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. 2022 Dec 14;4(1):100362. doi: 10.1016/j.xinn.2022.100362

Upgrading heterogeneous Ni catalysts with thiol modification

Pengpeng Ruan 1,4, Bili Chen 1,4, Qin Zhou 2, Hansong Zhang 1, Yahao Wang 1, Kunlong Liu 1, Wenting Zhou 1, Ruixuan Qin 1, Zhi Liu 2, Gang Fu 1,3,∗, Nanfeng Zheng 1,3,∗∗
PMCID: PMC9830375  PMID: 36636490

Abstract

Precious metal catalysts are the cornerstone of many industrial processes. Replacing precious metal catalysts with earth-abundant metals is one of key challenges for the green and sustainable development of chemical industry. We report in this work a surprisingly effective strategy toward the development of cost-effective, air-stable, and efficient Ni catalysts by simple surface modification with thiols. The as-prepared catalysts exhibit unprecedentedly high activity and selectivity in the reductive amination of aldehydes/ketones. The thiol modification can not only prevent the deep oxidation of Ni surface to endow the catalyst with long shelf life in air but can also allow the reductive amination to proceed via a non-contact mechanism to selectively produce primary amines. The catalytic performance is far superior to that of precious and non-precious metal catalysts reported in the literature. The wide application scope and high catalytic performance of the developed Ni catalysts make them highly promising for the low-cost, green production of high-value amines in chemical industry.

Keywords: metal heterogeneous catalyst, earth-abundant metal, thiol, surface modification, reductive amination of aldehydes/ketones

Graphical abstract

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Public summary

  • •

    Thiol modification of heterogeneous Ni catalysts creates an unexpected promotional effect.

  • •

    Improved activity and selectivity in the reductive amination of aldehydes/ketones are achieved.

  • •

    Thiol modification prevents the deep oxidation of Ni catalysts and thus improves stability in air.

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    A non-contact catalytic mechanism through proton-coupled electron transfer process is revealed.

  • •

    The developed thiol modification strategy can be applied to develop low-cost Ni and Co catalysts.

Introduction

The development of industrial heterogeneous catalysts using Earth-abundant metals (eg, Ni, iron) has attracted increasing research attention1,2,3,4,5,6,7,8,9,10,11,12,13 but heavily suffers from their easy air oxidation and thus deactivation. With no doubt, the surface modification is expected to provide an effective strategy to enhance their catalytic performance with long shelf life in air by the electronic effect or steric hindrance of organic ligand.14,15,16,17,18,19,20,21 In the field of heterogeneous catalysis, thiols have been generally considered as poisoning agents for metal catalysts and are only used when necessary to improve the catalytic selectivity. However, by using Ni nanocrystals with well-defined exposure surface as the model catalyst, we demonstrate in this work that the thiol modification not only prevents the oxidative deactivation of the Ni surface to allow the catalyst to be highly stable with long shelf life in air but also induces an unexpected non-contact hydrogenation mechanism to improve the catalytic selectivity toward primary amines. More importantly, the simple thiol modification strategy can be well extended to various Ni nanomaterial systems (ie, Raney Ni, supported Ni nanoparticles, and even Ni carbide) to fabricate cost-effective practical Ni catalysts toward the green synthesis of a wide range of functional primary amines via the reductive amination of aldehydes or ketones.22,23,24,25,26,27,28,29

Results and discussion

Fabrication and catalytic performance of thiol-modified Ni nanocrystals

In this work, Ni nanocrystals with well-defined exposure surface were first synthesized via thermolysis of Ni acetylacetonate in the presence of oleylamine in 1-octadecene.30 Transmission electron microscopy (Figure 1A) and X-ray diffraction (Figures S1 and S2) analyses revealed that the as-obtained Ni nanocrystals (denoted as Ni NCs) had a nanoplate morphology with hexagonal close-packed (hcp) crystal structure. The major exposure surface of the NCs is hcp Ni(0001) with Ni atoms in two-dimensional close packing. The Ni NCs were then surface modified with thiols by immersing them in a solution of thiol (eg, 1-octanethiol, 1-butanethiol). It should be noted that the hcp lattice of the Ni NCs after the thiol modification was well maintained (Figures S1E, S1F, and S2). Such a situation is different from the case for the Pd nanosheets treated with aromatic thiol in which the amorphization of Pd lattice caused by S doping was clearly observed.20 The presence of thiols on the Ni NCs was confirmed by X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis. While the XPS spectrum of the Ni NCs modified with 1-octanethiol (denoted as Ni–SC8 NCs) exhibited an obvious doublet S 2p peak that can be assigned to chemisorbed thiolate species (Figure S3),31 the thermogravimetric analysis revealed an obviously enhanced loss weight at 250°C due to the presence of thiols (Figure S4).

Figure 1.

Figure 1

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Structure characterizations and hydrogenation performance of thiol-modified Ni nanocrystals

(A) TEM image of Ni–SC8 NCs.

(B) The possible reaction pathways for the reductive amination of benzaldehyde catalyzed by Ni–SR NC.

(C) The product distribution of benzaldehyde reductive amination catalyzed by Ni NCs, air-oxidized Ni NCs modified by n-octanethiol (Ni–SC8), H2 pre-reduced Ni NCs modified by n-octanethiol (Ni–H2–SC8) after reacting for 60 min.

(D) The TOF of benzaldehyde reductive amination catalyzed by Ni NCs, air-oxidized Ni NCs modified by n-octanethiol (Ni–SC8) and 5 wt % Ru/C and Pd/C. TOF is calculated based on metal dispersion and at the reaction time of 40 min except the Pd/C is 20 min.

(E) Hydrogenation performance for Ni–SC8 NCs with different modification times, and Ru/C and Pd/C catalysts. Reaction condition: 1 mmol aldehyde, 23 mg catalyst for Ni and 10.6 mg catalyst for Ru/C and Pd/C, 3 mL ethanol, 300 μL 25 wt % ammonium hydroxide, 1 mL H2O, 80°C, 1.5 MPa H2.

(F) Apparent activation energy of N-methyl-1-phenylmethanimine hydrogenation on the Ni nanocrystal catalysts with and without thiol modification.

To evaluate whether the thiol modification would modulate the catalytic performance of Ni NCs, the reductive amination of benzaldehyde was chosen as the target reaction owing to its industrial value and complexity with multiple side reactions involved (Figure 1B). Ni NCs were supported on MgO to avoid aggregation during catalysis (Figures S5, S6, and S7). As shown in Figure 1C, while the unmodified Ni NCs gave a yield of 52% to benzylamine, the Ni–SC8 NCs prepared with modification time of 7 h offered a surprisingly improved yield of 96% under the same condition. Such a catalytic performance was far superior to that of commercial noble metal catalysts (eg, Ru/C, Pd/C) that exhibited a very poor selectivity (<40%) toward benzylamine (Figures 1D and 1E and S8), which can be explained by the enhanced hydrogenation of C=O over the Ru/C or Pd/C catalyst.

Unexpectedly, the catalytic performance of thiol-modified Ni NCs was even positively correlated with the surface thiolate coverage, which was estimated by the combined characterizations of S/Ni ratio by inductively coupled plasma optical emission spectroscopy and the surface Ni dispersion by CO titration (Figure S9). As illustrated in Figure S10A, while the surface thiolate coverage reached the highest level at ∼20% at the modification time of 5 h, the as-modified Ni–SC8 catalyst achieved the highest catalytic activity with the apparent activation energy of N-methyl-1-phenylmethanimine hydrogenation greatly reduced from 64 to 27 kJ/mol (Figures 1E and 1F and S11). No poisoning in the activity was revealed even if the modification time was increased up to 7 h using 1 equiv of thiol for the modification (Figure S10B).

While not poisoning Ni NCs, the thiol modification rendered the catalyst with extremely high selectivity toward the production of primary amine in the reductive amination of benzaldehyde. The competitive side reactions, ie, the hydrogenation of benzaldehyde to benzyl alcohol and condensation product dimer to secondary amine, were almost shut down after the thiol modification (Figures S12 and S13). The promoting effect of the thiol modification on both activity and selectivity toward the production of primary amine is unprecedented. It should be noted that the enhanced catalysis reported in this work was not merely observed for specific thiol. Different thiols (eg, 1-butanethiol, benzenethiol) were also successfully used for the surface modification to create catalysts with significantly enhanced performance (Figure S14). With the use of only 3.9 equiv of ammonia, the Ni–SC8 catalyst displayed a turnover frequency (TOF) of 47.8 h−1 at 80°C under 15 atm H2, much higher than those of non-noble metal catalysts reported in the literature (Table S1).26,27,28,29 Moreover, the Ni–SC8 catalyst was successfully applied to catalyze the reductive amination of a wide range of aromatic or non-aromatic aldehydes/ketones bearing different functional groups (Figure S15). The Ni–SC8 catalyst exhibited an excellent stability with no decay in both selectivity and activity after recycling (Figure S16A).

Structure characterizations of thiol-modified Ni catalysts

What was not expected, however, is that if the Ni NCs were pre-reduced by H2 (80°C, 3 atm H2, 2 h) before the thiol modification, the as-obtained Ni–H2–SC8 catalyst exhibited an extremely poor activity for the reductive amination (Figure 1C). Therefore, the presence of surface Ni(II) species before modification was critical to prevent thiol poisoning. The characteristic absorption peak at 407.4 nm of the UV-visible spectrum proved the existence of Ni(II)–SR complexes in modification solution (Figure S17). As revealed by Raman spectra, the appearance of vibration peaks below 400 cm−1 suggested the formation of Ni(II)–SR bonds upon the surface of Ni–SC8 NCs (Figure 2A). These results indicated that the surface oxide species was leached partially and that the tetracoordinate planar Ni(II)–SR motifs like Ni(II) thiolate complexes were generated with the thiol modification.

Figure 2.

Figure 2

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Surface structure of the thiol-modified Ni NC catalyst

(A) Raman spectra of Ni-SC8 NCs, Ni(SC8)2 complex, and NiO.

(B) In situ XPS O 1s spectra of Ni–SC8 NCs treated at different temperatures under H2 atmosphere.

(C) The Ni 2p3/2 XPS of freshly prepared Ni–SC8 NCs.

(D) In situ Ni 2p3/2 XPS of Ni–SC8 NCs under H2 atmosphere at 100°C.

(E) Structure illustration of thiol-modified Ni surface upon air oxidation (up) and H2 treatment (down). Color legend: Ni in cyan and dark cyan, S in yellow, O in red, C in gray, and H in white and pink.

Besides thiolates, the presence of surface O species was revealed on the Ni–SC8 catalyst by in situ XPS measurements under H2 atmosphere (Figure 2B). While there was no obvious O signal of lattice NiO (normally at 529.4 eV), four different types of oxygen species, ie, physically adsorbed H2O, surface Ni–O and Ni–OH species, and OH species bound on Ni(II)–SR, were observed on Ni–SC8 at room temperature. Under 5 mbar H2, when the temperature was raised to 100°C, the XPS signals of surface Ni–O and Ni–OH disappeared with the increased signal of physically adsorbed H2O, and at the same time, the content of surface Ni(II) was also reduced (Figures 2C and 2D). Those results suggest the chemical reduction of surface Ni–O and Ni–OH species happened under H2. However, the OH species bounded on Ni(II)–SR existed in great quantity on the Ni–SC8 surface (Figure 2D) and surprisingly even survived at 200°C, well consistent with the presence of Ni(II) in the XPS spectra (Figure S18). In sharp contrast, the OH and Ni(II) signals of Ni NCs/nanoparticles without thiol modification disappeared upon H2 treatment at 200°C, although an intense lattice NiO signal was observed at room temperature (Figures S19, S20, and S21). Those results indicated the thiol can stabilize surface Ni–OH under H2 at high temperature. Similarly, an obvious optical density vibration signal was detected on Ni–SC8 NCs under D2 (1 atm) at 80°C by the in situ Fourier transform infrared spectra (Figure S22).

Taking all these together, the presence of NiO species was important to the formation of Ni(II)–SR motifs during the thiol modification process. The as-generated surface Ni(II)–SR motifs helped to not only effectively suppress the deep oxidation of Ni surface in air into NiO but also to stabilize surface OH species on Ni surface under H2 at elevated temperatures. More importantly, the presence of Ni(II)–SR motifs did not prevent the access and activation of small molecules such as H2, D2, and CO (Figure S23). As illustrated in Figure 2E, although the metallic Ni surface on Ni–SC8 might be slightly oxidized upon air exposure, the presence of Ni(II)–SR motifs helped to prevent the deep oxidation of metallic Ni so that the oxidized Ni surface was readily recovered to a catalytically metallic surface after H2 treatment under mild conditions.

Mechanistic insights into the promotional effect of thiol modification

To understand how the thiol modification played a critical role in the catalysis, we carried out spin-polarized density functional theory (DFT) calculations using the Venna Ab initio Simulation Package.32 A (3 × 4) periodic supercell of four-layer hcp Ni(0001) slab with the surface covered by Ni2(μ2-RS)2(OH)4 motifs (Figures 2E and S24) at 1/6 thiol coverage was built by considering the following facts: (1) Ni NCs had hcp Ni(0001) as the major exposure surface; (2) the surface thiol coverage was estimated to be ∼20%; (3) Ni(II)–SR complexes favor the square planar coordination geometry; and (4) abundant OH species bound on Ni(II)–SR motifs were revealed by XPS. Although hcp Ni(0001) is quite fully covered by Ni2(μ2-RS)2(OH)4 motifs at the thiol coverage of 1/6, H2 can still access the metallic Ni surface underneath (Figure S25). Consistent with the experimental results, the imine and aldehyde were not accessible to metallic Ni surface underneath the Ni2(μ2-RS)2(OH)4 motifs, so the non-contact hydrogenation mechanism was proposed for the reductive amination on the thiol-modified Ni surface.

In the non-contact mechanism, the hydrogenation occurs between the reactant and the OH groups of Ni2(μ2-RS)2(OH)4 motifs, while the metallic Ni still plays the key roles in activating H2 to deliver activated hydrogen species. Considering the easy reaction of NH3 with aldehyde to yield imine, the high selectivity toward primary amine in the reductive amination of aldehyde is related to the preferential hydrogenation of the C=N bond in imine on the thiol-modified Ni surface over the C=O bond in aldehyde. Indeed, our calculations suggested that the first-step hydrogenation of benzenemethanimine was thermodynamically more favorable than benzaldehyde over hcp Ni(0001) modified with Ni2(μ2-RS)2(OH)4 motifs (Figure 3A). While the hydrogenation on the O end of benzaldehyde was strongly endothermic by 0.98 eV, the hydrogenation on the N end of benzenemethanimine was slightly endothermic by 0.17 eV. Such a large energy difference can be explained by the fact that the C=N bond is weaker than the C=O bond. In addition, the first H addition on benzenemethanimine can be stabilized by forming a favorable Oδ−⋅⋅⋅Hδ+⋅⋅⋅Nδ− structure (Figures S26 and S27).

Figure 3.

Figure 3

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Mechanism for the preferential hydrogenation of imines on the thiol-modified Ni catalyst

(A) Non-contact mechanism of benzenemethanimine and benzaldehyde hydrogenation on thiol-modified Ni(0001).

(B) Horiuti–Polanyi mechanism of benzenemethanimine and benzaldehyde hydrogenation on Ni(0001) surface.

(C) Kinetic isotope effect of Ni–SC8 catalyzed hydrogenation of N-benzylidene methylamine.

(D) Hammett plot of Ni–SC8 catalyzed reductive amination of benzaldehydes with different functional groups.

DFT calculations showed that the first and second H additions for benzenemethanimine need to surmount only 0.25 and 0.85 eV barriers on the thiol-modified surface. The consumed (NiO)–H species can be replenished by H atoms on the metallic Ni surface by overcoming an energy barrier of ∼0.8 eV (Figure 3A, S28 and S29). These findings nicely explain why the Ni–SC8 catalyst exhibited high hydrogenation activity. Moreover, the steric hindrance caused by the thiol modification would prevent the hydrogenation of dimer from being hydrogenated to secondary amine (Figure 2B). In contrast to the non-contact mechanism on thiol-modified Ni(0001), the hydrogenation on Ni(0001) still followed the Horiuti–Polanyi mechanism, in which two H atoms would add into the unsaturated C=X bonds one by one. (Figures 3B, S30 and S31). Bader charge analysis showed that the H atoms on Ni(0001) were negatively charged by −0.25 a.u., different from positively charged (NiO)–H species on the thiol-modified Ni(0001). Thus, the hydrogenation on Ni(0001) and thiol-modified Ni(0001) should exhibit different chemoselectivity. As shown in Figure 3A, the hydrogenation of benzenemethanimine and benzaldehyde on Ni(0001) would be competitive and need to overcome relatively high barriers in TS2′ (1.2–1.4 eV), explaining the experimental observation of poor selectivity and poor activity on Ni NCs. Thus, both electronic and steric effects render the thiol-modified Ni catalyst with high activity and high selectivity toward primary amine.

The proposed non-contact mechanism was verified by the large kinetic isotope effect of 5.7 for the N-methyl-1-phenylmethanimine hydrogenation catalyzed by the thiol-modified Ni catalyst (Figure 3C and S32). Moreover, the Hammett plot against σ(p) displayed a linear relationship with a negative slope,33 confirming that the imine hydrogenation involved slightly more proton-transfer than electron-transfer character as expected from the proton-coupled electron transport mechanism (Figures 3D and S33).34,35 As expected, the hydrogenation of benzonitrile on the thiol-modified Ni catalyst was suppressed, although the unmodified Ni catalyst exhibited reasonable activity (Figure S34). While a slower reaction rate was observed over the Ni catalyst, the reductive amination of 2-methylbenzaldehyde with larger steric hindrance proceeded faster than benzaldehyde over the Ni–SC8 catalyst (Figure S35). All these results confirmed that the non-contact mechanism can account for the unique selectivity in imine hydrogenation catalyzed by the thiol-modified Ni catalyst.

DFT calculations also suggested that the deep oxidation of Ni can be effectively suppressed by the presence of surface Ni–SR motifs (Figures S36 and S37). Such a capability is important to fabricate air-stable Ni catalysts for practical applications. As demonstrated by both DFT calculations (Figure S38) and in situ XPS measurements discussed above (Figures 2C and 2D), H2 can still be activated to reduce surface oxide species and further regenerate the metallic Ni surface, although the Ni surface might be slightly oxidized in air. Considering that Ni nanocatalysts, for example Raney Ni, are highly flammable and easily deactivated in air due to the formation of a continuous oxide passivating layer, such surface reactivity of the thiol-modified Ni surface is crucial to endow Ni catalysts with a long shelf life without special storage conditions in air. Indeed, the Ni(II) XPS signal of the Ni–SR catalyst stored in air for 30 days displayed a similar intensity to that for 15 days (Figure S39). No obvious decay in the catalytic performance was revealed on the Ni–SR catalyst stored in air for different periods (Figure S40).

Application of the modification strategy to create low-cost catalysts

Most importantly, the strategy developed in this work is applicable to modify Ni catalysts in different forms, eg, low-cost supported Ni/C catalyst (Figure S41) and Ni carbide (Figures S42, S43, and S44) and even supported Co/C catalyst. The thiol-modified Ni and cobalt catalysts displayed higher activity and amine selectivity (95.3%–97.1%) than their unmodified counterparts (75.6%–82.9%) (Figures S45 and S46). As demonstrated in Figure 4, with the use of the thiol-modified Ni/C catalyst, a wide range of primary amines have been successfully synthesized in high yield and selectivity via the reductive amination of their ketone or aldehyde counterparts under mild conditions, providing a green alternative to the industrial production of amines.

Figure 4.

Figure 4

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Wide substrate scope for the reductive amination catalyzed by thiol-modified Ni/C catalyst

(A) Reductive amination of aldehydes and ketones. Conditions: 2 mmol substrate, 6 mg 20 wt % Ni–SC8/C (1 mol % Ni, thiol modification time 5 h), 1 mL NH3⸱H2O (25 wt %, 13 mmol), 3 mL MeOH, 80°C, 15 atm H2, and 3 h. The GC yield was based on carbonyl compound. Condition 1: 12 mg 20 wt % Ni-SC8/C (2 mol % Ni, thiol modification time 5 h), 1.5 mL NH3⸱H2O (20 mmol). Condition 2: 30 mg 20 wt % Ni-SC4/C (5 mol % Ni, thiol modification time 5 h), reaction time is 30 min. Condition 3: 18 mg 20 wt % Ni–SC4/C (3 mol % Ni, thiol modification time 5 h), 2 mL 7 M NH3 methanol solution (14 mmol NH3) and 2 mL methanol, 80°C, 20 atm H2, and 3 h.

(B) Reductive amination of keto acid. Conditions: 2 mmol substrate, 21 mg 20 wt % Ni–SC4/C (3.5 mol % Ni, thiol modification time 3 h), 2 mL 7 M NH3 methanol solution (14 mmol NH3), and 4 mL methanol, 80°C, 20 atm H2, and 3 h.

(C) Reactions of amines with formaldehyde in H2. Conditions: 2 mmol substrate, 6 mg 20 wt % Ni–SC4/C (1 mol % Ni, thiol modification time 1 h), 400 to 800 μl formaldehyde aqueous formaldehyde (37%) (4.0 equiv for primary amine and 2.0 equiv for secondary amine), 80°C, 20 atm H2, 2 h. The GC yield was based on amine using dodecane as internal standard. Condition 4: 2 mol % Ni, reaction time is 3 h. Condition 5: 3.5 mol % Ni, reaction time is 24 h. An asterisk (∗) indicates isolated yield.

Methods

Preparation of hcp Ni NC

240 mg Ni(acac)2 was added into a mixture containing 1.6 mL oleylamine and 8 mL 1-octadecene in Ar atmosphere. After stirring for 30 min, the solution was heated up to 240 °C and then kept at the temperature for 20 min under Ar flow (80 mL/min). The black solution was naturally cooled to room temperature and washed with ethanol and n-hexane several times. The as-obtained hcp Ni NCs was further dispersed in ethanol for the thiol modification. To be used in catalysis, the hcp Ni NCs were supported on MgO, ZnO or TiO2 to prevent their aggregation.

Preparation of carbon-supported 20 wt% Ni catalyst

The 20 wt% Ni/C supported catalyst was synthesized through the hydrogen thermal reduction method. In a typical synthesis, Ni(NO3)2⋅6H2O (1.0 g) was dissolved in 30 mL ethanol. 0.8 g of carbon support was then added into the solution. The mixed solution was evaporated to dryness at 75 °C. The residual black solid was then heated to 400 °C at a rate of 4 K·min−1 and kept at 400 °C for 120 min under 5% H2/Ar flow (80 mL/min). After cooled naturally to room temperature, the as-obtained Ni/C catalyst was purged with nitrogen (80 mL/min) for 60 min and then air (20 mL/min) for 3 min. The as-synthesized Ni/C catalyst was modified with thiol immediately.

Thiol-modified Ni catalyst

The pre-made Ni nanomaterials were dispersed in the ethanol solution of thiol with the molar ratio of Ni/thiol of 1. The concentration of thiol solution used for the modification was 0.1 M. The mixture was stirred over a certain period at 45 °C under N2 to make sure that thiol was adsorbed on the surface of Ni. After the modification, the thiol-modified Ni-SR NCs were separated by centrifugation and washed several times by ethanol and n-hexane. The as-obtained Ni-SR NCs were further loaded on metal oxide supports (MgO, ZnO or TiO2) with 5 wt% loading to prevent the aggregation of Ni NCs.

Reductive amination of aldehyde

In a typical reaction, aldehyde (3 mmol), ammonia (1 mL, 13 mmol) and Ni catalyst (2 mol% Ni, modification time 5 h) were fully mixed in 9 mL methanol by ultrasonication. The mixture was then placed in a 25 mL Teflon lined high-pressure reactor which was flushed three times by H2. The H2 pressure was adjusted to 1.5 MPa for the catalysis. After the reaction was stirred at 80 °C for certain time, 100 μL reaction solution was taken out with pipette to monitor the reaction progress using GC-MS. After the reaction, the mixture was centrifuged to collect the solution phase. The crude mixture was purified by flash column chromatography on silica gel to give the primary amine product.

Reductive amination of ketone

In a typical reaction, ketone (2 mmol), 2 mL of 7 M ammonia in methanol (14 mmol), and Ni catalyst (3 mol% Ni, modification time 3 h) were fully mixed in 2 mL methanol by ultrasonication. The mixture was then placed in a 25 mL Teflon lined high-pressure reactor which was flushed three times by H2. The H2 pressure was adjusted to 2.0 MPa for the catalysis. After the reaction was stirred at 80 °C for certain time, 100 μL reaction solution was taken out with pipette to monitor the reaction progress through GC-MS. After the reaction, the mixture was centrifuged to collect the solution phase. The crude mixture was purified by flash column chromatography on silica gel to give the alcohol product.

Reductive amination of keto acid

In a typical reaction, keto acid (2 mmol), 2 mL of 7 M ammonia in methanol (14 mmol), and Ni catalyst (3.5 mol% Ni, modification time 3 h) were fully mixed in 3 mL methanol by ultrasonication. The mixture was then placed in a 25 mL Teflon lined high-pressure reactor which was flushed three times by H2. The H2 pressure was then adjusted to 2.0 MPa for the catalysis. After the reaction was stirred at 80 °C for certain time, 100 μL reaction solution was taken out with pipette to monitor the reaction progress through GC-MS. After the reaction, the mixture was centrifuged to collect the solution phase. The crude mixture was purified by flash column chromatography on silica gel to give the amine product.

Reaction of amine with formaldehyde

In a typical reaction, amine (2 mmol), 280 to 560 uL of aqueous formaldehyde (37%) (5.6 mmol for primary amine, 2.8 mmol for secondary amine), and Ni catalyst (1 mol% Ni, modification time 1 h) were fully mixed in 3 mL methanol by ultrasonication. The mixture was then placed in a 25 mL Teflon lined high-pressure reactor which was flushed three times by H2. The H2 pressure was adjusted to 2.0 MPa for the catalysis. After the reaction was stirred at 80 °C for certain time, 100 μL reaction solution was taken out with pipette to monitor the reaction progress through GC-MS. After the reaction, the mixture was centrifuged to collect the solution phase. The crude mixture was purified by flash column chromatography on silica gel to give the amine product.

Hydrogenation of aldehyde

In a typical reaction, aldehyde (1 mmol), 12 mg of 5wt% Ni NC/MgO or Ni-SC8 NC/MgO (1 mol% Ni) were added in 5 mL ethanol, which was then placed in a 25 mL Teflon Lined high-pressure reactor and flushed three times by H2. The H2 pressure was adjusted to 1.5 MPa for the catalysis. After the reaction was stirred at 80 °C at certain time, 100 μL reaction solution was taken out with pipette to monitor the reaction progress through GC-MS.

Hydrogenation of imine

In a typical reaction, imine (1 mmol), 12 mg of 5wt% Ni NC/MgO or Ni-SC8 NC/MgO (1 mol% Ni) were added into 5 mL ethanol solution, which was then placed in a 25 mL Teflon Lined high-pressure reactor and flushed three times by H2. The H2 pressure was then adjusted to 1.5 MPa for the catalysis. After the reaction was stirred at 80 °C at certain time, 100 μL reaction solution was taken out pipette to monitor the reaction progress through GC-MS.

Hydrogenation of nitrile

In a typical reaction, nitrile (1 mmol), 12 mg of 5wt% Ni NC/MgO or Ni-SC8 NC/MgO (1 mol% Ni) mixed with 5 mL ethanol were added into a 25 mL Teflon Lined high-pressure reactor. The H2 pressure was adjusted to 1.5 MPa for the catalysis. After the reaction was stirred at 80 °C at certain time, 100 μL reaction solution was taken out with pipette to monitor the reaction progress through GC-MS.

Conclusion

In conclusion, we have developed an effective thiol-modification strategy to adjust the aldehyde/ketone reductive amination performance of Ni-based catalysts. Detailed studies demonstrated the thiol modification of Ni NCs with partially oxidized surfaces led to the formation of unique HO–Ni(II)–SR surface motifs, which can survive at elevated temperatures under H2 and further assist the proton transfer from the metallic Ni surface to imines without the need of contacting metallic Ni sites. Such an unexpected non-contact hydrogenation mechanism greatly reduced the apparent activation energy of imine hydrogenation but shut down the hydrogenation of the C=O bond or dimer due to the huge steric hindrance of thiol. Therefore, both activity and selectivity toward primary amines were obviously improved via the simple thiol modification. Moreover, the as-generated surface Ni(II)–SR motifs can effectively suppress the deep oxidation of Ni so that the Ni–SR catalyst can be stored in air for 30 days with no obvious decay of catalytic activity. Most importantly, the simple modification strategy can be easily extended to other heterogeneous catalysts based on Ni and Co. With the possible production of low-cost carbon-supported Ni/C or Co/C catalysts in large scale, the cost-effective preparation of bioactive amine drugs via the reductive amination of aldehydes/ketones with the use of air-stable non-precious metal catalysts is expected to be achieved in the future.

Acknowledgments

The project was supported by the National Natural Science Foundation of China (21890752, 21731005, 21721001, 22072116, 92045303, 22132004, and 22002126), the National Key R&D Program of China (2017YFA0207302 and 2017YFA0207303), and the fundamental research funds for Central Universities (20720180026). N.Z. acknowledges support from the Tencent Foundation through the XPLORER PRIZE.

Author contributions

N.Z. conceived and supervised the research project. P.R. synthesized and characterized the samples and investigated the catalytic performances. G.F. supervised the DFT calculations and analyzed the computational results together with B.C. Q.Z. and Z.L. contributed to the XPS measurements. H.Z. and Y.W. contributed to the catalyst preparations. K.L. contributed to the Fourier transform infrared measurements. W.Z. and R.Q. contributed the analysis of Hammett plot. N.Z., G.F., P.R., and B.C. wrote and revised the manuscript.

Declaration of interests

The authors declare no competing interests.

Published Online: December 14, 2022

Footnotes

Contributor Information

Gang Fu, Email: gfu@xmu.edu.cn.

Nanfeng Zheng, Email: nfzheng@xmu.edu.cn.

Lead contact website

http://nfzheng.xmu.edu.cn

Supplemental information

Document S1. Supporting materials and methods, Figures S1–S47, Tables S1 and S2
mmc1.pdf (10.2MB, pdf)
Document S2. Article plus supplemental information
mmc2.pdf (12MB, pdf)

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Document S1. Supporting materials and methods, Figures S1–S47, Tables S1 and S2
mmc1.pdf (10.2MB, pdf)
Document S2. Article plus supplemental information
mmc2.pdf (12MB, pdf)

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