KR101614891B1 - Method for preparing of carbonyl compound - Google Patents

Abstract

The present invention relates to a method for producing a carbonyl compound. More particularly, the present invention relates to a method for producing a carbonyl compound having a trifluoromethyl group introduced at the? -Position, which can realize a high yield while simplifying the reaction under mild conditions under visible light and photocatalyst, And a method for producing a carbonyl compound having high economical efficiency.

Description

TECHNICAL FIELD The present invention relates to a method for preparing a carbonyl compound,

The present invention relates to a method for producing a carbonyl compound. More particularly, the present invention relates to a method for producing a carbonyl compound having a high economic efficiency by using a photocatalyst to simplify the reaction while exhibiting a high yield.

Compounds containing trifluoromethyl (CF ₃ ) groups have unique properties in agrochemicals, pharmaceuticals and materials fields and are therefore of great value for industrial use. Therefore, studies to introduce trifluoromethyl groups into compounds have been limited to organic fluorine chemistry It has been known as an important task.

More specifically, when the trifluoromethyl group is introduced into medicines or pesticides, the activities such as metabolic stability, lipophilicity, bioavailability, and binding selectivity are improved Which has attracted great interest in the field of medicine and agriculture.

Carbonyl compounds, on the other hand, are interesting compounds because of their wide variety of applications and can be used as versatile intermediates in subsequent reactions. Particularly, carbonyl including a trifluoromethyl group is a compound which has an enhanced activity or can be converted into various components through a reaction, and is a subject of attention. The introduction of the trifluoromethyl group into the alpha (alpha) position of the carbonyl compound is relatively well known, but introduction of the trifluoromethyl group into the beta (beta) site is not easy due to the nature of the trifluoromethyl group, Is not known.

An example of a multi-step reaction such as the following reaction is known as an example of making a carbonyl compound containing a trifluoromethyl group in the beta position (Journal of Fluorine Chemistry, Volume 152, Pages 56-61).

However, the above reaction is a reduction of the propargyl alcohol substituted with a trifluoromethyl group, and the reaction condition must be carried out under extreme conditions of -78 ° C.

In addition, there is a multi-step reaction using Grignard reaction etc. However, there is a disadvantage that the kinds of functional groups present in the reactant affect the reaction and thus the reactant is limited.

The present invention relates to a process for producing a carbonyl compound in which a trifluoromethyl group is introduced at a beta (beta) position, a method for producing a carbonyl compound capable of realizing a high yield while simplifying the reaction under mild conditions under visible light and photocatalyst The purpose is to provide.

According to the present invention,

(2), comprising the step of irradiating a visible light to a reaction mixture comprising a propargyl alcohol compound represented by the following formula (1), trifluoroiodomethane, a reducing agent, and a photocatalyst Of a carbonyl compound.

[Chemical Formula 1]

 (2)

In the above Formulas 1 and 2,

R is alkyl of 1 to 20 carbon atoms; Aryl having 6 to 20 carbon atoms; Alkylaryl having 7 to 20 carbon atoms; Arylalkyl having 7 to 20 carbon atoms; Alkoxy having 1 to 20 carbon atoms; Aryloxy having 6 to 20 carbon atoms; Alkoxyaryl having 6 to 20 carbon atoms; Cycloalkyl having 3 to 20 carbon atoms; Heterocycloalkyl having 3 to 20 carbon atoms; Heteroaryl having 5 to 20 carbon atoms; Halogenated alkyl having 1 to 20 carbon atoms; And halogenated aryl having 6 to 20 carbon atoms.

According to the present invention, it is possible to provide a process for producing a carbonyl compound in which a trifluoromethyl group is introduced at the? -Position in a one-step reaction. The method for producing the carbonyl compound can be carried out under mild conditions under visible light and photocatalyst, thereby realizing a high yield while simplifying the reaction.

The carbonyl compound containing the fluoroalkyl group prepared by the production method of the present invention can be utilized in various fields such as medicine, medicine, pesticide, and material field.

Hereinafter, a method for producing a carbonyl compound according to a specific embodiment of the present invention will be described in detail.

The method for producing a carbonyl compound of the present invention comprises the steps of irradiating a reaction mixture containing a propargyl alcohol compound represented by the following formula (1), trifluoroiodomethane, a reducing agent, and a photocatalyst to visible light Wherein the carbonyl compound is represented by the following formula (2).

[Chemical Formula 1]

(2)

In the above Formulas 1 and 2,

R is alkyl of 1 to 20 carbon atoms; Aryl having 6 to 20 carbon atoms; Alkylaryl having 7 to 20 carbon atoms; Arylalkyl having 7 to 20 carbon atoms; Alkoxy having 1 to 20 carbon atoms; Aryloxy having 6 to 20 carbon atoms; Alkoxyaryl having 6 to 20 carbon atoms; Cycloalkyl having 3 to 20 carbon atoms; Heterocycloalkyl having 3 to 20 carbon atoms; Heteroaryl having 5 to 20 carbon atoms; Halogenated alkyl having 1 to 20 carbon atoms; And halogenated aryl having 6 to 20 carbon atoms.

More specifically, in the method for producing a carbonyl compound of the present invention, the photocatalyst functions together with a visible light and a reducing agent to convert the trifluoroiodomethane (CF ₃ I) compound into a trifluoromethyl radical (CF ₃ ) And the trifluoromethyl radical may react with the triple bond of the propargylic alcohol to form an intermediate in which the trifluoromethyl group is substituted. Then, the intermediate forms an allylic alcohol having a trifluoromethyl group, and the migration of alkenes and the keto-enolototo head (tautomerism) occur continuously under the same conditions as the radical reaction, A carbonyl compound into which a fluoromethyl group is introduced can be finally formed.

According to one embodiment of the present invention, R is alkyl having 1 to 20 carbon atoms; Aryl having 6 to 20 carbon atoms; Alkylaryl having 7 to 20 carbon atoms; Arylalkyl having 7 to 20 carbon atoms; Alkoxy having 1 to 20 carbon atoms; Aryloxy having 6 to 20 carbon atoms; Alkoxyaryl having 6 to 20 carbon atoms; Cycloalkyl having 3 to 20 carbon atoms; Heterocycloalkyl having 3 to 20 carbon atoms; Heteroaryl having 5 to 20 carbon atoms; Halogenated alkyl having 1 to 20 carbon atoms; And halogenated aryl having 6 to 20 carbon atoms, but is not limited thereto. Preferably, R is an aliphatic alkyl group or an aryl group containing or not having a substituent, for example, aryl having 6 to 20 carbon atoms; Alkylaryl having 7 to 20 carbon atoms; Arylalkyl having 7 to 20 carbon atoms; Aryloxy having 6 to 20 carbon atoms; Alkoxyaryl having 6 to 20 carbon atoms; Heteroaryl having 5 to 20 carbon atoms; And halogenated aryl of 6 to 20 carbon atoms.

The process for producing a carbonyl compound of the present invention has an advantage that it can be applied to a propargyl alcohol having an aryl group as a substituent in a high yield and without being limited by the kind of a substituent bonded to the aryl group.

It is preferable that the trifluoroiodomethane is contained in an amount of about 2 moles or more, for example, about 2 moles to about 4 moles, relative to 1 mole of the propargyl alcohol compound, because the reaction yield can be increased. When the trifluoroiodomethane is contained in an amount less than the above-mentioned 2 molar amount relative to the propargyl alcohol compound, the reaction is not terminated and the reaction yield may be low. When the amount of the trifluoroiodomethane is excessively larger than 4 mol, And it is economically undesirable.

In the process for producing a carbonyl compound according to the present invention, the photocatalyst is a substance which absorbs light and promotes a chemical reaction. In the visible light, trifluoroiodomethane is converted into a trifluoromethyl radical, A waxy alcohol compound can be formed from a carbonyl compound having a trifluoromethyl group introduced at the? -Position.

Ir (ppy) ₃ , Ir (ppy) ₂ (dtb-bpy)] PF ₆ , [Ir (ppy) _{(dfppy) 2 (phen)]} PF 6, Ir (dF-ppy) 3, [Ru (bpy) 3] Cl 2, or _{[Ru (Phen) 3] Cl} 2 And the like. In particular, Ru (bpy) ₃ Cl ₂ and Ru (Phen) ₃ Cl ₂ may be more preferable because they are inexpensive, have a mild reaction condition and exhibit high yield.

The photocatalyst may include about 0.1 to about 3 mol% of the reaction mixture containing the propanol alcohol compound, the reducing agent, and trifluoroiodomethane. The photocatalyst is a material that receives light in the visible light region to promote a chemical reaction and remains as it is before and after the reaction. Even in a small amount of the above range, the reaction can be sufficiently promoted, and the economical efficiency of the reaction can be enhanced.

The ruthenium or iridium photocatalyst may serve both as a catalyst for radical reaction introducing a trifluoromethyl group and as a catalyst for inducing the shift of an alkene. Therefore, by reacting the photocatalyst having the two functions with the propanol alcohol compound, it is possible to easily form a carbonyl compound containing a trifluoromethyl group at the? -Position from the propanol alcohol compound without going through a complicated process with various reaction additives Thereby reducing the cost of process design and the cost of producing the final product.

In the process for preparing the carbonyl compound of the present invention, the reaction mixture is selected from DBU (1,8-diazabicyclo- [5,4,0] -un-dec-7-ene), DIPEA (diisopropylethylamine) triethylamine), or TMEDA (N, N, N ', N'etramethylethylenediamine).

It is preferable that the reducing agent is contained in an amount of 2 mol or more, for example, about 2 to 10 mol, per mol of the propargyl alcohol compound, because the reaction yield can be increased. When the reducing agent is contained in an amount less than the above-mentioned 2 molar amount relative to the propanolic alcohol compound, the reaction yield may be low, and when it is excessively more than 10 molar, it is economically undesirable and the yield improving effect may be insignificant have.

The reaction mixture may further contain a solvent. Specific examples of the solvent include DMF (dimethylformamide), MeCN (methyl cyanide), CH ₂ Cl ₂ (dichloromethane), MeOH (methanol), EtOH (ethanol), THF (tetrahydrofuran) or mixtures thereof. The solvent can be easily mixed by dissolving the reaction mixture, and the reaction can be assisted by appropriately maintaining the concentration of the intermediate trifluoromethyl radical. And, the concentration of the solvent is about 0.05 to about 1 M, which is preferable because it can help the progress of the reaction and faithfully perform the role of the solvent.

The reaction mixture is irradiated with visible light to proceed the reaction.

The step of irradiating the visible light may use a general incandescent lamp, a fluorescent lamp, a blue LED, or the like. The reaction mixture containing the propargyl alcohol compound, trifluoroiodomethane, a reducing agent and a photocatalyst may be placed near an incandescent lamp or the like So that visible light can be irradiated. The visible light may then be irradiated with the reaction mixture for about 2 hours to about 48 hours, preferably about 10 hours to about 24 hours.

As described above, the method of forming a carbonyl compound by irradiating a visible light to a reaction mixture containing a propargyl alcohol compound, trifluoroiodomethane, a reducing agent and a photocatalyst does not require special conditions such as temperature and pressure, Can be carried out without limitation under conditions known to be used conventionally in the synthesis or the introduction reaction of a specific functional group. Particularly, the process can be carried out under mild conditions of room temperature and normal pressure, so that a carbonyl compound having a trifluoromethyl group introduced into the? -Position can be prepared more easily.

Hereinafter, the present invention will be described in more detail in the following examples. However, the following examples are illustrative of the present invention, and the present invention is not limited by the following examples.

< Example >

Carbonyl  Preparation of compounds

Example  One

[Ru (bpy) ₃ ] Cl ₂ (1 mol% based on the total reaction mixture), DMF (5 mL, 0.1 M) and DBU (5 mol) were added to a test tube filled with 1-phenylprop-2-yn- mmol, added to 10 equiv.), followed by _{mixing. CF 3 I (1.5 mmol,} 3 equiv). The test tube was placed under a blue LED or the like at room temperature and reacted at room temperature for 24 hours.

Through the NMR analysis of the obtained compound, it was confirmed that 4,4,4-trifluoro-1-phenylbutan-1-one having a trifluoromethyl group introduced at the? -Position was obtained, and the yield was determined.

^{1 H NMR (400 MHz, CDCl} 3): δ8.00-7.96 (m, 2H), 7.61 (t, J = 7.6 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 3.27 (t, J = 8.0 Hz, 2H), 2.60 (qt, J = 10.8, 8.0 Hz, 2H)

^{13 C NMR (101 MHz, CDCl} 3): δ196.56, 136.28, 133.84, 128.99, 128.22, 127.20 (q, J = 276.5 Hz), 31.43 (q, J = 2.6 Hz), 28.55 (q, J = 29.7 Hz)

^{19 F NMR (377 MHz, CDCl} 3): δ-66.39

Example  2

The reaction was carried out in the same manner as in Example 1 except that MeCN (5 mL, 0.1 M) was used instead of DMF as a solvent.

Example  3

The reaction was carried out in the same manner as in Example 1 except that MeCN (2.5 mL) and THF (2.5 mL) were used as the solvent instead of DMF

Example  4

The catalyst was replaced with [Ru (bpy) ₃ ] Cl ₂ Instead of 1 mol% [Ru (Phen) ₃ ] Cl ₂ 1 mol% was used as a catalyst, the reaction was carried out in the same manner as in Example 3

Example  5

The catalyst was replaced with [Ru (bpy) ₃ ] Cl ₂ The reaction was carried out in the same manner as in Example 3, except that 1 mol% of fac- Ir (ppy) ₃ was used instead of 1 mol%

Example  6

The catalyst was replaced with [Ru (bpy) ₃ ] Cl ₂ [Ir (ppy) ₂ (dtb-bpy)] PF ₆ 1 mol% was used as a catalyst.

Example  7

The catalyst was replaced with [Ru (bpy) ₃ ] Cl ₂ (Ir (dfppy) ₂ (phen)] PF ₆ 1 mol% was used as a catalyst.

Example  8

The catalyst was replaced with [Ru (bpy) ₃ ] Cl ₂ The reaction was carried out in the same manner as in Example 3, except that 1 mol% of fac- Ir (df-ppy) _{3 was} used instead of 1 mol%.

Example  9 to 17

Instead of 1-phenylprop-2-yn-1-ol as the reactant, another propidic alcohol compound may be used, or the catalyst may be [Ru (bpy) ₃ ] Cl ₂ Instead of 1 mol% [Ru (bpy) ₃ ] Cl ₂ 2 mol% was used as the catalyst.

The main reaction conditions of the above Examples 1 to 17 and the yields of the obtained compounds are shown in Table 1 below.

Propargyl alcohol compound menstruum Photocatalyst reducing agent yield Example 1

DMF [Ru (bpy) ₃ ] Cl ₂
(1 mol%) DBU 90% Example 2

MeCN [Ru (bpy) ₃ ] Cl ₂
(1 mol%) DBU 61% Example 3

MeCN + THF [Ru (bpy) ₃ ] Cl ₂
(1 mol%) DBU 52% Example 4

MeCN + THF [Ru (Phen) ₃ ] Cl ₂
(1 mol%) DBU 67% Example 5

MeCN + THF fac- Ir (ppy) ₃
(1 mol%) DBU 88% Example 6

MeCN + THF [Ir (ppy) ₂ (dtb-bpy)] PF ₆
(1 mol%) DBU 85% Example 7

MeCN + THF [Ir (dfppy) ₂ (phen)] PF ₆
(1 mol%) DBU 60% Example 8

MeCN + THF fac- Ir (dF-ppy) ₃
(1 mol%) DBU 67% Example 9

DMF [Ru (bpy) ₃ ] Cl ₂
(2 mol%) DBU 70% Example 10

DMF [Ru (bpy) ₃ ] Cl ₂
(2 mol%) DBU 60% Example 11

DMF [Ru (bpy) ₃ ] Cl ₂
(2 mol%) DBU 65% Example 12

DMF [Ru (bpy) ₃ ] Cl ₂
(2 mol%) DBU 51% Example 13

DMF [Ru (bpy) ₃ ] Cl ₂
(2 mol%) DBU 50% Example 14

DMF [Ru (bpy) ₃ ] Cl ₂
(2 mol%) DBU 56% Example 15

DMF [Ru (bpy) ₃ ] Cl ₂
(2 mol%) DBU 20% Example 16

DMF [Ru (bpy) ₃ ] Cl ₂
(2 mol%) DBU 25% Example 17

DMF [Ru (bpy) ₃ ] Cl ₂
(2 mol%) DBU 20%

As shown in Table 1, when the propargyl alcohol compound was converted into a carbonyl compound having a trifluoromethyl group introduced into the? -Position using a photocatalyst and visible light according to the production method of the present invention, The reaction can be simplified under the mild conditions of the irradiation, and a high yield can be obtained, so that it can be used in the production of carbonyl compounds having various substituents to suit the application.

Especially, it was confirmed that propargyl alcohol containing an aryl substituent shows high reactivity.

Claims (6)

A process for producing a photocatalyst comprising the steps of irradiating a visible light to a reaction mixture comprising a propargyl alcohol compound represented by the following formula (1), trifluoroiodomethane, a reducing agent, and a photocatalyst,
Wherein the photocatalyst comprises ruthenium or iridium,
The reducing agent is selected from the group consisting of DBU (1,8-diazabicyclo- [5,4,0] -un-dec-7-ene), DIPEA (diisopropylethylamine), TEA &Quot; tetramethylethylenediamine &quot;),&lt; / RTI &gt;
[Chemical Formula 1]

(2)

In the above Formulas 1 and 2,
R is alkyl of 1 to 20 carbon atoms; Aryl having 6 to 20 carbon atoms; Alkylaryl having 7 to 20 carbon atoms; Arylalkyl having 7 to 20 carbon atoms; Alkoxy having 1 to 20 carbon atoms; Aryloxy having 6 to 20 carbon atoms; Alkoxyaryl having 7 to 20 carbon atoms; Cycloalkyl having 3 to 20 carbon atoms; Heterocycloalkyl having 3 to 20 carbon atoms; Heteroaryl having 5 to 20 carbon atoms; Halogenated alkyl having 1 to 20 carbon atoms; And halogenated aryl having 6 to 20 carbon atoms.
delete The method according to claim 1,
The photocatalyst is _{Ir (ppy) 3, [Ir} (ppy) 2 (dtb-bpy)] PF 6, [Ir (dfppy) 2 (phen)] PF 6, Ir (dF-ppy) 3, [Ru (bpy) ₃ ] Cl ₂ , and [Ru (Phen) ₃ ] Cl ₂ .
delete The method according to claim 1,
The reaction mixture further comprises at least one solvent selected from the group consisting of DMF (dimethylformamide), MeCN (methyl cyanide), CH ₂ Cl ₂ (dichloromethane), MeOH (methanol), EtOH &Lt; / RTI &gt;
The method according to claim 1,
Wherein the photocatalyst is contained in an amount of 0.1 to 3 mol% based on the reaction mixture.