JPS61106540A - Production of cycloalkanecarboxylic acid ester - Google Patents

Abstract

PURPOSE:2-Halogenocycloalkanone is brought into contact with an inorganic strong base in an alcohol to effect ring contraction, then combined with an acid and the product is extracted with a hydrophobic organic solvent and distilled to give the titled compound in high efficiency. CONSTITUTION:2-Halogenocycloalkanone is brought into contact with an inorganic strong base such as sodium hydroxide to give a cycloalkanecarboxylic acid salt with a ring contracted by 1atom. Then, the resultant reaction mixture is combined with an acid such as hydrochloric acid to effect hydrolysis of the resultant salt to give a cycloalkanecarboxylic acid and/or ester. The carboxylic acid and/or ester produced is extracted with a hydrophobic organic solvent such as benzene and the extract is subjected to distillation to give the objective cycloalkanecarboxylic acid ester. When the cycloalkane carboxylic acid is in an organic solvent, esterification of the acid with an alcohol during distillation process occurs to give the objective ester.

Description

Detailed Description of the Invention (Industrial Application Field) The present invention relates to a method for producing a cycloalkane carboxylic acid ester, and more specifically, the present invention relates to a method for producing a cycloalkane carboxylic acid ester, and more specifically, the present invention relates to a method for producing a cycloalkane carboxylic acid ester, and more specifically, a method for producing a cycloalkane carboxylic acid ester by contacting a 2-halogenocycloalkanone with a strong inorganic base in the presence of an alcohol. This invention relates to a method for producing a cycloalkane carginate compound having one fewer member by ring condensation.

(Prior Art) Cycloalkanecarboxylic acid esters such as cyclobentanecardic acid and cyclohexanecarboxylic acid are subjected to a 7-Favorskli rearrangement reaction.

As a method for further synthesis, there has conventionally been a method in which a 2-halogenocycloalkanone having a larger number of members than the target compound is reacted with sodium alcoholade in an alcohol solvent (Gohsen and Vaughan, Org Synthesis, 39y 37 (1959)* M
, Jaeknsan.

J-As C-8-70t 497 (1948) *
R-B-Lof tfleld.

J, A, C, S, 73, 4707 (1951), etc.]
It has been known.

(Problems to be Solved by the Invention) However, since these methods use sodium alcoholade, they must be carried out in a completely non-aqueous system, which requires dehydration and drying of the solvent and the equipment used, including the reactor. Process control was complicated, such as internal drying and explosion-proof measures to prevent the generation of hydrogen gas when producing sodium alcolade, and the use of expensive alcolade was economically disadvantageous.

Therefore, the present inventors conducted intensive studies to improve these drawbacks, and as a result, even when using an inexpensive base such as hydroxide (IJ), it is possible to achieve extremely high efficiency by adopting a specific process. It was discovered that the desired ester could be easily obtained, and the present invention was completed.

(Means for Solving the Problems) Thus, according to the present invention, a cycloalkanecarboxylic acid having one member smaller in number is produced by contacting a 2-halogenocycloalkanone with a strong inorganic base in the presence of an alcohol and condensing it. Step (A) of synthesizing a salt, adding an acid to the reaction solution of step (A)/chloroalkanka, #&/ff&“
/'t &H'"""""*g-rxi step (B), step of extracting the generated cycloalkane carboxylic acid and/or its ester into a hydrophobic organic solvent (C), and heating the extract solution. A method for producing a cycloalkane carboxylic acid ester is provided, which comprises a step (D) of distilling to obtain a cycloalkane carboxylic acid ester.

In the present invention, first, in step (5)), a cycloalkane cargenate having one fewer member is synthesized by ring-condensing a 2-halogenocycloalkanone in the presence of an alcohol. Examples of the 2-halogenocycloalkanone used in the reaction include compounds in which the α-position is substituted with a salt, bromine, or iodine, such as cyclopentanone, cyclohexanone, cycloalkanone, and cyclooctanone. Alkyl substituents such as ethyl, butyl, and butyl substituents are also included.

Specific examples of alcohols that can be used include methanol, ethanol, and Solono J? Examples include alcohol, butanol, pentanol, hexanol, octatool, lauryl alcohol, cyclopentanol, cyclohexanol, and benzyl alcohol, among which those having 8 or less carbon atoms are preferred.

Further, if necessary, other organic solvents that are inert to bases may be mixed with the alcohol.

Specific examples thereof include hydrocarbons such as diethyl ether, dibutyl ether, diphenyl ether, tetrahydrofura, ethers, benzene, toluene, xylene, hexane, and cyclohexane.

The amount of alcohol used can be selected as appropriate, but it is usually 1 to 20% of the 2-halogenocycloalkanone compound used as the raw material.
It is twice the mole amount, preferably 2 to 12 times the mole amount, and as the amount used decreases, it becomes difficult to control the reaction and the amount of high-boiling by-products increases. This problem can be alleviated by using other organic solvents.

The method of adding alcohol can be selected as appropriate. For example, there is a method in which a free strong base is present in the reactor from the beginning, a method in which a part or all of the base is added at the same time as the 2-halogenocycloalkanone compound as a raw material, etc. In the present invention, water is present or not. Although the Fadelsky reaction proceeds regardless of the amount, it is usually controlled to be at most 3 times the weight of the 2-710gutcycloalkanone, preferably at most 2 times the weight. Excessive amounts of water may result in reduced yields.

The strong inorganic base used in the present invention is 7Amerski'-
Any of those commonly used in reactions may be used,
Specific examples include lithium hydroxide, sodium hydroxide,
Examples include alkali metal hydroxides such as potassium hydroxide, carbonates such as sodium carbonate, potassium carbonate, potassium bicarbonate, etc., and among them, alkali metal hydroxides are preferred. Such a base is generally used in an amount of 1 to 6 equivalents, preferably 2 to 4 equivalents, based on the 2-halogenocycloalkanone compound as a raw material.

The reaction conditions for the process are not particularly limited, but the reaction temperature is usually 10°C to 100°C, preferably 25 to 8°C.
The reaction is carried out at 0° C. and atmospheric pressure, and the 2-no-lognocycloalkanone compound is added in the presence of an alcohol and a strong base over a period of 15 minutes to 5 hours, preferably 30 minutes to 3 hours.

Conversely, a method of gradually adding a strong base can also be used.

After the reaction of the process reactant is completed, an acid is added to the reaction solution containing the generated cycloalkane carboxylate to hydrolyze the carboxylate (process B). This hydrolysis can be carried out according to a conventional method, usually by adding an aqueous solution of a strong acid such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, para-toluenesulfonic acid, etc. at room temperature or the reaction temperature for synthesizing the carbinate. used.

Through this reaction, the cycloalkane carboxylate produced in the process is converted into cycloalkane carboxylic acid, and depending on the conditions, the carboxylic acid is reacted with the alcohol in the system to convert it into cycloalkane carboxylic acid or binic acid ester. . Cycloalkanecar'41gy□0, O. Engineering, eh. , 1, ~6, it is preferable to control the reaction temperature below 40°C, and cycloalkanka/L/? When the objective is to obtain a phosphoric acid ester, it is preferable to control the - of the system to 1 to 5 and the reaction temperature to 4°C or higher, more preferably 50°C or higher.

The product in step (B) may be a cycloalkanecarboxylic acid, its ester, or a mixture thereof, but the ease of separation in step C), the reduction of losses in the aqueous phase, the step 0) From the standpoint of preventing corrosion of equipment, etc., it is desirable to increase the ester content as much as possible.

Cycloalkanecarboxylic acid obtained in step (D) and/or
or its ester is then selectively extracted into a hydrophobic inert solvent by contacting the solvent (step C).

The solvent used is an organic solvent that is hydrophobic and capable of extracting the cycloalkane carboxylic acid and/or its ester. Hydrophobicity means that the solubility in filtrate water at room temperature is 1.
Hydrocarbons such as benzene, toluene, xylene, pentane, ) n-hexane, octane, cyclohexane, cyclohentane, diethyl ether, diptyle ether, butanol,
Examples include polar solvents such as hexanol and octatool.

If the alcohol used in the reaction (process product) is hydrophobic, it will be automatically extracted into the hydrophobic alcohol without adding another hydrophobic solvent, but if a highly hydrophilic alcohol is used in the reaction is extracted by adding a hydrophobic organic solvent to the reaction solution. The amount of the hydrophobic organic solvent to be used can be selected as appropriate, but it is usually 0.5% based on the generated cycloalkane carboxylic acid and/or its ester.
~50 times by weight, preferably 2 to 30 times by weight.

In addition, the addition method may be generally O~50, a method of adding it all at once into the reactor or extraction separator under normal pressure, a method of adding it in parts, and a method of adding it in parts. It may also be added in advance.

By this operation, the cyfuroacarboxylic acid and/or its ester in the reaction solution are extracted into the organic solvent,
The strong acid contained in the reaction solution migrates into the aqueous phase. On this occasion,
Cycloalkanecarboxylic acids are slightly soluble in water, but cycloalkanecarboxylic acid esters are hardly soluble in water, so the separation operation is easier than with the former, and there is less loss in the aqueous phase.

The organic phase recovered in the process is then washed with water if necessary. As a result of this measure, 2
- Hydroxycycloalkanones can be removed more completely.

Next, the desired cycloalkane carboxylic acid ester can be obtained by distillation under heating according to a conventional method (Step D). If the substance contained in the organic phase is a cycloalkane carboxylic acid ester, it can be distilled according to a conventional method. However, if it is present as a cycloalkane carboxylic acid, it undergoes esterification with the alcohol present in the organic phase during this process. What are the distillation heating conditions for that purpose? The temperature of the tom solution is 60°C to 2500°C, preferably I/is.

°C to 180 °C, and an acid catalyst is added if necessary.

(Effects of the Invention) Thus, according to the present invention, a cycloalkane carboxylic acid ester can be efficiently obtained using an inexpensive base and a simple operation.

The present invention will be explained in more detail with reference to Examples below. Note that parts and sections in the examples are based on weight unless otherwise specified.

Example 1 200 parts (NωH2,5
mol) and 500 parts of n-butanol, and under atmospheric pressure,
2-chlorocyclohexanone 10 without stirring at 70℃
0 part (0.75 mol) was added over 2 hours to carry out Fadelsky reaction.

This reaction produced the sodium salt of cyclointanecarbic acid (Process A). After the reaction is complete, add 10% hydrochloric acid 6
40 parts were added over 30 minutes, and the mixture was further stirred at 70'°C for 1 hour (Step B), then cooled to room temperature and the aqueous and organic phases were separated (Step C).
After washing with water to remove by-products such as adipoine,
580 parts of a n-butanol solution of cyclopentanecarboxylic acid n-butyl ester was obtained. It was confirmed by quantitative analysis using gas quamography that 83 parts (molar yield based on 2-chlorocyclohexanone: 65.1%) of the carboxylic acid ester were present in n-butanol at this time.

Next, n-butyl alcohol was distilled off under a reduced pressure of 100 mmHg, and then distilled under a reduced pressure of 15 mmHg. , molar yield 58
．． (Process D).

Example 2 Into the same reactor as in Example 1, 1 ml of hydroxide was added.
00 parts (1,65 soles) and isopropyl alcohol 4
00 parts and 100 parts of toluene were added, stirred at 50°C under atmospheric pressure, and then 100 parts of 2-chlorocyclohexanone (0
, 75 mol) over 2 hours.

and reacted (process A). After the reaction, 5 polyhydrochloric acid 68
0 part was added over 30 minutes, and the mixture was further stirred at 50° C. for 1 hour, and then cooled to room temperature (Process B).

400 parts of toluene was added to this reaction solution, and the cyclobentanecarboxylic acid inglobil ester produced in the reaction was extracted into the toluene phase and separated as a toluene solution (Step C). 80 parts (2-chlorocyclohexanone standard molar yield 68
．． 4%) was confirmed by gas chromatography.

In the same manner as in Example 1, isoamyl alcohol and toluene were distilled off, followed by distillation under reduced pressure of 15IIIHg, and at a distillation temperature of 72 to 75°C, 72.3g of cyclobentanecarbic acid isopropyl ester (purity: 98.2,
A molar yield of 60.7 h) was obtained (Process D).

Example 3 Into a reactor similar to Example 1, 100% of IJ (hydroxide) was added.
(1,65 mol), 400 parts of isoamyl alcohol, and 100 parts of toluene were added, and while stirring at 60°C under atmospheric pressure, 100 parts of 2-chlorocyclohexanone (0,7
After the reaction was completed, 340 parts of 10% hydrochloric acid was added at 40°C over 30 minutes with stirring, and the mixture was further stirred for 1 hour (Process B). The aqueous and organic phases were separated by cooling to room temperature (
Process C). 43.8 parts of cyclopentanecarbic acid in the isoamyl alcohol and toluene mixture (MoAJe1
51.2%) and cyclointane carbic acid isoamyl ester, 17.7. It was confirmed by chromatography that 12.8 parts (molar yield: 12.8 parts) were present. Next, the mixture was heated under normal pressure to remove toluene and isoamyl alcohol head-to-head (distillation solution temperature was about 160°C at maximum, and esterification of tecyclopentanecarboxylic acid progressed during this process) at 15 mmHg. 108-11 cyclopentanecarpinic acid inamyl ester under reduced pressure
At a distillation temperature of 0°C, 78.0 parts (purity 98.5%, molar yield after isolation 55.7 parts) were obtained (Process D).

Claims (1)

[Claims] A process (A) of synthesizing a cycloalkane carboxylate having one member smaller by contacting a 1,2-halogenocycloalkanone with a strong inorganic base in the presence of an alcohol to cause ring condensation; A process (B) of adding an acid to the reaction solution to synthesize a cycloalkane carboxylic acid and/or its ester, a process (B) of extracting the generated cycloalkane carboxylic acid and/or its ester into a hydrophobic organic solvent (
A method for producing a cycloalkane carboxylic acid ester, which comprises the following steps: C) and step (D) of distilling the extract under heating to obtain a cycloalkane carboxylic acid ester.