Alpha-iodine substituted carboxylic acids

Abstract

Provided is an alpha-iodine-substituted carboxylic acid having excellent stability with respect to heat, light, and the like. The [alpha]-iodine-substituted carboxylic acid according to the present invention is represented by general formula (1) (in the formula, R1 and R2 each independently represent a hydrogen atom, a carboxyl group, an aliphatic group or an aromatic group, and the [alpha]-iodine-substituted carboxylic acid has a water content in the range of 0.1-15.0 mass% and an acid component content in the range of 0.15-3.0 mass%. [Chemical Formula 1]

Description

Technical Field

[0001] This invention relates to an α-iodine-substituted carboxylic acid. Background Technology

[0002] Iodine and iodine compounds are widely used in various applications such as bactericides, contrast agents, pigments, pharmaceuticals, pesticides, charge transport materials, oxidants, precision polymerization, and catalysts due to their unique properties such as physiological activity, antibacterial properties, X-ray absorption capacity, and high reactivity (e.g., see Non-Patent Literature 1).

[0003] Previous technical documents

[0004] Non-patent literature

[0005] Non-Patent Literature 1: "Functional and Application Development of Iodine Compounds", CMC Publishing CO.,LTD., First Edition Released October 30, 2005 Summary of the Invention

[0006] The technical problem to be solved by the invention

[0007] In organoiodine compounds, α-iodine-substituted carboxylic acids are useful as free radical generators or molecular weight controllers in living radical polymerization (also known as controlled free radical polymerization), as well as as raw materials or intermediates in the synthesis of various fine chemicals. However, α-iodine-substituted carboxylic acids are easily decomposed when exposed to heat, light, or redox conditions, and their stability (long-term shelf life) still has room for improvement.

[0008] The purpose of this invention is to provide an α-iodine-substituted carboxylic acid that is stable to heat or light and whose decomposition is inhibited.

[0009] Through repeated and in-depth research, the inventors discovered that by including α-iodine-substituted carboxylic acids within a specific range of water and acid components, the aforementioned problem can be solved, thus completing this invention.

[0010] means for solving technical problems

[0011] The present invention has the following solution.

[0012] [1] An α-iodine-substituted carboxylic acid, represented by the following general formula (1),

[0013] [Chemical Formula 1]

[0014]

[0015] In the formula, R 1 and R 2 Each can independently represent a hydrogen atom, a carboxyl group, an aliphatic group, or an aromatic group.

[0016] The α-iodine-substituted carboxylic acid has a water content in the range of 0.1 to 15.0% by mass and an acid content in the range of 0.15 to 3.0% by mass.

[0017] [2] According to the α-iodine-substituted carboxylic acid described in [1], wherein the acid dissociation constant (pKa) of the acid component is 2.8 or less.

[0018] [3] According to [1] or [2], the α-iodine-substituted carboxylic acid, wherein the acid component is an inorganic acid.

[0019] [4] A method for stabilizing an α-iodine-substituted carboxylic acid, wherein the α-iodine-substituted carboxylic acid represented by the following general formula (1) contains water in the range of 0.1 to 15.0% by mass and contains an acid component in the range of 0.15 to 3.0% by mass.

[0020] [Chemical Formula 2]

[0021]

[0022] In the formula, R 1 and R 2 Each can be independently represented by a hydrogen atom, carboxyl group, aliphatic group, or aromatic group.

[0023] Effects of the Invention

[0024] According to the present invention, it is possible to provide an α-iodine-substituted carboxylic acid that is stable to heat or light and whose decomposition is suppressed. Detailed Implementation

[0025] This invention relates to an α-iodine-substituted carboxylic acid, represented by the following general formula (1).

[0026] [Chemical Formula 3]

[0027]

[0028] In the formula, R 1 and R 2 Each of the hydrogen atom, carboxyl group, aliphatic group or aromatic group is independently represented, and the water content of the α-iodine-substituted carboxylic acid is in the range of 0.1 to 15.0% by mass, and the acid content is in the range of 0.15 to 3.0% by mass.

[0029] The α-iodine-substituted carboxylic acid of the present invention exhibits excellent stability to heat or light, its decomposition is suppressed, and its coloring is inhibited even after long-term storage.

[0030] The exact reasons for this effect are not yet clear, but it can be inferred that the dissociation equilibrium of the carboxyl group in α-iodine-substituted carboxylic acids in the presence of water tends to the side where hydrogen ions do not dissociate due to the presence of acid components within a certain range. Therefore, the stability of α-iodine-substituted carboxylic acids is improved, and the decomposition of iodine is suppressed.

[0031] In general formula (1), as R 1 and R 2 Aliphatic groups, which can be represented independently, include straight-chain or branched aliphatic hydrocarbon groups and alicyclic hydrocarbon groups.

[0032] The number of carbon atoms in the straight-chain or branched aliphatic hydrocarbon group is preferably 1 to 12, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-hexyl, n-octyl, 2-ethylhexyl, decyl, dodecyl, etc.

[0033] The alicyclic hydrocarbon group preferably has 3 to 12 carbon atoms, and examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, and dicyclohexyl.

[0034] Among them, as an aliphatic group, a straight-chain or branched aliphatic hydrocarbon group with 1 to 12 carbon atoms is preferred, and methyl, ethyl, propyl, and butyl are more preferred.

[0035] In general formula (1), as R 1 and R 2 Aromatic groups that can be represented independently include aromatic hydrocarbon groups and aromatic heterocyclic groups.

[0036] The number of carbon atoms in the aromatic hydrocarbon group is preferably 6 to 20, for example, phenyl, naphthyl, biphenyl, anthracene, phenanthryl, azulene, terphenyl, etc.

[0037] The number of carbon atoms in the aromatic heterocyclic group is preferably 6 to 20, and examples include furanyl, thiophene, pyrrole, pyrazolyl, pyridinyl, imidazole, isoxazolyl, thiazolyl, thiadiazolyl, benzofuranyl, indolyl, benzothiazolyl, carbazoleyl, etc.

[0038] The aforementioned aliphatic or aromatic groups may also have substituents. Examples of such substituents include hydroxyl, cyano, carboxyl, and nitro groups; halogen atoms such as fluorine, chlorine, bromine, and iodine atoms; alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; and alkoxy groups such as methoxy, ethoxy, propoxy, butoxy, isopropoxy, isobutoxy, tert-butoxy, sec-butoxy, isopentoxy, neopentoxy, tert-pentoxy, and 1,2-dimethylpropoxy.

[0039] Furthermore, in general formula (1), R 1and R 2 They can also bond together to form a ring structure. Examples of such ring structures include cyclopentane rings, cyclohexane rings, tetrahydrofuran rings, dioxane rings, pyrrolidine rings, piperidine rings, oxazolidine rings, piperazine rings, morpholine rings, thiazolidinyl rings, tetrahydrothiophene rings, pyrrole rings, triazole rings, and piperazineone rings.

[0040] Specific examples of α-iodosubstituted carboxylic acids represented by general formula (1) include 2-iodoacetic acid, 2-iodopropionic acid, 2-iodo-2-methylpropionic acid, 2-iodovallic acid, 2-iodo-2-phenylacetic acid, 2-iodomalonic acid, 2-iodo-2-methylmalonic acid, 2,5-diiodohexanoic acid, 2,5-diiodo-2,5-dimethylhexanoic acid, 2-iodoacetoacetic acid, 2-iodo-2-methylacetoacetic acid, etc.

[0041] From the viewpoint of further maximizing the stabilizing effect of the present invention, 2-iodo-2-methylpropionic acid, 2-iodo-2-phenylacetic acid, 2-iodo-2-methylmalonic acid, and 2-iodo-2-methylacetoacetic acid are preferred as α-iodine-substituted carboxylic acids.

[0042] The acid component present in water along with α-iodine-substituted carboxylic acids is an acid other than α-iodine-substituted carboxylic acids. It can be an organic acid or an inorganic acid, including Brønsted acids and Lewis acids. In this invention, when a Lewis acid is used as the acid component, sometimes an inorganic acid is generated by coexisting it with water, and this inorganic acid performs the stabilizing effect of this invention. For example, when using aluminum chloride, coexisting it with water will produce hydrogen chloride, which performs the same function as hydrochloric acid.

[0043] As the acid component, in this invention, from the viewpoint of further improving the stability of α-iodine-substituted carboxylic acids to heat or light, an acid with an acid dissociation constant (pKa) of 2.8 or less is preferred. The lower limit of the acid dissociation constant (pKa) is not strictly limited in meaning, but from the viewpoint of processability, -9 or higher is preferred. Furthermore, the acid dissociation constant (pKa) is the value at 25°C shown in the revised 6th edition of the Handbook of Chemistry (released January 20, 2021). Also, in the case of an acid with a valence of 2 or higher, pKa in this specification refers to the value of pKa1 (the first dissociation stage).

[0044] Preferred acid components include, for example, hydrobromic acid, hydrochloric acid, sulfuric acid, phosphoric acid, trifluoroacetic acid, trichloroacetic acid, and oxalic acid.

[0045] From the viewpoints of being inexpensive and industrially readily available, easy to control the content of acid components, and easy to achieve the effects of the present invention, inorganic acids are preferred, and sulfuric acid (-3.29) or hydrochloric acid (-5.9) are even more preferred. Here, the values ​​in parentheses represent the pKa values ​​of each acid.

[0046] In this invention, the acid content of the α-iodine-substituted carboxylic acid is 0.15% by mass or more, preferably 0.2% by mass or more, and more preferably 0.3% by mass or more. The acid content is 3.0% by mass or less, preferably 2.0% by mass or less, and more preferably 1.0% by mass or less.

[0047] Furthermore, the α-iodine-substituted carboxylic acid in this invention has a water content of 0.1% by mass or more, preferably 0.5% by mass or more, and more preferably 1.0% by mass or more. The water content is 15.0% by mass or less, preferably 10.0% by mass or less, and more preferably 5.0% by mass or less.

[0048] In this invention, from the viewpoint of further improving stability to heat or light, being able to suppress decomposition and suppressing discoloration even after long-term storage, it is preferable that the water content of the α-iodine-substituted carboxylic acid is in the range of 0.1 to 5.0% by mass, and the content of the acid component is in the range of 0.15 to 1.0% by mass.

[0049] In other words, the α-iodine-substituted carboxylic acid of the present invention can also be described as a composition containing specific amounts of α-iodine-substituted carboxylic acid, water, and an acid component. That is, in the present invention, the content of the acid component and the water content of the α-iodine-substituted carboxylic acid are both within the above-mentioned range, thereby exhibiting excellent stability to heat or light, suppressing decomposition, and inhibiting discoloration even after long-term storage.

[0050] α-Iodine-substituted carboxylic acids can be manufactured, for example, by the method described in International Publication No. 2018 / 180547. The α-iodine-substituted carboxylic acids of the present invention are obtained by adding water and an acid component to the obtained α-iodine-substituted carboxylic acids within the above-specified amounts.

[0051] Here, water and acid can be added directly to the obtained α-iodine-substituted carboxylic acid, or they can be contacted as an aqueous solution obtained by dissolving the acid in water with the α-iodine-substituted carboxylic acid obtained by a known method. From an operational point of view, it is preferable to contact the α-iodine-substituted carboxylic acid obtained by a known method with an aqueous solution obtained by dissolving the acid in water.

[0052] There is no particular limitation on the contact time when the aqueous solution obtained by dissolving the acid component in water is brought into contact with the solution, but from the viewpoint of operability or productivity, it is generally preferred to be in the range of 1 minute to 24 hours. Furthermore, from the viewpoint of suppressing heat generation, the contact temperature is generally preferred to be in the range of 0°C to 40°C, and more preferably in the range of 0°C to 20°C.

[0053] After contacting an aqueous solution obtained by dissolving the acid component in water, the α-iodine-substituted carboxylic acid of the present invention is obtained by conventional separation operations such as filtration and centrifugation.

[0054] The control of water content and acid content in obtaining the α-iodine-substituted carboxylic acid of the present invention can be achieved, for example, by adjusting the amounts of water and acid used during contact (preferably by adjusting the concentration of the acid in an aqueous solution obtained by dissolving the acid in water). Furthermore, when separating after contacting the water and acid, the separation operation can be performed to a degree where water and acid residue remain within the range specified in the present invention. Alternatively, the separation operation can be performed in a state where excessive water residue remains, followed by distillation to remove water under reduced pressure, and the water content adjusted to the range specified in the present invention.

[0055] The α-iodine-substituted carboxylic acids of the present invention are useful as raw materials or intermediates for the synthesis of various fine chemicals. Furthermore, the α-iodine-substituted carboxylic acids of the present invention are useful, for example, as free radical generators or molecular weight control agents in living radical polymerization.

[0056] Here, in the living radical polymerization, azo compounds such as azoisobutyronitrile; inorganic peroxides such as hydrogen peroxide, potassium persulfate, and ammonium persulfate; organic peroxides such as benzoyl peroxide, di-tert-butyl peroxide, and cumene hydrogen peroxide; redox catalysts; radical polymerization initiators and the α-iodine-substituted carboxylic acids of the present invention can be used simultaneously.

[0057] Furthermore, monomers capable of free radical polymerization include, for example, (meth)acrylic acid, methyl (meth)acrylate, ethyl (meth)acrylate, butyl (meth)acrylate, hydroxyethyl (meth)acrylate, (meth)acrylamide, (meth)acrylonitrile, and other (meth)acrylic acid derivatives such as salts, esters, amides, or nitriles thereof; styrene or styrene derivatives such as styrene, α-methylstyrene, o-methylstyrene, p-methylstyrene, hydroxystyrene, and dichlorostyrene; olefins such as ethylene, propylene, butene, isobutene, hexene, octene, decene, dodecene, pinene, limonene, and indene; dienes such as butadiene, isoprene, cyclopentadiene, dicyclopentadiene, and ethylidene norbornene; vinyl esters such as vinyl acetate and vinyl neopentanoate; vinyl ethers such as butyl vinyl ether; and so on.

[0058] The α-iodine-substituted carboxylic acid of the present invention can be effectively used as a free radical generator or molecular weight control agent in the living free radical polymerization of the above monomers.

[0059] The present invention also provides a method for stabilizing an α-iodine-substituted carboxylic acid, wherein the α-iodine-substituted carboxylic acid represented by the general formula (1) contains water in the range of 0.1 to 15.0% by mass and contains acid components in the range of 0.15 to 3.0% by mass.

[0060] For example, α-iodine-substituted carboxylic acids obtained by the method described in International Publication No. 2018 / 180547 contain water and acid components within the above-mentioned range, thereby improving the stability of α-iodine-substituted carboxylic acids to heat or light, inhibiting decomposition, and suppressing discoloration even after long-term storage.

[0061] The details of α-iodine-substituted carboxylic acids, acid components, and methods containing water and acid components within the above-mentioned range are as described above.

[0062] Example

[0063] The present invention will now be specifically described through examples. However, the present invention is not limited to the examples described below. The analyses in each evaluation were performed as follows.

[0064] 〔purity〕

[0065] The samples obtained in each example and comparative example were dissolved in dichloromethane, and the peak area values ​​of the chromatograms were calculated based on gas chromatography analysis. The determination conditions are as follows.

[0066] Equipment: Shimadzu Corporation, "GC-2010"

[0067] Tubing: HP-ULTRA1 (manufactured by Agilent Technologies, Inc., 25m × 0.32mm I.D.)

[0068] Carrier gas: Helium

[0069] Temperature: Hold at 50℃ for 3 minutes → Increase temperature at 30℃ / minute → Hold at 250℃

[0070] Detector: Flame Ionization Detector (FID)

[0071] [Free iodine content]

[0072] 2g of the sample obtained in each example and comparative example was accurately weighed and mixed with 18g of 1,2-dichloroethane (DCE) to completely dissolve the sample and prepare a solution. The absorbance of the solution (498nm, 700nm) was measured using an absorbance meter (JASCO Corporation “V-730iRM”). The free iodine concentration (ppm) in the sample was determined using DCE solutions with varying iodine concentrations based on a separately prepared absorbance calibration curve.

[0073] <Manufacturing Example 1: Manufacturing of 2-iodo-2-methylpropionic acid>

[0074] 10.0 parts by weight of 2-bromo-2-methylpropionic acid were dissolved in 160 parts by weight of acetone. 44.9 parts by weight of sodium iodide were added to the solution, and the mixture was stirred at 55°C for 18 hours. Acetone was removed from the reaction mixture by distillation under reduced pressure, and the residue was separated by adding dichloromethane and water.

[0075] The organic layer was washed with saturated brine, dried with sodium sulfate, and then concentrated to obtain 10.1 parts by mass of 2-iodo-2-methylpropionic acid in the form of crystals.

[0076] [Example 1]

[0077] 100 parts by mass of an aqueous sulfuric acid solution (concentration 17.4% by mass) was added to 100 parts by mass of 2-iodo-2-methylpropionic acid obtained by the method of Manufacturing Example 1, and the mixture was stirred at 5°C for 30 minutes. Then, the mixture was centrifuged at 390G for 10 minutes to obtain 2-iodo-2-methylpropionic acid with a water content of 4.23% by mass and an acid content (sulfuric acid content) of 0.21% by mass.

[0078] Here, the moisture content is calculated by weighing a specified amount of 2-iodo-2-methylpropionic acid, placing it in a desiccator using phosphorus pentoxide as a desiccant to achieve a constant mass, and taking into account the mass loss before and after drying. Furthermore, the acid content is calculated based on the moisture content calculated above.

[0079] [Examples 2-3]

[0080] In Example 1, hydrochloric acid or oxalic acid aqueous solution was used instead of sulfuric acid aqueous solution. Otherwise, the same operation as in Example 1 was performed to obtain 2-iodo-2-methylpropionic acid with the water content and acid content shown in Table 1.

[0081] [Comparative Example 1]

[0082] In Example 1, pure water was used instead of sulfuric acid aqueous solution. Otherwise, the same operation as in Example 1 was performed to obtain 2-iodo-2-methylpropionic acid with the water content shown in Table 1.

[0083] <Evaluation Example 1>

[0084] The 2-iodo-2-methylpropionic acid obtained in Examples 1-3 and Comparative Example 1 was placed in a 6 ml sample vial under argon atmosphere and capped. The vial was then placed in a constant temperature bath at 40°C and the purity was measured after standing (0 days), 4 days, and 10 days to evaluate its stability.

[0085] The results are shown in Table 1. The α-iodine-substituted carboxylic acids that meet the requirements of this invention exhibit excellent thermal stability. On the other hand, it is evident that when the acid content is absent but the water content is within the range specified in this invention, the purity decreases over time, and thermal stability cannot be maintained.

[0086] [Table 1]

[0087]

[0088] ※1: Relative value with the analysis value of day 0 as 100.

[0089] [Examples 4-6, Comparative Example 2]

[0090] In Example 1, an aqueous solution with varying sulfuric acid concentration was used. Otherwise, the same procedures as in Example 1 were performed to obtain 2-iodo-2-methylpropionic acid with the water content and acid content shown in Table 2.

[0091] <Evaluation Example 2>

[0092] The 2-iodo-2-methylpropionic acid obtained in Examples 4-6 and Comparative Example 2 was placed in a 6 ml sample vial under argon atmosphere and capped. The vial was then placed in a constant temperature bath at 40°C. The changes in purity and free iodine content over time were tracked after standing (0 days), 6 days, and 20 days to evaluate the stability.

[0093] The results are shown in Table 2. The α-iodine-substituted carboxylic acids that meet the requirements of this invention exhibit excellent thermal stability, and coloring is also suppressed. On the other hand, according to Comparative Example 2, if the content of sulfuric acid, as an acid component, is below the range specified in this invention, the generation of free iodine increases, becoming the main cause of coloring.

[0094] [Table 2]

[0095]

[0096] ※1: Relative value with the analysis value of day 0 as 100.

[0097] Industrial availability

[0098] The α-iodine-substituted carboxylic acids of the present invention exhibit excellent stability and can be effectively used, for example, as free radical generators or molecular weight control agents in living radical polymerization, and as raw materials or intermediates in the manufacture of various fine chemicals.

Claims

1. An α-iodine-substituted carboxylic acid, represented by the following general formula (1), [Chemical Formula 1] In the formula, R 1 and R 2 Each can independently represent a hydrogen atom, a carboxyl group, an aliphatic group, or an aromatic group. The α-iodine-substituted carboxylic acid has a water content in the range of 0.1 to 15.0% by mass and an acid content in the range of 0.15 to 3.0% by mass.

2. The α-iodine-substituted carboxylic acid according to claim 1, wherein, The acid component has an acid dissociation constant (pKa) of less than 2.

8.

3. The α-iodine-substituted carboxylic acid according to claim 1 or 2, wherein, The acid component is an inorganic acid.

4. A method for stabilizing α-iodine-substituted carboxylic acids, wherein, The α-iodine-substituted carboxylic acid represented by the following general formula (1) contains water in the range of 0.1% to 15.0% by mass and an acid component in the range of 0.15% to 3.0% by mass. [Chemical Formula 2] In the formula, R 1 and R 2 Each can be independently represented by a hydrogen atom, carboxyl group, aliphatic group, or aromatic group.

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