Superparamagnetic nanoparticles as a recyclable catalyst: A new access to phenol esters via cross dehydrogenative coupling reactions

All reagents and starting materials were obtained commercially from Sigma-Aldrich and Merck, and were used as received without any further purification unless otherwise noted. Nitrogen physisorption measurements were conducted using a Micromeritics 2020 volumetric adsorption analyzer system. Samples were pretreated by heating under vacuum at 150 oC for 3 h. X-ray powder diffraction (XRD) patterns were recorded using a Cu Kα radiation source on a D8 Advance Bruker powder diffractometer. Elemental analysis with atomic absorption spectrometry (AAS) was performed on an AA-6800 Shimadzu. Magnetic properties were measured with a EV11 vibrating sample magnetometer (VSM) at room temperature. Scanning electron


Introduction
Esters and their derivatives are prevalent structures existing in diverse collections of biologically active molecules, with a broad range of applications in many elds such as pharmaceutical chemicals, fragrance chemicals, agricultural chemicals, and functional materials. [1][2][3] Phenol esters are conventionally generated from phenols and carboxylic acid derivatives utilizing a considerable quantity of bases, showing numerous drawbacks, and therefore, synthetic pathways to these skeletons must be improved. 4,5 Benzothiazole derivatives are precious heterocyclic scaffolds present in numerous natural products or synthetic chemicals, offering valuable biological activities. 6,7 Organic structures containing both phenol ester and benzothiazole moieties would benet from both functional parts in terms of pharmaceutical and biological activities. Overcoming drawbacks of traditional synthetic approaches where two functional groups must be pre-installed in the reactants, coupling reactions via direct C-H bond activation should provide more efficacious synthetic routes for these valuable skeletons. 8,9 Previously, Ali and et al. developed the rst illustration of a synthetic method to produce structures containing both carbamates and benzothiazoles via the Cu(OAC) 2 -catalyzed coupling reaction between dialkylformamides and phenols having benzothiazole directing substituents (Scheme 1a). 10 Zheng et al. also synthesized phenol esters possessing cyano, azo, and pyridine moieties by using the Cu(OAC) 2 -catalyzed transformation between aldehydes and 2-substituted phenols. 11 Certainly, the eld still remains to be explored, in which recyclable catalysts should be investigated for these transformations.
Catalysis has an essential role in the chemical industry, since it contributes cost-effective, environmentally benign, and selective routes for what are contrastingly expensive, ecohazardous, or even unapproachable. [12][13][14] As inspired by green chemistry principles, utilizing heterogeneous catalysts is favored owing to the possibility of separation and reusability. [15][16][17] "Nanocatalysis" has appeared as an speedily expanding area throughout the last few years, in which nanoparticles have been considered as alternative candidates, combining benets from both homogeneous and heterogeneous catalysts. [18][19][20] Nevertheless, because of their nanometerscaled sizes, the isolation from liquid phase and the reutilizing of the nanoparticles is undoubtedly challenging, and more efforts are needed to solve this issue. 21,22 Superparamagnetic nanoparticles as catalysts would link the merit of superior reactivity and good dispersion in reaction media with straightforward isolation procedure by using magnets. 23,24 Certainly, both functionalized and unfunctionalized superparamagnetic nanoparticles have been utilized as catalysts for numerous organic reactions. [25][26][27][28] We recently performed the coupling reaction between dialkylformamides and phenols having benzothiazole directing substituents utilizing nano CuFe 2 O 4 catalyst (Scheme 1a). 29 In this work, we would like to describe the direct synthesis of chemical structures containing both phenol ester and benzothiazole moieties via cross dehydrogenative coupling reactions, in the presence of CuFe 2 O 4 superparamagnetic nanoparticles as recyclable catalyst (Scheme 1b).
To our best knowledge, these reactions were not previously reported in the literature.

Experimental
CuFe 2 O 4 superparamagnetic nanoparticles were obtained from Sigma-Aldrich. The nanoparticles was subsequently characterized by employing different analysis methods (see Fig. S1-S4 in ESI †). In an illustrative catalytic run, a solution of 2-(benzo[d] thiazol-2-yl)phenol (0.0568 g, 0.25 mmol) and benzaldehyde (0.0795 g, 0.75 mmol) in p-xylene (0.5 mL) was introduced into a pressurized vial as reactor. The catalyst was then added to the solution, and the reactor was shaken to disperse the solid catalyst into the liquid phase. The catalyst quantity was utilized based on the copper/2-(benzo[d]thiazol-2-yl)phenol mole ratio. Aer that, tert-butyl hydroperoxide (tBuOOH, 70% wt. in water; 0.145 mL, 1.0 mmol) as an oxidant was added. The vial was magnetically stirred under argon at 80 C for 24 h. The mixture was then cooled down to ambient temperature, and diphenyl ether (0.0425 g, 0.25 mmol) as internal standard was introduced. Samples were withdrawn, and quenched with water (1 mL). Organic constituents were extracted into ethyl acetate (2 mL), dried with anhydrous Na 2 SO 4 to remove any water residue, and analyzed by GC regarding diphenyl ether. The major product, 2-(benzo[d]thiazol-2-yl)phenyl benzoate, was puried by column chromatography. 1 H NMR, 13 C NMR, and GC-MS analyses were also conducted to verify product structure. For the catalyst reutilizing experiment, the superparamagnetic nanoparticles were collected by decantation using a permanent magnet, washed carefully with p-xylene and methanol, heated at 150 C under vacuum on a Schlenk line for 6 h, and then reused as catalyst for new experiment.

Results and discussion
The CuFe 2 O 4 superparamagnetic nanoparticles were explored as a heterogeneous catalyst for the cross dehydrogenative coupling reaction between 2-(benzo[d]thiazol-2-yl)phenol and benzaldehyde to produce 2-(benzo[d]thiazol-2-yl)phenyl benzoate as the major product (Scheme 1b). Initially, the inuence of solvent on the formation of the hybrid benzothiazole-phenol ester was investigated, having conducted the reaction in various solvents, including DMSO, dichlorobenzene, tert-butanol, DMA, dioxane, and p-xylene (entries 1-6, Table 1). Indeed, liquid-phase organic transformations utilizing metal catalysts are generally affected by the reaction solvents. Zheng et al. previously synthesized phenol esters possessing cyano, azo, and pyridine moieties, and demonstrated that solvent expressed a noticeable inuence on the transformation, in which DMSO emerged as the best solvent. 11 The reaction was performed at 100 C for 24 h, with 2 equivalents of benzaldehyde, at 3 mol% catalyst, in the presence of 4 equivalents of aqueous tert-butyl hydroperoxide as oxidant. Compared to other solvents, p-xylene should be the solvent of choice, and the reaction conducted in this solvent generated 2-(benzo[d]thiazol-2-yl)phenyl benzoate in 66% yield aer 24 h (entry 6, Table 1). Next, we tried to improve the yield of the desired product by changing the reaction temperature (entries 7-12). The reaction conducted at room temperature afforded only 11% yield aer 24 h (entry 7, Table 1). As anticipated, boosting the temperature caused a noticeable enhancement in the generation of the expected product. Best yield was achieved when the reaction temperature was extended to 80 C (entry 10, Table 1). It was noticed that increasing the temperature to over 80 C did not favor the transformation (entries 11 and 12, Table 1). Indeed, Zheng et al. previously performed the Cu(OAc) 2 -catalyzed oxidative esterication of ortho-formyl phenols with aldehydes, and pointed out that the coupling reaction should be conducted at 80 C. 30 Next, the required catalyst amount was investigated for the cross dehydrogenative coupling transformation (entries 13-18, Table 1). It should be emphasized that the reaction could not progress in the absence of the catalyst, and only 3% yield of the major product was detected aer 24 h (entry 13, Table 1). This observation veried that the catalyst should be compulsory for the transformation. Low yield of the expected product was recorded for the reaction utilizing 1 mol% catalyst (entry 14, Table 1). This value could be upgraded to 89% for the reaction conducted with 5 mol% catalyst (entry 16, Table 1). Extending the catalyst quantity to 7 mol% or 10 mol% was not needed, as the yield of 2-(benzo[d]thiazol-2-yl)phenyl benzoate was not augmented markedly (entries 17 and 18, Table 1). It should be noted that 10 mol% catalyst was previously employed for similar transformations, 11,30 while the cross dehydrogenative coupling with dialkylformamides reacquired 5 mol% catalyst. 10 Concerning other reactions via C-H bond activation, an oxidant should be compulsory for the reaction. We therefore studied the inuence of oxidant on the transformation (entries 19-24, Table  1). Compared to other oxidants, tert-butyl hydroperoxide in water expressed better performance, producing 2-(benzo[d] thiazol-2-yl)phenyl benzoate in 89% yield (entry 19, Table 1). Indeed, tert-butyl hydroperoxide was also the oxidant of choice in previous works. 10,11,30 Having these results, we also explored the inuence of oxidant concentration on the transformation (entries 25-29, Table 1). The reaction could not proceed without an oxidant, and no trace quantity of the expected product was detected aer 24 h (entry 25, Table 1). Best result was recorded when 4 equivalents of the oxidant was present in the reaction mixture (entry 28, Table 1). However, extending the quantity of the oxidant to more than 4 equivalents did not favor the generation of 2-(benzo[d]thiazol-2-yl)phenyl benzoate (entry 29, Table 1).
Since the cross dehydrogenative coupling reaction utilizing the superparamagnetic nanoparticle catalyst was conducted in solvent, an important issue is the potentiality that a number of active sites might go into solution phase, and they would be responsible for the formation of the expected product. To verify if leaching of active sites was a serious problem for the reaction, a control experiment was implemented to assess the contribution of homogeneous catalysis. If more 2-(benzo[d]thiazol-2-yl) phenyl benzoate was produced aer the catalyst was isolated, this might imply that the active species were in solution phase rather than on the solid superparamagnetic nanoparticle catalyst. The reaction was performed in p-xylene at 80 C for 24 h, in the presence of 4 equivalents of aqueous tert-butyl hydroperoxide as oxidant, at 5 mol% catalyst, with 3 equivalents of benzaldehyde. The liquid phase was removed from the solid catalyst aer 4 h reaction time by magnetic decantation, and subsequently added to a new and clean reactor. The mixture was consequently stirred at 80 C for an additional 20 h to verify if more 2-(benzo[d]thiazol-2-yl)phenyl benzoate was generated under this condition. Certainly, almost no additional product was recorded aer the catalyst was isolated. These data veried that the cross dehydrogenative coupling transformation required the presence of the superparamagnetic nanoparticle catalyst, and almost no product was produced via homogeneous catalysis (Fig. 1).
To achieve more information for the possible pathway of the cross dehydrogenative coupling reaction between 2-(benzo[d] thiazol-2-yl)phenol and benzaldehyde to produce 2-(benzo[d] thiazol-2-yl)phenyl benzoate, additional mechanistic studies were then performed. The reaction was conducted in p-xylene at 80 C for 24 h, in the presence of 4 equivalents of aqueous tertbutyl hydroperoxide as oxidant, at 5 mol% catalyst, with 3 equivalents of benzaldehyde. It was noted that 36% yield was recorded for the rst 4 hour reaction time. Aer that, (2,2,6,6tetramethylpiperidin-1-yl)oxy (TEMPO) or curcumin as a radical trapping reagent was added to the reactor, and the mixture was consequently stirred at 80 C for an additional 20 h. Under these Fig. 1 Leaching studies verified that 2-(benzo[d]thiazol-2-yl)phenyl benzoate was not generated after the catalyst was isolated. conditions, 36% yield was detected (Fig. 2). In another experiment series, TEMPO or curcumin was added to the reaction mixture at the beginning of the reaction. It was noticed that less than 3% yield of 2-(benzo[d]thiazol-2-yl)phenyl benzoate was detected aer 24 h. These data suggested that the antioxidant would decompose the radicals produced in the catalytic cycle, thus terminating the transformation. Based on these observations and the literature, 10       thiazol-2-yl)phenyl benzoate was produced with 86% yield in the 8 th catalytic run (Fig. 3). The fact that the CuFe 2 O 4 nanoparticles could be reutilized many times was accordingly of signicance, as compared with organic transformations using conventional homogeneous catalysts. The scope of this protocol was subsequently expanded to the cross dehydrogenative coupling reaction between 2-(benzo[d] thiazol-2-yl)phenol and several benzaldehydes utilizing the CuFe 2 O 4 nanoparticles ( Table 3). The reaction was conducted in  Table 3) was achieved for the case of furan-2-carbaldehyde. As shown in the proposed mechanism (Scheme 2), the benzothiazole moiety worked as a directing group for the transformation. We then decided to explore the cross dehydrogenative reaction of phenols containing benzoxazole moiety.  Table 3) was produced in 59% yield for the case of thiophene-2-carbaldehyde.

Conclusions
CuFe 2 O 4 superparamagnetic nanoparticles exhibited high catalytic efficiency in the direct synthesis of chemical structures containing both phenol ester and benzothiazole moieties via cross dehydrogenative coupling reactions. Several substrates were reactive towards the transformation in the presence of the nano catalyst, including benzaldehyde, benzyl alcohol, dibenzyl ether, 2-oxo-2-phenylacetaldehyde, and 2-iodo-1phenylethanone. To our best knowledge, these reactions were not previously reported in the literature. The CuFe 2 O 4 superparamagnetic nanoparticles were more active than nano NiFe 2 O 4 , nano CoFe 2 O 4 , and nano Fe 2 O 3 . Moreover, the nano CuFe 2 O 4 catalyst also offered higher catalytic efficiency than numerous conventional homogeneous catalysts. At the end of each catalytic reaction, the nano CuFe 2 O 4 was isolated from the reaction mixture by utilizing a magnet. It was possible to reutilize the recovered catalyst numerous times for the cross dehydrogenative coupling reaction without a remarkable deterioration in catalytic performance. The fact that chemical structures containing both phenol ester and benzothiazole moieties were achieved using a recyclable nano catalyst was accordingly of signicance.

Conflicts of interest
There are no conicts to declare.