KR20120125573A - Novel method for preparing selenyl-substituted aromatic aldehyde compounds - Google Patents

Abstract

PURPOSE: A manufacturing method of selenyl-substituted aromatic aldehyde-based compound is provided to obtain selenyl-sbustituted aromatic aldehyde-based compound with high yield while minimizing generation of byproduct of a reaction. CONSTITUTION: A manufacturing method of selenyl-substituted aromatic aldehyde-based compound indicated in chemical formula 4 comprises: a step of preparing a reaction mixture comprising diselenide compound represented by A-Se-Se-A, solvent and a reducing agent; and a step of adding and reacting aromatic aldehyde-based starting material and base into the reaction mixture. The equivalent ratio of the diselenide compound and the reducing agent in the reaction mixture is 1:1/3-3.

Description

Novel method for producing selenyl-substituted aromatic aldehyde compounds {NOVEL METHOD FOR PREPARING SELENYL-SUBSTITUTED AROMATIC ALDEHYDE COMPOUNDS}

The present invention relates to a novel process for preparing selenyl-substituted aromatic aldehyde-based compounds, specifically, to form a selenolate nucleophile to nucleophilic aromatic aldehyde-based starting materials A novel process for the preparation of selenyl-substituted aromatic aldehyde compounds comprising substitution.

Recently, chalcogen chemistry has attracted great attention in the field of organic chemistry, and among the organic chalcogens, the biological activity of selenium (Se) is an emerging field of interest. Since the first synthesis of a nontoxic glutathione peroxide analog named Ebselene (2-phenylbenzisoselenazole-3 (2H) -one) (Ebselene (2-phenylbenzisoselenazol-3 (2H) -one), a stable organic selenium compound Considerable effort is being made to develop.

Among the organic selenium compounds, selenyl-substituted aromatic aldehyde compounds are good intermediates for the synthesis of benzoselenophenes having various biological activities. The selenyl-substituted aromatic aldehyde-based compound may be obtained by nucleophilic substitution of an aromatic aldehyde-based starting material using a selenolate nucleophile represented by A-Se ⁻ , wherein the selenolate nucleophile Can be formed by reducing the Se-Se bond of the diselenide compound represented by the general formula A-Se-Se-A.

Reduction of the Se-Se bond of the diselenide compound to form selenolate nucleophiles can be achieved based on several reducing agents such as NaBH ₄ , LiEt ₃ BH. In addition, metals such as indium, lanthanum, and samarium and salts thereof may also be used to reduce the Se-Se bond of the diselenide compound. However, it is difficult to obtain a selenyl-substituted aromatic aldehyde compound using the conventional methods described above. When these methods are used, the Se-Se bond of the diselenide compound is reduced and the aromatic aldehyde starting material is used. This is because the free aldehyde group of can be reduced or converted to another functional group. On the other hand, some catalytic processes may also be applied to reduce the Se-Se bond of the diselenide compound, but most of these catalytic processes have to undergo severe reaction conditions.

Herein, A-Se ^- Selenium carbonyl Using Selenium play rate nucleophile (selenolate nucleophile) represented by-A method for preparing a substituted aromatic aldehyde compound, di-selenide compound of Se-Se bonds are reduced to the celecoxib Solving the problem that the free aldehyde group of the aromatic aldehyde-based starting material is reduced or converted to another functional group at the same time as the oleate nucleophile is formed, a novel production method capable of producing a selenyl-substituted aromatic aldehyde-based compound with high yield is provided. To provide. Specifically, a selenolate nucleophile represented by A-Se ^- by reducing a diselenide compound represented by the general formula A-Se-Se-A using a substance containing a thiol group as a reducing agent. And a nucleophilic substitution of an aromatic aldehyde-based starting material using the selenolate nucleophile, to provide a novel process for preparing a selenyl-substituted aromatic aldehyde-based compound.

However, the problems to be solved by the present invention are not limited to the above-mentioned problems, and other problems not mentioned can be clearly understood by those skilled in the art from the following description.

One aspect of the present application, a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent is prepared, and the reaction mixture is represented by the following Chemical Formulas 1 to 3 Seleyl-substituted aromatic aldehyde represented by any one of the following formulas (4) to (6) corresponding to each of the above formulas (1) to (3), comprising adding and reacting the aromatic aldehyde-based starting material represented by either Methods for the preparation of selenyl-substituted aromatic aldehyde) compounds are provided:

[Formula 1]

[Formula 2]

(3)

[Formula 4]

[Chemical Formula 5]

[Formula 6]

Among the above formulas, R ₁ to R ₈ , A, A ₁ , A ₂ , and X are each specifically defined below.

In one embodiment of the present application, a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent is prepared, and the aromatic aldehyde starting material of Formula 1 is added to the reaction mixture. And a method of preparing a selenyl-substituted aromatic aldehyde-based compound of formula (4) comprising adding and reacting with a base:

[Formula 1]

[Formula 4]

Among the above equations,

R ₁ to R ₄ are each independently H; Aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl group, C _1-10 - alkoxy group, and an ether electron donor is selected from the group consisting of groups here (electron donating group); Or an electron withdrawing group selected from the group consisting of halo, nitro, cyano, and carbonyl groups,

Substituted with an alkyl group-A is C _{1 -10} which may be substituted - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl} group, an allyl group, an aromatic group, one or two C _{1 -10} An aromatic ring group, an aromatic ring group substituted with a halo group, or an aromatic ring group substituted with a nitro group,

A ₁ is C, or N,

X is a halo group.

Another embodiment of the present application is to prepare a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent, and to the reaction mixture, an aromatic aldehyde starting material of Formula 2 And a method of preparing a selenyl-substituted aromatic aldehyde-based compound of formula (5) comprising adding and reacting with a base:

[Formula 2]

[Chemical Formula 5]

Among the above equations,

R ₅ and R ₆ are each independently H; Aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl, C _{1 -10} - alkoxy group, and an ether electron donor is selected from the group consisting of groups here; Or an electron withdrawing group selected from the group consisting of a halo group, a nitro group, a cyano group, and a carbonyl group,

Substituted with an alkyl group-A is C _{1 -10} which may be substituted - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl} group, an allyl group, an aromatic group, one or two C _{1 -10} An aromatic ring group, an aromatic ring group substituted with a halo group, or an aromatic ring group substituted with a nitro group,

A ₁ is C, or N,

X is a halo group.

Another embodiment of the present application is to prepare a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent, and to the reaction mixture, an aromatic aldehyde starting material of Formula 3 And a method of preparing a selenyl-substituted aromatic aldehyde-based compound of Formula 6, which comprises adding and reacting with a base:

(3)

[Formula 6]

Among the above equations,

R ₇ and R ₈ are each independently H; Aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl, C _{1 -10} - alkoxy group, and an ether electron donor is selected from the group consisting of groups here; Or an electron withdrawing group selected from the group consisting of a halo group, a nitro group, a cyano group, and a carbonyl group,

Substituted with an alkyl group-A is C _{1 -10} which may be substituted - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl} group, an allyl group, an aromatic group, one or two C _{1 -10} An aromatic ring group, an aromatic ring group substituted with a halo group, or an aromatic ring group substituted with a nitro group,

A ₂ is O, S, or Se,

X is a halo group.

Another aspect of the present application provides a selenyl-substituted aromatic aldehyde compound represented by any one of the following Chemical Formulas 4 to 6.

[Formula 4]

[Chemical Formula 5]

[Formula 6]

Among the above equations,

R ₁ to R ₈ are each independently H; Aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl group, C _1-10 - alkoxy group, and an ether electron donor is selected from the group consisting of groups here; Or an electron withdrawing group selected from the group consisting of a halo group, a nitro group, a cyano group, and a carbonyl group,

Substituted with an alkyl group-A is C _{1 -10} which may be substituted - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl} group, an allyl group, an aromatic group, one or two C _{1 -10} An aromatic ring group, an aromatic ring group substituted with a halo group, or an aromatic ring group substituted with a nitro group,

A ₁ is C, or N,

A ₂ is O, S, or Se,

X is a halo group.

Herein, the selenate nucleophile represented by A-Se ⁻ is formed by reducing the diselenide compound represented by the general formula A-Se-Se-A using a substance containing a thiol group as a reducing agent. A novel process for the preparation of selenyl-substituted aromatic aldehyde compounds, including nucleophilic substitution of aromatic aldehyde-based starting materials using the selenolate nucleophiles, is provided.

The novel process for producing a selenyl-substituted aromatic aldehyde-based compound according to the present application, by using a material containing a thiol group as a reducing agent, so that the free aldehyde group of the aromatic aldehyde-based starting material is not reduced or converted into another functional group Se-Se bonds of the selenide compounds can be selectively reduced to significantly increase the yield of selenyl-substituted aromatic aldehyde compounds compared with the use of reducing agents such as NaBH ₄ and LiEt ₃ BH. have. In addition, by using the diselenide compound represented by the general formula A-Se-Se-A as a substance for forming the selenolate nucleophile, ease of handling and sufficient reactivity can be ensured. In addition, by adding the base, the reducing agent containing the thiol group may be negatively charged thiolate (RS ⁻ ) to enhance its reducing power. On the other hand, the thiolate has a problem that is more reactive to the diselenide compound. Therefore, the present application solves the problem by adding the base during the reaction after the addition of the aromatic aldehyde-based starting material, by allowing the thiolate to attack the aryl group of the aromatic aldehyde-based starting material to selectively undergo a nucleophilic substitution reaction The yield of the final product was improved.

In addition, in the present application, in order to increase the yield of the selenyl-substituted aromatic aldehyde-based compound which is the final product, it is advantageous to use a strong base when the aromatic aldehyde-based starting material includes an electron donating substituent, whereas the aromatic aldehyde-based It is advantageous to use weak bases when the starting materials contain electron withdrawing substituents. That is, the yield of the final product can be increased by adjusting the type of the base used according to the properties of the substituent of the aromatic aldehyde starting material.

The selenyl-substituted aromatic aldehyde compounds obtained in high yield while minimizing reaction by-products according to the present application can be used as useful intermediates in the synthesis of benzoselenophenes having various biological activities.

Hereinafter, embodiments and examples of the present application will be described in detail so that those skilled in the art can easily practice the present invention. It should be understood, however, that the present invention may be embodied in many different forms and is not limited to the embodiments and examples described herein.

Throughout the specification, when a part is said to "include" a certain component, it means that it can further include other components, without excluding other components unless specifically stated otherwise.

As used herein, the terms "about", "substantially", and the like, are used at, or in proximity to, the numerical values of the preparations and material tolerances inherent in the meanings mentioned, and assist in the understanding of the present application. In order to prevent the unfair use of unscrupulous infringers. Also, throughout the present specification, the phrase " step "or" step "does not mean" step for.

In the present application, "C _{1 -10} - group" and "optionally substituted C _{1 -10} - alkyl group" in the "C _1-10 - alkyl group" are, respectively, a linear or branched, saturated or unsaturated, It may be an alkyl group having 1 to 10 carbon atoms, for example, may include methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, or isomers thereof, but is not limited thereto. .

In the present application, "which may be substituted with a C _{1 -10} - alkyl group" in substituent group may have is, for example, an alkyl group, a hydroxy group, an alkoxy group, a haloalkyl group, a nitrile group, a nitro group; Alternatively, the aryl group may be substituted with an alkyl group, a hydroxy group, an alkoxy group, a halo group, a nitrile group, or a nitro group, but is not limited thereto. Further, in the present application, "which may be substituted with a C _{1 -10} - alkyl group" is not intended to be one having a double bond or triple bond, but limited.

In the present application, "C _{1 -10} - alkylene group" is a linear or branched, saturated or unsaturated, may be alkylene date of 1 to 10 carbon atoms, e.g., methylene, ethylene, propylene, butylene, It may include, but is not limited to, pentylene, hexylene, hexylene, octylene, nonylene, decylene, or isomers thereof.

In the present application, "C _{1 -10-alkoxycarbonyl} group" defined above - but may be to include a "C _{1 -10} alkyl group" and oxygen atom-bonded alkoxy group, without being limited thereto.

As used herein, "halo group" may be, but is not limited to, F, Cl, Br, or I.

In the present application, the "aromatic hydrocarbon group" and the "aromatic ring group" which may have a substituent each have a phenyl group which may have a substituent, a benzyl group which may have a substituent, a toluyl group which may have a substituent, and a substituent It may be a styrenyl group, or a naphthalene group which may have a substituent, but is not limited thereto.

In the present application, "C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl"} is defined above may be a group containing a - - "alkyl group C _{1 -10"} "C _{1 -10} alkoxy group" and However, the present invention is not limited thereto.

In the present application, "allyl group" is an allyl group, that is, C _{3 -10} having a carbon number of 3 to 10, but it is not to notify group, limited.

In one embodiment of the present application, a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent is prepared, and the aromatic aldehyde of Formula 1 is added to the reaction mixture. Provided is a method for preparing a selenyl-substituted aromatic aldehyde compound of Formula 4, including reacting with a system starting material and adding a base:

[Formula 1]

[Formula 4]

Among the above equations,

R ₁ to R ₄ are each independently H; Aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl group, C _1-10 - alkoxy group, and an ether electron donor is selected from the group consisting of groups here (electron donating group); Or an electron withdrawing group selected from the group consisting of halo, nitro, cyano, and carbonyl groups,

Substituted with an alkyl group-A is C _{1 -10} which may be substituted - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl} group, an allyl group, an aromatic group, one or two C _{1 -10} An aromatic ring group, an aromatic ring group substituted with a halo group, or an aromatic ring group substituted with a nitro group,

A ₁ is C, or N,

X is a halo group.

For example, A is optionally substituted C _{1 -10-alkyl} group substituted by a - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl,} C _{3 -10-allyl} group, C _{1 -10} Benzyl group, benzyl group substituted with halo group, benzyl group substituted with nitro group, or benzyl group, but is not limited thereto.

Another embodiment of the present application is to prepare a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent, and to the reaction mixture, an aromatic aldehyde starting material of Formula 2 And a method of preparing a selenyl-substituted aromatic aldehyde-based compound of formula (5) comprising adding and reacting with a base:

[Formula 2]

[Chemical Formula 5]

Among the above equations,

R ₅ and R ₆ are each independently H; Aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl group, C _1-10 - alkoxy group, and an ether electron donor is selected from the group consisting of groups here; Or an electron withdrawing group selected from the group consisting of a halo group, a nitro group, a cyano group, and a carbonyl group,

Substituted with an alkyl group-A is C _{1 -10} which may be substituted - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl} group, an allyl group, an aromatic group, one or two C _{1 -10} An aromatic ring group, an aromatic ring group substituted with a halo group, or an aromatic ring group substituted with a nitro group,

A ₁ is C, or N,

X is a halo group.

For example, A is optionally substituted C _{1 -10-alkyl} group substituted by a - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl,} C _{3 -10-allyl} group, C _{1 -10} Benzyl group, benzyl group substituted with halo group, benzyl group substituted with nitro group, or benzyl group, but is not limited thereto.

Another embodiment of the present application is to prepare a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent, and to the reaction mixture, an aromatic aldehyde starting material of Formula 3 And a method of preparing a selenyl-substituted aromatic aldehyde-based compound of Formula 6, which comprises adding and reacting with a base:

(3)

[Formula 6]

Among the above equations,

R ₇ and R ₈ are each independently H; Aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl, C _{1 -10} - alkoxy group, and an ether electron donor is selected from the group consisting of groups here; Or an electron withdrawing group selected from the group consisting of a halo group, a nitro group, a cyano group, and a carbonyl group,

Substituted with an alkyl group-A is C _{1 -10} which may be substituted - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl} group, an allyl group, an aromatic group, one or two C _{1 -10} An aromatic ring group, an aromatic ring group substituted with a halo group, or an aromatic ring group substituted with a nitro group,

A ₂ is O, S, or Se,

X is a halo group.

For example, A is optionally substituted C _{1 -10-alkyl} group substituted by a - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl,} C _{3 -10-allyl} group, C _{1 -10} Benzyl group, benzyl group substituted with halo group, benzyl group substituted with nitro group, or benzyl group, but is not limited thereto.

In one embodiment of the present application, the base may be added sequentially after the aromatic aldehyde-based starting material to the reaction mixture, but is not limited thereto. For example, the base used to prepare the selenyl-substituted aromatic aldehyde-based compound may be added sequentially after stirring by adding the aromatic aldehyde-based starting material to the reaction mixture, but is not limited thereto. no. The stirring time may be 10 minutes or more, but is not limited thereto. The addition of the base allows the reducing agent containing the thiol group to be converted into a negatively charged thiolate (RS ⁻ ), thereby improving its reducing power.

For example, the reaction for producing the thiolate anion using a reducing agent containing a thiol group as the reducing agent can be illustrated as the following reaction mechanism:

On the other hand, the thiolate anion has a problem that the reactivity to the diselenide compound is stronger. That is, when the base is added from the step of preparing the reaction mixture, which is the first step of the reaction, or when the base is added to the reaction mixture together with the aromatic aldehyde-based starting material, the thiolate anion is the aromatic aldehyde-based The yield of the final target product can be lowered by first reacting with the diselenide compound rather than attacking the aryl group of the starting material. Therefore, the problem is solved by adding the aromatic aldehyde-based starting material and stirring for a predetermined time, and then adding a base in the middle of the reaction, so that the thiolate anion attacks the aryl group of the aromatic aldehyde-based starting material and the nucleophilic substitution reaction By selectively occurring, the yield of the final product can be improved.

For this reason, in one embodiment of the present application provides a method for preparing a selenyl-substituted aromatic aldehyde-based compound in which the aromatic aldehyde-based starting material is added to the reaction mixture and stirred, and then the base is sequentially added. However, the manufacturing method of the present application is not limited thereto. For example, when an aromatic aldehyde-based starting material is added to the reaction mixture including a diselenide compound, a solvent, and a reducing agent, and the base is added after stirring for a predetermined time, the aromatic aldehyde-based starting material is included within a few minutes. It was observed that the nucleophilic substitution reaction was preferred at the halo position, resulting in the formation of the desired reaction product, the selenyl-substituted aromatic aldehyde-based compound.

In one embodiment of the present application, the solvent may be selected and used without particular limitation as long as it can easily dissolve the diselenide compound and the reducing agent included in the reaction mixture. For example, the solvent is dimethylformaldehyde (DMF), dimethylsulfoxide (DMSO), tetrahydrofuran (THF), CH ₂ Cl ₂ , CH ₃ CN, CH ₃ NO ₂ , CHCl ₃ , ClCH ₂ CH ₂ Cl , Alcohols, aromatic solvents, and combinations thereof may be included, but is not limited thereto. For example, the alcohols may include methanol, ethanol, propanol, or butanol, and the aromatic solvent may include benzene, toluene, or derivatives thereof, but is not limited thereto.

In one embodiment of the present application, the reducing agent may include a thiol group, but is not limited thereto. For example, the reducing agent may include a material containing one or more thiol groups, but is not limited thereto. For example, the reducing agent may include a substance containing one or two thiol groups, for example, dithiothreitol (DTT), an isomer of dithiothreitol, cysteine, N -acetylcysteine , N-balk-cysteine (N -Boc-cysteine) and, but could be to include alkane dithiols such as a derivative, or 1,4-butane dithiol or 1,6-dithiol nucleic acid of a similar cysteine, limited to It is not. In order to prepare the selenyl-substituted aromatic aldehyde-based compound, in the prior art, some reducing agents that do not contain a thiol group such as NaBH ₄ , LiEt ₃ BH have been used. Also, metals such as indium, lanthanum, and samarium and salts thereof have been used to reduce Se-Se bonds of the diselenide compounds to produce selenate nucleophiles. However, it is difficult to obtain a selenyl-substituted aromatic aldehyde compound using the conventional methods described above. When these methods are used, the Se-Se bond of the diselenide compound is reduced and the aromatic aldehyde starting material is used. This is because the free aldehyde group of can be reduced or converted to another functional group. Herein, by using a substance containing a thiol group as described above as a reducing agent instead of the conventional methods described above, the free aldehyde group of the aromatic aldehyde-based starting material is prevented from being reduced or converted into other functional groups, Se-Se bonds of the amide compounds could be selectively reduced, resulting in a significant increase in the yield of the desired reaction product. That is, by using a material containing a thiol group as the reducing agent, it is possible to increase the yield of the selenyl-substituted aromatic aldehyde compound and minimize unnecessary side reactions.

In one embodiment of the present application, in order to increase the yield of the selenyl-substituted aromatic aldehyde-based compound that is the final product, it is advantageous to use a strong base when the aromatic aldehyde-based starting material includes an electron donating substituent, while the aromatic When the aldehyde-based starting material includes an electron withdrawing substituent, it is advantageous to use a weak base, but is not limited thereto. That is, by adjusting the type of the base to be used according to the properties of the substituent of the aromatic aldehyde starting material, the yield of the desired reaction product can be increased.

In one embodiment of the present application, each of the substituents R ₁ to R ₄ of the formula 1 wherein the aromatic aldehyde-based starting material is independently an aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl, C _{1 -10} - alkoxy group, , And an electron donor group selected from the group consisting of an ether group, and the base may include a strong base, but is not limited thereto.

In one embodiment of the present application, each of the substituents R ₅ and R ₆ of the aromatic aldehyde-based starting material in the above formula (2) are independently an aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl, C _{1 -10} - alkoxy group, , And an electron donor group selected from the group consisting of an ether group, and the base may include a strong base, but is not limited thereto.

In one embodiment of the present application, substituents R ₇ and R ₈ of Chemical Formula 3 which are the aromatic aldehyde-based starting materials Each independently represent an aromatic hydrocarbon group, an amine group, C _{1 -10-one} which is to contain the electron donor is selected from an alkoxy group, and the group consisting of a polyether, wherein the base comprises a strong base - alkyl, C _{1 -10} May be, but is not limited thereto.

For example, the strong base may be DBU (1,8-diazabicyclo [5,4,0] undec-7-ene), KOH, NaOH, Ca (OH) ₂ , Ba (OH) ₂ , KOtBu, or a combination thereof It may be to include, but is not limited thereto.

In one embodiment of the present application, each of the substituents R ₁ to R ₄ of the formula 1 which is the aromatic aldehyde-based starting material independently includes an electron withdrawing group selected from the group consisting of a halo group, a nitro group, a cyano group, and a carbonyl group The base may include a weak base, but is not limited thereto.

In one embodiment of the present application, each of the substituents R ₅ and R ₆ of Formula 2 which is the aromatic aldehyde-based starting material independently includes an electron withdrawing group selected from the group consisting of a halo group, a nitro group, a cyano group, and a carbonyl group The base may include a weak base, but is not limited thereto.

In one embodiment of the present application, substituents R ₇ and R ₈ of Chemical Formula 3 which are the aromatic aldehyde-based starting materials Each independently includes an electron withdrawing group selected from the group consisting of a halo group, a nitro group, a cyano group, and a carbonyl group, and the base may include a weak base, but is not limited thereto.

For example, the weak base may include, but is not limited to, K ₂ CO ₃ , KHCO ₃ , Na ₂ CO ₃ , NaHCO ₃ , NaOEt, NH ₄ OH, or a combination thereof.

For example, when using a material containing an electron donating substituent as the aromatic aldehyde-based starting material, using a weak base such as NaOEt it is difficult to obtain the desired product, while using a strong base such as DBU in a high yield It may be prepared, but is not limited thereto.

In one embodiment of the present application, preparing the reaction mixture may be performed at room temperature to 100 ° C, but is not limited thereto. In addition, in one embodiment of the present application, the reaction by adding the aromatic aldehyde-based starting material, and the base to the reaction mixture may be carried out at room temperature to 100 ℃, but is not limited thereto.

The selection of the reaction temperature does not have a direct effect on obtaining a desired product in high yield in the reaction, and thus the reaction temperature can be selected without particular limitation as long as it is not in a temperature range that does not greatly limit the reactivity. For example, the reaction mixture is prepared and stirred at room temperature, the aromatic aldehyde-based starting material is added to the reaction mixture and stirred at room temperature for a predetermined time, and then the base is added and the mixture is stirred at room temperature. Aromatic aldehyde-based compounds may be prepared, but are not limited thereto.

In one embodiment of the present application, the diselenide compound and the reducing agent in the reaction mixture may be included in an equivalent ratio of about 1: about 1/3 to about 3, but is not limited thereto. For example, the diselenide compound and the reducing agent may be included in the reaction mixture in an equivalent ratio of about 1: about 1/3 to about 3, or about 1: about 1/3 to about 2, but the present application is limited thereto. It doesn't happen.

The equivalent ratio of the diselenide compound and the reducing agent may be controlled without particular limitation in a range sufficient to reduce the Se-Se bond of the diselenide compound as the reducing agent to form a selenoleate nucleophile required for a nucleophilic substitution reaction. In addition, the equivalent ratio may vary depending on the type of diselenide compound and / or the type of reducing agent.

In one embodiment of the present application, the method for producing a selenyl-substituted aromatic aldehyde-based compound, the diselenide compound represented by the general formula A-Se-Se-A contained in the reaction mixture is the reducing agent the reduction is a-Se by ^- forming a celecoxib play rate nucleophile (selenolate nucleophile) represented by, and the selenide play rate nucleophile by substituting a nucleophilic reaction with the aromatic aldehyde-based starting materials the celecoxib carbonyl-based substituted aromatic aldehyde It may be to form a compound, but is not limited thereto. Among the reaction steps provided in the embodiment, the mechanism of the reaction in which the diselenide compound is reduced by the reducing agent to form the selenoleate nucleophile is shown in the following scheme. For example, the following scheme is shown using dimethyldiselenide (DMDS) as the diselenide compound and dithiothreitol (DTT) as the reducing agent, but the present application is not limited thereto.

Another aspect of the present application provides a selenyl-substituted aromatic aldehyde-based compound represented by any one of Formulas 4 to 6 below:

[Formula 4]

[Chemical Formula 5]

[Formula 6]

Among the above equations,

R ₁ to R ₈ are each independently H; Aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl group, C _1-10 - alkoxy group, and an ether electron donor is selected from the group consisting of groups here (electron donating group); Or an electron withdrawing group selected from the group consisting of halo, nitro, cyano, and carbonyl groups,

Substituted with an alkyl group-A is C _{1 -10} which may be substituted - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl} group, an allyl group, an aromatic group, one or two C _{1 -10} An aromatic ring group, an aromatic ring group substituted with a halo group, or an aromatic ring group substituted with a nitro group,

A ₁ is C, or N,

A ₂ is O, S, or Se,

X is a halo group.

For example, A is optionally substituted C _{1 -10-alkyl} group substituted by a - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl,} C _{3 -10-allyl} group, C _{1 -10} Benzyl group, benzyl group substituted with halo group, benzyl group substituted with nitro group, or benzyl group, but is not limited thereto.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present application is not limited thereto.

[ Example ]

All of the reagents used in this example are those commercially available, and unless otherwise specified, are used without special purification.

Synthesis Process

Hereinafter, the selenyl-substituted aromatic aldehyde compounds disclosed in the examples were prepared by the synthesis process as follows.

First, in order to prepare the reaction mixture, each of the diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent was prepared. A diselenide compound represented by the general formula A-Se-Se-A in the reaction mixture, wherein A is 1.2 equivalents of methyl group (1.2 eq. Me), 0.6 equivalents of phenyl group (0.6 eq. Ph), or 0.6 A diselenide compound having an equivalent benzyl group (0.6 eq. Bn) was used. As the solvent in the reaction mixture, anhydrous ethanol (EtOH) or dimethylformaldehyde (DMF) was used. As a reducing agent in the reaction mixture, 1 eq of dithiothreitol (dithiothreitol, DTT), 1 equivalent of N - acetyl cysteine (N -acetylcysteine), or one equivalent of 1,4-butane dithiol (1,4-butanedithiol ) Was used.

More specifically, the diselenide compound represented by the general formula A-Se-Se-A and the reducing agent were added to 2 mL of the solvent in the reaction mixture. In the diselenide compound, when the functional group A is a methyl group, the equivalent ratio of the diselenide compound and the reducing agent was 1.2: 1. On the other hand, when the functional group A in the diselenide compound is a phenyl group or a benzyl group, the equivalent ratio of the diselenide compound and the reducing agent was 0.6: 1. The reaction mixture was stirred for 30 minutes, at which time the temperature was maintained at room temperature, or 80 ° C.

After preparing the reaction mixture, an aromatic aldehyde compound, which is a starting material for preparing the selenyl-substituted aromatic aldehyde compound, was added to the reaction mixture at once and stirred for 15 minutes. The temperature at the time of stirring was maintained at room temperature or 80 degreeC in this case also.

A strong base DBU, a weak base K ₂ CO ₃ , or a weak base NaOEt was used as the base to be added after the starting material was added to the reaction mixture and stirred. The base was added to the reaction mixture by 2 equivalents at room temperature and stirred for 15 minutes. The temperature at the time of stirring was maintained at room temperature or 80 degreeC in this case also.

After adding the base and agitating, it was confirmed by thin layer chromatography (TLC) that the starting material was consumed completely. The solvent contained in the reaction mixture was removed under vacuum, and the crude solid was extracted three times with 25 mL of dichloromethane: water (1: 1) solvent. The organic phase collected through the extraction process was dried using MgSO ₄ in anhydrous environment, and the solvent was evaporated in vacuo. The residue was purified by column chromatography using silica gel column. The pure product, ie the selenyl-substituted aromatic aldehyde compound to be prepared in this example was eluted with ethyl acetate and hexane, the yields are shown in Tables 1 to 3 below.

The yield of the selenyl-substituted aromatic aldehyde-based compound was different depending on the experimental conditions. Specifically, what was used as the diselenide compound, the solvent, and the reducing agent included in the reaction mixture, and the aromatic aldehyde starting material added to the reaction mixture, and what was used as the base, respectively, in the reaction yield Affected. Analyze the effect of the type of reducing agent on the yield through Experimental Example 1, the effect of the type of base on the yield through Experimental Example 2, the kind of diselenide compound through Experimental Example 3, and The effect of the type of aromatic aldehyde-based starting material on the yield can be analyzed, which will be described in more detail below.

[ Experimental Example  One]

In Experimental Example 1, in order to produce 2-methylselenyl-5-nitro-benzaldehyde, as in the above reaction scheme, dimethyl diselenide (A) was used as the diselenide compound. dimethyldiselenide, DMDS, MeSeSeMe) and 5-nitro-2-chloro-benzaldehyde were used as the aromatic aldehyde-based starting materials. The other materials, ie, the solvent, the reducing agent, and the base, were tested in various ways without being fixed. The differences in% yields of the products resulting from these differences in reaction conditions are shown in Table 1 below:

Entry
D MDS
( eq .) Reducing agent ( eq .) Base ( eq .) menstruum Time (h) Temperature
(° C) product
(%yield) One
(Comparative Example) One NaBH ₄ (One) NaOEt EtOH 5 60 0 2
(Comparative Example) 2 NaBH ₄ (2) - EtOH 24 Room temperature 3 3
(Comparative Example) 2 NaBH ₄ (2) - DMF 24 Room temperature 5 4
(Comparative Example) One NaBH ₄ (One) - THF 6 60 0 5
(Comparative Example) One - K ₂ CO ₃ (2.5) DMF 14 0 - 6
(Example) One DTT  (One) NaOEt  (2) EtOH 4 Room temperature 85 7
(Example) One DTT  (2) NaOEt  (2) DMF One Room temperature 85 8
(Example) 1.2 DTT  (One) K ₂ CO ₃ (2.5) DMF One Room temperature 85 9
(Example) 1.2 DTT  (One) DBU  (2) DMF 3 Room temperature 84 10
(Example) One N -Acetylcysteine (2) NaOEt  (2) DMF One Room temperature 79 11
(Example) 1.2 N -Acetylcysteine (2) DBU  (2) DMF 3 Room temperature 79 12
(Example) One 1,4- Butanedithiol  (2) NaOEt  (2) DMF 2 Room temperature 82 13
(Example) 1.2 1,4- Butanedithiol  (2) DBU  (2) DMF 3 Room temperature 82

As shown in Table 1, in Entry 1, NaBH ₄ was used as a reducing agent for reducing the Se-Se bond of dimethyldiselenide (DMDS), which is a diselenide compound. In this case, the se-se bond is reduced to form a selenolate nucleophile, and a nucleophilic substitution reaction occurs to synthesize 2-methyl selenyl-5-nitro-benzaldehyde, which is a desired reaction product, by the reducing agent. Alcohol was produced by the reduction of the free aldehyde group of 5-nitro-2-chloro-benzaldehyde used as starting material. In addition, when NaBH ₄ was used as the reducing agent in a high temperature environment, a reaction of the Cannizzaro type tended to be preferred, and almost no desired product was obtained (entry 1, entry 4, and entry 4 in Table 1). Reference). It was confirmed through the above experiment that even if NaBH ₄ was used as the reducing agent, even if the reaction conditions such as solvent, reaction time, temperature, and equivalent of the base were changed, the desired reaction could not be obtained to obtain the desired reaction product ( Entry 1 to entry 4 of Table 1).

On the other hand, in the entries 6 to 13, the reducing agent was changed, and as a result, satisfactory results were obtained in terms of yield. Specifically, in entries 6 to 9, dithiothreitol (DTT) was used as the reducing agent. In this case, a side reaction in which the free aldehyde group of the aromatic aldehyde-based starting material is reduced or converted into another functional group by the reducing agent is Not occurring, the yield of the desired reaction product increased significantly. As long as dithiothreitol (DTT) was used as the reducing agent, even if the reaction conditions such as the base and the solvent used were changed, the yield of the product was always maintained at a high level. Further, the reducing agent N - acetyl cysteine (N -acetylcysteine), or even when a 1,4-butane dithiol replace a different material containing a thiol, such as (1,4-butanedithiol), high yield of the desired product It can be obtained (see entry 10 to entry 13 in Table 1).

Based on the experimental results of Experimental Example 1 shown in Table 1 above, materials such as dithiothreitol, N -acetylcysteine, or 1,4-butanedithiol, which are thiol-containing materials, are selected as the reducing agent. In the case of using the aldehyde-based starting material, since the free aldehyde group of the aromatic aldehyde starting material is not reduced or converted to other functional groups, no side reaction occurs, so that the desired reaction product, selenyl-substituted aromatic aldehyde compound, can be obtained in high yield. Could.

[ Experimental Example  2]

In Experimental Example 2, the diselenide compound was synthesized to synthesize 4,5-methylenedioxy-2-methylselanyl-benzaldehyde (4,5-methylenedioxy-2-methylselanyl-benzaldehyde) as in the above scheme. Dimethyldiselenide (DMDS, MeSeSeMe) was used as the aromatic aldehyde-based starting material 4,5-methylenedioxy-2-bromo-benzaldehyde (4,5-methylenedioxy-2-bromo-benzaldehyde ) Was used. The other materials, ie, the solvent, the reducing agent, and the base, were tested in various ways without being fixed. The differences in% yields of the products resulting from these differences in reaction conditions are shown in Table 2 below:

Entry
(Example) Reducing agent ( eq .) Base ( eq .) menstruum DMDS
( eq .) time
(h) Temperature
(° C) product
(% Yield) One DTT  (One) NaOEt  (2) EtOH One 24 Room temperature - 2 DTT  (One) NaOEt  (2) DMF One 24 Room temperature - 3 DTT  (One) NaOEt  (2) DMF One 24 60 - 4 DTT  (One) DBU  (2) DMF One One Room temperature 80 5 DTT  (One) DBU  (2.5) DMF 1.2 One Room temperature 82 6 N- Acetylcysteine (2) DBU  (2.5) DMF 1.5 3 Room temperature 56 7 1,4- Butanedithiol  (2) DBU  (2.5) DMF 1.5 3 Room temperature 60

As shown in Table 2, in entries 1 to 3, dithiothreitol (DTT) is used as a reducing agent for reducing the Se-Se bond of dimethyldiselenide (DMDS), which is a diselenide compound. Was used. According to Experimental Example 1, when a reducing agent containing a thiol group is used, a desired product should be obtained in high yield. In the above entries 1 to 3, even though dithiothritol is used as a reducing agent containing two thiol groups, Nonetheless, the desired product could not be obtained. Specifically, by-products were produced in the case of entry 1 and entry 2, which were tested at room temperature, and in the case of entry 3, which was tested at a high temperature of 60 ° C., an ethoxide substitution reaction by NaOEt, which is a base, occurred, resulting in an ethyl ether analog. It became. Through the experimental results of the above entries 1 to 3, it was confirmed that even if a reducing agent containing a thiol group was used, the desired product could not be obtained without using an appropriate base.

On the other hand, as can be seen from the experimental results of the entry 4 to entry 7, using the appropriate base, the desired product can be obtained in high yield without changing the other reaction conditions of the entry 1 to entry 3. Specifically, when the aldehyde-based starting material is an aromatic aldehyde compound having an electron donating substituent such as 4,5-methylenedioxy-2-bromo-benzaldehyde, a strong base such as DBU must be used to obtain a high desired product. Yields were obtained (see entries 4 through 7 in Table 2), and weak bases such as NaOEt did not yield the desired product (see entries 1 through 3 in Table 2).

Based on the experimental results of Experimental Example 2 shown in Table 2, by selecting a material such as dithiothreitol, N -acetylcysteine, or 1,4-butanedithiol which is a substance containing a thiol group as the reducing agent Even when used, it was not possible to obtain the desired product in high yield unconditionally, and the selection of the base also acted as an important reaction condition. Specifically, when an aromatic aldehyde compound having an electron donating substituent is used as a starting material, a strong base can be used to obtain selenyl-substituted aromatic aldehyde compound which is a desired product in high yield.

In addition, although not shown in Table 2, it was confirmed through the Experimental Example 2 that the base addition process has a significant effect on the reactivity of the reaction of the selenyl-substituted aromatic aldehyde compound. Specifically, when the base is added to the reaction mixture including the diselenide, the solvent, and the reducing agent in the reaction, and the aldehyde-based starting material, nucleophilic substitution at the halo position included in the aromatic aldehyde-based starting material within a few minutes. It was observed that the desired reaction product formed as the reaction was preferred. It has also been observed that the yield of the product gradually decreases over time after addition of the base. Based on the results obtained in Experimental Example 2, it can be confirmed that in the reaction for producing the selenyl-substituted aromatic aldehyde-based compound, the selection of the type of base and the addition of base significantly influence the reactivity of the reaction. there was.

[ Experimental Example  3]

In Experimental Example 3, to prepare a selenyl-substituted aromatic aldehyde-based compound, dithiothreitol (DTT) was used as the reducing agent, and dimethylformaldehyde (DMF) was used as the solvent. The diselenide compound represented by the general formula A-Se-Se-A, the aromatic aldehyde-based starting material, and the base were experimented with various changes without being fixed to one. Specifically, as the diselenide compound, dimethyldiselenide in which functional group A is a methyl group (Me), diphenyldiselenide in which functional group A is a phenyl group (Ph), or functional group A is a benzyl group ( Dibenzyldiselenide (Bn) was used. In addition, as the aromatic aldehyde-based starting material, various aromatic aldehyde-based materials having an electron donating substituent or an electron withdrawing substituent were used, and their specific chemical formulas are shown in Table 3 below. As the base, weak base K ₂ CO ₃ , or strong base DBU was used, and in each case 2.5 equivalents were used. The difference in the% yield of the product due to the difference in the reaction conditions is as shown in Table 3 below. In Table 3 below, reaction condition A is a case where K ₂ CO ₃ is used as the base and the reaction temperature is maintained at 80 ° C., and reaction condition A ′ is K ₂ CO ₃ as the base and the reaction temperature is adjusted to room temperature. Reaction condition B is when DBU is used as the base and the reaction temperature is maintained at room temperature, and reaction condition C is when DBU is used as the base and the reaction temperature is maintained at 80 ° C .:

Entry
(Example) Aldehyde
Starting material Diselenide
Functional group A ( eq .) Reaction conditions Yield (%) One

Me  (1.2) B 84 2

Ph  (0.6) C 80 3

Bn  (0.6) C 58 4

Me  (1.2) B 97 5

Me  (1.2) A ' 79 6

Me  (1.2) A ' 85 7

Ph  (0.6) A 97 8

Bn  (0.6) A 69 9

4- Cl - Bn  (0.6) A 68 10

4- NO ₂ - Bn  (0.6) A 60 11

3- Me - Bn  (0.6) A 96 12

3,5- diMe - Bn  (0.6) A 96 13

Me  (1.2) A ' 75 14

Ph  (0.6) A ' 74 15

Bn  (0.6) A ' 73 16

4- Cl - Bn  (0.6) A ' 68 17

3- Me - Bn  (0.6) A ' 70 18

3,5- diMe - Bn  (0.6) A ' 71 19

Me  (1.2) B 85 20

Me  (1.2) B 60 21

Me  (1.2) B 92 22

Me  (1.2) B 60 23

Ph  (0.6) C 62 24

Bn  (0.6) C 39 25

Me  (1.2) B 82 26

Ph  (0.6) C 60 27

Bn  (0.6) C 40 28

Me  (1.2) B 67 29

Me  (1.2) A ' 67 30

Me  (1.2) A ' 70 31

Ph  (0.6) A ' 62 32

Me  (1.2) A ' 78 33

Me  (1.2) A ' 92

<Created in entries 1 to 33 described in Table 3 above, Selenyl Of substituted aromatic aldehyde compounds ^One H NMR  And ¹³ C NMR  Analytical Data>

[Entry 1] 2- Methylselanyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.27 (s, 3H), 7.32 (td, 1H, J = 8.0, 1.0), 7.43 (d, 1H, J = 8.0), 7.47 (td, 1H, J = 8.5, 1.5), 7.77 (dd, 1H, J = 8.0, 1.5), 10.12 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 5.43, 124.45, 127.48, 133.42, 133.85, 135.08, 138.26, 192.04.

[Entry 2] 2- Phenylselanyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 7.03 (d, 1H, J = 8.0), 7.30-7.32 (m, 2H), 7.41-7.44 (m, 3H), 7.65 (dd, 2H, J = 8.0, 1.5), 7.83 (dd, 1H, J = 7.0, 2.0), 10.19 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 125.49, 128.18, 129.07, 129.81, 130.02, 133.76, 133.81, 134.94, 136.73, 139.55, 192.54.

[Entry 3] 2- Benzylselanyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 4.12 (s, 2H), 7.21-7.29 (m, 5H), 7.36 (dd, 1H, J = 7.5, 1.0), 7.46 (dd, 1H, J = 6.0, 1.5), 7.57 (d, 1H, J = 8.0), 7.80 (dd, 1H, J = 7.5, 1.5), 10.11 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 30.70, 126.09, 127.18, 128.66, 129.12, 130.94, 133.84, 133.93, 135.06, 136.89, 137.86, 192.73.

[Entry 4] 2- Methylselanyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.27 (s, 3H), 7.32 (td, 1H, J = 8.0, 1.0), 7.43 (d, 1H, J = 8.0), 7.47 (td, 1H, J = 8.5, 1.5), 7.77 (dd, 1H, J = 8.0, 1.5), 10.12 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 5.43, 124.45, 127.48, 133.42, 133.85, 135.08, 138.26, 192.04.

[Entry 5] 2- Methylselanyl -6- nitro - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.26 (s, 3H), 7.27 (d, 1H, J = 1.0), 7.34-7.39 (m, 2H), 10.66 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 4.57, 124.29, 124.65, 127.98, 131.91, 139.26, 141.08, 189.01.

[Entry 6] 2- methylselenyl -5- nitro - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.40 (s, 1H), 7.61 (d, 1H, J = 9.0), 8.29 (dd, 1H, J = 8.5, 2.5), 8.64 (d, 1H, J = 2.5), 10.18 (s, 1 H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 6.54, 126.99, 128.13, 129.91, 133.90, 145.06, 149.42, 190.44.

[Entry 7] 5- Nitro -2- phenylselanyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 7.10 (d, 1H, J = 8.5), 7.47-7.56 (m, 3H), 7.68 (dd, 2H, J = 8.5, 2.0), 8.05 (dd, 1H, J = 8.5, 2.5), 8.66 (d, 1H, J = 2.5), 10.22 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 126.13, 126.47, 129.23, 129.56, 129.73, 129.92, 132.68, 136.69, 144.94, 150.06, 190.08.

[Entry 8] 2- Benzylselanyl -5- nitro - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 4.19 (s, 2H), 7.12-7.22 (m, 5H), 7.99-8.04 (m, 2H), 8.58 (d, 1H, J = 2.0), 10.12 (s , 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 29.65, 126.09, 126.67, 127.92, 128.17, 128.43, 128.47, 133.16, 134.23, 144.36, 148.10, 189.47.

Entry 9 2- (4- Chloro - benzylselanyl ) -5- nitro - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 4.22 (s, 2H), 7.29-7.34 (m, 4H), 7.68 (d, 1H, J = 9.0), 8.27 (dd, 1H, J = 8.5, 2.5) , 8.65 (d, 1 H, J = 2.5), 10.16 (s, 1 H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 27.48, 124.94, 126.88, 127.00, 127.35, 128.25, 131.33, 131.61, 131.90, 143.21, 146.41, 188.23.

[Entry 10] 5- Nitro -2- (4- nitro - benzylselanyl ) - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 4.32 (s, 2H), 7.57 (d, 2H, J = 9.0), 7.66 (d, 1H, J = 9.0), 8.21 (d, 2H, J = 8.5) , 8.31 (dd, 1H, J = 9.0, 2.5), 8.68 (d, 1H, J = 2.5), 10.17 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 29.48, 124.22, 127.40, 129.01, 129.88, 130.09, 134.18, 143.35, 145.69, 147.44, 147.76, 190.93.

Entry 11 2- (3- Methyl - benzylselanyl ) -5- nitro - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.34 (s, 3H), 4.22 (s, 2H), 7.09 (d, 1H, J = 7.0), 7.17-7.23 (m, 3H), 7.72 (d, 1H , J = 9.0), 8.27 (dd, 1H, J = 9.0, 2.5), 8.64 (d, 1H, J = 2.5), 10.15 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 19.68, 29.01, 124.51, 125.36, 126.69, 127.17, 127.69, 127.77, 128.16, 132.43, 133.38, 137.04, 143.68, 147.62, 188.72.

Entry 12 2- (3,5- Dimethyl - benzylselanyl ) -5- nitro - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.29 (s, 6H), 4.18 (s, 2H), 6.91 (s, 1H), 6.99 (s, 2H), 7.72 (d, 1H, J = 8.5), 8.26 (dd, 1H, J = 8.5, 2.5), 8.63 (d, 1H, J = 2.5), 10.15 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 21.14, 30.63, 126.90, 127.00, 129.32, 129.35, 129.39, 134.07, 134.86, 138.50, 145.25, 149.44, 190.38.

Entry 13 2- Methylselanyl -5- trifluoromethyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.34 (s, 3H), 7.56 (d, 1H, J = 8.5), 7.68 (dd, 1H, J = 8.5, 1.0), 8.02 (s, 1H), 10.16 (s, 1 H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 5.72, 124.44, 126.57, 126.61, 126.83, 127.10, 127.36, 127.77, 129.16, 129.19, 131.51, 131.54, 133.65, 143.99, 190.74.

[Entry 14] 2- Phenylselanyl -5- trifluoromethyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 7.09 (d, 1H, J = 8.5), 7.44-7.52 (m, 4H), 7.67-7.68 (m, 2H), 7.68 (s, 1H), 8.05 (s , 1H), 10.20 (s, 1 H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 120.64, 125.22, 125.80, 126.07, 127.64, 127.67, 127.70, 127.87, 128.11, 128.26, 129.75, 129.77, 131.43, 135.24, 143.65, 189.30.

[Entry 15] 2- Benzylselanyl -5- trifluoromethyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 4.21 (s, 2H), 7.27-7.37 (m, 5H), 7.67-7.71 (m, 2H), 8.05 (s, 1H), 10.13 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 29.30, 126.18, 127.52, 127.84, 128.37, 128.39, 129.02, 129.64, 133.29, 134.68, 189.92.

[Entry 16] 2- (4- Chloro - phenylselanyl ) -5- trifluoromethyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 4.16 (s, 2H), 7.26 (s, 1H), 7.27 (s, 3H), 7.63-7.70 (m, 2H), 8.05 (s, 1H), 10.15 ( s, 1 H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 27.76, 120.67, 122.84, 126.23, 126.50, 127.17, 127.88, 127.91, 127.94, 127.96, 128.07, 128.64, 129.40, 129.42, 129.45, 131.50, 132.62, 15977, 132.77 .

Entry 17 2- (3- Methyl - benzylselanyl ) -5- trifluoromethyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.23 (s, 3H), 4.06 (s, 2H), 6.97 (d, 1H, J = 7.5), 7.04 (s, 1H), 7.05 (s, 1H), 7.10-7.17 (m, 1 H), 7.57-7.61 (m, 2 H), 7.94 (s, 1 H), 10.04 (s, 1 H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 21.30, 30.90, 124.69, 126.15, 128.26, 128.70, 129.64, 129.67, 129.86, 130.42, 130.86, 134.63, 135.80, 138.54, 191.60, 207.05.

[Entry 18] 2- (3,5- Dimethyl - benzylylselanyl ) -5- trifluoromethyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.28 (s, 6H), 4.12 (s, 2H), 6.89 (s, 1H), 6.94 (s, 2H), 7.66-7.71 (m, 2H), 8.04 ( s, 1 H), 10.13 (s, 1 H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 20.13, 29.61, 121.55, 123.66, 127.00, 128.12, 128.57, 128.59, 129.39, 129.73, 129.76, 133.57, 134.54, 137.36, 190.18.

[Entry 19] 5- Methyl -2- methylselanyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.27 (s, 3H), 2.39 (s, 3H), 7.31 (d, 1H, J = 8), 7.35 (d, 1H, J = 8), 7.61 (s , 1H), 10.13 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 5.20, 19.72, 127.56, 133.55, 133.93, 134.14, 134.18, 134.76, 191.85.

[Entry 20] 3- Methoxy -2- methylselanyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.29 (s, 3H), 3.96 (s, 3H), 7.09 (d, 1H, J = 8.0), 7.41 (t, 1H, J = 8.0), 7.53 (d , 1H, J = 7.5), 10.67 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 9.40, 56.34, 115.56, 120.92, 124.27, 129.44, 138.67, 160.21, 194.05.

[Entry 21] 4- Methoxy -2- methylselanyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.22 (s, 3H), 3.86 (s, 3H), 6.78 (dd, 1H, J = 8.5, 2.5), 6.87 (d, 1H, J = 2.0), 7.67 (d, 1 H, J = 8.5), 9.93 (s, 1 H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 3.53, 53.44, 107.55, 111.57, 125.89, 135.57, 138.76, 161.64, 188.50.

[Entry 22] 5- Methoxy -2- methylselanyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.29 (s, 3H), 3.86 (s, 3H), 7.10 (dd, 1H, J = 8.5, 3.0), 7.37 (d, 1H, J = 3.0), 7.44 (d, 1 H, J = 9.0), 10.26 (s, 1 H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 5.05, 53.36, 114.60, 119.16, 125.76, 129.41, 133.35, 156.02, 190.28.

[Entry 23] 5- Methoxy -2- phenylselanyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 3.87 (s, 3H), 7.01 (dd, 1H, J = 9.0, 3.0), 7.28 (s, 1H), 7.33-7.34 (m, 3H), 7.44 (d , 1H, J = 3.0), 7.48-7.50 (m, 2H), 10.33 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 55.53, 115.75, 121.66, 127.38, 128.00, 129.66, 130.40, 133.97, 134.89, 136.06, 159.09, 192.83.

[Entry 24] 2- Benzylselanyl -5- methoxy - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 3.85 (s, 3H), 4.00 (s, 2H), 7.04-7.08 (m, 3H), 7.18-7.22 (m, 3H), 7.36 (d, 1H, J = 3.0), 7.53 (d, 1 H, J = 9.0), 10.09 (s, 1 H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 31.83, 54.30, 112.10, 120.36, 124.40, 125.81, 127.24, 127.56, 136.17, 136.41, 136.67, 158.46, 191.97.

[Entry 25] 6- Methylselanyl - benzo [1,3] dioxole-5- carbaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) 2.16 (s, 3H), 5.96 (s, 2H), 6.82 (s, 1H), 7.13 (s, 1H), ∂ 9.92 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 6.66, 101.60, 108.77, 111.34, 128.29, 133.30, 145.82, 152.20, 189.58.

[Entry 26] 6- Phenylselanyl - benzo [1,3] dioxole-5- carbaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 6.01 (s, 2H), 6.64 (s, 1H), 7.31 (s, 1H), 7.36-7.39 (m, 3H), 7.56-7.58 (m, 2H), 10.11 (s, 1 H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 100.98, 110.26, 110.48, 127.49, 127.70, 128.15, 128.56, 132.84, 134.09, 145.90, 151.60, 189.35.

[Entry 27] 6- ( Benzylselanyl ) - benzo [1,3] dioxole-5- carbaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 4.04 (s, 2H), 6.07 (s, 2H), 7.15 (s, 1H), 7.16 (s, 1H), 7.21-7.25 (m, 3H), 7.30 ( s, 1 H), 9.99 (s, 1 H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 31.66, 101.00, 108.43, 112.80, 125.98, 127.35, 127.67, 130.03, 130.13, 135.95, 146.69, 151.30, 190.01.

[Entry 28] 4,5- Dimethoxy -2- methylselanyl - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.32 (s, 3H), 3.94 (s, 3H), 3.99 (s, 3H), 7.00 (s, 1H), 7.36 (s, 1H) 10.20 (s, 1H ); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 7.80, 56.15, 56.18, 113.16, 113.91, 128.32, 131.02, 147.87, 153.82, 191.14.

[Entry 29] 4- Methylselanyl -3- nitro - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.40 (s, 3H), 7.67 (d, 1H, J = 8.5), 8.03 (dd, 1H, J = 8.5, 2), 8.77 (d, 1H, J = 1.5), 10.04 (s, 1 H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 8.10, 128.15, 129.27, 131.83, 133.62, 143.47, 146.57, 189.28.

[Entry 30] 2- Methylselanyl - pyridine -3- carbaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.42 (s, 3H), 7.20 (dd, 1H, J = 7.5, 4.5), 7.95 (dd, 1H, J = 7.5, 1.5), 8.60 (dd, 1H, J = 4.5, 1.5), 10.10 (s, 1 H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 3.61, 117.42, 128.67, 139.74, 151.54, 158.87, 189.35.

[Entry 31] 2- Phenylselanyl - pyridine -3- carbaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 7.22 (dd, 1H, J = 7.5, 4.5), 7.39-7.42 (m, 3H), 7.65-7.66 (m, 2H), 8.02 (dd, 1H, J = 7.5, 1.5), 8.47 (dd, 1H, J = 5.0, 2.0), 10.20 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 118.04, 125.68, 126.62, 127.03, 127.91, 134.41, 139.09, 151.60, 158.99, 189.16.

[Entry 32] 3- Methylselanyl - furan -2- carbaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.32 (s, 3H), 6.57 (d, 1H, J = 1.5), 7.60 (d, 1H, J = 2.0), 9.76 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 5.68, 113.32, 126.00, 147.16, 148.39, 177.40.

[Entry 33] 3- Methylselanyl - thiophene -2- carbaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) ∂ 2.41 (s, 3H), 7.13 (d, 1H, J = 5.0), 7.72 (d, 1H, J = 5.0), 9.98 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) ∂ 7.65, 130.13, 134.50, 136.28, 138.39, 182.25.

According to Table 3, which summarizes the experimental results of Experimental Example 3, when dimethyldiselenide or diphenyldiselenide is used as the diselenide compound, the reaction proceeds smoothly to obtain a desired product in high yield. there was. However, when dibenzyl diselenide was used as the diselenide compound, the yield of the reaction product was affected by the kind of the aromatic aldehyde-based starting material. Specifically, in the case of using a dibenzyl diselenide as the diselenide compound and a substance having an aromatic hydrocarbon group, an amine group, or an ether group as an electron donating substituent as the aromatic aldehyde starting material, the aromatic aldehyde starting The nucleophilic substitution of the halo of the material by the nucleophile benzylselenolate was difficult, resulting in a low yield of the desired product (see entry 24 and entry 27 in Table 3). This result is 3-methyl-dibenzyldiselenide (3-Me-Bn in Table 3) and 3,5-dimethyl-benzyldiselenide substituted with some functional groups of the dibenzyl diselenide (Table 3). 3,5-diMe-Bn of 3), 4-nitro-dibenzyldiselenide (4-NO ₂ -Bn of Table 3), or 4-chloro-dibenzyldiselenide (4-Cl- of Table 3) The same was true when Bn) was used as the diselenide compound. The reason why the yield of the product is observed in these cases is low, firstly, the benzyl selenoleate which is a selenolate nucleophile produced by the reduction of Se-Se bond of dibenzyl diselenide used as the diselenide compound, It is not as strong as other selenolate nucleophiles. It is also because the electron density in the aromatic aldehyde-based starting material having an electron donating substituent is much higher at the position of the halo group where nucleophilic substitution should occur by the selenolate nucleophile as compared to the position of the free aldehyde group. For these reasons, in the case of using dibenzyl diselenide as the diselenide compound and using a substance having an electron donating substituent as the aromatic aldehyde-based starting material, the reaction proceeds in a different route, so that the desired product is selenyl-substituted. The yield of the aromatic aldehyde-based compound was lowered, and instead the cannizzaro type of by-products and products was formed.

In view of the above experimental results of Experimental Example 3 shown in Table 3, in order to prepare the selenyl-substituted aromatic aldehyde-based compound of the desired product in high yield, the aromatic aldehyde-based starting material and the diselenide compound It was also found that the selection of is important. Specifically, in the case of using a substance having an electron donating substituent as the aromatic aldehyde-based starting material, it is not preferable to use dibenzyl diselenide as the diselenide compound, dimethyl diselenide or diphenyl diselenide. It can be used to obtain the desired product in high yield.

It will be understood by those of ordinary skill in the art that the foregoing description of the embodiments is for illustrative purposes and that those skilled in the art can easily modify the invention without departing from the spirit or essential characteristics thereof. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single type may be implemented in a distributed manner, and similarly, components described as distributed may be implemented in a combined form.

The scope of the present invention is defined by the appended claims rather than the detailed description, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be interpreted as being included in the scope of the present invention .

Claims (18)

Preparing a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent;
Reacting the reaction mixture by adding an aromatic aldehyde starting material of Formula 1, and a base:
Method for preparing a selenyl-substituted aromatic aldehyde compound of the formula (4) comprising:
[Formula 1]

[Chemical Formula 4]

Among the above formulas,
R ₁ to R ₄ are each independently H; Aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl group, C _1-10 - alkoxy group, and an ether electron donor is selected from the group consisting of groups here (electron donating group); Or an electron withdrawing group selected from the group consisting of halo, nitro, cyano, and carbonyl groups,
Substituted with an alkyl group-A is C _{1 -10} which may be substituted - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl} group, an allyl group, an aromatic group, one or two C _{1 -10} An aromatic ring group, an aromatic ring group substituted with a halo group, or an aromatic ring group substituted with a nitro group,
A ₁ is C, or N,
X is a halo group.
Preparing a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent;
Reacting the reaction mixture by adding an aromatic aldehyde starting material of Formula 2, and a base:
A method of preparing a selenyl-substituted aromatic aldehyde compound of Formula 5 comprising:
(2)

[Chemical Formula 5]

Among the above formulas,
R ₅ and R ₆ are each independently H; Aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl, C _{1 -10} - alkoxy group, and an ether electron donor is selected from the group consisting of groups here; Or an electron withdrawing group selected from the group consisting of a halo group, a nitro group, a cyano group, and a carbonyl group,
Substituted with an alkyl group-A is C _{1 -10} which may be substituted - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl} group, an allyl group, an aromatic group, one or two C _{1 -10} An aromatic ring group, an aromatic ring group substituted with a halo group, or an aromatic ring group substituted with a nitro group,
A ₁ is C, or N,
X is a halo group.
Preparing a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent;
Reacting the reaction mixture by adding an aromatic aldehyde-based starting material, and a base of the formula (3):
A method of preparing a selenyl-substituted aromatic aldehyde compound of Formula 6 comprising:
(3)

[Chemical Formula 6]

Among the above formulas,
R ₇ and R ₈ are each independently H; Aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl, C _{1 -10} - alkoxy group, and an ether electron donor is selected from the group consisting of groups here; Or an electron withdrawing group selected from the group consisting of a halo group, a nitro group, a cyano group, and a carbonyl group,
Substituted with an alkyl group-A is C _{1 -10} which may be substituted - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl} group, an allyl group, an aromatic group, one or two C _{1 -10} An aromatic ring group, an aromatic ring group substituted with a halo group, or an aromatic ring group substituted with a nitro group,
A ₂ is O, S, or Se,
X is a halo group.
The method according to any one of claims 1 to 3,
Wherein the base is added to the reaction mixture after the addition of the aromatic aldehyde-based starting material, a method for producing a selenyl-substituted aromatic aldehyde-based compound.
The method according to any one of claims 1 to 3,
The solvent is dimethylformaldehyde (DMF), dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), CH ₂ Cl ₂ , CH ₃ CN, CH ₃ NO ₂ , CHCl ₃ , ClCH ₂ CH ₂ Cl, alcohols A method for producing a selenyl-substituted aromatic aldehyde-based compound, comprising one selected from the group consisting of, an aromatic solvent, and a combination thereof.
The method according to any one of claims 1 to 3,
The reducing agent is a method for producing a selenyl-substituted aromatic aldehyde-based compound, containing a thiol group.
The method of claim 1,
Substituents R ₁ to R ₄ of Formula 1 each independently include an electron withdrawing group selected from the group consisting of a halo group, a nitro group, a cyano group, and a carbonyl group, wherein the base includes a weak base, selenyl A process for producing a substituted aromatic aldehyde compound.
The method of claim 2,
Substituents R ₅ and R _{6 in} Formula 2 each independently include an electron withdrawing group selected from the group consisting of a halo group, a nitro group, a cyano group, and a carbonyl group, wherein the base includes a weak base, selenyl A process for producing a substituted aromatic aldehyde compound.
The method of claim 3, wherein
Substituents R ₇ and R ₈ of Formula 3 Each independently includes an electron withdrawing group selected from the group consisting of a halo group, a nitro group, a cyano group, and a carbonyl group, and the base includes a weak base group, wherein the selenyl-substituted aromatic aldehyde compound is prepared. .
The method of claim 1,
Each of R ₁ to R ₄ substituents of the above formula is independently an aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl, C _{1 -10} - alkoxy group, and containing an electron donor selected from the group consisting of a polyether And wherein the base comprises a strong base, a process for producing a selenyl-substituted aromatic aldehyde-based compound.
The method of claim 2,
Each of the substituents R ₅ and R ₆ in Formula 2 are independently an aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl, C _{1 -10} - alkoxy group, and containing an electron donor selected from the group consisting of a polyether And wherein the base comprises a strong base, a process for producing a selenyl-substituted aromatic aldehyde-based compound.
The method of claim 3, wherein
Substituents R ₇ and R ₈ of Formula 3 Each independently represent an aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl, C _{1 -10} - is to include the electron donor is selected from an alkoxy group, and the group consisting of a polyether, the base comprises a strong base Process for the preparation of phosphorus, selenyl-substituted aromatic aldehyde compounds.
10. The method according to any one of claims 7 to 9,
The weak base is K ₂ CO ₃ , KHCO ₃ , Na ₂ CO ₃ , NaHCO ₃ , NaOEt, NH ₄ OH, or a combination thereof, the method for producing a selenyl-substituted aromatic aldehyde-based compound.
13. The method according to any one of claims 10 to 12,
The strong base includes DBU (1,8-diazabicyclo [5,4,0] undec-7-ene), KOH, NaOH, Ca (OH) ₂ , Ba (OH) ₂ , KOtBu, or a combination thereof. The method for producing a selenyl-substituted aromatic aldehyde compound.
The method according to any one of claims 1 to 3,
The preparation of the reaction mixture and the addition of the aromatic aldehyde-based starting material and the base to the reaction mixture are each independently carried out at room temperature to 100 ° C, wherein the selenyl-substituted aromatic aldehyde-based chemical Manufacturing method.
The method according to any one of claims 1 to 3,
The diselenide compound and the reducing agent in the reaction mixture is included in the equivalent ratio of 1: 1/3 to 3, the method of producing a selenyl-substituted aromatic aldehyde-based compound.
The method according to any one of claims 1 to 3,
The diselenide compound represented by the general formula A-Se-Se-A included in the reaction mixture is reduced by the reducing agent to form a selenolate nucleophile represented by A-Se ⁻ , and Selenolate nucleophile is a nucleophilic substitution reaction with the aromatic aldehyde-based starting material to form the selenyl-substituted aromatic aldehyde-based compound, a method for producing a selenyl-substituted aromatic aldehyde-based compound.
Selenyl-substituted aromatic aldehyde-based compound represented by any one of the following formula 4 to formula 6:
[Chemical Formula 4]

[Chemical Formula 5]

[Chemical Formula 6]

Among the above formulas,
R ₁ to R ₈ are each independently H; Aromatic hydrocarbon group, an amine group, C _{1 -10} - alkyl group, C _1-10 - alkoxy group, and an ether electron donor is selected from the group consisting of groups here (electron donating group); Or an electron withdrawing group selected from the group consisting of halo, nitro, cyano, and carbonyl groups,
Substituted with an alkyl group-A is C _{1 -10} which may be substituted - alkyl, C _{1 -10-alkoxycarbonyl} -C _{1 -10-alkyl} group, an allyl group, an aromatic group, one or two C _{1 -10} An aromatic ring group, an aromatic ring group substituted with a halo group, or an aromatic ring group substituted with a nitro group,
A ₁ is C, or N,
A ₂ is O, S, or Se,
X is a halo group.