Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic halides
Reexamination Certificate
2001-01-25
2002-07-16
Killos, Paul J. (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic halides
C562S852000, C562S849000, C562S861000, C562S864000, C562S493000
Reexamination Certificate
active
06420601
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to a process for the preparation of 3,5-bis-(trifluoromethyl)benzoyl chlorides from the corresponding 3,5-dimethylbenzoic acids and to novel 3,5-bis(trihalogenomethyl)- and 3,5-dimethylbenzoyl halides that arise as intermediates in the process. In the text below, 3,5-bis(trifluoromethyl)benzoyl chlorides are also referred to as BTBs.
BTBs are intermediates for the preparation of pharmaceutical and agrochemical active ingredients and photoresist compositions.
The preparation of BTBs from the corresponding 3,5-bis(trifluoromethyl)benzoic acid by chlorination is known (see, for example, J. Med. Chem., 38, 3106 (1995)). This acid can be obtained in two different ways, by
(a) metallizing 1-bromo-3,5-bis(trifluoromethyl)benzene with magnesium or lithium (see Bull. Soc. Chim. Fr., 1962 (587) and Chem. Ber., 129, 233 (1996)) and then reacting with carbon dioxide or, in the presence of a palladium catalyst, with carbon monoxide and water (see JP-OS 09/67,297) or
(b) reacting 3,5-bis(trifluoromethyl)benzene with a mixture of butyllithium and potassium t-butoxide (see Synlett, 1990, 747) or only with butyllithium (see J. Organomet. Chem., 67, 321 (1974)) and then with carbon dioxide.
These processes for the preparation of BTBs are less suitable for the industrial scale because in all cases organometallic compounds have to be prepared and handled, which is possible only with great technological expenditure. Moreover, 3,5-bis(trifluoromethyl)benzene and the corresponding 1-bromo compound can be prepared only by a complex route. Added to this is the danger of the exothermic decomposition of meta-trifluoromethyl-substituted phenyl-magnesium and -lithium compounds, which likewise require great expenditure for somewhat reliable control.
It is also known that 3,5-bis(trifluoromethyl)benzoyl fluorides can be prepared by selectively hydrolyzing 1,3,5-tris(trichloromethyl)benzenes with water to give 3,5-bis(trichloromethyl)benzoyl chlorides (see German Patent Specification 705,650) and then carrying out a complete chlorine/fluorine exchange with hydrogen fluoride or antimony trifluoride (see German Patent Specification 707,955). Whether and, where appropriate, how the corresponding benzoyl chlorides (“BTBs”) can be obtained from 3,5-bis-(trifluoromethyl)-benzoyl fluorides is not known.
There is therefore a need for a process for the preparation of BTBs that can be reliably carried out on an industrial scale without particular complexity and that starts from readily accessible starting materials.
SUMMARY OF THE INVENTION
We have now found a process for the preparation of 3,5-bis(trifluoromethyl)benzoyl chlorides of formula (I)
wherein
X is hydrogen, fluorine, or chlorine, comprising
(1) converting 3,5-dimethylbenzoic acids of formula (V)
wherein
X has the meaning given for formula (I),
into the corresponding acid chlorides of formula (IV)
wherein
X has the meaning given for formula (I),
(2) completely free-radically chlorinating the acid chlorides of formula (IV) in the side chains to give 3,5-bis(trichloromethyl)benzoyl chlorides of formula (III)
wherein
X has the meaning given for formula (I),
(3) fluorinating the 3,5-bis(trichloromethyl)benzoyl chlorides of formula (III) with anhydrous hydrogen fluoride and/or antimony pentafluoride to give 3,5-bis(trifluoromethyl)benzoyl fluorides of formula (II)
wherein
X has the meaning given for formula (I), and
(4) reacting the 3,5-bis(trifluoromethyl)benzoyl fluorides of formula (II) with silicon tetrachloride in the presence of a further Lewis acid to give the compounds of formula (I).
In formulas (I) to (V), X is preferably hydrogen.
DETAILED DESCRIPTION OF THE INVENTION
The first stage of the process according to the invention, the preparation of the acid chlorides of the formula (IV) from the benzoic acids (V), can be carried out analogously to known processes for the preparation of carbonyl chlorides from carboxylic acids. One possibility for the reaction of 3,5-dimethylbenzoic acid with phosphorus pentachloride is known from Can. J. Chem., 41, 2962 (1963) and another with thionyl chloride is known from J. Org. Chem., 24, 1301 (1959). These reactions can be carried out analogously for compounds in which X is fluorine or chlorine. The benzoic acids of the formula (V) required to carry out the first stage can be prepared by known processes or analogously thereto. 3,5-Dimethylbenzoic acid is commercially available.
The conversion to the acid halides of the formula (IV) can be carried out with chlorinating reagents, for example, with thionyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, oxalyl chloride or phosgene. Preference is given to using thionyl chloride or oxalyl chloride, the reaction products of which (hydrogen chloride and sulfur dioxide or hydrogen chloride, carbon monoxide and carbon dioxide respectively) are readily volatile and therefore can be removed easily.
The conversion to the acid chlorides of formula (IV) is preferably carried out in the presence of a diluent. Suitable for this purpose are inert organic solvents or mixtures thereof. By way of example, mention may be made of aliphatic, alicyclic, and aromatic hydrocarbons, such as petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylenes and Decalin, halogenated hydrocarbons, such as chlorobenzene, dichlorobenzenes, methylene chloride, chloroform, tetrachloromethane, dichloroethane, trichloroethane and tetrachloroethylene, ethers, such as diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane, diethylene glycol dimethyl ether and anisole, esters, such as methyl acetate, ethyl acetate and butyl acetate, and sulfones, such as sulfolane. Per mole of benzoic acid of the formula (V), 50 to 150 ml of diluent, for example, can be used.
It is advantageous to use an excess of the chlorinating reagent, for example, 1.1 to 10 mol (preferably 1.2 to 3 mol) of chlorinating reagent per mole of the benzoic acid of the formula (V).
The reaction temperature for this stage can be varied within a relatively wide range. For example, it can be between 0 and 150° C., preferably between 20 and 120° C.
The work-up following the reaction can, for example, be carried out by distillation. If the preferred chlorinating reagents are used, it is possible to readily distill off their excess and the diluent which may be present, and to use the distillation residue as crude product in the next stage.
The second stage of the process according to the invention, the side-chain chlorination of the 3,5-dimethylbenzoyl chlorides of the formula (IV), is novel. This side-chain chlorination is carried out as a free-radical reaction. This can be achieved as a result of elevated temperature, irradiation by a light source, and/or addition of a free-radical initiator. Examples of suitable light sources are incandescent lamps, preferably halogen lamps and medium- and high-pressure mercury vapour lamps. Suitable free-radical initiators are, for example, benzoyl peroxide, di-tert-butyl peroxide, 2,2-aza-bis(isobutyronitrile), and 2-phenylazo-2,4-dimethyl-4-methoxy-valeronitrile. Preference is given to using a light source at elevated temperature. The reaction temperature can, for example, be between 80 and 250° C., preferably 100 to 220° C., particularly preferably between 110 and 190° C. Here, it is advantageous to start the chlorination at relatively low temperatures, for example, 80 to 140° C., and to continue to the end at relatively high temperatures, for example, 160 to 250° C.
The chlorinating agent used in this stage is generally elemental chlorine.
Per mole of dimethylbenzoyl chloride of the formula (IV), it is possible, for example, to use 6.3 to 18 mol (preferably 7.2 to 12 mol) of chlorine gas.
For work-up after the reaction it is possible to displace any excess chlorine, e.g., by introducing an inert gas, such as nitrogen, or by applying a vacuum. Crude product obtainable in this way can be used directly in the next reaction stage, although, if desired, it can also be pu
Marhold Albrecht
Stölting Jörn
Bayer Aktiengesellschaft
Gil Joseph C.
Henderson Richard E. L.
Killos Paul J.
Reyes Hector M
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