JPS6354331A - Production of 1,1-difluorocyclohexane - Google Patents

Abstract

PURPOSE:To obtain the titled compound in high yield and selectivity, by using cyclohexanone as a raw material and combining an acylalation process, a fluorination process and a trifluoroacetic acid recovering process. CONSTITUTION:Cyclohexanone is made to react with trifluoroacetic anhydride preferably at 0-150 deg.C and the obtained, 1,1-bis(trifluoroacetoxy)cyclohexane is made to react with hydrogen fluoride (containing <=10wt%, especially <=1wt% water) or a mixture of hydrogen fluoride and an amine preferably at -40-+100 deg.C to obtain the objective compound and trifluoroacetic acid. The trifluoroacetic acid is reacted with a dehydration agent (e.g. phosphorus pentoxide) and the obtained trifluoroacetic anhydride is recovered by distillation, etc., and used as a raw material for the acylalation process.

Description

Detailed Description of the Invention [Industrial Application Field] The invention BAIIi'' relates to a method for producing 1,1-difluorocyclohexane. More specifically, it relates to a method for producing 1,1-difluorocyclohexane in high yield using cyclohexanone as a raw material. .

[Conventional technology]

Conventional reaction of i,i-difluorocyclohexane and sulfur tetrafluoride (Journal of Organic Chemistry, Vol. 36, p. 818 (197
1) and the reaction between cyclohexanone and molybdenum hexafluoride (Tetrahedron, Vol. 27, p. 6965 (1971)
)) or the reaction of 1-chlorocyclohexene with hydrogen fluoride (Helvetica Himica Acta, Vol. 46, 18
18 (1963)).

[Problems to be solved by the present invention]

However, conventional methods had several drawbacks.

For example, methods using sulfur tetrafluoride or molybdenum gold hexafluoride require extremely harsh reaction conditions for the synthesis of these fluorinating agents, and are difficult to implement industrially. For example, the production of sulfur tetra7ide is usually done by charging Hastelloy C autoclave sulfur, sodium fluoride, and chlorine, and then heating it for a long time (finally at 225-250°C).
), the reaction mixture was distilled at low temperature to obtain the product sulfur tetrafluoride (boiling point -40°C). (Journal of the American Chemical Society, Vol. 82, p. 539 (1960)) In addition, less than half of the fluorine atoms contained in these fluorinating reagents are actually introduced into the cyclohexane ring. Only. Taking the reaction of sulfur tetrafluoride and cyclohexanone as an example, sulfur tetrafluoride is converted to thionyl difluoride by fluorination of cyclohexanone, as shown in the following formula, but this substance no longer has fluorination reaction activity. . When producing 1,1-difluorocyclohexane industrially, it is necessary to recover all of the expensive fluorine atoms, and therefore the raw material sulfur tetrafluoride must be synthesized again from the above-mentioned thionyl fluoride. Many.

However, this requires an extremely complicated recovery process in which the alkali metal fluoride is completely produced by alkali hydrolysis of thionyl heptadide and then used as part of the raw material for the above-mentioned sulfur tetrafluoride production process. Similarly, when producing 1,1-difluorocyclohexane by the reaction of molybdenum hexafluoride and cyclohexanone, a complicated recovery process is required, and the amount of alkali metal fluoride produced in the recovery process is smaller than that of tetrafluoride. Even more than in the case of sulfur. Furthermore, reactions using sulfur tetrafluoride require a pressure-resistant reaction vessel, and methods using molybdenum hexafluoride have the problem of recovering molybdenum, which is a heavy metal.

Another conventional technique for producing 1.1-difluorocyclohexane involves the reaction of 1-chlorocyclohexene with hydrogen fluoride, and although the reaction proceeds under relatively mild reaction conditions, the yield is good. do not have. Moreover, 1-chlorocyclohexene used as a raw material is usually produced from phosphorus pentachloride and cyclohexanone, which are expensive chlorinating reagents, and therefore it is difficult to produce it industrially.

[Failure to solve the problem]

The present inventors have conducted intensive research on a method for producing 1,1-difluorocyclohexane using cyclohexane as a raw material, and as a result, by combining an acylation process, a fluorination process, and a trifluoroacetic acid recovery process, the objective has been achieved. High yield of 1,1-difluorocyclohexane
They discovered that it can be produced with high selectivity and completed the present invention.

That is, in producing 1゜1-difluorocyclohexane from cyclohexanone, the present invention deals with (■) an acylar which obtains di-1,1-bis(trifluoroacetoxy)cyclohexane by reacting cyclohexanone with trifluoroacetic anhydride. (1.1-bis(trifluoroacetoxy))
By reacting hydrogen fluoride with cyclohexane, 1
．． Includes a fluorination step to obtain 1-difluorocyclohexane and trifluoroacetic acid, and (1) a trifluoroacetic acid recovery step to obtain trifluoroacetic anhydride by reacting the trifluoroacetic acid produced in (II) above with a dehydrating agent. The present invention provides a method for producing 1,1-difluorocyclohexane, characterized in that:

The acylation step in the present invention consists of a method for producing 1,1-bis(trifluoro7toxy)cyclohexane by reacting cyclohexanone with trifluoroacetic anhydride as shown in formula (1).

This acylation step can be carried out without solvent, but
Solvents that do not adversely affect the reaction can also be used.

Examples include diethyl ether, tetrahydrofuran, biphenyl ether, carbon disulfide, methylene chloride, chloroform, carbon tetrachloride, dichloroethane,
Halogenated hydrocarbons such as trichloroethane and tetrachloroethane; Halodanated aromatic hydrocarbons such as chlorobenzene, dichlorobenzene, bromobenzene, and chloronaphthalene; Nitro compounds such as nitrobenzene, nitrotoluene, and nitromethane; Aliphatic hydrocarbons such as hexane alicyclic hydrocarbons such as cyclohexane are used.

Cyclohexanone used as a raw material in the acylation step may be produced by any method.

The quantitative ratio of cyclohexanone and trifluoroacetic anhydride used as raw materials in the acylation step is usually 0.01 to 100, preferably 0.1 to 50, expressed as a molar ratio of trifluoroacetic anhydride to cyclohexanone.

It is also good to add a catalyst. Examples of catalysts include carboxylic acids such as trifluoroacetic acid and trichloroacetic acid;
Lewis acids such as boron trifluoride, organic sulfonic acids such as p-toluenesulfonic acid, methanesulfonic acid, )IJ fluoromethanesulfonic acid, and mineral acids such as sulfuric acid can all be used.

The reaction temperature and reaction time when performing the entire acylation process vary depending on the ratio of raw materials and the presence or absence of a solvent, but usually -
The temperature is 40 to 250°C for 5 minutes to 500 hours, preferably 0 to 150°C for 10 minutes to 200 hours.

The fluorination step in the present invention consists of a method for producing 1,1-difluorocyclohexane by reacting 1,1-bis(trifluoroacetoxy)cyclohexane with hydrogen fluoride, as shown in formula (2).

As shown in the above formula, the fluorination process involves reacting 1 mole of 1,1-bis(trifluoroacetoxy)cyclohexane with 2 moles of hydrogen fluoride to form 1 mole of 1-difluorocyclohexane and 2 moles of trifluoroacetic acid. Moles and total production. The reaction products, 1,1-difluorocyclohexane and trifluoroacetic acid, can be easily purified by conventional separation operations such as distillation.

The hydrogen fluoride used in the fluorination step may have any composition as long as it contains all hydrogen fluoride. Usually, hydrogen fluoride or a mixture of hydrogen fluoride and an amine is used, preferably anhydrous hydrogen fluoride or a mixture of anhydrous hydrogen fluoride and an amine.

The hydrogen fluoride used in the fluorination step usually has a water content of 103 IC or less, preferably 3% by weight or less,
More preferably, 1 mfik% or less is used.

Examples of amines that can be mixed with hydrogen fluoride in the fluorination step include aliphatic amines such as methylamine, ethylamine, progylamine, isopropylamine, butylamine, and cyclohexylamine; dimethylamine, diethylamine, Aliphatic secondary amines such as dipropylamine, diisopropylamine, dibutylamine, morpholine, piperidine, zeperazine, dicyclohexylamine; trimethylamine, triethylamine, trizorogylamine, tributylamine, tricyclohexylamine, 1,4-cyazubicyclo [2゜2.2] Aliphatic tertiary amines such as octane (DABCO); aniline,
Examples include aromatic amines such as diphenylamine and triphenylamine; nitrogen-containing aromatic compounds such as gylysine, 2-picoline, 6-picoline, 4-picoline, quinoline, methylquinolines, and melamine. In particular, butylamine, cyclohexylamine, diethylamine, digtylamine, triethylamine, tributylamine, aniline, pyridine, picolines, and melamine are preferably used.

The hydrogen heptadide-amine mixture that can be used in the fluorination process refers to the above-mentioned mixture of hydrogen fluoride and amine gold, but its composition is usually expressed as a molar ratio of hydrogen fluoride molecules to amine. The number used is 0.1 to 100, preferably 1 to 50.

In the fluorination step, it is also preferable to add the acid as a total catalyst for the purpose of speeding up the reaction rate. Such acids include formic acid, fluoroacetic acid, difluoroacetic acid,
Carboxylic acids such as trifluoroacetic acid, chloroacetic acid, dichloroacetic acid, and trichloroacetic acid; Sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid, trichloromethanesulfonic acid, and paratoluenesulfonic acid; hydrochloric acid,
Mineral acids such as acids; Lewis acids such as boron trifluoride, aluminum chloride, aluminum fluoride, titanium trichloride, titanium tetrachloride, iron trichloride, iron trifluoride, and the like. In the fluorination step, trifluoroacetic acid is produced as a by-product as the reaction progresses, so it is particularly preferable to use trifluoroacetic acid as an acid catalyst in order to facilitate IRI of the reaction mixture. Furthermore, since trifluoroacetic acid produced as a by-product also acts as a catalyst, the amount of acid catalyst added may be small.

In the fluorination step, metal fluorides such as cesium fluoride, rubidium fluoride, potassium fluoride, and sodium fluoride can also be added.

The fluorination step can be carried out without a solvent, and a solvent that does not adversely affect the force ζ reaction can also be used. For example, diethyl ether, tetrahydro7rane, biphenyl ether natonoethers; methylene chloride, chloroform, carbon tetrachloride, dichloroethane, trichloroethane,
Halogenated hydrocarbons such as tetrachloroethane and fluorocarbons; Halogenated aromatic hydrocarbons such as chlorobenzene and dichlorobenzenato; Aliphatic hydrocarbons such as hexane, octane, and decane; Aromatic carbons such as benzene, toluene, and xylene Hydrogen; alicyclic hydrocarbons such as cyclohexane are used.

The quantitative ratio of 1,1-bis(trifluoroacetoxy)cyclohexane and hydrogen fluoride used in the fluorination step is expressed as the molar ratio of hydrogen fluoride molecules to 1,1-bis(trifluoroacetoxycyclohexane). The number is usually 0.1 to 2000, preferably 2 to 1000.

When an acid catalyst is added in the fluorination step, the amount varies depending on the acidity of the acid catalyst used, but is usually expressed as a molar ratio of the acid catalyst used to 1,1-bis(trifluoroacetoxy)cyclohexane. 0.000
1 to 1, preferably 0.001 to 0.1 is sufficient.

The reaction temperature and reaction time when carrying out the fluorination step vary depending on the quantitative ratio of the raw materials and hydrogen heptadide used, the presence or absence of a catalyst, the type of catalyst, the presence or absence of a solvent, etc., but are usually -76°C to 150°C.
, 5 minutes to 100 hours, preferably -40°C to 1
00°C for 5 minutes to 50 hours.

The trifluoroacetic acid recovery step in the present invention consists of obtaining trifluoroacetic anhydride by reacting the trifluoroacetic acid produced in the fluorination step with a dehydrating agent.

The dehydrating agent used in the trifluoroacetic acid recovery process may be one that can dehydrate trifluoroacetic acid to produce trifluoroacetic anhydride, and the type is not specified. Xylcarposiimide, methoxyacetylene, phosphorus pentate, etc. can be used. In the case of phosphorus pentoxide, it is particularly preferable because it can be recovered as phosphoric acid after dehydration.

The quantitative ratio of trifluoroacetic acid and dehydrating agent used in the trifluoroacetic acid recovery step may vary depending on the dehydrating ability of the dehydrating agent used and the dehydrating conditions.

Here, the dehydration ability is defined as the number of moles of the dehydrating agent required to dehydrate one molecule of water from two molecules of trifluoroacetic acid, and this will be referred to as the dehydration equivalent. The ratio of trifluoroacetic acid used in this trifluoroacetic acid recovery step to the dehydration equivalent of the dehydrating agent is usually 0.1 to 100, expressed as the ratio of the dehydrating equivalent of the dehydrating agent to trifluoroacetic acid. However, in order to improve the trifluoroacetic acid recovery efficiency, it is preferable to make the above ratio high, and from an economic point of view, a too large ratio is not preferable. Therefore, preferably the value of the above ratio is 1 to 20. range is used.

The reaction temperature and time in the trifluoroacetic acid recovery process vary depending on the type and amount of dehydrating agent used, but are usually 0.
-300℃, 5 minutes to 100 hours, preferably 10
-150°C, 10 minutes - 50 hours.

Trifluoroacetic anhydride produced in the trifluoroacetic acid recovery step can be easily distilled off from the reaction mixture by distillation or the like, and can be used as a raw material for the acylation step. That is, since trifluoroacetic anhydride can be efficiently circulated and reused, there is little loss. Furthermore, the amount of by-products that cannot be recycled is extremely small, which is favorable from a geoeconomic perspective.

〔Effect of the invention〕

According to the present invention, 1,1-difluorocyclohexane, which was conventionally difficult to synthesize, can be produced from cyclohexanone and hydrogen fluoride in high yield and high selectivity.

〔Example〕

EXAMPLES The present invention will be specifically described with reference to Examples below.

Example 1 Cyclohexanone 51.6,? (0,526 mol)
and 291.1 g (1.39 mol) of trifluoroacetic anhydride were placed in a reactor in which the system was previously purged with gold nitrogen.
After stirring at °C for 3 hours, the mixture was stored at 25 °C for 72 hours. After all unreacted trifluoroacetic anhydride was distilled off, the reaction mixture was distilled to obtain cyclohexanone 2.5.
9 (0,025 mol) and 154.9 (0.50 mol) of 1,1-bis(trifluoroacetoxy)cyclohexane were obtained.

Anhydrous hydrogen fluoride-Giridine mixture (hydrogen fluoride content 70% by weight) 600.9
(containing 21 moles of hydrogen fluoride), cooled to -30°C, and then added 1,1-bis(trifluoroacetoxy)cyclohexane 1549 (0.50 moles) with stirring.
and 2.679 (0.02 mol) of trifluoroacetic acid were added. After maintaining the reaction temperature at t-30°C for 2 hours while stirring, the temperature was gradually increased to 20°C in 1 hour, and further maintained at 20°C for 2 hours. By rectifying the reaction mixture, trifluoroacetic acid 114.0 <
9 (1.0 mol) (!: 58.8.9 (0.49 mol) 1 of 1,1-difluorocyclohexane was obtained.

Phosphorus pentoxide 170.0.9 (1
, 20 mol and the above trifluoroacetic acid 114.0,!
17 (1.0 mol) was added, heated with stirring, and while maintaining the reaction temperature at 70° C., all of the low-boiling products distilled out were collected in a dry ice-acetone trap.

After heating and stirring for 5 hours, all components distilled out were analyzed and found to be 102.9j of trifluoroacetic anhydride;
(0,490 mol) was produced.

This example shows that 1,1-difluorocyclohexane is obtained from cyclohexanone at a conversion rate of 95% and a selectivity of 98%, and that trifluoroacetic anhydride is obtained from trifluoroacetic acid produced by the reaction at a yield of 98%. % recovery.

Example 2 Cyclohexanone 392.6 g (1,00 mol) Trifluoroacetic anhydride 21009 (10,0 mol)
The mixture was placed in a reactor in which the inside of the system had been purged with gold nitrogen in advance, and the mixture was stirred at 25°C for 3 hours, and then cooled at 25°C for 72 hours. The composition of the reaction mixture ([) after all unreacted trifluoroacetic anhydride was distilled off was cyclohexanone 15.79 (0,1
6 molar and 1,1-bis(trifluoroacetoxy)cyclohexane 1183. ! i' (3.84 mol).

Anhydrous hydrogen fluoride 39 was added to the reactor whose system was replaced with nitrogen in advance.
00. ! ;'(195 moles)? After cooling to -60°C, the above reaction mixture containing 1,1-bis(trifluoroacetoxycyclohexane) was mixed with stirring.
6≦I) was added. Temperature 't-30' while stirring
After being kept at 20° C. for 2 hours, the temperature was gradually raised to 20° C. in 1 hour, and the temperature was further kept at 20° C. for 4 hours. By rectifying the entire reaction mixture, anhydrous hydrogen fluoride 374
6g, trifluoroco (fL8876&<7.68mol)
, cyclohexanone 15.0.9 (0.15 mol),
456 g of 1,1-difluorocyclohexane (3,8
0 mol) was obtained.

1300 g of phosphorus pentoxide (9,1
5 mol) and the above trifluoroacetic acid 876.9 (7,
Add 68 mol) k, heat with stirring, and raise the reaction temperature to 70 mol).
While maintaining the temperature at °C, all of the low-boiling products distilled out were collected in a dry ice-acetone trap.

After heating and stirring for a total of 6 hours, the distilled components were analyzed and found to be 790 g (3,76 g) of trifluoroacetic anhydride.
mole) was generated.

This example shows that 1,1-difluorocyclohexane can be obtained with a conversion rate of 95% and a selectivity of 99% based on the total cyclohexanone, and that trifluoroacetic anhydride can be obtained from trifluoroacetic acid produced by the reaction in a high yield. It shows that the recovery rate is 98%.

Claims (2)

[Claims] (1) In producing 1,1-difluorocyclohexane from cyclohexanone, (I) an acylation step in which 1,1-bis(trifluoroacetoxy)cyclohexane is obtained by reacting cyclohexanone with trifluoroacetic anhydride; II) By reacting the 1,1-bis(trifluoroacetoxy)cyclohexane with hydrogen fluoride, 1,1
- a fluorination step to obtain difluorocyclohexane and trifluoroacetic acid, and (III) a trifluoroacetic acid recovery step to obtain trifluoroacetic anhydride by reacting the trifluoroacetic acid produced in (II) with a dehydrating agent. A method for producing 1,1-difluorocyclohexane, characterized in that: (2) The method according to claim 1, wherein the fluorination step is carried out in the presence of an acid catalyst.