Ultra-small mesoporous silica nanoparticles (MSNs) have been synthesized at room temperature with particle sizes ranging from 28 to 45 nm. These MSNs have been employed as heterogeneous supports for palladium and gold nanocatalysts. The colloidal nature of the MSNs is highly useful for catalytic applications as it allows for better mass transfer properties and a more uniform distribution of the nanocatalysts in solution. The two nanocatalysts were evaluated in the cycloisomerization of alkynoic acids and demonstrated to produce the corresponding alkylidene lactones in good to excellent yields under mild conditions. In addition to their high activity, the catalysts exhibit low degree of metal leaching and straight-forward recycling, which highlight the practical utility of MSNs as supports for nanocatalysts.
Transition metal-based catalysis has played a central role in advancing the field of organic synthesis, by allowing for the development of new types of reactions that have not been possible to achieve by classic chemistry.1 Moreover, transition metal catalysis has enabled protocols that display unprecedented efficiency and selectivity, which can often be performed under very mild reaction conditions. Recently, significant attention has been directed towards transition metal nanoparticles as they have shown to be promising catalysts for a wide range of organic transformations.2 The work in nanocatalysis has been greatly facilitated by the rapid progress in the field of nanotechnology during the past decades, which has provided a variety of size- and shape-selective methods for synthesizing metal nanoparticles.2(e),3 However, some challenges still remain in the synthesis of nanosized transition metal particles, where one of the most crucial issues concerns how to prevent the nanoparticles from aggregating during the catalytic conditions, which generally translates into reduced catalytic activity over time.
A simple and efficient way to avoid aggregation of nanoparticles is to immobilize them on a heterogeneous support, and this methodology also brings several practical advantages such as simpler separation of the catalyst from the reaction mixture and the possibility of catalyst recycling. To date, a wide range of porous solid supports has been developed for the immobilization of metal-based nanocatalysts, which includes carbon-based materials,4 metal-organic frameworks,5 metal oxides,6 polymers,7 and silica.8
Inorganic porous materials have been used as supports because of their uniform porosity, size/shape selectivity, and significant thermal stability. However, the microporous system of traditional porous materials brings some drawbacks, such as slow diffusion of reactants and hindered access to and subsequent exit from the active sites located within the material. Consequently, a variety of novel mesoporous materials have been developed to overcome these drawbacks associated with microporous systems. The hierarchical porosity of these supports will increase the mass transfer rate, enlarge the external surface area, and enhance the volume of the reactors, which has significant advantages in organic reactions. Therefore, mesoporous silica has emerged as one of the most promising supports for transition metal nanoparticles owing to their good thermal stability, high surface area, tunable pore sizes, and straight-forward synthetic routes. In comparison to conventional mesoporous silica, mesoporous silica nanoparticles (MSNs) are expected to have better accessibility for reactants and a more uniform distribution in the reaction media (in liquid phase) because of their colloidal nature.
Herein, we present the preparation of an ultra-small MSN material with particle sizes between 28 and 45 nm and its application as a support for Au and Pd nanocatalysts. In this study, the cycloisomerization of alkynoic acids was chosen as the model reaction for the catalytic evaluation of synthesized catalysts.
The MSN material was synthesized at room temperature using the two surfactants, cetyl trimethylammonium bromide (CTAB) and F127, as structure directing agent and particle stabilization agent, respectively. The porosity of the MSNs was obtained by removing the surfactants from the pores of the MSNs under calcination. A pH adjustment protocol was applied to avoid aggregation of the MSNs, which could be thoroughly dispersed in aqueous solution, allowing them to be studied by dynamic light scattering (DLS). The MSNs form spherical particles with a narrow size distribution in the range of 35–45 nm, as depicted by DLS (Figure 1(a)). High-resolution scanning electron microscopy (HRSEM) analysis, on the other hand, showed that these nanoparticles were in sizes ranging from 28 to 45 nm (Figure S19), which is slightly smaller than those given by DLS, because this technique presents the size of particles together with a thin electric dipole layer from the solvent which is not visible by HRSEM. Scanning transmission electron microscopy (STEM) demonstrated that the mesopores were uniformly distributed with the diameters ranging from 2 to 4 nm (Figure 1(b)). N2 adsorption/desorption indicated a typical type IV isotherm of the MSNs with a specific surface area of 331 m2 g−1 and a total pore volume of 1.83 cm3 g−1 contributed by both mesopores and macropores (Figure S29). 3D electron tomography was performed on Pd loaded MSNs, and the reconstructured tomogram clearly shows that the mesopores are open to the external surface of the MSNs (Movie S19 and Figure S39).
(a) DLS of MSNs in water solution and (b) STEM image of MSNs showing its morphology and uniformly distributed mesostructures.
(a) DLS of MSNs in water solution and (b) STEM image of MSNs showing its morphology and uniformly distributed mesostructures.
After amino-functionalization, the specific surface area of AmP-MSN (AmP = aminopropyl) decreased to 234 m2 g−1 and total pore volume to 1.60 cm3 g−1, as obtained from the N2 adsorption/desorption isotherm of the AmP-MSN (Figure S2). Because the major decrease of the specific area and pore volume occurred in the range between 0.8 and 1.0 relative pressure, the decrease is mainly attributed by the incorporation of aminopropyl groups in the macropores between the MSNs. This indicates that mainly the external surfaces of the MSN material, not the mesopores of the MSNs are functionalized with aminopropyl groups.
Both the Pd and Au loaded samples, denoted as Pd-AmP-MSN and Au-AmP-MSN, respectively, kept the same morphology as that of the MSNs. The vast majority of the Pd nanoparticles were found to possess a narrow size distribution from 1 to 2 nm (Figure 2(a)). In order to locate the positions of the Pd nanoparticles, electron tomography was performed using STEM images, which shows that the Pd nanoparticles are dispersed homogeneously on the external surface of the MSNs (Figures S49 and S59, and Movie S29). Both small Au nanoparticles (1–2 nm in size) and large Au nanoparticles (about 5–10 nm in size) were observed in the STEM image of the Au-AmP-MSN (Figure 2(b)). The larger nanoparticles are most likely a result of aggregation of smaller Au nanoparticles.
STEM images of Pd-MSN (a) and Au-MSN (b). The Pd and Au nanoparticles are shown in white contrast.
STEM images of Pd-MSN (a) and Au-MSN (b). The Pd and Au nanoparticles are shown in white contrast.
The cycloisomerization of alkynoic acids into their corresponding alkylidene lactones was chosen as the model transformation for the catalytic evaluation of the Pd-AmP-MSN. Previous literature reports have shown that both homogeneous10 and heterogeneous11 Pd catalysts can effectively mediate this cycloisomerization reaction, making it an excellent choice for studying the activity and the robustness of the Pd-AmP-MSN. This transformation is also interesting from a practical perspective as it allows for straight-forward access to the γ-alkylidene lactone motif, which is a key fragment found in a variety of biologically active natural products.12
The colloidal nature of the nanosized MSN support contributed to the improvement of the catalytic properties of the corresponding nanocatalyst. A study was conducted on the cycloisomerization of 4-pentynoic acid 1a into γ-methylene-γ-butyrolactone 1b, where the activity of the Pd-AmP-MSN nanocatalyst was compared to those of Pd-AmP-MCF (MCF = mesocellular foam)13 and commercially available Pd/C (Figure 3). To our delight, the Pd-AmP-MSN nanocatalyst was found to be the most efficient catalyst in the comparison study, giving 93% conversion after only 60 min at 40 °C. We ascribe the high catalytic activity of the Pd-AmP-MSN to the colloidal nature of the AmP-MSN material, which allows for a better dispersion of the catalyst in the reaction medium and enables more expedient access of the reactants to the catalytic sites. The Pd-AmP-MCF that contains a similar Pd nanoparticle size distribution (1.5–3.0 nm) as the Pd-AmP-MSN also performed well in this study, although it gave a noticeably slower reaction. The lower activity of the Pd-AmP-MCF catalyst is ascribed to the larger size of the AmP-MCF particles, which resulted in worse dispersion properties compared to the AmP-MSN support. In the case of the commercial Pd/C, the larger mean size of the Pd nanoparticles was invoked as the main explanation for its poor performance. However, this heterogeneous Pd catalyst is also composed of micrometer-sized support particles, which might also contribute to the lower catalytic activity.
Cycloisomerization of 4-pentynoic acid 1a at 40 °C for 60 min. In a typical experiment, 4-pentynoic acid (0.40 mmol), a heterogeneous metal catalyst (1 mol. % Pd, Pd-AmP-MSN (•), Pd-AmP-MCF (■), and Pd/C (▴)) and triethylamine (0.10 mmol) were mixed in CH2Cl2 (1 ml). The progress of the reaction was periodically monitored by withdrawal of aliquots for 1H-nuclear magnetic resonance (NMR)-analysis.
Cycloisomerization of 4-pentynoic acid 1a at 40 °C for 60 min. In a typical experiment, 4-pentynoic acid (0.40 mmol), a heterogeneous metal catalyst (1 mol. % Pd, Pd-AmP-MSN (•), Pd-AmP-MCF (■), and Pd/C (▴)) and triethylamine (0.10 mmol) were mixed in CH2Cl2 (1 ml). The progress of the reaction was periodically monitored by withdrawal of aliquots for 1H-nuclear magnetic resonance (NMR)-analysis.
After establishing that the Pd-AmP-MSN constituted the superior catalyst choice, we studied the scope of the catalytic protocol (Figure 4). As demonstrated above, the standard substrate 1a could be efficiently cycloisomerized by the Pd-AmP-MSN catalyst, leading to a quantitative yield of γ-methylene-γ-butyrolactone 1b within 1.5 h (Table I, entry 1). Increasing the
chain length of the alkynoic acid by one methylene group resulted in a significantly less efficient cycloisomerization reaction, which despite increased catalyst loading, longer reaction time, and elevated temperature only produced the six-membered ring lactone 2b in 50% yield (Table I, entry 2). This finding is in line with previous studies, which have shown that it is generally more challenging to form six-membered ring products in comparison to the corresponding five-membered ones.10(a),11(a),14 The Pd-AmP-MSN catalyst also proved capable of cyclizing the terminally substituted pentynoic acid 3a, which occurred by complete (Z)-selectivity (Table I, entry 3). However, a longer reaction time (16 h) and a higher reaction temperature (50 °C) were needed to ensure a high yield of the desired lactone product. Interestingly, the cycloisomerization of the Boc-protected amino acid derivative 4a proceeded remarkably well, and the corresponding product lactone 4b could be obtained in a good yield of 79%, when performing the reaction at 40 °C for 6 h (Table I, entry 4).
The cycloisomerization of 4-pentynoic acid 1a, first cycle (•) and fourth cycle (■).
The cycloisomerization of 4-pentynoic acid 1a, first cycle (•) and fourth cycle (■).
Cycloisomerization of a condensed scope of acetylenic acids catalyzed by Pd(0)-AmP-MSN.a
 | ||||||
|---|---|---|---|---|---|---|
| Entry | Substrate | Product | Pd loading (mol. %) | Time (h) | Temperature (°C) | Yield (%)b |
| 1 |  |  | 1.0 | 1.5 | 40 | 99 |
| 2 |  |  | 2.0 | 24 | 50 | 50 |
| 3 |  |  | 1.0 | 16 | 50 | 85 |
| 4 |  |  | 1.0 | 6 | 40 | 79 |
| ||||||
|---|---|---|---|---|---|---|
| Entry | Substrate | Product | Pd loading (mol. %) | Time (h) | Temperature (°C) | Yield (%)b |
| 1 | | | 1.0 | 1.5 | 40 | 99 |
| 2 | | | 2.0 | 24 | 50 | 50 |
| 3 | | | 1.0 | 16 | 50 | 85 |
| 4 | | | 1.0 | 6 | 40 | 79 |
Reaction conditions: alkynoic acid (0.40 mmol), triethylamine (0.10 mmol), Pd-AmP-MSN (see table), 1,3,5-trime toxybenzene (internal standard, 0.10 mmol), and CH2Cl2 (1 ml) were added to a microwave vial, which were sealed and heated in an oil bath according to the temperatures and times given in the table.
The yields of the reactions were determined by 1H-NMR using the internal standard.
To establish the practical utility of the Pd-AmP-MSN catalyst, factors such as leaching and recyclability were examined. Gratifyingly, inductively coupled plasma-optical emission spectroscopy (ICP-OES) analysis of the reaction solution showed that the developed Pd nanocatalyst only exhibited a minor leaching of 1.1 ppm, demonstrating its high structural stability under the employed catalytic conditions. The recyclability of the Pd-AmP-MSN was assessed by subjecting the catalyst to four subsequent reaction cycles. In the first three cycles, each reaction was stirred for 120 min before it was stopped, and the conversion was determined by 1H-nuclear magnetic resonance spectroscopy (1H-NMR). During the final cycle (the 4th cycle), the reaction was periodically sampled after 10, 30, 60, and 120 min, to allow for a kinetic comparison of the activity between unused and the recycled catalyst. The reactions involving the Pd nanocatalyst displayed gradually decreased efficiency over the four cycles, with 99%, 80%, 73%, and 59% conversion after a full reaction time of 120 min, respectively. This decrease in efficiency was further demonstrated by comparing the kinetic profile of the reaction during the first and fourth cycles, which shows a clear decrease in the activity of approximately four times (Figure 4). There are two possible reasons that could explain the decrease in catalytic activity over consecutive use, i.e., the agglomeration of the Pd nanoparticles and/or a passivation of the metal surface. The Pd nanoparticles were studied after the catalytic experiments by TEM, and these images showed that the recycled Pd-AmP-MSN exhibited comparable particle distribution and morphology as the fresh samples (in Figure 2(a)), suggesting that catalyst deactivation instead comes from passivation of the metal surface under the employed catalytic conditions.
To demonstrate the versatility of the developed AmP-MSN material, its possible use as a support for other transition metal nanoparticles was also investigated. A corresponding Au nanocatalyst was prepared by treating the AmP-MSN material with HAuCl4 and subsequently reducing it with NaOH-activated NaBH4 at 0 °C. This Au nanocatalyst was also proved to be an efficient and stable catalyst for the cycloisomerization of 4-pentynoic acid 1a, by giving 83% yield of the desired lactone 1b after 2 h with a small leaching of 8.1 ppm (Scheme 1). However, the Au nanocatalyst exhibited a reduced activity over multiple re-uses in the cycloisomerization of 4-pentynoic acid 1a.
Cycloisomerization of 4-pentynoic acid 1a into γ-methylene-γ-butyrolactone 1b catalyzed by Au-AmP-MSN.
Cycloisomerization of 4-pentynoic acid 1a into γ-methylene-γ-butyrolactone 1b catalyzed by Au-AmP-MSN.
In summary, MSNs have been synthesized, characterized, and applied as a support for heterogeneous catalysts. From this material, two metal nanocatalysts comprised of Pd and Au nanoparticles were prepared and used in the cycloisomerization of a small library of alkynoic acids into their corresponding alkylidene lactones in good to excellent yields. The colloidal nature of the MSNs led to better catalytic properties of the corresponding Pd nanocatalyst, which was ascribed to a more efficient transfer of reactant molecules to the catalytic sites and improved dispersion dynamics. Although the metal nanocatalysts were found to display low metal leaching, they exhibited a decreased activity upon recycling, which was attributed to a passivation of the metal surface under the catalytic conditions. Thus, this deactivation was not caused by the degradation of MSNs or aggregation of the metal nanoparticles. Motivated by these promising results, we will continue to look into further application of the MSNs as supports for other catalytic species and their potential use in organic synthesis.
This work was supported by the Swedish Research Council (VR), the Swedish Governmental Agency for Innovation Systems (VINNOVA), and the Knut & Alice Wallenberg Foundation through the project grants CMCSU and 3DEM-NATUR and a grant for purchasing the TEM. Dr. F. Gao thanks the VINNMER program of VINNOVA.
