KR100718770B1 - Method for preparing keto-isophorone - Google Patents

Abstract

The present invention provides a keto-isophorone from β-isophorone through an oxidation reaction in which oxygen or air is injected using a catalyst in which CuCl ₂ or CuCl is mixed alone or with CuI in the presence of a reaction solvent, a base and a desiccant, 4-hydroxy isophorone, which is a byproduct of the reaction, is washed with water, and then a high yield and high purity method for preparing keto-isophorone isolating keto-isophorone from an organic layer. The use of a catalyst comprising CuCl ₂ or CuCl alone or in combination with CuI according to the present invention produces only 4-hydroxy isophorone as reaction byproduct, which can be economically prepared with high purity keto-isophorone by washing it off completely with water. have.

β-isophorone, keto-isophorone, CuCl 2 / CuCl, CuI, 4-hydroxy isophorone

Description

Method for preparing keto-isophorone {Method for preparing keto-isophorone}

The present invention provides high yield and high purity of 3,5,5-trimethylcyclohex-2-ene-1,4-dione (3,5,5-trimethylcyclohex-2-en-1,4-dione (hereinafter referred to as "keto -Isophorone "), and more specifically, an oxidation reaction using β-isophorone, a reactant, using CuCl ₂ or CuCl alone or a catalyst mixed with CuI, as shown in Scheme 1 below. It relates to a method for economically preparing high yield and high purity keto-isophorone through.

Keto-isophorone is trimethylhydroquinone (hereinafter referred to as "TMHQ") or trimethylhydroquinone diacetate (hereinafter referred to as "TMHQ") which produces α-tocopherol through condensation with isophytol under appropriate catalytic conditions. TMHQDA ") is an important intermediate product.

The production method of TMHQ or TMHQDA is classified into two methods using trimethylphenol (hereinafter referred to as "TMP") and α-isophorone depending on the reaction starting material.

In the method using TMP, TMHQ is prepared by a two-step reaction as in Scheme 2 below, and TMP itself is relatively expensive, and the yield of the oxidation step, which is the first step in Scheme 2, is not high, and a large amount of by-products are generated during oxidation. Therefore, although the reaction is simple in two steps, it is judged that there is no great advantage in the commercialization process.

On the other hand, the reaction using α-isophorone as a reaction starting material requires three steps of isomerization, oxidation and esterification as shown in Scheme 3 below, but the starting material α-isophorone is cheaper than TMP, Increasing the yield of each reaction is relatively competitive in terms of cost                         

The present invention relates to an oxidation reaction which is the second step in the above scheme for preparing TMHQDA from α-isophorone.

Keto-isophorone (KIP), which is an intermediate material necessary for preparing TMHQDA in Scheme 3, can generally be prepared by two methods, the first method of directly oxidizing α-isophorone, and another method. β-isophorone is prepared by isomerization of α-isophorone, followed by oxidation of β-isophorone. However, the second method is known to be more competitive because the first method, which has been directly oxidized α-isophorone to produce keto-isophorone, has very low values in conversion and selectivity.

The method for preparing keto-isophorone by oxidizing β-isophorone has been continuously developed until now, and more research has been conducted recently. The contents of the research so far are as follows.

Roche manufactured keto-isophorone through the oxidation reaction of α-isophorone using phosphomolybdic acid or silicomolybdic acid as a catalyst in Swiss Patent No. 616661. The yield was announced to be about 55%. This manufacturing technique has the advantage that the isomerization reaction in the reaction step can be omitted, but the cost of the compound (MoO ₃ , Ce (III) acetylacetonate, etc.) used as a catalyst and an additive is expensive and the yield is low have. The reaction rate is also very slow.

Roche also prepared keto-isophorone in US Pat. No. 4,036,361 in the yield of 75.5% by oxidation with oxygen in the presence of carbon black and base.

Firmenich SA, in US Pat. No. 4010205, uses a acetate type of transition metal and Cu alone or a support such as SiO ₂ , C, Mg, or the like for keto- Isophorone was prepared, but the yield was low, about 28 to 55%.

Daicel Co., Ltd. discloses a catalyst based on Mn salen of alkylene diamine having 2 to 8 carbon atoms and arylenediamine having 6 to 12 carbon atoms or N, N'-bissalicylidene in European Patent Publication No. 0962440A1. Keto-isophorone was prepared by oxidation of β-isophorone. This manufacturing technique has a good yield of about 65 to 90%. However, the manufacturing process of the Mn-ligand composite used as a catalyst is complicated, and the price is expensive.

Degussa, in US Pat. No. 58,74632, prepared a keto-isophorone with up to 92% yield in the presence of an additive using a Mn salen of N, N'-bissalicylidene as a catalyst. This yield is the reaction yield, and it is believed that a decrease in yield of some of the separations will occur. This manufacturing technique has the disadvantage that the catalyst is expensive and the manufacturing process is complicated in the same manner except for the die cell and the additive.

Accordingly, in the present invention, a keto-isophorone is prepared through an oxidation reaction of injecting oxygen or air using a catalyst in which CuCl ₂ or CuCl is mixed with CuI alone or CuI from β-isophorone as a reactant, and the only by-product of the reaction. Phosphorus 4-hydroxy isophorone was washed with water and keto-isophorone was separated from the organic layer to develop β-isophorone in high yield and high purity.

Accordingly, an object of the present invention is to provide a method for producing high yield and high purity keto-isophorone through oxidation from β-isophorone.

It is still another object of the present invention to design a manufacturing process and a refining process smoothly, and to develop a process that is easy and cost-competitive for commercialization by lowering manufacturing costs.

In order to achieve the above object, the method of the present invention uses a catalyst containing CuCl ₂ or CuCl alone or a mixture of CuI to react the reactants in a nonpolar hydrocarbon-based reaction solvent, a base and a desiccant, and β-isophorone as a reactant. Oxidation reaction is terminated within about 4 hours by injecting oxygen or air into the solution slowly at room temperature with stirring to generate bubbles. The product is filtered, washed with water and extracted with ethyl acetate. It consists of manufacturing the above high purity keto-isophorone.

Looking at the present invention in more detail as follows.

The present invention relates to a second step oxidation reaction on obtaining TMHQDA from α-isophorone as in Scheme 3 above.

According to the present invention, β-isophorone has two pathways for generating keto-isophorone through an oxidation reaction, when directly oxidizing and passing through two intermediates, as shown in Scheme 4 below.

As shown in Scheme 4, part of β-isophorone is directly oxidized to keto-isophorone, and part of keto-isophorone is prepared through intermediates 1 and 2, and intermediate 2 is completely converted into keto-isophorone. It is not converted and part of it remains. This reaction product, 4-hydroxy isophorone, can be washed with water to obtain almost pure keto-isophorone.

Accordingly, the present inventors prepared keto-isophorone from β-isophorone through an oxidation reaction in which oxygen or air was injected using a catalyst containing CuCl ₂ or CuCl alone or mixed with CuI in the presence of a reaction solvent, a base, and a desiccant. In addition, 4-hydroxy isophorone, a by-product of the reaction, was washed with water, and then keto-isophorone was separated from the organic layer to develop a method of preparing keto-isophorone in high yield and high purity.

In the present invention, a catalyst in which CuCl ₂ or CuCl was used alone or mixed with CuI was used. At this time, the difference between CuCl ₂ and CuCl did not appear significantly, and CuI was added to improve the selectivity of the reaction. The amount of the catalyst used is 0.01 mol to 1 mol based on 1 mol of β-isophorone for CuCl ₂ or CuCl, and 0.002 mol to 0.5 mol based on 1 mol of β-isophorone for CuI. The CuCl ₂ or CuCl and CuI do not have a difference in the reproducibility of the reaction as a result of drying after filtration and is believed to contribute to lower the manufacturing cost of the present invention.

An important point in the present invention is the miscibility of the reaction solution of CuCl ₂ / CuCl and CuI as a catalyst. The catalyst has the best mixing property in the polar solvent, but when the polar solvent is used, the reaction proceeds considerably rapidly, resulting in severe exotherm and thus many side reactions. In addition, when using a base (triethylamine or pyridine) as a solvent and base instead of a polar solvent, it was confirmed that the reaction proceeds rapidly and many side reactions proceed.

In order to prevent this, in the present invention, a non-polar aliphatic hydrocarbon having 5 to 15 carbon atoms such as n-pentane, n-hexane, n-heptane, cyclohexane, or aromatic hydrocarbon having 6 to 15 carbon atoms such as benzene or toluene is used as the reaction solvent. Preferably, non-reactive hydrocarbons such as n-pentane, n-hexane, n-heptane are used to suppress side reactions.

In terms of the base used, the base plays a role in the production of 4-hydroxy isophorone by the ring-opening reaction in the isophorone epoxide produced by the reaction mechanism. It is also believed that the catalysts contribute to the uniform dispersion of the catalyst. Bases used in the present invention include amines such as triethylamine, tributylamine and triphenylamine, pyridine and piperidine, and preferably triethylamine. The amount of base used is preferably 0.5 to 10 moles, more preferably 3 to 5 moles per 1 mole of β-isophorone.

Moisture generated as the oxidation progresses adversely affects the oxidation reaction in two ways. The first problem is that the water is hydrated to the catalyst to lower the reactivity of the catalyst. In this case, the reverse isomerization reaction in which β-isophorone is converted to α-isophorone is performed. Secondly, since the affinity of water and catalyst is much greater than the affinity of solvent and catalyst, the catalyst aggregates with water and sticks to the reactor wall, preventing further reactions. This effect is considered to be greater, to solve this problem was solved by removing the water generated by using a certain amount of the desiccant. At this time, the desiccant used did not show a big difference depending on the type, but basic NaHCO ₃ and Na ₂ CO ₃ were somewhat suitable in terms of effects and ease of treatment, and molecular sieves could be used.

The reaction temperature was suitable for room temperature reaction, but as the reaction proceeded as an exothermic reaction, the temperature rose to 60 to 70 ° C. In addition, when the temperature was increased, it was confirmed that the side reaction proceeded, and when kept at room temperature (optionally cooling), the conversion rate of the reaction was reduced and the progress of the side reaction was confirmed.

Regarding the reactor pressure and the flow rate of oxygen, it was confirmed that the pressure and the oxygen flow rate were not significantly influenced when the mixing effect of the reactor was not affected by the flow rate of the oxygen.

In addition, in the present invention, when air is used instead of oxygen, similar results were obtained except that the reaction time was delayed.

In the case of separation of the reaction product, the 4-hydroxy isophorone produced by the side reaction was washed with water to move to the entire water layer to obtain almost pure keto-isophorone. At this time, the extraction of the water layer with ethyl acetate was able to recover high-purity 4-hydroxy isophorone, and it was confirmed that there is almost no keto-isophorone transfer to the water layer.

Hereinafter, the present invention will be described in more detail with reference to the following examples, but the scope of the present invention is not limited to the following examples.

Example 1                     

3.45 g (25 mmol) β-isophorone and 0.67 g (5 mmol) CuCl ₂ , 0.285 g (1.5 mmol) CuI, 12.68 g (125 mmol) NEt ₃ , 40 ml n-heptane and a molecular sieve (Molecular sieve 4Å) in a 250 ml reactor ) 5.175 g (150% by weight) is added and oxygen is injected into the reaction solution through an injector, followed by stirring for 5 hours. The reaction product was identified by GC to obtain a conversion rate of 100% and a selectivity of 86.7% (reaction yield 86.7%). The catalyst was recovered by filtration, and the reaction product was washed with water to remove keto-isophorone 3.22 from the organic layer. g (total yield 84.7%) was obtained and the purity was 99.5%.

Example 2

The reaction was carried out under the same conditions as in Example 1 while reducing the amount of catalyst used. As a result, the concentration of the catalyst did not show a significant difference up to 0.05 mole with respect to 1 mole of β-isophorone, and the experimental results are shown in Table 1 below.

Production yield according to the change of catalyst concentration Example Reaction condition Catalyst concentration (mol) Reaction temperature (℃) Response time (hrs) % Conversion Selectivity (%) One Β-IP: 3.45 g (25 mmol) n-heptane 40 ml molecular sieve 5.175 gNEt ₃ 12.68 g CuCl ₂ : 5 mmol (0.2 mol) CuI: 1.5 mmol (0.06 mol) Room temperature 5 100 86.7 2 Same as above CuCl ₂ : 2.5 mmol (0.1 mol) CuI: 0.75 mmol (0.03 mol) Room temperature 5 100 87 3 Same as above CuCl ₂ : 1.25 mmol (0.05 mol) CuI: 0.375 mmol (0.015 mol) Room temperature 5 100 89

As shown in Table 1, there was almost no difference in reaction time and reactivity even when the amount of catalyst decreased from 0.2 mol / 0.06 mol of CuCl ₂ to 0.05 mol / 0.015 mol, respectively, relative to 1 mol of β-isophorone.

Example 3

Under the same conditions as in Example 1, an oxidation reaction was performed while changing the amount of base (NEt ₃ ). As a result, the amount of base showed a tendency to decrease in conversion, and the results are shown in Table 2 below.

Production yield according to the type and amount of base used Example Reaction condition Base concentration (mol) Reaction temperature (℃) Response time (hrs) % Conversion Selectivity (%) One Β-IP: 3.45 g (25 mmol) Molecular sieve: 5.175 gCuCl ₂ : 5 mmolCuI: 1.5 mmol Pyridine: 100ml Room temperature 6 100 60 2 Same as above NEt ₃ : 125 mmol (5 mol) Room temperature 5 100 86.7 3 Same as above NEt ₃ : 75 mmol (3 mol) Room temperature 5 98.5 85.3 4 Same as above NEt ₃ : 25 mmol (1 mol) Room temperature 5 92.1 85

Example 4

The oxidation reaction was performed by changing the type of desiccant under the same conditions as in Example 1, and the results are shown in Table 3 below.

Production yield according to the change of desiccant Example Reaction condition Desiccant (parts by weight) Reaction temperature (℃) Response time (hrs) % Conversion Selectivity (%) One Β-IP: 3.45 g (25 mmol) n-heptane 40 ml NEt ₃ : 125 mmol CuCl ₂ : 5 mmol CuI 1.5 mmol No use Room temperature 9 95.2 75.5 2 Same as above Molecular sieve: 5.175 g (150 parts by weight) Room temperature 5 100 86.7 3 Same as above NaHCO ₃ : 5.175g (150 parts by weight) Room temperature 5 100 84.3 4 Same as above Na ₂ CO ₃ : 5.175g (150 parts by weight) Room temperature 5 100 87.6

When the desiccant is not used, the reaction time is long, and the conversion and selectivity are low. The state of the reaction product also showed a state in which the catalyst was agglomerated on the reactor wall and was difficult to recover.

However, when the desiccant was used, similar reaction results were shown regardless of the type.

Example 5

Oxidation reaction was carried out by changing the type of solvent under the same conditions as in Example 1, and the results are shown in Table 4 below.

Yield according to the change of solvent Example Reaction condition menstruum                                              Reaction temperature (℃) Response time (hrs) % Conversion Selectivity (%) One Β-IP: 3.45 g (25 mmol) Na ₂ CO ₃ : 5.175 gNEt ₃ : 125 mmolCuCl ₂ : 5 mmolCuI: 1.5 mmol n-heptane: 40 ml Room temperature 5 100 86.7 2 Same as above 40 ml of n-hexane Room temperature 5 100 85.8 3 Same as above Methyl Isobutyl Ketone 40ml Room temperature One 100 71.6 4 Same as above Diglyme 40ml Room temperature 3 100 43.8 5 Same as above Toluene 40ml Room temperature 3 100 55.7 6 Same as above Dimethylformamide 40ml Room temperature One 100 11.1

As shown in the table, when the non-polar hydrocarbon was used as the solvent, it was the best in terms of production yield. In the case of using other polar solvents, the reaction time was shortened, but showed low values in terms of selectivity. When the polar solvent is used, the reaction proceeds abruptly, and the side reaction proceeds a lot and thus the selectivity decreases.

Example 6

The reaction was performed while injecting air instead of oxygen under the same conditions as in Example 1. As a result, the reaction time was increased to 10 hours, but the yield was 99.5%, and the selectivity was 85.8.

As described above, in the present invention, a keto-isophorone is prepared from the reactant β-isophorone through an oxidation reaction using a catalyst containing CuCl ₂ or CuCl alone or mixed with CuI, and the only by-product of the reaction is 4- High yield and high purity keto-isophorone can be obtained by washing the hydroxy isophorone with water and separating the keto-isophorone from the organic layer.

Compared with the prior art, this is a compound widely used commercially for a variety of purposes, in which a catalyst containing CuCl ₂ or CuCl alone or mixed with CuI is inexpensive, and can be reused after being recovered by filtration and drying. It is expected to improve the economic production of keto-isophorone because it is relatively inexpensive and is easily removed by simply washing with water 4-hydroxy isophorone, the only by-product that lowers the purity of the product after the reaction.

Claims (10)

In the presence of a reaction solvent, a base and a desiccant, a keto-isophorone was prepared from β-isophorone through an oxidation reaction in which CuCl ₂ or CuCl was mixed with CuI alone or mixed with CuI, and oxygen or air was injected. A method of producing keto-isophorone, comprising washing 4-hydroxy isophorone as a byproduct with water and then separating keto-isophorone from the organic layer. 2. The keto of claim 1, wherein the amount of CuCl ₂ or CuCl is used in an amount of 0.01 to 1 mol based on 1 mol of β-isophorone, and 0.002 mol to 0.5 mol based on 1 mol of β-isophorone. -Preparation of isophorone. The method of claim 1, wherein the reaction solvent is a non-polar aliphatic hydrocarbon having 5 to 15 carbon atoms or an aromatic hydrocarbon having 6 to 15 carbon atoms. The method for preparing keto-isophorone according to claim 3, wherein the aliphatic hydrocarbon is n-pentane, n-hexane or n-heptane. The method of claim 1, wherein the base is triethylamine, tributylamine, triphenylamine, pyridine or piperidine. The method of claim 5, wherein the base is triethylamine. The method of claim 5, wherein the base is used in an amount of 0.5 to 10 moles based on 1 mole of β-isophorone. The method of claim 7, wherein the base is used in an amount of 3 to 5 moles based on 1 mole of β-isophorone. The method of claim 1, wherein the desiccant is molecular sieve, NaHCO ₃ or Na ₂ CO _{3 The} method for producing keto-isophorone. delete