Z ¹ , Z ² and Z ³ are preferably an amide group and a phenyl group from the viewpoint of the selectivity of the reaction.
In the general formulas (1) and (2), m, n and p each independently represent 0 or 1. The number of m, n and p can be selected according to the purpose of use of the amide compound to be produced. From the viewpoint of reactivity, at least one of m, n and p is preferably 0, more preferably at least 2 is 0, and particularly preferably all 0.
In the general formulas (1) and (2), R ¹ , R ² and R ³ are each independently a hydrogen atom or a saturated or unsaturated straight chain having 1 to 20 carbon atoms which may have a substituent. A chain or branched hydrocarbon group is shown.
R ¹ , R ^2, and R ³ may have a structure that matches the intended use of the amide compound to be produced. From the viewpoint of reactivity, at least one of R ¹ , R ² and R ³ is preferably a hydrogen atom, and more preferably at least two are hydrogen atoms.
In addition, as R ¹ , R ² and R ³ , at least one is preferably a hydrocarbon group represented by the following general formula (5) from the viewpoint of obtaining a triamide compound.

In the general formula (5), X ³ represents a halogen atom or —OR ⁵ (R ⁵ is as defined above). As the halogen atom and R ^{5, the same} as the preferred examples of the halogen atom of X ¹ and X ² and R ⁵ can be mentioned.
q represents an integer of 0 to 3. q may have a structure that matches the purpose of use of the amide compound to be produced, but is preferably 1 to 3 from the viewpoint of reactivity.
Examples of the substituent for the hydrocarbon group of R ¹ , R ² and R ³ include a hydroxyl group, an ether group, an ester group, a carbonyl group, an amino group, an amide group, and a phenyl group.

Examples of the carboxylic acid derivative represented by the general formula (1) include hexane-1,3,6-tricarboxylic acid, butane-1,2,4-tricarboxylic acid, glutaric acid, dimethyl glutarate, and glutamic acid methyl ester. Is mentioned.
Examples of the carboxylic acid derivative represented by the general formula (2) include acid anhydrides of the above carboxylic acids.

The amine used as a starting material in the present invention is represented by the general formula (3).
In the general formula (3), R ⁴ is a saturated or unsaturated straight chain having 1 to 24 carbon atoms which may contain at least one selected from a hydroxyl group, an ether group, an ester group, an amino group, and an amide group. A chain or branched hydrocarbon group is shown.

Examples of the linear saturated hydrocarbon group include hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, icosyl, docosyl, tetracosyl and the like.
Examples of the branched saturated hydrocarbon group include methylpentyl, methylhexyl, ethylhexyl, methylnonyl, dimethyloctyl, tetramethyloctyl, methyldodecyl, dimethylundecyl, trimethyldecyl, hexyldecyl, methylpentadecyl, dimethyltetradecyl, Examples include trimethyltridecyl, tetramethyldodecyl, octyldodecyl, decyltetradecyl and the like.
Examples of the linear or branched unsaturated hydrocarbon group include hexenyl, octenyl, decenyl, dodecenyl, tetradecenyl, hexadecenyl, octadecenyl, icocenyl, dococenyl, tetracosenyl, methylpentenyl, methylhexenyl, ethylhexenyl, methylnonenyl, and dimethyl. Examples include octenyl and tetramethyloctenyl.

Examples of the linear or branched saturated hydrocarbon group having a hydroxyl group include, for example, hydroxyhexyl, hydroxyoctyl, hydroxydecyl, hydroxydodecyl, hydroxytetradecyl, hydroxyhexadecyl, hydroxyoctadecyl, hydroxyicosyl, hydroxydocosyl , Hydroxytetracosyl, hydroxymethylpentyl, hydroxymethylhexyl, hydroxyethylhexyl, hydroxymethylnonyl, hydroxydimethyloctyl, hydroxytetramethyloctyl and the like.
Examples of the linear or branched unsaturated hydrocarbon group having a hydroxyl group include hydroxyhexenyl, hydroxyoctenyl, hydroxydecenyl, hydroxydodecenyl, hydroxytetradecenyl, and hydroxyhexadecenyl. , Hydroxyoctadecenyl, hydroxyicosenyl, hydroxydocosenyl, hydroxytetracocenyl, hydroxymethylpentenyl and the like.

Examples of the hydrocarbon group having an ether group include (ethylhexyloxy) ethyl, dodecyloxyethyl, octadecyloxyethyl, octadecyloxypropyl, [(octadecyloxy) ethyloxy] ethyl, octadecenyloxypropyl, and the like. Is mentioned.
Examples of the hydrocarbon group having an ester group include a 2-stearoyloxyethyl group.
Examples of the hydrocarbon group having an amino group include N, N-dioctyl-3-aminopropyl group.
Examples of the hydrocarbon group having an amide group include N-octadecylylaminoethyl, N-dodecylylaminopropyl, N-octadecenyloylaminopropyl, and N- (2-ethylhexanoyl) aminoethyl. Can be mentioned.
In the hydrocarbon group, the position of the branch, the position of the unsaturated bond, the position of the hydroxyl group, the ether group, the ester group, the amino group, and the amide group are not particularly limited.

In the general formula (3), R ⁴ may have a structure that matches the intended use of the amide compound to be produced. In the present invention, from the viewpoint that the aging temperature in the aging step described below is a temperature equal to or lower than the melting point of the amine represented by the general formula (3), R ⁴ is saturated or saturated with ^{4 to} 24 carbon atoms. The hydrocarbon group having an unsaturated linear or branched hydrocarbon group and an ether group is preferred, and further a saturated or unsaturated linear or branched carbonized carbon having 10 to 24 carbon atoms in total. The hydrocarbon group having a hydrogen group and an ether group is preferred. Of these, octadecyloxyethylene, octadecyloxypropylene, cetyl, and stearyl are particularly preferable.
The amine may be used alone or in combination of two or more depending on the purpose of use of the amide compound to be produced.

  The amount of the amine used is preferably 1 equivalent or more based on the carboxyl group of the carboxylic acid derivative from the viewpoint of selectively synthesizing an amide compound, and preferably 1.1 moles or more from the viewpoint of the reaction rate. Furthermore, 1.2 mol or more is preferable.

In the amidation reaction, a solvent such as a higher alcohol, preferably stearyl alcohol, can be used for the purpose of increasing the reaction rate, but it is desirable not to use a solvent from the viewpoints of economy and post-treatment.
Moreover, an acid can be used as a catalyst for the purpose of increasing the reaction rate. As the catalyst, general mineral acids and organic acids can be used. For example, examples of the mineral acid include hydrochloric acid, sulfuric acid, and phosphoric acid, and examples of the organic acid include acetic acid, citric acid, and paratoluenesulfonic acid.
Although there is no restriction | limiting in particular as a usage-amount of a catalyst, From a viewpoint of manufacturing cost, Preferably it is 10 mass% or less with respect to a reaction mixture.
From the viewpoint of improving the conversion rate of the carboxylic acid derivative, the reaction temperature is preferably raised to a temperature higher than the temperature at which the reaction mixture is melted and brought into a liquid state. The reaction temperature is generally 120 to 220 ° C, preferably 130 to 200 ° C.
From the viewpoint of the reaction rate, it is preferable to carry out the reaction while stirring the system and mixing thoroughly.
The reaction time varies depending on the reactivity of the raw materials, the mixing ratio, the presence or absence of a catalyst, and the reaction temperature, but it is preferable to continue until the composition of the reaction mixture does not change from the viewpoint of production cost. The reaction time is usually 1 to 30 hours.

[Aging process]
In the reaction mixture obtained by the amidation reaction, in addition to the target amide compound represented by the general formula (4), the following general formula (6)

(In the formula, Z ¹ , Z ² and Z ³ , m, n and p, and R ^{1 to} R ⁴ are the same as above.)
An intramolecular imide compound represented by

In the production method of the present invention, after the amidation reaction described above, a step of aging the reaction mixture is performed. The intramolecular imide compound is quickly converted to the target amide compound by the aging step.
As the intramolecular imide compound, the reaction mixture of the amidation reaction described above may be used as it is, or may be used after being purified and isolated from the mixture.

In this step, from the viewpoint of reaction yield, aging is preferably performed by adding the amine represented by the general formula (3).
Specific examples and preferred examples of the amine used in this step include the same amines used in the amidation reaction described above.
The amount of amine used is preferably an equivalent or more with respect to the intramolecular imide compound from the viewpoint of reaction yield, more preferably 2 or more mole equivalent, and further preferably 5 or more mole equivalent from the viewpoint of the aging rate.
Moreover, from a viewpoint of manufacturing cost and a post-process, 10 molar equivalent or less is preferable, and also 8 molar equivalent or less is preferable.

In this step, it is possible to use a solvent such as a higher alcohol, preferably stearyl alcohol, but it is preferable to perform aging in the absence of a solvent from the viewpoint of reaction rate and production cost. When a solvent is used in the amidation reaction described above, it is preferable to perform aging after removing the solvent.
In this step, the acid described in the amidation reaction can be used as a catalyst for the purpose of increasing the aging rate. Although there is no restriction | limiting in particular as the usage-amount of a catalyst, Preferably it is 10 mass% or less with respect to the reaction mixture from an economical viewpoint.
In this step, water can be added for the purpose of increasing the aging rate. From the viewpoint of preventing a decrease in yield due to a competitive hydrolysis reaction of an intramolecular imide compound caused by the addition of water, the amount of water used is preferably 5% by mass or less, more preferably Add so that it becomes 1 mass% or less.

This step proceeds in a solidified state at a temperature below the melting point of the carboxylic acid derivative and amine used. At this time, the reaction mixture that has been in the liquid state in the amidation reaction can be cooled and aged as it is, but in consideration of subsequent handling, it is flaked while cooling, or flaked after cooling. Can also be aged.
For the purpose of homogenizing the reaction mixture used in this step, if the mixture is solid, it can be stirred in the form of flakes or powders. Further, the mixture can be heated to a temperature equal to or higher than the melting point of the carboxylic acid derivative and amine used, and mixed in a liquid state. In this case, after cooling and solidification, it is not necessary to stir.
In this step, for example, when the purpose of using the amide compound is a gelling agent for an oily substrate, the system may appear to be solidified even at a temperature higher than the melting point of the amine used. At this time, if centrifugal separation or the like is performed, phase separation is observed and the solidification may not be achieved. In such a case, ripening proceeds more rapidly by completely solidifying the system.

The aging temperature in this step is preferably lower than the melting point of the carboxylic acid derivative and amine used, from the viewpoint that freezing point depression can occur when the system is a mixture. Although the degree of freezing point depression varies depending on the composition of the mixture, it is more preferably a temperature that is 5 ° C. or lower than the melting point.
On the other hand, since the reaction rate has a positive correlation with the temperature, the temperature is preferably as high as possible within the above range. Therefore, the aging temperature is preferably 5 ° C. to 50 ° C. lower than the melting point of the carboxylic acid derivative and amine used, and more preferably 5 ° C. to 30 ° C. lower than the melting point of the carboxylic acid derivative and amine used. preferable.
The aging time varies depending on the reactivity of the compound, the presence or absence of a catalyst and water, the amount of amine used, the reaction temperature, the remaining allowable amount of imide, etc., but is usually 0.5 hours to 2 weeks. The aging time is preferably 2 hours to 1 week from the viewpoint of production cost.

〔Evaluation methods〕
The composition ratio of triamide compound / intramolecular imide compound / diamide monocarboxylic acid compound in the amidation reaction mixture after aging obtained in each Example was measured by high performance liquid chromatography (HPLC).

Example 1
[Amidation reaction]
To a 500 mL four-necked round bottom flask equipped with a dehydrating tube, 22.4 g of 1,3,6-hexanetricarboxylic acid (mp 112 ° C.) and 3-octadecyloxy-1-propylamine [mp; 46.2 ° C. (Mettler) FP62 type melting point measuring instrument)] / stearyl alcohol = 87.1 / 12.9 (mass ratio) mixture was added 127.6 g and reacted at 170 ° C. while dehydrating. The composition ratio (mass ratio) in the mixture after 22 hours was determined based on HPLC, amine analysis, and water content analysis: triamide compound / intramolecular imide compound / diamide monocarboxylic acid compound / amine / water / alcohol = 54.5 / 18 3 / 1.3 / 14.4 / 0.2 / 11.2.
[Aging process]
1.0 g of the amidation reaction mixture [composition ratio (mass ratio): triamide compound / intramolecular imide compound / diamide monocarboxylic acid compound = 76.5 / 21.1 / 2.4] and 3-octadecyloxy- 0.73 g of a 1-propylamine / stearyl alcohol = 87.1 / 12.9 (mass ratio) mixture was placed in a sample tube and heated to 130 ° C. to be uniformly dissolved. Thereafter, the mixture was cooled to 40 ° C. and solidified, and then aged at 40 ° C. for 24 hours. The results are shown in Table 1.

Example 2
2.2 g of the amidation reaction mixture obtained by the amidation reaction of Example 1 and 1.8 g of 3-octadecyloxy-1-propylamine / stearyl alcohol = 87.1 / 12.9 (mass ratio) The sample was put into a sample tube and heated up to 130 ° C. to dissolve uniformly. After cooling to 25 ° C. and solidifying, the mixture was aged at 25 ° C. for 24 hours. The results are shown in Table 1.

Example 3
In the aging step, the same procedure as in Example 2 was performed except that 15 mg of water was further added as a raw material. The results are shown in Table 1.

Comparative Example 1
In the aging step, the same procedure as in Example 1 was carried out except that the temperature was raised to 130 ° C. to uniformly dissolve, then the temperature was raised to 170 ° C. and then aging was performed at 170 ° C. for 24 hours. The results are shown in Table 1.

Comparative Example 2
In the aging step, the same procedure as in Example 1 was carried out except that the temperature was raised to 130 ° C. to uniformly dissolve, then cooled to 50 ° C., solidified, and then aged at 50 ° C. for 24 hours. The results are shown in Table 1.

  From Examples 1 and 2 and Comparative Examples 1 and 2, the intramolecular imide compound is rapidly converted to an amide compound at a melting point or less of the raw material amine, and from Example 3, aging in the aging step is performed by adding water. You can see that the speed is accelerated.

  By the production method of the present invention, it is possible to efficiently produce an amide compound that is useful as a gelling agent for an oily base material in the cosmetic field and the like.

Claims (6)

A method for producing an amide compound by reacting a carboxylic acid derivative represented by the following general formula (1) with an amine represented by the following general formula (3), wherein the carboxylic acid derivative and the The manufacturing method of the amide compound represented by following General formula (4) including the process of aging a reaction mixture at the temperature below the melting | fusing point of an amine.
[Wherein, X ¹ and X ² are each independently a halogen atom, or —OR ⁵ (R ⁵ is a hydrogen atom, or a saturated or unsaturated group having 1 to 5 carbon atoms which may have a substituent. A linear or branched hydrocarbon group) , m, n and p each represent 0 , and any one of R ¹ , R ² and R ³ represents the following general formula (5); The remaining two represent hydrogen atoms. ]
(In the formula, R ⁴ represents a saturated or unsaturated linear or branched hydrocarbon group having 10 to 24 carbon atoms which may contain an ether group .)
(In the formula , m, n and p each independently represent 0, and R ⁴ is independently the same as defined above. Any one of R ¹ , R ² and R ^{3 represents} the following general formula (5 ′); The remaining two represent hydrogen atoms. )
[Wherein , X ³ represents a halogen atom or —OR ⁵ (R ⁵ is as defined above), and q represents an integer of 1 to 3. ]
(Wherein R ⁴ and q are the same as above). The method for producing an amide compound according to claim 1 , wherein water is added in the aging step. R in the general formulas (1) and (5) ^Five The amide compound of Claim 1 or 2 which shows a C1-C3 saturated or unsaturated linear or branched hydrocarbon group which may have a hydrogen atom or a substituent. Manufacturing method. The carboxylic acid derivative represented by the general formula (1) is hexane-1,3,6-tricarboxylic acid or butane-1,2,4-tricarboxylic acid according to any one of claims 1 to 3. A method for producing an amide compound. R in the general formulas (3), (4) and (5 ') ^Four The manufacturing method of the amide compound in any one of Claims 1-4 whose is octadecyloxyethylene, octadecyloxypropylene, cetyl, or stearyl. The amide compound represented by the general formula (4) is hexane-1,3,6-tricarboxylic acid tri (3′-octadecyloxypropyl) amide, hexane-1,3,6-tricarboxylic acid trioctadecylamide, The manufacture of an amide compound according to any one of claims 1 to 4, which is hexane-1,3,6-tricarboxylic acid tri (2'-ethylhexyl) amide or hexane-1,3,6-tricarboxylic acid tridodecylamide. Method.