GB2241952A

GB2241952A - Preparation of fluoroanilines

Info

Publication number: GB2241952A
Application number: GB9101256A
Authority: GB
Inventors: Daniel Levin; John Stewart Moilliet
Original assignee: Imperial Chemical Industries Ltd
Current assignee: Imperial Chemical Industries Ltd
Priority date: 1990-03-15
Filing date: 1991-01-21
Publication date: 1991-09-18
Also published as: GB9101256D0; GB9005839D0

Abstract

A process for the preparation of a compound of Formula A: <IMAGE> which comprises reductive fluorination of a compound of Formula B: <IMAGE> wherein X<1> and X<2> are independently selected from @ H or any substituent which does not interfere with the @ reductive fluorination; and Z<1> and Z<2> are each independently selected @ from H or an electron donating group.

Description

FLUOROANILINES This invention relates to a process for the preparation of a fluoroaniline by simultaneous reduction and ring fluorination (reductive fluorination) of the corresponding nitrobenzene.

According to the present invention there is provided a process for the preparation of a compound of Formula A:

Formula A which comprises reductive fluorination of a compound of Formula B;

Formula B wherein X and X are independently selected from H or any substituent which does not interfere with the reductive fluorination; and Z and Z are each independently selected from H or an electron donating group.

In the compound of Formula A it is preferred that one of X1 and X2 is an electron withdrawing group or hydrogen; the other group may be any substituent which does not interfere with the reductive fluorination.

It is preferred that when X1 and X2 is an electron withdrawing group it is selected from halogen, -NO2, -CF31 -CN, -OR; where R is H or C1~6-alkyl. It is especially preferred that the electron withdrawing group is -F or -C1.

It is preferred that when X1 or X2 is another group which does not interfere with the reductive fluorination it is selected from hydrogen, or unbranched or branched C1 -alkyl.

It is preferred that z and z are each independently hydrogen or selected from groups such as unbranched or branched C1-6-alkyl, -COOor 0 groups. It is especially preferred that Z and Z are each independently -H or -CR3.

Examples of fluoroanilines which may be prepared by the process of the invention include: 2,4-difluoroaniline 2-chloro-4-fluoroaniline 2-bromo-4-fluoroaniline 2,4,6-trifluoroaniline 2-chloro-4,6-difluoroaniline 3-methyl-4-fluoroaniline 3,5-dimethyl-4-fluoroaniline 2-fluoro-3-methyl-4-fluoroaniline 2-chloro-3-methyl-4-fluoroaniline 2-fluoro-3,5-dimethyl-4-fluoroaniline 2-chloro-3,5-dimethyl-4-fluoroaniline and examples of nitrobenzenes from which they may be prepared include: 2-fluoronitrobenzene 2-chloronitrobenzene 2-bromonitrobenzene 2,6-difluoronitrobenzene 2-chloro-6-fluoronitrobenzene 3-methylnitrobenzene 3,5-dimethylnitrobenzene 2-fluoro-3-methylnitrobenzene 2-chloro-3-methylnitrobenzene 2-fluoro-3,5-dimethylnitrobenzene 2-chloro-3, 5-dimethylnitrobenzene.

The process is preferably performed by reacting the nitrobenzene of Formula B with hydrogen and hydrogen fluoride in the presence of a hydrogenation catalyst under pressure and at a temperature below BO0C. The catalyst may optionally be partially deactivated by addition of sulphur compounds. This deactivation lowers the amount of by-product formation.

The hydrogen fluoride should have low water content, preferably less than 2% and more preferably less than 1% and especially less than 0.1t.

The hydrogenation catalysts which are suitable for use in the process of the invention are metals such as platinum, palladium, ruthenium, rhodium, osmium and iridium and the oxides of these metals.

The catalysts may be used alone as their oxides or on a support material such as carbon, aluminium oxide, aluminium fluoride, calcium fluoride, barium sulphate and calcium sulphate. The loading of metal catalyst on support material is preferably in the range O.lie to 10% by weight, more preferably 1-5% and especially 3-5%.

The catalysts may be partially deactivated by pre-treatment with sulphur compounds such as thiourea, thiophen and dimethyl sulphoxide or with heavy metal salts such as those of barium, lead and cadmium. Alternatively the sulphur compounds or heavy metal salts may be added directly to the reaction mixture. The reaction is preferably carried out at temperatures from -200C to 80C, more preferably up to 60 C and especially from 20-500C. The reaction is preferably carried out at a pressure of up to 200 psig, and more preferably from 30 to 120 psig.

When the reaction has been completed the product may be isolated in any convenient manner. For example the reaction mixture may be cooled to OOC, the reactor vented, the reaction mixture neutralised in ice cold ammonia solution and the product steam distilled from the reaction mixture.

Alternatively the hydrogen fluoride may first be distilled from the reaction mixture, the residual organic material neutralised and the product recovered by steam distillation.

The steam distillate contains the desired 4-fluoroaniline derivative and aniline by-products. The 4-fluoroaniline derivative may be purified by any convenient means; for example, by partial neutralisation and extraction into any suitable water immiscible solvent, by crystallisation or by distillation.

The invention is illustrated by the following examples.

Examples The general procedure for the reductive fluorination of nitrobenzene derivatives is as follows: The nitrobenzene derivative (10 parts) was charged to an autoclave with catalyst (0.15 parts of Pt2O or 1.0 part of 1% Pt/C) and the sulphur compound added as required.

Hydrogen fluoride (70 parts) was added to the autoclave before stirring for 5 minutes to mix the reactants and pressurising to 120 psig with hydrogen. The hydrogen pressure was maintained between 30 and 120 psig until there was no further hydrogen uptake.

The autoclave was cooled to OOC and vented. The reaction mixture was added to ice (100 parts). The resulting solution was added slowly to a stirred solution of 880 ammonia (400 parts). The resulting mixture was steam distilled to yield the fluoroaniline derivative.

Examples 1-11 are tabulated below: Table 1

Ex. Nitro- Catalyst Sulphur Temp Yield of Yield benzene type compound C fluorinated of derivative (parts) aniline aniline derivative 1 3-Me PtO2 none 20-30 3-Me-4-F 46 46 2 3-Me PtO2 Thiourea (0.04) .. 3-Me-4-! 69 12 3 3,5-diMe PtO2 none .l 3,5-diMe 55 30 -4-F 4 3,5-diMe PtO2 Thiourea (0.04) " " 85 0 5 2-Me PtO2 Thiourea (0.04) " 2-Me-4-F 61 14 6 2-F PtO2 none 20-25 2,4-diF 47 18 7 2-F PtO2 Thiourea (0.051) " 68 17 8 2-F PtO2 Thiourea (0.027) " 61 22 9 2-F 1% Pt/C none " " 28 22 10 2-F 1% Pt/C Thiourea (0.020) " " 31 17 11 2-C1 PtO2 none 20-30 2-C1-4-F 57 12 Comparative Examples 1-4 are tabulated below: Table 2

Ex. Nitro- Catalyst Sulphur Temp Yield of Yield benzene type compound C fluorinated of derivative (parts) aniline aniline derivative 1 3-F PtO2 none 20-30 3,4-diF 7 45 2 3-F PtO2 Thiourea (0.04) 3,4-diF 4 62 3 3-Cl PtO2 none 20-40 3-C1-4-F 0 96 4 3-CF3 PtO2 none 20-35 3-CF3-4-F 0 96

Claims

CLAIMS 1. A process for the preparation of a compound of Formula A:

Fo rmu I a A which comprises reductive fluorination of a compound of Formula B:

Formula B wherein X1 and X2 are independently selected from H or any substituent which does not interfere with the reductive fluorination; and Z and Z are each independently selected from H or an electron donating group.