Ultrasound and Radiation-Induced Catalytic Oxidation of 1-Phenylethanol to Acetophenone with Iron-Containing Particulate Catalysts

Iron-containing particulate catalysts of 0.1–1 µm size were prepared by wet and ball-milling procedures from common salts and characterized by FTIR, TGA, UV-Vis, PXRD, FEG-SEM, and XPS analyses. It was found that when the wet method was used, semi-spherical magnetic nanoparticles were formed, whereas the mechanochemical method resulted in the formation of nonmagnetic microscale needles and rectangles. Catalytic activity of the prepared materials in the oxidation of 1-phenylethanol to acetophenone was assessed under conventional heating, microwave (MW) irradiation, ultrasound (US), and oscillating magnetic field of high frequency (induction heating). In general, the catalysts obtained by wet methods exhibit lower activities, whereas the materials prepared by ball milling afford better acetophenone yields (up to 83%). A significant increase in yield (up to 4 times) was observed under the induction heating if compared to conventional heating. The study demonstrated that MW, US irradiations, and induction heating may have great potential as alternative ways to activate the catalytic system for alcohol oxidation. The possibility of the synthesized material to be magnetically recoverable has been also verified.


Introduction
Alcohols and related compounds, e.g., diols or benzoins, are among the most abundant and used starting synthetic materials, and their partial oxidation can provide a significant added value to a number of chemical processes, since many aldehydes, ketones, and carboxylic acids are important by themselves and also can be used for further processing [1][2][3]. Generally, alcohols are relatively cheap The PXRD spectra of 3 and 4 (Figures 1, S6 and S7) reveal that most of the peaks correspond to the ferric oxyhydroxide FeO(OH), akaganeite Fe +3 O(OH) with some iron oxide hydroxide goethite Fe +3 O(OH) and cubic magnetite Fe3O4 as traces [21]. The oxyhydroxide prepared from ferric chloride is usually the β polymorph (akaganeite), often in the form of thin needles [21].
According to the performed SEM imaging, the prepared materials possess distinctive morphologies: spherical particles are observed for 1 and 2 (Figure 2a,b) and needles and rectangles for 3 and 4 (Figure 2c,d). The needle like morphology may be due to the formation of goethite α-FeOOH [22]. The PXRD spectra of 3 and 4 ( Figure 1, Figure S6 and S7) reveal that most of the peaks correspond to the ferric oxyhydroxide FeO(OH), akaganeite Fe +3 O(OH) with some iron oxide hydroxide goethite Fe +3 O(OH) and cubic magnetite Fe 3 O 4 as traces [21]. The oxyhydroxide prepared from ferric chloride is usually the β polymorph (akaganeite), often in the form of thin needles [21].
According to the performed SEM imaging, the prepared materials possess distinctive morphologies: spherical particles are observed for 1 and 2 (Figure 2a  The PXRD spectra of 3 and 4 (Figures 1, S6 and S7) reveal that most of the peaks correspond to the ferric oxyhydroxide FeO(OH), akaganeite Fe +3 O(OH) with some iron oxide hydroxide goethite Fe +3 O(OH) and cubic magnetite Fe3O4 as traces [21]. The oxyhydroxide prepared from ferric chloride is usually the β polymorph (akaganeite), often in the form of thin needles [21].
According to the performed SEM imaging, the prepared materials possess distinctive morphologies: spherical particles are observed for 1 and 2 (Figure 2a,b) and needles and rectangles for 3 and 4 (Figure 2c,d). The needle like morphology may be due to the formation of goethite α-FeOOH [22]. For the XPS studies of samples 1 and 2, the charge shifts were corrected using as reference the binding energy (BE) of aliphatic carbon, centered at 285 eV. The use of such BE reference for samples 3 and 4 was not enough to shift Fe 2p regions to sound corrected positions; the main peak being around 712 eV, which is slightly larger than the reported BE for Fe 3+ [21]. In Figure 3, Fe 2p regions for samples 3 and 4 are plotted using a different charge correction, adopted to reach a compromise between the information taken from the quantification (Table 1), the qualitative analysis of spectra and previous results obtained for different iron species [23]. For these samples, the BE of the carbonaceous graphitized contamination was set to 284.4 eV, which seems to yield coherent results for all the other elements. Moreover, the samples, where the reference BE was needed to be 284.4 eV, show a much lower charge accumulation. The two facts are compatible with each other since an overlayer of graphite on the samples would increase the electron conduction at the surface. It seems that a longer ball milling process promotes the graphitization of the carbon contaminations.  For the XPS studies of samples 1 and 2, the charge shifts were corrected using as reference the binding energy (BE) of aliphatic carbon, centered at 285 eV. The use of such BE reference for samples 3 and 4 was not enough to shift Fe 2p regions to sound corrected positions; the main peak being around 712 eV, which is slightly larger than the reported BE for Fe 3+ [21]. In Figure 3, Fe 2p regions for samples 3 and 4 are plotted using a different charge correction, adopted to reach a compromise between the information taken from the quantification (Table 1), the qualitative analysis of spectra and previous results obtained for different iron species [23]. For these samples, the BE of the carbonaceous graphitized contamination was set to 284.4 eV, which seems to yield coherent results for all the other elements. Moreover, the samples, where the reference BE was needed to be 284.4 eV, show a much lower charge accumulation. The two facts are compatible with each other since an overlayer of graphite on the samples would increase the electron conduction at the surface. It seems that a longer ball milling process promotes the graphitization of the carbon contaminations. For the XPS studies of samples 1 and 2, the charge shifts were corrected using as reference the binding energy (BE) of aliphatic carbon, centered at 285 eV. The use of such BE reference for samples 3 and 4 was not enough to shift Fe 2p regions to sound corrected positions; the main peak being around 712 eV, which is slightly larger than the reported BE for Fe 3+ [21]. In Figure 3, Fe 2p regions for samples 3 and 4 are plotted using a different charge correction, adopted to reach a compromise between the information taken from the quantification (Table 1), the qualitative analysis of spectra and previous results obtained for different iron species [23]. For these samples, the BE of the carbonaceous graphitized contamination was set to 284.4 eV, which seems to yield coherent results for all the other elements. Moreover, the samples, where the reference BE was needed to be 284.4 eV, show a much lower charge accumulation. The two facts are compatible with each other since an overlayer of graphite on the samples would increase the electron conduction at the surface. It seems that a longer ball milling process promotes the graphitization of the carbon contaminations.   Both Fe 2p regions of 1 and 2 look like that of Fe 3 O 4 analyzed previously [23], with Fe 2p 3/2 components being centered at 710.9 ± 0.2 eV. The overall quantification (Table 1) shows that almost no Cl, N, and S remain, which is compatible with the reaction of the iron precursors and consequent production of the iron oxide, mainly Fe 3 O 4 with some traces of the Fe(II) salt. Two main differences exist between 1 and 2; the presence of a relatively high quantity of Na in 1, which is absent in 2; and a larger amount of carbonaceous species in 2. It is worth noting that the ratio O 530 eV /Fe between the relative amount of oxygen bound to iron (found at 530.0 ± 0.1 eV) and iron in 1 is the same (within the experimental error) as the nominal ratio in Fe 3 O 4 (1.33). In 2, this ratio is larger, because the relative amount of iron is underestimated because of the intense O KLL Auger peak around 743 eV (for the spectra acquired with Mg Kα). This outline is an overlapping of multiple peaks at the high BE side of Fe 2p 1/2 , which cannot be quantified in this case.
The profiles of 3 and 4 are closer to Fe(II) species, as attested by the Fe(II) spectrum analyzed previously [23]. However, significant amounts of Cl (BE~198.7 eV) remain in samples, particularly in 3 with a Cl/Fe atomic ratio of 2.7, which is close to the nominal one in FeCl 3 . Additionally, the nitrogen amount is relatively high in both 3 and 4 (BE between 400.7 and 402.2 eV), and some sulphur from sulphate groups (BE~169 eV) is detected. These results led to the assignments indicated in Figure 3; while in 1 and 2 the main peaks are from the mixed Fe(II, III) oxide (Fe 3 O 4 ), in 3 and 4, the main peak is attributed to Fe 3+ from the FeCl 3 precursor mixed with some Fe 2+ from the other precursor.

Catalysts Screening
The prepared materials 1-4 and, for comparative purposes, the starting iron salts FeCl 3 ·6H 2 O, FeSO 4 ·(NH 4 ) 2 (SO 4 )·6H 2 O, and anhydrous FeCl 3 were screened for the microwave-assisted oxidation of 1-phenylethanol using tert-butyl hydroperoxide (1 eq. of t-BuOOH, aq. 70%) as oxidant. We choose the mentioned model reaction and particular experimental conditions (Scheme 1, Table 2) because of our longstanding interest in such type of reactions and previous experience [2,4,9,[12][13][14][15]24,25]. Blank experiment (in the absence of any catalyst), was undertaken and no conversion was observed ( Table 2, entry 1). Additionally, the effect of the catalyst amount, ranging from 0.05 to 5 mmol, was also studied ( Table 2). Among the studied materials, the catalysts 1 and 2, obtained by the wet and combined methods, exhibit the lowest activities (yields up to ca. 3 and 11% for 1 and 2, respectively), whereas the catalysts 3 and 4 obtained by ball milling perform better with acetophenone yields of 58 and 65%, respectively (

Catalysts Screening
The prepared materials 1-4 and, for comparative purposes, the starting iron salts FeCl3·6H2O, FeSO4·(NH4)2(SO4)·6H2O, and anhydrous FeCl3 were screened for the microwave-assisted oxidation of 1-phenylethanol using tert-butyl hydroperoxide (1 eq. of t-BuOOH, aq. 70%) as oxidant. We choose the mentioned model reaction and particular experimental conditions (Scheme 1, Table 2) because of our longstanding interest in such type of reactions and previous experience [2,4,9,[12][13][14][15]24,25]. Blank experiment (in the absence of any catalyst), was undertaken and no conversion was observed ( Table  2, entry 1). Additionally, the effect of the catalyst amount, ranging from 0.05 to 5 mmol, was also studied ( Table 2). Among the studied materials, the catalysts 1 and 2, obtained by the wet and combined methods, exhibit the lowest activities (yields up to ca. 3 and 11% for 1 and 2, respectively), whereas the catalysts 3 and 4 obtained by ball milling perform better with acetophenone yields of 58 and 65%, respectively ( Table 2, entries 15 and 19). Scheme 1. Solvent-free oxidation of 1-phenylethanol to acetophenone. Scheme 1. Solvent-free oxidation of 1-phenylethanol to acetophenone. The modest performance of 1 and 2 can be related to the presence of magnetite (Table S2), which favors agglomeration of particles, and consequently the surface reduction. Besides, lower solubility can also play a negative role. In contrast, in 3 and 4, the mechanochemical treatment promotes the iron hydroxide and oxyhydroxide formation, which were shown to be active catalysts for various oxidation reactions [26].

Optimization of Parameters
As it can be expected, the yields grow with increase of the catalyst amount, e.g., from 25% and 19% to 58% and 65% upon changing the amount of catalyst from 0.05 mmol to 0.33 mmol ( Figure 4, Table 2, entries 13-16, for 3, and 17-20, for 4, respectively). However, beyond 0.33 mmol of catalyst, the yields do not grow substantially. Thus, the reaction parameters for the most active catalysts 3 and 4 were further optimized considering this amount of catalyst (0.33 mmol).

7
The modest performance of 1 and 2 can be related to the presence of magnetite (Table S2), which favors agglomeration of particles, and consequently the surface reduction. Besides, lower solubility can also play a negative role. In contrast, in 3 and 4, the mechanochemical treatment promotes the iron hydroxide and oxyhydroxide formation, which were shown to be active catalysts for various oxidation reactions [26].

Optimization of Parameters
As it can be expected, the yields grow with increase of the catalyst amount, e.g., from 25% and 19% to 58% and 65% upon changing the amount of catalyst from 0.05 mmol to 0.33 mmol ( Figure 4, Table 2, entries 13-16, for 3, and 17-20, for 4, respectively). However, beyond 0.33 mmol of catalyst, the yields do not grow substantially. Thus, the reaction parameters for the most active catalysts 3 and 4 were further optimized considering this amount of catalyst (0.33 mmol). The temperature effect for catalysts 3 and 4 (Table 3, Figure 5a) was studied at 60, 80, 100, and 120 °C, and 80 °C was found to be the best option since the use of higher temperatures (100 and 120 °C) did not result in a significant increase in the product yield. The reaction was also carried out at different times (0.5-3 h), and it was demonstrated that more than half of the alcohol had been converted to ketone after a period of 0.5 h ( Table 3, entries 1-4 and entries 13-16, for 3 and 4, respectively). After 1.5 h, more than 70% of 1-phenylethanol had been converted, and then the conversion increases insignificantly for 4, and even decreases for 3 (Table 3, Figure 5b). The amount of acetophenone obtained can be slightly increased from 65 to 72% when the amount of t-BuOOH oxidant was doubled with the other conditions being the same (Table 3, entries 23 and 26), while application of aq. 30% H2O2 or NaOCl as oxidants led to a sharp yield decrease to ca. 7 and 3%, The temperature effect for catalysts 3 and 4 (Table 3, Figure 5a) was studied at 60, 80, 100, and 120 • C, and 80 • C was found to be the best option since the use of higher temperatures (100 and 120 • C) did not result in a significant increase in the product yield. The reaction was also carried out at different times (0.5-3 h), and it was demonstrated that more than half of the alcohol had been converted to ketone after a period of 0.5 h ( Table 3, entries 1-4 and entries 13-16, for 3 and 4, respectively). After 1.5 h, more than 70% of 1-phenylethanol had been converted, and then the conversion increases insignificantly for 4, and even decreases for 3 (Table 3, Figure 5b). The amount of acetophenone obtained can be slightly increased from 65 to 72% when the amount of t-BuOOH oxidant was doubled with the other conditions being the same (Table 3, entries 23 and 26), while application of aq. 30% H 2 O 2 or NaOCl as oxidants led to a sharp yield decrease to ca. 7 and 3%, respectively (Table 3, entries 28 and 29). This decrease in conversion may be due to the fast decomposition of the oxidants at high temperatures.
BuOOH molar ratio = 1:2. f Under air and without other oxidants apart from dioxygen from atmosphere. g Using H2O2 30% aq. solution as an oxidant (1:1). h Using NaOCl as an oxidant (1:1). Several additives were also tested as possible promoters (Table 3). Thus, nitric (HNO3) [2,7,9,12,27] and pyrazinecarboxylic (Hpca) acids [27], 2,2,6,6-tetramethylpiperydil-1-oxyl (TEMPO) and K2CO3 [27][28][29][30] were chosen as the most promising additives (promoters) of the reaction. It was found that the additives have different effects, either of promotion or inhibition. Thus, the addition of nitric acid (0.125 mmol) has a small beneficial effect on both catalytic systems, resulting, for  Several additives were also tested as possible promoters (Table 3). Thus, nitric (HNO 3 ) [2,7,9,12,27] and pyrazinecarboxylic (Hpca) acids [27], 2,2,6,6-tetramethylpiperydil-1-oxyl (TEMPO) and K 2 CO 3 [27][28][29][30] were chosen as the most promising additives (promoters) of the reaction. It was found that the additives have different effects, either of promotion or inhibition. Thus, the addition of nitric acid (0.125 mmol) has a small beneficial effect on both catalytic systems, resulting, for example, in a maximum yield of 67 and 68% for 3 and 4, respectively (Table 3, entries 5 and 17, Figure 6). In contrast, Hpca has the opposite effect, i.e., a slight yield drop is observed (Table 3, entries 7 and 20). The radical TEMPO promoter caused a minor increase in the acetophenone yield for both catalytic systems, being more pronounced for the catalyst 3. Since the TEMPO radical does not hamper the catalytic activity, the involvement of the free hydroxyl radical in the reaction mechanism is unlikely. The reaction can eventually involve a Fe(IV)=O species, also responsible for the high selectivity [31]. The promoting effect of TEMPO is known to occur in some copper-catalyzed alcohol oxidations where it acts as an H-abstractor from the metal coordinated alkoxide M-OCH(Me)Ph leading to the derived radical species M-OC • (Me)Ph and then to acetophenone Ph(Me)C=O upon an electron transfer [32]. The influence of carbon nanotubes (CNTs) on the catalytic activity of 4 also provides some promoting effect with a yield growth from 68 to 88% (Figure 7). Several additives were also tested as possible promoters (Table 3). Thus, nitric (HNO3) [2,7,9,12,27] and pyrazinecarboxylic (Hpca) acids [27], 2,2,6,6-tetramethylpiperydil-1-oxyl (TEMPO) and K2CO3 [27][28][29][30] were chosen as the most promising additives (promoters) of the reaction. It was found that the additives have different effects, either of promotion or inhibition. Thus, the addition of nitric acid (0.125 mmol) has a small beneficial effect on both catalytic systems, resulting, for example, in a maximum yield of 67 and 68% for 3 and 4, respectively (Table 3, entries 5 and 17, Figure  6). In contrast, Hpca has the opposite effect, i.e., a slight yield drop is observed (Table 3, entries 7 and 20). The radical TEMPO promoter caused a minor increase in the acetophenone yield for both catalytic systems, being more pronounced for the catalyst 3. Since the TEMPO radical does not hamper the catalytic activity, the involvement of the free hydroxyl radical in the reaction mechanism is unlikely. The reaction can eventually involve a Fe(IV)=O species, also responsible for the high selectivity [31]. The promoting effect of TEMPO is known to occur in some copper-catalyzed alcohol oxidations where it acts as an H-abstractor from the metal coordinated alkoxide M-OCH(Me)Ph leading to the derived radical species M-OC • (Me)Ph and then to acetophenone Ph(Me)C=O upon an electron transfer [32]. The influence of carbon nanotubes (CNTs) on the catalytic activity of 4 also provides some promoting effect with a yield growth from 68 to 88% (Figure 7).

Effect of the Energy Input
The effect of activating energy input on the catalytic output (Table 4, Figure 8) was controversial for different systems. Thus, the inductive heating increases the yield for catalyst 1 two-fold, while MW and US irradiations have no noticeable impact (Table 4, entries 1-4). The effect of inductive heating on the catalyst 2 is even more pronounced, i.e., yield raises more than four times from 9 to 41 %, whereas other types of activating irradiations do not influence much (Table 4, entries 6-10). The catalytic system 3 appears to be the one that preferably responds to ultrasound activation (Table 4,

Effect of the Energy Input
The effect of activating energy input on the catalytic output (Table 4, Figure 8) was controversial for different systems. Thus, the inductive heating increases the yield for catalyst 1 two-fold, while MW and US irradiations have no noticeable impact (Table 4, entries 1-4). The effect of inductive heating on the catalyst 2 is even more pronounced, i.e., yield raises more than four times from 9 to 41%, whereas other types of activating irradiations do not influence much (Table 4, entries 6-10). The catalytic system 3 appears to be the one that preferably responds to ultrasound activation (Table 4, entries [11][12][13][14][15]. Finally, the catalyst 4 responds equally to all three types of activating inputs (Table 4, entries [16][17][18][19][20]. For comparative purpose, oxidation of 1-phenylethanol to acetophenone was also performed by mechanochemical treatment (500 rpm, 10 spheres of 10 mm diameter, with rotational inversions every 5 min) in the presence of 1-4, at room temperature (Table 4, entries 5, 10, 15, and 20). Although the yields obtained by the ball-milling (BM) are modest (up to 17%), it should be noted that they were reached at room temperature, at which the other techniques yielded a residual amount of acetophenone. For now, it is difficult to draw any certain conclusion why the studied catalytic systems behave differently, and an additional thorough study will be performed in the future to address this point.   The catalytic behavior of the materials 1 or 2 synthesized by wet or combined methods differ from those obtained by ball milling (3 and 4). As described above, in 1 and 2 there is the mixed Fe(II,III) oxide (Fe 3 O 4 ), while 3 and 4 are composed of Fe 3+ (originated from FeCl 3 precursor) mixed with some Fe 2+ from the FeSO 4 ·(NH 4 ) 2 ·6H 2 O precursor. Fe 3 O 4 is a metastable phase of iron oxide, which has an inverse spinel structure (space group Fd-3m) [33], and at the applied reaction conditions is ferrimagnetic [34], hence, it can agglomerate and respond to activation with a magnetic field of high frequency, in agreement with the obtained data (Table 4).

Catalyst Recycling Studies
To check the possibility of reutilization of the most active catalysts 3 and 4, we repeated the oxidation experiments after separation of the catalyst by centrifugation with subsequent washing with hexane and consecutive addition of new portions of substrate and oxidant. The iron composites become less efficient upon each new addition of 1-phenylethanol. However, after the third addition of the substrate (Table S3, Figure 9), the conversion of 1-phenylethanol is still observed to a good extent.
which has an inverse spinel structure (space group Fd-3m) [33], and at the applied reaction conditions is ferrimagnetic [34], hence, it can agglomerate and respond to activation with a magnetic field of high frequency, in agreement with the obtained data (Table 4).

Catalyst Recycling Studies
To check the possibility of reutilization of the most active catalysts 3 and 4, we repeated the oxidation experiments after separation of the catalyst by centrifugation with subsequent washing with hexane and consecutive addition of new portions of substrate and oxidant. The iron composites become less efficient upon each new addition of 1-phenylethanol. However, after the third addition of the substrate (Table S3, Figure 9), the conversion of 1-phenylethanol is still observed to a good extent.   reaction was stopped, the formed precipitate was washed with water and ethanol and dried overnight at 80 • C. 2: Total of 0.39 g (1 mmol) (NH 4 ) 2 Fe(SO 4 ) 2 ·6H 2 O and 0.54 g (2 mmol) FeCl 3 ·6H 2 O were treated in ball mill (500 rpm, 10 spheres of 10 mm diameter) at room temperature for 10 min, with rotational inversions every 5 min. The thus obtained orange solid was transferred to a glass vial and 2 mL of deionized water were added. Then 1 M NaOH was added until pH 10-12 and the suspension was stirred for 30 min. After that, the formed black precipitate was filtered off, washed with water and ethanol, and dried overnight at 80 • C.

Catalytic Studies
The microwave-assisted oxidations were performed in a cylindric Pyrex tube to which 5 mmol 1-phenylethanol, 50-500 µmol catalyst and 5 mmol of 70% aq. solution of t-BuOOH were added in this order. The tube was then sealed and kept for 1 h at 80 • C under microwave irradiation (5-10 W). Finally, 5 mL of MeCN (to extract substrate and products from the reaction mixture) and 300 µL of benzaldehyde (internal standard) were added. The obtained mixture was stirred for 5 min and then a sample (1 µL) was taken from the organic phase and analyzed by GC using benzaldehyde as an internal standard method.
Under the optimized conditions, several energy inputs were tested. A total of 2.5 mmol 1-phenylethanol, 0.33 mmol catalyst, and 2.5 mmol of 70% aq. solution of t-BuOOH were added to a 10 mL Pyrex reactor and the reaction proceeded under US irradiation at 80 • C for 1h. Induction heating was performed as follows: the reaction mixture was added to a 10 mL glass vial as indicated above and the vial was placed on the center of the induction hob covered with a steel plate with a hole. The device was turned on with an induction power of 200 W for 1 h. The temperature was measured at the end of the reaction being ca. 70 • C. For reactions under conventional heating, a 10 mL glass reactor with the reaction mixture analogous to the ones described above was placed into an oil bath and heated for 1 h at 80 • C. At the end the product was extracted with MeCN and analyzed by GC with benzaldehyde used as an internal standard.

Conclusions
Wet, dry, and combined synthetic methods were used to prepare iron materials with different compositions, particle sizes (0.1-1 µm), shapes (semi-spherical, needles, and rectangles), and magnetic susceptibilities (paramagnetic or diamagnetic). Moreover, the materials prepared by wet, dry, and combined methods from the same starting materials (namely (NH 4 ) 2 Fe(SO 4 ) 2 ·6H 2 O and FeCl 3 ·6H 2 O) catalytically behave differently; the dry mechanochemical preparation, can increase the catalytic activity more than six-fold. It is also demonstrated that the activation of catalysts by ultrasounds and an oscillating magnetic field of high frequency can significantly increase the overall effectiveness of a catalytic system. Finally, the prepared catalysts can be magnetically recovered and reused at least three times.
Supplementary Materials: The following are available online. Preparation details, FTIR, and UV-vis spectra, thermogravimetric analysis data, X-ray diffraction patterns, magnetic susceptibilities, and data on influence of various factors on the catalytic activity. Funding: This research was funded by Fundação para a Ciência e a Tecnologia, Portugal UIDB/00100/2020, UIDB/04565/2020 and PTDC/QUI-QIN/29778/2017 projects.