Carbon defects enhanced TEMPO redox cycles for high-efficiency urotropine electrosynthesis

Carbon defects enhanced TEMPO redox cycles for high-efficiency urotropine electrosynthesis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Carbon defects enhanced TEMPO redox cycles for high-efficiency urotropine electrosynthesis Mufan Li, Shiyun Li, Guangsheng Liu, Chuhao Liu, Yifan Fu, Yixuan Fu, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6615715/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Nov, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Electrocatalysis provides a sustainable alternative route to produce nitrogen-containing molecules. However, poor carbon-nitrogen (C-N) coupling selectivity and limited current density pose challenges to its widespread adoption. Herein, we introduce a carbon-defect enhanced 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) mediated tandem process to tackle both problems. Our hetero-homogeneous system achieved an exceptional Faraday efficiency of ~99% with industrial-level current density of ~0.6 A·cm −2 for electrosynthesis of urotropine. In situ near ambient pressure X-ray photoelectron spectroscopy and density functional theory calculations revealed that the boosted activity originated from the oxidation of TEMPOH on the carbon defective sites, which accelerated the redox cycling of the molecular mediator for urotropine formation. Life cycle assessment indicates that the electrosynthesis of urotropine reduces CO 2 emissions by up to 30.7% compared to conventional industrial processes. This work highlights the unique catalytic effect of carbon defects on the redox cycling of TEMPO, facilitates electrocatalytic C-N coupling at record selectivity and rate, and offers new insights for designing efficient electrochemical mediated oxidation processes and C-N coupling reactions. Physical sciences/Chemistry/Electrochemistry/Electrocatalysis Physical sciences/Chemistry/Catalysis/Electrocatalysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Main Electrocatalytic synthesis of nitrogen-containing (N-containing) molecules like amide, amine, and amino acid through carbon-nitrogen (C-N) coupling reactions has recently attracted extensive interest 1 – 5 . It provides a viable strategy for the decarbonization of the chemical industry by utilizing renewable energy 6 (Fig. 1 a). However, direct electrochemical synthesis of N-containing molecules encounters substantial challenges: (i) the adsorption and activation of multiple reactants on the electrode lead to prevalent side reactions 3 , 4 and limited current density 4 , 7 ; and (ii) the initiation of electron transfer process requires high overpotentials 8 , 9 . Consequently, achieving high selectivity and current density sufficient for industrial-scale production remains a formidable obstacle 1 – 5 . Correspondingly, mediation strategy (Supplementary Fig. 1), i.e., enabling substrate conversion using redox-prone mediator molecules, could effectively reduce overpotential and improve selectivity 8 , 10 , 11 , while the application of mediated processes have been hampered by limited current density 10 , 11 . 2,2,6,6-Tetramethylpiperidine N-oxyl (TEMPO), an excellent metal-free oxidative mediators featuring a stable free radical 12 (Fig. 1 b), is widely used in organic synthesis 13 for converting alcohols into aldehydes, ketones and acids. However, the slow electron transfer rate 12 , 14 of the hydroxylamine species (TEMPOH) formed after the oxoammonium species (TEMPO+) oxidizes the substrate and limits the rate of the TEMPO redox cycles on the electrode surface (Fig. 1 c and Supplementary Fig. 2). Here, we report a hetero-homogeneous tandem C-N coupling process with accelerated TEMPO redox cycles catalyzed by carbon vacancy defects on graphene (Fig. 1 b). This process has achieved, to the best of our knowledge, the highest electrocatalytic C-N coupling performance (Supplementary Fig. 3) reported to date, that is, the Faraday efficiency (FE) ~ 99% and the current density ~ 0.6 A·cm − 2 , exceeding a yield rate of 261.5 mg·cm − 2 ·h − 1 . Exceptional efficiency of C-N coupling benefits from the unique design of the electrochemical process, i.e., highly selective TEMPO redox cycles and efficient carbon defects catalysis: (i) The utilization of TEMPO spatio-temporally decouples C-N coupling from electrooxidation, which circumvents reaction rate constraints from limited active sites for heterogeneous reactions and minimizes intermediate adsorption on the electrode, decreasing the direct oxidation of by-products on electrode (Fig. 1 b). (ii) Notably, we present the first report and provide the evidence of the accelerated TEMPO redox cycles by carbon defects. In situ near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) experiments, quasi in situ electron paramagnetic resonance (EPR) and density functional theory (DFT) calculations confirm that carbon vacancy defect sites on graphene surface can adsorb TEMPOH and significantly lower the oxidation overpotential by transforming the sluggish outer-sphere (OS) oxidation process of TEMPOH oxidation into a rapid inner-sphere (IS) reaction (Fig. 1 c). We then achieve gram-scale urotropine synthesis with a flow cell, validating the industrial application potential. Life cycle assessment (LCA) indicates that the electrochemical production of urotropine powered by renewable energy reduces overall greenhouse gases (GHGs) emissions by 30.7%, compared to conventional thermal catalytic routes. Techno-economic analysis (TEA) confirms its economic viability, with overall profit of $ 623.8 per ton of urotropine. Furthermore, we demonstrate that this method can be applied to the production of other N-containing organic molecules, highlighting its broad applicability and versatility. Results TEMPO-mediated urotropine electrosynthesis We first verified the capability of TEMPO to oxidize methanol and demonstrated the TEMPO redox cycles (Supplementary Fig. 2). In Fig. 2 a, a pair of redox peaks appeared in the cyclic voltammetry (CV) curve at an equilibrium potential of ~ 1.2 V (vs. RHE, potential hereafter is referenced to the RHE scale unless otherwise specified) while only TEMPO was added, representing a redox couple of TEMPO and TEMPO+ (Supplementary Fig. 2a), compared to the negative control (blank = electrolyte only). No obvious oxidation peaks were detected until ~ 1.9 V when solely added methanol with a glassy carbon (GC) electrode. This shows that TEMPO oxidizes at a less positive potential than methanol 15 . When methanol is present in the TEMPO-containing electrolyte, the oxidation peak current is multiplied while the peak potential remains largely unchanged. The pronounced enhancing effect of methanol on the TEMPO electrooxidation indicates that it undergoes an electrochemical-chemical pathway 16 , where TEMPOH, the product of the reaction between methanol and TEMPO + 12 , is reoxidized at the anode, thereby enabling multiple redox cycles of TEMPO during the anodic scan in CV. (Fig. 1 b,c and Supplementary Fig. 2). Subsequently, we confirmed that the TEMPO redox cycles could be used for electrochemical C-N coupling reactions including urotropine production. C-N coupling product was extracted from an electrolyte containing TEMPO, methanol, and ammonia after a constant current electrolysis (see Methods), and was identified as urotropine using nuclear magnetic resonance (NMR, Fig. 2 b and Supplementary Fig. 4) and high-resolution Fourier transform mass spectrometry (HRFTMS) (Fig. 2 c and Supplementary Table 1). Isotope labeling experiments reveal that urotropine produced in electrolysis originates from methanol and ammonia (Fig. 2 c, Supplementary Figs. 5 and 6). Linear correlations between urotropine concentration and electrolysis time (Supplementary Figs. 7 and 8) further verified that the C-N coupling products were produced from the electrolysis process. To highlight the pivotal role of TEMPO in the electrochemical production of urotropine, we conducted control experiments. Product analysis (Fig. 2 d and Supplementary Table 2) revealed that metal electrodes barely produced urotropine in the absence of TEMPO, while carbon materials showed an FE for urotropine of ~ 20%. When TEMPO was added, urotropine production was found to increase on all electrodes (Fig. 2 d and Supplementary Table 2), with carbon materials exceeding the highest FE of ~ 97%, underscoring the decisive role of TEMPO. Byproducts including formamide and formate were detected (Supplementary Fig. 9) to determine the mechanism of high efficiency of TEMPO related reaction. Both formamide and formate were detected in electrolysis in the absence of TEMPO (Supplementary Fig. 9a), consistent with a previous report 17 , which yields formamide at the FE of ~ 40% with methanol and ammonia and shows that the intermediates were adsorbed and further oxidized on the electrode (Fig. 2 e). Another critical raw material for urotropine production, ammonia, undergoes no significant oxidation in the TEMPO-mediated system (Supplementary Fig. 10 − 13), thereby preventing selectivity losses for urotropine. However, formamide, which yielded from the oxidation of the C-N coupling intermediate (aminomethanol, Fig. 2 e) from the reaction of formaldehyde and ammonia 17 , was negligible when TEMPO was present in the electrolyte (Supplementary Fig. 9b). Based on these results, we hypothesize that aminomethanol exhibits different reaction pathways depending on its location (Fig. 2 e), given that the TEMPO transfer the methanol (thus the related C-N coupling intermediates) oxidation location from the anode to the electrolyte (Fig. 1 b and Supplementary Fig. 1): (i) Oxidation of aminomethanol will be expected if it stays near and then is adsorbed on the electrode surface at positive potentials. (ii) In contrast, aminomethanol dehydrated and further react with ammonia and formaldehyde in the electrolyte and ultimately yield urotropine. We then determined the FE of formamide in different stirring rates (Supplementary Fig. 14) in the presence of TEMPO with a view to corroborating this assertion. The stirring would enhance the diffusion of the intermediates away from the electrode surface by convection, and thus reducing the probability of their adsorption and subsequent oxidation to form formamide at the electrode. As shown in Supplementary Fig. 14, compared to 0 rpm, about 90% less formamide was detected in the electrolysis products at 1600 rpm on a rotating disk electrode (RDE), conforming our proposed mechanism in Fig. 2 e. The reduction of byproducts is attributed to the fact that TEMPO transfers the reaction location and prevents overoxidation of C-N coupling intermediate. Besides, the structure selectivity of TEMPO is also indispensable. In light of structure-sensitive reaction rate of TEMPO + and alcohols 8 , 18 , i.e., reaction rate of primary alcohols is higher than that of secondary alcohols, the high efficiency of C-N coupling reaction is partially attributed to the steric hinderance of the intermediate and TEMPO+. Given that aminomethanol is structured with an amino group that replaces the hydrogen on methanol (Fig. 2 e) and thus takes a larger space, the steric hinderance thus prevents further oxidation of aminomethanol, which yield the formamide, by TEMPO+. We demonstrated this by changing the order of ammonia addition (Supplementary Fig. 15), as no formamide was detected when ammonia was added after the electrolysis. We also noted that the FE of formate (~ 20%) was higher when ammonia was added later compared to added former (< 3%), that is, the adding of ammonia reduced the overoxidation of formaldehyde by forming aminomethanol. Accelerated TEMPO redox cycles We then optimized the reaction conditions by employing various derivatives of TEMPO (Supplementary Fig. 16), and varying concentration of TEMPO (Supplementary Fig. 17). Effects of pH and concentration of methanol and ammonia were investigated as well (Supplementary Fig. 18 and Supplementary Fig. 19). Notably, when using the reduced graphene oxide (rGO) as anode, we were able to maintain an FE of ~ 99% at a current density of 0.6 A·cm − 2 at the potential of 1.6 V (Fig. 2 f), exceeding a yield rate of 261.5 mg·cm − 2 ·h − 1 . No obvious byproducts from non-Faradaic process were found (Supplementary Fig. 20), and a carbon balance of 94.0% was calculated (Supplementary Fig. 21 and Supplementary Table 3). This efficiency is significantly higher than existing reports on directly C-N coupling reactions at electrode surfaces (Supplementary Fig. 3). Among those results, it is interesting that pristine graphene (Gr) and rGO exhibited similar FE (> 99%) but distinct current densities (Supplementary Figs. 22 and 23). We confirmed our observation that rGO and Gr differ at reactivity when TEMPO is present(Fig. 3 a,b). As is shown in Fig. 3 b (catalysts were cast on RDE and test at 1600 rpm), anode currents of both materials remained similar until methanol was added to the TEMPO-containing electrolyte, with rGO exhibiting a ~ 40% higher current density, consistent with product analysis in urotropine synthesis (Supplementary Fig. 22). As both materials displayed similar current density when methanol and TEMPO was respectively present in the electrolyte, their reactivity to the oxidation of methanol and TEMPO remained the same. Moreover, the double-layer capacitance (C dl ) of Gr and rGO was measured as 10.42 and 11.41 mF·cm − 2 (Supplementary Fig. 24), respectively, indicating that the influence of the electrochemical specific surface area can be excluded. The evidence shows that the difference in activity between the two materials is observed only when methanol and TEMPO are both present in the electrolyte. As discussed earlier, the addition of methanol initiated the TEMPO redox cycle. The observed activity differences may be related to variations in the state of the TEMPO redox cycling on different anode surfaces. As shown in Supplementary Fig. 2, to achieve cyclic TEMPO redox, both TEMPO and TEMPOH oxidation are required. Therefore, to gain a deeper understanding of the TEMPO redox cycle, we extended the CV potential range to investigate the interconversion among the three TEMPO species (Fig. 3 a). Notably, a distinct pair of redox peaks (yellow stars in Fig. 3 a) appeared on the CV curve of rGO at potentials significantly lower relative to the redox peaks of TEMPO/TEMPO+, while Gr displayed a reduction peak (grey star in Fig. 3 a) but in absence of a corresponding oxidation peak. This more negative pair of redox peaks (yellow stars in Fig. 3 a) were attributed to the redox reactions between TEMPOH and TEMPO 19 . The absence of the TEMPOH oxidation peak on Gr may be due to slow electron transfer in the TEMPOH/TEMPO redox reaction 14 . Even at higher potentials, however, no oxidation peak belonging to TEMPOH oxidation was observed on Gr (Fig. 3 a), suggesting that the overpotential of the TEMPOH oxidation peak might be substantial. So far, for the TEMPO redox cycle, we can conclude that (i) both materials exhibit similar capabilities for oxidizing TEMPO to TEMPO + and (ii) they display varying efficiencies for oxidizing TEMPOH to TEMPO (rGO can while Gr cannot). Given that the reaction between TEMPO + and methanol is a homogeneous chemical reaction 12 independent of the electrode material, the activity difference between the two materials is manifested solely in the oxidation process of TEMPOH to TEMPO, within the TEMPO redox cycle. Based on these discussions, it is postulated that the current difference is a consequence of the varying rates of TEMPOH oxidation to TEMPO on different electrode surfaces, i.e., the TEMPO redox cycles are accelerated on rGO surface (Fig. 3 c). To confirm the proposed mechanism depicted in Fig. 3 c, in situ surface-enhanced infrared absorption spectroscopy (SEIRAS) was conducted to monitor the TEMPO-related species under electrochemical conditions (Fig. 3 d). In the spectra (Fig. 3 d left), the oxidation and reduction processes of TEMPO-containing electrolyte led to negative absorption band around 2900 cm − 1 . As shown in the Fourier transform infrared (FTIR) reference spectrum of TEMPO (inset in Fig. 3 d left), the characteristic absorption peaks are observed around 2900 cm − 1 . Accordingly, the series of peaks at 2900 cm − 1 in the in situ SEIRAS spectra were attributed to TEMPO (Fig. 3 d left), with negative peaks representing the consumption of TEMPO near the electrode surface. When TEMPO is replaced with TEMPOH, an increase in the absorption peaks attributed to TEMPO is observed under oxidative potential (Supplementary Fig. 25). These findings demonstrate that in situ SEIRAS is capable of qualitatively probing the concentration of TEMPO concentration near the electrode surface. Specifically, an increase in the set of peaks at 2900 cm − 1 corresponds to an elevated TEMPO concentration, whereas the emergence of negative bands indicates a reduction in concentration (Fig. 3 d right). Subsequently, stepwise oxidative potentials were applied to anodes modified with Gr and rGO, respectively, in a mixed TEMPO/TEMPOH electrolyte (Fig. 3 e and Supplementary Note 1). The concentration of TEMPO on the surface of the Gr electrode decreases progressively, while on the rGO electrode, it initially increases, followed by a slight decline at higher potentials. These findings were well-aligned with observations in Fig. 3 a and also support the proposed reaction mechanism in Fig. 3 c as discussed below. For the Gr anode, the inability to oxidize TEMPOH lead to continue consumption of TEMPO, resulting in a decrease in the peaks around 2900 cm − 1 . For the rGO anode, however, owing its ability to oxidize TEMPOH into TEMPO, an enhanced TEMPO-related signal was observed. As the potential increased, rGO began oxidizing TEMPO, leading to the depletion of TEMPO and a relative inversion of the peak intensity toward negative values. The mechanistic hypothesis proposed in Fig. 3 c suggests that rGO exhibits a higher oxidation rate for TEMPOH than that of Gr. However, the precise impact of this enhanced oxidation rate on the TEMPO redox cycling, specifically, the concentration dynamics of TEMPO species throughout the complete cycle (as illustrated by the arrow symbols in Fig. 3 c), remains unclear. The in situ SEIRAS experiments only provided TEMPO-related information, thereby limiting our investigation of the whole TEMPO redox cycle. To address this, we have employed the multiple approaches including in situ ultraviolet-visible (UV-Vis) spectroscopy, quasi in situ EPR spectroscopy and rotating ring-disk electrode (RRDE) experiments, to detect the concentration changes of TEMPOH and TEMPO + species. We first highlighted the significant disparity in the spectral sensitivity of TEMPO-related species (Supplementary Fig. 26) using in situ UV-Vis spectroscopy, where TEMPO and TEMPO + showed similar but significantly higher absorbance than TEMPOH around the 244 nm absorption peak. As TEMPO + was consumed by the addition of MeOH, in situ monitor of the electrolyte absorbance enables the determination of the TEMPO/TEMPOH concentration. In Fig. 3 f, the absorbance with Gr was significantly lower than that with rGO, indicating that electrolyte with Gr anode contained more TEMPOH, while the electrolyte with rGO anode contained more TEMPO. Since TEMPO carries a stable unpaired electron, quasi in situ EPR is well-suited for probing variations in TEMPO concentration. The results (Fig. 3 g) demonstrated that the TEMPO concentration with rGO electrode was significantly higher than that with Gr electrode, with the same electrolyte as used in the in situ UV-Vis experiments. This inference is further confirmed by the detection of TEMPOH with 1 H-NMR test (Supplementary Figs. 27 and 28). These results here exhibit excellent consistency in accordance with the deduction that TEMPOH would accumulate on Gr electrode so less TEMPO was detected, based on the mechanism in Fig. 3 c. It is TEMPO + that reacts with methanol in the TEMPO redox cycle (Supplementary Fig. 2), thus determining the actual methanol oxidation rate and, consequently, the C-N coupling rate. To this end, we conducted electrochemical CV experiments using a RRDE in the collection mode (see Methods and Supplementary Note 2). By applying different potentials to the peripheral ring electrode, the active species convectively transported from the disk electrode to the ring electrode can be detected (schematic diagram in Fig. 3 h), enabling the determination of species concentrations at the disk electrode surface. Initially, based on the CV curves in Fig. 3 a, we set the ring potential at 1.0 V to enable the reduction of TEMPO + detached from the disk and prevent the oxidation of TEMPOH. A more significant reduction currents were observed on rGO decorated disk electrode, indicating that rGO can provide a higher concentration of TEMPO + during the electrolysis. We then designed another RRDE experiment to collect the TEMPOH on ring electrode. In brief, given that Gr and rGO both oxidize TEMPO but only rGO can oxidize TEMPOH, the TEMPOH oxidation current can be resolved by minus ring current with rGO with the ring current with Gr. The current density curves representing the TEMPOH concentration shown in Fig. 3 i were in conformity with our expectations that TEMPOH accumulated on Gr electrode and thus lead to a higher concentration. Mechanism of carbon defects catalyzed TEMPOH oxidation Having demonstrated the principle behind rGO's ability to accelerate the TEMPO redox cycle, we now turn to investigating the catalytic mechanism. Comparison of the two materials across various characterizations (Fig. 4a and Supplementary Fig. 29) reveals that rGO displays significant differences in the Raman spectrum. The D band in the Raman spectrum of rGO is more pronounced (Fig. 4a), indicating that rGO has a significantly richer presence of defects on its surface. Results from in situ Raman spectroscopy show that the structure of both Gr and rGO remain unchanged during electrolysis (Supplementary Fig. 30). We subsequently broadened the scope of carbon materials to further establish the correlation between the carbon defects and the catalytic activity of TEMPOH (Supplementary Fig. 31). Accordingly, materials exhibiting a significant D band display the characteristic TEMPOH/TEMPO redox peaks in the CV, while those lacking the D band do not. Together, those results suggest that carbon defects are the active sites for the catalytic oxidation of TEMPOH by rGO. From the discussion of the aforementioned evidence, all the carbon materials are capable of effectively oxidizing TEMPO (Supplementary Fig. 31). This corresponds to the oxidation of TEMPO being independent of the electrode material, a characteristic feature of an OS reaction 20 . In contrast, the oxidation of TEMPOH has been shown to be promoted by carbon defects, which is surface sensitive. This indicates that TEMPOH and carbon defects may have strong interaction like adsorption, which aligning more closely with the characteristics of an IS reaction 21 . To validate the hypothesis with OS and IS process involved, surfactants experiments were conducted (Supplementary Fig. 32 − 36, and Supplementary Note 3). Surfactants can adsorb onto the surface of graphene-related materials 22 – 24 , hindering the interaction between the reactants and the electrode surface, thereby aiding in the determination of the electrochemical reaction mechanism, i.e., distinguishing between the OS and IS processes 21 . An appropriate surfactant should significantly reduce the activity of IS reactions, while having a minimal effect on OS reactions 21 . A significant decrease in the reversibility of the TEMPOH/TEMPO redox couple was observed upon the addition of 1 mM surfactants (CTAB or CTAC) to the system (Supplementary Fig. 32a), while the reversibility of the TEMPO/TEMPO + redox couple remained largely unchanged (Supplementary Fig. 36). Furthermore, at the same surfactant concentration (1 mM), it was observed that the reversibility of the TEMPOH/TEMPO redox couple decreased with the increase in the molecular size of the surfactant (Supplementary Fig. 32c). These results validate the hypothesis that the oxidation of TEMPO follows an OS mechanism and indicate that the TEMPOH oxidation on carbon defects occurs via an IS mechanism, i.e., involving a direct interaction between TEMPOH and carbon defects during the oxidation process. To verify the IS oxidation process of TEMPOH on carbon defects and to investigate the underlying interaction mechanism, we conducted in situ NAP-XPS measurements (see Methods and Supplementary Note 4). Compared to the OCP, specific absorption signals in the C1s, N1s, and O1s spectra showed significant changes within the reaction potential range (highlighted in yellow in Fig. 4b). The intensities of the signals at 287.1 eV in C1s, 400.1 eV in N1s, and 531.6 eV in O1s decreased monotonically with increasing potential, which is consistent with the trend observed for the TEMPOH concentration in Fig. 3 i. In situ Raman spectroscopy has demonstrated that the rGO structure undergoes no significant changes (Supplementary Fig. 30), while XPS results indicate that both N and O are nearly absent from the rGO structure (Supplementary Fig. 29). Considering that TEMPOH molecules are continuously introduced into the XPS chamber, this signal change cannot be attributed to the consumption of TEMPOH in the gas phase. After excluding these possibilities, we attribute these signal changes to the interaction between TEMPOH and the catalyst, hypothesizing that the signal variation may result from the binding of TEMPOH to carbon defects and its subsequent consumption (Fig. 4c). Specifically, the peak at 287.1 eV is attribute to the signal of C-O 25 . While the C-O structure does not exist in TEMPOH (Fig. 1 ) or rGO (Supplementary Fig. 29), the adsorption structure of TEMPOH on rGO should be formed during the interaction of TEMPOH and rGO, with the O atom bonding to a C atom at the carbon defect site (TEMPO* in Fig. 4c) after the dehydrogenation of the hydroxyl group of TEMPOH, given that the TEMPOH oxidation on rGO is proved to be pH-dependent (Supplementary Fig. 37). The signal of C-O almost disappeared at 0.6 V, indicating that the TEMPO* desorbed from the rGO and form TEMPO. Accordingly, the N1s signal at 400.1 eV and O1s signal at 531.6 eV were associated with the adsorbed state of TEMPO (TEMPO* in Fig. 4b). Integrating the results from the in situ NAP-XPS experiment, we infer that TEMPOH can be adsorbed at defect sites (thus confirm the IS reaction) and desorb after oxidation with increasing potential, as is shown in the schematic diagram in Fig. 4c. The assignments of the other peaks are given in Supplementary Note 4. To further solidate the conclusion above, quasi in situ EPR experiments were conducted to probe the interaction of TEMPOH/TEMPO with the carbon surface (with/without carbon defects), as shown in Fig. 4d,e and Supplementary Fig. 38. When the same mass of carbon materials (Gr and rGO) were added to TEMPO solutions of the same concentration, the EPR responses of the solutions were entirely different (Fig. 4d, II and Supplementary Fig. 38): the EPR signal of the TEMPO solution with rGO was almost completely quenched (Fig. 4d, II), while the EPR signal of the TEMPO solution with Gr showed no obvious change (Supplementary Fig. 38), indicating that carbon defects can effectively adsorb TEMPO (Fig. 4e, II). Moreover, the quenching of the EPR signal (Fig. 4d, II), i.e., the disappearance of unpaired electrons, suggests that the binding site between the carbon defect and TEMPO must be the O· in the TEMPO structure (Fig. 4e, II), which carries the unpaired electron. This finding is fully consistent with the C-O-N structure inferred from our NAP-XPS data (Fig. 4c) and aligns well with reported results 26 . Notably, when TEMPOH were added (Fig. 4d, III) in the mixture of TEMPO + rGO (Fig. 4d, II), the EPR signal dramatically restored (Fig. 4d, III). This indicates that the TEMPO originally adsorbed on the carbon defects has desorbed, as TEMPOH contributed little to the EPR spectra (Fig. 4d, IV), demonstrating that the adsorption of TEMPOH on carbon defects is stronger than that of TEMPO (Fig. 4e, III), which is consistent with the adsorption energy differences obtained from our DFT calculations discussed below. Furthermore, NMR experiments show similar results and support our conclusion as well (see Supplementary Fig. 39). To better understand the interactions between TEMPOH and defect sites on graphene during this process, DFT analysis was conducted (Fig. 4f,g and Supplementary Fig. 40 − 42) to gain more insights at the atomic level. Besides perfect graphene layer, two representative carbon defects, Stone-Wales defect and carbon vacancy defect are considered, based on reported research 27 , 28 , as shown in Fig. 4f. The perfect graphene, as expected, energetically unfavorably adsorbed TEMPO (see Supplementary Fig. 41), consist with our previous results (Fig. 3 a, 4d, and Supplementary Fig. 38, 39). Therefore, TEMPOH oxidation on Gr occurs exclusively through an OS reaction with a slow electron transfer rate 14 . Subsequently, we investigated the defects' interaction with TEMPO species. Surprisingly, DFT analysis indicates that the Stone-Wales defects display a similar pattern as that of the perfect graphene (see Supplementary Fig. 41). In contrast, graphene featuring a carbon vacancy defect shows distinctly different interactions (Fig. 4f), as TEMPOH can favorably adsorb onto carbon atoms adjacent to the vacancy site (Supplementary Fig. 41), suggesting that such defect sites may stabilize TEMPO adsorption (thus an IS process) and potentially promote TEMPOH oxidation. We further analyzed the oxidation process of TEMPOH on graphene with a carbon vacancy under two applied potentials (− 0.45 V vs. SHE and 0.45 V vs. SHE), correspond respectively to the potential without and with TEMPOH oxidation, based on the CV behavior shown in Fig. 3 a. As depicted in Fig. 4g, at a potential of − 0.45 V, the adsorbed TEMPO intermediate (denoted as TEMPO*) exhibits lower energy compared to both TEMPOH and TEMPO in solvent, indicating that TEMPO* represents the most thermodynamically stable state under these conditions (consistent with EPR and NMR results in Fig. 4d and Supplementary Fig. 39). At the higher potential of 0.45 V, this trend persists, with TEMPO* becoming even more energetically favorable (compared to TEMPOH), suggesting that increasing the applied potential enhances the thermodynamic driving force for TEMPOH oxidation. Quantitatively, the energy difference between TEMPOH and TEMPO increases significantly from 0.11 eV at − 0.45 V to 0.35 eV at 0.45 V (Fig. 4g), further confirming that a higher potential strengthens the tendency for TEMPOH to be oxidized to TEMPO. Additionally, we analyzed the variations in charge distribution with increasing applied potential. The corresponding charges of each component at − 0.45 V and 0.45 V are summarized in Supplementary Table 4. For all examined configurations—including TEMPOH/rGO, TEMPO*/rGO, and TEMPO/rGO—the total charge decreases as the potential increases from − 0.45 V to 0.45 V, confirming oxidation of the system under elevated potentials. Notably, the charge on the reduced graphene oxide (rGO) component significantly decreases with increasing applied potential, indicating an enhanced oxidation capability of rGO at higher potentials. Industrial-scale N-containing chemicals electrosynthesis To demonstrate the industrial potential of urotropine electrosynthesis, we conducted flow cell experiments for scaled-up production (Fig. 5 a and Supplementary Fig. 43). In near-neutral conditions (Fig. 5 b), TEMPO-mediated oxidation demonstrates significant lower overpotential compare to commercial OER catalysts. Subsequently, a 20-hour continuous electrolysis was conducted (Fig. 5 c). Both FE and the cell potential remained stable. The decrease in electrolyte pH caused by the anodic reaction slows the electrooxidation of TEMPOH (Supplementary Fig. 37), so the final potential is higher than that at the start during each electrolysis session (Fig. 5 c). As expected, after adding KOH and NH 3 to restore the pH, the cell potential decreased (Fig. 5 c). Finally, we obtained 15.89 g of urotropine from the electrolyte, achieving an FE of 91.1%, with a calculated yield rate of 198.6 mg·cm − 2 ·h − 1 . We also performed LCA to compare the GHG emissions between electrochemical and conventional processes. The Methods and Supplementary Note 5 present the LCA methodology and data sources. Notably, when the power grid is fully decarbonized, there is a 30.7% reduction (Fig. 5 d) in carbon emissions relative to the conventional process. TEA was carried out to evaluate the economic potential (see Methods and Supplementary Note 6). The electrocatalytic protocol yields a profit of $ 459.3 per ton of urotropine with $ 164.5 from the hydrogen benefits (Fig. 5 e), thereby confirming the commercial viability of electrocatalytic urotropine production. To further demonstrate the applicability of TEMPO-mediated electrosynthesis, different carbon and nitrogen sources for C-N coupling reactions were used to explore the substrate scope (Supplementary Table 5). The efficiency of the C-N coupling reactions exhibits a broad distribution (Supplementary Note 7). Among them, using ethanol and ammonia also allowed for an industry-level production of acetaldehyde ammonia trimer, another versatile chemical 29 . Discussion In summary, we have developed a new highly efficient C-N coupling reaction method with accelerated TEMPO redox cycle catalyzed by carbon defects. For the first time, we reported the realization of the industry-level C-N coupling electrosynthesis efficiency (FE ~ 99%, current density ~ 0.6 A·cm − ²). We demonstrate that mediator TEMPO reduces oxidation overpotential and minimizes the by-products compare to direct oxidation. Enhanced C-N coupling reaction rate was realized as TEMPO redox cycles were accelerated by carbon defects. We demonstrated that carbon defects catalyzed the electrooxidation of TEMPOH by transfer a sluggish OS process into a rapid IS reaction, thus promoting the redox cycle. LCA results indicate that urotropine electrosynthesis reduces the GHGs emission by 30.7% compared to conventional routes. Our unique electrocatalytic method in this work enables industrial-level electrosynthesis of N-containing chemicals including urotropine and acetaldehyde ammonia trimer, highlighting the promise of redox mediators in facilitating efficient electrosynthesis reactions. Methods Chemicals and materials Gr was purchased from Suzhou TANFENG Graphene Tech Co., Ltd. KH 2 PO 4 , MeOH, acetonitrile (ACN), maleic acid (MA), methyl viologen dichloride (Mv + /Mv 2+ ), and ammonia were gained from Shanghai Aladdin Co., Ltd. TEMPO, 4-NH 2 -TEMPO, 4-NHCOCH 3 -TEMPO, 4-O-TEMPO, 9-Azabicyclo[3.3.1]nonane N-oxyl (ABNO), and N-Hydroxyphthalimide (NHPI) were purchased from Shanghai Sigma-Aldrich Co. H 3 PO 4 , KOH, and carbon nanotubes (CNTs, Multi-walled) were provided by Shanghai Macklin Biochemical Co., Ltd. Deuterated water (D 2 O), 15 N labeled ammonium chloride ( 15 NH 4 Cl), deuterated methanol (CD 3 OD) and deuterated dimethyl sulfoxide (DMSO-d 6 ) were purchased from Anhui Senrise Technology Co., Ltd. Porous carbon (PC), rGO, highly oriented pyrolytic graphite (HOPG) were purchased from Jiangsu XFNANO Materials Tech. Co., Ltd. TGPH060H hydrophilic carbon paper (CP), VXC-72 carbon black (CB), nickel foam, Nafion D520 dispersion, Nafion N117, and Fumasep FAA-3-PK-75 were gained from SCI Materials Hub. Metal foils (Pt, Au, Pb, Fe, Co, Ni, Cu, Zn, and Ti) were gained from Beijing Zhongke Yannuo New Material Technology Co., Ltd. Solutions containing TEMPO were freshly prepared daily and ultrasonicated for > 2 h to ensure complete dissolution. All solutions were filtered through a 0.22 µm organic filter membrane to remove any insoluble impurities. An 18.2 MΩ·cm resistivity of ultrapure (UP) water prepared in the lab by an ultrapure water system was used to prepare all solutions. Electrode preparation All carbon materials were purified prior to use as follows: ultrasonically dispersed in 1 M HCl for 1 h, stirred for 24 h, and then centrifuged to remove the acid solution. The filtrate was washed with UP water until the supernatant turned neutral. Then, the suspension was rapidly cooled and solidified using liquid nitrogen, followed by freeze-drying under vacuum conditions to ensure complete desiccation and avoid agglomeration. The preparation of the electrodes requires the use of two different ink formulations, one for the RDE and the other for the standard electrode. To prepare the RDE electrode, typically, the catalyst (5.0 mg) is dispersed in 975 µL of IPA and ultrasonicated for 1 h to achieve a uniform suspension. Subsequently, 25 µL of Nafion D520 dispersion (5.0 wt%) is added to the suspension, followed by an additional 0.5 h of ultrasonication to obtain the final ink. Using a micropipette, 10 µL of the ink is deposited onto the surface of a clean glassy carbon RDE and dried in air at room temperature. The ink preparation method for the synthetic electrode used in electrolysis is similar, with the difference being that the catalyst amount is reduced to 2.5 mg. The dispersion is prepared using a mixture of 595 µL IPA and 395 µL EtOH. The amount of Nafion D520 dispersion (5.0 wt%) used is 10 µL. Subsequently, an appropriate amount of the ink is spray-cast onto a graphite felt using an airbrush and dried overnight in a vacuum oven to obtain the electrode. Finally, the graphite felt was cut to the desired size (1 × 1 or 2 × 2 cm 2 ) for use in different electrolytic cells (H-cell or Flow cell). Electrochemical measurements Electrochemical measurements in H-cell were carried out using CHI760E with a CHI680D amplifier. The two-compartment cell from Tianjin Ida Co., Ltd. was separated by Nafion N117 membrane (Supplementary Fig. 44). The reference electrode used was Ag/AgCl (saturated KCl), and the counter electrode was a graphite rod. To increase the mass transport of the reactant to the electrode, a 4 cm Type-A magnetic stir bar was used to vigorously stir the electrolyte at 1600 rpm. In RDE and RRDE experiments, the catalyst inks were cast on a GC disk of RDE and RRDE (on the Pt ring of RRDE in some experiments) from PINE Research Instrumentation, Inc. (attached to PINE MSR rotator, typically set at 1600 rpm) and used as a working electrode. Details were provided in Supplementary Note 2. A commercial water electrolysis flow cell was modified for the electrochemical production of urotropine. The electrolyzer is composed of a stainless steel support layer, a titanium-plated stainless steel current collector, an anode electrode, an ion exchange membrane, a cathode electrode, another titanium-plated stainless steel current collector, and a second stainless steel support layer. Silicone and PTFE films are used to isolate the electrodes from the ion exchange membrane and the stainless steel layers from the current collectors, ensuring insulation and preventing liquid and gas leakage. The stainless steel support layers are secured with screws that are insulated using heat shrink tubing. After assembly, the insulation is verified using a multimeter to ensure proper isolation. Unless otherwise stated, electrolysis was conducted with an electrolyte of 0.5 M KH 2 PO 4 , 1 M ammonia, 2 M methanol, and 37.5 mM TEMPO, with pH adjusting to 9 using H 3 PO 4 and KOH. Potential data was iR corrected by the uncompensated resistance, where i is the current flowing through the electrolyte and R is the resistance of the electrolyte solution. The resistance (R) was determined as the intersection of the curve with the real axis of the Nyquist plot of data from potentiostatic electrochemical impedance spectroscopy at 0 V vs. Ag/AgCl between 1 MHz and 1 Hz with an amplitude of 10 mV. Current densities were calculated with respect to the catalyst-covered geometric area of the working electrode. All the potentials were converted to the RHE scale: Potential RHE = Potenrial Ag/AgCl + 0.197 + 0.059 × pH (V). Before each electrolysis experiment, Ar was bubbled through the electrolyte at a rate of > 100 sccm for 15 minutes. After the reaction started, the Ar flow rate was maintained at ~ 10 sccm to ensure an inert atmosphere within the cell chamber. Product quantification Liquid products (urotropine, formic acid, and formamide) from electrocatalysis were detected using 1 H NMR spectra with a Bruker 500 MHz NMR spectrometer. 1 H NMR spectra were collected using a water suppression mode (delay time between pulses (d1) = 5 s; 256 scans). NMR samples were prepared by adding 400 µL electrolyte after electrolysis to an NMR tube containing 50 µL 10 mM MA (as the internal standard) and 50 µL D 2 O (or DMSO-d 6 in some samples). 13 C, 14 N, and 15 N NMR experiments were conducted on a Bruker 600 MHz NMR spectrometer, in which the sample was dissolved in D 2 O, and the scan number set in experiments was 512, 2048, and 256 for 13 C, 14 N, and 15 N spectrum, respectively. To more accurately determine the yield of urotropine, we also performed quantitative analysis using high-performance liquid chromatography (HPLC). Detailed parameters: ChromCore NH 2 column from NanoChrom, ACN:H 2 O = 9:1, 1.5 mL·min − 1 , 40°C, and 195 nm. A 5 mL sample of the post-reaction electrolyte was taken and vacuum-dried at 60°C. The resulting solid was collected, ground, and then redissolved in 5 mL of ACN. The solution was subsequently filtered through a 0.22 µm filter membrane, and the filtrate was subjected to quantitative analysis by HPLC (Supplementary Fig. 45 − 47). The FE is the ratio of the number of electrons transferred for the formation of a product to the total amount of electricity passing through the circuit (Q). The FE for the products was calculated using the equation: FE (%) = (c product × n product × V × F) × 100% / (Q + c TEMPOH × V × F), where F is the Faraday constant (96485 C·mol − 1 ), n product is the number of electrons when one molecule of product formed, c product and c TEMPOH is the concentration of product and TEMPOH measured by NMR or HPLC, and V is the volume of electrolyte. Characterization The XPS measurements were performed on a Thermo Fisher escalab 250xi. EPR measurements were performed with a Bruker EMX PLUS spectrometer. Scanning electron microscopy (SEM) imaging was carried out using a ZEISS Merlin Compact microscope, while transmission electron microscopy (TEM) was conducted with a Hitachi HT-7700 instrument. FTIR was executed using a Thermo Fisher Nicolet iS50 spectrometer, and Raman spectroscopy was performed with a Thermo Fisher DXRxi Raman spectrometer. HRFTMS was accomplished with a Bruker Solarix XR mass spectrometer. In situ UV-Vis spectroscopy In situ UV-Vis spectroscopy experiments were conducted using an electrocatalytic cuvette (Fig. 2 f) with a Shimadzu UV3600Plus. The working electrode used was a custom-made carbon paper with perforations measuring 3 × 5 mm 2 . The micropores on the carbon paper were created using a handheld drill with a micro drill bit, spaced ~ 0.5 mm apart. It was essential to ensure sufficient light could pass through the carbon paper to achieve adequate sensitivity while maintaining the paper's integrity and durability. For UV-Vis spectroscopy, the modification of the working electrode was performed with an ink identical to that used for RDE modification, with an application volume of ~ 10 µL. The reference electrode was an Ag/AgCl electrode (KCl saturated), and the counter electrode was a Pt wire. Each time a new working electrode was used, baseline calibration was required. All tests were conducted using a standard cuvette filled with UP water as the reference. In situ SEIRAS In situ SEIRAS tests were conducted in a home-designed spectro-electrochemical cell with a three-electrode configuration, as shown in Supplementary Fig. 48, using a Bruker INVENIO FTIR spectrometer equipped with a liquid-nitrogen-cooled mercury cadmium telluride detector. A BioLogic SP-150e potentiostat was used to control experiment potential. The working electrodes for SEIRAS investigations were prepared using the ink identical to that in the RDE test by drop-casting onto the SEIRA active Au films, following the methods described in previous studies 30 . The reference electrode employed was a SCE, while the working electrode consisted of a metal film on a Si attenuated total reflectance prism. The counter electrode utilized was a graphite rod. All spectra were obtained by co-adding 128 scans at a 4 cm − 1 spectral resolution and presented in absorbance units where a positive and negative peak signifies an increase and decrease in the interfacial species, respectively. During the test, Ar was kept bubbling into the electrolyte, and the electrolyte was mechanically stirred. In situ Raman spectroscopy In situ Raman spectroscopy tests were conducted in a custom-designed three-electrode Raman spectroscope flow cell, as shown in Supplementary Fig. 49. In this setup, the electrolyte layer between the monochromatic laser and film surface is as thin as 5 mm to avoid the attenuation of scattering light. This flow cell also has two compartments that are separated by a piece of Nafion N117. Then, a GC electrode with different decorations was used, with a graphite rod as the counter electrode in an anodic cell and a saturated Ag/AgCl as the reference electrode. Raman spectroscope tests were performed on a LabRAM HR Evolution microscope (Horiba Jobin Yvon) equipped with a 633 nm He-Ne laser, a 50X objective (NA = 0.55), and a CCD detector. The scanning range is 100 − 3800 cm − 1 for each spectrum, and the acquisition time was set to 30 s for each spectrum. During the test, the fresh electrolyte pre-saturated with Ar gas was kept flowing across the cell using a peristaltic pump. In situ NAP-XPS The in situ NAP-XPS experiments were performed at the ambient pressure photoelectron spectroscopy (APPES) Endstation of the BL02B01 Beamline at the Shanghai Synchrotron Radiation Facility (SSRF). The bending magnet beamline delivers soft X-rays with photon flux around 1 × 10 11 photons/s @ E/∆E = 3700 and a tightly focused beam spot size (~ 200 × 75 µm 2 ). In a typical NAP-XPS experiment, high-resolution photoemission spectra with a pass energy of 20 eV were recorded with the incident X-ray energies of 660 eV. Generally, under working conditions, the analysis chamber was filled with gases up to mbar range via a back-filling configuration. The analysis chamber was separated from a differentially pumped electrostatic lens system and a hemispherical electron analyzer (Phoibos 150, Specs, Germany) via a physical aperture (0.3 mm, DI). A 100 nm-thick silicon nitride window was used to separate the beamline from the analysis chamber. A custom-built three-electrode in-situ reaction cell was used in the NAP-XPS experiment illustrated in Supplementary Fig. 50. Degassed electrolyte (0.1 M KH 2 PO4, pH = 9) was filled into the reaction chamber, where the reference electrode (Ag/AgCl) and counter electrode (Pt) was immersed. Commercial anion exchange membrane (Fumasep FAA-3-PK-75) was used to separate the two chambers. During the experiment, adding a certain amount of TEMPOH to the electrolyte and introducing a small amount of TEMPOH (~ 0.2 mbar) into the XPS testing chamber ensured a sufficient quantity of TEMPOH. The electrolyte here was in the absence of both ammonia and methanol to avoid potential interruption. Prior to an NAP-XPS experiment, the in situ reaction cell was tested for electrochemical performance that resembles the electrocatalytic reactions. CasaXPS software was used for spectral analysis and data processing. The binding energy scale was referred to that of carbon species from polymers (284.5 eV, AEM C-C signal) and Gaussian-Lorentzian line shape with Shirley background was used in the spectral fittings. Life-cycle assessment Life-cycle assessment was conducted using IMPACT World + Midpoint 1.03 method 31 . The cradle-to-gate GWP is selected as the main impact category for the LCA, as urotropine is an important raw chemical material. Details are provided in Supplementary Note 5. Techno-economic analysis Techno-economic analysis was used to assess the economic value of urotropine from the electrosynthesis of methanol and ammonia. A modified model 32 , 33 from Sargent et al. was adopted to evaluate the cost and benefit of urotropine production with renewable electricity. Details are given in Supplementary Note 6. Computational details In our calculations, the graphene/water electrochemical interface is modeled using a √3R(30°,60°) (2 × 4) graphene unit cell, with 20 pre-equilibrated explicit water molecules placed above the graphene to represent the interfacial solvation structure. The water molecules are modeled using the TIP4P force field 34 , forming a slab approximately 9 Å thick. The defected graphene is created by removing one carbon atom from the perfect graphene lattice. Periodic electronic structure calculations were performed using DFT with the PBE functional 35 and PAW pseudopotentials 36 , as implemented in the VASP program (version 6.3.2) 37 . A DFT-D3 correction 38 was applied to better account for dispersion interactions. The convergence criterion for self-consistent field (SCF) electronic minimization was set to 10⁻⁵ eV. Due to the relatively large system size and sampling requirements, only the Γ-point 39 was sampled in the reciprocal space of the Brillouin zone, and a plane-wave cutoff energy of 450 eV was used. The solvation effects and electrolyte distribution beyond the slab regions were described using a hybrid explicit-implicit solvent model (SOLHYBRID) 40 , as implemented in the revised VASPsol code 41 – 43 . The relative dielectric constant was set to 78.4, corresponding to water under ambient conditions, and the Debye length was taken as 3 Å, corresponding to a bulk electrolyte concentration of 1 M. The TPOT algorithm 40 , implemented in the VASP program, was used to control the electrode potential. Declarations Acknowledgements This work was supported financially by National Natural Science Foundation of China No. 22372004, Beijing Natural Science Foundation No. Z240027. We thank the BL02B Beamline at Shanghai Synchrotron Radiation Facility (SSRF) supported by National Science Foundation of China (NSFC, 11227902) for the in situ NAP-XPS measurements. The authors thank the NMR facility of National Center for Protein Sciences at Peking University for assistance with Dr. Hongwei Li. The calculations were performed using the Expanse supercomputer at the San Diego Supercomputer Center (SDSC) at University of California San Diego, through ACCESS allocations of MAT240028. Author information These authors contributed equally: Shiyun Li, Guangsheng Liu, Chuhao Liu. Authors and Affiliations College of Chemistry and Molecular Engineering, Peking University; Beijing, 100871, China Shiyun Li, Yifan Fu, Yixuan Fu, Yifei Xu, Chengyu Li, Bingjun Xu, & Mufan Li* Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, CA 92093, USA Guangsheng Liu & Wan-Lu Li Program of Materials Science and Engineering, University of California San Diego, La Jolla, CA 92093, USA Guangsheng Liu & Wan-Lu Li Laser Micro/Nano-Fabrication Laboratory, School of Mechanical Engineering, Beijing Institute of Technology; Beijing, 10081, China Xueqiang Zhang Institute of Molecular Engineering Plus, College of Chemistry, Fuzhou University, Fuzhou 350108, China Chuhao Liu Contributions S.L. and M.L. conceived and coordinated all stages of this research. S.L. and G.L. wrote the manuscript. M.L., B.X. and W.-L.L. revised the paper. S.L. conducted most of the experimental work. 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Journal of Chemical Physics 151 (2019). Mathew, K., Sundararaman, R., Letchworth-Weaver, K., Arias, T. A. & Hennig, R. G. Implicit solvation model for density-functional study of nanocrystal surfaces and reaction pathways. Journal of Chemical Physics 140 (2014). Additional Declarations There is NO Competing Interest. Supplementary Files ManuscriptSupplementaryinformation.docx Supplementary information Cite Share Download PDF Status: Published Journal Publication published 26 Nov, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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University","correspondingAuthor":false,"prefix":"","firstName":"Yifan","middleName":"","lastName":"Fu","suffix":""},{"id":465140844,"identity":"c10406d7-8672-4db1-8633-4670954fc15a","order_by":5,"name":"Yixuan Fu","email":"","orcid":"","institution":"Peking University","correspondingAuthor":false,"prefix":"","firstName":"Yixuan","middleName":"","lastName":"Fu","suffix":""},{"id":465140845,"identity":"6c72919d-f8fd-4fbc-a1f5-ade531b21d55","order_by":6,"name":"Yifei Xu","email":"","orcid":"https://orcid.org/0000-0002-4331-0645","institution":"Peking University","correspondingAuthor":false,"prefix":"","firstName":"Yifei","middleName":"","lastName":"Xu","suffix":""},{"id":465140846,"identity":"c3bcf301-4d44-42d1-a13f-f633aa617797","order_by":7,"name":"Chengyu Li","email":"","orcid":"","institution":"Peking University","correspondingAuthor":false,"prefix":"","firstName":"Chengyu","middleName":"","lastName":"Li","suffix":""},{"id":465140847,"identity":"eff21712-93b4-4731-8c8f-35eef05be9f5","order_by":8,"name":"Xueqiang Zhang","email":"","orcid":"","institution":"Beijing Institute of Technology","correspondingAuthor":false,"prefix":"","firstName":"Xueqiang","middleName":"","lastName":"Zhang","suffix":""},{"id":465140848,"identity":"f714917a-e077-4b8c-98aa-b02e4f25ef16","order_by":9,"name":"Bingjun Xu","email":"","orcid":"https://orcid.org/0000-0002-2303-257X","institution":"College of Chemistry and Molecular Engineering, Peking University","correspondingAuthor":false,"prefix":"","firstName":"Bingjun","middleName":"","lastName":"Xu","suffix":""},{"id":465140849,"identity":"8b16cf18-0454-43b9-b835-bb26c73021ed","order_by":10,"name":"Wan-Lu Li","email":"","orcid":"https://orcid.org/0000-0003-0098-0670","institution":"University of California, San Diego","correspondingAuthor":false,"prefix":"","firstName":"Wan-Lu","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2025-05-08 01:55:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6615715/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6615715/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41467-025-65638-7","type":"published","date":"2025-11-26T05:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":83824566,"identity":"2e8438cd-d56b-4190-8017-22bff94741db","added_by":"auto","created_at":"2025-06-03 09:45:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":679371,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSchematic diagrams of TEMPO mediated electrocatalytic C-N coupling reaction. a,\u003c/strong\u003e Urotropine synthesis with industrial process and electrocatalytic method present in this work. \u003cstrong\u003eb, \u003c/strong\u003eTEMPO mediated electrosynthesis of N containing molecules including urotropine. \u003cstrong\u003ec, \u003c/strong\u003eCarbon defects enhanced TEMPO redox cycles and accelerated C-N coupling process.\u003c/p\u003e","description":"","filename":"Picture1.png","url":"https://assets-eu.researchsquare.com/files/rs-6615715/v1/3d4e565ea10cdad9562d6f2f.png"},{"id":83825156,"identity":"516f61ff-c65f-4f8e-8a57-1892a19adce8","added_by":"auto","created_at":"2025-06-03 09:53:39","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":683762,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTEMPO-mediated urotropine electrosynthesis.\u003c/strong\u003e \u003cstrong\u003ea,\u003c/strong\u003e CV of different electrolyte (Blank = KH\u003csub\u003e2\u003c/sub\u003ePO\u003csub\u003e4\u003c/sub\u003e). \u003cstrong\u003eb,\u003c/strong\u003e \u003csup\u003e1\u003c/sup\u003eH NMR detection of urotropine from electrolysis and the standard sample. \u003cstrong\u003ec,\u003c/strong\u003e HRFTMS results of electrolysis products using substrates of NH\u003csub\u003e3\u003c/sub\u003e and \u003csup\u003e15\u003c/sup\u003eNH\u003csub\u003e3\u003c/sub\u003e, respectively. \u003cstrong\u003ed,\u003c/strong\u003e FE of urotropine using different electrodes with and without the addition of TEMPO. \u003cstrong\u003ee,\u003c/strong\u003e Schematic diagram of different pathways near the electrode surface. \u003cstrong\u003ef,\u003c/strong\u003e Current density-dependent urotropine FE and electrolysis potential. The error bars correspond to the standard deviation of at least three independent measurements, and the center value for the error bars is the average of the three independent measurements.\u003c/p\u003e","description":"","filename":"Picture2.png","url":"https://assets-eu.researchsquare.com/files/rs-6615715/v1/bfe93ea8ecdb16063baf2a83.png"},{"id":83823560,"identity":"92465353-b4d4-469c-849b-6f4826bd8fed","added_by":"auto","created_at":"2025-06-03 09:37:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1105502,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAccelerated TEMPO redox cycles.\u003c/strong\u003e \u003cstrong\u003ea,\u003c/strong\u003e CV curves of Gr and rGO in the presence of TEMPO. \u003cstrong\u003eb,\u003c/strong\u003e LSV curves using RDE with Gr and rGO in different electrolytes. \u003cstrong\u003ec,\u003c/strong\u003e Schematic diagram of accelerated TEMPO redox cycles on rGO compared to Gr. \u003cstrong\u003ed,e\u003c/strong\u003e In situ SEIRAS study. OCP spectra are acquired before electrolysis. \u003cstrong\u003ed,\u003c/strong\u003e SEIRAS spectra of TEMPO oxidation and reduction in the absence of MeOH. Blue to yellow in the figure indicates a signal increase, and vice versa. The blue curve inset is the FTIR spectrum of commercial TEMPO. A simple illustration is given on the right of this figure. \u003cstrong\u003ee,\u003c/strong\u003eSEIRAS spectra of Gr and rGO decorated electrode (TEMPO + TEMPOH + MeOH). \u003cstrong\u003ef,\u003c/strong\u003eIn situ UV-Vis spectrum analysis of electrolysis with anode of Gr and rGO (TEMPO + MeOH). \u003cstrong\u003eg,\u003c/strong\u003e Quasi in situ EPR signals of TEMPO in electrolyte TEMPO + MeOH). \u003cstrong\u003eh,i\u003c/strong\u003e Detection of concentration of TEMPO derivatives generated from disc electrode using RRDE technique (TEMPO + MeOH). The current of TEMPO+\u003cstrong\u003e \u003c/strong\u003e(\u003cstrong\u003eh\u003c/strong\u003e) reduction and TEMPOH (\u003cstrong\u003ei\u003c/strong\u003e) oxidation in electrolysis with Gr and rGO, respectively, is collected.\u003c/p\u003e","description":"","filename":"Picture3.png","url":"https://assets-eu.researchsquare.com/files/rs-6615715/v1/93ec28d90f74380b2874b5f3.png"},{"id":83824568,"identity":"365e4fc2-184d-4e04-bb33-8fc12e1ceeb4","added_by":"auto","created_at":"2025-06-03 09:45:39","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1321201,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMechanism of carbon defects catalytic TEMPOH oxidation.\u003c/strong\u003e \u003cstrong\u003ea,\u003c/strong\u003eRaman spectra of Gr and rGO. \u003cstrong\u003eb,\u003c/strong\u003e In situ NAP-XPS study of TEMPOH oxidation on carbon defects. \u003cstrong\u003ec,\u003c/strong\u003e Schematic diagram of TEMPOH adsorption, oxidation, and dissociation processes on the carbon defects.\u003cstrong\u003e d, \u003c/strong\u003eEPR study of the influence of carbon defects on TEMPO related species. \u003cstrong\u003ee, \u003c/strong\u003eSchematic diagram of the interaction of TEMPO, TEMPOH and carbon defects during the EPR study. \u003cstrong\u003ef\u003c/strong\u003e, Schematic diagram of perfect graphene and defective graphene (Stone-Wales and carbon vacancy defects) and their adsorption ability of TEMPO/TEMPOH. \u003cstrong\u003eg\u003c/strong\u003e, Computational analysis of TEMPO species on defective graphene (carbon vacancy defect) under different external potentials.\u003c/p\u003e","description":"","filename":"Picture4.png","url":"https://assets-eu.researchsquare.com/files/rs-6615715/v1/8832eb997dbe31aeb037312f.png"},{"id":83823562,"identity":"aed51bf6-018a-4b4b-b77d-bd74b9645d15","added_by":"auto","created_at":"2025-06-03 09:37:39","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":629682,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIndustrial-scale urotropine electrosynthesis.\u003c/strong\u003e \u003cstrong\u003ea,\u003c/strong\u003eSchematic diagram of urotropine electrolysis coupling with HER. \u003cstrong\u003eb,\u003c/strong\u003e Comparison of LSV curves of commercial OER catalysts in a neutral pH electrolyte and rGO in the electrolysis of urotropine. \u003cstrong\u003ec,\u003c/strong\u003e FE of urotropine and the potential of the flow cell during a 20-hour electrolysis process. \u003cstrong\u003ed,\u003c/strong\u003e LCA results of urotropine production. \u003cstrong\u003ee,\u003c/strong\u003e Urotropine electrosynthesis cost levelized as a function of FE and renewable energy cost from TEA.\u003c/p\u003e","description":"","filename":"Picture5.png","url":"https://assets-eu.researchsquare.com/files/rs-6615715/v1/bdd6714b64bb7f99e87603be.png"},{"id":96885684,"identity":"d00c334f-e612-4af5-812b-e80e336a5e37","added_by":"auto","created_at":"2025-11-27 08:11:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5590069,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6615715/v1/311cf3b1-564d-4c23-8fef-442a9f4159a4.pdf"},{"id":83823563,"identity":"a46e83cf-4200-4ce3-af2e-5a0b4d708918","added_by":"auto","created_at":"2025-06-03 09:37:39","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":7390894,"visible":true,"origin":"","legend":"Supplementary information","description":"","filename":"ManuscriptSupplementaryinformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-6615715/v1/c78449c9da5a7ee36d65c385.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Carbon defects enhanced TEMPO redox cycles for high-efficiency urotropine electrosynthesis","fulltext":[{"header":"Main","content":"\u003cp\u003eElectrocatalytic synthesis of nitrogen-containing (N-containing) molecules like amide, amine, and amino acid through carbon-nitrogen (C-N) coupling reactions has recently attracted extensive interest\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. It provides a viable strategy for the decarbonization of the chemical industry by utilizing renewable energy\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). However, direct electrochemical synthesis of N-containing molecules encounters substantial challenges: (i) the adsorption and activation of multiple reactants on the electrode lead to prevalent side reactions\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e and limited current density\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e; and (ii) the initiation of electron transfer process requires high overpotentials\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Consequently, achieving high selectivity and current density sufficient for industrial-scale production remains a formidable obstacle\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCorrespondingly, mediation strategy (Supplementary Fig.\u0026nbsp;1), i.e., enabling substrate conversion using redox-prone mediator molecules, could effectively reduce overpotential and improve selectivity\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e, while the application of mediated processes have been hampered by limited current density\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. 2,2,6,6-Tetramethylpiperidine N-oxyl (TEMPO), an excellent metal-free oxidative mediators featuring a stable free radical\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb), is widely used in organic synthesis\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e for converting alcohols into aldehydes, ketones and acids. However, the slow electron transfer rate\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e of the hydroxylamine species (TEMPOH) formed after the oxoammonium species (TEMPO+) oxidizes the substrate and limits the rate of the TEMPO redox cycles on the electrode surface (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec and Supplementary Fig.\u0026nbsp;2).\u003c/p\u003e \u003cp\u003eHere, we report a hetero-homogeneous tandem C-N coupling process with accelerated TEMPO redox cycles catalyzed by carbon vacancy defects on graphene (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb). This process has achieved, to the best of our knowledge, the highest electrocatalytic C-N coupling performance (Supplementary Fig.\u0026nbsp;3) reported to date, that is, the Faraday efficiency (FE)\u0026thinsp;~\u0026thinsp;99% and the current density\u0026thinsp;~\u0026thinsp;0.6 A\u0026middot;cm\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003e, exceeding a yield rate of 261.5 mg\u0026middot;cm\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003e\u0026middot;h\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e. Exceptional efficiency of C-N coupling benefits from the unique design of the electrochemical process, i.e., highly selective TEMPO redox cycles and efficient carbon defects catalysis: (i) The utilization of TEMPO spatio-temporally decouples C-N coupling from electrooxidation, which circumvents reaction rate constraints from limited active sites for heterogeneous reactions and minimizes intermediate adsorption on the electrode, decreasing the direct oxidation of by-products on electrode (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb). (ii) Notably, we present the first report and provide the evidence of the accelerated TEMPO redox cycles by carbon defects. In situ near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) experiments, quasi in situ electron paramagnetic resonance (EPR) and density functional theory (DFT) calculations confirm that carbon vacancy defect sites on graphene surface can adsorb TEMPOH and significantly lower the oxidation overpotential by transforming the sluggish outer-sphere (OS) oxidation process of TEMPOH oxidation into a rapid inner-sphere (IS) reaction (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec).\u003c/p\u003e \u003cp\u003eWe then achieve gram-scale urotropine synthesis with a flow cell, validating the industrial application potential. Life cycle assessment (LCA) indicates that the electrochemical production of urotropine powered by renewable energy reduces overall greenhouse gases (GHGs) emissions by 30.7%, compared to conventional thermal catalytic routes. Techno-economic analysis (TEA) confirms its economic viability, with overall profit of \u003cspan\u003e$\u003c/span\u003e623.8 per ton of urotropine. Furthermore, we demonstrate that this method can be applied to the production of other N-containing organic molecules, highlighting its broad applicability and versatility.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eTEMPO-mediated urotropine electrosynthesis\u003c/h2\u003e \u003cp\u003eWe first verified the capability of TEMPO to oxidize methanol and demonstrated the TEMPO redox cycles (Supplementary Fig.\u0026nbsp;2). In Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea, a pair of redox peaks appeared in the cyclic voltammetry (CV) curve at an equilibrium potential of ~ 1.2 V (vs. RHE, potential hereafter is referenced to the RHE scale unless otherwise specified) while only TEMPO was added, representing a redox couple of TEMPO and TEMPO+ (Supplementary Fig.\u0026nbsp;2a), compared to the negative control (blank = electrolyte only). No obvious oxidation peaks were detected until ~ 1.9 V when solely added methanol with a glassy carbon (GC) electrode. This shows that TEMPO oxidizes at a less positive potential than methanol\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. When methanol is present in the TEMPO-containing electrolyte, the oxidation peak current is multiplied while the peak potential remains largely unchanged. The pronounced enhancing effect of methanol on the TEMPO electrooxidation indicates that it undergoes an electrochemical-chemical pathway\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e, where TEMPOH, the product of the reaction between methanol and TEMPO + \u003csup\u003e12\u003c/sup\u003e, is reoxidized at the anode, thereby enabling multiple redox cycles of TEMPO during the anodic scan in CV. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb,c and Supplementary Fig.\u0026nbsp;2).\u003c/p\u003e \u003cp\u003eSubsequently, we confirmed that the TEMPO redox cycles could be used for electrochemical C-N coupling reactions including urotropine production. C-N coupling product was extracted from an electrolyte containing TEMPO, methanol, and ammonia after a constant current electrolysis (see Methods), and was identified as urotropine using nuclear magnetic resonance (NMR, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb and Supplementary Fig.\u0026nbsp;4) and high-resolution Fourier transform mass spectrometry (HRFTMS) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec and Supplementary Table\u0026nbsp;1). Isotope labeling experiments reveal that urotropine produced in electrolysis originates from methanol and ammonia (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec, Supplementary Figs.\u0026nbsp;5 and 6). Linear correlations between urotropine concentration and electrolysis time (Supplementary Figs.\u0026nbsp;7 and 8) further verified that the C-N coupling products were produced from the electrolysis process.\u003c/p\u003e \u003cp\u003eTo highlight the pivotal role of TEMPO in the electrochemical production of urotropine, we conducted control experiments. Product analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed and Supplementary Table\u0026nbsp;2) revealed that metal electrodes barely produced urotropine in the absence of TEMPO, while carbon materials showed an FE for urotropine of ~ 20%. When TEMPO was added, urotropine production was found to increase on all electrodes (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed and Supplementary Table\u0026nbsp;2), with carbon materials exceeding the highest FE of ~ 97%, underscoring the decisive role of TEMPO.\u003c/p\u003e \u003cp\u003eByproducts including formamide and formate were detected (Supplementary Fig.\u0026nbsp;9) to determine the mechanism of high efficiency of TEMPO related reaction. Both formamide and formate were detected in electrolysis in the absence of TEMPO (Supplementary Fig.\u0026nbsp;9a), consistent with a previous report\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e, which yields formamide at the FE of ~ 40% with methanol and ammonia and shows that the intermediates were adsorbed and further oxidized on the electrode (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee). Another critical raw material for urotropine production, ammonia, undergoes no significant oxidation in the TEMPO-mediated system (Supplementary Fig.\u0026nbsp;10 − 13), thereby preventing selectivity losses for urotropine. However, formamide, which yielded from the oxidation of the C-N coupling intermediate (aminomethanol, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee) from the reaction of formaldehyde and ammonia\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e, was negligible when TEMPO was present in the electrolyte (Supplementary Fig.\u0026nbsp;9b).\u003c/p\u003e \u003cp\u003eBased on these results, we hypothesize that aminomethanol exhibits different reaction pathways depending on its location (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee), given that the TEMPO transfer the methanol (thus the related C-N coupling intermediates) oxidation location from the anode to the electrolyte (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb and Supplementary Fig.\u0026nbsp;1): (i) Oxidation of aminomethanol will be expected if it stays near and then is adsorbed on the electrode surface at positive potentials. (ii) In contrast, aminomethanol dehydrated and further react with ammonia and formaldehyde in the electrolyte and ultimately yield urotropine. We then determined the FE of formamide in different stirring rates (Supplementary Fig.\u0026nbsp;14) in the presence of TEMPO with a view to corroborating this assertion. The stirring would enhance the diffusion of the intermediates away from the electrode surface by convection, and thus reducing the probability of their adsorption and subsequent oxidation to form formamide at the electrode. As shown in Supplementary Fig.\u0026nbsp;14, compared to 0 rpm, about 90% less formamide was detected in the electrolysis products at 1600 rpm on a rotating disk electrode (RDE), conforming our proposed mechanism in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee. The reduction of byproducts is attributed to the fact that TEMPO transfers the reaction location and prevents overoxidation of C-N coupling intermediate. Besides, the structure selectivity of TEMPO is also indispensable. In light of structure-sensitive reaction rate of TEMPO + and alcohols\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e, i.e., reaction rate of primary alcohols is higher than that of secondary alcohols, the high efficiency of C-N coupling reaction is partially attributed to the steric hinderance of the intermediate and TEMPO+. Given that aminomethanol is structured with an amino group that replaces the hydrogen on methanol (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee) and thus takes a larger space, the steric hinderance thus prevents further oxidation of aminomethanol, which yield the formamide, by TEMPO+. We demonstrated this by changing the order of ammonia addition (Supplementary Fig.\u0026nbsp;15), as no formamide was detected when ammonia was added after the electrolysis. We also noted that the FE of formate (~ 20%) was higher when ammonia was added later compared to added former (\u0026lt; 3%), that is, the adding of ammonia reduced the overoxidation of formaldehyde by forming aminomethanol.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAccelerated TEMPO redox cycles\u003c/h3\u003e\n\u003cp\u003eWe then optimized the reaction conditions by employing various derivatives of TEMPO (Supplementary Fig.\u0026nbsp;16), and varying concentration of TEMPO (Supplementary Fig.\u0026nbsp;17). Effects of pH and concentration of methanol and ammonia were investigated as well (Supplementary Fig.\u0026nbsp;18 and Supplementary Fig.\u0026nbsp;19). Notably, when using the reduced graphene oxide (rGO) as anode, we were able to maintain an FE of ~ 99% at a current density of 0.6 A·cm\u003csup\u003e− 2\u003c/sup\u003e at the potential of 1.6 V (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ef), exceeding a yield rate of 261.5 mg·cm\u003csup\u003e− 2\u003c/sup\u003e·h\u003csup\u003e− 1\u003c/sup\u003e. No obvious byproducts from non-Faradaic process were found (Supplementary Fig.\u0026nbsp;20), and a carbon balance of 94.0% was calculated (Supplementary Fig.\u0026nbsp;21 and Supplementary Table\u0026nbsp;3). This efficiency is significantly higher than existing reports on directly C-N coupling reactions at electrode surfaces (Supplementary Fig.\u0026nbsp;3). Among those results, it is interesting that pristine graphene (Gr) and rGO exhibited similar FE (\u0026gt; 99%) but distinct current densities (Supplementary Figs.\u0026nbsp;22 and 23).\u003c/p\u003e \u003cp\u003eWe confirmed our observation that rGO and Gr differ at reactivity when TEMPO is present(Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea,b). As is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb (catalysts were cast on RDE and test at 1600 rpm), anode currents of both materials remained similar until methanol was added to the TEMPO-containing electrolyte, with rGO exhibiting a ~ 40% higher current density, consistent with product analysis in urotropine synthesis (Supplementary Fig.\u0026nbsp;22). As both materials displayed similar current density when methanol and TEMPO was respectively present in the electrolyte, their reactivity to the oxidation of methanol and TEMPO remained the same. Moreover, the double-layer capacitance (C\u003csub\u003edl\u003c/sub\u003e) of Gr and rGO was measured as 10.42 and 11.41 mF·cm\u003csup\u003e− 2\u003c/sup\u003e (Supplementary Fig.\u0026nbsp;24), respectively, indicating that the influence of the electrochemical specific surface area can be excluded. The evidence shows that the difference in activity between the two materials is observed only when methanol and TEMPO are both present in the electrolyte. As discussed earlier, the addition of methanol initiated the TEMPO redox cycle. The observed activity differences may be related to variations in the state of the TEMPO redox cycling on different anode surfaces. As shown in Supplementary Fig.\u0026nbsp;2, to achieve cyclic TEMPO redox, both TEMPO and TEMPOH oxidation are required. Therefore, to gain a deeper understanding of the TEMPO redox cycle, we extended the CV potential range to investigate the interconversion among the three TEMPO species (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). Notably, a distinct pair of redox peaks (yellow stars in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea) appeared on the CV curve of rGO at potentials significantly lower relative to the redox peaks of TEMPO/TEMPO+, while Gr displayed a reduction peak (grey star in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea) but in absence of a corresponding oxidation peak. This more negative pair of redox peaks (yellow stars in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea) were attributed to the redox reactions between TEMPOH and TEMPO\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. The absence of the TEMPOH oxidation peak on Gr may be due to slow electron transfer in the TEMPOH/TEMPO redox reaction\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Even at higher potentials, however, no oxidation peak belonging to TEMPOH oxidation was observed on Gr (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea), suggesting that the overpotential of the TEMPOH oxidation peak might be substantial. So far, for the TEMPO redox cycle, we can conclude that (i) both materials exhibit similar capabilities for oxidizing TEMPO to TEMPO + and (ii) they display varying efficiencies for oxidizing TEMPOH to TEMPO (rGO can while Gr cannot). Given that the reaction between TEMPO + and methanol is a homogeneous chemical reaction\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e independent of the electrode material, the activity difference between the two materials is manifested solely in the oxidation process of TEMPOH to TEMPO, within the TEMPO redox cycle. Based on these discussions, it is postulated that the current difference is a consequence of the varying rates of TEMPOH oxidation to TEMPO on different electrode surfaces, i.e., the TEMPO redox cycles are accelerated on rGO surface (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec).\u003c/p\u003e \u003cp\u003eTo confirm the proposed mechanism depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec, in situ surface-enhanced infrared absorption spectroscopy (SEIRAS) was conducted to monitor the TEMPO-related species under electrochemical conditions (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed). In the spectra (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed left), the oxidation and reduction processes of TEMPO-containing electrolyte led to negative absorption band around 2900 cm\u003csup\u003e− 1\u003c/sup\u003e. As shown in the Fourier transform infrared (FTIR) reference spectrum of TEMPO (inset in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed left), the characteristic absorption peaks are observed around 2900 cm\u003csup\u003e− 1\u003c/sup\u003e. Accordingly, the series of peaks at 2900 cm\u003csup\u003e− 1\u003c/sup\u003e in the in situ SEIRAS spectra were attributed to TEMPO (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed left), with negative peaks representing the consumption of TEMPO near the electrode surface. When TEMPO is replaced with TEMPOH, an increase in the absorption peaks attributed to TEMPO is observed under oxidative potential (Supplementary Fig.\u0026nbsp;25). These findings demonstrate that in situ SEIRAS is capable of qualitatively probing the concentration of TEMPO concentration near the electrode surface. Specifically, an increase in the set of peaks at 2900 cm\u003csup\u003e− 1\u003c/sup\u003e corresponds to an elevated TEMPO concentration, whereas the emergence of negative bands indicates a reduction in concentration (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed right). Subsequently, stepwise oxidative potentials were applied to anodes modified with Gr and rGO, respectively, in a mixed TEMPO/TEMPOH electrolyte (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ee and Supplementary Note 1). The concentration of TEMPO on the surface of the Gr electrode decreases progressively, while on the rGO electrode, it initially increases, followed by a slight decline at higher potentials. These findings were well-aligned with observations in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea and also support the proposed reaction mechanism in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec as discussed below. For the Gr anode, the inability to oxidize TEMPOH lead to continue consumption of TEMPO, resulting in a decrease in the peaks around 2900 cm\u003csup\u003e− 1\u003c/sup\u003e. For the rGO anode, however, owing its ability to oxidize TEMPOH into TEMPO, an enhanced TEMPO-related signal was observed. As the potential increased, rGO began oxidizing TEMPO, leading to the depletion of TEMPO and a relative inversion of the peak intensity toward negative values.\u003c/p\u003e \u003cp\u003eThe mechanistic hypothesis proposed in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec suggests that rGO exhibits a higher oxidation rate for TEMPOH than that of Gr. However, the precise impact of this enhanced oxidation rate on the TEMPO redox cycling, specifically, the concentration dynamics of TEMPO species throughout the complete cycle (as illustrated by the arrow symbols in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec), remains unclear. The in situ SEIRAS experiments only provided TEMPO-related information, thereby limiting our investigation of the whole TEMPO redox cycle. To address this, we have employed the multiple approaches including in situ ultraviolet-visible (UV-Vis) spectroscopy, quasi in situ EPR spectroscopy and rotating ring-disk electrode (RRDE) experiments, to detect the concentration changes of TEMPOH and TEMPO + species.\u003c/p\u003e \u003cp\u003eWe first highlighted the significant disparity in the spectral sensitivity of TEMPO-related species (Supplementary Fig.\u0026nbsp;26) using in situ UV-Vis spectroscopy, where TEMPO and TEMPO + showed similar but significantly higher absorbance than TEMPOH around the 244 nm absorption peak. As TEMPO + was consumed by the addition of MeOH, in situ monitor of the electrolyte absorbance enables the determination of the TEMPO/TEMPOH concentration. In Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ef, the absorbance with Gr was significantly lower than that with rGO, indicating that electrolyte with Gr anode contained more TEMPOH, while the electrolyte with rGO anode contained more TEMPO. Since TEMPO carries a stable unpaired electron, quasi in situ EPR is well-suited for probing variations in TEMPO concentration. The results (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eg) demonstrated that the TEMPO concentration with rGO electrode was significantly higher than that with Gr electrode, with the same electrolyte as used in the in situ UV-Vis experiments. This inference is further confirmed by the detection of TEMPOH with \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003eH-NMR test (Supplementary Figs.\u0026nbsp;27 and 28). These results here exhibit excellent consistency in accordance with the deduction that TEMPOH would accumulate on Gr electrode so less TEMPO was detected, based on the mechanism in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec.\u003c/p\u003e \u003cp\u003eIt is TEMPO + that reacts with methanol in the TEMPO redox cycle (Supplementary Fig.\u0026nbsp;2), thus determining the actual methanol oxidation rate and, consequently, the C-N coupling rate. To this end, we conducted electrochemical CV experiments using a RRDE in the collection mode (see Methods and Supplementary Note 2). By applying different potentials to the peripheral ring electrode, the active species convectively transported from the disk electrode to the ring electrode can be detected (schematic diagram in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eh), enabling the determination of species concentrations at the disk electrode surface. Initially, based on the CV curves in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea, we set the ring potential at 1.0 V to enable the reduction of TEMPO + detached from the disk and prevent the oxidation of TEMPOH. A more significant reduction currents were observed on rGO decorated disk electrode, indicating that rGO can provide a higher concentration of TEMPO + during the electrolysis. We then designed another RRDE experiment to collect the TEMPOH on ring electrode. In brief, given that Gr and rGO both oxidize TEMPO but only rGO can oxidize TEMPOH, the TEMPOH oxidation current can be resolved by minus ring current with rGO with the ring current with Gr. The current density curves representing the TEMPOH concentration shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ei were in conformity with our expectations that TEMPOH accumulated on Gr electrode and thus lead to a higher concentration.\u003c/p\u003e\n\u003ch3\u003eMechanism of carbon defects catalyzed TEMPOH oxidation\u003c/h3\u003e\n\u003cp\u003eHaving demonstrated the principle behind rGO's ability to accelerate the TEMPO redox cycle, we now turn to investigating the catalytic mechanism. Comparison of the two materials across various characterizations (Fig.\u0026nbsp;4a and Supplementary Fig.\u0026nbsp;29) reveals that rGO displays significant differences in the Raman spectrum. The D band in the Raman spectrum of rGO is more pronounced (Fig.\u0026nbsp;4a), indicating that rGO has a significantly richer presence of defects on its surface. Results from in situ Raman spectroscopy show that the structure of both Gr and rGO remain unchanged during electrolysis (Supplementary Fig.\u0026nbsp;30). We subsequently broadened the scope of carbon materials to further establish the correlation between the carbon defects and the catalytic activity of TEMPOH (Supplementary Fig.\u0026nbsp;31). Accordingly, materials exhibiting a significant D band display the characteristic TEMPOH/TEMPO redox peaks in the CV, while those lacking the D band do not. Together, those results suggest that carbon defects are the active sites for the catalytic oxidation of TEMPOH by rGO.\u003c/p\u003e \u003cp\u003eFrom the discussion of the aforementioned evidence, all the carbon materials are capable of effectively oxidizing TEMPO (Supplementary Fig.\u0026nbsp;31). This corresponds to the oxidation of TEMPO being independent of the electrode material, a characteristic feature of an OS reaction\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. In contrast, the oxidation of TEMPOH has been shown to be promoted by carbon defects, which is surface sensitive. This indicates that TEMPOH and carbon defects may have strong interaction like adsorption, which aligning more closely with the characteristics of an IS reaction\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. To validate the hypothesis with OS and IS process involved, surfactants experiments were conducted (Supplementary Fig.\u0026nbsp;32 − 36, and Supplementary Note 3). Surfactants can adsorb onto the surface of graphene-related materials\u003csup\u003e\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e–\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e, hindering the interaction between the reactants and the electrode surface, thereby aiding in the determination of the electrochemical reaction mechanism, i.e., distinguishing between the OS and IS processes\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. An appropriate surfactant should significantly reduce the activity of IS reactions, while having a minimal effect on OS reactions\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. A significant decrease in the reversibility of the TEMPOH/TEMPO redox couple was observed upon the addition of 1 mM surfactants (CTAB or CTAC) to the system (Supplementary Fig.\u0026nbsp;32a), while the reversibility of the TEMPO/TEMPO + redox couple remained largely unchanged (Supplementary Fig.\u0026nbsp;36). Furthermore, at the same surfactant concentration (1 mM), it was observed that the reversibility of the TEMPOH/TEMPO redox couple decreased with the increase in the molecular size of the surfactant (Supplementary Fig.\u0026nbsp;32c). These results validate the hypothesis that the oxidation of TEMPO follows an OS mechanism and indicate that the TEMPOH oxidation on carbon defects occurs via an IS mechanism, i.e., involving a direct interaction between TEMPOH and carbon defects during the oxidation process.\u003c/p\u003e \u003cp\u003eTo verify the IS oxidation process of TEMPOH on carbon defects and to investigate the underlying interaction mechanism, we conducted in situ NAP-XPS measurements (see Methods and Supplementary Note 4). Compared to the OCP, specific absorption signals in the C1s, N1s, and O1s spectra showed significant changes within the reaction potential range (highlighted in yellow in Fig.\u0026nbsp;4b). The intensities of the signals at 287.1 eV in C1s, 400.1 eV in N1s, and 531.6 eV in O1s decreased monotonically with increasing potential, which is consistent with the trend observed for the TEMPOH concentration in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ei. In situ Raman spectroscopy has demonstrated that the rGO structure undergoes no significant changes (Supplementary Fig.\u0026nbsp;30), while XPS results indicate that both N and O are nearly absent from the rGO structure (Supplementary Fig.\u0026nbsp;29). Considering that TEMPOH molecules are continuously introduced into the XPS chamber, this signal change cannot be attributed to the consumption of TEMPOH in the gas phase. After excluding these possibilities, we attribute these signal changes to the interaction between TEMPOH and the catalyst, hypothesizing that the signal variation may result from the binding of TEMPOH to carbon defects and its subsequent consumption (Fig.\u0026nbsp;4c). Specifically, the peak at 287.1 eV is attribute to the signal of C-O\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. While the C-O structure does not exist in TEMPOH (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) or rGO (Supplementary Fig.\u0026nbsp;29), the adsorption structure of TEMPOH on rGO should be formed during the interaction of TEMPOH and rGO, with the O atom bonding to a C atom at the carbon defect site (TEMPO* in Fig.\u0026nbsp;4c) after the dehydrogenation of the hydroxyl group of TEMPOH, given that the TEMPOH oxidation on rGO is proved to be pH-dependent (Supplementary Fig.\u0026nbsp;37). The signal of C-O almost disappeared at 0.6 V, indicating that the TEMPO* desorbed from the rGO and form TEMPO. Accordingly, the N1s signal at 400.1 eV and O1s signal at 531.6 eV were associated with the adsorbed state of TEMPO (TEMPO* in Fig.\u0026nbsp;4b). Integrating the results from the in situ NAP-XPS experiment, we infer that TEMPOH can be adsorbed at defect sites (thus confirm the IS reaction) and desorb after oxidation with increasing potential, as is shown in the schematic diagram in Fig.\u0026nbsp;4c. The assignments of the other peaks are given in Supplementary Note 4.\u003c/p\u003e \u003cp\u003eTo further solidate the conclusion above, quasi in situ EPR experiments were conducted to probe the interaction of TEMPOH/TEMPO with the carbon surface (with/without carbon defects), as shown in Fig.\u0026nbsp;4d,e and Supplementary Fig.\u0026nbsp;38. When the same mass of carbon materials (Gr and rGO) were added to TEMPO solutions of the same concentration, the EPR responses of the solutions were entirely different (Fig.\u0026nbsp;4d, II and Supplementary Fig.\u0026nbsp;38): the EPR signal of the TEMPO solution with rGO was almost completely quenched (Fig.\u0026nbsp;4d, II), while the EPR signal of the TEMPO solution with Gr showed no obvious change (Supplementary Fig.\u0026nbsp;38), indicating that carbon defects can effectively adsorb TEMPO (Fig.\u0026nbsp;4e, II). Moreover, the quenching of the EPR signal (Fig.\u0026nbsp;4d, II), i.e., the disappearance of unpaired electrons, suggests that the binding site between the carbon defect and TEMPO must be the O· in the TEMPO structure (Fig.\u0026nbsp;4e, II), which carries the unpaired electron. This finding is fully consistent with the C-O-N structure inferred from our NAP-XPS data (Fig.\u0026nbsp;4c) and aligns well with reported results\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Notably, when TEMPOH were added (Fig.\u0026nbsp;4d, III) in the mixture of TEMPO + rGO (Fig.\u0026nbsp;4d, II), the EPR signal dramatically restored (Fig.\u0026nbsp;4d, III). This indicates that the TEMPO originally adsorbed on the carbon defects has desorbed, as TEMPOH contributed little to the EPR spectra (Fig.\u0026nbsp;4d, IV), demonstrating that the adsorption of TEMPOH on carbon defects is stronger than that of TEMPO (Fig.\u0026nbsp;4e, III), which is consistent with the adsorption energy differences obtained from our DFT calculations discussed below. Furthermore, NMR experiments show similar results and support our conclusion as well (see Supplementary Fig.\u0026nbsp;39).\u003c/p\u003e \u003cp\u003eTo better understand the interactions between TEMPOH and defect sites on graphene during this process, DFT analysis was conducted (Fig.\u0026nbsp;4f,g and Supplementary Fig.\u0026nbsp;40 − 42) to gain more insights at the atomic level. Besides perfect graphene layer, two representative carbon defects, Stone-Wales defect and carbon vacancy defect are considered, based on reported research\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e, as shown in Fig.\u0026nbsp;4f. The perfect graphene, as expected, energetically unfavorably adsorbed TEMPO (see Supplementary Fig.\u0026nbsp;41), consist with our previous results (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea, 4d, and Supplementary Fig.\u0026nbsp;38, 39). Therefore, TEMPOH oxidation on Gr occurs exclusively through an OS reaction with a slow electron transfer rate\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Subsequently, we investigated the defects' interaction with TEMPO species. Surprisingly, DFT analysis indicates that the Stone-Wales defects display a similar pattern as that of the perfect graphene (see Supplementary Fig.\u0026nbsp;41). In contrast, graphene featuring a carbon vacancy defect shows distinctly different interactions (Fig.\u0026nbsp;4f), as TEMPOH can favorably adsorb onto carbon atoms adjacent to the vacancy site (Supplementary Fig.\u0026nbsp;41), suggesting that such defect sites may stabilize TEMPO adsorption (thus an IS process) and potentially promote TEMPOH oxidation.\u003c/p\u003e \u003cp\u003eWe further analyzed the oxidation process of TEMPOH on graphene with a carbon vacancy under two applied potentials (− 0.45 V vs. SHE and 0.45 V vs. SHE), correspond respectively to the potential without and with TEMPOH oxidation, based on the CV behavior shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea. As depicted in Fig.\u0026nbsp;4g, at a potential of − 0.45 V, the adsorbed TEMPO intermediate (denoted as TEMPO*) exhibits lower energy compared to both TEMPOH and TEMPO in solvent, indicating that TEMPO* represents the most thermodynamically stable state under these conditions (consistent with EPR and NMR results in Fig.\u0026nbsp;4d and Supplementary Fig.\u0026nbsp;39). At the higher potential of 0.45 V, this trend persists, with TEMPO* becoming even more energetically favorable (compared to TEMPOH), suggesting that increasing the applied potential enhances the thermodynamic driving force for TEMPOH oxidation. Quantitatively, the energy difference between TEMPOH and TEMPO increases significantly from 0.11 eV at − 0.45 V to 0.35 eV at 0.45 V (Fig.\u0026nbsp;4g), further confirming that a higher potential strengthens the tendency for TEMPOH to be oxidized to TEMPO. Additionally, we analyzed the variations in charge distribution with increasing applied potential. The corresponding charges of each component at − 0.45 V and 0.45 V are summarized in Supplementary Table\u0026nbsp;4. For all examined configurations—including TEMPOH/rGO, TEMPO*/rGO, and TEMPO/rGO—the total charge decreases as the potential increases from − 0.45 V to 0.45 V, confirming oxidation of the system under elevated potentials. Notably, the charge on the reduced graphene oxide (rGO) component significantly decreases with increasing applied potential, indicating an enhanced oxidation capability of rGO at higher potentials.\u003c/p\u003e\n\u003ch3\u003eIndustrial-scale N-containing chemicals electrosynthesis\u003c/h3\u003e\n\u003cp\u003eTo demonstrate the industrial potential of urotropine electrosynthesis, we conducted flow cell experiments for scaled-up production (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003ea and Supplementary Fig.\u0026nbsp;43). In near-neutral conditions (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003eb), TEMPO-mediated oxidation demonstrates significant lower overpotential compare to commercial OER catalysts. Subsequently, a 20-hour continuous electrolysis was conducted (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003ec). Both FE and the cell potential remained stable. The decrease in electrolyte pH caused by the anodic reaction slows the electrooxidation of TEMPOH (Supplementary Fig.\u0026nbsp;37), so the final potential is higher than that at the start during each electrolysis session (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003ec). As expected, after adding KOH and NH\u003csub\u003e3\u003c/sub\u003e to restore the pH, the cell potential decreased (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003ec). Finally, we obtained 15.89 g of urotropine from the electrolyte, achieving an FE of 91.1%, with a calculated yield rate of 198.6 mg·cm\u003csup\u003e− 2\u003c/sup\u003e·h\u003csup\u003e− 1\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWe also performed LCA to compare the GHG emissions between electrochemical and conventional processes. The Methods and Supplementary Note 5 present the LCA methodology and data sources. Notably, when the power grid is fully decarbonized, there is a 30.7% reduction (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003ed) in carbon emissions relative to the conventional process. TEA was carried out to evaluate the economic potential (see Methods and Supplementary Note 6). The electrocatalytic protocol yields a profit of \u003cspan\u003e$\u003c/span\u003e459.3 per ton of urotropine with \u003cspan\u003e$\u003c/span\u003e164.5 from the hydrogen benefits (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003ee), thereby confirming the commercial viability of electrocatalytic urotropine production.\u003c/p\u003e \u003cp\u003eTo further demonstrate the applicability of TEMPO-mediated electrosynthesis, different carbon and nitrogen sources for C-N coupling reactions were used to explore the substrate scope (Supplementary Table\u0026nbsp;5). The efficiency of the C-N coupling reactions exhibits a broad distribution (Supplementary Note 7). Among them, using ethanol and ammonia also allowed for an industry-level production of acetaldehyde ammonia trimer, another versatile chemical\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn summary, we have developed a new highly efficient C-N coupling reaction method with accelerated TEMPO redox cycle catalyzed by carbon defects. For the first time, we reported the realization of the industry-level C-N coupling electrosynthesis efficiency (FE ~ 99%, current density ~ 0.6 A·cm\u003csup\u003e−\u003c/sup\u003e²). We demonstrate that mediator TEMPO reduces oxidation overpotential and minimizes the by-products compare to direct oxidation. Enhanced C-N coupling reaction rate was realized as TEMPO redox cycles were accelerated by carbon defects. We demonstrated that carbon defects catalyzed the electrooxidation of TEMPOH by transfer a sluggish OS process into a rapid IS reaction, thus promoting the redox cycle. LCA results indicate that urotropine electrosynthesis reduces the GHGs emission by 30.7% compared to conventional routes. Our unique electrocatalytic method in this work enables industrial-level electrosynthesis of N-containing chemicals including urotropine and acetaldehyde ammonia trimer, highlighting the promise of redox mediators in facilitating efficient electrosynthesis reactions.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003c/div\u003e \u003c/div\u003e\n\n\n\n\n\n\n\n\n\n\n\n"},{"header":"Methods","content":"\u003ch2\u003eChemicals and materials\u003c/h2\u003e\u003cp\u003eGr was purchased from Suzhou TANFENG Graphene Tech Co., Ltd. KH\u003csub\u003e2\u003c/sub\u003ePO\u003csub\u003e4\u003c/sub\u003e, MeOH, acetonitrile (ACN), maleic acid (MA), methyl viologen dichloride (Mv\u003csup\u003e+\u003c/sup\u003e/Mv\u003csup\u003e2+\u003c/sup\u003e), and ammonia were gained from Shanghai Aladdin Co., Ltd. TEMPO, 4-NH\u003csub\u003e2\u003c/sub\u003e-TEMPO, 4-NHCOCH\u003csub\u003e3\u003c/sub\u003e-TEMPO, 4-O-TEMPO, 9-Azabicyclo[3.3.1]nonane N-oxyl (ABNO), and N-Hydroxyphthalimide (NHPI) were purchased from Shanghai Sigma-Aldrich Co. H\u003csub\u003e3\u003c/sub\u003ePO\u003csub\u003e4\u003c/sub\u003e, KOH, and carbon nanotubes (CNTs, Multi-walled) were provided by Shanghai Macklin Biochemical Co., Ltd. Deuterated water (D\u003csub\u003e2\u003c/sub\u003eO), \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003eN labeled ammonium chloride (\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003eNH\u003csub\u003e4\u003c/sub\u003eCl), deuterated methanol (CD\u003csub\u003e3\u003c/sub\u003eOD) and deuterated dimethyl sulfoxide (DMSO-d\u003csub\u003e6\u003c/sub\u003e) were purchased from Anhui Senrise Technology Co., Ltd. Porous carbon (PC), rGO, highly oriented pyrolytic graphite (HOPG) were purchased from Jiangsu XFNANO Materials Tech. Co., Ltd. TGPH060H hydrophilic carbon paper (CP), VXC-72 carbon black (CB), nickel foam, Nafion D520 dispersion, Nafion N117, and Fumasep FAA-3-PK-75 were gained from SCI Materials Hub. Metal foils (Pt, Au, Pb, Fe, Co, Ni, Cu, Zn, and Ti) were gained from Beijing Zhongke Yannuo New Material Technology Co., Ltd. Solutions containing TEMPO were freshly prepared daily and ultrasonicated for \u0026gt; 2 h to ensure complete dissolution. All solutions were filtered through a 0.22 µm organic filter membrane to remove any insoluble impurities. An 18.2 MΩ·cm resistivity of ultrapure (UP) water prepared in the lab by an ultrapure water system was used to prepare all solutions.\u003c/p\u003e\u003ch3\u003eElectrode preparation\u003c/h3\u003e\u003cp\u003eAll carbon materials were purified prior to use as follows: ultrasonically dispersed in 1 M HCl for 1 h, stirred for 24 h, and then centrifuged to remove the acid solution. The filtrate was washed with UP water until the supernatant turned neutral. Then, the suspension was rapidly cooled and solidified using liquid nitrogen, followed by freeze-drying under vacuum conditions to ensure complete desiccation and avoid agglomeration. The preparation of the electrodes requires the use of two different ink formulations, one for the RDE and the other for the standard electrode. To prepare the RDE electrode, typically, the catalyst (5.0 mg) is dispersed in 975 µL of IPA and ultrasonicated for 1 h to achieve a uniform suspension. Subsequently, 25 µL of Nafion D520 dispersion (5.0 wt%) is added to the suspension, followed by an additional 0.5 h of ultrasonication to obtain the final ink. Using a micropipette, 10 µL of the ink is deposited onto the surface of a clean glassy carbon RDE and dried in air at room temperature. The ink preparation method for the synthetic electrode used in electrolysis is similar, with the difference being that the catalyst amount is reduced to 2.5 mg. The dispersion is prepared using a mixture of 595 µL IPA and 395 µL EtOH. The amount of Nafion D520 dispersion (5.0 wt%) used is 10 µL. Subsequently, an appropriate amount of the ink is spray-cast onto a graphite felt using an airbrush and dried overnight in a vacuum oven to obtain the electrode. Finally, the graphite felt was cut to the desired size (1 × 1 or 2 × 2 cm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e) for use in different electrolytic cells (H-cell or Flow cell).\u003c/p\u003e\u003ch2\u003eElectrochemical measurements\u003c/h2\u003e\u003cp\u003eElectrochemical measurements in H-cell were carried out using CHI760E with a CHI680D amplifier. The two-compartment cell from Tianjin Ida Co., Ltd. was separated by Nafion N117 membrane (Supplementary Fig.\u0026nbsp;44). The reference electrode used was Ag/AgCl (saturated KCl), and the counter electrode was a graphite rod. To increase the mass transport of the reactant to the electrode, a 4 cm Type-A magnetic stir bar was used to vigorously stir the electrolyte at 1600 rpm. In RDE and RRDE experiments, the catalyst inks were cast on a GC disk of RDE and RRDE (on the Pt ring of RRDE in some experiments) from PINE Research Instrumentation, Inc. (attached to PINE MSR rotator, typically set at 1600 rpm) and used as a working electrode. Details were provided in Supplementary Note 2. A commercial water electrolysis flow cell was modified for the electrochemical production of urotropine. The electrolyzer is composed of a stainless steel support layer, a titanium-plated stainless steel current collector, an anode electrode, an ion exchange membrane, a cathode electrode, another titanium-plated stainless steel current collector, and a second stainless steel support layer. Silicone and PTFE films are used to isolate the electrodes from the ion exchange membrane and the stainless steel layers from the current collectors, ensuring insulation and preventing liquid and gas leakage. The stainless steel support layers are secured with screws that are insulated using heat shrink tubing. After assembly, the insulation is verified using a multimeter to ensure proper isolation.\u003c/p\u003e\u003cp\u003eUnless otherwise stated, electrolysis was conducted with an electrolyte of 0.5 M KH\u003csub\u003e2\u003c/sub\u003ePO\u003csub\u003e4\u003c/sub\u003e, 1 M ammonia, 2 M methanol, and 37.5 mM TEMPO, with pH adjusting to 9 using H\u003csub\u003e3\u003c/sub\u003ePO\u003csub\u003e4\u003c/sub\u003e and KOH. Potential data was iR corrected by the uncompensated resistance, where i is the current flowing through the electrolyte and R is the resistance of the electrolyte solution. The resistance (R) was determined as the intersection of the curve with the real axis of the Nyquist plot of data from potentiostatic electrochemical impedance spectroscopy at 0 V vs. Ag/AgCl between 1 MHz and 1 Hz with an amplitude of 10 mV. Current densities were calculated with respect to the catalyst-covered geometric area of the working electrode. All the potentials were converted to the RHE scale: Potential\u003csub\u003eRHE\u003c/sub\u003e = Potenrial\u003csub\u003eAg/AgCl\u003c/sub\u003e + 0.197 + 0.059 × pH (V). Before each electrolysis experiment, Ar was bubbled through the electrolyte at a rate of \u0026gt; 100 sccm for 15 minutes. After the reaction started, the Ar flow rate was maintained at ~ 10 sccm to ensure an inert atmosphere within the cell chamber.\u003c/p\u003e\u003ch2\u003eProduct quantification\u003c/h2\u003e\u003cp\u003eLiquid products (urotropine, formic acid, and formamide) from electrocatalysis were detected using \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003eH NMR spectra with a Bruker 500 MHz NMR spectrometer. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003eH NMR spectra were collected using a water suppression mode (delay time between pulses (d1) = 5 s; 256 scans). NMR samples were prepared by adding 400 µL electrolyte after electrolysis to an NMR tube containing 50 µL 10 mM MA (as the internal standard) and 50 µL D\u003csub\u003e2\u003c/sub\u003eO (or DMSO-d\u003csub\u003e6\u003c/sub\u003e in some samples). \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003eC, \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003eN, and \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003eN NMR experiments were conducted on a Bruker 600 MHz NMR spectrometer, in which the sample was dissolved in D\u003csub\u003e2\u003c/sub\u003eO, and the scan number set in experiments was 512, 2048, and 256 for \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003eC, \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003eN, and \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003eN spectrum, respectively. To more accurately determine the yield of urotropine, we also performed quantitative analysis using high-performance liquid chromatography (HPLC). Detailed parameters: ChromCore NH\u003csub\u003e2\u003c/sub\u003e column from NanoChrom, ACN:H\u003csub\u003e2\u003c/sub\u003eO = 9:1, 1.5 mL·min\u003csup\u003e− 1\u003c/sup\u003e, 40°C, and 195 nm. A 5 mL sample of the post-reaction electrolyte was taken and vacuum-dried at 60°C. The resulting solid was collected, ground, and then redissolved in 5 mL of ACN. The solution was subsequently filtered through a 0.22 µm filter membrane, and the filtrate was subjected to quantitative analysis by HPLC (Supplementary Fig.\u0026nbsp;45 − 47). The FE is the ratio of the number of electrons transferred for the formation of a product to the total amount of electricity passing through the circuit (Q). The FE for the products was calculated using the equation: FE (%) = (c\u003csub\u003eproduct\u003c/sub\u003e × n\u003csub\u003eproduct\u003c/sub\u003e × V × F) × 100% / (Q + c\u003csub\u003eTEMPOH\u003c/sub\u003e × V × F), where F is the Faraday constant (96485 C·mol\u003csup\u003e− 1\u003c/sup\u003e), n\u003csub\u003eproduct\u003c/sub\u003e is the number of electrons when one molecule of product formed, c\u003csub\u003eproduct\u003c/sub\u003e and c\u003csub\u003eTEMPOH\u003c/sub\u003e is the concentration of product and TEMPOH measured by NMR or HPLC, and V is the volume of electrolyte.\u003c/p\u003e\u003ch2\u003eCharacterization\u003c/h2\u003e\u003cp\u003eThe XPS measurements were performed on a Thermo Fisher escalab 250xi. EPR measurements were performed with a Bruker EMX PLUS spectrometer. Scanning electron microscopy (SEM) imaging was carried out using a ZEISS Merlin Compact microscope, while transmission electron microscopy (TEM) was conducted with a Hitachi HT-7700 instrument. FTIR was executed using a Thermo Fisher Nicolet iS50 spectrometer, and Raman spectroscopy was performed with a Thermo Fisher DXRxi Raman spectrometer. HRFTMS was accomplished with a Bruker Solarix XR mass spectrometer.\u003c/p\u003e\u003ch2\u003eIn situ UV-Vis spectroscopy\u003c/h2\u003e\u003cp\u003eIn situ UV-Vis spectroscopy experiments were conducted using an electrocatalytic cuvette (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ef) with a Shimadzu UV3600Plus. The working electrode used was a custom-made carbon paper with perforations measuring 3 × 5 mm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. The micropores on the carbon paper were created using a handheld drill with a micro drill bit, spaced ~ 0.5 mm apart. It was essential to ensure sufficient light could pass through the carbon paper to achieve adequate sensitivity while maintaining the paper's integrity and durability. For UV-Vis spectroscopy, the modification of the working electrode was performed with an ink identical to that used for RDE modification, with an application volume of ~ 10 µL. The reference electrode was an Ag/AgCl electrode (KCl saturated), and the counter electrode was a Pt wire. Each time a new working electrode was used, baseline calibration was required. All tests were conducted using a standard cuvette filled with UP water as the reference.\u003c/p\u003e\u003ch2\u003eIn situ SEIRAS\u003c/h2\u003e\u003cp\u003eIn situ SEIRAS tests were conducted in a home-designed spectro-electrochemical cell with a three-electrode configuration, as shown in Supplementary Fig.\u0026nbsp;48, using a Bruker INVENIO FTIR spectrometer equipped with a liquid-nitrogen-cooled mercury cadmium telluride detector. A BioLogic SP-150e potentiostat was used to control experiment potential. The working electrodes for SEIRAS investigations were prepared using the ink identical to that in the RDE test by drop-casting onto the SEIRA active Au films, following the methods described in previous studies\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. The reference electrode employed was a SCE, while the working electrode consisted of a metal film on a Si attenuated total reflectance prism. The counter electrode utilized was a graphite rod. All spectra were obtained by co-adding 128 scans at a 4 cm\u003csup\u003e− 1\u003c/sup\u003e spectral resolution and presented in absorbance units where a positive and negative peak signifies an increase and decrease in the interfacial species, respectively. During the test, Ar was kept bubbling into the electrolyte, and the electrolyte was mechanically stirred.\u003c/p\u003e\u003ch2\u003eIn situ Raman spectroscopy\u003c/h2\u003e\u003cp\u003eIn situ Raman spectroscopy tests were conducted in a custom-designed three-electrode Raman spectroscope flow cell, as shown in Supplementary Fig.\u0026nbsp;49. In this setup, the electrolyte layer between the monochromatic laser and film surface is as thin as 5 mm to avoid the attenuation of scattering light. This flow cell also has two compartments that are separated by a piece of Nafion N117. Then, a GC electrode with different decorations was used, with a graphite rod as the counter electrode in an anodic cell and a saturated Ag/AgCl as the reference electrode. Raman spectroscope tests were performed on a LabRAM HR Evolution microscope (Horiba Jobin Yvon) equipped with a 633 nm He-Ne laser, a 50X objective (NA = 0.55), and a CCD detector. The scanning range is 100 − 3800 cm\u003csup\u003e− 1\u003c/sup\u003e for each spectrum, and the acquisition time was set to 30 s for each spectrum. During the test, the fresh electrolyte pre-saturated with Ar gas was kept flowing across the cell using a peristaltic pump.\u003c/p\u003e\u003ch2\u003eIn situ NAP-XPS\u003c/h2\u003e\u003cp\u003eThe in situ NAP-XPS experiments were performed at the ambient pressure photoelectron spectroscopy (APPES) Endstation of the BL02B01 Beamline at the Shanghai Synchrotron Radiation Facility (SSRF). The bending magnet beamline delivers soft X-rays with photon flux around 1 × 10\u003csup\u003e11\u003c/sup\u003e photons/s @ E/∆E = 3700 and a tightly focused beam spot size (~ 200 × 75 µm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e). In a typical NAP-XPS experiment, high-resolution photoemission spectra with a pass energy of 20 eV were recorded with the incident X-ray energies of 660 eV. Generally, under working conditions, the analysis chamber was filled with gases up to mbar range via a back-filling configuration. The analysis chamber was separated from a differentially pumped electrostatic lens system and a hemispherical electron analyzer (Phoibos 150, Specs, Germany) via a physical aperture (0.3 mm, DI). A 100 nm-thick silicon nitride window was used to separate the beamline from the analysis chamber.\u003c/p\u003e\u003cp\u003eA custom-built three-electrode in-situ reaction cell was used in the NAP-XPS experiment illustrated in Supplementary Fig.\u0026nbsp;50. Degassed electrolyte (0.1 M KH\u003csub\u003e2\u003c/sub\u003ePO4, pH = 9) was filled into the reaction chamber, where the reference electrode (Ag/AgCl) and counter electrode (Pt) was immersed. Commercial anion exchange membrane (Fumasep FAA-3-PK-75) was used to separate the two chambers. During the experiment, adding a certain amount of TEMPOH to the electrolyte and introducing a small amount of TEMPOH (~ 0.2 mbar) into the XPS testing chamber ensured a sufficient quantity of TEMPOH. The electrolyte here was in the absence of both ammonia and methanol to avoid potential interruption. Prior to an NAP-XPS experiment, the in situ reaction cell was tested for electrochemical performance that resembles the electrocatalytic reactions.\u003c/p\u003e\u003cp\u003eCasaXPS software was used for spectral analysis and data processing. The binding energy scale was referred to that of carbon species from polymers (284.5 eV, AEM C-C signal) and Gaussian-Lorentzian line shape with Shirley background was used in the spectral fittings.\u003c/p\u003e\u003ch2\u003eLife-cycle assessment\u003c/h2\u003e\u003cp\u003eLife-cycle assessment was conducted using IMPACT World + Midpoint 1.03 method\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. The cradle-to-gate GWP is selected as the main impact category for the LCA, as urotropine is an important raw chemical material. Details are provided in Supplementary Note 5.\u003c/p\u003e\u003ch2\u003eTechno-economic analysis\u003c/h2\u003e\u003cp\u003eTechno-economic analysis was used to assess the economic value of urotropine from the electrosynthesis of methanol and ammonia. A modified model\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e from Sargent et al. was adopted to evaluate the cost and benefit of urotropine production with renewable electricity. Details are given in Supplementary Note 6.\u003c/p\u003e\u003ch2\u003eComputational details\u003c/h2\u003e\u003cp\u003eIn our calculations, the graphene/water electrochemical interface is modeled using a √3R(30°,60°) (2 × 4) graphene unit cell, with 20 pre-equilibrated explicit water molecules placed above the graphene to represent the interfacial solvation structure. The water molecules are modeled using the TIP4P force field\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e, forming a slab approximately 9 Å thick. The defected graphene is created by removing one carbon atom from the perfect graphene lattice.\u003c/p\u003e\u003cp\u003ePeriodic electronic structure calculations were performed using DFT with the PBE functional\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e and PAW pseudopotentials\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e, as implemented in the VASP program (version 6.3.2)\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e. A DFT-D3 correction\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e was applied to better account for dispersion interactions. The convergence criterion for self-consistent field (SCF) electronic minimization was set to 10⁻⁵ eV. Due to the relatively large system size and sampling requirements, only the Γ-point\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e was sampled in the reciprocal space of the Brillouin zone, and a plane-wave cutoff energy of 450 eV was used. The solvation effects and electrolyte distribution beyond the slab regions were described using a hybrid explicit-implicit solvent model (SOLHYBRID)\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e, as implemented in the revised VASPsol code\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e41\u003c/span\u003e–\u003cspan class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e. The relative dielectric constant was set to 78.4, corresponding to water under ambient conditions, and the Debye length was taken as 3 Å, corresponding to a bulk electrolyte concentration of 1 M. The TPOT algorithm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e, implemented in the VASP program, was used to control the electrode potential.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eThis work was supported financially by\u0026nbsp;National Natural Science Foundation of China No. 22372004, Beijing Natural Science Foundation No. Z240027. We thank the BL02B Beamline at\u0026nbsp;Shanghai Synchrotron Radiation Facility (SSRF) supported by National Science Foundation of China (NSFC, 11227902)\u0026nbsp;for the in situ NAP-XPS measurements. The authors thank the NMR facility of National Center for Protein Sciences at Peking University for assistance with Dr. Hongwei Li. The calculations were performed using the Expanse supercomputer at the San Diego Supercomputer Center (SDSC) at University of California San Diego, through ACCESS allocations of MAT240028.\u003c/p\u003e\n\u003ch2\u003eAuthor information\u003c/h2\u003e\n\u003cp\u003eThese authors contributed equally: Shiyun Li, Guangsheng Liu, Chuhao Liu.\u003c/p\u003e\n\u003cp\u003eAuthors and Affiliations\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCollege of Chemistry and Molecular Engineering, Peking University; Beijing, 100871, China\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eShiyun Li, Yifan Fu, Yixuan Fu, Yifei Xu, Chengyu Li, Bingjun Xu, \u0026amp; Mufan Li*\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, CA 92093, USA\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGuangsheng Liu \u0026amp; Wan-Lu Li\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProgram of Materials Science and Engineering, University of California San Diego, La Jolla, CA 92093, USA\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGuangsheng Liu \u0026amp; Wan-Lu Li\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLaser Micro/Nano-Fabrication Laboratory, School of Mechanical Engineering, Beijing Institute of Technology; Beijing, 10081, China\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXueqiang Zhang\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitute of Molecular Engineering Plus, College of Chemistry, Fuzhou University, Fuzhou 350108, China\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChuhao Liu\u003c/p\u003e\n\u003cp\u003eContributions\u003c/p\u003e\n\u003cp\u003eS.L. and M.L. conceived and coordinated all stages of this research. S.L. and G.L. wrote the manuscript. M.L., B.X. and W.-L.L. revised the paper. S.L. conducted most of the experimental work. G.L. performed the DFT calculations supervised by W.-L.L. Chuhao L. and Y.X. conducted the in situ SEIRAS and in situ Raman spectroscopy, respectively. Yifan F. and Yixuan F. helped analyzing the data and exploring the reaction mechanism. Chengyu L. helped to analyze FTIR data. All authors discussed the results and contributed to the final manuscript.\u003c/p\u003e\n\u003cp\u003eCorresponding authors\u003c/p\u003e\n\u003cp\u003eCorrespondence to Xueqiang Zhang, Bingjun Xu, Wan-Lu Li or Mufan Li.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLi, J. 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However, poor carbon-nitrogen (C-N) coupling selectivity and limited current density pose challenges to its widespread adoption. Herein, we introduce a carbon-defect enhanced 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) mediated tandem process to tackle both problems. Our hetero-homogeneous system achieved an exceptional Faraday efficiency of ~99% with industrial-level current density of ~0.6 A·cm\u003csup\u003e−2\u003c/sup\u003e for electrosynthesis of urotropine. In situ near ambient pressure X-ray photoelectron spectroscopy and density functional theory calculations revealed that the boosted activity originated from the oxidation of TEMPOH on the carbon defective sites, which accelerated the redox cycling of the molecular mediator for urotropine formation. Life cycle assessment indicates that the electrosynthesis of urotropine reduces CO\u003csub\u003e2\u003c/sub\u003e emissions by up to 30.7% compared to conventional industrial processes. This work highlights the unique catalytic effect of carbon defects on the redox cycling of TEMPO, facilitates electrocatalytic C-N coupling at record selectivity and rate, and offers new insights for designing efficient electrochemical mediated oxidation processes and C-N coupling reactions.\u003c/p\u003e","manuscriptTitle":"Carbon defects enhanced TEMPO redox cycles for high-efficiency urotropine electrosynthesis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-03 09:37:35","doi":"10.21203/rs.3.rs-6615715/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"575e49c5-a3b5-4829-bb1b-5a7cc69f015f","owner":[],"postedDate":"June 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":49375519,"name":"Physical sciences/Chemistry/Electrochemistry/Electrocatalysis"},{"id":49375520,"name":"Physical sciences/Chemistry/Catalysis/Electrocatalysis"}],"tags":[],"updatedAt":"2025-11-27T08:11:29+00:00","versionOfRecord":{"articleIdentity":"rs-6615715","link":"https://doi.org/10.1038/s41467-025-65638-7","journal":{"identity":"nature-communications","isVorOnly":false,"title":"Nature Communications"},"publishedOn":"2025-11-26 05:00:00","publishedOnDateReadable":"November 26th, 2025"},"versionCreatedAt":"2025-06-03 09:37:35","video":"","vorDoi":"10.1038/s41467-025-65638-7","vorDoiUrl":"https://doi.org/10.1038/s41467-025-65638-7","workflowStages":[]},"version":"v1","identity":"rs-6615715","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6615715","identity":"rs-6615715","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}