MgAl-Layered Double Hydroxide Solid Base Catalysts for Henry Reaction: A Green Protocol

: A series of MgAl-layered double hydroxide (MgAl-HT), the calcined form at 500 ◦ C (MgAlO x ), and the rehydrated one at 25 ◦ C (MgAl-HT-RH) were synthesized. Physicochemical properties of the catalysts were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Surface area of the as-synthesized, calcined, and rehydrated catalysts was determined by N 2 physisorption at − 196 ◦ C. CO 2 temperature-programmed desorption (CO 2 -TPD) was applied to determine the basic sites of catalysts. The catalytic test reaction was carried out using benzaldehyde and their derivatives with nitromethane and their derivatives. The Henry products (1–15) were obtained in a very good yield using MgAl-HT-RH catalyst either by conventional method at 90 ◦ C in liquid phase or under microwave irradiation method. The mesoporous structure and basic nature of the rehydrated solid catalyst were responsible for its superior catalytic efﬁciency. The robust nature was determined by using the same catalyst ﬁve times, where the product % yield was almost unchanged signiﬁcantly.


Introduction
The fine chemical industry has experienced remarkable interest over the past few years due to the high requirements for products like pharmaceuticals, pesticides, fragrances, flavorings, and food additives [1].
The classical methods for the C-C coupling in the Henry reaction using soluble bases such as alkali metal hydroxides, carbonates, bicarbonates, alkoxides, alkaline earth metal hydroxide, aluminium ethoxides, complexes, and also organic bases such as primary, secondary, and tertiary amines, usually resulted in dehydrated products [2]. Therefore, careful control of the basic properties of the reaction medium is vital to obtain better yields of β-nitroalcohols. However, the efforts done by the researchers in the literature required longer reaction times and produced moderate yields [3,4]. The stoichiometric organic synthesis that largely applied so far resulted in large quantities of inorganic salts as byproducts; the disposal of such material causes a serious problem due to the important environmental issues [5]. The homogenous catalytic methodologies reported in the literature have many disadvantages, such as disposal of waste and difficulty recovering the catalyst from the products. In the last decade, there were notable improvements in the development of heterogeneous catalysts for the Henry reaction [6].
The extraordinary growth in the industry's struggle has pushed researchers to advance more effective catalytic processes in the synthesis of fine chemicals. The products of the Henry reaction,

Elemental Chemical Analysis (ICP)
ICP analysis of MgAl-HT was achieved to govern its chemical composition. The analysis discovered that the Mg/Al molar ratio in the solid was 2.8, which is very near to the minimal molar composition of the as-synthesized Mg/Al molar ratio of 3 in the precipitate. This result confirmed the efficacy of the preparation procedure.

X-ray Diffraction (XRD)
X-ray powder diffraction patterns of the as-synthesized MgAl-HT, thermally treated at 500 • C (MgAlO x ), and rehydrated MgAl-HT-RH catalysts are shown in Figure 1 [22]. Thanks to the memory effect, the hydration of the calcined materials using an aqueous alkaline solution of NaOH led to the formation of a layered double hydroxide-like structure of lower intensity than the original MgAl-HT material. In the present study, we intended to hydrate the calcined material in aqueous alkaline solution to maintain the structure of the layered material and improve its basic nature by introduction of some terminal hydroxyl ions (Brönsted basic sites) [23]. The crystallite size derived from the Scherrer equation [24] showed that MgAl-HT-RH is much lower in size (20 nm) than MgAl-HT (160 nm). The pronounced decrease in the crystallite size of the rehydrated layered double hydroxide structure could improve the catalytic performance towards the Henry reaction.

Scanning Electron Microscopy (SEM)
SEM images of all the investigated catalysts are given in Figure 2. The hydrothermal treatment under autogenous pressure at 170 • C for the coprecipitated MgAl-HT sample (Figure 2A) resulted in the formation of uniform hexagonal platelets of the layered material with 180 nm particle size. The calcination of MgAl-HT led to a pronounced collapse in the layered structure due to the removal of the interlayer anions and thermal decomposition of the hydroxide carbonate into the corresponding metal oxides (MgAlO x ) ( Figure 2C) [22]. Alkaline treatment of the mixed oxide led to the building of the interlayer gallery between hexagonal platelets of relatively small particle size (20 nm) for MgAl-HT-RH ( Figure 2B).

N 2 Physisorption
N 2 adsorption/desorption isotherms of all the synthesized materials are given in Figure 3. Mesoporous isotherms of Type IV were detected. H3-hysteresis was recorded, which is characteristic of the occurrence of open, relatively large pores that could facilitate reactant/product diffusion through the catalysts [15]. BET surface area of all the investigated solid materials was calculated and is depicted in Table 1. MgAl-HT showed the smallest surface area of all samples (84 m 2 /g), while the calcined sample (MgAlO x ) recorded the biggest BET surface area (167 m 2 /g). The obvious rise in surface area was allocated to the creation of craters through the layers due to development of CO 2 and H 2 O [25]. Rehydration of the calcined layered double hydroxide in the alkaline solution by mechanical stirring at room temperature led to an increase in surface area as a result of the breaking of particles and a noticeable exfoliation of the crystals [26].  The measure of the basicity of the diverse solids was attained by TPD of CO 2 . It is well known that types of basic sites can be detected by CO 2 uptake, which is related to diverse types of carbonate coordination in the lamellar interplanetary of layered double hydroxide. The monodentate, bidentate, and bicarbonate anions are often fashioned through the saturation of CO 2 to the basic materials [27]. Monodentate and bidentate carbonate creation contains low-coordination oxygen anions and are then considered as strong basic sites and the creation of bicarbonate anions involves surface hydroxyl groups [28]. The MgAl-HT sample displayed four desorption peaks of relatively low intensity ( Figure 4). The low temperature peaks in the range 150-400 • C could be attributed to the desorption of weakly confined CO 2 and breakdown of remaining carbonate ions existing in the MgAl-HT sample [29]. The other two desorption peaks at 450 • C and 665 • C were mostly credited to bicarbonate groups fashioned by the contact of CO 2 with hydroxyl groups in the MgAl-HT and the progress of powerfully attached surface metal carbonate species, respectively. The calcined catalyst (MgAlO x ) presented three desorption peaks at 150 • C, 420 • C, and between 510 and 520 • C. The desorption peak at about 420 • C can be accredited to the influence of mostly bidentate carbonate species, together with bicarbonate species. The attendance of a peak at 540 • C is owed to the occurrence of monodentate species. The presence of the two peaks signified the occurrence of OH − groups with diverse strengths. The differences in CO 2 uptake values between as-synthesized and calcined catalysts can be credited to the presence of misdeeds or linear imperfections in the platelets of the calcined sample. SEM images showed the collapse in the layered structure of hydrotalcite upon thermal treatment at 500 • C. The high intensities of peaks at high temperature could be explained by the formation of Lewis basic sites due to the MgO formation as complemented by XRD data. As we observed, the hydration of the calcined metal oxides (MgAl-HT-RH) resulted in a material with high peak intensity at 420 • C, 500 • C, and a small peak at 620 • C. The pronounced increase in the peak intensity at 420 • C could be attributed to the formation of terminal Brönsted OH − basic sites together with some Lewis basic sites at high desorption temperature [18]. The pronounced increase in low-and high-temperature basic sites of MgAl-HT-RH could provide superior catalytic activity for this particular catalyst towards solid base catalyzed Henry reactions.

Catalytic Activity Study
The Henry reaction is a base-catalyzed, C-C bond-forming reaction between nitroalkanes and aldehydes or ketones. The catalytic efficacy of MgAl-HT, MgAlO x , and MgAl-HT-RH was tested for the Henry reaction (Scheme 1). The reaction between nitroalkanes (1a-c) with different aromatic aldehydes (2a-e) in the presencew of all the catalysts was carried out utilizing conventional methods and solvent-free, microwave-assisted reactions to attain only a single isolable product in each case (as investigated by TLC). The identified products were 2-methyl-2-nitro-1-arylpropan-1-ol derivatives (3a-e) in the case of 2-nitropropane as a reactant, or 2-nitro-vinylbenzene and 2-nitroprop-1-enylbenzene derivatives (4a-j) in the cases of nitromethane and nitroethane as reactants, respectively. All the structures of the isolated products 3a-e and 4a-j were elucidated using IR, 1 H NMR, 13 C NMR, and MS analyses. The IR showed a characteristic band for OH groups for 3a-e products, which was not recorded for products 4a-j. The mass bands of the isolated products displayed peaks matching their molecular ions.
The catalytic reaction using different investigated catalysts were carried out between 1a and 2a under conventional and microwave irradiation and the obtained results are given in Table 2. It is revealed from this table that the MgAl-HT-RH catalyst resulted in satisfactory yields of the products. The reaction carried out under microwave irradiation exhibited improved yield (99%) in a very short reaction time (14 min) in comparison to the conventional conditions (90%, 5 h). Therefore, this specific catalyst was nominated as the greatest catalyst to assess the other reactions and the obtained results are briefed in Figure 5. It is seen from Figure 5 that MgAl-HT-RH displays an effectual activity and higher % yield in assessment to the reported data [21]. The comparison between this particular catalyst (MgAl-HT-RH) and other heterogeneous catalysts used to catalyze the Henry reaction reported in literature is presented in Table 3. The data obtained from this table revealed that the MgAl-HT-RH catalyst is the best heterogenous catalyst ever used until now for the synthesized Henry products presented in Table 3. The advanced activity of this catalyst is owed to the high surface area (134 m 2 /g) and strong Lewis and Brönsted basic sites associated with this catalyst. The hydration of MgAlO x resulted in the formation of terminal OH − that increased the basicity of the catalyst [22], accordingly enhancing the catalytic activity of MgAl-HT-RH towards the Henry reaction.    [37] It was vital to study the stability of MgAl-HT-RH catalysts under the microwave operation. Therefore, a particular reaction between 1a and 2a was repeated five times with a redeveloped catalyst. The solid catalyst was subsequently filtered and washed by ethanol for each catalytic cycle, then dried in vacuo. The recovered catalyst was tested numerous times (five periods). The catalytic activity was recorded for the time of the achievement of the reaction and the results attained are given in Figure 6.  Figure 6 shows that the redeveloped catalyst achieved the reaction capably underneath constant reaction conditions even being subsequently utilized for five times. The observed decay in the catalytic activity was recorded after recycling the catalyst for the fifth time. Our previous studies using XRD technique for the reused catalysts in Aza-Michael addition reactions showed that the reused catalyst was contaminated by organic moieties being adsorbed on the catalyst active sites and caused the temporary poisoning of the regenerated catalyst [15]. The minor deterioration detected in the catalytic action of the MgAl-HT-RH catalyst after reuse for five times could be assigned to the temporary poisoning from organic poisons and/or to the loss in weight by the filtration/washing process.

Reagents
All chemicals used were of analytical grade purchased from Sigma Alderich (Dorset, UK).

Catalyst Synthesis
Catalysts were prepared by coprecipitation methods as in the literature [38,39]. Mixing of magnesium nitrate Mg (NO 3

Catalyst Characterization
The chemical analysis of the prepared solid catalysts was evaluated by using ICP-AES, Optima 7300DV (Perkin Elmmer Corporation, Waltham, MA, USA) apparatus. X-ray diffraction (XRD) analysis using a Bruker diffractometer (Bruker D8 advance target, Bruker, Karlsruhe, Germany) was utilized using Cu Kα1 and a monochromator (λ = 1.5405 Å) at 40 kV and 40 mA. Particle size of the solid was calculated by means of Scherrer Equation: D = Bλ/β 1/2 cosθ, where D is the average particle size of the solid phase under examination, B is the Scherrer constant (0.89), λ is wavelength of the X-ray beam used (1.5405 Å), β 1/2 is the full width at half maximum (FWHM) of the peak, and θ is the angle of diffraction.
A JEOL JSM840A instrument (JEOL, Tokyo, Japan) Scanning Electron Microscope (SEM) was utilized to investigate the morphology of solid samples. Prior to each measurement, the sample was placed on an aluminum block utilizing carbon tape. Physisorption of N 2 at −196 • C using a NOVA 3200e automated gas sorption system (Quantachrome, Boynton Beach, FL, USA) was applied to investigate the pore structure of the solids. Before every measurement, adsorbent was pretreated at 150 • C for 6 h. The Brunauer-Emmett-Teller (BET) equation was applied to determine the specific surface area, while the average pore radius was deduced from the equation: 2V p /S BET , as V p is the total pore volume (at P/P 0 = 0.98). CO 2 TPD analysis was performed using CHEMBET 3000 (Quantachrome, FL, USA). Outgassing of the sample at 100 • C (1 h) was performed while passing helium to detach physisorbed water. Then the saturation of the sample with the CO 2 at 120 • C occurred. The temperature-programmed desorption was simply achieved by ramping the adsorbent temperature at 10 • C/min to 800 • C.

Characterization of Reaction Products
All melting points of the reaction products were measured on a Gallenkamp melting point apparatus and were uncorrected. 1 H NMR spectra, 13 C NMR spectra were recorded on a Bruker AM250 NMR spectrometer (Bruker, Karlsruhe, Germany) using CDCl 3 as solvent for the samples. Mass spectra were recorded on Shimadzu LCMS-QP 800 LC-MS (Kyoto, Kyoto Prefecture, Japan), IR for the synthesized compounds were recorded in potassium bromide discs on a Shimadzu FTIR 8101 PC infrared spectrophotometer. Elemental analysis was obtained using a PerkinElmer 2400 II series CHN Analyser (Waltham, MA, USA). Thin-layer chromatography (TLC) was carried out on precoated Merck silica gel F254 plates. Microwave experiments were carried out using CEM Discover Labmate TM microwave apparatus (300 W with ChemDriver TM Software).

Method A: Conventional Method
A mixture of aldehydes 2a-e (10 mmol), nitroalkanes 1a-c (10 mmol), and 0.2 g of catalyst were heated together in a three-necked, round-bottomed flask at 90 • C. The progress of the reaction was monitored by TLC. Upon completion of the reaction, the mixture was cooled and the product was extracted by dissolution in hot alcohol. The catalyst was filtered off and washed by alcohol prior to drying and reuse. After evaporation of volatile materials under vacuum, compounds 3a-e and 4a-j were recrystallized from the EtOH/DMF mixture.

Conclusions
In brief, solid base catalysts from the layered double hydroxide family, MgAl-HT, its calcined mixture (MgAlO x ), and activated alkali-treated oxide mixture (MgAl-HT-RH) were successfully synthesized and fully characterized using different techniques. The Henry reaction between benzaldehyde and nitromethane over solid base catalysts was attained. MgAl-HT-RH catalyst gave a precious advantage over all other solid base catalysts utilizing conventional or microwave-assisted reaction conditions. The microwave irradiation technique introduced high yields of β-alcohol derivatives using the layered double hydroxide catalysts in a very short time. Novel Henry products were synthesized in good yield (96%) in the current work for the first time. The relatively large surface area, mesoporous nature, and strong basic sites of rehydrated catalyst (MgAl-HT-RH) were responsible for the power of catalytic activity. The catalyst was reusable and its activity could be sustained after five catalytic cycles. The catalysts' superior efficiency and sustainability for carbon-carbon coupling via the Henry reaction makes them a promising candidate for further coupling reactions.