KR100194516B1 - Method of preparing ketone - Google Patents

Abstract

The present invention relates to a method for preparing a ketone by adding a transition metal catalyst to an alcohol and an alken, wherein a little rhodium metal catalyst is added to an alcohol and an alken as a raw material, and 2-aminopyridine derivative is used as an additive. Put together, the reaction mixture is heated to about 80 to 200 degrees Celsius 6 to 330 hours to obtain a ketone compound as a product, the present invention is to prepare a ketone in the step of administering a 2-aminopyridine derivative as an additive This can greatly reduce the manufacturing cost of ketones.

Description

Method of preparing ketone

The present invention relates to a method for preparing a ketone by putting a transition metal catalyst in a primary alkyl alcohol and an alkene.

One of the most common methods of preparing ketones from primary alcohols is to first make primary alkyl alcohols using a mild oxidizing agent such as pyridinium chloro chromate (PCC), and to convert these aldehydes to alkyls. It reacts with an organometallic compound, a nucleophilic reagent such as metal, to make secondary alkyl alcohol, and then oxidizes the secondary alkyl alcohol with an oxidizing agent to form a ketone.

However, this method has a disadvantage of not only having to go through several reaction steps but also generating many unnecessary by-products during the reaction.

The present invention is to simply reduce the multi-step reaction as described above in one step and to provide a method for preparing a ketone that can proceed in a moderate reaction conditions. The synthesis of ketones through the reaction of primary alkyl alcohols and olefins under a transition metal catalyst as in the present invention is a reaction that cannot be found in the present invention. There is no bar.

In the present invention, a small amount of a transition metal catalyst is added to primary alkyl alcohol and alkene as raw materials, and 2-aminopyridine or a derivative thereof is added to the reaction mixture. It is to provide a method for producing a ketone that can be obtained in a high yield by heating for 6 hours to 330 hours without solvent to about -200 ℃.

Such a feature of the present invention is to react by adding a 2-aminopyridine derivative as an additive or a catalyst with a transition metal catalyst.

The primary alkyl alcohol as the starting material may be either an aromatic alcohol such as benzyl alcohol or 2-naphthalene methanol or an aliphatic alcohol. In the case of both alcohols, especially aliphatic alcohols, it is preferable to add a base such as potassium carbonate (K ₂ CO ₃ ) additionally with the aforementioned additives as described below. Alkenes were able to convert not only various 1-alkenes including 1-pentene but also internal alkenes such as cyclohexane to ketones.

Usually a metal catalyst as the phosphorus trihalide rhodium _{(Ⅲ) · (RhX 3,} X = Cl, B r, I) or preferred to employ a hydrate thereof, and, at this time, the phosphine compound, such as a tree re-triphenylphosphine (PPh ₃₎ Should be put together. It is presumed that rhodium trihalide (III) tristriphenylphosphinedium (I) halide is produced in the reactor, which acts as a reaction catalyst. Therefore, the actual working rhodium catalyst species is considered to be rhodium monovalent, and it can be seen that the reaction proceeds even by directly using a tristriphenylphosphine rhodium (I) halide catalyst. The phosphine-containing rhodium (I) catalyst may be made by adding phosphine to a rhodium + monovalent catalyst such as bis (cyclooctene) rhodium (I) halide in the reactor.

2-aminopyridine or a derivative thereof is mixed with the transition metal catalyst as an additive, which is the core of the present invention. As the 2-aminopyridine or its derivatives as such an additive, various amine derivatives can be widely used, but it was found that it is more preferable to use 2-amino-3-picolin during such induction. When the 2-aminopyridine derivative administered as an additive is used less than the equivalent of aldehyde, although the reaction rate decreases, the reaction proceeds. As 2-aminopyridine or a derivative thereof, one having a substituent such as aliphatic or aromatic in the 3, 4 or 5 position of pyridine may be used.

No organic solvent was used in all reactions and this can also be said to be a feature of the invention. However, when the reactants are solid or gas rather than liquid or depending on the reaction conditions, a solvent such as toluene, tetrahydrofuran or benzene may be used.

It is assumed that the reaction in the present invention proceeds in two stages: first, one molecule of olefins oxidizes the primary alkyl alcohol to aldehyde, and then another molecule of olefins with the aid of aldehyde and 2-aminopyridine derivative. It is estimated that ketones are finally produced by performing the misfire reaction.

The oxidation of aldehydes of primary alkylalcohols is thought to be carried out under olefins and transition metal catalysts. Similar reactions include Oppenauer oxidation (Muller, P. Goday, J. Tetrahedron Lett. 1981, 22, 2361.) Oppena-type oxidation is a reaction in which the hydroxyl group of an alcohol is converted to a carbonyl group while the hydrogen of the alcohol group moves to an olefin or ketone used as a hydrogen acceptor in the presence of a metal catalyst. In this reaction, the excess alkenes are oxidized by the oxidation of alcohol through the reaction of fenore to hydrogen acceptor to generate aldehyde, and the resulting aldehyde is subjected to hydroacylation of alkenes with rhodium catalyst, phosphine compound, 2-aminopyridine derivative. It is presumed to carry out under additives to produce ketones (Suggs, JWJ Am Chem Soc. 1979, 101, 489. Suggs, JW United States Patent (1980), 4,241,206). It can be explained that it acts as oxidation of alcohol, that is, hydrogen acceptor, and the other participates in hydroacylation reaction. Therefore, the amount of the olefin should be at least twice as large as the alcohol, the more it can be seen that the higher the speed or yield.

Looking at the expected reaction mechanism in the present invention is shown in Figure 1.

The primary alkyl alcohol is aldehyde oxidized through hydrogen transfer reaction between the rhodium catalyst and the olefin, and the resulting aldehyde is condensed with 2-aminopyridine derivative to produce intermediate aldehyde and water. Aldimin reacts with alkenes under a catalyst to produce ketamine through hydroiminoacylation, which is hydrolyzed by the water produced at the beginning of the reaction to regenerate 2-aminopyridine derivatives to produce the resulting ketone compound. do. Thus, 2-aminopyridine derivatives can only be reused since they are used only as a tool for catalysts. The invention is characterized in that all of the above reactions proceed in one step.

When the present invention is described in detail according to various embodiments as follows.

Example 1

[Synthesis of 1-phenyl-1-heptanone via benzyl alcohol and 1-hexene under a catalyst of rhodium trichloride (III) hydrate (RhCl ₃ · H ₂ O) and 2-amino-3-picoline]

51.7 mg (0.48 mmol) 2-amino-3-picolin, 51.7 mg (0.48 mmol) benzyl alcohol, 62.7 mg (0.24 mmol) triphenylphosphine, 10 mg (0.048 mmol) in a 0.5 mL small pressure reactor (10 mol% relative to benzyl alcohol) add rhodium trichloride (III) hydrate (RhCl ₃ · H 2 _O ), add 402 mg (4.8 mmol) of 1-hexene, and stop the stopper.

The mixture is heated to 130 ° C. for 72 hours with stirring. After tumbling, the resultant was purified by silica gel column chromatography (hexane: ethyl acetate = 5: 2 eluent) to give 1-phenyl-1-heptanone as a yellow oil in a yield of 86% (85.5 DEG C; 0.45 mmol).

The result of the reaction of various alkenes and benzyl alcohol under the above reaction conditions is as follows.

Example 2

[Synthesis of 1-phenyl-1-heptanone by reaction of benzyl alcohol and 1-pentene under a catalyst of chlorotris (triphenylphosphine) rhodiun (I) (Wilkinson complex) and 2-amino-3-picolin

26 mg (0.028 mmol) of tristriphenylphosphinedium (1) chloride were added to a 0.5 mL small pressure reactor, and 200 mg (1.9 mmol) of benzyl alcohol was added thereto. Subsequently, 30.3 mg (0.281 mmol) of 2-amino-3-picolin and 200 mg (2.9 mmol) of 1-pentene are added, and the stopper is closed. The mixture is heated to 100 ° C. for 145 hours with stirring.

After the reaction, the solvent was blown out of the mixture by an evaporator, and purified by silica gel column chromatography (ratio of hexane and ethyl acetate = 5: 2) to give 18.3 mg (0.104 mmol) of pale yellow oil, 1-phenyl-1-hexanone. Get it. In this case the turnover of the product for the tristriphenylphosphinedium (1) chloride catalyst is 3.7.

Example 3

[Synthesis of 1-phenyl-1-hexanone over time at 100 ° C. of benzyl alcohol and 1-pentene under a catalyst of rhodium trichloride (III) hydrate (RhCl.HO) and 2-amino-3-picolin.

31.0 mg (0.29 mmol) 2-amino-3-picolin, 200 mg (1.9 mmol) benzyl alcohol, 37.6 mg (0.14 mmol) triphenylphosphine, 6 mg (0.029 mmol) in a 0.5 mL small pressure reactor (10 mol% relative to benzyl alcohol) rhodium trichloride (III) hydrate (RhCl.H2) is added, 200 mg (2.9 mmol) of 1-pentene is added, and the stopper is closed. The mixture is allowed to react by varying the time to 100 ° C. with stirring. After the reaction was performed under the conditions shown in the following table, the resultant was purified by silica gel column chromatography (hexane: ethyl acetate = eluent of 5: 2) to obtain 1-phenyl-1-hexanone having the result shown in the following table.

Example 4

1-phenyl-1 under conditions in which benzyl alcohol and 1-pentene were added water at 100 ° C. for 60 hours under a catalyst of rhodium trichloride (III) hydrate (RhCl · HO) and 2-amino-3-picolin. -Synthesis of heptanone]

Turnover increased from 5.1 to 10.1 when 43. mg (2.39 mmol) of water was added in the same reaction conditions as in Example 3 (60 hours) and in the experimental method.

Example 5

[Synthesis of 1-phenyl-1-heptanone at a temperature of benzyl alcohol and 1-hexene under a catalyst of rhodium trichloride (III) hydrate (RhCl.HO) and 2-amino-3-picolin]

51.7 mg (0.48 mmol) 2-amino-3-picolin, 51.7 mg (0.48 mmol) benzyl alcohol, 62.7 mg (0.24 mmol) triphenylphosphine, 10 mg (0.048 mmol) in a 0.5 mL small pressure reactor (10 mol% of benzyl alcohol) rhodium trichloride (III) hydrate (RhCl.H2) is added, 402 mg (4.8 mmol) of 1-hexene is added, and the stopper is closed. The mixture is heated at various temperatures for 12 hours with stirring. The reaction was carried out at different reaction temperatures, and then purified by silica gel column chromatography (hexane: ethyl acetate = eluent of 5: 2) to obtain 1-phenyl-1-heptanone.

Example 6

[1- (4-methoxyphenyl) -1 through reaction of 4-methoxybenzyl alcohol and 1-pentene under a catalyst of rhodium trichloride (III) hydrate (RhCl.HO) and 2-amino-3-picolin -Synthesis of hexanon]

51.7 mg (0.48 mmol) 2-amino-3-picolin, 66.17 mg (0.48 mmol) 4-methoxybenzyl alcohol, 62.7 mg (0.24 mmol) triphenylphosphine, 10 mg in a 0.5 mL small pressure reactor (0.048 mmol) (10 mol% relative to para-ennis alcohol) is added rhodium trichloride (III) hydrate (RhCl.HO), 335 mg (4.8 mmol) of 1-pentene is added, and the stopper is closed. The mixture is heated to 130 ° C. for 72 hours with stirring. After the reaction, the mixture was purified by silica gel column chromatography (hexane: ethyl acetate = eluent of 5: 2) to obtain 1- (4-methoxyphenyl) -1-hexanone in a yield of 56% (55.6 mg; 0.270 mmol). .

The results of using various alcohols under the same reaction conditions are as follows.

Example 7

[1-phenyl-3- via reaction of 3-phenylpropanol and 1-pentene added potassium carbonate as a base under the catalyst of rhodium trichloride (III) hydrate (RhCl.HO) and 2-amino-3-picolin Synthesis of Octanone]

51.7 mg (0.48 mmol) 2-amino-3-picolin, 64.5 mg (0.48 mmol) 3-phenylpropanol, 62.7 mg (0.24 mmol) triphenylphosphine, 10 mg (0.048) in a 0.5 mL small pressure reactor mmol) (10 mol% relative to 3-phenylpropanol) of rhodium trichloride (III) hydrate (RhCl.HO) (3) chloride, and 13.2 mg (0.096 mmol) of potassium carbonate was added, followed by 335 mg. (4.8mmol) of 1-pentene is added and the stopper closed. The mixture is heated to 130 ° C. for 72 hours with stirring.

After the reaction, the mixture was purified by silica gel column chromatography (hexane: ethyl acetate = eluent of 5: 2) to obtain 1-phenyl-3-octanone in a yield of 67% (64.3 mg; 0.32 mmol). It was found that a much larger amount of 1-phenyl-3-octanone can be obtained than the yield of 7.7% when not.

Example 8

[Synthesis of 1-phenyl-hexanone according to the amount of 4-methoxybenzyl alcohol and 1-pentene under a catalyst of rhodium trichloride (III) hydrate (RhCl.HO) and 2-amino-3-picoline]

31 mg (0.29 mmol) 2-amino-3-picolin, 62 mg (0.57 mmol) benzyl alcohol, 37.6 mg (0.14 mmol) triphenylphosphine, 6 mg (0.029 mmol) in a 0.5 mL small pressure reactor (5 mol% relative to benzyl alcohol) rhodium trichloride (III) hydrate (RhCl.HO) is added, and the amount of 1-pentene is added and the stopper is closed. The mixture is heated to 130 ° C. for 72 hours while stirring.

After the reaction, the yield of 1-phenyl-1-hexanone obtained by purification by silica gel column chromatography (hexane: ethyl acetate = eluent of 5: 2) was shown in the table below.

Example 9

[Synthesis of 1-phenyl-1-hexanone via benzyl alcohol and 1-pentene added phase change catalyst under the catalyst of rhodium trichloride (III) hydrate (RhCl.HO) and 2-amino-3-picolin]

73% higher than the yield when no phase transfer catalyst was added, such as 3 mg (0.013 mmol) of benzyltriethylamine chloride, in the same reaction conditions and experimental methods as in Table 3 of Example 8. Yield 1-phenyl-1-hexanone in% yield.

Example 10

[Synthesis of aldehydes and ketones via methanol and 2.3.4.5.6-pentafluorostyrene under the catalyst of rhodium trichloride (III) hydrate (RhCl.HO) and 2-amino-3-picolin]

In a 0.5 mL small pressure reactor, 31 mg (0.29 mmol) of 2-amino-3-picolin, 200 mg (6.25 mmol) of methanol, 37.6 mg (0.14 mmol) of triphenylphosphine, 6 mg (0.029 mmol) of Rhodium trichloride (III) hydrate (RhCl.HO) and 600 mg (3.09 mmol) of 2,3,4,5,6-pentafluorostyrene are added and the stopper is closed. The mixture is heated to 130 ° C. for 40 hours with stirring. After the reaction, the composition of the reaction mixture was confirmed by gas chromatography, indicating that aldehyde and ketone were obtained.

Purified by silica gel column chromatography (hexane: ethyl acetate = eluent of 5: 2) to 3- (2,3,4,5,6-pentafluorophenyl) -1-propionaldehyde and bis-2- (2,3,4, 5,6-pentafluorophenyl) ethylketone was obtained with turnovers of 1.2 and 4.3, respectively.

Example 11

[Synthesis of ketones via methanol and vinyl cyclohexane under the catalyst of rhodium trichloride (III) hydrate (RhCl.HO) and 2-amino-3-picoline]

In a 0.5 mL small pressure reactor, 31 mg (0.29 mmol) of 2-amino-3-picolin, 72 mg (2.3 mmol) of methanol, 37.6 mg (0.14 mmol) of triphenylphosphine, 6 mg (0.029 mmol) of Rhodium trichloride (III), hydrate (RhCl, HO), 341 mg (3.1 mmol) of vinyl cyclohexane were added, and the stopper was closed. The mixture is heated to 130 ° C. for 72 hours with stirring. After the reaction, the residue was purified by silica gel column chromatography (hexane: ethyl acetate = eluent of 5: 2) to obtain dicyclohexylethyl ketone as a turnover of 4.3.

The summary of the embodiment is as follows.

Alkene and benzyl alcohol as in Example 1 were added to the reactor, followed by 50 mol% of 100 mol% of 2-amino-3-picolin and 10 mol% of rhodium (III) hydrate (RhCl.HO) catalyst. After triphenylphosphine was added, the reaction mixture was reacted at 130 ° C. for 72 hours, and the product was purified to obtain a ketone. At this time, various alkenes could be used to obtain various ketones.

As shown in Example 2, not only the rhodium trichloride (III) hydrate (RhCl-HO) catalyst but also the rhodium monovalent catalyst were able to proceed with the same reaction.

As shown in Example 3, when water was added under constant reaction conditions, ketones were obtained in a higher yield.

As shown in Example 4, when the reaction time was increased under constant reaction conditions, ketones were obtained at higher yields.

As shown in Example 5, when water was added under constant reaction conditions, ketones were obtained in a higher yield.

As shown in Example 6, various alcohols, such as 1-alkanol, aromatic ethanol and methanol containing a hetero ring, were applied to the present invention to obtain a ketone.

As shown in Example 7, when a basic additive such as potassium carbonate (KCO) was added, ketones were obtained in higher yield under reaction conditions without addition thereof.

As shown in Example 8, when water was added under constant reaction conditions, ketones were obtained at higher yields.

As shown in Example 9, ketones were obtained in higher yield when a phase transfer catalyst was added to assist in mixing the raw materials of the rhodium 3 catalyst.

As shown in Example 10, when methol was used as the alcohol, a ketone was obtained together with the aldehyde.

As shown in Example 11, only methanol was obtained by using methanol as the alcohol and vinyl cyclohexane as the alkene.

The present invention is an entirely new method of synthesizing ketones from alcohol, and the conventional ketone production method, which was able to synthesize ketones from alcohol only through a multistage reaction, is shortened in one step, so that all the reactions can be completed in one reactor in the reaction process. This reaction also shows the selectivity to produce only linear alkylketones.

Furthermore, the present invention can react even in moderate reaction conditions without the need for a high pressure reaction when the reactant is not a gas can be produced ketone without using a high pressure reactor can significantly reduce the reactor manufacturing cost. Although it does not matter even if a solvent is used in the reaction, since the reactant is mainly a liquid alcohol, the reaction can be performed without using a solvent, which has the advantage of reducing the reactor to a minimum. The alcohol is converted directly into the ketone, which is almost a product, and some of the olefins that acted as hydrogen acceptors are saturated hydrocarbons, but can be easily blown off after the reaction. This means that no by-products are generated and it is considered as the best way to reduce environmental pollution in the future because it is a process that does not generate pollutants.

The alcohol which can be applied to the present invention is not only a special alcohol but also has the advantage of being widely applicable to almost all alcohols such as aliphatic alcohols, heterocyclic alcohols, organometallic alcohols, as well as aromatic alcohols. Reaction with not only terminal olefins such as alkenes but also internal olefins such as cyclohexene has the advantage of being applicable to a wide range of olefins.

Claims (9)

Primary alkyl alcohols and alkenes as starting materials add rhodium and phosphine compounds as catalysts, and a small amount of transition metal catalyst is added thereto, and 2-aminopyridine or a derivative thereof is added as an additive, and the above reaction mixture is weakened. Method of producing a ketone to obtain a ketone compound as a product while heating for 6 to 330 hours at about 80 to 180 degrees Celsius. 2. The method of claim 1, wherein the alcohol is an aliphatic primary alkyl alcohol comprising aromatic primary alkyl alcohol or methanol. The method of claim 1, wherein the alkene is a method for producing a ketone, characterized in that the olefin (olefin) having an aromatic or aliphatic group. The method for producing a ketone according to any one of claims 1 to 3, wherein the transition metal catalyst is a rhodium monovalent catalyst. Claim 1 to claim 3 Compounds according to any one of, wherein the transition metal catalyst is a phosphorus trihalide rhodium _{(Ⅲ) · (RhX 3,} X = Cl, B r, I) or the hydrate thereof, to put together a phosphine compound Ketone production method characterized in that. The method for producing a ketone according to any one of claims 1 to 3, wherein the transition metal catalyst is a rhodium monovalent catalyst and a phosphine compound is added thereto. The 2-aminopyridine or derivative thereof as an additive is a 2-aminopyridine derivative having a substituent such as aliphatic or aromatic at the 3,4,5-position, according to any one of claims 1 to 3 Ketones are produced. The method for producing a ketone according to any one of claims 1 to 3, wherein a base including potassium carbonate (K ₂ CO ₃ ) is further added as an additive. The ketone production method according to any one of claims 1 to 3, wherein water is added together with a phase change catalyst such as benzyltriethylamine chloride as an additive.