Integrated electrochemical porous solid electrolyte reactor and packed bed reactor for efficient synthesis of nylon-6 precursor

Domain: chemistry
Published: 2026-03-05
Editorial outcome: minor_revision

Abstract
The current production of cyclohexanone oxime (CyO), an essential precursor in the global nylon-6 industry, relies on processes that utilize toxic substrates and hazardous oxidizing agents. Here we present a continuous process and reactor design, with integrated electrochemical porous solid electrolyte reactor (PSER) and packed bed reactor (PBR), for an electrolyte-free, scalable, and efficient generation of high-purity CyO product from cyclohexanone (CyH), oxygen and ammonia. By electrochemically converting oxygen into high-purity hydrogen peroxide in a PSER, followed by a direct feeding into a downstream PBR for CyH ammoximation without any intermediate purification steps, we are able to obtain electrolyte-free CyO products. In an integrated 25-cm² PSER (six times larger than our previous design) and a titanium silicate-1 filled PBR system, we successfully demonstrate high CyO product selectivity of 97.2%, high yield of 93.6%, as well as high peroxide utilization efficiency of 96.3%. By operating the PSER under 125 mA/cm2, up to 28.3 mmol/h of CyO production rate can be achieved. Efficient conversions of a broad range of other aliphatic and aromatic ketone substrates are also demonstrated in this integrated PSER-PBR reactor system.

Introduction
Cyclohexanone oxime (CyO), a vital precursor for producing nylon-6, is globally manufactured on a scale of approximately six million tons annually1. This compound is synthesized primarily through the rapid reaction between cyclohexanone (CyH) and hydroxylamine (NH2OH), as illustrated in Fig. 1. In traditional CyO production, the major challenges stem from the instability of the intermediate NH2OH, which is prone to hazardous decomposition2. To mitigate these risks, processes typically incorporate acid stabilization using sulfuric or phosphoric acid and subsequent neutralization steps, which not only increase production costs but also result in the generation of low-value byproducts (Fig. 1a)3,4. Recent research has increasingly focused on the in-situ generation of NH2OH and its direct conversion with CyH to CyO, thereby simplifying the manufacturing process and reducing byproduct formation. Typically, two main pathways, including nitrogen oxides reduction and ammonia oxidation have been identified for synthesizing hydroxylamine (NH2OH) using various nitrogen sources and the in-situ production of CyO (Fig. 1a–c). The first pathway involves the chemical or electrochemical reduction of NOx, such as NO, NO2−, or NO3− from different nitrogen sources5–15. These methods, however, often suffer from over-reduction to undesired ammonia (NH3), presenting significant challenges in achieving satisfactory conversion rates and efficiencies towards NH2OH and CyO production rate. To achieve a higher current density, additional salts are required as NO is consumed, which will lead to an increase in the separation process steps and investment costs. Additionally, nitrogen oxides predominantly stem from the oxidation of NH3 in industry, suggesting the low overall energy efficiency of this synthetic route. The second pathway, which directly utilizes NH3 to synthesize NH2OH in a single oxidation step, could significantly improve the energy efficiency by avoiding multiple oxidation and reduction steps16,17, and promise a greener and more sustainable pathway towards CyO synthesis.

One of the primary challenges in industrializing the NH3 oxidation pathway for CyO production revolves around the selection and method of applying the oxidants18. Among different types of oxidants, hydrogen peroxide (H2O2) emerges as a particularly promising candidate, owing not only to its ability to facilitate efficient and rapid conversion of NH3 to NH2OH and subsequent in-situ reactions, but also due to its inherent environmental benignity and no harmful byproducts19–21. However, the transportation, handling, and storage of concentrated H2O2 from centralized production facilities to end-users poses significant challenges. Given its rapid decomposition, especially under high concentrations, H2O2 is typically stabilized with acids (e.g., phosphoric or phthalic), chelating agent (e.g., nitrilotriacetates, citrates), or colloidal silica, etc.22,23. These stabilizers not only introduce impurities in the chemical synthesis of CyO but also potentially limit the reactivity and the stability of the catalyst, reducing the reactor’s lifespan due to corrosion24. Additionally, H2O2 is mainly produced through the energy-intensive anthraquinone process, which emits roughly three tons of carbon dioxide per ton of H2O2, accounting for hydrogen usage, on-site energy consumption, and off-site energy losses due to decomposition25. In 2022, Lewis, Liu, and Hutchings introduced a groundbreaking method, leveraging the in-situ generation of H2O2 from a mixture of H2 and O2 using a gold-palladium catalyst for the oxidation of NH3 during the CyH ammoximation process, which presented a promising approach to mitigating the challenges of long-distance oxidant transport (Fig. 1c)26. Despite their innovative reaction process design, the high-pressure requirements for the mixed H2 and O2 gases, the expensive Au-Pd catalyst, and the relatively low oxime production rate (0.68–1.4 mmol/h) still need further improvement for large-scale applications. Very recently, Yuan and co-workers described an electrocatalytic ORR for CyO synthesis by purging oxygen gas into the NH4HCO3 solution under a relatively low current density, which has an inherent limitation due to the oxygen mass transfer issue (Fig. 1c)27.

Here, we present a continuous process and reactor design, integrating an electrochemical porous solid electrolyte reactor (PSER) with a packed bed reactor (PBR), for a direct, continuous, and highly efficient generation of high-purity CyO from CyH ammoximation (Fig. 1d). The PSER electrochemically generated electrolyte- and impurity-free H2O2 solutions with tunable concentrations directly from oxygen and water. Meanwhile, the downstream PBR, a widely used industrial reactor for heterogeneous catalytic systems, facilitated the subsequent ammoximation of CyH28. The electrochemically generated H2O2 (eH2O2) was directly co-fed with NH3 and CyH into a PBR filled with TS-1 catalyst, a widely used commercialized catalyst for ketone ammoximation reactions in industry3, enabling highly selective and high-yield production of CyO. Compared to batch reactors and continuous-stirred tank reactors (or continuous slurry reactors) reported for CyO production29, our PSER-PBR system offers several key advantages, including continuous operation, lower operating costs, a more compact design, and the elimination of catalyst-liquid separation, which simplifies downstream processing. Importantly, no impurity of sulfuric acid, phosphoric acid or other H2O2 stabilizers are involved in the entire process, eliminating the need for extensive downstream separation steps.

Through our PSER-PBR system, CyO can be continuously produced with a high CyH conversion of 96.3%, CyO selectivity of 97.2%, CyO yield of 93.6%, and H2O2 utilization efficiency of 96.3%, at a H2O2 electrolysis current density of 12 mA/cm2 in the PSER. The current density can be increased to an industrially-relevant level of 125 mA/cm2 (a total of 3.1 A with 25 cm2 electrode), where CyO was produced at a rate of 28.3 mmol/h (1.132 mmol/(h·cm2); 3.2 g/h) from our lab-scale prototype reactor while delivering a 68.1% CyH conversion, 96.9% CyO selectivity, 65.9% CyO yield, and 60.6% H2O2 utilization efficiency. The reduced performance under higher current condition could come from the increased amount of O2 bubbles generated from the decomposition of H2O2, which decreases the reactant remaining time on the surface of TS-1 catalyst. Remarkably, this CyO production rate (at 125 mA/cm2, FE of 50.3%, 1.132 mmol/(h·cm2)) greatly surpassed prior benchmarks (Supplementary Table 1), suggesting its potential for practical applications. A techno-economic analysis (TEA) demonstrated the PSER-PBR strategy for CyO production is profitable with a rather low cost of 2196 $/ton under a 0.1 $/kWh electricity fee (CyO market price is around 9700 $/ton)30. The use of cheapest nitrogen source—NH3 (except N2) and low cost of H2O2 production from our PESR reactor are the main reason for benefits.

Results
PBR optimization
To ensure the seamless integration of the two units in our system, we first optimized the PBR and electrochemical H2O2 synthesis sections independently, focusing on the operating range of mutual interest. As shown in Fig. 2a, our system utilizes a PBR with a 6.4 mm diameter, packed with commercial TS-1 catalyst (Supplementary Fig. 1), which is renowned for its effectiveness in ammoximation reactions. Within the reactor, TS-1 catalyzes the reaction between NH3 and H2O2 to form active NH2OH, which subsequently reacts with CyH to yield CyO. Key ammoximation factors, including reactant concentrations, reaction rate (governed by intrinsic kinetics, temperature, catalyst loading, etc.), and residence time (determined by the reactor length and feeding rates), are analyzed in our PBR system. During the process, the H2O2 utilization efficiency is determined by KMnO4 titration (based on excess H2O2); the substrate (CyH) conversion, target product (CyO) selectivity, yield and production rate are analyzed by 1H-NMR spectroscopy; the NH3 and other nitrogen sources were analyzed by GC and UV–vis (see detailed parameter definitions in “Methods”, Supplementary Figs. 2–15).

The optimization reaction started with a mixture of 0.2 M CyH, 0.4 M NH3·H2O and 0.26 M commercial H2O2 (cH2O2) at a constant flow rate of 0.5 mL/min into a PBR containing 1.5 g TS-1 at 80 °C with a two-hour continuous detection, resulting a stable ammoximation performance after 0.5 h with a CyH conversion up to 91.7%, a CyO selectivity over 96.0%, production rate around 5.0 mmol/h and yield of 88.0%, and an approximately H2O2 utilization efficiency of 74.8% (based on 0.26 M H2O2 usage) (Fig. 2b, c and Supplementary Fig. 16). Without specific instruction, we selected the one-hour reaction for further comparison. Although the reaction scale increased from 0.2 moles to 0.8 moles, high performance was maintained with a CyO selectivity of above 96%, a CyO concentration up to 0.23 M, and high production rate of 18.2 mmol/h, a slightly decreased CyH conversion from 91.7% to 85.9% and a CyO yield from 88.0% to 84.3% (Fig. 2b, c and Supplementary Figs. 16–18). It was noteworthy that the pre-added carbon source CyH goes into three parts: the target product CyO, the detected unreacted CyH, and the missing part perhaps coming from the 1H-NMR measurement error, the evaporation of CyH, and the precipitation of over-concentrated CyO. The analysis comes from the optimization of temperature when using a high input concentration of 0.8 M CyH. Theoretically, higher temperatures enhance reaction rates, leading to greater conversion and yield. As expected, the CyO yield was low at approximately 36.8% at 25 °C, increased to above 78.9% at 40 °C, and reached a maximum yield of 84.3% at 80 °C (Fig. 2d and Supplementary Figs. 19 and 20). Notably, in addition to the detected hydrocarbons CyH and CyO, Fig. 2d shows a “carbon loss” fraction (yellow column), initially attributed to measurement errors from 1H-NMR analysis observing no other byproducts (Supplementary Fig. 2). This “carbon loss” increased from 1.6% at 80 °C (possibly due to the measurement error) to 8.7% at 40 °C and further to 14.6% at 25 °C, showing the factor of increasing CyO deposition (mainly because of the decreased CyO solubility) (Supplementary Fig. 21). Although 40 °C was sufficient for a high yield of CyO, we used 80 °C in subsequent tests to minimize the loss fraction unless otherwise specified.

Catalyst loading is also a crucial factor in the PBR system. As shown in Fig. 2e, the CyO yield remained stable at around 80% when reducing TS-1 usage from 1.5 to 0.1 g, with the highest catalytic efficiency of 161 mmol·h−1·gcat−1 achieved at 0.1 g TS-1, albeit with a slightly decreased yield of 74.3% (Supplementary Figs. 22–24). To assess the impact of catalyst diffusion within the PBR, we mixed 0.2 g TS-1 with varying amounts of structurally similar SiO2, presenting a different PBR length from 4 cm to 14 cm. The result confirmed that TS-1 diffusion does not significantly affect catalytic performance (Supplementary Figs. 25 and 26).

To further enhance the CyO productivity, we screened commonly used alcohols from the nylon-6 production industry to improve CyH and CyO solubility (Fig. 2f, g and Supplementary Fig. 27). Among them, t-BuOH demonstrated a superior performance, yielding 75%, slightly lower than in water but still the most effective among tested alcohols. With t-BuOH, the CyO yield increased from 75% at 0.8 M CyH to over 80% at 3.2 M CyH (Fig. 2g and Supplementary Fig. 28). Therefore, to optimize performance, we used H2O as the solvent for tests with CyH concentrations below 0.8 M and t-BuOH for the concentrations above 0.8 M. A slight improvement in performance was observed with increased of H2O2 concentration. As shown in Fig. 2h, i, when processing 3.2 M CyH, reducing the H2O2:CyH ratio from 1.3:1 to 1:1 led to a slightly decreased yield from 80% to 71% but an improved H2O2 utilization efficiency from 64% to 73% (Fig. 2e, f). At 80 °C, when 4.1 M H2O2/CyH (1:1) reacted with 7.6 M NH3·H2O, we could achieve a conversion of 82.8%, a yield of 82.1%, H2O2 utilization efficiency of 82.1% and productivity of 91.8 mmol/h (10.4 g/h) (Fig. 2h and Supplementary Fig. 28d, e). To maximize H2O2 utilization efficiency and improve overall Faradaic efficiency (FE), we maintained an H2O2/CyH ratio of 1:1 in subsequent tests unless otherwise specified.

The scaled-up PSER for H2O2 production
Having a clear understanding of the PBR parameters, we next investigated the electrochemical 2e−-oxygen reduction reaction (ORR) for H2O2 production. To guarantee the high purity of H2O2, we adopted the three-chamber PSER, where the middle chamber was separated by an anion exchange membrane (AEM) and a cation exchange membrane (CEM). In the PSER, as illustrated in Fig. 3a, the middle chamber was filled with PSE instead of traditional liquid electrolyte, significantly reducing the ionic impurities in the H2O2 product. On the cathode side, a gas diffusion layer (GDL) bearing carbon black served as the cathodic catalyst, facilitating the reduction of gaseous O2 into HO2− species via a two-electron transfer and further avoiding the gas mass transfer issue. The generated HO2− penetrated through the AEM into the middle chamber. On the anode side, a commercial IrO2 onto GDL was used to produce H+ through water oxidation, which subsequently reacted with the HO2− to form H2O2. The combination of the stable and low cost carbon black catalyst and the long-term operability of commercial IrO2 substantially reduced H2O2 production costs. Additionally, the tunable current density allowed for on-demand H2O2 generation at the required concentration, eliminating the need for dilution from high commercial concentrations. Most importantly, since H2O2 was produced with high purity, no additional separation steps were required between the PSER and PBR.

To enable direct integration with the PBR, the H2O2 production rate in the PSER need to be closely matched with the H2O2 input rate required for the ammoximation reaction, as discussed in the previous section. To ensure sufficient supply of H2O2, we scaled-up the PSER reactor to a reaction area of 25 cm2 and evaluated its electrochemical performance (Supplementary Fig. 29). We optimized the electrochemically in-situ generated H2O2 concentration by tunning the current density with a fixed a DI water flow rate of 0.5 mL/min in our PSER for better integration with CyH ammoxidation reaction in the PBR. At a current density of 12 mA/cm2, the PSER continuously produced H2O2 at a concentration of approximately 0.2 M, corresponding to a production rate of 5.6 mmol/h, with a FE of 96.0% at a cell voltage of only 1.8 V. Increasing the current density to 56 mA/cm2 yielded 0.8 M H2O2 (23 mmol/h) with a high FE of 87.9%. Further scaling to 125 mA/cm2 (the current goes to 3.1 ampere) resulted in a high H2O2 concentration of 1.6 M with a H2O2 production rate of 45 mmol/h at 2.7 V, although with a slightly decreased FE of 75.5% possibly due to the high product concentration and rising temperature (Fig. 3b–d). Although higher H2O2 concentration (up to 30 wt%, 9.8 M) in PSER reactor has been demonstrated in our previous work31, we still use 1.6 M eH2O2 to perform the following CyH ammoximation without regulating the water flow rate to coordinate feeding rate of NH3 and CyH (Supplementary Fig. 30).

The PSER-PBR system for CyH ammoximation with electrochemically in-situ generated H2O2
Having established the electrochemical H2O2 generation part and the following CyH ammoximation with H2O2, we further coupled the PSER with the PBR to validate the complete on-site ammoximation process. As illustrated in Fig. 3a, the tandem reaction was initially investigated with co-feeding electrochemically generated 0.2 M H2O2 (eH2O2) at 12 mA/cm2, 0.2 M CyH (in water), and 0.4 M NH3·H2O with the same flow rate into a PBR with 1.5 g TS-1. High performance was achieved (Fig. 3e–g): 96.3% H2O2 utilization efficiency, 96.3% CyH conversion, 93.6% CyO yield, and 97.2% CyO selectivity. Notably, this surpassed the performance obtained using excess commercial cH2O2 (Fig. 2b, c and Supplementary Fig. 16): 74.8% H2O2 utilization efficiency (calculation based on 1.30 equivalents of cH2O2), 91.7% CyH conversion, 88.0% CyO yield, and 96.0% CyO selectivity. According to previous experimental results (Fig. 2h, i), more amounts of oxidants were beneficial for the CyH ammoximation, however, the electrochemically generated H2O2 (1.0 eq eH2O2) by PSER achieved even better performance than that with commercial H2O2 (1.3 eq cH2O2). This result evidenced that the electrochemically in-situ generated pure eH2O2 is more reaction-positive than cH2O2 bearing stabilizer, which could partially sacrifice the oxidation ability or interfere the activity of the catalyst. A more direct contraction is from the reaction of 0.8 M CyH (in t-BuOH) with 1 equivalent of cH2O2 (Fig. 2h, i) and 1 equivalent of eH2O2 at 56 mA/cm2 current density (Fig. 3e–g), as below: c 63.7% vs. e 81.2% H2O2 utilization efficiency, c 64.3% vs. e 81.2% CyH conversion, c 63.6% vs. e 79.0% CyO yield, c 13.9 mmol/h vs. e 16.9 mmol/h CyO production rate and c 99.0% vs. e 97.4% CyO selectivity.

When applying an industrial current density of 125 mA/cm2 (3.1 A) in PSER, the obtained eH2O2 (1.6 M) showed a similar CyH ammoximation performance with 1.6 M cH2O2: c 69.0% vs. e 60.6% H2O2 utilization efficiency, c 69.6% vs. e 68.1% CyH conversion, c 67.8% vs. e 65.9% CyO yield, c 29.6 mmol/h vs. e 28.3 mmol/h CyO production rate and c 97.4% vs. e 96.9% CyO selectivity. The decreased performance may come from the higher decomposition rate of concentrated eH2O2 into lots of O2 bubbles over cH2O2 bearing stabilizer, which could lead to the contact opportunity between catalyst and liquid and also the reduced amounts of oxidants—H2O2 (Supplementary Fig. 31 and Supplementary Tables 2 and 3).

Another important parameter, total Faradaic efficiency (namely, an electron-to-oxime efficiency) was also calculated, achieving a high FE of up to 92.4% with 0.2 M eH2O2 at 12 mA/cm2, a good FE value of 72.5% with 0.8 M eH2O2 at 56 mA/cm2, and a still acceptable FE of 50.3% with 1.6 M eH2O2 at 125 mA/cm2 (Fig. 3g), which outperformed the overall CyO Faraday efficiency of electrochemically generated NH2OH from NO (NO/NO2−/NO3−) reduction (Table S1) 5–13. Although previous reports showed high FE (26% to 68%) when applying low current density (<60 mA/cm2), the CyO production rates were low from 0.02 mmol/(h·cm2) to 0.28 mmol/(h·cm2). Previous studies also showed the improved CyO production rates from 0.19 to 0.59 mmol/(h·cm2) at high current density from 200 mA/cm2 to 500 mA/cm2, but delivered a lower FE (1.5%–20%) than 50.3% in our PSER-PBR system at 125 mA/cm2 with 1.13 mmol/(h·cm2). High current density would exacerbate the competitive electroreduction of NO into NH3 instead of NH2OH, which further reduced the CyH ammoximation performance 5–13. Very recently, Liu and Chen reported high FE (>90%) during the NO3RR process above 200 mA/cm2, however, minor by-products of NH3 need to be removed 14,32. Compared to blubbing O2 into NH4HCO3 at a relative low current density (<15 mA/cm2) 27, our one-pass and electrolyte-free PSER design for 2e−-ORR without any O2 mass transfer issues showed its powerfulness in industry.

The PSER-PBR system application evaluation for other ketone oximes production and equipment stability
Beyond cyclohexanone oxime, other organic oximes also play essential roles in chemical and industrial synthesis. To explore the versatility of the PSER-PBR system, we tested its performance in producing various oximes (Fig. 4a and Supplementary Figs. 32–36). Specifically, other cycloketones (5-membered and 7-membered ketones), acyclic ketones, and benzyl ketones were reacted with eH2O2 to yield their corresponding oximes. As shown in Fig. 4b, high selectivity was achieved across all tested substrates, exceeding 98%. Acetone and 3-pentanone exhibited high conversion and yield of above 80%. cycloketones and PhCHO showed relatively lower yields and conversions, and further optimization of reaction conditions may be necessary for these species.

Delivering good stability of this integrated system is more challenging than each of the independent reactor. Since the PSER was enlarged to 25 cm2 in our work, it was more challenging to produce H2O2 stably than the smaller size of reactors we demonstrated before 33–35. Encouragingly, the FE of H2O2 maintained above 80% at 60 mA/cm2 for over 100 h, with cell voltages stabilizing at 2.0 V (Supplementary Fig. 37). When coupled with a PBR, the system maintained a H2O2 utilization efficiency of around 80%, consistent CyO yield of around 80%, CyO selectivity above 95%, CyO production rate of 16 mmol/h for 30 h (Fig. 4c). This represents 0.384 mol of total ketone oxime production every day, which is higher than previous reports, such as 0.216 mol/day 9 and 0.158 mol/day 10 using NOx, 0.032 mol/day 27 using NH4HCO3 and 0.034 mol/day 26 using NH3. Over extended operation, the TS-1, a robust commercial catalyst, may still experience activity loss and require regeneration, traditionally necessitating process interruptions for catalyst separation and reactivation 29,36. However, our modular design ensures continuous operation by allowing seamless PBR replacement. The used TS-1 could be replaced, reactivated, and reused, analogous to swapping a fully charged battery in electric device, eliminating downtime for recharging.

Moreover, to clarify the economic potential of the PSER-PBR setup for producing CyO, we performed a preliminary techno-economic analysis (TEA) based on the performance of our PSER-PBR reactor at 125 mA/cm2 (Fig. 4c and Supplementary TEA Note). We also considered our previous PSER TEA for H2O2 production 31 and Shi’s work 27 for evaluation of CyO economic benefits. Our strategy was demonstrated to produce CyO with a rather low cost of 2196 $/ton under a 0.1 $/kWh electricity fee (2533 $/ton, even with 0.2 $/kWh), which is very profitable in consideration the market price of CyO (~9700 $/ton) 30. The main reason comes from the use of cheapest nitrogen source—NH3 and low cost of H2O2 producing strategy from our PESR reactor.

Methods
Chemicals and materials
Titanium Silicalite-1 (TS-1) was purchased from ACS Material. was purchased from Sigma. Oxygen (>99.9%) was purchased form Airgas. Solid electrolyte (Amberchrom® 50WX8, 200–400 mesh, hydrogen form), DMSO, 0.1 N KMnO4 standardized solution, Nafion 117 solution (5%), methanol, ethanol, isopropanol (IPA), and tert-butyl alcohol (t-BuOH) were all purchased from Sigma-Aldrich. D2O (99.9% D) was purchased from Cambridge Isotope Laboratories, Inc. SiO2 (70–230 mesh) was purchased from Beantown Chemical. Sigracet 28 BC gas diffusion layer (GDL) and Nafion 1110 was purchased from Fuel Cell Store. Carbon black (BP2000) was purchased from Cabot Corporation. Anion exchange membrane (AEM) (Sustainion® X37-50 Grade T) and IrO2 on carbon paper was purchased from Dioxide Materials.

2e−-ORR catalyst preparation
15 mg BP2000, 120 μL 5% Nafion 117, and 4 mL IPA were added to a 10 mL glass vial and sonicated for 1 h. Subsequently, this ink was sprayed onto a GDL (6.0 × 6.0 cm2) via a spray gun. Finally, it was dried and cut into 5.0 × 5.0 cm2 (density of ORR catalyst is around 0.41 mg/cm2) species as cathode.

Ammoximation catalyst (TS-1) characterization
Scanning electron microscope (SEM) spectra were performed on a FEI Quanta 400 field emission scanning electron microscope.

2e−-ORR for producing H2O2
A BioLogic VMP3 workstation was employed to record the electrochemical response without IR compensation. Gas diffusion layer (GDL, 25 cm2) loaded with BP2000 was used as ORR catalyst and commercial IrO2 onto GDL (25 cm2) was used as OER (oxygen evolution reaction) catalyst. The three-chamber solid electrolyte cell was composed of a cathode chamber, an anode chamber, and a middle layer filled with the mixture of solid electrolyte, which was separated by an anion exchange membrane and a cation exchange membrane. The cathode chamber was fed with an O2 flow rate of 20 mL/min and the anode chamber was fed with a 1.0 mL/min DI water flow rate. DI water with a certain flow rate was purged into the middle layer to get certain concentration of H2O2 at applied current densities. The concentration was analyzed through the titration of H2O2 with 0.1 N KMnO4.

H2O2 concentration was measured by standard potassium permanganate (0.1 N KMnO4 solution, Sigma-Aldrich) titration process, according to following equation:
2KMnO4 + 5H2O2 + 3H2SO4 → 2MnSO4 + K2SO4 + 5O2 + 8H2O (1)

Ammoximation process to obtain the ketone oximes in a packed bed reactor
The standard reaction condition is as follows, 0.2 M-4.1 M cyclohexanone (in water), commercial or electrochemically generated H2O2 (1.0–1.3 equiv.) and NH3·H2O (2.0 equiv.) were merged with the same flow rate of 0.45–0.47 mL/min into a packed bed reactor filled with TS-1 catalyst (or the mixture of TS-1 and SiO2 to maintain a certain length of PBR) at different temperatures. After the reaction, the solution was analyzed by NMR spectra, which were recorded on a 500 MHz SB Liquid Bruker Advance NMR spectrometer and using a water suppression technology.

The calculation of H2O2 Faradaic efficiency, ketone conversion, ketone oxime selectivity, yield and Faradaic efficiency, and H2O2 utilization efficiency.

H2O2 Faradaic efficiency (%) = (Conc.H2O2 (mol/L) × Flow rate (L/s) × 2 × 96485 C/mol) / jtotal (mA) × 100 (2)
(Conc.H2O2 (mol/L) is the concentration of generated H2O2 from the titration of KMnO4).

Ketone conversion (%) = converted ketone (mol/s) / overall ketone (mol/s) = (Conc.before ketone (mol/L) × FRbefore ketone (L/s) − Conc.after ketone (mol/L) × FRafter ketone (L/s)) / (Conc.before ketone (mol/L) × FRbefore ketone (L/s)) × 100% (3)
(Conc.before ketone (mol/L), FRbefore ketone (L/s), Conc.after ketone (mol/L), FRafter ketone (L/s) represent the concentration and flow rate of ketones before reaction, and the merged concentration and flow rate after the PBR reactor).

Ketone oxime selectivity (%) = generated oxime (mol/s) / converted ketone (mol/s) = (Conc.after oxime (mol/L) × FRafter oxime (L/s)) / (Conc.before ketone (mol/L) × FRbefore ketone (L/s) − Conc.after ketone (mol/L) × FRafter ketone (L/s)) × 100% (4)
(Conc.after oxime (mol/L), FRafter oxime (L/s), Conc.before ketone (mol/L), FRbefore ketone (L/s) represent the concentration and flow rate of generated oxime, the concentration and flow rate of ketones before reaction, and the merged concentration and flow rate after the PBR reactor).

Ketone oxime yield (%) = generated oxime (mol/s) / overall ketone (mol/s) = (Conc.after oxime (mol/L) × FRafter oxime (L/s)) / (Conc.before ketone (mol/L) × FRbefore ketone (L/s)) × 100% (5)
(Conc.after oxime (mol/L), FRafter oxime (L/s), Conc.before ketone (mol/L), FRbefore ketone (L/s) represent the concentration and flow rate of generated oxime, the concentration and flow rate of ketones before reaction, and the merged concentration and flow rate after the PBR reactor).

Ketone oxime Faradaic efficiency (%) = (Conc.after oxime (mol/L) × FRafter oxime (L/s) × 2 × 96485 C/mol) / jtotal (mA) × 100 (6)
(Conc.after oxime (mol/L) and FRafter oxime (L/s) represent the concentration and flow rate of generated oxime, jtotal (mA) represents the current density of in-situ 2e−-ORR generated H2O2 for the ketone oximes synthesis. From the whole process of O2 electroreduction and ketone oxime synthesis, only two electrons were involved).

H2O2 utilization efficiency (%) = consumed ketone (mol/s) / overall H2O2 (mol/s) = (Conc.before ketone (mol/L) × FRbefore ketone (L/s) − Conc.after ketone (mol/L) × FRafter ketone (L/s)) / (Conc.before H2O2 (mol/L) × FRbefore H2O2 (L/s)) × 100% (7)
(Conc.before ketone (mol/L), FRbefore ketone (L/s), Conc.after ketone (mol/L), FRafter ketone (L/s), Conc.before H2O2 (mol/L), FRbefore H2O2 (L/s), represent the concentration and flow rate of ketones before reaction, the merged concentration and flow rate after the PBR reactor, and the overall concentration and flow rate of H2O2 in the system).

Peer review rounds
[{"round": 1, "reviewer_comments": {"reviewer_1": "The authors reported an interesting strategy to synthesize cyclohexanone oxime by a tandem PSER-PBR system. The\nmetrics of reaction rate and selectivity and upscaled reaction performance are impressive, up to 28 mmol/h production rate at\n125 mA/cm2 (ORR current density), while also showing versatility for other aliphatic/aromatic ketones. Moreover, compared\nwith previous work on electroreduction of NOx or oxidation of NH3 for the synthesis of cyclohexanone oximes using\nelectrolyte to reduce system impedance, their design of solid electrolyte cell could avoid the use of salts, which largely\nreduce the purification step and cost. I consider the findings interesting and relevant to the energy community and chemistry.\nOverall, I think this work is worth to be published in Nature Communication after minor revision. To improve this work, there\nare some suggestions:\n1.Why does the in-situ electrochemically generated H2O2 exhibit superior H2O2 utilization efficiency, CyH conversion rate,\nand CyO yield, compared to externally added commercial H2O2?\n2.Are there competing reactions where NH2OH undergoes over-oxidation to form N2 or other by-products?\n3.The manuscript mentions potential activity loss of TS-1 catalyst necessitating regeneration after long-term use. What is the\nmain cause of TS-1 catalyst deactivation?\n4.The statement of “the CyO yield remained stable at around 80% when reducing TS-1 usage from 1.5 g to 0.05 g”at Page 8\nLine 162-163 was not consistent with the Figure 2e. By using 0.05 g TS-1, the yield was just higher than 20%.", "reviewer_2": "In this work, the authors developed a prototype tandem system that integrates electrochemical hydrogen peroxide (H₂O₂) \nproduction with the synthesis of cyclohexanone oxime (CyO). This approach appears promising, achieving high Faradaic \nefficiency (FE), selectivity, and CyO production rates. The paper may be considered for publication after the following issues \nare addressed:\n1. The proposed process is frequently compared to other methods based on the highest FE, selectivity, and production rates \nreported in this study. However, these peak values were obtained under different reaction conditions. For instance, the \nhighest FE was achieved at low current densities—conditions that yielded lower production rates—while the highest \nproduction rate was observed at high current densities but with significantly lower FE. These selective comparisons lack \nobjectivity and risk overstating the advantages of the process. A more systematic and balanced comparison is needed, \nideally incorporating a techno-economic analysis to assess the overall viability of the process relative to existing \ntechnologies.\n2. Ammonia (NH₃) is a key reactant in this process, and its utilization efficiency should be reported. Including this metric is \nessential for assessing the overall material efficiency and sustainability of the system.\n3. Lines 101–110: The observed declines in CyH conversion, CyO yield, and H₂O₂ utilization efficiency at higher current \ndensities should be discussed in greater depth. The authors should explore the underlying reasons for these trends and their \nimplications for the practical application of the system.\n4. Lines 251–266: The authors propose that electrochemically produced H₂O₂ (eH₂O₂) performs better than chemically \nsynthesized H₂O₂ (cH₂O₂) due to the absence of stabilizers. This conclusion is based on the improved performance \nobserved with 1.0 eq eH₂O₂ compared to cH₂O₂. However, at higher concentrations (1.6 M), eH₂O₂ shows inferior \nperformance to cH₂O₂. The impact of stabilizers should be more thoroughly evaluated, and the causes of reduced \nperformance at high eH₂O₂ concentrations should be clearly explained.", "reviewer_3": "The authors presented an integrated PSER-PBR reactor system for the generation of CyO. The proposed PSER-PBR\nreactor system exhibits outstanding performance through the systematic optimization of operating parameters. Nevertheless,\nI have several questions concerning the reaction design and the organization of this manuscript.\n1.The author pointed out when applying a current density of 125 mAcm-2 in PSER, the high concentrated eH2O2 might\ndecompose into lots of O2 bubbles. What is the upper limit of the concentration of eH2O2 that can be generated using the\nPSER device? Will this upper limit restrict the large-scale application?\n2.Will the eH2O2 cause the failure of AEM, CEM and PSE?\n3.The commonly used electrochemical devices for generating H2O2 employ gas diffusion electrodes and liquid electrolytes.\nCompared to these, the PSER device has additional AEM and PSE components, making it more complex. What are the\ndisadvantages of using the common electrochemical reduction devices for H2O2 generation?\n4.In the PSER-PBR system proposed by the author, the two parts seem to be independent. What are the key parameters or\ncomponents that link the two parts together? When others want to cite or further optimize this system, what aspects should\nthey focus on?\n5.The article lacks a systematic comparison between different process routes, especially in terms of technological\ncharacteristic, rather than simply listing production comparisons. After all, for large-scale industrial production, it is not only\nnecessary to have excellent technical parameters, but also to consider economic feasibility.\n6.The authors should point out the scientific points of the research."}, "author_response": "We thank the editor and reviewers for their constructive comments which have helped us\nto greatly improve the quality and depth of our manuscript. We have revised these accordingly.\nThe responses to editor's comments were included in the track-changed manuscript. Below, we\naddress the points raised by reviewers one by one.\nReviewer #1\nRemarks to the Author:\nThe authors reported an interesting strategy to synthesize cyclohexanone oxime by a tandem\nPSER-PBR system. The metrics of reaction rate and selectivity and upscaled reaction\nperformance are impressive, up to 28 mmol/h production rate at 125 mA/cm2 (ORR current\ndensity), while also showing versatility for other aliphatic/aromatic ketones. Moreover,\ncompared with previous work on electroreduction of NOx or oxidation of NH3 for the synthesis\nof cyclohexanone oximes using electrolyte to reduce system impedance, their design of solid\nelectrolyte cell could avoid the use of salts, which largely reduce the purification step and cost.\nI consider the findings interesting and relevant to the energy community and chemistry. Overall,\nI think this work is worth to be published in Nature Communication after minor revision. To\nimprove this work, there are some suggestions:\nResponse: We highly appreciate the reviewer's praise and constructive comments. In this revised\nversion of the manuscript, we have addressed all questions raised by the reviewer and clearly\ndifferentiated our design from previous reports to resolve the reviewer's major concern, which\nhas dramatically improved the depth and rigor of this work.\nComment 1. Why does the in-situ electrochemically generated H O exhibit superior H O\n2 2 2 2\nutilization efficiency, CyH conversion rate, and CyO yield, compared to externally added\ncommercial H O ?\n2 2\nResponse: During the cyclohexanone ammoxidation reaction, H O played the role of oxidizing\n2 2\nNH3 to the intermediate NH OH on the surface of the TS-1 catalyst. Compared with commercial\n2 2 2 2\ndown the decomposition of H O and extend its oxidation reaction time with NH on the surface\n2 2 3\nof TS-1. Based on our one-pass design, the H O retaining time on the surface of TS-1 could\n2 2\naffect the performance, resulting in slightly decreased performance than the in-situ generated\nfresh H O .\n2 2\nThe following text has been added to the revised supplementary information:\nSupplementary Table 3. The decreased performance of stabilizers\nEntry CyH Conversion CyO Yield Condition\n1 96.3% 93.6% 0.2M eH O (Fig. 3e and 3f)\n2 2\n2 91.7% 86.4% 0.2M eH O + stabilizers\n2 2\n3 91.7% 88.0% 0.2M cH O (Fig. 2b and 2c)\n2 2\nReaction (entry 2): 50 mL electrochemically in-situ generated eH O (0.2 M) + 30.0 mg\n2 2\nNaH PO (5 mM) +10 mg Na EDTA·2H O (≈0.5 mM) to mimic commercial stabilizers.\n2 4 2 2\nNote: The stabilizer may slightly decrease the reaction performance by affecting the reactivity\nof H O .\n2 2\nComment 2. Are there competing reactions where NH OH undergoes over-oxidation to form N\n2 2\nor other by-products?\nResponse: GC and UV-Vis analysis of the nitrogen sources suggested that 7% of the NH OH\n2\nwas converted to NO -, while almost no N or NO - was generated. We have included the\n2 2 3\nexperimental details of the nitrogen sources analysis in our revised manuscript and SI.\nThe following text has been added to the revised manuscript:\n“the NH and other nitrogen sources were analyzed by GC and UV-vis (see detailed\n3\nparameter definitions in Methods, Supplementary Fig. 2-15)”\nThe following texts and figures have been added to the revised supplementary information:\nSupplementary Figure 11. a, The experiment details for the gaseous nitrogen source analysis.\nb, The GC analysis: O at 6.35 min, N at 6.83 min; blank reaction (black), Ar atmosphere (red),\n2 2\nand ammoximation reaction under Ar atmosphere (blue). Although a little O was observed, no\n2\npurging H O ).\n2 2\nThe nitrogen source analysis\nAccording to our previous work11, we next use UV-vis to analyze the possible liquid nitrogen\nsources.\nThe experiment of 0.2 M CyO with 2 equiv. NH under standard conditions was performed to\n3\ntest the nitrogen source, which may go into N , NO -, NO -. The detection method was based on\n2 3 2\nour previous method.\nNH : indophenol blue method with modification: 1 mL of the diluted sample was mixed with\n3\n1 mL of 1 M NaOH, 5 wt.% salicylic acid and 5 wt.% sodium citrate solution. Then, 0.5 mL\nof 0.05 M NaClO solution and 0.1 mL of 1.0 wt.% C FeN Na O (sodium nitroferricyanide)\n5 6 2\nsolution was added and left to rest for 2 h under ambient conditions.\nNO -: a mixture of p-aminobenzenesulfonamide (4 g), N-(1-naphthyl) ethylenediamine\n2\ndihydrochloride (0.2 g), deionized water (50 mL), and phosphoric acid (10 mL, ρ = 1.685 g∙mL-\n1) was used as the color reagent. Next, 40 µl of the color reagent was added to the 2.0 mL sample\nsolution, mixed thoroughly, and rested for 20 min at ambient conditions.\nNO -: 40 µl of 1 M HCl with 4.0 µl of 0.8 wt.% sulfamic acid solution was added and mixed\n3\nwith 2.0 mL of the diluted sample and rested for 20 min at ambient conditions. The absorption\nintensities at wavelengths of 220 and 275 nm. The final absorbance was calculated using the\nequation: A = A – A .\n220nm 275nm\nSupplementary Figure 12. The concentration-absorbance UV-vis calibration curve of NH\n3\nusing different concentrations of NH ∙H O solutions as standards. a, UV-vis curves of\n3 2\nindophenol assays with NH + ions. b, linear fitting results of the calibration curve.\n2\nusing different concentrations of KNO solutions as standards. a, UV-vis curves of indophenol\n2\nassays with NO - ions. b, linear fitting results of the calibration curve.\n3\nusing different concentrations of KNO solutions as standards. a, UV-vis curves of indophenol\n3\nassays with NO - ions. b, linear fitting results of the calibration curve.\nbefore reaction (black line) and after reaction (red line). (a) NH + (0.477 mol/L and 0.312 mol/L);\n4\n(b) NO - (0 mol/L and 0.011 mol/L) (c) NO - (0 mol/L and 0 mol/L).\n2 3\nNote: As we use the mole ratio of CyH:H O :NH (1:1:2), the following Extra NH was\n2 2 3 3\nanalyzed as one representative and not analyzed case by case.\nThe utilization of NH for CyO production was:\nnNH +(overall)-nNH +(remaining)- nNO -- nNO -- nN\n4 4 2 3 2\n= ×100%\nnNH +(overall)-nNH +(remaining)\n4 4\n0.477−0.312−0.011−0−0\n= ×100% = 93%\n0.477−0.312\nComment 3. The manuscript mentions potential activity loss of TS-1 catalyst necessitating\nregeneration after long-term use. What is the main cause of TS-1 catalyst deactivation?\nResponse: Previous work from Copéret group (Nature 2020, 586, 708–713) explained how TS-\n1 catalyst with MFI framework structure activates H O . The deactivation of the TS-1 catalyst\n2 2\nwas mainly from the deposition of organic chemicals like CyH or CyO on the catalyst surface\nand in the pores, which blocked the active sites and prevented the reactants from entering, thus\nreducing the catalytic activity. However, the deactivated industrial TS-1 catalyst could be re-\nactivated (see Ref. Appl Catal a-Gen 2011, 394, 1-8.). Two more articles have been cited and the\nfollowing text has been modified in the revised manuscript.\n“Over extended operation, the TS-1, a robust commercial catalyst, may still experience activity\nloss and require regeneration, traditionally necessitating process interruptions for catalyst\nseparation and reactivation36,37.”\nComment 4. The statement of “the CyO yield remained stable at around 80% when reducing TS-\n1 usage from 1.5 g to 0.05 g” at Page 8 Line 162-163 was not consistent with the Figure 2e. By\nusing 0.05 g TS-1, the yield was just higher than 20%.\nResponse: The statement has been updated in the revised manuscript: “the CyO yield remained\nstable at around 80% when reducing TS-1 usage from 1.5 g to 0.1 g, with the highest catalytic\nefficiency of 161 mmol∙h-1∙g -1 achieved at 0.1 g TS-1, albeit with a slightly decreased yield of\ncat\n74.3%”\nReviewer #2\nRemarks to the Author:\nIn this work, the authors developed a prototype tandem system that integrates\nelectrochemical hydrogen peroxide (H₂O₂) production with the synthesis of cyclohexanone\noxime (CyO). This approach appears promising, achieving high Faradaic efficiency (FE),\nselectivity, and CyO production rates. The paper may be considered for publication after the\nfollowing issues are addressed:\nResponse: We highly appreciate the reviewer's praise and constructive comments. In this revised\nversion of the manuscript, we have addressed all questions raised by the reviewer and clearly\ndifferentiated our design from previous reports to resolve the reviewer's major concern, which\nhas dramatically improved the depth and rigor of this work.\nComment 1. The proposed process is frequently compared to other methods based on the highest\nFE, selectivity, and production rates reported in this study. However, these peak values were\nobtained under different reaction conditions. For instance, the highest FE was achieved at low\ncurrent densities—conditions that yielded lower production rates—while the highest production\nrate was observed at high current densities but with significantly lower FE. These selective\ncomparisons lack objectivity and risk overstating the advantages of the process. A more\nsystematic and balanced comparison is needed, ideally incorporating a techno-economic analysis\nto assess the overall viability of the process relative to existing technologies.\nResponse: The comparison between previous works and our work under low and high current\nconditions has been listed in the supplementary table 1 previously. Moreover, a TEA has been\nupdated in the revised manuscript and supplementary information.\nThe following text and figure have been updated in the revised manuscript:\n“Moreover, to clarify the economic potential of the PSER-PBR setup for producing CyO,\nwe performed a preliminary techno-economic analysis (TEA) based on the performance of our\nPSER-PBR reactor at 125 mA/cm2 (Fig. 4c and Supplementary TEA Note). We also considered\nour previous PSER TEA for H O production32 and Shi’s work28 for evaluation of CyO economic\n2 2\nbenefits. Our strategy was demonstrated to produce CyO with a rather low cost of 2196 $/ton\nunder a 0.1 $/kWh electricity fee (2533 $/ton, even with 0.2 $/kWh), which is very profitable in\nconsideration the market price of CyO (~9700 $/ton)31. The main reason comes from the use of\ncheapest nitrogen source—NH and low cost of H O producing strategy from our PESR reactor.”\n3 2 2\nFig.4| Production of other ketone oximes and the long-term experiment. a, The PSER-PBR\nsystem for the ammoximation of other ketones. Ketone conversion, oxime yield, and oxime\nselectivity for the ammoximation reaction. b, Long-term cascade reaction for cyclohexanone\noxime at 60 mA/cm2 in the PSER-PBR system. Reaction conditions: O flow rate of 20 sccm,\n2\ncurrent density of 60 mA/cm2, 0.5 mL/min flow rate of DI water to obtain 0.85 mol/L eH O , 0.85\n2 2\nmL/min flow rate of 0.8 M ketones in t-BuOH, 0.5 mL/min flow rate of 1.6 M NH ∙H O, 1.5 g\n3 2\nTS-1 at 80℃. c, Plant-gate levelized cost per ton of CyO from TEA at 125 mA/cm2.\nThe following text and figure have been updated in the revised Supplementary Information:\nSupplementary Table 1. Selective previous ketone oxime synthesis method from\nelectrochemical NO reduction1-9 and NH oxidation10\nx 3\nSupplementary TEA Note13-15:\nTo have a rough estimation of the cyclohexanone oxime (CyO) cost from a mole ratio of\nhydrogen peroxide (H O ): cyclohexanone (CyH): ammonia (NH ) = (1:1:2) using our PSE\n2 2 3\nreactor and PBR equipment, we assumed a cell operation of 125 mA/cm2 with a H O FE of 75%\n2 2\nand cell voltage of 2.7 V, providing a CyO yield of 65.9%. Assuming a CyO production rate of\n1000 kg/day, the H O production rate is:\n2 2\n1000 𝑘𝑔/𝑑𝑎𝑦 34.01 𝑔/𝑚𝑜𝑙\nH O production rate = × = 456.1 𝑘𝑔/𝑑𝑎𝑦\n2 2 113.16 𝑔/𝑚𝑜𝑙 65.9%\nthe total current needed is:\n456.1𝑘𝑔/𝑑𝑎𝑦 1000 𝑚𝑜𝑙/𝑘𝑚𝑜𝑙 2𝑒− ×96485 𝐶/𝑚𝑜𝑙\n𝑇𝑜𝑡𝑎𝑙 𝑐𝑢𝑟𝑟𝑒𝑛𝑡 = × × = 39933 𝐴\n24×3600 𝑠/𝑑𝑎𝑦 34.01 𝑘𝑔/𝑘𝑚𝑜𝑙 75%\nThe electrolyzer area needed is the total current divided by the current density:\n39933𝐴 𝑚2\n𝑇𝑜𝑡𝑎𝑙 𝑒𝑙𝑒𝑐𝑡𝑟𝑜𝑙𝑦𝑧𝑒𝑟 𝑎𝑟𝑒𝑎 = × = 31.95 𝑚2\n0.125 𝐴/𝑐𝑚2 104𝑐𝑚2\nThe power needed is given from P=UI, the cell voltage is 2.7 V for 125 mA/cm2:\n𝑊\n𝑃𝑜𝑤𝑒𝑟 = 𝑉𝑜𝑙𝑡𝑎𝑔𝑒×39933 𝐴 × = 2.7×39933 = 107.8 𝑘𝑊\n103 𝑘𝑊\nThe water flow rate for the OER reaction is:\n39933 𝐴 0.018 𝑘𝑔 24×3600 𝑠\n𝐻 𝑂 𝑓𝑙𝑜𝑤 𝑟𝑎𝑡𝑒 = × × = 321.8 𝑘𝑔/𝑑𝑎𝑦\n2 2𝑒− ×96485 𝐶/𝑚𝑜𝑙 𝑚𝑜𝑙 𝑑𝑎𝑦\nThe water flow rate for the middle layer H O dilution reaction (H O concentration, 1.6 M,\n2 2 2 2\n5.44%) is:\n456.1 𝑘𝑔/𝑑𝑎𝑦\n𝐻 𝑂 𝑓𝑙𝑜𝑤 𝑟𝑎𝑡𝑒 = −456.1 𝑘𝑔/𝑑𝑎𝑦 = 7928 𝑘𝑔/𝑑𝑎𝑦\n2 5.44%\nThe O mass flow rate for the cathodic ORR is:\n2\n39933 𝐴 0.032 𝑘𝑔 24×3600 𝑠\n𝑂 𝑚𝑎𝑠𝑠 𝑓𝑙𝑜𝑤 𝑟𝑎𝑡𝑒 = × × = 572.2 𝑘𝑔/𝑑𝑎𝑦\n2 2×96485 𝐶/𝑚𝑜𝑙 𝑚𝑜𝑙 𝑑𝑎𝑦\nCyclohexanone has a CyO selectivity of 96.9%, so the consumed cyclohexanone is:\n1000 𝑘𝑔/𝑑𝑎𝑦 98.15 𝑔/𝑚𝑜𝑙\nConsumed cyclohexanone = × = 895.1 𝑘𝑔/𝑑𝑎𝑦\n113.16 𝑔/𝑚𝑜𝑙 96.9%\n0.781 𝑔/𝑚𝐿×1000 𝑚𝐿/𝐿\nt𝐵𝑢𝑂𝐻 𝑓𝑙𝑜𝑤 𝑟𝑎𝑡𝑒 = ( −1)×895.1 𝑘𝑔/𝑑𝑎𝑦\n98.15 𝑘𝑔/𝑘𝑚𝑜𝑙 ×1.6 𝑚𝑜𝑙/𝐿\n= 1698.3 𝑘𝑔/𝑑𝑎𝑦\nt-BuOH could be reused, we assume the recycling cost account for 30% of the consumed t-BuOH\ncost\n1000 𝑘𝑔/𝑑𝑎𝑦\nConsumed ammonia = ×17.03 𝑔/𝑚𝑜𝑙 = 150.5 𝑘𝑔/𝑑𝑎𝑦\n113.16 𝑔/𝑚𝑜𝑙\nThe water flow rate for the NH dilution reaction (H O concentration, 3.2 M) is:\n3 2 2\n0.91 𝑔/𝑚𝐿×1000 𝑚𝐿/𝐿\n𝐻 𝑂 𝑓𝑙𝑜𝑤 𝑟𝑎𝑡𝑒 = ( −1)×150.5 𝑘𝑔/𝑑𝑎𝑦 = 2362.5 𝑘𝑔/𝑑𝑎𝑦\n2 17.03 𝑘𝑔/𝑘𝑚𝑜𝑙 ×3.2 𝑚𝑜𝑙/𝐿\n1. Equipment cost\nFrom the DOE H A analysis for distributed grid electrolysis,13 the electrolyzer cost for the stack\n2\ncomponent is 7722$/m2 with an Uninstallation factor = 12%. While our PSE reactor has one\nadditional AEM and PSE layer than conventional PEM water electrolyzers, we do not need to\ndo the harsh hydrogen evolution reaction on the cathode, thus our cathode catalyst and GDL\nwould be cheaper than those used in water electrolyzers. Therefore, the final cost of our\nelectrolyzer should be similar to PEM water electrolyzers (see our previous TEA)16. According\nto the DOE H A PEM Electrolyzer Stacks and Systems analysis, the electrolyzer cost per m2 can\n2\nbe calculated as below:\n𝐶𝑜𝑠𝑡 ($/𝑚2) = 𝑅𝑒𝑝𝑜𝑟𝑡𝑒𝑑 𝑐𝑜𝑠𝑡 ($/𝑘𝑊)×𝑅𝑒𝑝𝑜𝑟𝑡𝑒𝑑 𝑝𝑜𝑤𝑒𝑟 𝑑𝑒𝑛𝑠𝑖𝑡𝑦 (𝑘𝑊/𝑚2)\n= 143 $/𝑘𝑊 ×3 𝐴/𝑐𝑚2 ×1.8 𝑉×104𝑐𝑚2/𝑚2 = 7722$/𝑚2.\nAt 125 mA cm−2, the total electrolyzer area is 14.58 m2 and the total cost is (assuming 12% of\nthe uninstalled capital cost):\n𝑃𝑆𝐸 𝑒𝑙𝑒𝑐𝑡𝑟𝑜𝑙𝑦𝑧𝑒𝑟 𝑐𝑜𝑠𝑡 = 𝐸𝑙𝑒𝑐𝑡𝑟𝑜𝑙𝑦𝑧𝑒𝑟 𝑎𝑟𝑒𝑎×𝐶𝑜𝑠𝑡 ($/𝑚2)×(1+𝑢𝑛𝑖𝑛𝑠𝑡𝑎𝑙𝑙𝑒𝑑 𝑓𝑎𝑐𝑡𝑜𝑟)\n== 31.9 𝑚2 ×7722 $/𝑚2 ×(1+0.12) = 276296 $\nPBR equipment contains quite cheap plastic tube (assuming 30 $) and TS-1 (555 $/kg), which\ncould be reused. Assuming the catalytic efficiency for CyO production is 161 mmol∙h-1∙g -1 and\ncat\nthe commercial TS-1 catalytic activity last 500 h 17, the reactivation of TS-1 accounts for 30%\nof catalyst cost. The cost of PBR cost for running 500 h is:\n1000 𝑘𝑔/𝑑𝑎𝑦 555 $/kg\n𝑃𝐵𝑅 𝑐𝑜𝑠𝑡 = × +30 $ = 1299 $\n500ℎ 113.16 𝑘𝑔/𝑘𝑚𝑜𝑙 0.161 𝑚𝑜𝑙/(ℎ×𝑔 )×24 ℎ/𝑑𝑎𝑦\n𝑐𝑎𝑡\nThe cost of PBR cost for running 20 years is:\n20×350×24 ℎ𝑜𝑢𝑟𝑠\n𝑃𝐵𝑅 𝑐𝑜𝑠𝑡 = 1299 $+( −1)×1299 $×30% = 131879 $\n20 𝑦𝑒𝑎𝑟𝑠 500 ℎ𝑜𝑢𝑟𝑠\nHerein, the capital recovery factor (CRF) is based on a discount rate (denoted as i; we use 10%\nfor all the CRF calculations) and the material lifetime (20 years).\n𝑖(1+𝑖)𝑦𝑒𝑎𝑟 0.1×1.120\n𝐶𝑅𝐹 = = = 0.1175\n𝑃𝑆𝐸 𝑒𝑙𝑒𝑐𝑡𝑟𝑜𝑙𝑦𝑧𝑒𝑟 (1+𝑖)𝑦𝑒𝑎𝑟 −1 1.140 −1\n0.1175\n𝐸𝐹𝑞𝑢𝑖𝑝𝑚𝑒𝑛𝑡 𝑐𝑜𝑠𝑡 = (276296 $+131879 $)× = 137.0 $/𝑑𝑎𝑦\n𝑝𝑒𝑟 𝑡𝑜𝑛 𝐶𝑦𝑂 350 𝑑𝑎𝑦\nBalance of plant cost\nFrom the DOE H A analysis for distributed grid electrolysis, the BOP cost (including mechanical\nis:\n𝐵𝑂𝑃 𝑐𝑎𝑝𝑖𝑡𝑎𝑙 𝑐𝑜𝑠𝑡 = 𝐸𝑙𝑒𝑐𝑡𝑟𝑜𝑙𝑦𝑧𝑒𝑟 𝑎𝑟𝑒𝑎 ×𝑅𝑒𝑓𝑒𝑟𝑒𝑛𝑐𝑒 𝑐𝑜𝑠𝑡×(1+𝑢𝑛𝑖𝑛𝑠𝑡𝑎𝑙𝑙𝑒𝑑 𝑓𝑎𝑐𝑡𝑜𝑟)\n= 31.9 𝑚2 ×4914 $/𝑚2 ×(1+12%) = 175825 $\nHerein, the capital recovery factor (CRF) is based on a discount rate (denoted as i; we use 10%\nfor all the CRF calculations) and the material lifetime (20 years).\n0.1175\n𝐵𝑂𝑃 𝑐𝑎𝑝𝑖𝑡𝑎𝑙 𝑐𝑜𝑠𝑡 = 175825 $× = 59.0 $/𝑑𝑎𝑦\n𝑝𝑒𝑟 𝑡𝑜𝑛 𝐶𝑦𝑂 350 𝑑𝑎𝑦\nTherefore, the overall capital cost is 196.1 $ per ton CyO\n.\n2. Electricity cost\nThe electricity cost is calculated from the power requirement and the price of electricity,\nassuming the electricity price is 10 cent kWh−1:\n𝐸𝑙𝑒𝑐𝑡𝑟𝑖𝑐𝑖𝑡𝑦 𝑐𝑜𝑠𝑡 = 107.82 𝑘𝑊 ×24 ℎ𝑟/𝑑𝑎𝑦×0.10$/𝑘𝑊ℎ = 258.8 $/𝑑𝑎𝑦\n𝑝𝑒𝑟 𝑡𝑜𝑛 𝐶𝑌𝑂\n3. CyO separation cost\nThe separation cost is assumed to be 30% of the electricity cost:\n𝐶𝑦𝑂 𝑠𝑒𝑝𝑒𝑟𝑎𝑡𝑖𝑜𝑛 𝑐𝑜𝑠𝑡 = 258.8 $/𝑑𝑎𝑦×30% = 77.6 $/𝑑𝑎𝑦\n𝑝𝑒𝑟 𝑡𝑜𝑛 𝐶𝑌𝑂\n3. Input chemicals cost\nFor the input chemicals cost, we account for the cost from the consumed H O and O . The water\n2 2\nprice is estimated as $ 0.003 per liter18, and the O price is estimated as $80/ton19.\n2\n𝐶𝑜𝑠𝑡 𝑜𝑓 𝑐𝑜𝑛𝑠𝑢𝑚𝑒𝑑 𝐻 𝑂 = 0.003 $/kg ×(321.8+797.5+2362.5) kg/day = 31.8 $/day\n2\n𝐶𝑜𝑠𝑡 𝑜𝑓 𝑐𝑜𝑛𝑠𝑢𝑚𝑒𝑑 𝑂 = 0.08 $/kg×572.15 kg/day = 45.8 $/day\n2\n𝐶𝑜𝑠𝑡 𝑜𝑓 𝑐𝑜𝑛𝑠𝑢𝑚𝑒𝑑 𝐶𝑦𝐻 = 1.16 $/kg ×895.1 kg/day = 1038.3 $/day\n𝐶𝑜𝑠𝑡 𝑜𝑓 𝑐𝑜𝑛𝑠𝑢𝑚𝑒𝑑 𝑁𝐻 = 0.31 $/kg×150.5 kg/day = 46.8 $/day\n3\n𝐶𝑜𝑠𝑡 𝑜𝑓 𝑡𝐵𝑢𝑂𝐻 𝑠𝑜𝑙𝑣𝑒𝑛𝑡 = 0.85 $/kg ×1698.3 kg/day×30% = 431.7 $/day\n𝑂𝑣𝑒𝑟𝑎𝑙𝑙 𝑐𝑜𝑠𝑡 𝑜𝑓 𝑐𝑜𝑚𝑝𝑜𝑛𝑒𝑛𝑡 = 31.8+45.8+1038.3+46.8+431.7 = 1594.3 $/𝑑𝑎𝑦\n4. Stack replacement cost\nFor the stack replacement cost, assuming 15% of the uninstall cost for 10 years20,21.\n15%\n𝑆𝑡𝑎𝑐𝑘 𝑟𝑒𝑝𝑙𝑎𝑐𝑒𝑚𝑒𝑛𝑡 𝑐𝑜𝑠𝑡 = 276296 $× = 11.8 $/𝑑𝑎𝑦\n10 𝑦𝑟×350 𝑑𝑎𝑦/𝑦𝑟\n5. Other operational costs\nOther operational costs, such as labor and maintenance, are assumed to be 5% of the electrolyzer\ncost per ton of H O and 5% of the PBR reactor cost per ton of CyO:\n2 2\n0.05\n𝑂𝑡ℎ𝑒𝑟 𝑐𝑜𝑠𝑡 = (276296+131879)$× = 58.3 $/𝑑𝑎𝑦\n𝑝𝑒𝑟 𝑡𝑜𝑛 𝐶𝑦𝑂 350\nThus, the overall cost to obtain 1000 kg CyO/day using O , CyH and NH is:\n2 3\n𝑂𝑣𝑒𝑟𝑎𝑙𝑙 𝑐𝑜𝑠𝑡\n𝑝𝑒𝑟 𝑡𝑜𝑛 𝐶𝑦𝑂\n= 196.1 $+258.8 $+77.6 $+1594.3 $+11.8 $+58.3 $ = 2196.9 $\nComment 2. Ammonia (NH₃) is a key reactant in this process, and its utilization efficiency should\nbe reported. Including this metric is essential for assessing the overall material efficiency and\nsustainability of the system.\nResponse: We appreciate the reviewer’s constructive advice. Due to the reaction ratio of\nCyH:H O :NH (1:1:2), we emphasize the analysis of CyH and H O . The Extra NH source\n2 2 3 2 2 3\nwas analyzed as one representative and not analyzed case by case.\nGC and UV-Vis analysis of the nitrogen sources suggested that 7% of the NH was converted to\n2 2 3\nof ammonia, up to 93%.\nThe following text has been added in the revised manuscript:\n“the NH and other nitrogen sources were analyzed by GC and UV-vis (see detailed\n3\nparameter definitions in Methods, Supplementary Fig. 2-15)”\nThe following texts and figures have been added in the revised supplementary information:\nSupplementary Figure 11. a, The experiment details for the gaseous nitrogen source analysis.\nb, The GC analysis: O at 6.35 min, N at 6.83 min; blank reaction (black), Ar atmosphere (red),\n2 2\nand ammoximation reaction under Ar atmosphere (blue). Although a little O was observed, no\n2\npurging H O ).\n2 2\nThe nitrogen source analysis\nAccording to our previous work11, we next use UV-vis to analyze the possible liquid nitrogen\nsources.\nThe experiment of 0.2 M CyO with 2 equiv. NH under standard conditions were performed to\n3\ntest the nitrogen source, which may go into N , NO -, NO -. The detection method was based on\n2 3 2\nour previous method.\nNH : indophenol blue method with modification: 1 mL of the diluted sample was mixed with\n3\n1 mL of 1 M NaOH, 5 wt.% salicylic acid and 5 wt.% sodium citrate solution. Then, 0.5 mL\nof 0.05 M NaClO solution and 0.1 mL of 1.0 wt.% C FeN Na O (sodium nitroferricyanide)\n5 6 2\nsolution was added and left to rest for 2 h under ambient conditions.\nNO -: a mixture of p-aminobenzenesulfonamide (4 g), N-(1-naphthyl) ethylenediamine\n2\ndihydrochloride (0.2 g), deionized water (50 mL), and phosphoric acid (10 mL, ρ = 1.685 g∙mL-\n1) was used as the color reagent. Next, 40 µl of the color reagent was added to the 2.0 mL sample\nsolution, mixed thoroughly, and rested for 20 min at ambient conditions.\nNO -: 40 µl of 1 M HCl with 4.0 µl of 0.8 wt.% sulfamic acid solution was added and mixed\n3\nwith 2.0 mL of the diluted sample and rested for 20 min at ambient conditions. The absorption\nintensities at wavelengths of 220 and 275 nm. The final absorbance was calculated using the\nequation: A = A – A .\n220nm 275nm\nSupplementary Figure 12. The concentration-absorbance UV-vis calibration curve of NH\n3\nusing different concentrations of NH ∙H O solutions as standards. a, UV-vis curves of\n3 2\nindophenol assays with NH + ions. b, linear fitting results of the calibration curve.\n2\nusing different concentrations of KNO solutions as standards. a, UV-vis curves of indophenol\n2\nassays with NO - ions. b, linear fitting results of the calibration curve.\n3\nusing different concentrations of KNO solutions as standards. a, UV-vis curves of indophenol\n3\nassays with NO - ions. b, linear fitting results of the calibration curve.\nbefore reaction (black line) and after reaction (red line). (a) NH + (0.477 mol/L and 0.312 mol/L);\n4\n(b) NO - (0 mol/L and 0.011 mol/L) (c) NO - (0 mol/L and 0 mol/L).\n2 3\nNote: As we use the mole ratio of CyH:H O :NH (1:1:2), the following Extra NH was\n2 2 3 3\nanalyzed as one representative and not analyzed case by case.\nThe utilization of NH for CyO production was:\nnNH +(overall)-nNH +(remaining)- nNO -- nNO -- nN\n4 4 2 3 2\n= ×100%\nnNH +(overall)-nNH +(remaining)\n4 4\n0.477−0.312−0.011−0−0\n= ×100% = 93%\n0.477−0.312\nComment 3. Lines 101–110: The observed declines in CyH conversion, CyO yield, and H₂O₂\nutilization efficiency at higher current densities should be discussed in greater depth. The authors\nshould explore the underlying reasons for these trends and their implications for the practical\napplication of the system.\nResponse: The following statement has been added into the revised manuscript: “…… while\ndelivering a 68.1% CyH conversion, 96.9% CyO selectivity, 65.9% CyO yield, and 60.6% H O\n2 2\nutilization efficiency. The reduced performance under higher current conditions could come from\nthe increased amount of O bubbles generated from the decomposition of H O , which decreases\n2 2 2\nthe reactant’s residence time on the surface of TS-1 catalyst. Remarkably, this CyO production\nrate (at 125 mA/cm2, FE of 50.3%, 1.132 mmol/(h∙cm2)) greatly surpassed prior benchmarks\n(Supplementary Table 1), suggesting its potential for practical applications. Compared with the\nbatch reactor or the flow reactor, which normally require recycling the reaction mixture, the one-\npass PSER-PBR design could avoid the reactants re-feed into the electrochemical cells, which\nprevents the sensitive reactant or product from over-reacting.”\nComment 4. Lines 251–266: The authors propose that electrochemically produced H₂O₂ (eH₂O₂) performs better than chemically synthesized H₂O₂ (cH₂O₂) due to the absence of stabilizers. This conclusion is based on the improved performance observed with 1.0 eq eH₂O₂ compared to cH₂O₂. However, at higher concentrations (1.6 M), eH₂O₂ shows inferior performance to cH₂O₂. The impact of stabilizers should be more thoroughly evaluated, and the causes of reduced performance at high eH₂O₂ concentrations should be clearly explained.\nResponse: During the cyclohexanone ammoxidation reaction, H O played a role of oxidizing\n2 2\nNH to the intermediate NH OH on the surface of TS-1 catalyst. On the other hand, H O has\n3 2 2 2\nthe self-decomposition issue, generating O bubbles. During the process, we could observe a\n2\nphenomenon that when using a low concentration of H O (0.2 M) in the PBR, almost no O\n2 2 2\nbubbles were observed, but more bubbles with a higher concentration (1.6 M). The increased\namount of generated O gas may prevent the reactants from attacking TS-1 catalyst. Compared\n2\nwith commercial H O , the in-situ electrochemically generated H O has no stabilizer, which\n2 2 2 2\ncould slow down the rate of H O self-decomposition and extend the oxidation reaction time\n2 2\nwith NH on the surface of TS-1. (1) Under low H O concentration with less gas interference,\n3 2 2\nthe in-situ generated fresh H O reacted with NH on the surface of TS-1 more active than\n2 2 3\ncommercial H O containing stabilizer. Under higher concentration, the in-situ generated H O\n2 2 2 2\nwithout stabilizer generated more O bubbles than commercial ones, which reduced the reacting\n2\nchances of reactants with TS-1. This is the reason why it happens.\nThe following text has been updated in the manuscript: “The decreased performance may come\nfrom the higher decomposition rate of concentrated eH O into lots of O bubbles over cH O\n2 2 2 2 2\nbearing stabilizer, which could lead to the contact opportunity between catalyst and liquid and\nalso the reduced amounts of oxidants—H O (Supplementary Fig. 31 and Supplementary\n2 2\nTable 2 and 3)”\nThe following text and figures have been updated in the supplementary information:\nSupplementary Figure 31. a, previous 1H-NMR data from Fig. 2h (1.6 M commercial cH O\n2 2\nreacted with 1.6 M CyH. b, 0.5 sccm O was co-fed with 1.6 M CyH, 1.6 M commercial cH O\n2 2 2\nand 3.2 M NH into the PBR to test the bubbles effect on the reaction at 70 oC; 1H-NMR analysis.\n1 69.6% 67.8% 1.6M cH O (Fig. 2h)\n2 2\n2 54.0% 52.6% 1.6M cH O + 0.5 sccm O\n2 2 2\n3 68.1% 65.9% 1.6M eH O (Fig. 3f)\n2 2\nNote: The external O into the PBR decreased obviously the CyO production from CyO:CyH\n2\n(2.1:1) to (1.15:1). This result showed the self-decomposition of H O into O bubbles may affect\n2 2 2\nthe performance by reducing the contact opportunity between catalyst and liquid feedstock.\nSupplementary Table 3. The decreased performance by stabilizers\nEntry CyH Conversion CyO Yield Condition\n1 96.3% 93.6% 0.2M eH O (Fig. 3e and 3f)\n2 2\n2 91.7% 86.4% 0.2M eH O +commercial stabilizer\n2 2\n3 91.7% 88.0% 0.2M cH O (Fig. 2b and 2c)\n2 2\nReaction (entry 2): 50 mL electrochemically in-situ generated eH O (0.2 M) + 30.0 mg\n2 2\nNaH PO (5 mM) + 10 mg Na₂EDTA·2H₂O (≈0.5 mM) to mimic commercial stabilizer.\n2 4\nNote: The stabilizer may slightly decrease the reaction performance by affecting the reactivity\nof H O .\n2 2\nReviewer #3\nRemarks to the Author:\nThe authors presented an integrated PSER-PBR reactor system for the generation of CyO.\nThe proposed PSER-PBR reactor system exhibits outstanding performance through the\nsystematic optimization of operating parameters. Nevertheless, I have several questions\nconcerning the reaction design and the organization of this manuscript.\nComment 1. The author pointed out when applying a current density of 125 mAcm-2 in PSER,\nthe high concentrated eH2O2 might decompose into lots of O2 bubbles. What is the upper limit\nof the concentration of eH2O2 that can be generated using the PSER device? Will this upper\nlimit restrict the large-scale application?\nResponse: The H O was decomposed into O bubbles slightly, but heavily after the packed bed\n2 2 2\nreactor, which may be from H O self-decomposition. The PSER could generate 9.8 M H O (30\n2 2 2 2\nwt%) (Please see the recent article from our group regarding to PSER for H O generation: ACS\n2 2\nCatal. 2025, 15, 4560−4569). The highly pure H O (30 wt%) from PSER actually could go to\n2 2\nthe commercial level.\nThe following text has been updated in the supplementary information:\nSupplementary Figure 30. a, The H O concentration and FE with higher current density\n2 2 H2O2\nunder the standard condition: a 25 cm2 electrode area (5.0 cm × 5.0 cm), a continuous DI water\nfeed at 0.5 mL/min, a middle chamber filled with porous solid electrolyte (5.0 cm × 5.0 cm ×\n0.25 cm), and O flow rate of 20 sccm. b, The temperature at the surface of the cathode metal\n2\nplate increased to 33.8 ℃ at 200 mA/cm2.\nNote: When the current density goes to 160 mA/cm2, the obtained H O concentration was not\n2 2\nimproved significantly. We observed a higher temperature due to the impedance. However, this\nis not the limitation of PSER for getting higher H O concentration. By controlling other\n2 2\nconditions such as DI water flow rate in the middle layer, the cooling recycling system, etc., we\ncould obtain the commercial level of H O concentration (30 wt%, 9.8M), see our previous\n2 2\nwork12.\nComment 2. Will the eH2O2 cause the failure of AEM, CEM and PSE?\nResponse: In the recent article from our group (ACS Catal. 2025, 15, 4560−4569), PSER with\nAEM and CEM could produce 30 wt% eH O under 100 mA/cm2 for 1000 hours. Over a longer\n2 2\ntime, it may lead to the failure of AEM. The CEM (Nafion 117) or PSE could be reused without\ndamage.\nComment 3. The commonly used electrochemical devices for generating H2O2 employ gas\ndiffusion electrodes and liquid electrolytes. Compared to these, the PSER device has additional\nAEM and PSE components, making it more complex. What are the disadvantages of using the\ncommon electrochemical reduction devices for H2O2 generation?\nResponse: MEA devices and PSER have different advantages and disadvantages. From a single-\npass mode for generating tons of H O , tons of liquid electrolytes may be introduced into the\n2 2\nMEA devices and removed after reaction, which will increase the purification fee. By the way,\nduring the purification step, the H O could undergo self-decomposition, and the target H O\n2 2 2 2\nconcentration may be decreased. However, the PSER devices for generating tons of H O only\n2 2\nneed tons of water and obtain the target concentration without purification. The H O generated\n2 2\nfrom PSER was pure and may be directly used in some special situations, such as space stations,\nhouseholds, and medical care. Limited to current technology, the choices of PSE components are\nnot as extensive as those of the liquid electrolyte.\nComment 4. In the PSER-PBR system proposed by the author, the two parts seem to be\nindependent. What are the key parameters or components that link the two parts together? When\nothers want to cite or further optimize this system, what aspects should they focus on?\nResponse: Although we investigate the PSER and the PBR system independently, the PSER-\nPBR system showed the integration of H O electrosynthesis with downstream reactions, which\n2 2\ncould enhance the efficiency of the chemical process when compared with the commercial H O .\n2 2\nPrecise control of the mole ratio of NH , eH O and CyH by controlling the concentration and\n3 2 2,\nflow rate is important for the cascade system. Our system described a cascade reaction of eH O\n2 2\nwith cyclohexanone, providing a guideline for other chemical reactions. Further optimization of\nthis system includes developing a more active catalyst for other chemical reactions, like amino\nacid synthesis, and the parameter optimization of PBR to cooperate with the eH O generation.\n2 2\nComment 5. The article lacks a systematic comparison between different process routes,\nespecially in terms of technological characteristic, rather than simply listing production\ncomparisons. After all, for large-scale industrial production, it is not only necessary to have\nexcellent technical parameters, but also to consider economic feasibility.\nResponse: A TEA has been updated in the revised manuscript and supplementary information\nThe following text and figure have been updated in the revised manuscript:\n“Moreover, to clarify the economic potential of the PSER-PBR setup for producing CyO,\nwe performed a preliminary techno-economic analysis (TEA) based on the performance of our\nPSER-PBR reactor at 125 mA/cm2 (Fig. 4c and Supplementary TEA Note). We also considered\nour previous PSER TEA for H O production32 and Shi’s work28 for the evaluation of CyO\n2 2\neconomic benefits. Our strategy was demonstrated to produce CyO with a rather low cost of\n2196 $/ton under a 0.1 $/kWh electricity fee (2533 $/ton, even with 0.2 $/kWh), which is very\nprofitable in consideration of the market price of CyO (~9700 $/ton)31. The main reason comes\nfrom the use of a cheaper nitrogen source—NH and the low cost of H O producing strategy\n3 2 2\nfrom our PESR reactor.”\nFig.4| Production of other ketone oximes and the long-term experiment. a, The PSER-PBR\nsystem for the ammoximation of other ketones. Ketone conversion, oxime yield, and oxime\nselectivity for the ammoximation reaction. b, Long-term cascade reaction for cyclohexanone\noxime at 60 mA/cm2 in the PSER-PBR system. Reaction conditions: O flow rate of 20 sccm,\n2\ncurrent density of 60 mA/cm2, 0.5 mL/min flow rate of DI water to obtain 0.85 mol/L eH O , 0.85\n2 2\nmL/min flow rate of 0.8 M ketones in t-BuOH, 0.5 mL/min flow rate of 1.6 M NH ∙H O, 1.5 g\n3 2\nTS-1 at 80℃. c, Plant-gate levelized cost per ton of CyO from TEA at 125 mA/cm2.\nThe following text and figure have been updated in the revised Supplementary Information:\nSupplementary TEA Note13-15:\nTo have a rough estimation of the cyclohexanone oxime (CyO) cost from a mole ratio of\nhydrogen peroxide (H O ): cyclohexanone (CyH): ammonia (NH ) = (1:1:2) using our PSE\n2 2 3\nreactor and PBR equipment, we assumed a cell operation of 125 mA/cm2 with a H O FE of 75%\n2 2\nand cell voltage of 2.7 V, providing a CyO yield of 65.9%. Assuming a CyO production rate of\n1000 kg/day, the H O production rate is:\n2 2\n1000 𝑘𝑔/𝑑𝑎𝑦 34.01 𝑔/𝑚𝑜𝑙\nH O production rate = × = 456.1 𝑘𝑔/𝑑𝑎𝑦\n2 2 113.16 𝑔/𝑚𝑜𝑙 65.9%\nthe total current needed is:\n456.1𝑘𝑔/𝑑𝑎𝑦 1000 𝑚𝑜𝑙/𝑘𝑚𝑜𝑙 2𝑒− ×96485 𝐶/𝑚𝑜𝑙\n𝑇𝑜𝑡𝑎𝑙 𝑐𝑢𝑟𝑟𝑒𝑛𝑡 = × × = 39933 𝐴\n24×3600 𝑠/𝑑𝑎𝑦 34.01 𝑘𝑔/𝑘𝑚𝑜𝑙 75%\nThe electrolyzer area needed is the total current divided by the current density:\n39933𝐴 𝑚2\n𝑇𝑜𝑡𝑎𝑙 𝑒𝑙𝑒𝑐𝑡𝑟𝑜𝑙𝑦𝑧𝑒𝑟 𝑎𝑟𝑒𝑎 = × = 31.95 𝑚2\n0.125 𝐴/𝑐𝑚2 104𝑐𝑚2\nThe power needed is given from P=UI, the cell voltage is 2.7 V for 125 mA/cm2:\n𝑊\n𝑃𝑜𝑤𝑒𝑟 = 𝑉𝑜𝑙𝑡𝑎𝑔𝑒×39933 𝐴 × = 2.7×39933 = 107.8 𝑘𝑊\n103 𝑘𝑊\nThe water flow rate for the OER reaction is:\n39933 𝐴 0.018 𝑘𝑔 24×3600 𝑠\n𝐻 𝑂 𝑓𝑙𝑜𝑤 𝑟𝑎𝑡𝑒 = × × = 321.8 𝑘𝑔/𝑑𝑎𝑦\n2 2𝑒− ×96485 𝐶/𝑚𝑜𝑙 𝑚𝑜𝑙 𝑑𝑎𝑦\nThe water flow rate for the middle layer H O dilution reaction (H O concentration, 1.6 M,\n2 2 2 2\n5.44%) is:\n456.1 𝑘𝑔/𝑑𝑎𝑦\n𝐻 𝑂 𝑓𝑙𝑜𝑤 𝑟𝑎𝑡𝑒 = −456.1 𝑘𝑔/𝑑𝑎𝑦 = 7928 𝑘𝑔/𝑑𝑎𝑦\n2 5.44%\nThe O mass flow rate for the cathodic ORR is:\n2\n39933 𝐴 0.032 𝑘𝑔 24×3600 𝑠\n𝑂 𝑚𝑎𝑠𝑠 𝑓𝑙𝑜𝑤 𝑟𝑎𝑡𝑒 = × × = 572.2 𝑘𝑔/𝑑𝑎𝑦\n2 2×96485 𝐶/𝑚𝑜𝑙 𝑚𝑜𝑙 𝑑𝑎𝑦\nCyclohexanone has a CyO selectivity of 96.9%, so the consumed cyclohexanone is:\n1000 𝑘𝑔/𝑑𝑎𝑦 98.15 𝑔/𝑚𝑜𝑙\nConsumed cyclohexanone = × = 895.1 𝑘𝑔/𝑑𝑎𝑦\n113.16 𝑔/𝑚𝑜𝑙 96.9%\n0.781 𝑔/𝑚𝐿×1000 𝑚𝐿/𝐿\nt𝐵𝑢𝑂𝐻 𝑓𝑙𝑜𝑤 𝑟𝑎𝑡𝑒 = ( −1)×895.1 𝑘𝑔/𝑑𝑎𝑦\n98.15 𝑘𝑔/𝑘𝑚𝑜𝑙 ×1.6 𝑚𝑜𝑙/𝐿\n= 1698.3 𝑘𝑔/𝑑𝑎𝑦\nt-BuOH could be reused, we assume the recycling cost accounts for 30% of the consumed t-\nBuOH cost\n1000 𝑘𝑔/𝑑𝑎𝑦\nConsumed ammonia = ×17.03 𝑔/𝑚𝑜𝑙 = 150.5 𝑘𝑔/𝑑𝑎𝑦\n113.16 𝑔/𝑚𝑜𝑙\nThe water flow rate for the NH dilution reaction (H O concentration, 3.2 M) is:\n3 2 2\n0.91 𝑔/𝑚𝐿×1000 𝑚𝐿/𝐿\n𝐻 𝑂 𝑓𝑙𝑜𝑤 𝑟𝑎𝑡𝑒 = ( −1)×150.5 𝑘𝑔/𝑑𝑎𝑦 = 2362.5 𝑘𝑔/𝑑𝑎𝑦\n2 17.03 𝑘𝑔/𝑘𝑚𝑜𝑙 ×3.2 𝑚𝑜𝑙/𝐿\n1. Equipment cost\nFrom the DOE H A analysis for distributed grid electrolysis,13 the electrolyzer cost for the stack\n2\ncomponent is 7722$/m2 with an Uninstallation factor = 12%. While our PSE reactor has one\nadditional AEM and PSE layer than conventional PEM water electrolyzers, we do not need to\ndo the harsh hydrogen evolution reaction on the cathode, thus our cathode catalyst and GDL\nwould be cheaper than those used in water electrolyzers. Therefore, the final cost of our\nelectrolyzer should be similar to PEM water electrolyzers (see our previous TEA)16. According\nto the DOE H A PEM Electrolyzer Stacks and Systems analysis, the electrolyzer cost per m2 can\n2\nbe calculated as below:\n𝐶𝑜𝑠𝑡 ($/𝑚2) = 𝑅𝑒𝑝𝑜𝑟𝑡𝑒𝑑 𝑐𝑜𝑠𝑡 ($/𝑘𝑊)×𝑅𝑒𝑝𝑜𝑟𝑡𝑒𝑑 𝑝𝑜𝑤𝑒𝑟 𝑑𝑒𝑛𝑠𝑖𝑡𝑦 (𝑘𝑊/𝑚2)\n= 143 $/𝑘𝑊 ×3 𝐴/𝑐𝑚2 ×1.8 𝑉×104𝑐𝑚2/𝑚2 = 7722$/𝑚2.\nAt 125 mA cm−2, the total electrolyzer area is 14.58 m2 and the total cost is (assuming 12% of\nthe uninstalled capital cost):\n𝑃𝑆𝐸 𝑒𝑙𝑒𝑐𝑡𝑟𝑜𝑙𝑦𝑧𝑒𝑟 𝑐𝑜𝑠𝑡 = 𝐸𝑙𝑒𝑐𝑡𝑟𝑜𝑙𝑦𝑧𝑒𝑟 𝑎𝑟𝑒𝑎×𝐶𝑜𝑠𝑡 ($/𝑚2)×(1+𝑢𝑛𝑖𝑛𝑠𝑡𝑎𝑙𝑙𝑒𝑑 𝑓𝑎𝑐𝑡𝑜𝑟)\n== 31.9 𝑚2 ×7722 $/𝑚2 ×(1+0.12) = 276296 $\nPBR equipment contains quite cheap plastic tube (assuming 30 $) and TS-1 (555 $/kg), which\ncould be reused. Assuming the catalytic efficiency for CyO production is 161 mmol∙h-1∙g -1 and\ncat\nthe commercial TS-1 catalytic activity last 500 h17, the reactivation of TS-1 accounts for 30% of\ncatalyst cost. The cost of PBR cost for running 500 h is:\n1000 𝑘𝑔/𝑑𝑎𝑦 555 $/kg\n𝑃𝐵𝑅 𝑐𝑜𝑠𝑡 = × +30 $ = 1299 $\n500ℎ 113.16 𝑘𝑔/𝑘𝑚𝑜𝑙 0.161 𝑚𝑜𝑙/(ℎ×𝑔 )×24 ℎ/𝑑𝑎𝑦\n𝑐𝑎𝑡\nThe cost of PBR cost for running 20 years is:\n20×350×24 ℎ𝑜𝑢𝑟𝑠\n𝑃𝐵𝑅 𝑐𝑜𝑠𝑡 = 1299 $+( −1)×1299 $×30% = 131879 $\n20 𝑦𝑒𝑎𝑟𝑠 500 ℎ𝑜𝑢𝑟𝑠\nHerein, the capital recovery factor (CRF) is based on a discount rate (denoted as i; we use 10%\nfor all the CRF calculations) and the material lifetime (20 years).\n𝑖(1+𝑖)𝑦𝑒𝑎𝑟 0.1×1.120\n𝐶𝑅𝐹 = = = 0.1175\n𝑃𝑆𝐸 𝑒𝑙𝑒𝑐𝑡𝑟𝑜𝑙𝑦𝑧𝑒𝑟 (1+𝑖)𝑦𝑒𝑎𝑟 −1 1.140 −1\n0.1175\n𝐸𝐹𝑞𝑢𝑖𝑝𝑚𝑒𝑛𝑡 𝑐𝑜𝑠𝑡 = (276296 $+131879 $)× = 137.0 $/𝑑𝑎𝑦\n𝑝𝑒𝑟 𝑡𝑜𝑛 𝐶𝑦𝑂 350 𝑑𝑎𝑦\nBalance of plant cost\nFrom the DOE H A analysis for distributed grid electrolysis, the BOP cost (including mechanical\nis:\n𝐵𝑂𝑃 𝑐𝑎𝑝𝑖𝑡𝑎𝑙 𝑐𝑜𝑠𝑡 = 𝐸𝑙𝑒𝑐𝑡𝑟𝑜𝑙𝑦𝑧𝑒𝑟 𝑎𝑟𝑒𝑎 ×𝑅𝑒𝑓𝑒𝑟𝑒𝑛𝑐𝑒 𝑐𝑜𝑠𝑡×(1+𝑢𝑛𝑖𝑛𝑠𝑡𝑎𝑙𝑙𝑒𝑑 𝑓𝑎𝑐𝑡𝑜𝑟)\n= 31.9 𝑚2 ×4914 $/𝑚2 ×(1+12%) = 175825 $\nHerein, the capital recovery factor (CRF) is based on a discount rate (denoted as i; we use 10%\nfor all the CRF calculations) and the material lifetime (20 years).\n0.1175\n𝐵𝑂𝑃 𝑐𝑎𝑝𝑖𝑡𝑎𝑙 𝑐𝑜𝑠𝑡 = 175825 $× = 59.0 $/𝑑𝑎𝑦\n𝑝𝑒𝑟 𝑡𝑜𝑛 𝐶𝑦𝑂 350 𝑑𝑎𝑦\nTherefore, the overall capital cost is 196.1 $ per ton CyO\n.\n2. Electricity cost\nThe electricity cost is calculated from the power requirement and the price of electricity,\nassuming the electricity price is 10 cents kWh−1:\n𝐸𝑙𝑒𝑐𝑡𝑟𝑖𝑐𝑖𝑡𝑦 𝑐𝑜𝑠𝑡 = 107.82 𝑘𝑊 ×24 ℎ𝑟/𝑑𝑎𝑦×0.10$/𝑘𝑊ℎ = 258.8 $/𝑑𝑎𝑦\n𝑝𝑒𝑟 𝑡𝑜𝑛 𝐶𝑌𝑂\n3. CyO separation cost\nThe separation cost is assumed to be 30% of the electricity cost:\n𝐶𝑦𝑂 𝑠𝑒𝑝𝑒𝑟𝑎𝑡𝑖𝑜𝑛 𝑐𝑜𝑠𝑡 = 258.8 $/𝑑𝑎𝑦×30% = 77.6 $/𝑑𝑎𝑦\n𝑝𝑒𝑟 𝑡𝑜𝑛 𝐶𝑌𝑂\n3. Input chemicals cost\nFor the input chemicals cost, we account for the cost of the consumed H O and O . The water\n2 2\nprice is estimated as $ 0.003 per liter18, and the O price is estimated as $80/ton19.\n2\n𝐶𝑜𝑠𝑡 𝑜𝑓 𝑐𝑜𝑛𝑠𝑢𝑚𝑒𝑑 𝐻 𝑂 = 0.003 $/kg ×(321.8+797.5+2362.5) kg/day = 31.8 $/day\n2\n𝐶𝑜𝑠𝑡 𝑜𝑓 𝑐𝑜𝑛𝑠𝑢𝑚𝑒𝑑 𝑂 = 0.08 $/kg×572.15 kg/day = 45.8 $/day\n2\n𝐶𝑜𝑠𝑡 𝑜𝑓 𝑐𝑜𝑛𝑠𝑢𝑚𝑒𝑑 𝐶𝑦𝐻 = 1.16 $/kg ×895.1 kg/day = 1038.3 $/day\n𝐶𝑜𝑠𝑡 𝑜𝑓 𝑐𝑜𝑛𝑠𝑢𝑚𝑒𝑑 𝑁𝐻 = 0.31 $/kg×150.5 kg/day = 46.8 $/day\n3\n𝐶𝑜𝑠𝑡 𝑜𝑓 𝑡𝐵𝑢𝑂𝐻 𝑠𝑜𝑙𝑣𝑒𝑛𝑡 = 0.85 $/kg ×1698.3 kg/day×30% = 431.7 $/day\n𝑂𝑣𝑒𝑟𝑎𝑙𝑙 𝑐𝑜𝑠𝑡 𝑜𝑓 𝑐𝑜𝑚𝑝𝑜𝑛𝑒𝑛𝑡 = 31.8+45.8+1038.3+46.8+431.7 = 1594.3 $/𝑑𝑎𝑦\n4. Stack replacement cost\nFor the stack replacement cost, assuming 15% of the uninstall cost for 10 years20,21.\n15%\n𝑆𝑡𝑎𝑐𝑘 𝑟𝑒𝑝𝑙𝑎𝑐𝑒𝑚𝑒𝑛𝑡 𝑐𝑜𝑠𝑡 = 276296 $× = 11.8 $/𝑑𝑎𝑦\n10 𝑦𝑟×350 𝑑𝑎𝑦/𝑦𝑟\n5. Other operational costs\nOther operational costs, such as labor and maintenance, are assumed to be 5% of the electrolyzer\ncost per ton of H O and 5% of the PBR reactor cost per ton of CyO:\n2 2\n0.05\n𝑂𝑡ℎ𝑒𝑟 𝑐𝑜𝑠𝑡 = (276296+131879)$× = 58.3 $/𝑑𝑎𝑦\n𝑝𝑒𝑟 𝑡𝑜𝑛 𝐶𝑦𝑂 350\nThus, the overall cost to obtain 1000 kg CyO/day using O , CyH, and NH is:\n2 3\n𝑂𝑣𝑒𝑟𝑎𝑙𝑙 𝑐𝑜𝑠𝑡\n𝑝𝑒𝑟 𝑡𝑜𝑛 𝐶𝑦𝑂\n= 196.1 $+258.8 $+77.6 $+1594.3 $+11.8 $+58.3 $ = 2196.9 $\nComment 6. The authors should point out the scientific points of the research.\nResponse: 1) Our strategy employed the cheapest nitrogen sources—NH (except N ) and\n3 2\nelectrochemically in-situ generated H O largely decrease the CyO production cost to 2196.9\n2 2\n$/ton (0.1 $/kWh electricity cost). For comparison, in Shi’s TEA (Sci. Adv. 10, eado1755 (2024)),\n1385 $ of NH HCO was needed to produce one ton of CyO (we only need 46.8 $/ton ); 2)\n4 3 CyO\nCompared with directly using commercial H O bearing stabilizer, the in-situ generated eH O\n2 2 2 2\nfrom PSER showed better performance of nylon-6 precursor synthesis in PBR. 3) For the cascade\nreaction of the in-situ generated eH O and downstream chemical reaction, PSER system could\n2 2\navoid the possible influence of liquid electrolyte on the downstream chemical reactions. 4) NO -\nx\nelectroreduction for nylon-6 synthesis typically needs recycling liquid electrolyte containing\nsubstrate, intermediate, and product into the system, which may cause more issues, such as side\nreactions from sensitive compounds, over-reduction of intermediate. Our one-pass mode of\nPESR to generate pure H O without a liquid electrolyte, with the chemical reaction in the\n2 2\nfollowing reactor, could avoid such issues. By the way, the direct use of NH as nitrogen source\n3\nother than NO - that is from NH industrially is more energy-saving.\nx 3\nThe following statements were added in the summary part: “By using one-pass PSER-PBR\nsystem for cascade reaction, our research described slightly higher H O utilization efficiency\n2 2\nthan commercial H O , successfully avoided the liquid electrolyte interruption and electrolyte\n2 2\nseparation in commonly used electrochemical devices and greatly reduced the risk of potential\nside reaction from the reactants recycling. Moreover, according to the TEA, the use of cheapest\nnitrogen source (NH ) and electrochemically in-situ generated H O could largely decrease the\n3 2 2\nCyO production cost to 2196.9 $/ton (0.1 $/kWh electricity cost)”"}, {"round": 2, "reviewer_comments": {"reviewer_1": "I am writing to convey my final recommendation regarding the manuscript \"Integrated electrochemical porous solid\nelectrolyte reactor and packed bed reactor for efficient synthesis of nylon-6 precursor\" (Manuscript ID: NCOMMS-25-\n46089A) following the authors' revision.\nHaving thoroughly reviewed the authors' point-by-point responses and the revised manuscript, I am highly impressed with\nthe quality and thoroughness of their revisions. The authors have addressed all the reviewers' concerns comprehensively\nand effectively.\nThe revisions have substantially improved the manuscript, elevating its quality and impact. The work now presents a\ncompelling story, with well-supported claims that meet the high standards of Nature Communications.", "reviewer_2": "The authors have adequately addressed my comments and the paper can now be considered for publication."}, "author_response": ""}]

Decision letter