Organic hypervalent chlorine(V) compounds, methods for preparing the same, and use of the same as an electrophile

Abstract

To provide novel hypervalent organochlorine (V) compounds and methods for synthesizing them. [Solution] The compound represented by the following formula (I). R1-ClO2(I) (In the formula, R1 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted tertiary alkyl group.)

Description

Technical Field

[0001] The present invention relates to novel organo-hypervalent chlorine(V) compounds and methods for their preparation. The present invention also relates to their use as electrophiles for reacting with nucleophiles.

Background Art

[0002] Trivalent and pentavalent hypervalent organoiodine compounds function as excellent oxidants / electrophiles by driving the reduction to stable monovalent iodine compounds. Among them, diaryliodonium(III) (1 in Figure 1) is widely used in organic synthesis as an excellent reagent that can introduce various nucleophiles regardless of the electronic state of the aromatic ring due to its high electron-withdrawing property and leaving ability (Figure 1). In contrast, there are very few research examples of homologous hypervalent organochlorine compounds. Although a few syntheses and reactions have been reported for diarylchloronium(III) (2 in Figure 1) and perchlorylarenes(VII) (3 in Figure 1) (Non-Patent Documents 1 and 2), there have been no reported examples of hypervalent organochlorine(V) compounds.

Prior Art Documents

Non-Patent Documents

[0003]

Non-Patent Document 1

Non-Patent Document 2

Disclosure of the Invention

Problems to be Solved by the Invention

[0004] An object of the present invention is to provide novel hypervalent organochlorine(V) compounds and a method for synthesizing the same.

Means for Solving the Problems

[0005] In order to achieve the above object, the present inventors utilized the high arylation ability of diaryliodonium(III) and considered synthesizing a hypervalent organochlorine(V) compound (4 in FIG. 1) by reacting with a ClO2 , salt. As a result, it was found that chloraryl arene(V), which is a hypervalent organochlorine(V) compound, can be synthesized. In addition, the present inventors also found that an alkane compound having a chloraryl group can be synthesized by reacting an alkyl halide with a ClO2 - salt.

[0006] That is, the present invention has the following constitution. [1] A compound represented by the following formula (I). R1-ClO2 (I) (In the formula, R1 represents a substituted or unsubstituted aryl group or a substituted or unsubstituted tertiary alkyl group.) [2] The compound according to [1], represented by the following formula (Ia). TIFF2026048512000001.tif41153 (In the formula, R2 represents a monovalent substituent, and when n is 2 or more, each R2 may be the same or different; n represents an integer from 0 to 5.) <​​​​​​​​​The compound according to [1], wherein the tertiary alkyl group is an adamantyl group, a [lmn]bicyclopentyl group, a triphenylmethyl group, a cubyl group, a cyclopropyl group, or a cyclobutyl group. [5] (i) In a solution of the compound represented by the following formula (1), (a) at least one selected from methachloroperbenzoic acid, sodium perborate, oxone, sodium hypochlorite, potassium peroxodisulfate, sodium periodate, or Selectfluor, and (b) at least one selected from p-toluenesulfonic acid, trifluoromethanesulfonic acid, trifluoroacetic acid, or acetic acid The steps include adding [a certain compound], followed by adding 1,3,5-trimethoxybenzene to obtain a compound represented by formula (2), and TIFF2026048512000002.tif69155(ii) The compound represented by formula (2) is ClO2 - A step of reacting with a salt containing A method for preparing a compound represented by formula (Ia), which includes [the specified compound]. TIFF2026048512000003.tif42151(In equations (1), (2) and (Ia), R2 represents a monovalent substituent, and if n is 2 or greater, each R2 may be the same or different; n represents an integer between 0 and 5. [6] The compound represented by formula (Ia) is Nu - A method for preparing a compound represented by formula (II) by reacting it with a nucleophile represented by . TIFF2026048512000004.tif71163(In equations (Ia) and (II), R2 represents a monovalent substituent, and if n is 2 or greater, each R2 may be the same or different; n represents an integer between 0 and 5; Nu represents the substituent corresponding to the nucleophile. [7] The preparation method according to [6], wherein the nucleophile is a hard nucleophile. [Effects of the Invention]

[0007] The present invention makes it possible to provide novel hypervalent organochlorine (V) compounds and methods for synthesizing them. Furthermore, the hypervalent organochlorine (V) compounds obtained in this invention can be used as excellent electrophiles that can react with various nucleophiles. [Brief explanation of the drawing]

[0008] [Figure 1] The structures of various hypervalent halogen compounds are shown. [Figure 2] The crystal structure of 4-chlorylbiphenyl is shown. Embodiments for carrying out the invention

[0009] 1. Hypervalent organochlorine(V) compounds One embodiment of the present invention is a compound represented by the following formula (I) (hereinafter also referred to as "the compound of the present invention"). R1-ClO2(I)

[0010] In formula (I), R1 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted tertiary alkyl group.

[0011] Preferred aryl groups include phenyl, biphenyl, naphthyl, phenantrenyl, and anthracenyl groups.

[0012] If R1 is a substituted or unsubstituted aryl group, the compound of formula (I) can also be represented by the following formula (Ia). TIFF2026048512000005.tif45140

[0013] As will be described later in the synthesis method for the compound of formula (Ia), the present invention's synthesis method, which can synthesize the compound of formula (Ia), has been found to be applicable to various aromatic rings, such as aromatic rings having electron-withdrawing groups and aromatic rings having electron-donating groups. Therefore, R2 in formula (Ia) may be any monovalent substituent. Here, if n is 2 or greater, each R2 may be the same or different.

[0014] For example, R2 can be a halogen, an optionally substituted alkyl group, an optionally substituted phenyl group, or an ester group (-CO-OR3; R3 is selected from the group consisting of alkyl groups and carboxyl groups having 1 to 3 carbon atoms).

[0015] The halogen is preferably fluorine or chlorine.

[0016] Preferably, alkyl groups that may have substituents are alkyl groups having 1 to 15 carbon atoms that may have substituents, more preferably alkyl groups having 1 to 10 carbon atoms that may have substituents, and even more preferably alkyl groups having 1 to 6 carbon atoms that may have substituents. Examples of preferred alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, and tert-butyl groups. Furthermore, examples of substituents on alkyl groups include fluorine and chlorine. Examples of alkyl groups having substituents include trifluoromethyl, benzyl, diphenylmethyl, and (methoxycarbonyl)methyl groups.

[0017] Examples of phenyl groups that may have substituents include chlorophenyl groups, fluorophenyl groups, and methoxycarbonylphenyl groups.

[0018] Furthermore, if R2 consists of two adjacent alkyl groups on the benzene ring, these alkyl groups may together form a polycyclic aromatic ring with the benzene ring of formula (Ia), which may have substituents. Examples of polycyclic aromatic rings include naphthyl groups, phenantrenyl groups, and anthracenyl groups, with naphthyl groups being preferred.

[0019] n represents an integer between 0 and 5. In one preferred aspect of the compound of the present invention, n is 0 or 1.

[0020] If R1 is a substituted or unsubstituted alkyl group, it must be a tertiary alkyl group. This is because the RClO2 structure is difficult to decompose, and compounds with the RRCH-ClO2 structure are expected to be unstable (R represents an alkyl group). Preferred tertiary alkyl groups include adamantyl, [lmn]bicyclopentyl, triphenylmethyl, cubyl, cyclopropyl, or cyclobutyl groups. These bridgehead substrates are preferred because they readily generate cations and facilitate the introduction of ClO2. As the adamantyl group, a 1-bromoadamantyl group can be used.

[0021] 2. Method for synthesizing the compound of the present invention (1) Method for synthesizing the compound represented by formula (Ia) Another embodiment of the present invention is (i) a solution of a compound represented by the following formula (1) containing (a) at least one selected from methachloroperbenzoic acid, sodium perborate, oxone, sodium hypochlorite, potassium peroxodisulfate, sodium periodate or Selectfluor, and (b) at least one selected from p-toluenesulfonic acid, trifluoromethanesulfonic acid, trifluoroacetic acid, or acetic acid The steps include adding [a certain compound], followed by adding 1,3,5-trimethoxybenzene to obtain a compound represented by formula (2), and TIFF2026048512000006.tif66151(ii) The compound represented by formula (2) is ClO2 - A step of reacting with a salt containing This is a method for preparing a compound represented by formula (Ia), which includes (hereinafter also referred to as "Preparation Method 1 of the present invention"). TIFF2026048512000007.tif41154

[0022] In equations (1), (2), and (Ia), R2 represents a monovalent substituent, and when n is 2 or greater, each R2 may be the same or different, and n represents an integer from 0 to 5.

[0023] As a result of various studies conducted by the inventors, diaryliodan(III) represented by formula (2) (7 in the following synthesis scheme example) having a dummy ligand TMP group was synthesized by sequentially reacting iodoarene represented by formula (1) (5 in the following synthesis scheme example) with compound (a) (i.e., at least one compound selected from metachloroperbenzoic acid, sodium perborate, oxone (persulfate), sodium hypochlorite, potassium peroxodisulfate, sodium periodate, or Selectfluor), compound (b) (at least one compound selected from p-toluenesulfonic acid, trifluoromethanesulfonic acid, trifluoroacetic acid, or acetic acid), and 1,3,5-trimethoxybenzene (TMP-H, 6 in the following synthesis scheme example) (DR Stuart, et al. J. Org. Chem. 2016, 81, 1998.), followed by ClO2 - We found that chlorylarene (V), represented by formula (Ia) (example 4 in the following synthesis scheme), can be synthesized in good yield by reacting it with a salt containing (e.g., sodium chlorite). The TMP group of the dummy ligand is not converted to ClO2, allowing for the selective introduction of a ClO2 group onto a desired aryl group. This reaction proceeds via a mechanism called ligand coupling, which is difficult to carry out with electron-rich aromatic rings. Because the TMP group is very electron-rich, it does not react even when treated with various nucleophiles, and in preparation method 1 of the present invention, it is considered possible to selectively introduce a ClO2 group onto a desired aryl group.

[0024] Example of a synthesis scheme TIFF2026048512000008.tif26166R represents a monovalent substituent.

[0025] Furthermore, investigations into the substrate applicability of this reaction revealed that it can be applied to a wide range of aromatic rings regardless of their electronic state, from substrates with electron-withdrawing groups that favor the ligand coupling transition state to those with electron-donating groups. Therefore, in the above synthesis scheme, various monovalent substituents can be introduced into the benzene ring as R (corresponding to R2 in formulas (1), (2), and (Ia)).

[0026] As described in detail for the compounds of the present invention, R2 can be selected from, for example, a halogen, an optionally substituted alkyl group, an optionally substituted phenyl group, or an ester group (-CO-OR3; R3 is selected from the group consisting of alkyl groups having 1 to 3 carbon atoms and carboxyl groups).

[0027] The halogen is preferably fluorine or chlorine.

[0028] Preferably, alkyl groups that may have substituents are alkyl groups having 1 to 15 carbon atoms that may have substituents, more preferably alkyl groups having 1 to 10 carbon atoms that may have substituents, and even more preferably alkyl groups having 1 to 6 carbon atoms that may have substituents. Examples of preferred alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, and tert-butyl groups. Furthermore, examples of substituents on alkyl groups include fluorine and chlorine. Examples of alkyl groups having substituents include trifluoromethyl, benzyl, diphenylmethyl, and (methoxycarbonyl)methyl groups.

[0029] Examples of phenyl groups that may have substituents include chlorophenyl groups, fluorophenyl groups, and methoxycarbonylphenyl groups.

[0030] Furthermore, if R2 consists of two adjacent alkyl groups on the benzene ring, these alkyl groups may together form a polycyclic aromatic ring with the benzene ring of formula (Ia), which may have substituents. Examples of polycyclic aromatic rings include naphthyl groups, phenantrenyl groups, and anthracenyl groups, with naphthyl groups being preferred.

[0031] n represents an integer between 0 and 5. In one preferred aspect of the compound of the present invention, n is 0 or 1.

[0032] In step (i), a solution is prepared by dissolving the compound represented by formula (1) in an organic solvent such as MeCN, dichloroethane, or acetic acid. Compound (a) (i.e., at least one compound selected from metachloroperbenzoic acid, sodium perborate, oxone (persulfate), sodium hypochlorite, potassium peroxodisulfate, sodium periodate, or Selectfluor) and compound (b) (at least one compound selected from p-toluenesulfonic acid, trifluoromethanesulfonic acid, trifluoroacetic acid, or acetic acid) are added to the solution, followed by the addition of 1,3,5-trimethoxybenzene (TMP-H) to allow the reaction to proceed. The amount of m-CPBA, TsOH, and TMP-H to be added is preferably 1 to 1.1 equivalents of the compound represented by formula (1). The preferred order of addition is to add compound (a) and compound (b) first, stir the solution for a predetermined time, and then add TMP-H.

[0033] The reaction temperature is preferably from room temperature to 80 °C, more preferably 80 °C, and the reaction time is preferably about 30 minutes to 1 hour.

[0034] After the reaction is completed, the compound of formula (2) is usually purified by decantation, washing with an organic solvent such as diethyl ether, etc., and then subjected to the step (ii).

[0035] In the step (ii), an organic solvent or a mixed solvent of an organic solvent and water (for example, a mixed solvent of dichloroethane and water) is added to the mixture of the compound of formula (2) and a salt containing ClO₂ (for example, NaClO₂), and the mixture is vigorously stirred at a predetermined temperature for a predetermined time to allow the reaction to proceed. - As the salt containing ClO₂, in addition to NaClO₂, AgClO₂ can also be used. ClO₂ - As the salt containing ClO₂, in addition to NaClO₂, AgClO₂ can also be used. ClO₂ - The addition amount of the salt containing ClO₂ is preferably 5 to 10 equivalents relative to the amount of the compound of formula (2).

[0036] The reaction temperature is preferably about room temperature to 50 °C, and the reaction time is preferably about 12 hours to 72 hours.

[0037] After the reaction is completed, usually, the reaction mixture is poured into water, extracted with an organic solvent such as dichloromethane, and purified to recover the compound of formula (Ia).

[0038] (2) A method for synthesizing the compound of the present invention in which R¹ is a substituted or unsubstituted tertiary alkyl group. The compound of the present invention in which R¹ is a substituted or unsubstituted primary or secondary alkyl group can be obtained by the reaction of an alkyl halide with a ClO₂ salt. - In this case, as the ClO₂ salt, for example, silver chlorite etc. can be used. In this case, as the ClO₂ salt, for example, silver chlorite etc. can be used. - As the salt containing ClO₂, for example, silver chlorite etc. can be used. Furthermore, as alkyl halides, 1-bromoadamantane, bromo[1.1.1]bicyclopentane, bromo[2.2.2]bicyclooctane, bromo[3.1.1]bicycloheptane, bromocubane, trityl bromide, etc. can be used.

[0039] ClO2 - The amount of salt containing the specified compound added is preferably 2 to 5 equivalents relative to the amount of the halogenated alkane.

[0040] 3. Use of the compound of the present invention In the compounds of the present invention, particularly the compound represented by formula (Ia), the ClO2 group was found to be a strongly electron-withdrawing group comparable to that of the cyano and nitro groups. On the other hand, electrochemical measurements and reactions with reducing agents revealed that the ClO2 group, unlike the nitro group, has almost no oxidizing ability. Therefore, the inventors investigated the reactivity of chlorylarene (V) with various nucleophiles and found that it acts as an excellent electrophilic arylating agent with respect to various nucleophiles, preferably hard nucleophiles.

[0041] That is, another embodiment of the present invention involves a compound represented by formula (Ia) being Nu - This method involves reacting a nucleophile represented by the formula (II) with the compound represented by the formula (hereinafter also referred to as "Preparation Method 2 of the present invention"). TIFF2026048512000009.tif73158

[0042] In equations (Ia) and (II), R2 represents a monovalent substituent, and if n is 2 or greater, each R2 may be the same or different. n represents an integer between 0 and 5. Details regarding R2 and n are the same as those described in detail for the compounds of the present invention.

[0043] Nu represents the substituent corresponding to the nucleophile. The nucleophile is Nu - Since it is an anion represented by Nu, the substituent corresponding to the nucleophile is Nu- This refers to the part from which the negative charge has been removed.

[0044] As a nucleophile, a hard nucleophile is preferable. Preferably, such a nucleophile is a fluoride ion (F - ), chloride ions (Cl - ), alkoxide ions, hydroxide ions (HO - ), hydride ion (H - ), sulfide ions (S 2- ), cyanide ion (CN - ), azide ion (N3 - ), carboxylate ion (RCOO - :R is an alkyl group, such as a methyl group. Alkoxide ions include RO - (R is an alkyl group, such as a methyl group), PhO - It contains (phenoxide ions).

[0045] The amount of nucleophile added relative to the amount of compound represented by formula (Ia) can be appropriately determined depending on the type of nucleophile, but for example, it is 1 to 10 equivalents.

[0046] A compound represented by formula (Ia) is dissolved in a suitable organic solvent (ethanol, acetonitrile, DMSO, etc.), and to this solution, the compound used as the ion source for the nucleophile is added.

[0047] Examples of compounds used as ion sources for nucleophiles include, but are not limited to, potassium fluoride and tetrabutylammonium fluoride for fluoride ions, potassium phenoxide for phenoxide ions, sodium methoxide for methoxide ions, sodium hydroxide for hydroxide ions, sodium borohydride for hydride ions, sodium sulfide for sulfide ions, sodium cyanide for cyanide ions, and sodium azide for azide ions.

[0048] In the preparation method 2 of the present invention, the reaction temperature is preferably around room temperature to 100°C, and the reaction time is preferably around 1 to 24 hours.

[0049] Thus, the compounds of the present invention, particularly the compound represented by formula (Ia), act as excellent electrophilic arylating agents for various nucleophiles (preferably hard nucleophiles). In particular, with diaryliodan(III), F - While the reaction with requires high temperatures (usually above 100°C), the reaction with 4-chlorylbiphenyl, a compound of formula (Ia), as shown in the examples, can be carried out at room temperature.

[0050] Furthermore, as mentioned above, the compounds of the present invention are the first to introduce the -ClO2 functional group into an organic compound. Moreover, since -ClO2 has properties similar to those of a nitro group (-NO2), it is conceivable to use -ClO2 as a functional group to replace the nitro group, and the compounds of the present invention have high utility. [Examples]

[0051] The present invention will be described below based on examples, but the present invention is not limited to these examples.

[0052] 1. Samples and measuring instruments (1) Reagents Sodium chlorite: Purchased from Kanto Chemical. Silver chlorite: Prepared from sodium chlorite and silver nitrate. p-toluenesulfonic acid: Purchased from Tokyo Chemical Industry Co., Ltd. 1,3,5-Trimethoxybenzene: Purchased from Tokyo Chemical Industry Co., Ltd. Metachloroperbenzoic acid: Purchased from Fujifilm Wako Pure Chemical Industries. Arial iodide: Purchased from Tokyo Chemical Industry Co., Ltd. Alkyl bromide: Purchased from Tokyo Chemical Industry Co., Ltd. Dichloromethane: Purchased from Kanto Chemical. Acetonitrile: Purchased from Kanto Chemical. Deuterated chloroform: Purchased from Kanto Chemical.

[0053] (2) Measuring equipment NMR spectrum: Bruker Avance Neo FT-IR spectrum: JASCO FT / IR4700 ESI mass spectrum: Bruker Compact X-ray crystal analysis: Rigaku Synergy S

[0054] [Synthesis Example 1] 1. diaryl-λ 3 - Synthesis of iodane <Typical example> diaryl-λ 3 -The following shows a typical synthesis scheme for iodane.

[0055] TIFF2026048512000010.tif26168

[0056] To a solution of 4-iodobiphenyl (1.40 g, 4.99 mmol) dissolved in MeCN (5.0 mL), TsOH-H2O (0.973 g, 5.12 mmol) and m-CPBA (69%, 1.28 g, 5.12 mmol) were added while stirring, and the mixture was heated at 77°C for 30 minutes. Next, 1,3,5-trimethoxybenzene (0.947 g, 5.12 mmol) was added, and the mixture was stirred at the same temperature for another 5 minutes. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure to obtain a solid residue. The residue was washed several times with diethyl ether by decantation, and 4-biphenyl(1,3,5-trimethoxyphenyl)(tosyl)-λ 3 - Iodane (2.59 g, 84%) was obtained as a white solid. Further recrystallization with dichloromethane-hexane yielded the pure desired product as colorless needle-shaped crystals. 1H NMR (500 MHz, CDCl3) δ 7.97 (d, J = 8.7 Hz, 2H), 7.76 (d, J = 8.2 Hz, 2H), 7.52 (m, 4H), 7.47 (m, 2H), 7.42 (dd, J = 7.2, 1.5 Hz, 1H), 7.13 (d, J = 8.2 Hz, 2H), 6.21 (s, 2H), 3.93 (s, 6H), 3.90 (s, 3H), 2.33 (s, 3H) ppm.

[0057] 2. General synthetic methods for the synthesis of chlorylarenes <Typical examples> TIFF2026048512000011.tif24156

[0058] diaryl-λ 3 - A mixture of iodane (0.96 g, 1.56 mmol) and NaClO2 (1.50 g, 16.6 mmol) was mixed with dichloroethane (13.5 mL) and water (1.5 mL), and the mixture was vigorously stirred at 50°C for 72 hours. After cooling to room temperature, the reaction mixture was poured into water and extracted three times with dichloromethane. The combined organic layer was filtered and concentrated under reduced pressure to obtain an oily substance containing the target product (73% (determined using 1,1,2,2-tetrachloroethane as an internal standard)). 1 The yield of the 1H NMR spectrum was obtained. Subsequently, ethyl acetate:hexane (1:4, R) was used. f 4-chlorylbiphenyl (154 mg, 45%) was isolated as colorless needle-shaped crystals by purification using column chromatography with a coefficient of 0.42.

[0059] Mp. 115-117 C; 1 H NMR (500 MHz, CDCl3) δ 7.93 (d, J = 8.8 Hz, 2H), 7.83 (d, J = 8.8 Hz, 2H), 7.60 (dd, J = 8.0, 1.4 Hz, 2H), 7.50 (dd, J = 8.0. 7.2 Hz, 2H), 7.45 (tt, J = 7.2, 1.4 Hz, 1H) ppm.

[0060] [Synthesis Example 2] Using iodobenzene (1.1 g, 5.5 mmol), the diaryl-λ shown in Synthesis Example 1 was synthesized. 3 -Following the typical example of iodane synthesis, phenyl(1,3,5-trimethoxyphenyl)(tosyl)-λ 3 - Iodane (2.8g, 94%) was obtained as a white solid. TIFF2026048512000012.tif23164

[0061] Phenyl(1,3,5-trimethoxyphenyl)(tosyl)-λ 3 -Yordan: 1 H NMR (500 MHz, CDCl3) δ 7.89 (dd, J = 8.5, 1.0 Hz, 2H), 7.73 (d, J = 8.0 Hz, 2H), 7.46 (tt, J = 7.4, 1.0 Hz, 1H), 7.32 (dd, J = 8.5, 7.4 Hz, 2H), 7.1 (d, J = 8.0 Hz, 2H), 6.17 (s, 2H), 3.88 (s, 6H), 3.87 (s, 3H), 2.33 (s, 3H) ppm.

[0062] The aryl-λ obtained above 3 -Using iodane (g, mmol), chlorylbenzene with the following structure was synthesized according to the general synthesis method for chlorylarene shown in Synthesis Example 1. 1 ¹H NMR yield: 76%) was obtained as a colorless oil. TIFF2026048512000013.tif21157

[0063] 1 H NMR (500 MHz, CDCl3) δ 7.90-7.85 (2H, m), 7.71-7.63 (3H, m) ppm; 13 C NMR (125 MHz, CDCl3) δ 165.4, 133.5, 130.5, 120.4 ppm.

[0064] [Synthesis Example 3] Following the general synthesis method for chlorylarene shown in Synthesis Example 1, 4-chloryltoluene with the following structure was synthesized ( 1 ¹H NMR yield: 78%): Obtained as a pale yellow microcrystalline solid (recrystallized from CH2Cl2-hexane). TIFF2026048512000014.tif19160

[0065] mp. 36-37℃; 1 H NMR (500 MHz, CDCl3) δ 7.75 (d, J = 8.7 Hz, 2H), 7.43(d, J = 8.7 Hz, 2H), 2.48 (s, 3H) ppm.

[0066] [Synthesis Example 4] Following the general synthesis method for chlorylarene shown in Synthesis Example 1, 4-chloryltoluene with the following structure was synthesized ( 1 ¹H NMR yield: 78%): Obtained as a pale yellow microcrystalline solid (recrystallized from CH2Cl2-hexane). TIFF2026048512000015.tif21163

[0067] 4-Methyl chlorylbenzoate ( 1 HNMR yield 56%): White solid; 1 H NMR (500 MHz, CDCl3) δ 8.32 (d, J = 8.6 Hz, 2H), 7.96 (d, J = 8.6 Hz, 2H), 3.99 (s, 3H) ppm.

[0068] [Synthesis Example 5] Hydrolysis of methyl 4-chlorylbenzoate: TIFF2026048512000016.tif26160

[0069] A 0.33 M aqueous solution of methyl 4-chlorylbenzoate (100 mg, 0.495 mmol) was added to a 3.0 mL solution of MeCN, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted once with dichloromethane, and the separated aqueous phase was acidified to approximately pH 1 and extracted twice with ethyl acetate. The combined organic phase was dried, filtered, and concentrated under reduced pressure to obtain 4-chlorylbenzoic acid (72.5 mg, 78%) as a brown solid. Further purification was performed by recrystallization at 80°C using ethyl acetate-hexane to obtain the pure target product as colorless needle-shaped crystals. Mp. 217-218 ℃ (decomp.); 1 H NMR (500 MHz, CDCl3) δ 8.35 (d, J = 8.8 Hz, 2H), 7.98 (d, J = 8.8 Hz, 2H) ppm.

[0070] Including the chlorylarene (V) obtained in Synthesis Examples 1-5, the diaryl-λ shown in Synthesis Example 1 3 The following table summarizes the structures and yields of various chlorylarenes (V) synthesized using a typical example of iodane synthesis and the general synthetic method for chlorylarene synthesis shown in Synthesis Example 1.

[0071] [Table 1]

[0072] The yields in Table 1 are 1 The 1H NMR yield is shown, with the reaction temperature and time in parentheses indicating the synthesis of chlorylarene. Furthermore, for the 4f compound, the reaction time of 48 hours, as shown in Table 1, yielded almost the same results as in Example 1.

[0073] [Synthesis Example 6] 1-Chloryladamantane was synthesized using the following synthesis scheme.

[0074] TIFF2026048512000018.tif27156

[0075] To a solution of 1-bromoadamantane (47.1 mg, 0.22 mmol) in dichloromethane (1.5 mL), silver chlorite (115.5 mg, 0.66 mmol) was added at room temperature, and the suspension was vigorously stirred for 48 hours. The reaction mixture was filtered and concentrated under reduced pressure to obtain a pale yellow solid. Further purification by silica gel column chromatography (hexane) yielded 1-chloryladamantane (25.8 mg, 58%) as a white microcrystalline solid.

[0076] 1 H NMR (CDCl3, 600 MHz) δ 2.05-2.15 (m, 9H), 1.70-1.64 (m, 6H) ppm; 13 C NMR (CDCl3, 150 MHz) δ 69.0, 47.8, 35.7, 31.8 ppm; IR (ATR) 2906, 2852, 1450, 1342, 1293, 1030, 826, 690, 473 cm -1 .

[0077] [Example 1] Chlorylarene (V) is a stable solid / liquid at room temperature for extended periods and exhibits excellent solubility in low-polarity solvents such as toluene and ether. Furthermore, 1 H / 13 The almost complete lack of concentration dependence in the chemical shift of the 13C NMR spectrum suggests that the intermolecular interactions are weak. Therefore, when the solid structure of 4f (Table 1) obtained in Synthesis Example 1 was examined by X-ray crystallography, it was found, as expected, that the ClO2 group does not form clear intermolecular interactions (Figure 2). This is a characteristic in contrast to the related IO2 group, which forms a strong network due to hypervalence bonds. Furthermore, the bond angles between C1-C11-O1 / O2 and O1-C11-O2 are both close to 109°, suggesting that it adopts an onium structure, similar to other third-period elements. Upon closer examination of the properties of the obtained chlorylarene (V), it was found that the ClO2 group is a strongly electron-withdrawing group comparable to the cyano and nitro groups. On the other hand, electrochemical measurements and reactions with reducing agents revealed that the ClO2 group, unlike the nitro group, has almost no oxidizing ability. Next, we investigated the reactivity of chlorylarene (V) with various nucleophiles.

[0078] [Example 2] Reaction of chlorylarene (V) with nucleophiles (1) Fluorination Fluorination of 4-chlorylbiphenyl was performed using the following synthesis scheme.

[0079] TIFF2026048512000019.tif27160

[0080] To a solution of 4-chlorylbiphenyl (10.6 mg, 0.048 mmol) in MeCN (1.0 mL), TBAF-3H2O (57.0 mg, 0.181 mmol) was added under an argon atmosphere, and the mixture was stirred at 50°C for 24 hours. The reaction mixture was analyzed using AcOEt as an internal standard. 1 ¹H NMR analysis confirmed the formation of 4-fluorobiphenyl (yield 98%).

[0081] (2) O-arylation (nucleophilic substitution by phenoxide ion) O-arylation of 4-chlorylbiphenyl was performed using the following synthetic scheme.

[0082] TIFF2026048512000020.tif30158

[0083] To a solution of 4-chlorylbiphenyl (14.1 mg, 0.064 mmol) in MeCN (1.0 mL), potassium phenoxide (17.1 mg, 0.129 mmol) was added under an argon atmosphere, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was analyzed using AcOEt as an internal standard. 1¹H NMR analysis confirmed the formation of 4-biphenyl(phenyl) ether (yield 85%).

[0084] (3) O-arylation (nucleophilic substitution by methoxide ions) O-arylation of 4-chlorylbiphenyl was performed using the following synthetic scheme.

[0085] TIFF2026048512000021.tif28159

[0086] To a solution of 4-chlorylbiphenyl (11.2 mg, 0.051 mmol) in MeCN (1.0 mL), a methanol solution of 5.0 M sodium methoxide (50 μL, 0.25 mmol) was added under an argon atmosphere, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was analyzed using AcOEt as an internal standard. 1 ¹H NMR analysis confirmed the formation of 4-biphenyl methyl ether (yield 92%).

[0087] (4) Hydrogenation (nucleophilic substitution by boron hydride ions) 4-chlorylbiphenyl was hydrogenated using the following synthesis scheme.

[0088] TIFF2026048512000022.tif31165

[0089] To a solution of 4-chlorylbiphenyl (5.4 mg, 0.024 mmol) in EtOH (1.0 mL), sodium borohydride (2.0 mg, 0.053 mmol) was added under an argon atmosphere, and the mixture was stirred at room temperature for 21 hours. The reaction mixture was analyzed using AcOEt as an internal standard. 1 ¹H NMR analysis confirmed the quantitative formation of biphenyl.

[0090] (5) S-arylation (nucleophilic substitution by sodium sulfide ions) S-arylation of 4-chlorylbiphenyl was performed using the following synthetic scheme.

[0091] TIFF2026048512000023.tif25166

[0092] To a solution of 4-chlorylbiphenyl (5.5 mg, 0.025 mmol) in DMSO (1.0 mL), sodium sulfide (1.0 mg, 0.013 mmol) was added under an argon atmosphere, and the reaction mixture was stirred at 100°C for 23 hours. After cooling to room temperature, the reaction mixture was analyzed using AcOEt as an internal standard. 1 ¹H NMR analysis confirmed the formation of di(4-biphenyl) sulfide (yield 66%).

[0093] (6) Cyanation (nucleophilic substitution by cyanide ions) The following synthetic scheme was used to perform the cyanation of 4-chlorylbiphenyl.

[0094] TIFF2026048512000024.tif30166

[0095] To a solution of 4-chlorylbiphenyl (10.0 mg, 0.045 mmol) in DMSO (1.0 mL), potassium cyanide (5.9 mg, 0.091 mmol) was added under an argon atmosphere, and the mixture was stirred at 100°C for 3.5 hours. After cooling to room temperature, the reaction mixture was analyzed using methanol as an internal standard. 1 ¹H NMR analysis confirmed the formation of 4-cyanobiphenyl (yield 78%).

[0096] (7) N-arylation (nucleophilic substitution by azide ions) N-arylation of 4-chlorylbiphenyl was performed using the following synthetic scheme.

[0097] TIFF2026048512000025.tif29159

[0098] To a solution of 4-chlorylbiphenyl (11.6 mg, 0.053 mmol) in DMSO (1.0 mL), sodium azide (6.1 mg, 0.094 mmol) was added under an argon atmosphere, and the mixture was stirred at 100°C for 21 hours. After cooling to room temperature, the reaction mixture was analyzed using methanol as an internal standard. 1 ¹H NMR analysis confirmed the formation of 4-azide biphenyl (yield 88%).

[0099] As described above, chlorylarene (V), a hypervalent organochlorine compound (V) obtained in this invention, has been found to act as an excellent electrophilic arylating agent for various nucleophiles.

Claims

1. The compound represented by the following formula (I). R １ -ClO ２ (I) (In the formula, R １ (This represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted tertiary alkyl group.)

2. The compound according to claim 1, represented by the following formula (Ia). (In the formula, R ２ represents a monovalent substituent, and if n is 2 or greater, each R ２ They may be the same or different; n represents an integer between 0 and 5.

3. R ２ However, halogens, optionally substituted alkyl groups, optionally substituted phenyl groups, ester groups (-CO-OR ３ ;R ３ It is selected from the group consisting of alkyl groups and carboxyl groups having 1 to 3 carbon atoms. When n is 2 or more, each R ２ may be the same or different, Here, R ２ The compound according to claim 2, wherein if the alkyl groups are two adjacent alkyl groups on a benzene ring, these alkyl groups may together form a polycyclic aromatic ring with the benzene ring of formula (Ia), which may have substituents.

4. The compound according to claim 1, wherein the tertiary alkyl group is an adamantyl group, a [l.m.n]bicyclopentyl group, a triphenylmethyl group, a cubyl group, a cyclopropyl group, or a cyclobutyl group.

5. (i) In a solution of the compound represented by the following formula (1), (a) at least one selected from methachloroperbenzoic acid, sodium perborate, oxone, sodium hypochlorite, potassium peroxodisulfate, sodium periodate, or Selectfluor, and (b) at least one selected from p-toluenesulfonic acid, trifluoromethanesulfonic acid, trifluoroacetic acid, or acetic acid The steps include adding [a certain compound], followed by adding 1,3,5-trimethoxybenzene to obtain a compound represented by formula (2), and (ii) The compound represented by formula (2) is ClO ２ － A step of reacting with a salt containing A method for preparing a compound represented by formula (Ia), which includes [the specified compound]. (In equations (1), (2), and (Ia), R ２ represents a monovalent substituent, and if n is 2 or greater, each R ２ They may be the same or different; n represents an integer between 0 and 5.

6. The compound represented by formula (Ia) is L － A method for preparing a compound represented by formula (II) by reacting it with a nucleophile represented by . (In equations (Ia) and (II), R ２ represents a monovalent substituent, and if n is 2 or greater, each R ２ They may be the same or different; n represents an integer from 0 to 5; Nu represents the substituent corresponding to the nucleophile.

7. The preparation method according to claim 6, wherein the nucleophile is a hard nucleophile.

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