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Use of a Mesoporous Material for Organic Synthesis Tomasz Witula and Krister Holmberg* Department of Materials and Surface Chemistry, Chalmers University of Technology, SE-412 96 Go¨ teborg, Sweden Received November 9, 2004. In Final Form: February 23, 2005 A common problem in synthetic organic chemistry is attaining proper contact between lipophilic organic compounds and inorganic salts. Various strategies, for example, phase transfer catalysis (Starks, C. M.; Liotta, C. L.; Halpern, M. Phase Transfer Catalysis: Fundamentals, Applications and Industrial Perspectives; Chapman & Hall: New York, 1994) or use of a microheterogeneous medium such as a microemulsion (Ha¨ger, M.; Currie, F.; Holmberg, K. Organic Reactions in Microemulsions. In Colloid Chemistry II; Antonietti, M., Ed.; Topics in Current Chemistry 227; Springer-Verlag: Heidelberg, 2003; p 53) have been worked out to tackle the issue. Here, we report that mesoporous solid materials made from surfactant self-assembly can be used as medium for such reactions. The material is made from silica, and the pore size is large, relatively uniform, and can be controlled with a high degree of precision by the choice of surfactant that is being used as template (Palmqvist, A. E. C. Curr. Opin. Colloid Interface Sci. 2003, 8, 145). The pores are hydrophilic and are filled with an aqueous solution containing the inorganic salt. The porous material is dispersed in the lipophilic organic substrate, that is, 4-tert-butylbenzyl bromide, or in a hydrocarbon solution of this substrate. The reaction occurs at the hydrophilic/lipophilic interface, and, because the interface is large, the reaction is fast. A considerable advantage with this new reaction medium is that the workup procedure is extremely facile. After the reaction is completed, the solid is simply removed by filtering or centrifugation.
Introduction There is considerable current interest in the use of micelles, microemulsions, surfactant liquid crystals, and other microheterogeneous liquids as media for organic synthesis. Such systems may give large rate enhancements as compared to reactions in conventional media, mainly due to high local concentration of the reactants in the interfacial zone where the reaction occurs.1-6 The different types of self-organized surfactant systems are particularly useful as reaction media when one of the reactants is a lipophilic organic compound, soluble in hydrophobic media but insoluble in water and other polar solvents, and the other reactant is a polar compound, such as an inorganic salt, that is insoluble in most organic solvents. These microheterogeneous, single-phase media all have both polar and nonpolar domains in which reactants of different solubility characteristics can dissolve. The high reactivity obtained is mainly due to the large interface between the domains. The incompatible reactants will meet at the interface, and it has been demonstrated that there is a good correlation between the total interfacial area of a microemulsion and the rate of a substitution reaction.7 Use of microheterogeneous media can be seen as an alternative to phase transfer catalysis, that is, use of a
two-phase system with added phase transfer agent. The two approaches can also be combined, in which case high reactivity may be obtained.8 All reactions performed in organized surfactant systems suffer from one major drawback, however, the sometimes complicated procedure to separate the surfactant from the product. The presence of the surfactant makes the workup tedious because both extractions and chromatographic separations become complicated when a surface active compound is present in high concentration. To a certain extent, the same problem exists for reactions performed using phase transfer catalysis. Removal of the phase transfer agent is sometimes a nontrivial issue. The aim of the present work is to explore the possibility of performing an organic reaction in a surfactant-free nanostructured medium. The medium is mesoporous silica made from a block copolymer self-assembly. The solid, mesoporous material can be said to be the replica of the surfactant liquid crystal, and the dimensions are roughly the same. A bimolecular substitution reaction, involving one polar and one nonpolar reactant, is performed in the mesoporous material, and the rate obtained is compared to that obtained in the liquid crystalline phase used as template.
* Corresponding author. Tel.: +46 317722969. Fax: +46 31160062. E-mail:
[email protected].
Experimental Section
(1) Starks, C. M.; Liotta, C. L.; Halpern, M. Phase Transfer Catalysis: Fundamentals, Applications and Industrial Perspectives; Chapman & Hall: New York, 1994. (2) Ha¨ger, M.; Currie, F.; Holmberg, K. Organic Reactions in Microemulsions. In Colloid Chemistry II; Antonietti, M., Ed.; Topics in Current Chemistry 227; Springer-Verlag: Heidelberg, 2003; p 53. (3) Palmqvist, A. E. C. Curr. Opin. Colloid Interface Sci. 2003, 8, 145. (4) Menger, F. M.; Erlington, A. R. J. Am. Chem. Soc. 1991, 113, 9621. (5) Schoma¨cker, R. Mikroemulsionen als Medium fu¨r chemische Reaktionen. Nachr. Chem., Tech. Lab. 1992, 40, 1344. (6) Sjo¨blom, J.; Lindberg, R.; Friberg, S. E. Adv. Colloid Interface Sci. 1996, 95, 125. (7) Bode, G.; Lade, M.; Schoma¨cker, R. Chem. Eng. Technol. 2000, 23, 405.
Reagents and Analysis Techniques. The triblock copolymer Pluronic 105, which is poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) with the composition (EO)37(PO)58(EO)37, was obtained from BASF. 4-tert-Butylbenzyl bromide (4-TBBB, purity 97%), tetraethyl orthosilicate (TEOS), CDCl3, and HCl were supplied by Aldrich. Potassium iodide (KI) was purchased from Merck. n-Butanol was purchased from Fluka. All reagents were used as received. Transmission electron microscopy (TEM) was performed on a JEOL 1200 EX II at 120 kV microscope, and specimens were prepared by crushing of the material, dispersing the powder in (8) Ha¨ger, M.; Holmberg, K. Chem.sEur. J. 2004, 10, 5460.
10.1021/la0472504 CCC: $30.25 © 2005 American Chemical Society Published on Web 04/02/2005
Use of a Mesoporous Material for Organic Synthesis ethanol, and placing a drop of the dispersion onto a Holey carbon grid followed by drying at room temperature. Small-angle X-ray scattering (SAXS) measurements were performed using a Kratky compact small angle system (HECUS MBraun, Graz, Austria) instrument equipped with a positionsensitive detector containing 1024 channels of 55 µm width. A monochromator with a nickel filter was used to select the Cu KR radiation (λ ) 1.542 Å) provided by the generator at 50 kV and 40 mA. The sample to detector distance was 282 mm. The samples were prepared in a paste holder with thin mica windows. The camera volume and the sample were held under vacuum to minimize the scatter from the air. The specific surface areas were determined by the BET method (after Brunauer, Emmett, and Teller) using an ASAP 2010 instrument (accelarated surface area porosimetry system). The pore size distributions were calculated from the N2 desorption using the BJH (after Barrett-Joyner-Halenda) method.9 Preparation of the Hexagonal Mesoporous Material. Pluronic 105 (4.0 g) was dissolved in water (30 g) and a 2 M HCl solution (120 g) under stirring at 35 °C. Tetraethyl orthosilicate (8.50 g) was added, and stirring was continued at 35 °C for 20 h. The mixture was aged at 80 °C overnight without stirring. The solid product was recovered (1.8 g), washed with water, and air-dried at room temperature. Calcination was carried out by slowly increasing the temperature from room temperature to 500 °C during 2 h followed by heating at 500 °C for 17 h. Substitution Reaction in the Hexagonal Liquid Crystalline Phase. For a Ratio 1:1 between KI and 4-TBBB: 4-tertButylbenzyl bromide (0.275 g, 1.2 mmol, 1 equiv) was added to Pluronic 105 (0.632 g) and placed in a closed bottle, which was heated to above the melting point (about 40 °C). A solution of potassium iodide (0.195 g, 1.2 mmol, 1 equiv) in water (0.535 g) was added, and the mixture was vigorously stirred for 1 min. For a Ratio 10:1 between KI and 4-TBBB: 4-tert-Butylbenzyl bromide (0.0275 g, 1.2 mmol, 1 equiv) was added to Pluronic 105 (0.632 g) and placed in a closed bottle, which was heated to above the melting point (about 40 °C). A solution of potassium iodide (0.195 g, 1.2 mmol, 1 equiv) in water (0.535 g) was added, and the mixture was vigorously stirred for 1 min. Samples of the reaction mixture were taken at different times and added to a 10-fold volume excess of CDCl3. The aqueous phase was removed, and the organic phase was dried with MgSO4. After filtration, the CDCl3 solution was analyzed by NMR. Substitution Reaction in the Hexagonal Mesoporous Material. For a 1:1 Ratio between KI and 4-TBBB: Potassium iodide (0.12 g of a 50% aqueous solution, 1 equiv) was added dropwise to the mesoporous material (0.1 g), and the slurry was left for 24 h. 4-tert-Butylbenzyl bromide (0.082 g, 1 equiv) was added, and the suspension was continuously shaken at room temperature. Samples taken at various time intervals were added to a 10-fold volume excess of CDCl3. The organic phase was separated and dried with MgSO4. After filtration, the CDCl3 solution was analyzed by NMR. To assess the mass balance of the reaction, one experiment was carried out for 80 h without collection of samples. The CDCl3 solution obtained after removing the mesoporous material by filtration was evaporated, the residue was weighed, and the ratio of starting material (4-tert-butylbenzylbromide) and product (4-tert-butylbenzyliodide) was determined by NMR; see below. For a 10:1 Ratio between KI and 4-TBBB: Potassium iodide (0.12 g of a 50% aqueous solution, 10 equiv) was added dropwise to the mesoporous material (0.1 g), and the slurry was left for 24 h. 4-tert-Butylbenzyl bromide was dissolved in hexane, an amount corresponding to 0.0082 g, 1 equiv of 4-tert-butylbenzyl bromide in 0.03 g of hexane was added, and the suspension was continuously shaken at room temperature. Samples taken at various intervals were added to a 10-fold volume excess of CDCl3. The organic phase was separated and dried with MgSO4. After filtration, the CDCl3 solution was analyzed by NMR. To assess the mass balance of the reaction, one experiment was carried out for 80 h without collection of samples. The CDCl3 solution obtained after removing the mesoporous material by filtration was evaporated, the residue was weighed, and the ratio of starting (9) Barrett, E. P.; Joyner, L. G.; Halenda, P. P. J. Am. Chem. Soc. 1951, 73, 373.
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Figure 1. Micrographs of the liquid crystalline phase obtained by a microscope equipped with a polarization filter (left), and the mesoporous material obtained by TEM (right). Both images are typical of a hexagonal geometry. material (4-tert-butylbenzylbromide) and product (4-tert-butylbenzyliodide) was determined by NMR; see below. The 4-tert-butylbenzyl bromide to 4-tert-butylbenzyl iodide ratio was analyzed by means of 1H NMR using a 400 MHz Varian spectrometer. The chemical shifts for -CH2I and -CH2Br were 4.46 and 4.50 ppm, respectively. All measurements were performed at room temperature.
Results and Discussion Mesoporous silica with hexagonal geometry was synthesized from a micellar solution of the block copolymer (EO)37(PO)58(EO)37, where EO and PO denote oxyethylene and oxypropylene, respectively. This amphiphilic polymer is known to form a hexagonal liquid crystalline phase between 48 and 66 wt % polymer in water.10 Inspection in a polarized microscope showed that the existence region of this liquid crystalline phase did not change much neither when pure water was replaced by an aqueous solution of the silica precursor (for preparation of the mesoporous solid) nor when the reactants were added to the wateramphiphilic polymer system (for reaction in the liquid crystalline phase). The silica precursor, tetraethyl orthosilicate, underwent spontaneous polymerization in the surfactant solution, forming a silica-block copolymer composite material. The polymer was removed by washing. After calcination, an entirely organics-free porous silica was obtained. The material obtained was characterized by powder X-ray diffraction, transmission electron microscopy (TEM), and determination of specific surface area and pore size. The powder diffraction measurement gave the diffraction pattern with peaks at 2Θ: 1.12, 1.94, and 2.22. Figure 1 shows that both the liquid crystalline phase and the mesoporous material exhibit hexagonal geometry. The BET surface area was found to be 809 m2/g. The pore volume was 0.93 cm3/g, and the average pore diameter was 46 Å. Figure 2 shows that the pore size distribution is narrow, indicating proper control of the synthesis. Because the pores correspond to the hydrophobic domains of the liquid crystalline phase, the pore diameter should be approximately equal to the hydrophobic segment of the block copolymer. The polyoxypropylene block of the polymer contains an average of 58 oxypropylene units. This means less than 1 Å per -O-CH(CH3)-CH2- unit. This is of course much less than the theoretical value and indicates that the polyoxypropylene chains are far from linear. Similar dimensions have been reported before for related systems.11,12 (10) Alexandridis, P.; Zhou, D.; Khan, A. Langmuir 1996, 12, 2690. (11) Flodstro¨m, K.; Alfredsson, V. Microporous Mesoporous Mater. 2003, 59, 167. (12) Flodstro¨m, K.; Alfredsson, V.; Ka¨llrot, N. J. Am. Chem. Soc. 2003, 125, 4402.
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Figure 2. Pore size distribution of the mesoporous material. Figure 4. The reaction between 4-tert-butylbenzyl bromide and potassium iodide was studied by 1H NMR, monitoring the decrease of the -CH2Br signal and the increase of the -CH2I signal.
Figure 3. Reaction profiles for reaction between 4-tertbutylbenzyl bromide and potassium iodide using a 1:1 (top) or a 1:10 (bottom) molar ratio of the reactants. The reactions were performed in a hexagonal liquid crystalline phase (LC), a microemulsion (microemulsion), a mesoporous material with hexagonal symmetry (mesoporous), and, for the reaction where a 1:10 molar ratio of reactants is used, a two-phase system.
The mesoporous material, as well as the corresponding hexagonal liquid crystalline phase, was used as media for a nucleophilic substitution reaction. Two reference systems were used: a microemulsion based on a nonionic surfactant and a surfactant-free oil-water two-phase system. The reaction profiles are shown in Figure 3. The curves for the microemulsion and the two-phase reactions are taken from previous work in our laboratory.13 The reaction studied is a typical nucleophilic substitution involving a lipophilic organic compound and an inorganic salt: reaction between 4-tert-butylbenzyl bro(13) Ha¨ger, M.; Olsson, U.; Holmberg, K. Langmuir 2004, 20, 6107.
mide (4-TBBB) and potassium iodide (KI). We have previously investigated this reaction in some detail using different types of surfactant self-assembly systems as reaction media, and we have shown that the reaction proceeds well in such microheterogeneous systems.13,14 We have also performed the reaction in a range of organic solvents with different polarity (and without surfactant), and by comparing the reaction rates obtained in the different solvents we could establish that the mechanism is that of a second-order nucleophilic substitution reaction.13 The reaction was monitored by 1H NMR, following the rise of the -CH2I signal and the decay of the -CH2Br signal, as illustrated in Figure 4. There was good correspondence between the increase of the -CH2I signal and the decrease of the -CH2Br signal, which indicates that side reactions are not important. The most likely side reaction is probably hydrolysis of 4-TBBA into the corresponding benzyl alcohol. If this reaction would occur in parallel to the formation of the benzyl iodide, the monitoring of the latter reaction would be distorted because there would then not be full equivalence in terms of NMR signal intensity between disappearance of -CH2Br and appearance of -CH2I. The peak of -CH2OH methylene protons appears somewhat more downfield than that of -CH2Br, at 4.58 ppm. No peak appeared at that frequency in either the system based on mesoporous material or the liquid crystal-based system. As can be seen from Figure 3, top, where equimolar concentrations of the reactants have been used, the rates are in the order liquid crystal . mesoporous material ) microemulsion. Using a 10:1 ratio of KI to 4-TBBB (Figure 3, bottom), the order is liquid crystal . mesoporous material > microemulsion > two-phase system. The curve for reaction in the slurry of mesoporous materials at a 10:1 molar ratio of reactants deviates considerably from an ideal curve of loss of starting material for an SN2 reaction. We believe that the deviation is due to difficulties in collecting representative samples from the reaction mixture, which is in the form of a concentrated suspension. Even if this curve cannot be used to determine the rate constant in a quantitative way, the set of curves shown in Figure 3 allows one to make the qualitative statement that the liquid crystalline phase is an extremely efficient (14) Ha¨ger, M.; Currie, F.; Holmberg, K. Colloids Surf., A 2004, 250, 163.
Use of a Mesoporous Material for Organic Synthesis
reaction medium and that the slurry of mesoporous material and the microemulsion gives approximately the same reaction rate. To provide a quantitative assessment of the extent of the reaction in the slurry of mesoporous material, the absolute amounts of the starting material, TBBB, and of the product, 4-tert-butylbenzyl iodide (4TBBI), were determined. The total recoveries of substrate + product for the reactions with 1:1 and 10:1 molar ratios of reactants were 95% and 92%, respectively. It is interesting that the reaction runs so well in the slurry of mesoporous material. The surfactant-based reaction media, and in particular microemulsions, are dynamic systems, and their usefulness as media for organic reactions may be due both to the large oil-water interface and to the dynamics of the interface, with surfactants going in and out and surfactant monolayers disintegrating and reforming. No such dynamics are present in the medium based on the solid silica material. The porous material is filled with the aqueous solution of KI, and the material is mechanically dispersed in a nonpolar medium, which is either the lipophilic reactant as such or a solution of the lipophilic reactant in hydrocarbon. Potassium iodide has negligible solubility in the nonpolar medium and 4-tert-butylbenzyl bromide is virtually insoluble in water,13 which means that the reactants must meet and react at the pore openings. The product obtained, 4-TBBI, is lipophilic and will partition into the nonpolar medium. An attractive feature of the reaction in the slurry of mesoporous material is the ease of the workup procedure. After completed reaction, the solid particles are filtered off (and washed with hydrocarbon to remove adsorbed product and/or starting material). The residue remaining after evaporation of the solvent is the reaction mixture with no contamination of auxiliary substances, such as surfactants or phase transfer agents. As will be demonstrated in a separate paper, the mesoporous solid can be reused several times without much loss of efficiency. A facile workup procedure may seem trivial but should not
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be ignored. Surfactant self-assembly systems, such as microemulsions and liquid crystalline phases, contain high concentrations of amphiphiles that may give rise to foaming or persistent emulsions during the workup. Likewise, phase transfer agents are sometimes difficult to quantitatively remove from the product. If separation of surfactants, quaternary ammonium compounds, crown ethers, or other reaction aids involves time-consuming operations, the organic chemist will appreciate this alternative approach to overcome reactant incompatibility. Further work to elucidate in more detail the scope and limitations of slurries of mesoporous materials as media for reactions between incompatible reactants is underway in our laboratory. Conclusions The reaction between 4-TBBB and KI, which is sluggish in a simple two-phase system, is fast in the system based on a slurry of a mesoporous material with hexagonal geometry. It was found to be fast also in a microemulsion and fast when the hexagonal liquid crystalline phase that corresponded to the mesoporous material was used as reaction medium. Even if the slurry of mesoporous material did not give a higher reaction rate than the systems based on surfactant self-assembly, the former reaction medium is more attractive from a practical point of view. The extremely facile workup after completed reaction, filtering followed by evaporation of the solvent, makes it a useful tool in preparative organic synthesis. Mesoporous materials are today being explored for a variety of applications, out of which catalysis is the most prominent. We here demonstrate that such materials also have a potential for use as medium for reactions between incompatible reactants. Acknowledgment. We thank the Swedish Foundation for Strategic Research through its Colloid and Interface Technology Program for financial support for T.W. LA0472504
