Photocatalytic C-N coupling from stable and transient intermediates for gram-scale acetamide synthesis

Abstract

Electro/photocatalytic C-N coupling acts as a key build-block to the next generation of chemicals like amides for wide applications in energy, pharmaceuticals and chemical industries. However, the uncontrolled intermediates coupling challenges the efficient amide production regarding yield or selectivity. Here we propose a photocatalytic radical addition route, where the fundamental active species, including oxygen and photogenerated electron-hole pairs, are regulated for selective intermediates generation and efficient acetamide synthesis from mild co-oxidation of CH₃CH₂OH and NH₃. Sufficient CH₃CH₂OH is provided to accumulate the stable intermediate (CH₃CHO). Meanwhile, the limited NH₃ concentration ensures the controllable generation and fast addition of the transient radical (^●NH₂) on CH₃CHO. Through the directed coupling of stable-transient intermediates, the acetamide synthesis rate is pushed forward to a hundred-mmol level (105.61 ± 4.86 mmol·g_cat^-1·h^-1) with a selectivity of 99.17% ± 0.39%, reaching a gram-scale yield (1.82 g) of acetamide. These results illuminate valuable opportunities for the photocatalysis-driven synthetic industry.

Fig. 1. Schematic diagram.

Illustration for the coupling of stable and transient intermediates for acetamide photosynthesis.

Fig. 2. Efficiency evaluation for acetamide photosynthesis.

a catalyst dosage-dependent unit production rate; CH₃CONH₂ selectivity evaluation regarding the N-(b) and C-sources (c), respectively; d Efficiency comparison between different catalytic routes for photocatalytic C-N coupling, including the targets of production rate and selectivity, the corresponding research works are listed and cited in  Supplementary Information (Supplementary Table 3)^–; e Long-term stability test. f XRD pattern and the image (inset) of the collected CH₃CONH₂ sample with rotary evaporation after the long-term stability test. The respective standard curves for detecting the reaction species using ion chromatography (IC, NH₄⁺, NO₂⁻, NO₃⁻, CH₃COOH, and NH₂OH, Supplementary Figs. 31–35) are provided in  Supplementary Information. The error bars in (a–c) were drawn based on the calculated standard error of two parallel tests.

Fig. 3. In situ ATR-FTIR investigation for revealing the reaction coordinates.

Time-dependent IR signals for the individual ethanol oxidation reaction (EOR, a), ammonia oxidation reaction (AOR, b), and combined EOR and AOR (c), respectively; Normalized results of the IR signals of COO⁻ (d), NO₃⁻ (e), C=O (f), and -NH₂ (g), respectively. The full spectra of the adsorption and photocatalysis process are provided in Supplementary Information for individual EOR (Supplementary Fig. 37), individual AOR (Supplementary Fig. 38), and combined EOR and AOR (Supplementary Fig. 39), respectively.

Fig. 4. The mechanisms of O₂ regulation for generating the coupling intermediates.

a O₂ proportion-dependent CH₃CONH₂ yield; DMPO-trapping (with D-labeling, images above) and TEMP-trapping (images below) in situ EPR experiments under the O₂ proportion of 0% (b), 75% (c), and 100% (d) respectively. The error bars in (a) were drawn based on the calculated standard error of two parallel tests.

Fig. 5. Transformation and coupling mechanism for the C- and N-intermediates.

a Control experiments for CH₃CONH₂ synthesis by replacing CH₃CH₂OH with CH₃CHO as the C-source; GC (b) and ¹H NMR (c) results with D- (images right) and H-labeling (images left) respectively; d DMPO-trapping in situ EPR experiments with ¹⁴N- (image above) and ¹⁵N-labeling (image below) respectively; e in situ EPR spectra for e⁻-induced TEMPO consumption with (image below) and without (image above) NH₃ provision respectively; f HR-MS results for CH₃CONH₂ detection with ¹⁴N- (image above) and ¹⁵N-labeling (image below) respectively; g Proposed reaction pathways of CH₃CH₂OH and NH₃ co-oxidation for intermediates coupling and CH₃CONH₂ synthesis. The error bars in (e) were drawn based on the calculated standard error of two parallel tests.