CN1747910A - Preparation method of iodine compound and preparation process of high-purity 5-iodo-2-methylbenzoic acid - Google Patents

Abstract

Provided is a method for preparing iodine compounds, wherein iodine reacts with a substrate in the presence of a porous material with a pore diameter of 500 nm or less, or in the presence of the aforementioned porous material and an oxidizing agent, and high-purity 5-iodo-2-formazol A process for the preparation of phenylbenzoic acid comprising an iodination reaction step carried out by the above method, a crystal precipitation and separation step wherein the product is precipitated by adding water or cooling and subsequent separation, and wherein the separated crystals are treated with an organic solvent A purification step of recrystallization was performed. According to the production method of the above-mentioned iodine compound, iodine can be introduced into various substrates with high selectivity. Since it is unnecessary to use noble metals and special reagents, this reaction can be easily carried out on an industrial scale, and high-purity products can be obtained. In addition, the process of the present invention including iodination reaction, separation and purification steps makes it possible to easily obtain high-purity 5-iodo-2-methylbenzoic acid in high yield, which can be used in functional chemical products such as pharmaceuticals. The steps including iodination reaction, separation and purification are characterized in that they are simple in process, have a small purification load, and are very advantageous for industrial implementation.

Description

The preparation method of iodine compound and the preparation technology of high-purity 5-iodo-2-methylbenzoic acid

Background of the invention

The invention relates to a method for directly and selectively preparing iodine compounds using iodine, and a preparation process for high-purity 5-iodo-2-methylbenzoic acid. Iodine compounds are important compounds that are widely used as medicines such as contrast agents and therapeutic agents for thyroid diseases, hygienic materials for antifungal and antifungal purposes, electronic materials, optical functional materials, etchant, for life Catalysts and materials for chemical reactions in the fields of science, electro-, information-communication, environment and energy. And besides its use as pharmaceuticals and agricultural chemicals, high purity 5-iodo-2-methylbenzoic acid is a useful raw material for various performance chemicals.

related technology

Compounds containing fluorine or iodine atoms have characteristics not observed in other halogen-containing compounds. For example, fluorine atoms are small in size and high in electronegativity, and thus, the stability of the bonds and the resulting physiologically active performance make them useful in a variety of different fields, including medicine and electronic materials. In contrast, iodine atoms are large in size and amphoteric, and are believed to have multiple oxidation states. Compared with fluorine, chlorine and bromine, its oxidation potential is low, therefore, various reactivity and function correlations can be expected. In addition, iodine has low toxicity and, therefore, is widely used in many fields related to medicine, electronic communication, environment and energy.

Well-known iodination methods include, for example, direct iodination with iodine or iodine monochloride, vapor-phase oxygen iodination and halogen-iodine exchange of compounds with halogen atoms with iodides such as HI, KI or alkali metal iodides (K. Matsuoka, Elements of Iodine, Supplementary Revised Second Edition, 1992, published by Kasumigaseki Shuppan Co. Ltd.).

The direct iodination method described in the above-mentioned Elements of Iodine is, for example, a method in which a substrate is dissolved in sulfuric acid and iodine is added thereto; a substrate is dissolved in sulfuric acid and an alkali metal iodide and iodine are added thereto. methods of alkali metal iodates; and methods of iodination of aromatic rings using sulfur iodide and nitric acid. However, in the above methods, the selectivity and yield of the reaction are not satisfactory, and there is no description in Elements of Iodine that can be applicable to various substrates and effective iodination method.

As examples of the iodination of aromatic carboxylic acids, it includes the direct iodination of benzoic acid in sulfuric acid with iodine monochloride and silver sulfate (Synthesis, No.5, p.748, 1999); The method of using sulfuric acid and iodine monochloride to carry out the method of direct iodination of benzoic acid (Russian Journal of Org.Chem., 34 (7), 1988); and using manganese dioxide, potassium permanganate or nitric acid as oxidant and Iodine together in acetic acid (for iodination) method (method using MnO ₂ and KMnO ₄ : Bull.Chem.Soc.Japan, vol.72, p.115, 1999, method using HNO ₃ : Zh.Obsch. Khim. Obshchest, vol. 17, p. 464, ₁₉₇₂ and the method using _H2SO4 : J. Am. Chem. Soc., vol. 90, p. 6187, 1968).

However, among the above methods using sulfuric acid, the method of direct iodination of benzoic acid using iodine monochloride and silver sulfate has so many problems in practical use that the selectivity is low even when the reaction is carried out at a low temperature close to 0°C. Very low, the yield is only 57%, and besides, expensive silver sulfate has to be used.

Relatively inexpensive iodine monochloride is used in the direct iodination method using sulfuric acid and iodine monochloride, but the reaction yield is only about 43%. Besides that, in many cases, chlorine is generated in addition to iodine, and it is difficult to perform iodination reaction selectively.

Also, in the method of iodination in acetic acid using manganese dioxide, potassium permanganate or nitric acid as an oxidizing agent together with iodine, expensive silver sulfate is not used in acetic acid solvent, and the reaction can be carried out relatively easily, but Neither the selectivity nor the yield of the reaction may be satisfactory.

In order to make halogenation, especially of aromatic compounds, not limited to selective iodination, the use of zeolites has been proposed. Proposed, for example, is a method of using zeolite when chlorinating benzene and monochlorinated benzene with chlorine gas to produce p-dichlorobenzene (Japanese Patent Laid-Open No. 213815/2001), using zeolites Y and L to pass methane Vapor-phase oxygen chlorination generates the method of methyl chloride (Japanese Patent Publication No.227850/1992), and the method (Japanese Patent Publication No.253929/ 1992).

It has been observed in the above process that selectivity is improved by using zeolites, but not to a satisfactory degree. Besides, when the halogen atom is changed from chlorine to bromine, hardly the same selectivity can be expected. What currently exists does not provide a highly versatile selective halogenation technique. In addition, it has been proposed to improve the selectivity by using zeolite in the iodination reaction. Available, for example, is the reaction of toluene with iodine monochloride in the presence of zeolites (Catalysis Letters, vol. A method of naphthalene (Journal of Catalysis, vol.147, p.186, 1994), and a method of producing p-diiodobenzene from benzene or benzene iodide (Japanese Patent Laid-Open No. 219241/1984).

However, in the above method of reacting toluene and iodine monochloride in the presence of zeolite, since iodine monochloride is used in the reaction, the reaction product is a mixture of chloride and iodide, and the selectivity is not high. The method for generating naphthalene iodide by vapor-phase oxygen iodination of naphthalene and the method for generating p-diiodobenzene from benzene or iodized benzene are related to vapor-phase oxygen iodination, and the conversion rate is less than 50%.

In addition, methods for isomerizing aromatic iodine compounds using zeolites X, Y and L have also been proposed (Japanese Patent Nos. 2559483 and 2559484). The above method can obtain the target product, however, isomers different from the target product are abundant both in kind and amount, and they remain at a level where the selectivity is not very good.

Thus, it is well known that, in general processes, if zeolites are used in liquid-phase direct iodination, vapor-phase oxyiodination, and isomerization of aromatic iodides, the selectivity is relatively improved but hardly expected to be effective. methods for introducing iodine, and the existing situation is that no specific highly selective iodination method applicable to aromatic compounds having functional groups has been observed.

A first object of the present invention is to provide an iodination process which allows the desired iodination reaction to be carried out with high selectivity and efficiency and which is versatile enough to be carried out industrially.

Next, the known synthetic method of 5-iodo-2-methylbenzoic acid is a method of reacting iodine and 2-methylbenzoic acid in the presence of sodium nitrite and oleum (Journal of the Indian Chemical Society, p.503-504, 1930), and a method of reacting potassium iodide and 2-methylbenzoic acid in the presence of thallium (III) trifluoroacetate (Journal of the Chemical Society, Perkin Transactions I., p.2405-2409, 1974). However, the yield is as low as 18% in the former method, and the latter method has problems in that the yield is as low as 33% and besides, thallium salt which is very toxic is used. Neither of these methods is suitable for the industrial process of 5-iodo-2-methylbenzoic acid.

Considered suitable as a process for the preparation of 5-iodo-2-methylbenzoic acid, in addition to the above-mentioned methods, there is the so-called Sandmeyer method which is generally recognized as the iodination method of aromatic compounds and dediazotization of aromatic amines. reaction (Organic Syntheses, Collective Volume II, p.351, 1943), the method of carrying out iodine exchange reaction after carrying out chlorination or bromination (Organic Syntheses, Collective Volume V, p.478, 1973), and making iodine monochloride Method for carrying out the reaction (Russian Journal of Organic Chemistry, 34(7), p.997-999, 1998). Among these methods, the Sandmeyer and halogen exchange methods require multiple steps, and therefore, the process is complicated, causing them many problems as an industrial method. The process using iodine monochloride is expected to be a simple one-step reaction, but its reactivity with aromatic compounds with electron-withdrawing groups, such as benzoic acid, is low and is not expected to have high performance. For example, in the above-mentioned Russian Journal of Organic Chemistry, the iodination of benzoic acid was carried out, and the yield of 3-iodo-benzoic acid remained about 43%, so that, if applied to 2-methylbenzoic acid, it is expected that High yields could not be obtained.

During the preparation of 5-iodo-2-methylbenzoic acid, the by-product 3-iodo-2-methylbenzoic acid, an isomer, is difficult to separate from 5-iodo-2-methylbenzoic acid and be purified. Therefore, the problem involved therein is that the product purity and isolation yield are compromised, however, there is no way to reduce the amount of regioisomer by-products in any of the general methods shown above. A known method for regioselectively separating aromatic compounds is a method of reacting iodine monochloride in the presence of zeolite (Catalysis Letters, vol.40, p.257, 1996). methods of iodination (Japanese Patent Publication No. 219241/1984 and Japanese Patent Publication (by PCT) No. 502819/1989), however, none of them can keep the selectivity of the reaction at a satisfactory level, And there are almost no reaction examples of compounds containing electro-withdrawing groups such as 2-methylbenzoic acid.

The second object of the present invention is to provide a kind of industrial preparation method, by this method, by carrying out the selective iodination of 2-methylbenzoic acid to generate high-purity 5-iodo-2-methylbenzoic acid, can The product is readily obtained in high purity, and the process involved in this method is simple.

Contents of the invention

In order to solve the above problems, the inventors have carried out extensive and in-depth research and found that the appropriate use of specific oxoacids such as iodic acid and periodic acid as oxidants can be combined with porous materials with regular pore structures, such as microporous materials such as β-type zeolite etc., can selectively iodide not only aromatic hydrocarbons, but also various substrates such as halides and carboxylic acids. It is selectively carried out under the coexistence of iodine and iodic acid and/or periodic acid, and high purity 5-iodo-2-methanol can be easily obtained by combining simple purification steps such as crystallization by addition of water or cooling benzoic acid. Therefore, the inventors have completed the present invention.

That is, the present invention relates to a preparation method of an iodine compound and a preparation process of high-purity 5-iodo-2-methylbenzoic acid.

(1) A method for producing an iodine compound, wherein iodine reacts with a substrate in the presence of a porous material having a pore diameter of 500 nm or less, or in the presence of the aforementioned porous material and an oxidizing agent.

(2) The method for producing an iodine compound as described in the above item (1), wherein the porous material is a microporous material with a pore diameter of 0.5-2 nm.

(3) The production method of an iodine compound as described in the above item (1), wherein the porous material is zeolite beta or zeolite beta which may contain elements other than Si, Al and O constituting the framework.

(4) The method for producing an iodine compound as described in the above item (1), wherein the porous material is a mesoporous material with a pore diameter exceeding 2 nm.

(5) The preparation method of the iodine compound as described in the above item (1), wherein the oxidizing agent is at least one oxygen-containing compound selected from the group consisting of iodic acid, periodic acid, persulfuric acid, persulfate, nitric acid and molecular oxygen. Acidic compounds.

(6) The preparation method of the iodine compound as described in item (1) above, wherein said substrate is made of at least one selected from aromatic hydrocarbons, condensed polycyclic aromatic hydrocarbons, polycyclic aromatic hydrocarbons, containing by the following formula (1) Compound composition of heterocyclic hydrocarbons or their derivatives:

R-Ar-X (1)

(Wherein, R represents a hydrogen atom, a halogen atom, an alkyl group that may have a substituent, a cycloalkyl group or an aryl group; Ar represents an aromatic monocyclic ring, a polycyclic ring or a fused ring, or a polycyclic structure or a heterocyclic ring The aromatic group of the group; X represents a hydrogen atom, a halogen atom or is selected from carboxyl, formyl, hydroxyl, nitro, hydroxymethyl, cyano, amino, alkoxy, alkoxycarbonyl, acyl, acyloxy group, alkylsulfonyl and alkylsulfonyloxy functional groups; R and X may be the same or may exist in multiples).

(7) The preparation method of the iodine compound as described in the above item (6), wherein the substrate is composed of at least one compound selected from the group consisting of benzene, fluorobenzene, chlorobenzene, bromobenzene, benzonitrile, Phthalonitrile, isophthalonitrile, toluene, xylene, cumene, biphenyl, naphthalene, anthracene, methylnaphthalene, dimethylnaphthalene, methylbenzoic acid, dimethylbenzoic acid, biphenyl Formic acid, biphenyl dicarboxylic acid, naphthoic acid, and naphthalene dicarboxylic acid.

(8) The preparation method of the iodine compound as described in above-mentioned (2), wherein iodine and 2-methylbenzoic acid react under the existence of the microporous material of 0.5-2nm and iodic acid and/or periodic acid in aperture .

(9) The preparation process of high-purity 5-iodo-2-methylbenzoic acid is characterized in that it includes the step of carrying out iodination reaction by the method described in item (8) above, wherein by adding water or cooling and then A crystal precipitation and separation step in which the product is precipitated, and a purification step in which the separated crystals are recrystallized from an organic solvent.

(10) The preparation process of high-purity 5-iodo-2-methylbenzoic acid as described in item (9), wherein the solvent used for recrystallization is selected from acetic acid, acetic acid-water mixed solvent, 2-propanol and 2 -Any one of propanol-water mixed solvents.

(11) High-purity 5-iodo-2-methylbenzoic acid produced by the process as described in the above item (9), wherein the purity is 99% or more, and iodine, iodine contained as impurities The total amount of compounds, inorganic salts, and transition metal compounds is 500 ppm or less.

BEST MODE FOR CARRYING OUT THE INVENTION

First, the method for producing an iodine compound of the present invention is characterized in that iodine is reacted with a substrate in the presence of a porous material having a pore diameter of 500 nm or less, or in the presence of the aforementioned porous material and an oxidizing agent.

Aromatic hydrocarbons, fused polycyclic aromatic hydrocarbons, polycyclic aromatic hydrocarbons, hydrocarbons containing heterocycles represented by the following formula (1) or derivatives thereof are suitable as substrates in the method for preparing iodine compounds of the present invention:

R-Ar-X (1)

In formula (1), R represents a hydrogen atom, a halogen atom, an alkyl group which may have a substituent, a cycloalkyl group or an aryl group. The above-mentioned alkyl, cycloalkyl or aryl is a saturated, unsaturated, aliphatic or alicyclic alkyl group containing 1-32 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, butyl , pentyl, hexyl, heptyl, octyl, 2-ethylhexyl, decyl, cyclohexyl, bicyclohexyl, norbornyl and decalyl. They can carry functional groups such as halogen, hydroxyl, nitro, amino and sulfonyl. The halogen atom is fluorine, chlorine, bromine or iodine.

In formula (1), X represents a hydrogen atom, a halogen atom, carboxyl, hydroxyl, nitro, methylol, cyano, amino, alkoxy, alkoxycarbonyl, acyl, acyloxy, alkylsulfonyl or Alkylsulfonyloxy; R and X may be the same or there may be more than one.

Ar represents an aromatic monocyclic, polycyclic or condensed ring, or an aromatic group having a polycyclic structure or a heterocyclic group.

That is, aromatic compounds which may have substituents or hydrocarbons having a heterocycle, halogenated hydrocarbons, carboxylic acids, nitriles and alcohols correspond to the substrate represented by formula (1). More specifically, they include benzene, fluorobenzene, chlorobenzene, bromobenzene, benzonitrile, phthalonitrile, isophthalonitrile, toluene, xylene, cumene, biphenyl, naphthalene, anthracene, formazan Dimethylnaphthalene, Dimethylnaphthalene, Toluic Acid, Dimethylbenzoic Acid, Dibenzoic Acid, Biphenyldicarboxylic Acid, Naphthoic Acid, and Naphthalenedicarboxylic Acid.

Unsaturated double bonds may be contained in a part of the molecular structure of the substrate, as in cyclohexene and thiophene, and unsaturated triple bonds may be contained therein. Of course, the present invention will not be limited to the specific examples described above.

In the production method of the iodine compound of the present invention, a porous material having a pore diameter of 500 nm or less is used together with the substrate. Such porous materials are compounds having nanoscale pore diameters among microporous materials, mesoporous materials, and microporous materials each having a so-called regular pore structure.

Such structural materials include zeolites, which are hitherto known microporous materials. Specific examples thereof include, expressed in IUPAC codes, ABW, AEI, AFX, APC, ATN, ATT, ATV, AWW, CHA, DDR, EAB, ERI, GIS, JBW, KFI, LEV, each having an eight-membered ring structure, LTA, MER, MON, PAU, PHI, RHO, RTE, RTH, and VNI, CHI, LOV, RSN, and VSV each having a nine-membered ring structure, each having a ten-membered ring structure, DAC, EPI, FER, LAU, MEL, MFI, MFS, MTT, NES, TON and WEI, AFS, AFY, ATO, CAN, GME, MAZ, MEI, MTW, OFF, RON and VET each having a twelve-membered ring structure. More specifically, they include Chabazite, zeolites A, X, Y and L, mordenite, and zeolite beta. Compounds with a pore diameter of 0.5-2 nm are preferred, and beta-type zeolite is particularly preferred.

Preferred is zeolite beta in which the ratio of Si atoms to Al atoms constituting the framework is 5 or more, particularly preferred is zeolite beta in which the ratio is 10-30. Beta-type zeolite in which the ratio of Si atoms to Al atoms exceeds 30 can also be used without causing any problem. Also suitable are compounds in which the backbone atoms are replaced by other atoms, or into which other atoms other than the backbone atoms, such as Na, K, Cs, Ca, Mg, Ti, Compounds of Sn, Fe, Ni, Zn, Pd, Ag, etc.

Depending on the size of the substrate, it is preferred to use mesoporous materials with large pore diameters exceeding 2 nm. Examples thereof are, for example, mesoporous silica such as, FSM-16, KSW-1 and KSM-2, MCM-41, MCM-48 and MCM-50 commonly known as MS41S, mesoporous alumina, mesoporous titania and mesoporous organic silica mixture.

In the production method of the iodine compound of the present invention, an oxidizing agent is used in order to increase the reactivity of iodine. Preferred as oxidizing agents are iodic acid, periodic acid, nitric acid, persulfuric acid, persulfates such as sodium persulfate, potassium persulfate and ammonium persulfate, oxysalts containing hydrogen peroxide and molecular oxygen, particularly preferably iodine acid and periodic acid. The substrate is preferably iodized with a system containing zeolite beta and iodic acid or periodic acid selected from the above-mentioned compounds, and a system containing them and, if necessary, an inorganic acid such as sulfuric acid or nitric acid.

The iodination reaction can be performed by a batch system, a semi-batch system or a continuous system, and the reaction can be performed in a liquid phase or a gas phase system. However, the iodination of the various oxyiodinations is generally preferred to be carried out in the liquid phase in view of efficient use of the reactor.

The amount of iodine used in the iodination reaction is preferably 0.5 moles or more of iodine per mole of the target substrate, however, it may be used in a state of stoichiometric excess or less than stoichiometric.

Porous material with regular pore structure---microporous material and mesoporous material, such as zeolite, the amount is preferably in the range of 0.05-0.5 weight part per 1 weight part of substrate. However, if it is used in an amount of 0.5 parts by weight or more, no particular trouble will arise except for cost effectiveness.

The oxidizing agent is preferably used in an amount of 0.01-1 mole, particularly preferably 0.1-0.5 mole, based on the substrate. To increase the conversion of the substrates, mineral acids can be used in combination with iodic acid or periodic acid, preferably as oxidizing agent. If the usage-amount of an inorganic acid increases, the selectivity of reaction will fall, Therefore, it is not preferable to use it in excess. When an inorganic acid such as sulfuric acid or nitric acid is used in combination with iodic acid or periodic acid, the amount thereof is preferably 10% by weight or less based on the substrate, particularly preferably 1 to 2% by weight.

In order to accelerate the iodination reaction, it is not necessarily necessary to use a solvent, but it is preferable to use a solvent in order to improve reaction efficiency and stirring effect and to suppress a rise in temperature. Preferable solvents are aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, aromatic halogenated hydrocarbons, nitriles, ethers, carboxylic acids and water, and can be appropriately selected and used therefrom. When iodic or periodic acid is used as the oxidizing agent, a particularly preferred solvent is acetic acid. Usually, the amount of the solvent used is 2-10 times that of the substrate, but the amount of the solvent used may fall outside this range.

In the preparation method of the iodine compound of the present invention, raw materials such as a substrate, iodine and an oxidizing agent, and a zeolite catalyst which is a regular porous material can be added at one time to carry out the reaction. The raw materials such as substrate, iodine and oxidizing agent can be added separately or continuously. Usually, the reaction temperature is preferably 250°C or lower, particularly preferably 80 to 200°C in the case of a liquid phase reaction. In the case of gas phase reactions, 200-400° C. is preferred. After completion of the iodination reaction, common isolation and purification steps such as filtration, solvent removal and crystallization can be performed to obtain the expected pure product.

In the present invention, when 2-methylbenzoic acid is used as a substrate to prepare high-purity 5-iodo-2-methylbenzoic acid for use in medicines, electronic materials, functional materials, etc., by subjecting the iodination reaction to This can be effectively achieved by combining a step of precipitating the product by addition of water or cooling, and a purification step of recrystallization by water and an organic solvent such as 2-propanol.

For the raw material used as the preparation of 5-iodo-2-methylbenzoic acid --- the substrate 2-methylbenzoic acid will not be particularly limited, as long as it is industrially available, and, in order to improve the final product The purity of the compound is preferably 98% or higher.

The above-mentioned preparation method of iodine compound is used as the iodination reaction step for the preparation of high-purity 5-iodo-2-methylbenzoic acid, and the above-mentioned microporous material, especially β-type zeolite, is preferably used as the porous material.

In the iodination reaction of 2-methylbenzoic acid, in addition to the iodination in the presence of microporous materials, the reaction will also be carried out in the coexistence of iodic acid and/or periodic acid. The iodination reaction is only carried out with iodine, but due to the compounds with electron-withdrawing groups, such as the low reactivity of 2-methylbenzoic acid, it has to be improved by the coexistence of iodic acid and/or periodic acid. reactivity. In addition, the reactivity can be further enhanced by appropriately adding mineral acids such as sulfuric acid or nitric acid.

In the above-mentioned iodination reaction step, any one of iodine, iodic acid, and periodic acid is solid at room temperature, and they may be used in the reaction as they are in solid form, or they may be dissolved or suspended in a suitable solvent , and then use the .

In performing the iodination reaction, various systems such as a batch system, a semi-batch system, a fully mixed flow system and a fixed bed flow system can be used. The reaction system can be selected according to the production scale. In the case of small-scale production, the batch system is suitable. When carrying out large-scale production, it is more effective to use a completely mixed flow system to pour a fixed-bed fluid system to continuously react.

The reaction temperature of the iodination reaction of 2-methylbenzoic acid is in the range of 50-200°C, preferably 70-150°C. In addition, when the temperature is lower than the above range, the reaction proceeds, but a satisfactory reaction rate cannot be obtained. When the temperature is higher than the above range, side reactions such as generation of high-boiling point components increase, and therefore, this is not preferable. The reaction pressure (in terms of absolute pressure) is in the range of 0.05-20 atm, preferably 0.1-10 atm.

The melting point of 2-methylbenzoic acid is 105°C, and when the reaction is carried out at a temperature above this melting point, no reaction solvent is necessary. In general, it is preferred to use organic solvents which are inert to the iodination, acetic acid, trifluoroacetic acid, dichloromethane, carbon tetrachloride, dichlorobenzene and chlorobenzene (which can be) used. The solvent is used in an amount of preferably 0.5-100 parts by weight, more preferably 1-50 parts by weight, per part by weight of 2-methylbenzoic acid.

In the iodination reaction of 2-methylbenzoic acid, the amount of iodine will not be particularly limited, and in order to increase the conversion rate of 2-methylbenzoic acid, it is 0.5 mole or more per mole of 2-methylbenzoic acid, preferably 1 Moore or more. The amount of iodic acid and/or periodic acid used is preferably 0.01-1 mol, more preferably 0.05-0.5 mol, per mol of iodine.

The microporous material is used in an amount of 0.05 part by weight or more, preferably 0.1 part by weight or more, per 1 part by weight of 2-methylbenzoic acid as a substrate. If the amount of the microporous material is less than the above range, satisfactory reactivity cannot be obtained, and at the same time, 5-iodo-2-methylbenzoic acid cannot be obtained selectively. When the microporous material is suspended to carry out the reaction, the reaction mixture obtained after the reaction can be easily separated from the microporous material by common methods such as sedimentation, centrifugation, filtration and the like. The separated microporous material can be recycled to the reaction system, and in this case, it can be recycled after undergoing necessary treatment such as removal of attached organic substances by washing with an appropriate solvent or roasting in air.

After the iodination reaction of 2-methylbenzoic acid, adding mineral acid such as sulfuric acid to the above reaction system can further accelerate the reaction rate. In this case, the inorganic acid is suitably added in an amount of 0.005-0.05 parts by weight per 1 part by weight of 2-methylbenzoic acid. If the amount of the inorganic acid added is less than the above range, the effect of accelerating the reaction rate is less likely to be obtained. When it is larger than the above-mentioned range, by-products are likely to cause adverse effects on the expected selectivity of 5-iodo-2-methylbenzoic acid, which is not preferable.

In carrying out the iodination reaction of 2-methylbenzoic acid, adopt the reaction system such as batch system, semi-batch system and complete mixing flow system, the reaction time that usually adopts in batch system and semi-batch system is 1-20 hour, This is also the residence time employed in fully mixed flow systems, typically with an LHSV (Liquid Space Velocity) of 0.05-1 h ^-1 .

The preparation process of high-purity 5-iodo-2-methylbenzoic acid of the present invention comprises the above-mentioned iodination reaction step, wherein the crystal precipitation and separation step wherein the product is precipitated by adding water or cooling, and wherein the organic solvent is used to treat The isolated crystals are subjected to the separation and purification steps of recrystallization. That is, 5-iodo-2-methylbenzoic acid can be isolated by adding water to the reaction mixture after carrying out the reaction by the method or by cooling the reaction mixture, and by recrystallizing the separated crystals Purification is further performed to obtain highly pure 5-iodo-2-methylbenzoic acid.

In the crystal recovery step, 5-iodo-2-methylbenzoic acid is precipitated by adding 1 to 10 parts by weight of water per part by weight of the reaction mixture, and recovered by filtration. When water is added, iodine precipitates out and in some cases mixes with 5-iodo-2-methylbenzoic acid, which can be prevented by adding sodium sulfite or sodium thiosulfate to the reaction mixture in advance come out. Sodium sulfite or sodium thiosulfate is added in an amount of 0.05 part or less per 1 part by weight of iodine used in the reaction. In addition to the method of adding water, recovery of the crystals can be achieved by cooling the reaction mixture to a temperature of 90°C or lower. After cooling to 90°C or lower, the precipitated crystals were recovered by filtration.

The recovered crystals are purified by recrystallization from an organic solvent. The organic solvent used for recrystallization may be any solvent as long as it can dissolve 5-iodo-2-methylbenzoic acid. Acetic acid, acetic acid-water mixed solvent, 2-propanol and 2-propanol-water mixed solvent are suitably used. The solvent is used in an appropriate amount of 1-30 parts by weight, preferably 5-20 parts by weight, per 1 part by weight of recovered crystals. The crystallization operation is performed by heating the recovered crystals with a solvent at a temperature of 40° C. or higher and mixing them until they are completely dissolved, after which the solution is cooled to precipitate crystals. The cooling temperature is set at a temperature 20° C. or more lower than the temperature at which the crystals are completely dissolved when heated and mixed. Precipitated crystals were recovered by filtration and dried to obtain the product.

The 5-iodo-2-methylbenzoic acid obtained by the above process can have a very high purity, that is, a purity of 99% or higher, and iodine, iodine compounds, inorganic salts, and transition metal compounds contained in the form of impurities The total amount is 500ppm or less.

In the preparation method of the iodine compound of the present invention, iodine can be introduced into various substrates with high selectivity, and in the case of substrates other than 2-methylbenzoic acid, it can be obtained by almost the same operation containing Iodine compounds with less impurities.

Next, the present invention will be described in more detail through examples. However, the following examples shall not limit the present invention in any way.

A. Iodination of Aromatic Carboxylic Acids

Example 1: 2-methylbenzoic acid

Add acetic acid (100 grams), H-beta zeolite (4.6 grams), iodine (20.2 grams, 0.16 moles), 2-methylbenzoic acid (20 grams , 0.15 mol), periodate dihydrate (7.3 g, 0.03 mol) and sulfuric acid (0.24 g), which were mixed well and stirred at room temperature. The temperature of the mixture was raised to 110°C in a heating mantle, after which the reaction was carried out for 1 hour. Then, the reaction was carried out at the reflux temperature of acetic acid (about 118° C.) for 5 hours.

After the reaction, the reaction mixture was filtered to recover the H-beta zeolite, and 10% by weight aqueous sodium sulfite (100 ml) was added to the filtrate to treat the remaining iodine. Next, water (800 g) was added thereto to precipitate crystals, which were then filtered and recovered.

The crystals and filtrate thus obtained were analyzed by HPLC (High Pressure Liquid Chromatography) to study the improvement of properties, and it was found that the conversion rate of 2-methylbenzoic acid was 88%, for the product of 5-iodo-2-methylbenzoic acid The yield was 72%, 6% for 3-iodo-2-methylbenzoic acid; the ratio of (5-iodo/3-iodo) regioisomer was 12.

Comparative Example 1: 2-Methylbenzoic acid: case where H-β zeolite is not used

The same method as in Example 1 was carried out except that H-beta zeolite was not used therein. 98% conversion of 2-methylbenzoic acid, 66% product yield for 5-iodo-2-methylbenzoic acid, 25% product yield for 3-iodo-2-methylbenzoic acid ; (5-iodo/3-iodo) regioisomer ratio 2.6.

Example 2: 3-methylbenzoic acid

The same method as in Example 1 was carried out except that 3-methylbenzoic acid (20 g, 0.15 mol) was used as a reactant. 50% conversion of 3-methylbenzoic acid, 40% yield for 6-iodo-3-methylbenzoic acid 1) and 8% yield for other iodide regioisomers 2); The ratio of 1)/2) is 5.

Comparative Example 2: 3-Methylbenzoic acid: case where H-β zeolite is not used

The same method as in Example 2 was carried out except that H-beta zeolite was not used therein. 56% conversion of 3-methylbenzoic acid, 33% yield for 6-iodo-3-methylbenzoic acid 1) and 16% yield for the other iodide regioisomer 2); The ratio of 1)/2) is 2.1.

Example 3: 2,4-dimethylbenzoic acid

The same method as in Example 1 was carried out except that 2,4-dimethylbenzoic acid (22.5 g, 0.15 mol) was used as a reactant. 98% conversion of 2,4-dimethylbenzoic acid, 88% yield for 5-iodo-2,4-dimethylbenzoic acid 1) and 2) for other iodide regioisomers The yield was 7%. The ratio of 1)/2) is 12.6.

Comparative Example 3: 2,4-dimethylbenzoic acid: case where H-β zeolite is not used

The same method as in Example 3 was carried out except that H-beta zeolite was not used therein. 96% conversion of 2,4-dimethylbenzoic acid, 81% yield for 5-iodo-2,4-dimethylbenzoic acid 1) and 81% for other iodide regioisomers 2) The yield was 8%; the ratio 1)/2) was 10.

B. Iodination of aromatic hydrocarbons

Embodiment 4: Toluene

The same method as in Example 1 was carried out except that toluene (13.8 g, 0.15 mol) was used as a reactant. The conversion of toluene was 98%, the yield was 82% for 4-iodo-toluene 1) and 9% for the other iodide regioisomer 2); the ratio 1)/2) was 9.1.

Comparative Example 4: Toluene: case where H-β zeolite is not used

The same method as in Example 4 was carried out except that H-beta zeolite was not used therein. The conversion of toluene was 100%, the yield was 56% for 4-iodo-toluene 1) and 39% for the other iodide regioisomer 2); the ratio 1)/2) was 1.4.

Embodiment 5: o-xylene

The same method as in Example 1 was carried out except that o-xylene (15.9 g, 0.15 mol) was used as a reactant. 99% conversion of o-xylene, 92% yield for 4-iodo-1,2-dimethylbenzene 1) and 6% yield for the other iodide regioisomer 2);1 )/2) ratio is 15.

Comparative Example 5: o-xylene: case where H-β zeolite is not used

The same method as in Example 5 was carried out except that H-beta zeolite was not used therein. 100% conversion of o-xylene, 78% yield for 4-iodo-1,2-dimethylbenzene 1) and 16% yield for the other iodide regioisomer 2);1 )/2) ratio is 4.9.

Embodiment 6: Biphenyl

The same method as in Example 1 was carried out except that biphenyl (23.1 g, 0.15 mol) was used as a reactant. The conversion of biphenyl was 99%, the yield was 92% for 4-iodo-biphenyl 1) and 5% for the other iodide regioisomer 2); the ratio of 1)/2) was 18.4.

C. Iodination of Halogenated Aromatic Hydrocarbons

Embodiment 7: Fluorobenzene

The same method as in Example 1 was carried out except that fluorobenzene (14.4 g, 0.15 mol) was used as a reactant. The conversion of fluorobenzene was 65%, the yield for 4-iodo-fluorobenzene 1) was 52%, and the yield for other iodide regioisomer 2) was 3%; the ratio of 1)/2) was 17.3.

Comparative Example 6: Fluorobenzene: case where H-β zeolite is not used

The same method as in Example 7 was carried out except that H-beta zeolite was not used therein. The conversion of fluorobenzene was 63%, the yield for 4-iodo-fluorobenzene 1) was 42%, and the yield for the other iodide regioisomer 2) was 6%; the ratio of 1)/2) was 7.

D. Iodination of nitriles

Example 8: 2-methylbenzene cyanide

The same method as in Example 1 was carried out except that 2-methylbenzene cyanide (15.5 g, 0.15 mol) was used as a reactant. 82% conversion of 2-methylbenzenecyanide, 69% yield for 5-iodo-2-methylbenzenecyanide 1) and 6% yield for the other iodide regioisomer 2) %; the ratio of 1)/2) is 11.5.

Comparative Example 7: 2-methylbenzene cyanide: the case where H-β zeolite is not used

The same method as in Example 8 was carried out except that H-beta zeolite was not used therein. 92% conversion of 2-methylbenzene cyanide, 61% yield for 5-iodo-2-methylbenzene cyanide 1) and 24% yield for the other iodide regioisomer 2) %; the ratio of 1)/2) is 2.5.

E. Iodination Using Oxidizing Agents Other Than Periodic Acid

Example 9: Oxidation with iodic acid

The same method as in Example 1 was carried out, except that iodic acid (5.3 g, 0.03 mol) was used instead of periodic acid as the oxidizing agent. The conversion of 2-methylbenzoic acid was 78%, the yield for 5-iodo-2-methylbenzoic acid 1) was 69%, and the yield for other iodide regioisomers 2) was 3%; The ratio of 1)/2) is 23.

Comparative Example 8: Oxidation with iodic acid: Case without using H-β zeolite

The same method as in Example 9 was carried out except that H-beta zeolite was not used therein. 79% conversion of 2-methylbenzoic acid, 53% yield for 5-iodo-2-methylbenzoic acid 1) and 23% yield for the other iodide regioisomer 2); The ratio of 1)/2) is 2.3.

Example 10: Oxidation with sodium persulfate

Using the same equipment as Example 1, and adding acetic acid (90 g), water (10 g), H-beta zeolite (2.3 g), iodine (10.3 g, 0.08 mol), 2-methylbenzoic acid (10 g , 0.074 mol), sodium persulfate (11.8 g, 0.05 mol) and sulfuric acid (0.12 g). After they were well mixed and stirred at room temperature, the temperature of the mixture was raised to 90° C., and then the reaction was performed for 5 hours. In addition, the reaction was further performed at 110° C. for 8 hours, after which the reaction was terminated. The H-beta zeolite was isolated by filtration and the remaining iodine was treated with 10% by weight aqueous sodium sulfite. Next, 800 ml of water was added thereto, and the precipitated crystals were filtered.

The conversion of 2-methylbenzoic acid was 86%, the yield for 5-iodo-2-methylbenzoic acid 1) was 64%, and the yield for 3-iodo-2-methylbenzoic acid 2) was 12%; the ratio 1)/2) is 5.3.

F. Iodination when using zeolites other than H-beta zeolite

Examples 11-14

The same method as in Example 1 was carried out except that mordenite, Y, L and ZSM-5, which are porous materials, were used therein instead of H-beta zeolite. When the corresponding zeolites are used, the ratio of the (5-iodine/3-iodine) regioisomers is shown below.

Mordenite (Example 11) 5.0

Zeolite Y (Example 12) 4.8

Zeolite L (Example 13) 5.2

ZSM-5 (Example 14) 4.0

In the case of the H-beta zeolite (Example 1), the ratio of the (5-iodine/3-iodine) regioisomer was 12, when no zeolite was used (Comparative Example 1), the ratio was 2.6. It was found that the selectivity is also high when zeolites other than H-beta are used.

G. Preparation of highly pure 5-iodo-2-methylbenzoic acid

Example 15

Implement the same method as in Example 1, except that sulfuric acid is not used therein; replace periodic acid with 8.8 grams of iodic acid; and the reaction is carried out for 3 hours at the reflux temperature (115° C.) of acetic acid, and the results are as follows :

The conversion rate of 2-methylbenzoic acid is 70%

The yield of 5-iodo-2-methylbenzoic acid is 65%

The yield of 3-iodo-2-methylbenzoic acid 2%

(5-iodo/3-iodo) regioisomer ratio 33

The purity of 5-iodo-2-methylbenzoic acid crystals is 97%

By recrystallizing the above-mentioned 5-iodo-2-methylbenzoic acid crystals with a purity of 97% in a solvent of water:2-propanol=1:1 (weight ratio), 5-iodo with a purity of 99% or higher is obtained -2-Methylbenzoic acid.

The above recrystallized 5-iodo-2-methylbenzoic acid product contained 4 ppm free iodine. ICP full-element analysis of this crystal showed that no Li, Na, K, Mg, Ca, Sr, Ba, Sc, Y, Ti, Zr, V, Nb, Cr, Mo, W, Mn, Fe, Ru, Co, Rh, Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, Al, In, Si, Sn, Pb, P, Sb, and S, and all groups 1 and 2 of the periodic table The contents of group elements are all 1 ppm or less.

Example 16

Add 50 grams of acetic acid, 10 grams of 2-methylbenzoic acid, 10.4 grams of iodine, 3.7 grams of periodic acid, 2.2 grams of H-beta zeolite, and 0.12 grams of sulfuric acid in a 100 milliliter three-necked flask equipped with a reflux condenser, and These were reacted at the reflux temperature (115° C.) of acetic acid for 6 hours. After the reaction, H-beta zeolite was separated by filtration, 20 g of 10% by weight sodium sulfite aqueous solution and 250 ml of water were added to the filtrate and cooled to room temperature. The precipitated crystals were recovered by filtration to obtain 15 g (weight after drying) of the product. The recovered crystals and mother liquor were analyzed by HPLC (High Pressure Liquid Chromatography) for evaluation and the results were as follows:

Conversion rate of 2-methylbenzoic acid 85%

The yield of 5-iodo-2-methylbenzoic acid 70%

The yield of 3-iodo-2-methylbenzoic acid 7%

(5-iodo/3-iodo) regioisomer ratio 10

The purity of 5-iodo-2-methylbenzoic acid crystals is 95%

Example 17

13 g of the recovered product were obtained in the same manner as in Example 16, except that 4.3 g of iodic acid was used instead of periodic acid. As a result of the analysis, the following data were obtained:

The conversion rate of 2-methylbenzoic acid is 80%

The yield of 5-iodo-2-methylbenzoic acid 72%

The yield of 3-iodo-2-methylbenzoic acid 3%

(5-iodo/3-iodo) regioisomer ratio 24

The purity of 5-iodo-2-methylbenzoic acid crystals is 95%

Embodiment 18: cooling crystallization

The reaction was carried out under the same conditions as in Example 16, except that the amount of acetic acid added was 40 g, and the filtrate was cooled to room temperature after the H-beta zeolite was separated. Precipitated crystals were recovered by filtration to obtain 10 g of product. As a result of the analysis, the following data were obtained:

Conversion rate of 2-methylbenzoic acid 88%

The yield of 5-iodo-2-methylbenzoic acid 72%

The yield of 3-iodo-2-methylbenzoic acid 8%

(5-iodo/3-iodo) regioisomer ratio 9

The purity of 5-iodo-2-methylbenzoic acid crystals is 95%

Comparative example 9: iodine monochloride (IC1 method)

25 ml of 30% by weight sulfuric acid and 1.36 g (10 mmol) of 2-methylbenzoic acid were suspended in a 100 ml three-necked flask equipped with a reflux condenser, and 2.4 g (15 mmol) of 2-methylbenzoic acid were added dropwise within 40 minutes. ) iodine monochloride dissolved in 5 g of acetic acid. The reaction was carried out at 90°C for 5 hours, and the reaction mixture was poured into 90 ml of water. The precipitate was filtered and washed with aqueous sodium sulfite to give a crystalline solid product (yield: 1.6 g). The solid was analyzed and the product was found to have the following distribution:

2-Methylbenzoic acid 33%

5-Chloro-2-methylbenzoic acid 13%

3-Chloro-2-methylbenzoic acid 9%

5-iodo-2-methylbenzoic acid 38%

3-iodo-2-methylbenzoic acid 5%

Other 2%

The above mixture was purified by recrystallization from acetic acid or isopropanol in an attempt to isolate 5-iodo-2-methylbenzoic acid. However, there was little improvement in the purity of the mixture, and it was difficult to obtain 5-iodo-2-methylbenzoic acid.

Comparative example 10 (NaI-NaIO ₄ /sulfuric acid method)

Using the same equipment as in Example 16, 1.36 g of 2-methylbenzoic acid was dissolved in 9 ml of acetic acid. The temperature of the mixture was kept at 85°C, and 11 ml of concentrated sulfuric acid was added dropwise thereto over 25 minutes. Further, 0.6 g of sodium periodate was added thereto, and then a solution obtained by dissolving 1.1 g of sodium iodide in 5 ml of acetic acid was added dropwise thereto over 10 minutes. Thereafter, the reaction was carried out for 2 hours, and after cooling, the reaction mixture was poured into 90 ml of water, and the resulting cloudy mixture was filtered. 1 g of sodium sulfite was added thereto to remove unreacted iodine. After drying, the product obtained above was analyzed to give the following data:

2-Methylbenzoic acid 35%

5-iodo-2-methylbenzoic acid 37%

3-iodo-2-methylbenzoic acid 18%

Other 5%

An attempt was made to obtain 5-iodo-2-methylbenzoic acid from the above mixture as in Example 11, but the purity was hardly improved and 5-iodo-2-methylbenzoic acid was not obtained.

Comparative example 11 (no zeolite)

The reaction was carried out in the same manner as in Example 16 to obtain 15 g of product, except that H-beta zeolite was not used. As a result of the analysis, the following data were obtained:

Conversion rate of 2-methylbenzoic acid 85%

The yield of 5-iodo-2-methylbenzoic acid 56%

The yield of 3-iodo-2-methylbenzoic acid 20%

(5-iodo/3-iodo) regioisomer ratio 2.8

The purity of 5-iodo-2-methylbenzoic acid crystals is 80%

Comparative example 12 (no oxidizing agent)

The reaction was carried out in the same manner as in Example 16 to obtain 0.8 g of product, except that periodic acid was not used. As a result of the analysis, the following data were obtained:

Conversion rate of 2-methylbenzoic acid 5%

The yield of 5-iodo-2-methylbenzoic acid 3%

Yield of 3-iodo-2-methylbenzoic acid 0.9%

(5-iodo/3-iodo) regioisomer ratio 3.3

The purity of 5-iodo-2-methylbenzoic acid crystals is 75%

Example 19: Crystal Purification/Water-IPA

The 15 grams of 5-iodo-2-methylbenzoic acid crystals obtained in Example 16 with a purity of 95% were dissolved in 210 grams of water at 70° C.: in a solvent of 2-propanol=1: 1 (weight ratio), The solution was kept overnight at room temperature. 10 g of precipitated crystals were recovered by filtration and analyzed by HPLC to find that the purity of 5-iodo-2-methylbenzoic acid was 99%.

1 g of crystals obtained above with a purity of 99% was dissolved in 25 ml of methanol, and 25 ml of 4% KI aqueous solution and 5 ml of 17% sulfuric acid were added thereto. Then, the solution was titrated with a 0.02M aqueous solution of sodium thiosulfate to find that it contained 5 ppm of free iodine. According to ICP full elemental analysis, Li, Na, K, Mg, Ca, Sr, Ba, Sc, Y, Ti, Zr, V, Nb, Cr, Mo, W, Mn, Fe, Ru, Co, Rh were not detected , Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, Al, In, Si, Sn, Pb, P, Sb and S, and the content of all elements of Group 1 and Group 2 of the periodic table is 1ppm or below.

Example 20: Crystal Purification/Acetic Acid

10 g of 5-iodo-2-methylbenzoic acid crystals with a purity of 95% obtained in Example 18 were dissolved in 210 g of acetic acid at 70° C., and the solution was kept at room temperature overnight. 6 g of precipitated crystals were recovered by filtration and analyzed by HPLC to find that the purity of 5-iodo-2-methylbenzoic acid was 99%.

One gram of crystals obtained above with a purity of 99% was analyzed in the same manner as in Example 19, and it was found that 10 ppm of free iodine was contained therein. According to ICP full elemental analysis, Li, Na, K, Mg, Ca, Sr, Ba, Sc, Y, Ti, Zr, V, Nb, Cr, Mo, W, Mn, Fe, Ru, Co, Rh were not detected , Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, Al, In, Si, Sn, Pb, P, Sb and S, and the content of all elements of Group 1 and Group 2 of the periodic table is 1ppm or below.

Industrial Applicability

According to the preparation method of the iodine compound of the present invention, iodine can be introduced into various substrates with high selectivity. Since it is unnecessary to use noble metals and special reagents, this reaction can be easily carried out on an industrial scale, and high-purity products can be obtained.

Furthermore, the process of the present invention including iodination reaction, separation and purification steps makes it possible to easily obtain high-purity 5-iodo-2-methylbenzoic acid in high yield, which can be used in functional chemical products such as pharmaceuticals. The steps including iodination reaction, separation and purification are characterized in that they are simple in process, have a small purification load, and are very advantageous for industrial implementation.

Claims (11)

1. the preparation method of an iodine compound, wherein iodine and substrate the aperture be 500nm or following porous material in the presence of, or in the presence of above-mentioned porous material and oxygenant, react.

2. the preparation method of iodine compound as claimed in claim 1, wherein said porous material is that the aperture is the poromerics of 0.5-2nm.

3. the preparation method of iodine compound as claimed in claim 1, wherein said porous material is the zeolite beta that zeolite beta maybe can comprise the element that is different from the Si, the Al that form skeleton and O.

4. the preparation method of iodine compound as claimed in claim 1, wherein said porous material is the mesopore material that the aperture surpasses 2nm.

5. the preparation method of iodine compound as claimed in claim 1, wherein said oxygenant is at least a compound that is selected from the oxygen acid of being made up of acid iodide, Periodic acid, persulfuric acid, persulphate, nitric acid and molecular oxygen.

6. the preparation method of iodine compound as claimed in claim 1, wherein said substrate is by at least aly being selected from aromatic hydrocarbons, fused polycycle aromatic hydrocarbons, polycyclic aromatic hydrocarbons, containing by the compound of the heterocyclic hydrocarbon or derivatives thereof of following formula (1) expression and form:

R-Ar-X (1)

Wherein, R represents hydrogen atom, and halogen atom can have substituent alkyl, cycloalkyl or aryl; Ar represents aromatic monocyclic, encircles or fused rings more, or has the aromatic group of polynuclear plane or heterocyclic group; X represents hydrogen atom, halogen atom or be selected from the functional group of carboxyl, formyl radical, hydroxyl, nitro, methylol, cyano group, amino, alkoxyl group, alkoxy carbonyl, acyl group, acyloxy, alkyl sulphonyl and alkylsulfonyloxy; R and X can be identical or can exist a plurality of.

7. the preparation method of iodine compound as claimed in claim 6, wherein said substrate is made up of at least a compound that is selected from the following stated: benzene, fluorobenzene, chlorobenzene, bromobenzene, benzonitrile, phthalonitrile, Isophthalodinitrile, toluene, dimethylbenzene, isopropyl benzene, biphenyl, naphthalene, anthracene, methylnaphthalene, dimethylnaphthalene, tolyl acid, mesitylenic acid, diphenic acid, biphenyl dicarboxylic acid, naphthoic acid, and naphthalic acid.

8. the preparation method of iodine compound as claimed in claim 2, wherein iodine and 2-tolyl acid the aperture be the poromerics of 0.5-2nm and acid iodide and/or Periodic acid in the presence of react.

9. the preparation technology of high purity 5-iodo-2-tolyl acid, it is characterized in that comprising, carry out the step of iodination reaction by the described method of claim 8, wherein by adding entry or cool off and then separate crystal settling and the separating step that product is precipitated out, and the purification step that wherein with organic solvent isolated crystal is carried out recrystallization.

10. the preparation technology of high purity 5-iodo-2-tolyl acid as claimed in claim 9, the solvent that wherein is used for recrystallization is selected from any of acetate, acetate-water mixed solvent, 2-propyl alcohol and 2-propyl alcohol-water mixed solvent.

11. high purity 5-iodo-2-tolyl acid by prepared as claimed in claim 9, wherein said purity is 99% or higher, and the total amount of iodine, iodine compound, inorganic salt and transistion metal compound in being included in the impurity form is 500ppm or lower.