C–C bond coupling with sp³ C–H bond via active intermediates from CO₂ hydrogenation

Abstract

Compared to the sluggish kinetics observed in methanol-mediated side-chain alkylation of methyl groups with sp³ C–H bonds, CO₂ hydrogenation emerges as a sustainable alternative strategy, yet it remains a challenge. Here, as far as we know, it is first reported that using CO₂ hydrogenation replacing methanol can conduct the side-chain alkylation of 4-methylpyridine (MEPY) over a binary metal oxide-zeolite Zn₄₀Zr₆₀O/CsX tandem catalyst (ZZO/CsX). This ZZO/CsX catalyst can achieve 19.6% MEPY single-pass conversion and 82% 4-ethylpyridine (ETPY) selectivity by using CO₂ hydrogenation, which is 6.5 times more active than methanol as an alkylation agent. The excellent catalytic performance is realized on the basis of the dual functions of the tandem catalyst: hydrogenation of CO₂ on the ZZO and activation of sp³ C–H bond and C–C bond coupling on the CsX zeolite. The thermodynamic and kinetic coupling between the tandem reactions enables the highly efficient CO₂ hydrogenation and C–C bond coupling. In-situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and density functional theory (DFT) calculations suggest that the CH_xO* (CH₂O*) species, rather than methanol produced from CO₂ hydrogenation, is the key intermediate to achieve the C–C bond coupling.

CO2 hydrogenation has emerged as a sustainable alternative for side-chain alkylation of methyl groups. Here, the authors present the side-chain alkylation of 4-methylpyridine using CO2 hydrogenation as a substitute for methanol, facilitated by a Zn40Zr60O/CsX tandem catalyst.

Introduction

CO₂ has become a strategic carbon resource for the fabrication of high-value-added chemicals, not just as a greenhouse gas^1,2. The proposal on carbon capture and utilization (CCU) has received increasing attention worldwide^3–7. Utilization of CO₂ as a feedstock to synthesize various valuable products, such as methanol^8–31, higher acohols^32–36, lower olefins^37–43, and aromatics^44–48, is emerging as a complementary alternative to fossil-derived chemical production. However, CO₂ is located at the bottom of the energetics ladder in thermodynamics, which requires considerable Gibbs energy (CO₂ ∆_fG^o = -393.5 kJ/mol) input to convert it. The employment of H₂ derived from renewable energy can make the conversion of CO₂ thermodynamically possible and practically significant^49–60.

Methanol, a critical platform chemical synthesized by CO₂ hydrogenation, can be used as an alkylation agent for methylation of toluene to paraxylene^61–63 and side-chain alkylation of 4-methylpyridine (MEPY) to 4-ethylpyridine (ETPY). However, compared with the methylation of toluene, the side-alkylation of MEPY is more difficult because of the inert sp³ C–H bond of MEPY. More importantly, side-chain alkylation of MEPY using methanol requires the first dehydrogenation of methanol to formaldehyde, which is thermodynamically and kinetically unfavorable^64–67. Although formaldehyde was also considered as an alkylation agent⁶⁸, its toxicity limited its application. ETPY and its derivatives are important intermediates of agricultural chemicals and medicines, such as antihistamine^69,70. The current synthesis procedure involves the reaction of pyridine and acetic anhydride with zinc, producing an amount of waste and thus is not environment-friendly⁷¹. Therefore, it is crucial to develop new strategies to replace methanol and formaldehyde to achieve efficient side-chain alkylation.

It has been reported that toluene can be methylated by CO₂ and H₂ over dual-functional catalyst ZnZrO/ZSM-5⁷². The results demonstrate that the reactive methylation species (H₃CO*) are generated more easily by CO₂ hydrogenation than by methanol dehydrogenation. Our group also reported that the hydrogenation of CO₂ can synthesize the lower olefins and aromatics over tandem catalysts, with CH_xO species as a key intermediate governing the thermodynamics and kinetics of C–C bond coupling^39,45. Considering the key to overcome the disadvantages of using methanol or formaldehyde as agents, CH_xO species formed by CO₂ hydrogenation should be adopted to carry out the side-chain alkylation of MEPY.

This work highlights the potential for utilization of the greenhouse gas CO₂ as alternative C1 resource. The critical intermediates through hydrogenation of CO₂ enables the side-chain alkylation of MEPY to ETPY over tandem catalysts. The optimized ZZO/CsX catalyst shows the MEPY conversion of 19.6% and ETPY selectivity of 82% through CO₂ hydrogenation, which is far higher than by using methanol as an alkylation agent (Conversion of 3.0% and ETPY selectivity of 61% by using CsX catalyst). DFT calculation further confirms that the formation of CH_xO* (CH₂O*) intermediate species through CO₂ hydrogenation boosts the side-chain alkylation of MEPY.

Results and discussion

A series of χ%ZnO-ZrO₂ binary oxides (χ% represent molar percentage of Zn, metal base; and ZnO-ZrO₂ denoted as the ZnZrO) were prepared by the sol-gel method⁷³, the CsX zeolite was prepared by ion-exchange of X zeolite with CsOH⁷⁴ (the detailed preparation was shown in Methods). Tandem catalysts were obtained through physical mixing of ZnZrO and CsX^39,45. In a typical tandem catalysis process, both CO₂ hydrogenation and 4-methylpyridine (MEPY) methylation reaction were carried out in a fixed-bed reactor. The catalytic performances of series tandem catalysts were evaluated, as shown in Fig. 1. The performance of ZnZrO/CsX tandem catalysts increases firstly and then decreases with increasing the Zn/(Zn+Zr) molar ratio (Fig. 1a). The catalytic activity achieves the optimized results with the MEPY conversion of 12.8% and ETPY selectivity of 86% when the Zn/(Zn+Zr) molar ratio is close to 40%. Hereafter, the Zn/(Zn+Zr) molar ratio of 40% represents the optimized catalyst (Zn₄₀Zr₆₀O/CsX denoted as the ZZO/CsX) for ZnZrO/CsX tandem catalysts. With increasing the reaction temperature, the conversion of MEPY varies greatly and the selectivity of ETPY changes slightly. The highest conversion of MEPY is reached at 380 °C (Fig. 1b). The varying of the mass ratio of ZZO and CsX also affects the catalytic performance of the ZZO/CsX tandem catalysts slightly, and the optimized mass ratio of ZZO/CsX is 1/6, while the mass content of CsX is far higher than ZZO (Fig. 1c), and the gas hourly space velocity (GHSV) and pressure were also evaluated (Supplementary Fig. 1a, Supplementary Fig. 1b, Supplementary Information). Figure 1d (left panel) shows a representative result that the side-chain alkylation of MEPY gives 82% selectivity for ETPY at the MEPY single-pass conversion of 19.6% under reaction conditions of 2 MPa, 0.6 h⁻¹, and 380 °C. This reaction over the ZZO catalyst only produces trace ETPY and side-product DMPY, while no ETPY is detected for CsX alone, indicating the tandem catalyst can efficiently convert MEPY with CO₂ hydrogenation to ETPY. Figure 1d (right panel) shows that the methanol and CO are produced through CO₂ hydrogenation on ZZO catalyst, while only large amounts of CO and trace methane are detected over CsX. These results lead us to conclude that tandem reactions take place on the ZZO/CsX tandem catalyst: ZZO generates methanol from CO₂ hydrogenation, and CsX is responsible for the MEPY conversion and C–C bond coupling. Though this tandem catalyst shows the deactivation behavior due to coke formation⁶⁷ (Supplementary Fig. 2a, Supplementary Fig. 3), this coke formation may arise from the conversion of intermediates (CH₂O* species) during the CO₂ hydrogenation process on the zeolite, as well as from the coupling of the pyridine ring through intermediates (CH₂O*) in CO₂ hydrogenation, ultimately leading to deactivation. The catalytic activity can be regenerated through the thermal treatment of catalysts with air (Supplementary Fig. 2b).

Fig. 1. Catalytic performance of the tandem catalysts.

a Catalytic activity on χ%ZnZrO/CsX with different Zn/(Zn+Zr) molar ratios at 350 °C; m (ZnZrO): m (CsX) = 1: 9. b The effect of temperature on the catalytical performance; m (ZZO): m (CsX) = 1: 6. c Catalytic activity of ZZO/CsX with different m (ZZO): m (CsX) mass ratios at 350 °C. d Side-alkylation of MEPY with CO₂ hydrogenation over ZZO/CsX (m (ZZO): m (CsX) = 1: 6), ZZO, CsX. CO₂ hydrogenation at 380 °C on ZZO and CsX, respectively, GHSV = 16,000 mL g⁻¹ h⁻¹; Standard reaction conditions: VHSV = 0.6 mL g⁻¹ h⁻¹, P = 2.0 MPa, H₂/CO₂/Ar = 72/24/4 and GHSV = 16000 mL g⁻¹ h⁻¹. The color shadings represent the selectivity, and the red square represents the conversion.

Powder X-ray diffraction (XRD) patterns (Fig. 1a) of χ%ZnZrO (with ZnO molar content of 5%) show the same phase structure of tetragonal ZrO₂ (t-ZrO₂)^8,75 and the XRD from the (101) spacing of ZrO₂ slightly shifts to the higher angle in comparison with t-ZrO₂ (Supplementary Fig. 4a), indicating that it is in solid solution structure^8,76. Raman spectra^8,75,77 also confirm the presence of tetragonal phase ZrO₂ (Supplementary Fig. 4b). With increasing the content of ZnO (>5%) in χ%ZnZrO, a new phase that assigned to ZnO was observed and gradually dominated (Fig. 1a, Supplementary Fig. 4a, Supplementary Fig. 4b), showing the co-existence of ZnO and ZnZrO solid solution phase, and the X-ray photoelectron spectroscopy (XPS) results of ZnZrO indicate the presence of oxidation state of Zn²⁺ and Zr⁴⁺ species (Supplementary Fig. 5). The ion-exchanged NaX after CsOH treatment (CsX) shows the same FAU framework structure of pristine NaX with high crystallinity⁷⁴ (Fig. 2b). In addition, a new peak centered at 25.6° was observed, which can be attributed to the Cs₂O phase (PDF number 09-0104), the XRD of mixed ZZO/CsX sample showed the almost similar signal to the CsX, and the three new peaks were mainly attributed to the ZZO (Supplementary Fig. 6). The XPS results of CsX show the two different Cs species on CsX^74,78–80, the peak centered at 724.34 eV can be attributed to the cesium ions (Cs⁺) that balances the negative charge of the zeolite framework through replacing the Na⁺, while the peak centered at 725.15 eV can be assigned to Cs₂O that deposited on CsX (Fig. 2c, Supplementary Fig. 7). X-ray absorption near-edge structure (XANES) measurement was further performed to characterize the oxidation state of Cs^81,82. As shown in Fig. 2d, the Cs K-edge for both CsX-L (CsX-L was exchanged with low concentration 0.04 mol/L CsOH) and CsX (CsX was exchanged with concentration 0.4 mol/L CsOH) catalysts are located at the low-energy positions as compared with that of the Cs₂CO₃ standard sample, indicating the lower oxidation states of the CsX catalyst, which is consistent with the XPS result. The particle size of ZZO is in the range of 10–30 nm (Fig. 2e), and HRSTEM shows (101) facet is the dominant surface exposed in t-ZrO₂, the HAADF-STEM displays that the Zn and Zr elements are relatively uniformly distributed in ZZO particles (Fig. 2i, j) with the presence of trace ZnO particles. The prepared CsX shows the nanosphere morphology ranging from 2 to 5 μm (Fig. 2k, l). The two components of tandem catalysts fabricated by physical mixing of ZZO and CsX keep their individual structures. Due to the smaller nanoparticles of ZZO compared to CsX, the ZZO particles are highly dispersed on the outer surface of CsX in ZZO/CsX tandem catalysts (Fig. 2m, n).

Fig. 2. Catalyst characterization.

a XRD patterns of individual χ%ZnZrO; PDF number: t-ZrO₂, 49-1642; ZnO, 36–1451. b XRD patterns of CsX and NaX, respectively. c XPS spectra of Cs species for individual CsX zeolite. d The Cs K-edge for individual CsX-L and CsX catalysts. e The TEM (f, g) high-resolution STEM of individual ZZO catalyst and (h–j) aberration-corrected scanning TEM–high-angle annular dark-field images and element distribution of individual ZZO catalyst; Scanning electron microscopy images of individual CsX (k, l). m, n Scanning electron microscopy images of mixed ZZO/CsX (1:6).

To investigate the function of CsX in ZZO/CsX tandem catalysts, the NaX exchanged with different metal cations were employed to construct tandem catalysts. The ZZO/CsX tandem catalysts give the maximum conversion of MEPY and STY of ETPY, indicating that CsX shows the highest activity for the activation of sp³ C–H bond and C–C bond coupling (Fig. 3a). This performance was associated with its strong basic properties among these modified X zeolites. To understand the critical effect of Cs species of CsX for the C–C bond coupling, the Cs₂O-SiO₂ catalyst was prepared by depositing Cs₂O on the surface of SiO₂. Unfortunately, the ZZO/Cs₂O-SiO₂ tandem catalysts show no activity for side-chain alkylation of MEPY through CO₂ hydrogenation (Fig. 3b). On the contrary, the CsX-L catalyst with a lower content of Cs was controllably prepared, and the Cs species are mainly Cs⁺. Compared with ZZO/Cs₂O-SiO₂, ZZO/CsX-L tandem catalysts show an MEPY conversion of 16%, which is slightly lower than the ZZO/CsX (Fig. 3b). These results suggest that the Cs⁺ balanced the negative charge of zeolite framework, rather than the Cs₂O species deposited on CsX, is responsible for MEPY activation and C–C bond coupling. The base and acid properties of ZnZrO and CsX were conducted by using CO₂-TPD and NH₃-TPD (Supplementary Fig. 8, Supplementary Fig. 9), the Fourier transform infrared (FTIR) spectroscopy of adsorbed pyridine⁷⁵ was further performed to distinguish the strength of acid sites for NaX and CsX. Figure 3c, d shows the bands at 1592 and 1442 cm⁻¹ for NaX (Fig. 3c) and at 1579 and 1438 cm⁻¹ for CsX (Fig. 3d), indicating the existence of the Lewis acid sites on both NaX and CsX. With increasing the desorption temperature of pyridine from 50 to 100 and 200 °C, the intensity of peaks for all acid sites decreases. Further increasing the desorption temperature from 200 to 300 and 400 °C, obvious signals of pyridine adsorbed on NaX can still be observed, however, pyridine has completely desorbed on the CsX, indicating the weaker Lewis acidity of CsX than NaX. It is known that these peaks of Lewis acid sites can be assigned to the adsorption of pyridine on the Na⁺ and Cs⁺ sites in NaX and CsX through the N atom of pyridine. Thus, it is deduced that, compared with NaX, the weaker adsorption of the pyridine moiety of MEPY on CsX facilitates the sp³ C–H bond activation and C–C bond formation over Cs⁺ sites under the reaction temperature of 380 °C.

Fig. 3. The effect of different zeolites on catalytical performance and the results of FT-IR spectra.

a Side-alkylation of MEPY on tandem catalysts with different cation-exchanged X zeolite, m (ZZO): m (LiX, NaX, KX, CsX, MgX or CaX) = 1: 9. b Side-alkylation of MEPY on ZZO/CsX (1: 6), ZZO/Cs₂O-SiO₂ (1: 6), ZZO/CsX-L (1: 6), T = 380 °C. Standard reaction conditions: VHSV = 0.6 mL g⁻¹ h⁻¹, P = 2.0 MPa, H₂/CO₂/Ar = 72/24/4 and GHSV = 16,000 mL g⁻¹ h⁻¹. c, d FT-IR spectra of adsorbed pyridine at different temperatures for individual X and CsX zeolites; Lewis Acid (LA); The color shadings represent the selectivity, and the red square represents the conversion.

In order to understand the working mechanism of the tandem catalyst^39,45, the side-chain alkylation of MEPY with CO₂ hydrogenation on ZZO/CsX and with methanol on CsX was compared at the same reaction temperature of 380 °C (Fig. 4a). Surprisingly, we found that the conversion of MEPY with CO₂ hydrogenation on ZZO/CsX is 6.5 times of the side-chain alkylation with methanol on CsX, indicating that the side-chain alkylation of MEPY with CO₂ hydrogenation does not undergo the same reaction pathway with methanol as an intermediate. To further clarify the tandem catalysis, the catalytic activity of the tandem catalyst was compared with the different proximity of the two components in a tubular fixed-bed reactor (Fig. 4b). When ZZO and CsX were mixed in a granule (200−450 μm), the conversion of MEPY decreases sharply from 19.6 to 12% (Fig. 4b, I and II). The conversion of MEPY decreases continuously when the two components of ZZO and CsX are placed as dual bed layers (Fig. 4b, III). When ZZO and CsX particulates are separated in space with a quartz sand layer (Fig. 4b, IV), the conversion of MEPY severely deteriorates. The conversion of MEPY drops dramatically with decreasing the contact area of the two components, suggesting that the excellent conversion of MEPY for tandem catalyst is due to the effective synergy between ZZO and CsX, which further implies that the gaseous methanol is not the main intermediate for side-chain alkylation of MEPY.

Fig. 4. The tandem reaction coupling.

a Side-alkylation of MEPY with CO₂ hydrogenation on ZZO/CsX and with methanol on CsX (molar ratio of methanol to MEPY is 1:1, VHSV was calculated as 0.6 mL g⁻¹ h⁻¹ based on MEPY). b Side-alkylation of MEPY with CO₂ hydrogenation over ZZO/CsX, integrated catalyst components ZZO and CsX with different proximity. Standard reaction conditions: VHSV = 0.6 mL g⁻¹ h⁻¹, P = 2.0 MPa, T = 380 °C, H₂/CO₂/Ar = 72/24/4 and GHSV = 16000 mL g⁻¹ h⁻¹, m (ZZO): m (CsX) = 1: 6; (ZZO/CsX denoted as the ZZO/CsX). The color shadings represent the selectivity, and the red square represents the conversion; (I): ZZO and CsX were mixed in powder; (II): ZZO and CsX were mixed in a granule; (III): ZZO and CsX are placed as dual bed layers; (IV): ZZO and CsX particulates are separated in space with a quartz sand layer.

To understand the coupling mechanism in reaction kinetics, the surface species formed on ZZO were detected by an in-situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS)^8,83 (Fig. 5). The HCOO* and CH₃O* species are distinctly observed for ZZO (Fig. 5a, b). The IR peaks at 1599 and 1368 cm⁻¹ are assigned to the asymmetric and symmetric OCO stretching vibrations of adsorbed bidentate HCOO* species, respectively. The peaks at 2884 and 1387 cm⁻¹ are assigned to the stretching vibration ν(CH) and bending vibration δ(CH), respectively. The peaks at 2938 and 2828 cm⁻¹ are attributed to CH₃O* species. The peaks at 2884 and 2828 cm⁻¹ were used to determining the tendency of changes of HCOO* and H₃CO* species, meanwhile, the products were also detected by mass spectrometry (MS)^8,83. As seen in Fig. 5c, when CO₂ + H₂ was switched to CO₂ + D₂, the HCOO* and CH₃O* species decrease, while the DCOO* and CD₃O* species increase, and the D-substituted products were also detected by MS. When CO₂ + H₂ was switched to D₂, the HCOO* and H₃CO* species gradually decrease (Fig. 5d). Correspondingly, two new peaks at 2165 and 2052 cm⁻¹ for DCOO* and CD₃O* species appear, and then decrease slowly (Fig. 5e, f). Also, the D-substituted products show the same tendency of DCOO* and CD₃O* species (Fig. 5f). According to these evidences, the CO₂ hydrogenation mainly undergoes the formate reaction pathway, and the CH_xO* (CH₂O*) species is the key intermediate for the hydrogenation of HCOO* to CH₃O*, the synergetic effect between Zn and Zr sites play a key role for generating the key intermediates CH_xO^8,39,45,83.

Fig. 5. Characterization of surface species.

a, b In-situ DRIFT spectra of surface species formed from the CO₂ + H₂ reaction on individual ZZO catalyst. (c) DRIFT-MS of CO₂ + H₂ and subsequently switched to CO₂ + D₂ reactions on individual ZZO catalyst. d, e In situ DRIFT spectra of surface species from CO₂ + H₂ and subsequently switched to D₂ on individual ZZO catalyst. f DRIFT-MS of CO₂ + H₂ and subsequently switched to D₂ on individual ZZO catalyst. Reaction conditions: ZZO catalyst, 300 °C, 20 ml/min Ar + 10 ml/min CO₂ + 30 ml/min H₂ (D₂).

According to the above results, it is suggested that the CH_xO* (CH₂O*) as key intermediates in CO₂ hydrogenation conduct the coupling of kinetics between the two components of ZZO and CsX of tandem catalysts. To further confirm this speculation, Density functional theory (DFT) calculations were performed to understand the reaction mechanism^84–88 (details in the Supplementary Information). The two major intermediates, i.e., CH₂O* and methanol, which can transfer from ZZO into the micropore of CsX, were evaluated. Using methanol as the intermediate involves the dehydrogenation of methanol to formaldehyde species (CH₂O*) in CsX. With the adsorption of the oxygen atom of methanol on Cs⁺ of CsX, the C–H and O–H bonds were activated, which resulted in the dehydrogenation of CH₃OH* and the formation of CH₂O* and two H* (Fig. 6 a2). It is found that the dehydrogenation of CH₃OH* to CH₂O* and H* needs to overcome an extremely high activation barrier of 437 kJ/mol (Fig. 6b). Although coupling of H* species to molecular H₂ can stabilize the system (Fig. 6 a3), the formation of CH₂O* and H₂ from CH₃OH is still an endothermic reaction process on Cs⁺. These results strongly suggest that the dehydrogenation of methanol to CH₂O* is thermodynamically and kinetically unfavorable over the CsX catalytic component.

Fig. 6. Results of DFT calculations.

a Optimized geometries of all reaction intermediates and transition states. Reaction Gibbs free energy diagram (T = 380 °C, P = 2.0 Mpa) of (b): methanol dehydrogenation process over CsX zeolite. c CH₂O reacting with MEPY on CsX zeolite.

In principle, according to our previous works^39,45 and above experimental results, it is proposed that the CH₂O* can be as the intermediate to participate the C–C bond coupling over zeolite. Compared with methanol, the CH₂O* as the intermediate can avoid the thermodynamically unfavorable dehydrogenation of methanol. As shown in Fig. 6, firstly, the CH₂O* adsorbs on Cs⁺ of CsX channel by forming the O-Cs bond, and MEPY* interacts with CsX through binding of N with Cs⁺, as well as the H (CH₃) activated by the O (Si–O–Al) of CsX zeolite (Fig. 6c, b1). With the attacking of the C of -CH₃ moiety to the C site of CH₂O*, the H (CH₃) also binds with the O (CH₂O*) and forms a four-numbered ring (H–C–C–O), which is the transition state for the C–C bond coupling (Fig. 6c, bTS1). The formation of HOCH₂-CH₂py* needs to overcome an activation barrier of 270 kJ/mol with the cleavage of C–H bond (CH₃) and the formation of O (CH₂O*)-H (CH₃) bond (Fig. 6c, b2), which is energetically the most difficult reaction step. The dehydration of HOCH₂-CH₂py* occurs smoothly with protonating the OH group (Fig. 6c, bTS2), and the VYPY* is formed with the cleavage of the C-O bond (H₂O* formation) (Fig. 6c, b3). The ETPY* was produced with the desorption of H₂O* (Fig. 6c, b4) and the hydrogenation of VYPY* (Fig. 6c, b5). Finally, the product ETPY* is formed through hydrogenation (Fig. 6c, b6), and the formaldehyde route experiments also verified this mechanism (Supplementary Fig. 10). In addition, the pathways for by-product formation are also proposed and shown in Supplementary Fig. 11.

DFT results suggest that the synthesis of ETPY through CH₂O* intermediate only needs to overcome the highest activation energy barrier of 270 kJ/mol, which is far lower than that of methanol dehydrogenation to CH₂O (437 kJ/mol) (Fig. 6b). Therefore, it is concluded that the key intermediate for realizing the kinetics coupling of ZZO/CsX tandem catalysts is CH₂O* but not methanol. Based on the surface reaction kinetics and DFT calculations, it is proposed that the tandem reaction proceeds as follows in Fig. 7: Firstly, the generation of key intermediates CH_xO species via CO₂ hydrogenation mainly takes place on the ZnZrO catalyst, and then migrate/transfer on to the CsX catalyst; Secondly, the CsX catalyst activates of sp³ C–H bond of the 4-methylpyridine (MEPY) to form the carbanion; Finally, the coupling of C–C bond occurs between the migrated/transferred CH_xO species and the carbanion on the CsX catalyst to produce the 4-ethylpyridine (ETPY).

Fig. 7. Proposed side-alkylation of MEPY with CO₂ hydrogenation on ZZO/CsX.

The generation of key intermediates CH_xO species via CO₂ hydrogenation take place on ZnZrO catalyst; The CsX catalyst activates of sp³ C–H bond of the 4-methylpyridine (MEPY) form the carbanion; The coupling of C–C bond occurs between the migrated/transferred CH_xO species and the carbanion on CsX catalyst to produce the 4-ethylpyridine (ETPY).

In summary, the direct synthesis of ETPY through CO₂ hydrogenation and sp³ C–H bond activation of MEPY was realized by a tandem catalyst, Zn₄₀Zr₆₀O/CsX. CO₂ and H₂ were activated on Zn₄₀Zr₆₀O and the activation of the sp³ C–H bond and coupling of C–C bond were conducted on CsX. The selectivity of ETPY can reach 82 % with the MEPY conversion of 19.6%. Compared with the direct methanol route, the synthesis of ETPY through CO₂ hydrogenation shows a 6.5-fold enhancement of MEPY conversion. The migrating of the key CH_xO* (CH₂O*) intermediate modulate the coupling of thermodynamics and kinetics of tandem catalysis, significantly facilitating the activation of sp³ C–H bond and coupling of C–C bond. This work highlights the potential of key intermediate CH_xO* (CH₂O*) generated in situ through CO₂ hydrogenation. It enables the C–C bond coupling by activating the sp³ C–H bond, opening a new avenue for synthesizing high-value-added chemicals through CO₂ hydrogenation.

Methods

Chemicals

Zn(NO₃)₂·6H₂O, Ca(NO₃)₂·4H₂O, Mg(NO₃)₂·4H₂O, were purchased Sinopharm (China), Zr(NO₃)₄·5H₂O, citric acid, 4-methylpyridine, diphenyl, cesium hydroxide, LiOH, KOH, were obtained from Macklin Biochemical, PVP (polyvinyl pyrrolidone) K30, average molecular weight 5800 were obtained from Sigma-Aldrich, CO₂/H₂/Ar [24/72/4(v/v/v)] were obtained from Lanzhou Yulong Gas Co., Ltd.

Preparation of catalysts

A series of χ%ZnO-ZrO₂ catalysts (χ% represent molar percentage of Zn, metal base) were synthesized by using the sol-gel method⁷³. Typically, 11.9 g Zn(NO₃)₂·6H₂O, 25.8 g Zr(NO₃)₄·5H₂O, 38.4 g citric acid and 10.0 g PVP were dissolved in 100 mL deionized water at 50 °C (Zn²⁺+Zr⁴⁺=1 mol/L) under the vigorously stir. After Zn(NO₃)₂·6H₂O, Zr(NO₃)₄·5H₂O, citric acid and PVP completely dissolved, the mixture was mildly evaporated at 90 °C until a viscous gel was obtained. Then, the sample was dried at 200 °C for 5 h, grind, and calcined at 600 °C at a rate of 5 °C/min for 10 h.

CsX catalysts were prepared by the ion exchange of NaX (from Nankai Catalysts；13X) with two times. The detailed preparation procedures are as follows: 30 g NaX was treated in a 250 mL eggplant shaped flask at 80 °C for 2.5 h with a 0.4 mol/L solution of cesium hydroxide (liquid/solid ratio: 5 mL/g). The slurries were centrifuged and washed with deionized for three times. Then, the samples obtained dried at 80 °C overnight and calcined in air at 540 °C for 3 h. The second ion exchange procedure is same as the above-mentioned process. LiX obtained with a 0.4 mol/L solution of LiOH; KX obtained with a 0.4 mol/L solution of KOH; CaX obtained with a 0.4 mol/L solution of Ca(NO₃)₂·4H₂O; MgX obtained with a 0.4 mol/L solution of Mg(NO₃)₂·4H₂O, the other conditions are same as the procedure of CsX; CsX-L was exchanged only one times with 0.04 mol/L CsOH, and the other conditions are same as the procedure of CsX.

Finally, the ZnZrO catalyst and the CsX catalyst were ground in an agate mortar for about 0.5 h to fully mix to obtain the physical mixed ZnZrO/CsX catalyst.

Catalyst Evaluation

Catalytic performance was evaluated on a high-pressure fixed-bed reactor equipped with a quartz sample tube (The diameter:10 mm). Typically, 1.0 g catalyst (40-80 mesh) were loaded into the quartz sample tube without mixed quartz sand. Before evaluating the catalytical performances, raised to the specified temperature under the protection of argon. For the investigation of 4-methylpyridine side chain alkylation with CO₂ and H₂, a mixture gas of CO₂/H₂/Ar [24/72/4(v/v/v)] was induced into a quartz sample tube, and then 4-methylpyridine was carried into reaction tube (393 K) at a constant flow rate by using a piston pump. Typically, the reaction was conducted at 653 K and 2 MPa, with a GHSV of 16000 mL·g^-1·hour^-1 and 4-methylpyridine volume hourly space velocity (VHSV) of 0.6 mL g^-1·hour^-1. Before collecting the samples, the reaction is firstly running for 2.5 hours to reach a steady state, and then collected the sample for the next 8 h. The sample was condensed at −20 °C by using a cooling condenser. In the qualitative and quantitative analysis, we use diphenyl as an internal standard to determine the N balance, and the N balance was above 96%. The liquid products were analyzed by using the gas chromatography, the conversion of 4-methylpyridine was calculated as follows:

$$Conv.=1-\frac{f_1{A}_1}{{\sum }_i^7{f}_i{A}_i}$$ 1

where f₁–f₇ refer to the 4-methylpyridine, 1,4-dimethylpiperidine, 4-ethylpyridine, 4-isopropylpyridine, 4-vinylpyridine, 4-(tert-butyl) pyridine and 2,4-dimethylpyridine molar correction factor respectively. A_i refers to the peak area in FID of product-i.

The selectivity calculation method is as follows:

$${Sel.}_i=\frac{f_i{A}_i}{{\sum }_i^6{f}_i{A}_i}$$ 2

where f₁–f₆ refer to the, 4-dimethylpiperidine, 4-ethylpyridine, 4-isopropylpyridine, 4-vinylpyridine, 4-(tert-butyl) pyridine and 2,4-dimethylpyridine molar correction factor respectively. A_i refers to the peak area in FID of product-i.

The space-time yield (STY) defined as quantity of product per unit mass per unit time (mg.g⁻¹·h⁻¹), the STY of 4-ethylpyridine (ETPY) was denoted as STY(ETPY), and the highest space-time yield (STY) of ETPY is 106 mg.g⁻¹·h⁻¹ for ZZO/CsX(1:6) tandem catalyst at 380 °C in Fig. 1b.

The catalysts (ZnZrO, CsX or ZnZrO/CsX) used in the catalyst evaluation were provided in Figs. 1–5 in the main text and Supplementary Information.

Powder x-ray diffraction (XRD)

The XRD results were collected on a Philips PW1050/81 diffractometer operating in Bragg-Brentano focusing geometry and using CuKα radiation (λ = 1.5418 Å) from a generator operating at 40 kV and 30 mA.

Aberration-corrected high-angle annular dark-field (HAADF)-scanning

Aberration-corrected HAADF-STEM images and STEM-EDX mapping images were captured using a probe aberration-corrected STEM (Cubed Titan G2 60-300, FEI, USA) operated at 300 kV.

The morphology of the catalyst was observed by SEM. Manufacturer: Thermo Fisher Scientific, Instrument Model: Apreo S, Electron Gun: Field Emission FEG, Accelerating Voltage 200–30 kV.

Brunauer–Emmett–Teller (BET)

The specific surface area and pore size distribution of the samples were determined by N₂ physisorption instrument (MicrotracBEL, BELSORP-mini II). Before the N₂ physisorption, the catalysts (~0.2 g) were degassed at 300 °C for 2 h. The specific surface area and the pore size distribution were calculated by the Brunauer- Emmett-Teller (BET) and the DFT methods, respectively.

Temperature programmed desorption (TPD)

CO₂ and NH₃ Temperature-programed desorption (TPD) were performed on a Micrometrics ASAP 2920 unit. Firstly, 100 mg catalyst was placed in a quartz reactor and pretreated at 400 °C for 3 h under argon, and then cool down to 50 °C; Secondly, the argon was switched to CO₂/NH₃ (10 vol % in He) for 1 h at 50 °C with a 50 mL/min; Then, CO₂/NH₃ was switched to He and kept at 50 °C for 1 h to remove the physisorbed CO₂/NH₃, and when the baseline was stable, the temperature was heated to 800 °C at a heating rate of 10 °C min⁻¹ under He, and the signal of desorption for CO₂/NH₃ was detected by a thermal conductivity detector (TCD).

X-ray photoelectron spectroscopy (XPS)

XPS was performed using a Thermo ESCALAB 250Xi with Al K radiation (15 kV, 10.8 mA, hν = 1486.6 eV) under an ultrahigh vacuum (5 × 10^–7 Pa), calibrated internally by the carbon deposit C(1 s) (Eb = 284.8 eV).

The catalysts (ZnZrO, CsX or ZnZrO/CsX) used in the catalyst characterization were provided in Fig. 1-5 in the main text and Supplementary Information.

Fourier transform infrared (FTIR) spectra

FTIR spectra of pyridine was performed for both NaX and CsX zeolites. The sample (about 30 mg) was pressed into a wafer, and then treated under vacuum at 400 °C for 1 h. After cooling to 50 °C, pyridine was introduced to the transmission cell until saturation. Then, the signal vs. the reference signal was recorded at different temperature (100 °C, 200 °C, 300 °C and 400 °C) until the signal unchanged.

Author contributions

Q.M. and J.C. contributed equally. Q.M. and J.C. conceived and conducted the experiments, and analyzed data; X.W., J.X., R.Z., Z.M., and H.Y. offered the help in the experiments and data analysis; W.F. and J.Z. conducted the EXAFS experiments, and analyzed data; G.L. conducted the DFT calculations, and analyzed data; J.B. offered the help in the DFT calculations. The manuscript was written by Z.L.; Z.L. and C.L. proposed the project, analyzed data and revised the manuscript.

Peer review

Peer review information

Nature Communications thanks Lei Li who co-reviewed with Zhe Hong; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. A peer review file is available.

Data availability

All data needed to support the findings of this study are included in the main text or in the Supplementary Information. Any additional information may be available from the corresponding authors upon request.

Competing interests

The authors declare no competing interests.

Supplementary information

The online version contains supplementary material available at 10.1038/s41467-024-55640-w.