CATALYSTS FOR CHEMICAL REACTIONS IN A WATER-SURFACTANT MIXTURE

Abstract

The present invention is directed to reaction mixtures comprising a water-surfactant mixture, wherein the catalyst comprises a compound with solubilizing groups. This technology improves the solubility of the reaction components in the water-surfactant mixture and thereby, greatly increases the productivity and selectivity of the chemical reaction.

Claims

1. A reaction mixture comprising one or more reactants, a catalyst and a surfactant-water mixture, wherein the catalyst is (a) a coupling reagent comprising one or more solubilizing groups; or (b) a metal ion in complex with a ligand comprising one or more solubilizing groups; wherein the solubilizing group comprises a C.sub.5-50 alkyl group or a poly(alkylene glycol) group with 2 to 20 repeating units.

2. The reaction mixture according to claim 1, wherein the solubilizing group comprises a C.sub.5-50 alkyl group and has one or more of the following features: (i) the alkyl group is linear; (ii) the alkyl group comprises 8-15 carbon atoms, in particular 10-14 carbon atoms, especially 12 carbon atoms; (iii) it is substituted with one or more groups selected from methoxy, ethoxy, propoxy, hydroxy, amino optionally substituted with one or two of methyl, ethyl and/or propyl, in particular methoxy, ethoxy or hydroxy; (iv) it is 12-methoxydodecyl or dodecyl.

3. The reaction mixture according to claim 1, wherein the solubilizing group comprises a poly(alkylene glycol) group with 2 to 20 repeating units and has one or more of the following features: (i) the poly(alkylene glycol) group is a poly(ethylene glycol) group or poly(propylene glycol) group, in particular a poly(ethylene glycol) group; (ii) the poly(alkylene glycol) group has 3 to 8 repeating units, in particular 4 to 6 repeating units; (iii) it is substituted with one or more groups selected from methyl, ethyl, propyl, methoxy, ethoxy, propoxy, hydroxy, amino optionally substituted with one or two of methyl, ethyl and/or propyl, in particular methyl, ethyl or propyl; (iv) it is a poly(ethylene glycol) group with 4 to 6 repeating units, optionally substituted with methyl or ethyl at the terminal oxygen.

4. The reaction mixture according to claim 1, wherein the solubilizing group is attached to the remaining part of the coupling reagent or ligand via an ether, amine, ester or amide bond.

5. The reaction mixture according to claim 1, wherein the coupling reagent or ligand comprises one or two solubilizing groups.

6. The reaction mixture according to claim 1, wherein the catalyst is a coupling reagent which is a 1,3,5-triazine derivative which optionally has one or more of the following features: (i) it comprises a quaternary amine, in particular attached to the 2-position of the triazine ring, which preferably is a trimethylamino or N-methyl-N-morpholino group; (ii) it is substituted with methyl, ethyl, propyl, methoxy, ethoxy and/or propoxy at the 4- and/or the 6-position of the triazine ring; (iii) the solubilizing group is attached to the quaternary amine and/or the 4- and/or 6-position of the triazine ring

7. The reaction mixture according to claim 1, wherein the catalyst is a metal ion in complex with a ligand which is selected from the group consisting of a biphenyl compound, an N-heterocyclic carbene compound and a bipyridine compound.

8. The reaction mixture according to claim 1, wherein the metal ion of the catalyst is selected from the group con listing of copper ion, ruthenium ion, rhodium ion, palladium ion, nickel ion, zinc ion, gold ion, manganese ion, iron ion and cobalt ion.

9. The reaction mixture according to claim 1, wherein the surfactant is a non-ionic surfactant comprising a hydrophilic part and a hydrophobic part, wherein preferably the hydrophilic part of the surfactant comprises a polyethylene glycol moiety.

10. The reaction mixture according to claim 1, wherein the surfactant is selected from the group consisting of (DL--) tocopherol polyethylene glycol succinate (TPGS) such as TPGS-750-M, TPGS-1000 and TPGS-1500; Triton X-100, polyethylene glycol alkyl ether such as Brij, polyethylene glycol ester such as polyethylene glycol (15)-hydroxystearate (Solutol HS 15), Tween such as Tween 20 or Tween 80, sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), phase transfer surfactants (PTS) (e.g. sodium deoxycholate), polyoxyethanyl ubiquinol sebacate (PQS) and functionalized PQS, polyethylene glycol (PEG) and various derivatives such as C4-azo-PEG, octanoic acid and other long alkyl chain acids, and b-sitosterol methoxyethyleneglycol succinate (Nok).

11. The reaction mixture according to claim 1, wherein the concentration of the surfactant in the surfactant-water mixture is 0.5 to 5% (w/w).

12. The reaction mixture according to claim 1, wherein the reaction mixture comprising one reactant or two reactants.

13. The reaction mixture according to claim 1, further comprising an organic solvent.

14. The reaction mixture according to claim 1, wherein the reaction mixture is a homogeneous mixture.

15. The reaction mixture according to claim 1, wherein the reaction mixture is a colloidal suspension.

16. A method of performing a chemical reaction, comprising the steps of (a) providing a reaction mixture according to claim 1, and (b) allowing the chemical reaction to proceed.

17. The method according to claim 16, further comprising the step of isolating the product of the chemical reaction.

18. The method according to claim 16, wherein the reaction mixture is a homogeneous mixture throughout the entire chemical reaction.

19. The method according to claim 16, wherein the reaction mixture is a colloidal suspension throughout the entire chemical reaction.

20. A method of increasing the yield of a chemical reaction performed in a surfactant-water mixture, comprising the steps of (a) providing a reaction mixture comprising one or more reactants, a catalyst, and a surfactant-water mixture, wherein the catalyst is a coupling reagent comprising one or more solubilizing groups, or a metal ion in complex with a ligand comprising one or more solubilizing groups; wherein the solubilizing group comprises a C.sub.5-50 alkyl group or a poly(alkylene glycol) group with 2 to 20 repeating units; and (b) allowing the chemical reaction to proceed.

21. A method of decreasing the amount of side products produced in a chemical reaction performed in a surfactant-water mixture, comprising the steps of (a) providing a reaction mixture comprising one or more reactants, a catalyst, and a surfactant-water mixture, wherein the catalyst is a coupling reagent comprising one or more solubilizing groups, or a metal ion in complex with a ligand comprising one or more solubilizing groups; wherein the solubilizing group comprises a C.sub.5-50 alkyl group or a poly(alkylene glycol) group with 2 to 20 repeating units; and (b) allowing the chemical reaction to proceed.

22. The method according to claim 20, wherein the reaction mixture is a reaction mixture as defined in claim 1.

23. The method according to claim 20 or 21, comprising the method of performing a chemical reaction according to claim 16.

Description

FIGURES

[0089] FIG. 1 shows the chemoselective conversion of 4-bromobenzoic acid with 0.5 eq 3-methylphenol and 0.5 eq 3-ethylaniline using triazine 6c (A) or 6h (B) as coupling reagent in TPGS-750-M in water (2 wt %). In (A) the overall conversion (triangles) and the conversions into the amide (diamond) and the ester (circle) is shown. In (B) no conversion into the ester was observed, so that the conversion into the amide is identical to the overall conversion.

EXAMPLES

[0090] To a mixture of carboxylic acid (1 eq), NaHCO.sub.3, (1 eq), and amine (1.1 eq) in TPGS-750-M (2% in water, 10 eq V) was added triazine (1.1 eq) in solution in a water-miscible co-solvent (1 eq V). The reaction was allowed to stir at 25 C. until completion (typically 2 to 5 hours). At completion, the product was either precipitated by the addition of more water, or extracted in isopropyl acetate, and filtered through a short plug of silica to provide the desired amide product.

[0091] A variety of derivatized triazines (6b to 6h) were compared with the reference one (6a) on the following challenging model transformation:

##STR00005##

[0092] The following triazine derivatives were evaluated, giving the indicated conversion ratio:

##STR00006## ##STR00007##

[0093] The conversions were monitored as a direct indicator of the yield (no competitive side-reaction). This demonstrated that tailoring the reagent for the medium had a profound impact on its outcome.

[0094] Amidation was then performed with different amines and carboxylic acids using the coupling reagent 6c or 6h, respectively. Conversion ratios were as follows:

##STR00008## ##STR00009##

[0095] We demonstrated here that the non-participating side-chains had the most profound impact, and always showed as good or better selectivity and yield.

[0096] Another and even more spectacular feature is the selectivity that ensues. On the highly demanding reaction below, triazine 6c or 6h, respectively, was used as coupling reagent and the formation of amide and ester was monitored.

##STR00010##

[0097] The results are shown in FIG. 1. As can be seen, saw almost perfect selectivity was obtained in the case of triazine 6h (FIG. 1B). This is all the more remarkable as it is almost impossible to obtain with any other conditions. Also with triazine 6c, only a very small amount of ester was obtained (FIG. 1A).