Enhancing Cascade Reaction Efficiency by Local pH Regulation for Integrated Anodic H₂O₂ Generation and Ammoximation

Abstract

Cascade reaction strategies integrating electrochemistry with chemical transformations offer routes for the synthesis of value‐added chemicals. However, the efficiencies of such integrated processes get compromised due to competitive electrochemical reactions and incompatibility between electrochemical and chemical transformations. We report an integrated electrochemical–chemical coupling of anodic H₂O₂ generation with ammoximation for oxime synthesis. An FTO/Sb₂WO₆ anode was designed and optimized to anodically produce H₂O₂ with a maximum Faradaic efficiency (FE) of 87%. H₂O₂ from the anode oxidizes NH₃ to NH₂OH, which subsequently reacts with cyclohexanone to yield cyclohexanone oxime with 99% selectivity and a maximum electron efficiency (EE) of 81%. Continuous and adjustable H₂O₂ input ensures synchronization with the ammonia oxidation reaction while minimizing over‐oxidation of the reaction intermediates. Operando scanning electrochemical microscopy (SECM) revealed local pH shifts caused by the proton‐coupled electron transfer and its effect on the FE of H₂O₂ synthesis and competing NH₃ oxidation, providing mechanistic insights for optimizing the reaction microenvironment. By regulating the electrolyte composition to modulate the interfacial pH, side reactions were suppressed and H₂O₂ generation was promoted, thereby enhancing cascade selectivity. This work highlights local pH regulation as a tool to improve reaction compatibility and efficiency in cascade electrosynthesis.

This work integrates anodic H₂O₂ generation with ammoximation for efficient oxime synthesis. By regulating the local pH through electrolyte engineering, the system achieves 81% electron efficiency (EE) and 98% H₂O₂ utilization, offering a generalizable strategy for cascade electrochemical–chemical processes.

Introduction

The synthesis of valuable precursors for important chemicals often involves complex reaction sequences.^{[ 1} , ^{2 ]} In general, achieving the activation of multiple reactants and the formation of new chemical bonds in a single step remains challenging. Cascade reactions, which enable sequential chemical bond transformations toward final products, offer an intensified approach for synthesizing numerous precursors, particularly valuable ring molecules.^{[ 3} , ⁴ , ^{5 ]} These reactions can be achieved via spatial integration of active sites on a heterogeneous catalyst or by temporal coupling of electrochemical steps with chemical reactions in the bulk solution.^{[ 6} , ⁷ , ⁸ , ^{9 ]} Integrating electrocatalysis with subsequent chemical conversions, or vice versa, has emerged as a promising route for synthesizing chemical commodities that are difficult to access via single‐step electrocatalysis or that rely heavily on stringent catalyst design or noble metals. For example, direct electrochemical oxidation of ethylene to ethylene oxide suffers from uncontrolled over‐oxidation and by‐product formation. Leow et al. addressed this by using Cl₂ generated at the anode as a diffusional redox mediator, leading to hypochloride mediated partial oxidation with an overall Faradaic efficiency (FE) of ∼70%.^{[ 10 ]} Similarly, direct electrochemical generation of propylene oxide (PO) from propylene suffers from poor FE and dependence on Pd/Pt‐based catalysts.^{[ 11 ]} Chi et al. developed a cascade method involving electrolysis for bromine generation followed by chemical conversion of propylene to PO with an FE as high as 91%.^{[ 12 ]}

Cyclohexanone oxime is a crucial intermediate for producing caprolactam, a key monomer for nylon‐6 production. The global market for nylon‐6 is projected to reach USD 26040 million by 2032, expanding at a compound annual growth rate (CAGR) of 5.9%. Conventionally, cyclohexanone oxime is synthesized via the reaction of cyclohexanone with costly hydroxylamine sulfate under harsh conditions using explosive H₂ and a noble metal catalyst at high temperatures, raising safety and cost concerns (Scheme 1a).^{[ 13 ]} Alternatively, hydroxylamine (NH₂OH), the essential intermediate for cyclohexanone ammoximation, can be generated either by electrochemical reduction of NO_x species (NO, NO₂ ⁻, and NO₃ ⁻)^{[ 5} , ¹⁴ , ¹⁵ , ¹⁶ , ^{17 ]} or by oxidation of NH₃ by means of H₂O₂.^{[ 18 ]} The NO_x reduction route (Scheme 1d) suffers from poor selectivity due to over‐reduction of NH₂OH to NH₃.^{[ 15} , ^{19 ]} In contrast, oxidizing NH₃ with the green oxidant H₂O₂ holds high potential for highly selective production of NH₂OH (Scheme 1b,c).^{[ 7} , ^{18 ]} Lewis et al. have demonstrated in situ H₂O₂ generation from H₂ and O₂ over titanium silicalite‐1 (TS‐1) supported Au‐Pd nanoparticles for cyclohexanone ammoximation (Scheme 1b).^{[ 7 ]}

Scheme 1.

Strategies for cyclohexanone oxime synthesis by integrating thermocatalysis/electrocatalysis with chemical reactions. a) Cyclohexanone‐hydroxylamine method using hydroxylamine sulfate. b) Cyclohexanone ammoximation by in situ generated H₂O₂ from H₂ and O₂. c) Cyclohexanone ammoximation by in situ generated H₂O₂ from electrochemical O₂ reduction. d) Electrosynthesis of NH₂OH by NO_x reduction. e) Proposed anodic H₂O₂ generation and the integration with cyclohexanone ammoximation.

Anodic H₂O₂ generation offers a safe, green alternative that can be seamlessly integrated with ammoximation. In this approach, H₂O₂ produced at the anode oxidizes NH₃ to NH₂OH on TS‐1, which subsequently reacts with cyclohexanone to yield cyclohexanone oxime. The advantage lies in avoiding gaseous reactant handling, explosive oxidants, and toxic chemicals. Additionally, in situ H₂O₂ generation ensures a continuous and tunable H₂O₂ supply to match the ammonia oxidation rate while minimizing the over‐oxidation of the intermediate, NH₂OH.

Nevertheless, integrating anodic H₂O₂ generation with the ammoximation reaction leads to unforeseen complications. On the one hand, the competitive oxygen evolution reaction (OER), shown in Equation (1) below, and the oxidation of NH₃/NH₄ ⁺ (Equations (2), (3), (4)) are thermodynamically more favorable than anodic H₂O₂ formation, which can limit the overall efficiency for H₂O₂/NH₂OH generation. On the other hand, the compatibilities of the catalysts involved in cascade reactions and their respective reaction conditions are critical requirements for high overall efficiency of the integrated process. (Please refer to Equation 2, ref^{[ 20 ]}; Equation 3 and 4, ref^{[ 21 ]} for further details)

$$2{\mathrm{H}}_2\mathrm{O}\rightleftharpoons {\mathrm{O}}_2+4{\mathrm{H}}^{+}+4{\mathrm{e}}^{-}{\mathrm{E}}^0=1.23\text{V versus RHE}$$ (1)

$$\begin{array}{cc}& {{\mathrm{NH}}_4}^{+}\left(\text{aq}\right)+2{\mathrm{H}}_2\mathrm{O}\rightleftharpoons {{\mathrm{NO}}_2}^{-}\left(\text{aq}\right)+8{\mathrm{H}}^{+}+6{\mathrm{e}}^{-}\hfill \\ & {\mathrm{E}}^0=0.65\text{V versus SHE}\hfill \end{array}$$ (2)

$$\begin{array}{cc}& 2\mathrm{N}{\mathrm{H}}_3\left(\text{aq}\right)\rightleftharpoons {\mathrm{N}}_2\left(\mathrm{g}\right)+6{\mathrm{H}}^{+}+6{\mathrm{e}}^{-}\hfill \\ & {\mathrm{E}}^0=0.092\text{V versus RHE}\hfill \end{array}$$ (3)

$$\begin{array}{cc}& 2\mathrm{N}{\mathrm{H}}_3+6\mathrm{O}{\mathrm{H}}^{-}\rightleftharpoons {\mathrm{N}}_2\left(\mathrm{g}\right)+6{\mathrm{H}}_2\mathrm{O}+6{\mathrm{e}}^{-}\hfill \\ & {\mathrm{E}}^0=0.092\text{V versus RHE}\hfill \end{array}$$ (4)

$$2{\mathrm{H}}_2\mathrm{O}\rightleftharpoons {\mathrm{H}}_2{\mathrm{O}}_2+2{\mathrm{H}}^{+}+2{\mathrm{e}}^{-}{\mathrm{E}}^0=1.76\text{V versus RHE}$$ (5)

Here, we report an integrated strategy for anodic H₂O₂ generation‐assisted cyclohexanone ammoximation, achieving ∼99% selectivity for cyclohexanone oxime and an overall electron efficiency (EE) of 81%. The FTO‐supported Sb₂WO₆ film was developed and optimized as the anode, providing a maximum FE of 87% for H₂O₂ generation in a KHCO₃/K₂CO₃ mixture, while exhibiting low selectivity toward the oxidation of NH₃/NH₄ ⁺. The incompatibility between highly efficient H₂O₂ formation at the anode and subsequent ammoximation presents a key challenge in integrating these reactions into a cascade. This was addressed by electrolyte engineering guided by operando scanning electrochemical microscopy (SECM). SECM‐based local pH investigations revealed the H₂O₂ generation mechanism and were used to optimize the H₂O₂ generation rate. Moreover, oxidation of NH₃/NH₄ ⁺ was effectively suppressed by tuning the anolyte pH, the buffer capacity, and the NH₄ ⁺ concentration. Furthermore, this strategy enabled efficient ammoximation of various ketones beyond cyclohexanone, demonstrating broad substrate applicability and providing a scalable platform for integrated green synthesis. This method avoids the high H₂O₂ concentration, transportation, and storage but still relies on H₂ and expensive noble metals. This highlights the need for safer and more cost‐effective alternatives.

Results and Discussion

Anode Material Characterizations

Sb₂WO₆ crystallizes in a layered Aurivillius‐type structure, consisting of perovskite‐like [WO₄]²⁻ sheets alternately stacked with [Sb₂O₂]²⁺ layers. In this framework, W centers are tetrahedrally coordinated, and the [WO₄]²⁻ layers in Sb₂WO₆ are reported to induce a more distorted lattice compared to other members of Aurivillius oxides.^{[ 22 ]} This suggests the presence of more unsaturated surface sites favorable for interfacial catalytic reactions. The basis for choosing Sb₂WO₆ can be found in the Experimental Section in the Supporting Information. The X‐ray diffraction (XRD) pattern of the catalyst film matches well with the reference pattern of Sb₂WO₆ (PDF#47–1680) (Figure 1a),^{[ 22 ]} confirming the successful synthesis of phase‐pure Sb₂WO₆ grown on FTO via a hydrothermal method. The SEM image (Figure 1b) reveals a clustered columnar morphology of the film. Energy‐dispersive X‐ray (EDX) mapping of the front side of the anode film confirms the homogeneous distribution of the W, Sb, and O (Figure 1c). Cross‐sectional SEM images clearly distinguish the catalyst layer and the underlying FTO substrate. The thickness of the Sb₂WO₆ layer is approximately 340 nm (Figure 1d). High‐resolution transmission electron microscopy (HRTEM) images (Figure 1e) show two sets of lattice fringes with inter‐planar spacing of 0.332 and 0.298 nm, which can be indexed to the (1$\overline{1}$1) and (1$\overline{1}\overline{2}$) facets of Sb₂WO₆, respectively. X‐ray photoelectron spectroscopy (XPS) was employed to analyze the valence states of the freshly prepared anode and the anode after performance evaluation (Figure 1f). The high‐resolution Sb 3d spectrum of the fresh sample can be deconvoluted into two main peaks at 539.8 and 530.5 eV, with a spin‐orbit splitting of 9.3 eV, corresponding to Sb³⁺ 3d _3/2 and Sb³⁺ 3d _5/2, respectively.^{[ 23} , ^{24 ]} After electrolysis, the Sb 3d spectrum exhibits a negligible change in the Sb oxidation state. The additional peak at 532.7 eV in the O 1s region is attributed to adsorbed bicarbonate anions on the anode surface. The high‐resolution W 4f spectra (Figure S1) of both samples show the presence of mixed W⁵⁺ and W⁶⁺ valence states, with a W⁶⁺/W⁵⁺ ratio of approximately 6:4 in both cases, indicating that the valence state of W remains stable under electrolysis at high potentials. The stability of Sb₂WO₆ at harsh oxidation conditions was further evaluated by quantifying the concentration of leached metal(s) in the anolyte. Inductively coupled plasma mass spectrometry (ICP‐MS) analysis revealed that after 3 h of electrolysis at 2.83 V versus RHE, the concentration of leached Sb and W in the anolyte was at trace levels (around 300 ppb), indicating a good stability of the catalyst under operational conditions.

Figure 1.

Catalyst characterization: a) The XRD pattern of the prepared FTO‐supported Sb₂WO₆ film (FTO/Sb₂WO₆). b) SEM images of the Sb₂WO₆ film. c) EDX images showing the distribution of Sb, W, and O on FTO. d) EDX images showing the distribution of Si, Sn, and W at the cross‐section of FTO/Sb₂WO₆. e) High‐resolution TEM image of Sb₂WO₆ scraped from FTO/Sb₂WO₆. f) High‐resolution XPS spectra of the Sb 3d region before and after electrolysis.

Anodic H₂O₂ Generation Performance

The pH influences multiple steps involved in cyclohexanone oxime production, including the H₂O₂ production rate, ammonia speciation, NH₂OH reactivity, and ammoximation kinetics. To systematically investigate the pH effect, we first examined the H₂O₂ generation performance at FTO/Sb₂WO₆ anode. Previous studies have demonstrated that the anolyte composition critically influences the FE of anodic H₂O₂ generation,^{[ 25} , ²⁶ , ²⁷ , ²⁸ , ^{29 ]} and the H₂O₂ formation may proceed through various reaction pathways, and intermediates, including hydroxyl radical, HCO₃ ⁻, or CO₃ ²⁻‐mediated mechanisms.^{[ 25} , ³⁰ , ³¹ , ^{32 ]} To eliminate the influence of competitive ammonia oxidation, we used KHCO₃/K₂CO₃ mixtures as anolytes to elucidate the interplay between anolyte components and H₂O₂ generation efficiency at FTO/Sb₂WO₆ anode. The H₂O₂ generation performance of FTO/Sb₂WO₆ was evaluated in electrolytes containing the same total concentration of HCO₃ ⁻/CO₃ ²⁻ but at different pH values (Figure 2a–c). For comparison, the performance of bare FTO was also assessed as a reference. The results show that the FTO/Sb₂WO₆ anode consistently exhibited higher H₂O₂ FE than bare FTO in all tested anolytes, demonstrating the intrinsic high selectivity of the Sb₂WO₆ film toward H₂O₂ formation. Specifically, in 2.0 M KHCO₃, the FTO/Sb₂WO₆ anode achieved an H₂O₂ FE of 40%–50% within the potential range of 2.50 to 2.90 V versus RHE. In a mixture of KHCO₃/K₂CO₃ with a pH of 10 (Figure 2b), the anode exhibits even higher H₂O₂ FE, exceeding 60% over a broad potential range (2.65 to 3.10 V versus RHE). Switching to a pure K₂CO₃ anolyte (Figure 2c) did not result in a further increase in H₂O₂ FE. Instead, a steady increase was observed, with FE rising from 30% at 2.60 V to 60% at 2.92 V versus RHE. These results clearly demonstrate that carbonate‐based electrolytes at pH 10 promote H₂O₂ generation at FTO/Sb₂WO₆ anode.

Figure 2.

H₂O₂ FE of FTO/Sb₂WO₆ anode and local distribution of carbonate species. a)–c) Comparison of H₂O₂ FE of FTO and FTO/Sb₂WO₆ anodes in different anolytes. The FE toward H₂O₂ generation of FTO/Sb₂WO₆ anodes and operando changes in the equilibrium mole fractions of HCO₃ ⁻/CO₃ ²⁻ anions as a function of substrate potential (E _sub) in d) 2.0 M KHCO₃, e) a mixture of 2.0 M KHCO₃ and 2.0 M K₂CO₃ with a pH value of 10, and f) 2.0 M K₂CO₃. The total concentration of carbonate‐based species for the three solutions is 2.0 M. g)–i) The H₂O₂ FE as a function of current density in carbonate‐based solution at pH 10 with different buffer capacity.

Investigation of Local pH Variations During H₂O₂ Generation

It is expected that the intrinsic layered structure of Sb₂WO₆, through its distinct surface terminations, along with the electrolyte composition and the turnover frequency of the electrochemical reactions, collectively regulate the local pH. In our experiments, we used the same catalyst to investigate the effects of electrolyte composition and applied potential on H₂O₂ selectivity. Therefore, the influence of the catalyst structure is not supposed to interfere with the absolute changes in local pH. During H₂O₂ generation, the oxidation of H₂O, OH⁻, or HCO₃ ⁻/CO₃ ²⁻ species at the anode surface releases protons, resulting in a shift in the acid–base equilibrium in the anode microenvironment. Consequently, the distribution of anionic species in the vicinity of an operating anode deviates from that in the bulk anolyte. Operando local pH investigation provides critical insights into identifying the dominant species at the reaction interface under conditions favoring H₂O₂ formation at the FTO/Sb₂WO₆ anode and elucidating the associated reaction pathways. To this end, operando local pH measurements were performed using an Au microelectrode positioned in close proximity to an operating FTO/Sb₂WO₆ anode in carbonate‐buffered solutions of different pH values (for further details, see Experimental Section, Supporting Information). The local pH variation as a function of applied anode potentials, i.e., substrate potentials (E _sub), was systematically studied in three anolytes.

As shown in Figure S2, a distinct anodic shift in the reduction peak potential of the Au tip (E(Au‐O_xRed)) was observed for all cases as the anode potential was stepped from 1.5 to 3.0 V versus RHE, indicating progressive acidification within the anode microenvironment (for detailed descriptions, see Note S1). The decrease in local pH leads to the protonation of CO₃ ²⁻ and HCO₃ ⁻, forming HCO₃ ⁻ and H₂CO₃, respectively, in accordance with the second (pK _a = 10.3) and first (pK _a = 6.3) dissociation constants of carbonic acid.

The molar fraction variations of carbonate species as a function of E _sub were calculated based on the local pH measurements. For each anolyte, the interfacial molar fractions of HCO₃ ⁻ and CO₃ ²⁻ were correlated with the H₂O₂ FE at varying E _sub, as shown in Figure 2d–f. In 2.0 M KHCO₃ solution (Figure 2d), the local molar fraction of HCO₃ ⁻ starts decreasing at 2.83 V versus RHE, while the fraction of CO₃ ²⁻ remains consistently low. Notably, the H₂O₂ FE reaches a maximum at 2.8 V versus RHE, after which it follows the decline trend of interfacial HCO₃ ⁻ concentration, confirming a strong correlation between H₂O₂ FE and the availability of HCO₃ ⁻ species at the anode surface as previously discussed.^{[ 32 ]} In a carbonate‐buffered anolyte at pH 10 (Figure 2e), the molar fraction of HCO₃ ⁻ increases, while CO₃ ²⁻ decreases over the potential range from 2.0 to 3.2 V versus RHE, indicating the progressive transformation of CO₃ ²⁻ to HCO₃ ⁻ at the reaction interface. Correspondingly, the H₂O₂ FE exhibits an increasing trend, rising from 58% at 2.65 V to 76% at 3.0 V versus RHE. In 2.0 M K₂CO₃ solution (Figure 2f), distinct changes in the molar fractions of HCO₃ ⁻ and CO₃ ²⁻ were observed, again reflecting the transformation of CO₃ ²⁻ to HCO₃ ⁻ at the interface. Correspondingly, the H₂O₂ FE increases, confirming the key role of HCO₃ ⁻ in promoting H₂O₂ formation. The H₂O₂ FE at FTO/Sb₂WO₆ strongly depends on local HCO₃ ⁻ concentration rather than CO₃ ²⁻. Therefore, it is proposed that H₂O₂ formation on FTO/Sb₂WO₆ proceeds via a HCO₃ ⁻‐mediated reaction pathway, in which HCO₃ ⁻ is first oxidized to HCO₄ ⁻, followed by its hydrolysis to yield H₂O₂.^{[ 27 ]}

Based on the findings shown in Figure 2d–f, maintaining a high molar fraction of HCO₃ ⁻ at the anode surface is critical for facilitating anodic H₂O₂ formation. To further improve H₂O₂ FE over a wide potential window, a pH 10 carbonate electrolyte was selected, and its buffer capacity was increased to mitigate the rapid depletion of local HCO₃ ⁻ anions during electrolysis. As shown in Figure 2g–i, the H₂O₂ FE at the FTO/Sb₂WO₆ anode in pH 10 anolytes with varying carbonate concentrations was plotted against the current densities. It is found that increasing the total carbonate concentration from 2.0 M (Figure 2g) to 2.4 M (Figure 2i) leads to a significant enhancement in H₂O₂ FE. Further increasing the total carbonate concentration to 2.95 M (comprising 1.37 M HCO₃ ⁻ and 1.58 M CO₃ ²⁻) results in an additional improvement, achieving H₂O₂ FE of more than 80% over a current density range of 20 to 45 mA cm⁻².

Exploring NH₂OH Production via NH₃ Oxidation by H₂O₂

To evaluate hydroxylamine (NH₂OH) production through NH₃ oxidation using anodically in situ generated H₂O₂, NH₄HCO₃ was chosen to replace KHCO₃ and serve as the nitrogen source. Cyclohexanone oxime formation was investigated in a custom‐designed H‐type cell (Figure S3) filled with an anolyte containing 10 mM cyclohexanone, first in the absence of the catalyst TS‐1 in four different anolytes containing varying NH₃/NH₄ ⁺ concentrations and different HCO₃ ⁻/CO₃ ²⁻ molar ratios (the exact cation and anion concentrations for anolytes 1–4 are listed in Table S1). Linear sweep voltammetry (LSV) recorded with and without cyclohexanone shows negligible differences, indicating that cyclohexanone is unlikely to undergo direct oxidation at the FTO/Sb₂WO₆ anode (Figure S4). After electrolysis for 60 min, the anolyte was analyzed by ¹H nuclear magnetic resonance (¹H NMR). The NMR spectra (Figure S5) exhibited no detectable signals corresponding to cyclohexanone oxime, indicating that the critical intermediate, NH₂OH, was not generated in the four anolyte conditions. These findings suggest that neither direct NH₃ oxidation at the FTO/Sb₂WO₆ anode nor the presence of H₂O₂ alone is sufficient for the generation of NH₂OH and cyclohexanone oxime.

In subsequent experiments, TS‐1 was introduced into the anolyte to catalyze NH₃ oxidation to NH₂OH using anodically generated H₂O₂. As shown in Figure 3a, after electrolysis at 2.78 V versus RHE for 60 min, the oxime yield reaches 54% in anolyte 1 and 75% in anolyte 2, indicating that increasing the pH from 8.3 to 9.6 results in a 21% increase in oxime yield. Notably, the yield reaches 100% when the total HCO₃ ⁻/CO₃ ²⁻ concentration is increased from 2.0 M (anolytes 1 and 2) to above 3.3 M (anolytes 3 and 4). This improvement is attributed to the increased H₂O₂ generation rate in anolyte with higher buffer capacity, as discussed in Figure 2. Next, the selectivity of the oxidation reactions occurring at the FTO/Sb₂WO₆ anode was investigated (Figure 3b). The H₂O₂ FE reaches 31%, 41%, 67%, and 73% at 2.78 V versus RHE in anolytes 1, 2, 3, and 4, respectively. The missing FE is mainly due to the OER and the competing NH₃/NH₄ ⁺ oxidation, with the latter not only lowering the H₂O₂ selectivity but also reducing the availability of NH₃ for the ammoximation reaction.

Figure 3.

Cyclohexanone oxime synthesis in the anodic H₂O₂ system. a) Yield of cyclohexanone oxime after 60 min electrolysis at 2.78 V versus RHE in anolyte 1 to 4. The composition details of the electrolytes can be found in Table S1. b) FE and H₂O₂ generation rate of FTO/Sb₂WO₆ anodes at 2.78 V versus RHE in anolytes 1, 2, 3, and 4. c) FE of NO₂ ⁻ and NO₃ ⁻ at the FTO/Sb₂WO₆ anode at 2.78 V versus RHE in anolytes 3 and 4. d) Current density‐dependent cyclohexanone oxime yield and selectivity. e) ¹H NMR of cyclohexanone oxime standard and the anolyte before and after electrolysis. f) Current density‐dependent cyclohexanone oxime yield rate in anolyte 4 using FTO/Sb₂WO₆ as the anode. g) The molar ratio of HCO₃ ⁻/CO₃ ²⁻/H₂CO₃ and NH₃/NH₄ ⁺ as a function of pH. h) Local pH changes as a function of anode potential in anolyte 4. i) The local concentrations of HCO₃ ⁻ and NH₃ as a function of the anode potential.

Investigation of Ammonia Oxidation at the Anode

To further investigate direct ammonia oxidation at the anode, the FE for ammonia oxidation was examined using anolytes 3 and 4, as they exhibited a high FE of H₂O₂. As previously reported, NH₃ tends to be oxidized to NO, NO₂ ⁻, or NO₃ ⁻ on transition metal‐based catalysts at high overpotentials.^{[ 33 ]} The amount of formed NO₂ ⁻ and NO₃ ⁻ was quantified by means of ion chromatography. After electrolysis at 2.78 V versus RHE, no NO₃ ⁻ was detected in any of the anolytes (Figure 3c). When the NH₃/NH₄ ⁺ concentration decreases from 1.0 M (in anolyte 3) to 0.56 M (anolyte 4), the FE for NO₂ ⁻ correspondingly decreases from 15% to 4.5%. The relatively low FE for NO₂ ⁻ across the anolytes indicates that FTO/Sb₂WO₆ exhibits low activity toward NH₃/NH₄ ⁺ oxidation. The pH of the anolyte primarily governs the speciation of ammonia. NH₄ ⁺ is generally considered electrochemically inert,^{[ 34 ]} whereas NH₃ with the lone‐pair electrons is more readily adsorbed onto the catalyst surface at more alkaline conditions, thereby facilitating the NH₃ oxidation reaction.

Based on these results, anolyte 4 was selected for subsequent studies on cyclohexanone oxime formation. After 60 min of electrolysis (Figure 3d), the oxime yield reaches 6%, 15%, and 53% at current densities of 1.4, 4.5, and 9.9 mA cm⁻², respectively. Further increasing the current density leads to a complete conversion, achieving 100% oxime yield. As evidenced by the ¹H NMR spectra, cyclohexanone oxime was identified as the sole product in the reaction system (Figures 3e and S6), demonstrating 100% product selectivity. Subsequently, the yield rate of cyclohexanone oxime was quantified (Figure 3f), and interestingly, a strong correlation was observed between the cyclohexanone oxime yield (Figure 3f) and the H₂O₂ generation rate (Figure S7), suggesting that the H₂O₂ production is the rate‐determining step in the overall oxime formation process.

Operando Investigation of Local Anolyte Composition and its Impact on Anode Reactions

Changes in the local anolyte composition can significantly affect the H₂O₂ FE of FTO/Sb₂WO₆ anode, as revealed in Figure 2. Meanwhile, direct NH₃ oxidation is highly pH‐sensitive. Therefore, operando monitoring of the local anolyte composition is essential for understanding the competitive reactions occurring at the anode. As shown in Figure 3g, the speciation of NH₃/NH₄ ⁺ and HCO₃ ⁻/CO₃ ²⁻ is highly pH‐dependent, indicating that their concentrations dynamically change during electrolysis. To evaluate these variations, operando measurements of local pH in the vicinity of FTO/Sb₂WO₆ anode were conducted in anolyte 4 (details provided in Figure S8). As the anode potential stepped to higher potentials, the increasing oxidation current caused a more pronounced pH decrease (Figure 3h), with a shift in local pH from 10.6 at 2.2 V to 8.2 at 2.85 V versus RHE. Correspondingly, the local concentrations of NH₃ and HCO₃ ⁻ were calculated, as shown in Figure 3i. It reveals that the local concentration of HCO₃ ⁻ reaches its maximum near 2.85 V versus RHE, while the NH₃ concentration decreases to less than 0.05 M. In parallel, the H₂O₂ FE reaches its maximum, attributed to the high interfacial coverage of HCO₃ ⁻ and the conversion of NH₃ to NH₄ ⁺. The increasing acidification of the anode microenvironment suppresses NH₃ oxidation since NH₄ ⁺ cannot be directly oxidized.^{[ 35 ]} At neutral and acidic conditions, the hydration shell of NH₄ ⁺ hinders its adsorption onto the catalyst surface, thereby reducing catalytic activity. Additionally, NH₄ ⁺ oxidation requires prior deprotonation, which introduces an additional kinetic barrier, resulting in sluggish kinetics. Furthermore, the lower FE for NO₂ ⁻ observed in anolyte 4 compared to anolyte 3 could be ascribed to the low local concentration of NH₃.^{[ 36 ]} These findings collectively indicate that the inhibition of NH₃ oxidation and the promotion of H₂O₂ generation can be achieved simultaneously through interfacial pH regulation, governed by bulk pH, NH₄ ⁺ concentration, and buffer capacity of the anolyte.

Efficiency Analysis of H₂O₂ Utilization for NH₂OH Formation and Cyclohexanone Ammoximation

Furthermore, the atom utilization efficiency of H₂O₂ for NH₂OH formation was evaluated. The critical intermediate NH₂OH was detected and quantified by its oxidation at an Au microelectrode owing to the high electrocatalytic activity of Au toward NH₂OH oxidation.^{[ 37} , ^{38 ]} Details of the calibration procedure are provided in Figures S9 and S10; Note S2. Next, the Au tip was dipped in anolyte 4. As shown in Figure 4a, the NH₂OH concentration increases linearly as a function of electrolysis time. Meanwhile, the H₂O₂ concentration was also quantified (Figure 4b). Note that for H₂O₂ quantification, the analysis was performed in the absence of the TS‐1 catalyst. The H₂O₂ utilization efficiency for NH₂OH formation reaches approximately 98% in the presence of TS‐1, indicating the excellent compatibility between anodic H₂O₂ generation and the subsequent oxidation of NH₃ to NH₂OH. The non‐catalytic reaction between NH₂OH and cyclohexanone was investigated by monitoring the remaining NH₂OH concentration in the presence of cyclohexanone by means of the Au tip response.

Figure 4.

Overall EE and the applicability of the integrated system. a) Concentration of NH₂OH in anolyte 4 as a function of electrolysis time. The inset shows the CVs recorded at the Au tip, indicating the increasing amount of NH₂OH with electrolysis time. b) H₂O₂ concentration in anolyte 4 and the utilization efficiency of H₂O₂ for NH₂OH formation. c) Time‐dependent NH₂OH concentration in anolyte 4 in the absence or presence of 10 mM cyclohexanone. (a–c) FTO/Sb₂WO₆ anode polarized at 2.78 V versus RHE. d) EE for cyclohexanone oxime synthesis at different current densities. e) Schematic diagram for the coupled anodic H₂O₂ generation at the anode surface and the ammoximation reaction in the bulk solution. f) Synthesis of various ketone oximes through the anodic H₂O₂‐coupled cascade ammoximation.

As shown in Figures S11 and 4c, NH₂OH undergoes slow self‐decomposition in anolyte 4, with a 10% loss after 60 min at room temperature. In contrast, the addition of cyclohexanone led to rapid NH₂OH consumption, indicating the high reactivity of NH₂OH with cyclohexanone under the studied conditions. Kinetic analysis of the reaction between cyclohexanone and NH₂OH revealed first‐order kinetics with respect to NH₂OH concentration (Figure S12). This finding is consistent with the generally accepted reaction mechanism, wherein NH₂OH acts as the nucleophile and attacks the electrophilic carbonyl carbon of cyclohexanone to form a transient intermediate, followed by dehydration to yield the corresponding oxime. Under the used conditions, the nucleophilic addition step is presumed to be the rate‐determining step, suggesting that the reaction rate is governed by the NH₂OH concentration, which is ultimately determined by the H₂O₂ generation rate in the presence of a non‐limiting NH₃ supply. The integrated system achieves a maximum EE of 81% for cyclohexanone oxime formation at 28 mA cm⁻² current density, as shown in Figure 4d (details of the calculation are provided in the Supporting Information). This high EE is primarily attributed to the optimized electrolyte and the local acidification near the anode, which collectively suppress the OER and NH₃ oxidation while simultaneously enhancing both formation and utilization of H₂O₂. The pH gradient across the diffusion layer was also investigated using the SECM‐positioned Au tip. Without forced convection, the diffusion layer thickness in anolyte 4 was derived to be about 3 mm (Figure S13), likely due to the high buffer capacity. The pH gradient across the diffusion layer from the anode surface to the bulk solution is shown in Figure S13, reflecting the concentration gradients of NH₃ and HCO₃ ⁻/CO₃ ²⁻ species. We propose that the integrated system operates through spatial coupling of H₂O₂ generation at the anode surface, the oxidation of NH₃ to NH₂OH predominantly within the diffusion layer, and the subsequent ammoximation in the bulk solution. The high H₂O₂ utilization efficiency within the diffusion layer, where the pH remains in the optimal range of 9–10, is critical to the overall EE. Otherwise, at pH values exceeding 10, both H₂O₂ and NH₂OH are susceptible to decomposition, reducing overall efficiency.^{[ 26 ]}

Next, the durability of the FTO/Sb₂WO₆ anode was examined by performing consecutive cycling tests for the conversion of cyclohexanone to cyclohexanone oxime. As shown in Figure S14, the oxime yield remains above 90% throughout 10 consecutive cycles, confirming substantial stability of the Sb₂WO₆ film under operating conditions. The surface morphology and the LSV curves of the anode after the above cycles were examined. No obvious morphological changes were found compared to the as‐prepared Sb₂WO₆ film (Figures S15 and 1b), and the LSV curves (Figure S16) show only a slight decrease in the current density of the spent FTO/Sb₂WO₆ anode compared to the fresh one. To further assess the applicability of the H₂O₂ generation‐assisted ammoximation strategy, a variety of other substrates, including cyclooctanone, cyclopentanone, benzaldehyde, hydroxymethylfurfural, and pyruvic acid, was individually added to the anolyte. Remarkably, all the ketones and aldehydes were efficiently converted to their corresponding oximes with high yield (88%–100%) and excellent selectivity (>98%), as summarized in Figures 4f and S17.

Conclusions

We have developed an integrated electrochemical–chemical strategy coupling anodic in situ H₂O₂ generation with TS‐1 catalyzed NH₂OH formation, enabling direct ammoximation of cyclohexanone under mild conditions. An FTO/Sb₂WO₆ anode was developed and optimized, achieving a selectivity for H₂O₂ production as high as 87%. Operando SECM investigations revealed that regulating the NH₄ ⁺ concentration, anolyte pH, and buffer capacity effectively suppresses the competing NH₃ oxidation while enhancing H₂O₂ selectivity via microenvironment control. Guided by these insights, cyclohexanone oxime was produced with up to 100% yield and selectivity and a maximum EE of 81%. The system exhibits durability over ten consecutive cycles and broad applicability to various ketones and aldehydes, as confirmed by transforming various ketones and aldehydes into their corresponding oximes with high yields (88%–100%). This work not only provides new insights into the rational coupling of anodic H₂O₂ generation with fine chemical synthesis but also highlights the critical role of local pH regulation in maximizing cascade reaction efficiency by promoting target transformations and suppressing side reactions.

Conflict of Interests

The authors declare no conflict of interest.

Supporting information

Supporting Information

Dedicated to Prof. Alexander Kuhn, University of Bordeaux, on the occasion of his 60^th birthday

Li L., Zhang J., Santana Santos C., Zerdoumi R., Seisel S., Chandra S., Schuhmann W., Angew. Chem. Int. Ed. 2025, 64, e202515867. 10.1002/anie.202515867

Data Availability Statement

All data associated with this article are available from the authors with reasonable request.