Method for manufacturing 3-mercaptocarboxylic acid

Abstract

This invention provides a method for manufacturing 3-mercaptocarboxylic acid under industrially advantageous conditions. The invention comprises a method for manufacturing 3-mercaptocarboxylic acid represented by formula (1), which includes the following steps (A) and (B). Step (A) is the addition of a thiocarboxylic acid to the carbon-carbon unsaturated bond of an α,β-unsaturated carboxylic acid to obtain a thiocarboxylic acid ester. Step (B) is the hydrolysis reaction of the aforementioned thiocarboxylic acid ester by adding water and an acid catalyst, wherein the amount of acid catalyst during the reaction is 0.025 to 0.68 equivalents relative to the aforementioned thiocarboxylic acid ester, and the amount of water is 1.0 equivalent or more relative to the aforementioned thiocarboxylic acid ester. (R1 to R3 each independently represent hydrogen atoms or alkyl groups having 1 to 5 carbon atoms).

Description

Method for producing 3-mercapto carboxylic acid The present invention relates to a method for producing 3-mercapto carboxylic acid. A compound having a mercapto group and a carboxyl group can form an ester structure by reacting the carboxyl group with a hydroxyl group. By using a polyol as the hydroxyl group-containing compound, a compound having a plurality of mercapto groups can be obtained. The polyhydric thiol compound thus obtained is easily reactive with an epoxy group or an unsaturated double bond, etc., and can be used as a raw material for resins, thermosetting resins, photocurable resins, etc., and has high industrial value. Therefore, it is desired to establish an effective method for producing a compound having a mercapto group and a carboxyl group. As methods for synthesizing a compound having a mercapto group and a carboxyl group, known methods include an addition reaction of sodium sulfide and α,β-unsaturated carbonic acid, a reaction of sodium sulfide and β-halocarboxylic acid, an addition reaction of sodium sulfide and α,β-unsaturated carboxylic acid, a reaction of sodium sulfide and β-halocarboxylic acid, a method of hydrolyzing after an addition reaction of thiourea and α,β-unsaturated carboxylic acid, a method of hydrolyzing after an addition reaction of thio carboxylic acid and α,β-unsaturated carboxylic acid, and various other methods. Methods using α,β-unsaturated carboxylic acid and thio carboxylic acid as raw materials are disclosed in Non-Patent Documents 1 to 3. A synthesis example of 3-mercaptobutyric acid is disclosed in Non-Patent Document 1, but the hydrolysis of the thioester of the intermediate is carried out under alkaline conditions. In this case, the alkali salt of the product is neutralized and then extracted, which is costly and not suitable as an industrial production method. Synthesis examples of 2-mercaptomethylbutyric acid are described in Non-Patent Documents 2 and 3. In both cases, the thioester of the intermediate is hydrolyzed with an acid, but the yield is not sufficient. [Prior Art Documents] [Non-Patent Documents] Non-Patent Document 1: Biomacromolecules 2001, 2, 1061-1065 Non-Patent Document 2: Med. Chem. 11(2003)4685-4691 Non-Patent Document 3: Biochemistry 2007, 56, 6087-6097 [Problems to be Solved by the Invention] The present invention provides a method for producing 3-mercapto carboxylic acid under industrially advantageous conditions. [Means for Solving the Problems] As a result of repeated and active research by the present inventors to solve the above problems, the present invention has been completed. That is, the present invention relates to the following methods for producing 3-mercapto carboxylic acid of [1] to [7]. [1] A method for producing a 3-mercapto carboxylic acid represented by formula (1), which comprises the following steps (A) and (B). Step (A): A step of adding a thiocarboxylic acid to the carbon-carbon unsaturated bond of an α,β-unsaturated carboxylic acid to obtain a thiocarboxylic acid ester. Step (B): A step of adding water and an acid catalyst to the aforementioned thiocarboxylic acid ester and performing a hydrolysis reaction, and the hydrolysis reaction is carried out under the conditions that the amount of the acid catalyst during the reaction is 0.025 equivalent to 0.68 equivalent relative to the aforementioned thiocarboxylic acid ester, and the amount of the aforementioned water is 1.0 equivalent or more relative to the aforementioned thiocarboxylic acid ester. (R 1 ~R 3 each independently represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms). [2] The method for producing a 3-mercapto carboxylic acid according to [1], wherein the amount of water in the aforementioned step (B) is 1.0 equivalent to 5.5 equivalents relative to the aforementioned thiocarboxylic acid ester. [3] The method for producing a 3-mercapto carboxylic acid according to [1] or [2], wherein the addition reaction in the aforementioned step (A) is carried out in the presence of a solvent, and after the reaction, the aforementioned solvent is distilled off and then step (B) is carried out. [4] The method for producing a 3-mercapto carboxylic acid according to any one of [1] to [3], wherein the acid catalyst in the aforementioned step (B) is hydrochloric acid or sulfuric acid. [5] The method for producing a 3-mercapto carboxylic acid according to any one of [1] to [4], wherein the aforementioned thiocarboxylic acid is thioacetic acid. [6] The method for producing a 3-mercapto carboxylic acid according to any one of [1] to [5], wherein the aforementioned α,β-unsaturated carboxylic acid is crotonic acid. [7] The method for producing a 3-mercapto carboxylic acid according to [1] or [2], wherein the catalyst is sulfuric acid, the aforementioned thiocarboxylic acid is thioacetic acid, the aforementioned α,β-unsaturated carboxylic acid is crotonic acid, and the 3-mercapto carboxylic acid represented by formula (1) is 3-mercaptobutyric acid. [Advantages of the Invention] According to the present invention, a 3-mercapto carboxylic acid can be produced under industrially advantageous conditions. In this specification, when using "~" for a numerical range, the numerical values at both ends are the upper limit value and the lower limit value, respectively, and are included in the numerical range. In one embodiment of the present invention, the target 3-mercapto carboxylic acid is represented by formula (1). (R 1 ~R 3 each independently represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms). In formula (1), R 1 ~R 3 each independently represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms. R 1 and R 2 are preferably independently a hydrogen atom or an alkyl group having 1 to 3 carbon atoms. Moreover, preferably R 1 , R 2 one of them is a hydrogen atom. Preferably R 3 is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, preferably a hydrogen atom or a methyl group. Examples of the 3-mercapto carboxylic acid represented by the formula (1) include 3-mercaptopropionic acid, 3-mercaptoisobutyric acid, 3-mercaptobutyric acid, 3-mercapto-2-methylbutyric acid, 3-mercapto-3-methylbutyric acid, 3-mercaptopentanoic acid, 3-mercapto-2-methylpentanoic acid, 3-mercapto-4-methylpentanoic acid, 3-mercaptohexanoic acid, etc. Among these, from the viewpoint of the balance between reactivity and service life, 3-mercaptobutyric acid is preferred. <Step A> Step (A) is to carry out an addition reaction between the carbon-carbon unsaturated bond of an α,β-unsaturated carboxylic acid and a thiocarboxylic acid. As the α,β-unsaturated carboxylic acid as a raw material, an α,β-unsaturated carboxylic acid corresponding to the 3-mercapto carboxylic acid represented by the formula (1) of the target product is selected. Specific examples include acrylic acid, methacrylic acid, crotonic acid, angelic acid, tiglic acid, 3-methylcrotonic acid, 2-pentenoic acid, 2-methyl-2-pentenoic acid, 4-methyl-2-pentenoic acid, 2-hexenoic acid, etc. Among them, crotonic acid is preferred. Examples of the thiocarboxylic acid include thioacetic acid, thiopropionic acid, thiobenzoic acid, etc. Among them, thioacetic acid is preferred. The addition reaction between the α,β-unsaturated carboxylic acid and the thiocarboxylic acid is generally carried out in a solvent or without a solvent. A catalyst is not particularly required. When using a solvent, as the solvent, as long as it does not hinder the reaction between the α,β-unsaturated carboxylic acid and the thiocarboxylic acid, it is not limited. Specifically, aromatic hydrocarbon solvents such as toluene and xylene, and aliphatic hydrocarbon solvents such as hexane, heptane, octane, and cyclohexane can be used. Among them, toluene is preferred. The amount of the solvent is not particularly limited, but it is preferably 70% by mass or less relative to the entire reaction solution, more preferably 10 to 50% by mass. In step (A), a thiocarboxylic acid ester as an intermediate product is obtained. This thiocarboxylic acid ester adds a hydrogen atom to the α-position of the α,β-unsaturated carboxylic acid and forms a thiocarboxylic acid ester at the β-position. The reaction temperature is preferably 50 to 100 °C, more preferably 60 to 90 °C. The reaction time is not particularly limited as long as the reaction can be completed, and is preferably 2 to 8 hours. The thio carboxylic acid is preferably used in an excessive equivalent amount for the unsaturated bond of the α,β-unsaturated carboxylic acid. Preferably, it is 1.1 to 1.5 equivalents, more preferably 1.2 to 1.3 equivalents, relative to the unsaturated bond of the α,β-unsaturated carboxylic acid. If it is within the above range, since the α,β-unsaturated carboxylic acid reacts substantially, it is only necessary to remove the unreacted excessive thio carboxylic acid and the solvent. The reactant from which the thio carboxylic acid and the solvent have been removed can be directly supplied to step (B). <Step (B)> Step (B) is a step of hydrolyzing the thio carboxylic acid ester obtained in step (A) by reacting with water in the presence of an acid catalyst. Since water is used as the solvent in step (B), it is not necessary to use an additional solvent. When using a solvent, as long as it does not hinder this hydrolysis, it is not particularly limited, but aromatic hydrocarbon solvents such as toluene and xylene can be used. Examples of the acid catalyst include, for example, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, etc. Among them, hydrochloric acid and sulfuric acid are preferred. From the viewpoint that the acid remaining in trace amounts during distillation does not easily corrode the pipes and pumps, sulfuric acid is more preferred. From the viewpoint that the acid remaining in trace amounts during distillation is dissolved and stabilized in the content, hydrochloric acid is preferred. Water is preferably distilled water or ion-exchanged water. The temperature of the hydrolysis reaction is not particularly limited as long as the reaction can proceed, but is preferably 60 to 110 °C. The reaction time is not limited as long as it is the time for the hydrolysis reaction to be completed, but is preferably 2 to 10 hours. The amount of the acid catalyst used in the hydrolysis reaction is 0.025 equivalent to 0.68 equivalent relative to the thio carboxylic acid ester. The equivalent of the acid catalyst is the equivalent amount of the thio carboxylic acid bonded to the β-position ester of the α,β-unsaturated carboxylic acid. When the equivalent of the acid catalyst is less than 0.025 or greater than 0.68, the yield of 3-mercapto carboxylic acid decreases, so it is not good. The equivalent of the acid catalyst is more preferably 0.05 equivalent to 0.50 equivalent. The amount of water used in the hydrolysis reaction is not particularly limited as long as it is 1.0 equivalent or more relative to the thio carboxylic acid ester, but is preferably 1.0 equivalent to 5.5 equivalents, more preferably 1.5 equivalent to 5.0 equivalents. If it is within this range, the yield of 3-mercapto carboxylic acid will not decrease. After the hydrolysis reaction, the 3-mercapto carboxylic acid of the product can be extracted and isolated by an organic solvent such as toluene. Alternatively, the 3-mercapto carboxylic acid can be isolated by methods such as column chromatography or distillation. [Examples] Hereinafter, the present invention will be described in more detail with reference to examples and comparative examples, but the present invention is not limited to the following examples. [Example 1] Step (A) 100.0 g (1.16 mol) of crotonic acid and 110.5 g (1.45 mol) of thioacetic acid (CH 3 (C=O)SH) and 50 ml of toluene as a solvent were reacted in a three-necked flask equipped with a stirrer at 80 - 85 °C for 6 hours. Subsequently, the pressure was reduced to 3 kPa using a diaphragm pump, heated with a bath temperature of 40 °C, and toluene and unreacted thioacetic acid were removed by distillation under reduced pressure. 1 It was confirmed by ¹H-NMR that the unreacted crotonic acid was less than 1%. Therefore, the yield of the intermediate thioester ((3-acetylthio)butyric acid) was regarded as 100%. Step (B) In the flask containing the thioester of the reaction product used in step (A), concentrated hydrochloric acid and distilled water in the amounts shown in Table 1 were added, and a hydrolysis reaction was carried out at 100 °C for 3 hours. The equivalent of hydrogen chloride relative to the thioester was 0.50. Also, since the concentrated hydrochloric acid is a 35 mass% aqueous solution, the equivalent of the aforementioned acid was calculated based on the added mole number of hydrogen chloride. The water of the solvent of the concentrated hydrochloric acid and the water added separately were combined and calculated as the equivalent relative to the thioester. The progress of the hydrolysis was 1 traced by ¹H-NMR, and the reaction was completed when the reaction proceeded to more than 99%. Next, the reaction solution was extracted with the amount of toluene shown in Table 1, and the organic phase (toluene layer) was washed with the amount of distilled water and the number of times shown in Table 1. The organic phase was reduced to 3 kPa under reduced pressure using a diaphragm pump and heated at a bath temperature of 40 - 60 °C to distill off toluene and acetic acid. Subsequently, distillation was carried out under reduced pressure to 0.5 kPa using a vacuum pump, and 3-mercaptobutyric acid was obtained as the distillate. Also, the distillation temperature was 60 - 70 °C. The results (yield, yield, and yield (mass%) relative to the amount of raw materials used) are shown in Table 1. [Examples 2 - 6, Comparative Examples 1 - 9] In step (B), except for using concentrated sulfuric acid (98%) or concentrated hydrochloric acid instead of concentrated hydrochloric acid and changing to the conditions shown in Table 1 or Table 2, the production of 3-mercaptobutyric acid was carried out in the same manner as in Example 1. The results are shown in Table 1 and Table 2. [Comparative Examples 10 - 11] Step A The thioester was obtained in the same manner as in Example 1. Step B In the flask containing the thioester of the reaction product used in step (A), sodium hydroxide (solid) and distilled water in the amounts described in Table 3 were added, and a hydrolysis reaction was carried out under the reaction conditions described in Table 3. After the hydrolysis was completed, neutralization was carried out with concentrated hydrochloric acid in the amount described in Table 3. Then, the reaction solution was extracted with the amount of toluene shown in Table 3, and the organic phase (toluene layer) was washed with the amount of distilled water and the number of times shown in Table 3. The organic phase was reduced to 3 kPa under reduced pressure using a diaphragm pump and heated at a bath temperature of 40 - 60 °C to distill off toluene and acetic acid. Subsequently, distillation was carried out under reduced pressure to 0.5 kPa using a vacuum pump, and 3-mercaptobutyric acid was obtained as the distillate. Also, the distillation temperature was 60 - 70 °C. The results (yield, yield, and yield (mass%) relative to the amount of raw materials used) are shown in Table 3. According to Table 1, in the examples where the amount of acid catalyst during the reaction is 0.025 to 0.68 equivalents relative to the thioester carboxylic acid, the yields of 3-mercaptobutyric acid are all above 84%. On the other hand, according to Table 2, in Comparative Examples 1 to 9 where the equivalent of the acid catalyst is less than 0.025 or exceeds 0.68, the yields of 3-mercaptobutyric acid are all less than 80%. Moreover, according to Table 3, when sodium hydroxide, which is a base, is used in the hydrolysis reaction of Step B, the yield further decreases.

Claims

1. A method for manufacturing 3-mercaptocarboxylic acid represented by formula (1), comprising the following steps (A) and (B): Step (A) is the addition of a thiocarboxylic acid to the carbon-carbon unsaturated bond of an α,β-unsaturated carboxylic acid to obtain a thiocarboxylic acid ester; Step (B) is the addition of water and an acid catalyst to the aforementioned thiocarboxylic acid ester to carry out a hydrolysis reaction, wherein the hydrolysis reaction is carried out under the condition that the amount of acid catalyst during the reaction is 0.025 equivalents to 0.68 equivalents relative to the aforementioned thiocarboxylic acid ester, and the amount of water is 1.0 equivalents to 5.5 equivalents relative to the aforementioned thiocarboxylic acid ester, (R1 to R3 independently represent hydrogen atoms or alkyl groups with 1 to 5 carbon atoms respectively).

2. The method for manufacturing 3-mercaptocarboxylic acid as claimed in claim 1, wherein the addition reaction of step (A) is carried out in the presence of a solvent, and after the reaction, the solvent is distilled off before proceeding to step (B).

3. The method for manufacturing 3-mercaptocarboxylic acid as claimed in claim 1 or 2, wherein the acid catalyst in step (B) above is hydrochloric acid or sulfuric acid.

4. The method for manufacturing 3-mercaptocarboxylic acid as claimed in claim 1 or 2, wherein the aforementioned thiocarboxylic acid is thioacetic acid.

5. The method for manufacturing 3-mercaptocarboxylic acid as claimed in claim 1 or 2, wherein the aforementioned α,β-unsaturated carboxylic acid is crotonic acid.

6. The method for manufacturing 3-mercaptocarboxylic acid as claimed in claim 1 or 2, wherein the aforementioned acid catalyst is sulfuric acid, the aforementioned thiocarboxylic acid is thioacetic acid, the aforementioned α,β-unsaturated carboxylic acid is crotonic acid, and the aforementioned 3-mercaptocarboxylic acid represented by formula (1) is 3-mercaptobutyric acid.