JPS6144853B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing levulinic acid or an ester thereof from 4-pentenoic acid or an ester thereof.

Lebrilic acid and its esters are important as raw materials for fragrances and pharmaceuticals.

Conventionally, methods for producing levulinic acid include (1) a method of heat treating starch or molasses (for example, Org.
Syn.Coll.Vol.1, p335, etc.), (2) method of ring-opening furfuryl alcohol by heating in dilute acid (for example, Japanese Patent Publication No. 51-39205, etc.), (3) Decarboxylation of acetonylmalonic acid. There are methods to do this (for example, Japanese Patent Publication No. 17009/1983). However, method (1) involves many side reactions and has a low yield, and method (3) requires expensive starting materials, and it is difficult to say that either method is satisfactory as an industrial production method. In addition, although method (2) has a good yield, the reaction conditions are harsh.

As a result of intensive research by the present inventors to develop a method that does not have the above-mentioned problems in conventional methods, we found that by oxidizing 4-pentenoic acid or its ester using palladium chloride, copper chloride, and oxygen in an aqueous mixed solvent, discovered a method for obtaining levulinic acid or its ester, leading to the present invention.

An object of the present invention is to provide a method for producing levulinic acid or its ester by reaction under mild conditions starting from industrially easily and inexpensively available substances.

That is, the present invention, which has achieved the above object, is capable of producing 4-pentenoic acid or its ester represented by the general formula CH ₂ =CHCH ₂ CH ₂ CO ₂ R (R is a hydrogen atom or a lower alkyl group) in water or an aqueous mixed solvent. It is characterized by oxidation with palladium chloride in the presence of copper chloride and oxygen.

The reaction in the method of the present invention is thought to proceed as shown in the following equation.

CH ₂ = CHCH ₂ CH ₂ CO ₂ R+PdCl ₂ +H ₂ O→CH ₃ COCH ₂ CH ₂ CO ₂ R +Pd+2HCl …(1) Pd+2CuCl ₂ →PdCl ₂ +2CuCl …(2) 2CuCl+1/2O ₂ +2HCl→2CuCl ₂ +H ₂ O ……(3) As a total, CH ₂ = CHCH ₂ CH ₂ CO ₂ R + 1/2O ₂ → CH ₃ COCH ₂ CH ₂ CO ₂ R …(4) However, R is as described above.

That is, 4-pentenoic acid or its ester is easily oxidized with palladium chloride in the presence of water under mild conditions to form levulinic acid or its ester (Formula (1)). Palladium is reduced to a zero-valent state, but is reoxidized by cupric chloride to become palladium chloride (Formula (2)). Cupric chloride becomes cuprous chloride by oxidizing palladium, but it is easily oxidized by oxygen in the presence of hydrochloric acid (produced by formula (1)) to cupric chloride. Become. In total, 4-pentenoic acid or its ester is oxidized by oxygen only to levulinic acid or its ester, and no reagent is consumed.

4-Pentenoic acid or its ester used as a starting material in the present invention can also be obtained by the reaction of allyl halide and malonic acid ester, but it is cheaper to obtain dimethyl sebacate by the Kolbe electrolysis reaction of adipic acid monomethyl ester. Obtained as a by-product during manufacturing. That is, a mixture of methyl 4-pentenoate and methyl n-valerate is obtained as a low-boiling byproduct during the production of dimethyl sebacate;
This can be used directly as a starting material for the method of the present invention. After the oxidation reaction, methyl levulinate and methyl n-valerate can be easily separated.

When comparing 4-pentenoic acid and its ester used as a starting material, 4-pentenoic acid ester is preferable in terms of reaction yield. Examples of the 4-pentenoic acid ester include esters of lower alcohols having 1 to 8 carbon atoms, such as methyl 4-pentenoate,
Ethyl 4-pentenoate, isopropyl 4-pentenoate, etc. may be used, but methyl 4-pentenoate is most preferred from the viewpoint of industrial availability.
As a solvent, water alone, a two-layer mixed solvent such as water-carbon tetrachloride, water-benzene, water-chloroform, etc.
dimethylformamide, dimethyl sulfoxide,
A homogeneous mixed solvent of a polar aprotic solvent such as hexamethylphosphortriamide and water, a homogeneous mixed solvent of water and an alcohol such as methanol or ethanol, etc. are used, but from the viewpoint of reaction yield, - Carbon tetrachloride, water-benzene or water-dimethylformamide mixed solvents are preferred. On the other hand, from the viewpoint of ease of recovery and reuse of palladium chloride and copper chloride, two-layer mixed solvents such as water-carbon tetrachloride and water-benzene are preferred. Therefore, industrially, a water-carbon tetrachloride mixed solvent or a water-benzene mixed solvent is most preferred.

When using an aqueous mixed solvent, the ratio of water to organic solvent is 1:0.1 to 1:20 in a two-layer system such as water: carbon tetrachloride or water: benzene. For a homogeneous layer system such as a water:dimethylformamide system, a volume ratio of 1:2 to 1:15 is preferred. The amount of the aqueous mixed solvent to be used may be an amount that dissolves 4-pentenoic acid or its ester, palladium chloride, and copper chloride, and an amount that allows sufficient stirring.

When only water is used, the amount of solvent to be used is sufficient as long as it dissolves palladium chloride and copper chloride and allows sufficient stirring.

Palladium chloride used as an oxidizing agent in the present invention is oxidized once as shown in reaction formulas (1) and (2).
However, it is oxidized by copper chloride to become palladium chloride again. Therefore, the amount of palladium chloride used may be a catalytic amount, usually 4
- From 0.05 to 0.7 molar equivalents, preferably from 0.07 to 0.2 molar equivalents, based on the amount of pentenoic acid or its ester used.

As the copper chloride used in the present invention, cuprous chloride, cupric chloride, or a mixture thereof can be used, but cuprous chloride is preferable from the viewpoint of yield. On the other hand, cupric chloride is preferred from the standpoint of loss of expensive palladium catalyst.

It is not clear why the yield of the target product is improved by about 10% when cuprous chloride is used compared to when cupric chloride is used, but when cuprous chloride is used, the starting This is thought to be because chlorination of the raw material 4-pentenoic acid or its ester is suppressed.

Palladium lost during the reaction is contained in the products such as carbon tetrachloride layer, benzene layer, etc. When cuprous chloride is used, the escape of palladium into the organic layer is as much as 0.53 g-Pd/Kg-methyl levulinate, whereas when cupric chloride is used, it is 0.01 g-Pd/Kg-methyl levulinate.
The escape is less than Pd/Kg - methyl levulinate.
Therefore, from the standpoint of palladium loss, cupric chloride is preferred.

Therefore, it is difficult to say whether it is more advantageous to use cuprous chloride or cupric chloride as it depends on manufacturing conditions and other factors, but in general, it is better to use cuprous chloride or cupric chloride, which results in less loss of palladium. Cupric chloride is preferred. The amount of copper chloride used is usually 4
- From 0.1 to 3 molar equivalents, preferably from 0.4 to 1.5 molar equivalents, based on the amount of pentenoic acid or its ester used.

The method of the present invention is carried out at a temperature in the range of 0°C to 100°C, preferably 50 to 70°C from the viewpoint of reaction yield.

Although the present invention can be carried out under increased pressure or slightly reduced pressure, it is preferable to carry out the process at normal pressure in view of the reactor.

The amount of oxygen supplied is 500 to 4000 per reaction solution.
The amount may be about cc/min, and it is preferable to finely disperse and blow.

The product, levulinic acid or its ester, can be prepared by separation, distillation, or
It can be easily isolated and purified by conventional methods such as extraction, column chromatography, and gas chromatography.

The palladium chloride used in the reaction is, for example, water-
If a dimethylformamide-based mixed solvent is used, it is possible to reuse it after separating levulinic acid or its ester. It can also be precipitated as a complex and then separated and recovered. In addition, when using a two-layer solvent such as a water-carbon tetrachloride mixed solvent or a water-benzene mixed solvent, the organic layer and the aqueous layer are separated, and the aqueous layer is further treated with levulinic acid or with carbon tetrachloride or benzene. After the ester is extracted, it can be reused in the next oxidation reaction.

When only water is used, the reaction solution can be reused after extracting levulinic acid or its ester with a suitable organic solvent such as benzene, carbon tetrachloride, or ether.

As described above, when considering the recovery and reuse of palladium chloride and copper chloride, uniform layer type mixed solvents such as water-dimethylformamide type mixed solvents have problems in industrial implementation. Furthermore, considering the reaction yield, water-
Bilayer solvent mixtures such as carbon tetrachloride or water-benzene solvent mixtures are suitable for industrial practice.

Levulinic acid or its ester isolated and purified as a product may be used as a product as it is, or in the case of levulinic acid, it can be easily made into an ester with an appropriate alcohol by a conventional method. When it is obtained, it is extremely easy to hydrolyze it to levulinic acid using a conventional method.

When carrying out the method of the present invention, it goes without saying that the reaction operation can be carried out either batchwise or continuously.

The present invention provides the following advantages: (a) In order to use 4-pentenoic acid or its ester as a starting material, a by-product during the electrolytic production of dimethyl sebacate from monomethyl adipate can be used and is industrially available. It is very economical in that it can be started from inexpensive materials.

(b) using palladium chloride, a mild oxidizing agent;
Since the reoxidation can be easily carried out by simply consuming oxygen, the overall reaction conditions are mild and the reaction operation is easy.

Thus, the present invention has great significance in that it provides a very advantageous industrial process for producing levulinic acid or its ester.

The present invention will be explained in detail below with reference to Examples. Note that the terms used in the examples shall comply with the following definitions.

(1) Conversion rate Conversion rate = Number of moles of consumed 4-pentenoic acid or its ester / Number of moles of charged 4-pentenoic acid or its ester × 100 (%) (2) Selectivity Selectivity = Produced Number of moles of levulinic acid or its ester/number of moles of consumed 4-pentenoic acid or its ester x 100 (%) (3) Yield Yield = number of moles of levulinic acid or its ester produced/number of charged 4-pentenoic acid or its ester −Number of moles of pentenoic acid or its ester×
100 (%) Example 1 Palladium chloride in a 3-necked flask (capacity 1)
5.93g (33.4mmole), cupric chloride dihydrate 52.3
g (307 mmole), water 201.8 g, carbon tetrachloride 491.8
g, and 38.1 g (334 m
After adding the microbubbled oxygen in an oil bath, keep the internal temperature at 63℃ and stir thoroughly.
Bubbled at ml/min. After the reaction was carried out at 63°C for 2 hours, the reaction was continued for an additional 14 hours and 30 minutes at room temperature. The carbon tetrachloride layer was separated and the aqueous layer was extracted several times with carbon tetrachloride. The extracted carbon tetrachloride solution was combined with the previous carbon tetrachloride layer and carbon tetrachloride was distilled off by conventional distillation. Distill the residue under reduced pressure to a boiling point of 84-86℃/14
Methyl levulinate 30.2g as colorless liquid at mmHg
I got it. The isolated yield was 69.5%. Quantification by gas chromatography showed a conversion rate of 99.8% for methyl 4-pentenoate and selectivity for methyl levulinate.
It was 74.2%.

The distillation residue after distilling off methyl levulinate was transferred to a quartz beaker and the organic matter was combusted in an electric furnace. Next, aqua regia was added to the remaining ash and boiling and evaporation to dryness were repeated three times. Finally, the ash was dissolved in hydrochloric acid and palladium was determined by atomic absorption spectrometry. The amount of palladium that escaped into the carbon tetrachloride layer was 0.0029 g per 1 kg of methyl levulinate.

Example 2 492 g of carbon tetrachloride and methyl 4-pentenoate were added to the aqueous layer after carbon tetrachloride extraction in Example 1.
A reaction was carried out in the same manner as in Example 1 by adding 38.5 g (338 mmole). Analysis by gas chromatography showed that the conversion rate of methyl 4-pentenoate was 100.
%, and the selectivity for methyl levulinate was 75.1% (based on the newly added methyl 4-pentenoate).

Example 3 Palladium chloride was added to a 100 c.c. three-necked flask.
0.526g (2.97mmole), cupric chloride dihydrate 2.58
g (15.1 mmole), 4.11 g of water, 30.78 g of dimethylformamide, and 3.43 g of methyl 4-pentenoate.
After adding (30.1 mmole), the internal temperature was adjusted to 62℃ in an oil bath.
Microbubbled oxygen was blown in at a rate of 50 ml/min while maintaining the temperature at a constant temperature and stirring thoroughly. Analysis after 4 hours and 15 minutes of reaction revealed that the conversion rate of methyl 4-pentenoate was 98.8% and the selectivity of methyl levulinate was 62.0.
It was %.

Example 4 Palladium chloride 0.576 in a 100c.c. three neck flask
g (3.25 mmole), cupric chloride dihydrate 5.18 g
(30.4 mmole), 20.03 g of water, 47.75 g of carbon tetrachloride, and 3.09 g (30.9 mmole) of 4-pentenoic acid, and while keeping the internal temperature at 62°C in an oil bath and stirring thoroughly, microbubbled oxygen was added. was blown at a rate of 40 ml/min. After reacting for 5 hours and 30 minutes, diazomethane was blown into both the aqueous layer and the carbon tetrachloride layer and analysis revealed that the conversion rate of 4-pentenoic acid was 99.9% and the yield of levulinic acid was 9.8%.

Example 5 0.513 g of palladium chloride (28.9 m
mole) cupric chloride dihydrate 2.59g (15.2m
mole), water 2.16g, dimethylformamide 13.27g
and 3.00 g (30.0 mmole) of 4-pentenoic acid were charged, and while the internal temperature was kept at 60° C. and sufficient stirring was carried out in an oil bath, finely bubbled oxygen was blown in at a rate of 20 ml/min. After continuing the reaction for 5 hours and 30 minutes, analysis revealed that
The conversion rate of 4-pentenoic acid was 100%, and the yield of levulinic acid was 11.9%.

Example 6 Monomethyl adipate 400g, potassium hydroxide
A mixture of 14 g of methanol and 586 g of methanol was subjected to non-diaphragm electrolysis using a platinum anode at a current density of 10 A/dm ² and a liquid temperature of 55°C. By distilling the electrolyte, a 1:1 mixture of methyl 4-pentenoate and methyl n-valerate39
g and 207 g of dimethyl sebacate were obtained. To 23.0 g of the mixture of methyl 4-pentenoate and methyl n-valerate thus obtained, 1.56 g of palladium chloride, 18.5 g of cupric chloride dihydrate, 70.0 g of water, and 151.2 g of carbon tetrachloride were added, While keeping the internal temperature at 64℃ in an oil bath and stirring thoroughly, add 200% of microbubbled oxygen.
Bubbled at ml/min. After continuing the reaction at 64°C for 15 hours, the carbon tetrachloride layer was separated and the aqueous layer was extracted several times with carbon tetrachloride. The extracted carbon tetrachloride solution was combined with the previous carbon tetrachloride layer, and carbon tetrachloride was distilled off by atmospheric distillation. Subsequently, 10.2 g of methyl n-valerate was separated as a fraction at 126-127° C. under normal pressure. The residue was distilled under reduced pressure to obtain 9.23 g of methyl levulinate with a boiling point of 84-86°C/14 mmHg. The isolated yield was 70.4%. In quantitative determination by gas chromatography, 4
-The conversion rate of methyl pentenoate was 100%, and the yield of methyl levulinate was 75.0%.

Example 7 Equipped with a dropping funnel and a dame loin cooler
In a 100 c.c. flask, add 0.533 g of palladium chloride (3.01
mmole), cupric chloride dihydrate 2.67g (15.5m
mole), water 4.20g, dimethylformamide 31.2g
was placed in the oil bath, the internal temperature was maintained at 62°C, and microbubbled oxygen was continuously blown in at 100 ml/min while stirring sufficiently. While continuing to stir and blow oxygen, add 2 methyl 4-pentenoate from the dropping funnel.
It dripped for a while. After continued stirring for 4 hours, analysis revealed that the conversion rate of methyl 4-pentenoate was 99.0% and the selectivity of methyl levulinate was 60.8%.

Example 8 Palladium chloride 0.535g (3.02mmole), cupric chloride dihydrate 5.30g (30.9mmole), water 4.30g,
Example 3 A mixture of 30.8 g of dimethylformamide and 3.47 g (30.4 mmole) of methyl 4-pentenoate was prepared.
The reaction was carried out in the same manner as above at 62°C for 6 hours and 45 minutes. The results were a conversion rate of 98.9% for methyl 4-pentenoate and a selectivity for methyl levulinate of 60.6%.

Example 9 Palladium chloride 0.558g (3.15mmole), cupric chloride dihydrate 2.71g (15.8mmole), water 4.20g,
After reacting a mixture of 32.1 g of dimethylformamide and 3.26 g (28.6 mmole) of methyl 4-pentenoate at 5°C for 9 hours and 10 minutes in the same manner as in Example 3, 17
The reaction was carried out at ~21°C for 12 hours. The results were a conversion rate of methyl 4-pentenoate of 52.6% and a selectivity of methyl levulinate of 29.4%.

Example 10 A mixture of 0.536 g (3.02 mmole) of palladium chloride, 2.79 g (16.3 mmole) of cupric chloride dihydrate, 4.1 g of water, 31.0 g of dimethylformamide and 3.43 g (30.1 mmole) of methyl 4-pentenoate was prepared. In the same manner as in Example 3, the reaction was carried out at 82°C for 3 hours and 20 minutes. The results showed a conversion rate of methyl 4-pentenoate of 97.2% and a selectivity of methyl levulinate of 46.8%.

Example 11 Palladium chloride 0.640g (3.61mmole), cupric chloride dihydrate 5.36g (31.2mmole), water 20.3g,
49.5g of benzene and 3.82g of methyl 4-pentenoate
(33.5 mmole) was prepared in the same manner as in Example 3.
The reaction was carried out at 64°C for 13 hours. The results showed that the conversion rate of methyl 4-pentenoate was 99.7% and the selectivity of methyl levulinate was 80.0%.

Analysis of the benzene layer revealed that palladium escapes into the benzene layer per 1 kg of methyl levulinate.
It was 0.011g.

Example 12 Palladium chloride 3.26g (18.4mmole), cuprous chloride 16.02g (161.8mmole), water 104.2g, carbon tetrachloride 252.4g, 4-pentenoic acid 19.30g (169.3mmole)
mole) was reacted in the same manner as in Example 1 at 62°C for 8 hours. The results were a conversion rate of 99.9% for methyl 4-pentenoate and a selectivity of 90.6 for methyl levulinate.
It was %.

Analysis of the carbon tetrachloride layer revealed that the amount of palladium released into the carbon tetrachloride layer was 0.53 g per 1 kg of methyl levulinate.

Example 13 Palladium chloride 3.23g (18.2mmole), cuprous chloride 15.86g (160.2mmole), water 102.2g, benzene 253.8g and methyl 4-pentenoate 20.29g
(167.3 mmole) was prepared in the same manner as in Example 1.
When the reaction was carried out at 62°C for 10 hours, the conversion of methyl 4-pentenoate was 99.6% and the selectivity of methyl levulinate was 83.5%.

Example 14 Palladium chloride 0.533g (3.01mmole), cuprous chloride 3.02g (30.5mmole), water 4.1g, dimethylformamide 31.2g, methyl 4-pentenoate 3.46g
(30.3 mmole) was prepared in the same manner as in Example 3.
The reaction was carried out at 62°C for 4 hours and 40 minutes. The results showed that the conversion rate of methyl 4-pentenoate was 100% and the yield of methyl levulinate was 69.8%.

Example 15 Palladium chloride 0.661g (3.73mmole), cuprous chloride 3.71g (37.5mmole), water 22.1g, benzene
250.6 g and 4.24 g of methyl 4-pentenoate (37.2 m
mole) mixture at 62℃ in the same manner as in Example 1.
When reacted for 22 hours and 30 minutes, the conversion rate of methyl 4-pentenoate was 100% and the yield of methyl levulinate.
It was 85.7%.

Example 16 A mixture of 0.547 g (3.09 mmole) of palladium chloride, 2.76 g (16.1 mmole) of cupric chloride dihydrate, 35.2 g of water, and 3.53 g (31.0 mmole) of methyl 4-pentenoate was prepared in the same manner as in Example 3. The mixture was heated to 62°C for 5 hours and 30 minutes. The result is a conversion rate of 4-pentenoic acid of 100.
%, and the yield of methyl levulinate was 37.3%.

Claims (1)

[Claims] 1. In water or an aqueous mixed solvent, 4-pentenoic acid or its ester represented by the general formula CH ₂ =CHCH ₂ CH ₂ CO ₂ R (R is a hydrogen atom or a lower alkyl group) is mixed with copper chloride. and a method for producing levulinic acid or its ester represented by the general formula CH ₃ COCH ₂ CH ₂ CO ₂ R (R is the same as above), which comprises oxidizing with palladium chloride in the presence of oxygen. 2. The manufacturing method according to claim 1, wherein the aqueous mixed solvent is a water-carbon tetrachloride mixed solvent, a water-benzene mixed solvent, or a water-dimethylformamide mixed solvent. 3. The manufacturing method according to claim 2, wherein the aqueous mixed solvent is a water-carbon tetrachloride mixed solvent or a water-benzene mixed solvent. 4. The manufacturing method according to claim 1, wherein R is a lower alkyl group. 5. The manufacturing method according to claim 4, wherein the lower alkyl group is a methyl group. 6. The manufacturing method according to claim 1, wherein the oxidation is carried out at a temperature range of 50 to 70°C.