JPS6326113B2 - - Google Patents

Description

Detailed Description of the Invention (a) Industrial Application Field The present invention provides a 1,1-dichloro-2,2,2
The present invention relates to a method for producing trifluoroethyllithium (CF ₃ CCl ₂ Li, hereinafter abbreviated as 1,1-dichlorotrifluoroethyllithium).

In recent years, various medicines, agricultural chemicals, dyes, monomers for polymer compounds, etc. containing trifluoromethyl groups have been synthesized. Many of these compounds having a trifluoromethyl group have superior properties compared to compounds with similar structures that do not contain a trifluoromethyl group.

When synthesizing a compound having a trifluoromethyl group, the trifluoromethyl group must be introduced at some stage. Focusing on the change in the number of carbon atoms before and after the reaction, the reactions at the stage where a trifluoromethyl group is introduced are classified into those with an increase in the number of carbon atoms of 0, 1, 2, and 2.
There is more than that. Since the advantages and disadvantages of each individual reaction vary depending on the starting materials and the structure of the target compound, a variety of methods are needed industrially to introduce trifluoromethyl groups.

Examples of reactions in which the increase in the number of carbon atoms is 0 include the conversion of a trichloromethyl group to a trifluoromethyl group by antimony trifluoride, and the conversion of a carboxyl group to a trifluoromethyl group by sulfur tetrafluoride. . Examples of reactions in which the increment number is 1 include the addition of trifluoromethyl iodide to double and triple bonds. Examples of reagents that can be used in reactions where the number of carbon atoms increases by 2 include trifluoroacetic acid and its derivatives, which have electrophilic properties. Trifluoromethyl group-introducing agents with an increase in the number of carbon atoms of 2 and nucleophilic properties are usually
It is thought to have the structure CF ₃ CXYM (X, Y
is an element such as hydrogen or halogen. M is metal). 1,1-dichlorotrifluoroethyllithium produced by the method of the present invention is a type of trifluoromethyl group-introducing agent, and may be very useful depending on the structure of the target compound or its intermediate. It is.

(b) Prior art The conventionally known method for obtaining 1,1-dichlorotrifluoroethyllithium is 2,2
-It is lithiation of dichloro-1,1,1-trifluoroethane (CF ₃ CCl ₂ H, hereinafter abbreviated as 2,2-dichlorotrifluoroethane) (D.
Seyferth, DOMueller, and PMArmbrecht,
Jr., Organometal.Chem.Syn., 1 , 3 (1970-
(1971)), the reaction is shown by equation (1). In this report, _2,2 - _{dichlorotrifluoroethane} is dissolved in a mixed solvent of tetrahydrofuran _{and dimethyl} ether.
A hexane solution of n-butyllithium is added at 140 to -135°C.

Since 1,1-dichlorotrifluoroethyllithium is a compound that exists stably only at low temperatures,
Generally, it is necessary to convert it into a stable target compound by reacting it with an appropriate reagent immediately after production. Also 1,
The yield of 1-dichlorotrifluoroethyllithium is also estimated from the yield of the compound after conversion. In the above report, (1,1-dichloro-2,
2,2-trifluoroethyl)trimethylsilane (CF ₃ CCl ₂ Si(CH ₃ ) ₃ ) was obtained with a yield of 75% (value obtained by gas chromatography) and was also reacted with acetone. Possibly 3,3-dichloro-4,4,4-trifluoro-2-methyl-2-
Butanol (CF ₃ CCl ₂ C(CH ₃ ) ₂ OH) is obtained with a yield of 36%.

CF ₃ CCl ₂ Li+ClSi(CH ₃ ) ₃ → CF ₃ CCl ₂ Si(CH ₃ ) ₃ +LiCl (2) CF ₃ CCl ₂ Li+(CH ₃ ) ₂ CO→ CF ₃ CCl ₂ C(CH ₃ ) ₂ OH (3 ) (After hydrolysis) (C) Object of the Invention The above conventional method for producing 1,1-dichlorotrifluoroethyllithium has the following problems. (1) 2,2-dichlorotrifluoroethane used as a raw material is a compound that is relatively difficult to obtain, as the method for producing it is outlined below. (2) Special mixed solvents such as tetrahydrofuran-dimethyl ether are used. (3) Reaction temperature is -140
The temperature is extremely low at ~-135℃. (4) The yield of acetone addition product is as low as 36%. The most important problem among these is (1). In other words, it is thought that problems (2), (3), and (4) can be improved, but even if these points are improved, unless point (1) is resolved, 1,
The industrial utility of 1-dichlorotrifluoroethyllithium is limited.

The method for producing 2,2-dichlorotrifluoroethane (CF ₃ CCl ₂ H) includes (1) chlorination of CF ₃ CH ₃ , (2) reaction of CCl ₂ = CCl ₂ with hydrogen fluoride, (3) )
These include isomerization of CF ₂ ClCFClH, (4) reduction of CF ₃ CCl ₃ , and (5) thermal reaction of a mixture of CF ₃ CCl ₃ and CF ₃ CClH ₂ in the presence of a chromium catalyst. Among these methods, method (2) uses highly corrosive hydrogen fluoride, so it cannot be carried out with ordinary equipment for organic synthesis and requires special equipment. Therefore, (2) is one method for producing CF ₃ CCl ₂ H in large quantities, but it is often difficult to implement. Since method (1) tends to produce CF ₃ CCl ₃ , it is necessary to use method (5) in combination. On the other hand, method (4) has a good reduction yield (US Patent No. 3,391,204 and Published Patent Publication No. 1982-222,038),
In addition, its raw material, CF ₃ CCl ₃ , is 1,1,2-trichloro-
1,2,2-trifluoroethane (CF ₂ ClCFCl ₂ ,
It can be easily obtained in high yield from Freon 113) by isomerization using aluminum chloride (KHHellberg
and J.Massonne, Chem.Ztg., 98 , 209 (1969)).
In other words, method (4) is generally the easiest
This is thought to be the production route for CF ₃ CCl ₂ H.

_Therefore , in the conventional method, the production route _for 1,1-dichlorotrifluoroethyllithium tends _to be _CF3CCl3 → _CF3CCl2H → _CF3CCl2Li . If CF ₃ CCl ₃
If a method to directly produce CF ₃ CCl ₂ Li without going through CF ₃ CCl ₂ H could be found, its industrial benefits would be obvious.

(d) Structure of the invention In place of 2,2-dichlorotrifluoroethane, which was conventionally used to produce 1,1-dichlorotrifluoroethyllithium, the inventors produced it from a raw material that is easier to obtain. As a result of research into methods, a method using 1,1,1-trichlorotrifluoroethane as a raw material was discovered. That is, 1,1,1- in an aprotic organic solvent
By reacting trichlorotrifluoroethane with an organolithium compound, 1,1-dichlorotrifluoroethyllithium can be obtained, and the reaction is represented by formula (4).

CF ₃ CCl ₃ + RLi → CF ₃ CCl ₂ Li + RCl (4) What is important in the reaction conditions is the selection of the reaction temperature and reaction solvent. That is, 1,1-dichlorotrifluoroethyllithium is stable only at low temperatures, and in order to prevent decomposition, it is desirable to carry out the reaction at as low a temperature as possible. The required low temperatures are within the range easily obtained by using liquid nitrogen as a refrigerant, but the viscosity increases as the solvent approaches its melting point, making stirring difficult, making it difficult to carry out the reaction at too low a temperature. It cannot be done.

The actual method involves stirring 1,1,1-trichlorotrifluoroethane dissolved in an aprotic organic solvent while maintaining an appropriate internal temperature.
A solution of an organic lithium compound in an aprotic organic solvent may be added dropwise thereto. These aprotic organic solvents are preferably ethers, but hydrocarbons may be mixed therein. For example, as an organic lithium compound, n-butyllithium can be added dropwise in the form of a hexane solution.

Diethyl ether (hereinafter abbreviated as ether), a typical ether, has a melting point of -116℃,
If mechanical stirring is performed, the reaction can be carried out by cooling to about -110°C. As shown in Example 1, ether was actually used as a solvent, and approximately -110
When 1,1,1-trichlorotrifluoroethane was reacted with n-butyllithium while maintaining an internal temperature of 0.degree. C., 1,1-dichlorotrifluoroethyllithium was obtained as a viscous slurry. As a result of adding acetone to this while maintaining this low temperature, CF ₃ CCl ₂ C(CH ₃ ) ₂ OH (see formula (3)) was obtained with a yield of 61%. Therefore, the yield of 1,1,-dichlorotrifluoroethyllithium is higher than this.

The standard method is to generate 1,1-dichlorotrifluoroethyllithium once and then react it with an appropriate reagent to synthesize compounds of the type CF ₃ CCl ₂ A. . However, depending on the type of reagent, the reagent and 1,
It is also possible to mix 1,1-trichlorotrifluoroethane and add the organolithium compound to the solution. This often shortens the reaction time and simplifies the reaction operation, and also lowers the solidification temperature of the reaction system, making stirring easier. However, in order for this method to be applicable, the rate at which the organolithium compound reacts with 1,1,1-trichlorotrifluoroethane to produce 1,1-dichlorotrifluoroethyllithium is required. The rate of reaction with the reagent must be fairly slow.

Examples of reagents to which the above coexistence method can be applied include ketones and aldehydes. For example, as shown in Example 2, acetone and 1,
When an ether solution of n-butyllithium is added to an ether solution of a mixture with 1,1-trichlorotrifluoroethane at about -110°C, CF ₃ CCl ₂ C
( _CH3 ) _2OH was obtained in 62% yield. This yield agrees, within experimental error, with the yield obtained when 1,1-dichlorotrifluoroethyllithium is first produced and then acetone is added.

(e) Effect of the invention The effects of the present invention are listed below.

(1) 1,1,1-trichlorotrifluoroethane, which is a raw material for the method of the present invention, is generally easier to obtain than 2,2-dichlorotrifluoroethane, which is a raw material for conventional methods. Moreover, 2,2-dichlorotrifluoroethane is
At least when hydrogen fluoride is not used, 1,
It is easiest to synthesize from 1,1-trichlorotrifluoroethane. Therefore, the present invention
In many cases, it has the same effect as the ability to omit the reaction of synthesizing 2,2-dichlorotrifluoroethane from 1,1,1-trichlorotrifluoroethane.

(2) As a result of the reaction, the organolithium compound used as a reagent becomes the corresponding hydrogen compound in the conventional method (see formula (1)), but in the method of the present invention, it becomes the corresponding chloride (see formula (4)) . Therefore, in this method, after recovering this chloride, it is reacted with lithium,
Organolithium compounds can be regenerated.

(3) Although it is difficult to directly monitor the production reaction of 1,1-dichlorotrifluoroethyllithium, in the case of production by this method, it can be easily estimated from the amount of chloride produced.

(f) Examples Next, the present invention will be explained in more detail with reference to Examples.

Example 1 All reactions were carried out under a nitrogen atmosphere (Example 1
~5 common). A solution of 19 g (0.1 mol) of 1,1,1-trichlorotrifluoroethane in ether (100 ml) was placed in a 300 ml four-necked flask, mechanically stirred from the center of the flask, and placed in a liquid nitrogen cooling bath (stainless steel wide-mouthed brewer). , the height is adjustable). When the internal temperature dropped to around -110℃, we started dropping an ether solution (60 ml) containing about 0.1 mol of n-butyllithium, and controlled the internal temperature by controlling the dropping speed and the height of the cooling bath. was maintained at approximately -110°C. The dropwise addition was completed in 20 minutes, and a brown and viscous slurry of 1,1-dichlorotrifluoroethyllithium was obtained. A solution of 7 g (0.12 mol) of acetone in ether (20 ml) was added dropwise thereto over 20 minutes while maintaining the same internal temperature, and then the internal temperature was slowly raised. When the temperature reached approximately 0°C, the reaction mixture was poured into crushed ice and concentrated hydrochloric acid (10°C).
ml) mixture, the whole was shaken in a separatory funnel, the ether layer was washed with water, an aqueous solution of sodium bicarbonate, and dried over anhydrous sodium sulfate. Fractionally distill 93% of the ether solution into CF ₃ CCl ₂ C
12 g (61% yield) of (CH ₃ ) ₂ OH, boiling point 67-68°C/47 mmHg, was obtained. The melting point of this compound was approximately 30°C.

Example 2 1,1,1-trichlorotrifluoroethane 19
Into a solution of a mixture of n-butyllithium (0.1 mol) and 7 g (0.12 mol) of acetone in ether (100 ml) was added 10 ml of an ether solution (60 ml) containing about 0.1 mol of n-butyllithium, keeping the internal temperature at about -110°C. It was dripped in minutes. The reaction mixture was treated as in Example 1,
_CF3CCl2C ( _{CH3 ) 2OH} was obtained in 62% yield.

Example 3 A reaction on the same scale as in Example 2 (but using n-propylene lithium) was carried out using liquid nitrogen as a refrigerant and mechanical stirring, but in this example, dry ice-acetone was used as a refrigerant and a magnetic stirrer was used. The internal temperature was maintained in the range of -76 to -70°C. The yield of CF ₃ CCl ₂ C(CH ₃ ) ₂ OH obtained is
It was 44%.

Example 4 A slurry of 1,1-dichlorotrifluoroethyllithium was prepared in the same manner as in Example 1, and -110
A solution of 9 g (0.12 mol) of n-butyraldehyde in ether (20 ml) was added dropwise while maintaining an internal temperature of .degree. 93% of the ether solution obtained after work-up
was fractionated to obtain 2,2-dichloro-1,1,1-trifluoro-3-hexanol (CF ₃ CCl ₂ CH(OH)
_C3H7 - _n ), boiling point 73℃/23mmHg, 11.3g (yield
53%). The melting point of this compound was 56-58°C.

Example 5 1,1,1-trichlorotrifluoroethane 19
g (0.1 mol) and n-butyraldehyde 9 g
(0.12 mol) of n-propyllithium in ether (100 ml) was added at -110°C to an ether solution (60 ml) containing about 0.1 mol of n-propyllithium.
The yield of _{CF3CCl2CH (} OH) _C3H7 -n was ₄₆ %.

Claims (1)

[Claims] 1 1,1-dichloro-2, characterized by reacting 1,1,1-trichloro-2,2,2-trifluoroethane with an organolithium compound;
A method for producing 2,2-trifluoroethyllithium.