Organic compounds -- part of the class 532-570 series – Organic compounds – Unsubstituted hydrocarbyl chain between the ring and the -c-...
Patent
1993-01-04
1994-09-13
Bond, Robert T.
Organic compounds -- part of the class 532-570 series
Organic compounds
Unsubstituted hydrocarbyl chain between the ring and the -c-...
540455, 530317, C07D49814, C07K 512, A61K 3142
Patent
active
053470010
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
BACKGROUND OF THE INVENTION
26-[(2-Dialkylaminoalkyl)sulphonyl]-pristinamycins II.sub.B of general formula: ##STR2## in which Alk represents a linear or branched alkylene radical and R represents linear or branched alkyl radicals, these radicals containing 1 to 10 carbon atoms, are products known for their antibacterial activity and their synergistic action on the antibacterial activity of pristinamycin I.sub.A, as has been described in European Patent 191,662.
The pristinamycin II.sub.B derivatives of general formula (I) may be obtained by oxidation of the corresponding sulphide, in particular according to the teaching of European Patent 191,662, which describes the oxidation of a sulphide of general formula: ##STR3## in which Alk and R are defined as above, with hydrogen peroxide in the presence of selenium dioxide. The reaction is performed in an aqueous or organic medium, in particular in an alcohol.
According to British Patent Application 2,206,577, the pristinamycin II.sub.B derivatives of general formula (I) may also be obtained by oxidation of the corresponding sulphide of general formula (II) with hydrogen peroxide in the presence of an alkali metal tungstate such as sodium tungstate, in an aqueous medium, for example acetone/water or acetonitrile/water or in a water-immiscible solvent such as a chlorinated hydrocarbon, at a temperature ranging from -5.degree. C. to room temperature.
DESCRIPTION OF THE INVENTION
It has now been found that the oxidation reaction of the sulphide of general formula (II) leads to different oxidation products according to the conditions employed. It has, in effect, been demonstrated that the sulphone of pristinamycin II.sub.B, of general formula (I), may be obtained in considerably improved yields by effecting oxidation of the sulphide of pristinamycin II.sub.B with 3.5 to 20 equivalents of hydrogen peroxide in the presence of an alkali metal tungstate such as, for example, sodium tungstate, in a two-phase medium, at a temperature of between 10.degree. and 25.degree. C.
It is necessary for the oxidizing agent to be introduced in large excess relative to the quantity of product to be oxidised and, for this purpose, for the proportion of oxidising agent/co-oxidizing agent to be maintained within certain limits. Hydrogen peroxide is employed in the proportion of 3.5 to 20 equivalents per mole of sulphide of pristinamycin II.sub.B ; the proportion of sodium tungstate generally varies from 5 to 0.5%.
The two-phase medium consists of a chlorinated solvent/water mixture such as, for example, a methylene chloride/water mixture or dichloroethane/water mixture or chloroform/water mixture.
It can also consist of a water/water-immiscible alcohol mixture such as, for example, an n-butanol/water mixture.
It is advantageous to work in a 50:50 (by volume) water/chlorinated solvent mixture, but it is also possible to vary these proportions.
The preferred catalyst is sodium tungstate, but it should be understood that the reaction may also be carried out in the presence of potassium tungstate.
The outcome of this novel implementation of the process of oxidation of 26-[(2-dialkylaminoalkyl)sulphonyl]pristinamycin II.sub.B is a very large improvement in yields as a result of the catalysis in a heterogeneous medium in the presence of predetermined relative quantities of oxidizing agent/co-oxidizing agent. According to the new process, yields of more than 70% can be achieved.
EXAMPLES
The examples which follow, given without implied limitation, illustrate the present invention.
EXAMPLE 1
A solution of 5 mg (0.0151 mmol; 1 mol%) of sodium tungstate in hydrogen peroxide (30%; 1.71 g; 15.1 mmol; 10 equivalents) is added in the course one minute at room temperature to a solution of 1 g (1.51 mmol) of 26-[(2-diethylaminoethyl)thio]-pristinamycin II.sub.B in 10 cm.sup.3 of methylene chloride and 10 cm.sup.3 of water. The reaction is slightly exothermic at the beginning. The reaction mixture is stirred for 16 hours at room temperature.
An assay of the reaction mi
REFERENCES:
patent: 4866172 (1988-09-01), Chatterjee et al.
European Search Report.
Bond Robert T.
Rhone-Poulenc Rorer S.A.
LandOfFree
Process for preparing sulphonylpristinamycin II.sub.B 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 for preparing sulphonylpristinamycin II.sub.B, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for preparing sulphonylpristinamycin II.sub.B will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1121397