Controlled transfer-reduction of functional groups with ethanol by their interaction strength with the oxygen vacancies

Domain: neuroscience
Published: 2026-04-08
Editorial outcome: major_revision

Abstract
Controlled reduction of functional groups remains a significant challenge in catalytic chemistry. In this study, we report a novel method for selectively reducing various functional groups using biomass-derived ethanol, mediated by oxygen vacancies in highly dispersed molybdenum oxide on nitrogen-doped carbon. Selectivity for the reduction of four representative substrates, sulfoxides, pyridine N-oxides, nitro compounds, and alkynes is successfully controlled via temperature, yielding the corresponding sulfides, pyridines, amines, and alkenes with high yields. Mechanistic studies indicate that the reactivity of these substrates is directly correlated with their interaction strength with O in molybdenum oxides, which effectively adsorb and activate both ethanol and the substrates via Columb interactions and facilitates hydrogen-atom transfer from ethanol to these functional groups. DFT calculations further confirm that O in Mo/CN-600 significantly lowers the energy barriers for the H transfer from α-C -H in ethanol to substrates (0.76 eV vs. 2.04 eV), thereby enhancing reactivity. This strategy provides a green and sustainable approach to the controlled reduction of functional groups with strong practical potential.

Introduction
Catalytic hydrogenation is a cornerstone of the chemical industry, driving essential transformations in bulk and fine chemical production1-3. Molecular hydrogen (H ) is a clean and sustainable reductant that can be produced by water splitting, with only water as a byproduct. Generally, supported metal nanoparticles (e.g., Pt/C, Pd/C) are employed to facilely activate H molecules for reduction, while achieving high chemoselectivity remains challenging, especially for substrates containing multiple reducible functionalities or requiring partial hydrogenation1,2.

Typical examples include the selective reduction of nitro groups in 4-nitrostyrene without affecting C=C bonds, or the semihydrogenation of alkynes to alkenes. Therefore, great effort has been devoted to careful modification of supported metallic nanoparticles with the aim to get the high selectivity1. For example, forming bimetallic nanoparticles (Ir Ni SAA, RuNi) is reported to be an effective way to modulate noble metal catalysts for the selective reduction of the -NO group in 4-nitrostyrene to produce 4-vinylaniline4,5, in which the non-noble metals selective adsorped -NO group in a vertical mode, avoiding the hydrogenation of the C=C bond, and the noble metals functionalized in activating H molecules.

Except for H , alcohols are among the most attractive environmentally benign hydrogen donors due to their renewable origin. Among them, ethanol stands out for its economic viability and carbon-neutral scalability from biomass3. Unlike secondary alcohols like iso-propanol, ethanol has been rarely explored in transfer hydrogenation reactions, because of its inherent inertness and susceptibility to catalyst poisoning (Figure 1a). On the one hand, ethanol as a primary alcohol is much more inert than iso-propanol in transfer hydrogenation6. On the other hand, acetaldehyde, generated from ethanol dehydrogenation, can cause catalyst deactivation via metal-catalyzed decarbonylation, forming catalytically inactive metal-carbonyl species (Figure 1b)7,8. Existing methodologies for activating ethanol often rely on air- or moisture-sensitive noble metal complexes, encountering issues including dedicated preparation process, rigorous anaerobic/anhydrous conditions, and non-selective hydrogenation8-10. For example, deep hydrogenation of C≡C was observed with Ir catalysts, failing to obtain C=C bonds with high selectivity (Figure 1b)9,10. These challenges highlight an urgent need for innovative catalytic systems that efficiently and selectively utilize ethanol as a sustainable hydrogen donor.

Recently, reducible transition metal oxides such as CeO , ZrO and MoO have emerged as promising alternatives to supported metal nanoparticle catalysts for transfer hydrogenation11-13. Among them, MoO has been extensively investigated in hydrodeoxygenation reactions. A reverse Mars-van Krevelen mechanism was proposed involving the consumption of oxygen vacancies (O ) by abstracting oxygen atoms from oxygenate substrates via strong interaction and their regeneration by thermal treatment in the presence of H (typically above 400 °C)12. This strong affinity of O sites for oxygen atoms arises from the coulombic interaction between electron-deficient O sites and electron-rich oxygen atoms bearing lone-pair electrons. Therefore, it was reasonable to imply that defective MoO can efficiently adsorb and activate other electron-rich substrates or intermediates, including pyridine N-oxides, sulfoxides, nitro compounds, acetylide (from deprotonation of alkynes), and alkoxide (from deprotonation of alcohol). In this context, defective is promising for ethanol-mediated transfer hydrogenation of these functional groups, and the electron density on the substrate or intermediate may affect reaction activity, thereby offering a new avenue for modulating selectivity.

Our recent work showed that nitrogen-doped carbon support was promising for stabilizing transition metal sites, including single atoms, metallic nanoparticles, and metal oxides, exhibiting excellent catalytic performance in diverse reactions13-15. Herein, we employed nitrogen-doped carbon to disperse oxygen-deficient molybdenum oxides by a simple pyrolysis method. In ethanol-mediated transfer hydrogenation, these defective molybdenum oxides demonstrated tunable catalytic performance, allowing for temperature-dependent switching of activity across a broad substrate scope (Figure 1c), including various N-oxide, sulfur, nitro, and alkyne moieties with yields ranging from 91% to 99%. Experimental evidence indicated that O sites were responsible for the adsorption of these compounds, and the apparent activation energy was positively correlated with their adsorption strength at the O sites. DFT calculations further demonstrate that O in Mo/CN-600 plays a decisive role in reducing the energy barriers for ethanol-driven reduction of various functional groups. This work provides a novel insight into manipulating the hydrogenation of multifunctional group compounds and can inspire broad interest in designing defective metal oxides for transfer hydrogenation.

Results
Catalyst preparation and characterization

The nitrogen-doped carbon supported molybdenum oxides were prepared by the pyrolysis of the dicyanamide and ammonium molybdate composite at four representative temperatures (500, 600, 700, and 800 °C) under inert atmosphere (Figure 2a), and the as-prepared catalysts were labeled as Mo/CN-T, where T represents the pyrolysis temperatures. The color of the composite changed from white before the pyrolysis to brown after pyrolysis at 500 °C (Figure S1). As discussed below, the brown color of Mo/CN-500 was due to the presence of the yellow g-C N . In contrast, other Mo/CN-T samples are black due to the formation of black amorphous nitrogen-doped carbon at or beyond 600 °C. The Mo content in Mo/CN-500 was determined to be 8.3 wt.% by inductively coupled plasma-atomic emission spectrometry (ICP-AES), and it significantly increased to 16.2 wt.%, 18.4 wt.%, and 19.2 wt.% for Mo/CN-600, Mo/CN-700, and Mo/CN-800, respectively (Table S1). The increase of Mo content in the catalysts at higher pyrolysis temperatures should be caused by the release of more versatile gases and the phase transition of molybdenum species (β-MoO →MoO →MoC) as evidenced by the following characterizations.

Powder X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy analyses reveal that both the carbon nitride structure and Mo species strongly depend on the pyrolysis temperature (Figures 1b, S2, and S3). In Mo/CN-500, the characteristic diffraction peaks of g-C N at 2θ = 20.6° and 27.1°, corresponding to the (100) and (002) planes, are clearly observed (Figure S2), which is consistent with the FT-IR signals (Figure S3) of aromatic C=N/C-N (1200-1600 cm-1) stretching and C-N (809 cm-1) heterocycle vibrations16. However, these features weakened in Mo/CN-600 and disappeared in Mo/CN-700 and Mo/CN-800, indicating that the g-C N framework was destroyed at temperatures above 600 °C. The pyrolysis temperature also governed the evolution of Mo species. β-MoO is the dominant phase in Mo/CN-500, while partial transformation to MoO occurred at 600 °C17. With further temperature increase, MoO becomes the main species in Mo/CN-700, accompanied by the formation of MoC in Mo/CN-800 (Figures 1b and S2, see Note 1 in the Supporting Information for further discussion). Raman spectra were also used to identify the Mo species in the Mo/CN-T catalysts. Three weak peaks with the Raman shifts around 656, 820, and 950 cm-1 were assigned to the tri-coordinated oxygen (Mo -O), bi-coordinated oxygen (Mo -O, Mo-O-Mo), and MoO vibrations in Mo/CN-600 and Mo/CN-700, respectively (Figure S4)18. While Mo/CN-800 only showed an additional weak peak at 992 cm-1, attributed to the Mo-C vibration from MoC19, consistent with the XRD results. In conclusion, the Mo species changed from β-MoO to MoO as the pyrolysis temperature increased from 500 °C to 700 °C, and MoC was the dominant Mo species for Mo/CN-800. In addition, two prominent Raman bands at 1323~1341 cm-1 and 1582~1595 cm-1 were observed for the Mo/CN-600, Mo/CN-700, and Mo/CN-800 catalysts, corresponding to the D and G bands, which are associated with defective carbon and graphitic sp2 carbon, respectively14. The calculated I /I ratios were 1.47, 1.36, and 1.28 for Mo/CN-600, Mo/CN-700, and Mo/CN-800 (Figure S4). These results indicate that increasing the pyrolysis temperature promotes graphitization of the carbon framework in the Mo/CN-T catalysts. This trend is mainly attributed to the gradual decrease in nitrogen content at higher pyrolysis temperatures, which facilitates the formation of more ordered graphitic structures14,15. N adsorption-desorption analysis showed that the Mo/CN-T samples had interconnected micro/mesopores (Figure S5). The smallest total surface area of 262.1 m2/g was observed for Mo/CN-500 and increased significantly to 838.2 m2/g when pyrolysis was performed at 600 °C (Mo/CN-600, Table S1). Further increasing the pyrolysis temperature resulted in a slight decrease in the total surface area (Table S1).

Transmission electron microscopy (TEM) image of Mo/CN-500 shows a thick-layered structure (Figure S6a), while the other three Mo/CN-T (T = 600, 700, and 800) catalysts demonstrate a thin-layered structure (Figures 2, S6b and S6c). The representative scanning electron microscopy (SEM) image of Mo/CN-600 showed a loose structure with abundant pores (Figures 1c and S7). Results from TEM and SEM images were consistent with the N adsorption-desorption analysis. Mo/CN-500 with thick-layered structure had much smaller surface area than other three Mo/CN-T samples (Figure S5 and Table S1). TEM image of Mo/CN-500 did not show visible molybdenum oxide nanoparticles (Figure S6), while the small-sized β-MoO nanoparticles were clearly observed in the TEM image of Mo/CN-600 with the average size in 2.7 ± 0.5 (Figure 2d). The lattice fringe of 0.384 nm was measured in high-resolution TEM (HR-TEM) image of Mo/CN-600 (Figure 2e), corresponding to the interplanar distance of (110) plane of β-MoO 17, which was consistent with the XRD results (Figure 2b). MoC nanoparticles with an average size of 2.0 ± 0.4 nm were observed in the TEM image of Mo/CN-800. In addition, high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) images with Z contrast clearly showed the Mo species in bright color (Figures 2f and 2g). Energy-dispersive spectroscopy (EDS) elemental mapping also revealed that the Mo, N, C, and O were uniformly distributed on the carbon support of the Mo/CN-600 catalyst (Figure 2h).

The valence states of the surface elements in the catalysts were detected by X-ray photoelectron spectroscopy (XPS, see Note 2 in the Supporting Information for further discussion). Mo6+, Mo5+, and Mo4+ were identified in the Mo 3d XPS spectra for Mo/CN-500 and Mo/CN-600, whereas Mo2+ was the dominant species in Mo/CN-700 and Mo/CN-800 (Figures 2a & S8 and Tables S2 & S3)14. The average Mo oxidation states were calculated from the XPS results and decreased from 5.1 and 5.2 to 3.6 and 3.1 with increasing pyrolysis temperature, indicating a gradual reduction in molybdenum oxides. The remaining high-valence species in Mo/CN-800 likely arise from surface oxidation of MoC during air storage20. N 1s XPS spectra of Mo/CN-500, Mo/CN-600, and CN-600 showed sp2 aromatic N (C-N=C), tertiary N (-NC ), amino groups (-C-NH ), and g-C N π excitation at 398.8, 399.6, 400.9, and 405.1 eV, respectively (Figures S9, S10, and Table S4)21. Nitrogen content decreased with higher pyrolysis temperatures due to N release, and g-C N -related features vanished above 600 °C, forming pyridinic and graphitic N in Mo/CN-700 and Mo/CN-80022. C 1s spectra indicated g-C N characteristic peak (288.4 eV, N-C=N) in Mo/CN-500 and CN-600, which diminished at higher temperatures, with C-C/C=C (284.7 eV) dominating in Mo/CN-600, Mo/CN-700, and Mo/CN-800 (Figure S11 and Table S5)20,23,24. A new peak at 283.4 eV could be fitted in Mo/CN-700 and Mo/CN-800, corresponding to Mo-C bonds, consistent with XRD phase transitions (Figure 2b)14,24. O 1s spectra were deconvoluted into Mo-O (530.6 ~ 530.7 eV), oxygen vacancies (O , 531.4 eV), C=O/C-OH (532.2 eV), and C-O (533.3 ~ 533.4 eV) (Figures 3b, S12, and Table S6)25. O content decreased from ~20 at.% in Mo/CN-500 and Mo/CN-600 to 3.6 at. % and 1.5 at.% in Mo/CN-700, and Mo/CN-800, reflecting the transition from β-MoO to MoO and then MoC, leading to the gradual loss of oxygen vacancy sites at higher pyrolysis temperatures.

The extended X-ray absorption near-edge structure (XANES) and X-ray absorption fine structure (EXAFS) were further conducted at Mo K-edge to probe the local environment of Mo in representative Mo/CN-600 catalyst. A well-defined pre-edge peak at 20006.9 eV (peak A) was found in the Mo K edge XANES spectra of Mo/CN-600 and MoO reference (Figure 3c), assigning to the direct 1s to 4d quadrupole-allowed transitions and the dipole-allowed 1s hybridized (5p, 4d) states26. The absorption edge energy of Mo/CN-600 is close to the reference MoO . The two peaks at 20027.3 eV and 20039.1 eV (B and C) were discriminated in the absorption edge energy of the reference MoO 26, whereas the two peaks were not well resolved for Mo/CN-600. The broadening and overlap of peaks B and C in Mo/CN-600 indicated the presence of the disordered MoO structure, which was caused by O 27.

Pseudo-radial distribution of the distances in Mo/CN-600 was further investigated with Fourier-transformed (FT) k3-weighted EXAFS. k3-weighted FT-EXAFS for MoO reference shows two characteristic peaks at 1.2 Å and 1.5 Å (Figure 3d), both of which are lower than the Mo-Mo bond at 2.4 Å in Mo foil. The peaks at 1.2 Å and 1.5 Å are assigned to Mo-O band (Figure 3e, terminal oxygen atoms, -Mo=O) and Mo-O band (Figure 3e, bridge oxygen atoms, Mo-O-Mo), respectively27. A second major component was associated with the nearest Mo neighbors (Mo-Mo second shell distance). k3-weighted FT-EXAFS for Mo/CN-600 exhibited only one main peak at around 1.3 Å, which was close to the Mo-O band found in MoO reference. While the peak for Mo-O is missing in k3-weighted FT-EXAFS for Mo/CN-600, suggesting that the bridge oxygen atoms in the Mo-O-Mo bond were lost. The absence of a peak associated with the second shell of Mo also indicated that the O in Mo-O-Mo had disappeared to form the Mo-O -Mo site. As well known to us, the Mo=O bond should have higher binding energy than the Mo-O-Mo bond, thus the bridge oxygen atom in Mo-O-Mo should be removed in priority by the in-situ formed reductive gases such as CO, NH and H from the decomposition of the precursors at high temperature28. The EXAFS wavelet transform (WT) analysis (Figure S13) further revealed that the O in Mo/CN-600 should be generated from bridging oxygen sites (Mo-O band). It was noted that the peak intensity at 656 and 820 cm−1 in the Raman shift of the treated Mo/CN-600 catalyst by diphenyl sulfoxide became stronger (Figure S4), while the peaks for the terminal oxygen coordinated Mo (-Mo=O) did not significantly changed. The increase of the peak intensity at 656 and 820 cm−1 was due to the fill of the negative oxygen atom in diphenyl sulfoxide into the O sites, which suggested that that the oxygen vacancies sites in the Mo/CN-600 catalyst were derived from the removal of the bridging oxygen atoms in Mo-O-Mo bonds, in agreement with the XAFS results.

Catalytic activity test

The catalytic performance of the Mo/CN-T catalysts was initially evaluated in the reduction of diphenyl sulfoxide by ethanol (Table 1). The catalytic activity significantly increased from Mo/CN-500 to Mo/CN-600, and then greatly decreased over Mo/CN-700 and Mo/CN-800 (Table 1, entries 1 ~ 4). Quantitative conversion of diphenyl sulfoxide into diphenyl sulfide was obtained over Mo/CN-600 after 4 h at 150 °C (Table 1, entry 2). H was not detected in the gas phase after reaction, indicating that the transformation was a hydrogen atom transfer process. No reaction was observed over the Mo-free nitrogen-doped carbon support (Table 1, entry 5; abbreviated as CN-600, and the XRD, XPS, and ESR test shown in Figures S2, S10, and S14), suggesting that Mo species were the active sites, whilst nitrogen-doped carbon materials or defective carbon/ nitrogen exhibit no catalytic activity in this system. Commercial MoO and MoO showed no activity in the reduction of diphenyl sulfoxide by ethanol (Table 1, entries 6 & 7), and the absence of 1' was observed without the addition of diphenyl sulfoxide (Table 1, entry 8). Therefore, it can be concluded that the O sites in the defective MoO species are of great importance in the hydrogen atom transfer reaction.

Then, the relationship between the content of the O sites and catalytic activity in Mo/CN-T catalysts was investigated. Electron paramagnetic resonance (ESPR) technology was used to detect the O content in the catalysts. Two weak peaks with g values at g = 1.961 and g = 1.988 are observed in the EPR spectra of the Mo/CN-T catalysts (Figure 4), in association with typical five-coordinated Mo5+ species28, while they are not present in the EPR spectra of commercial MoO with Mo6+ and MoO with Mo4+. Interestingly, a peak with g= 2.002 was only observed in the EPR spectrum of Mo/CN-500, assigning to the defective sites of g-C N derived partial disorder (Figure S14)29. The peak with g = 2.005 was attributed to the signal of the O from molybdenum oxides in the Mo/CN-T catalysts (T = 500, 600, and 700)30. Mo/CN-600 showed the strongest intensity of O signal (Figure 4a), indicating it has the most abundant O sites. The intensity of O signal significantly weakened as the pyrolysis temperature increased and completely diminished at 800 °C due to the phase transition from MoO to MoC, in good agreement with the O 1s XPS fitting results. It should be emphasized that XPS primarily probes surface chemical states and relative surface defect densities, whereas EPR reflects the presence and evolution of paramagnetic defect centers in the bulk. The apparent discrepancies between the two techniques are therefore rationalized by their intrinsically different sampling depths, sensitivities, and detection mechanisms14,31.

Furthermore, the catalytic activities (turnover frequency, TOF) of the Mo/CN-T catalysts were correlated with the surface concentrations of Mo5+ and O , as quantified by Mo 3d and O 1s XPS (Figures 4b and S15). A nearly linear relationship between TOF and both Mo and O abundance was observed. The apparent deviation of Mo/CN-500 from this trend can be attributed to its thick-layered structure and much smaller surface area (262.4 m2 g-1) compared with the other catalysts (718.6–838.2 m2 g-1), which limits the accessibility of active sites. In contrast, Mo/CN-600 combines a high surface area with abundant porosity, facilitating efficient mass transport of reactants and products, and thereby enhancing catalytic performance. These results indicated that both O /Mo5+ density and surface area jointly govern the catalytic activity of the Mo/CN-T catalysts. For comparison, carbon-supported MoO without O sites (Mo/C-600), prepared by incipient wetness impregnation and calcination at 600 °C under N , exhibited no catalytic activity (Table 1, entry 9), further confirming the essential role of oxygen vacancies in the hydrogen atom transfer process.

The interaction between O in Mo/CN-600 and the substrates was further studied. Mo/CN-600 was first treated with the substrates under reaction conditions and then subjected to EPR characterization. The peak intensity of O in the treated Mo/CN-600 catalysts, whether by ethanol or diphenyl sulfoxide, decreased significantly in comparison with the untreated Mo/CN-600 (Figure 4c), which could be due to the filling of the negative oxygen atoms in ethanol or diphenyl sulfoxide into the O sites. This phenomenon was also confirmed by Raman results. The intensity of Raman peaks at 656 and 820 cm-1, corresponding to the bridge Mo-O-Mo bond, was noted to increase after treating Mo/CN-600 with diphenyl sulfoxide (Figure S4)28. However, the peaks associated with terminal oxygen coordinated Mo (-Mo=O) did not change significantly. These results suggested that the oxygen atoms in substrates should fill the bridged O sites (Mo-O -Mo) in accordance with the characterization results. Therefore, we can conclude that O in Mo/CN-600 plays a great role in the adsorption and activation of these substrates28.

Optimization of the reaction conditions

Then, the effect of the reaction temperature on the reduction of diphenyl sulfoxide by ethanol was studied over Mo/CN-600 (Table S7). The reaction proceeded sluggishly at 90 °C, affording a low conversion in 5.4% after 4 h. Then the conversion gradually increased with the increase of the reaction temperature, and the quantitative conversion was achieved within 4 h at 150 °C (Table S7, entry 6). The reduction of diphenyl sulfoxide into diphenyl sulfide proceeded smoothly at 120 °C with the full conversion after 10 h (Figure S16). Besides high activity, Mo/CN-600 also demonstrated excellent stability during the recycling experiments (Figure S17). The XRD, XPS, SEM, and TEM images of the recovered Mo/CN-600 catalyst (Figure S18, S19, and Table S1-S6) after fiveruns showed no significant change as compared with those from fresh sample (Figures 2c-2e). In particular, XPS results show that both the Mo species and the oxygen vacancy concentration remain largely unchanged after the catalytic cycles, further confirming the structural robustness and stability of the catalyst under the reaction conditions (Table S1-S6). No Mo leaching into the reaction solution was detected by ICP-AES analysis (Table S1). This high stability should be due to the strong interaction between the nitrogen-doped carbon support with the molybdenum oxides.

Besides ethanol, other aliphatic alcohols were also used as hydrogen donors for the reduction of diphenyl sulfoxide (Table S8). Methanol, the simplest alcohol with the highest dehydrogenation enthalpy, also gave similar diphenyl sulfoxide conversion as ethanol (Table S8, entries 1 & 2). The conversion decreased in the order of ethanol, n-propanol, n-butanol, and iso-propanol. Our results differed from the commonly reported results, in which iso-propanol as the secondary alcohol was more active hydrogen donor than primary alcohols6,8. This phenomenon was due to the different reaction mechanisms. For the supported metal nanoparticle catalysts, the reaction mechanism followed the dehydrogenation-hydrogenation process, in which hydrogen species from alcohols were first captured on the surface of metal nanoparticles and then transferred to the unsaturated groups in the substrates6. Therefore, iso-propanol as the secondary alcohol, demonstrated higher reactivity than the primary alcohols for its easier dehydrogenation. However, that was not the case in our method. The hydrogen atom transfer over Mo/CN-600 was promoted by the interaction between the oxygen atoms in alcohols and O in Mo/CN-600, in which the steric effect from alcohols may influence their reactivities. As discussed later, the key step in the deoxygenation of diphenyl sulfoxide by alcohols was the direct transfer of the α-C -H to diphenyl sulfoxide. Compared with primary alcohols in Table S8, iso-propanol with the largest steric hindrance should have the weakest interaction with O in Mo/CN-600, thus iso-propanol demonstrated the lowest reactivity in our study. To verify it, EPR signal of O over the treated Mo/CN-600 catalysts with iso-propanol or ethanol was compared. As expected, the peak intensity of O in the treated catalyst by ethanol was much weaker than that over the treated catalyst by iso-propanol (Figure 4c), confirming that ethanol had a stronger interaction with O in Mo/CN-600 than iso-propanol.

Kinetic studies

Furthermore, kinetic experiments were conducted. As ethanol was in excess, its concentration on the catalyst surface can be considered constant. Log (rate) was plotted versus log[diphenyl sulfoxide], giving rise to a straight line (R2 = 0.997), which indicated that the reduction of diphenyl sulfoxide should follow a pseudo-first-order reaction kinetics (Figure S20a). According to the Arrhenius plot, the apparent activation energy of the reduction of diphenyl sulfoxide was calculated to be 88.8 kJ/mol over Mo/CN-600 (Figure S20b). The dependence of alcohol concentration on the reduction of diphenyl sulfoxide was also studied. Because of the low boiling point of ethanol and high reaction temperature, its concentration in the reaction system could not be accurately controlled. Therefore, benzyl alcohol was used instead of ethanol to investigate the relationship between the reaction rate and the concentration of alcohol. The reactions were performed in toluene with an excessive amount of diphenyl sulfoxide. As shown in Figure S20c, a straight line could also be fitted after plotting log(rate) versus log[benzyl alcohol], indicating that consumption of benzyl alcohol followed a pseudo-first-order reaction kinetics. This pseudo-first-order dependence found for diphenyl sulfoxide and benzyl alcohol was in accordance with the fact that the reaction was started by the direct interaction of the oxygen atoms in diphenyl sulfoxide and alcohols with the O in Mo/CN-600 as discussed above (Figure 4)28. Kinetic isotopic experiments of the reduction of diphenyl sulfoxide were performed to study the difference in the abstraction of the two H atoms (α-C -H and O-H) from ethanol. A low kinetic isotopic effect (KIE) value of 1.45 was obtained for CH CH OD, while that was 3.19 for CH CD OD (Figure S20d). By deducting the contribution of -OD in CH CD OD, the approximate KIE value of CH CD OH to CH CH OH was calculated to be 2.74. These results indicated that the transfer of the α-C -H was significantly more difficult than the transfer of the active hydrogen (H+) in the hydroxyl group, suggesting that the former should be the rate-determining step.

Substrate scope

The excellent catalytic performance of Mo/CN-600 in the reduction of diphenyl sulfoxide motivated us to explore its applicability toward other sulfoxides and pyridine N-oxides. As summarized in Table 2a, a wide range of aromatic and aliphatic sulfoxides were efficiently converted into the corresponding sulfides with excellent yields (Pro. 1 ~ 15). Electronic effects from substrates were apparent: 4, 4′-dimethyldiphenyl sulfoxide bearing an electron-donating group showed lower reactivity than 4, 4′-dichlorodiphenyl sulfoxide containing an electron-withdrawing group (Pro. 2 vs. 3). Phenyl alkyl sulfoxides exhibited comparable activity to diphenyl sulfoxides (Pro. 1 vs. 6), likely due to reduced steric hindrance which compensated for their lower electron density at the sulfoxide moiety. Cyclic and dialkyl sulfoxides were also quantitatively deoxygenated to the corresponding sulfides (Pro. 13 ~ 15), demonstrating the broad substrate scope. The transfer reduction of pyridine N-oxide and its derivatives with ethanol was then investigated. Pyridine N-oxide could be reduced at a significantly lower temperature (60 °C), affording a conversion of 5.3% after 4 h and a relatively low apparent activation energy of 74.2 kJ/mol (Table S9 and Figure S21a). These results indicate that pyridine N-oxide was more easily reduced than diphenyl sulfoxide, which can be attributed to the stronger interaction between oxygen anions in pyridine N-oxide and O sites in Mo/CN-600. This conclusion is supported by the pronounced decrease in O EPR signal intensity after treatment with pyridine N-oxide (Figure 4d). Various substituted pyridine N-oxides were smoothly converted into the corresponding pyridines at 100 °C with high to quantitative yields (Pro. 16 ~ 27).

In contrast, the transfer reduction of nitrobenzene proved to be considerably more challenging. The reaction initiated at 100 °C, giving only 4.3% conversion after 4 h (Table S9), and exhibited a much higher apparent activation energy of 100.4 kJ/mol compared with diphenyl sulfoxide (88.8 kJ/mol) and pyridine N-oxide (74.2 kJ/mol) (Figure S21b). EPR analysis showed that O signal intensity remained relatively strong after treatment with nitrobenzene, indicating a much weaker interaction between O sites and nitrobenzene (Figure 4d). Consequently, the reduction of nitrobenzene was significantly less favorable.

Moreover, nitrobenzene reduction with ethanol afforded aniline with low selectivity, accompanied by byproducts such as N-phenylethanimine and 2-methylquinoline (Table S10). These byproducts arise from condensation between in-situ-generated aniline and acetaldehyde, as well as subsequent cyclization reactions32. To avoid these side reactions, iso-propanol was employed as an alternative hydrogen donor. Owing to the steric hindrance imposed by the acetone formed during dehydrogenation, side reactions were effectively inhibited. As a result, nitrobenzene was converted to aniline in 95.4% yield at 170 °C after 11 h (Pro. 28). Under these optimized conditions, a broad range of nitro compounds were successfully reduced to the corresponding primary amines with good to excellent yields (Table 2b). Nitroarenes bearing electron-donating substituents were less reactive than those containing electron-withdrawing groups (Pro. 29 ~ 34 vs. Pro. 35 ~ 46), and steric effects were observed for o-, m-, and p-substituted substrates. The protocol was also effective for highly substituted nitroarenes, fused-ring systems, heteroatom-containing nitro compounds, and cyclic and aliphatic nitro substrates (Pro. 47 ~ 53). Notably, Mo/CN-600 exhibited excellent tolerance toward vulnerable functional groups such as vinyl, alkyne, halogen, nitrile, and especially iodine substituents. This chemoselectivity is attributed to the preferential adsorption of nitro groups and alcohols on O sites (Figure 4d), where nitro groups can interact strongly through resonance structures containing negatively charged oxygen atoms, whereas nonpolar or weakly polar groups interact minimally33,34.

Encouraged by the high tolerance toward vinyl groups, Mo/CN-600 was further evaluated for the semi-hydrogenation of alkynes to alkenes using ethanol as the hydrogen donor. Based on Lewis acid-base interactions between Mo5+ centers adjacent to O sites and anionic species, the deprotonated RC≡C- intermediates were proposed to interact with O sites (Mo5+-O -Mo5+). Consistent with this hypothesis, treatment with phenylacetylene led to a detectable decrease in O signal intensity, albeit weaker than for oxygen-containing substrates, necessitating higher reaction temperature (160 °C, Table S9). Semi-hydrogenation of phenylacetylene proceeded at 210 °C to afford styrene with 96% selectivity at full conversion after 13 h (Pro. 54). Kinetic analysis revealed the highest activation energy (111.6 kJ/mol, Figure S21c) among the examined transformations. Nevertheless, the method displayed broad applicability, enabling selective semi-hydrogenation of diverse alkynes to alkenes without over-reduction or interference from other functional groups (Table 2c). In short, the catalytic performance achieved with Mo/CN-600 is superior to that of other O -rich metal oxide catalysts (Table S11, entries 1~ 4 vs. 5 ~ 9) as well as homogeneous catalysts. Moreover, compared with a series of heterogeneous Mo-based catalysts, Mo/CN-600 in this work employs ethanol as the hydrogen donor (Table S11, entries 1~ 4 vs. 10 ~ 12), which is potentially a more environmentally benign alternative to hydrazine hydrate (N H ·H O). In addition, defect sites and/or coordinatively unsaturated sites are likely the active centers responsible for this series of transfer hydrogenation reactions13,39-41. This study systematically emphasizes the unique role of oxygen vacancies in promoting hydrogen atom transfer from alcohols, which differentiates our system from previously reported MoO - or Mo O N - catalysts39-41.

Mechanism study

The starting reaction temperatures and the activation energies for the reduction of the four representative substrates both increased in the following order: pyridine N-oxide, diphenyl sulfoxide, nitrobenzene, and phenylacetylene (Table S9). As discussed above, the interaction strength of the substrates with O also increases in the same order. These results indicated there was a direct correlation between the reactivities of substrates and their interaction strength with the O (Figures 4 and S15). XRD, HR-TEM, and other studies indicate that the β-MoO (110) crystal plane exhibits structural stability42,43. Therefore, DFT calculations were performed to study these reduction reactions by ethanol on the (110) crystal face of a β-MoO model with O [hereinafter referred to as β-MoO -O (110)]. The reduction of pyridine N-oxide, with the lowest energy barrier, and the reduction of phenylacetylene, with the highest energy barrier, were used as the two representative reactions for DFT calculations (Figure S21). After removal of the bridge oxygen atom in Mo-O-Mo, the distance between the two Mo atoms of β-MoO (110) increased from 3.934 to 5.866 Å (Figure S22). Ab initio molecular dynamics (AIMD) simulation was further conducted to verify the proposed models, particularly under finite temperature conditions relevant to the reaction environment. As shown in Figure S23 (see Note 3 in the Supporting Information for further discussion), both perfect and oxygen-deficient β-MoO surfaces only indicated minor local distortions without bond breaking or lattice collapse, remaining structurally intact under thermal fluctuations, thereby confirming the reliability of the as-proposed models.

First, particular attention was paid to the significant role of O in these transformations over the perfect and defective β-MoO (110) crystal faces. As shown in Figure 5 and S24, employing temperature and saturated vapour pressure for free energy correction has a limited effect on DFT calculations. It was surprising to note the adsorption energies of ethanol and pyridine N-oxide on the perfect β-MoO (110) surface were even higher than those on the β-MoO -O (110), due to the strong affinity of them to Mo atom (Figure 5). In this case, the bridge oxygen atom was destroyed after the adsorption of pyridine N-oxide by the connection of the oxygen atom in pyridine N-oxide with the Mo atom (Figure 5a, Structure I-2). In both cases, the dissociation of “H” from the hydroxyl group (-OH) in ethanol to the basic site (O atom) in β-MoO was an easy step with low energy barriers (E = 0.01 eV for β-MoO (110) and E = 0.13 eV for β-MoO -O (110), Figure 5, TS1 vs. TS1*), in agreement with the isotopic kinetic experiments (Figure S20d). In both cases, the N-O bond in pyridine N-oxide was cleaved, and the oxygen atom bonded to the Mo atom. The cleavage of the N-O bond in pyridine N-oxide was also easy on a perfect β-MoO (110) surface with an E of 0.13 eV and on a β-MoO -O (110) surface with an E of 0.16 eV (Figure 5, TS2 vs. TS2*). The released pyridine molecule directly desorbed from the perfect β-MoO (110) surface, but it preferred to transfer to the neighboring adsorbed ethanol on the β-MoO -O (110) surface (Figure 5, I-5 vs. I-5*). The H atom from α-C -H in ethanol then transferred to the “N” atom in the neighbor pyridine molecule on the β-MoO -O (110) surface to generate the pyridine-H species with the energy barrier of 0.76 eV (Figure 5b, TS3*). In the meantime, acetaldehyde desorbed from the β-MoO -O (110) surface. After the release of acetaldehyde, the pyridine-H species bonded to the Mo atom on β-MoO -O (110) surface (Figure 5b, I-8*).

After detaching from pyridine N-oxide to the Mo atom, the oxygen could abstract an H atom in pyridine-H species via TS4* (E = 0.38 eV), and the generated pyridine molecule would desorb from the β-MoO -O (110) surface. Water molecule finally formed via the transportation of the initial adsorbed H atom on the basic “O” site from -OH in ethanol to the surface -OH group on the Mo site (TS5*, E = 1.07 eV/103.3 kJ mol-1), and desorbed from the β-MoO -O (110) surface with the desorption energy of 0.03 eV to finish the catalytic cycle. In contrast to the reaction on the β-MoO -O (110) surface, the H atom on the “O” atom in the Mo-O-Mo moiety first transferred to the desorbed oxygen atom on the Mo site (from pyridine N-oxide) (TS3, E = 1.36 eV; Figure 5a, I-6 ~ I-7), following by the H atom from α-C -H in ethanol (TS4, 2.04 eV; Figure 5a, I-7 ~ I-8). Worse still, the desorption energy of water on the perfect β-MoO (110) surface was also very high, up to 3.22 eV. It is notable that for the α-C -H transfer process, the energy barrier on the β-MoO -O (110) surface is significantly lower (Figure 5, TS3* vs. TS4; 0.76 eV vs. 2.04 eV), which can be attributed to enhanced charge redistribution, more delocalized electronic reorganization, and vacancy-induced electronic states near the Fermi level that effectively buffer electron transfer (Figures S25-S27).

According to the DFT calculation, it can be concluded that the O greatly lowered the energy barriers of abstracting two H atoms in ethanol molecule, especially for the H atom from α-C -H. The presence of O between two Mo atoms provides the free room and electronic flexibility for the pyridine-mediated transfer of the H atom from α-C -H to the desorbed “O” atom on the Mo sites at the other side. On the meanwhile, the flexible geometry of the β-MoO -O also benefited the transfer of the H atom on the basic “O” atom site in the catalyst to the desorbed “O” atom on the Mo sites.

Furthermore, the semi-hydrogenation of phenylacetylene by ethanol on the β-MoO -O (110) surface was also studied by DFT calculation. As shown in Figure S28, the adsorption energy of phenylacetylene on β-MoO -O (110) surface was lower than that of pyridine N-oxide (-0.77 vs. -1.61 eV; Figure S28, Structure I-2** vs. Figure 5b, Structure I-2*), in consistence with the EPR results (Figure 4d). On the meanwhile, phenylacetylene and ethanol adsorbed on the two Mo atom sites with O between them. DFT calculation revealed that the highest energy barrier of 1.44 eV (140.0 kJ mol-1) was the transfer of the H atom from α-C -H in ethanol (Figure S28, TS2**), which was much higher than that of the process in pyridine N-oxide (Figure 5b, TS5*). Therefore, DFT calculation also confirmed the transfer hydrogenation of phenylacetylene was much more difficult than the transfer hydrodeoxygenation of pyridine N-oxide, which is in good accordance with our experimental data (Table S12).

Based on the experimental results, DFT results, and previous reports13,35, the plausible mechanism was proposed for the reduction of sulfides, pyridine N-oxides, nitro compounds as well as the semi-hydrogenation of alkynes by ethanol over Mo/CN-600. Taking the reduction of pyridine N-oxide as an example, the possible mechanism is illustrated in Figure 6. Initially, pyridine N-oxide and ethanol adsorb on the O site between two Mo atoms in Mo-O -Mo by filling the negative oxygen atoms in the substrates into the O sites. Meanwhile, the H atom from the -OH group in ethanol transfers to the basic “O” atom sites in β-MoO -O such as Mo-O , to generate the adsorbed alkoxide ions (CH CH O-). Then, the oxygen atom in pyridine N-oxide is released and bonded to the Mo atom according to the above DFT calculation. Then two H atoms from α-C -H in CH CH O- and the bonded H atom in the basic “O” sites transfer to the desorbed “O” atom from pyridine N-oxide on the Mo site to generate one water molecule. Finally, the desorption of the formed water molecule from the catalyst surface finishes the catalytic cycle.

The application of our developed method

Then, the excellent catalytic performance of Mo/CN-600 was compared with commercial noble Pd/C and Pt/C catalysts. It was noted that commercial Pd/C and Pt/C catalysts delivered no reaction or negligible conversion over the four representative reactions with ethanol as the hydrogen donor at the same reaction temperatures (Table S13), suggesting O in Mo/CN-600 played a key role in the activation of alcohols as well as these functional groups in these substrates to promote these transfer reductions. However, that was not the case for the Pd/C and Pt/C catalysts, which requires to overcome high energy barrier to cut the hydrogen atoms directly from alcohols to the surface of Pd and Pt nanoparticles via the traditional dehydrogenation-hydrogenation process. As well known to us, Pt/C is robust in the activation of H molecules at room temperature44. The reduction of the four representative substrates by H was also performed over Pt/C. Except for diphenyl sulfoxide, quantitative conversions of other three substrates were achieved over Pt/C catalyst (Table S14). The failure in the hydrogenation of diphenyl sulfoxide over Pt/C was most likely due to the poison of Pt/C, because of the strong affinity of surfur atom in diphenyl sulfoxide to the Pt sites45. As shown in Figure 7a, Pt/C catalyst showed no selectivity towards these transformations. The hydrogenation of pyridine N-oxides gave 59.6% yield of pyridine, 40.4% yield of tetrahydropyridine (Table S14). Both the vinyl group and the nitro group in 4-nitrostyrene were reduced over Pt/C with H (Table S14). Semi-hydrogenation of phenylacetylene also failed over Pt/C, giving the quantitative yield of ethylbenzene with the full hydrogenation of the alkyne group (Table S14). The failure in controlled reduction of these substrates over Pt/C was due to the random adsorption of these substrates on the surface of Pt nanoparticles, and efforts to modulate the noble metal catalysts to selective adsorption and controlled reduction of the functional groups were devoted (Table S15)46-53. Obviously, our developed method demonstrated distinct advantages including the simple preparation of the catalyst with low cost, the use of biomass-derived ethanol as the hydrogen donor, and the controlled reduction of different functional groups at an appropriate temperature. For example, although alkynes and nitroarenes can both be reduced as discribed above, the chemo-selective reduction of nitro group rather than alkynyl group in 3-nitrophenylacetylene 3-ethynylaniline could be easily realized by choosing an appropriate temperature at 150 °C, only overcoming the energy barrier for the tranfer-reduction of -NO group (Table 2, Pro. 36).

Finally, the application of our method in the gram-scale synthesis of bio-active molecules was studied (Figure 7b). 4’-Aminochalcone, an anti-cancer drug54, was successfully obtained by the chemo-selective hydrogenation of the nitro group in 4’-nitrochalcone without affecting the vinyl and carbonyl groups (Pro. 70). N-(2-methyl-5-nitrophenyl)-4-(3-pyridyl)-2-pyrimidine amine (Pro. 71) is a key intermediate for Imatinib with an annual consumption amount of $561 million in 202355, and it was obtained in a yield of 95% via reduction of the corresponding nitro compound. Entacapone with the application of Parkinson's disease was successfully functionalized to the ammino product (Pro. 72; 1.2 g) in a yield of 91% without the reduction of ketone, vinyl, and nitrile groups. Pomalidomide and Lenalidomide with the use in the treatment of Multiple Myeloma were attained in yields of 94% from the reduction of corresponding nitro compounds (Pro. 73 & 74; 1.2~1.3 g)55. A two-step method was applied to synthesize Erlotinib in a yield of 91% (1.2 g, Pro. 75) 56, the epidermal growth factor receptor-tyrosine kinase inhibitor. The first key step is the chemo-selective reduction of nitro group rather than alkynyl group in 3-nitrophenylacetylene into 3-ethynylaniline in a yield of 97% (Figure S29), followed by the coupling reaction with 4-chloro-6,7-bis(2-methoxyethoxy) quinazoline via nucleophilic substitution to deliver Erlotinib56.

Methods
Materials

Ammonium molybdate tetrahydrate [(NH ) Mo O ·4H O] and dicyanamide were purchased from Aladdin Chemicals Co. Ltd. (Shanghai, China). All sulfoxides, pyridine N-oxides, nitro compounds, and alkynes were commercially supplied, and used directly without further purification. All reagents were used as received without further purification.

Catalyst preparation

Typically, dicyanamide (8.0 g) and ammonium molybdate tetrahydrate (140.0 mg) was homogeneously mixed by ball milling method. Then, the obtained composite was placed on an alumina boat in a quartz tube furnace and heated from room temperature to the set temperature with a ramping rate of 2 °C·min-1 under nitrogen atmosphere and then remained for 2 h. Finally, it was cooled down to 400 °C at 10 °C·min-1, and then to room temperature naturally in the air. The as-prepared catalysts were denoted as Mo/CN-T, where T represents the pyrolysis temperature. For comparison, the CN-600 catalyst was also prepared by the same procedure as for the preparation of Mo/CN-600 without (NH ) Mo O ·4H O. The Mo/C-600 catalyst was synthesized via incipient wet impregnation method of ammonium molybdate tetrahydrate (110.0 mg) onto active carbon (0.3 g), followed by calcination at 600 °C under N atmosphere to achieve a comparable Mo content to that of the Mo/CN-600 catalyst.

Catalyst Characterization

Transmission electron microscopy (TEM) was performed on a Talos F200X microscope operated at 200 kV, with samples dispersed in ethanol and deposited onto copper grids. Powder X-ray diffraction (XRD) patterns were recorded on a Bruker D8 Advance diffractometer using Cu Kα radiation over a 2θ range of 10° ~ 80° at a scanning rate of 0.016° s-1. N adsorption-desorption isotherms were measured at 77 K on a V-Sorb 2800P analyzer after degassing the samples at 150 °C for 12 h. X-ray photoelectron spectroscopy (XPS) was conducted on a Thermo VG ESCA MultiLab-2000 system with monochromatized Al Kα radiation (1486.6 eV), and binding energies were calibrated to the C 1s peak at 284.6 eV. Raman spectra were collected using a Thermo Fisher DXR spectrometer with 532 nm excitation. The Mo content was determined by ICP-AES (IRIS Intrepid II XSP). FT-IR spectra were obtained using the KBr pellet method, and EPR measurements were carried out on a Bruker EMXnano spectrometer.

The X-ray absorption spectra were collected on the beamline BL07A1 in NSRRC, and were provided technical support by Ceshigo Research Service “www.ceshigo.com”. The radiation was monochromatized by a Si (111) double-crystal monochromator. XANES and EXAFS data reduction and analysis were processed by IAthena software. The obtained XAFS data was processed in Athena (version 0.9.25) for background, pre-edge line and post-edge line calibrations. Then Fourier transformed fitting was carried out in Artemis (version 0.9.25)57. The k3 weighting, k-range of 3 ~ 12 Å-1 and R range of 1 ~ 3 Å were used for two shells fitting and 1 ~ 4 Å for 3 shells fitting of MoO .

General procedure of the transfer hydrogenation reactions

In a typical run, diphenyl sulfoxide (0.5 mmol), the Mo/CN-600 catalyst (20 mg), and ethanol (10 mL) were placed in a 40 mL stainless steel autoclave. The air in the autoclave was removed by flushing with N for 10 min and finally pressured with 10 bar N . The system was heated from room temperature to the set reaction temperature within ca. 4 min. Then the reaction was started for a certain time with a magnetic stirring rate of 1000 RPM. After the reaction, the vessel was cooled in an ice-bath and the pressure was released slowly to atmospheric pressure. The products were diluted with acetonitrile and analyzed by GC. Furthermore, the residue was purified by column chromatography on silica gel (200-300 mesh), eluting with a mixed solvent of n-hexane and ethyl acetate to afford the desired products. The isolated products were further identified by NMR spectra and GC-MS. For other types of transfer hydrogenation reactions, the same procedure was applied with different kinds of the substrates.

Analytic methods

Product analysis was carried out using an Agilent 7890A gas chromatograph equipped with an HP-5 cross-linked capillary column (30 m × 0.32 mm × 0.4 μm) and a flame ionization detector. N was employed as the carrier gas at a flow rate of 40 mL·min-1. The injector and detector temperatures were both set at 300 °C. The column temperature was programmed from 50 °C (held for 1.5 min) to 300 °C (held for 3 min) at a heating rate of 10 °C·min-1. Product contents were quantified using an internal standard. Product molecular weights and structures were analyzed by GC-MS (Thermo Scientific ISQ 7000), and structural identification was further confirmed by 1H and 13C NMR spectroscopy (Bruker TCI III 600 MHz).

Catalyst recycling experiments

After the reaction, the Mo/CN-600 catalyst was collected from the reaction mixture via centrifugation, and the spent Mo/CN-600 catalyst was washed with water and ethanol for three times, respectively. After this treatment, the recovered Mo/CN-600 catalyst was tested for the next run under identical reaction conditions.

Computational methods

All DFT calculations were carried out with generalized gradient approximation (GGA) of the Perdew-Burke-Ernzerhof (PBE) functional using the VASP (VASP 5.4.1) simulation package58. The approach of project-augmented-wave (PAW)59 was exploited to describe the interaction between core-electron and valence electron. According to the XRD and HR-TEM results (Figure 2), the supercell of (110) crystal face of β-MoO with O was constructed as the surface model. The X-ray absorption fine structure spectroscopy (XAFS) and EPR technologies demonstrated that the substrates adsorbed on the O sites (Figures 3 and 4). A plane-wave basis set was expanded with the kinetic cutoff energy of 400 eV on valence electronic states. K-point sampling parameters of two systems namely, β-MoO and β-MoO -O were tested using pyridine N-oxide (C H NO) chemisorption energy with 1 x 1 x 1, 2 x 2 x 1 and 3 x 3 x 1, and a k-point sampling of 2 x 2 x 1 was adopted with the convergence value less than 0.1 eV. The Methfessel-Paxton-approach with a fermi smearing width of 0.1 eV was used to determine partial occupancies on electronic states. The effect of van der Waals (vdW) interaction is significant for the reaction mechanism in our previous study60,61. Therefore, the DFT-D3 method of Grimme et al.62,63 was utilized to calculate all the energetics and structures of the intermediates and transition states. MoO (110) surface was chosen as the DFT model base on our XRD analysis. All surfaces were built using periodic slabs of four layers. The bottom two layers of atoms were fixed, and the top two layers were relaxed with a 15 Å vacuum region. The thickness of the slab was verified to be sufficient. In order to be consistent with our experimental data, we constructed O through removing oxygen atoms on the perfect MoO (110) surface. The energetics and structures were calculated using the conjugate-gradient algorithm until the Hellman Feynman forces on each atom less than 0.01 eV/Å. The transition states (TSs) were searched using the method called a constrained optimization scheme64,65. The transition states were confirmed by two rules: (i) all forces on atoms have been optimized to be less than 0.01 eV/Å; (ii) the total energy is a maximum along the reaction coordinate but a minimum with respect to all other degrees of freedom. All the optimized initial states, transition states and final states were verified by frequency analysis66 using a finite displacement method to the mass-weighted Hessian matrix.

Peer review rounds
[{"round": 1, "reviewer_comments": {"reviewer_1": "The manuscript, \"Controlled Transfer-Reduction of Functional Groups with Ethanol by Their Interaction Strength with Oxygen Vacancies,\" by Yuan et al., reports a detailed study using ethanol as a hydrogen donor to selectively reduce diverse functional groups over oxygen-vacancy-rich Mo/CN catalysts. The study integrates experimental characterization, kinetic analysis, and DFT calculations to clarify the role of oxygen vacancies in promoting hydrogen atom transfer from ethanol to reducible substrates.\nThis timely and relevant topic addresses green hydrogenation strategies using non-noble metal systems and renewable feedstocks. The results are in general technically sound and potentially impactful. However, the manuscript, in its current form, is too lengthy and lacks focus. It contains redundant descriptions and has language issues and inconsistent data interpretations, notably between XPS and EPR quantifications. The correlation between substrate reactivity and Ov interaction strength, the main novel aspect of this study, should be emphasized more sharply and supported quantitatively.\nAs a minor point, the manuscript would benefit significantly from professional language editing and structural condensation (especially in the introduction and results sections). More importantly the mechanistic discussion should be streamlined and better linked to experimental observations. For publication in a highly reputed journal like Nature Communications, the novelty statements should be made clearer by comparing it quantitatively with literature systems. In the present form publication is not advised.", "reviewer_2": "The manuscript presents the synthesis of nitrogen-doped carbon supported molybdenum oxides from the pyrolysis of dicyanamide and ammonium molybdate composite (Mo-CN-T). The authors performed EPR, XPS, EXAFS, and KIE to reveal possible active sites and surface reaction mechanisms. The work is systematically carried out and the MS is also nicely written. The results well support the authors'claim. However, some concerns need to be addressed prior to be considered for publication. major revision is necessary.\n1. Novelty of the work should be stated more clearly.\n2. The manuscript currently lacks a sufficient comparative analysis with relevant prior work on molybdenum oxide-based catalysts for transfer hydrogenation reactions. A table explicitly compares the catalytic performance with that reported in literature should be given and discussed. Detailed discussion regarding the proposed active sites in this work compared with those reported previously should be addressed, for example, DOI: 10.1039/D1GC02647J, 10.1039/D1DT03107D, 10.1016/j.inoche.2024.112416.\n3. The clarity and legibility of the XRD patterns (Figure 1b) are compromised due to the small scale. Displaying the patterns the data into separate figures would ensure that subtle peak shifts and full-width half-maxima (FWHM) are easily discernable for all individual samples.\n4. A significant inconsistency exists in the interpretation of the Raman data. The spectral assignments in the main text (lines 138-139) for the shifts at 656 and 820 cm-1 (Mo–O and Mo O, respectively) must be reconciled with the labels provided in the Supplementary Information (Fig. S4). Please ensure that this corrected assignment is carried consistently throughout the discussion (e.g., lines 331-334) to maintain scientific coherence.\n5. The discussion of the carbon structure, typically quantified by the ID/IG ratio, requires greater depth. For example, the authors should correlates the observed trends in the ID/IG across the sample series with the resulting catalytic performance or structural differences identified by other techniques.\n6. The authors should exercise with caution when quantitatively comparing oxygen vacancy (Ov) concentrations derived from XPS and EPR. As XPS is a surface-sensitive technique, while EPR is a bulk-sensitive technique. A direct comparison is methodologically unsound. This may also be one of the reasons for the discrepancy observed between the EPR and XPS results (lines 303-310).\n7. Figure 3b shows a nearly linear relationship between Ov content and TOF. Given that Ov content is intrinsically linked to the presence of reduced Mo species in Mo/CN samples, do the authors observe a similar correlation between the concentration of reduced Mo species and TOF? Please add a detailed discussion in the manuscript addressing this specific relationship.\n8. Recycling performance of the catalyst should be evaluated. Do the authors observe any changes of Mo and O species in the spent catalyst?", "reviewer_3": "This work focuses on method for the controlled reduction of functional groups using biomass-derived ethanol as the hydrogen donor. The general idea of the manuscript seems to be interesting. However, some issues throughout the text are present, in terms of manuscript structure and scientific content. Here are listed some comments:\n1. Abstract and Introduction: the novelty aspect is not clear. The main contribution of this paper should be explained. The novelty of this work compared to other similar investigations should be clearly mentioned.\n2. The work does not provide adequate description of DFT calculations, which is crucial for evaluating reliability and repeatability of their results.\n3. The authors claim that Ov provides \"free room\" for pyridine-mediated hydrogen atom transfer, however, the micro explanations for this are vague. The specific change path of the electronic structure during hydrogen transfer process should be further characterized by electron local function, charge density difference, and partial density of states.\n4. In Figure 4, only transition state energy barriers are presented, without showing the reaction free energy change at each step. Complete energy change data will provide essential support to determine whether each step of the reaction is exothermic or endothermic.\n5. The binding energy and phonon spectrum of perfect and defective β-MoO₃ model should be calculated, as structure stability is prerequisite for reliability and interpretability of computational results.\n6. The authors qualitatively compares energy barrier (unit eV) by DFT with apparent activation energy (unit kJ/mol) by experiments, a more quantitative comparison should be provided and/or discussed.\n7. The authors mention that oxygen vacancies provide both spatial and electronic environments, however, no investigation is conducted for the changes and the relationship of atomic configuration and electronic property."}, "author_response": "Responses to the referees\nReviewer #1 (Remarks to the Author):\nComment 1: The manuscript, \"Controlled Transfer-Reduction of Functional Groups with\nEthanol by Their Interaction Strength with Oxygen Vacancies,\" by Yuan et al., reports a detailed\nstudy using ethanol as a hydrogen donor to selectively reduce diverse functional groups over\noxygen-vacancy-rich Mo/CN catalysts. The study integrates experimental characterization,\nkinetic analysis, and DFT calculations to clarify the role of oxygen vacancies in promoting\nhydrogen atom transfer from ethanol to reducible substrates.\nResponse: Thank you for your comments. We appreciate your recognition of our work and its\ncomprehensive approach, integrating experiments, kinetics, and DFT calculations to elucidate\nthe role of oxygen vacancies in the catalytic process.\nComment 2: This timely and relevant topic addresses green hydrogenation strategies using\nnon-noble metal systems and renewable feedstocks. The results are in general technically sound\nand potentially impactful. However, the manuscript, in its current form, is too lengthy and lacks\nfocus. It contains redundant descriptions and has language issues and inconsistent data\ninterpretations, notably between XPS and EPR quantifications. The correlation between\nsubstrate reactivity and O interaction strength, the main novel aspect of this study, should be\nv\nemphasized more sharply and supported quantitatively.\nResponse: Thank you for your comments. We have carefully revised the manuscript to make\nit more concise and focused, removing redundant descriptions and improving language clarity.\nThe consistency between XPS and EPR data has been rechecked and corrected. In addition, we\nhave strengthened and quantified the discussion on the correlation between substrate reactivity\nand the strength of oxygen-vacancy interactions to better highlight the novelty of this work.\nComment 3: As a minor point, the manuscript would benefit significantly from professional\nlanguage editing and structural condensation (especially in the introduction and results\nsections). More importantly the mechanistic discussion should be streamlined and better linked\nto experimental observations. For publication in a highly reputed journal like Nature\nCommunications, the novelty statements should be made clearer by comparing it quantitatively\nwith literature systems. In the present form publication is not advised.\nResponse: Thank you for your insightful suggestions. We have carefully revised the manuscript\nwith professional language editing and structural condensation, particularly in the introduction\nand results sections. The mechanistic discussion has been streamlined and more closely linked\nto the experimental observations. Furthermore, we have clarified the novelty statements by\nadding quantitative comparisons with reported literature systems (Table S11). We believe these\nrevisions have significantly improved the clarity and overall quality of the manuscript.\nReviewer #2 (Remarks to the Author):\nThe manuscript presents the synthesis of nitrogen-doped carbon supported molybdenum oxides\nfrom the pyrolysis of dicyanamide and ammonium molybdate composite (Mo-CN-T). The\nauthors performed EPR, XPS, EXAFS, and KIE to reveal possible active sites and surface\nreaction mechanisms. The work is systematically carried out and the MS is also nicely written.\nThe results well support the authors' claim. However, some concerns need to be addressed prior\nto be considered for publication. major revision is necessary.\nResponse: We appreciate your recognition of the quality and systematic nature of our work.\nWe have carefully addressed all the concerns raised and made corresponding revisions in the\nmanuscript to further improve its clarity, accuracy, and completeness. We believe the revised\nmanuscript better supports our conclusions and meets the publication standards.\nComment 1: Novelty of the work should be stated more clearly.\nResponse: Thank you for your comments. According to your and Reviewer 1's questions 2 and\n3, we have revised the manuscript to clearly highlight the novelty of our work. Specifically, we\nemphasize that our study reveals the crucial role of oxygen vacancies in promoting hydrogen\natom transfer from ethanol to reducible substrates on non-noble-metal Mo-based catalysts.\nThese insights provide new mechanistic understanding and design principles for developing\ngreen hydrogenation catalysts.\nComment 2: The manuscript currently lacks a sufficient comparative analysis with relevant\nprior work on molybdenum oxide-based catalysts for transfer hydrogenation reactions. A table\nexplicitly compares the catalytic performance with that reported in literature should be given\nand discussed. Detailed discussion regarding the proposed active sites in this work compared\nwith those reported previously should be addressed, for example, DOI: 10.1039/D1GC02647J,\n10.1039/D1DT03107D, 10.1016/j.inoche.2024.112416.\nResponse: Thank you for your comments. In the revised manuscript, we have added a\ncomprehensive comparison table summarizing the catalytic performance of our Mo/CN-T\ncatalyst and other reported molybdenum oxide-based catalysts for transfer hydrogenation\nreactions (Table S11), including the references you suggested (DOI: 10.1039/D1GC02647J,\n10.1039/D1DT03107D, 10.1016/j.inoche.2024.112416). We have also expanded the\ndiscussion to highlight the distinct advantages of our catalyst, such as broader substrate scope,\nand superior selectivity under milder. Furthermore, we provide a detailed comparison of the\nproposed active sites, emphasizing the unique role of oxygen vacancies in facilitating hydrogen\natom transfer, which differentiates our system from previously reported MoO - or Mo O N -\n3 4 4 3\ncatalysts. The corresponding results and discussions have been added (pages 22-23).\nComment 3: The clarity and legibility of the XRD patterns (Figure 1b) are compromised due\nto the small scale. Displaying the patterns the data into separate figures would ensure that subtle\npeak shifts and full-width half-maxima (FWHM) are easily discernable for all individual\nsamples.\nResponse: Thank you for your comments. The XRD patterns have been reorganized, and the\ndata are now displayed separately in the Supporting Information (Figure S2a) to improve clarity\nand allow easier identification of subtle peak shifts and FWHM differences among individual\nsamples.\nComment 4: A significant inconsistency exists in the interpretation of the Raman data. The\nspectral assignments in the main text (lines 138-139) for the shifts at 656 and 820 cm-1 (Mo–O\nand Mo=O, respectively) must be reconciled with the labels provided in the Supplementary\nInformation (Fig. S4). Please ensure that this corrected assignment is carried consistently\nthroughout the discussion (e.g., lines 331-334) to maintain scientific coherence.\nResponse: Sorry for the missing information. The Raman data assignments have been carefully\nrechecked and corrected. The revised assignments are now consistent between the main text\nand the Supplementary Information (Figure S4), and the corresponding descriptions in the\ndiscussion have been updated accordingly (pages7-8).\nComment 5: The discussion of the carbon structure, typically quantified by the I /I ratio,\nD G\nrequires greater depth. For example, the authors should correlates the observed trends in the\nI /I across the sample series with the resulting catalytic performance or structural differences\nD G\nidentified by other techniques.\nResponse: Thank you for your comments. In the revised manuscript, we have expanded the\ndiscussion to explicitly correlate the evolution of the I /I ratio across the sample series with\nD G\nboth structural characteristics and catalytic performance. The I /I ratio is commonly\nD G\nassociated with the degree of structural disorder and defect density in carbon materials. In our\nsystem, the gradual change in I /I with increasing pyrolysis temperature reflects the\nD G\ntransformation of the nitrogen-doped carbon framework from relatively ordered g-C N\n3 4\nderived domains to more defective and partially graphitized carbon structures. In the\ncorresponding part, we have changed the original statement to:\n“In conclusion, the Mo species changed from β-MoO to MoO as the pyrolysis\n3 2\ntemperature increased from 500 °C to 700 °C, and MoC was the dominant Mo species for\nMo/CN-800. In addition, two prominent Raman bands at 1323~1341 cm-1 and 1582~1595 cm-\n1 were observed for the Mo/CN-600, Mo/CN-700, and Mo/CN-800 catalysts, corresponding to\nthe D and G bands, which are associated with defective carbon and graphitic sp2 carbon,\nrespectively14. The calculated I /I ratios were 1.47, 1.36, and 1.28 for Mo/CN-600, Mo/CN-\nD G\n700, and Mo/CN-800 (Figure S4). These results indicate that increasing the pyrolysis\ntemperature promotes graphitization of the carbon framework in the Mo/CN-T catalysts. This\ntrend is mainly attributed to the gradual decrease in nitrogen content at higher pyrolysis\ntemperatures, which facilitates the formation of more ordered graphitic structures14,15.”\nMoreover, no reaction was observed over the Mo-free nitrogen-doped carbon support\n(abbreviated as CN-600, XRD and XPS shown in Figure S2 and S10; Table 1, entry 5),\nsuggesting that Mo species were the active sites, whilst nitrogen-doped carbon materials or\ndefective carbon exhibit no catalytic activity in this system.\nComment 6: The authors should exercise with caution when quantitatively comparing oxygen\nvacancy (O ) concentrations derived from XPS and EPR. As XPS is a surface-sensitive\nv\ntechnique, while EPR is a bulk-sensitive technique. A direct comparison is methodologically\nunsound. This may also be one of the reasons for the discrepancy observed between the EPR\nand XPS results (lines 303-310).\nResponse: Thank you for your comments. In the revised manuscript, we have carefully\ncorrected and clarified this issue. We have removed any statements implying a strict\nquantitative comparison between XPS- and EPR-derived O concentrations and instead\nv\nreframed the discussion to emphasize their complementary nature. Specifically, XPS is now\ndiscussed as providing information on the surface chemical states and relative surface defect\ndensity, while EPR is interpreted as reflecting the presence and evolution of paramagnetic\ndefect centres in the bulk. The observed differences are now explicitly attributed to the distinct\nsampling depths, sensitivities, and detection principles of the two techniques.\nFurthermore, we have revised the relevant section (page 14) to avoid overinterpretation\nand to present a more scientifically rigorous and methodologically sound interpretation. The\nrevised text highlights that both techniques consistently support the presence and evolution of\noxygen vacancies, but should not be used for direct one-to-one quantitative comparison. This\nclarification improves the accuracy, coherence, and reliability of the discussion.\nWe sincerely appreciate the reviewer’s comment, which has helped us strengthen the\nmethodological rigor and scientific clarity of the manuscript.\nComment 7: Figure 3b shows a nearly linear relationship between O content and TOF. Given\nv\nthat O content is intrinsically linked to the presence of reduced Mo species in Mo/CN samples,\nv\ndo the authors observe a similar correlation between the concentration of reduced Mo species\nand TOF? Please add a detailed discussion in the manuscript addressing this specific\nrelationship.\nResponse: Thank you for this insightful comment. We agree with the reviewer that the\nconcentration of reduced Mo species is intrinsically related to the Ov content. Upon careful\nanalysis, we indeed observe a similar positive correlation between the proportion of reduced\nMo species (Mo5+, as quantified by Mo 3d XPS) and the TOF values across the Mo/CN-T series\n(Figure S14). This trend is consistent with the Ov-TOF relationship shown in Figure 3b, as the\ngeneration of oxygen vacancies is accompanied by partial reduction of Mo centers to maintain\ncharge neutrality. We have now added a detailed discussion in the revised manuscript to\nexplicitly clarify this correlation, emphasizing that reduced Mo species and O act\nv\nsynergistically as coupled structural–electronic features governing catalytic activity (page 14).\nComment 8: Recycling performance of the catalyst should be evaluated. Do the authors\nobserve any changes of Mo and O species in the spent catalyst?\nResponse: Thank you for your comments. Recycling experiments were conducted at both low\nand high conversion levels, and the results showed that the catalyst exhibited no noticeable loss\nof activity after five consecutive cycles (Figure S16). The SEM and TEM images (Figures 2c-\n2e) of the recovered Mo/CN-600 catalyst after five runs, showed no significant change as\ncompared with those from the fresh sample (Figure S17). No leaching of Mo into the reaction\nsolution was observed by ICP-AES analysis. This high stability should be due to the strong\ninteraction between the nitrogen-doped carbon support with the molybdenum oxides.\nReviewer #3 (Remarks to the Author):\nThis work focuses on method for the controlled reduction of functional groups using biomass-\nderived ethanol as the hydrogen donor. The general idea of the manuscript seems to be\ninteresting. However, some issues throughout the text are present, in terms of manuscript\nstructure and scientific content. Here are listed some comments:\nComment 1: Abstract and Introduction: the novelty aspect is not clear. The main contribution\nof this paper should be explained. The novelty of this work compared to other similar\ninvestigations should be clearly mentioned.\nResponse: Thank you for your comments. In the revised version, we have thoroughly rewritten\nthe Abstract and Introduction sections to highlight the novelty and main contribution of this\nwork clearly. Specifically, we now emphasize that this study demonstrates the use of oxygen-\nvacancy-rich nitrogen-doped carbon supported MoO catalysts (Mo/CN-T) for selective\n3\ntransfer hydrogenation using ethanol as both solvent and hydrogen donor, achieving high\nselectivity toward partially reduced products that are typically prone to over-hydrogenation.\nWe further clarify that, unlike previous Mo-based systems, our catalyst combines tunable\noxygen vacancies and strong metal–support interactions to promote hydrogen atom transfer\n(HAT) processes rather than molecular hydrogen activation. Comparative discussion with\nexisting literature has also been added to underscore how our system advances the design of\nnon-noble, sustainable catalytic platforms for green hydrogenation chemistry (Table S11 and\n15).\nComment 2: The work does not provide adequate description of DFT calculations, which is\ncrucial for evaluating reliability and repeatability of their results.\nResponse: Thank you for this valuable comment. In the revised manuscript, we have\nsubstantially expanded the Computational Details section to provide a clearer and more\ncomprehensive description of the DFT methodology (page 34). We specify how adsorption\nenergies, charge density differences, and transition states were calculated and verified. The\nrevised section also clarifies the procedure used to model hydrogen atom transfer (HAT) and\nthe role of oxygen vacancies in modifying the electronic structure (Figures R1-R4). These\nadditions ensure the reproducibility and transparency of our DFT results, and improve the\noverall reliability of the computational analysis.\nComment 3: The authors claim that O provides \"free room\" for pyridine-mediated hydrogen\nv\natom transfer, however, the micro explanations for this are vague. The specific change path of\nthe electronic structure during hydrogen transfer process should be further characterized by\nelectron local function, charge density difference, and partial density of states.\nResponse: Thank you for your comments. We agree that the initial description of the “free\nroom” effect induced by oxygen vacancies (O ) was too qualitative. In the revised manuscript,\nv\nwe therefore performed a systematic electronic structure analysis, including charge density\ndifference with Bader charge analysis (Figure R1), electron localization function (ELF, Figure\nR2), and projected density of states (PDOS, Figure R3), to explicitly elucidate how oxygen\nvacancies modify the electronic structure during hydrogen transfer and how these changes are\ndirectly correlated with the activation barrier.\nOn the perfect β-MoO surface, the α-C -H transfer proceeds via direct hydrogen\n3 sp3\nabstraction by lattice oxygen and is associated with a high activation barrier of 2.04 eV. Charge\ndensity difference and Bader charge analyses show that the net charge redistribution at the\ntransition state is relatively limited, indicating that electron rearrangement during α-C -H\nsp3\nbond cleavage is strongly constrained. Correspondingly, ELF analysis reveals that hydrogen\ntransfer on the perfect surface requires a relatively localized electronic reorganization at the C\nα\nsite, implying a high energetic penalty for the abrupt breaking and formation of chemical bonds.\nIn addition, PDOS analysis shows a relatively low density of electronic states near the Fermi\nlevel, suggesting limited electronic flexibility to accommodate the transition-state electron\nredistribution. These factors collectively account for the high hydrogen transfer barrier on the\nperfect surface.\nFigure R1. (Figure S23) Comparison of difference charge density analysis and Bader charge\nanalysis between (a) the perfect β-MoO (110) surface and (b) the β-MoO -O (110) surface.\n3 3 v\nFigure R2. (Figure S24) Comparison of ELF Analysis at the Cα Site between (a) the perfect\nβ-MoO (110) surface and (b) the β-MoO -O (110) surface.\n3 3 v\nFigure R3. (Figure S25) Comparison diagram of PDOS between(a) the perfect β-MoO (110)\n3\nsurface and (b) the β-MoO -O (110) surface.\n3 v\nIn contrast, on the O -containing β-MoO surface, the hydrogen transfer barrier is\nv 3\nsignificantly reduced to 0.76 eV. Charge density difference and Bader charge analyses\ndemonstrate a substantially larger charge redistribution at the transition state, indicating that\nthe defective surface can accommodate electron rearrangement more effectively. Importantly,\nELF analysis shows no pronounced electron localization at the C site, suggesting that\nα\nhydrogen transfer proceeds via a more delocalized and gradual electronic reorganization rather\nthan a highly localized bond-to-bond process. Meanwhile, PDOS analysis reveals that oxygen\nvacancies introduce additional electronic states near the Fermi level, which act as accessible\nelectronic reservoirs to transiently accept or donate electrons during hydrogen transfer.\nAs a result, the O -containing surface provides an electronically flexible environment that\nv\nstabilizes the transition state by buffering electron redistribution, thereby lowering the\ntransition-state energy and reducing the activation barrier from 2.04 eV to 0.76 eV. These\nresults clarify that the “free room” effect of oxygen vacancies originates from enhanced\nelectronic flexibility rather than purely geometric space. Corresponding analyses and\ndiscussions have been added to the revised manuscript.\nComment 4: In Figure 4, only transition state energy barriers are presented, without showing\nthe reaction free energy change at each step. Complete energy change data will provide\nessential support to determine whether each step of the reaction is exothermic or endothermic.\nResponse: Thank you for your comments. In the revised manuscript, we have supplemented\nFigure 4 with the corresponding reaction free energy changes for each elementary step along\nthe reaction pathway (page 25). The complete free energy profile, including both transition\nstate energy barriers and the relative energies of all intermediates, is now provided to clearly\nindicate whether each step is thermodynamically exothermic or endothermic. These additional\ndata allow a more comprehensive evaluation of the reaction energetics and further support the\nproposed reaction mechanism. The detailed free energy values have also been included in the\nSupporting Information for clarity and completeness (Figure S22).\nComment 5: The binding energy and phonon spectrum of perfect and defective β-MoO model\n3\nshould be calculated, as structure stability is prerequisite for reliability and interpretability of\ncomputational results.\nResponse: We greatly appreciate the reviewer’s valuable suggestion regarding the verification\nof structural stability. We fully agree that ensuring the structural stability of the perfect and\ndefective MoO models is a prerequisite for the reliability and interpretability of our\n3\ncomputational results. XRD, HR-TEM, and other studies indicate that the β-MoO (110) crystal\n3\nplane exhibits structural stability (Ref: Comput. Mater. Sci., 2017, 130, 242-248; Phys. Chem.\nChem. Phys., 2005, 7, 3819-3828.). Therefore, DFT calculation was resorted to studying these\nreduction reactions by ethanol on the (110) crystal face of β-MoO model with O . To\n3 v\nrigorously verify the robustness of our models, particularly under finite temperature conditions\nrelevant to the reaction environment, we performed Ab Initio Molecular Dynamics (AIMD)\nsimulations. While phonon spectrum analysis provides insight into dynamic stability at 0 K,\nAIMD simulations offer a direct assessment of thermal stability, ensuring that the structures\nremain intact against thermal fluctuations. As shown in Figure R1, we monitored the structural\nevolution of both the perfect and defective MoO surfaces over the simulation period. For the\n3\nperfect surface (Figure R4a): The structure exhibits excellent thermal stability. The atoms\noscillate around their equilibrium positions, maintaining the integrity of the lattice framework\nwithout any bond breaking or reconstruction. For the defective surface (Figure R4b), even with\nthe introduction of oxygen vacancies, the local structure remains robust. Although slight local\ndistortions are observed due to thermal vibrations, the overall lattice framework is preserved,\nand no structural collapse occurs. These AIMD results confirm that both the perfect and\noxygen-deficient MoO models possess sufficient structural stability, ensuring the reliability of\n3\nour subsequent property calculations.\nFigure R4. (Figure S21) Snapshots of the structure after AIMD simulations for (a) the perfect\nβ-MoO surface and (b) the defective β-MoO surface with oxygen vacancies. The simulations\n3 3\nwere conducted at 483.15 K. The structures remained stable with no significant distortion\nobserved after 1 ps of simulation, confirming the robustness of the models.\nComment 6: The authors qualitatively compares energy barrier (unit eV) by DFT with apparent\nactivation energy (unit kJ/mol) by experiments, a more quantitative comparison should be\nprovided and/or discussed.\nResponse: Thank you for your comments. We appreciate the reviewer’s suggestion to improve\nthe quantitative comparison between the DFT calculated energy barriers (in eV) and the\nexperimentally measured apparent activation energies (in kJ·mol-1). In the revised manuscript,\nwe have converted all calculated barriers from eV to kJ·mol-1 (1 eV = 96.5 kJ·mol-1) to enable\na direct comparison (Table S12). The discussion has been expanded to correlate the DFT-\nderived transition states with experimentally observed kinetics, showing consistent trends\nbetween the lower energy barriers on MoO -O and the reduced apparent activation energies\n3 v\nobtained experimentally. This quantitative comparison strengthens the reliability of our\nmechanistic interpretation and highlights the synergy between theory and experiment in\nelucidating the catalytic role of oxygen vacancies.\nTable S12. Comparison of activation energies obtained from experiments and DFT calculations\nActivation energies (kJ mol-1)\nEntry Substrates\nExperiments DFT calculations\n1 74.2 103.3\n2 88.8\n3 100.4\n4 111.6 140.0\nComment 7: The authors mention that oxygen vacancies provide both spatial and electronic\nenvironments, however, no investigation is conducted for the changes and the relationship of\natomic configuration and electronic property.\nResponse: Thank you for this insightful comment. In the revised manuscript, we have added\nDFT analyses of electron local function, charge density difference, and partial density of states\n(Figures R1-R3) to illustrate how the formation of O alters the local atomic and electronic\nv\nenvironments of Mo sites. The results show that O formation leads to localized electron\nv\nenrichment around adjacent Mo atoms, increasing their electron density and enhancing the\nability to activate O-H and α-C -H bonds. These new results strengthen the mechanistic\nsp3\nunderstanding by explicitly linking the structural configuration of O to its electronic effects\nv\nand catalytic function.\nConsidering all the above statements, our developed method demonstrated superior\nadvantages and novelties in broad substrate scope, high catalytic efficiency, and novel\nMoO catalysts, which led to the unique interamolecule hydride transfer mechanism.\nWith best regards,\nProf. Zehui Zhang &Jianguo Wang"}, {"round": 2, "reviewer_comments": {"reviewer_1": "I am satisfied with the made changes and agree to publication.", "reviewer_2": "Further clarifications are still needed for the following issues.\n1. Please provide a comparative analysis of the XRD and XPS spectra for both the fresh and spent samples as this would clarify the structural and electronic basis of the catalyst's durability and substantiate the author’s claim of high catalytic stability. The state and concentration of Mo species and Ov (before and after the reaction) should also be compared and discussed.\n2. For the correlation with TOF, it is recommended to utilize peak area percentages (relative ratios) rather than absolute peak areas for Ov and Mo5+. Using normalized values ensures a more accurate and valid comparison across different samples.\n3. Regarding the EPR results, have the authors checked the possibility that the observed signal may originate from unpaired electrons on C(sp2) induced by nitrogen vacancies? To clarify this, please include and discuss a comparison with the EPR spectrum of the CN-600 control sample.", "reviewer_3": "The current version can be accepted."}, "author_response": "Responses to the referees\nReviewer #1:\nI am satisfied with the made changes and agree to publication.\nResponse: Thanks for your valuable comments, which have improved our manuscript\na lot.\nReviewer #2:\nFurther clarifications are still needed for the following issues.\nComment 1. Please provide a comparative analysis of the XRD and XPS spectra for\nboth the fresh and spent samples as this would clarify the structural and electronic basis\nof the catalyst's durability and substantiate the author’s claim of high catalytic stability.\nThe state and concentration of Mo species and O (before and after the reaction) should\nv\nalso be compared and discussed.\nResponse: We thank the reviewer for this constructive suggestion. In accordance with\nthe reviewer’s recommendation, we have performed a detailed comparative analysis\nof the XRD spectra of both the fresh and spent catalysts. The corresponding results have\nnow been added to the revised manuscript (Figure S18a), together with a more\ncomprehensive discussion. The XRD pattern of the spent catalyst closely resembles that\nof the fresh sample, with no detectable formation of impurity phases or crystalline\nMoO species. The characteristic diffraction peaks remain unchanged in both position\nx\nand intensity within experimental error, indicating that the bulk crystal structure is well\npreserved after the catalytic reaction. No peak broadening or shift associated with lattice\ncollapse or phase reconstruction was observed. These results demonstrate that the\ncatalyst maintains its structural integrity under the reaction conditions, thereby\nsupporting its excellent durability.\nMoreover, the recycling experiments were conducted at both low and high\nconversion levels, and the results showed that the catalyst exhibited no noticeable loss\nof activity after five consecutive cycles (Figure S17). The SEM and TEM images of the\nrecovered Mo/CN-600 catalyst after five runs, showed no significant change as\ncompared with those from the fresh sample (Figure S18). No leaching of Mo into the\nreaction solution was observed by ICP-AES analysis. This high stability should be due\nto the strong interaction between the nitrogen-doped carbon support with the\nmolybdenum oxides.\nIn addition, the previous studies have demonstrated that oxygen vacancies can be\nregenerated through in situ redox cycling, thereby enabling their stable persistence\nunder reaction conditions (e.g., refer to Adv. Mater., 2022, 34(50), 2107956; Nat.\nCommun., 2025, 16(1), 2963; Nature, 2025, 640(8060), 947-953). In summary, the\nunchanged crystal phase (evidenced by XRD), stable structure, and activity collectively\ndemonstrate that both the bulk framework and surface-active sites remain intact after\nprolonged reaction. Therefore, the high catalytic stability arises from the intrinsic\nstructural robustness of the Mo-O framework and the reversible redox properties of Mo\nspecies, without irreversible phase transformation.\nComment 2. For the correlation with TOF, it is recommended to utilize peak area\npercentages (relative ratios) rather than absolute peak areas for O and Mo5+.\nv\nUsing normalized values ensures a more accurate and valid comparison across different\nsamples.\nResponse: We appreciate the reviewer’s valuable suggestion regarding the use of\nnormalized peak area percentages. However, in the present study, the total Mo loading\nvaries among different catalysts. Under such circumstances, directly comparing surface\npeak area percentages (i.e., relative ratios of O or Mo5+) may not accurately reflect the\nv\nactual density of active sites. Normalization within each individual sample inherently\nconstrains the relative ratios to the total detected Mo or O species, which can obscure\ndifferences in the absolute concentration of catalytically relevant sites across samples\nwith different Mo contents (Ref: Angew. Chem. Int. Ed., 2022, 61(3), e202111021; ACS\nCatal., 2022, 12(10), 5864-5886.)\nAs TOF is intrinsically related to the number of accessible active centers, a\nmeaningful structure–activity correlation requires consideration of both the chemical\nstate and the total amount of Mo species. Therefore, we have retained the discussion\nbased on absolute peak areas and complemented it with Mo loading information to\nprovide a more realistic comparison of active site density. This clarification has been\nincorporated into the revised manuscript.\nComment 3. Regarding the EPR results, have the authors checked the possibility that\nthe observed signal may originate from unpaired electrons on C(sp2) induced by\nnitrogen vacancies? To clarify this, please include and discuss a comparison with the\nEPR spectrum of the CN-600 control sample.\nResponse: Thank you for this insightful comment. We have measured the EPR\nspectrum of the CN-600 control sample under identical conditions. Notably, CN-600\nexhibits no detectable signal corresponding to oxygen vacancies or C(sp2)-related\nunpaired electrons (Figure S14). The characteristic EPR signal is observed only in the\nMo-containing sample, indicating that it originates from defect sites associated with\nMo-O environments rather than intrinsic defects in the CN-600 support. These results\nhave been added to the revised manuscript to clarify this point (page 13).\nReviewer #3:\nThe current version can be accepted.\nResponse: Thanks for your valuable comments which improve our manuscript a lot.\nWe hope that you find the revised manuscript acceptable and make a favorable\ndecision.\nWith best regards,\nProf. Zehui Zhang & Jianguo Wang"}, {"round": 3, "reviewer_comments": {"reviewer_2": "The current findings are much clearer, though the inclusion of the aforementioned oxygen vacancy concentration and XPS results of fresh and spent samples (from comment 1) would further strengthen the work. The MS's quality is acceptable for publication."}, "author_response": "Response: Thank you for the positive evaluation and helpful suggestion. In response,\nwe have included additional characterization of the spent catalysts to further strengthen\nthe manuscript (Figure S19). Specifically, the oxygen vacancy concentration and\ncomparative XPS analyses before and after the reaction have now been added and\ndiscussed in the revised manuscript (Figures 3a, 3b, S19, and Table S1-S6). The results\nshow that both the Mo species and the oxygen vacancy concentration remain largely\nunchanged after the catalytic cycles, further confirming the structural robustness and\nstability of the catalyst under the reaction conditions. We believe these additional data\nstrengthen the structure–stability correlation presented in this work.\nWe hope that you find the revised manuscript acceptable and make a favorable\ndecision.\nWith best regards,\nProf. Zehui Zhang & Jianguo Wang"}]

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