Method for producing 3-mercaptocarboxylic acid
By using the addition reaction of α,β-unsaturated carboxylic acids with thiocarboxylic acids and acid-catalyzed hydrolysis, the problems of high production cost and insufficient yield of 3-mercaptocarboxylic acids in the existing technology have been solved, realizing efficient and low-cost industrial production.
Patent Information
- Application Number
- CN202480022829.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2023-04-13
- Filing Date
- 2024-03-29
- Publication Date
- 2025-11-04
AI Technical Summary
Existing technologies for manufacturing 3-mercaptocarboxylic acid suffer from high costs and insufficient yields, especially since neutralization under alkaline conditions is unsuitable for industrial manufacturing.
An addition reaction of α,β-unsaturated carboxylic acids with thiocarboxylic acids was carried out, followed by a hydrolysis reaction in the presence of an acid catalyst and water. The amounts of acid catalyst and water were controlled within a specific range. Steps (A) and (B) were performed to obtain 3-mercaptocarboxylic acids in high yield.
This enabled the efficient production of 3-mercaptocarboxylic acid under industrially favorable conditions, improving yield and reducing cost.
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Figure CN120897904A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to a production method of 3-mercapto carboxylic acid. BACKGROUND
[0002] A compound having a mercapto group and a carboxylic acid group can form an ester structure by reacting the carboxylic acid group with a hydroxyl group. By using a polyhydric alcohol as a hydroxyl group-containing compound, a compound having multiple mercapto groups can be obtained. The polyhydric mercaptan compound thus obtained is easily reacted with an epoxy group or an unsaturated double bond, etc., and is useful as a raw material for a resin, a thermosetting resin, a photocurable resin, etc., and has a high industrial value.
[0003] Therefore, it is desirable to establish a production method for efficiently producing a compound having a mercapto group and a carboxylic acid group.
[0004] As a method of synthesizing a compound having a mercapto group and a carboxylic acid group, various methods such as an addition reaction of sodium sulfide with an α,β-unsaturated carboxylic acid, a reaction of sodium sulfide with a β-halocarboxylic acid, an addition reaction of sodium sulfide with an α,β-unsaturated carboxylic acid, a reaction of sodium sulfide with a β-halocarboxylic acid, a method of hydrolyzing after an addition reaction of thiocarboxylic acid with an α,β-unsaturated carboxylic acid, and a method of hydrolyzing after an addition reaction of thiocarboxylic acid with an α,β-unsaturated carboxylic acid are known.
[0005] A method using an α,β-unsaturated carboxylic acid and a thiocarboxylic acid as a raw material is disclosed in Non-Patent Literatures 1 to 3. In Non-Patent Literature 1, a synthesis example of 3-mercapto-n-butyric acid is disclosed, but the hydrolysis of a thioester as an intermediate is performed under alkaline conditions. In this case, the base salt as a product is subjected to neutralization treatment and then extracted, so that the cost is consumed, and it is not suitable as an industrial production method. In Non-Patent Literatures 2 and 3, synthesis examples of 2-mercapto-methyl-n-butyric acid are described. In both cases, a thioester as an intermediate is hydrolyzed with an acid, but it cannot be said that the yield is sufficient.
[0006] [Related Art Documents]
[0007] [Non-Patent Literature]
[0008] Non-Patent Literature 1: Biomacromolecules 2001, 2, 1061-1065
[0009] Non-Patent Literature 2: Med. Chem. 11 (2003) 4685-4691
[0010] Non-Patent Literature 3: Biochemistry 2007, 56, 6087-6097 SUMMARY
[0011] [Problems to be Solved by the Invention]
[0012] The present application provides a method for producing 3-mercapto carboxylic acid under industrially advantageous conditions.
[0013] [Means for solving the problems]
[0014] The present inventors have made intensive studies in order to solve the above problems, and as a result, have completed the present application.
[0015] That is, the present application relates to a method for producing 3-mercapto carboxylic acid according to the following solutions [1] to [7].
[0016] [1] A method for producing 3-mercapto carboxylic acid represented by formula (1), comprising the following steps (A) and (B),
[0017] (A) a step of adding a thiocarboxylic acid to a carbon-carbon unsaturated bond of an α,β-unsaturated carboxylic acid to obtain a thiocarboxylic acid ester,
[0018] (B) a step of performing a hydrolysis reaction by adding water and an acid catalyst to the thiocarboxylic acid ester, the hydrolysis reaction being performed under conditions where the amount of the acid catalyst is 0.025 to 0.68 equivalents relative to the thiocarboxylic acid ester and the amount of the water is 1.0 equivalent or more relative to the thiocarboxylic acid ester at the time of the reaction,
[0019]
[0020] R 1 ~R 3 each independently represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.
[0021] [2] The method for producing 3-mercapto carboxylic acid according to [1], wherein the amount of the water in the step (B) is 1.0 to 5.5 equivalents relative to the thiocarboxylic acid ester.
[0022] [3] The method for producing 3-mercapto carboxylic acid according to [1] or [2], wherein the addition reaction in the step (A) is performed in the presence of a solvent, and after the reaction, the step (B) is performed after distilling and removing the solvent.
[0023] [4] The method for producing 3-mercapto carboxylic acid according to any one of [1] to [3], wherein the acid catalyst in the step (B) is hydrochloric acid or sulfuric acid.
[0024] [5] The method for producing 3-mercapto carboxylic acid according to any one of [1] to [4], wherein the thiocarboxylic acid is thioacetic acid.
[0025] [6] The method for producing 3-mercapto carboxylic acid according to any one of [1] to [5], wherein the α,β-unsaturated carboxylic acid is crotonic acid.
[0026] [7] The production method of 3-mercapto carboxylic acid according to [1] or [2], wherein the acid catalyst is sulfuric acid, the thiocarboxylic acid is thioacetic acid, the α,β-unsaturated carboxylic acid is crotonic acid, and the 3-mercapto carboxylic acid represented by formula (1) is 3-mercapto-n-butyric acid.
[0027] [Effects of Invention]
[0028] According to the present application, 3-mercapto carboxylic acid can be produced under industrially advantageous conditions. DETAILED DESCRIPTION
[0029] In the present specification, when "~" is used with respect to 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.
[0030] In one embodiment of the present application, the 3-mercapto carboxylic acid of interest is represented by formula (1).
[0031]
[0032] (R 1 ~R 3 each independently represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.
[0033] 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 each independently represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms. Furthermore, it is preferable that R 1 , R 2 one of R 3 is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and preferably a hydrogen atom or a methyl group.
[0034] As the 3-mercapto carboxylic acid represented by formula (1), 3-mercapto propionic acid, 3-mercapto isobutyric acid, 3-mercapto-n-butyric acid, 3-mercapto-2-methyl-n-butyric acid, 3-mercapto-3-methyl-n-butyric acid, 3-mercapto-n-pentanoic acid, 3-mercapto-2-methyl-n-pentanoic acid, 3-mercapto-4-methyl-n-pentanoic acid, 3-mercapto hexanoic acid, and the like can be exemplified. Among these, 3-mercapto-n-butyric acid is preferable from the viewpoint of the balance between reactivity and service life.
[0035] <Step A>
[0036] In step (A), the carbon-carbon unsaturated bond of the α,β-unsaturated carboxylic acid is subjected to an addition reaction with the thiocarboxylic acid.
[0037] As the α,β-unsaturated carboxylic acid as a raw material, an α,β-unsaturated carboxylic acid corresponding to the 3-mercapto carboxylic acid of the object represented by the formula (1) is selected. Specifically, acrylic acid, methacrylic acid, crotonic acid, angelic acid, tiglic acid, 3-methyl crotonic acid, 2-pentenoic acid, 2-methyl-2-pentenoic acid, 4-methyl-2-pentenoic acid, 2-hexenoic acid, and the like can be exemplified. Among them, crotonic acid is preferred.
[0038] As the thio carboxylic acid, thioacetic acid, thiopropionic acid, thio benzoic acid, and the like can be exemplified. Among them, thioacetic acid is preferred.
[0039] The addition reaction of the α,β-unsaturated carboxylic acid and the thio carboxylic acid is generally carried out in a solvent or without a solvent. The catalyst is not particularly required.
[0040] When a solvent is used, as the solvent, there is no particular limitation as long as it does not hinder the reaction of the α,β-unsaturated carboxylic acid and the thio carboxylic acid. Specifically, an aromatic hydrocarbon-based solvent such as toluene, xylene, an aliphatic hydrocarbon-based solvent such as hexane, heptane, octane, cyclohexane, and the like can be used. Among them, toluene is preferred. The amount of the solvent is not particularly limited, but it is preferred to be 70% by mass or less, and more preferably 10 to 50% by mass, with respect to the total of the reaction solution.
[0041] In the step (A), a thio carboxylic acid ester as an intermediate product is obtained. The thio carboxylic acid ester adds a hydrogen atom at the α position of the α,β-unsaturated carboxylic acid and forms a thio carboxylic acid ester at the β position.
[0042] The reaction temperature is preferably 50 to 100°C. More preferably, it is 60 to 90°C.
[0043] The reaction time is not particularly limited as long as the reaction is completed. It is preferably 2 to 8 hours.
[0044] The thio carboxylic acid is preferably used in an excess equivalent with respect to the unsaturated bond of the α,β-unsaturated carboxylic acid. It is preferably 1.1 to 1.5 equivalents, and more preferably 1.2 to 1.3 equivalents, with respect 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 is substantially completely reacted, only the unreacted excess thio carboxylic acid and the solvent need to be removed. The reactant from which the thio carboxylic acid and the solvent are removed can be directly supplied to the step (B).
[0045] <Step (B)>
[0046] The step (B) is a step in which the thio carboxylic acid ester obtained in the step (A) is reacted with water in the presence of an acid catalyst to perform hydrolysis. Since water is a solvent in the step (B), a solvent can also be used without particular limitation. When a solvent is used, an aromatic hydrocarbon-based solvent such as toluene, xylene, and the like can be used without particular limitation as long as it does not hinder the formal hydrolysis.
[0047] As the acid catalyst, for example, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, and the like can be exemplified. Among them, hydrochloric acid and sulfuric acid are preferred, from the viewpoint that the trace amount of the acid remaining at the time of distillation does not easily corrode the piping and pump, and sulfuric acid is more preferred, from the viewpoint that the trace amount of the acid remaining at the time of distillation is easily stabilized in the content, and hydrochloric acid is preferred, from the viewpoint that the trace amount of the acid remaining at the time of distillation is easily stabilized in the content.
[0048] The water is preferably distilled water or ion-exchanged water.
[0049] The temperature of the hydrolysis reaction is not particularly limited as long as it is a condition under which the reaction proceeds, but is preferably from 60 to 110°C. The reaction time is not limited as long as it is a time in which the hydrolysis reaction is completed, but is preferably from 2 to 10 hours.
[0050] The amount of the acid catalyst used in the hydrolysis reaction is from 0.025 equivalent to 0.68 equivalent relative to the thio carboxylate. The equivalent of the acid catalyst is the equivalent amount relative to the ester bond of the thio carboxylic acid at the β position of the α,β-unsaturated carboxylic acid. When the equivalent of the acid catalyst is less than 0.025 or more than 0.68, it is not suitable because the yield of the 3-mercapto carboxylic acid decreases. The equivalent of the acid catalyst is more preferably from 0.05 equivalent to 0.50 equivalent.
[0051] The amount of the water used in the hydrolysis reaction is not particularly limited as long as it is 1.0 equivalent or more relative to the thio carboxylate, but is preferably from 1.0 equivalent to 5.5 equivalent, and more preferably from 1.5 equivalent to 5.0 equivalent. If it is within this range, the yield of the 3-mercapto carboxylic acid does not decrease.
[0052] After the hydrolysis reaction, the 3-mercapto carboxylic acid of the product can be separated by extraction with an organic solvent such as toluene. Alternatively, the 3-mercapto carboxylic acid can be separated by column chromatography or distillation.
[0053] Examples
[0054] Hereinafter, the present application will be described in more detail by way of examples and comparative examples, but the present application is not limited to the following examples.
[0055] [Example 1]
[0056] Step (A)
[0057] A three-necked flask equipped with a stirrer was charged with 100.0 g (1.16 mol) of crotonic acid, 110.5 g (1.45 mol) of thioacetic acid (CH3(C=O)SH), and 50 ml of toluene as a solvent, and the mixture was reacted at 80 to 85°C for 6 hours. Subsequently, the toluene and unreacted thioacetic acid were distilled off under reduced pressure of 3 kPa with heating at a bath temperature of 40°C using a diaphragm pump. The residual thio carboxylate was confirmed by H-NMR to be 0.5% or less. 1 The unreacted crotonic acid was confirmed by H-NMR to be less than 1%. Therefore, the yield of the thio carboxylate ((3-acetylthio) n-butyric acid) as an intermediate was regarded as 100%.
[0058] Step (B)
[0059] To the flask containing the reaction product, thioester, used in Step (A), the amounts of concentrated hydrochloric acid and distilled water shown in Table 1 were added, and a hydrolysis reaction was performed at 100°C for 3 hours. The equivalent of hydrogen chloride with respect to the thioester was 0.50. In addition, since the concentrated hydrochloric acid was a 35 mass% aqueous solution, the equivalent of the acid was calculated based on the number of moles of hydrogen chloride added. The water as a solvent for the concentrated hydrochloric acid and the water additionally added were combined and the equivalent with respect to the thioester was calculated. The hydrolysis was performed so that the pH of the reaction solution was 1.0 or less. 1 H-NMR tracking was performed, and the reaction was completed when the reaction proceeded to 99% or more. 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 and number of times of distilled water shown in Table 1. The organic phase was reduced in pressure to 3 kPa with a diaphragm pump, heated at a bath temperature of 40 to 60°C, and distilled to remove toluene and acetic acid. Subsequently, distillation was performed under reduced pressure to 0.5 kPa with a vacuum pump, and 3-mercapto-n-butyric acid was obtained as a distillate component. In addition, the distillation temperature was 60 to 70°C. The results (yield, recovery, and recovery amount (mass%) with respect to the amount of raw material used) are shown in Table 1.
[0060] [Examples 2 to 6, Comparative Examples 1 to 9]
[0061] In Step (B), the production of 3-mercapto-n-butyric acid was performed in the same manner as in Example 1, except that concentrated sulfuric acid (98%) or concentrated hydrochloric acid was used instead of concentrated hydrochloric acid, and the conditions shown in Table 1 or Table 2 were changed. The results are shown in Table 1 and Table 2.
[0062]
[0063] [Comparative Examples 10 to 11]
[0064] Step A
[0065] The thioester was obtained in the same manner as in Example 1.
[0066] Step B
[0067] In the flask containing the thioester as a reaction product used in step (A), sodium hydroxide (solid) and distilled water were added in the amounts described in Table 3, and a hydrolysis reaction was performed under the reaction conditions described in Table 3. After the hydrolysis was completed, neutralization was performed with concentrated hydrochloric acid in the amount described in Table 3. Subsequently, the reaction solution was extracted with toluene in the amount described in Table 3, and the organic phase (toluene layer) was washed with distilled water in the amount and number of times described in Table 3. The organic phase was heated at a bath temperature of 40 to 60°C under reduced pressure of 3 kPa using a diaphragm pump, and toluene and acetic acid were distilled off. Subsequently, distillation was performed under reduced pressure of 0.5 kPa using a vacuum pump, and 3-mercapto-n-butyric acid was obtained as a distillate component. The distillation temperature was 60 to 70°C. The results (amount of recovery, yield, and amount of recovery (mass %) relative to the amount of raw material used) are shown in Table 3.
[0068]
[0069] According to Table 1, the yield of 3-mercapto-n-butyric acid in the examples was 84% or more, when the amount of acid catalyst was 0.025 to 0.68 equivalents relative to the thioester. On the other hand, according to Table 2, the yield of 3-mercapto-n-butyric acid was less than 80% in Comparative Examples 1 to 9, in which the equivalent of acid catalyst was less than 0.025 or more than 0.68. Furthermore, according to Table 3, the yield was further reduced when sodium hydroxide was used as a base in the hydrolysis reaction of step B.
Claims
1. A method for producing a 3-mercaptocarboxylic acid represented by formula (1), comprising the following steps A and B, Step A: The step of adding thiocarboxylic acids to the carbon-carbon unsaturated bonds of α,β-unsaturated carboxylic acids to obtain thiocarboxylic acid esters. Step B: The step of hydrolyzing the thiocarboxylic acid ester by adding water and an acid catalyst, wherein the hydrolysis reaction is carried out under the conditions that the amount of acid catalyst is 0.025 to 0.68 equivalents relative to the thiocarboxylic acid ester and the amount of water is 1.0 equivalent or more relative to the thiocarboxylic acid ester. R 1 ~R 3 Each can be independently represented by an alkyl group having 1 to 5 hydrogen atoms or carbon atoms.
2. The method for producing 3-mercaptocarboxylic acid according to claim 1, wherein the amount of water in step B is 1.0 to 5.5 equivalents relative to the thiocarboxylic acid ester.
3. The method for producing 3-mercaptocarboxylic acid as described in claim 1 or 2, wherein the addition reaction in step A is carried out in the presence of a solvent, and after the reaction, the solvent is removed by distillation before proceeding to step B.
4. The method for producing 3-mercaptocarboxylic acid according to claim 1 or 2, wherein the acid catalyst in step B is hydrochloric acid or sulfuric acid.
5. The method for manufacturing 3-mercaptocarboxylic acid as described in claim 1 or 2, wherein the thiocarboxylic acid is thioacetic acid.
6. The method for manufacturing 3-mercaptocarboxylic acid as described in claim 1 or 2, wherein the α,β-unsaturated carboxylic acid is crotonic acid.
7. The method for manufacturing 3-mercaptocarboxylic acid according to claim 1 or 2, wherein the acid catalyst is sulfuric acid, the thiocarboxylic acid is thioacetic acid, the α,β-unsaturated carboxylic acid is crotonic acid, and the 3-mercaptocarboxylic acid represented by formula (1) is 3-mercaptobutyric acid.