Mixed Oxides as Catalysts for the Condensation of Cyclohexanol and Benzaldehyde to Obtain a Claisen–Schmidt Condensation Product

Abstract

Acid–base M²⁺MgAlO and M²⁺AlO mixed oxides (where M²⁺ = Mg, Cu, Co, Zn, and Ni) were obtained by thermal decomposition of the corresponding layered double hydroxide (LDH) precursors and used as catalysts for cyclohexanol and benzaldehyde condensation under solvent-free conditions. The catalysts were characterized by X-ray diffraction (XRD), X-ray fluorescence (XRF), scanning electron microscopy (SEM), and temperature-programmed desorption of CO₂ (TPD-CO₂). Gas chromatography–mass spectroscopy (GC/MS) was used for the identification and quantification of the product mixtures. In the reaction of cyclohexanol and benzaldehyde on M²⁺MgAlO and MgAlO catalysts, a 2,6-dibenzylidene-cyclohexanone was obtained as the main product as a result of consecutive one-pot dehydrogenation of cyclohexanol to cyclohexanone and subsequent Claisen–Schmidt condensation. In the reaction mixture obtained in the presence of NiAlO, CoAlO, and ZnAlO catalysts, a cyclohexyl ester of 6-hydroxyhexanoic acid was detected together with the main product. This is most likely a by-product obtained after the oxidation, ring opening, and subsequent esterification of the cyclohexanol.

1. Introduction

Over the last decade, considerable effort has been devoted to the study and the development of cleaner and more efficient routes to the production of fine chemicals [1]. In this sense, the design of multifunctional catalytic materials has been presented as a possible way to reduce the number of synthetic steps and to realize one-pot synthetic operations. These one-pot processes allow for different reactions to be carried out in a single vessel without purification between the steps, avoiding stop-and-go reactions and providing economic and environmental benefits [2,3]. The realization of such types of processes requires the use of alternatives to conventional homogeneous acids and bases. Therefore, layered double hydroxides (LDHs), also known as hydrotalcite minerals, have recently been extensively studied with particular regard to achievements in the application of these materials in fine and specialty chemical synthesis. As heterogeneous catalytic systems, they have inherently superior advantages as green, reusable, and inexpensive materials [4,5,6].

Hydrotalcites are anionic clay materials first synthesized by Feitknecht [7]. These compounds are represented by the general formula [M(II)_1−X M(III)_X(OH)₂]^X+(A)ⁿ⁻_x/n·mH₂O, where the divalent ion can be Mg²⁺, Ni²⁺, Zn²⁺, Cu²⁺, Co²⁺, or Mn²⁺, the trivalent ion can be Al³⁺, Fe³⁺, Cr³⁺, or V³⁺, the compensating anions CO₃²⁻, NO₃⁻, OH⁻, Cl⁻, etc., and x can have values ranging between 0.15 and 0.40. This is a layered structure with positively charged brucite-like layers, where M²⁺ cations are replaced by M³⁺ cations and the interlayers contain the charge-balancing anions and water molecules [8].

The thermal decomposition of LDH leads to the formation of mixed oxides, which are often found to be more active as catalysts than their precursors. The acid–basic properties of the mixed oxides depend on the nature and ratio of the divalent and trivalent cations. Lewis acidity occurs as a result of the iconicity of the element–oxygen bond. The surface basicity, associated with the anionic charge of the oxygen species, has the same origin. Therefore, Lewis acidity is generally associated with basicity. The ionic oxides have both basicity and Lewis acidity, but these two opposite properties are balanced differently [9]. The balance between these two properties depends mainly on the polarizing power (charge/radius) of both cations. Obviously, if both cations are highly polarizing, the Lewis acidity will predominate, whereas if both are weakly polarizing (large radius, low charge), the basicity will predominate. When a highly polarizing cation is combined with a weakly polarizing one (both entering the oxide in close packing), these two properties will mix. The introduction of transition metal cations, such as Cu²⁺, Co²⁺, Ni²⁺, and Zn²⁺, will alter the acid–base equilibrium of the LDH materials. CO₂- and NH₃-TPD experiments show that the introduction of transition metal cations into the mixed oxides leads to the accentuation of their acidic character [3,10].

On the other hand, the introduction of transition metal cations such as Zn and Cu into the MgAl mixed oxides alters and impacts the performance of reactions such as hydrogen transfer from a donor molecule (usually a secondary alcohol) to the acceptor one [3] and dehydrogenation or dehydration of alcohols and coupling of alcohols and aldehydes [11,12,13].

Catalysts based on transition metals, such as mixed oxides, are used in many economically important sectors, including the pharmaceutical, agrochemical, and petrochemical industries, etc. [14,15,16,17,18,19]. Several different solid base catalysts, such as SnCl₄ [20], Mg/Al- and MgZnAl-LDH [21,22], and solid NaOH [23], have been reported in the literature for the synthesis of bis(benzylidene)cycloalkanones. The Claisen–Schmidt condensation reaction is the classical method used for the synthesis of bis-(benzylidene)-alkanones. In most cases, they have been obtained by coupling carbonyl compounds in the presence of catalysts possessing suitable strong acid and base sites. There are only a few studies in which these compounds have been obtained by the interaction of alcohols with aldehydes in the presence of RhCl(PPh₃)₃/BF₃·OEt₂ catalysts [24,25] and over the K₂CO₃, where the authors have assumed a combinatorial mechanism involving the Meerwein–Ponndorf–Verley reduction, reverse Oppenauer oxidation, and Claisen–Schmidt condensation of secondary alcohols with aryl-aldehydes [26].

The aim of this research work was to study coupling reactions between cyclohexanol as a secondary alcohol and carbonyl compound benzaldehyde over mixed oxides M²⁺MgAlO (M²⁺ = Cu, Co, Zn, Ni) and M²⁺AlO (M²⁺ = Mg, Co, Zn, Ni) with high transition metal contents. By means of this selected reaction, we have attempted to realize a single-pod dehydrogenation reaction of cyclohexanol followed by Claisen–Schmidt condensation of the obtained cyclohexanone with benzaldehyde. In this research, we have used cyclohexanol as a cheap reagent to obtain the 2,6-dibenzylidene cyclohexanone.

2. Results and Discussion

2.1. Characterization of Catalysts

The XRD pattern of MgAl LDH (Figure 1a) corresponds to the powder diffraction data of hydrotalcite (ICDD card No 70-2151). The observed d₀₀₃ (8.03 Å) distance, larger than that of hydrotalcite (7.78 Å), reflects the presence of NO₃⁻ in the interlayer space [27]. The powder XRD patterns of M²⁺MgAl LDH are similar to those of MgAl LDH. The absence of impurity phases and the d₁₁₀ value data indicate successful incorporation of the various transition metals into the LDH structure. According to the symmetry of the hydrotalcite R − 3 m (a = 2 × d₁₁₀), the calculated values for the parameter a correlated with the ionic radii of the cations (

Table 1. Powder XRD data of M²⁺MgAl LDH and their calcined form.

Sample	a = 2 × d110, Å	c = 3 × d003, Å	D *, Å
			003	110
MgAl LDH	3.060	24.090	62.74	186.75
ZnMgAl LDH	3.060	24.093	88.41	214.39
NiMgAl LDH	3.052	24.090	76.09	151.61
CoMgAl LDH	3.060	24.091	62.73	196.05
CuMgAl LDH	3.058	24.092	83.64	214.47
Sample	a = 2 × d200, Å		D *, Å
			200	220
MgAlO	4.194		56.03	68.08
ZnMgAlO	4.192		59.26	71.35
NiMgAlO	4.188		57.01	68.08
CoMgAlO	4.192		41.84	46.52
CuMgAlO	4.192		50.25	60.83

D * represents the mean crystallite size (derived from the Debye–Scherrer equation) determined from the FWHM of the given reflections.

). The crystal size measured by the Scherrer equation is in accordance with the size of plate crystals observed by SEM (Figure 1a).

The XRD patterns of all calcined M²⁺MgAl LDH show that a mixed oxide with a periclase-type structure (Fd3m) was formed (Figure 1b). The calculated parameter a is consistent with the ionic radii of the cations (Table 1). The SEM data suggest preservation of the dimensions of the original plate crystals (Figure 1a), but the dimensions measured by the Scherrer equation are significantly smaller than those of the original samples (Table 1) as a result of the thermal phase transformation [27,28].

The powder XRD patterns of M²⁺Al LDH reveal the formation of a single crystalline phase LDH with a hydrotalcite-type structure (Figure 2a). The samples obtained under the same synthesis conditions have different degrees of crystallinity and some specific morphological features. ZnAl LDH has the highest degree of crystallinity, which is clearly visible in the SEM photograph of the sample.

The lowest degree of crystallinity is observed for NiAl LDH, which is represented by its typical thin crystals forming rose-like aggregates (Figure 2a). Thermal treatment of M²⁺Al LDH results in the formation of mixed oxides of different structural type. The mixed MgAlO and NiAlO catalysts exhibit a periclase-type structure (Fd3m), the structure of ZnAlO samples is of zincite type (P6₃mc), and CoAl LDH thermally converts to mixed oxide with a spinel-type structure (Fd3m) (Figure 2b).

The chemical composition of the investigated mixed oxides is presented in

Table 2. Chemical composition of the catalysts.

Catalyst	M2+/(M2+ + Mg + Al)		(M2+ + Mg)/Al		TB * mmol/g	Catalyst	M2+/Al		TB * mmol/g
	Theor.	Exp.	Theor.	Exp.			Theor.	Exp.
CuMgAlO	0.1	0.13	3	3.2	93.9	MgAlO	3	2.9	114.3
CoMgAlO	0.1	0.13	3	3.2	76.8	CoAlO	3	3.2	33.4
ZnMgAlO	0.1	0.12	3	3.4	103.5	ZnAlO	3	3.2	55.4
NiMgAlO	0.1	0.12	3	3.1	92.3	NiAlO	3	3.1	23.1

TB *: total basicity; M²⁺ = Co²⁺, Zn²⁺, Ni²⁺.

. The obtained results show that for the M²⁺MgAlO samples, the molar ratio (M²⁺ + Mg)/Al is slightly higher than that used in the preparation. The transition metal content of the catalysts was slightly higher than the theoretical one.

The basic characteristics of M²⁺MgAlO and M²⁺AlO oxides were determined using the TPD of CO₂ (Figure 3). The total concentration of basic centers (TB, in mmol/g) is shown in Table 1. The resulting values show that the amounts of evolved CO₂ on MgAlO and M²⁺MgAlO samples were significantly higher than those on M²⁺AlO (M²⁺ = Co, Zn, Ni) and were in the range between 114.3 mmol/g and 23.1 mmol/g, with MgAlO and NiAlO showing the highest and the lowest values, respectively. Based on our TPD results, the surface basicity of the mixed oxides used may be described as “weak” basic sites for CO₂ desorption occurring at about 100–150 °C, “medium” basic sites for CO₂ desorption occurring in the range between 150 °C and 250 °C, and “strong” basic sites above 250 °C [29]. Mixed oxides containing Lewis acid cations, such as CoAlO, ZnAlO, and NiAlO, presented abundant base sites of weak strength, and CO₂ desorption occurred at about 100 °C. The mixed oxides CuMgAlO, CoMgAlO, ZnMgAlO, NiMgAlO, and MgAlO containing Mg²⁺, which is a less electronegative cation, showed higher peaks corresponding mainly to medium-strength and strong basic sites. No correlation was observed between the basicity of the M²⁺MgAlO and the electronegativity of the transition cation. For the MAlO samples, the measured basicity followed the electronegativity of M²⁺.

The highest total basicity was observed for MgAlO and ZnMgAlO oxides, followed by CuMgAlO and NiMgAlO, with comparable concentrations of centers; consequently, CoMgAlO and, finally, ZnAlO, CoAlO, and NiAlO had the lowest concentrations of basic centers. Obviously, the introduction of the transition cations in the M²⁺MgAlO structures decreased the total concentration of basic centers, and the number of medium-strength acid–base pairs increased when M²⁺-O²⁻ pairs were introduced due to the higher electronegativity of M²⁺ cations as compared to Mg²⁺. Mixed oxides containing Lewis acidic cations, such as CuAlO, CoAlO, ZnAlO, and NiAlO, presented low base sites, and CO₂ desorption occurred at about 100 °C.

2.2. Catalytic Activity

Condensation of Cyclohexanol and Benzaldehyde

The solvent-free condensation reaction of cyclohexanol and benzaldehyde was performed to evaluate the correlation between the acid–basic properties of the prepared mixed oxides and their catalytic characteristics in an acid–basic catalyzed reaction. The only product obtained on M²⁺MgAlO and MgAlO was 2,6-dibenzylidenecyclohexanone. The product 2,6-dibenzylidene-cyclohexanone was identified by its mass spectrum (MS (EI): [M]⁺. m/z = 274(81), 273(100), 245(8), 217(20), 203(6), 141(7), 128(11), 115(23), 102(5), 91(9), 77(5), 65(3), 51(3)). No by-products of oxidation were identified in the analyzed reaction mixtures. It is already known that in the presence of mixed oxides and in air, benzaldehyde can be converted to benzoic acid and cyclohexanol to adipic acid [4,30]. The conversion of cyclohexanol and the amount of the main product expressed in percent are shown in Figure 4.

The conversion reached 97% of the reaction for CoMgAlO and decreased to 4% in the presence of ZnAlO. The conversions achieved with the different mixed oxides are ranked as follows: CoMgAlO > CuMgAlO > NiMgAlO > ZnMgAlO > MgAlO > CoAlO > NiAlO > ZnAlO, and almost the same order is also valid for obtaining 2,6-dibenzylidene-cyclohexanon. The results show that mixed oxides containing Mg and transition metals—M²⁺MgAlO type—are active and selective with respect to the Claisen–Schmidt condensation product. The lower conversion values observed for M²⁺AlO types of catalysts compared to the MgAlO and M²⁺MgAlO types must be related to the lower intrinsic basic character, which decreased their ability to abstract a proton from the hydroxyl group of cyclohexanol and start the dehydrogenation reaction (Figure 5). The different conversion percentage of cyclohexanol to cyclohexanone, and its subsequent interaction with benzaldehyde in reactions with M²⁺MgAlO owing to one type of structure (periclase-like), could be assumed to be due to the transition metal in the catalysts. In the case of M²⁺AlO, the realization of the conversion is most probably controlled by the structure type of the catalysts. The observed lowest conversion on ZnAlO could be affected by the tetrahedral Zn²⁺ coordination in the zincite structure. The CoAlO mixed oxide is represented by a spinel structure, causing an oxidation of 2/3 of the cobalt Co²⁺ to Co³⁺. According to the TPD results, MgAlO and M²⁺MgAlO possess acid–base centers of medium strength of M²⁺-O²⁻ type, which are suitable for the successful initiation of the dehydrogenation reaction.

We assume that the reaction producing the main product begins with the non-oxidative dehydrogenation of cyclohexanol to the ketone (Scheme 1A). The first step involves the adsorption of cyclohexanol over catalyst and the interaction of the hydroxyl group with lattice oxygen and adjacent metal species. This probably occurs with the participation of magnesium or transition metals, which are involved in the formation of medium-strength Lewis base centers. In the next step, hydride transfer from cyclohexanol to the catalytic surface occurs, and it is probable that the alcohol is converted to the alkanone in situ, and then, the Claisen–Schmidt reaction is initiated (Scheme 1B).

As already described in the literature, the cyclohexanone conversion increases rapidly in the beginning and reaches a plateau after 100 min. In addition, the Claisen–Schmidt reaction proceeds through successive steps in which hydrogen is first abstracted from an α-position of cyclohexanone to form the nucleophilic species. The nucleophile then interacts with the carbonyl function of benzaldehyde, generating the mono-condensed product 2-benzylidene-cyclohexanone and then proceeds via strong base sites to the di-condensed product, and after 60 min, only this product is available [21]. Based on these observations, we decided to run our experiments for 120 min.

As a by-product of the oxidation and self-condensation of cyclohexanol, cyclohexyl ester of 6-hydroxyhexanoic acid was detected on NiAlO, CoAlO, and ZnAlO. The detected amounts were 23%, 18%, and 15%, respectively. A possible reaction mechanism is presented in Scheme 2.

In the course of the reaction, some of the cyclohexanol apparently undergoes oxidation, most likely involving oxygen from the air. Based on our previous studies, we assume that the reaction could probably be initiated by the adsorption of cyclohexanol and oxygen molecules on the catalyst surface and the simultaneous release of hydroperoxide with the participation of the acid–base pairs from the catalytic surface. The oxidation to hydroperoxide proceeds at the secondary carbon atom in position 2. This effect might be related to the adsorption of the cyclohexanol molecules on medium-strength or strong Lewis basic sites followed by cyclohexyl ring opening [30].

3. Materials and Methods

3.1. Synthesis of the Catalysts

The LDH precursors of the catalysts used were prepared by a co-precipitation method at room temperature [8]. The M²⁺MgAl-LDHs were synthesized by the following procedure: aqueous solutions as Mg(NO₃)₂·6H₂O and Al(NO₃)₃·9H₂O ((M²⁺ + Mg)/Al = 3 at 1 M) were added dropwise at a rate of 600 rpm into a beaker containing a transition metal nitrate solution such as Co(NO₃)₂·6H₂O, Ni(NO₃)₂·6H₂O and Zn(NO₃)₂·6H₂O. The pH was maintained at 10 ± 0.2 with an appropriate volume of 1M NaOH solution. The M²⁺/(M²⁺ + Mg + Al) atomic ratio was 0.1, and the transition metal content was 10% in terms of cations. The resulting precipitates were aged in their mother liquor at 90 °C in an air atmosphere for 24 h, cooled to room temperature, and filtered and washed repeatedly with distilled water to remove residual nitrates and sodium and to achieve a pH of 7. The solids were then dried in an oven at 90 °C for 18 h. The corresponding mixed oxides (MMgAlO) were then obtained by calcination at 500 °C for 2 h in air.

The M²⁺Al-LDH precursors were prepared by dropwise mixing of two solutions, with the first solution containing 1M transition metal (M²⁺) nitrate, such as Mg(NO₃)₂·6H₂O, Co(NO₃)₂·6H₂O, Ni(NO₃)₂·6H₂O, Zn(NO₃)₂·6H₂O, and Al(NO₃)₃·9H₂O (M²⁺/Al = 3), and 1 M NaOH as the second solution.

Typically, a 60 mL aqueous solution contained Mg(NO₃)₂·6H₂O or transition metal nitrate and Al(NO₃)₃·9H₂O (0.75/0.25 molar ratio) and approximately 120 mL of 1 M NaOH. The two solutions were added dropwise with stirring to 50 mL of distilled water at room temperature. The addition was carried out over 1.0–1.5 h, and the pH values of the resulting mixed solutions were maintained at about 8. The resulting slurries were hydrothermally treated in their mother liquor at 90 °C for 24 h, filtered, washed repeatedly, and then dried at 90 °C for 18 h in air. The corresponding mixed oxides (M²⁺AlO) were obtained by calcination of the dried samples for 2 h at different temperatures. MgAlO was obtained at 500 °C, while CoAlO, NiAlO, and ZnAlO were obtained at 350 °C, respectively. The calcination temperatures were chosen to produce mixed oxides rather than single element oxides [31]. Finally, all the mixed oxides were finely ground in an agate mortar and stored in a desiccator.

3.2. Characterization of the Catalysts

Powder X-ray diffraction measurements were performed to study the structures of the catalysts using a BRUKER instrument (Billerica, MA, USA) with filtered Co-Kα radiation. It was operated with 0.02° (2θ) steps in the interval of 4–80 2θ angular range with 1.5 s counting time per step. The specialized Diffrac.EVA version 5.2.0.5 software was used for qualitative phase composition determination. The morphology was investigated using a scanning electron microscope (SEM) JEOL—model JSM-6010PLUS/LA (Akishima, Japan) fitted with an energy-dispersive spectrometer (EDS).

The metal contents (Mg, Al, Zn, Co, Ni, and Cu) of the catalyst samples were determined by XRF using an EDXRF Epsilon 3XLE, Omnian 3SW instrument (Malvern Panalytical, Malvern, UK). The measurements were conducted on glass disks of lithium borates. The results are summarized in Table 1.

Temperature programmed desorption (TPD) of 10% CO₂ in argon was performed using an ABB model AO2040 infrared gas analyzer (Zurich, Switzerland). The TPD was performed under conditions where diffusion limitations and re-adsorption could be neglected. All TPD experiments were performed with a 0.05 g sample with an average particle size of 250–500 µm mesh. The carrier gas flow velocity was 25 mL/min, and the linear temperature rise rate was 25 °C/min. Prior to the TPD experiments, the samples were pretreated by raising the temperature to 350 °C in an argon stream. This temperature was maintained in the gas environment for 1 h. The catalyst was then cooled to room temperature. After pre-treatment of the samples, the following steps were performed: adsorption of CO₂ at room temperature (RT)—30 min; temperature programmed desorption (TPD) from RT—350 °C; slow cooling of the catalyst to RT; cleaning of the catalyst surface with Ar (about 30 min); adsorption of CO₂ at 100 °C—30 min; slow cooling of the catalyst to RT; cleaning of the catalyst surface with Ar (about 30 min); adsorption of CO₂ at 100 °C—30 min; and TPD from 100—350 °C. To determine the number of basic sites of the mixed oxides using CO₂-TPD, the peaks in the TPD curve corresponding to the desorption of CO₂ from basic sites on the mixed oxides were identified. The area under the peaks was integrated to determine the total amount of desorbed CO₂. The total amount of desorbed CO₂ was used to calculate the number of basic sites on the mixed oxides. Each molecule of CO₂ desorbed corresponded to one basic site on the material.

3.3. Reaction Procedure—Condensation of Cyclohexanol and Benzaldehyde

Each mixed oxide catalyst was activated at 350 °C for 1 h before the reaction. The condensation of cyclohexanol (0.035 mol, >99%, Sigma-Aldrich, St. Louis, MO, USA), benzaldehyde (0.035 mol ReagentPlus >99%, Sigma-Aldrich), and catalyst (250 mg) was studied under solvent-free conditions. The weight ratio of catalyst to reagents was 1/30. The reactions were carried out in a three-necked round-bottom flask equipped with a water-cooled reflux condenser. The resulting mixture was rapidly heated to 150 °C under vigorous stirring (600 rpm) in an oil bath equipped with an automatic temperature control system. The reaction time for all experiments was 2 h.

Gas chromatography–mass spectroscopy (GC/MS) was used to identify and quantify the reaction products. The GC/MS analyses were performed on an HP 6890 chromatograph with an HP 5973 mass selective detector (Agilent, Santa Clara, CA, USA). The column used was HP-5/MS (Agilent), 30 m × 0.250 mm × 0.25 µm. The mass balances, calculated after a reaction time of 2 h, were always higher than 95%.

4. Conclusions

The results presented here show that M²⁺MgAlO and MAlO mixed oxides, where M²⁺ are Mg²⁺, Zn²⁺, Cu²⁺, Ni²⁺, and Co²⁺ cations, are active and convenient in working with catalysts for the solvent-free coupling reaction of cyclohexanol and benzaldehyde. In the presence of M²⁺MgAlO with a periclase-like structure and MgAlO, the only product was a 2,6-dibenzylidene-cyclohexanone. The use of cyclohexanol as a secondary alcohol instead of cyclohexanone (alkanone) to obtain Claisen–Schmidt condensation products can serve as an alternative route for one-pot reaction. The first step of the reaction mechanism is most probably dehydrogenation of cyclohexanol to cyclohexanone (oxidation of cyclohexanol), which proceeds on metal centers. The most efficient catalysts for the preparation of the Claisen–Schmidt product proved to be CoMgAlO, CuMgAlO, NiMgAlO, ZnMgAlO, and MgAlO. The conversion rate reached 97% on CoMgAlO and CuMgAlO (83%) catalysts after a 2 h reaction time at 150 °C. Obviously, the catalytic behaviors were a consequence of the participation of medium strength acid–base active sites with the participation of transition metal cations. Cyclohexanol ester of 6-hydroxyhexanoic acid was detected as a by-product resulting from the oxidation of cyclohexanol accompanied by subsequent ring opening and esterification. This by-product was found only in MAlO-NiAlO, CoAlO, and ZnAlO type catalysts, with the highest amount in the presence of NiAlO.