Method for producing carboxylic acid chloride

Abstract

To provide a novel method for producing a carboxylic acid chloride with high purity and superior hue (APHA) in high yield.SOLUTION: A method for producing a carboxylic acid chloride includes the following steps: (A) reacting an aliphatic branched carboxylic acid with 8 to 26 carbon atoms and phosphorus oxychloride in the presence of an amide compound to synthesize a carboxylic acid chloride and (B) purifying the resultant carboxylic acid chloride by phase separation in an organic solvent.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a method for producing a carboxylic acid chloride. [Background technology]

[0002] Carboxylic acid chlorides are industrially important intermediates in the synthesis of many chemical products, such as cosmetic bases, organic peroxides, alkyl ketene dimers, etc. These carboxylic acid chlorides are obtained by reacting carboxylic acids with chlorinating agents such as phosphorus chloride, phosgene, or thionyl chloride (hereinafter sometimes referred to as Cl-agents).

[0003] Phosgene is difficult to handle due to its high toxicity. Thionyl chloride can easily produce carboxylic acid chloride, but it is inevitable that sulfur, which adversely affects the hue, is mixed in, and in order to remove the sulfur content to a level that can be used as a raw material for color couplers, a decrease in yield is unavoidable (see Patent Document 1).

[0004] Phosphorus chloride includes phosphorus pentachloride, phosphorus trichloride, and phosphorus oxychloride, each of which has the following problems (see Patent Document 2).

[0005] Phosphorus pentachloride is the most reactive, and can convert carboxylic acids almost completely to carboxylic acid chlorides with a small excess amount, but because it is non-volatile, it is difficult to separate the excess. In addition, it is more expensive than other phosphorus chlorides, and its available chlorine content is low at 20%, making it economically disadvantageous. In addition, because it is a hygroscopic solid, it is difficult to handle compared to other phosphorus chlorides.

[0006] Phosphorus trichloride is the most economically advantageous because all the chlorine is effectively used, and the color of the product obtained is good, so it is widely used industrially. However, since it is less reactive than phosphorus pentachloride, when high purity is required, purification by distillation after the reaction is required, which reduces the yield.

[0007] Phosphorus oxychloride has excellent reactivity when a catalyst such as N,N-dimethylformamide is used; however, the by-product is mainly candy-like metaphosphoric acid, and the reaction mixture becomes a highly viscous slurry. Therefore, it takes a long time to remove the metaphosphoric acid after standing and separating. In addition, poor separation during removal results in the loss of carboxylic acid chloride, resulting in a low yield.

[0008] Patent Document 2 proposes a production method for obtaining a carboxylic acid chloride with high purity and good hue (low coloration) in high yield by reacting a linear aliphatic carboxylic acid with phosphorus trichloride and subsequently reacting it with a small amount of phosphorus oxychloride. However, this production method involves two reaction steps, and therefore there remains a problem with production efficiency.

[0009] Therefore, it is desirable to develop a more efficient method for producing carboxylic acid chlorides with high purity and good color (less coloration) in high yield. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] JP 2003-26630 A [Patent Document 2] Japanese Patent Application Publication No. 10-287611 Summary of the Invention [Problem to be solved by the invention]

[0011] The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a new method for producing a carboxylic acid chloride having high purity and good color (APHA) in a high yield. [Means for solving the problem]

[0012] Means for Solving the Problems The present inventors have conducted extensive research in order to achieve the above object, and as a result have found that a carboxylic acid chloride having high purity and good hue can be obtained in high yield by reacting a specific carboxylic acid with phosphorus oxychloride in the presence of an amide compound and then purifying the synthesized carboxylic acid chloride with an organic solvent by liquid separation, thereby completing the present invention.

[0013] That is, the present invention provides the following method for producing a carboxylic acid chloride. 1. A method for producing carboxylic acid chloride, comprising: (A) a step of reacting an aliphatic branched carboxylic acid having 8 to 26 carbon atoms with phosphorus oxychloride in the presence of an amide compound to synthesize carboxylic acid chloride; and (B) a step of separating and purifying the obtained carboxylic acid chloride with an organic solvent. 2. A method for producing a carboxylic acid chloride according to claim 1, wherein the aliphatic branched carboxylic acid is represented by the following formula (1) and the aliphatic branched carboxylic acid chloride is represented by the following formula (2). [ka] (In the formula, R 1 and R 2 each independently represents a linear or branched alkyl group having 3 to 12 carbon atoms. 3. R ​​above 1 and R 2 wherein each of the above is independently a linear or branched alkyl group having 5 to 12 carbon atoms. 4. The method for producing a carboxylic acid chloride according to any one of 1 to 3, wherein the amide compound is N,N-dimethylformamide. 5. The method for producing a carboxylic acid chloride according to any one of 1 to 4, wherein the amide compound is a catalyst and a solvent. 6. The method for producing a carboxylic acid chloride according to any one of 1 to 5, wherein in the step (A), the reaction temperature is 15 to 55°C. 7. The method for producing a carboxylic acid chloride according to any one of 1 to 6, wherein the amount of the amide compound used is 0.2 to 10 equivalents relative to the phosphorus oxychloride. 8. The method for producing a carboxylic acid chloride according to any one of 1 to 7, wherein in the step (B), a hydrophobic solvent and a hydrophilic solvent are used as the organic solvent. 9. The method for producing a carboxylic acid chloride according to claim 8, wherein the hydrophobic solvent is at least one selected from the group consisting of aliphatic hydrocarbons having 5 to 16 carbon atoms and monocyclic aromatic hydrocarbons having 6 to 12 carbon atoms, and the hydrophilic solvent is at least one selected from the group consisting of nitriles, esters, ethers, ketones and amides. 10. The method for producing a carboxylic acid chloride according to claim 9, wherein the hydrophobic solvent is heptane and the hydrophilic solvent is acetonitrile. Effect of the Invention

[0014] According to the production method of the present invention, a carboxylic acid chloride having high purity and good color can be obtained in high yield by a simple method. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] The method for producing a carboxylic acid chloride of the present invention comprises the steps of (A) reacting an aliphatic branched carboxylic acid having 8 to 26 carbon atoms with phosphorus oxychloride in the presence of an amide compound to synthesize a carboxylic acid chloride, and (B) separating and purifying the resulting carboxylic acid chloride with an organic solvent. Each step will be described in detail below.

[0016] (A) Process The step (A) is a step of synthesizing a carboxylic acid chloride by reacting an aliphatic branched carboxylic acid having 8 to 26 carbon atoms with phosphorus oxychloride in the presence of an amide compound.

[0017] The above-mentioned aliphatic branched carboxylic acid having 8 to 26 carbon atoms is preferably one represented by the following formula (1).

[0018] [ka]

[0019] In the formula, R1 and R 2 each independently represents a linear or branched alkyl group having 3 to 12 carbon atoms, and preferably a linear or branched alkyl group having 5 to 12 carbon atoms.

[0020] Examples of the linear or branched alkyl group having 3 to 12 carbon atoms include an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an n-hexyl group, an n-heptyl group, an n-octyl group, an n-nonyl group, an n-decyl group, an n-undecyl group, an n-dodecyl group, a (1,3,3-trimethyl)butyl group, a (3,5,5-trimethyl)hexyl group, a (4,5-dimethyl)hexyl group, a (6,7-dimethyl)octyl group, a 6-methyloctyl group, and a 4-methylhexyl group.

[0021] Specific examples of the above aliphatic branched carboxylic acid include those represented by the following formulas (1-1) to (1-6), but are not limited thereto.

[0022] [ka]

[0023] In the present invention, phosphorus oxychloride is used as the chlorinating agent from the viewpoints of the color and yield of the resulting carboxylic acid chloride.

[0024] Considering the yield of the carboxylic acid chloride obtained, the amount of the phosphorus oxychloride used is preferably 0.5 to 1.0 equivalent relative to the aliphatic branched carboxylic acid, and more preferably 0.6 to 0.8 equivalent.

[0025] The amide compound acts as a catalyst for the reaction between the aliphatic branched carboxylic acid and phosphorus oxychloride. The amide compound is not particularly limited as long as it functions as a catalyst for the chlorination reaction of the carboxylic acid and as a reaction solvent, but N,N-dialkylamide is preferred in consideration of the color and yield of the resulting carboxylic acid chloride.

[0026] Specific examples of N,N-dialkylamides include N,N-dimethylformamide (DMF), N,N-diethylformamide, N,N-dimethylacetamide (DMAc), N-methylformanilide, and the like. N,N-dimethylformamide is preferred because of its high reactivity and ease of industrial availability.

[0027] The amide compound is a compound that functions as a catalyst for promoting the reaction between the aliphatic branched carboxylic acid and phosphorus oxychloride. In the present invention, however, it is preferable to use one that also functions as a solvent, such as the above-mentioned N,N-dialkylamide.

[0028] The amount of the amide compound used is usually an effective amount as a catalyst, but when it also serves as a solvent, it is preferably 0.2 to 10 equivalents, more preferably 1.5 to 3.0 equivalents, based on phosphorus oxychloride.

[0029] In the above step (A), an organic solvent (excluding those corresponding to the above amide compound) can be used within a range that does not impair the effects of the present invention. However, in the present invention, it is preferable not to use the above organic solvent and to use the above amide compound as a solvent in consideration of production efficiency, because of the following points: the cost of materials increases, the organic solvent needs to be removed in the step (B) described below, and the organic solvent increases the volume of the reaction solution, requiring larger equipment.

[0030] Examples of the organic solvent that can be used in the above step (A) include heptane, toluene, cyclohexane, and acetonitrile.

[0031] In step (A), the carboxylic acid and phosphorus oxychloride are reacted in the presence of the amide compound, and the method of mixing the components is not particularly limited. In the present invention, in order to control the amount of reactive species present in the reaction system, a method is preferred in which a carboxylic acid, an amide compound, and, if necessary, an organic solvent are mixed, and then a predetermined amount of phosphorus oxychloride is added to the resulting mixture. In addition, when mixing the components, from the viewpoint of temperature control due to heat generation during the reaction, it is preferable to gradually add the components by means of dropwise addition rather than adding them all at once.

[0032] The reaction temperature in the above reaction is preferably 15 to 55°C, more preferably 35 to 55°C, in consideration of the yield of the obtained carboxylic acid chloride and minimizing its coloration. The reaction time is not particularly limited as long as the above reaction can be completed, but is usually about 30 minutes to 20 hours, and in consideration of the production efficiency and the color of the carboxylic acid chloride, it is preferably about 30 minutes to 5 hours, more preferably about 1 to 3 hours. The above reaction time is measured from the time when all the necessary raw materials have been charged.

[0033] In the step (A), a carboxylic acid chloride represented by the following formula (2) is obtained by the above-mentioned method.

[0034] [ka] (In the formula, R 1 and R 2 is the same as above.)

[0035] Specific examples of the aliphatic branched carboxylic acid chloride represented by the above formula (2) include those represented by the following formulas (2-1) to (2-6), but are not limited thereto.

[0036] [ka]

[0037] In the above step (A), a specific carboxylic acid and phosphorus oxychloride are used as raw materials for the synthesis of carboxylic acid chloride, and thus carboxylic acid chloride with a better hue can be obtained compared to conventional methods. However, for applications such as cosmetic bases, a better hue (lower hue) is required, so the following separation and purification step (B) is carried out to further lower the hue.

[0038] (B) Process In the step (B), an organic solvent is added to the reaction solution obtained in the step (A) to separate and purify the target carboxylic acid chloride. In the step (B) of the present invention, usually, only an organic solvent that does not react with the carboxylic acid chloride is used as the solvent. In this case, the presence of a small amount of water contained in the organic solvent is not denied.

[0039] The organic solvent may be selected from hydrophilic and hydrophobic solvents according to the state of the reaction solution, and may be a combination of hydrophilic and hydrophobic solvents as necessary. In the present invention, the hydrophobic and hydrophilic solvents are liquid at room temperature, are immiscible with each other, and are not particularly limited in the selection of the solvents as long as separation and purification can be achieved.

[0040] Examples of the hydrophilic solvent include nitriles, esters, ethers, ketones, and amides.

[0041] Examples of the nitrile solvent include acetonitrile and propionitrile.

[0042] Examples of the ester solvent include methyl acetate, diethylene glycol monoethyl ether acetate, and diethylene glycol monobutyl ether acetate.

[0043] Examples of the ether solvent include diethyl ether, diisopropyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane, and propylene glycol monomethyl ether acetate.

[0044] Examples of the ketone solvent include acetone, methyl ethyl ketone, and cyclohexanone.

[0045] Examples of the amide solvent include N,N-dimethylformamide, N,N-dimethylacetamide, N,N-dimethylisobutylamide, N-methyl-2-pyrrolidone, and 1,3-dimethyl-2-imidazolidinone.

[0046] Other preferred hydrophilic solvents besides those mentioned above include dimethyl sulfoxide and the like.

[0047] As the hydrophilic solvent, from the viewpoint of liquid separation, nitriles are preferable, and acetonitrile is more preferable.

[0048] The above hydrophilic solvents may be used alone or in combination of two or more.

[0049] Examples of the hydrophobic solvent include aliphatic hydrocarbons having 5 to 16 carbon atoms and monocyclic aromatic hydrocarbons having 6 to 12 carbon atoms.

[0050] Examples of the aliphatic hydrocarbons having 5 to 16 carbon atoms include pentane, hexane, heptane, octane, nonane, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, cyclohexane, and cyclohexene.

[0051] Examples of the monocyclic aromatic hydrocarbons having 6 to 12 carbon atoms include benzene, toluene, xylene, ethylbenzene, tert-butylbenzene, and 1,3,5-triethylbenzene.

[0052] In the present invention, from the viewpoint of liquid separation, aliphatic hydrocarbons having 5 to 16 carbon atoms are preferred, aliphatic hydrocarbons having 5 to 8 carbon atoms are more preferred, and heptane, hexane, pentane and cyclohexane are even more preferred.

[0053] The above hydrophobic solvents may be used alone or in combination of two or more kinds.

[0054] As the organic solvent, it is preferable to select an appropriate solvent from the above-mentioned hydrophobic solvents and hydrophilic solvents according to the state of the reaction solution obtained in the step (A). If necessary, a hydrophobic solvent and a hydrophilic solvent may be used in combination, and if the target hue is not achieved by one separation purification, the same or different organic solvents may be used multiple times.

[0055] An example of a preferred embodiment of separation purification is as follows. In the step (A), when N,N-dialkylamide such as N,N-dimethylformamide also serves as a reaction solvent, the resulting reaction solution mainly consists of an upper layer of the target carboxylic acid chloride and a lower layer of by-products derived from dialkylamide and phosphorus oxychloride. In this case, it is preferable to carry out separation and purification using a nitrile such as acetonitrile, which is highly compatible with the lower layer. In addition, if the desired hue is not obtained by the separation and purification using the above-mentioned nitriles, the separation and purification can be repeated using aliphatic hydrocarbons having 5 to 16 carbon atoms, such as pentane, heptane, or hexane, until the desired hue is obtained.

[0056] The color (APHA) of the carboxylic acid chloride after carrying out the above step (B) is usually 200 or less, and in consideration of use in a cosmetic base, it is preferably 30 or less, and more preferably 15 or less. EXAMPLES

[0057] The present invention will be described in more detail below with reference to examples and comparative examples, but the present invention is not limited to the following examples.

[0058] The reagents used are as follows: Isopalmitic acid: Nissan Chemical Co., Ltd. Phosphorus oxychloride: Junsei Chemical Co., Ltd. N,N-Dimethylformamide (DMF): Kanto Chemical Co., Ltd. (1st grade) N,N-Dimethylacetamide (DMAc): Kanto Chemical Co., Ltd. (1st grade) Normal heptane: Kanto Chemical Co., Ltd. (first grade) Acetonitrile: Kanto Chemical Co., Ltd. (special grade) Thionyl chloride: manufactured by Tokyo Chemical Industry Co., Ltd. Phosphorus trichloride: Tokyo Chemical Industry Co., Ltd.

[0059] The analytical methods and instruments used in the examples are as follows. [1] Gas chromatography (GC) In Examples 1-12, GC was used to calculate the quantitative yield of isopalmitoyl chloride. [GC conditions] Equipment: GC-2010 (Shimadzu Corporation) Column: Capillary column HP-1 (30 m × 0.32 mm Φ × 0.25 μm) (Agilent Technologies, Inc.) Column temperature: The column temperature was controlled using a temperature rise program. The temperature was raised from an initial temperature of 150° C. at a rate of 10° C. / min to a final temperature of 300° C., which was then maintained for 3 minutes. Injection temperature: 300℃ Detector temperature: 300℃ Total flow: 48.6mL / min Split ratio: 1 / 20 Carrier gas: Helium Detection method: FID method Injection volume: 2μL Retention time: Isopalmitic acid methyl ester 5.2 minutes [How to create a calibration curve] Pour about 5 mL of heptane into a 50 mL measuring flask in advance, and accurately weigh out about 150 mg of the standard isopalmitic acid methyl ester into the 50 mL measuring flask and make up to volume with methanol (stock solution). From the stock solution, 20 mL is taken using a volumetric pipette and transferred to a 50 mL measuring flask, and the volume is adjusted to constant with methanol (Level 3 solution). From the stock solution, 10 mL is taken using a volumetric pipette and transferred to a 50 mL measuring flask, and the volume is adjusted to constant with methanol (Level 2 solution). From the stock solution, 5 mL is taken using a volumetric pipette and transferred to a 50 mL measuring flask, and the volume is adjusted to constant with methanol (Level 1 solution). Levels 1 to 3 solutions are measured under GC conditions. For each sample of levels 1 to 3 solutions, the area value of isopalmitic acid methyl ester is plotted on the Y axis, and the weight of isopalmitic acid methyl ester is plotted on the X axis, and a linear regression line is created using the least squares method to create a calibration curve. (R 2 value ≥ 0.9990). [Analysis solution preparation method] Put about 5 mL of heptane into a 50 mL measuring flask in advance, weigh out about 150 mg of isopalmitic acid chloride into a 50 mL measuring flask, and add methanol to the constant volume (stock solution). Take 10 mL of the stock solution using a volumetric pipette, transfer it to a 50 mL measuring flask, and add methanol to the constant volume. Analyze the prepared analysis solution under GC conditions, and calculate the content of isopalmitic acid chloride from the area value of the calibration curve. [2] APHA (Hazen unit color number) Equipment: Transmission color meter TZ 6000 (manufactured by Nippon Denshoku Industries Co., Ltd.) The color of isopalmitic acid chloride was evaluated using APHA. Taking into account the use of the product, the target APHA was set at ≦200.

[0060] [Example 1] Synthesis of isopalmitic acid chloride (A) Process: In a 200 mL reaction vessel, 38.3 g (0.25 mol) of phosphorus oxychloride was charged under a nitrogen atmosphere and stirred at room temperature. After 18.2 g (0.25 mol) of DMF was added dropwise over 1 hour, the mixture in the reaction vessel was heated to 50°C. 80.0 g (0.31 mol) of isopalmitic acid was added dropwise over 1 hour, and the reaction was carried out at 50°C for 3 hours. The resulting reaction solution was a two-phase system consisting of an isopalmitic acid chloride layer (upper layer) and a layer (lower layer) containing by-products derived from DMF and phosphorus oxychloride. (B) Process: 40.0 g of acetonitrile, which is highly compatible with the lower layer, was added to the resulting reaction solution and stirred at room temperature for 30 minutes. After stopping the stirring, the upper layer obtained by standing and separating had an APHA of 100, and the quantitative yield of isopalmitic acid chloride was 99.2%.

[0061] [Example 2] Synthesis of isopalmitic acid chloride (A) Process: The reaction was carried out in the same manner as in Example 1, except that 18.2 g (0.25 mol) of DMF was changed to 21.7 g (0.25 mol) of DMAc. Since a delay in the reaction was observed, the reaction time was extended from 3 hours to 18 hours. The resulting reaction solution was a two-phase system consisting of an isopalmitic acid chloride layer (upper layer) and a layer (lower layer) containing by-products derived from DMAc and phosphorus oxychloride, and precipitates were observed. (B) Process: The same procedure was carried out as in Example 1. The APHA of the resulting upper layer was 151, and the quantitative yield of isopalmitic acid chloride was 96.3%.

[0062] [Example 3] Synthesis of isopalmitic acid chloride (A) Process: In a 200 mL reaction vessel, 28.7 g (0.19 mol) of phosphorus oxychloride was charged under a nitrogen atmosphere and stirred at room temperature. After 20.5 g (0.28 mol) of DMF was added dropwise over 1 hour, the mixture in the reaction vessel was heated to 50°C. 60.0 g (0.23 mol) of isopalmitic acid was added dropwise over 1 hour, and the reaction was carried out at 50°C for 3 hours. The resulting reaction solution was a two-phase system similar to that in Example 1. (B) Process: Except for changing the amount of acetonitrile from 40.0 g to 30.0 g, the same procedure as in Example 1 was carried out. The APHA of the obtained upper layer was 84, and the quantitative yield of isopalmitic acid chloride was 98.2%.

[0063] [Example 4] Synthesis of isopalmitic acid chloride A process: The reaction was carried out in the same manner as in Example 3, except that the amount of DMF charged was changed from 20.5 g (0.28 mol) to 27.4 g (0.37 mol). B process: The same procedure was carried out as in Example 3. The APHA of the resulting upper layer was 64, and the quantitative yield of isopalmitic acid chloride was 98.2%.

[0064] [Example 5] Synthesis of isopalmitic acid chloride (A) Process: The reaction was carried out in the same manner as in Example 3, except that the amount of DMF charged was changed from 20.5 g (0.28 mol) to 41.0 g (0.56 mol). (B) Process: The same procedure was carried out as in Example 3. The APHA of the resulting upper layer was 66, and the quantitative yield of isopalmitic acid chloride was 96.9%.

[0065] [Example 6] Synthesis of isopalmitic acid chloride (A) Process: In a 300 mL reaction vessel, 80.0 g (0.31 mol) of isopalmitic acid and 31.9 g (0.44 mol) of DMF were charged under a nitrogen atmosphere and stirred. After the reaction mixture was heated to 35° C., 33.5 g (0.22 mol) of phosphorus oxychloride was added dropwise over 2 hours and reacted at 35° C. for 3 hours. The resulting reaction mixture was a two-phase system similar to that in Example 1. (B) Process: Except for changing the amount of acetonitrile from 40.0 g to 20.0 g, the same procedure as in Example 1 was carried out. The APHA of the obtained upper layer was 83, and the quantitative yield of isopalmitic acid chloride was 100.5%.

[0066] [Example 7] Synthesis of isopalmitic acid chloride (A) Process: The reaction was carried out in the same manner as in Example 6, except that the reaction temperature was changed from 35°C to 45°C. (B) Process: The same procedure was carried out as in Example 6. The APHA of the upper layer obtained was 102, and the quantitative yield of isopalmitic acid chloride was 100.2%.

[0067] [Example 8] Synthesis of isopalmitic acid chloride A process: In a 200 mL reaction vessel, 60.0 g (0.23 mol) of isopalmitic acid and 23.9 g (0.33 mol) of DMF were charged under a nitrogen atmosphere and stirred. After the reaction mixture was heated to 50° C., 25.1 g (0.16 mol) of phosphorus oxychloride was added dropwise over 2 hours and reacted at 50° C. for 3 hours. The resulting reaction mixture was a two-phase system similar to that in Example 1. (B) Process: Except for changing the amount of acetonitrile from 40.0 g to 15.0 g, the same procedure as in Example 1 was carried out. The APHA of the obtained upper layer was 105, and the quantitative yield of isopalmitic acid chloride was 100.2%.

[0068] [Example 9] Synthesis of isopalmitic acid chloride (A) Process: The reaction was carried out in the same manner as in Example 6, except that the reaction temperature was changed from 35°C to 55°C. (B) Process: The same procedure was carried out as in Example 6. The APHA of the resulting upper layer was 127, and the quantitative yield of isopalmitic acid chloride was 99.2%.

[0069] [Example 10] Synthesis of isopalmitic acid chloride (A) Process: In a 100 mL reaction vessel, 30.0 g (0.12 mol) of isopalmitic acid and 13.7 g (0.19 mol) of DMF were charged under a nitrogen atmosphere and stirred. After the reaction mixture was heated to 50°C, 14.4 g (0.09 mol) of phosphorus oxychloride was added dropwise over 1 hour, and the mixture was allowed to react at 50°C for 7 hours. The resulting reaction mixture was a two-phase system similar to that in Example 1. (B) Process: 《Separation purification》 The same procedure was carried out as in Example 8. The APHA of the upper layer obtained in the first separation and purification was 29, and the quantitative yield of isopalmitic acid chloride was 97.9%. {Additional separation and purification 1st and 2nd times} In order to further reduce APHA, 45.0 g of heptane and 15.0 g of acetonitrile were added to the obtained upper layer, and a separation operation was performed to obtain a heptane layer for the first additional separation purification. 15.0 g of acetonitrile was added to the obtained heptane layer, and the same operation was performed. When the obtained heptane layer for the second additional separation purification was concentrated, isopalmitic acid chloride with an APHA of 15 was obtained in a quantitative yield of 96.6%.

[0070] [Example 11] Synthesis of isopalmitic acid chloride (A) Process: The reaction was carried out in the same manner as in Example 10. (B) Process: 《Separation purification》 The same procedure as in Example 10 was carried out to obtain an upper layer from the first separation purification. {Additional separation and purification 1st and 2nd times} The same procedure as in Example 10 was carried out, except that the amount of acetonitrile was changed from 15.0 g to 7.5 g. The upper layer obtained from the third additional separation purification was concentrated to obtain isopalmitic acid chloride with an APHA of 14 in a quantitative yield of 96.6%.

[0071] [Example 12] Synthesis of isopalmitic acid chloride (A) Process: In a 1 L reaction vessel, 150.0 g (0.58 mol) of isopalmitic acid and 68.4 g (0.94 mol) of DMF were charged under a nitrogen atmosphere and stirred. After the reaction mixture was heated to 50°C, 71.8 g (0.47 mol) of phosphorus oxychloride was added dropwise over 1 hour, and the mixture was allowed to react at 50°C for 4.5 hours. The resulting reaction mixture was a two-phase system similar to that in Example 1. (B) Process: 《Separation purification》 Except for changing the amount of acetonitrile from 15.0 g to 37.5 g, the same operation as in Example 10 was carried out. The APHA of the upper layer obtained in the first separation purification was 37, and the quantitative yield of isopalmitic acid chloride was 99.6%. {Additional separation and purification 1st and 2nd times} The same procedure as in Example 10 was carried out, except that the amount of heptane was changed from 45.0 g to 222.5 g and the amount of acetonitrile was changed from 15.0 g to 37.5 g. The upper layer obtained from the third additional separation purification was concentrated to obtain isopalmitic acid chloride with an APHA of 13 in a quantitative yield of 98.0%.

[0072] [Table 1] *1: Amount used relative to isopalmitic acid *2: Amount used relative to phosphorus oxychloride (POCl3)

[0073] As shown in Table 1, according to the production method of the present invention, isopalmitic acid chloride with low APHA was obtained with high quantitative yield. The APHA was lower when DMF was used as the amide compound, and isopalmitic acid chloride with low APHA was obtained when the amount of DMF added was 2 equivalents or more relative to phosphorus oxychloride. Furthermore, the APHA of the obtained isopalmitic acid chloride tended to increase as the reaction temperature increased, but the APHA did not increase significantly at 55°C or lower.

[0074] Furthermore, as shown in Examples 10 to 12, isopalmitic acid chloride could be obtained in high yield and with a low color (APHA≦30) by selecting heptane as the hydrophobic organic solvent and acetonitrile as the hydrophilic organic solvent and carrying out additional separation and purification.

[0075] [Comparative Example 1] Synthesis of isopalmitic acid chloride (A) Process: In a 200 mL reaction vessel, 50.0 g (0.20 mol) of isopalmitic acid was charged under a nitrogen atmosphere and stirred. After the isopalmitic acid in the reaction vessel was heated to 55-60°C, 32.5 g (0.27 mol) of thionyl chloride was added dropwise and reacted at 60°C for 2 hours. After that, the mixture was cooled to 30°C to obtain a reaction liquid containing isopalmitic acid chloride of APHA999. (B) Process: {First and second separation and purification steps} To the obtained reaction liquid, 50.0 g of heptane and 25.0 g of acetonitrile were added, and the mixture was stirred at 20 to 30°C for 30 minutes. After stopping the stirring, the mixture was left to stand and separated. The upper layer obtained from the first separation purification was concentrated to obtain isopalmitic acid chloride with an APHA of 999. The same operation was performed on the obtained isopalmitic acid chloride. The upper layer obtained from the second separation purification was concentrated to obtain isopalmitic acid chloride with an APHA of 999.

[0076] [Comparative Example 2] Synthesis of isopalmitic acid chloride (A) Process: In a 300 mL reaction vessel, 120.0 g (0.47 mol) of isopalmitic acid and 1.0 g (0.01 mol) of DMF were charged under a nitrogen atmosphere and stirred at 20 to 25° C. 66.8 g (0.56 mol) of thionyl chloride was added dropwise over 1 hour, and the mixture was reacted at 20 to 25° C. for 3 hours. A reaction liquid containing isopalmitic acid chloride of APHA906 was obtained. (B) Process: {First, second and third separation and purification steps} 240.0 g of heptane and 120.0 g of acetonitrile were added to the obtained reaction liquid and stirred at room temperature for 30 minutes. After stopping the stirring, the mixture was left to stand and separated. The APHA of the heptane layer obtained in the first separation purification was 175 (the APHA when heptane was concentrated and removed was calculated to be 525). Acetonitrile was added to the obtained heptane layer, and the same operation was repeated twice in total. The APHA of the heptane layer from the second separation purification was 163. (The calculated APHA when heptane is concentrated and removed is equivalent to 489.) The APHA of the heptane layer from the third separation purification was 147. (The calculated APHA when heptane is concentrated and removed is equivalent to 441.)

[0077] [Comparative Example 3] Synthesis of isopalmitic acid chloride (A) Process: In a 300 mL reaction vessel, 120.0 g (0.47 mol) of isopalmitic acid and 27.4 g (0.37 mol) of DMF were charged under a nitrogen atmosphere and stirred at 20 to 25° C. 66.8 g (0.56 mol) of thionyl chloride was added dropwise over 3 hours, and the mixture was reacted at 20 to 25° C. for 3 hours. A reaction liquid containing APHA999 isopalmitic acid chloride was obtained. (B) Process: {First, second and third separation and purification steps} The same procedure as in Comparative Example 2 was carried out except that the amount of heptane was changed from 240.0 g to 120.0 g and the amount of acetonitrile was changed from 120.0 g to 60.0 g. The APHA of the obtained heptane layer is as follows. APHA 553 in the heptane layer from the first separation purification (The APHA calculated when heptane is concentrated and removed is equivalent to 999.) APHA 319 in the heptane layer from the first separation purification (The APHA calculated when heptane is concentrated and removed is equivalent to 638.) APHA 292 in the heptane layer from the first separation purification (The APHA calculated when heptane is concentrated and removed is equivalent to 584.)

[0078] [Comparative Example 4] Synthesis of isopalmitic acid chloride (A) Process: In a 100 mL reaction vessel, 30.0 g (0.12 mol) of isopalmitic acid was charged under a nitrogen atmosphere and stirred. After heating the inside of the reaction vessel to 45-50°C, 9.6 g (0.07 mol) of phosphorus trichloride was added dropwise over 2 hours, and the mixture was allowed to react at 45-50°C for 3 hours. A reaction liquid was obtained in which highly viscous oil-out components containing phosphorous acid derived from phosphorus trichloride had precipitated. The APHA of the reaction liquid excluding the oil-out components was 26. (B) Process: 15.0 g of acetonitrile was added to the resulting reaction liquid to check whether separation was possible, but the highly viscous oil-out component did not dissolve, and separation and purification could not be performed.

[0079] [Comparative Example 5] Synthesis of isopalmitic acid chloride (A) Process: In a test tube, 1.00 g (3.9 mmol) of isopalmitic acid, 0.43 g (3.1 mmol) of phosphorus trichloride, and 0.11 g (1.6 mmol) of DMF were charged under a nitrogen atmosphere and stirred. The mixture in the test tube was heated to 45-50°C and then reacted for 3 hours. A highly viscous precipitate was observed on the wall of the test tube. Since the reaction conditions described are not suitable for scale-up, separation and purification were not performed.

[0080] [Comparative Example 6] Synthesis of isopalmitic acid chloride (A) Process: The reaction was carried out in the same manner as in Comparative Example 5, except that the amount of DMF added was changed from 0.11 g (1.6 mmol) to 0.22 g (3.1 mmol). Highly viscous precipitates were observed on the walls of the test tube. Since the reaction conditions described were not suitable for scale-up, separation and purification were not carried out.

[0081] [Table 2] *1: Amount used relative to isopalmitic acid *2: Amount used relative to chlorination agent *3: The APHA of the obtained organic layer was measured, and the APHA of the isopalmitic acid chloride obtained by removing heptane by concentration was converted and calculated. In Comparative Example 2, approximately twice the amount of heptane was used relative to the amount of isopalmitic acid chloride obtained, so that the APHA of the isopalmitic acid chloride after concentration was three times the APHA of the organic layer. In Comparative Example 3, approximately one amount of heptane was used relative to the amount of isopalmitic acid chloride obtained, so that the APHA of the isopalmitic acid chloride after concentration was two times the APHA of the organic layer.

[0082] When thionyl chloride was used as the chloride-containing agent, the reaction solution became significantly colored, and the color did not improve even when purification was performed by separation with heptane and acetonitrile. When phosphorus trichloride was used as the chloride-containing agent, the by-product derived from phosphorus trichloride did not dissolve in acetonitrile, and purification by separation with heptane and acetonitrile was not possible.

Claims

1. A method for producing a carboxylic acid chloride, comprising: (A) a step of reacting an aliphatic branched carboxylic acid having 8 to 26 carbon atoms with phosphorus oxychloride in the presence of an amide compound to synthesize a carboxylic acid chloride; and (B) a step of separating and purifying the obtained carboxylic acid chloride with an organic solvent.

2. 2. The method for producing a carboxylic acid chloride according to claim 1, wherein the aliphatic branched carboxylic acid is represented by the following formula (1), and the aliphatic branched carboxylic acid chloride is represented by the following formula (2): 【Chemistry 1】 (In the formula, R 1 and R 2 each independently represents a linear or branched alkyl group having 3 to 12 carbon atoms.

3. The above R 1 and R 2 The method for producing a carboxylic acid chloride according to claim 2, wherein each of the alkyl groups is independently a linear or branched alkyl group having 5 to 12 carbon atoms.

4. 2. The method for producing a carboxylic acid chloride according to claim 1, wherein the amide compound is N,N-dimethylformamide.

5. 2. The method for producing a carboxylic acid chloride according to claim 1, wherein the amide compound serves as a catalyst and a solvent.

6. 2. The method for producing a carboxylic acid chloride according to claim 1, wherein the reaction temperature in step (A) is 15 to 55° C.

7. 2. The method for producing a carboxylic acid chloride according to claim 1, wherein the amount of the amide compound used is 0.2 to 10 equivalents relative to the phosphorus oxychloride.

8. 2. The method for producing a carboxylic acid chloride according to claim 1, wherein a hydrophobic solvent and a hydrophilic solvent are used as the organic solvent in the step (B).

9. 9. The method for producing a carboxylic acid chloride according to claim 8, wherein the hydrophobic solvent is at least one selected from the group consisting of aliphatic hydrocarbons having 5 to 16 carbon atoms and monocyclic aromatic hydrocarbons having 6 to 12 carbon atoms, and the hydrophilic solvent is at least one selected from the group consisting of nitriles, esters, ethers, ketones and amides.

10. 10. The method for producing a carboxylic acid chloride according to claim 9, wherein the hydrophobic solvent is heptane and the hydrophilic solvent is acetonitrile.

Images