FORMULATIONS FOR METAL CATALYSIS IN WATER COMPRISING A SURFACTANT AND A LIPOPHILIC COMPOUND

Abstract

A dry formulation obtained by desiccation of an emulsion comprises at least one surfactant, at least one lipophilic compound, and at least one metal catalyst. The dry formulation may be used to carry out a catalysed reaction in an aqueous medium. The dry formulation has a water content of less than (10) wt% relative to the total weight of the dry formulation, and wherein: - the at least one surfactant is selected from the group comprising dendrimers of Dendri-TAC type, oligomers of F,TACn or H,TACn type, TPGS 1000, TPGS 750 M, surfactants derived from sugars and/or amino acids, and combinations thereof; - the at least one lipophilic compound is selected from the group comprising lipids, hydrophobic complexing agents and combinations thereof; and - the metal catalyst comprises a metal selected from Groups (3) to (12) of the Periodic Table.

Claims

1. A dry formulation comprising at least one surfactant, at least one lipophilic compound and at least one metal catalyst, wherein the dry formulation has a water content of less than 10 wt%, with respect to the total weight of the dry formulation, and wherein: the at least one surfactant is selected from the group comprising dendrimers of Dendri-TAC type, oligomers of F.sub.iTAC.sub.n or H.sub.iTAC.sub.n type, TPGS 1000, TPGS 750 M, surfactants derived from sugars and/or amino acids, and combinations thereof; the at least one lipophilic compound is selected from the group comprising lipids, hydrophobic complexing agents and combinations thereof; and the at least one metal catalyst comprises a metal selected from Groups 3 to 12 of the Periodic Table.

2. The dry formulation according to claim 1, wherein the lipid is selected from the group comprising glycerol mono-, di- or triesters, or glycerol derivatives, citric acid mono-, di-, tri- or tetraesters or citric acid derivatives, fatty acids, monoesters of fatty acids, sterides, sphingolipids, glycerophospholipids, polyketides, saccharolipids, lipids derived from prenol, essential oils, fat substitutes, waxes and combinations thereof.

3. The dry formulation according to claim 1, wherein the hydrophobic complexing agent is selected from the group comprising trialkyl phosphates and dialkyl sulfides.

4. The dry formulation according to claim 1 , wherein the at least one lipophilic compound is present in a percentage by weight, with respect to the total weight of the dry formulation, of at least 50 wt%.

5. The dry formulation according to claim 1 , wherein the at least one metal catalyst originates from a source selected from the group comprising a metal-accumulating plant, a metal-accumulating fungus or a metal-accumulating alga, material resulting from the recycling of electronic waste, polluted surface or ground water comprising a predetermined concentration of metals, an ore and combinations thereof.

6. The dry formulation according to claim 1 , wherein the at least one metal catalyst comprises a metal selected from the group consisting of copper, iron and combinations thereof.

7. A method for for carrying out a catalyzed reaction in an aqueous medium, the method comprising carrying out a catalyzed reaction in an aqueous medium with the dry formulation, wherein the dry formulation is as defined in claim 1.

8. The method according to claim 7, comprising bringing together water with the dry formulation, resulting in the formation of an emulsion comprising: a discontinuous phase comprising droplets including the at least one surfactant, the at least one lipophilic compound and the at least one metal catalyst; and a continuous aqueous phase.

9. The method according to claim 8, further comprising a step of ultracentrifugation of the emulsion.

10. The method according to claim 8, wherein the droplets exhibit a mean diameter D of between 100 nm and 3000 nm.

11. The method according to claim 8 , wherein the reaction allows forming a C—C bond, a C—N bond, a C—O bond or a C—S bond.

12. A method for for carrying out a catalyzed reaction in an aqueous medium with a dry formulation obtained by drying an emulsion, wherein the dry formulation comprises at least one surfactant and at least one lipophilic compound, wherein: the at least one surfactant is selected from the group comprising dendrimers of Dendri-TAC type, oligomers of F.sub.iTAC.sub.n or H.sub.iTAC.sub.n type, TPGS 1000, TPGS 750 M, surfactants derived from sugars and/or amino acids, and combinations thereof; the at least one lipophilic compound is selected from the group comprising lipids, hydrophobic complexing agents and combinations thereof; the method comprising the following steps: bringing together water with the dry formulation, resulting in the formation of an emulsion comprising: a discontinuous phase comprising droplets including the at least one surfactant and the at least one lipophilic compound, and a continuous aqueous phase; bringing together at least one metal catalyst comprising a metal selected from Groups 3 to 12 of the Periodic Table with the dry formulation or with the emulsion formed by bringing together water with the dry formulation.

13. A process for obtaining a dry formulation according to claim 1, comprising the following steps: providing a mixture comprising water, at least one surfactant, at least one lipophilic compound and a source comprising at least one metal catalyst; emulsifying the mixture, resulting in the formation of an emulsion; wherein the emulsion comprises: a continuous aqueous phase; and a discontinuous lipid phase comprising the at least one lipophilic compound, the at least one surfactant and the at least one metal catalyst extracted from the source during the emulsifying; and drying the emulsion; wherein: the at least one surfactant is selected from the group comprising dendrimers of Dendri-TAC type, oligomers of F.sub.iTAC.sub.n or H.sub.iTAC.sub.n type, TPGS 1000, TPGS 750 M, surfactants derived from sugars and/or amino acids, and combinations thereof; the at least one lipophilic compound is selected from the group comprising lipids, hydrophobic complexing agents and combinations thereof; and the at least one metal catalyst comprises a metal selected from Groups 3 to 12 of the Periodic Table.

14. The process according to claim 13, wherein drying the emulsion consists of freeze-drying the emulsion.

15. A method for carrying out a catalyzed reaction, the method comprising carrying out a catalyzed reaction in an aqueous medium with the dry formulation obtained by the process according to claim 13.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0062] [FIG. 1] represents a diagram illustrating an embodiment of the dry formulation according to the first aspect of the present description, used to carry out a catalyzed reaction in an aqueous medium, and obtained in this embodiment by a process comprising the sonication of a mixture and the lyophilization of an emulsion.

DETAILED DESCRIPTION

[0063] In the following detailed description of the embodiments of the present description, numerous specific details are set out in order to provide a more thorough understanding of the present description. However, it will be apparent to a person skilled in the art that the present description can be implemented without these specific details. In other cases, well-known features have not been described in detail to avoid needlessly complicating the description.

[0064] The present description provides non-limiting embodiments of dry formulations and of uses of dry formulations for carrying out catalyzed reactions in an aqueous medium.

I. Examples of Use of a Dry Formulation for Carrying Out a Catalyzed Reaction in An Aqueous Medium

[0065] Examples 1-3 below relate to embodiments of the use of a dry formulation for carrying out a catalyzed reaction in an aqueous medium according to the third aspect of the present description. In examples 1-3, the dry formulation obtained by drying an emulsion comprises a surfactant and a lipophilic compound.

[0066] The use of the dry formulation includes the following steps: [0067] bringing together water with the dry formulation, resulting in the formation of an emulsion comprising a discontinuous phase, comprising droplets including the at least one surfactant and the at least one lipophilic compound, and a continuous aqueous phase; [0068] bringing together at least one metal catalyst with the dry formulation or with the emulsion formed by bringing together water with the dry formulation.

I.a. Process for Obtaining the Dry Formulation of Examples 1-3

[0069] The process for obtaining the dry formulations used in examples 1-3 is described in detail below. The process comprises the provision of a mixture comprising water (4 ml), a surfactant dissolved in the water (H12TAC7, 100 mg) and a lipophilic compound (tributyl O-acetylcitrate, 0.2 ml). The mixture is subsequently subjected to the action of ultrasound by immersing therein an ultrasound probe (Bioblock Scientific, Vibracell 7504). The ultrasound probe (Ø= 13 mm) is placed in the centrifuge tube in an ice bath for 16.75 minutes (in pulsed mode, corresponding to 2 minutes of sonication in total). The duty cycle applied is 11.94% and the sonication intensity is 60% (450 W). After having withdrawn the ultrasound probe from the emulsion, the emulsion is centrifuged (5 min at 17 000 G, followed by 5 min at 26 000 G) in example 1 or is not centrifuged in examples 2 and 3. The emulsion or the supernatant resulting from the centrifugation are aliquoted in fractions of 500 .Math.l. These aliquots are subsequently placed in the freezer for 12 h and then lyophilized for 24 h. The dry formulation is provided in the form of a powder obtained by lyophilization of a nanoemulsion. After addition of a volume of water equivalent to the volume of the starting aliquot (500 .Math.l), the rehydrated emulsion contains a discontinuous phase composed of droplets with a mean diameter D equal to 239 ± 6 nm (PI = 0.249) for the case of example 1 (emulsion having undergone a centrifugation step before lyophilization) and with a mean diameter D equal to 741 ± 29 nm (PI = 0.236) and 790 ± 32 nm (PI = 0.223) for the case of examples 2 and 3 respectively (not having undergone centrifugation before lyophilization).

I.b. Use of the Dry Formulation in Catalysis in Examples 1-3

[0070] The dry formulation (10 to 12 mg) indicated in part I.a. is subsequently rehydrated by addition of 0.5 ml of water, resulting in the formation of an emulsion.

[0071] Three catalyzed reactions in an aqueous medium are presented below. The first two are Buchwald-Hartwig cross-coupling reactions (examples 1 and 2) and the third is an Ullmann cross-coupling (example 3).

Example 1

[0072] Bromotoluene 1 (61 .Math.l, 1 eq) is added to the emulsion formed by the addition of water to the dry formulation. The base tBuONa (74.3 mg), the metal catalyst with palladium in solid form (Pd(Cinnamyl)Cl).sub.2 (2.8 mg) and the phosphorus ligand tBuXPhos (9.3 mg), then the amide 4—MeO—Ph—C(O)NH.sub.2 (90.7 mg), are added to the emulsion. The medium is then brought to 50° C. and stirred (1200 rev/min) for 16 h. The yield of the reaction in coupling product 2 was established at 99% (119.4 mg) by HPLC (caffeine was used as external standard).

##STR00001##

[0073] In comparison, the same reaction involving micelles of TPGS-750-M (10 mg/0.5 ml of water), a commercial surfactant described in the literature for micellar catalysis, gives a yield of 92%. Similarly, the micellar catalysis of the same reaction involving this time the surfactants H12TAC6 or H12TAC9 (under conventional micellar catalysis conditions, i.e. without lipophilic compound) gives in both cases a yield of 84%.

Example 2

[0074] The reagents of the reaction, i.e. the pyridazine 3 (95 mg, 1 eq) and the amine Ph-(CH.sub.2).sub.3-NH.sub.2 (85 .Math.l, 1.2 eq) are added to the emulsion formed by the addition of water to the dry formulation. A metal catalyst with palladium in solid form ((Pd(Cinnamyl)Cl).sub.2, 2.8 mg), a phosphorus ligand (tBuXPhos, 9.3 mg) and the base tBuONa (72.1 mg) are subsequently added to the emulsion. The medium is then brought to 50° C. and stirred (1200 rev/min) for 16 h. The yield of the reaction was established at 76% (110.6 mg) by HPLC (caffeine was used as external standard).

##STR00002##

[0075] In comparison, the same reaction involving micelles of TPGS-750-M (10 mg/0.5 ml of water), a commercial surfactant described in the literature for micellar catalysis, gives a yield of only 15%, which reflects the marked improvement in catalysis conferred by the dry formulation. In addition, the replacement of the dry formulation by an equivalent amount of lipophilic compound (tributyl O-acetylcitrate, 10 mg/0.5 ml of water) results in the formation of the product 4 with a very low yield of 8%.

Example 3

[0076] The pyrazinamide 5 (184 mg, 3 eq) and the iodotoluene 6 (64 .Math.l, 1 eq) are added to the emulsion formed by the addition of water to the dry formulation. A metal catalyst with copper in solid form (CuBr.sub.2, 11.2 mg), a diamine ligand L2 (7.1 mg), an additive (D-glucose, 9.0 mg) and a base tBuONa are added to the emulsion. The medium is then brought to 50° C. and stirred (1200 rev/min) for 20 h. Purification is carried out by column chromatography on silica gel with the following eluent: n-heptane/ethyl acetate (7/3 to 5/5). After evaporation, the coupling product is recovered in the form of a white solid (43 mg, 40%).

##STR00003##

[0077] In comparison, the same reaction involving micelles of TPGS-750-M (10 mg/0.5 ml of water), a commercial surfactant described in the literature for micellar catalysis, gives a comparable yield of 41%.

II. Illustration of a Process for the Formation of Dryformulations According to The Present Description and of Their Use in the Context of Catalysis in an Aqueous Medium

II. A. Illustration of the Preparation of a Dry Formulation and of Its Use in Catalysis

[0078] FIG. 1 illustrates an embodiment of a dry formulation according to the first aspect of the present description, referenced 400 in the figure, obtained by drying an emulsion. The dry formulation 400 comprises a surfactant, a lipophilic compound and a metal catalyst. The dry formulation 400 is obtained by a process comprising the provision of a mixture contained in a container 5 and comprising water 1, a surfactant 3, a lipophilic compound 4 and a source 2, i.e., in this example, a piece of a metal-hyperaccumulating plant comprising a metal catalyst 21. The process additionally comprises emulsifying the mixture, carried out by sonication in this case, through an ultrasonic rod 6, capable of emitting ultrasonic waves 7. The sonication of the mixture results in the formation of an emulsion comprising a continuous aqueous phase 10 and a discontinuous phase comprising droplets 40 of core-shell type. As shown in FIG. 1, the droplets 40 consist of an oily core stabilized by a surfactant shell, exhibiting a certain content of metal catalyst 21. The metal catalyst 21 as represented in FIG. 1 is present exclusively at the core of the droplet. However, in other embodiments of the present description, the metal catalyst can be present solely at the shell of the droplet. In other embodiments, the metal catalyst can be found both at the core and the shell of the droplet.

[0079] The process for obtaining the dry formulation 400 further comprises a step of lyophilization of the emulsion, resulting in the formation of a dry formulation 400 which can be stored in the form of an easily transportable powder. The addition of water to this dry formulation, i.e. the rehydration, results in the formation of an emulsion exhibiting substantially the same features as before drying. However, in other embodiments of the use of the dry formulation than that illustrated by FIG. 1, the rehydration of the emulsion can result in an emulsion exhibiting different features from the emulsion before drying, e.g. in terms of mean diameter D and of polydispersity index.

II. B. Exemplary Process for Obtaining a Dry Formulation Comprising a Metal

[0080] The source comprising the at least one metal catalyst is, in this example, material resulting from the recycling of electronic waste, and is provided in the form of a micellar solution. Such a source results from the extraction of an aqueous multimetal solution prepared by the applicants - supposed to represent material resulting from the recycling of electronic waste -, followed by the back extraction of the organic phase which has been used to extract the at least one metal catalyst and which comprises, besides the at least metal catalyst, at least one organic solvent and/or at least one hydrophobic complexing agent.

1. Extraction of Pd From a Multimetal Solution

[0081] 24.9 mg of palladium nitrate dihydrate, 723.4 mg of iron nitrate nonahydrate and 732.6 mg of copper nitrate dihydrate are weighed out in a 100 ml flask. Everything is dissolved with a nitric acid solution (1 M - 2 M or 3 M). The solution is aliquoted and then quantitatively determined by ICP-AES (Inductively Coupled Plasma - Atomic Emission Spectroscopy/Spectrometer). The solution contains 2000 ppm of copper (Cu), 1000 ppm of iron (Fe) and 100 ppm of palladium (Pd).

[0082] The multimetal solution is brought into contact with an organic phase dimethyl-dibutyl-tetradecyl-1,3-malonamide (DMDBTDMA, 0.5 M/toluene) or bis(2-ethylhexyl) sulfoxide (BESO, 0.2 M/n-heptane) in a 15 ml plastic tube with a ratio of the volumes Vorganic/Vaqueous = 1/1. The mixture is stirred vigorously using an IKA-Vibrax VXR stirrer at 1200 revolutions.min.sup.-1 for 1 h. The two resulting phases (aqueous phase 1 and organic phase 1) are then separated.

2. Back Extraction of Pd From a Multimetal Solution

[0083] The organic phase 1 is brought into contact with an aqueous solution containing the surfactant H12TAC5 (2 wt%) with a ratio of the volumes Vorganic/Vaqueous = 1/1. The mixture is stirred vigorously using an IKA-Vibrax VXR stirrer at 1200 revolutions.min.sup.-1 for 1 h min. The mixture is subsequently centrifuged and the two resulting phases (aqueous micellar solution and organic phase 2) are separated.

3. Preparation of the Dry Formulation Containing Recycling Palladium

[0084] The aqueous micellar solution containing palladium (4 ml) is brought into contact with a solution of lipophilic compound, i.e. tributyl O-acetylcitrate (0.2 ml), then the mixture is subjected in an ice bath to the action of ultrasound using an ultrasound probe (Bioblock Scientific, Vibracell 7504) with a diameter of 13 mm for 16.75 min (in pulsed mode, corresponding to 2 minutes of sonication in total). The duty cycle applied is 11.94% and the sonication intensity is 60% (450 W). After having withdrawn the ultrasound probe from the emulsion, the emulsion can be directly aliquoted (500 .Math.l) or else it can be centrifuged (5 min at 17 000 G, followed by 5 min at 26 000 G). The emulsion is quantitatively determined by ICP-AES before centrifugation. Its Pd concentration, thus measured, is approximately 8 mM. The emulsion or the supernatant resulting from the centrifugation are aliquoted in fractions of 500 .Math.l. These aliquots are subsequently placed in the freezer for 12 h and then lyophilized for 24 h. The dry formulation is provided in the form of a powder obtained by lyophilization of a nanoemulsion. After addition of a volume of water equivalent to the volume of the starting aliquot (500 .Math.l), the rehydrated emulsion contains a discontinuous phase composed of droplets with a mean diameter D equal to 660 nm (PI equal to 0.26).

II.c. Use of the Dry Formulation in Catalysis in Example 4

[0085] The dry formulation indicated in part II.b. (resulting from the lyophilization of a 500 .Math.l aliquot of emulsion) is subsequently rehydrated by addition of 0.5 ml of water, resulting in the formation of an emulsion.

[0086] Example 4 below describes an example of application of the dry formulation for carrying out a catalyzed reaction in an aqueous medium, namely a Suzuki-Miyaura cross-coupling.

Example 4

[0087] The dry formulation containing the palladium is dissolved in 0.5 ml of water in a 4 ml vial. Then, 3-bromoanisole 8 (1 eq, 68.013 mg, 46.27 microliters, 0.36 mmol), triethylamine NEt.sub.3 (4 eq, 147.19 mg, 202.18 microliters, 1.45 mmol), phenylboronic acid 9 (1.5 eq, 66.507 mg, 0.55 mmol) and tri(tert-butyl)phosphonium tetrafluoroborate (0.044 eq, 4.64 mg, 0.016 mmol) are successively added. The reaction mixture is stirred at 22° C. for 18 h. The reaction mixture is then extracted twice with 3 ml of diethyl ether. The organic phases are combined and then evaporated under vacuum. The crude reaction product thus obtained is then purified by chromatography on silica gel with the eluent pentane:dichloromethane in order to obtain the expected compound 10 with a yield of 30%.

##STR00004##

III. Measurement of the Mean Diameter D of the Droplets and of the Polydispersity Index PI of the Emulsion

[0088] For each of the emulsions described above produced by addition of water to the dry formulations of examples 1-3, the mean diameter D of the droplets and the polydispersity index of the emulsion are measured by dynamic light scattering (DLS) using a Nanosizer Nano-S (Malvern Instrument). An aliquot of emulsion is diluted by 10 in milliQ® water, is placed in a 45 .Math.l quartz cell and undergoes 6 measurements of 15 seconds each. The hydrodynamic diameter or mean diameter D was obtained by averaging the results of the 6 measurements. The measurements were taken at an angle of 173° using a laser, the wavelength of which is 633 nm. The data of the DLS are calculated on an intensity basis. The polydispersity index (or PI) corresponds to the ratio of the square of the standard deviation to the square of the mean diameter D of the droplets.