Electrochemical C–N coupling via adsorption modulation: selective synthesis of amines from biomass-derived 5-hydroxymethylfurfural

Domain: chemistry
Published: 2026-01-21
Editorial outcome: major_revision

Abstract
The electrochemical C–N coupling of biomass-derived 5-hydroxymethylfurfural (HMF) with methylamine offers a promising sustainable route to value-added amines. However, achieving high selectivity remains challenging due to competing side reactions, including C=O hydrogenation and C–C dimerization. This paper describes tailoring the surface structure of Ag catalysts to modulate HMF adsorption and intermediate hydrogenation behavior and thus enhancing C–N coupling selectivity. Ag nanoparticles, predominantly exposing the (111) facet, exhibit higher selectivity compared with Ag nanocubes mainly enclosed by (100) planes. The Ag (111) facet favors the C–N coupling pathway by regulating both adsorption geometry and hydrogenation ability. In-situ Raman spectroscopy and density functional theory (DFT) calculations reveal that an η1(C)-aldehyde adsorption configuration, dominant on Ag (111), enhances carbonyl electrophilicity and facilitates C=O polarization, promoting nucleophilic attack by methylamine. In contrast, the η2(C,O)–aldehyde configuration, more common on Ag (100), stabilizes the C=O bond, limiting its reactivity. Moreover, Ag (111) shows enhanced imine hydrogenation activity, further improving amine selectivity. This study highlights the significance of facet-dependent adsorption modulation in steering reaction pathways and advancing sustainable electrochemical synthesis.

Introduction
Amines are fine chemicals extensively applied in chemical, pharmaceutical, agrochemical, and material industries1–3. Among various amines, 5-[(methylamino)methyl]−2-furanmethanol (MAMF) serves as a key chemical for the synthesis of the pharmaceutical Ranitidine4. MAMF could be fabricated by the reductive amination of HMF with methylamine5,6. However, traditional production routes often rely on hazardous reducing agents and harsh reaction conditions, leading to high energy consumption and severe side reactions4,7. Electrochemical approaches enable controlled C–N bond formation through potential modulation and catalyst design, offering sustainable MAMF synthesis under ambient conditions with electrons as clean reductants8–10.

The electro-reductive amination of HMF can proceed either via a one-step direct reaction between HMF and methylamine or through a two-step route in which HMF first undergoes spontaneous condensation with methylamine to generate an intermediate imine, followed by its electrochemical reduction on the catalyst surface. However, during reductive conditions, the local pH near the cathode rises due to hydroxide accumulation11, making the imine intermediate susceptible to hydrolysis at the interface. This hydrolytic back-reaction regenerates HMF and methylamine, rendering the two-step pathway kinetically indistinguishable from the one-step process. Moreover, the two-step approach generally requires prolonged reaction times and additional separation steps, complicating the overall synthesis12,13. Unwanted side reactions may also occur: two imine molecules can couple to form diamine species, while the primary amine product may further condense with unreacted imine to yield a secondary imine that can be subsequently hydrogenated into a secondary amine. Moreover, imines may undergo polymerization or trimerization in solutions, leading to complex product mixtures, which have been reported previously (Supplementary Fig. 1)12. Considering these factors, the one-step electrolysis strategy was adopted and systematically investigated in this work.

In addition to reaction pathways, the hydrogenation ability of catalysts could also affect the product distribution of electrocatalytic C–N coupling13–15. Insufficient hydrogenation capability hinders the timely reduction of imine intermediate, facilitating its hydrolysis back to HMF and methylamine, thereby lowering overall selectivity toward MAMF. Comparative studies in thermal reductive amination systems have demonstrated that a moderate and directional hydrogenation ability is optimal for locking the rate-determining step at the selective hydrogenation of C=N, which maximizes primary amine formation and suppresses over-hydrogenation and other side reactions16.

Before the catalyst design, different metal electrocatalysts have been investigated for this reaction (Pt, Cu, Sn, Zn, and Ag)9,17. However, a lack of rational catalyst design has resulted in the easy occurrence of side reactions and low selectivity of C–N coupling18,19. To overcome these performance limitations, it is essential to understand the reaction from a mechanistic perspective. Previous studies have shown that enhancing the nucleophilic attack step is critical for effectively improving the overall selectivity of electrochemical C–N coupling reactions9,17. Taking the electrochemical C–N coupling of HMF and methylamine as an example, the reaction pathway involves multiple steps (Fig. 1)3,17. Typically, HMF could be activated by the catalyst, forming the absorbed HMF (HMF*)9,12. Then, the target product MAMF could be synthesized through two key steps13–15: (1) nucleophilic addition reaction of methylamine with the carbonyl group of HMF* to form the aldimine intermediate, and (2) subsequent reduction of the aldimine with protons from the electrolyte and electrons from the electrode to produce the MAMF (Fig. 1a). However, the hydrogenation and dimerization of HMF would compete with the desired C–N coupling reaction to form 2,5-bis(hydroxymethyl)furan (BHMF) and bis(hydroxymethyl)hydrofuroin (BHH), respectively, leading to low selectivity (Fig. 1b,c)16,20,21. Therefore, precise modulation of the aldehyde carbonyl reactivity and the catalyst’s hydrogenation ability to facilitate nucleophilic attack and subsequent imine conversion could be a useful strategy for enhancing the selectivity of electrochemical C–N coupling.

Tuning the adsorption behaviors of substrates on the catalyst surface has been proven essential for changing the electrochemical reaction pathways22,23. For example, the adsorption configuration of HMF is different on various metal electrodes, affecting the elongation of the aldehyde C=O bond, which impacts the reaction pathways24,25. This phenomenon provides a general idea of improving the selectivity of C–N coupling of HMF with methylamine by designing catalysts with appropriate substrate absorption configuration26–28. Adjusting the hydrogenation ability of the intermediate could further affect the product distribution. Among different catalyst design strategies29–31, facet engineering could precisely control substrate adsorption configurations and hydrogenation owing to the specific atomic arrangements and electronic structures of a certain facet32,33. For example, Koper et al. revealed that facet-dependent adsorption configurations of organic ketones govern electrochemical reduction selectivity on Pt surfaces34. Acetophenone was horizontally adsorbed on Pt(111) with the compacted adsorption of the phenyl ring, enhancing carbonyl reduction. In contrast, the vertical adsorption configuration of 4-acetylpyridine on Pt(100) increases the distance between the carbonyl functional group and the catalyst surface, thereby suppressing reduction activity compared to acetophenone. Therefore, these facet-dependent adsorption effects highlight a general structure-selectivity relationship, underscoring that a mechanistic understanding of how adsorption configurations govern intermediate activation and hydrogenation is essential for rationally designing catalysts with improved selectivity for the electrochemical C–N coupling of HMF with methylamine.

In this work, Ag catalysts with well-defined structures and preferentially exposed facets are fabricated to investigate the impact of the adsorption behaviors of substrates and hydrogenation ability of intermediates on the selectivity of the C–N coupling reaction9,35.

Results
To rationalize the choice of the one-step C–N coupling pathway, comparative electrolysis experiments were conducted using an Ag foil to evaluate the selectivity between direct coupling and the two-step route via the pre-formed imine intermediate. The direct electrochemical coupling between HMF and methylamine exhibited an FE of 62.3%, significantly higher than the 39.8% obtained for the imine-mediated process. In contrast, the two-step reaction yielded a more complex product distribution (Supplementary Fig. 2), likely due to secondary condensation leading to diamine or triamine species. To further elucidate the role of adsorption properties in governing C–N coupling activity, a series of metal foils (Fe, Ni, Cu, Pt, Zn, Sn, Ag, Cd, and In) with distinct adsorption affinities toward HMF were systematically examined17. Among those metals, Ag demonstrates relatively good electrocatalytic performance in the C–N coupling reaction, achieving the highest partial current density of 13 mA cm–2 and FE of 62.3% for MAMF production due to the moderate HMF adsorption strength among tested metal foils (Supplementary Fig. 3)16,40. To further investigate the impact of adsorption behavior of HMF on the electrochemical C–N coupling, Ag NP and Ag nanocubes (Ag NC) with varied exposed facets and surface electronic structures were successfully fabricated. Scanning electron microscopy (SEM) images revealed that Ag NP exhibits an early spherical morphology with an average diameter of approximately 30 nm, whereas Ag NC exhibits cubic shapes (Fig. 2a, b). Transmission electron microscopy (TEM) characterization (Fig. 2c–f and Supplementary Fig. 4) further confirms that Ag NP and Ag NC exhibit distinct morphologies. High-resolution TEM (HRTEM) images and the corresponding fast Fourier transform (FFT) patterns (Fig. 2d, f) provide evidence of the surface structures (Supplementary Fig. 5). Ag NP exhibits a lattice spacing of 0.24 nm, corresponding to the (111) crystallographic plane of Ag. On the other hand, Ag NC shows a lattice spacing of 0.21 nm, which corresponds to the (200) plane of Ag41. Additionally, the primary diffraction peaks in the X-ray diffraction (XRD) patterns confirm that Ag NP and Ag NC mainly expose the (111) and (100) facets, respectively (Fig. 2g). X-ray photoelectron spectroscopy (XPS) characterization (Fig. 1h) was conducted to confirm that Ag in these catalysts exists in the metallic state32,42. These results demonstrate the successful synthesis of Ag catalysts with well-controlled crystal structures.

Electrochemical activity tests for the C–N coupling reaction of HMF with methylamine were conducted in a three-electrode H-cell (Supplementary Fig. 6), using a 0.5 M phosphate buffer solution as the electrolyte (see the Methods for more details)9,12. The liquid and gaseous products were quantified by liquid chromatography (LC) and gas chromatography (GC), respectively (Supplementary Figs. 7–14). The methylamine concentration was optimized, and 1000 mM was selected according to the performance tests (Supplementary Fig. 15). Linear sweep voltammetry (LSV) curves (Fig. 3a and Supplementary Fig. 16) indicate that both Ag NP and Ag NC exhibit enhanced current densities upon the addition of HMF, suggesting that the electrochemical C–N coupling of HMF with methylamine requires a lower overpotential compared to the hydrogen evolution reaction (HER). Ag NP achieves a current density of ~20 mA cm–2 at –0.45 V vs. RHE, which is higher than that of Ag NC (~14 mA cm–2). Notably, the Ag NC exhibits a higher current density of HMF reduction as the potential becomes more negative (lower than –0.45 V), suggesting that direct HMF reduction might be more favorable on Ag NC.

Ag NP and Ag NC with different surface structures exhibit distinct selectivity and product distributions in the electrochemical C–N coupling reaction of HMF and methylamine (Fig. 3b, c). Tests at a wide range of potentials (–0.35 V to –0.75 V vs. RHE) demonstrate that Ag NP shows better performance in both selectivity and FE of electrochemical C–N coupling compared to Ag NC. The highest FE of 89.2% could be achieved by Ag NP with a selectivity of 90.2% at –0.45 V vs. RHE (Fig. 2b), which outperforms most previously reported C–N coupling systems (Supplementary Table S1)9,17–19,36. Regarding the distribution of products, Ag NC shows a higher FE of BHH than Ag NP at various voltages (Fig. 3c), with more BHH produced at low potentials (–0.35 V and –0.45 V vs. RHE). Furthermore, Ag NC exhibits a rising trend in BHMF production even in the presence of methylamine at higher potentials (–0.55 V to –0.75 V vs. RHE). These results indicate that, on Ag NCs, the aldehyde group of HMF preferentially undergoes hydrogenation to BHMF or dimerization to BHH, which is likely attributable to the strong interaction between the catalyst surface and the C=O moiety16,33,40. Additionally, introducing BHMF into the electrolyte with methylamine at reductive potentials eliminates the possibility of MAMF production from BHMF (Supplementary Fig. 17), indicating that these two reactions are competitive on Ag catalysts. Furthermore, Ag NP possesses a slightly smaller electrochemically active surface area (ECSA) than Ag NC (Supplementary Fig. 18), suggesting that Ag NP has a better intrinsic performance. Therefore, the higher production rate of MAMF on Ag NP suggests that the adsorption behavior on Ag NP favors the C–N coupling process (Fig. 3d). During stability tests, Ag NP shows the steady production of MAMF with a consistent FE (>85%) over 24 h (Fig. 3e), higher than that of the Ag NC (Fig. 3e, f). The morphology and crystal structure of the Ag catalysts remain unchanged (Supplementary Figs. 19 and 20), suggesting the importance of the exposed facet for the promoted activity. The results above indicate that the adsorption behaviors of HMF seem to be essential for selectivity. To validate the generality of our findings, we broadened the substrate scope to several furfural derivatives and varied the nitrogen source. With 2-furaldehyde and 5-methylfurfural as substrates and methylamine as the nucleophile, Ag NP delivered FEs of 63.0% and 81.0% toward the corresponding amines, whereas Ag NC afforded lower FEs of 50.4% and 69.1%, respectively (Supplementary Fig. 21a, b). Replacing methylamine with ammonia as the nitrogen source in the coupling reaction with HMF preserved a high MAMF FE of 65.3% on Ag NP, higher than that of 29.1% on Ag NC (Supplementary Fig. 21c). Taken together, these results validate a facet-governed adsorption-reactivity paradigm. The Ag NP surface favors the η1(C)-aldehyde configuration, translates into favorable product selectivity across distinct furfural substrates and nitrogen sources, indicating the versatility of facet engineering for electrochemical amination (Supplementary Fig. 21d).

To further support this hypothesis, it is necessary to elucidate the intrinsic reaction mechanism of C–N coupling and how the HMF adsorption behavior affect the performance.

To further investigate the reaction mechanism of electrochemical C–N coupling, kinetics studies were carried out on Ag catalysts. The Tafel slopes (Fig. 4a, b) for Ag NP (157 mV dec–1) and Ag NC (168 mV dec–1) are lower compared to blank counterparts of Ag NP and Ag NC (179 mV dec–1 and 182 mV dec–1). This reduction in Tafel slopes demonstrates that the electrochemical C–N coupling of HMF with methylamine is kinetically more favorable than HER. Notably, the smaller Tafel slope of Ag NP than Ag NC implies more favorable kinetics of Ag NP for C–N coupling12,28,34. This result is further supported by the electrochemical impedance spectroscopy (EIS) study (Fig. 4c and Supplementary Fig. 22). The Ag NPs exhibit a reduced charge-transfer resistance (R=12.4 Ω) compared to Ag NCs (R=18.7 Ω), indicating enhanced interfacial electron transfer efficiency during the C–N coupling process43,44. Furthermore, electrochemical experiments with H/D kinetic isotope effect (KIE) studies were conducted on the Ag NP catalyst. The cathodic shift of 145 mV (Fig. 4d) suggests that the proton-coupled electron transfer step is significant for the C–N coupling reaction, indicating the important role of proton dynamics in the reduction of the HMF intermediate and C–N bond formation17,36,45,46. Besides, time-resolved 1H NMR spectroscopic characterization of the reaction mixture was performed under operando electrochemical conditions (Supplementary Fig. 23). The results show that the imine intermediate remains at a consistently low concentration throughout the electrochemical reaction, exhibiting a gradual decline as electrolysis proceeds. This behavior can be attributed to the continuous conversion and hydrolysis of the imine at the electrode–electrolyte interface, where the elevated local pH promotes hydrolytic decomposition. In contrast, the imine concentration remains nearly constant in the absence of applied potential, confirming that electrolysis induces its consumption (Supplementary Fig. 24).

According to Fick’s first law, we have calculated the local alkalinity during the reaction47. It was found that the local pH elevated to nearly 12.6 at –0.45 V vs. RHE (Supplementary Fig. 25a, see the Methods for more detials). To further verify this observation, the imine was synthesized independently and introduced into electrolyte solutions with pH 11.0 and 12.6. The imine remained relatively stable at pH 11.0 but underwent hydrolysis under pH 12.6 conditions (Supplementary Fig. 25). Considering the enhanced local alkalinity near the cathode during electrolysis, these results substantiate our rationale for adopting a one-step C–N coupling strategy and highlight the critical importance of controlling the interfacial adsorption configuration and hydrogenation ability to achieve high selectivity36,48,49.

Kinetic analysis of the reaction process shows that a decline in FE for C–N coupling correlates with the concentration decrease of HMF as consumed during electrolysis (Fig. 4e), accompanied by a rise in HER activity. This trend further supports the conclusion that the C–N coupling reaction follows the inner-sphere route17,36,45. Further validation is provided by the dependence of the MAMF partial current density on the HMF concentration. In the low-concentration regime (Fig. 4f), a logarithmic slope of 0.62 is observed, which is close to the theoretical value of 0.5 predicted by Langmuir–Hinshelwood kinetics for bimolecular surface reactions. This agreement suggests that the surface adsorption of HMF becomes a key rate-limiting factor under these conditions5,49. At higher HMF concentrations, side reactions like polymerization and reduction increase, inhibiting the C–N coupling reaction23. These findings collectively demonstrate that HMF adsorption modulated by catalyst surface properties directly affects the competition between C–N coupling and side reactions.

To clarify the adsorption behavior of HMF on Ag NP and Ag NC, spectroscopic studies were carried out. Before the in situ experiments for the C–N coupling reaction, the Raman spectra of HMF, methylamine, and possible products (MAMF and BHMF) were first collected to confirm key peaks for further experiments (Supplementary Fig. 26). Raman spectroscopy enables precise detection of adsorption-induced spectral perturbations, including frequency shifts and intensity variation, by leveraging its high sensitivity to molecular vibrational modes50. Notably, Ag NP and NC exhibit distinct spectral responses to HMF adsorption (Fig. 5a). For Ag NP, peaks at 976 cm–1 and 1526 cm–1 are attributed to the C–C stretching of the furan ring. The peak at 1022 cm–1 is attributed to the C–H stretching of the furan ring. These results show that HMF is adsorbed on Ag NP with the horizontally tilted furan ring51,52. This adsorption configuration shows that the C–C end of the furan ring is closer to the catalyst surface on Ag NP, with the absence of the peak at 718 cm–1 attributed to C–O–C stretching. For Ag NC, the appearance of the peak at 718 cm–1 and the disappearance of peaks at 976 cm–1 and 1526 cm–1 confirm that the C–O–C end of the furan ring interacts more closely with the catalyst surface53. The peak at 1002 cm–1 is attributed to the hydroxymethyl group54,55. The absence of a peak at 1526 cm–1 on Ag NC could suggest that Ag NC preferentially adsorbs the oxygen-containing bonds (C–O–C of the furan ring, C–OH of the alcohol, and C=O of the aldehyde)56. These results show that the adsorption configuration of HMF is strongly dependent on the Ag catalysts, possibly owing to the different surface structures.

The varied adsorption configurations of HMF could be further supported by the results of density functional theory (DFT) calculations (Fig. 5b). DFT results reveal that HMF preferentially adopts the η1(C)-aldehyde adsorption mode on Ag NP, where the furan ring tilts horizontally and the aldehyde group of HMF coordinates monodentate to the catalyst surface through the carbonyl carbon atom. Additionally, Ag NC stabilizes the η2(C,O)-aldehyde configuration, in which the C atom and the O atom of the carbonyl group are together bonded to the surface. These distinct adsorption modes could influence the interaction strength and orientation of the C=O group with catalytic sites57,58. Furthermore, the calculated adsorption energy difference (Fig. 5b) indicates that the thermodynamic stabilization of the η1(C)-aldehyde configuration, which concurrently improves both the activation efficiency and adsorption stability of the C=O group during prolonged electrolysis35,59. Therefore, it is proposed that the Ag catalysts affect the selectivity of the C–N coupling reaction by controlling the adsorption mode of the aldehyde group of HMF.

To further understand the mechanism of structure-influenced adsorption configurations in steering C–N coupling reaction, in situ Raman spectroscopy investigations were carried out at the potentials from –0.15 V to –0.75 V vs. RHE with an interval of 0.1 V (Fig. 5c, d). Adsorbed species on the Ag surface are observed under reduction conditions. The C–C, C–H vibrations of the furan ring observed at open circuit potential (Fig. 5c) could all be found at a similar Raman shift as those found in Fig. 4a, suggesting that HMF is adsorbed on Ag NP via η1(C)-aldehyde configuration in the electrochemical C–N coupling process. The peaks for aldehyde (1391 cm–1 and ~1670 cm–1) and furan ring (1523 cm–1) are observed from –0.15 V to –0.75 V vs. RHE, indicating a stabilized adsorption on Ag NP at a wide potential range (Fig. 5c)60. For Ag NC, peaks of HMF appear at 718 cm–1, 1002 cm–1, and 1506 cm–1, consistent with η2(C, O)-aldehyde adsorption mode (Fig. 5d). Control experiments without HMF are investigated under the same applied potential. The peak at ca. 1300 cm–1 (Supplementary Fig. 27), attributed to the wagging of –NH260,61 and stable adsorption of methylamine, eliminates the concerns about the identification of adsorption configurations and the influence of methylamine adsorption.

Upon applying the negative potential, peaks at 1452 cm–1 attributed to symmetric stretching of the C–N bond are detected at –0.15 V to –0.75 V vs. RHE, demonstrating the generation of MAMF (Supplementary Fig. 26c). The surface-enhanced Raman scattering (SERS) effect amplifies the furan ring vibration at 1562 cm–1 in generated MAMF46, demonstrating that the reaction occurs preferentially near the Ag NP surface rather than in bulk solution. Additionally, the relatively lower intensity of the peak of the C–N bond in MAMF on Ag NC (peak at 1452 cm–1) corresponds to the lower coverage of MAMF under operando conditions25,47, implying that the reaction did not favor the C–N coupling (Fig. 5e). In particular, the vibration peak at 1589 cm–1, assigned to the hydrogenation product BHMF (Supplementary Fig. 26d), is absent in the Raman spectra of Ag NP (Fig. 5d), indicating that the η1(C)-aldehyde adsorption configuration effectively suppresses the competing hydrogenation pathway. However, the peak of BHMF was observed on Ag NC from –0.25 V to –0.65 V vs. RHE, indicating that the C–N coupling reaction was inhibited by the hydrogenation of HMF.

The Raman peak at 1678 cm–1 attributed to the stretching mode of C=O in HMF (blue curve in Fig. 5a) shows a 3 cm–1 red shift on Ag NP (Fig. 5c)50,62. The red shift is assigned to the adsorption of HMF through the carbonyl π* antibonding orbital and indicates the weakening of C=O bond on Ag NP25,63. Compared to Ag NP, the 9 cm–1 red shift of C=O on Ag NC indicates a stronger interaction (Fig. 5d)50,53. Furthermore, the relatively larger stark tuning (Supplementary Fig. 28) of Ag NC demonstrates the excessive interaction of aldehyde53,64, leading to the cleavage of C=O to form BHH or BHMF16,28. This divergence in binding geometry directly modulates the polarization degree of the C=O group. The η1(C)-aldehyde adsorption on Ag NP induces moderate electron withdrawal from the carbonyl moiety compared to the η2(C, O)-aldehyde adsorption on Ag NC, thereby enhancing its susceptibility to nucleophilic attack by absorbed methylamine (Fig. 1a) rather than the hydrogenation (Fig. 1b) and dimerization (Fig. 1c)16,26.

To further exclude how the adsorption configuration affects the selectivity, DFT calculations were carried out. The results reveal that the nucleophilic attack of methylamine on adsorbed HMF over Ag NP exhibits a Gibbs free energy barrier of –0.28 eV that is lower than –0.14 eV on Ag NC. Considering potential contribution from the trace facet of (110), the C–N coupling energy barrier on Ag (110) was also considered. It showed that the C–N coupling energy barrier is –0.17 eV, higher than that on Ag (111). The hydrogenation barrier of the imine is also calculated. Ag (111) surface exhibits the lowest hydrogenation energy barrier (0.07 eV), markedly lower than those on Ag (100) (0.24 eV) and Ag (110) (0.13 eV). Such a low barrier facilitates the rapid hydrogenation of the imine intermediate, thereby accelerating the overall conversion and enhancing the C–N coupling selectivity (Supplementary Fig. 29)23,65. As a result, Ag NP stabilizes η1(C)-aldehyde adsorption configuration with optimal interaction of C=O for C–N coupling, whereas Ag NC favors η2(C, O)-aldehyde configurations that steer reactions toward hydrogenation.

These spectroscopic and computational results highlight that the adsorption configuration of HMF could play a crucial role in affecting the selectivity of electrochemical C–N coupling. As shown in Fig. 5e, HMF tends to absorb on the Ag NP via η1(C)-aldehyde configuration. Due to the moderate adsorption strength of C=O, nucleophilic attack of methylamine would occur preferentially. Thereafter, hydrogen atom transfer (HAT) would transfer H* on the electrode to the adsorbed organic species rapidly to converting imine to respective amines48,56. The mechanism of Ag NP gives clear evidence that η1(C)-aldehyde adsorption configuration favors generating the C–N bond and suppressing the side reactions. Furthermore, the stronger polarization of aldehyde C=O on Ag NC contributes to straight HAT to form BHH and BHMF rather than coupling with methylamine. Given the reaction pathways for C–N coupling, MAMF would not be generated once the straight HAT to aldehyde happens (Fig. 1). The specific structures of catalyst surfaces impact the C–N coupling selectivity by controlling HMF adsorption configurations and imine hydrogenation that differentially activate the C=O group for the nucleophilic attack28,62. Therefore, manipulating the adsorption configuration of HMF and the hydrogenation of imine on Ag catalysts could enhance the FE of electrochemical C–N coupling of HMF with methylamine.

In this work, we rationalized the choice of a one-step C–N coupling pathway by directly comparing it with the conventional two-step process via the imine intermediate. Building on this understanding, we achieved highly efficient electrochemical C–N coupling of HMF with methylamine by tailoring the adsorption configuration of HMF on Ag catalysts predominantly exposing the (111) facet. A high FE of 89.2% for MAMF with a selectivity of 90.2% could be achieved by Ag NP with exposed Ag (111) facet. Kinetics studies reveal that the C–N coupling follows an inner-sphere mechanism, where the adsorption behavior of HMF and hydrogenation of imine could play a crucial role in affecting the product distribution. In situ Raman spectroscopy and DFT calculations reveal that the η1(C)-aldehyde adsorption configuration of HMF on Ag NP leads to an optimal interaction strength of the functional aldehyde group with the catalyst surface. Besides, the better imine hydrogenation on Ag NP further helps to convert the imine to the respective amines. Thus, the polarization of the C=O could be optimized to facilitate the C–N bond formation while suppressing side reactions such as hydrogenation and dimerization. This work offers new insights into how substrate adsorption configuration regulates the selectivity of electrochemical C–N coupling between HMF and methylamine. These findings could potentially guide the design of efficient catalysts for electrochemical organic synthesis. Future efforts should focus on enabling green substrates, creating pathways to more valuable products, and designing scalable systems like the membrane electrode assembly (MEA), which will collectively pave the way for the industrial deployment of electrochemical C–N coupling technology.

Methods
Materials
AgNO3 (>99.8%), methylamine (40 wt.% in H2O), and acetone (HPLC) were purchased from Tianjin Jiangtian Chemical Technology Co., Ltd. (China). 5-Hydroxymethylfurfural (99%), CF3COOAg (98%) and polyvinylpyrrolidone (PVP, Mv=55,000–58,000, 98%) were purchased from Meryer (Shanghai) Biochemical Technology Co., Ltd. K2HPO4 (98%), 5-[(methylamino)methyl]-2-furanmethanol (95%), 2,5-bis(hydroxymethyl)furan (98%) were purchased from Bide Pharmatech Ltd. NaOH (99%), ethylene glycol (HPLC), acetonitrile (HPLC) and NaCl (99%) were purchased from Aladdin Industrial Co. Ltd. NaHS (68–72%), ammonium formate (>99%) were purchased from Energy Chemical (Anhui, China). Sodium citrate (>99%) was purchased from J&K Scientific Ltd. L(+)-Ascorbic acid was purchased from Tianjin Guangfu Technology Development Co. Ltd. (China). KOH (96%) was purchased from Macklin Inc. (Shanghai, China). All gases used in this paper were from Air Liquide Co. Ltd., and all reagents except 5-[(methylamino)methyl]-2-furanmethanol (MAMF) were used directly without further purification.

Synthesis of Ag NP and Ag NC
Ag NP was synthesized using L(+)-ascorbic acid as the reductant and sodium citrate anhydrous as the stabilizer. Typically, 0.23 g ascorbic acid and 0.77 g sodium citrate anhydrous were dissolved in 200 mL of deionized water, and the pH of the solution was adjusted to 11 by adding 0.1 mol L–1 NaOH solution66. Subsequently, 4 mL of 0.5 mol L–1 aqueous solution of AgNO3 was added dropwise under continuous stirring (900 rpm) in a 30°C water bath. The solution immediately changed from colorless to black, indicating the formation of Ag nanoparticles. After 150 min of reaction, the product was collected by centrifugation at 9000 rpm for 5 min, washed repeatedly with ethanol and deionized water, and finally redispersed after a second centrifugation at the same speed to obtain purified Ag NP.

In a standard synthesis for Ag NC, 25 mL of ethylene glycol (EG) was added into a flask and heated for 40 min under magnetic stirring in an oil bath set to 142°C. A stable temperature of approximately 138°C was measured for the reaction solution. Other reagents were separately dissolved in EG and sequentially introduced into the flask using a pipette. Specifically, 0.3 mL of NaHS solution (3.5 mM) was added first. After 4 min, 2.5 mL of NaCl solution (3 mM) was introduced, followed by the addition of 6.25 mL of PVP solution (20 mg mL–1) 2 min later. After another 2 min, 2 mL of CF3COOAg solution (282 mM) were introduced. Finally, 2.5 mL of NaBr solution (3 mM) was added after 5 min of delay. Note that the NaHS solution was prepared right before its injection. During the entire process, the flask was capped with a glass stopper except during the addition of reagents. After growth for 15 min, the synthesis was quenched by immersing the flask in an ice-water bath. The solution was split into four portions, and 125 mg of PVP was dissolved in each fraction. This is necessary in order to prevent aggregation during the washing steps. The products were precipitated with acetone and collected by centrifugation at 8000 rpm for 6 min, followed by washing with DI water and centrifuging at 12000 rpm for 10 min twice to remove the remaining precursor, EG, and excessive PVP67. Since the use of NaBr during the synthesis, the product solution was centrifuged twice at 9000 rpm for 10 min to separate the insoluble AgBr precipitate from the Ag NC solution.

Fabrication of electrodes
For the preparation of electrodes, 30 mg of catalyst (Ag NP or Ag NC) with 160 μL of Nafion (5 wt.%) were dispersed in 3 mL of ethanol. After 40 min of sonication in an ice water bath, the catalyst ink was sprayed onto carbon paper at a set temperature of 78°C. The loadings of the catalysts were controlled to be 1 mg cm–2.

Activity evaluation
The electrochemical performances of all the samples were tested using the AutoLAB electrochemical analyzer and carried out in an H-type cell. The anolyte (20 mL of buffer solution) and the catholyte (20 mL of buffer solution containing 20 mM HMF and methylamine) were separated by a bipolar membrane (BPM, Fumasep FBM-PK, Fumatech). Since the pKa of CH3NH3+ is about 10.6, adjusting the solution pH to 11±0.2 ensures a significant portion of the amine to present as a base form to react with HMF to form aldimine. The electrolyte was freshly prepared the same day before the experiment. The 0.5 M phosphate buffer solution was prepared by using K2HPO4 and adjusting the pH to 11.0 with KOH. And pH of the solution was monitored before (11.0±0.2) and after (11.1±0.3) adding the methylamine to make sure no obvious change was observed.

The catholyte was stirred for 10 min with Ar protection before electrolysis. Carbon rod and Ag/AgCl (saturated KCl) electrodes were used as the anode and the reference electrode, respectively. The carbon paper of the working electrode was cut into a size of 2 cm2, and the geometric surface area for activity tests is 1.5 cm2. The backside of the carbon paper is covered with Kapton tape. All the tests for electrochemical C–N coupling of HMF with methylamine were conducted under magnetic stirring at 1200 rpm. The electrochemical impedance spectroscopy (EIS) measurements were performed with a 5 mV amplitude and a frequency range from 10,000 to 0.1 Hz. All the potentials in this paper were provided without iR corrected and converted to the reversible hydrogen electrode (RHE) through the following equation:

E RHE = E Ag/AgCl + 0.197 + 0.059 × pH (1)

Product identification and quantification
During the reaction, the catholyte was continually stirred at 1200 rpm with Ar as the protective gas and carrier gas (flow rate: 5 sccm). The products were quantified after the amount of electrons flowing through the cathode reached 20 C as controlled by a potentiostat (Autolab PGSTAT204, Metrohm). Gaseous products were analyzed with online gas chromatography (GC7890B, Agilent Technologies, Inc.). For quantification of liquid products, the collected catholyte was first subjected to rotary evaporation at 40°C to remove residual methylamine. Subsequently, the obtained liquid products were diluted fivefold and analyzed by high-performance liquid chromatography (HPLC, Agilent Technologies 1200 Infinity) equipped with a variable wavelength detector (VWD). The products were analyzed with a C18 column. The mobile phase is acetonitrile/DI water/5% ammonium formate (V/V/V=6:1:3) solution with a flow rate of 0.5 mL min–1. The formation of products was further ensured by mass spectrometry (MS) and 1H nuclear magnetic resonance (1H NMR) spectroscopy.

The FE, selectivity and production rate are calculated according to Eqs. (2)–(6):

FE H2 = 2n H2 × F / Q × 100% (2)

FE MAMF = 2n MAMF × F / Q × 100% (3)

FE BHMF = 2n BHMF × F / Q × 100% (4)

Selectivity MAMF = n MAMF / (n0 HMF - n HMF) × 100% (5)

Production rate MAMF (mg cm–2 h–1) = m MAMF / (S catalyst × t) (6)

where the n MAMF, n BHMF and n HMF represent the mole amounts of MAMF, BHMF after the electrolysis. The n0 HMF represent the mole amount of HMF before reaction. The Y HMF represents the yield of HMF. Q refers to the total charge. F is Faraday’s constant. S catalyst is the geometric area of the catalyst loaded on the electrode, and t is the reaction time.

Characterizations
Scanning electron microscopy (SEM, Regulus 8100) was employed to characterize the morphology of the catalysts. Transmission electron microscopy (TEM, JEOL JEM-2100F) was used to characterize the structure of the catalysts. X-ray powder diffraction (XRD; Bruker D8 Focus, Cu Kα radiation (λ=1.54056 Å) at 40 kV and 40 mA) and X-ray photoelectron spectroscopy with an Al Kα X-ray source (XPS, EscaLab MK) were applied to characterize the structure and valence states of the as-prepared catalysts. XRD spectra were collected over a 2θ range of 10–80° at a scanning speed of 10°/min. The binding energy was calibrated using the C 1s photoelectron peak at 284.6 eV as the reference.

In situ Raman spectroscopy
In situ Raman experiments were carried out in a custom-designed H-cell electrolyzer, using 0.5 M phosphate buffer solution as the electrolyte. The in situ Raman samples of Ag NP and Ag NC were prepared on Ag foil. The electrode was encased in a PEEK fitting, with an exposed geometric surface area of 1 cm2. A platinum wire and an Ag/AgCl electrode (saturated KCl, Gaoss union) were used as the counter and the reference electrode, respectively. Electrochemical measurements were carried out with a potentiostat CompactStat.e20250, IVIUM. The Raman tests were performed on a Confocal Raman Microscopy (RENISHAW, inVia reflex) equipped with a 532 nm He-Ne laser. The signal acquisition time is 51 s for each Raman spectrum.

Calculation of local pH
Potassium phosphite (K2HPO4) is derived from phosphorous acid (H3PO3), a diprotic acid possessing only two acidic protons (pKa1 ≈ 1.3, pKa2 ≈ 6.7). Under strongly alkaline conditions (pH=11.0), the phosphite species exists almost entirely in its fully deprotonated form (HPO32–), far well outside its effective buffering range. As a result, the phosphite electrolyte provides negligible buffering capacity. Consequently, the local pH increase near the cathode is governed primarily by the generation and diffusion of OH– produced during electrochemical reactions. For the OH– generation flux, J OH–, each electron transferred at the cathode approximately produces one OH– ion. Therefore,

J OH– = i / F (6)

where i is the current density and F is the Faradic constant (96495 C mol–1).

One-dimensional steady-state diffusion balance model was adopted in this manuscript. Fast ion coupling (electroneutral diffusion) was assumed. Therefore,

J OH– = Deff (C Surface – C bulk) / δ

where the parameters could be used as 19: bulk pH=11.0, C bulk = 10–3 M; diffusion layer thickness δ=100 µm; Deff = 5.27 × 10–9 m2 s–1; pH Surface = 14 + log10 (C Surface).

Computational model
Ag(111) and Ag(100) surface was modeled by a (3√3×3√3)R30° supercell and a 6×5 supercell, respectively. All surface models were composed of 4 layers of atoms with 2 uppermost layers relaxed. The metal slabs were separated by a ~20 Å vacuum space. The Brillouin zone was sampled at a 3×3×1 k-point mesh with Γ-centered for hexagonal supercells and Monkhorst-Pack for orthorhombic supercells. The Gibbs free energy under ambient conditions was corrected using a computational hydrogen electrode (CHE) model68.

DFT calculations
Density functional theory (DFT) calculations were performed utilizing the Vienna Ab Initio Simulation Package (VASP) in conjunction with the projector augmented wave (PAW) method69,70. The revised Perdew–Burke–Ernzerhof (RPBE)71 exchange-correlation functional was applied, and the dispersion effects were accounted for by employing the semi-empirical D3 method72,73. For this method, the consideration of a Hubbard U parameter is typically not necessary. The cutoff energy was set to 450 eV. The convergence threshold of electronic and force was set to 10−6 eV atom–1 and 0.02 eV Å–1, respectively. The Methfessel-Paxton smearing was applied with a smearing width of 0.15 eV. Related information is attached in Supplementary Data 1.

Data availability
The data that support the findings of this study are available within the paper and supplementary information. Additional data are available from the corresponding author on request. Source data are provided with this paper.

Peer review rounds
[{"round": 1, "reviewer_comments": {"reviewer_1": "In this manuscript, the authors reported an electrocatalytic system to synthesize amine from HMF and methylamine using Ag nanoparticles (denoted as Ag NPs). Although the Faraday efficiency and production rate are considerable, this reaction is not novel and extremely non-challenging. The most critical issue is that the C-N coupling reaction is likely to be a spontaneous reaction process, where the electrocatalyst mainly completes the hydrogenation reaction step, which conflicts with the proposed mechanism in this manuscript. As a result, we can not recommend that the current form of the manuscript be published on the Nature Communications. The following questions should be considered and be clearly reported:\n1. Given the well-documented rapidity of amine-aldehyde condensation reactions under ambient conditions, a critical question arises regarding the authors' reported system containing concurrent HMF and methylamine: does the imine intermediate predominate in the reaction medium under these conditions? To conclusively address this mechanistic consideration, the authors should provide supporting evidence including (but not limited to) time-resolved 1H NMR spectroscopic characterization of the reaction mixture, complemented by comparative kinetic studies and/or mass spectrometric analysis of intermediate species.\n2. A second mechanistic concern pertains to the potential influence of stoichiometric parameters. Specifically, the rationale for selecting the current methylamine/HMF molar ratio requires clarification. Have the authors systematically explored reactant stoichiometry optimization (e.g., elevated methylamine concentrations)? To substantiate the claimed catalytic specificity, control experiments comparing Faradaic efficiencies across (i) varied methylamine concentrations and (ii) different metal electrodes (including non-noble counterparts) should be supplemented, alongside detailed kinetic isotope effect analyses.\n3. The obvious difference between Figure 4c and Figure 4d is puzzling. Even if there are differences in the dominant adsorption configurations on the catalyst surface, it does not mean that other adsorption configurations do not exist. However, we could not observe any signals around ~1024 cm-1 which could be attributed to the furan ring of C-H, we recommend that the authors clarify this issue clearly.\n4. Given the established morphological sensitivity of electrocatalytic systems (e.g., Ag nanoparticles vs. nanocubes differentially exposing {111}/{100} facets), has rigorous morphological characterization (including crystallographic orientation and particle size distribution) been performed to ensure structural homogeneity across the metal electrodes in Figure S1? This is particularly critical as substrate-dependent variations in active site geometry and surface energy landscapes could artificially modulate Faradaic efficiency trends.\n5. Computing energies of adsorbed species uses the harmonic approximation, which can be very sensitive to low-frequency modes. If the used cutoff is too small then the entropy of the adsorbate will be substantially over-estimated. The authors do compute the energy, and the many difference is only 0.2 eV, which is much close to the typical DFT error of ~0.2 eV, and this conclusion could easily change if a different functional or U value is used. In other words, it is not conclusive evidence.\n6. Computational Refinement: Although the theoretical calculations align with experimental outcomes, they fail to rationalize the high selectivity toward MAMF. We suggest: (i) Incorporating energy profiles for methylamine’s nucleophilic attack on the aldehyde group to quantify activation barriers. (ii) Comparing energy differences between hydrogenation and nucleophilic pathways to elucidate competitive reaction dynamics.\n7. Substrate Scope Expansion: Additional substrate screening experiments are necessary to validate the universality of their design strategy for aldehyde-based C–N coupling reactions. Testing structurally diverse aldehydes would clarify whether the observed mechanism is generalizable.\nMinor: the widely accepted resolution of HRTEM is 0.01 nm. Please correct the statements in Figure 1b and Figure 1d. All spelling and grammar in the manuscript should be thoroughly checked, such as “0.205n m” in Figure 1d. The authors' work still has some font issues that need to be corrected. Italicize “in situ” (e.g., Line 6 of Conclusions). Replace hyphens with en dashes for chemical bonds (e.g., “C-N” → C–N in the SI).", "reviewer_2": "This manuscript reports on modulating the adsorption behavior of substrates by tailoring the surface structure of silver (Ag) catalysts, thereby significantly enhancing the electrochemical C–N coupling of biomass-derived 5-hydroxymethylfurfural (HMF) with methylamine to produce 5-[(methylamino)methyl]-2-furanmethanol (MAMF). The optimized Ag nanoparticles (NPs), predominantly exposing the (111) facet, exhibit an impressive Faradaic efficiency (FE) of 89.2% and a selectivity of 90.1% for C–N coupling at −0.45 V vs. RHE. This performance is among the best reported to date. Systematic in situ spectroscopic investigations combined with DFT calculations reveal that HMF adsorbs onto the Ag(111) surface in a distinct η¹(C)-aldehyde configuration. This specific adsorption mode increases the electrophilicity of the carbonyl carbon, facilitating C=O bond polarization and promoting nucleophilic attack by methylamine, thereby enhancing catalytic activity. Overall, this work offers a novel strategy for modulating reactant adsorption to achieve selective electrochemical organic synthesis. It holds the potential to inspire the development of high-performance electrocatalysts. I recommend the publication after revisions, as outlined in the following comments.\n1.Since the Ag NPs and Ag NCs exhibit different morphologies, their electrochemically active surface areas are likely to differ, which could affect their catalytic performance. The authors are encouraged to provide ECSA data to clarify whether this factor plays a substantial role in the observed activity differences.\n2.The effect of methylamine concentration on the reaction performance is not discussed. As the adsorption of methylamine may also influence the C-N coupling process, the authors should consider including a discussion or experimental results addressing this variable.\n3.The manuscript presents charge-transfer resistance values derived from electrochemical impedance spectroscopy (EIS), but lacks information about the fitting procedure, including the equivalent circuit used and the associated standard errors. Providing these details would strengthen the credibility of the analysis.\n4.The manuscript reports selectivity values, but does not clarify whether these are calculated based on carbon-containing products, nitrogen-containing products, or total product yield. The authors should explicitly state the basis for the selectivity calculation.\n5.The authors present a comparison of linear sweep voltammetry (LSV) curves for the C-N coupling and HMF reduction reactions on Ag NPs (Supplementary Fig. 14). However, the corresponding data for Ag NCs are missing. Including this comparison would provide a more complete picture of the performance differences between the two catalysts.\n6.Several key experimental procedures are insufficiently described. For instance, the rotary steaming step used before liquid product quantification (mentioned in Supplementary Fig. 11) is not included in the Methods section, and specific operating parameters are not provided. Additionally, variables used in Equations (2)-(6) are not clearly defined. The authors should revise the manuscript to address these omissions.\n7.Error bars are absent in the Faradaic efficiency data presented in Fig. 3e,f. To demonstrate reproducibility and data reliability, the authors should include error bars.", "reviewer_3": "The manuscript describes tailoring the surface structure of Ag catalysts to modulate HMF adsorption behavior significantly enhances C–N coupling selectivity. It presents a compelling study on facet-dependent C–N coupling but requires revisions to address methodological gaps, clarify mechanistic claims, and contextualize performance metrics. Following are some comments on this work.\n1. The manuscript is generally well-structured, but the figures and schemes need clearer labeling. For example, Scheme I (page 3) is referenced but not included in the main text, which may confuse readers. Figure 2d and 2e are described as showing \"potential-dependent production rate\" and \"stability tests,\" but the axes labels in the figure are unclear. Please ensure all axes and legends are explicitly defined.\n2. The introduction lacks a focused discussion on recent advances in electrochemical C–N coupling, particularly for biomass-derived substrates. Highlighting specific challenges in HMF amination (e.g., overhydrogenation, dimerization) and how this work addresses them would sharpen the novelty.\n3. While facet-dependent adsorption modulation is not novel, its application to electrochemical C-N coupling of HMF is innovative. However, the introduction lacks a critical comparison with recent works on similar systems (e.g., Cu or Pd catalysts for HMF upgrading). A table comparing FE/selectivity with prior studies would better contextualize the advancements.\n4. The synthesis methods for Ag NP and Ag NC are well-documented, but the absence of TEM/SEM images in the main text (relegated to Supplementary Figs. 2–3) weakens the immediate validation of morphology. Key characterization data (e.g., lattice spacing, XRD peaks) should be highlighted in the main text. Stability tests over 10 cycles (Fig. 2e, f) are insufficient to claim long-term durability. Additional data (e.g., 24-hour chronoamperometry) would strengthen the practical relevance.\n5. The authors attribute the high selectivity to η¹(C)-aldehyde adsorption but do not fully address how methylamine adsorption influences the reaction. Competitive adsorption between HMF and methylamine could alter pathways; this should be discussed. Product quantification relies on LC/GC, but potential intermediates (e.g., aldimine) are not tracked. Including time-dependent product distribution would clarify reaction kinetics.\n6. The DFT calculations lack methodological details (e.g., functional, basis set, slab models). A brief description in the main text or Methods section should be provided for reproducibility.\n7. The proposed mechanism assumes direct nucleophilic attack by methylamine on adsorbed HMF but does not address the role of protonation states or pH effects. Experiments varying pH could elucidate how proton availability impacts aldimine formation and reduction.\n8. The manuscript does not consider potential surface reconstruction of Ag NPs/NCs under operating conditions. XPS or post-reaction TEM of used catalysts would verify structural stability and rule out facet restructuring during electrolysis. Competitive adsorption between HMF and methylamine is ignored. Surface coverage studies (e.g., via electrochemical quartz crystal microbalance) could clarify whether methylamine adsorption limits reaction rates.\n9. The use of a three-electrode H-cell with a bipolar membrane may not reflect industrially relevant conditions. Testing in a flow cell or membrane electrode assembly (MEA) would better demonstrate scalability.\n10. The environmental impact of using methylamine (a toxic reagent) is not addressed. Exploring greener amine sources (e.g., ammonia) or coupling with renewable NH₃ synthesis could enhance sustainability."}, "author_response": "We sincerely thank the reviewer for the important comments. We have carefully revised this manuscript and improved the related details according to the insightful suggestions. Detailed responses to the comments are listed below.\n\nSpecific Comment R1-1: Given the well-documented rapidity of amine-aldehyde condensation reactions under ambient conditions, a critical question arises regarding the authors’ reported system containing concurrent HMF and methylamine: does the imine intermediate predominate in the reaction medium under these conditions? To conclusively address this mechanistic consideration, the authors should provide supporting evidence including (but not limited to) time-resolved 1H NMR spectroscopic characterization of the reaction mixture, complemented by comparative kinetic studies and/or mass spectrometric analysis of intermediate species.\nResponse: We thank the reviewer for the insightful comments. We agree that amine-aldehyde condensation reactions can proceed rapidly under certain conditions, particularly in anhydrous or acidic environments (Patai, S. (Ed.). The Chemistry of Carbon Nitrogen Double Bonds, 1970, John Wiley & Sons.). However, an aqueous phosphate buffer solution at pH 11 was used in our research. Under this specific condition, the equilibrium for imine formation can be less favorable or slower than commonly assumed, especially when competing with the hydrogenation of the aldehyde (ACS Catal., 2016, 6,1840). Therefore, imine intermediate should not predominate in the reaction medium. To support this idea, additional experiments were conducted.\nAccording to the reviewer’s suggestion, time-resolved 1H NMR spectroscopic characterization of the reaction mixture was performed under operando electrochemical conditions. The results show that the imine content stays at a consistently low level throughout the electrochemical reaction with a general decreasing trend (Supplementary Fig. 19). This phenomenon suggests that the imine intermediate does not predominate in the reaction medium. Additionally, time-resolved Raman spectroscopy of the reaction solution without applied potential was collected (Fig. R1). The results show that the concentration of the imine intermediate remains constantly low in the bulk solution under non-electrochemical conditions, confirming that the equilibrium for reversible imine formation reaction is less favorable in this reaction condition.\nCollectively, these results suggest that spontaneously formed imine intermediates in the bulk solution should not be the reason for the high production rate obtained in our study. Thus, the reductive coupling between HMF and methylamine is an electrocatalytic process that occurs at the surface of the electrode, with the adsorption behavior of the HMF molecule as one of the key influencing factors on the performance.\nWith the conclusion discussed above, a detailed kinetic study and mass spectrometric analysis of the key imine intermediate are important to further support the idea of adsorption-configuration-induced impact toward intermediate formation, as suggested by the reviewer. However, accurate quantification of the intermediates formed at the surface during the reaction is hard to realize in this study. Fortunately, the in situ Raman spectroscopy provides direct and compelling evidence to support the main idea of this work (Fig. 4c, d). The observed distinct spectral changes, particularly the redshift of the C=O stretching frequency of HMF adsorbed on Ag NP (Fig. 4c), unequivocally indicate a weakening and polarization of the carbonyl bond upon adsorption. This activation is precisely what enhances the electrophilicity of the carbonyl carbon and facilitates the subsequent nucleophilic attack by methylamine. The dramatic differences in product distribution and selectivity observed between Ag NP and Ag NC (Fig. 2b, c) further corroborate this surface-mediated activation. This distinct catalytic behavior strongly supports that the catalyst surface actively steers the reaction pathway by modulating HMF adsorption. Revisions of the manuscript are as follows:\nManuscript Lines 209-214.\nBesides, time-resolved 1H NMR spectroscopic characterization of the reaction mixture was performed under operando electrochemical conditions (Supplementary Fig. 19). The result shows that the imine content stays at a consistently low level throughout the electrochemical reaction with a general decreasing trend, suggesting the reductive coupling between HMF and methylamine is an electrocatalytic process that occurs at the surface of the electrode.\nSI Lines 161-164:\nSupplementary Fig. 19. Time-resolved 1H NMR for the electrolyte during the C–N coupling on Ag NP with (a) 5, (b) 10, (c) 20, (d) 40, and (e) 60 C charge passed. (f) The concentration of imine as the amount of charge passed.\nFig. R1. Time-resolved Raman spectra of the electrolyte without electrocatalytic reaction.\n\nSpecific Comment R1-2: A second mechanistic concern pertains to the potential influence of stoichiometric parameters. Specifically, the rationale for selecting the current methylamine/HMF molar ratio requires clarification. Have the authors systematically explored reactant stoichiometry optimization (e.g., elevated methylamine concentrations)? To substantiate the claimed catalytic specificity, control experiments comparing Faradaic efficiencies across (i) varied methylamine concentrations and (ii) different metal electrodes (including non-noble counterparts) should be supplemented, alongside detailed kinetic isotope effect analyses.\nResponse: We thank the reviewer for the insightful comments. We have systematically explored the influence of methylamine concentration on the electrochemical C–N coupling reaction. Our results identified 1000 mM as the optimal methylamine concentration (Supplementary Fig. 12).\nRegarding control experiments with different metal electrodes, we have performed a comprehensive comparison. As shown in Supplementary Fig. 1, we evaluated various commercial metal foils (Fe, Ni, Cu, Pt, Zn, Sn, Ag, Cd, and In) for the electrochemical C–N coupling of HMF with methylamine. These initial screening experiments clearly demonstrated that Ag exhibits exceptional electrocatalytic performance, achieving the highest partial current density and Faradaic efficiency for MAMF production among the tested metals. This superior performance was attributed to the moderate HMF adsorption strength on Ag, which is a critical finding that guided our subsequent in-depth study focusing on facet-controlled Ag catalysts and their impact on the adsorption configuration of the substrate.\nFurthermore, we have conducted kinetic isotope effect (KIE) analyses on the Ag NP catalyst, as presented in Fig. 3d. The observed cathodic shift of 145 mV when replacing H O with D O strongly indicates that a proton-coupled electron transfer (PCET) step is essential for the C–N coupling reaction. This analysis underscores the important role of proton dynamics in the reduction of the aldimine intermediate and C–N bond formation, providing mechanistic insight into the rate-determining step and solidifying the inner-sphere mechanism proposed in our manuscript. Due to the limitations of the experimental conditions, KIE analyses with other substrates could not be conducted in our lab. We are sorry for the unfeasible of the corresponding experiments. Revisions of the manuscript are as follows:\nManuscript Lines 147-148:\nThe methylamine concentration was selected to be 1000 mM (Supplementary Fig. 12).\nSI Lines 134-136:\nSupplementary Fig. 12. Electrochemical performance of Ag NP for C–N coupling of HMF with methylamine at various methylamine concentrations.\nSupplementary Fig. 1. Partial current (left) and Faradaic efficiency (right) toward MAMF and BHMF on different metal electrodes for electrochemical C–N coupling between HMF and methylamine at –0.45 vs. reversible hydrogen electrode (RHE).\nFigure 3d. Comparison of LSV curves on Ag NP for C–N coupling reaction in the electrolyte with H O and D O.\n\nSpecific Comment R1-3: The obvious difference between Figure 4c and Figure 4d is puzzling. Even if there are differences in the dominant adsorption configurations on the catalyst surface, it does not mean that other adsorption configurations do not exist. However, we could not observe any signals around ~1024 cm–1 which could be attributed to the furan ring of C-H, we recommend that the authors clarify this issue clearly.\nResponse: We thank the reviewer for the thoughtful comments. The distinct differences between the in situ Raman spectra of Ag NP (Fig. 4c) and Ag NC (Fig. 4d) are important and serve as direct spectroscopic evidence supporting our proposed facet-dependent adsorption configurations of HMF. As stated in our manuscript, for Ag NP, the peak at 1022 cm–1 is consistently observed and attributed to the C–H stretching of the furan ring (Fig. 4a). This spectral feature is indicative of the η1(C)-aldehyde adsorption configuration, where the furan ring adopts a horizontally tilted orientation relative to the catalyst surface, allowing for the detection of its C–H vibrations. This peak remains visible across the investigated potential range in Fig. 4c. In contrast, for Ag NC, the Raman spectra (Fig. 4d) exhibit a prominent peak at 1002 cm–1, which we attribute to the hydroxymethyl group, and the appearance of a peak at 718 cm–1 corresponding to the C–O–C stretching of the furan ring. Concurrently, the furan ring C–H stretching peak around ~1022/1024 cm–1 is indeed absent or significantly diminished on Ag NC. This distinct spectral profile on Ag NC strongly supports the η2(C,O)-aldehyde adsorption configuration. In this mode, the C–O–C end of the furan ring, along with the hydroxymethyl group, interacts more closely with the catalyst surface. This different orientation of the furan ring, where it is less horizontally oriented or more directly interacting through its oxygen-containing functionalities, would naturally lead to a reduced signal from the furan ring C–H stretching, as its vibrational mode might be less enhanced by surface-enhanced Raman scattering (SERS) or its orientation is less favorable for detection compared to other interacting groups.\nWhile it is plausible that other minor adsorption configurations might coexist, the dominant and distinct adsorption modes on Ag NP and Ag NC, as unequivocally evidenced by these clear and reproducible spectroscopic differences, are responsible for dictating the observed dramatic differences in reaction selectivity. The consistent correlation between these unique spectral fingerprints and the vastly different product distributions (high MAMF selectivity on Ag NP vs. favoring BHMF/BHH on Ag NC) strongly supports our conclusion that the adsorption configuration is the critical factor steering the reaction pathway. Revisions of the manuscript are as follows:\nManuscript Lines 247-249:\nFor Ag NP, peaks at 976 cm–1 and 1526 cm–1 are attributed to the C–C stretching of the furan ring. The peak at 1022 cm–1 is attributed to the C–H stretching of the furan ring. These results show that HMF is adsorbed on Ag NP with the horizontally tilted furan ring.\n\nSpecific Comment R1-4: Given the established morphological sensitivity of electrocatalytic systems (e.g., Ag nanoparticles vs. nanocubes differentially exposing {111}/{100} facets), has rigorous morphological characterization (including crystallographic orientation and particle size distribution) been performed to ensure structural homogeneity across the metal electrodes in Figure S1? This is particularly critical as substrate-dependent variations in active site geometry and surface energy landscapes could artificially modulate Faradaic efficiency trends.\nResponse: We thank the reviewer for the insightful comments. We would like to clarify that the data presented in Supplementary Figure 1 corresponds to the initial screening experiments conducted using commercial bulk metal foils (Fe, Ni, Cu, Pt, Zn, Sn, Ag, Cd, and In), not synthesized nanoparticles. Therefore, concerns regarding particle size distribution are not applicable to this specific set of experiments. While we acknowledge that the surface of commercial metal foils may exhibit a distribution of crystallographic orientations, the primary purpose of this initial screening was to identify a metal with moderate HMF interaction strength as a promising candidate for selective C–N coupling. The data demonstrated the outperforming performance of Ag among these bulk materials.\nFor the Ag NP and Ag NC catalysts, which are the model catalysts of interest, we have indeed performed rigorous and comprehensive morphological and crystallographic characterizations, as shown in Fig. 1 of the main manuscript. Scanning electron microscopy (SEM), High-resolution transmission electron microscopy (HRTEM) images, corresponding fast Fourier transform (FFT) patterns, and X-ray diffraction (XRD) analysis (Fig. 1b, d, e) conclusively demonstrate that Ag NP predominantly exposes the (111) crystallographic plane, while Ag NC primarily exposes the (100) facet. Additionally, we also conducted characterization of catalysts after reactions (Supplementary Figs. 16–17). These results confirm the stability of Ag NP and Ag NC, demonstrating no significant facet reconstruction and consistent exposed facets throughout the reaction. This meticulous control and thorough characterization of exposed facets were paramount to our investigation of facet-dependent adsorption configurations and their impact on selectivity, which is the central theme and novelty of this manuscript. Revisions of the manuscript are as follows:\nManuscript Lines 112-114:\nDifferent metal foils (i.e., Fe, Ni, Cu, Pt, Zn, Sn, Ag, Cd, and In) with varied adsorption interactions with the HMF molecule were compared first to reveal the influence of adsorption properties on the activity of the C–N coupling reaction\nFig. 1 Characterization of electrocatalysts. (a-b) SEM images and corresponding size distributions of as-prepared Ag NP (a) and Ag NC (b). (c-f) TEM (c, e) and HRTEM (d, f) images of Ag NP (c,d) and Ag NC (e,f). (g) XPS spectra of as-prepared Ag NP and Ag NC. (h) XRD patterns of Ag NP and Ag NC (JCPDF#04–0783).\n\nSpecific Comment R1-5: Computing energies of adsorbed species uses the harmonic approximation, which can be very sensitive to low-frequency modes. If the used cutoff is too small then the entropy of the adsorbate will be substantially over-estimated. The authors do compute the energy, and the many difference is only 0.2 eV, which is much close to the typical DFT error of ~0.2 eV, and this conclusion could easily change if a different functional or U value is used. In other words, it is not conclusive evidence.\nResponse: We thank the reviewer for the helpful comments. We fully agree with the inherent limitations of the harmonic approximation, particularly concerning its potential sensitivity to low-frequency modes and the estimation of adsorbate entropy. Therefore, we verified our evidence in four aspects: (1) The adsorption energies of HMF on the (100) and (111) surfaces obtained from Density Functional Theory (DFT) calculations (ΔE ) are -1.86 eV and -1.68 eV, respectively, DFT with a difference of 0.18 eV, which is the main contributor to the variation of ~ 0.20 eV in adsorption energy rather than the entropy parts. (2) We calculated the contribution of each vibrational mode to the entropy for the adsorbed HMF on both surfaces (Table R1). For vibrations with a wave number below 50 cm-1, whether treated as 50 cm-1 or ignored, the energy difference of T S between HMF* on the (100) and (111) surfaces does not exceed 0.07 eV. The contribution of computed entropy to the difference in adsorption energy is negligible. (3) To rule out the influ⋅ence of different functionals on the results, we further repeat our computation using the PBE functional, and the adsorption energies on the (100) and (111) surfaces are calculated to be -1.94 eV and -1.79 eV, respectively, with a difference of approximately 0.15 eV. It is worth noting that for metallic catalysts like Ag, the consideration of a Hubbard U parameter is typically not necessary, as electron localization issues that necessitate its use are generally absent. (4) We repeated the calculations at different adsorption sites five times, and the standard deviations of the adsorption energies on the (100) and (111) surfaces were 0.03 eV and 0.01 eV, respectively, ensuring the robustness and statistical significance of our calculated adsorption energies. It clearly indicates that η2(C,O)-aldehyde configuration leads to excessive adsorption of HMF, which promotes direct hydrogenation to form BHMF and BHH (Fig. 4b). The explanation of this section and our revision of the manuscript are as follows:\nManuscript Lines 346-351:\nFigure 4b The adsorption energy of HMF with corresponding adsorption configurations on Ag NP and Ag NC.\nTable R1 The vibrational wave numbers of HMF adsorbed on Ag (100) and Ag (111), as well as their contributions to the Gibbs free energy.\nAg 100 Ag 111\nν (cm-1) T⋅S (eV) ν (cm-1) T⋅S (eV)\n3557.69 0.000 3725.72 0.000\n3188.77 0.000 3191.85 0.000\n3175.69 0.000 3179.54 0.000\n2972.07 0.000 2955.48 0.000\n2915.57 0.000 2911.82 0.000\n2843.40 0.000 2825.51 0.000\n1606.25 0.000 1633.80 0.000\n1526.96 0.000 1541.51 0.000\n1484.55 0.000 1494.89 0.000\n1431.75 0.000 1441.14 0.000\n1375.11 0.000 1388.59 0.000\n1368.90 0.000 1372.41 0.000\n1324.23 0.000 1335.36 0.000\n1266.96 0.000 1269.46 0.000\n1247.46 0.000 1229.68 0.000\n1205.86 0.001 1213.19 0.001\n1173.54 0.001 1170.32 0.001\n1154.02 0.001 1164.23 0.001\n1022.16 0.001 1021.40 0.001\n987.84 0.001 980.29 0.001\n963.54 0.001 971.45 0.001\n942.87 0.002 945.09 0.002\n926.54 0.002 937.93 0.002\n916.34 0.002 917.23 0.002\n851.50 0.002 859.05 0.002\n778.10 0.003 783.06 0.003\n761.09 0.003 752.22 0.003\n668.46 0.004 702.19 0.004\n607.61 0.006 617.62 0.005\n591.91 0.006 603.34 0.006\n501.09 0.008 488.53 0.009\n432.70 0.011 412.70 0.012\n332.45 0.016 326.01 0.017\n318.10 0.017 280.21 0.020\n265.27 0.021 213.24 0.026\n194.71 0.028 164.41 0.032\n161.33 0.033 153.60 0.034\n139.65 0.036 130.96 0.038\n115.99 0.041 86.12 0.048\n100.11 0.045 83.47 0.049\n87.34 0.048 62.46 0.057\n79.79 0.050 31.09 0.074\n73.12 0.053 28.62 0.077\n39.59 0.068 21.04 0.084\n13.01 0.097 5.98 0.117\nSI Lines 56-59:\nThe revised Perdew–Burke–Ernzerhof (RPBE)3 exchange-correlation functional was applied and the dispersion effects were accounted by employing semi-empirical D3 method.4, 5 For this method, the consideration of a Hubbard U parameter is typically not necessary.\n3. Hammer, B., Hansen L. B., Nørskov J. K. Improved adsorption energetics within density-functional theory using revised Perdew-Burke-Ernzerhof functionals. Phys. Rev. B 59, 7413-7421 (1999).\n4. Grimme, S., Ehrlich S., Goerigk L. Effect of the damping function in dispersion corrected density functional theory. J. Comput. Chem. 32, 1456-1465 (2011).\n5. Grimme, S., Antony J., Ehrlich S., Krieg H. A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu. J. Phys. D: Appl. Phys. 132, (2010).\n\nSpecific Comment R1-6: Computational Refinement: Although the theoretical calculations align with experimental outcomes, they fail to rationalize the high selectivity toward MAMF. We suggest: (i) Incorporating energy profiles for methylamine’s nucleophilic attack on the aldehyde group to quantify activation barriers. (ii) Comparing energy differences between hydrogenation and nucleophilic pathways to elucidate competitive reaction dynamics.\nResponse: We thank the reviewer for the insightful suggestions. We thoroughly considered the elementary steps of the nucleophilic attack and the hydrogenation steps during the C–N coupling reaction on different samples (Supplementary Fig. 23). The results show that the nucleophilic attack of methylamine on the absorbed HMF by Ag NP, through the Inter1a* and Inter2* intermediates, is thermodynamically more favorable than on Ag NC. At the same time, the hydrogenation step, through the formation of Inter1b*, on Ag NP is less favorable, indicating the good performance of Ag NP to suppress the direct hydrogenation and self-coupling side reactions. All these results support the conclusions of this work. The explanation of this section and our revision of the manuscript are as follows:\nManuscript Lines 321-326:\nFree energy calculations show that the nucleophilic attack of methylamine on the absorbed HMF by Ag NP is thermodynamically more favorable than on Ag NC. At the same time, the hydrogenation step on Ag NP is less favorable, indicating the good performance of Ag NP to suppress the direct hydrogenation and self-coupling side reactions. (Supplementary Fig. 23).23,67\nSI Lines 178-181:\nSupplementary Fig. 23. Free energy diagram of the electrochemical C–N coupling of HMF with methylamine on Ag NP (red curve) and Ag NC (blue curve).\n\nSpecific Comment R1-7: Substrate Scope Expansion: Additional substrate screening experiments are necessary to validate the universality of their design strategy for aldehyde-based C–N coupling reactions. Testing structurally diverse aldehydes would clarify whether the observed mechanism is generalizable.\nResponse: We thank the reviewer for the valuable comments. The study of the reaction between HMF and methylamine was driven by the high added value of its corresponding amine product, 5-[(methylamino)methyl]-2-furanmethanol (MAMF), which serves as a key chemical for the synthesis of the pharmaceutical Ranitidine. This consideration was stated in the Introduction section.\nWhile we acknowledge the high utility and value of other aldehyde-based C–N coupling reactions, the current work focuses on the fundamental mechanistic insights of adsorption engineering of reactants for selective C–N coupling. Our findings establish that controlling the HMF adsorption mode (η1(C)-aldehyde vs. η2(C,O)-aldehyde) is critical for favoring C–N coupling. We believe tuning the absorption behavior should be a universal strategy for promoting heterogeneous electrochemical C–N coupling reactions. However, this universality might not be proved by testing the catalytic performance using the Ag NP and Ag NC catalysts in this work with varied aldehyde or amine substrates. The adsorption configuration tuning should be achieved by specifically designing the electrocatalyst for the target substrate. For a reaction of interest, we need to analyze the features of the substrate molecule (such as the existence of aromatic ring, the length of the alkyl chain, etc) to guide the fabrication of a specific catalyst structure, which requires a series of systematic investigations. Such a proof might be out of the scope of our current work. We will conduct related studies to further verify the effectiveness of adsorption tuning for electrochemical organic synthesis. To emphasize this point, we have added the related discussion on the future direction in the revised manuscript.\nManuscript Lines 367-370:\nFuture efforts should focus on enabling green substrates, creating pathways to more valuable products, and designing scalable systems like the membrane electrode assembly (MEA), which will collectively pave the way for the industrial deployment of electrochemical C–N coupling technology.\n\nSpecific Minor Comments: The widely accepted resolution of HRTEM is 0.01 nm. Please correct the statements in Figure 1b and Figure 1d. All spelling and grammar in the manuscript should be thoroughly checked, such as “0.205n m” in Figure 1d. The authors' work still has some font issues that need to be corrected. Italicize “in situ” (e.g., Line 6 of Conclusions). Replace hyphens with en dashes for chemical bonds (e.g., “C-N” → C–N in the SI).\nResponse: We thank the reviewer for the detailed comments. We have thoroughly reviewed and revised the manuscript according to all the suggestions:\n1. HRTEM Resolution: We appreciate the clarification regarding HRTEM resolution. Related information has been updated in Fig. 1 (please find the details in the response to Specific Comment R1-4).\n2. Spelling and Grammar: All spelling and grammatical errors, including the specific example of “0.205n m” in Figure 1d, have been carefully checked and corrected throughout the manuscript. (find in the response to Specific Comment R1-4).\n3. Font Issues: All the expressions “in situ” are consistently italicized (e.g., in the Conclusions section and elsewhere). We have also replaced hyphens with en dashes for chemical bonds (e.g., “C–N”) as appropriate throughout the main text and Supplementary Information. Any remaining font issues and possible flaws have been thoroughly checked and corrected.\n\nSpecific Comment R2-1: Since the Ag NPs and Ag NCs exhibit different morphologies, their electrochemically active surface areas are likely to differ, which could affect their catalytic performance. The authors are encouraged to provide ECSA data to clarify whether this factor plays a substantial role in the observed activity differences.\nResponse: We thank the reviewer for the helpful comments. In this study, all reported current densities are normalized to the geometric surface area of the electrode (1.5 cm2). Additionally, we have measured the double-layer capacitance (C ) for both catalysts (Supplementary Fig. 15), dl which indicates that the Ag NP possesses a slightly smaller ECSA than the Ag NC. This result further supports that Ag NP has a better intrinsic performance, and the difference in C–N coupling selectivity is primarily driven by the distinct adsorption configurations modulated by the exposed facets. The explanation of this section and our revision of the manuscript are as follows:\nManuscript Lines 174-176:\nFurthermore, Ag NP possesses a slightly smaller electrochemically active surface area (ECSA) than Ag NC (Supplementary Fig. 15), suggesting that Ag NP has a better intrinsic performance.\nSI Lines 146-149:\nSupplementary Fig. 15. The CV profiles for (a) Ag NP and (b) Ag NC. Sweeping rates are 20, 40, 60, 80, and 100 mV s−1. Double-layer capacitance measurements of (c) Ag NP and (d) Ag NC.\n\nSpecific Comment R2-2: The effect of methylamine concentration on the reaction performance is not discussed. As the adsorption of methylamine may also influence the C-N coupling process, the authors should consider including a discussion or experimental results addressing this variable.\nResponse: We thank the reviewer for the inspiring comments. We have systematically explored the influence of methylamine concentration on the electrochemical C–N coupling reaction. Our results identified 1000 mM as the optimal methylamine concentration (Supplementary Fig. 12). This specific concentration was chosen to ensure an abundant supply of the nucleophile (methylamine), which is crucial for effectively promoting the desired C–N coupling reaction against competing pathways. Revisions of the manuscript are as follows:\nManuscript Lines 147-148:\nThe methylamine concentration was selected to be 1000 mM (Supplementary Fig. 12).\nSI Page Lines 134-136:\nSupplementary Fig. 12. Electrochemical performance of Ag NP for C–N coupling of HMF with methylamine at various methylamine concentrations.\n\nSpecific Comment R2-3: The manuscript presents charge-transfer resistance values derived from electrochemical impedance spectroscopy (EIS), but lacks information about the fitting procedure, including the equivalent circuit used and the associated standard errors. Providing these details would strengthen the credibility of the analysis.\nResponse: We thank the reviewer for the beneficial comments. We agree that providing these details will enhance the credibility of our analysis. The EIS data presented in Figure 3c were fitted using a Randles equivalent circuit model. The equivalent circuit mode is shown in Supplementary Fig. 18. The explanation of this section and our revision of the manuscript are as follows:\nManuscript Lines 200-204:\nThis result is further supported by the electrochemical impedance spectroscopy (EIS) study (Fig. 3c and Supplementary Fig. 18). The Ag NPs exhibit a reduced charge-transfer resistance (R = 12.6 Ω, error: 6.3%) compared to Ag NCs (R = 18.7 Ω, error: 5.6%), indicating enhanced interfacial electron transfer efficiency during the C–N coupling process.\nSI Lines 158-159:\nSupplementary Fig. 18. Equivalent circuit model used in the fitting of EIS.\n\nSpecific Comment R2-4: The manuscript reports selectivity values, but does not clarify whether these are calculated based on carbon-containing products, nitrogen-containing products, or total product yield. The authors should explicitly state the basis for the selectivity calculation.\nResponse: We thank the reviewer for the significant comments. We appreciate the reviewer’s request for clarification on the basis of our selectivity calculations and apologize for this oversight. We provided clarification on the calculation formula based on the carbon-containing substrate for the selectivity in the “Product identification and quantification” section of the Methods section. The explanation of this section and our revision of the manuscript are as follows:\nManuscript Lines 442-452:\nThe FE, selectivity and production rate are calculated according to Eqs. (2) – (6):\n（2）\n2𝑛𝑛𝐻𝐻2×F\nFEH2 = Q ×100%\n（3）\nMAMF\n2nMAMF×F\n𝖥𝖥𝖥𝖥 = 𝖰𝖰 ×100%\n（4）\n2nBHMF×F\nFEBHMF= Q ×100%\n（5）\nnMAMF\nSelectivityMAMF=𝑛𝑛𝐻𝐻 0 𝐻𝐻𝐻𝐻×𝑦𝑦𝐻𝐻𝐻𝐻𝐻𝐻×100%\n（6）\nMAMF\n−2 −1 𝑚𝑚𝐻𝐻𝑀𝑀𝐻𝐻𝐻𝐻\nProduction rate (𝑚𝑚𝑚𝑚𝑐𝑐𝑚𝑚 ℎ )=𝑆𝑆𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶×𝑡𝑡×100%\nwhere the , and represents the mole amounts of MAMF and BHMF after the electrolysis n . MThAeM F re n pBrHesMeFnts the mole amount of HMF before reaction. The y HMF represents 0\nthe yield of HMF.\n𝑛𝑛\nQ𝐻𝐻𝐻𝐻 r𝐻𝐻efers to the total charge. F is Faraday’s constant. S\ncatalyst\nis the geometric area\nof the catalyst loaded on the electrode, and t is the reaction time.\n\nSpecific Comment R2-5: The authors present a comparison of linear sweep voltammetry (LSV) curves for the C-N coupling and HMF reduction reactions on Ag NPs (Supplementary Fig. 14). However, the corresponding data for Ag NCs are missing. Including this comparison would provide a more complete picture of the performance differences between the two catalysts.\nResponse: We thank the reviewer for the insightful comments. We agree that including the corresponding linear sweep voltammetry (LSV) curves for Ag NCs, comparing the C–N coupling reaction (with HMF and methylamine) and the background HMF reduction or hydrogen evolution reaction (without HMF), would provide a more complete and direct comparison of the electrochemical behavior of the two catalysts. Therefore, the results were collected and presented in Fig 2a and Supplementary Fig. 13. The results indicate that the C–N coupling reaction exhibits a lower onset potential compared to the hydrogenation of HMF. However, as the applied potential becomes increasingly negative, the HMF reduction reaction consistently shows a larger current density. This kinetic preference for HMF reduction on Ag NC is in perfect agreement with our overall findings that Ag NC favors side reactions, particularly hydrogenation (BHMF), due to its distinct η2(C,O)-aldehyde adsorption configuration. This further supports our mechanistic proposal that the specific adsorption mode on Ag NC leads to an activation of the C=O bond that is more prone to direct reduction rather than nucleophilic attack by methylamine, thereby explaining the lower C–N coupling selectivity observed on Ag NC. The explanation of this section and our revision of the manuscript are as follows:\nManuscript Lines 149-157:\nLinear sweep voltammetry (LSV) curves (Fig. 2a and Supplementary Fig. 13) indicate that both Ag NP and Ag NC exhibit enhanced current densities upon the addition of HMF, suggesting that the electrochemical C–N coupling of HMF with methylamine requires a lower overpotential compared to the hydrogen evolution reaction (HER). Ag NP achieves a current density of 20 mA cm–2 at –0.45 V vs. RHE, which is higher than that of Ag NC (~14 mA cm–2). Notably, the Ag NC exhibits a higher current density of HMF reduction as the potential becomes more negative (lower than –0.45 V), suggesting that direct HMF reduction might be more favorable on Ag NC.\nSI Lines 138-141:\nSupplementary Fig. 13. LSV curves of (a) Ag NP and (b) Ag NC for electrochemical C–N coupling reaction and electroreduction of HMF.\n\nSpecific Comment R2-6: Several key experimental procedures are insufficiently described. For instance, the rotary steaming step used before liquid product quantification (mentioned in Supplementary Fig. 11) is not included in the Methods section, and specific operating parameters are not provided. Additionally, variables used in Equations (2)-(6) are not clearly defined. The authors should revise the manuscript to address these omissions.\nResponse: We thank the reviewer for the practical comments. We acknowledge that clarity and completeness in methodology are crucial for reproducibility. We have revised the manuscript to address these points comprehensively. Revisions of the manuscript are as follows:\nManuscript Lines 433-438:\nFor quantification of liquid products, the collected catholyte was first subjected to rotary evaporation at 40 °C to remove residual methylamine. Subsequently, the obtained liquid products were diluted fivefold and analyzed by high-performance liquid chromatography (HPLC, Agilent Technologies 1200 Infinity) equipped with a variable wavelength detector (VWD).\nManuscript Lines 448-452:\nThe , and represents the mole amounts of MAMF and BHMF after the electrolysis.\nThe represents the mole amount of HMF before reaction. The represents the yield of\nHMFn. M 0Q A r M e F fers to nth B e H t M o F tal charge. F is Faraday’s constant. M is the catalyst loading. S is the catalyst\narea.𝑛𝑛 t 𝐻𝐻 i 𝐻𝐻 s 𝐻𝐻 the reaction time. 𝑦𝑦𝐻𝐻𝐻𝐻𝐻𝐻\n\nSpecific Comment R2-7: Error bars are absent in the Faradaic efficiency data presented in Fig. 3e,f. To demonstrate reproducibility and data reliability, the authors should include error bars.\nResponse:\nWe thank the reviewer for the valuable comments. We apologize for the oversight in omitting error bars from the Faradaic efficiency data presented in Figure 3e and 3f. We agree that including error bars is essential for demonstrating the reproducibility and reliability of our data. All experiments were performed in at least three parallel repeated runs, and the error bars represent the standard deviation of these results, consistent with the error bars already present in other figures (e.g., Fig. 2b, c, e, f and Fig. 3a, b, c, d). The explanation of this section and our revision of the manuscript are as follows:\nManuscript Lines 216-220:\nFig. 3 Electrokinetic studies for C–N coupling reaction. (e) Partial current density and FE of MAMF as a function of the charges passed. (f) The relationship between HMF concentration and partial current density of MAMF, and the corresponding FE of MAMF. The error bars represent the standard deviation of three parallel repeated results.\n\nSpecific Comment R3-1: The manuscript is generally well-structured, but the figures and schemes need clearer labeling. For example, Scheme I (page 3) is referenced but not included in the main text, which may confuse readers. Figure 2d and 2e are described as showing \"potential-dependent production rate\" and \"stability tests,\" but the axes labels in the figure are unclear. Please ensure all axes and legends are explicitly defined.\nResponse: We thank the reviewer for the valuable comments. According to the suggestions, in the third paragraph of the Introduction, we refer to Scheme 1 to illustrate the pathways for the C–N coupling reaction and its competing side reactions involved in this work, with the image shown alongside. During the discussion of the results, we also refer to Scheme 1 to clarify the impact of the adsorption behavior on the reaction mechanism. Regarding Fig. 2d and 2e, we have revised the figure caption to clearly explain the content, thereby enhancing the readability and interpretability of the data. We have double-checked the manuscript formatting to ensure its clear visibility and proper integration for all readers. Revisions of the manuscript are as follows:\nManuscript Lines 55-57:\nScheme 1 Schematic illustration of reaction pathways that generate (a) MAMF, (b) BHMF, and (c) BHH for heterogeneous electrochemical C–N coupling of HMF and methylamine.\nManuscript Lines 320-321:\nThe η1(C)-aldehyde adsorption on Ag NP induces moderate electron withdrawal from the carbonyl moiety compared to the η2(C,O)-aldehyde adsorption on Ag NC, thereby enhancing its susceptibility to nucleophilic attack by absorbed methylamine (Scheme 1a) rather than the hydrogenation (Scheme 1b) and dimerization (Scheme 1c).19,26\nManuscript Lines 185-190:\nFig. 2 Catalytic performance of Ag NP and Ag NC. (a) LSV curves of Ag NP and Ag NC in the electrolyte (phosphate buffer solution with methylamine) with or without 20 mM HMF. (b, c) Product FEs and MAMF selectivity as a function of potential over Ag NP (b) and Ag NC (c). (d) Production rate of MAMF over Ag NP and Ag NC at different potentials. (e, f) Stability tests of Ag NP (e) and Ag NC (f) showing the change of Faradaic efficiency of MAMF with the progress of the reaction. The error bars represent the standard deviation of three parallel repeated results.\n\nSpecific Comment R3-2: The introduction lacks a focused discussion on recent advances in electrochemical C–N coupling, particularly for biomass-derived substrates. Highlighting specific challenges in HMF amination (e.g., overhydrogenation, dimerization) and how this work addresses them would sharpen the novelty.\nResponse: We thank the reviewer for the instructive comments. In the Introduction, we have summarized the current challenges of low selectivity and their underlying causes, primarily stemming from competing side reactions like C=O hydrogenation and C–C dimerization. We then introduce the specific work that addresses these problems through the analysis of the reaction mechanism. The subsequent paragraph further elucidates our strategy for tackling this issue, focusing on precise adsorption configuration modulation. Corresponding revisions of the manuscript are as follows:\nManuscript Lines 59-76:\nMany electrocatalysts have been investigated for this reaction (Pt, Cu, Sn, Zn, and Ag).9,11\nHowever, a lack of rational catalyst design has resulted in the easy occurrence of side reactions and low selectivity of C–N coupling12,13. Mechanistic studies have demonstrated that promoting the nucleophilic attack step is crucial for effectively enhancing the overall selectivity of C–N coupling reactions11,14. Taking the electrochemical C–N coupling of HMF and methylamine as an example, the reaction pathway involves multiple steps (Scheme 1).3,11 Typically, HMF can be activated by the catalyst, forming the absorbed HMF (HMF*).9,15 Then, the target product MAMF is synthesized through two key steps16-18: (1) nucleophilic addition reaction of methylamine with the carbonyl group of HMF* to form the aldimine intermediate, and (2) subsequent reduction of the aldimine with protons from the electrolyte and electrons from the electrode to produce the MAMF (Scheme 1a). However, the hydrogenation and dimerization of HMF compete with the desired C–N coupling reaction to form 2,5-bis(hydroxymethyl)furan (BHMF) and bis(hydroxymethyl)hydrofuroin (BHH), respectively, leading to low selectivity (Scheme 1b, c).19-21 Therefore, precisely modulating the reactivity of the target aldehyde carbonyl group to facilitate nucleophilic attack becomes a key strategy for improving the selectivity of electrochemical C–N coupling.\n\nSpecific Comment R3-3: While facet-dependent adsorption modulation is not novel, its application to electrochemical C-N coupling of HMF is innovative. However, the introduction lacks a critical comparison with recent works on similar systems (e.g., Cu or Pd catalysts for HMF upgrading). A table comparing FE/selectivity with prior studies would better contextualize the advancements.\nResponse: We thank the reviewer for the helpful suggestion. We agree that a critical comparison with recent works would further contextualize the advancements of our study. Therefore, we have cited and explained some recent related works (see the response to Specific Comment R3-2). Besides, we have added a comprehensive comparison table (Supplementary Table S1). This table summarizes the performance metrics (specifically Faradaic efficiency and selectivity) of our Ag NP catalyst alongside other relevant reported catalysts for electrochemical C–N coupling of HMF or similar biomass-derived aldehydes, including those utilizing different metal catalysts (e.g., Cu, Pd, or other noble/non-noble metals) and various reaction conditions. This direct comparison will clearly highlight the superior performance achieved by our Ag NP catalyst, particularly its exceptional selectivity for MAMF. The explanation of this section and our revision of the manuscript are as follows:\nManuscript Lines 162-164:\nThe highest FE of 89.2% could be achieved by Ag NP with a selectivity of 90.2% at –0.45 V vs. RHE (Fig. 2b), which outperforms most previously reported catalysts (Supplementary Table S1).9,11-13,36\nSI Lines 183-184:\nSupplementary Table S1\nThe electrochemical biomass C–N coupling performance of recent catalysts\nBiomass-based Nitrogen FE of C–N coupling\nCatalysts Ref\nmolecule source product (%)\nRu NPs α-hydroxyl acids NH 43 7\n2 2\nAg benzaldehyde NH 80 9\n3\n2-ketoglutaric\nCNTs NH 90 10\n3\nacid\nCu acetophenone CH NH 83 11\n3 2\n5-\nNH CH CH\n2 2\nTiS hydroxymethylfur 34 12\n2\nfural\n5-\nThis\nAg NP hydroxymethylfur CH NH 90\n3 2\nwork\nfural\nSupplementary References\n7. Deng, W., et al. Catalytic amino acid production from biomass-derived intermediates. Proceedings of the National Academy of Sciences 115, 5093-5098 (2018).\n8. Fukushima, T., Yamauchi M. Electrosynthesis of amino acids from biomass-derivable acids on titanium dioxide. Chem. Comm. 55, 14721-14724 (2019).\n9. Schiffer, Z. J., Chung M., Steinberg K., Manthiram K. Selective electrochemical reductive amination of benzaldehyde at heterogeneous metal surfaces. Chem. Catal. 3, (2023).\n10. Xiao, Y., et al. Electrocatalytic amino acid synthesis from biomass-derivable keto acids over ball milled carbon nanotubes. Green Chem. 25, 3117-3126 (2023).\n11. Kim, T., et al. Mechanistic investigation of electrocatalytic reductive amination at copper electrode. Chem. Comm. 59, 4818-4821 (2023).\n12. Zhang, M., et al. Designed TiS2 nanosheets for efficient electrocatalytic reductive amination of biomass-derived furfurals. Green Chem. 24, 9570-9578 (2022).\n\nSpecific Comment R3-4: The synthesis methods for Ag NP and Ag NC are well-documented, but the absence of TEM/SEM images in the main text (relegated to Supplementary Figs. 2–3) weakens the immediate validation of morphology. Key characterization data (e.g., lattice spacing, XRD peaks) should be highlighted in the main text. Stability tests over 10 cycles (Fig. 2e, f) are insufficient to claim long-term durability. Additional data (e.g., 24-hour chronoamperometry) would strengthen the practical relevance.\nResponse: We thank the reviewer for the insightful comments. We have revised the manuscript to include SEM images and their corresponding particle size distributions directly in the main text (Figure 1a–b). The key high-resolution TEM (HRTEM) images and their corresponding fast Fourier transform (FFT) patterns (Figure 1c–f), along with the X-ray diffraction (XRD) patterns (Figure 1g), are also presented in the main text. These data provide immediate and conclusive evidence of the distinct morphologies, lattice spacings, and predominant crystallographic facets of the obtained samples. Additionally, we have performed and included 24-hour stability tests to further strengthen the demonstration of long-term durability and practical relevance. The explanation of this section and our revision of the manuscript are as follows:\nManuscript lines 121-123:\nScanning electron microscopy (SEM) images revealed that Ag NP exhibits a nearly spherical morphology with an average diameter of approximately 30 nm, whereas Ag NC exhibits cubic shapes (Fig. 1a–b).\nManuscript Lines 137-141:\nFig. 1 Characterization of electrocatalysts. (a-b) SEM images and corresponding size distributions of as-prepared Ag NP (a) and Ag NC (b). (c-f) TEM (c, e) and HRTEM (d, f) images of Ag NP (c,d) and Ag NC (e,f). (g) XPS spectra of as-prepared Ag NP and Ag NC. (h) XRD patterns of Ag NP and Ag NC (JCPDF#04–0783).\nManuscript Lines 186-191:\nFig. 2 Catalytic performance of Ag NP and Ag NC. (a) LSV curves of Ag NP and Ag NC in the electrolyte (phosphate buffer solution with methylamine) with or without 20 mM HMF. (b, c) Product FEs and MAMF selectivity as a function of potential over Ag NP (b) and Ag NC (c). (d) Production rate of MAMF over Ag NP and Ag NC at different potentials. (e, f) Stability tests of Ag NP (e) and Ag NC (f) showing the change of Faradaic efficiency of MAMF with the progress of the reaction. The error bars represent the standard deviation of three parallel repeated results.\n\nSpecific Comment R3-5: The authors attribute the high selectivity to η¹(C)-aldehyde adsorption but do not fully address how methylamine adsorption influences the reaction. Competitive adsorption between HMF and methylamine could alter pathways; this should be discussed. Product quantification relies on LC/GC, but potential intermediates (e.g., aldimine) are not tracked. Including time-dependent product distribution would clarify reaction kinetics.\nResponse: We thank the reviewer for the significant comments. We have systematically optimized the methylamine concentration to 1000 mM, ensuring an abundant supply of the nucleophile. Furthermore, our in situ Raman control experiments (Supplementary Figure 21) clearly show the characteristic peaks of methylamine, indicating its stable and sufficient adsorption on the catalyst surface under reaction conditions.\nRegarding the tracking of potential intermediates like aldimine, we have performed time-resolved 1H NMR spectroscopic characterization of the reaction mixture under operando electrochemical conditions. The results show that the imine content stays at a consistently low level throughout the electrochemical reaction with a general decreasing trend (Supplementary Fig. 19). This observation indicates that relying solely on spontaneously formed imine intermediates in the bulk solution is insufficient to account for the observed product formation rate and consumption during the electrochemical process. The η1(C)-aldehyde adsorption configuration of HMF on Ag NP appropriately promotes the polarization of the C=O bond, thereby facilitating the nucleophilic attack by methylamine and enhancing the overall selectivity of the C–N coupling reaction. The dramatic differences in product distribution and selectivity observed between Ag NP and Ag NC (Fig. 2b, c) further corroborate this surface-mediated activation. This distinct catalytic behavior strongly supports that the catalyst surface actively steers the reaction pathway by modulating HMF adsorption. The explanation of this section and our revision of the manuscript are as follows:\nManuscript Lines 147-148:\nThe methylamine concentration was selected to be 1000 mM (Supplementary Fig. 12).\nSI Page Lines 134-136:\nSupplementary Fig. 12. Electrochemical performance of Ag NP for C–N coupling of HMF with methylamine at various methylamine concentrations.\nManuscript Lines 209-214:\nBesides, time-resolved 1H NMR spectroscopic characterization of the reaction mixture was performed under operando electrochemical conditions (Supplementary Fig. 19). The result shows that the imine content stays at a consistently low level throughout the electrochemical reaction with a general decreasing trend, suggesting the reductive coupling between HMF and methylamine is an electrocatalytic process that occurs at the surface of the electrode.\nSI Lines 160-163:\nSupplementary Fig. 19. (a-e) Time-resolved 1H NMR for the electrolyte during the C–N coupling on Ag NP. (f) The concentration of imine as charge passed.\n\nSpecific Comment R3-6: The DFT calculations lack methodological details (e.g., functional, basis set, slab models). A brief description in the main text or Methods section should be provided for reproducibility.\nResponse: We thank the reviewer for the helpful comments. We agree that providing comprehensive details is crucial for reproducibility and transparency. We have revised the “Computational Methods” subsection in the revised Supplementary Information. This section now includes all essential parameters and settings used in our DFT calculations. The explanation of this section and our revision of the manuscript are as follows:\nSI Lines 53-69:\nComputational setup and methods.\nDensity functional theory methods. Density functional theory (DFT) calculations were performed utilizing the Vienna Ab Initio Simulation Package (VASP) in conjunction with the projector augmented wave (PAW) method.1, 2 The revised Perdew–Burke–Ernzerhof (RPBE)3 exchange-correlation functional was applied and the dispersion effects were accounted by employing semi-empirical D3 method.4, 5 For this method, the consideration of a Hubbard U parameter is typically not necessary. The cutoff energy was set to 450 eV. The convergence threshold of electronic and force was set to 10−6 eV atom–1 and 0.02 eV Å–1, respectively. The Methfessel-Paxton smearing was applied with a smearing width of 0.15 eV.\nComputational model. Ag(111) and Ag(100) surface was modeled by a (3√3×3√3)R30° supercell and a 6×5 supercell, respectively. All surface models were composed of 4 layers atoms with 2 uppermost layers relaxed. The metal slabs were separated by a ~20 Å vacuum space. The Brillouin zone was sampled at a 3×3×1 k-point mesh with Γ-centered for hexagonal supercells and Monkhorst Pack for orthorhombic supercells. The Gibbs free energy under ambient conditions was corrected using a computational hydrogen electrode (CHE) model.6\n\nSpecific Comment R3-7: The proposed mechanism assumes direct nucleophilic attack by methylamine on adsorbed HMF but does not address the role of protonation states or pH effects. Experiments varying pH could elucidate how proton availability impacts aldimine formation and reduction.\nResponse: We thank the reviewer for the constructive comments. We chose pH 11 for the reaction electrolyte because at this pH (which is above the pKa of methylamine, ~10.6), a significant portion of methylamine is present in its neutral, nucleophilic form (CH NH ), which is essential for its efficient nucleophilic attack on the HMF carbonyl group to form the aldimine intermediate. This optimized pH condition ensures the availability of the active nucleophile.\nFurthermore, our kinetic isotope effect (KIE) studies (Fig. 3d) provide direct evidence for the involvement of protons in the reaction mechanism. The observed cathodic shift of 145 mV upon switching from H O to D O strongly indicates that a proton-coupled electron transfer (PCET) step is significant for the C–N coupling reaction. This confirms the important role of proton dynamics in the reduction of the aldimine intermediate and the overall C–N bond formation, thus addressing the involvement of proton availability in our proposed inner-sphere mechanism.\nWhile systematic experiments varying pH across a wider range could indeed provide further detailed insights into how proton availability specifically impacts aldimine formation and subsequent reduction, our current study primarily focuses on elucidating the pivotal role of HMF adsorption configurations in steering reaction selectivity at an optimized pH. Exploring the full pH dependence is a valuable and logical direction for future research to further refine the understanding of the complex interplay between surface adsorption, electron transfer, and proton dynamics. The explanation of this section and our revision of the manuscript are as follows:\nManuscript Lines 412-414:\nSince the pK of CH NH + is about 10.6, adjusting the solution pH to 11 ensures a significant portion of the amine to present as a base form to react with HMF to form aldimine.\nManuscript Lines 204-208:\nFurthermore, electrochemical experiments with H/D kinetic isotope effect (KIE) studies were conducted on the Ag NP catalyst. The cathodic shift of 145 mV (Fig. 3d) suggests that the proton-coupled electron transfer step is significant for the C–N coupling reaction, indicating the important role of proton dynamics in the reduction of the HMF intermediate and C–N bond formation.\n\nSpecific Comment R3-8: The manuscript does not consider potential surface reconstruction of Ag NPs/NCs under operating conditions. XPS or post-reaction TEM of used catalysts would verify structural stability and rule out facet restructuring during electrolysis. Competitive adsorption between HMF and methylamine is ignored. Surface coverage studies (e.g., via electrochemical quartz crystal microbalance) could clarify whether methylamine adsorption limits reaction rates.\nResponse: We thank the reviewer for the important comments. Regarding potential surface reconstruction of Ag NP/NC under operating conditions, we have addressed this critical aspect with abundant experiments. As detailed in the “Result and Discussion” section and supported by Supplementary Figures 16–17, we performed post-reaction morphological and crystallographic characterization (TEM and XRD) of the used catalysts after 10 cycles of electrolysis. These results conclusively demonstrate that the morphology and crystal structure, including the predominant exposed facets, of both Ag NP and Ag NC remain almost unchanged. This robust structural stability under operando conditions ensures that the observed facet-dependent catalytic performance and selectivity are genuinely attributable to the intrinsic properties of the as-synthesized crystal facets rather than dynamic reconstruction.\nAdditionally, regarding the competitive adsorption behavior of substrates, our systematic optimization of methylamine concentration (to 1000 mM) ensures its abundant supply, and in situ Raman spectroscopy (Supplementary Figure 21, response to Specific Comment R3-5) confirms its stable adsorption on the catalyst surface. Furthermore, our HMF concentration dependence study (Figure 3f) indicates that HMF adsorption is a key limiting factor at lower concentrations, following Langmuir-Hinshelwood kinetics. These findings collectively suggest that under our optimized conditions, methylamine adsorption is not the rate-limiting step, and the primary kinetic and selectivity control stems from the activation and adsorption configuration of HMF. While techniques like electrochemical quartz crystal microbalance (EQCM) could offer further quantitative insights into surface coverage, we could not conduct this experiment due to the limitations of the resources. It would be a valuable direction for more in-depth kinetic studies in the future, building upon the fundamental mechanistic understanding established in this work.\n\nSpecific Comment R3-9: The use of a three-electrode H-cell with a bipolar membrane may not reflect industrially relevant conditions. Testing in a flow cell or membrane electrode assembly (MEA) would better demonstrate scalability.\nResponse: We thank the reviewer for the beneficial comments. We agree with the reviewer that a three-electrode H-cell setup may not directly reflect industrially relevant conditions or demonstrate immediate scalability. However, it is important to emphasize that the primary objective of this fundamental research is to elucidate the intricate reaction mechanism of electrochemical C–N coupling, particularly the pivotal role of substrate adsorption configurations. Indeed, we have already performed preliminary investigations into the electrocatalytic C–N coupling reaction in a membrane electrode assembly (MEA) setup, utilizing the same reaction conditions but at higher HMF substrate concentrations (Fig. R2a). Our activity test results from the MEA system indicate a significant enhancement in reaction current and rate, primarily due to the reduced resistance afforded by the thin liquid film within the MEA, which effectively lowers the ohmic drop (Fig. R2b). However, we observed a decrease in reaction selectivity under these high substrate concentration conditions in the MEA, which we attribute to limitations in the current catalyst design when operating at such elevated concentrations and current densities.\nThis observation highlights a new set of challenges that require further catalyst engineering specific to MEA operation. Consequently, we have dedicated another work (Chem. Eng. Sci., 317, 122039) specifically to the study of electrocatalytic C–N coupling reactions within membrane electrode reactors. In that work, we are focusing on introducing modifications, such as the incorporation of Ru, to enhance the adsorption and activation of imine intermediates, thereby aiming to establish a robust electrocatalytic C–N coupling system capable of operating efficiently under high substrate concentrations and high current densities (Fig R2c). Therefore, while demonstrating scalability in MEA is undoubtedly crucial for the eventual practical application, the current manuscript remains focused on providing the fundamental mechanistic understanding of adsorption engineering in the H-cell, which serves as the essential groundwork for future advancements in MEA-based systems. Our subsequent work directly addresses the scalability and high-concentration challenges in MEA, building upon the mechanistic insights gained from this study. We have added the related discussion on the future direction in the revised manuscript.\nFig. R2 Electrocatalytic C–N coupling reaction between HMF and methylamine in a membrane electrode assembly (a) Conversion of HMF and selectivity of MAMF for Ag NP with varying loadings in MEA under HMF concentration of 0.1 M and current density of 80 mA cm⁻2. (b) Conversion of HMF and selectivity of MAMF in MEA on Ag NP. (c) Schematic illustration of the effective modulation of substrate adsorption configurations by Ag NP and the synergistic enhancement of imine intermediate adsorption by Ru.\nManuscript Lines 367-370:\nFuture efforts should focus on enabling green substrates, creating pathways to more valuable products, and designing scalable systems like the membrane electrode assembly (MEA), which will collectively pave the way for the industrial deployment of electrochemical C–N coupling technology.\n\nSpecific Comment R3-10: The environmental impact of using methylamine (a toxic reagent) is not addressed. Exploring greener amine sources (e.g., ammonia) or coupling with renewable NH₃ synthesis could enhance sustainability.\nResponse: We thank the reviewer for the meaningful comments. Our selection of methylamine as the nitrogen source in this study was primarily driven by the high added value of the target product, 5-[(methylamino)methyl]-2-furanmethanol (MAMF), which is a key intermediate for the synthesis of the pharmaceutical Ranitidine. This specific application highlights a direct pathway to a high-value chemical from biomass. Our current work focuses on establishing the fundamental mechanistic principles of adsorption engineering for selective C–N coupling. While exploring greener and more sustainable amine sources, such as aqueous ammonia or even coupling with electrochemical ammonia synthesis from renewable feedstocks, represents a highly significant and promising direction for future research. A key challenge with using ammonia as an N source is the difficulty in selectively obtaining specific primary or secondary amine products. This would undoubtedly enhance the overall sustainability profile of electrochemical C–N coupling processes, and is a direction we are committed to investigating in our future work. We have added the related discussion on the future direction in the revised manuscript.\nManuscript Lines 367-370:\nFuture efforts should focus on enabling green substrates, creating pathways to more valuable products, and designing scalable systems like the membrane electrode assembly (MEA), which will collectively pave the way for the industrial deployment of electrochemical C–N coupling technology."}, {"round": 2, "reviewer_comments": {"reviewer_1": "In reviewing the responses, we note that the authors are trying to improve their work and have corrected several issues. However, our major concerns remain unresolved. We still hold the view that the authors seem to be insufficiently informed regarding the issues we highlighted in our previous comment. Moreover, the revisions to the mechanistic discussion and theoretical calculations lack justification, which is highly irresponsible and further exacerbates our concerns regarding the reliability of the data. The following comments should be taken for more consideration.\n1. The authors emphasize that the difference in exposed crystal facets between Ag NPs and Ag NCs is key to altering selectivity, suggesting that the (111) facet dominates the high selectivity in hydrogenation reactions. However, due to facet heterogeneity, we believe that this interpretation overstates the data. The potential contribution of the (200) facet, or even involvement of the (220) facet, cannot be ruled out. Furthermore, synergistic effects between different crystal facets may also play a role. Clearly, attributing the regulation of selectivity solely to a single facet is unreasonable.\n2. The authors propose that the adsorption pattern of furan on the Ag surface is critical for selectivity. However, the current experimental evidence may not sufficiently support this claim. Therefore, we believe the authors should expand the substrate scope and verify the generality of their proposed synthetic strategy, particularly by exploring furan-related structures.\n3. Regarding the experiment tracking intermediates via 1H NMR, we find the results puzzling. If the imine is a key intermediate, its concentration should remain relatively stable during continuous generations. The authors need to explain this observation.\n4. Additionally, concerning the imine intermediate, we suggest that the authors should directly use it as a reactant in electrocatalytic selective reduction to validate the mechanism. We are particularly concerned about whether this species can remain stable under alkaline electrolytic conditions.\n5. Furthermore, the central challenge of this reaction remains unclear. While the authors assert that controlling selectivity is a major obstacle in the direct reduction process, this issue would be bypassed by using the pre-synthesized imine as the substrate. Moreover, the formation of the imine itself does not appear difficult, and the authors acknowledge its spontaneous formation under specific conditions. Hence, the significance of this study remains unclear to us.\nThe authors should address the aforementioned questions seriously and directly and persuade me about the reliability and validity of all the data. Additionally, the findings presented here starkly diverge from the rigorous expectations and stringent standards that are synonymous with the high-impact, prestigious Nature Communications. These discrepancies underscore a significant departure from the normative benchmarks that the scientific community anticipates from publications within this esteemed domain, highlighting a need for alignment with the journal's commitment to publishing only the most groundbreaking and impactful research.", "reviewer_2": "The authors have fully addressed my concerns. I think the current version is suitable for publication in Nature Communications", "reviewer_3": "The authors have addressed all my concerns reasonably well. I do not have further comments. Congratulations to the authors for the nice piece of contribution."}, "author_response": "Response to R1: We sincerely appreciate the reviewer’s insightful comments and helpful suggestions. We apologize if our previous revision did not sufficiently articulate the justification for our mechanistic discussion and theoretical calculations. We have now extensively revised the manuscript to improve the rigorous nature of our findings. Detailed responses to each point are listed below.\n\nResponse to R1-1: We sincerely appreciate the reviewer’s valuable comments. We fully agree that the selectivity could not be dictated by a single crystallographic facet and that the inevitable co-exposed facets may also contribute. In this work, our aim is to elucidate how the dominant exposed facet of the Ag catalyst modulates substrate adsorption and thereby steers the reaction pathway. Specifically, we seek to demonstrate that facet engineering provides an effective strategy to enhance the selectivity of electrochemical C–N coupling reactions. To this end, we synthesized Ag nanoparticles (Ag NPs) and Ag nanocubes (Ag NCs) that predominantly expose the (111) and (100) facets, respectively. Since the existence of corresponding diffraction peaks in the XRD pattern does not surely mean the material exposes certain facets, we have supplemented additional HRTEM analyses (Supplementary Fig. 4). These results further confirm that Ag NPs mainly expose the (111) facet, while Ag NCs are largely enclosed by (100) facets, in line with our previous findings. Moreover, activity tests, in situ Raman spectroscopy, and DFT calculations collectively show that the η1(C)–CHO adsorption configuration of HMF on Ag(111) could play a significant role in promoting the C–N coupling pathway.\nWe acknowledge, however, that trace amounts of other facets still exist and could, in principle, influence the reaction. To assess the magnitude of this effect, we performed DFT calculations to compare the reaction energy barriers for C–N coupling on Ag(110), Ag(100), and Ag(111) surfaces (Supplementary Fig. 28). The results indicate that the reaction barrier on Ag(111) is –0.28 eV, lower than –0.14 eV and –0.17 eV on Ag(100) and Ag(110), respectively, underscoring the key role of the (111) facet in facilitating the C–N coupling process. In addition, we examined the facet-dependent hydrogenation behavior. DFT calculations show that Ag(111) exhibits the lowest hydrogenation energy barrier (0.07 eV), compared with Ag(100) (0.24 eV) and Ag(110) (0.13 eV). This low barrier enables rapid hydrogenation of the imine intermediate, thereby accelerating overall conversion and enhancing C–N coupling selectivity. These results suggest that possible contributions from minor facets such as (220)/(110) are not expected to significantly alter the overall product distribution.\nNevertheless, we agree that synergistic effects between different facets cannot be completely excluded. We apologize for not explicitly addressing this point in the original manuscript. In the revised version, we have carefully moderated our statements and clarified the potential role of co-existing facets to improve the scientific rigor and balance of our discussion.\n\nResponse to R1-2: We sincerely appreciate the reviewer’s valuable suggestions. To further verify the generality of our catalytic strategy, we expanded the substrate scope to include 2-furaldehyde and 5-methylfurfural. With 2-furaldehyde and 5-methylfurfural as substrates and methylamine as the nucleophile, Ag NP delivered FEs of 63.0% and 81.0% toward the corresponding amines, whereas Ag NC afforded lower FEs of 50.4% and 69.1%, respectively (Supplementary Fig. 20a,b). Replacing methylamine with ammonia as the nitrogen source in the coupling reaction with HMF preserved a high amine FE of 65.3% on Ag NP, higher than that of 29.1% on Ag NC (Supplementary Fig. 20c). Taken together, these results validate a facet-governed adsorption-reactivity paradigm. The Ag NP surface favors the η1(C)–CHO configuration, translates into superior product selectivity across distinct furfural substrates and nitrogen sources, indicating the versatility of facet engineering for electrochemical amination (Supplementary Fig. 20d). The corresponding discussion has been incorporated into the revised manuscript to strengthen the scientific rigor and completeness of our study.\n\nResponse to R1-3: We sincerely appreciate the reviewer’s valuable suggestions. In principle, the concentration of imine intermediates can become time-independent under steady-state conditions, as has been well documented for thermal catalytic reductive amination (Refs: Chem. Rev. 1963, 63, 489-510; Chem Catal. 2023, 3, 100500). When the system operates under steady-state conditions, the imine concentration can be treated as quasi-steady. However, in an electrocatalytic system, such a steady-state imine concentration can only be maintained when (i) the reaction rate at the electrode surface is constant, (ii) the diffusion layer thickness has been stabilized, and (iii) the concentration gradient no longer varies with time.\nIn our batch reactor and under the applied reaction conditions, these steady-state criteria are not fully satisfied. The imine intermediate is continuously generated, but it can simultaneously undergo hydrolysis at the electrode surface or further reduction to the amine product under the applied potential (Ref: Chem Catal. 2023, 3, 100500). In addition, partial adsorption of the imine species on the electrode surface perturbs its concentration in the liquid phase. As a result, the time-dependent 1H NMR signal of the imine reflects a non-steady interplay among formation, hydrolysis, and electroreduction processes, rather than a simple steady-state condition.\nMoreover, during electrolysis with a Chronopotentiometry method, the current density gradually decreases as the substrate in the vicinity of the electrode is consumed and mass-transport limitations evolve. This change in current density directly alters the rate of imine formation and consumption, further reinforcing the intrinsically dynamic character of the system. Consequently, the electrochemical reactor exhibits complex, time-dependent behavior, and the imine concentration is not expected to remain strictly constant.\nTo test this interpretation, we additionally performed 1H NMR measurements under non-electrolytic conditions (Supplementary Fig. 23). In the absence of electrolysis, the imine concentration remains nearly constant, with only minor fluctuations, consistent with a dynamic balance between imine formation and hydrolysis.\nTo improve the clarity of our proposed mechanism and to rationalize the NMR observations, we have incorporated these considerations and the new control experiments into the revised manuscript.\n\nResponse to R1-4: We sincerely appreciate the reviewer’s valuable suggestions. To directly verify the formation and reactivity of the imine intermediate, we first synthesized it via the condensation of 5-hydroxymethylfurfural (HMF, 1 mmol) and methylamine (CH NH , 10 mmol) in 3 mL of ethanol under reflux at 50 °C for 6 h (Ref: New J. Chem. 2023, 47, 18995–19004). The as-synthesized imine was then subjected to electrochemical reduction at –0.45 V vs. RHE in 0.5 M K HPO electrolyte (pH 11). The direct imine reduction produces MAMF with a FE of 39.8%, demonstrating that the imine is a kinetically competent and mechanistically relevant intermediate in the electrochemical reductive C–N coupling between HMF and methylamine.\nMoreover, the BHMF and BHH were also detected after the electrolysis (Supplementary Fig. 1). To rationalize the formation of BHMF and BHH, we propose that the imine undergoes partial hydrolysis at the alkaline electrode interface during electrolysis, regenerating HMF and methylamine. The regenerated HMF can then follow competitive reduction and coupling pathways, giving BHMF and BHH as side products (Supplementary Scheme 1). To validate this hypothesis, we evaluated the stability of the imine under different pH conditions by 1H NMR spectroscopy (Supplementary Fig. 24). The imine remained largely stable in K HPO electrolyte at pH 11.0, which corresponds to the bulk electrolyte used in our electrocatalytic experiments. Under operating conditions, however, hydroxide ions (OH–) accumulate near the cathode, and the local pH can increase to approximately 12.6 at a current density of 20 mA cm–2 (see Supplementary Information for details). When the imine was introduced into an electrolyte adjusted to pH 12.6, the 1H NMR spectra showed partial and gradual hydrolysis back to HMF and methylamine, indicating reduced stability under these more strongly alkaline conditions and kinetically redirecting the system toward pathways analogous to the direct HMF reduction process.\nIn addition, diamine and triamine products were also detected during the electrocatalytic reduction of the isolated imine (Supplementary Scheme 1). We attribute this phenomenon to the relatively high local concentration of imine at the electrode–electrolyte interface: when the hydrogenation rate is not sufficient to timely convert all imine to the corresponding amine, secondary C–N coupling between imine-derived species becomes more likely, leading to dimer and trimer formation. Similar behavior has been reported when imines are used as direct precursors for electrochemical amine synthesis (Ref: Chem Catal. 2023, 3, 100500; Chem. Commun. 2023, 59, 4818–4821; Org. Biomol. Chem. 2020, 18, 5832–5837).\nThese insights highlight that the electrochemical C–N coupling could be a favorable way to produce MAMF through the hydrogenation of the “on-site” generated imine by the reaction between HMF and methylamine with appropriate local concentration. Therefore, steering the adsorption configuration of HMF so that the C–N coupling step is favored at the catalyst–electrolyte interface is crucial for suppressing competing hydrogenation and dimerization pathways, thereby enhancing overall performance. In parallel, finely tuning the hydrogenation activity toward the imine intermediate is equally important to rapidly funnel this species into the desired amine product and to minimize its further coupling into higher oligomers.\nTo show the stability of the imine intermediate and enhance the clarity of the reason why we chose the direct C–N coupling approach instead of the imine routine, relative discussions have been incorporated into the revised version.\n\nResponse to R1-5: We appreciate the reviewer’s insightful comments and apologize for not clearly articulating the central challenge and innovation of our work. We agree that employing pre-synthesized imines is a convenient strategy in thermocatalysis to bypass the competing hydrogenation pathways of HMF. However, under electrocatalytic conditions, the situation is different. During electrolysis, OH– is continuously generated and accumulates at the electrode–electrolyte interface, leading to a markedly elevated local pH (≈12.6 at 20 mA cm–2). The increased local alkalinity promotes hydrolysis of the imine back to HMF and methylamine, thereby redirecting the reaction network toward direct amination of HMF with methylamine and leading to BHMF and BHH formation. In addition, at high interfacial imine concentrations, competing self-condensation of imine molecules can yield diamine and triamine by-products, further complicating the product distribution and diminishing overall selectivity. Such over-condensation behavior has been documented not only in thermocatalytic systems but also under electrocatalytic conditions (Chem Catal. 2023, 3, 100500; Chem. Commun. 2023, 59, 4818–4821; Org. Biomol. Chem. 2020, 18, 5832–5837). Moreover, some imines exhibit lower solubility in aqueous electrolytes than the corresponding amines and aldehydes, which restricts their effective interfacial concentration and further limits their applicability as isolated substrates.\nFrom a practical standpoint, the conventional synthesis of the imine requires refluxing in organic solvents at elevated temperature for several hours, resulting in relatively low productivity. By contrast, our strategy enables a faster, simpler, and more selective route by directly constructing the C–N bond via in situ control of the HMF adsorption configuration on Ag catalysts, without the need to isolate and handle a metastable imine intermediate.\nTo substantiate these arguments, we synthesized the imine and examined its stability in electrolytes of different pH by 1H NMR spectroscopy (Supplementary Fig. 24). The imine remained largely intact at pH 11.0, corresponding to the bulk K HPO electrolyte used in our electrocatalytic experiments. However, at pH 12.6, representative of the locally alkaline environment near the cathode at 20 mA cm–2, the 1H NMR spectra revealed gradual, partial hydrolysis, indicating reduced stability under these more strongly alkaline conditions. This observation implies that when a pre-synthesized imine is used as the starting substrate, a significant fraction will hydrolyze back to HMF under operating conditions, effectively steering the reaction network back toward direct coupling between HMF and methylamine at the catalyst–electrolyte interface.\nOn this basis, we propose a strategy in which (i) the adsorption configuration of HMF on Ag is tailored to favor interfacial C–N bond formation, and (ii) the hydrogenation activity toward the imine intermediate is judiciously tuned to rapidly convert it into the desired amine while suppressing further coupling into higher oligomers. In other words, facet-dependent control of aldehyde adsorption, combined with regulated imine hydrogenation kinetics, provides an effective handle to steer the reaction network toward the target C–N coupling product while minimizing side reactions. To clarify why we adopted the direct C–N coupling route rather than an imine-based approach, we have incorporated these mechanistic considerations and design principles into the revised manuscript."}, {"round": 3, "reviewer_comments": {"reviewer_1": "The authors have addressed all my comments.Thus, I'd like to recommend its publication in the current form."}, "author_response": ""}]

Decision letter
Reviewer # 1:
General Comment R1: In this manuscript, the authors reported an electrocatalytic system to
synthesize amine from HMF and methylamine using Ag nanoparticles (denoted as Ag NPs).
Although the Faraday efficiency and production rate are considerable, this reaction is not novel
and extremely non-challenging. The most critical issue is that the C–N coupling reaction is likely
to be a spontaneous reaction process, where the electrocatalyst mainly completes the
hydrogenation reaction step, which conflicts with the proposed mechanism in this manuscript. As
a result, we can not recommend that the current form of the manuscript be published on the Nature
Communications. The following questions should be considered and be clearly reported.
Response: We sincerely thank the reviewer for the important comments. We have carefully revised
this manuscript and improved the related details according to the insightful suggestions. Detailed
responses to the comments are listed below.
Specific Comment R1-1: Given the well-documented rapidity of amine-aldehyde condensation
reactions under ambient conditions, a critical question arises regarding the authors’ reported
system containing concurrent HMF and methylamine: does the imine intermediate predominate in
the reaction medium under these conditions? To conclusively address this mechanistic
consideration, the authors should provide supporting evidence including (but not limited to) time-
resolved 1H NMR spectroscopic characterization of the reaction mixture, complemented by
comparative kinetic studies and/or mass spectrometric analysis of intermediate species.
Response: We thank the reviewer for the insightful comments. We agree that amine-aldehyde
condensation reactions can proceed rapidly under certain conditions, particularly in anhydrous or
acidic environments (Patai, S. (Ed.). The Chemistry of Carbon Nitrogen Double Bonds, 1970, John
Wiley & Sons.). However, an aqueous phosphate buffer solution at pH 11 was used in our research.
Under this specific condition, the equilibrium for imine formation can be less favorable or slower
than commonly assumed, especially when competing with the hydrogenation of the aldehyde (ACS
Catal., 2016, 6,1840). Therefore, imine intermediate should not predominate in the reaction
medium. To support this idea, additional experiments were conducted.
According to the reviewer’s suggestion, time-resolved 1H NMR spectroscopic
characterization of the reaction mixture was performed under operando electrochemical conditions.
The results show that the imine content stays at a consistently low level throughout the
electrochemical reaction with a general decreasing trend (Supplementary Fig. 19). This
phenomenon suggests that the imine intermediate does not predominate in the reaction medium.
Additionally, time-resolved Raman spectroscopy of the reaction solution without applied potential
was collected (Fig. R1). The results show that the concentration of the imine intermediate remains
constantly low in the bulk solution under non-electrochemical conditions, confirming that the
equilibrium for reversible imine formation reaction is less favorable in this reaction condition.
Collectively, these results suggest that spontaneously formed imine intermediates in the bulk
solution should not be the reason for the high production rate obtained in our study. Thus, the
reductive coupling between HMF and methylamine is an electrocatalytic process that occurs at the
surface of the electrode, with the adsorption behavior of the HMF molecule as one of the key
influencing factors on the performance.
With the conclusion discussed above, a detailed kinetic study and mass spectrometric analysis
of the key imine intermediate are important to further support the idea of adsorption-configuration-
induced impact toward intermediate formation, as suggested by the reviewer. However, accurate
quantification of the intermediates formed at the surface during the reaction is hard to realize in
this study. Fortunately, the in situ Raman spectroscopy provides direct and compelling evidence to
support the main idea of this work (Fig. 4c, d). The observed distinct spectral changes, particularly
the redshift of the C=O stretching frequency of HMF adsorbed on Ag NP (Fig. 4c), unequivocally
indicate a weakening and polarization of the carbonyl bond upon adsorption. This activation is
precisely what enhances the electrophilicity of the carbonyl carbon and facilitates the subsequent
nucleophilic attack by methylamine. The dramatic differences in product distribution and
selectivity observed between Ag NP and Ag NC (Fig. 2b, c) further corroborate this surface-
mediated activation. This distinct catalytic behavior strongly supports that the catalyst surface
actively steers the reaction pathway by modulating HMF adsorption. Revisions of the manuscript
are as follows:
Manuscript Lines 209-214.
Besides, time-resolved 1H NMR spectroscopic characterization of the reaction mixture was
performed under operando electrochemical conditions (Supplementary Fig. 19). The result shows
that the imine content stays at a consistently low level throughout the electrochemical reaction
with a general decreasing trend, suggesting the reductive coupling between HMF and methylamine
is an electrocatalytic process that occurs at the surface of the electrode.
SI Lines 161-164:
Supplementary Fig. 19. Time-resolved 1H NMR for the electrolyte during the C–N coupling on
Ag NP with (a) 5, (b) 10, (c) 20, (d) 40, and (e) 60 C charge passed. (f) The concentration of imine
as the amount of charge passed.
Fig. R1. Time-resolved Raman spectra of the electrolyte without electrocatalytic reaction.
Specific Comment R1-2: A second mechanistic concern pertains to the potential influence of
stoichiometric parameters. Specifically, the rationale for selecting the current methylamine/HMF
molar ratio requires clarification. Have the authors systematically explored reactant
stoichiometry optimization (e.g., elevated methylamine concentrations)? To substantiate the
claimed catalytic specificity, control experiments comparing Faradaic efficiencies across (i)
varied methylamine concentrations and (ii) different metal electrodes (including non-noble
counterparts) should be supplemented, alongside detailed kinetic isotope effect analyses.
Response: We thank the reviewer for the insightful comments. We have systematically explored
the influence of methylamine concentration on the electrochemical C–N coupling reaction. Our
results identified 1000 mM as the optimal methylamine concentration (Supplementary Fig. 12).
Regarding control experiments with different metal electrodes, we have performed a
comprehensive comparison. As shown in Supplementary Fig. 1, we evaluated various
commercial metal foils (Fe, Ni, Cu, Pt, Zn, Sn, Ag, Cd, and In) for the electrochemical C–N
coupling of HMF with methylamine. These initial screening experiments clearly demonstrated that
Ag exhibits exceptional electrocatalytic performance, achieving the highest partial current density
and Faradaic efficiency for MAMF production among the tested metals. This superior performance
was attributed to the moderate HMF adsorption strength on Ag, which is a critical finding that
guided our subsequent in-depth study focusing on facet-controlled Ag catalysts and their impact
on the adsorption configuration of the substrate.
Furthermore, we have conducted kinetic isotope effect (KIE) analyses on the Ag NP catalyst,
as presented in Fig. 3d. The observed cathodic shift of 145 mV when replacing H O with D O
2 2
strongly indicates that a proton-coupled electron transfer (PCET) step is essential for the C–N
coupling reaction. This analysis underscores the important role of proton dynamics in the reduction
of the aldimine intermediate and C–N bond formation, providing mechanistic insight into the rate-
determining step and solidifying the inner-sphere mechanism proposed in our manuscript. Due to
the limitations of the experimental conditions, KIE analyses with other substrates could not be
conducted in our lab. We are sorry for the unfeasible of the corresponding experiments. Revisions
of the manuscript are as follows:
Manuscript Lines 147-148:
The methylamine concentration was selected to be 1000 mM (Supplementary Fig. 12).
SI Lines 134-136:
Supplementary Fig. 12. Electrochemical performance of Ag NP for C–N coupling of HMF with
methylamine at various methylamine concentrations.
Supplementary Fig. 1. Partial current (left) and Faradaic efficiency (right) toward MAMF and
BHMF on different metal electrodes for electrochemical C–N coupling between HMF and
methylamine at –0.45 vs. reversible hydrogen electrode (RHE).
Figure 3d. Comparison of LSV curves on Ag NP for C–N coupling reaction in the electrolyte with
H O and D O.
2 2
Specific Comment R1-3: The obvious difference between Figure 4c and Figure 4d is puzzling.
Even if there are differences in the dominant adsorption configurations on the catalyst surface, it
does not mean that other adsorption configurations do not exist. However, we could not observe
any signals around ~1024 cm–1 which could be attributed to the furan ring of C-H, we recommend
that the authors clarify this issue clearly.
Response: We thank the reviewer for the thoughtful comments. The distinct differences between
the in situ Raman spectra of Ag NP (Fig. 4c) and Ag NC (Fig. 4d) are important and serve as direct
spectroscopic evidence supporting our proposed facet-dependent adsorption configurations of
HMF. As stated in our manuscript, for Ag NP, the peak at 1022 cm–1 is consistently observed and
attributed to the C–H stretching of the furan ring (Fig. 4a). This spectral feature is indicative of the
η1(C)-aldehyde adsorption configuration, where the furan ring adopts a horizontally tilted
orientation relative to the catalyst surface, allowing for the detection of its C–H vibrations. This
peak remains visible across the investigated potential range in Fig. 4c. In contrast, for Ag NC, the
Raman spectra (Fig. 4d) exhibit a prominent peak at 1002 cm–1, which we attribute to the
hydroxymethyl group, and the appearance of a peak at 718 cm–1 corresponding to the C–O–C
stretching of the furan ring. Concurrently, the furan ring C–H stretching peak around ~1022/1024
cm–1 is indeed absent or significantly diminished on Ag NC. This distinct spectral profile on Ag
NC strongly supports the η2(C,O)-aldehyde adsorption configuration. In this mode, the C–O–C
end of the furan ring, along with the hydroxymethyl group, interacts more closely with the catalyst
surface. This different orientation of the furan ring, where it is less horizontally oriented or more
directly interacting through its oxygen-containing functionalities, would naturally lead to a
reduced signal from the furan ring C–H stretching, as its vibrational mode might be less enhanced
by surface-enhanced Raman scattering (SERS) or its orientation is less favorable for detection
compared to other interacting groups.
While it is plausible that other minor adsorption configurations might coexist, the dominant
and distinct adsorption modes on Ag NP and Ag NC, as unequivocally evidenced by these clear
and reproducible spectroscopic differences, are responsible for dictating the observed dramatic
differences in reaction selectivity. The consistent correlation between these unique spectral
fingerprints and the vastly different product distributions (high MAMF selectivity on Ag NP vs.
favoring BHMF/BHH on Ag NC) strongly supports our conclusion that the adsorption
configuration is the critical factor steering the reaction pathway. Revisions of the manuscript are
as follows:
Manuscript Lines 247-249:
For Ag NP, peaks at 976 cm–1 and 1526 cm–1 are attributed to the C–C stretching of the furan ring.
The peak at 1022 cm–1 is attributed to the C–H stretching of the furan ring. These results show that
HMF is adsorbed on Ag NP with the horizontally tilted furan ring.
Specific Comment R1-4: Given the established morphological sensitivity of electrocatalytic
systems (e.g., Ag nanoparticles vs. nanocubes differentially exposing {111}/{100} facets), has
rigorous morphological characterization (including crystallographic orientation and particle size
distribution) been performed to ensure structural homogeneity across the metal electrodes in
Figure S1? This is particularly critical as substrate-dependent variations in active site geometry
and surface energy landscapes could artificially modulate Faradaic efficiency trends.
Response: We thank the reviewer for the insightful comments. We would like to clarify that the
data presented in Supplementary Figure 1 corresponds to the initial screening experiments
conducted using commercial bulk metal foils (Fe, Ni, Cu, Pt, Zn, Sn, Ag, Cd, and In), not
synthesized nanoparticles. Therefore, concerns regarding particle size distribution are not
applicable to this specific set of experiments. While we acknowledge that the surface of
commercial metal foils may exhibit a distribution of crystallographic orientations, the primary
purpose of this initial screening was to identify a metal with moderate HMF interaction strength
as a promising candidate for selective C–N coupling. The data demonstrated the outperforming
performance of Ag among these bulk materials.
For the Ag NP and Ag NC catalysts, which are the model catalysts of interest, we have indeed
performed rigorous and comprehensive morphological and crystallographic characterizations, as
shown in Fig. 1 of the main manuscript. Scanning electron microscopy (SEM), High-resolution
transmission electron microscopy (HRTEM) images, corresponding fast Fourier transform (FFT)
patterns, and X-ray diffraction (XRD) analysis (Fig. 1b, d, e) conclusively demonstrate that Ag NP
predominantly exposes the (111) crystallographic plane, while Ag NC primarily exposes the (100)
facet. Additionally, we also conducted characterization of catalysts after reactions (Supplementary
Figs. 16–17). These results confirm the stability of Ag NP and Ag NC, demonstrating no significant
facet reconstruction and consistent exposed facets throughout the reaction. This meticulous control
and thorough characterization of exposed facets were paramount to our investigation of facet-
dependent adsorption configurations and their impact on selectivity, which is the central theme and
novelty of this manuscript. Revisions of the manuscript are as follows:
Manuscript Lines 112-114:
Different metal foils (i.e., Fe, Ni, Cu, Pt, Zn, Sn, Ag, Cd, and In) with varied adsorption interactions
with the HMF molecule were compared first to reveal the influence of adsorption properties on
the activity of the C–N coupling reaction
Fig. 1 Characterization of electrocatalysts. (a-b) SEM images and corresponding size distributions of as-prepared
Ag NP (a) and Ag NC (b). (c-f) TEM (c, e) and HRTEM (d, f) images of Ag NP (c,d) and Ag NC (e,f). (g) XPS
spectra of as-prepared Ag NP and Ag NC. (h) XRD patterns of Ag NP and Ag NC (JCPDF#04–0783).
Specific Comment R1-5: Computing energies of adsorbed species uses the harmonic
approximation, which can be very sensitive to low-frequency modes. If the used cutoff is too small
then the entropy of the adsorbate will be substantially over-estimated. The authors do compute the
energy, and the many difference is only 0.2 eV, which is much close to the typical DFT error of
~0.2 eV, and this conclusion could easily change if a different functional or U value is used. In
other words, it is not conclusive evidence.
Response: We thank the reviewer for the helpful comments. We fully agree with the inherent
limitations of the harmonic approximation, particularly concerning its potential sensitivity to low-
frequency modes and the estimation of adsorbate entropy. Therefore, we verified our evidence in
four aspects: (1) The adsorption energies of HMF on the (100) and (111) surfaces obtained from
Density Functional Theory (DFT) calculations (ΔE ) are -1.86 eV and -1.68 eV, respectively,
DFT
with a difference of 0.18 eV, which is the main contributor to the variation of ~ 0.20 eV in
adsorption energy rather than the entropy parts. (2) We calculated the contribution of each
vibrational mode to the entropy for the adsorbed HMF on both surfaces (Table R1). For vibrations
with a wave number below 50 cm-1, whether treated as 50 cm-1 or ignored, the energy difference
of T S between HMF* on the (100) and (111) surfaces does not exceed 0.07 eV. The contribution
of computed entropy to the difference in adsorption energy is negligible. (3) To rule out the
influ⋅ence of different functionals on the results, we further repeat our computation using the PBE
functional, and the adsorption energies on the (100) and (111) surfaces are calculated to be -1.94
eV and -1.79 eV, respectively, with a difference of approximately 0.15 eV. It is worth noting that
for metallic catalysts like Ag, the consideration of a Hubbard U parameter is typically not necessary,
as electron localization issues that necessitate its use are generally absent. (4) We repeated the
calculations at different adsorption sites five times, and the standard deviations of the adsorption
energies on the (100) and (111) surfaces were 0.03 eV and 0.01 eV, respectively, ensuring the
robustness and statistical significance of our calculated adsorption energies. It clearly indicates
that η2(C,O)-aldehyde configuration leads to excessive adsorption of HMF, which promotes direct
hydrogenation to form BHMF and BHH (Fig. 4b). The explanation of this section and our revision
of the manuscript are as follows:
Manuscript Lines 346-351:
Figure 4b The adsorption energy of HMF with corresponding adsorption configurations on Ag NP and Ag NC.
Table R1 The vibrational wave numbers of HMF adsorbed on Ag (100) and Ag (111), as well as their
contributions to the Gibbs free energy.
Ag 100 Ag 111
ν (cm-1) T⋅S (eV) ν (cm-1) T⋅S (eV)
3557.69 0.000 3725.72 0.000
3188.77 0.000 3191.85 0.000
3175.69 0.000 3179.54 0.000
2972.07 0.000 2955.48 0.000
2915.57 0.000 2911.82 0.000
2843.40 0.000 2825.51 0.000
1606.25 0.000 1633.80 0.000
1526.96 0.000 1541.51 0.000
1484.55 0.000 1494.89 0.000
1431.75 0.000 1441.14 0.000
1375.11 0.000 1388.59 0.000
1368.90 0.000 1372.41 0.000
1324.23 0.000 1335.36 0.000
1266.96 0.000 1269.46 0.000
1247.46 0.000 1229.68 0.000
1205.86 0.001 1213.19 0.001
1173.54 0.001 1170.32 0.001
1154.02 0.001 1164.23 0.001
1022.16 0.001 1021.40 0.001
987.84 0.001 980.29 0.001
963.54 0.001 971.45 0.001
942.87 0.002 945.09 0.002
926.54 0.002 937.93 0.002
916.34 0.002 917.23 0.002
851.50 0.002 859.05 0.002
778.10 0.003 783.06 0.003
761.09 0.003 752.22 0.003
668.46 0.004 702.19 0.004
607.61 0.006 617.62 0.005
591.91 0.006 603.34 0.006
501.09 0.008 488.53 0.009
432.70 0.011 412.70 0.012
332.45 0.016 326.01 0.017
318.10 0.017 280.21 0.020
265.27 0.021 213.24 0.026
194.71 0.028 164.41 0.032
161.33 0.033 153.60 0.034
139.65 0.036 130.96 0.038
115.99 0.041 86.12 0.048
100.11 0.045 83.47 0.049
87.34 0.048 62.46 0.057
79.79 0.050 31.09 0.074
73.12 0.053 28.62 0.077
39.59 0.068 21.04 0.084
13.01 0.097 5.98 0.117
SI Lines 56-59:
The revised Perdew–Burke–Ernzerhof (RPBE)3 exchange-correlation functional was applied and
the dispersion effects were accounted by employing semi-empirical D3 method.4, 5 For this method,
the consideration of a Hubbard U parameter is typically not necessary.
3. Hammer, B., Hansen L. B., Nørskov J. K. Improved adsorption energetics within density-
functional theory using revised Perdew-Burke-Ernzerhof functionals. Phys. Rev. B 59,
7413-7421 (1999).
4. Grimme, S., Ehrlich S., Goerigk L. Effect of the damping function in dispersion corrected
density functional theory. J. Comput. Chem. 32, 1456-1465 (2011).
5. Grimme, S., Antony J., Ehrlich S., Krieg H. A consistent and accurate ab initio
parametrization of density functional dispersion correction (DFT-D) for the 94 elements
H-Pu. J. Phys. D: Appl. Phys. 132, (2010).
Specific Comment R1-6: Computational Refinement: Although the theoretical calculations align
with experimental outcomes, they fail to rationalize the high selectivity toward MAMF. We suggest:
(i) Incorporating energy profiles for methylamine’s nucleophilic attack on the aldehyde group to
quantify activation barriers. (ii) Comparing energy differences between hydrogenation and
nucleophilic pathways to elucidate competitive reaction dynamics.
Response: We thank the reviewer for the insightful suggestions. We thoroughly considered the
elementary steps of the nucleophilic attack and the hydrogenation steps during the C–N coupling
reaction on different samples (Supplementary Fig. 23). The results show that the nucleophilic
attack of methylamine on the absorbed HMF by Ag NP, through the Inter1a* and Inter2*
intermediates, is thermodynamically more favorable than on Ag NC. At the same time, the
hydrogenation step, through the formation of Inter1b*, on Ag NP is less favorable, indicating the
good performance of Ag NP to suppress the direct hydrogenation and self-coupling side reactions.
All these results support the conclusions of this work. The explanation of this section and our
revision of the manuscript are as follows:
Manuscript Lines 321-326:
Free energy calculations show that the nucleophilic attack of methylamine on the absorbed HMF
by Ag NP is thermodynamically more favorable than on Ag NC. At the same time, the
hydrogenation step on Ag NP is less favorable, indicating the good performance of Ag NP to
suppress the direct hydrogenation and self-coupling side reactions. (Supplementary Fig. 23).23,67
SI Lines 178-181:
Supplementary Fig. 23. Free energy diagram of the electrochemical C–N coupling of HMF with
methylamine on Ag NP (red curve) and Ag NC (blue curve).
Specific Comment R1-7: Substrate Scope Expansion: Additional substrate screening experiments
are necessary to validate the universality of their design strategy for aldehyde-based C–N coupling
reactions. Testing structurally diverse aldehydes would clarify whether the observed mechanism
is generalizable.
Response: We thank the reviewer for the valuable comments. The study of the reaction between
HMF and methylamine was driven by the high added value of its corresponding amine product, 5-
[(methylamino)methyl]-2-furanmethanol (MAMF), which serves as a key chemical for the
synthesis of the pharmaceutical Ranitidine. This consideration was stated in the Introduction
section.
While we acknowledge the high utility and value of other aldehyde-based C–N coupling
reactions, the current work focuses on the fundamental mechanistic insights of adsorption
engineering of reactants for selective C–N coupling. Our findings establish that controlling the
HMF adsorption mode (η1(C)-aldehyde vs. η2(C,O)-aldehyde) is critical for favoring C–N
coupling. We believe tuning the absorption behavior should be a universal strategy for promoting
heterogeneous electrochemical C–N coupling reactions. However, this universality might not be
proved by testing the catalytic performance using the Ag NP and Ag NC catalysts in this work with
varied aldehyde or amine substrates. The adsorption configuration tuning should be achieved by
specifically designing the electrocatalyst for the target substrate. For a reaction of interest, we need
to analyze the features of the substrate molecule (such as the existence of aromatic ring, the length
of the alkyl chain, etc) to guide the fabrication of a specific catalyst structure, which requires a
series of systematic investigations. Such a proof might be out of the scope of our current work.
We will conduct related studies to further verify the effectiveness of adsorption tuning for
electrochemical organic synthesis. To emphasize this point, we have added the related discussion
on the future direction in the revised manuscript.
Manuscript Lines 367-370:
Future efforts should focus on enabling green substrates, creating pathways to more valuable
products, and designing scalable systems like the membrane electrode assembly (MEA), which
will collectively pave the way for the industrial deployment of electrochemical C–N coupling
technology.
Specific Minor Comments: The widely accepted resolution of HRTEM is 0.01 nm. Please correct
the statements in Figure 1b and Figure 1d. All spelling and grammar in the manuscript should be
thoroughly checked, such as “0.205n m” in Figure 1d. The authors' work still has some font issues
that need to be corrected. Italicize “in situ” (e.g., Line 6 of Conclusions). Replace hyphens with
en dashes for chemical bonds (e.g., “C-N” → C–N in the SI).
Response: We thank the reviewer for the detailed comments. We have thoroughly reviewed and
revised the manuscript according to all the suggestions:
1. HRTEM Resolution: We appreciate the clarification regarding HRTEM resolution. Related
information has been updated in Fig. 1 (please find the details in the response to Specific
Comment R1-4).
2. Spelling and Grammar: All spelling and grammatical errors, including the specific example
of “0.205n m” in Figure 1d, have been carefully checked and corrected throughout the
manuscript. (find in the response to Specific Comment R1-4).
3. Font Issues: All the expressions “in situ” are consistently italicized (e.g., in the Conclusions
section and elsewhere). We have also replaced hyphens with en dashes for chemical bonds
(e.g., “C–N”) as appropriate throughout the main text and Supplementary Information. Any
remaining font issues and possible flaws have been thoroughly checked and corrected.
Reviewer # 2:
General Comment R2: This manuscript reports on modulating the adsorption behavior of
substrates by tailoring the surface structure of silver (Ag) catalysts, thereby significantly
enhancing the electrochemical C–N coupling of biomass-derived 5-hydroxymethylfurfural (HMF)
with methylamine to produce 5-[(methylamino)methyl]-2-furanmethanol (MAMF). The optimized
Ag nanoparticles (NPs), predominantly exposing the (111) facet, exhibit an impressive Faradaic
efficiency (FE) of 89.2% and a selectivity of 90.1% for C–N coupling at −0.45 V vs. RHE. This
performance is among the best reported to date. Systematic in situ spectroscopic investigations
combined with DFT calculations reveal that HMF adsorbs onto the Ag(111) surface in a distinct
η¹(C)-aldehyde configuration. This specific adsorption mode increases the electrophilicity of the
carbonyl carbon, facilitating C=O bond polarization and promoting nucleophilic attack by
methylamine, thereby enhancing catalytic activity. Overall, this work offers a novel strategy for
modulating reactant adsorption to achieve selective electrochemical organic synthesis. It holds the
potential to inspire the development of high-performance electrocatalysts. I recommend the
publication after revisions, as outlined in the following comments.
Response: We sincerely thank the reviewer for the comments. We have carefully revised this
manuscript and improved the related details according to the insightful suggestions. Detailed
responses to the comments are listed below.
Specific Comment R2-1: Since the Ag NPs and Ag NCs exhibit different morphologies, their
electrochemically active surface areas are likely to differ, which could affect their catalytic
performance. The authors are encouraged to provide ECSA data to clarify whether this factor
plays a substantial role in the observed activity differences.
Response: We thank the reviewer for the helpful comments. In this study, all reported current
densities are normalized to the geometric surface area of the electrode (1.5 cm2). Additionally, we
have measured the double-layer capacitance (C ) for both catalysts (Supplementary Fig. 15),
dl
which indicates that the Ag NP possesses a slightly smaller ECSA than the Ag NC. This result
further supports that Ag NP has a better intrinsic performance, and the difference in C–N coupling
selectivity is primarily driven by the distinct adsorption configurations modulated by the exposed
facets. The explanation of this section and our revision of the manuscript are as follows:
Manuscript Lines 174-176:
Furthermore, Ag NP possesses a slightly smaller electrochemically active surface area (ECSA)
than Ag NC (Supplementary Fig. 15), suggesting that Ag NP has a better intrinsic performance.
SI Lines 146-149:
Supplementary Fig. 15. The CV profiles for (a) Ag NP and (b) Ag NC. Sweeping rates are 20, 40, 60, 80, and
100 mV s−1. Double-layer capacitance measurements of (c) Ag NP and (d) Ag NC.
Specific Comment R2-2: The effect of methylamine concentration on the reaction performance
is not discussed. As the adsorption of methylamine may also influence the C-N coupling process,
the authors should consider including a discussion or experimental results addressing this
variable.
Response: We thank the reviewer for the inspiring comments. We have systematically explored
the influence of methylamine concentration on the electrochemical C–N coupling reaction. Our
results identified 1000 mM as the optimal methylamine concentration (Supplementary Fig. 12).
This specific concentration was chosen to ensure an abundant supply of the nucleophile
(methylamine), which is crucial for effectively promoting the desired C–N coupling reaction
against competing pathways. Revisions of the manuscript are as follows:
Manuscript Lines 147-148:
The methylamine concentration was selected to be 1000 mM (Supplementary Fig. 12).
SI Page Lines 134-136:
Supplementary Fig. 12. Electrochemical performance of Ag NP for C–N coupling of HMF with
methylamine at various methylamine concentrations.
Specific Comment R2-3: The manuscript presents charge-transfer resistance values derived from
electrochemical impedance spectroscopy (EIS), but lacks information about the fitting procedure,
including the equivalent circuit used and the associated standard errors. Providing these details
would strengthen the credibility of the analysis.
Response: We thank the reviewer for the beneficial comments. We agree that providing these
details will enhance the credibility of our analysis. The EIS data presented in Figure 3c were fitted
using a Randles equivalent circuit model. The equivalent circuit mode is shown in Supplementary
Fig. 18. The explanation of this section and our revision of the manuscript are as follows:
Manuscript Lines 200-204:
This result is further supported by the electrochemical impedance spectroscopy (EIS) study (Fig.
3c and Supplementary Fig. 18). The Ag NPs exhibit a reduced charge-transfer resistance (R =
12.6 Ω, error: 6.3%) compared to Ag NCs (R = 18.7 Ω, error: 5.6%), indicating enhanced
interfacial electron transfer efficiency during the C–N coupling process.
SI Lines 158-159:
Supplementary Fig. 18. Equivalent circuit model used in the fitting of EIS.
Specific Comment R2-4: The manuscript reports selectivity values, but does not clarify whether
these are calculated based on carbon-containing products, nitrogen-containing products, or total
product yield. The authors should explicitly state the basis for the selectivity calculation.
Response: We thank the reviewer for the significant comments. We appreciate the reviewer’s
request for clarification on the basis of our selectivity calculations and apologize for this oversight.
We provided clarification on the calculation formula based on the carbon-containing substrate for
the selectivity in the “Product identification and quantification” section of the Methods section.
The explanation of this section and our revision of the manuscript are as follows:
Manuscript Lines 442-452:
The FE, selectivity and production rate are calculated according to Eqs. (2) – (6):
（2）
2𝑛𝑛𝐻𝐻2×F
FEH2 = Q ×100%
（3）
MAMF
2nMAMF×F
𝖥𝖥𝖥𝖥 = 𝖰𝖰 ×100%
（4）
2nBHMF×F
FEBHMF= Q ×100%
（5）
nMAMF
SelectivityMAMF=𝑛𝑛𝐻𝐻 0 𝐻𝐻𝐻𝐻×𝑦𝑦𝐻𝐻𝐻𝐻𝐻𝐻×100%
（6）
MAMF
−2 −1 𝑚𝑚𝐻𝐻𝑀𝑀𝐻𝐻𝐻𝐻
Production rate (𝑚𝑚𝑚𝑚𝑐𝑐𝑚𝑚 ℎ )=𝑆𝑆𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶×𝑡𝑡×100%
where the , and represents the mole amounts of MAMF and BHMF after the
electrolysis n . MThAeM F re n pBrHesMeFnts the mole amount of HMF before reaction. The y HMF represents
0
the yield of HMF.
𝑛𝑛
Q𝐻𝐻𝐻𝐻 r𝐻𝐻efers to the total charge. F is Faraday’s constant. S
catalyst
is the geometric area
of the catalyst loaded on the electrode, and t is the reaction time.
Specific Comment R2-5: The authors present a comparison of linear sweep voltammetry (LSV)
curves for the C-N coupling and HMF reduction reactions on Ag NPs (Supplementary Fig. 14).
However, the corresponding data for Ag NCs are missing. Including this comparison would
provide a more complete picture of the performance differences between the two catalysts.
Response: We thank the reviewer for the insightful comments. We agree that including the
corresponding linear sweep voltammetry (LSV) curves for Ag NCs, comparing the C–N coupling
reaction (with HMF and methylamine) and the background HMF reduction or hydrogen evolution
reaction (without HMF), would provide a more complete and direct comparison of the
electrochemical behavior of the two catalysts. Therefore, the results were collected and presented
in Fig 2a and Supplementary Fig. 13. The results indicate that the C–N coupling reaction exhibits
a lower onset potential compared to the hydrogenation of HMF. However, as the applied potential
becomes increasingly negative, the HMF reduction reaction consistently shows a larger current
density. This kinetic preference for HMF reduction on Ag NC is in perfect agreement with our
overall findings that Ag NC favors side reactions, particularly hydrogenation (BHMF), due to its
distinct η2(C,O)-aldehyde adsorption configuration. This further supports our mechanistic
proposal that the specific adsorption mode on Ag NC leads to an activation of the C=O bond that
is more prone to direct reduction rather than nucleophilic attack by methylamine, thereby
explaining the lower C–N coupling selectivity observed on Ag NC. The explanation of this section
and our revision of the manuscript are as follows:
Manuscript Lines 149-157:
Linear sweep voltammetry (LSV) curves (Fig. 2a and Supplementary Fig. 13) indicate that both
Ag NP and Ag NC exhibit enhanced current densities upon the addition of HMF, suggesting that
the electrochemical C–N coupling of HMF with methylamine requires a lower overpotential
compared to the hydrogen evolution reaction (HER). Ag NP achieves a current density of 20 mA
cm–2 at –0.45 V vs. RHE, which is higher than that of Ag NC (~14 mA cm–2). Notably, the Ag NC
exhibits a higher current density of HMF reduction as the potential becomes more negative (lower
than –0.45 V), suggesting that direct HMF reduction might be more favorable on Ag NC.
SI Lines 138-141:
Supplementary Fig. 13. LSV curves of (a) Ag NP and (b) Ag NC for electrochemical C–N
coupling reaction and electroreduction of HMF.
Specific Comment R2-6: Several key experimental procedures are insufficiently described. For
instance, the rotary steaming step used before liquid product quantification (mentioned in
Supplementary Fig. 11) is not included in the Methods section, and specific operating parameters
are not provided. Additionally, variables used in Equations (2)-(6) are not clearly defined. The
authors should revise the manuscript to address these omissions.
Response: We thank the reviewer for the practical comments. We acknowledge that clarity and
completeness in methodology are crucial for reproducibility. We have revised the manuscript to
address these points comprehensively. Revisions of the manuscript are as follows:
Manuscript Lines 433-438:
For quantification of liquid products, the collected catholyte was first subjected to rotary
evaporation at 40 °C to remove residual methylamine. Subsequently, the obtained liquid products
were diluted fivefold and analyzed by high-performance liquid chromatography (HPLC, Agilent
Technologies 1200 Infinity) equipped with a variable wavelength detector (VWD).
Manuscript Lines 448-452:
The , and represents the mole amounts of MAMF and BHMF after the electrolysis.
The represents the mole amount of HMF before reaction. The represents the yield of
HMFn. M 0Q A r M e F fers to nth B e H t M o F tal charge. F is Faraday’s constant. M is the catalyst loading. S is the catalyst
area.𝑛𝑛 t 𝐻𝐻 i 𝐻𝐻 s 𝐻𝐻 the reaction time. 𝑦𝑦𝐻𝐻𝐻𝐻𝐻𝐻
Specific Comment R2-7: Error bars are absent in the Faradaic efficiency data presented in Fig.
3e,f. To demonstrate reproducibility and data reliability, the authors should include error bars.
Response:
We thank the reviewer for the valuable comments. We apologize for the oversight in omitting
error bars from the Faradaic efficiency data presented in Figure 3e and 3f. We agree that including
error bars is essential for demonstrating the reproducibility and reliability of our data. All
experiments were performed in at least three parallel repeated runs, and the error bars represent
the standard deviation of these results, consistent with the error bars already present in other figures
(e.g., Fig. 2b, c, e, f and Fig. 3a, b, c, d). The explanation of this section and our revision of the
manuscript are as follows:
Manuscript Lines 216-220:
Fig. 3 Electrokinetic studies for C–N coupling reaction. (e) Partial current density and FE of MAMF as a function
of the charges passed. (f) The relationship between HMF concentration and partial current density of MAMF, and the
corresponding FE of MAMF. The error bars represent the standard deviation of three parallel repeated results.
Reviewer # 3:
General Comment R3: The manuscript describes tailoring the surface structure of Ag catalysts
to modulate HMF adsorption behavior significantly enhances C–N coupling selectivity. It presents
a compelling study on facet-dependent C–N coupling but requires revisions to address
methodological gaps, clarify mechanistic claims, and contextualize performance metrics.
Following are some comments on this work.
Response: We sincerely thank the reviewer for the comments. We have carefully revised this
manuscript and improved the related details according to the insightful suggestions. Detailed
responses to the comments are listed below.
Specific Comment R3-1: The manuscript is generally well-structured, but the figures and
schemes need clearer labeling. For example, Scheme I (page 3) is referenced but not included in
the main text, which may confuse readers. Figure 2d and 2e are described as showing "potential-dependent production rate" and "stability tests," but the axes labels in the figure are unclear.
Please ensure all axes and legends are explicitly defined.
Response: We thank the reviewer for the valuable comments. According to the suggestions, in the
third paragraph of the Introduction, we refer to Scheme 1 to illustrate the pathways for the C–N
coupling reaction and its competing side reactions involved in this work, with the image shown
alongside. During the discussion of the results, we also refer to Scheme 1 to clarify the impact of
the adsorption behavior on the reaction mechanism. Regarding Fig. 2d and 2e, we have revised
the figure caption to clearly explain the content, thereby enhancing the readability and
interpretability of the data. We have double-checked the manuscript formatting to ensure its clear
visibility and proper integration for all readers. Revisions of the manuscript are as follows:
Manuscript Lines 55-57:
Scheme 1 Schematic illustration of reaction pathways that generate (a) MAMF, (b) BHMF, and (c)
BHH for heterogeneous electrochemical C–N coupling of HMF and methylamine.
Manuscript Lines 320-321:
The η1(C)-aldehyde adsorption on Ag NP induces moderate electron withdrawal from the carbonyl
moiety compared to the η2(C,O)-aldehyde adsorption on Ag NC, thereby enhancing its
susceptibility to nucleophilic attack by absorbed methylamine (Scheme 1a) rather than the
hydrogenation (Scheme 1b) and dimerization (Scheme 1c).19,26
Manuscript Lines 185-190:
Fig. 2 Catalytic performance of Ag NP and Ag NC. (a) LSV curves of Ag NP and Ag NC in the electrolyte
(phosphate buffer solution with methylamine) with or without 20 mM HMF. (b, c) Product FEs and MAMF selectivity
as a function of potential over Ag NP (b) and Ag NC (c). (d) Production rate of MAMF over Ag NP and Ag NC at
different potentials. (e, f) Stability tests of Ag NP (e) and Ag NC (f) showing the change of Faradaic efficiency of
MAMF with the progress of the reaction. The error bars represent the standard deviation of three parallel repeated
results.
Specific Comment R3-2: The introduction lacks a focused discussion on recent advances in
electrochemical C–N coupling, particularly for biomass-derived substrates. Highlighting specific
challenges in HMF amination (e.g., overhydrogenation, dimerization) and how this work
addresses them would sharpen the novelty.
Response: We thank the reviewer for the instructive comments. In the Introduction, we have
summarized the current challenges of low selectivity and their underlying causes, primarily
stemming from competing side reactions like C=O hydrogenation and C–C dimerization. We then
introduce the specific work that addresses these problems through the analysis of the reaction
mechanism. The subsequent paragraph further elucidates our strategy for tackling this issue,
focusing on precise adsorption configuration modulation. Corresponding revisions of the
manuscript are as follows:
Manuscript Lines 59-76:
Many electrocatalysts have been investigated for this reaction (Pt, Cu, Sn, Zn, and Ag).9,11
However, a lack of rational catalyst design has resulted in the easy occurrence of side reactions
and low selectivity of C–N coupling12,13. Mechanistic studies have demonstrated that promoting
the nucleophilic attack step is crucial for effectively enhancing the overall selectivity of C–N
coupling reactions11,14. Taking the electrochemical C–N coupling of HMF and methylamine as an
example, the reaction pathway involves multiple steps (Scheme 1).3,11 Typically, HMF can be
activated by the catalyst, forming the absorbed HMF (HMF*).9,15 Then, the target product MAMF
is synthesized through two key steps16-18: (1) nucleophilic addition reaction of methylamine with
the carbonyl group of HMF* to form the aldimine intermediate, and (2) subsequent reduction of
the aldimine with protons from the electrolyte and electrons from the electrode to produce the
MAMF (Scheme 1a). However, the hydrogenation and dimerization of HMF compete with the
desired C–N coupling reaction to form 2,5-bis(hydroxymethyl)furan (BHMF) and
bis(hydroxymethyl)hydrofuroin (BHH), respectively, leading to low selectivity (Scheme 1b, c).19-
nucleophilic attack becomes a key strategy for improving the selectivity of electrochemical C–N
coupling.
Specific Comment R3-3: While facet-dependent adsorption modulation is not novel, its
application to electrochemical C-N coupling of HMF is innovative. However, the introduction
lacks a critical comparison with recent works on similar systems (e.g., Cu or Pd catalysts for HMF
upgrading). A table comparing FE/selectivity with prior studies would better contextualize the
advancements.
Response: We thank the reviewer for the helpful suggestion. We agree that a critical comparison
with recent works would further contextualize the advancements of our study. Therefore, we have
cited and explained some recent related works (see the response to Specific Comment R3-2).
Besides, we have added a comprehensive comparison table (Supplementary Table S1). This table
summarizes the performance metrics (specifically Faradaic efficiency and selectivity) of our Ag
NP catalyst alongside other relevant reported catalysts for electrochemical C–N coupling of HMF
or similar biomass-derived aldehydes, including those utilizing different metal catalysts (e.g., Cu,
Pd, or other noble/non-noble metals) and various reaction conditions. This direct comparison will
clearly highlight the superior performance achieved by our Ag NP catalyst, particularly its
exceptional selectivity for MAMF. The explanation of this section and our revision of the
manuscript are as follows:
Manuscript Lines 162-164:
The highest FE of 89.2% could be achieved by Ag NP with a selectivity of 90.2% at –0.45 V vs.
RHE (Fig. 2b), which outperforms most previously reported catalysts (Supplementary Table
S1).9,11-13,36
SI Lines 183-184:
Supplementary Table S1
The electrochemical biomass C–N coupling performance of recent catalysts
Biomass-based Nitrogen FE of C–N coupling
Catalysts Ref
molecule source product (%)
Ru NPs α-hydroxyl acids NH 43 7
2 2
Ag benzaldehyde NH 80 9
3
2-ketoglutaric
CNTs NH 90 10
3
acid
Cu acetophenone CH NH 83 11
3 2
5-
NH CH CH
2 2
TiS hydroxymethylfur 34 12
2
fural
5-
This
Ag NP hydroxymethylfur CH NH 90
3 2
work
fural
Supplementary References
7. Deng, W., et al. Catalytic amino acid production from biomass-derived intermediates.
Proceedings of the National Academy of Sciences 115, 5093-5098 (2018).
8. Fukushima, T., Yamauchi M. Electrosynthesis of amino acids from biomass-derivable
acids on titanium dioxide. Chem. Comm. 55, 14721-14724 (2019).
9. Schiffer, Z. J., Chung M., Steinberg K., Manthiram K. Selective electrochemical reductive
amination of benzaldehyde at heterogeneous metal surfaces. Chem. Catal. 3, (2023).
10. Xiao, Y., et al. Electrocatalytic amino acid synthesis from biomass-derivable keto acids
over ball milled carbon nanotubes. Green Chem. 25, 3117-3126 (2023).
11. Kim, T., et al. Mechanistic investigation of electrocatalytic reductive amination at copper
electrode. Chem. Comm. 59, 4818-4821 (2023).
12. Zhang, M., et al. Designed TiS2 nanosheets for efficient electrocatalytic reductive
amination of biomass-derived furfurals. Green Chem. 24, 9570-9578 (2022).
Specific Comment R3-4: The synthesis methods for Ag NP and Ag NC are well-documented, but
the absence of TEM/SEM images in the main text (relegated to Supplementary Figs. 2–3) weakens
the immediate validation of morphology. Key characterization data (e.g., lattice spacing, XRD peaks)
should be highlighted in the main text. Stability tests over 10 cycles (Fig. 2e, f) are insufficient to
claim long-term durability. Additional data (e.g., 24-hour chronoamperometry) would strengthen
the practical relevance.
Response: We thank the reviewer for the insightful comments. We have revised the manuscript to
include SEM images and their corresponding particle size distributions directly in the main text
(Figure 1a–b). The key high-resolution TEM (HRTEM) images and their corresponding fast
Fourier transform (FFT) patterns (Figure 1c–f), along with the X-ray diffraction (XRD) patterns
(Figure 1g), are also presented in the main text. These data provide immediate and conclusive
evidence of the distinct morphologies, lattice spacings, and predominant crystallographic facets of
the obtained samples. Additionally, we have performed and included 24-hour stability tests to
further strengthen the demonstration of long-term durability and practical relevance. The
explanation of this section and our revision of the manuscript are as follows:
Manuscript lines 121-123:
Scanning electron microscopy (SEM) images revealed that Ag NP exhibits a nearly spherical
morphology with an average diameter of approximately 30 nm, whereas Ag NC exhibits cubic
shapes (Fig. 1a–b).
Manuscript Lines 137-141:
Fig. 1 Characterization of electrocatalysts. (a-b) SEM images and corresponding size distributions of as-prepared
Ag NP (a) and Ag NC (b). (c-f) TEM (c, e) and HRTEM (d, f) images of Ag NP (c,d) and Ag NC (e,f). (g) XPS
spectra of as-prepared Ag NP and Ag NC. (h) XRD patterns of Ag NP and Ag NC (JCPDF#04–0783).
Manuscript Lines 186-191:
Fig. 2 Catalytic performance of Ag NP and Ag NC. (a) LSV curves of Ag NP and Ag NC in the electrolyte
(phosphate buffer solution with methylamine) with or without 20 mM HMF. (b, c) Product FEs and MAMF selectivity
as a function of potential over Ag NP (b) and Ag NC (c). (d) Production rate of MAMF over Ag NP and Ag NC at
different potentials. (e, f) Stability tests of Ag NP (e) and Ag NC (f) showing the change of Faradaic efficiency of
MAMF with the progress of the reaction. The error bars represent the standard deviation of three parallel repeated
results.
Specific Comment R3-5: The authors attribute the high selectivity to η¹(C)-aldehyde adsorption
but do not fully address how methylamine adsorption influences the reaction. Competitive
adsorption between HMF and methylamine could alter pathways; this should be discussed.
Product quantification relies on LC/GC, but potential intermediates (e.g., aldimine) are not
tracked. Including time-dependent product distribution would clarify reaction kinetics.
Response: We thank the reviewer for the significant comments. We have systematically optimized
the methylamine concentration to 1000 mM, ensuring an abundant supply of the nucleophile.
Furthermore, our in situ Raman control experiments (Supplementary Figure 21) clearly show the
characteristic peaks of methylamine, indicating its stable and sufficient adsorption on the catalyst
surface under reaction conditions.
Regarding the tracking of potential intermediates like aldimine, we have performed time-
resolved 1H NMR spectroscopic characterization of the reaction mixture under operando
electrochemical conditions. The results show that the imine content stays at a consistently low
level throughout the electrochemical reaction with a general decreasing trend (Supplementary
Fig. 19). This observation indicates that relying solely on spontaneously formed imine
intermediates in the bulk solution is insufficient to account for the observed product formation rate
and consumption during the electrochemical process. The η1(C)-aldehyde adsorption configuration
of HMF on Ag NP appropriately promotes the polarization of the C=O bond, thereby facilitating
the nucleophilic attack by methylamine and enhancing the overall selectivity of the C–N coupling
reaction. The dramatic differences in product distribution and selectivity observed between Ag NP
and Ag NC (Fig. 2b, c) further corroborate this surface-mediated activation. This distinct catalytic
behavior strongly supports that the catalyst surface actively steers the reaction pathway by
modulating HMF adsorption. The explanation of this section and our revision of the manuscript
are as follows:
Manuscript Lines 147-148:
The methylamine concentration was selected to be 1000 mM (Supplementary Fig. 12).
SI Page Lines 134-136:
Supplementary Fig. 12. Electrochemical performance of Ag NP for C–N coupling of HMF with
methylamine at various methylamine concentrations.
Manuscript Lines 209-214:
Besides, time-resolved 1H NMR spectroscopic characterization of the reaction mixture was
performed under operando electrochemical conditions (Supplementary Fig. 19). The result shows
that the imine content stays at a consistently low level throughout the electrochemical reaction
with a general decreasing trend, suggesting the reductive coupling between HMF and methylamine
is an electrocatalytic process that occurs at the surface of the electrode.
SI Lines 160-163:
Supplementary Fig. 19. (a-e) Time-resolved 1H NMR for the electrolyte during the C–N coupling
on Ag NP. (f) The concentration of imine as charge passed.
Specific Comment R3-6: The DFT calculations lack methodological details (e.g., functional,
basis set, slab models). A brief description in the main text or Methods section should be provided
for reproducibility.
Response: We thank the reviewer for the helpful comments. We agree that providing
comprehensive details is crucial for reproducibility and transparency. We have revised the
“Computational Methods” subsection in the revised Supplementary Information. This section now
includes all essential parameters and settings used in our DFT calculations. The explanation of this
section and our revision of the manuscript are as follows:
SI Lines 53-69:
Computational setup and methods.
Density functional theory methods. Density functional theory (DFT) calculations were
performed utilizing the Vienna Ab Initio Simulation Package (VASP) in conjunction with the
projector augmented wave (PAW) method.1, 2 The revised Perdew–Burke–Ernzerhof (RPBE)3
exchange-correlation functional was applied and the dispersion effects were accounted by
employing semi-empirical D3 method.4, 5 For this method, the consideration of a Hubbard U
parameter is typically not necessary. The cutoff energy was set to 450 eV. The convergence
threshold of electronic and force was set to 10−6 eV atom–1 and 0.02 eV Å–1, respectively. The
Methfessel-Paxton smearing was applied with a smearing width of 0.15 eV.
Computational model. Ag(111) and Ag(100) surface was modeled by a (3√3×3√3)R30° supercell
and a 6×5 supercell, respectively. All surface models were composed of 4 layers atoms with 2
uppermost layers relaxed. The metal slabs were separated by a ~20 Å vacuum space. The Brillouin
zone was sampled at a 3×3×1 k-point mesh with Γ-centered for hexagonal supercells and
Monkhorst Pack for orthorhombic supercells. The Gibbs free energy under ambient conditions was
corrected using a computational hydrogen electrode (CHE) model.6
Specific Comment R3-7: The proposed mechanism assumes direct nucleophilic attack by
methylamine on adsorbed HMF but does not address the role of protonation states or pH effects.
Experiments varying pH could elucidate how proton availability impacts aldimine formation and
reduction.
Response: We thank the reviewer for the constructive comments. We chose pH 11 for the reaction
electrolyte because at this pH (which is above the pKa of methylamine, ~10.6), a significant
portion of methylamine is present in its neutral, nucleophilic form (CH NH ), which is essential
3 2
for its efficient nucleophilic attack on the HMF carbonyl group to form the aldimine intermediate.
This optimized pH condition ensures the availability of the active nucleophile.
Furthermore, our kinetic isotope effect (KIE) studies (Fig. 3d) provide direct evidence for the
involvement of protons in the reaction mechanism. The observed cathodic shift of 145 mV upon
switching from H O to D O strongly indicates that a proton-coupled electron transfer (PCET) step
2 2
is significant for the C–N coupling reaction. This confirms the important role of proton dynamics
in the reduction of the aldimine intermediate and the overall C–N bond formation, thus addressing
the involvement of proton availability in our proposed inner-sphere mechanism.
While systematic experiments varying pH across a wider range could indeed provide further
detailed insights into how proton availability specifically impacts aldimine formation and
subsequent reduction, our current study primarily focuses on elucidating the pivotal role of HMF
adsorption configurations in steering reaction selectivity at an optimized pH. Exploring the full pH
dependence is a valuable and logical direction for future research to further refine the
understanding of the complex interplay between surface adsorption, electron transfer, and proton
dynamics. The explanation of this section and our revision of the manuscript are as follows:
Manuscript Lines 412-414:
Since the pK of CH NH + is about 10.6, adjusting the solution pH to 11 ensures a significant
a 3 3
portion of the amine to present as a base form to react with HMF to form aldimine.
Manuscript Lines 204-208:
Furthermore, electrochemical experiments with H/D kinetic isotope effect (KIE) studies were
conducted on the Ag NP catalyst. The cathodic shift of 145 mV (Fig. 3d) suggests that the proton-
coupled electron transfer step is significant for the C–N coupling reaction, indicating the important
role of proton dynamics in the reduction of the HMF intermediate and C–N bond formation.
Specific Comment R3-8: The manuscript does not consider potential surface reconstruction of
Ag NPs/NCs under operating conditions. XPS or post-reaction TEM of used catalysts would verify
structural stability and rule out facet restructuring during electrolysis. Competitive adsorption
between HMF and methylamine is ignored. Surface coverage studies (e.g., via electrochemical
quartz crystal microbalance) could clarify whether methylamine adsorption limits reaction rates.
Response: We thank the reviewer for the important comments. Regarding potential surface
reconstruction of Ag NP/NC under operating conditions, we have addressed this critical aspect
with abundant experiments. As detailed in the “Result and Discussion” section and supported by
Supplementary Figures 16–17, we performed post-reaction morphological and crystallographic
characterization (TEM and XRD) of the used catalysts after 10 cycles of electrolysis. These results
conclusively demonstrate that the morphology and crystal structure, including the predominant
exposed facets, of both Ag NP and Ag NC remain almost unchanged. This robust structural
stability under operando conditions ensures that the observed facet-dependent catalytic
performance and selectivity are genuinely attributable to the intrinsic properties of the as-
synthesized crystal facets rather than dynamic reconstruction.
Additionally, regarding the competitive adsorption behavior of substrates, our systematic
optimization of methylamine concentration (to 1000 mM) ensures its abundant supply, and in situ
Raman spectroscopy (Supplementary Figure 21, response to Specific Comment R3-5) confirms
its stable adsorption on the catalyst surface. Furthermore, our HMF concentration dependence
study (Figure 3f) indicates that HMF adsorption is a key limiting factor at lower concentrations,
following Langmuir-Hinshelwood kinetics. These findings collectively suggest that under our
optimized conditions, methylamine adsorption is not the rate-limiting step, and the primary kinetic
and selectivity control stems from the activation and adsorption configuration of HMF. While
techniques like electrochemical quartz crystal microbalance (EQCM) could offer further
quantitative insights into surface coverage, we could not conduct this experiment due to the
limitations of the resources. It would be a valuable direction for more in-depth kinetic studies in
the future, building upon the fundamental mechanistic understanding established in this work.
Specific Comment R3-9: The use of a three-electrode H-cell with a bipolar membrane may not
reflect industrially relevant conditions. Testing in a flow cell or membrane electrode assembly
(MEA) would better demonstrate scalability.
Response: We thank the reviewer for the beneficial comments. We agree with the reviewer that a
three-electrode H-cell setup may not directly reflect industrially relevant conditions or demonstrate
immediate scalability. However, it is important to emphasize that the primary objective of this
fundamental research is to elucidate the intricate reaction mechanism of electrochemical C–N
coupling, particularly the pivotal role of substrate adsorption configurations. Indeed, we have
already performed preliminary investigations into the electrocatalytic C–N coupling reaction in a
membrane electrode assembly (MEA) setup, utilizing the same reaction conditions but at higher
HMF substrate concentrations (Fig. R2a). Our activity test results from the MEA system indicate
a significant enhancement in reaction current and rate, primarily due to the reduced resistance
afforded by the thin liquid film within the MEA, which effectively lowers the ohmic drop (Fig.
R2b). However, we observed a decrease in reaction selectivity under these high substrate
concentration conditions in the MEA, which we attribute to limitations in the current catalyst
design when operating at such elevated concentrations and current densities.
This observation highlights a new set of challenges that require further catalyst engineering
specific to MEA operation. Consequently, we have dedicated another work (Chem. Eng. Sci., 317,
122039) specifically to the study of electrocatalytic C–N coupling reactions within membrane
electrode reactors. In that work, we are focusing on introducing modifications, such as the
incorporation of Ru, to enhance the adsorption and activation of imine intermediates, thereby
aiming to establish a robust electrocatalytic C–N coupling system capable of operating efficiently
under high substrate concentrations and high current densities (Fig R2c). Therefore, while
demonstrating scalability in MEA is undoubtedly crucial for the eventual practical application,
the current manuscript remains focused on providing the fundamental mechanistic understanding of
adsorption engineering in the H-cell, which serves as the essential groundwork for future
advancements in MEA-based systems. Our subsequent work directly addresses the scalability and
high-concentration challenges in MEA, building upon the mechanistic insights gained from this
study. We have added the related discussion on the future direction in the revised manuscript.
Fig. R2 Electrocatalytic C–N coupling reaction between HMF and methylamine in a
membrane electrode assembly (a) Conversion of HMF and selectivity of MAMF for Ag NP with
varying loadings in MEA under HMF concentration of 0.1 M and current density of 80 mA cm⁻2.
(b) Conversion of HMF and selectivity of MAMF in MEA on Ag NP. (c) Schematic illustration
of the effective modulation of substrate adsorption configurations by Ag NP and the synergistic
enhancement of imine intermediate adsorption by Ru.
Manuscript Lines 367-370:
Future efforts should focus on enabling green substrates, creating pathways to more valuable
products, and designing scalable systems like the membrane electrode assembly (MEA), which
will collectively pave the way for the industrial deployment of electrochemical C–N coupling
technology.
Specific Comment R3-10: The environmental impact of using methylamine (a toxic reagent) is
not addressed. Exploring greener amine sources (e.g., ammonia) or coupling with renewable NH₃
synthesis could enhance sustainability.
Response: We thank the reviewer for the meaningful comments. Our selection of methylamine as
the nitrogen source in this study was primarily driven by the high added value of the target product,
5-[(methylamino)methyl]-2-furanmethanol (MAMF), which is a key intermediate for the synthesis
of the pharmaceutical Ranitidine. This specific application highlights a direct pathway to a high-
value chemical from biomass. Our current work focuses on establishing the fundamental
mechanistic principles of adsorption engineering for selective C–N coupling. While exploring
greener and more sustainable amine sources, such as aqueous ammonia or even coupling with
electrochemical ammonia synthesis from renewable feedstocks, represents a highly significant and
promising direction for future research. A key challenge with using ammonia as an N source is the
difficulty in selectively obtaining specific primary or secondary amine products. This would
undoubtedly enhance the overall sustainability profile of electrochemical C–N coupling processes,
and is a direction we are committed to investigating in our future work. We have added the related
discussion on the future direction in the revised manuscript.
Manuscript Lines 367-370:
Future efforts should focus on enabling green substrates, creating pathways to more valuable
products, and designing scalable systems like the membrane electrode assembly (MEA), which
will collectively pave the way for the industrial deployment of electrochemical C–N coupling
technology.
Response to reviewers
Reviewer 1:
General Comments R1: In reviewing the responses, we note that the authors are trying to improve
their work and have corrected several issues. However, our major concerns remain unresolved. We
still hold the view that the authors seem to be insufficiently informed regarding the issues we
highlighted in our previous comment. Moreover, the revisions to the mechanistic discussion and
theoretical calculations lack justification, which is highly irresponsible and further exacerbates our
concerns regarding the reliability of the data. The following comments should be taken for more
consideration.
Response to R1: We sincerely appreciate the reviewer’s insightful comments and helpful
suggestions. We apologize if our previous revision did not sufficiently articulate the justification
for our mechanistic discussion and theoretical calculations. We have now extensively revised the
manuscript to improve the rigorous nature of our findings. Detailed responses to each point are
listed below.
Specific Comments R1-1: The authors emphasize that the difference in exposed crystal facets
between Ag NPs and Ag NCs is key to altering selectivity, suggesting that the (111) facet dominates
the high selectivity in hydrogenation reactions. However, due to facet heterogeneity, we believe
that this interpretation overstates the data. The potential contribution of the (200) facet, or even
involvement of the (220) facet, cannot be ruled out. Furthermore, synergistic effects between
different crystal facets may also play a role. Clearly, attributing the regulation of selectivity solely
to a single facet is unreasonable.
Response to R1-1: We sincerely appreciate the reviewer’s valuable comments. We fully agree that
the selectivity could not be dictated by a single crystallographic facet and that the inevitable co-
exposed facets may also contribute. In this work, our aim is to elucidate how the dominant exposed
facet of the Ag catalyst modulates substrate adsorption and thereby steers the reaction pathway.
Specifically, we seek to demonstrate that facet engineering provides an effective strategy to
enhance the selectivity of electrochemical C–N coupling reactions. To this end, we synthesized Ag
nanoparticles (Ag NPs) and Ag nanocubes (Ag NCs) that predominantly expose the (111) and (100)
facets, respectively. Since the existence of corresponding diffraction peaks in the XRD pattern
does not surely mean the material exposes certain facets, we have supplemented additional
HRTEM analyses (Supplementary Fig. 4). These results further confirm that Ag NPs mainly
expose the (111) facet, while Ag NCs are largely enclosed by (100) facets, in line with our previous
findings. Moreover, activity tests, in situ Raman spectroscopy, and DFT calculations collectively
show that the η1(C)–CHO adsorption configuration of HMF on Ag(111) could play a significant
role in promoting the C–N coupling pathway.
We acknowledge, however, that trace amounts of other facets still exist and could, in principle,
influence the reaction. To assess the magnitude of this effect, we performed DFT calculations to
compare the reaction energy barriers for C–N coupling on Ag(110), Ag(100), and Ag(111) surfaces
(Supplementary Fig. 28). The results indicate that the reaction barrier on Ag(111) is –0.28 eV,
lower than –0.14 eV and –0.17 eV on Ag(100) and Ag(110), respectively, underscoring the key
role of the (111) facet in facilitating the C–N coupling process. In addition, we examined the facet-
dependent hydrogenation behavior. DFT calculations show that Ag(111) exhibits the lowest
hydrogenation energy barrier (0.07 eV), compared with Ag(100) (0.24 eV) and Ag(110) (0.13 eV).
This low barrier enables rapid hydrogenation of the imine intermediate, thereby accelerating
overall conversion and enhancing C–N coupling selectivity. These results suggest that possible
contributions from minor facets such as (220)/(110) are not expected to significantly alter the
overall product distribution.
Nevertheless, we agree that synergistic effects between different facets cannot be completely
excluded. We apologize for not explicitly addressing this point in the original manuscript. In the
revised version, we have carefully moderated our statements and clarified the potential role of co-
existing facets to improve the scientific rigor and balance of our discussion.
Specifically:
On Page 2, Line 29,
The electrochemical C–N coupling of biomass-derived 5-hydroxymethylfurfural (HMF) with
methylamine offers a promising sustainable route to value-added amines. However, selectivity
remains a critical challenge due to competing side reactions, including C=O hydrogenation and C–
C dimerization, which could be modulated by reactant adsorption configurations as well as
intermediate hydrogenation.
On Page 4, Line 79,
In addition to reaction pathways, the hydrogenation ability of catalysts could also affect the product
distribution of electrocatalytic C–N coupling.16-18 Insufficient hydrogenation capability hinders the
timely reduction of imine intermediate, facilitating its hydrolysis back to HMF and methylamine,
thereby lowering overall selectivity toward MAMF. Comparative studies in thermal reductive
amination systems have demonstrated that a moderate and directional hydrogenation ability is
optimal for locking the rate-determining step at the selective hydrogenation of C=N, which
maximizes primary amine formation and suppresses over-hydrogenation and other side
reactions.19
On Page 4, Line 91,
Mechanistic studies have demonstrated that promoting the nucleophilic attack step could be crucial
for effectively enhancing the overall selectivity of C–N coupling reactions.12, 15
On Page 5, Line 103,
Therefore, precise modulation of the aldehyde carbonyl reactivity and the catalyst’s hydrogenation
ability to facilitate nucleophilic attack and subsequent imine conversion could be a useful strategy
for enhancing the selectivity of electrochemical C–N coupling.
On Page 5, Line 113,
Adjusting the hydrogenation ability of the intermediate could further affect the product’s
distribution.
On Page 5, Line 123,
Therefore, understanding the mechanism of how adsorption configurations impact reaction
selectivity could guide the design of efficient catalysts for the electrochemical C–N coupling of
HMF and methylamine.
On Page 17, Line 388,
To further exclude how the adsorption configuration affects the selectivity, DFT calculations were
carried out. The results reveal that the nucleophilic attack of methylamine on adsorbed HMF over
Ag NP exhibits a Gibbs free energy barrier of –0.28 eV that is lower than –0.14 eV on Ag NC.
Considering potential contribution from the trace facet of (110), the C–N coupling energy barrier
on Ag (110) was also considered. It showed that the C–N coupling energy barrier is –0.17 eV,
higher than that on Ag(111). The hydrogenation barrier of imine is also calculated. Ag(111) surface
exhibits the lowest hydrogenation energy barrier (0.07 eV), markedly lower than those on Ag(100)
(0.24 eV) and Ag(110) (0.13 eV). Such a low barrier facilitates the rapid hydrogenation of the
imine intermediate, thereby accelerating the overall conversion and enhancing the C–N coupling
selectivity (Supplementary Fig. 28).31, 75
On page 18, Line 417,
Therefore, manipulating the adsorption configuration of HMF and the hydrogenation of imine on
Ag catalysts could enhance the FE of electrochemical C–N coupling of HMF with methylamine.
On page 18, Line 434,
Besides, the better imine hydrogenation on Ag NP further helps to convert the imine to the
respective amines.
References:
16. Abdine, R. A. A., Hedouin G., Colobert F., Wencel-Delord J. Metal-Catalyzed Asymmetric
Hydrogenation of C=N Bonds. ACS Catal. 11, 215-247 (2021).
17. Qi, H., et al. Highly selective and robust single-atom catalyst Ru /NC for reductive amination
1
of aldehydes/ketones. Nat. Commun. 12, 3295 (2021).
18. Moriana Herraiz, C., et al. Chemoenzymatic synthesis of amino-esters as precursors of
ammonium salt-based surfactants from 5-hydroxymethylfurfural (HMF). Green Chem. 26, 9118-
9131 (2024).
19. Xue, Z., et al. Efficient light-driven reductive amination of furfural to furfurylamine over
ruthenium-cluster catalyst. J. Energy Chem. 76, 239-248 (2023).
Supplementary Fig. 4. HRTEM images of (a-d) Ag NC and (e-h) Ag NP.
Supplementary Fig. 28. Free energy diagram of the electrochemical C–N coupling of HMF with
methylamine on Ag(111) (red curve), Ag(100) (blue curve), and Ag (110) (green curve).
Specific Comments R1-2: The authors propose that the adsorption pattern of furan on the Ag
surface is critical for selectivity. However, the current experimental evidence may not sufficiently
support this claim. Therefore, we believe the authors should expand the substrate scope and verify
the generality of their proposed synthetic strategy, particularly by exploring furan-related
structures.
Response to R1-2: We sincerely appreciate the reviewer’s insightful suggestions. To further verify
the generality of our catalytic strategy, we expanded the substrate scope to include 2-furaldehyde
and 5-methylfurfural. With 2-furaldehyde and 5-methylfurfural as substrates and methylamine as
the nucleophile, Ag NP delivered FEs of 63.0% and 81.0% toward the corresponding amines,
whereas Ag NC afforded lower FEs of 50.4% and 69.1%, respectively (Supplementary Fig. 20a,b).
Replacing methylamine with ammonia as the nitrogen source in the coupling reaction with HMF
preserved a high amine FE of 65.3% on Ag NP, higher than that of 29.1% on Ag NC
(Supplementary Fig. 20c). Taken together, these results validate a facet-governed adsorption-
reactivity paradigm. The Ag NP surface favors the η1(C)–CHO configuration, translates into
superior product selectivity across distinct furfural substrates and nitrogen sources, indicating the
versatility of facet engineering for electrochemical amination (Supplementary Fig. 20d). The
corresponding discussion has been incorporated into the revised manuscript to strengthen the
scientific rigor and completeness of our study.
Specifically:
On Page 8, Line 222
To validate the generality of our findings, we broadened the substrate scope to furfural derivatives
and varied the nitrogen source. With 2-furaldehyde and 5-methylfurfural as substrates and
methylamine as the nucleophile, Ag NP delivered FEs of 63.0% and 81.0% toward the
corresponding amines, whereas Ag NC afforded lower FEs of 50.4% and 69.1%, respectively
(Supplementary Fig. 20a,b). Replacing methylamine with ammonia as the nitrogen source in the
coupling reaction with HMF preserved a high amine FE of 65.3% on Ag NP, higher than that of
29.1% on Ag NC (Supplementary Fig. 20c). Taken together, these results validate a facet-
governed adsorption-reactivity paradigm. The Ag NP surface favors the η1(C)–CHO configuration,
translates into superior product selectivity across distinct furfural substrates and nitrogen sources,
indicating the versatility of facet engineering for electrochemical amination (Supplementary Fig.
20d). To further support this hypothesis, it is necessary to elucidate the intrinsic reaction
mechanism of C–N coupling and how the HMF adsorption behavior affects the reaction.
Supplementary Fig. 20. 1H NMR results of substrate scope extension experiments with (a) 2-
furaldehyde and methylamine, (b) 5-methylfurfural and methylamine, and (c) HMF and NH on
substrate scope extension experiments were conducted in 0.5 M K HPO solution with 20 mmol
2 3
relative aldehydes and 1000 mM relative nitrogen source. The performance tests were carried out
at –1.3 V (–0.45 V vs. RHE).
Specific Comments R1-3: Regarding the experiment tracking intermediates via 1H NMR, we find
the results puzzling. If the imine is a key intermediate, its concentration should remain relatively
stable during continuous generations. The authors need to explain this observation.
Response to R1-3: We sincerely appreciate the reviewer’s valuable suggestions. In principle, the
concentration of imine intermediates can become time-independent under steady-state conditions,
as has been well documented for thermal catalytic reductive amination (Refs: Chem. Rev. 1963,
63, 489-510; Chem Catal. 2023, 3, 100500). When the system operates under steady-state
conditions, the imine concentration can be treated as quasi-steady. However, in an electrocatalytic
system, such a steady-state imine concentration can only be maintained when (i) the reaction rate
at the electrode surface is constant, (ii) the diffusion layer thickness has been stabilized, and (iii)
the concentration gradient no longer varies with time.
In our batch reactor and under the applied reaction conditions, these steady-state criteria are
not fully satisfied. The imine intermediate is continuously generated, but it can simultaneously
undergo hydrolysis at the electrode surface or further reduction to the amine product under the
applied potential (Ref: Chem Catal. 2023, 3, 100500). In addition, partial adsorption of the imine
species on the electrode surface perturbs its concentration in the liquid phase. As a result, the time-
dependent 1H NMR signal of the imine reflects a non-steady interplay among formation,
hydrolysis, and electroreduction processes, rather than a simple steady-state condition.
Moreover, during electrolysis with a Chronopotentiometry method, the current density
gradually decreases as the substrate in the vicinity of the electrode is consumed and mass-transport
limitations evolve. This change in current density directly alters the rate of imine formation and
consumption, further reinforcing the intrinsically dynamic character of the system. Consequently,
the electrochemical reactor exhibits complex, time-dependent behavior, and the imine
concentration is not expected to remain strictly constant.
To test this interpretation, we additionally performed 1H NMR measurements under non-
electrolytic conditions (Supplementary Fig. 23). In the absence of electrolysis, the imine
concentration remains nearly constant, with only minor fluctuations, consistent with a dynamic
balance between imine formation and hydrolysis.
To improve the clarity of our proposed mechanism and to rationalize the NMR observations,
we have incorporated these considerations and the new control experiments into the revised
manuscript.
Specifically:
on Page 9, Line 260
The results show that the imine intermediate remains at a consistently low concentration
throughout the electrochemical reaction, exhibiting a gradual decline as electrolysis proceeds.
This behavior can be attributed to the continuous conversion and hydrolysis of the imine at the
electrode–electrolyte interface, where the elevated local pH promotes hydrolytic decomposition.
In contrast, the imine concentration remains nearly constant in the absence of applied potential,
confirming that electrolysis induces its consumption (Supplementary Fig. 23).
Supplementary Fig. 23. Time-resolved 1H NMR for the electrolyte without electrolysis for (a) 30,
(b) 40, (c) 50, (d) 60 min. (e) The concentration of imine at different durations passed.
Specific Comments R1-4: Additionally, concerning the imine intermediate, we suggest that the
authors should directly use it as a reactant in electrocatalytic selective reduction to validate the
mechanism. We are particularly concerned about whether this species can remain stable under
alkaline electrolytic conditions.
Response to R1-4: We sincerely appreciate the reviewer’s valuable suggestions. To directly verify
the formation and reactivity of the imine intermediate, we first synthesized it via the condensation
of 5-hydroxymethylfurfural (HMF, 1 mmol) and methylamine (CH NH , 10 mmol) in 3 mL of
3 2
ethanol under reflux at 50 °C for 6 h (Ref: New J. Chem. 2023, 47, 18995–19004). The as-
synthesized imine was then subjected to electrochemical reduction at –0.45 V vs. RHE in 0.5 M
K HPO electrolyte (pH 11). The direct imine reduction produces MAMF with a FE of 39.8%,
2 3
demonstrating that the imine is a kinetically competent and mechanistically relevant intermediate
in the electrochemical reductive C–N coupling between HMF and methylamine.
Moreover, the BHMF and BHH were also detected after the electrolysis (Supplementary Fig.
1). To rationalize the formation of BHMF and BHH, we propose that the imine undergoes partial
hydrolysis at the alkaline electrode interface during electrolysis, regenerating HMF and
methylamine. The regenerated HMF can then follow competitive reduction and coupling pathways,
giving BHMF and BHH as side products (Supplementary Scheme 1). To validate this hypothesis,
we evaluated the stability of the imine under different pH conditions by 1H NMR spectroscopy
(Supplementary Fig. 24). The imine remained largely stable in K HPO electrolyte at pH 11.0,
2 3
which corresponds to the bulk electrolyte used in our electrocatalytic experiments. Under operating
conditions, however, hydroxide ions (OH–) accumulate near the cathode, and the local pH can
increase to approximately 12.6 at a current density of 20 mA cm–2 (see Supplementary Information
for details). When the imine was introduced into an electrolyte adjusted to pH 12.6, the 1H NMR
spectra showed partial and gradual hydrolysis back to HMF and methylamine, indicating reduced
stability under these more strongly alkaline conditions and kinetically redirecting the system
toward pathways analogous to the direct HMF reduction process.
In addition, diamine and triamine products were also detected during the electrocatalytic
reduction of the isolated imine (Supplementary Scheme 1). We attribute this phenomenon to the
relatively high local concentration of imine at the electrode–electrolyte interface: when the
hydrogenation rate is not sufficient to timely convert all imine to the corresponding amine,
secondary C–N coupling between imine-derived species becomes more likely, leading to dimer
and trimer formation. Similar behavior has been reported when imines are used as direct precursors
for electrochemical amine synthesis (Ref: Chem Catal. 2023, 3, 100500; Chem. Commun. 2023,
59, 4818–4821; Org. Biomol. Chem. 2020, 18, 5832–5837).
These insights highlight that the electrochemical C–N coupling could be a favorable way to
produce MAMF through the hydrogenation of the “on-site” generated imine by the reaction
between HMF and methylamine with appropriate local concentration. Therefore, steering the
adsorption configuration of HMF so that the C–N coupling step is favored at the catalyst–
electrolyte interface is crucial for suppressing competing hydrogenation and dimerization
pathways, thereby enhancing overall performance. In parallel, finely tuning the hydrogenation
activity toward the imine intermediate is equally important to rapidly funnel this species into the
desired amine product and to minimize its further coupling into higher oligomers.
To show the stability of the imine intermediate and enhance the clarity of the reason why we
chose the direct C–N coupling approach instead of the imine routine, relative discussions have
been incorporated into the revised version.
Specifically:
On Page 6, Line 143
To rationalize the choice of the one-step C–N coupling pathway, comparative electrolysis
experiments were conducted using an Ag catalyst to evaluate the selectivity between direct
coupling and the two-step route via the pre-formed imine intermediate. The direct electrochemical
coupling between HMF and methylamine exhibited a FE of 62.3%, significantly higher than the
39.8% obtained for the imine-mediated process. In contrast, the two-step reaction yielded a more
complex product distribution (Supplementary Fig. 1), likely due to secondary condensation
leading to diamine or triamine species. To further elucidate the role of adsorption properties in
governing C–N coupling activity, a series of metal foils (Fe, Ni, Cu, Pt, Zn, Sn, Ag, Cd, and In)
with distinct adsorption affinities toward HMF were systematically examined.12
On Page 11, Lin 267
According to Fick's first law, we have calculated the local alkalinity during the reaction.58 It was
found that the local pH elevated to nearly 12.6 at –0.45 V vs. RHE (Supplementary Fig. 24a,
details in Supplementary Information). To further verify this observation, the imine was
synthesized independently and introduced into electrolyte solutions with pH = 11.0 and 12.6.
The imine remained relatively stable at pH = 11.0 but underwent hydrolysis back to HMF and
methylamine under pH = 12.6 conditions (Supplementary Fig. 24). Considering the enhanced
local alkalinity near the cathode during electrolysis, these results substantiate our rationale for
adopting a one-step C–N coupling strategy and highlight the critical importance of controlling the
interfacial adsorption configuration and hydrogenation ability to achieve high selectivity. 37, 50, 51
On Page 7 Line 422
In this work, we first rationalized the choice of a one-step C–N coupling pathway by directly
comparing it with the conventional two-step process via the imine intermediate. Building on this
understanding, we achieved highly efficient electrochemical C–N coupling of HMF with
methylamine by tailoring the adsorption configuration of HMF on Ag catalysts predominantly
exposing the (111) facet.
Supplementary Scheme 1 Schematic illustration of imine reaction pathways that generate (a)
BHH, (b) BHMF, and (c) N-methyl-bis({[(5-(hydroxymethyl)furan-2-yl)methoxy]methyl}) amine
(d) N,N′-dimethyl-1,2-bis(5-(hydroxymethyl)furan-2-yl)ethane-1,2-diamine, (e) trimers.
Supplementary Fig. 1. Product analysis for electrochemical imine reduction in 0.5 M
K HPO solution. The concentration of the imine is 20 mmol L–1, and the cathode material is
2 3
commercial Ag foil.
Supplementary Fig. 24. 1H NMR spectra of (a) imine, (b) imine in K HPO electrolyte with pH
2 3
11.0 for 30 min, and (c) imine in K HPO electrolyte with pH 12.6. (d) Local pH for the reaction
2 3
at different current densities (Details in Calculation of local pH)
In Supplementary Information
Calculation of local pH
The potassium phosphite (K HPO ) originates from phosphorous acid (H PO ), which has only
2 3 3 3
two acidic hydrogens (pK ≈ 1.3, pK ≈ 6.7)
a1 a2
At pH = 11.0 conditions, nearly all species exist as HPO 2–, far beyond its buffering range.
the cathode is dominated by OH– generation and diffusion.
For the OH– generation flux:
Each electron transferred at the cathode approximately produces one OH– ion.
J – = 𝑖 (mol m–2 s–1)
OH
𝐹
Where i is the current density (A cm–2) and F = 96495 C mol–1.
One-dimensional steady-state diffusion balance model was adopted in this manuscript. Fast ion
coupling (electroneutral diffusion) was assumed.
J – = – D
𝐶𝑆𝑢𝑟𝑓𝑎𝑐𝑒−𝐶𝑏𝑢𝑙𝑘
OH eff
𝛿
C = C +
𝐽𝑂𝐻−𝛿
surf bulk
𝐷𝑒𝑓𝑓
Parameters8:
Bulk pH = 11, 𝐶𝑏𝑢𝑙𝑘 = 10–3M; Diffusion layer thickness: δ = 100 µm; D = 5.27×10–9 m2 s–1;
𝑂𝐻− eff
𝑠𝑢𝑟𝑓
𝐶
pH = 14 + log ( 𝑂𝐻−)
surf 10
𝑀
References:
14. Welch, A. J., et al. Operando Local pH Measurement within Gas Diffusion Electrodes
Performing Electrochemical Carbon Dioxide Reduction. Phys. Chem. C. 125, 20896-20904 (2021).
15. Schiffer, Z. J., Chung M., Steinberg K., Manthiram K. Selective electrochemical reductive
amination of benzaldehyde at heterogeneous metal surfaces. Chem Catal. 3, 100500 (2023).
58. Yuan, T., et al. The effect of specific adsorption of halide ions on electrochemical CO
2
reduction Chem. Sci.13, 8117-8123 (2022).
Specific Comments R1-5: Furthermore, the central challenge of this reaction remains unclear.
While the authors assert that controlling selectivity is a major obstacle in the direct reduction
process, this issue would be bypassed by using the pre-synthesized imine as the substrate. Moreover,
the formation of the imine itself does not appear difficult, and the authors acknowledge its
spontaneous formation under specific conditions. Hence, the significance of this study remains
unclear to us.
Response to R1-5: We appreciate the reviewer’s insightful comments and apologize for not
clearly articulating the central challenge and innovation of our work. We agree that employing
pre-synthesized imines is a convenient strategy in thermocatalysis to bypass the competing
hydrogenation pathways of HMF. However, under electrocatalytic conditions, the situation is
different. During electrolysis, OH– is continuously generated and accumulates at the electrode–
electrolyte interface, leading to a markedly elevated local pH (≈12.6 at 20 mA cm–2). The
increased local alkalinity promotes hydrolysis of the imine back to HMF and methylamine, thereby
redirecting the reaction network toward direct amination of HMF with methylamine and leading
to BHMF and BHH formation. In addition, at high interfacial imine concentrations, competing
self-condensation of imine molecules can yield diamine and triamine by-products, further
complicating the product distribution and diminishing overall selectivity. Such over-condensation
behavior has been documented not only in thermocatalytic systems but also under electrocatalytic
conditions (Chem Catal. 2023, 3, 100500; Chem. Commun. 2023, 59, 4818–4821; Org. Biomol.
Chem. 2020, 18, 5832–5837). Moreover, some imines exhibit lower solubility in aqueous
electrolytes than the corresponding amines and aldehydes, which restricts their effective interfacial
concentration and further limits their applicability as isolated substrates.
From a practical standpoint, the conventional synthesis of the imine requires refluxing in
organic solvents at elevated temperature for several hours, resulting in relatively low productivity.
By contrast, our strategy enables a faster, simpler, and more selective route by directly constructing
the C–N bond via in situ control of the HMF adsorption configuration on Ag catalysts, without the
need to isolate and handle a metastable imine intermediate.
To substantiate these arguments, we synthesized the imine and examined its stability in
electrolytes of different pH by 1H NMR spectroscopy (Supplementary Fig. 24). The imine
remained largely intact at pH 11.0, corresponding to the bulk K HPO electrolyte used in our
2 3
electrocatalytic experiments. However, at pH 12.6, representative of the locally alkaline
environment near the cathode at 20 mA cm–2, the 1H NMR spectra revealed gradual, partial
hydrolysis, indicating reduced stability under these more strongly alkaline conditions. This
observation implies that when a pre-synthesized imine is used as the starting substrate, a significant
fraction will hydrolyze back to HMF under operating conditions, effectively steering the reaction
network back toward direct coupling between HMF and methylamine at the catalyst–electrolyte
interface.
On this basis, we propose a strategy in which (i) the adsorption configuration of HMF on Ag
is tailored to favor interfacial C–N bond formation, and (ii) the hydrogenation activity toward the
imine intermediate is judiciously tuned to rapidly convert it into the desired amine while
suppressing further coupling into higher oligomers. In other words, facet-dependent control of
aldehyde adsorption, combined with regulated imine hydrogenation kinetics, provides an effective
handle to steer the reaction network toward the target C–N coupling product while minimizing
side reactions. To clarify why we adopted the direct C–N coupling route rather than an imine-
based approach, we have incorporated these mechanistic considerations and design principles into
the revised manuscript.
Specifically:
On Page 3, Line 62
The electro-reductive amination of HMF can proceed either via a one-step direct reaction between
HMF and methylamine or through a two-step route in which HMF first undergoes spontaneous
condensation with methylamine to generate an imine intermediate, followed by its electrochemical
reduction on the catalyst surface. However, during reductive conditions, the local pH near the
cathode rises due to hydroxide accumulation,14 making the imine intermediate susceptible to
hydrolysis at the interface. This hydrolysis regenerates HMF and methylamine, rendering the two-
step pathway kinetically indistinguishable from the one-step process. Moreover, the two-step
approach generally requires prolonged reaction times and additional separation steps, complicating
the overall synthesis. Unwanted side reactions may also occur: two imine molecules can couple to
form diamine species, while the primary amine product may further condense with unreacted imine
to yield a secondary imine that can be subsequently hydrogenated into a secondary amine. In
addition, imines may undergo polymerization or trimerization in solutions, leading to complex
product mixtures (Supplementary Scheme 1).15 Considering these factors, the one-step
electrolysis strategy was adopted and systematically investigated in this work.
On Page 6, Line 143
To rationalize the choice of the one-step C–N coupling pathway, comparative electrolysis
experiments were conducted using an Ag catalyst to evaluate the selectivity between direct
coupling and the two-step route via the pre-formed imine intermediate. The direct electrochemical
coupling between HMF and methylamine exhibited a Faradaic efficiency of 62.3%, significantly
higher than the 39.8% obtained for the imine-mediated process. In contrast, the two-step reaction
yielded a more complex product distribution (Supplementary Fig. 1), likely due to secondary
condensation leading to diamine or triamine species. To further elucidate the role of adsorption
properties in governing C–N coupling activity, a series of metal foils (Fe, Ni, Cu, Pt, Zn, Sn, Ag,
Cd, and In) with distinct adsorption affinities toward HMF were systematically examined.12
On Page 7, Line 422
In this work, we first rationalized the choice of a one-step C–N coupling pathway by directly
comparing it with the conventional two-step process via the imine intermediate. Building on this
understanding, we achieved highly efficient electrochemical C–N coupling of HMF with
methylamine by tailoring the adsorption configuration of HMF on Ag catalysts predominantly
exposing the (111) facet.
Supplementary Scheme 1 Schematic illustration of imine reaction pathways that generate (a)
BHH, (b) BHMF, and (c) N-methyl-bis({[(5-(hydroxymethyl)furan-2-yl)methoxy]methyl}) amine
(d) N,N′-dimethyl-1,2-bis(5-(hydroxymethyl)furan-2-yl)ethane-1,2-diamine, (e) trimers.
Supplementary Fig. 1. Product analysis for electrochemical imine reduction in 0.5 M
K HPO solution. The concentration of the imine is 20 mmol L–1, and the cathode material is
2 3
commercial Ag foil.
References:
14. Welch, A. J., et al. Operando Local pH Measurement within Gas Diffusion Electrodes
Performing Electrochemical Carbon Dioxide Reduction. Phys. Chem. C. 125, 20896-20904 (2021).
15. Schiffer, Z. J., Chung M., Steinberg K., Manthiram K. Selective electrochemical reductive
amination of benzaldehyde at heterogeneous metal surfaces. Chem Catal. 3, 100500 (2023).