ORGANOMETALLIC GELS

Abstract

This invention relates to gels encapsulating organometallic reagents, particularly organolithium reagents. The invention also relates to methods of making said gels and methods of using said gels. The gels are particularly useful in organic synthesis being easier to handle than the organometallic reagent solutions typically used.

Claims

1. A gel, the gel comprising: a solid phase comprising an inert supramolecular gelating agent; and a liquid phase comprising an inert organic solvent and an organometallic reagent.

2. A gel of claim 1, wherein the organometallic reagent is an organolithium reagent.

3. A gel of claim 2, wherein the organolithium reagent is selected from n-butyl lithium, methyl lithium and phenyl lithium.

4. A gel of claim 1, wherein the organometallic reagent is a Grignard reagent.

5. A gel according to claim 1, wherein the gelating agent is a C20-C50 alkane or a mixture of C20-C50 alkanes.

6. A gel of claim 5, wherein the gelating agent is hexatriacontane (C36H74).

7. A gel according to claim 1, wherein the organic solvent may be an organic solvent that does not comprise any X2-H groups, where X2 is a heteroatom.

8. A gel of claim 7, wherein the organic solvent is selected from hexanes, heptanes, cyclohexane, toluene, diethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran and 2-methyltetrahydrofuran.

9. A gel according to claim 1, wherein the concentration of the organometallic reagent within the liquid phase is in the range 0.25 M to 3 M.

10. A gel according to claim 1, wherein the gelating agent is present at an amount in the range from 3% wt/vol to 50% wt/vol of the gel.

11. A gel according to claim 1, wherein the gelating agent is present at an amount in the range from 10% wt/vol to 25% wt/vol of the gel.

12. A method of making a gel according to claim 1, the method comprising: mixing the gelating agent with a solution of the organometallic reagent in the organic solvent; heating the mixture; and cooling the mixture to form the gel.

13. A method of claim 12, wherein the mixture is heated to a temperature below the boiling point of the organic solvent.

14. A method of claim 12, wherein the steps of mixing, heating and cooling the mixture are conducted under an inert atmosphere.

15. A gel comprising: a solid phase comprising an inert supramolecular gelating agent; and a liquid phase comprising an inert organic solvent and an organometallic reagent, wherein the gel is obtainable by the method of claim 14.

16. A method of performing a step of an organic synthesis, the method comprising: reacting an organic species with a gel as in claim 1.

17. A method of claim 16, wherein the reaction mixture is agitated in such a way that the gel remains intact.

18. A use of a gel of claim 1 in a step of an organic synthesis.

19. A use of an inert supramolecular gelating agent to stabilise an organometallic reagent.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0065] Embodiments of the invention are further described hereinafter with reference to the accompanying drawings, in which:

[0066] FIG. 1 shows organogels formed using hexatriacontane as a gelating agent: a) T.sub.gel values of C.sub.36H.sub.74 dibutyl ether gels with various concentration of C.sub.36H.sub.74, inset shows structure of hexatriacontane gelator. b) SEM image of C.sub.36H.sub.74 hexane gel (10% wt/vol) showing lamellar self-assembly (scale bar 5 μm).

[0067] FIG. 2 shows the screening of organolithium gel stability under ambient conditions: a) Determined by .sup.1H NMR spectroscopy based on relative integrals of the CH.sub.3 group in product and starting material. b) PhLi solution (1.9 M in dibutyl ether) was placed directly into the vial and was stirred under air at room temperature before 2′-methoxyacetophenone 1 was added. c) Vial containing a gel was closed with a lid after 30 min exposure to air.

[0068] FIG. 3 shows some nucleophilic addition reactions using organolithium gels in a vial: a) Reaction with 2′-methoxyacetophenone 1. Table footnotes: a Conversion determined by .sup.1H NMR spectroscopy based on relative integrals of the CH.sub.3 group in product and starting material, b Commercial n-BuLi solution (1.6 M in hexane) was used, c Gel partly dried out, d Vial containing a gel was closed with a lid after 5 min exposure to air. b) Reaction with benzophenone 3—gel was exposed to air for 30 min, conversion in brackets was obtained after 5 min exposure of the gel to air and then closing the vial with a lid and used after 30 min, conversion determined by .sup.1H NMR spectroscopy. c) Reaction with N-benzylideneaniline 5—gel was exposed to air for 30 min prior to using, conversion determined by .sup.1H NMR spectroscopy.

[0069] FIG. 4 shows PhLi gel blocks: a) Illustrative preparation of PhLi gel block (0.95 mmol). b) Stability of PhLi gel blocks under different storage conditions and subsequent reaction with 2′-methoxyacetophenone 1. The conversion was determined by .sup.1H NMR spectroscopy based on relative integrals of the CH.sub.3 group in product and starting material. c) PhLi gel block placed in a beaker filled with water. d) PhLi gel block after 30 min in water.

[0070] FIG. 5 shows the use of organolithium gel capsules in various organic reactions: a) Addition of organolithium capsules to benzonitrile 7. Yields were determined by .sup.1H NMR spectroscopy with DMF as an internal standard. b) Synthesis of 870 mg of Orphenadrine 11 using a PhLi gel block (9.5 mmol). c) Bromine-lithium exchange performed using n-BuLi gel capsule. d) Wittig reaction using n-BuLi gel capsule. e) LDA preparation using n-BuLi gel capsule and subsequent reaction with methyl 2-phenylacetate 15. Yields were determined by .sup.1H NMR spectroscopy with DMF as an internal standard. f) α-C—H bond difunctionalization of pyrrolidine using both PhLi and n-BuLi gel capsules.

DETAILED DESCRIPTION

[0071] Throughout this specification the term inert atmosphere refers to an atmosphere free of water and oxygen. An inert atmosphere will typically be an atmosphere of dry nitrogen or dry argon. Conversely, ‘ambient’ condition means exposed to air, i.e. air that contains water vapour and oxygen.

[0072] Throughout this specification, the term ‘supramolecular gelating agent’ refers to a non-polymeric gelating agent that forms the solid phase of a gel in which the individual molecules that form the solid phase associate with one another via non-covalent intramolecular forces, e.g. hydrogen bonds, dipole-dipole interactions, and Van der Waals forces.

[0073] Throughout the description and claims of this specification, the words “comprise” and “contain” and variations of them mean “including but not limited to”, and they are not intended to (and do not) exclude other moieties, additives, components, integers or steps. Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.

[0074] Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

[0075] The reader's attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

Examples

[0076] We studied the minimum gelation concentration of C.sub.36H.sub.74 in dibutyl ether and hexane. These are the solvents most commonly used for the storage of organolithium reagents. In both cases, stable gels were obtained after a heat-cool cycle at concentrations of ca. 3% wt/vol. In addition, the T.sub.gel values of these gels were 35-55° C. depending on the concentration of the gelator (FIG. 1a). These relatively low T.sub.gel values are desirable for use as organolithium delivery vehicles as they enable easy thermal processing for this class of gels and rapid gel breakdown in the reaction solution (vide infra).

[0077] The gels exhibited lamellar platelet-type aggregates (FIG. 1b) when imaged by scanning electron microscopy. In order to prepare an organolithium-loaded gel, a simple procedure combining C.sub.36H.sub.74 gelator, organolithium reagent (from a commercial solution) and additional solvent was developed. Thus, an oven-dried vial (7 mL, 2 cm diameter, 4.2 cm height) with stirrer bar was charged with the C.sub.36H.sub.74 gelator, closed with a rubber septum and flushed with nitrogen. Anhydrous, degassed solvent (hexane or dibutyl ether, <50 ppm of H.sub.2O) was added, followed by the organolithium reagent (PhLi in dibutyl ether or n-BuLi in hexane). The vial was carefully heated under a nitrogen atmosphere until all of the gelator had dissolved, and it was then immediately placed in an ice-water bath until the organogel formed. As a result, in each case, we were able to obtain a stable gel with an incorporated organolithium reagent in a vial. Furthermore, based on titration experiments, it was evident that decomposition of the organolithium reagents during the preparation of the gel was negligible.

[0078] Encouraged by the successful formation of organolithium gels, we tested their stability and reactivity under ambient conditions. Initially, a gel incorporating PhLi (1.6 mmol, 2 equiv.) and performed a nucleophilic addition reaction with 2′-methoxyacetophenone 1 was used (FIG. 2). In all examples, the gel was exposed to the air for the specified time, after which the neat reagent was placed on the top of the gel in the vial. After rapid stirring for only 5 s, which led to the mechanical breakdown of the gel, the mixture was extracted and analysed by .sup.1H NMR spectroscopy to determine the conversion to product 2a. As shown in FIG. 2, the gel network provides the incorporated organolithium reagents with significant additional stability in ambient conditions. Exposure of the gel to air at ambient conditions for 30 min and subsequent reaction with 2′-methoxyacetophenone resulted in 92% conversion to 2a (Entry 1). In contrast, when the standard PhLi solution in dibutyl ether was placed in the vial and exposed to ambient air (in a fumehood, 22° C.) for 30 min, only traces of 2a were observed (Entry 2). Prolonging the exposure time of the gel to 2 hours did not cause any significant loss in PhLi activity (Entries 3 and 4). However, overnight exposure resulted in the partial evaporation of the solvent (dibutyl ether) and subsequent damage to the gel network together with the decomposition of PhLi (Entry 5). This drawback could be easily addressed by closing the vial with a lid to prevent evaporation. As a result, a gel that was exposed for 30 min to ambient air and then stored in a closed vial overnight still showed excellent activity: 95% conversion to 2a (Entry 6). Surprisingly, even after a much longer storage time (25 days) under these ambient conditions, the degradation of PhLi inside the gel was still negligible and a 92% conversion to 2a was obtained (Entry 7).

[0079] Using a similar approach, a C.sub.36H.sub.74 gel with incorporated n-BuLi was prepared. The stability and reactivity of this gel under ambient conditions was evaluated by reaction with 2′-methoxyacetophenone 1 (FIG. 3a). The results obtained suggest that the n-BuLi is highly stabilised within the gel and decomposition is limited since the conversion to 2b after 25 days storage under ambient conditions (77%, entry 5) was similar to the reaction using n-BuLi solution (79%, entry 1). A similar reactivity trend was observed for PhLi and n-BuLi organogels using benzophenone 3 or N-benzylideneaniline 5 (FIGS. 3b and 3c).

[0080] In the synthetic reactions described in detail above, the reagents were placed on the top of the organolithium gel which had been formed within a vial. The obtained results demonstrate that under this experimental set-up the organolithium reagent within the gel is highly stabilised. However, for general and practical use, we wanted to prepare gel ‘blocks’ loaded with a specified amount of organolithium reagent that could be directly and simply transferred to another reaction vessel (such as a round-bottomed flask) containing the other reagents. To achieve this, the original organolithium gel formation procedure was modified enabling us to prepare the gel inside a plastic syringe (FIG. 4a). Increasing the concentration of the C.sub.36H.sub.74 gelator from 2.8% wt/vol to 16% wt/vol and diluting the PhLi to 0.6 M concentration resulted in the formation of a PhLi gel block that was mechanically stable under ambient conditions and could be easily transferred. It was also possible to incorporate n-BuLi into a gel block using a similar procedure and concentration of the reagents. Other methods for the formation of gel blocks could also easily be envisaged.

[0081] With a successful laboratory-scale method for the preparation of gel blocks, we tested their stability and reactivity in a range of nucleophilic addition reactions. The organolithium gel blocks were easily added to the stirred solutions of the reagents under ambient conditions and on breaking the gel block down with stirring, the organolithium reagent was released into the solution. Using organolithium gel blocks of both PhLi and n-BuLi, reactions with 2′-methoxyacetophenone 1 (FIG. 4b), benzophenone 3 or N-benzylideneaniline 5 under ambient conditions proceeded with high conversions (77-98%) even after exposure of the gel blocks to air or prolonged storage. Storage of the gel blocks in an inert atmosphere, by leaving them in the vial closed with a plastic lid, was an effective way of maintaining the activity. After finishing these reactions, the C.sub.36H.sub.74 gelator was easily removed by filtration and simple flash silica gel chromatography, eluting first with hexane to remove C.sub.36H.sub.74, and then with 1:1 hexanedichloromethane to obtain the desired product. This was demonstrated for the reaction of PhLi with benzophenone (99% conversion to 4a, 98% isolated yield of 4a.

[0082] To further demonstrate the protective ability of the gel network, the PhLi gel block was immersed in a beaker of water for 30 min (FIG. 4c). After that time, the capsule was removed from the water, dried with a paper towel (FIG. 4d) and directly used in a reaction with 2′-methoxyacetophenone 1. The observed conversion to 2a (49%) was lower than the standard reaction. Presumably, PhLi located at the surface of the block partly decomposes upon contact with water. However, the fact that the reaction still proceeds in reasonable yield is evidence of the very high stability of the PhLi that is inside the gel block and the protective effect of encapsulation within the gel. Increasing the loading of the C.sub.36H.sub.74 gelator to 33% wt/vol and performing the same experiment led to very good conversions of 69%. Clearly, these gel blocks could potentially be further stabilised by coating them with an inert layer, to prevent decomposition at the surface, indeed we demonstrated that coating the gel blocks with paraffin led to ‘filled capsules’ that gave conversions of 84% after exposure to water. However, we reason there are significant advantages of working with gel blocks rather than filled capsules.

[0083] Importantly, unlike the ‘drilled-out’ paraffin capsule technology previously reported by Buchwald and co-workers (Sather, A. C., Lee, H. G., Colombe, J. R., Zhang, A. & Buchwald, S. L. Dosage delivery of sensitive reagents enables glove-box-free synthesis. Nature 524, 208, doi:10.1038/nature14654 (2015)), our gel blocks should have an even distribution of reagent through the gel. As a result, this should make it possible to subdivide the storage capsule to facilitate accurate dosing of the organolithium into the desired reaction. In terms of application of the technology, this is important as it demonstrates that a single large batch of gel could be produced ‘in-house’ (or by a chemical supply company), packaged and stored (and shipped) in an appropriate way, and then subdivided into the precise amounts required by the end-user and used in multiple different reactions. To demonstrate the equal distribution of reagent through the gel, a PhLi gel block was carefully cut into three equivalent pieces using a razor blade. Each of these pieces (approx. 2.1 equiv.) was used in a separate reaction with 2′-methoxyacetophenone 1 to give 2a in conversions of 96%, 97% and 98%.

[0084] The gel capsules also enable slower release of the organolithium reagent into the reaction mixture as demonstrated by ReactIR experiments. When the commercially available PhLi solution was added, the reaction was immediately complete. On the other hand, when the PhLi gel capsule was added and the mixture was carefully stirred (enabling mixing but not destroying the gel capsule), slow product formation (over 2 hours) was observed, clearly indicating slow release of the PhLi into the reaction mixture. This behaviour could be of particular interest in the reactions where slow or controlled addition of an organometallic reagent is important.

[0085] The PhLi and n-BuLi organolithium gel blocks have also been used in other, slightly more challenging reactions (FIG. 5). For example, reaction of the PhLi and n-BuLi organolithium gel blocks with benzonitrile 7 followed by hydrolysis resulted in the formation of ketones 3 and 8 in 96% and 87% yields, respectively (FIG. 5a). We also scaled-up the preparation of the PhLi gel blocks (to 9.5 mmol of PhLi encapsulated, see Example 6) and used this gel in the synthesis of 870 mg of the anticholinergic and antihistamine drug Orphenadrine 11 (FIG. 5b). The first step, the addition of PhLi via a gel block, was performed without the use of any protective inert atmosphere or low temperature, and after alkylation with 2-(N,N-dimethylamino)ethylchloride, Orphenadrine 11 was obtained in 68% yield over the two steps. To show that the organolithium gel blocks are also compatible with other types of reactions, we performed a bromine-lithium exchange reaction with 4-bromoanisole 12 using the n-BuLi gel block at −78° C. under an inert atmosphere followed by trapping the intermediate aryllithium with 4-methoxybenzaldehyde to give alcohol 13 in 99% yield (FIG. 5c). The n-BuLi gel capsule was also successfully used in a Wittig reaction resulting in product 14 formation in 98% yield (FIG. 5d). To show another possible application, we used a n-BuLi gel capsule for the in situ LDA formation and subsequent alkylation reaction of ethyl 2-phenylacetate 15. The successful formation of LDA was proved by absence of the starting material 15 in the reaction mixture after the reaction. Only mono- and di-substituted products 16a and 16b were obtained in 68% and 9% yield, respectively.

[0086] Finally, we successfully utilized both the PhLi and n-BuLi gels for a three-step, double α-C—H functionalization of pyrrolidine (FIG. 5d). In the first step, using Seidel's approach with the PhLi gel block, deprotonation of the pyrrolidine 17 by PhLi followed by hydride transfer to Ph.sub.2CO as a hydride acceptor and addition of PhLi to the in situ-generated imine, provided 2-phenylpyrrolidine 18 in 37% yield. 2-Phenylpyrrolidine 18 was then Boc-protected to give compound 19 and then lithiated using a n-BuLi gel block. Subsequent reaction with ethyl chloroformate gave α-disubstituted pyrrolidine 20 in 78% yield.

[0087] In summary sensitive organolithium reagents can be successfully incorporated within organogel delivery vehicles. The gel network provides significant stability towards ambient conditions and, as a result, these organolithium gel blocks have the potential to be used without the need for many of the special working protocols usually necessary for this type of chemistry. Our gel-phase approach has several advantages, including solvent compatibility, simple manufacture and even distribution of reagents through the gel for effective subdivision and accurate reaction dosing. The use of gels as simple delivery vehicles for hazardous organometallic reagents has the potential to make these widely-used reactions safer and more accessible, and enabling the more widespread use of these synthetic methods.

Example 1—General Procedure for the Preparation of the Organolithium Gel in a Vial

[0088] A 5 mL vial with stirrer bar was dried in the oven and let to cool under a nitrogen atmosphere. The vial was charged with 80.0 mg (0.16 mmol) of gelator C.sub.36H.sub.74, closed with a rubber septum and flushed with nitrogen via a needle for 5 min. Anhydrous and degassed solvent (2 mL of dibutyl ether in case of PhLi or 1 mL of hexane in case of n-BuLi) was added through the septum followed by the addition of organolithium reagent (0.84 mL of PhLi or 1 mL of n-BuLi). The vial (kept under nitrogen atmosphere via balloon) was carefully heated until all the gelator dissolved and then was immediately placed in iced water for 1 min until the organogel formed.

Example 2— Illustrative Method for Use of Organolithium Gel in a Vial in an Organic Reaction: Addition of 2′-Ethoxyacetophenone to PhLi

[0089] The PhLi (1.6 mmol) gel was prepared in a vial according to the general procedure of Example 1. The organolithium gel was exposed to air by removing the rubber septum. After the specified time, 2′-methoxyacetophenone 1 (0.8 mmol, 110.4 μL) was added on the top of the gel at room temperature and under air. The mixture was intensively stirred for 5 s before the reaction was quenched by the addition of water (0.5 mL). The organic compounds were extracted with dibutyl ether and dried with magnesium sulphate. Most of the gelator C.sub.36H.sub.74 was successfully removed during the filtration using glass funnel and filtration paper. The crude reaction mixture obtained after evaporation of the solvent was analysed by .sup.1H NMR to determine the conversion.

Example 3—Preparation of the Robust Organolithium Gel

[0090] A 5 mL vial with was dried in the oven and let to cool under a nitrogen atmosphere. The vial was charged with 250.0 mg (0.49 mmol) of gelator C.sub.36H.sub.74, closed with a rubber septum and flushed with nitrogen via a needle for 5 min. Anhydrous and degassed solvent (1 mL of dibutyl ether in case of PhLi or 1 mL of hexane in case of n-BuLi) was added through the septum followed by the addition of organolithium reagent (0.50 mL of PhLi or 0.6 mL of n-BuLi). The vial was carefully heated until all the gelator dissolved. The hot hydrosol was quickly transferred via needle to a 2 mL syringe (previously flushed with inert and pre-heated at the oven) and still kept under the nitrogen atmosphere. The syringe was immediately placed in iced water for 1 min until the organogel formed. The organolithium gel was kept in the syringe under the nitrogen atmosphere prior to use. In order to use the organolithium gel, the upper part of the syringe was carefully cut with scissors and gel was taken away.

Example 4—Illustrative Method for Use of Robust Organolithium Gel in an Organic Reaction: Addition of Robust n-BuLi Gel to Benzophenone

[0091] The n-BuLi (0.96 mmol) gel was prepared according to the general procedure of Example 3. After brief exposure to air (10 s), the gel was carefully placed in a 5 mL round-bottom flask containing benzophenone 3 (0.48 mmol, 0.0875 g) in 2 mL of dry hexane under ambient conditions. The mixture was intensively stirred for 5 min before the reaction was quenched by the addition of water (0.5 mL). The organic compounds were extracted with dibutyl ether and dried with magnesium sulphate. Most of the gelator C.sub.36H.sub.74 was successfully removed during the filtration using glass funnel and filtration paper. The crude reaction mixture obtained after evaporation of the solvent was analysed by .sup.1H NMR to determine the conversion. Compound 4b: 75%.

Example 5—Additional Paraffin Coating of Robust Organolithium Gel

[0092] Paraffin wax (mp. 43-95° C.) was melted in a beaker and used to prepare empty paraffin capsule using a glass rod. This capsule was filled with a phenyllithium organogel capsule (made using the general procedure of Example 3 from C.sub.36H.sub.74—166.7 mg, dry dibutyl ether-0.67 mL, phenyllithium—0.33 mL). The paraffin capsule was sealed with a heated glass rod and quickly immersed in a melted paraffin three times (Figure S43 c and d). After cooling, the gel was immersed in water for 30 min in order to test its stability (not a required step). The gel was then removed from water and carefully dried with a paper towel. Paraffin capsule with phenyllithium gel was used for the reaction with 2′-methoxyacetophenone 1 (0.317 mmol) in 5 mL of dry dibutyl ether as described before (however, using a spatula was necessary to break down the gel). The conversion was 84%.

Example 6—Scale-Up Procedure for the Preparation of Robust PhLi Gel

[0093] A 25 mL round-bottom flask that was dried in the oven and let to cool under a nitrogen atmosphere was charged with 2.5 g (4.9 mmol) of gelator C.sub.36H.sub.74, closed with a rubber septum and flushed with nitrogen via a needle for 5 min. Anhydrous and degassed dibutyl ether (10 mL) was added through the septum followed by the addition of PhLI (5 mL, 9.5 mmol). The flask was carefully heated until all the gelator dissolved. The hot hydrosol was quickly transferred via needle to 20 mL syringe (previously flushed with inert and pre-heated at the oven) and still kept under the nitrogen atmosphere. The syringe was immediately placed in iced water for 1 min until the organogel formed. The organolithium gel was kept in the syringe under the nitrogen atmosphere prior to use. In order to use the organolithium gel, the upper part of the syringe was carefully cut with scissors and gel was taken away.

Example 7—General Procedure for the Preparation of the Grignard Gel in a Vial

[0094] A 5 mL vial with stirrer bar was dried in the oven and let to cool under a nitrogen atmosphere. The vial was charged with 143 mg (0.28 mmol) of gelator C.sub.36H.sub.74, closed with a rubber septum and flushed with nitrogen via a needle for 5 min. Then, a solution of vinylmagnesium bromide (1.43 mL, 0.7 M in THF) was added through the septum. The vial (kept under nitrogen atmosphere—balloon) was carefully heated until all the gelator dissolved and then was immediately placed in iced water for 1 min until the organogel formed.

Example 8— Illustrative Method for Use of Grignard Gel in a Vial in an Organic Reaction: Addition of 2-Ethoxyacetophenone to Vinylmagnesium Bromide

[0095] The vinylmagnesium bromide (1.0 mmol) gel was prepared in a vial according to the general procedure of Example 1. The Grignard gel was exposed to air by removing the rubber septum. After the specified time, the gel was carefully put to the 10 mL round-bottom flask containing 2′-methoxyacetophenone 1 (0.5 mmol, 68.9 μL) in 3 mL of dry THF. The mixture was intensively stirred for 5 s before the reaction was quenched by the addition of water (0.5 mL). The organic compounds were extracted with diethyl ether and dried with magnesium sulphate. Most of the gelator C.sub.36H.sub.74 was successfully removed during the filtration using glass funnel and filtration paper. The crude reaction mixture obtained after evaporation of the solvent was analysed by .sup.1H NMR to determine the conversion.

[0096] When the gel was exposed to air for 3 seconds, a conversion of 99% was obtained. When the gel was exposed to air for 5 minutes, a conversion of 88% was obtained.

Example 9—General Procedure for the Preparation of the PhMgCl Gel in a Vial

[0097] A 5 mL vial with stirrer bar was dried in the oven and let to cool under a nitrogen atmosphere. The vial was charged with 100 mg (0.20 mmol) of gelator C.sub.36H.sub.74, closed with a rubber septum and flushed with nitrogen via a needle for 5 min. Then, a solution of phenylmagnesium chloride (1.5 mL, 1 M in 2-MeTHF) was added through the septum. The vial (kept under nitrogen atmosphere—balloon) was carefully heated until all the gelator dissolved and then was immediately placed in iced water for 1 min until the organogel formed.

[0098] Similarly, PhMgCl gels with different wt/vol loading of the gelating agent (10%, 8.3%, 6.7%, 5.7% and 5%) were prepared. All of them were robust enough to transfer them into another reaction vessel.