Active Base Hybrid Organosilica Materials based on Pyrrolidine Builder Units for Fine Chemicals Production

The catalytic activity of “pyrrolidine type” fragments included or anchored in the mesoporous silica supports or polymeric frameworks have been fully reported for enantioselective transformation. Nevertheless, low attention was focused on their catalytic abilities to perform base‐catalyzed reaction. Accordingly, hybrid materials including pyrrolidine fragments in the mesoporous silica supports were prepared following different synthesis methods, such as micellar and fluoride sol‐gel routes in absence of structural directing agents. Their great catalytic performance was explored for various base‐catalyzed reactions to the formation of C−C bond through Knoevenagel, Claisen‐Schmidt and Henry condensations under microwave irradiation. The benefits of microwave irradiation combined with suitable catalytic properties of pyrrolidine hybrid materials with strong base sites and high accessibility to active centers, allowed carrying out successfully base‐catalyzed condensation reactions for the production of fine chemicals. Moreover, the hybrid catalyst exhibited high selectivity and good stability over different catalytic cycles contributing to environmental sustainability.


Introduction
The area of hybrid materials in which organic and inorganic units are conjugated in their structure, perfectly assembled and regularly distributed in their framework, allows the generation of new families of materials, often with associated intrinsic porosity, that exhibit unique physico-chemical properties and reactivity, and above all, different from that of the building units in homogeneous phase when they are found separately. [1] This fact is favored by the positive synergy established between the active functional builders that make up the structure of the materials, where aspects such as the molecular distance between the different building units, their distribution and location in the network and the morphology of the structure in which they are integrated are keys in the properties of the hybrid organic-inorganic materials finally obtained. [2,3] The appropriate combination of different builder units, organic and inorganic, through condensation, hydrothermal, solvothermal or even self-assembly processes allowed the generation of new families of advanced materials with varied properties and topologies, such as metal-organic materials (MOFs), coordination polymers, modified covalent organic frameworks (COFs) or mesoporous periodic organosilicas (PMOs), among the main ones. [4][5][6] These hybrid solids have found application in a large number of fields related to the adsorption-separation of gases, catalysis (including photocatalysis and electrocatalysis), sensors, molecular photodynamics or storage, covering aspects ranging from processes related to the specific production of chemicals through environmentally friendly catalytic routes to their intervention in green energy generation processes acting as efficient membranes in fuel cells, citing only a few relevant examples. [7] Base-catalyzed reactions allow the production of a large variety of products with high value added of interest in different sectors of chemical industry such as pharmaceuticals, fine chemicals, polymers, paints, drugs, cosmetics and ingredients for food. The main homogeneous bases usually used are NaOH, KOH, and trimethylamine in aqueous or alcoholic solution owing to their catalytic properties and low cost. [8] For the past century, with industrial revolution, humans have caused most of global warming by releasing greenhouse gases which levels are higher now than at any time in the last 800,000 years. Therefore, the urgency of caring for the planet, focusing on carbon neutrality and green chemistry principles that promote atomic efficiency, the use of non-toxic, degradable and environmentally friendly substances, as well as the utilization of catalysts, make the development of new robust and efficient hybrid functional catalysts crucial. Thus, the design and development of solid catalysts will allow avoiding the generation of large amount of waste, equipment corrosion, use of toxic substances and achieving easy catalyst separation from reaction products and recycling as well as higher process selectivity leading to environmentally benign and economical pathway being of large interest for chemical industry and scientific community.
Among all the possibilities offered by hybrid materials, their ability to house different active centers, perfectly stabilized and accessible, in their structure, coexisting in the same solid matrix, allows the creation of multi-functional materials with high potential to carry out consecutive chemical processes, using a single reusable catalytic systems that act as a linear vector of combined reactive pathways. [9] Furthermore, the conjunction of alternate hydrophobic and hydrophilic sub-domains in the porous network, distributed homogeneously, facilitates the existence of high concentration gradients of substrates in active areas of the solid hybrid catalysts, favoring the performing of highly intensified chemical processes. The presence of nanospaces, in this type of organic-inorganic materials, would also facilitate a high selectivity associated with the formation of more energetically favorable intermediate species for obtaining specific products with high conversion. All this implies the performance of hybrid materials as true molecular machines acting in nanoconfined environments. [10] Particularly relevant has been the development of new families of porous organosilicas, using suitable precursors based on bridged silsesquioxanes or disilanes, (R'O) 3 SiÀ RÀ Si(OR') 3 , which contain highly reactive terminal siloxane groups that facilitate their co-condensation and integration into the structure in which they are present. These precursors, moreover, contain organic bridge-type fragments with associated functional active centers, which are included in the walls of the porous structure. [11] Besides the catalysts efficiency, the heating is an important parameter in the chemical conversions. In the last two decades, microwave technology was implanted for many chemical processes due to the benefits of microwave heating over conventional ovens such as higher rates of reaction, better yields and higher selectivity, high reproducibility owing to the homogeneity of microwave irradiation and finally energy saver. [2] Microwave energy provides efficient internal heat transfer by direct interaction of the electric field with all of the components of reaction system substrates, solvents and catalysts through dipolar rotation and ionic conduction. Accordingly, in this work, we describe the great catalytic activity of different hybrid materials containing pyrrolidine-type builder units in the framework with suitable catalytic properties for various base catalyzed reactions to the formation of CÀ C bond through Knoevenagel, Claisen-Schmidt and Henry condensations under microwave irradiation. We previously reported the preparation of hybrid materials incorporating pyrrolidine fragments in different mesoporous silica frameworks as well as their potential as enantioselective base catalysts for Michael addition. [3,4] Fluoride sol-gel route without structure-directing agents was followed to obtain non ordered mesoporous hybrid materials (N.O) and different structure-directing agents through suitable micellar processes were employed for the preparation of ordered materials (PMO-MCM-41 and PMO-SBA-15). Therefore, the benefits of microwave irradiation combined with suitable catalytic properties of pyrrolidine hybrid materials with strong base sites and high accessibility to active centers, allowed carrying out successfully base-catalyzed condensation reactions to the production of fine chemicals. Moreover, the hybrid catalyst exhibited high selectivity and good stability over different catalytic cycles contributing to environmental sustainability (Scheme 1). To evaluate the green aspects of a chemical process, some green chemistry metrics were established to quantify its efficiency or environmental performance such as atom economy, reaction mass efficiency or environmental factor (E factor). The reaction mass efficiency decreases dramatically on going downstream from bulk to fine chemicals and specialties such as pharmaceuticals because of the production involves multi-step syntheses and the use of stoichiometric reagents, excess of reactant and neutralization steps. In contrast, E factor that is the ratio of the mass of waste per mass of product increases rapidly and is in the range 5-50 for fine chemicals and 25-200 for pharmaceuticals. The use of catalytic process is a great strategy to maximize reaction mass efficiency and E factor. Therefore, we evaluated the E factor for the Scheme 1. Pyrrolidine hybrid material as sustainable, efficient and stable base catalyst for the production of fine chemicals.

ChemCatChem
Full Papers doi.org/10.1002/cctc.202101031 different processes studied in this work. The solvent and catalyst were not taken into account in the calculations since they can be fully reused after distillation or filtration, respectively.

Synthesis and characterization
In this work, we report the catalytic activity of different hybrid materials containing pyrrolidine-type builder units in the framework. The pyrrolidine fragments were included in the mesoporous silica supports following different synthesis methods, being the physico-chemical properties and potential reactivity as base catalysts of the synthesized organic-inorganic materials previously characterized. [5] Non ordered mesoporous hybrid materials were obtained through fluoride sol-gel route without structure-directing agents (N.O), while the ordered materials were synthesized in the presence of different structure-directing agents through suitable micellar processes (PMO-MCM-41 and PMO-SBA-15) (Scheme 2).
Specifically, for the preparation of the hybrid materials was necessary the previous synthesis of a bis-silylated monomer used as an organosilicon precursor, which contained pyrrolidine-type fragments (PyrSil) like an organic bridge between reactive terminal siloxane groups (Scheme S1). In detail, nonordered mesoporous hybrid materials were synthesized through a sol-gel process under soft conditions at neutral pH and at room temperature, acting the fluoride ions like a mineralizing agent and in absence of structure directing agents. These synthesis conditions favored the formation of penta-coordinated organosilicon species, which were reactive intermediates that allowed the rapid gelation of the synthesis gel. After the aging period at 36°C, facilitating the assembly of the PyrSil monomers, the formation of non-ordered mesoporous structures (N.O), containing base pyrrolidine builder units in their framework, was achieved.
On the other hand, ordered hybrid materials with MCM-41and SBA-15 morphologies (PMO-MCM-41 and PMO-SBA-15) were obtained by the employ of long chain neutral amine surfactants or block copolymers, respectively, through micellar processes in presence of the organosilicon bis-silylated precursor (PyrSil). In this latter case, the long-range order of the mesoporous hybrid materials decreased remarkably with the increase of the amount of pyrrolidine builder fragments incorporated in the network (from 5 mol.% to 30 mol.% of PyrSil), such as it is appreciated from X-ray diffraction patterns ( Figure S1).
The micrographs obtained from transmission electronic microscopy (TEM) evidenced that the mesoporous distribution of the hybrid materials was present in the solids which were obtained with up to 5 mol.% of PyrSil in the synthesis gel, although it was observed a marked disorder and non-homogeneous distribution of internal channels. In the ordered hybrids, cavities of approximately 30-100 Å were appreciated, remembering SBA-15 or M41S topology ( Figure S2). In the non-ordered mesoporous hybrid materials, an irregular morphology was detected, being present cavities of different internal diameters. Scheme 2. Different synthesis routes for the mesoporous-hybrid materials containing pyrrolidine builder units incorporated in the framework. [12] ChemCatChem Full Papers doi.org/10.1002/cctc.202101031 Chemical analysis (C, H, N, S) of the mesoporous hybrid materials showed that the organic content was higher when the amount of bis-silylated precursor (PyrSil) used in the synthesis process was more elevated (Table S1). The results confirmed that the extraction methodologies used to remove the internal surfactant molecules of hybrid materials with M41S and SBA-15 topologies were not completely effective. Overall, this drawback was more marked in the samples with lower number of pyrrolidine units inserted in the framework (5 mol.% of PyrSil), being this fact associated to the poorer order level achieved for the hybrid solids with a higher content of structural pyrrolidine moieties, which facilitated the removing of internal surfactants. In the case of non-ordered hybrid materials obtained in a fluoride medium in absence of structural directing agents, the organic content came exclusively from organosilicon precursor (PyrSil), being estimated a C/N molar ratio of 4.3 that was coincident with the theoretical value of pyrrolidine units. These results confirmed that the organic units were preserved as they were initially after their integration in the hybrid framework.
Thermogravimetric analysis (TGA) curves and their corresponding derivatives (DTA) of the hybrid mesoporous materials prepared confirmed that the thermal stability of the solids was established between 300°C and 500°C, considering the main weight losses ( Figure S3). In detail, first weight loss was centered at 250-300°C, corresponding to the residues of organic molecules used as structure directing agents (I), after the extraction post-synthesis processes. The second main weight loss (II), located in the temperature range of 300-500°C, was assigned to the inserted pyrrolidine moieties included in the network from PyrSil monomer used in the synthesis. In the case of the organic-inorganic materials prepared in absence of organic templates, only one weight loss was appreciated at 300-500°C attributed to pyrrolidine builder fragments units inserted in the framework.
The presence and the integrity of the pyrrolidine fragments included in the framework of the porous hybrid materials was also evidenced by the NMR spectroscopic results ( Figure S4). In fact, the 13 C NMR spectra showed the chemical shifts corresponding to all carbon atoms from the organosilicon precursor (PyrSil), being corroborated that the pyrrolidine organic units remained intact in the structure of the hybrids with the same composition as in the initial PyrSil precursor. Moreover, it was confirmed from 29 Si NMR spectra ( Figure S5) that silyl-pyrrolidine moieties were covalently inserted into the architecture of the solids, being appreciated chemical shifts in the range between À 60 and À 80 ppm corresponding to T-type species of silicon atoms such as T 1 (CÀ Si(OH) 2 (OSi)), T 2 (CÀ Si(OH)(OSi) 2 ) and T 3 (CÀ Si(OSi) 3 ). These spectroscopic results confirmed that the silyl-pyrrolidine groups were covalently included into the walls of the organic-inorganic materials through an effective hydrolysis and condensation process established between bis-silylated organosilicon precursors (PyrSil) and TMOS or TEOS used as purely siliceous sources. Specific surface area and free porous volume were analyzed in the hybrid materials from the nitrogen adsorption isotherms ( Figure S6), being confirmed the mesoporous character of the solids. In all cases, it was detected that the accessibility of the internal porosity decreased substantially as the concentration of pyrrolidine groups present in the framework was higher, observing the collapse in the porous structure when 30 mol.% of PyrSil was used in the preparation process. Remarkably, in the case of non-ordered hybrid materials, the BET surface area achieved up to~640 m 2 /g À 1 (Table S2). The analysis of the distribution of the BJH pore diameter allowed establishing that the hybrid materials exhibited diameters between 75-110 Å for SBA-15-type and 30-40 Å for M41S-type and non-ordered hybrid materials such as it was hoped for this class of mesoporous materials ( Figure S6). The obtained results showed that the inclusion of pyrrolidine builder units in the structure of the solids markedly influenced the textural properties and porous nature of the organic-inorganic materials.

Knoevenagel condensation
Knoevenagel condensation is a specific aldol reaction between carbonyl compound and active methylene compound that produces alkenes and is a very useful tool in organic synthesis to form CÀ C bonds. [13,14] Knoevenagel condensation is usually catalyzed by nitrogen-based catalysts, categorized as tertiary amines, secondary amines, primary amines, and ammonium salts, and involves deprotonation of the active methylene compound to create a carbanion which, in turn, attacks the carbonyl compound. Homogeneous amines present certain toxicity and, taking into account the principles of green chemistry, there is a permanent interest in developing environmentally friendly processes using heterogeneous catalysts due to their advantageous characteristics such as activity and selectivity, robustness, easy recovery, possibility to recycle minimizing waste and its impact on the environment, opportunity to operate in flow and improvement of process costs.
Through Knoevenagel condensation, a wide brand of chemically and biologically important products were prepared such as α-cyanocinnamates, α,β-unsaturated esters, α,β-unsaturated nitriles and cinnamic acid, with great purposes such as perfumes, cosmetics, pesticides, antifungal and antibacterial products, antivirals, antioxidants, anticancer activity and cytotoxic capacity. [15][16][17][18][19] Furthermore, Knoevenagel reaction is a complementary tool in the characterization of base catalysts and allows the evaluation of their basic strength owing to the use of active methylene compounds with different functional groups modifying the acidity of the acidic protons. With this purpose, the basic properties of the different hybrid catalysts in the Knoevenagel condensation between benzaldehyde and diethyl malonate (DEM) was explored (Scheme 3). The presence of two ester groups induces a decrease in the acidity of the acid protons and implies that the base involved in the Knoevenagel condensation has to present a high basic strength, since in the case of diethyl malonate the acid proton pKa is close to 13. Firstly, the reaction conditions (temperature, solvent and heating mode) were optimized in the presence of the nonordered material with a 5 % of PyrSil fragments (N.O-5 %). The use of green and bio solvent such as ethanol, methanol or water is environmentally friendly preferred. Regarding the high temperature process required, the volatility of the solvent and the fact that water is a product of reaction, attempts to perform the reaction in ethanol were spent but low catalytic performance was observed (Table S3, Entries 7-8). However, in the bibliography, different tools and guides have been published for green solvent selection to reduce the use of the most hazardous solvents, as well as European regulation introduced restrictions on toluene, chloroform and dichloromethane. Likewise, anisole may be considered a green solvent as reported by the GlaxoSmithKline solvent sustainability guide. [20] The best catalytic results were achieved with diethyl malonate/ benzaldehyde ratio = 0.83, 20 mol.% of catalyst, anisole as solvent and 200°C under microwave heating (MW) that allowed greatly reducing the reaction time reaching 94 % total yield within 3 h (Table S3). Thus, under the same reaction conditions, the catalytic performance of different catalysts with a 5 % of the pyrrolidine moiety in the framework, PMO-MCM-41 and PMO-SBA-15 mesoporous hybrid materials, was explored (Table 1 (Table 1, Entries 3, 6 and 9).
In all the cases, the main product of the reaction was the monocarboxylic ester derivative 2 (EBA). This product is usually obtained via Doebner-Knoevenagel condensation between benzaldehyde and malonic acid in the presence of piperidine. [21] When the Knoevenagel reaction was carried out in the presence of non-ordered materials (N.O) with 5 and 10 wt.% of PyrSil content, the ratio EBA (2)/DEBM (1) products was closed to 7.5 and 1.7 at complete conversion, respectively. Nevertheless, in the presence of MCM-41 type hybrid material with 5, 10 and 30 wt.% of PyrSil content, the ratio EBA (2)/DEBM (1) products was 3.8, 4.9 and 29.7 at complete conversion. For hybrid materials obtained in presence of surfactant as structuredirecting agent, with topology M41S (PMO-MCM-41), the nitrogen adsorption isotherms revealed that the specific surface area and the pore volume decreased markedly when increased the amount of pyrrolidine groups inserted in the framework. Then, materials with highest content of silyl-pyrrolidine fragments exhibited lowest BET surface. Moreover, it was notable that solids obtained with 5 or 10 mol.% of PyrSil monomers exhibited similar BET area, and lower that it could be expected due to probably the incomplete removal of surfactant molecules which blocked partially the pores and accessibility to active basic centers. Nevertheless, M41S type materials with a 30 mol.% of PyrSil fragments showed BET surfaces higher than non-ordered material, attributed to the better achieved organization owing to the presence of structure directing agents. According to the nitrogen adsorption results, the catalytic data showed that decarboxylation process is controlled by diffusion constrains and the number of active sites since in the presence of mesoporous ordered materials with high inserted pyrrolidine groups the ratio EBA (2)/DEBM (1) products was 29.
These results showed that void shapes and sizes controlled the diffusion of reactants and products in addition to confining transition states and reactive intermediates. Therefore, the differences in initial reaction rates and chemoselectivity exhibited by the different basic materials reflect differences in the geometry and accessibility to the active centers. Figure 1 illustrates the trend of 1 and 2 yield versus conversion reached over different type of hybrid catalysts with different PyrSil content and the influence of accessibility to active centers and number of active sites. When diffusion limitations are met, the dicarboxylic ester 1 derivative was the main product, in contrast, when higher accessibility and optimum content in the number of basic sites exist, the main product was the monocarboxylic ester 2 derivative. Kinetic curves (Figures S7-S9, Figure 2) revealed that N.O-5 % and PMO-MCM-41-5 % exhibited the best catalytic performance for Knoevenagel Scheme 3. Knoevenagel condensation between benzaldehyde and diethyl malonate. reaction with good 83 % and 79 % 2 yield, and 0.3 mol L À 1 h À 1 and 0.2 mol L À 1 h À 1 initial rate, respectively. Besides very similar results were achieved for both materials, from synthetic strategy standpoints and costs, N.O-5 % was determined as the more suitable catalyst since it can be synthesized easily without structure directing agents avoiding washing and extraction process, exhibiting higher accessibility at lowest pyrrolidine inserted moieties (Table S2). Finally, the stability and recyclability of the N.O-5 % was examined. The results showed that the mesoporous hybrid catalyst could be reused for four consecutive cycles without observing activity loss ( Figure 3) and preserving the initial structure of the catalyst (Table S4). A leaching test confirmed the stability of included PyrSil fragments in the silicon framework since diethyl malonate conversion remained constant after hot filtration ( Figure S10). To evaluate the sustainability of the Knoevenagel reaction herein set up, E factor was determined and close to 0.66 corresponding to reaction mass efficiency up to 54.6 %.
To explore the scope of N.O-5 % hybrid catalyst to promote Knoevenagel reaction and prepare different functionalized intermediates, the reaction between ethyl cyanoacetate and DEM with aliphatic aldehydes was investigated. The main issue is the self-condensation of aliphatic aldehydes having α-hydrogen with the consequent decrease of process efficiency. Therefore, various aldehydes were selected with or without αhydrogen and the reaction performed in the presence of N.O-5 % hybrid catalyst, under microwave irradiation (Schemes 4 and 5). The results summarized in the Tables 2 and 3 illustrate the great potential of N.O-5 % hybrid material to catalyze Knoevenagel condensation with high product yield and selectivity. In the case of heptanal, self-condensation was  The high catalytic performance exhibited by N.O-5 % to carry out the Knoevenagel condensation between diethyl malonate and benzaldehyde demonstrated the high basic strength of the pyrrolidine fragment included in the hybrid material and good stability observed for recycling study. These results evidence the suitable catalytic properties of the N.O-5 % hybrid material with strong base active sites to perform base-catalyzed reactions and especially, the formation of carboncarbon bonds which is crucial to produce valuable α,βunsaturated compounds and which requires strong base catalysts. Therefore, to continue other reactions of CÀ C bond formation are explored.

Nitroalkenes synthesis
Taking into account the high basic strength of pyrrolidine based hybrid materials exhibited for Knoevenagel condensation, the catalytic ability of N.O-5 % catalyst was explored to carry out another CÀ C coupling to obtain nitroaldol compounds that is nearly analogous to the aldol reaction. The Henry reaction involves the deprotonation of the nitroalkane on the α-carbon position usually catalyzed by soluble bases such as alkali metal hydroxides, carbonates, alkoxides, alkaline earth metal hydroxide, and organic bases such as primary, secondary and tertiary amines. [22] The Henry reaction is a widely used synthetic tool in organic chemistry to produce nitroaldol intermediates of great synthetic value as primary precursors for subsequent reactions (oxidation/reduction, dehydration and condensation), while the nitro groups also give rise to a multitude of functionalities leading to products and intermediates with wide application in commodities, pharmaceuticals, agrochemicals and perfumes. Given the high catalytic activity demonstrated by the N.O-5 % hybrid material for Knoevenagel condensation, it could be expected that this material would have suitable catalytic properties for the Henry reaction. Accordingly, a study of optimization of reaction conditions was performed and allowed preparing β-nitro-styrene with 100 % yield, with      (Table S5). Therefore, the scope of suitable catalytic properties of the hybrid material was evaluated with different benzaldehyde derivatives containing different functional groups in the para position of the aromatic ring. The influence of electron donating groups through mesomeric (-OMe) and inductive effects (-Me), and electron withdrawing groups through mesomeric (-NO 2 ) and inductive effects (-Br) was explored. All reactions were carried out within short reaction times (3-9 h) and > 99 % nitroalkene selectivity. Usually, resonance effect is stronger that inductive effect, except for the case of halogen as it could be observed in the present study. In the presence of OMe group, exhibiting electron-releasing effect inducing deactivation of carbonyl group, 86 % nitroalkene yield was achieved in longer reaction time 9 h ( To show the scope of N.O-5 % hybrid material as catalyst to promote Henry reaction, experiments involving nitromethane and aliphatic aldehydes were investigated (Scheme 6). As above-mentioned, the main issue is the self-condensation of aliphatic aldehydes having α-hydrogen with the consequent decrease of process selectivity. The results summarized in the Table 5 illustrate the great potential of N.O-5 % hybrid material to catalyze Henry reaction with high product yield and selectivity. The worst yield and selectivity were reached when heptanal was used because of the thermodynamically favored self-condensation up to 27 %.

Claisen-Schmidt condensation
Taking into account the suitable catalytic features of PyrSilhybrid materials for the aldol-type condensation, the Claisen-Schmidt condensation was explored to the production of substrates with a wide range of application in the pharmaceutical industry such as chalcones that exhibit interesting biological activities [23] such as antimalarial, [24] anti-inflammatory, [25] cytotoxic, [26,27] anticancer. [28,29] Chalcones contain a three carbon α, β-unsaturated carbonyl system and are obtained from the condensation of aromatic aldehyde with acetophenones in the presence of a catalyst, leading to a variety of chemicals such as pyrazoline, isoxazole and heterocyclic compounds. Chalcones are usually synthesized through Claisen-Schmidt condensation in the presence of base catalysts such as barium hydroxides, [30] hydrotalcites [31] and natural phosphates [32] or using Lewis acids such as RuCl 3 [33] and TiCl 4 . The Claisen-Schmidt reaction is a specific aldol condensation between an aldehyde or ketone having an α-hydrogen with an aromatic carbonyl compound lacking an α-hydrogen catalyzed by base involving the deprotonation of the aldehyde or ketone derivative on the αcarbon position. [34] Therefore, the catalytic properties of N.O-5 % were examined for the synthesis of chalcone 3 via Claisen-Schmidt reaction between acetophenone and benzaldehyde under   Figure S11). Using the same reaction conditions, the synthesis of different substituted chalcones of interest due to their biological properties were prepared with high ketone derivative conversion and 99 % chalcone selectivity (Table 6, Scheme 7). The results showed that when the benzaldehyde derivative with electron donating substituents like hydroxy-and methoxy-groups (Table 6, Entries 2-4), the reaction time increased due to the presence of an electronically enriched aromatic ring together with steric effect. In contrast, when the Claisen-Schmidt condensation was performed between non-condensable aldehyde with substituted electron withdrawing groups in the aromatic ring and a hindered ketone (acetonaphthone), maximum conversion was achieved at shorter reaction time than reaction involving ketones with electron donor groups. Therefore, 93 % and 89 % conversions were reached after 8 h of reaction time (Table 6, Entries 5 and 6). These results showed the suitable catalytic properties and stability of N.O-5 % hybrid catalyst to carry out the synthesis of chalcones derivatives under moderate reaction conditions within few hours. The sustainability of the Claisen-Schmidt condensation was evaluated and reaction mass efficiency was up to 53 % corresponding to E factor close to 0.84 for the chalcones production.

1,3,5-trisubstituted pyrazole and pyrazoline synthesis
Chalcones, besides being the central core for a wide range of biological compounds, give rise to a new family of compounds by reacting with hydrazine derivatives incorporating pyrazoline and/or pyrazole moieties leading to compounds with new biological activities and promising pharmacological, agrochemical, and analytical applications (Scheme 8). [35][36][37] The condensation between chalcone derivative and substituted hydrazine usually produced tri-substituted pyrazoline, further converted into pyrazole through oxidative aromatization in the presence of oxidizing agents such as zirconium nitrate, [38] activated carbon, [39] Pd/C, [40] HIO 3 and I 2 O 5 . [41] Therefore, the catalytic performance of N.O-5 % hybrid catalyst to carry out the reaction between chalcones and hydrazines derivatives was explored. Moreover, a study of optimization of reaction conditions to maximize pyrazoles yield was performed. Accordingly, the catalytic behavior of N.O-5 % hybrid catalyst was evaluated controlling the nature of reaction atmosphere (air, inert atmosphere (N 2 ) and oxidant atmosphere   Table 7, Entries 1, 3, 6-11). Moreover, when oxygen atmosphere was applied, maximum selectivity up to 95 % towards 1,3,5-triphenyl-pyrazole was reached (Table 7, Entries 2, 4 and 12). Therefore, taking advantage of benefits of nonoxidant and oxidant atmosphere, under which a maximum yield to 1,3,5-triphenyl-pyrazoline and pyrazole were achieved, respectively, an experiment was then set up under nitrogen for the first hour and under oxygen for the following 2.5 h. Thus, maximum 97 % chalcone conversion, 88 % and 9 %, 1,3,5triphenyl-pyrazole and pyrazoline yield were reached, respectively ( Figure 6; Table 7     preparation of pyrazole through oxidative aromatization free metal process. Finally, an attempt of three steps, one-pot, consecutive reaction of Claisen-Schmidt condensation, chalcone and phenylhydrazine condensation and cyclisation followed by oxidative aromatization to the preparation of tri-phenyl pirazoline and pyrazole was successfully accomplished. After 5 h of reaction time, in toluene, 200°C (MW) and complete conversion of acetophenone, the corresponding amount of phenylhydrazine was added to the reaction medium, to finally reach of 89 % chalcone conversion, 74 % of 1,3,5-triphenyl pyrazole and 15 % of pyrazoline yields, after first 3 h under nitrogen atmosphere followed by 1 h under oxygen atmosphere (Table 7, Entry 16). The sustainability of the condensation-cyclisation of chalcone and hydrazine followed by oxidative aromatization to produce mainly pyrazole and pyrazoline was evaluated, and reaction mass efficiency was up to 19 % corresponding to E factor close to 5.2 because of the high excess of hydrazine derivatives used. For the multistep one pot process, the reaction mass efficiency was close to 15.6 % corresponding to E factor around 5.4. The decrease in the efficiency of the process was attributed to the high excess of hydrazine derivative required.

Conclusion
The study of Knoevenagel reaction allowed evaluating the high strength of base active sites owing to the incorporation of pyrrolidine fragments in different mesoporous hybrid materials, obtained through micellar and fluoride sol-gel routes in absence of structural directing agents. N.O-5 % hybrid catalyst exhibited the best catalytic properties, considering catalytic performance and synthetic strategy standpoints and costs. In addition, the base properties of the hybrid catalyst allowed to obtain six different nitroalkenes with > 99 % selectivity towards the trans-product. The hybrid catalyst exhibited very high catalytic properties and stability to synthesize valuable α, βunsaturated compounds with large broad of applications such as different types of chalcones with high synthetic value, α, βunsaturated esters and nitroalkenes. Furthermore, the synthesis of 1,3,5-trisubtitued pyrazoles and pyrazolines derivatives could be prepared with high yield and maximum selectivity, through 3-consecutive steps-one pot process, by combining an inert and oxidizing atmosphere. The catalyst was able to carry out a Claisen Schmidt, hydrazine addition-intramolecular cyclization and oxidative aromatization tandem reaction to obtain 1,3,5trisubstituted pyrazole. The ability to carry out different basecatalyzed reactions combined to their ability to perform enantioselective reactions already reported, showed the high activity, selectivity, robustness and versatility of the synthesized mesoporous hybrid catalyst in different fields of chemistry.

Characterization techniques
All reagents were purchased from commercial suppliers and used without further purification. CHN content was determined with a Carlo Erba 1106 elemental analyzer. Thermogravimetric and differential thermal analysis (TGA-DTA) were performed in an air stream with a Mettler Toledo TGA/SDTA 851E analyzer. Nitrogen adsorption isotherms were obtained at 77 K with a Micromeritics ASAP 2010 volumetric adsorption apparatus. Before the analysis, the solids were outgassed for 12 hours at 80°C. The BET specific surface area was determined from the nitrogen adsorption data using the relative pressure range from 0.04 to 0.2. The total pore volume was evaluated from the amount of N 2 adsorbed at relative pressures around 0.99. External surface area and micropore volume were determined from t-plot method in the t range 3.5-5. The pore diameter and the pore size distribution were obtained using the Barret-Joyner-Halenda (BJH) methodology using adsorption branches of the isotherms. Solid state MAS-NMR spectra were obtained at room temperature under magic angle spinning (MAS) in a Brucker AV-400 spectrometer. Organic solutions were concentrated at reduced pressure using Büchi rotary evaporator.

Preparation of PMO-MCM-41 hybrid materials
Mesoporous PMO-MCM-41 hybrid materials were synthesized by co-condensation of bis-silylated precursor PyrSyl and TMOS with hexadecylamine as templating agent together with iPrOH, EtOH and water. [43] On the one hand, solution 1 was composed by TMOS and PyrSil compound solved with iPrOH and EtOH, being stirred at room temperature until homogeneity. On the other hand, solution 2 was composed by hexadecylamine solved with water at 40°C for

Preparation of PMO-SBA-15 hybrid materials
Mesoporous PMO-SBA-15 hybrid materials were synthesized by cocondensation of chiral bis-silylated PyrSil and TMOS together with block copolymer P123 as templating agent. [

Preparation of mesoporous N.O hybrid materials
Non-ordered hybrid mesoporous organic-inorganic materials, N.O, were prepared from an initial mixture of tetramethoxysilane (TMOS) as silica precursor and the suitable amount of bis-silylated precursor PyrSil ((R'O) 3 Si-R-Si(OR') 3 ), as bridged disilane, in methanol. [45] After dissolution of precursors, a water solution of NH 4 F was incorporated dropwise to the solution containing organosilicon alkoxide compound under vigorous stirring. The reaction mixture presented the next molar composition: 1[(1-x)TMOS + xPyrSyl]: 4 MeOH: 4 H 2 O: 0.00313 NH 4 F (x % SiO 2 mol respect to SiO 2 total mol) where the Si/ NH 4 F and TMOS/disilane ratios were 479 and 4, respectively. Hydrolysis and condensation of the silicon species were performed under vigorous and continuous stirring in a glass beaker at room temperature. Agitation was maintained until gelation. The gel was aged for 24 h at 36°C and, finally, dried at 150°C for another 24 h. The obtained fine brown powder was profusely washed with ethanol and water in successive steps to remove the siloxane molecules which were not incorporated in the solids. Finally, solids were dried at 60°C overnight.

General information about catalytic processes
The reaction products were identified by GC and GC-MS (Shimadzu, GCMS QP2010 Ultra), and liquid NMR. The 1 H and 13 C NMR spectra were recorded on a Bruker 300 spectrometer and the chemical shifts were given in ppm relative to the residual proton solvent signals. The data for the 1 H NMR spectra were given as follows: chemical shift (δ, ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quadruplet, m = multiplet, dd = double doublet, dddd = double doublet doublet), coupling constant and integration. All the reactions were carried out under an inert atmosphere of N 2 unless otherwise indicated, as well as all the solvents used were anhydrous, by using the MBraun 800 solvent purification system (SPS). For the reactions carried out carried out by microwave, the Biotage Initiator + microwave oven was used.

Catalytic tests
The calculation of conversion, yield and selectivity were performed from GC analysis (GC-2010-Ultra, Shimadzu, equipped with an FID and HP-5 column (0.25 mm × 0.25 μm × 30 m)) using dodecane as standard.

Knoevenagel condensation. General procedure
The reaction was carried out in sealed conical type 5 mL microwave vials with the presence of magnetic stirrers in the Biotage Initiator + microwave. Diethyl malonate (0.1 mmol) was added to the reaction vial, with benzaldehyde (0.12 mmol) and 20 mol.% of hybrid catalyst containing pyrrolidine units in its structure, in 1 mL of anisole at 200°C under microwave heating. The products obtained were isolated by means of silica plates with an eluting phase (20 : 1) of hexane: ethyl acetate. The resulting products were analyzed by GC, GCMS and NMR.

Claisen-Schmidt reaction. General procedure
The reaction was carried out in sealed conical type 5 mL microwave vials with the presence of magnetic stirrers in the Biotage Initiator + microwave. The production of chalcones was carried out by mixing an aromatic ketone (acetophenone derivatives) (0.1 mmol) and a non-condensable aldehyde (benzaldehyde derivatives) (0.23 mmol) with 20 mol.% of N.O-5 % as catalyst in 0.4 mL of toluene, at 200°C under microwave. The chalcones were identified by GC and GC-MS (Shimadzu, GCMS QP2010 Ultra).

Synthesis of 1,3,5-triphenylpyrazole. General procedure
The reaction was carried out in sealed conical type 5 mL microwave vials with the presence of magnetic stirrers in the Biotage Initiator + microwave. In the reaction vial (E)-chalcone (0.1 mmol) was added together with the phenylhydrazine (1.23 mmol) with 20 mol.% of N.O-5 % as catalyst and 1 mL of toluene in an inert atmosphere of N 2 during 2 h at 200°C under microwave irradiation. The reaction was followed by GC and at 90 % conversions the atmosphere was changed from inert gas (N 2 ) to oxidant (O 2 , 1 atm ) and prolonged 1 h, at 200°C (MW). The catalyst was filtered off and the mixture was treated with a NaHCO 3 solution (saturated) and the compound extracted with ethyl acetate (three times). The organic phase was dried with anhydrous MgSO 4 and, subsequently, concentrated on a rotary evaporator and purified by a column of silica chromatography with an eluent phase (30: 1) (hexane: AcOEt), to obtain the 1,3,5-triphenylpyrazole, as a white solid. 1 H NMR (300 MHz, CDCl 3 ) δ 7.85 (m, 2H), 7.41-7.14 (m, 13H), 6.75 (s, 1H). 13

Henry reaction. General procedure
The reaction was carried out in sealed 3 mL vials with the presence of magnetic stirrers on heating plates. Benzaldehyde derivatives (0.1 mmol) and nitromethane (0.4 mmol) in 20 mol.% of N.O-5 % were added to the reaction vial as catalyst at 150°C and toluene as solvent. The reaction was monitored by GC and the products isolated by means of silica plates with an eluting phase (4 : 1) (hexane : AcOEt).