There has been an increasing emphasis among researchers from both academia and industry to design synthetic strategies keeping in view the principles of “Green Chemistry” . Adopting the principles of green chemistry means to reduce or eliminate the generation and use of hazardous substances. In recent years, replacement of hazardous solvents with environmentally benign solvents   or development of solvent-free syntheses    is one of the major focus areas of Green Chemistry. In other cases, the use of heterogeneous catalysts under solvent-free conditions is becoming very popular as it has many advantages: reduced pollution, reusability, high selectivity, low cost, and simplicity in process and in handling. These factors are especially important in industry.
The 1,1-diacetates (acylals) have been introduced as a suitable protection group for aldehyde because of their remarkable stability to neutral and basic conditions . In addition, they can be converted into other useful functional groups by reaction with appropriate nucleophiles  and used as carbonyl surrogates for asymmetric synthesis . 1,1-Diacetates, on the other hand, are ambident substrates containing two types of reactive carbon centres, the carbon atom of the protected aldehyde function and the carbonyl group in the ester moieties . The relative acid stability of 1,1-diacetates is another interesting feature of such 1,1-diacetates in the field of protection-deprotection chemistry .
The synthesis of acylals is usually achieved via the reaction of an aldehyde with acetic anhydride (AC2O) in the presence of a protic acid    , Lewis acids  -  , or heterogeneous catalyst  - . Many of reported methods, however, involve strongly acidic or oxidizing conditions, corrosive reagents, high temperature, high catalyst loading, longer reaction time and cumbersome procedures. In view of these, the search for finding a cost-effective, mild and simple protocol for synthesis of acylals from aldehydes is still relevant.
In recent years, we have used the synthetic phosphates (hydroxyapatite (HAP) and fluorapatite (FAP)) alone, doped and modified by metal salts as the heterogeneous catalysts for several reactions, such as Knoevenagel condensation   , Friedel-Crafts alkylation    , Michael addition   , hydration of nitriles to amides  , and Cross aldol Condensation . In this work, we wish to report a mild, convenient and green methodology for the synthesis and deprotection of acylals from aromatic aldehydes using ZnCl2/FAP, ZnBr2/FAP, ZnCl2/HAP and ZnBr2/HAP.
2. Results and Discussion
The catalytic activity of the materials prepared has been evaluated in the protection of aromatic aldehydes. First of all, we have tested the apatite (FAP or HAP) alone in the catalysis of the synthesis of acylals (Table 1). The yields obtained are poor. To enhance the activity of apatite (FAP or HAP), the later was doped with different Lewis acids. For an initial evaluation of the activity of ZnBr2/apatite different experiments were carried out using varying values of catalyst weight in the protection of benzaldehyde with acetic anhydride (Table 1). The yield of product 2a increased as weight of catalyst increased. This result indicate the positive effect of the catalyst in this transformation, we have chosen 0.1 g of the catalyst for further study.
To explore the scope of this methodology the protection of different substrates was investigated. To appreciate the important enhancement of the activity of the doped materials, we have carried out synthesis of acylals with ZnCl2/FAP, ZnBr2/FAP, ZnCl2/HAP and ZnBr2/HAP in the same condition (Table 2). The positive effect of doped solid catalysts can be observed in all cases. The yields obtained are high (86% - 97%) at room temperature except for the product required relatively longer reaction time (entry 2e) at 70˚C, possibly owing to the strong electron-withdrawing nitro substituent (see Table 2). Meanwhile, the presence of electron-donating groups (entry 2b, 2d, 2g, Table 2) increases the yields, demonstrating the participation of both the aldehydes and the acetic anhydride in the rate controlling step of the reaction. Furthermore, α, β-unsatured aldehydes, such as cinnamaldehyde (Table 2, product 2f) and acid sensitive aldehydes, such as furfural (Table 2, product 2c) reacted well without any decomposition or polymerization under the selected reaction conditions.
To evaluate the influence of the metal halide in the activity of the doped material, we have compared the yields obtained in the synthesis of product 2a using ZnCl2/HAP, ZnBr2/HAP, ZnCl2/FAP and ZnBr2/FAP. Thus the kinetic curves of these reactions as shown in Figure 1, indicate clearly the promoting effect of Lewis acids, ZnBr2/HAP appear to be somewhat the more active catalyst. Reuse of ZnBr2/HAP was studied in the synthesis of product 2a. The yields obtained were 94%, 76% and 69% using the fresh catalyst and reused for the first and the second time, respectively. The decrease of the yields can be explained by the accumulation of organic substrates over the active sites of the catalyst.
Figure 1. Kinetic curves of product 2a synthesis using HAP and FAP doped with ZnCl2 and ZnBr2.
Table 1. Effect of the weight of ZnBr2/HAP and ZnBr2/FAP in the synthesis of product 2a.
Table 2. Preparation of 1,1-diacetates from aldehydes.
aAll 1,1-diacetates were identified by their 1H NMR, 13C NMR spectra. bIsolated yield. cThe reaction mixture was stirred at 70˚C.
Recently, microwave-assisted solvent-free synthesis in organic reactions has been of growing interest as an efficient, economic and clean procedure (“green chemistry”)     . For these reasons, we have tried the method for deprotection of geminal-diacetates catalyzed by same supports FAP, HAP, ZnBr2/FAP, ZnCl2/FAP, ZnBr2/HAP and ZnCl2/HAP). The results are summarized in Table 3. The reaction were completed within 3 min for
Table 3. Regeneration of aldehydes from 1,1-diacetates.
ZnX2/apatite (P = 300 W) and high yields (82% - 96%) of regeneration of aldehydes. Whereas, similar reaction in the presence of apatite alone (P = 500 W) afforded moderate yields of product (49% - 63%) within 10 min of irradiation time.
It was noticed that there was no reaction under microwave without catalyst, and to what was observed in traditional heating without solvent. This shows a certain synergy between catalyst and the microwave. It is thus completely reasonable to think that the effect of the temperature is a determining factor to promote this transformation. Unfortunately, domestic microwave was used and therefore it was impossible to measure the exact temperature during the reaction.
In conclusion, we have developed a clean and easy method for the synthesis of geminal-diacetates from aldehydes in solvent free conditions, and regeneration of aromatic aldehydes from the corresponding acylals in microwave irradiation using metal halides doped apatite (HAP or FAP) as heterogeneous catalysts. The positive effect of doping the apatite with ZnCl2 and ZnBr2 has been observed, and the comparison of these materials indicates that ZnBr2/HAP is the best catalyst for this reaction. The use of metal halides doped apatite offers diverse advantages including simplicity of operation due to the heterogeneous nature of reaction, easy workup and high yields.
3.1. Preparation and Characterization of the Catalysts
3.1.1. Preparation and Characterization of HAP
The synthesis of hydroxyapatite  is carried out by reaction between diammonium phosphate and calcium nitrate in presence of ammonia. An amount of 250 ml of aqueous solutions containing 7.92 g of diammonium phosphate, maintained at a pH greater than 12 by addition of ammonium hydroxide (70 ml), were dropped under constant stirring into 150 ml of a solution containing 23.6 g of calcium nitrate (Ca(NO3)2H2O). The suspension was refluxed for 4 h. Distilled water (DW) was used to prepare the solutions. The obtained hydroxyapatite was filtered, washed with DW, dried overnight at 80˚C and calcined in air at 800˚C for 1 h before use.
The structure of the obtained hydroxyapatite was confirmed by X-ray diffraction, infrared spectroscopy and chemical analysis. The hydroxyapatite crystallized in the hexagonal system with the space group P63/m. The lattice parameters of the prepared HAP are in excellent agreement with standard data: a = 6.883 A˚ and c = 9.422 A˚. Surface area of the calcined HAP was determined by the BET method from the adsorption-desorption isotherm of nitrogen at its liquid temperature (77 K), and was found to be S = 35 m2・g−1.
3.1.2. Preparation and Characterization of FAP
FAP was prepared by the co-precipitation method as previously reported . The structure of the obtained FAP was confirmed by X-ray diffraction, infrared spectroscopy and chemical analysis. The fluorapatite crystallized in the hexagonal system with the space group P63/m. The lattice parameters of the prepared FAP are in excellent agreement with standard data: a = 9.364 A˚ and c = 6.893 A˚. Surface area of the calcined FAP was determined by the BET method, and was found to be S = 15 m2・g−1.
3.2. Preparation of ZnX2/Apatite (ZnX2/HAP or ZnX2/FAP) [X = Br, Cl]
The preparation of ZnX2/apatite was as follows: 10 mmol of ZnX2 and 10 g of apatite (FAP or HAP) were mixed in 100 mL of water and then evaporated to dryness and dried for 2 h at 150˚C before use.
The XRD patterns of ZnX2/apatite are similar to that of apatite   . The modification of the apatite by ZnX2 impregnation does not change the crystalline structure of the solid material. The intensity of typical diffraction peaks did not significantly change indicating no disorganization of the crystalline structure of apatite. It should be noted that no ZnX2 phases were detected on the doped materials in all cases, indicating that ZnX2 was highly dispersed in the solid apatite.
3.3. Procedure for the Preparation of 1.1-Diacetates
A typical procedure for the preparation of 1,1-diacetates is a follows: the aldehyde (3 mmol) and acetic anhydride (9 mmol) were placed in a two-necked flask with stirring at room temperature. The catalyst (200 mg of apatite (HAP or FAP) or 100 mg of (ZnX2/FAP or ZnX2/HAP) was added and obtained mixture was maintained at room temperature (only for entry 2e a temperature at 70˚C was needed) for the appropriate time (see Table 2). After the completion of the reaction was monitored by TLC (hexane/ethyl acetate 5% - 20%), Et2O was added to the mixture and filtered, and then the catalyst was again washed with Et2O and collected for reuse. Evaporation of the solvent followed by column chromatography on silica gel afforded the pure compound corresponding to 1,1-diacetates.
3.4. Procedure for Deprotection of 1.1-Diacetates
A typical procedure for the regeneration of aldehydes from 1,1-diacetates is a follows: 0.5 g of synthetic phosphates were placed, at 500 w for (HAP or FAP) or 350 w for (ZnX2/FAP or ZnX2/HAP) in a domestic microwave oven, for the appropriate time (Table 3). After the completion of the reaction was monitored by TLC (hexane/ethyl acetate 5% - 20%), Et2O was added to the mixture and filtered. Evaporation of the solvent followed by column chromatography on silica gel afforded the pure compound corresponding to aldehydes.
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