FR2799459A1 - Perfluoroalkane sulfonylation method for use in synthesis of perhalogenated sulfanilide, comprises contacting nucleophile with reagent comprising sulfonyl halide, organic base and optional solvent - Google Patents

Abstract

The method comprises contacting nucleophile (preferably with N as nucleophile atom) with reagent comprising, by successive or simultaneous addition, heavy sulfonyl halide (preferably sulfonyl chloride) and organic base comprising metalloid atom M having resonance with a pi bond binding two atoms (preferably imine bond) of which at least one is the atom of element of group VB of Periodic System. The organic part of sulfonyl halide is perhalogenated, preferably perfluorinated, at the C atom bound to S. The acid associated with nucleophile has pKa up to 7, preferably 5. The N atom of nucleophile is bound to electro-attracting group, preferably selected from electron-poor aryl and sulfonyl groups. The metalloid atom M is preferably trivalent atom of group VB, especially tri-substituted N atom. Contacting nucleophile with reagent is preferably conducted in organic solvent, preferably of weakly polar type, and especially miscible with water (at most 10 wt. %, preferably at most 2 wt. %). An Independent claim is also included for the reagent used in method as claimed, which in addition to successively or simultaneously added components as described above, also contains solvent, or mixture of solvents of weak polarity, weak solubility in water and preferably containing no chlorinated aliphatic chain.

Description

 PROCESS <B> AND </ B> REACTIVE <B> USEFUL FOR THE <B> SYNTHESIS <B> OF </ B> PERHALOGEN SULFANILIDE <B> ON THE CARBON DOOR </ B> <B> BY THE ATOM OF The present invention relates to a process for the sulfonylation of various nucleophiles, in particular nitrogenous nucleophiles. It relates more particularly to the sulfonylation of amines and more particularly anilines lato sensu, that is to say the amines linked to an aromatic ring.

The reaction is also directed to a perhalosulfonylation reagent. Thus, the present invention relates more particularly to a sulfonylation reaction of an amine carrying an electron-withdrawing radical, especially when its amine functions are rendered soft, for example by the presence of an aryl radical (the amine then entering the subcategory of anilines). The present invention also relates to the perhalosulfonylation of the very particular amine that is ammonia, to lead to either amide or imide.

The synthesis of these sulfonamide derivatives is often difficult, especially when starting from sulfonyl halide. Most often, the direct reactions are failures and this in particular with sulfonyl chlorides, especially when the organic part of the sulfonyls is highly electro-attracting, especially in the case where the sulfur-bearing atom of the sulphonyl function is perhalogenous. and more particularly when it is perfluorinated. The explanation for these failures seems to be related to the oxidative nature of the sulfonyl halides, especially trifluoromethanesulfonyl which, like sulphuryl chloride, is an effective oxidant.

Therefore, one of the aims of the present invention is to provide a process which makes it possible to obtain sulfonamides of the above type by using sulfonyl halides, in particular when these halides are heavy halides (i.e. halides corresponding to a halogen of atomic number at least equal to that of chlorine).

It is preferred to use sulfonyl chlorides for economic as well as technical reasons. The technique has also been transposed for the synthesis of perfluorosulfonimides.

These and other objects which will appear later are achieved by a process of sulfonylation comprising a step of contacting a nucleophile whose nucleophilic atom is a nitrogen, with a reagent comprising for successive or simultaneous addition - a halide heavy (that is to say a halogenide whose atomic number is at least equal to that of chlorine), sulfonyl, preferably sulfonyl chloride and - an organic base comprising a trivalent atom of column V (column of the nitrogen in the Mendeleyev table) atom whose doublet is conjugated directly or indirectly to a bond connecting two atoms, at least one of which is an atom of column V, and - in that the organic part of said sulphonyl is perhalogenated, advantageously perfluorinated on carbon carried by sulfur.

The present invention is particularly advantageous for nucleophiles whose associated acid has a pKa at most equal to about 7, advantageously to 6, preferably to 5, more preferably to 4. It is also of interest for oxidizable nucleophiles and more generally when it is desired to use an oxidizable reagent.

Indeed, these nucleophiles are in general particularly difficult to sulfonylate. In particular, the invention is of interest for nucleophiles whose nitrogen is connected to an electro-attractor group.

This electron-withdrawing group may especially be chosen from aryls, advantageously depleted in electrons and sulphonyls.

Said organic base comprising a trivalent atom of the V column whose doublet is conjugated to a bond may be used either as a base or as a catalyst for the reaction.

Indeed, the sulfonylation reaction gives off a hydrohalic acid that salifies the nucleophile and makes the nucleophile more or less inert. It is therefore desirable to add bases (in quantity and in kind) which will make it possible to release the nucleophile of the various acids present in the reaction medium so that it fully plays its role of nucleophile.

Said organic base having a trivalent atom of the V-conjugated column is such that said trivalent atom of the V-column is a trisubstituted atom and forms a tertiary base.

According to a particularly advantageous embodiment of the present invention, said bond connecting two atoms is the bond of an imine function.

It is preferable that this imine function be arranged in such a way that the nitrogens are as far as possible, in other words, that the nitrogen of the imine function is that of the two atoms connected by the bond which is furthest from the trivalent atom of column V. What has just been said about the imine function is general for all the atoms of the column V connected by the bond, in the case where the bond comprises a carbon atom and a atom of column V.

According to the present invention, it is preferred that the organic base comprising a trivalent atom of column V whose doublet is conjugated to a bond has a chain or a backbone, of formula> N- [C = C] n C = N- with n equal to zero or an integer selected from the closed range (i.e. including the boundaries) 1 to 4, preferably from 1 to 3, preferably from 1 to 2. Preferably the preceding sequence responds to the formula> N- [C (R1) = C (R2)] nC (R3) = N- where n is zero or an integer selected in the closed range (i.e., including the boundaries) 1 to 4, preferably 1 to 3, preferably 1 to 2 and wherein RI, R2 and R3 similar or different, are selected from hydrocarbon derivatives, preferably alkyl of at most 4 carbon atoms and hydrogen. Advantageously, according to the method, said trivalent atom of column V forms or constitutes a tertiary amine.

More specifically, it is desirable that said organic base comprising a trivalent atom of the V column whose doublet is conjugated to a bond constitutes a molecule of the following formula (R5) (R4) N- [C (R1) = C (R2) nC = N-R6 with n equal to zero or an integer selected from the closed range (i.e. including the boundaries) 1 to 4, preferably 1 to 3, preferably 1 to 2 and where R 1, R 2 and R 6, which are similar or different, are chosen from hydrocarbon groups, advantageously alkyl groups of at most 4 carbon atoms, and hydrogen, and where R 4 and R 5, which are identical or different, are chosen from hydrocarbon groups, advantageously alkyl groups. at most 4 carbon atoms, one or two of the substituents R1, R2, R3, R4, R5 and R6 may be connected to other substituent (s) remaining to form one or more rings.

The catalytic effect observed is particularly marked when said bond connecting two atoms is intracyclic, especially when it is intracyclic in an aromatic ring. This is particularly the case for pyridine rings and rings derived therefrom such as quinoline or isoquinoline.

The organic base comprising a trivalent atom of the V column whose doublet is conjugated to a bond may advantageously be dialkylaminopyridines, in particular in the para or ortho position (that is to say in position 2 or 4 of the pyridine); the DBU also gives an interesting result.

Although the present invention can be used to form customary sulfonimides, this reaction is particularly advantageous in the case of the formation of an amide or imide function from a nucleophilic substrate, especially aniline, and more particularly when this aniline is linked to an aromatic ring depleted in electrons.

This depletion can be correlated with the introduction of a heteroatom into the ring (in the case of 6-membered rings) or by the presence of substituents on the nucleus carrying the aniline sulphonyler function of substituent (s) generally electro-attractor (s).

In the case of an electronic depletion of a 6-membered ring by the introduction of a heteroatom, it should be pointed out that the or, more precisely, the substrates can be autocatalytic, that is to say that they may not require the presence of an amine according to the present invention.

With regard to the depletion by the substituents, it may be given by way of indication that the invention is particularly well suited for the treatment of arylamines in which the substituents, outside the nucleophilic function to be sulfonylated, of the nucleus carrying nucleophile are such that the sum of their Hammett constants p is at least 0.14, preferably 0.20, preferably 0.30.

When this sum of Hammett constants reaches values greater than 1, the reaction becomes particularly lazy, so it is preferable that the sum of the Hammett constants of the amine functional ring is at most 1, preferably at most equal to 0.9, more preferably at most equal to 0.7.

When the organic base comprising a trivalent atom of column V whose doublet is conjugated, directly or indirectly, to a bond is used as a catalyst (that is to say, it is used in sub-stoichiometric amount, more generally in an amount of between 1% and 1% of the QS [stoichiometric amount], advantageously between 1100 and 1110 of QS), it is then necessary to provide another base so that the reaction with respect to the nucleophilic substrate is the most complete possible.

In this case, the reagent used further comprises, for successive or simultaneous addition, an organic base that is preferably non-alkylatable. In particular, the non-alkylatable organic base may be hindered dialkylphosphines, trialkylphosphines, phosphonium hydroxides, hindered dialkylamines, trialkylamines or ammonium hydroxides. The concept of congestion of dialkylphosphines or dialkylamines congested so that they are not alkylatable is well known to those skilled in the art.

In a large number of cases, and especially when using solvents, it is preferable that said non-alkylatable base is liposoluble and has at least one significant benzene solubility (symbol "s" in the "Handbook of Chemistry and Physics" ), advantageously high (symbol "v" in the "Handbook of Chemistry and Physics") high.

As has been seen previously, it is most often desirable to carry out the contacting in an organic solvent. This solvent is advantageously little polar and, preferably, poorly miscible with water. More particularly, it is desirable that at most 10% by weight, advantageously at most 5%, preferably at most 2% by weight, be miscible with water.

The amounts of base to be added, the amount of non-alkylatable base involved during the reaction is advantageously at least equal to the amount necessary to neutralize the hydrohalic acid released.

In other words, the amount of base must be sufficient to ensure that the nucleophile is always present in the free state (i.e., as a true nucleophile) throughout the reaction.

The techniques targeted by the present invention are particularly well suited to sulphonylation by perfluorinated alkylsulfonyl chlorides, in particular perfluorinated on carbon carried by sulfur.

The most usable chloride is triflyl chloride (CF3SO2Cl). More generally, the organic part of the sulfonyl chloride corresponds to the formula (Rf).

By Rf is meant a radical of formula GEA - (CX2) p - where X, which are similar or different, represent a chlorine, a fluorine or a radical of formula CnF2n + 1 with n being at most equal to 5, preferably greater than 2, with the proviso that at least one of the X is fluorine; where p represents an integer at most equal to 2; where GEA represents an electron-withdrawing group whose possible functions are inert under the reaction conditions, advantageously fluorine or a perfluorinated residue of formula CnF2n + 1 with n being at most equal to 8, advantageously to 5.

The total carbon number of Rf is advantageously between 1 and 15, preferably between 1 and 10 ore.

The present invention also provides a reagent useful for the implementation of the method according to the invention. This reagent comprises for successive or simultaneous addition # a heavy halide (that is to say whose atomic number is at least equal to that of chlorine), sulfonyl advantageously sulfonyl chloride and # an organic base comprising a trivalent atom of column V (column of nitrogen) whose doublet is conjugated directly or indirectly to a bond n connecting two atoms of which at least one is an atom of column V; the organic part of said sulphonyl being perhalogenated, advantageously perfluorinated, on the carbon carried by the sulfur.

The reagent according to the present invention may further comprise, also for successive or simultaneous addition, a solvent. This solvent, including the solvent mixture, is advantageously slightly polar and selected from those having a low solubility in water. In some cases, the chlorinated aliphatic chains are unsatisfactory.

As touchstone of the polarity, it can be specified that said low polar solvent is chosen from those, or mixtures thereof, whose polarity (Etf expressed in kcallmol) is at most equal to 40, (advantageously with two significant digits) .

These low polar solvents are usually chosen from oxygenated organic compounds, in particular ethers, esters, or even ketones, hydrocarbons, including petroleum fractions, aromatic hydrocarbons halogenated on the medium. The latter are particularly interesting, especially substituted benzenes and halogenated hydrocarbons on the nucleus.

Which has just been described above is particularly suitable for anilines, especially those in which said nitrogen atom is connected to a 6-membered aromatic, preferably homocyclic, preferably benzene non-condensed, are advantageously depleted in electrons as has already been specified above. Overall, given the possible substituents particularly well suited to amines connected to an aryl whose electron richness is at most equal to a parachlorophenyl (richness assessed using Hammett's sigma p constants).

Among the most commonly used electron-attracting groups, mention may be made of halogens (chlorine and fluorine), esters (of the CO-OR type), ketones, amides which are not likely to interfere with sulphonylation, and perhalogenated alkyls on the carbon bonded directly to the nucleus, including perfluorinated alkyls on the atom close to the nucleus, nitriles, groups with a sulfone function or phosphone directly linked to the nucleus.

The technique is mainly aimed at the sulfonylation of anilines lato sensu (that is to say amines carried by an aryl), but this teaching has also been transposed to the sulfonamidation of ammonia (-que) and the sulfimidation of the sulfonamides. In this case, the latter are advantageously, in the form of an organic base salt, non-alkylatable (it is the base which is non-alkylatable).

Under these conditions, the nitrogen carries a hydrogen or more preferably a negative charge (anion), whereas in the case of the anilines which was referred to above, the aniline function comprises at least one hydrogen, preferably two, for reasons of steric hindrance.

The use of said organic base comprising a trivalent atom of the V column whose doublet is conjugated to a n-bond makes it possible to perform, with a good yield, the double sulfonylation of the nucleophiles which are twice substitutable (such as ammonia and primary amines). ). The preferred operating conditions are those described in the international patent application published by WIPO under WO98152886, using at least partially as base said organic base having a trivalent atom of column V whose doublet is conjugated to a bond 7c. .

For reasons of occupational hygiene, aliphatic chlorinated derivatives are in general to be avoided, although they constitute a family of solvent giving good results, although it is not the most efficient family, because their solubility, and in particular that of methylene chloride, is of the order of 2% by volume, ie 2.6% by weight.

As far as solvents are concerned, solvents with a reducing character should be avoided as far as possible.

The reaction can be carried out from -20 ° C. to about 200 ° C., more generally from 0 ° to about 100 ° C.

It is easier to work at ambient temperature and pressure but one can also be under different, higher pressures. It can also work in a closed chamber (such as autoclave or sealed tube) and under autogenous pressure.

The following nonlimiting examples illustrate the invention. <U> EXAMPLES </ U> <U> Preparation of </ U> acetamido-5-dimethyl-2,4-trifluoromethanesulfonanilide <I> - <U> Reaction in the presence of </ U> </ I> catalyst In a reactor 350 g of dichloromethane, 50.1 g of amino-5-dimethyl-2,4-acetanilide and 6.9 g of dimethylamino-4-pyridine are successively charged. The suspension obtained is then stirred and cooled to 10 ° C. 57.4 g of triethylamine are then added for 15 minutes at <B> 1 </ B> 0 ° C. A solution of 56.8 g of trifluoromethanesulfonyl chloride in 59 g of dichloromethane is then poured in 2 hours while maintaining the temperature of the medium at 10 ° C.

The medium is then stirred for 2 hours at 10 ° C., then the temperature is allowed to rise to 20 ° C. and stirring is continued for 2 hours.

The medium is acidified in the reactor by adding 265 g of a 4.2% aqueous solution of HCl.

The precipitate formed is then filtered and rinsed (3 times) with deionized water and then with dichloromethane. It is then dried at 95 ° C. under reduced pressure.

67 g of a beige solid are thus obtained, ie an isolated yield of 77%. Characteristic of the compound: Fusion = 180 C.

<I> - <U> Reaction in the absence of catalyst </ U> </ I> The above conditions are repeated but in the absence of 4-dimethylaminopyridine.

Analysis of the reaction medium shows a 90% degradation of trifluoromethanesulfonyl chloride.

Expected product yield well below 10%.

<U> Preparation of </ U> methyl chloro-5- (N-trifluoromethylsulfonyl) amino-2 <U> benzoate </ U> <I> - <U> Reaction </ U> </ I> <U> in the presence of <I> catalyst </ I> </ U> In a reactor, 17 g of methyl chloro-5-anthranilate, 120 g of dichloromethane, 2.26 g of 4-dimethylaminopyridine and then 18.5 g are successively charged. g of trifluoromethanesulfonyl chloride. The solution is stirred at 15 ° C. and a solution of 18.7 g of triethylamine in 19 g of dichloromethane is poured over 3 h. After addition, the mixture is stirred for 3 h at 15 ° C. and then for 10 h at room temperature.

The medium is then washed successively with 150 g of deionized water, with 100 g of a concentrated hydrochloric acid solution and then again with 160 g of deionized water.

The solvent is removed under reduced pressure.

27.7 g of a yellowish solid are thus obtained, ie an isolated crude yield of 95%.

Characteristic of the compound: Fusion = <B> 81'C. </ B> - <U> Reaction <I> in the absence of catalyst </ I> </ U> 1l Reaction with triethylamine The previous conditions are repeated but in the absence of 4-dimethylaminopyridine.

Analysis of the reaction medium shows a total degradation of trifluoromethanesulfonyl chloride.

The expected product has not been formed.

Reaction with diisopropylethylamine In the same way, the test in the absence of catalyst and in the presence of diisopropylethylamine does not lead to the expected product.

Reaction with 1,4-diazabicyclo [2,2,2] octane or DABCO Again the expected product is not formed.

<U> Preparation of bis </ U> trifluoromethanesulfonimide <U> d </ U> trialkyl <U> ammonium </ U> - <U> Catalyzed reaction </ U> <U> Example 1 </ U> In a reactor 9.3 g of triethylamine (0.092 M), 0.56 g of 4-dimethylaminopyridine and 45 g of dichloromethane are charged. Then 1.38 g (0.092 M) of ammonia are added. The solution obtained is stirred at 0 C.

The trifluoromethanesulfonyl chloride (15.5 g, that is 0092 M) diluted in 10 ml of dichloromethane is then added in 2 hours at 0 ° C., then the reaction is continued for 3 h at room temperature.

Analysis of the reaction medium shows a trifluoromethanesulfinate impurity level of 2%.

The reaction medium is treated twice with 15 ml of a 12% aqueous HCl solution and then 3 times with 15 ml of water. The residual organic phase is concentrated under reduced pressure to give 13.65 g of triethylammonium trifluoromethanesulfonimide, which is in the form of a liquid, or an isolated yield of 80%.

The purity of the compound obtained is 98%. <U> Example 2 </ U> The procedure of Example 1 is repeated but replacing the dichloromethane with dioxane. The reaction medium is analyzed after dilution with water: the yield of bis trifluoromethanesulfonimide at the end of the reaction is 51%, with a trifluoromethanesulphinate content of 6%. <U> Catalyzed Reaction <U> Example 3 </ U> COMPARATIVE The procedure of Example 1 is repeated but without the use of 4-dimethylaminopyridine.

The bis-trifluoromethanesulfonimide yield at the end of the reaction is 47%, with a trifluoromethanesulphinate content of 21%.

<U> Comparative Example 4 </ U> The procedure 3 is repeated but using diisopropyl ethylamine as a base to replace triethylamine.

The yield of bis trifluoromethanesulfonimide at the end of the reaction is 51%, with a trifluoromethanesulphinate content of 21%.

<U> Comparative Example 5 </ U> 11.8 g of trifluoromethanesulfonyl chloride (0.07 M) are charged to the reactor and 33.9 g of triethylamine (0.0336 M) are subsequently added at 0.degree. 10 minutes.

The medium is stirred for a further 10 minutes at 0 ° C. and then 0.5 g (0.029 M) of ammonia is added. The reaction is exothermic. The medium is then heated at 65 ° C. for 4 hours.

Compounds resulting from the oxidative degradation of amines are observed. The majority product is trifluoromethanesulfinate with a level of 57%.

The presence of bis trifluoromethanesulfonimide is not demonstrated, which implies a reaction yield of less than 2%, or even zero.

Claims (32)

<B> <U> CLAIMS </ U> </ B> 1. sulfonylation process, characterized in that it comprises a step of contacting a nucleophile whose nucleophilic atom is advantageously a nitrogen with a reagent comprising for successive or simultaneous addition - a heavy halide (this is that is to say, the atomic number of which is at least equal to that of the chlorine) of sulphonyl, advantageously sulphonyl chloride and; an organic base comprising a trivalent atom of column V whose doublet is conjugated, directly or indirectly, to a bond connecting two atoms, at least one of which is an atom of column V; and in that the organic part of said sulphonyl is perhalogenated, advantageously perfluorinated, on the carbon carried by the sulfur. 2. Method according to claim 1, characterized in that the associated acid of said nucleophile has a pKa at most equal to about 7, preferably to 6, preferably to 5. 3. Method according to claims 1 and 2, characterized in that said nitrogen of said nucleophile is connected to an electro-attractor group. 4. Method according to claim 3, characterized in that said electron-withdrawing group is selected from aryl advantageously depleted electrons and sulfonyls. 5. Process according to claims 1 to 4, characterized in that said trivalent atom of column V is a trisubstituted atom. 6. Process according to claims 1 to 5, characterized in that said trivalent atom of column V is a trisubstituted nitrogen. 7. Method according to claims 1 to 6, characterized in that said bond connecting two atoms is the bond of an imine. 8. Process according to claims 1 to 7, characterized in that said organic base comprising a trivalent atom of column V (column of nitrogen) whose doublet is conjugated directly or indirectly to a bond comprises a sequence of formula> N- [C = C] nC = N- with n equal to zero or an integer selected from the closed range (i.e. including the boundaries) 1 to 4, preferably 1 to 3, preferably 1 to 2. 9. Process according to claims 1 to 7, characterized in that said organic base comprising a trivalent atom of column V (column of nitrogen) whose doublet is conjugated directly or indirectly to a bond comprises a sequence of formula> N- [C (R1) = C (R2)] nC (R3) = N- where n is equal to zero or an integer selected from the closed range (i.e. including the boundaries) 1 to 4, preferably from 1 to 3, preferably from 1 to 2 and wherein R 1, R 2 and R 3, which are identical or different, are chosen from hydrocarbon derivatives, advantageously alkyl of at most 4 carbon atoms and hydrogen. 10. Process according to claims 1 to 9, characterized in that said trivalent atom of column V is tertiary (forms a tertiary base). 11. Process according to claims 1 to 10, characterized in that said trivalent atom of column V is a tertiary amine (form a tertiary amine). 12. Process according to claims 1 to 11, characterized in that said organic base comprising a trivalent atom of column V (column of nitrogen) whose doublet is conjugated directly or indirectly to a bond comprises a sequence of formula ( R5) (R4) N- [C (R1) = C (R2) 1 ,, -C = N-R6 where n is zero or an integer selected from the closed range (i.e. terminals) 1 to 4, advantageously from 1 to 3, preferably from 1 to 2 and wherein R 1, R 2 and R 6, which are similar or different, are chosen from hydrocarbon groups, advantageously alkyl groups of at most 4 carbon atoms, and hydrogen and where R4 and R5, which are similar or different, are chosen from hydrocarbon groups, advantageously alkyl groups of at most 4 carbon atoms, one or two of the substituents R 1, R 2, R 3, R 4, R 5 and R 6, which can be connected to other substituent (s) remaining to form one or more rings. 13. The method of claims 1 to 12, characterized in that said bond connecting two atoms is intracyclic. 14. The method of claims 1 to 13, characterized in that said bond connecting two atoms is intracyclic of an aromatic ring. 15. The method of claim 14, characterized in that said cycle is a pyridine ring. 16. Process according to claims 1 to 15, characterized in that said base is chosen from para- or ortho- or di-alkylaminopyridines and DBU. 17. Process according to claims 1 to 16, characterized in that said nucleophile has a nitrogen atom as nucleophilic atom. 18. The method of claims 1 to 16, characterized in that said nucleophile is selected from ammonia and / or a sulfonimide. 19. Process according to claims 1 to 16, characterized in that said nucleophile is ammonia and in that it is perfluorosulfonated twice. 20. Process according to claims 1 to 20, characterized in that said nucleophile is an arylamine in which the substituents, outside the nucleophilic function, of the nucleophilic atom carrying ring are such that the sum of their Hammett constants p is at least equal to 0.14, advantageously to 0.20. 21. The method of claims 1 to 17, characterized in that said reagent further comprises, for successive or simultaneous addition a non-alkylatable organic base. 22. The method of claim 21, characterized in that said non-alkylatable organic base is selected from hindered dialkylphosphines, trialkylphosphines, phosphonium hydroxides, hindered dialkylamines, trialkylamines, ammonium hydroxides. 23. The method of claim 1 to 22, characterized in that said non-alkylatable base is liposoluble and has at least one solubility in significant benzene (symbol "s" in the "Handbook of Chemistry and Physics"), preferably (symbol "v" in the "Handbook of Chemistry and Physics") elevated. 24. Process according to claims 1 to 23, characterized in that said contacting is carried out in an organic solvent, advantageously slightly polar, preferably not miscible with water (at most 10% by weight, advantageously at most 5% by weight). % by weight, preferably at most 2% by weight). 25. The method of claims 1 to 24, characterized in that the amount of said non-alkylatable and liposoluble base involved during the reaction is at least equal to the amount necessary to neutralize the hydrohalic acid released. 26. Process according to claims 1 to 25, characterized in that the organic part of said sulfonyl chloride is perfluorinated on the carbon carried by the sulfur. 27. Process according to claims 1 to 26, characterized in that the organic part of said sulfonyl chloride is chosen from radicals of formula (Rf) GEA - (CX2) p- - where the same or different Xs represent a chlorine, a fluorine or a radical of formula CnF2n + 1 with n being at most equal to 5, preferably 2, with the proviso that at least one of X is fluorine; where p represents an integer at most equal to 2; where GEA represents an electron-withdrawing group whose possible functions are inert under the reaction conditions, advantageously fluorine or a perfluorinated residue of formula C, F2n + 1, with n being at most equal to 8, advantageously to 5, the total carbon number of Rf being advantageously between 1 and 15, preferably between 1 and 10. 28. A reagent useful for carrying out the process according to claims 1 to 27, characterized in that it comprises for successive or simultaneous addition # a heavy halide (that is to say whose atomic number is at least equal to that of the chlorine) sulfonyl, preferably sulfonyl chloride and # an organic base having a trivalent atom of column V (column of nitrogen) whose doublet is conjugated directly or indirectly to a bond n connecting two atoms of which at at least one is an atom of column V; and in that the organic part of said sulfonyl is perhalogenated, advantageously perfluorinated on the carbon carried by the sulfur. 29. Reagent according to claim 28, characterized in that it comprises, in addition, for successive or simultaneous addition a solvent, said solvent, including solvent mixture, being slightly polar and selected from those having low solubility in water. water, and advantageously not having a chlorinated aliphatic chain. 30. Reagent according to claim 29, characterized in that said low polar solvent is chosen from those whose polarity (Eft expressed in kcal per mol) is at most equal to 40 (advantageously two significant digits). 31. Reagent according to claims 29 and 30, characterized in that said low polar solvent is chosen from oxygenated organic compounds, (especially ethers, esters, even ketones), hydrocarbons (including petroleum fractions), aromatic hydrocarbons halogenated on the nucleus. 32. Reagent according to claims 29 to 31, characterized in that said low polar solvent is selected from substituted benzenes and halogenated hydrocarbons on the core.