TW201139338A - Process for production of halogenated aromatic compounds - Google Patents

Abstract

Provided is a process for the production of halogenated aromatic compounds by replacing aromatic hydrogen atoms of an aromatic compound by halogen atoms regioselectively and directly in a simple manner in high yield. The process is highly safe, less costly, easy, and suitable for industrial mass-production. The process is characterized by mixing an N,N'-dihalogenohydantoin with an aromatic compound in the presence of a Lewis acid to replace at least partially the aromatic hydrogen atoms of the aromatic compound by halogen atoms.

Description

[Technical Field] The present invention relates to a method for producing a halogenated aromatic compound in which an aromatic ring hydrogen of an aromatic compound is substituted with a halogen atom. [Prior Art] The organic halide 'especially an organic iodide is an excellent precursor exhibiting high reactivity in a cross-coupling reaction using a transition metal as a catalyst' as a synthetic physiologically active natural substance or a pharmaceutical active ingredient intermediate or the like. Key compound. As for the coupling reaction with an organic iodide, it is known that a Suzuki-Miyaura coupling reaction with an organoboron compound is represented by a palladium catalyst, and a coupling reaction with a Tamaro of Grignard reagent (Grignard) is known. Coupling reaction with the root of the organic zinc compound (Negi shi), and various reaction reactions such as the Kosugi-Migita Stille coupling reaction with the organotin compound. The iodine is introduced into the iodine to prepare the organic iodide, especially the iodine. Aromatic compounds are not easy. For example, an iodine simple substance or N-iodosuccinimide which is generally used as an iodinating agent for an unsaturated hydrocarbon compound has a low iodination reactivity or a positional selectivity to an aromatic compound, and requires a plurality of complicated The reaction step is a high price and is not suitable for most problems such as industrial iodination. The present inventors, in Non-Patent Document 1, disclose a chemical formula [I] as shown below: -5- 201139338 [Chemical 1] hbf4

Hg-Si〇2

Cn+i order Ο Barluenga reagent BF4

A simple and fully positional selective iodinating agent of the binaphthyl-bis(diarylphosphine) (BIPAP) dioxide derivative of the bis(pyridine)iodine boron tetrafluoride (Barluenga) reagent. In the binaphthyl skeleton of BIpAP dioxide, the diarylphosphonium group (P〇-Ar2) substituted by the second position is a pull electron group, so although the 4, 4' and 5, 5' positions are It is possible to introduce iodine. Using this iodinating agent, the 5,5' position will be selected and iodinated in high yield. However, the preparation of the iodinating agent requires the use of mercury which is highly toxic to the environmental load, and therefore has a problem that it is not suitable for the production of iodine in aromatic compounds in practical industries. Further, it is also desired to introduce iodine into an aromatic compound such as a Binaphthene derivative or a benzene derivative or a biphenyl derivative, which is a B IP AP dioxide derivative, with a selective and safe iodinating agent. Or a simple method of introducing iodine into an aromatic compound such as a triarylamine which is useful as a constituent material of an organic electroluminescence (EL) element but which is difficult to iodize. [Prior Art Document] [Non-Patent Document] [Non-Patent Document 1] Toyoshi Shimada etc.,

S -6 - 201139338

Journal of Organic Chemistry., 70, 1 〇 1 7 8 - 1 0 1 8 1 (2 0 0 5 ) ° [Problem to be Solved by the Invention] The present invention has been made to solve the above problems, and It is an object of the invention to provide a method for producing a halogenated aromatic compound which is highly safe and inexpensive by subjecting an aromatic ring hydrogen of an aromatic compound to halogen substitution at a positional and direct high yield and simple yield. A method for producing a halogenated aromatic compound suitable for mass production in a simple industry. [Means for Solving the Problem] The method for producing a halogenated aromatic compound of the present invention which is carried out in order to achieve the above object is characterized in that it is in the presence of Lewis acid 'by mixing N, N' - Dihalogenated carbendazim and an aromatic compound, wherein at least a part of the aromatic ring hydrogen of the aromatic compound is substituted with a halogen. The method for producing a halogenated aromatic compound, characterized in that the above-mentioned hydrazine, hydrazine-dihalogenated carbendazim is hydrazine, Νι_diiodo-5,5-dialkylacetyl carbazide, hydrazine, hydrazine ,-Dibromo-5,5-dialkylethylene carbazide, or hydrazine, hydrazine, -dichloro-5,5-dialkylethylene carbazide. The method for producing a halogenated aromatic compound, wherein the Lewis acid is selected from at least one of a metal halide, a semimetal halide, an organic sulfonic acid metal salt, and an organic sulfonic acid metal salt. A method for producing a halogenated aromatic compound, characterized in that, in the case of "the aforementioned Lewis acid is the metal halide or the organic sulfonic acid metal salt" in 201139338, the metal is Al, Sc, Ti, Fe, Zn, Zr, When Nb, In, Sn, and/or Bi is the above-described semimetal halide or the above organic sulfonic acid metal salt, the semimetal is B and/or Si. The method for producing a halogenated aromatic compound, wherein the aromatic compound has an alkyl group, an alkenyl group, an alkoxy group, an aralkyl group, a hydroxyl group, a dialkylamino group or a diarylamine group. a phenyl derivative, a binaphthyl derivative, or a combination of at least one of a dialkylphosphino group, a dialkylphosphonium group, a diarylphosphonium group, and a diarylphosphonium group or a substituent. a benzene derivative or a triarylamine derivative. The method for producing a halogenated aromatic compound, wherein the halogenated aromatic compound is a compound represented by the following chemical formulas (1) to (6):

(In each of the chemical formulas (1) to (6), X is the same or different iodine atom, bromine atom and chlorine atom or a hydrogen atom, and at least one X in one molecule is the halogen atom; R is the same or not -8 - 201139338 and the alkyl group having a carbon number of 1 to 18; Ar is an aryl group, respectively. In the method for producing a halogenated aromatic compound, the compound of the above formula (2) is a compound represented by the above chemical formula (2), which is characterized by the following chemical formula (2-1) to (2-3) Show any of the compounds:

Further, the halogenated aromatic compound is characterized in that it is one of the compounds represented by the following chemical formulas (2-1) to (2-3):

Further, the halogenating agent of the same aromatic compound is characterized in that it is composed of hydrazine, Ν'-dihalogenated carbendazim and Lewis acid, and is an aromatic ring hydrogen of the aromatic -9 - 201139338 compound. At least a portion is substituted with a halogen. [Effect of the Invention] The method for producing a halogenated aromatic compound according to the present invention can be derived from a range of a laboratory scale to an industrial scale, such as a derivative, a biphenyl derivative or a binaphthyl derivative having or without a substituent. The aromatic ring hydrogen of the aromatic compound of the compound or the triarylamine derivative is directly substituted by halogen in a simple single-slot method, and the desired aromatic compound can be obtained in a positional selectivity and in high yield.

According to the method for producing a halogenated aromatic compound, various halogenated aromatic compounds which are useful as a physiologically active natural substance, an intermediate of a pharmaceutical active ingredient, a raw material component of an asymmetric catalyst, or a raw material component of an organic electroluminescence device can be obtained. . And 'as long as it is simply post-treated, it can obtain the desired quality of the toothed aromatic compound D. The method of manufacturing the halogenated aromatic compound does not use harmful heavy metals, which is a kind of safety. It does not pollute the environment and can be obtained at a low cost. In particular, the triarylamine derivative obtained by the method for producing a halogenated aromatic compound can be used as a raw material component of an organic electroluminescence device or a matrix for imparting functionality. The halogenating agent of the present invention used in the method for producing a halogenated aromatic compound is a reactive compound of N,N'-dihalogenated carbendazole having two halogenizable halogen atoms in a molecule of a simple structure. And a reaction-promoting catalyst with Lewis acid, each molecule of the reactive compound

S -10- 201139338 is a highly efficient and easy to modulate reagent that is inexpensive and safe. [Embodiment] Hereinafter, embodiments of the present invention will be described in detail, but the scope of the present invention is not limited to the embodiments. One form of a method for producing a halogenated aromatic compound suitable for the present invention is a method of mixing a halogenated compound composed of N,N'-diiodo-5,5-dimethylhydantoin and Lewis acid in a solvent. And an aromatic compound, whereby one of the aromatic ring hydrogens of the aromatic compound is halogen-substituted in a position-selective manner. The 5,5-dimethylethene p-substrate is treated with sodium hydroxide in an ice-cold state, and then reacted with iodine chloride (IC1) to obtain a high yield and simply >^,:^' - Diiodo-5,5-dimethylhydantoin. The ^^,:^-diiodo-5,5-dimethylhydantoin can be used as a benzene derivative such as a phenol, a binaphthyl derivative, a biphenyl derivative, an aromatic amine, and is rich in An iodinating agent for a matrix of various aromatic compounds such as an electronic cyclic heteroaromatic compound. N-iodosuccinimide, which is widely used as an iodinating agent, acts as an equivalent iodine source for a substrate to be iodinated, but N,N,-diiodo-5,5-dimethylethene Since urea reacts with two equivalents of iodine source and can react reliably, the reaction efficiency per molecule is good, and it is a useful and economical iodinating agent. As an example of N,N'-dihalogenated carbendazole, an example of n,N'-diiodo-5,5-dimethylhydantoin is shown, but it may also be a carbon number at the 5 position. An alkyl group of about 1 〇 or an aralkyl group such as a benzyl group is substituted by a compound, and the acetyl group is substituted. Among them, N,N,-diiodo-5,5-dialkylethylene carbazide, N,N'-monobromo-5,5-di-yard carbendazim, or N,N, _ Chlorine _5,5_two-yard carbendazim is preferred. In particular, N,N,-diiodo-5,5-dimethylhydantoin is preferred. For the amount of halogen to be introduced into the aromatic compound of the substrate, it is preferred to use ν5 to 1 mol of ν,Ν,-dihalide. The Lewis acid is an electron acceptor, preferably a metal such as a metal halide, a semimetal halide, a trifluoromethanesulfonic acid (TfOH) or an organic sulfonic acid such as methanesulfonic acid or p-toluenesulfonic acid. Salt 'semi-metal salts of such organic sulfonic acids. The metal halide or the organic sulfonic acid metal salt is preferably such that the metal is Al, Sc, Τ, Fe, Zn, Zr, Nb, In, Sn or Bi; the semimetal halide or the organic sulfonic acid semimetal salt is preferably Its metal is B, Si. More specifically, for example, a chloride of such a metal such as A1C13, TiCl4, FeCl3, ZnCl2, ZrCl4, NbCl5, or BiCl3, a bromide of such a metal such as BiBr3, and an iodide of such a metal as Bil3 are exemplified. a metal halide; or a semimetal halide such as BF3 or an ether complex thereof; or a trifluoromethane sulfonate such as Al(OTf) 3, Sc(OTf) 3, Bi(OTf) 3, In(OTf) 3 An acid metal salt; or a trifluoromethanesulfonic acid semimetal salt such as boron triflate or TfO-Si(CH3)3. It is also possible to use a metal salt or a semimetal salt of methanesulfonic acid or a metal salt or a semimetal salt of p-toluenesulfonic acid to replace the trifluoromethanesulfonate. For the aromatic compound 1 mole of the matrix, Lewis acid is preferably used from 1 m ο 1 % to 10 m ο 1 %. The solvent is not particularly limited as long as it does not inhibit halogen substitution, and examples thereof include a halogen solvent such as dichloromethane, 1,2-dichloroethane or chloroform; a ketone solvent such as acetone; and an ether system such as tetrahydrofuran. Solvent. Aroma

The S -12-201139338 compound is 1 part by weight, and the solvent is preferably used, for example, from 10 to 100 parts, more preferably from 37 to 53 parts by weight. The aromatic compound to be halogenated as the substrate is not particularly limited as long as it has a base, and examples thereof include a phenyl derivative such as anisole, a dinaphthyl derivative of a binaphthyl; a biphenyl derivative; (丁?八), or ^1<1',:^-tetraphenylbenzidine (butyl?8), or 11^-yl-indole, Ν'-bis(m-tolyl)benzidine (TPD) The triarylamine-derived aromatic compounds may also have a substituent. The substituent may be substituted by a halogen depending on the nature of the electron group or the electron withdrawing group. Examples of the substituent include a linear or branched chain having a carbon number of 1 to 18, and examples thereof include an alkyl group, an alkenyl group, an alkoxy group, an aralkyl group, a diamino group, and a dialkylphosphino group. Dialkylphosphonium; hydroxy; as having an aryl group, for example, a diarylamino group, a diarylphosphino group, a diphosphonium group. These substituents may also be further substituted by an alkyl group as described above. Hereinafter, the method for producing a halogenated aromatic compound will be more apparent. First, it is shown that iodization of anisole, which is the simplest aromatic compound in the matrix, is shown. 1 mole of anisole and 0.5 moles of ruthenium, osmium, and dimethyl carbendazim in the presence of a Lewis acid catalyst as an active agent such as a metal chloride The iodine is selectively introduced into the weight aromatic ring: such as a diamine diphenyl compound in a high yield or quantitatively, by allowing it to be carried out in dichloromethane for 12 hours. Push the aryl or cycloalkylphenyl aryl group -5,5- metal reaction 4 -13- 201139338 4_Iodoanisole. On the other hand, if no Lewis acid is present, the reaction is completely impossible. Next, the iodization of 2,2'-dimethoxy-m, i,-binaphthyl as an aromatic compound was shown. 1 mole of 2,2'-dimethoxy-1,1--binaphthyl with about 1 or 2 moles of N,N'-diiodo-5,5-dimethylethene Urea, in the presence of a metal halide such as a suitable metal chloride of its active agent or a Lewis acid of a metal triflate, is reacted in dichloromethane to obtain iodine as a main product. 6,6,-diiodo-2,2'-dimethoxy-oxime, ι·_ binaphthyl optionally introduced into the 6th, 6' position, and introduced into the 3rd, 3rd, and 6th, 6, 3,3',6,6--tetraiodo-2,2'-dimethoxy-1,1,-binaphthyl. On the other hand, if no Lewis acid is present, the reaction is completely impossible. Further, in place of Lewis acid, trifluoromethyl acid of Brensted acid is present, and the reaction is completely impossible. Therefore, it is speculated that iodination is carried out by the catalytic properties inherent in Lewis acid. The methyl 2,2'-dimethoxy-1,1,-binaphthyl can be easily deprotected with boron tribromide. This deprotected product is binaphthylquinone (BINOL) for asymmetric synthesis. A very important precursor in the reaction. Therefore, the 6,6,- or 3,3·,6,6·-iodinated by the direct iodination of N,N,-diin-5,5-dimethylhydantoin- The equivalent of 2,2'-dimethoxy-oxime, ιι·binaphthyl iodide bin〇l. This iodinated BINOL is known as a raw material for asymmetric catalysts, etc. 'Previously, the synthesis of 6,6'-diiodo-2,2'-dimethoxy-M,-binaphthene was utilized from B IN Ο L B I"2 is brominated and protected with methoxymethyl chloride

S -14- 201139338 Protection, lithiation with n-butyllithium, iodization with iodine, deprotection with hydrochloric acid, etc., in addition, 3,3',6,6'-iodide-2,2' -Dimethoxy-1,1'-binaphthyl nucleation is brominated by BINOL using Br2, protected with methoxymethyl chloride, lithiated with n-butyllithium and trimethyl chloride The decane is subjected to methylation, and is subjected to a plurality of steps such as reaction with 12 in the presence of second butyllithium, reaction with IC1, and deprotection with HC1. However, according to the method for producing a halogenated aromatic compound of the present invention, direct halogenation such as iodination can be easily carried out in only one step, which contributes to simplification of steps and labor saving. In particular, iodinated aromatic compounds have higher reactivity with cross-coupling reactions than brominated aromatic compounds, and are useful for various synthesis applications. The method for producing the halogenated aromatic compound can be derivatized into a halogenated aromatic compound regardless of the presence or absence of an asymmetric carbon, and in particular, does not undergo racemization from an asymmetric aromatic compound, but can be derived only from an asymmetric halogenated aromatic compound. . The obtained 6,6-diiodo-2,2'-dimethoxy-1,1'-binaphthyl is deprotected by methylation to give iodinated BIN OL, which can be a ligand for the catalyst. For example, a bipolar titanium Lewis acid catalyst derived from the asymmetrically iodinated BINOL, which is derived from an asymmetric 1,3-dipolar cycloaddition reaction of nitrone and methacrolein, results from iodine The electronic effect is shown to be much higher than the optical yield and positional selectivity of BINOL catalysts that have not been previously iodinated. In addition, a palmitic zirconium Lewis acid catalyst derived from the asymmetric iodinated BINOL, in acetaldehyde and trans-1-methoxy-3-trimethyldecyloxy-1,3-butadiene (Danishefsky In the Diels-alder reaction, -15-201139338 exhibits high asymmetric derivatization. Next, the iodination of BINAP dioxide is shown. 1 molar amount of BINAP dioxide as a substrate and about 1 mole of N,N,_diiodo-5,5-dimethylhydantoin, in the amount of 3 moles as its active agent In the presence of trifluoromethyl acid, it is reacted in dichloromethane for 2 hours, and the same iodine can be quantitatively obtained only at the 5, 5' position in the same manner as the 831 "1\1611§3 reagent using harmful mercury. 5,5·-diiodo-BINAP dioxide. However, the use of high-priced trifluoromethanesulfonic acid as an active agent for industrial iodization has economic problems, and trifluoromethanesulfonic acid, which is too strong acid, is lacking. The functional group resistance, the applicable matrix will be limited, however, the Lewis acid other than the brunitem acid has little influence on the functional groups of the matrix, and the applicable substrate is almost unlimited. Under such circumstances, the method for producing a halogenated aromatic compound according to the present invention uses a Lewis acid such as inexpensive aluminum chloride to carry out halogenation in a positionally selective high yield. In addition, according to the method for producing a halogenated aromatic compound of the present invention, a Lewis-containing aromatic compound, for example, a triarylamine derivative which is widely used as a constituent material of an organic electroluminescence device, can also be used in the same manner. The acid 'halogenated with N,N'. dihalogenated carbendazim. The organic electroluminescence device ' typically has a structure in which a transparent electrode, a hole transport layer, a light-emitting layer, an electron transport layer, and a cathode are laminated in this order on a glass substrate. The triarylamines constitute a hole transport layer and function as a hole transport material injected and transported from the anode receiving cavity. In order to effectively integrate triarylamines as hole transport layers, it is necessary to add them by such derivatization.

S -16- 201139338 Features. In the derivatization, if the triarylamine is a halide, it is very good as a hole transport layer, and can be used as a matrix for various coupling reactions, and can be widely and effectively imparted by various derivatizations. Electroluminescence function. [Examples] The examples actually carried out using a method for producing a halogenated aromatic compound suitable for the halogenating agent of the present invention will be described in detail below. First, the iodization of anisole, one of the simplest aromatic compounds, is bet. (Example 1) Anisole (54.1 mg, 0.5 mmol), hydrazine, hydrazine-diiodo-5,5-dimethylethyl urinary urea (93 mg, 0.25 mmol) and a dichlorocarbyl group as a substrate A mixture of (2 ml) was added with aluminum chloride (3.3 mg ^ 0.02 5 mmol) as a Lewis acid while stirring, and the mixture was stirred at room temperature for 1 hour to cause a reaction. The reaction was quenched by the addition of a saturated aqueous solution of sodium sulfite. After the aqueous layer was extracted with chloroform, the organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The crude product was isolated and purified by silica gel chromatography (developing solvent: chloroform) to obtain white crystalline 4-iodoanisole with a total yield of 90% and 2-iodoanisole as a colorless liquid. Body: 2-iodine construct = 93: 7). The measurement results of 1H-nuclear magnetic resonance spectrum (W-NMR) of the product were confirmed as follows. -17- 201139338 [4-Iodoanisole] 'H-NMR (400 MHz) (CDCh/TMS) δ (ppm) 3.78 (s, 3H), 6.68 (d, J = 9.2 Hz, 2H), 7.56 ( d, J = 9.2 Hz, 2H). [2-Iodoanisole] 'H-NMR (400 MHz) (CDCI3/TMS) δ (ppm) 3.87 (s, 3H), 6.68 -6.73 (m, 1H), 6.81-6.83 (m, 1H), 7.28-7.3 2 (m, 1 H), 7.75-7.78 (m, 1 H). (Examples 2 to 8 and Comparative Example 1) In the iodination reaction of the anisole of Example 1, except that the Lewis acid reagent described in Table 1 was used, the amount of dichloromethane used was 1.5 ml, and the stirring reaction was carried out. The reaction and identification were carried out in the same manner as in Example 1 except that the time was 12 hours. The results are summarized in Table 1.

CH

Table 1

5mol % Lewis acid 0.5 equivalent DIH

No. Total yield of Lewis acid (%) (4 iodine structure / 2 iodine structure) Example 1 Αία, 90 (93/7) 寅 Example 2 BF>*Etj〇87 (95/5) Example 3 FcCl* 87 (94/6) Example 4 AlCh 86 .(94/6) Example 5 ZrCL· 57 (94/6) Example 6 TiCU 92 (89/11) Example 7 ZoCb 66 (99 /1) Example 8 NbCls 88 (94/6) Ratio 1 No 0 - 11:1^'-di-5,5-dimethylhydantoin

S -18- 201139338 It can be seen from Table 1 that, as shown in Examples 2-8, the yield is almost the same when using 8?3·Et20, Feci3, A1C13, TiCl4, and NbCl5 as the Lewis acid for iodination, and 2, There was no difference in positional selectivity at the 4-position, but the yield was lowered when ZrCl4 or ZnCl2 was used as the Lewis acid. On the other hand, as shown in Comparative Example 1, anisole was not iodinated without using Lewis acid. Since anisole has an electron-donating methoxy group, it exhibits o-para-alignment 'in the presence of Lewis acid, by hydrazine, Ν·-diiodo-5,5-dimethylhydantoin 'It will cause iodination at position 2 or 4, although the 4-position iodine is the main product' but iodobenzoic acid will be obtained as a mixture of the two positional isomers. Therefore, AlCh, which is considered to be the easiest to handle and inexpensive and has excellent elemental tactics, is used as a Lewis acid, and the positional selectivity is improved by temperature control. (Example 9) Iodination was carried out in the same manner as in Example 1 except that the reaction temperature of Example 1 was changed from room temperature. The results are summarized in Table 2. [Table 2] Table 2 CH,-0 'Ό

5mo] % Lewis acid 0.5 When fi DIH , -. Ui

No. Lewis acid reaction temperature reaction time total receipts per '"" '(hours) (%) (4 digits commutative 19 / 2 positions instructor Zhao) «Example 1 A1C1, room temperature i 90 (93 / 7) Example 9 Αία, 01C 2 59 (9113) DIH : Ν, Ν '-three exchange. 5,5-dimethyl B group -19- 201139338 It can be seen from Table 2 that the reaction is carried out at 0 °C. Although the yield was lowered as compared with the reaction at room temperature, the para-selectivity, that is, the 4-position iodine complex was increased from 93% to 97%. Thus, the method for producing a halogenated aromatic compound of the present invention uses inexpensive Lewis acid as a catalyst and N,N'-diiodo-5,5-dimethylhydantoin having a small environmental load. Halogenation with positional selectivity and good yield can be achieved, so its practical price is very high. Next, the use of A1C13 as the Lewis acid was also used to investigate the iodination of the asymmetric 2,2'-dimethoxy-1,1'-binaphthylate having a more complex aromatic structure. (II Example 10~14) 2,2,-Dimethoxy-1,1,-binaphthyl (50 mg, 0.159 mmol), N,N'-diiodo-5,5-dimethylethyl A mixture of guanidine urea and dichloromethane (2 ml) was added as a Lewis acid A1C13 while stirring, and the mixture was stirred for reaction. The reaction conditions are shown in Table 3. The reaction mixture was quenched by the addition of a saturated aqueous solution of sodium sulfite. Then, after the aqueous layer was extracted with chloroform, the organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The composition of the product was measured by 1H-NMR, and its formation was shown in Table 3 in comparison with the quantitative results. (Comparative Examples 2 to 3) The same as Example 10 except that the Lewis acid of Example 1 was changed to not use Lewis acid or trifluoromethanesulfonic acid (TfOH).

-20- S 201139338 Reaction. The results are summarized in Table 3. [Table 3] Table 3

DIH (equivalent) AlCh (mol %) skin should be divided by yield Γη-nmr : %) No. Reaction temperature uan Μν 1MJ — (hours) unreacted 6,6, diiodide by-products Example 10 0.5 5 Room temperature 5 69 31 * Example 11 0.5 100 Room temperature 3 92 4 4 Example 12 1 100 Room temperature 5 72 12 16 Example 13 1 5 8〇r 3 90 6 4 «Example 14 1 100 80ΐ 5 69 16 15 Comparative Example 2 0.5 0 room temperature 6 100 - - Comparative Example 3 0.5 TfOH A1CW room temperature 6 100 - - 0111: Team 1^-diiodo-5,5-dimethylhydantoin As shown in Table 3, In Examples 1 to 14, although the yield was low, 6,6'-diiodo-2,2'-dimethoxy-1,1'-binaphthyl was obtained, and a small amount was estimated to be By-products of 3,3',6,6, tetraiodo-2,2'dimethoxy-1,1'-binaphthyl, in Comparative Example 2 without the use of Lewis acid, and the use of bromide acid Comparative Example 3, in which trifluoromethanesulfonic acid was used in place of Lewis acid, was completely incapable of causing deuteration. Next, the iodination of 2,2'-dimethoxy-1,1'-binaphthyl was investigated using various Lewis acids. (Example 1 5 ) 2,2'-dimethoxy-1,1'-binaphthyl (200 mg, 〇.636 mmol), -21 - 201139338 >}, > 1'-二姚-5, a mixture of 5-dimethyl-ethyl urinary urea (483111 §, 1.27111111 〇 1) and dichloromethane (8 ml), and added as a Lewis acid, Sc(OTf) 3 ( 12.3 mg, 0.0636 mmol), while stirring. The reaction was then continued by stirring at room temperature for 12 hours. The reaction mixture was quenched by the addition of a 1% by weight aqueous solution of sodium sulfite. Then, after extracting the aqueous layer with chloroform, the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and concentrated to give the product of 6,6-didi 2,2'-dimethoxy-1,1'-binaphthyl. The results of 1 H-NMR measurement of the product were as follows, and the structural formula was confirmed. 'H-NMR (270 MHz) (CDC13/TMS) δ (ppm) 3.76 (s, 6H), 6.77 (d, J = 8.9 Hz, 2H), 7.42 (d, J = 8.9 Hz, 2H), 7.44 ( d, J = 8.9 Hz, 2H), 7.85 (d, J = 8.9 Hz, 2H), 8.24 (s, 2H). (Examples 6 to 17) In addition to the Lewis acid of Example 15, and its use amount The amount of the diiodo-5,5-dimethylhydantoin used and the reaction time were the same as those described in Table 4 except that the conditions described in Table 4 were used, and iodization was carried out in the same manner as in Example 15. The results are summarized in Table 4.

S -22- 201139338 [Table 4] Table 4

No. DIH (equivalent) Lewis acid (mol %) Reaction time (hours) Yield Ch-nmr ; %) Unreacted 6,6. Diiodo-articular hip 3,3,6,6, tetraiodide Hip by-product Example 10 0.5 AlCh (5) 5 69 31 - 贲 Example Ϊ 5 2 Sc(OTf) 3 (5) 12 - 95 Trace expensive - Example 16 2 In(OTf)3 (10) 3.5 15 85 - - Example 17 2 Bi(OTF)3 (10) 3,5 - 40 52 8 DIH: Ν, Ν··二切·5,5-dimethylhydantoin As shown in Table 4, using Sc (OTf) 3 or In(OTf) 3 as Examples 15 to 16 of Lewis acid, only 6,6'-diiodo-2,2'-dimethoxy-1,1 can be obtained in a very high yield. '-binaphthyl, however, in Example 17 using Bi(OTf)3, in addition to obtaining 3,3',6,6'-tetraiodo-2,2'-dimethyl at a higher yield Oxy-1,1·-binaphthyl and a small amount of hexaodo-2,2'-dimethoxybinaphthalene which is presumed to be a by-product. In addition, when only 1 mol% of a catalytic amount of Bi(OTf)3 is used as the Lewis acid for the reaction, only 6,6'-diiodo-2,2'-dimethoxy can be obtained in a high yield and almost quantitatively. -1,1'-binaphthyl. Next, using Sc(OTf)3 as the Lewis acid, the positional selectivity of 6,6'-diiodo-2,2'-dimethoxy-1, fluorene-binaphthyl was increased. (Examples 1 8 to 2 6 ) In addition to the substrate of Example 15, 2,2 dimethoxy-1,1'-binaphthyl, anthracene, anthracene, diiodo-5,5·dimethylethene The amount of urea, Sc (〇Tf) 3 used, the solvent, the reaction temperature, and the reaction time were the same as in Example 15 except that the conditions described in Table 5 were -23-201139338. The results are summarized in # 5 = [Table 5] Table 5

No. Matrix (rog) DIH Sc(OTf)3 (equivalent) (mol Solvent reaction temperature Reaction time (hours) Yield ΓΗ-NMR: %) Unreacted by-product Example 18 50 1 5 CH: C1! Room temperature 3 40 60 - Example 19 50 1 5 ClCHaCHiCl 80ϊ 3 - 85 15 Example 20 50 2 5 CH: Ch Room temperature 12 - 95 Trace & 寅 Example 21 1000 2 , 5 CHaCli Room temperature 12 35 65 - Example 22 1000 2 10 CHiCh Room Temperature 12 - 95 - Example 23 1000 2 10 CH: Ch Room Temperature 12 21 79 - Example 24 1000 3 10 CHiCh Room Temperature 5 40 60 - Example 25 1000 3 10 CHiCh Room Temperature 5 21 79 Example 26 1000 3 30 CHiCh Room temperature 5 5 93 2 DIH : Ν, Ν·-diiodo·5,5. Dimethylhydantoin is known from Table 5, '6,6 can be obtained in a higher yield. - Two bowls of 2,2'-dimethoxy-1,1'-binaphthyl. Secondly, the use of Bi(OTf)3 as the Lewis acid' to improve the positional selectivity of 3,3',6,6,-tetraiodo-2,2'-dimethoxy-1, fluorene-binaphthalene . (Example 27) 2,2,-Dimethoxy-1,1 binaphthyl (100 mg, 3.18 mmol), 1^,1^,-di Yao-5,5-dimethyl A mixture of carbendazim (121〇1118, 3.181111110丨) and dichlorocarbyl (4〇ml) was cooled to 0 °C after 'Add-24- 201139338

Bi(OTf)3 (113.9 mg, 〇.3 18 mmol) was stirred at 0 °C for 1 hour. Then, 1 equivalent of N,N'-diiodo-5,5-dimethylhydantoin was added three times (total 3630 mg, 9.54 mmol) every one hour, and the mixture was stirred for 4 hours. Next, Ν,Ν·-diiodo-5,5-dimethylhydantoin (2 4 2 0 mg, 6.3 6 mm ο 1 ) and Bi(OTf) 3 (1 1 3.9 mg, 0.318 mmol) were added. ), stirring for 18 hours. The reaction mixture was quenched by adding a 10% by weight aqueous solution of sodium sulfite to the reaction mixture. Then, after extracting the aqueous layer with chloroform, the organic layer was washed with water and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and filtered and concentrated to give 2.47 g (yield 95%) of product 3,3 ',6,6'-tetraiodo-2,2'-dimethoxy-1, fluorene-binaphthyl. The results of 1H-NMR measurement of the product were as follows, and the structural formula was confirmed. 'H-NMR (270 MHz) (CDC13) <5 (ppm) 3.75 (s, 6H), 6.72 (d, J = 8.9 Hz, 2H), 7.44 (d, J = 8.9 Hz, 2H), 7.99 ( s, 2H), 8.47 (s, 2H). (Examples 28 to 45) The reaction conditions are: 2,2'-dimethoxy-1,1'-binaphthyl (0·159 mmol), meaning: ^- Diiodo-5,5-dimethylhydantoin and (0 butyl 3, in dichloromethane (2 ml); except 2,2'-dimethoxy-1 of Example 27, 1'-binaphthyl, chemical: ^-diiodo-5,5-dimethylhydantoin and 8 丨 (0 butyl hydrazine 3 used, solvent, reaction temperature and reaction time are as shown in Table 6 The conditions were the same as in Example 27, and the results were summarized in Table 6. -25- 201139338

No. Matrix (mg) DIH Bi(0Tf)j (when ft) (mol %> Reaction temperature Reaction time (hours) (Ή-NMR: %) Unreacted 6.6, diiodide structure 3, 3., 6.6 , tetraiodide β by-products, example 28, so 0.5 10 room temperature 3.5 49 51 - taste example 29 50 1 10 room temperature 2 8 91 1 Example 30 50 1 1 room temperature 3.5 15 83 2 - Example 31 50 1.5 10 Room temperature 2 - 65 30 5 Example 32 50 2 10 Room temperature 3.5 - 40 52 8 Carriage Example 33 50 3 10 Room temperature 2 - 9 79 12 Example 34 50 4 10 Room temperature 3.5 - - 88 12 Example 35 50 4 10 0X, 3.5 5 93 2 - Example 36 50 6 10 40t 3.5 - - Main product - Example 37 1000 1 10 Room temperature 3.5 11 89 - - Example 38 1000 1,05 1 ot 3.5 79 21 - - Example 39 1000 1.5 10 3.5 - 94 6 - Example 40 1000 1.5 10 -lot 7 45 55 - - Example 41 1000 1.5 5 -101C 3.5 75 25 - - Example 42 1000 4 10 03⁄4 3.5 - - 88 12 Example 43 1000 4 10 0TC 5 45 55 - «Example 44 1000 4 10 Room temperature 3.5 - 42 58 - Example 45 1000 6 20 QIC 24 - - 93 7 DIH ·· Ν,Ν·-二Iodine·5,5·dimethylhydantoin is known from Table 6 and can be higher The ratio of 3,3·,6,6·-tetraiodo-2,2,-dimethoxybinaphthalene was obtained, and the maximum yield was 93%. Based on these results, Ν,Ν'-diiodo-5 was suitably adjusted. , the reaction conditions such as the use amount of 5-dimethylhydantoin and Lewis acid, it is possible to separately produce 6,6, diiodo-2,2'-dimethoxy-1,1'-binaphthyl And 3,3',6,6'-tetraiodo-2,2,-dimethoxy-1,1'-binaphthyl. -26- 201139338 Secondly, 'Iodized aromatic compounds and other halogenated aromatic compounds In contrast, it is suitable for various derivatizations because of its high reactivity. Here, in order to impart a function to a triarylamine derivative which can be used as a raw material of an organic electroluminescence device, one of the simplest triarylamine derivatives is used. The triphenylamine is discussed for its iodination by N,N'-diiodo-5,5-dimethylethyl carbazide in the presence of a Lewis acid catalyst. (Example 46) p-triphenylamine (50 mg, 0.204 mmol), N,N--diiodo-5,5-dimethylhydantoin (23 2.3 mg, 0.611 mmol) and dichloromethane (2 ml) The mixture was added with Sc(OTf)3 (10.03 mg, 0.0204 mmol) at 0 ° C, and then stirred at room temperature for 3 hours to carry out a reaction. In the reaction mixture, the reaction was terminated by adding a 5% by weight aqueous solution of sodium sulfite at 〇 °C. Next, after extracting the aqueous layer with chloroform at room temperature, the mixed organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated to give the product 4,4',4"-triiodide Triphenylamine (1 2 1 _ 4 mg, yield 96%). The measurement result of 1 H_NMR of the product was as follows, and the structural formula was confirmed. 'H-NMIUCDCh) δ 7_54 (d, J = 8.91 Hz, 6H), 6.81 (d, J = 8.91 Hz, 6H). (Example 47) except that Sc(OTf)3 of Example 46 was replaced with 13.4. The product of 4,4,4"-triiodotriphenylamine (1 05.9 mg, yield 83%) was obtained in the same manner as in Example 46 except for Mg Bi ( OTf) 3 (0.0204 mmol). The results are summarized in Table 7. [Table 7] Table 7

Lewis acid DIH

No. DIH (equivalent) Lewis acid (mol%) Solvent reaction temperature Reaction time (hours) Yield (3⁄4) Example 46 3 Sc(OT〇j (10) CHiCh Room temperature 3 96 «Example 47 3 Bi( OTf)» (10) CH2CI2 room temperature 3 83 DIH : Ν, Ν·-diiodo·5,5· dimethyl acetylene urea According to Table 7, as the Lewis acid, regardless of the use of Sc(OTf)3, Any of Bi(OTf)3 can carry out tetraiodination of the triarylamine derivative in high yield. Second, to another triarylamine derivative ν, ν, ν', ν·-tetra (benzene Iodine iodination of biphenyl-4,4'-diamine (Examples 48-51) except that the triphenylamine of Example 46 was substituted to use 50 mg of N,N,N',N'- The tetrakis(phenyl)biphenyl-4,4'-diamine was subjected to iodization in the same manner as in Example 46 except that the reaction was carried out under the conditions shown in Table 8. The results are shown in Table 8.

S -28- 201139338 [Table 8]

Table 8 Lewis acid DIH , nhQ-〇-nv 0 〇

No. Matrix (mg) DIH (equivalent > Lewis acid (mol%) Solvent reaction temperature Reaction time (hours) Yield (%) Example 48 50 4.5 Sc(OTf)3 (10) CICHiCHiCl 40*0 3 100 Implementation Example 49 50 4.5 Sc(OTf)* (10) C1CHjCH: C1 80ΐ 3 100 Example 50 50 4.5 Bi(OTf)j (10) ClCHiCHaCl 40t 3 100 Example 51 50 4.5 Βί(ΟΤί)ϊ (10> ClCH: CHiCl 80t 3 100 Example 52 1000 4.5 Bi(OTfMlO) CICH2CH2CI 40"C 3 100 DIH : Ν,Ν·-diiodo-5,5.-dimethylhydantoin As shown in Table 8, no matter which one Ν,Ν,Ν',ΙΤ-tetrakis(p-iodophenyl)biphenyl-4,4'-diamine can be obtained quantitatively. Secondly, iodination is carried out on a large scale. (Example 5 2 ) ,Ν·,Ν'-tetrakis(phenyl)biphenyl-4,4'diamine (1 OOOmg, 2.0mmol), N,N'-diiodo-5,5-dimethylhydantoin (3 a mixture of 50 g, 9.21 mmol) and 1,2-dichloroethane (40 mL), after adding B i (Ο T f) 3 ( 1 〇m ο 1 % ) at 〇 ° C, The reaction was carried out by stirring at 40 ° C for 3 hours. The reaction was stopped by adding a 5 wt% aqueous solution of sodium sulfite in 反应 ° C in the reaction mixture. Then, after extracting the aqueous layer with chloroform at room temperature, the mixed organic layer was washed with a saturated aqueous solution of sodium chloride. After drying over anhydrous magnesium sulfate, filtered and concentrated to obtain quantitatively, 组成, Ν, Ν·-tetrakis(p-iodophenyl)biphenyl-4,4·-diamine (2280 mg). •29-C.+ , 201139338 The results of H-NMR and 13C-NMR measurements of the composition are as follows. Confirm its structural formula: 1 H-NMR (CDC13) δ 7.54 (d, J = 8.91 Hz, 8H), 7.45 (d, J = 8.64 Hz, 4H), 7.10 (d, J = 8.64 Hz, 4H), 6.87 (d, J = 8.91 Hz, 8H). 13C-NMR (CDC13) δ 86.00, 1 24.65, 1 25.85, 1 27.63, 135.51, 138.25, 145.69, 146.85. Also, all h-NMR and 13C-NMR systems use JEOL The JNN LA500 spectrometer or the JEOL EX-207 spectrometer (all manufactured by JEOL) was used for measurement. Thus, an aromatic compound having a complicated structure such as a binaphthyl derivative, or a biphenyl derivative, or a triarylamine derivative, using N,N'-dihalogenated carbendazim, such as trifluoromethanesulfonic acid In the presence of a strong acid, it is not impossible to carry out halogenation or to form a complex mixture, and in the presence of a Lewis acid such as a metal halide or a metal triflate, it can be expected. Halogenated. In addition, from another triarylamine derivative of ruthenium, Ν'-diphenyl-N,N'- _(3-tolyl)-1, the plant-hydrazine can also be sampled for tetrakiloan, or four By bromination, a product of the above chemical formula (2-2) or (2-3) can be obtained. [Industrial Applicability] The method for producing a halogenated aromatic compound of the present invention is useful for halogen substitution of an aromatic ring hydrogen of an aromatic compound which is difficult to be directly halogenated. The halogenated aromatic compound obtained by this method can be used as a physiological activity

S -30- 201139338 A natural or pharmaceutical active ingredient intermediate, or a ligand for an asymmetric catalyst, or a raw material for an organic electroluminescent element or a substrate for improving its functionality. -31 -

Claims (1)

201139338 VII. Application of the patent fang κ~ a method for producing a halogenated aromatic compound ' By mixing ν, ν, · dihalogenated carbendazim with an aromatic compound, the aromatic ring hydrogen of the aromatic compound is Halogen substitution. 2. The method for producing a halogenated aromatic compound according to claim 1, wherein the hydrazine, Ν'-dihalogenated carbendazim is 5,5-dialkylethylene carbazide, hydrazine, Ν'-dibromo- 5,5-Dialkyl or hydrazine, hydrazine, -dichloro-5,5.dialkylacetyl carbazide. 3. The halogenated aromatic method according to the first aspect of the invention, wherein the Lewis acid is any one of a metal halide, an organic sulfonic acid metal salt, and an organic sulfonic acid semimetal salt. 4. The halogenated aromatic method according to claim 3, wherein the Lewis acid is the metal halide sulfonic acid metal salt, and the metal is Al, Sc, Ti, Fe, Zn In 'Sn and/or Bi. Or, in the case of the aforementioned semimetal halide or acid semimetal salt, the semimetal is B and/or Si. 5. The method for producing a halogenated aromatic compound according to claim 1, wherein the aromatic compound has an alkyloxy group, an aralkyl group, a hydroxyl group, a dialkylamino group, a diarylamine sulfenyl group, a dialkyl group. The at least one substituent or unsubstituted of a phosphinyl group, a diarylphosphino group, and a diaryl tH is a benzene derivative, a biphenyl derivative, or a triarylamine derivative. The invention is characterized in that at least one part of the compound is stored by Lewis acid, Ν'-diiodo-ethyl carbazide, at least a compound selected from the semimetal halogenation of the compound or the aforementioned organic, Zr, Nb, the aforementioned organic a sulfonate compound, an alkenyl group, an alkyl group, a dialkylphosphonium group selected organism, a binaphthyl group S-32-201139338 6 · A method for producing a halogenated aromatic compound according to claim i, wherein the aforementioned halogenated aromatic The group compound is any one of the compounds represented by the following chemical formulas (1) to (6) '[Chemical Formula 1] (In each of the chemical formulas (1) to (6), X is a halogen atom or a hydrogen atom of any one of a bromine atom and a chlorine atom which are the same or different from each other, and at least one of X in one molecule is the aforementioned halogen atom, R is an alkyl group having 1 to 18 carbon atoms which are the same or different from each other, and each of Ar is an aryl group). (7) The method for producing a halogenated aromatic compound according to the sixth aspect of the invention, wherein the halogenated aromatic compound is represented by the above chemical formula (2) is represented by the following chemical formulas (2-1) to (2-3) Either, [Chemical 2] -33- 201139338 Q 0 N-〇-〇-N η3^·βΓ , b, CH, (2-.3) 8. A halogenated aromatic compound characterized by the following chemical formula (2-1)~(2) -3) Any one of them, [Chemical 3] I 〇 _ _ 0 N-hQ-QN 0 (2-1) QQ _ _ 0 Q _ _ H3c-C/ 1 _ 丨"O~CH3 H3C-A /V-Br Βγ-(/,)-CH, (2 2) 0 N Br-Q-( (2-.3) 9. A halogenated reagent of an aromatic compound characterized by N,N'- The halogenated intramethylene urea and Lewis acid are composed, and at least a part of the aromatic ring hydrogen of the aromatic compound is substituted by halogen. ST -34- 201139338 The four designated representative figures: (1) The designated representative figure of the case is: none ( b) A brief description of the symbol of the representative figure: No 201139338 If there is a chemical formula in the case of this case, please disclose the chemical formula that best shows the characteristics of the invention: none