Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2001-04-12
2002-03-26
Barts, Samuel (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C564S389000, C564S390000, C564S391000
Reexamination Certificate
active
06362372
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to a process for producing trifluoromethylbenzylamines useful in the pharmaceutical and agricultural chemical fields.
Numerous processes for obtaining primary amines by hydrogenation of nitrile compounds have been reported. In addition, numerous processes for obtaining primary amines of fluorine-containing aromatics from fluorine-containing aromatic nitrile compounds have also been reported.
J. Pharm. Sci., 54, 1204 (1965) discloses that a benzylamine (yield: 56-68.5%) is obtained by a catalytic hydrogenation of the corresponding trifluoromethylbenzonitrile in the presence of hydrogen chloride using a catalyst (palladium/carbon). In such a hydrogenation, selectivity is lowered, in case that a primary amine is obtained by a hydrogenation of a trifluoromethyl-containing nitrile compound. Therefore, a subsequent purification (e.g., distillation) becomes very complicated.
U.S. Pat. No. 6,175,041 B1 discloses a process for producing 3,5-bis(trifluoromethyl)benzylamine by a hydrogenation of 3,5-bis(trifluoromethyl)benzonitrile in the presence of ammonia in an organic solvent under a hydrogen pressurized condition (40 kg/cm
2
) using a Raney catalyst. This process requires such a high pressure.
Processes for obtaining trifluoromethylbenzylamines from aromatic nitrile compounds having a trifluoromethyl group have problems that remain to be solved, and an industrially useful process for producing trifluoromethylbenzylamines has yet to be established.
SUMMARY OF THE INVENTION
It is therefore an object of the present invention to provide a process for producing a trifluoromethylbenzylamine easily and inexpensively.
According to the present invention, there is provided a process for producing a trifluoromethylbenzylamine represented by the following general formula (1),
where each R independently represents a halogen selected from the group consisting of fluorine, chlorine, bromine and iodine, an alkyl group having a carbon atom number of 1-4, an alkoxy group having a carbon atom number of 1-4, an amino group, a hydroxyl group or a trifluoromethyl group, and n represents an integer from 0 to 4. The process comprises hydrogenating a trifluoromethylbenzonitrile by hydrogen in an organic solvent in the presence of ammonia and a catalyst comprising a platinum group element. The trifluoromethylbenzonitrile is represented by the following general formula (2),
where R and n are defined as above. With this process, it is possible to obtain the trifluoromethylbenzylamine at an extremely high yield.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The trifluoromethylbenzonitrile represented by the general formula (2) used in the present invention is a benzonitrile having at least one trifluoromethyl group. This benzonitrile may also have a substituent group that is inactive under the conditions of the hydrogenation of the present invention. Examples of such substituent group include halogens (i.e., fluorine, chlorine, bromine and iodine), alkyl groups each having a carbon atom number of 1-4, alkoxy groups each having a carbon atom number of 1-4, amino groups, hydroxyl groups and trifluoromethyl groups. Specific examples of the trifluoromethylbenzonitrile include 2-trifluoromethylbenzouitrile, 3-trifluoromethylbenzonitrile, 4-trifluoromethylbenzonitrile, 2-bromo-5-trifluoromethylbenzonitrile, 2-chloro-5-trifluoromethylbenzonitrile, 2-fluoro-5-trifluoromethylbenzonitrile, 4-iodo-2-trifluoromethylbenzonitrile, 4-iodo 3-trifluoromethylbenzonitrile, 2-methoxy-5-trifluoromethylbenzonitrile, 3-methoxy-4-trifluoromethylbenzonitrile, 4-hydroxy-2-trifluoromethylbenzonitrile, 4-methoxy-3-trifluoromethylbenzonitrile, 2-amino-3-trifluoromethylbenzonitrile, 2-amino-5-trifluoromethylbenzonitrile, 2-amino-6-trifluoromethylbenzonitrile, 3-amino-5-trifluoromethylbenzonitrile, 4-amino-2-trifluoromethylbenzonitrile, 4-amino-3-trifluoromethylbenzonitrile, 2,3-bis(trifluoromethyl)benzonitrile, 2,4-bis(trifluoromethyl)benzonitrile, 2,5-bis(trifluoromethyl)benzonitrile, 2,6-bis(trifluoromethyl)benzonitrile, 3,4-bis(trifluoromethyl)benzonitrile, 3,5-bis(trifluoromethyl)benzonitrile, 2,3,6-tris(trifluoromethyl)benzonitrile, 2,4,6-tris(trifluoromethyl)benzonitrile, 2,3,4,6-tetraquis(trifluoromethyl)benzonitrile, 2-amino-4,6-bis(trifluoromethyl)benzonitrile, 4-amino-3,5-bis(trifluoromethyl)benzonitrile and 4-chloro-3 5-bis(trifluoromethyl)benzonitrile. Of these, 3,5-bis(trifluoromethyl)benzonitrile, 3-trifluoromethylbenzonitrile, and 4-trifluoromethylbenzonitrile are particularly preferable. These trifluoromethylbenzonitriles having trifluoromethyl groups can be produced by various processes. For example, 2-trifluoromethylbenzonitrile can be obtained by fluorinating 2-trichloromethylbenzonitrile with antimony trifluoride, while 4-trifluoromethylbenzonitrile can be obtained by heating 4-trifluoromethylaniline diazoate with K
3
[Cu(CN)
4
].
The reaction of the benzonitrile compound is conducted by catalytic hydrogenation. Although both heterogeneous and homogeneous catalysts can be used as the catalyst of the catalytic hydrogenation, heterogeneous catalysts are preferable in consideration of their ease of removal. The catalyst used in the process of the invention contains a metal (active species) that is a platinum group element selected from ruthenium, rhodium, palladium, osmium, iridium, and platinum. Thus, metals or metal oxides such as palladium or platinum oxide, or these supported on a carrier such as activated carbon, alumina or diatomaceous earth, can be used. Examples of the catalyst include palladium-loaded activated carbon, palladium hydroxide-loaded activated carbon, palladium-loaded barium sulfate, palladium-loaded calcium carbonate, palladium-loaded strontium carbonate, palladium black, palladium-loaded silica gel, platinum dioxide, platinum-loaded activated carbon, platinum black, ruthenium-loaded activated carbon and rhodium-loaded activated carbon. Although the amount of the catalyst may vary according to its type, it is preferably 0.0001-10 moles, more preferably 0.001-1 mole, per 100 moles of the benzonitrile compound represented by the general formula (2).
Examples of the reaction solvent include alcohols, hydrocarbons, ethers, carboxylic acids, esters, amides, and water. Typical examples of these solvents include methanol, ethanol, benzene, toluene, xylene, ethyl benzene, isopropyl benzene, tetralin, mesitylene, tetrahydrofuran, diethyl ether, acetic acid, ethyl acetate and dimethylformamide, and two or more types of these solvents can be used in combination.
The process of the present invention can be carried out under pressurization by hydrogen. Upon this, a pressure of 0.5-25 MPa is preferable, while that of 1-10 MPa is more preferable. If the reaction pressure is less than 0.5 MPa, a longer time is required for reaction. If the reaction pressure exceeds 25 MPa, although there are no problems in terms of the reaction, this is not preferable with respect to the strength of the apparatus, reaction procedure and pressurization procedure.
The process of the present invention can be carried out at −20 to 100° C., preferably −20 to 50° C., more preferably in the vicinity of room temperature. Here, room temperature refers to the temperature in the absence of heating or cooling. If the reaction temperature is below −20° C., the reaction requires a longer period of time. If the reaction temperature is above 100° C., the amount of reaction by-products increases and the yield of the target product decreases correspondingly, thus making this undesirable.
In the process of the present invention, the amount of ammonia added is preferably 1-30 parts by weight to 100 parts by weight of the trifluoromethylbenzonitrile as the starting material. Although liquid ammonia is normally used, it may also be introduced as a gas. In addition, basic substance(s) can also be added to the reaction system. Examples of basic substances that can be used include hydroxides, oxides, carbonates and so forth of alkaline metals or alkaline earth metals. Specific
Kume Takashi
Narizuka Satoru
Barts Samuel
Central Glass Company Limited
Crowell & Moring LLP
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