Magnetically recoverable CuFe 2 O 4 nanoparticles as an efficient heterogeneous catalyst for green formylation of alcohols

© 2018 by the authors; licensee Growing Science, Canada.


Introduction
Functional group protection has a crucial role in the synthesis of different kind of organic and pharmaceutical compounds. 1Among the various protecting groups used for the hydroxyl function, formylation is one of the most common protecting methods because of easy and fast formation of formate and it's deprotection under mild conditions. 2,35][6][7][8] A literature review shows that formylation of hydroxyl group can take place by formylating agents in the presence of various reagents/catalysts such as K5CoW12O40•3H2O, 9 In(OTf)3, 10 silica triflate, 11 Bi(OTf)3, 12 Sc(OTf)3, 13 Ce(OTf)4, 14 Cu(NO3)2•3H2O, 15 bismuth(III) salts, 16 (NH4)8[CeW10O36]•20H2O, 17 p-TsCl, 18 TMSOTf, 19 chloral, 20 DBSA, 21 silica sulfuric acid, 22 Mg(HSO4)2, 23 Zr(HSO4)4, 24 RHA-[pmim]HSO4. 25Although, various procedures have been reported for formylation of alcohols, however, most of these methods suffer from using vigorous reaction conditions, organic solvents, heavy metal contamination, expensive reagents/catalysts, long reaction times and low yields.Solvent-free conditions often lead to clean and eco-friendly procedure which do not have to remove and recycle solvents and reduces the harmful effects to the environment.Thus, development of simple methods which utilize mild and low-cost reagents under solvent-free conditions is still a subject of interest.
4][35] CuFe2O4 has magnetic properties and it can be recovered easily from the reaction mixture using an external magnet. 36,37This nano-scale catalyst can be obtained by co-precipitation of copper(II) and iron(III) salts 38 and it also occurs naturally as a mineral.In line with the outlined strategies, herein, we wish to report an efficient and eco-friendly formylation of structurally diverse alcohols with formic acid in the presence of reusable CuFe2O4 under oil bath conditions (60-70 ˚C) (Scheme 1).

Results and Discussion
Though the protection of alcohols by formyl group has been extensively studied in the presence of various catalysts or formylating agents, however, a literature review shows that the capability of magnetically nanoparticles of CuFe2O4 for the titled transformation has not been investigated yet.Prompting by this idea, we therefore decided to study formylation of benzyl alcohol as a model compound by ethyl formate or formic acid as an available and inexpensive formylating agents in the presence of CuFe2O4 MNPs.Optimization experiments were carried out under different reaction conditions.The illustrated results in Table 1 show that progress of the formylation reaction in formic acid in comparison to ethyl formate is so prominent.In addition, using the molar ratio of PhCH2OH/CuFe2O4 (1:0.5) in HCO2H (0.5 mL) at oil bath (60-70 ˚C) is the requirement for completing conversion of benzyl alcohol to benzyl formate within 1 min (entry 10).Subsequently benzyl formate was obtained in 90 % isolated yield.It is noteworthy that under drastic conditions (refluxing formic acid, bp: 100-101 °C), the rate of formylation reaction was accelerated to some extent (entry 9).However, according to the fact; higher temperature requires higher cost, therefore, the mild reaction conditions mentioned in entry 10 was selected as the optimum of this formylating protocol.Encouraged by the result, the capability of HCO2H/CuFe2O4 system was more studied with the reaction of various benzylic primary and secondary alcohols possessing electron-releasing or withdrawing groups as well as aliphatic ones with formic acid at the optimized reaction conditions.Table 2 shows the general trend and versatility of this synthetic method.As seen, all reactions were carried out successfully in the presence of CuFe2O4 MNPs (0.5 mmol) within 1-120 min to afford the corresponding formyl esters in high to excellent yields (76-96 %).The table also shows that the effect of substitutions on aromatic rings is noteworthy.Electron-releasing groups accelerated the rate of formylation reaction and in contrast withdrawing substitutions prolonged the reaction times through the deactivation of aromatic rings.Moreover, aliphatic primary and secondary alcohols perform the formylation reaction faster than benzylic ones.Entries 17 and 18 show that protocol of HCO2H/CuFe2O4 is also efficient for formylation of hindered (borneol) and allylic alcohols (cinnamyl alcohol).a All reactions were carried out with the molar ratio of alcohol/CuFe2O4 (1:0.5) in formic acid (0.5 mL) under oil bath conditions (60-70 ˚C).b Yields refer to isolated pure products.
Nano catalysts have the ability to reuse in the reactions because of their active surfaces and high stability.In this study, recycling and reusability of CuFe2O4 MNPs were examined in the formylation of benzyl alcohol with formic acid at the optimized reaction conditions.After completion of the reaction, the nanocatalyst was recovered with an external magnetic field, washed with EtOAc for removing contaminants and then reused for second run of the formylation reaction.Fig. 1 represents the reusability of copper ferrite for five times without significant loss of its catalytic activity.

Fig. 1. Reusability of CuFe2O4 for Formylation of Benzyl Alcohol
CuFe2O4 nanoparticles were synthesized according to the reported procedure 35 and were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM).In FT-IR spectrum, the most intensive absorptions belong to the significant bands centered in 587 and 405 cm -1 at low energy.These characteristic features are assigned to vibrations of Cu-O bond in CuFe2O4 nanoparticles (Fig. 2).The absorption band at 587 cm -1 was attributed to stretching vibration of tetrahedral complexes and the absorption band at 405 cm -1 to that of octahedral complexes.The absorption band at 3420 cm -1 represents stretching vibration of surface OH groups.Calcination of CuFe2O4 at 900°C provided nanoparticles with an average size of 75 nm (calculated from Scherrer equation at 2θ = 37°).XRD spectrum of the prepared CuFe2O4 exactly demonstrated tetragonality of the standard spinel structure of CuFe2O4 (JCPDS card No. 34-0425) with a good crystallinity (Fig. 3).
The morphology and size distribution of the prepared nano CuFe2O4 was then investigated by scanning electron microscopy (SEM).Fig. (4a) shows that agglomeration in the prepared CuFe2O4 is high.The SEM analysis also exhibits that the size of nanoparticles varies from 75-116 nm.The TEM image of the sample is given in Fig. 4b.Suitability of this synthetic method was explored by a comparison of the formylation of benzyl alcohol catalysed with CuFe2O4 and other reported reagents (Table 3).Observation of the results shows that in view points of efficiency, availability and reusability of nanaocatalyst and mild reaction conditions the present protocol is more efficient or has a comparable efficiency.a All reactions were carried out with 1 mmol of alcohol.b Temperature of oil bath was 60-70 ˚C.
Although the exact mechanism of this synthetic protocol is not clear, however, we think that a depicted mechanism (Scheme 2) maybe play a role in the formylation of alcohols with formic acid.The mechanism shows that through the existing of hydroxyl groups on the surface of CuFe2O4 followed by dehydration with formic acid, the CuFe2O4-formate composite was prepared.Finally, nucleophilic attack of an alcohol with the prepared formate-composite produces the primarily nanocatalyst and formyl ester product.

Conclusions
In summary, we have shown that magnetically nanoparticles of CuFe2O4 as a recoverable heterogeneous catalyst can be used successfully for formylation of different kinds of alcohols with formic acid.All reactions were carried out successfully with the molar ratio of alcohol/CuFe2O4 (1:0.5) in formic acid (0.5 mL) under oil bath conditions (60-70 °C).The product formyl esters were obtained in 76-96 % yields within 1-120 min.Low cost of the preparation of nanocatalyst, its remarkable reusability, mild reaction conditions, high to excellent yield of the products, short reaction times as well as the benefits of using solvent-free conditions are the advantages which make this protocol a synthetically useful addition to the present methodologies.

Materials and Methods
All reagents and substrates were purchased from commercial sources and were used without further purification.FT-IR and 1 H/ 13 C NMR spectra were recorded on Thermo Nicolet Nexus 670 spectrophotometer and Bruker Avance 300 MHz spectrometer, respectively.The products were characterized by FT-IR and 1 H, 13 C NMR spectra followed by a comparison with authentic data.All yields refer to isolated pure products.TLC (silica gel 60 F254 aluminium sheet) was used for the purity determination of the substrates, products and the reaction monitoring.XRD pattern of CuFe2O4 was recorded on a Bruker D8-Advanced diffractometer with graphite-monochromatized Cu Kα radiation (λ = 1.54056Å) at room temperature.SEM images were determined on a LEO 1430 VP scanning electron microscopy.TEM images were recorded with a Philips CM30 at electron energy of 300 keV.

Preparation of CuFe2O4 nanoparticles
In a porcelain mortar, a mixture of Cu(CH3COO)2•H2O, Fe(NO3)3•9H2O, NaOH, and NaCl (with molar ratio of 1:2:8:2 respectively) was grounded together (50 min).The reaction was occurred during the combination of materials and it was associated by losing heat.The colour of mixtures gradually was changed from blue to brown.Finally, it was converted to a black paste and was washed with distilled water for several times.After filtration, the powder was dried at 80°C for 2 h and then calcinated at 300°C, 500°C, 600°C, 700°C, 800°C and 900°C for 2 h (20 min for each temperature) to generate the final CuFe2O4 MNPs (Scheme 3). 39Scheme 3. Synthesis of CuFe2O4 MNPs

A General procedure for solvent-free formylation of alcohols with HCO2H/CuFe2O4 system
In a round-bottom flask (10 mL) equipped with a magnetic stirrer, a solution of alcohol (1 mmol) and formic acid (0.5 mL) was prepared.To the resulting solution, CuFe2O4 MNPs (0.5 mmol) was then added and the mixture was stirred magnetically in oil bath (60-70 ˚C) for the appropriate time mentioned in Table 2.After completion of the reaction, EtOAc (2 mL) was added and the reaction mixture was stirred for 10 min.The nanocatalyst was then removed from the reaction mixture using an external magnet.The mixture was dried over anhydrous sodium sulfate and passed through a short column of silica gel.Evaporation of the solvent under reduced pressure affords the pure formate product in 76-96% yield.

Scheme 2 .
Scheme 2. A Proposed Mechanism for Formylation of Alcohols with Formic Acid

Table 1 .
Optimization experiments for formylation of benzyl alcohol to benzyl formate under different conditions a All reactions were carried out with 1 mmol of benzyl alcohol.b Temperature of oil bath was 60-70 ˚C.

Table 3 .
Comparison of the formylation of benzyl alcohol catalyzed by CuFe2O4 and other reported reagents a