4-cyano-2,5-difluoroaniline preparation process

Details 4-cyano-2,5-difluoroaniline preparation process 4-cyano-2,5-difluoroaniline preparation process

1998-02-20

2000-06-13

Ramsuer, Robert W.

Organic compounds -- part of the class 532-570 series

Organic compounds

Nitriles

C07C25500

Patent

active

060751606

DESCRIPTION:

BRIEF SUMMARY
The invention relates to a process for preparing 4-cyano-2,5-difluoroaniline, which is an intermediate in the preparation of herbicides or liquid crystals.
The known two-step process for preparing 4-cyano-2,5-difluoroaniline starts from 2,5-difluoroaniline (see EP-A1 0 224 001). In the first stage this is brominated to give 4-bromo-2,5-difluoroaniline. In the second stage, the bromine is replaced by cyano. In addition to an at least equimolar quantity of copper cyanide for the reaction, it also requires an approximately 5-fold molar quantity of 10% sodium cyanide solution for work-up. Significant disadvantages include the cost of copper cyanide and the processing of waste water, which is problematical not merely because of the copper which is bound as cyano complex, the lengthy extractive work-up, in particular the large amount of dichloromethane required, and the handling of large quantities of very poisonous sodium cyanide solution.
It has been found that 4-cyano-2,5-difluoroaniline is obtained in high yield and purity if 2,4,5-trifluorobenzonitrile is reacted with an excess of ammonia at elevated temperatures, optionally in the presence of a diluent.
Surprisingly, even a large excess of ammonia does not lead to a di- or triamine. Furthermore, it is very surprising that exchange only takes place selectively in the 4-position and not in the 2-position. Analogous reactions using 2,4-difluorobenzonitrile under the conditions according to the invention give the two possible amines in an approximate ratio of 1:1.
The 2,4,5-trifluorobenzonitrile which is required as starting material is commercially available and can be prepared, for example, from 2,4-dichloro-5-fluorobenzoyl chloride by fluorination, amidation and subsequent dehydration.
Suitable diluents for carrying out the reaction according to the invention are water, certain organic solvents and any mixtures thereof. Those which may be mentioned by way of example are: aliphatic, alicyclic or aromatic hydrocarbons, such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; halogenated hydrocarbons, such as, for example, chlorobenzene or dichlorobenzene; ethers, such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, 1,2-dimethoxyethane, diethylene glycol dimethyl ether, 1,2-diethoxyethane or anisole. In principle, the use of a diluent is preferred. Preferred solvents are dioxane, tetrahydrofuran, toluene and water.
The reaction is carried out at temperatures of from 50 to 150.degree. C., preferably from 80 to 130.degree. C.
The reaction is generally carried out at increased pressure. It is preferably carried out at pressures which correspond to at least the autogenous pressure of the reaction mixture at the reaction temperature. A pressure of from 2 to 50 bar gauge is particularly preferred.
In general, the reaction according to the invention is carried out using from 1.5 to 50 mol, preferably from 2 to 20 mol, of ammonia and, if desired, from 0.1 to 3 l, preferably from 0.3 to 2 l, of diluent per mole of 2,4,5-trifluorobenzonitrile.
In a preferred embodiment of the reaction step of the process according to the invention, the nitrile, with the diluent, is introduced into a sealed reaction vessel and heated to the reaction temperature. Liquid ammonia is then pumped in against the container pressure at such a rate that the internal temperature can be kept constant.
In a preferred embodiment of the work-up step of the process according to the invention, after the reaction is complete the system is cooled, the container is decompressed and the excess ammonia and the diluent are removed, if necessary under reduced pressure. To isolate the 4-cyano-2,5-difluoroaniline, the residue is stirred with water, and the crystals are separated off, slurried with water, separated off again and finally dried.
The 4-cyano-2,5-difluoroaniline which can be prepared by the process of the invention can be used, for example, as an

REFERENCES:
patent: 4504660 (1985-03-01), Klaubert et al.
Ohmori et al., Journal of Medicinal Chemistry, vol. 37, No. 4 (1994) pp. 467-475.

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