JP4104317B2 - Method for producing fluoroalkylamine - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing a fluoroalkylamine useful for intermediates such as medical and agricultural chemicals. More specifically, the present invention relates to a method for efficiently producing a fluoroalkylamine by reacting a fluoroalkyl halide and ammonia in the presence of an iodine compound.
[0002]
[Prior art]
Fluorine-containing amine compounds such as fluoroalkylamine are extremely useful compounds as intermediates for pharmaceutical pesticides and the like. Until now, as a method for producing a fluoroalkylamine, there are a method of hydroreducing a corresponding nitro compound or a nitrile compound, a method of reducing a corresponding amide compound with a metal hydride, or a method of reacting a corresponding halide with ammonia. Are known.
[0003]
For example, Izu. Akad. Nauk SSSR, Ser. Khim. 2, 250 (1966), J. Amer. Chem. Soc., 65, 1458 (1943) and US Pat. No. 3,532,755 include corresponding nitro compounds. Alternatively, a technique for hydrogenating a nitrile compound to selectively obtain a desired fluoroalkylamine is disclosed. In addition, J. Chem. Soc., 4014 (1952), Can. J. Chem., 32, 639 (1954) and J. Org. Chem., 24, 1256 (1959) include corresponding amide compounds as metal hydrogens. Techniques have been disclosed in which the desired fluoroalkylamine is selectively obtained by reduction with a fluoride. However, in the disclosed production process, the corresponding nitro compound, nitrile compound, and amide compound are very expensive or difficult to obtain, and thus are not necessarily suitable as an industrial production method.
[0004]
Furthermore, J. Org. Chem., 19, 391 (1954), Ind. Eng. Chem., 48, 209 (1956), and US Pat. No. 4,618,718 describe trifluoroethyl chloride as a fluoroalkylamine. A technique for reacting ammonia to selectively obtain trifluoroethylamine is disclosed. Trifluoroethyl chloride is industrially available, but has problems such as extremely long reaction time and low yield for producing the corresponding fluoroalkylamine, and is an excellent industrial production method. It's hard to say how. On the other hand, US Pat. No. 2,348,321 describes an example in which a corresponding halide and ammonia are reacted. However, although the reaction time is short, there is no description regarding the reaction pressure and reaction yield.
[0005]
[Problems to be solved by the invention]
The problem to be solved by the present invention is to provide a method for efficiently producing a corresponding fluoroalkylamine by reacting a fluoroalkyl halide with ammonia.
[0006]
[Means for Solving the Problems]
In view of such a current situation, the present inventors have conducted intensive studies. As a result, it has been surprisingly found that when a fluoroalkyl halide and ammonia are reacted in the presence of an iodine compound, the reaction time can be remarkably shortened even under known reaction conditions, and a high yield can be obtained. Was completed.
[0007]
That is, the present invention relates to a method for producing a fluoroalkylamine, characterized in that a fluoroalkylamine is produced by reacting a fluoroalkyl halide and ammonia in the presence of an iodine compound.
[0008]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, the present invention will be described in detail.
[0009]
In the present invention, a fluoroalkyl halide and ammonia are reacted in the presence of an iodine compound to produce a corresponding fluoroalkylamine.
[0010]
In the present invention, the fluoroalkyl group of the fluoroalkyl halide used as a raw material is a fluorinated hydrocarbon having 1 to 10 carbon atoms. Examples of these fluoroalkyl groups include methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, isobutyl, hexyl, cyclohexyl, octyl, and decyl groups containing fluorine atoms. It is done. The number and position of fluorine atoms contained in these fluoroalkyl groups are not limited. Of these, preferred fluoroalkyl groups are 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,2,2,2-tetrafluoroethyl, 3,3,3-trifluoropropyl, 2,3,3,3-pentafluoropropyl.
[0011]
Examples of the fluoroalkyl halide of the present invention include fluoroalkyl chloride and / or fluoroalkyl bromide.
[0012]
Iodine compound used as a catalyst in the present invention, iodine is Amin'you containing salt, at least one kind selected from a metal iodide salt. A commercially available solid reagent can be used as it is for iodine. As a Amin'you containing salt, ammonia, trimethylamine, triethylamine, tertiary alkyl amines such as dimethyl benzylamine, iodine salt of an amine, such as par-methyl ethylenediamines, and the like. Examples of the metal iodine salt include iodine salts such as alkali metals such as sodium, potassium and lithium, alkaline earth metals such as calcium, magnesium and barium, and amphoteric metals such as aluminum and zinc. Of these, sodium iodide and / or potassium iodide are preferred because they are readily available at low cost, are easy to handle, have high solubility in solvents, and are less toxic and can be discarded.
[0013]
In the present invention, a solvent is used if necessary. Solvents that can be used are water, ammonia, methanol, ethanol, n-propanol, isopropanol, glycol, ketones such as triethylene glycol, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, dichloromethane, dibromomethane, chloroform, bromoform, Halogenated hydrocarbons such as carbon tetrachloride, 1,2-dichloroethane, 1,1,2-trichloroethane, ethers such as dimethyl ether, diethyl ether, 1,4-dioxane and tetrahydrofuran, and aromatics such as benzene, toluene and xylene Examples include hydrocarbons, other aprotic polar solvents such as sulfolane, dimethylacetamide, dimethylformamide, N-methylpyrrolidone, and 1,3-dimethyl-2-imidazolidinone. Of these, N-methylpyrrolidone is preferable because it is highly polar, difficult to decompose even at high temperatures, has a high boiling point, dissolves a substrate and an iodine compound well, has high solubility in trifluoroethylamine, and is less corrosive to materials. 1,3-dimethyl-2-imidazolidinone or sulfolane.
[0014]
According to the present invention, the reaction method may be either a continuous reaction or a batch reaction. However, when the batch reaction is taken as an example, the raw material is charged into a pressure reactor and heated to carry out the reaction.
[0015]
First, in preparing raw materials, a solvent and an iodine compound are charged. The usage-amount of a solvent is 0.5-10.0 mol with respect to 1 mol of fluoroalkyl halides, Preferably, it is 1.0-3.0 mol. Moreover, although the usage-amount of an iodine compound is 0.01-30 mol with respect to 1 mol of fluoroalkyl halides, Preferably it is 0.1-5 mol. If it is less than 0.01 mol, no improvement in reaction rate and yield is observed. Moreover, even if it uses exceeding 30 mol, the improvement of reaction rate and a yield is not recognized, but it is not economical.
[0016]
The pressurized container is then replaced with an inert gas. Examples of the inert gas that can be used include nitrogen, argon, and hydrogen. Thereafter, raw material fluoroalkyl halide and ammonia are charged. At this time, the amount of ammonia to be used is 2.0 mol or more, preferably 2.5 to 4.0 mol, relative to 1 mol of the fluoroalkyl halide. Too much use is not preferable because it increases the reaction pressure. The pressure vessel filled with the raw material is heated and stirred to start the reaction. Although reaction temperature is not specifically limited, Usually, it is 120-260 degreeC, More preferably, it is 180-220 degreeC. The stirring speed is appropriately selected so that stirring is sufficiently performed. The reaction time is not particularly limited, but the reaction is usually completed in 4 to 10 hours. The reaction pressure is usually 20 to 150 KPa, depending on the type of substrate used in the reaction, the amount of ammonia, and the amount and type of solvent. After completion of the reaction, the pressurized reactor is sufficiently cooled and purged with excess ammonia, remaining inert gas, and unreacted raw material if remaining, to recover the reaction solution. From this reaction solution, a desired reaction product can be obtained by a conventional method.
[0017]
【Example】
EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, this invention is not limited only to these Examples. The names and abbreviations of the compounds used in Examples and Comparative Examples are shown below.
[0018]
TFEC: 2,2,2-trifluoroethyl chloride TFEB: 2,2,2-trifluoroethyl bromide TFAN: 2,2,2-trifluoroethylamine BTFAN: bis (2,2,2-trifluoroethyl) amine Example 1
A 300 ml stainless steel reaction vessel equipped with a thermometer and a stirrer was charged with 72 g of TFEC, 5 g of sodium iodide and 105 g of 1,3-dimethyl-2-imidazolidinone, and 37 g of ammonia gas was added. The reaction temperature was kept at 200 ° C. and reacted for 8 hours to obtain a reaction solution. During the reaction, the pressure changed from 99 KPa to 53 KPa. A part of the obtained reaction solution was collected and analyzed by gas chromatography as usual. The conversion of TFEC was 99.4%, the yield was TFAN 90.6%, and BTFAN 2.5%.
Example 2
In the same manner as in Example 1, 72 g of TFEC, 5 g of sodium iodide and 91 g of N-methylpyrrolidone were charged, and 39 g of ammonia gas was added. The reaction temperature was kept at 200 ° C. and reacted for 8 hours to obtain a reaction solution. During the reaction, the pressure changed from 93 KPa to 46 KPa. A part of the obtained reaction solution was collected and analyzed by gas chromatography as usual. The conversion of TFEC was 97.5%, the yields were TFAN 88.2%, and BTFAN 1.9%.
Example 3
As in Example 1, 99 g of TFEB, 5 g of sodium iodide and 105 g of 1,3-dimethyl-2-imidazolidinone were charged, and 39 g of ammonia gas was added. The reaction temperature was kept at 200 ° C. and reacted for 8 hours to obtain a reaction solution. During the reaction, the pressure changed from 101 KPa to 52 KPa. A part of the obtained reaction solution was collected and analyzed by gas chromatography as usual. The conversion of TFEC was 99.8%, the yields were TFAN 91.5%, and BTFAN 1.7%.
Comparative Example 1
In the same manner as in Example 1, 72 g of TFEC and 105 g of 1,3-dimethyl-2-imidazolidinone were charged, and 37 g of ammonia gas was added. The reaction temperature was kept at 200 ° C. and reacted for 8 hours to obtain a reaction solution. During the reaction, the pressure changed from 101 KPa to 68 KPa. A part of the obtained reaction solution was collected and analyzed by gas chromatography as usual. As a result, the conversion of TFEC was 82.3%, the yield was TFAN 73.8%, and BTFAN 0.9%.
Comparative Example 2
As in Comparative Example 1, 72 g of TFEC and 105 g of 1,3-dimethyl-2-imidazolidinone were charged, and 37 g of ammonia gas was added. The reaction temperature was kept at 200 ° C. and reacted for 48 hours to obtain a reaction solution. During the reaction, the pressure changed from 101 KPa to 61 KPa. A part of the obtained reaction solution was collected and analyzed by gas chromatography as usual. As a result, the conversion of TFEC was 91.0%, the yield was TFAN 80.9%, and BTFAN 1.2%.
[0019]
【The invention's effect】
In the process of producing a corresponding fluoroalkylamine by reacting a fluoroalkyl halide and ammonia, there is a problem that the reaction is very slow and the conversion and yield are not improved even if the reaction is carried out for a long time. According to the present invention, when this reaction is carried out in the presence of an iodine compound, the reaction time can be shortened, and the conversion rate and yield can be improved. For this reason, the manufacturing cost of the useful pharmaceutical which uses trifluoroalkylamine as a raw material can be reduced, The economic effect is large.

Claims (8)

A method for producing a fluoroalkylamine, comprising producing a fluoroalkylamine by reacting a fluoroalkyl halide and ammonia in the presence of at least one iodine compound selected from iodine, an amine iodine salt and a metal iodine salt . The method for producing a fluoroalkylamine according to claim 1, wherein the metal iodine salt is sodium iodide and / or potassium iodide. The method for producing a fluoroalkylamine according to claim 1 or 2 , wherein the fluoroalkyl halide is a fluoroalkyl halide having 1 to 10 carbon atoms. The method for producing a fluoroalkylamine according to any one of claims 1 to 3 , wherein the fluoroalkyl halide is fluoroalkyl chloride and / or fluoroalkyl bromide. The method for producing a fluoroalkylamine according to any one of claims 1 to 4 , wherein the fluoroalkylamine is produced using a solvent. The method for producing a fluoroalkylamine according to claim 5 , wherein the solvent is an aprotic polar solvent. The method for producing a fluoroalkylamine according to claim 6 , wherein the aprotic polar solvent is at least one selected from N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and sulfolane. . The method for producing a fluoroalkylamine according to any one of claims 1 to 7 , wherein the fluoroalkyl group of the fluoroalkyl halide is a 2,2,2-trifluoroethyl group.