KR20140143345A - Novel method for preparing selenyl-substituted aromatic aldehyde compounds - Google Patents

Abstract

The present invention relates to a novel method for preparing a selenyl-substituted aromatic aldehyde based compound. More specifically, the method incldues a step of nucleophilically substituting an aromatic aldehyde based starting material.

Description

TECHNICAL FIELD [0001] The present invention relates to a novel method for preparing a selenyl-substituted aromatic aldehyde-based compound,

The present invention relates to a novel process for the preparation of selenyl-substituted aromatic aldehyde-based compounds, and more particularly to a process for the preparation of selenolate nucleophiles to form an aromatic aldehyde- Substituted aromatic aldehyde-based compounds.

In recent years, chalcogen chemistry has attracted great interest in the field of organic chemistry, and the biological activity of selenium (Se) among the organic chalcogenides is of particular interest. After the first synthesis of non-toxic glutathione peroxide analogue, ebselene (2-phenylbenzisoselenazol-3 (2H) -one) (Ebselene (2-phenylbenzisoselenazol-3 Significant efforts are being made to develop.

Of these organic selenium compounds, selenyl-substituted aromatic aldehyde-based compounds are good intermediates in the synthesis of benzoselenophene derivatives having various biological activities. The selenyl-substituted aromatic aldehyde-based compound can be obtained by subjecting an aromatic aldehyde-based starting material to nucleophilic substitution using a selenolate nucleophile represented by A-Se ^- , wherein the selenolate nucleophile Can be formed by reducing the Se-Se bond of a diselenide compound represented by the general formula A-Se-Se-A.

Reducing the Se-Se bond of the diselenide compound to form a selenolate nucleophile can be achieved based on some reducing agents such as NaBH ₄ , LiEt ₃ BH. In addition, metals such as indium, lanthanum, and samarium and their salts 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-based compound by using the above-mentioned conventional methods. When these methods are used, the Se-Se bond of the diselenide compound is reduced and the aromatic aldehyde- Of the free aldehyde group may be reduced or converted to another functional group. On the other hand, some catalytic processes can also be applied to reduce the Se-Se bond of the diselenide compound, but such catalytic processes have been subject to harsh reaction conditions in most cases.

The present invention relates to a method for producing a selenyl-substituted aromatic aldehyde-based compound using a selenolate nucleophile represented by A-Se ^- in which a Se-Se bond of a diselenide compound is reduced, A novel process for producing a selenyl-substituted aromatic aldehyde-based compound at a high yield by solving the problem that a nolate nucleophile is formed and at the same time a free aldehyde group of an aromatic aldehyde-based starting material is reduced or converted to another functional group . Specifically, a substance containing a thiol group as a reducing agent is used to reduce a diselenide compound represented by the general formula A-Se-Se-A to form a selenolate nucleophile represented by A-Se ^- ), And nucleophilic substitution of the aromatic aldehyde-based starting material with 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 invention relates to a process for preparing a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent, Substituted aromatic aldehydes represented by any one of the following Chemical Formulas (4) to (6) corresponding to each of Chemical Formulas 1 to 3, which comprises reacting an aromatic aldehyde-based starting material represented by any one of selenyl-substituted aromatic aldehyde-based compounds:

[Chemical Formula 1]

(2)

(3)

[Chemical Formula 4]

[Chemical Formula 5]

[Chemical Formula 6]

In the above formulas, each of R ₁ to R ₈ , A, A ₁ , A ₂ , and X is specifically defined below.

One embodiment of the present invention relates to a process for preparing a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent and a reducing agent, and adding to the reaction mixture an aromatic aldehyde- Substituted aromatic aldehyde-based compounds of formula (4), which comprises reacting a compound of formula

[Chemical Formula 1]

[Chemical Formula 4]

Among the above equations,

R ₁ to R ₄ are each independently an electron donating group selected from the group consisting of H, an aromatic hydrocarbon group, an amino group, a C _{1 -10 -alkyl} group, and a C _{1 -10} -alkoxy group; Or an electron withdrawing group selected from the group consisting of a halo group, a fluoromethyl group, a nitro group, a cyano group, and a C _{1 -10} -alkylcarbonyl 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 invention is a process for preparing a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent and a reducing agent, and adding to the reaction mixture an aromatic aldehyde- Substituted aromatic aldehyde-based compounds of formula (5), comprising reacting a compound of formula

(2)

[Chemical Formula 5]

Among the above equations,

R ₅ and R ₆ are each independently selected from the group consisting of H, an aromatic hydrocarbon group, an amino group, a C _{1 -10 -alkyl} group, and a C _{1 -10} -alkoxy group; Or an electron-withdrawing group selected from the group consisting of a halo group, a fluoromethyl group, a nitro group, a cyano group, and a C _{1 -10} -alkylcarbonyl 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 invention is a process for preparing a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent, and adding to the reaction mixture an aromatic aldehyde- Substituted aromatic aldehyde-based compounds of formula (6), which comprises reacting a compound of formula < RTI ID = 0.0 >

(3)

[Chemical Formula 6]

Among the above equations,

R ₇ and R ₈ are each independently selected from the group consisting of H, an aromatic hydrocarbon group, an amino group, a C _{1 -10 -alkyl} group, and a C _{1 -10} -alkoxy group; Or an electron-withdrawing group selected from the group consisting of a halo group, a fluoromethyl group, a nitro group, a cyano group, and a C _{1 -10} -alkylcarbonyl 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 invention provides a selenyl-substituted aromatic aldehyde-based compound represented by any one of the following Chemical Formulas 4 to 6:

[Chemical Formula 4]

[Chemical Formula 5]

[Chemical Formula 6]

Among the above equations,

R ₁ to R ₈ are each independently selected from the group consisting of H, an aromatic hydrocarbon group, an amino group, a C _{1 -10 -alkyl} group, and a C _{1 -10} -alkoxy group; Or an electron-withdrawing group selected from the group consisting of a halo group, a fluoromethyl group, a nitro group, a cyano group, and a C _{1 -10} -alkylcarbonyl 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.

According to the present invention, a selenolate nucleophile represented by A-Se ^- is formed by reducing a diselenide compound represented by the general formula A-Se-Se-A by using a substance containing a thiol group as a reducing agent And subjecting the aromatic aldehyde-based starting material to nucleophilic substitution using the selenolate nucleophile to provide a novel process for preparing a selenyl-substituted aromatic aldehyde-based compound.

The novel process for preparing a selenyl-substituted aromatic aldehyde-based compound according to the present invention is characterized in that the use of a substance containing a thiol group as a reducing agent prevents the free aldehyde group of the aromatic aldehyde-based starting material from being reduced or converted into another functional group, It is possible to selectively reduce the Se-Se bond of the selenide compound and to remarkably increase the yield of the selenyl-substituted aromatic aldehyde compound compared with the conventional case using a reducing agent such as NaBH ₄ or LiEt ₃ BH have. Further, 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. Further, by adding the base, the reductant containing the thiol group can be converted to a negatively charged thiolate (RS ^- ), thereby enhancing its reducing power. On the other hand, the thiolate has a problem that it is more reactive to the diselenide compound. Accordingly, the present invention solves the above-mentioned problem by adding the base during the reaction after addition of the aromatic aldehyde-based starting material so that the thiolate attacks the aryl group of the aromatic aldehyde-based starting material to selectively cause the nucleophilic substitution reaction Thereby improving the yield of the final product.

Further, in the present invention, in order to increase the yield of the selenyl-substituted aromatic aldehyde-based compound as the final product, when the aromatic aldehyde-based starting material contains an electron donating substituent, it is advantageous to use a strong base, while the aromatic aldehyde- If the starting material comprises an electron-withdrawing substituent, it is advantageous to use a weak base. That is, the yield of the final product can be increased by controlling the type of the base to be used depending on the characteristics of the substituent of the aromatic aldehyde-based starting material.

The selenyl-substituted aromatic aldehyde-based compound obtained in a high yield while minimizing the reaction by-products according to the present invention can be used as an intermediate useful in the synthesis of benzoselenophene having various biological activities.

Hereinafter, embodiments and examples of the present invention will be described in detail so that those skilled in the art can easily carry out 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 an element is referred to as "comprising ", it means that it can include other elements as well, without excluding other elements unless specifically stated otherwise.

The terms " about ", "substantially ", etc. used to the extent that they are used herein are intended to be taken as their meanings when referring to manufacturing and material tolerances inherent in the meanings mentioned, Accurate or absolute numbers are used to prevent unauthorized exploitation by unauthorized intruders of the mentioned disclosure. 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, May be an alkyl group having 1 to 10 carbon atoms and may include, but is not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl or isomers thereof .

The substituent which the "C _{1 -10} -alkyl group which may be substituted" may have in the present invention includes, for example, an alkyl group, a hydroxy group, an alkoxy group, a halo group, a nitrile group and a nitro group; Or an aryl group substituted by an alkyl group, a hydroxy group, an alkoxy group, a halo group, a nitrile group, or a nitro group, but the present invention is not limited thereto. In addition, in the present specification, the "C _{1 -10} -alkyl group which may be substituted" may be a group having a double bond or a triple bond, but is not limited thereto.

As used herein, the "C _{1 -10} -alkylene group" may be a linear or branched, saturated or unsaturated, alkylene group having 1 to 10 carbon atoms, such as methylene, ethylene, propylene, But are not limited to, pentylene, hexylene, heptylene, octylene, nonylene, decylene, or isomers thereof.

In the present specification, the "C _{1 -10} -alkoxy group" may include, but is not limited to, the above-defined "C _{1 -10 -alkyl} group" and an alkoxy group bonded with an oxygen atom.

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

As used herein, the term "aromatic hydrocarbon group" and "aromatic ring group" which may have a substituent group are groups which may have a substituent, a benzyl group which may have a substituent, a toluyl group which may have a substituent, Or a naphthalene group which may have a substituent, but is not limited thereto.

In the present specification, the "C _{1 -10} -alkoxycarbonyl-C _{1 -10} -alkyl group" may be a carbonyl group including the above-defined "C _{1 -10} -alkoxy group" and "C _{1 -10} -alkyl group" , But is not limited thereto.

As used herein, the "allyl group" may be an allyl group having from 3 to 10 carbon atoms, ie, a C _{3 -10} -allyl group, but is not limited thereto.

An embodiment of the present invention is a method of preparing a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent and adding to the reaction mixture an aromatic aldehyde represented by the following formula (Selenyl-substituted aromatic aldehyde) -based compound of the following formula (4), which comprises reacting a starting material,

[Chemical Formula 1]

[Chemical Formula 4]

Among the above equations,

R ₁ to R ₄ are each independently an electron donating group selected from the group consisting of H, an aromatic hydrocarbon group, an amino group, a C _{1 -10 -alkyl} group, and a C _{1 -10} -alkoxy group; Or an electron withdrawing group selected from the group consisting of a halo group, a fluoromethyl group, a nitro group, a cyano group, and a C _{1 -10} -alkylcarbonyl 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 substituted with a C _{1 -10} -alkyl group, a C _{1 -10} -alkoxycarbonyl-C _{1 -10} -alkyl group, a C _{3 -10} -allyl group and a C _{1 -10-} A benzyl group substituted with a halo group, a benzyl group substituted with a nitro group, or a benzyl group, but is not limited thereto.

Another embodiment of the present invention is a process for preparing a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent and a reducing agent, and adding to the reaction mixture an aromatic aldehyde- Substituted aromatic aldehyde-based compounds of formula (5), comprising reacting a compound of formula

(2)

[Chemical Formula 5]

Among the above equations,

R ₅ and R ₆ are each independently selected from the group consisting of H, an aromatic hydrocarbon group, an ammonio group, a C _{1 -10} -alkyl group, and a C _{1 -10} -alkoxy group; Or an electron-withdrawing group selected from the group consisting of a halo group, a fluoromethyl group, a nitro group, a cyano group, and a C _{1 -10} -alkylcarbonyl 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 substituted with a C _{1 -10} -alkyl group, a C _{1 -10} -alkoxycarbonyl-C _{1 -10} -alkyl group, a C _{3 -10} -allyl group and a C _{1 -10-} A benzyl group substituted with a halo group, a benzyl group substituted with a nitro group, or a benzyl group, but is not limited thereto.

Another embodiment of the present invention is a process for preparing a reaction mixture comprising a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent, and adding to the reaction mixture an aromatic aldehyde- Substituted aromatic aldehyde-based compounds of formula (6), which comprises reacting a compound of formula < RTI ID = 0.0 >

(3)

[Chemical Formula 6]

Among the above equations,

R ₇ and R ₈ are each independently selected from the group consisting of H, an aromatic hydrocarbon group, an amino group, a C _{1 -10 -alkyl} group, and a C _{1 -10} -alkoxy group; Or an electron-withdrawing group selected from the group consisting of a halo group, a fluoromethyl group, a nitro group, a cyano group, and a C _{1 -10} -alkylcarbonyl 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 substituted with a C _{1 -10} -alkyl group, a C _{1 -10} -alkoxycarbonyl-C _{1 -10} -alkyl group, a C _{3 -10} -allyl group and a C _{1 -10-} A benzyl group substituted with a halo group, a benzyl group substituted with a nitro group, or a benzyl group, but is not limited thereto.

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

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

On the other hand, the thiolate anion has a problem in that it is more reactive to the diselenide compound. 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 added to the aromatic aldehyde- Rather than attacking the aryl group of the starting material, the yield of the final target product may be reduced by first reacting with the diselenide compound. Therefore, the above-mentioned problem is solved by adding the aromatic aldehyde-based starting material and stirring for a certain period of time and then adding a base during the reaction so that the thiolate anion attacks the aryl group of the aromatic aldehyde- And the yield of the final product can be improved by selectively performing the reaction.

For the above reasons, in one embodiment of the present invention, there is provided a process for preparing a selenyl-substituted aromatic aldehyde-based compound wherein the aromatic aldehyde-based starting material is added to the reaction mixture, stirred, and then the base is sequentially added , But the manufacturing method of the present invention is not limited thereto. For example, when an aromatic aldehyde-based starting material is added to the reaction mixture containing a diselenide compound, a solvent, and a reducing agent, stirring is carried out for a predetermined period of time, and the base is added, the aromatic aldehyde- Nucleophilic substitution reactions at the halo halide positions favored the formation of the desired reaction product, a selenyl-substituted aromatic aldehyde-based compound.

In one embodiment of the present invention, the solvent may be selected and used as long as it can dissolve the diselenide compound and the reducing agent easily contained in the reaction mixture. For example, the solvent can be selected from the group consisting of 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, but are not limited thereto. For example, the alcohols may include methanol, ethanol, propanol, or butanol, and the aromatic solvent may include, but is not limited to, benzene, toluene, or derivatives thereof.

In one embodiment of the present invention, the reducing agent may be one containing a thiol group, but is not limited thereto. For example, the reducing agent may include, but is not limited to, a material containing one or more thiol groups. For example, the reducing agent may comprise a material containing one or two thiol groups, such as 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, 1,6-hexane dithiol or a similar cysteine, limited to It is not. To prepare the selenyl-substituted aromatic aldehyde-based compounds, some reducing agents which do not contain thiol groups such as NaBH ₄ and LiEt ₃ BH have been used in the prior art. In addition, metals such as indium, lanthanum, and samarium, and salts thereof, were used to reduce the Se-Se bond of the diselenide compound to produce a selenolate nucleophile. However, it is difficult to obtain a selenyl-substituted aromatic aldehyde-based compound by using the above-mentioned conventional methods. When these methods are used, the Se-Se bond of the diselenide compound is reduced and the aromatic aldehyde- Of the free aldehyde group may be reduced or converted to another functional group. In the present invention, by using the above-mentioned thiol group-containing substance as a reducing agent instead of the above-mentioned conventional methods, it is possible to prevent the free aldehyde group of the aromatic aldehyde-based starting material from being reduced or converted into another functional group, The Se-Se bond of the nide compound can be selectively reduced, and as a result, the yield of the desired reaction product can be remarkably increased. 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-based compound and minimize unnecessary side reactions.

In one embodiment of the present invention, in order to increase the yield of the selenyl-substituted aromatic aldehyde-based compound as the final product, when the aromatic aldehyde-based starting material contains an electron donating substituent, it is advantageous to use a strong base, When the aldehyde-based starting material comprises an electron-withdrawing substituent, it is advantageous to use a weak base, but the present invention is not limited thereto. That is, the yield of a desired reaction product can be increased by controlling the kind of the base used according to the characteristics of the substituent group of the aromatic aldehyde-based starting material.

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 materials are, independently, H, an aromatic hydrocarbon group, an amino group, C _1-10 - alkyl group, and C _{1 -10} - An alkoxy 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 materials the above formula (2) are, independently, H, an aromatic hydrocarbon group, an amino group, C _{1 -10} - alkyl, and C _{1 -10} - An alkoxy group, and the base may include a strong base, but is not limited thereto.

In one embodiment of the present invention, the aromatic aldehyde-based starting materials R ₇ and R ₈ of Formula 3 Each independently comprise an electron donative group selected from the group consisting of H, an aromatic hydrocarbon group, an amino group, a C _{1 -10 -alkyl} group, and a C _{1 -10} -alkoxy group, , But is not limited thereto.

For example, the strong bases may be DBU (1,8-diazabicyclo [5,4,0] undec-7-ene), KOH, NaOH, Ca (OH) ₂ , Ba (OH) ₂ , KOtBu, But is not limited thereto.

In one embodiment of the present invention, each of the substituents R ₁ to R ₄ of the above formula (1) as the aromatic aldehyde-based starting material is independently a halo group, a fluoromethyl group, a nitro group, a cyano group, and a C _{1 -10} -alkylcarbonyl group And the base may include a weak base, but the present invention is not limited thereto.

In one embodiment of the present invention, each of the substituents R ₅ and R ₆ of Formula 2, which is the aromatic aldehyde-based starting material, is independently selected from the group consisting of a halo group, a fluoromethyl group, a nitro group, a cyano group, and a C _{1 -10} -alkylcarbonyl group And the base may include a weak base, but the present invention is not limited thereto.

In one embodiment of the present invention, the aromatic aldehyde-based starting materials R ₇ and R ₈ of Formula 3 Each independently include an electron attracting group selected from the group consisting of a halo group, a fluoromethyl group, a nitro group, a cyano group, and a C _{1 -10} -alkylcarbonyl group, and the base may include a weak base, But is not limited to.

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 combinations thereof.

For example, when a substance containing an electron donating substituent is used as the aromatic aldehyde-based starting material, it is difficult to obtain a desired product by using a weak base such as NaOEt, whereas when a strong base such as DBU is used, But is not limited thereto.

In one embodiment of the invention, the preparation of the reaction mixture may be performed at room temperature to 100 < 0 > C, but is not limited thereto. Further, in one embodiment of the present invention, the addition and reaction of the aromatic aldehyde-based starting material and the base to the reaction mixture may be performed at room temperature to 100 ° C, but is not limited thereto.

The selection of the reaction temperature does not directly affect the yield of the desired product in the reaction in a high yield, so that the reaction temperature can be selected without particular limitation, provided that the reaction temperature is not within a temperature range not greatly limiting the reactivity. For example, the reaction mixture is prepared, stirred at room temperature, and the aromatic aldehyde-based starting material is added to the reaction mixture. After stirring at room temperature for a predetermined time, the base is added and stirred at room temperature to obtain a selenyl-substituted The aromatic aldehyde-based compound can be produced, but is not limited thereto.

In one embodiment of the present invention, 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 are 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, It is not.

The equivalence ratios of the decene compound and the reducing agent can be adjusted without particular limitation in the range sufficient to reduce the Se-Se bond of the decene compound to form the selenolate nucleophile necessary for the nucleophilic substitution reaction as the reducing agent And the equivalence ratio may vary depending on the type of the decene compound and / or the kind of the reducing agent.

In one embodiment of the present invention, the method for preparing the selenyl-substituted aromatic aldehyde-based compound comprises reacting the diselenide compound represented by the general formula A-Se-Se-A contained in the reaction mixture with 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 But may be, but not limited to, < / RTI > 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 selenolate nucleophile is as shown in the following reaction formula. For example, the following reaction formula is shown using dimethyldiselenide (DMDS) as the diselenide compound and dithiothreitol (DTT) as the reducing agent, but the present invention is not limited thereto:

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

[Chemical Formula 4]

[Chemical Formula 5]

[Chemical Formula 6]

Among the above equations,

R ₁ to R ₈ are each independently an electron donating group selected from the group consisting of H, an aromatic hydrocarbon group, an amino group, a C _{1 -10 -alkyl} group, and a C _{1 -10} -alkoxy group; Or an electron withdrawing group selected from the group consisting of a halo group, a fluoromethyl group, a nitro group, a cyano group, and a C _{1 -10} -alkylcarbonyl 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.

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

Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.

[Example]

All of the reagents used in the present embodiment are generally commercially available, and in the absence of specific description, they are used without special purification.

<Synthesis Process>

Hereinafter, the selenyl-substituted aromatic aldehyde-based compounds disclosed in the Examples were prepared by the synthetic process as a whole.

First, to prepare the above reaction mixture, each of a diselenide compound represented by the general formula A-Se-Se-A, a solvent, and a reducing agent was prepared. (1.2 eq. Me), 0.6 equivalents of phenyl group (0.6 eq. Ph), or 0.6 equivalents of A in the reaction mixture as the diselenene compound represented by the general formula A-Se-Se- (0.6 eq. Bn) of benzyl group 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 ) Were 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. When the functional group A in the diselenide compound was a methyl group, the equivalence ratio of the diselenide compound to 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 to the reducing agent is 0.6: 1. The reaction mixture was stirred for 30 minutes and the temperature was kept at room temperature or 80 &lt; 0 &gt; C during the stirring.

After the reaction mixture was prepared, an aromatic aldehyde-based compound as a starting material for preparing the selenyl-substituted aromatic aldehyde-based compound was added to the reaction mixture at once and stirred for 15 minutes. The stirring temperature was maintained at room temperature or 80 DEG C in this case.

DBU, weak base K ₂ CO ₃ , or weak base NaOEt was used as the base added to the reaction mixture after the starting material was added and stirred. The base was added to the reaction mixture in two equivalents at room temperature and stirred for 15 minutes. The stirring temperature was maintained at room temperature or 80 DEG C in this case.

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

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

[Experimental Example 1]

In this Experimental Example 1, in order to prepare 2-methylselenyl-5-nitro-benzaldehyde as in the above reaction formula, dimethyl diselenide ( dimethyldiselenide, DMDS, MeSeSeMe) was used, and 5-nitro-2-chloro-benzaldehyde was used as the aromatic aldehyde-based starting material. The other materials, that is, the solvent, the reducing agent, and the base were experimentally modified in various ways without being fixed in one way. The% yield differences of the products due to such differences in reaction conditions are shown in Table 1 below:

Entry
DMDS
( 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, 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 to cause a nucleophilic substitution reaction to synthesize a desired reaction product, 2-methyl-selenyl-5-nitro-benzaldehyde, Reduction of the free aldehyde group of 5-nitro-2-chloro-benzaldehyde used as starting material gave the alcohol. In addition, when NaBH ₄ was used as the reducing agent in a high-temperature environment, the Cannizzaro type reaction tended to be favored, and almost no desired product was obtained (Entry 1 of Table 1 and Entry 4 Reference). It has been confirmed through experiments that the desired reaction product can not be obtained by proceeding with the desired reaction even when NaBH ₄ is used as the reducing agent and other reaction conditions such as the solvent, the reaction time, the temperature, the equivalent of the base and the like are changed See entries 1 through 4 in 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 the yield. Specifically, in entries 6 to 9, dithiothreitol (DTT) is 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 to another functional group by the reducing agent And the yield of the desired reaction product was remarkably increased. The yield of the product was always maintained at a high level even though dithiothreitol (DTT) was used as the reducing agent, and other reaction conditions such as base and solvent used were changed. 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 (See entries 10 through 13 of Table 1).

In view of the experimental results of Experimental Example 1 shown in Table 1, materials such as dithiothreitol, N -acetylcysteine, or 1,4-butane dithiol, which are thiol group-containing materials, Substituted aromatic aldehyde-based compound, which is a desired reaction product, can be obtained in a high yield because the free aldehyde group of the aromatic aldehyde-based starting material is reduced or converted into another functional group, I could.

[Experimental Example 2]

In the present Experimental Example 2, in order to synthesize 4,5-methylenedioxy-2-methylselanyl-benzaldehyde as described in the above reaction formula, the diselenide compound Dimethyldiselenide (DMDS, MeSeSeMe) was used as the aromatic aldehyde-based starting material, and 4,5-methylenedioxy-2-bromo-benzaldehyde ) Was used. The other materials, that is, the solvent, the reducing agent, and the base, were experimentally tested while varying them in a fixed manner. The% yield differences of the products due to such 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 the above-mentioned entries 1 to 3, dithiothreitol (DTT) was used as a reducing agent for reducing the Se-Se bond of dimethyldiselenide (DMDS), which is a diselenide compound, Were used. According to Experimental Example 1, when a reducing agent containing a thiol group is used, a desired product should be obtained in a high yield. In the case of the use of dithiothreitol, which is a reducing agent containing two thiol groups, Desired products could not be obtained though. Specifically, in the case of the entry 1 and the entry 2 which were experimented at room temperature, by-products were generated. In the case of the entry 3 which was conducted at a high temperature of 60 ° C, the ethoxide substitution reaction was caused by the base NaOEt, . Through the experimental results of the above-mentioned entries 1 to 3, it was confirmed that even if a reducing agent containing a thiol group is used, a desired product can not be obtained without using an appropriate base.

On the other hand, as can be seen from the experimental results of the above-mentioned entries 4 to 7, when a proper base is used, a desired product can be obtained at a high yield without changing the other reaction conditions of the entry 1 to the entry 3. Specifically, when the aldehyde-based starting material is an aromatic aldehyde-based compound having an electron-donating substituent such as 4,5-methylenedioxy-2-bromo-benzaldehyde, it is necessary to use a strong base such as DBU, (See entries 4 to 7 in Table 2) and using a weak base such as NaOEt (see entries 2 to 3 in Table 2).

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

Also, although not shown in Table 2, it was confirmed that the addition of a base through Experimental Example 2 significantly affects the reactivity of the reaction for preparing the selenyl-substituted aromatic aldehyde compound. Specifically, when a base is added to a reaction mixture containing a diselenide, a solvent, and a reducing agent, and an aldehyde-based starting material in the above reaction, nucleophilic substitution at a halo position included in the aromatic aldehyde- It was observed that the desired reaction product formed as the reaction was favored. It was also observed that the yield of the product gradually decreased over time after the addition of the base. From the results obtained in Experimental Example 2, it was confirmed that the selection of the type of base and the addition of base in the reaction for preparing the selenyl-substituted aromatic aldehyde compound significantly affect the reactivity of the reaction there was.

[Experimental Example 3]

In Experimental Example 3, dithiothreitol (DTT) was used as the reducing agent and dimethylformaldehyde (DMF) was used as the solvent to prepare a selenyl-substituted aromatic aldehyde-based compound. The diselenide compound represented by the general formula A-Se-Se-A, the aromatic aldehyde-based starting material, and the base were experimentally tested while variously changing without fixing them. Specifically, as the above-mentioned diselenide compound, dimethyldiselenide whose functional group A is a methyl group (Me), diphenyldiselenide whose functional group A is a phenyl group (Ph), or functional group A is a benzyl group Bn) dibenzyldiselenide was used. As the aromatic aldehyde-based starting material, various aromatic aldehyde-based materials having an electron donating substituent or an electron withdrawing substituent are used, and more specific formulas thereof are shown in Table 3 below. K ₂ CO ₃ , which is a weak base, or DBU, which is a strong base, was used as the base, and 2.5 equivalents of the base was used in all cases. The difference in the yield of the product due to the difference in the reaction conditions is as shown in Table 3 below. In the following Table 3, the reaction condition A is the case where K ₂ CO ₃ is used as the base and the reaction temperature is maintained at 80 ° C. The reaction condition A 'is K ₂ CO ₃ as the base and the reaction temperature is room temperature And the reaction condition B is the case where DBU is used as the base and the reaction temperature is maintained at room temperature and the reaction condition C is the case where DBU is used as the base and the reaction temperature is maintained at 80 ° C:

Entry
(Example) Aldehyde series
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

< ¹ H NMR and ¹³ C NMR analysis data of the selenyl-substituted aromatic aldehyde-based compounds produced in Entry 1 to Entry 33 listed in Table 3 above>

[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 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 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 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 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 ) 灌 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 ) 灌 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, IH, J = 8.5), 7.68 (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 , &Lt; / RTI &gt; 1H), 10.20 (s, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) 灌 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, 1H); ¹³ C NMR (125.7 MHz, CDCl ₃ ) 灌 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, 132.77, 141.59, 189.38 .

[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, 1H), 7.57-7.61 (m, 2H), 7.94 (s, 1H), 10.04 (s, 1H); 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- 메틸 세란 - benzaldehyde :

¹ H NMR (500.1 MHz, CDCl ₃ ) 隆 2.27 (s, 3H), 2.39 (s, 3H), 7.31 (d, 1H, J = 8), 7.35 , &Lt; / RTI &gt; 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- 메틸 세란 - 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 , &Lt; / RTI &gt; 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- 메틸 세란 - 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- 메틸 세란 - 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, 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 ) 隆 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- 메틸oxy - 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 = 3.0), 7.53 (d, 1H, J = 9.0), 10.09 (s, 1H); 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 ) 隆 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- 메틸 세란 - 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 - 피리딘 -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 - 피리딘 -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 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 ¹³ C NMR (125.7 MHz, CDCl ₃ )? 7.65, 130.13, 134.50, 136.28, 138.39, 182.25.

According to Table 3 summarizing the experimental results of Experimental Example 3, when dimethyl diselenide or diphenyl diselenide was used as the diselenide compound, the reaction proceeded smoothly to obtain a desired product in a high yield there was. However, when dibenzyldiselenide was used as the diselenide compound, the yield of the reaction product was influenced by the type of the aromatic aldehyde-based starting material. Specifically, the aromatic aldehyde-based starting material may be an electron donating substituent such as H, an aromatic hydrocarbon group, an amino group, a C _{1 -10 -alkyl} group, or a C _{1 -10} -alkoxy group Group, the halogen group of the aromatic aldehyde-based starting material was difficult to be nucleophilically substituted by the nucleophile benzylselenolate, and thus the yield of the desired product was observed to be low (see entry 24 and entry 27). These results indicate that 3-methyl-dibenzyl dicerenanide (3-Me-Bn in Table 3) and 3,5-dimethyl-dibenzyl dicerenanide 4-nitro-dibenzyldicellenide (4-NO ₂ -Bn in Table 3) or 4-chloro-dibenzyl diceranide (4-Cl- Bn) was used as the above-mentioned diselenide compound. In the above cases, the yield of the product is observed to be low because benzyl selenolate, which is the selenolate nucleophile produced by reducing the Se-Se bond of dibenzyl diselenide used as the diselenide compound, Because it is not as strong as other selenolate nucleophiles. In addition, the electron density in the aromatic aldehyde-based starting material having an electron donating substituent is also much higher at the position of the halo group in which nucleophilic substitution should occur due to the selenolate nucleophile than the position of the free aldehyde group. For these reasons, when dibenzyldiselenide is used as the diselenide compound and a substance having an electron donating substituent is used as the aromatic aldehyde-based starting material, the reaction proceeds in different routes to obtain a desired product, selenyl-substituted The yield of the aromatic aldehyde-based compound was lowered, and instead, a by-product and a canny-letter type of the product were formed.

Based on the experimental results of Experimental Example 3 shown in Table 3, in order to produce a selenyl-substituted aromatic aldehyde compound as a desired product in high yield, the aromatic aldehyde-based starting material and the diselenide compound Of the total population. Specifically, when a substance having an electron donating substituent is used as the aromatic aldehyde-based starting material, it is not preferable to use dibenzyldiselenide as the diselenide compound, and dimethyl diselenide or diphenyl diselenide The desired product could be obtained 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 entity may be distributed and implemented, and components described as being distributed may also 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 (1)

A selenyl-substituted aromatic aldehyde-based compound represented by any one of the following Chemical Formulas 4 to 6:
[Chemical Formula 4]

[Chemical Formula 5]

[Chemical Formula 6]

Among the above equations,
R ₁ to R ₈ are each independently an electron donating group selected from the group consisting of H, an aromatic hydrocarbon group, an amino group, a C _{1 -10 -alkyl} group, and a C _{1 -10} -alkoxy group; Or an electron withdrawing group selected from the group consisting of a halo group, a fluoromethyl group, a nitro group, a cyano group, and a C _{1 -10} -alkylcarbonyl 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, and when A ₁ is N, R ₄ or R ₆ substituted therefor is absent,
A ₂ is O, S, or Se.