JPS61122244A - Production of cycloalkanecarboxylic acid compound - Google Patents

Abstract

PURPOSE:To produce the titled compound from an inexpensive raw material, with simple operation, in an improved yield, by halogenating a cyclic ketone via specific steps such as a synthesizing step, separation of an organic phase from an aqueous phase, the ring-shrinkage of the intermediate product, etc. CONSTITUTION:The titled compound can be produced by (1) halogenating the cyclic ketone such as cyclopentanone with preferably chlorine in the presence of water to obtain 2-halogenoxycloalkanone, (2) separating the reaction liquid of the step (1) into the organic phase and the aqueous phase, (3) contacting the organic phase containing 2-halogenocycloalkanone and separated in the step (2) with astrong inorganic base, preferably in alkali metal hydroxide to effect the shrinkage of the ring to obtain a cycloalkanecarboxylic acid salt having smaller number of ring member than the cyclic ketone by one, and (4) optionally hydrolyzing the cycloalkanecarboxylic acid salt produced in the step (3).

Description

Detailed Description of the Invention (Industrial Field of Application) The present invention relates to a method for producing a cycloalkane carboxylic acid compound, and more specifically to a method for producing a cycloalkane carboxylic acid compound with high efficiency using simple operations. Technology) As a method for producing cycloalkanecarboxylic acids such as cyclopentanecarboxylic acid, cyclohexanecarboxylic acid, and cycloheptancarboxylic acid, there has traditionally been a method in which 2-halogenocycloalkanone is reacted with an alkali hydroxide in an alcohol solvent. There is (A, Favorssc
y st L J3 ojovsky, Bull.

Soc, ahim, Prone@, 18.615 (1
915)-).

This method is usually known as the Faborski rearrangement reaction (problem to be solved by the invention) The 2-halogeno7-chloroalkanone used as a raw material in this reaction is generally synthesized by halogenating a cyclic ketone. However, since it is a very thermally unstable substance, it is difficult to isolate in a high yield during distillation.
This can be solved by directly subjecting the reaction solution used to synthesize the halogenocloalkanone to the Faborski rearrangement reaction, but in that case, another problem is that a large amount of by-products are generated and the yield of the target product is significantly reduced. occurs.

Therefore, the inventors of the present invention sought to improve these shortcomings (as a result of intensive studies, they found that by adopting a specific 7o process, an efficient method for synthesizing cycloalkane carboxylic acid compounds starting from an inexpensive cyclic ketone) was developed. Thus, according to the present invention, a cyclic ketone is halogenated in the presence of water to synthesize a 2-halogenocycloalkanone. Step (B) of separating the reaction solution of step (A) into an organic phase and an aqueous phase, in which the 2-halogenocycloalkanone present in the organic phase is treated with a strong base in the presence of a polar organic bath. A process of synthesizing a cycloalkane carboxylate having one member smaller than the raw material cyclic ketone by contacting and condensing the cycloalkane. A manufacturing method is provided, characterized in that it comprises a process of synthesizing an acid (DJ).

As the raw material cyclic ketone used in the present invention,
Examples include 7clopentanone, cyclohexanone, fucloheptanone, cyclooctanone, cyclodecanone, and 4-methylcyclohexanone, and any ketone can be used as long as the hydrogen at the α-position can be easily substituted with a halogen.

The halogen used in the halogenation reaction in step (A) may be any halogen that can replace the hydrogen at the alpha position of the ketone, such as chlorine or bromine (chlorine is particularly preferred. It may be carried out according to a conventional method, and is usually carried out in a liquid phase in the presence of water at a reaction temperature of 0 to 90°C, preferably 10 to 60°C.The pressure is not limited at all, and it is usually carried out under atmospheric pressure. .

The reaction is started by adding gaseous I.logen to a mixture of cyclic ketone and water, and the conversion rate of the cyclic ketone is adjusted by the amount of halogen added. The amount of halogen used per mole of cyclic ketone is usually α8 to t3 moles, preferably α9 to 12 moles.
It is used at a ratio of 11 to 5 times by weight, preferably 5 to 3 times by weight, and if the amount used is too large, productivity may decrease, and if it is too small, selectivity may decrease◇ The reaction is preferably carried out under a strong stirring atmosphere, and the conversion rate of the cyclic ketone is preferably 80% or more.

In the present invention, following step (N), the reaction solution is separated into an organic phase and an aqueous phase in step (B).In the aqueous phase, unreacted cyclic ketone and generated 2-halogenocycloalkanone are contained. These organic substances are preferably dissolved and dissolved.The organic substances recovered here can be used as a solvent for the Faborski rearrangement reaction in the next step (C).◇On the other hand, the by-product hydrochloric acid in the aqueous phase can be used as a solvent for the Faborski rearrangement reaction in the next step (C). (Can be used to hydrolyze cycloalkane carboxylates in season.

The organic phase separated in step (B) is then subjected to the Faborski reaction in step (C1).The inorganic base used here may be any commonly used inorganic base, and specific examples include lithium hydroxide, Examples include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, and carbonates such as sodium carbonate, sodium bicarbonate, potassium carbonate, etc. Among them, alkali metal hydroxides are particularly prized.

Such a base is generally used in an amount of 15 to 6 equivalents, preferably 2 to 4 equivalents, based on the 2-halogeno-7 clohexanone compound. It is preferable to use the base in an anhydrous state; if it is used in the form of a water bath solution, the yield tends to decrease.

Although the reaction conditions are not limited to (but are not limited to), the reaction temperature is usually 10 to 150°C, preferably 40 to 120°C, and the reaction is carried out under atmospheric pressure.The polar organic solvent used in the reaction easily interacts with a base. There is no particular limitation as long as it does not react, and specific examples include methanol, ethanol, butanol, hexanol, octatool,
Alcohols such as lauryl alcohol, diethyl ether, cyphthyl ether, diphenyl ether,
Examples include ethers such as tetrahydrofuran, nitriles such as acetonitrile and benzonitrile, and as necessary, benzene, toluene, xylene, hexane,
A mixture of non-polar solvents such as cyclohexannatate can be used. Among these polar organic solvents, it is preferable to use alcohols, especially hydrophobic alcohols, from the viewpoint of improving the yield◇ The amount of such organic solvent to be used can be selected as appropriate, but it is usually 15-10 for cyclohexanone
The amount is preferably 1 to 51 times the amount by weight, and the smaller the amount used, the more difficult it becomes to control the reaction and the higher the amount of high-boiling by-products.

The organic solvent may be added from the beginning to the base aqueous solution in the reactor, or a part or all of it may be added simultaneously with the raw material 2-halogenocyclohexanone.

After the reaction is completed, the produced cycloalkane carboxylate is separated from the reaction system according to a conventional method. For example, a method of extraction into an aqueous phase by adding water to the reaction system is used.

The cycloalkane carboxylic acid salt extracted into the aqueous phase is hydrolyzed with acid in the process (Di) to synthesize cycloalkane carboxylic acid.The acid used is an aqueous solution of a strong acid such as hydrochloric acid, sulfuric acid, or phosphoric acid. However, it is reasonable to use the aqueous phase (ie, halogen acid aqueous solution) in step (B) as this water bath liquid.

(Effects of the Invention) Thus, according to the present invention, a fuchloroalkanecarboxylic acid compound can be obtained efficiently by starting from inexpensive raw materials and using simple operations.

The present invention will be explained in more detail below with reference to Examples. In addition, parts in Examples and Comparative Examples are based on weight unless otherwise specified. 300 parts of 7-chlorhexanone and 500 parts of water were added. Chlorine gas was added to the reaction liquid phase using a flow meter while stirring, and 200 parts of chlorine gas were added, which took 5 hours.

Since the reaction is exothermic, the flask was cooled in a constant temperature bath of ice water, and the reaction temperature was maintained at 25 °C. As determined by gas chromatography, the chlorination rate of 7-chlorohexanone was 91 molar, and the selectivity to 2-chlorocyclohexanone was 93 molar.The amount of organic phase was 403 parts, and the amount of aqueous phase was 597 parts. 100 parts of toluene was added to each of the aqueous phases taken out into separate containers to extract 90% of the organic matter in the aqueous phases.

Next, in order to perform the Faborski reaction, 50
0 parts of roohexanol, the toluene from which the aqueous phase was extracted, and 300 parts of anhydrous caustic soda were added. The organic phase separated in step B was added over a period of 2 hours while stirring.

The reaction temperature was maintained at 60°C in a hot water bath (process c).
.

After the reaction is complete, add 500 parts of water to dissolve the precipitated salt.
Sodium clopentanecarboxylate as a water bath solution 13
I got 00 copies.

Next, in order to measure the yield of sodium 7-clopentanecarboxylate, a portion of this water bath solution was taken and 55% of hydrochloric acid was added to P.
It was added little by little until H-5 was obtained, converted to cyclopentanecarboxylic acid, extracted with toluene, and the toluene phase was quantified by gas chromatography (conversion of sodium cyclopentanecarboxylate to 7-cyclopentanecarboxylic acid). (proceeds quantitatively). As a result, the molar yield of sodium cyclopentanecarboxylate was 66.2%.

Comparative Example 1 A chlorination reaction similar to that in Example 1 was carried out, and the reaction solution was placed in a distiller filled with a glass filler, and vacuum distillation was carried out at -750 HP and a temperature of 100°C. 2409 2-chlorofuclohexanone with 98% purity was obtained. The recovery rate by distillation was 7,011 mm, and a polymer was formed in the liquid at the bottom of the distiller, making it impossible to recover any more.

Next, the same Faborski reaction as in Example 1 was carried out, and 7
Sodium chlorhexanecarboxylate was quantitatively determined by gas chromatography, and a molar yield of 57.5% was obtained.

This result shows that distillation is not economical because the loss of intermediate products is large.

Comparative Example 2 600 parts of 7-chlorohexanone and 500 parts of water were added to the same reactor as in Example 1, and 260 parts of chlorine gas was added thereto. The reaction took 4 hours at 20°C.

After the reaction, the chlorination rate was measured by gas chromatography, and the selectivity to 2-chlorocyclohexanone was 70 molti at 100 molti.

Next, 500 parts of hexanol and 500 parts of non-caustic soda were added to the same apparatus as in Example 1, which was subjected to the Aborski reaction without separating the aqueous phase from the reaction solution, and the reaction solution was mixed with stirring. It was added over a period of 5 hours. The reaction temperature is 60
It was carried out at ℃. After the reaction was completed, quantitative determination by gas chromatography was performed in the same manner as in Example 1, and the molar yield of sodium fuclopentanecarboxylate was 9%.

Claims (1)

[Claims] 1. Process (A) of synthesizing 2-halogenocycloalkanone by halogenating a cyclic ketone in the presence of water, the process (
Step (B) of separating the reaction solution of A) into an organic phase and an aqueous phase, in which the 2-halogenocycloalkanone present in the organic phase is brought into contact with a strong inorganic base in the presence of a polar organic solvent to undergo ring condensation. A step (C) of synthesizing a cycloalkane carboxylate having one member smaller than the raw material cyclic ketone (C) and optionally a step (D) of hydrolyzing the cycloalkane carboxylate to synthesize a cycloalkane carboxylic acid. )
A method for producing a cycloalkane carboxylic acid compound, characterized by comprising the steps of: