Process and reagent useful for the synthesis of sulphanilide...

Details Process and reagent useful for the synthesis of sulphanilide... Process and reagent useful for the synthesis of sulphanilide...

2001-05-15

2002-06-04

O'Sullivan, Peter (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Sulfur halides

C252S182300, C540S579000, C546S134000, C546S181000, C546S182000, C546S348000, C562S822000, C564S082000, C564S083000

Reexamination Certificate

active

06399820

ABSTRACT:

The present invention relates to a process for sulphonylating various nucleophiles, in particular nitrogenous nucleophiles. The invention relates more particularly to the sulphonylation of amines and more particularly anilines in the broad sense, i.e. amines linked to an aromatic ring.
The reaction is also directed towards a perhalosulphonylating reagent. Thus, the present invention relates more particularly to a sulphonylation reaction of an amine bearing an electron-withdrawing radical, especially when its amino functions are made soft, for example by the presence of an aryl radical (the amine then falling into the sub-category of anilines). The present invention is also directed towards the perhalosulphonylation of the very specific amine which is ammonia, to give either the amide or the imide.
The synthesis of these derivatives of sulphonamide type is often difficult, especially when the starting material used is a sulphonyl halide. Direct reactions usually fail, in particular with sulphonyl chlorides, especially when the organic part of the sulphonyls is highly electron-withdrawing, as is the case in particular when the atom bearing the sulphur of the sulphonyl function is perhalogenated, and more particularly when it is perfluorinated.
The explanation for these failures appears to be associated with the oxidizing nature of sulphonyl halides, in particular of trifluoromethanesulphonyl halides, which, like sulphuryl chloride, is an efficient oxidizing agent.
Accordingly, one of the aims of the present invention is to provide a process for obtaining sulphonamides of the above type using sulphonyl halides, in particular when these halides are heavy halides (i.e. halides corresponding to a halogen with an atomic number at least equal to that of chlorine).
It is preferred to use sulphonyl chlorides, for both economic and technical reasons. The technique has also been transposed to the synthesis of perfluorosulphonimides.
These aims and others which will become apparent hereinbelow are achieved by means of a sulphonylation process comprising a step of placing a nucleophile, whose nucleophilic atom is a nitrogen, in contact with a reagent comprising, for successive or simultaneous addition:
a heavy halide (i.e. a halide whose atomic number is at least equal to that of chlorine), of sulphonyl, advantageously sulphonyl chloride, and
an organic base comprising a trivalent atom from column V (the nitrogen column in the Mendeleev table), the lone pair of this atom being conjugated directly or indirectly to a bond linking two atoms, at least one of which is an atom from column V, and
by the fact that the organic part of the said sulphonyl is perhalogenated, advantageously perfluorinated, on the carbon borne by the sulphur.
The present invention is particularly advantageous for nucleophiles whose conjugate acid has a pKa of not more than about 7, advantageously not more than 6, preferably not more than 5, more preferably not more than 4. It is also advantageous for the oxidizable nucleophiles, and more generally when it is desired to use an oxidizable reagent.
The reason for this is that these nucleophiles are generally particularly difficult to sulphonylate. In particular, the invention is advantageous for nucleophiles whose nitrogen is linked to an electron-withdrawing group.
This electron-withdrawing group can be chosen in particular from aryls, advantageously electron-depleted aryls, and sulphonyls.
The said organic base comprising a trivalent atom from column V whose lone pair is conjugated to a bond can be used either as a base or as a catalyst for the reaction.
The reason for this is that the sulphonylation reaction releases a halohydric acid which salifies the nucleophile and makes the nucleophile more or less inert. Thus, it is desirable to add bases (in quantity and in nature) which will make it possible to release the nucleophile from the various acids present in the reaction medium such that it can act fully as a nucleophile.
The said organic base comprising a trivalent atom from column V conjugated to a bond is such that the said trivalent atom from column V is a trisubstituted atom and it forms a tertiary base.
According to one particularly advantageous embodiment of the present invention, the said bond linking two atoms is the bond of an imine function.
It is preferable for this imine function to be arranged such that the nitrogens are as far apart as possible, in other words such that the nitrogen of the imine function is that of the two atoms linked via the bond which is furthest from the trivalent atom from column V. That which has just been stated regarding the imine function is general for all the atoms from column V linked via the bond, when the bond comprises a carbon atom and an atom from column V.
According to the present invention, it is preferable for the organic base comprising a trivalent atom from column V, whose lone pair is conjugated to a bond, to have a sequence or skeleton of formula >N—(C═C)
n
—C═N— with n=0 or an integer chosen in the closed range (i.e. comprising the limits) 1 to 4, advantageously from 1 to 3, preferably from 1 to 2. Preferably, the above sequence corresponds to the formula >N—(C(R
1
)═C(R
2
))n—C(R
3
)═N— with n=0 or an integer chosen in the closed range (i.e. comprising the limits) 1 to 4, advantageously from 1 to 3, preferably from 1 to 2, and in which R
1
, R
2
and R
3
, which may be identical or different, are chosen from hydrocarbon-based derivatives, advantageously alkyl derivatives containing not more than 4 carbon atoms, and hydrogen. Advantageously, according to the process, the said trivalent atom from column V forms or constitutes a tertiary amine.
More specifically, it is desirable for the said organic base comprising a trivalent atom from column V, whose lone pair is conjugated to a bond, to constitute a molecule of the following formula (R
5
)(R
4
)N—(C(R
1
)═C(R
2
))
n
—C═N—R
6
with n=0 or an integer chosen in the closed range (i.e. comprising the limits) 1 to 4, advantageously from 1 to 3, preferably from 1 to 2, and in which R
1
, R
2
and R
6
, which may be identical or different, are chosen from hydrocarbon-based groups, advantageously alkyl groups containing not more than 4 carbon atoms, and hydrogen, and in which R
4
and R
5
, which may be identical or different, are chosen from hydrocarbon-based groups, advantageously alkyl groups containing not more than 4 carbon atoms, one or two of the substituents R
1
, R
2
, R
3
, R
4
, R
5
and R
6
being able to be linked to other substituent(s) remaining to form one or more rings.
The observed catalytic effect is particularly pronounced when the said bond linking two atoms is endocyclic, especially when it is endocyclic 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 from column V whose lone pair is conjugated to a bond can advantageously be dialkylaminopyridines in particular in the para- or ortho-position (i.e. in position 2 or 4 of the pyridine); diazobicycloundecen (DBU)also gives an advantageous result.
Although the present invention can be used to form common sulphonimides, this reaction is particularly advantageous in the case of the formation of an amide or imide function starting with a nucleophilic substrate, in particular one consisting of an aniline, and more particularly when this aniline is linked to an electron-depleted aromatic ring.
This depletion can be correlated to the introduction of a hetero atom into the ring (in the case of 6-membered rings) or to the presence, on the ring bearing the aniline function to be sulphonylated, of substituent(s) which are electron-withdrawing overall.
In the case of an electronic depletion of a 6-membered ring by means of the introduction of a hetero atom, it should be pointed out that the substrate, or more specifically the substrates, can be autocatalytic, i.e. they may not require the presence of an amine according to the prese

Affiliated with

Also associated with

Rating

Process and reagent useful for the synthesis of sulphanilide... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Process and reagent useful for the synthesis of sulphanilide..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process and reagent useful for the synthesis of sulphanilide... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2949289