JP5598533B2 - Process for producing iodinated aromatic compounds - Google Patents

Description

  The present invention relates to a method for producing an iodinated aromatic compound useful as an intermediate of an organic synthetic compound and a material for organic electroluminescence.

  An iodinated aromatic compound in which an iodine atom is bonded to an aromatic compound has a wide demand as an important intermediate in the production of organic photoreceptors, dyes, agricultural chemicals, pharmaceuticals and the like used for materials for organic electroluminescence.

  In general, an iodinated aromatic compound can be directly iodinated from an aromatic compound or a corresponding aromatic amino compound can be synthesized by a Sandmeyer reaction. In the method of directly iodizing an aromatic compound, an oxidizing agent and an acid catalyst are used when the aromatic compound and the iodine compound are reacted. As an oxidizing agent to be used, a method using peracetic acid (see Non-Patent Document 1), a method using iodic acid (see Non-Patent Document 2), a method using periodic acid (see Non-Patent Document 3), and the like are known. However, these oxidizing agents are expensive and require treatment of the waste liquid, which is industrially expensive and economically disadvantageous. In addition, reactions using persulfate (see Patent Document 1) and hydrogen peroxide (see Patent Document 2) have also been reported, but these oxidants require attention in handling and yield of the reaction. Is also low. In the case of the Sandmeyer reaction (see Non-Patent Document 4), the number of stages of the reaction is large, the post-treatment after the reaction is complicated, and the efficiency is poor as an industrial production method.

  As another synthesis method of an iodinated aromatic compound, a halogen exchange reaction is known in which a chlorine atom of a chlorinated aromatic compound or a bromine atom of a brominated aromatic compound is exchanged for an iodine atom. For example, there are known methods of halogen exchange using sodium iodide, copper iodide and diamine (ligand) in an alcohol solvent or dioxane (see Non-Patent Documents 4, 5, and Patent Document 3). The cost is high because an expensive ligand is required, and the purification operation is not easy, so that it is not an industrially satisfactory method. Similarly, as a system in which a ligand is not added in a reaction using a copper catalyst, a method of performing halogen exchange using potassium iodide and copper iodide in hexamethylphosphoric triamide (see Non-Patent Document 6) has also been reported. However, hexamethylphosphoric triamide as a reaction solvent has a very high carcinogenicity and is harmful to the human body, and therefore has a problem as an industrial production method.

  Furthermore, when the substrate is sterically bulky, for example, when it has a structure such as the following general formula [4] according to the present invention, the reaction rate of the halogen exchange reaction is very slow. In particular, in a reaction in which a chlorine atom or a bromine atom substituted on the adjacent carbon of the condensed ring is exchanged for iodine as in the compound represented by the following general formula [5] according to the present invention, the reaction point is Since it is sterically crowded, the reactivity is low and the reaction hardly proceeds. In addition, in order to increase the reaction rate, the halogen exchange reaction may proceed by increasing the temperature or increasing the amount of the catalyst. It was very difficult to obtain a fluorinated aromatic compound in a high yield, and there was no satisfactory industrial production method.

Japanese Patent Laid-Open No. 49-14527 JP-A-63-91336 US Patent 6888032

Journal of American Chemical Society, 1968, 90, p6187 Liebigs Analen, 1960, 634, p84 Organic Synthesis, Collective Vol. VI, 1988, p700 Organic Synthesis, Collective Vol. II, 1943, p351 Journal of American Chemical Society, 2002, 124, p14844 Chemistry Letters, 1985, p411

  The present invention has been made in view of the above problems, and an object of the present invention is to produce an iodinated aromatic compound efficiently and safely without using a ligand and without using a solvent harmful to the human body. It is to provide a method that can. Furthermore, even when the substrate has a sterically bulky structure such as a condensed ring structure, it is an object of the present invention to provide a production method capable of suppressing the side reaction and obtaining the target iodinated aromatic compound in a high yield.

  The above object of the present invention can be achieved by the following constitution.

  1. A compound represented by the following general formula [1] and an alkali metal iodide salt are reacted in the presence of copper or a copper ion and a compound represented by the following general formula [2]. Compound production method.

(In the formula, Ar represents an aromatic hydrocarbon ring group or an aromatic heterocyclic group, X represents a chlorine atom or a bromine atom, and n represents an integer of 1 or more. R ₁ , R ₂ , R ₃ and R ₄ each independently represents an alkyl group or an aryl group, and R ₁ and R ₃ , R ₂ and R _4, and R ₃ and R ₄ may be bonded to each other to form a ring.
2. 2. The method for producing an iodinated aromatic compound according to the item 1, wherein the general formula [2] is represented by the following general formula [3].

(In the formula, R ₁ and R ₂ each independently represents an alkyl group or an aryl group.)
3. 3. The method for producing an iodinated aromatic compound according to 1 or 2, wherein the general formula [1] is represented by the following general formula [4].

(In the formula, X represents a chlorine atom or a bromine atom, Y represents an oxygen atom, a sulfur atom or N—R ₅ , R ₅ represents an alkyl group or an aryl group, W represents a substituent, m and n Represents an integer of 1 to 4.)
4). 4. The method for producing an iodinated aromatic compound according to 3 above, wherein the general formula [4] is represented by the following general formula [5].

(In the formula, X represents a chlorine atom or a bromine atom, Y represents an oxygen atom, a sulfur atom or N—R ₅ , R ₅ represents an alkyl group or an aryl group, W represents a substituent, and m represents 1) Represents an integer from 4 to 4.)
5. 5. The method for producing an iodinated aromatic compound as described in 4 above, wherein in the general formula [5], Y is an oxygen atom.

  ADVANTAGE OF THE INVENTION According to this invention, a ligand is unnecessary and the method which can manufacture an iodinated aromatic compound efficiently and safely can be provided, without using a solvent harmful | toxic to a human body. Furthermore, even when the substrate has a three-dimensionally bulky structure such as a condensed ring structure, it is possible to provide a production method in which side reactions are suppressed and the target iodinated aromatic compound can be obtained in high yield.

  The production method of an iodinated aromatic compound useful as an intermediate of an organic synthetic compound and a material for organic electroluminescence is a method of the present invention, which suppresses side reactions without using a solvent harmful to the human body, The aromatic compound is obtained in high yield and has an excellent effect.

  Hereinafter, although the form for implementing this invention is demonstrated, this invention is not limited to these.

  Hereinafter, the present invention will be described in more detail.

  In the general formula [1], Ar represents an aromatic hydrocarbon ring group or an aromatic heterocyclic group.

  Examples of the aromatic hydrocarbon ring group include benzene ring group, biphenyl ring group, naphthalene ring group, azulene ring group, anthracene ring group, phenanthrene ring group, pyrene ring group, chrysene ring group, naphthacene ring group, and triphenylene ring. Group, o-terphenyl ring group, m-terphenyl ring group, p-terphenyl ring group, acenaphthene ring group, coronene ring group, fluorene ring group, fluoranthrene ring group, pentacene ring group, perylene ring group, pentaphen Examples thereof include a ring group, a picene ring group, a pyranthrene ring group, an anthraanthrene ring group, a dibenzofuran ring group, a dibenzodiophene ring group, and a carbazole ring group.

  Examples of the aromatic heterocyclic group include a furan ring group, a thiophene ring group, a pyridine ring group, a pyridazine ring group, a pyrimidine ring group, a pyrazine ring group, a triazine ring group, an oxadiazole ring group, a triazole ring group, and an imidazole. Ring group, pyrazole ring group, thiazole ring group, indole ring group, benzimidazole ring group, benzothiazole ring group, benzoxazole ring group, quinoxaline ring group, quinazoline ring group, phthalazine ring group, benzofuran ring group, dibenzofuran ring group, Examples include a benzothiophene ring group, a dibenzothiophene ring group, and a carbazole ring group.

  These rings may have a substituent, and specific examples of the substituent include alkyl groups having 1 to 25 carbon atoms (methyl group, ethyl group, propyl group, isopropyl group, tert-butyl group, pentyl group). Hexyl group, octyl group, decyl group, dodecyl group, octadecyl group etc.), cycloalkyl group (cyclohexyl group, cyclopentyl group etc.), aryl group (phenyl group etc.), heteroaryl group (pyridyl group, thiazolyl group, oxazolyl group) Imidazolyl group, furyl group, pyrrolyl group, etc.), halogen atom (chlorine atom, bromine atom, iodine atom, fluorine atom etc.), alkoxy group (methoxy group, ethoxy group, propyloxy group etc.), aryloxy group (phenoxy group) Etc.), alkoxycarbonyl group (methyloxycarbonyl group, ethyloxycarbonyl group etc.), sulfo Namide group (methanesulfonamide group, ethanesulfonamide group, butanesulfonamide group, hexanesulfonamide group, cyclohexanesulfonamide group, benzenesulfonamide group, etc.), sulfamoyl group (aminosulfonyl group, methylaminosulfonyl group, dimethylaminosulfonyl group) Group, butylaminosulfonyl group, hexylaminosulfonyl group, cyclohexylaminosulfonyl group, phenylaminosulfonyl group, 2-pyridylaminosulfonyl group, etc.), carbamoyl group (aminocarbonyl group, methylaminocarbonyl group, dimethylaminocarbonyl group, propylaminocarbonyl) Group), amide group (acetamide group, propionamide group, benzamide group, etc.), sulfonyl group (methylsulfonyl group, ethylsulfonyl group, phenyl) Sulfonyl group, etc.), amino group (amino group, ethylamino group, dimethylamino group, etc.), a cyano group, a carboxyl group, and a hydroxyl group.

  Preferred as the aromatic hydrocarbon ring group and aromatic heterocyclic group represented by Ar are benzene ring group, naphthalene ring group, azulene ring group, anthracene ring group, phenanthrene ring group, benzothiazole ring group, benzoxazole ring Group, benzofuran ring group, dibenzofuran ring group, benzothiophene ring group, dibenzothiophene ring group, and carbazole ring group. Particularly preferred is a dibenzofuran ring group.

  In the general formula [1], X represents a chlorine atom or a bromine atom. n represents an integer of 1 or more. n is an integer of 1 or more and is not particularly limited since it depends on the structure of the compound represented by the general formula [1], but n is preferably 1 to 10, and more preferably 1 to 3.

In the general formula [2], R ₁ , R ₂ , R ₃ and R ₄ each independently represents an alkyl group or an aryl group, R ₁ and R ₃ , R ₂ and R ₄ and R ₃ and R ₄ are They may combine with each other to form a ring. Specific examples of the alkyl group include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, tert-butyl group, pentyl group, hexyl group, octyl group and decyl group. Can be mentioned. Specific examples of the aryl group include a phenyl group, a naphthyl group, and an anthracenyl group.

R ₁ and R ₃ and R ₂ and R ₄ may be bonded to each other to form a ring, and R ₁ and R ₃ and R ₂ and R ₄ may be bonded together with an adjacent nitrogen atom to form a ring. For example, a 5-7 membered ring is mentioned. Preferably, it is a 5-membered or 6-membered ring.

Examples of the ring formed by bonding R ₃ and R ₄ together with the adjacent urea bond include a 5- to 7-membered ring. The ring formed by bonding R ₃ and R ₄ together with the adjacent urea bond may be a single ring or a condensed polycycle.

R ₁ and R ₂ are preferably a methyl group, an ethyl group, or an isopropyl group, and most preferably a methyl group.

As R ₃ and R ₄ , R ₃ and R ₄ are preferably bonded together with an adjacent urea bond to form a ring, and the formed ring is more preferably a 5- or 6-membered ring, A structure represented by the general formula [3] is more preferable. In General Formula [3], R ₁ and R ₂ each independently represents an alkyl group or an aryl group. Specific examples of the alkyl group or aryl group represented by R ₁ and R ₂ include the groups cited as specific examples of the alkyl group or aryl group represented by R ₁ and R ₂ in the general formula [2] .

  In the present invention, when the compound represented by the general formula [2] or the general formula [3] is used as an additive in the reaction, the addition amount is based on 1 mol of the halide represented by the general formula [1]. 10 mol or more is preferable. Examples of the solvent for the reaction include dimethylformamide, dimethyl sulfoxide, dimethylacetamide, N-methylpyrrolidone, tetrahydrofuran, ethyl acetate, toluene and the like. Further, the amount of the compound represented by the general formula [2] or the general formula [3] may be increased and used as a solvent. The amount used is 5 to 10 times the amount of 1 g of halide. preferable.

In general formula [3], in particular, 1,3-dimethyl-2-imidazolidinone in which R ₁ and R ₂ are methyl groups has no carcinogenicity and is less harmful to the human body even when used as a solvent. And is most preferred in the present invention.

In the general formulas [4] and [5], X represents a chlorine atom or a bromine atom, Y represents an oxygen atom, a sulfur atom or N—R ₅ , and R ₅ represents an alkyl group or an aryl group. W represents a substituent.

Specific examples of the alkyl group represented by R ₅ include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, pentyl group, hexyl group, octyl group, decyl group and the like. Specific examples of the aryl group include a phenyl group and a naphthyl group.

  Y is preferably an oxygen atom.

  Specific examples of the substituent represented by W include an alkyl group having 1 to 25 carbon atoms, a cycloalkyl group, an aryl group, a heteroaryl group, a halogen atom, an alkoxy group, an aryloxy group, an amino group, a cyano group, and a carboxyl group. Group, hydroxyl group and the like. When there are a plurality of Ws, each W may be the same or different.

  Hereinafter, typical specific examples of the compounds represented by the general formulas [1], [4], and [5] according to the present invention are shown, but the present invention is not limited to these.

  In the following, typical specific examples of the compounds represented by the general formulas [2] and [3] according to the present invention are shown, but the present invention is not limited thereto.

  Examples of the alkali metal iodide used in the production method of the present invention include lithium iodide, sodium iodide, potassium iodide, cesium iodide and the like, preferably sodium iodide, potassium iodide, more preferably Is potassium iodide.

  Examples of the copper or copper ion used in the production method of the present invention include copper chloride (I), copper bromide (I), copper iodide (I), copper oxide (I), copper chloride (II), odor Examples thereof include copper (II) chloride, copper (II) sulfate, copper nitrate (II), copper acetate (II), copper hydroxide (II), etc., preferably copper (I) chloride, copper (I) bromide Copper (I) iodide, more preferably copper iodide.

  In the production method of the present invention, the alkali metal iodide salt is used in an amount of 1 mol to 20 mol, preferably 1 mol to 15 mol, and copper or copper ions from 1 mol to 1 mol of the halide represented by the general formula [1]. It is preferable to use in the range of 8 mol. The reaction temperature is usually preferably from 130 to 160 ° C, particularly preferably from 140 to 150 ° C.

  EXAMPLES The present invention will be specifically described below with reference to examples, but the embodiments of the present invention are not limited to these examples.

Example 1
[Synthesis of 4-iododibenzofuran] (Comparative Example)

  Under a nitrogen stream, 5.0 g (20 mmol) of Exemplified Compound 1-44, 19.0 (100 mmol) of copper iodide, 49.8 g (300 mmol) of potassium iodide, 50 ml of hexamethylphosphoric triamide (HMPA) were added. Stir at ˜150 ° C. for 12 hours. Next, tetrahydrofuran and saturated saline were added, the aqueous layer was removed, and the extracted organic layer was concentrated under reduced pressure. When the obtained product was analyzed by HPLC, 0.6 g (yield 10%) of the desired 4-iododibenzofuran and 2.9 g (yield 85%) of by-product (H form) were obtained.

Example 2
[Synthesis of 4-iododibenzofuran] (present invention)

  Under a nitrogen stream, Exemplified Compound 1-44 5.0 g (20 mmol), Copper Iodide 19.0 (100 mmol), Potassium Iodide 49.8 g (300 mmol), Exemplified Compound 2-1 (1,3-dimethyl-2-phenyl) 50 ml of imidazolidinone (hereinafter abbreviated as DMI) was added and stirred at 140 to 150 ° C. for 12 hours. Next, tetrahydrofuran and saturated saline were added, the aqueous layer was removed, and the extracted organic layer was concentrated under reduced pressure. When the obtained product was analyzed by HPLC, 5.5 (yield 92%) of the desired 4-iododibenzofuran and 0.1 g (yield 3%) of by-product (H form) were obtained.

¹ H-NMR (400 MHz, CDCl ₃ ): δ = 7.94 (t, 2H), 7.83 (d, 1H), 7.67 (d, 1H), 7.51 (dt, 1H), 7 .39 (t, 1H), 7.13 (t, 1H)
Example 3
[Synthesis of 2,6-diiododibenzofuran] (Comparative Example)

  Under a nitrogen stream, 7.4 g (20 mmol) of Exemplified Compound 1-47, 1.9 (10 mmol) of copper iodide, 6.0 g (40 mmol) of sodium iodide, (1R, 2R)-(−)-N, N ′ -2.9 g (20 mmol) of dimethylcyclohexane-1,2-diamine and 50 ml of dioxane were added and stirred at 110 ° C. for 20 hours. Next, tetrahydrofuran and saturated saline were added, the aqueous layer was removed, and the extracted organic layer was concentrated under reduced pressure. When the obtained product was analyzed by HPLC, the target 2,6-diiododibenzofuran was 1.7 g (yield 20%), and the by-product (H form) was 0.79 g (yield 2.3%). The rest was unreacted raw material.

Example 4
[Synthesis of 2,6-diiododibenzofuran] (present invention)

  Under a nitrogen stream, 7.4 g (20 mmol) of Exemplified Compound 1-47, 19.0 (100 mmol) of copper iodide, 49.8 g (300 mmol) of potassium iodide, and 50 ml of Exemplified Compound 2-1 (DMI) were added. Stir at ˜150 ° C. for 12 hours. Next, tetrahydrofuran and saturated saline were added, the aqueous layer was removed, and the extracted organic layer was concentrated under reduced pressure. When the obtained product was analyzed by HPLC, 8.2 g (yield 95%) of the desired 2,6-diiododibenzofuran and 0.7 g (yield 2%) of by-product (H form) were obtained. It was.

¹ H-NMR (400 MHz, CDCl ₃ ): δ = 8.26 (d, 1H), 7.87 (t, 1H), 7.86 (t, 1H), 7.78 (dd, 1H), 7 .45 (d, 1H), 7.14 (t, 1H)
Example 5
[Synthesis of iodobenzene] (the present invention)

  In a nitrogen stream, 2.2 g (20 mmol) of Exemplified Compound 1-1, 19.0 (100 mmol) of copper iodide, 49.8 g (300 mmol) of potassium iodide, 50 ml of Exemplified Compound 2-1 (DMI) were added. Stir at ˜150 ° C. for 12 hours. Next, tetrahydrofuran and saturated saline were added, the aqueous layer was removed, and the extracted organic layer was concentrated under reduced pressure. When the obtained product was analyzed by HPLC, 3.8 g (yield 94%) of the desired iodobenzene was obtained.

Mass spectrum; (API method, m / e (relative intensity)) 205 ((60) MH ⁺ )
Example 6
[Synthesis of N-phenyl-3-iodocarbazole] (Invention)

  Under a nitrogen stream, 6.4 g (20 mmol) of Exemplified Compound 1-20, 19.0 (100 mmol) of copper iodide, 49.8 g (300 mmol) of potassium iodide, and 50 ml of Exemplified Compound 2-1 (DMI) were added. Stir at ˜150 ° C. for 12 hours. Next, tetrahydrofuran and saturated saline were added, the aqueous layer was removed, and the extracted organic layer was concentrated under reduced pressure. When the obtained product was analyzed by HPLC, 6.9 g (yield 93%) of the target N-phenyl-3-iodocarbazole was obtained.

Mass spectrum; (API method, m / e (relative intensity)) 370 ((55) MH ⁺ )
Example 7
[Synthesis of 2-iodo-N-methyl-benzimidazole] (present invention)

  Under a nitrogen stream, 4.2 g (20 mmol) of Exemplified Compound 1-90, 19.0 (100 mmol) of copper iodide, 49.8 g (300 mmol) of potassium iodide, and 50 ml of Exemplified Compound 2-1 (DMI) were added. Stir at ˜150 ° C. for 12 hours. Next, tetrahydrofuran and saturated saline were added, the aqueous layer was removed, and the extracted organic layer was concentrated under reduced pressure. When the obtained product was analyzed by HPLC, 4.8 g (yield 94%) of the target N-phenyl-3-iodocarbazole was obtained.

Mass spectrum; (API method, m / e (relative intensity)) 259 ((45) MH ⁺ )
Identification of each compound in the examples was carried out by MASS spectrum and NMR spectrum, and it was confirmed to be the target compound and by-product (H form), respectively. Other exemplary compounds can also be synthesized according to the above method.

  From the above results, the by-product (H-form) from which iodine was eliminated was generated in the method of the comparative example, and the yield of the target iodo-form was decreased, but the by-product (H-form) was observed in the method of the present invention. Is hardly produced, and the target product is obtained in a high yield, which is superior to the comparative example. In the comparative example, a solvent harmful to the human body such as HMPA or dioxane is used, but it can be seen that the present invention is superior in that a safe solvent can be used in the present invention.

Claims (5)

A compound represented by the following general formula [1] and an alkali metal iodide salt are reacted in the presence of copper or a copper ion and a compound represented by the following general formula [2]. Compound production method.

(In the formula, Ar represents an aromatic hydrocarbon ring group or an aromatic heterocyclic group, X represents a chlorine atom or a bromine atom, and n represents an integer of 1 or more. R ₁ , R ₂ , R ₃ and R ₄ each independently represents an alkyl group or an aryl group, and R ₁ and R ₃ , R ₂ and R _4, and R ₃ and R ₄ may be bonded to each other to form a ring. The said general formula [2] is represented by the following general formula [3], The manufacturing method of the iodinated aromatic compound of Claim 1 characterized by the above-mentioned.

(In the formula, R ₁ and R ₂ each independently represents an alkyl group or an aryl group.) The said general formula [1] is represented by the following general formula [4], The manufacturing method of the iodinated aromatic compound of Claim 1 or 2 characterized by the above-mentioned.

(In the formula, X represents a chlorine atom or a bromine atom, Y represents an oxygen atom, a sulfur atom or N—R ₅ , R ₅ represents an alkyl group or an aryl group, W represents a substituent, m and n Represents an integer of 1 to 4.) The said general formula [4] is represented by the following general formula [5], The manufacturing method of the iodinated aromatic compound of Claim 3 characterized by the above-mentioned.

(In the formula, X represents a chlorine atom or a bromine atom, Y represents an oxygen atom, a sulfur atom or N—R ₅ , R ₅ represents an alkyl group or an aryl group, W represents a substituent, and m represents 1) Represents an integer from 4 to 4.)   In the said General formula [5], Y is an oxygen atom, The manufacturing method of the iodinated aromatic compound of Claim 4 characterized by the above-mentioned.