LU85214A1 - PROCESS FOR THE PREPARATION OF SULFONAMIDE GROUP ARYLOXYBENZOIC ACIDS - Google Patents

Description

* * * 1 »Γ Λ 2 D is fluorine, chlorine, orome, ioce; or a group CF-j, alkylthio, aikyisulfinyle, alkylsulfonyie, haloalkyle, sulfamoyl, formyle, alkylcarûonyle, Ci ·; or dimethylamino; E is hydrogen or haloalkyl, alkoxy, alkylisulfinyl, alkylsulfonyl, Ch, CF ^; W is a trivalent nitrogen atom or a group -C (G) =; G has one of the meanings given for Z; * 3 R is a phenyl, pyridyl or thienyl group optionally substituted by one or more halogen atoms, or alkyl groups, or nitro groups; or an alkylene or alkynyl radical having 2 to 4 carbon atoms or an alkyl radical of 1 to 4 carbon atoms, optionally substituted by one or more licit fucr, chlorine, 13 bromine or iodine, preferably CF ^, or by one or more "of the following substitutes: alkoxycaronyony of 2 to 3 carbon atoms, alkylcarbonyl of 2 to 5 carbon atoms, diaikylcarbamoyl in which the aikyl groups have ae i to 4 carbon atoms, alkylthio, aikyisulfinyle, alkylsul-2ü fonyle, each having from 1 to 4 carbon atoms, alkylcarbononyxy from 2 to 5 carbon atoms, or cyano.

According to known methods, the products of formula (1) can be prepared by reaction between 25 and 140 ° C. with an intermediate acid halide of formula: = 25 ---- i ZZ cox DO - <^ 7 ^ - A (II)

S E

5Û in which X is cniore, orume or iodine, and A, Z, Z, n, £, W have the meanings uéjà indicated, with a suifcnamioe of formula: r3so2nh2 (III) 33

V

3 where has the meaning already indicated, generally in the presence of an acid acceptor, in particular a tertiary amine such as Ν, Ν-dimethylaniline or pyridina, or an alkali metal carbonate such as anhydrous potassium carbonate, or an alkali metal fluoride such as cesium fluoride.

The compounds of formula (I) can then be alkylated in a known manner, for example by reaction of a diazoalkane of 1 to 4 carbon atoms, so as to provide the corresponding products substituted on the nitrogen atom Sulfonamide group by an alkyl group of 1 to 4 carbon atoms; the hydrogen atom of this same nitrogen atom can also be replaced by the alkali metal atoms, such as sodium, for example by the action of basic alkaline agents (thus obtained salts of compounds of formula ( I).

> This known process for condensing the products of formula (II) and (III) has various drawbacks, in particular poor yields. It is believed that it is generally the presence of acid acceptor which lowers the yield by 2ü the fact that it promotes the oiacylation reaction. In addition, the use of an acid acceptor makes isolation and purification of the end products more difficult and more expensive,

Another disadvantage of the known process is that it requires an additional reaction step to obtain the acid halide of formula (II) from the acid of formula (IV) defined below.

An object of the invention is to overcome the drawbacks of the known methods. Other advantages will become apparent in the discussion which follows.

It has now been found that these aims were to be achieved in whole or in part by the process according to the invention which consists in reacting an acid with this formula:

AT

5 7 \ _JZ 00011 D ~ v} - ° - © -Λ (IV)

E

* t 10 with a sulfonyl isocyanate (or isotniocyanate) oe formula: r3so2-n = c = y (V) oans where Y is the oxygen or sulfur atom, the 1 3 symooles fi, Z, Z, ü, E, G and A "'having the meanings already indicated. This process is generally carried out in the liquid phase, preferably in the presence of a catalyst, * and at a temperature such as the compound COY (ie say carbon dioxide when Y = 0 or caronyl sulfide when Y = 5), which forms during the reaction, is eliminated progressively and in gaseous or reaction medium.

A subfamily of products of formula (I) for the preparation of which the process according to the invention is * particularly suitable and advantageous, consists

by the products in the formula of which A is the atom r 25 hyarogenic or a group NQ2 or one atom bone chlorine; Z

is a halogen atom, and more particularly chlorine; Z ^ and E are the hydrogen atom; C is the group CF-j; R3 is an alkyl group most often having 1 to * A carbon atoms, especially Ch-j; t; is -Cii =.

The preferred reagents of formula (IV) and (V) are obviously chosen in such a way that the symools appearing in their formula have a semoluble meaning to that which has just been mentioned for the products of formula (I).

Among the useful catalysts, there may be mentioned, without implying any limitation: - tertiary amines such as triethyldmine, pyrioine, oine, Ν-dimethylaniüne, 1,4-diazabicyclo 5 (2,2,2) octane, or - tin derivatives, and in particular the alkoxy tin salts such as dibutyltin oiacetate, this dibutyltin oilaurate.

* The molar ratio of (IV) and (V) is generally between 0.8 and 1.2, preferably between 0.9 and 1.1; most often, these reagents are in stoichiometric proportions.

The molar ratio of catalyst to the bone formula (Iv) generally varies between G, Qui and 15 u, i, preferably between u, u and 0.05.

The reactants are preferably dissolved in an inert aprotic organic solvent having a boiling point greater than or equal to the reaction temperature, for example a liquid hydrocarbon, aliphatic or aromatic, chlorinated or not, such as benzene, toluene , xylenes, xylene mixtures, 1,2-dichloroetane, chlorobenzene, or an ether, or a nitrile; it is also possible to use a mixture of several solvents. The use of an inert solvent has the practical advantage of allowing better heat transfer in an industrial scale process; it also makes it possible to avoid local overheating or reaction medium.

As mentioned above, the temperature at which the process according to the invention is carried out is

Advantageously such as the compound of formula COY

(carbon dioxide or carbonyl sulfide) formed during the reaction is eliminated from the reaction medium in gaseous form as it is generated. This temperature is moreover lower than the decomposition temperature of the products of formula (IV), (V) and (I) involved in the process. It is advantageously lower

V

6 or brightens the boiling point of the solvent and therefore generally remains between 6G and 180 ° C, preferably between 70 and 15G ° C.

At the end of the reaction, the product of formula (I) can be isolated by any means known per se.

The process according to the invention is distinguished by the simplicity of the process for recovering the final product because it is generally insoluble in the hot reaction medium and is separated therefrom by crystallizing in a 1 pure form, so that this recovery is essentially annealed for filtration. This filtration can also be facilitated by aodition c "a non-solvent.

The following examples, given without implied limitation, illustrate the invention and show how it can be implemented. The angiosaxonne nomenclature v was used to designate the products by placing the figures indicating the position of the substituents before (and not after) the name of these substituents.

Example 1 2ü 5 g (0.0138 mole) acacia 5- [2 '-chloro-4' - (trifiuo-romethyl) phenoxy] -2-nitrobenzoic acid are suspended in 1 cm of toluene. A stirrer is then added at room temperature 1.9 g (G, 0158 mole) of methanesulfonyl isotiocyanate and G, 04 g (G, 0004 mole) of triethylamine. The reaction mixture is stirred for 10 minutes at boiling under reflux. Caroonyl sulfide degaije from the reaction medium as it is formed. After adding 20 cm of toluene, the precipitate formed is filtered, washed with toluene and then with aichioromethane.

5 c (0.0114 mole; yield 53 / „) of a solid olanc consisting of 5- [2'-cnloro-4 '- (trifluoro-methyl) phenoxy] -z-nitro-N-methanesulfonyloenzamide are thus obtained melting at 218 ° C. The structure of this product is confirmed by infrared and nuclear magnetic resonance.

7

V

Example?

By replacing in the process of Example 1 the 3 of methanesulfonyl isotniccyanate by 1.7 i ae metha-nesulfonyl Isocyanate (CH ^ SC-, N = C = 0), the preceding 5 N-methanesulfonylbenzamide is obtained with a yield ae 6ô ”.

*; &

Claims (8)

21. C0-NH-S02-R. U> E ’10 in which: A is hydroyene, fluorine, chlorine, orome, iüüe, a nitro group; -N = NCF. ; Nt; a diaikylamino group; an alxyl group; trialkylamnionio; alxyl-tnio, dlkylsulfinyle, alkyisulfonyle, dialkylsulfonio, cyanosulfonyle, alkanoyloxy, alkoxy, alkoxycarbonyle substituted, nitroso, aziae, CF3, -N = N-P- (OCH-j) 2 "acyl; 4, O Z is hyarogen, fluorine, chlorine, bromine, iodine, or an alkyl, alkoxy, alkylsulfinyl, alkyl-sulfonyl, CF- ^, h02, CN group; is hydrogen or halogen or an alkyl or dialkylamino group; 9 D is fluorine, chlorine, bromine, iodine; or a group CF ^, aikylthio, alkylsulfinyle, alkylsuifonyle, - haloalkyle, sulfamoyl, forrnyie, alkylcarbonyle, CN or dimethylamino; 5. is hydrogen or haloalkyl, alkoxy, alkylsulfinyl, alkylsuifonyl, CN, CF ^; fy is a trivalent nitrogen atom or a group -C (G) =; G has one of the meanings given for Z; »J ~ 0 'R is a phenyl, pyriuyl or tnienyl group, even IC substituted by one or more halogen atoms, or alkyl groups, or nitro groups; or an alkenyl or alkynyl radical having 2 to 4 carbon atoms or an alkyl radical of 1 to 4 carbon atoms optionally substituted by one or more atoms of this fluorine, chlorine, orome or iodine, preferably CF-j, or by one or more of the following substituents: alkoxycarbonyl from 2 to 5 carbon atoms, alkylcarbonyl üe 2 to 5 carbon atoms, dial-kylcarbamoyl in which the alkyl groups have this 1 to 4 carbon atoms, alxylthio, aikylsulfinyl, alkylsul-2u fonyl, each having 1 to 4 carbon atoms, alkyl-carbonyloxyl of 2 to 5 carbon atoms, or cyano, characterized in that an acioe of the formula is reacted: Z1 Z OOOH 25 D— / HP> —O- / vfV-A (IV) E with a sulfonyl isocyanate of formula: 30 R3S02-N = C = Y (V) r in which Y is the oxygen or sulfur atom and the symbols A, Z, Z, D, E, W, R3 have the same meanings as in the formula ( 1). ♦ k lu 2. Method according to claim 1) characterized in that it operates in the liquid phase at a temperature such that the compound Cür which forms during the reactiuii is eliminated as and when and squs form · '! »<7phjp fin u-, j 1 ΐαιι r 4 "r> £ înpr · eι 5 3) Method according to one of claims 1 to 2) characterizes in that operated on presence of a catalyst · 4. Method according to levcnüiualiuii 3) ccuaulérisé <„w - the catalyst is a tertiary amine or a u'aico.l- tin salt. 10 3) Process according to one ocs claims 3 to 4) charac terized in that the molar ratio of catalyst relative to the acioe of formula (IV) is between uä00l and 0.1, oe preferably between ü, 01 and u, 03. 6. Method according to one of claims i to P) character-ized in that the molar ratio S d * aC ioe oe formula (IV) and sulfonylisocyanate of formula (V) is between 0.8 and 1, 2, preferably between 0.3 and 1.1. 7. Method according to one of claims 1 to 6) characterized in that one operates in an aprotic organic solvent 2u inert having a boiling point greater than or equal to the reaction temperature. 8. Method according to claim 7) characterized in that the solvent is a liquid, aliphatic or aromatic hydrocarbon or an ether or a nitria. 9) Process according to one of claims 1 to 8) characterized in that, in formulas (I) and (7), A is the hydrogen or chlorine aroma or an ng2 group, Z is a halogen atom,, E and G are the ri * hyurooene atom, D is CFj.-st an aikyle group, ”. had -:,. n =.