Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Patent
1994-12-15
1996-06-18
Dees, Jose G.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
562456, C07C 5116
Patent
active
055279562
DESCRIPTION:
BRIEF SUMMARY
This application was filed under U.S.C. of the application Ser. No. PCT/GB93/01112 filed May 27, 1993.
The present invention relates to a process for the production of aromatic carboxylic acids and more particularly fluoro-substituted aromatic carboxylic acids.
Fluoro substituted aromatic carboxylic acids are intermediates in the manufacture of pharmaceuticals and/or agrochemicals. A number of processes for their production employ an alkyl substituted fluoroaromatic compound as starting material but these can require specialist equipment such as electrochemical cells, or elevated pressure or specialist techniques as in enzymatic oxidation.
In European Patent Application numbers EP-A-0 336 567 and EP-A-0 336 568 there are disclosed processes for selectively monobrominating or dibrominating an alkyl side chain of an aromatic compound substituted by an electron withdrawing group, viz o-nitrotoluene with aqueous hydrogen peroxide and a source of bromine under photolytic conditions. In accordance with accepted understanding of aromatic substitution reactions, the electron-withdrawing substituent on the benzene nucleus tended to deactivate the substrate, thereby inhibiting its ability to participate in substitution reactions. Although the reaction mixture included a significant aqueous phase, further reaction of the brominated products for example by hydrolysis was substantially avoided. Thus, the brominated products were available for further processing, for example to the eventual production of o-nitrobenzoic acid, but an overall conversion from alkyl to carboxylic acid required the addition of further and potentially cumbersome processing stages which inevitably introduces additional processing costs and reduces throughput in apparatus of a given size.
Surprisingly, it has been found that in a related class of alkylaromatic compounds nuclearly substituted by an electron withdrawing group, the alkyl group can be converted in a single stage to a carboxylic acid group, rather than requiring a series of stages.
According to the present invention there is provided a process for the conversion of a methyl substituent of an aromatic compound in which the aromatic compound is brought into contact with hydrogen peroxide and aqueous hydrogen bromide solution in the presence of means for generating bromine radicals from bromine molecules characterized in that the aromatic compound is nuclearly substituted by a fluoro group, the contact is effected at an elevated reaction temperature and hydrogen peroxide and aqueous hydrogen bromide solution are each employed in a mole ratio to the fluoro-substituted aromatic compound of greater than 2:1, whereby the methyl substituent is converted to a carboxylic acid substituent.
By the use of a process according to the present invention, the conversion of methyl to carboxylic acid substituent can be carried out in a single stage, despite the presence of a deactivating substituent.
The process of the present invention is particularly suited to the conversion of fluorotoluenes to fluorobenzoic acid, i.e. compounds meeting the general formula i to ii: ##STR1## Especially suitably, the fluoro substituent is ortho or para to the methyl substituent.
In general, hydrogen bromide is employed in a concentrated solution, advantageously greater than 15% w/w and in many practical instances greater than about 30% w/w. In general, bromide is present in a mole ratio to the fluorotoluene of from about 2.5:1 to about 7.5:1, and in some selected embodiments at from about 2.5:2 to about 3.5:1. It can be introduced as such or be obtained by in situ acidification of a soluble bromide salt, such as an alkali metal salt, or by in situ reduction of bromine. During the course of the reactions which take place in the single stage, bromide is oxidised to bromine which, it is believed, in a free-radical based reaction, brominates the methyl substituent of the fluorotoluene. The brominated substituent is subsequently hydrolysed or perhydrolysed, releasing bromide and oxidised through to the carboxylic acid, poss
REFERENCES:
patent: 4923580 (1990-05-01), Turner et al.
patent: 5092971 (1992-03-01), Turner et al.
Barts Samuel
Dees Jos,e G.
Solvay Interox Limited
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