Selective catalytic two-step process for ethylene glycol from carbon monoxide

Upgrading C1 chemicals (for example, CO, CO/H2, MeOH and CO2) with C–C bond formation is essential for the synthesis of bulk chemicals. In general, these industrially important processes (for example, Fischer Tropsch) proceed at drastic reaction conditions (>250 °C; high pressure) and suffer from low selectivity, which makes high capital investment necessary and requires additional purifications. Here, a different strategy for the preparation of ethylene glycol (EG) via initial oxidative coupling and subsequent reduction is presented. Separating coupling and reduction steps allows for a completely selective formation of EG (99%) from CO. This two-step catalytic procedure makes use of a Pd-catalysed oxycarbonylation of amines to oxamides at room temperature (RT) and subsequent Ru- or Fe-catalysed hydrogenation to EG. Notably, in the first step the required amines can be efficiently reused. The presented stepwise oxamide-mediated coupling provides the basis for a new strategy for selective upgrading of C1 chemicals.

Supplementary Table 4. Effect of iodine source on Pd-catalyzed oxidative carbonylation of piperidine.

Supplementary Table 14
Variation of reaction conditions in step 2 using the reaction mixture of step 1 as the starting material.
Discussion: Notably, the hydrogenation of 2 in toluene is more efficient than in THF when using isolated 2 as the reactant. Therefore, we investigated the solvent effect with the reaction mixture of step 1 as the reactant (entry 1: THF, entry 2: THF/toluene, entry 3: toluene). Unfortunately, in all cases only low conversion of 2 was detected (5-28%). However, after short filtration (2-3 cm silica gel) to remove undissolved Pd particles EG was obtained in 98% yield as detected by 1 H NMR. When increasing the amount of the reaction mixture of step 1 from 6 mL to 20 mL, the reaction gave 92% yield of EG (entry 5).
Entry Procedure for "one-pot" production of EG Conv.(%) a Yield/% b 1 After hydrogenation, 20 mL THF was added to 6 mL of the THF reaction mixture of step 1. Then, the newly resulting mixture was added to a 100 mL autoclave which was charged with 58 mg Ru-MACHO and 22.4 mg KO t Bu. After the autoclave was flushed with H 2 three times and pressurized with H 2 to 50 bar, the reaction was performed at 160 o C for 20 h.

26
--2 After hydrogenation, 20 mL toluene was added to 6 mL of the THF reaction mixture of step 1. Then, the resulting mixture was added to a 100 mL autoclave which was charged with 58 mg Ru-MACHO and 22.4 mg KO t Bu. After the autoclave was flushed with H 2 three times and pressurized with H 2 to 50 bar, the reaction was performed at 160 o C for 20 h.

--3
After hydrogenation, the solvent was removed in vacuo from 6 mL of reaction mixture of step 1 followed by addition of 20 mL toluene. The resulting mixture was stirred at RT for 20 min and then added to a 100 mL autoclave which was charged with 58 mg Ru-MACHO and 22.4 mg KO t Bu. After the autoclave was flushed with H 2 three times and pressurized with H 2 to 50 bar, the reaction was performed at 160 o C for 20 h.

--4
After hydrogenation, THF was removed in vacuo from 6 mL of the reaction mixture of step 1 followed by addition of 20 mL toluene. The resulting mixture was stirred at RT for 20 min and then filtrated (silica gel, 2-3 cm). The filtrate was injected by syringe to a 100 mL autoclave which was charged with 58 mg Ru-MACHO and 22.4 mg KO t Bu. After the autoclave was flushed with H 2 three times and pressurized with H 2 to 50 bar, the reaction was performed at 160 o C for 20 h.
>99 98 5 After hydrogenation, THF was removed from 20 mL of the reaction mixture of step 1 followed by addition of 20 mL toluene. The resulting mixture was stirred at RT for 20 min and then filtrated through thin silica gel (2-3 cm). The filtrate was injected by syringe to a 100 mL autoclave which was charged with 58 mg Ru-MACHO and 22.4 mg KO t Bu. After the autoclave was flushed with H 2 three times and pressurized with H 2 to 50 bar, the reaction was performed at 160 o C for 20 h.

>99 92
a. Determined by GC using iso-octane as internal standard. b. 1 H NMR yield using tertbutanol as internal standard.

General information
Air-and moisture-sensitive syntheses were performed under argon atmosphere in heating gun vacuum dried glassware. Chemicals were purchased from Aldrich, Alfa, Acros or Strem.
Unless otherwise noted, all commercial reagents were used without further purification. 1 H and 13 C NMR spectra were recorded on Bruker Avance 300 (300 MHz) NMR spectrometers.
Chemical shifts δ (ppm) are given relative to solvent: references for benzene-d 6 were 2.09 ppm ( 1 H-NMR) and 30.60 ppm ( 13 C-NMR). 13 C-NMR spectra were acquired on a broad band decoupled mode. GC analysis was performed on a Agilent 7890A chromatograph with a a 29 m HP5 column. The products were isolated from the reaction mixture by solvent evaporation and further purified by recrystallization in vacuum. Complexes c-1, c-2, c-3, c-4, c-5 (in situ) were purchased and used directly. Complexes c-6 28 and c-10 38 were prepared based literature methods.
General procedure for Pd-catalyzed oxidative carbonylation of piperidine 1) Under argon atmosphere, vial (4 mL) was charged with palladium precursor and ligand (monodentate ligand: Pd/L = 1/2.2, bidentate ligand: Pd/L = 1/1.1). The solvent was injected into the vial by the syringe and the solution was stirred for 10 min at room temperature. Then K 2 CO 3 , nBu 4 NI, and piperidine were added into the reaction solution. The vial was placed in an alloyed plate, which was then transferred into an autoclave (300 mL). At room temperature, the autoclave was pressurized with air (25 bar) and CO (25 bar). The reaction was performed at room temperature for desired time. After the reaction finished, the pressure was carefully released. The yield and selectivity were measured by GC analysis using isooctane as internal standard.
2) Consecutive experiments (4 runs): 8.5 g of amine 1 (0.1 mol) was used in 100 mL THF in the presence of 31 mg Pd(acac) 2 (0.1 mol%), 68 mg (o-tol) 3 P (0.22 mol%), 0.9 g nBu 4 NI (2.5 mol%) and 0.7 g K 2 CO 3 (5 mol%). After reaction at room temperature for 12 h, the pressure was released. 95% Yield of 2 was observed by GC and to the mixture another portion of 1 (8.5 g) was added followed by re-pressurizing air and CO for 12 h of reaction. Similarly, two more portions of 1 were added to the same reactor after a specific period of time. Altogether, the whole procedure was done corresponding to 0.033 mol% of catalyst loading. After crystallization, 30.9 g of 2 was obtained with 92% yield (See chart below). , 3.15-3.24

Oxamide-mediated production of EG from CO via two steps
Step 1: In a 300 mL autoclave, 6.1 mg Pd(acac) 2 (0.02 mmol) and 244 mg P(o-tol) 3 (0.8 mmol) were dissolved in 100 mL THF. After the solution was stirred at room temperature for 10 min, 1.48 g n Bu 4 NI (4 mmol), 2.76 g K 2 CO 3 (20 mmol), and 5.0 mL piperidine (50 mmol) were added. The autoclave was pressurized with air (25 bar) and CO (25 bar). After the reaction was stirred at room temperature for 16 h, the pressure was released. 99% yield of the corresponding oxamide 2 was observed by GC. Another portion of 5 mL piperidine 1 (50 mmol) was added into the mixture followed by re-pressurizing air (25 bar) and CO (25 bar). The reaction mixture was stirred at room temperature for 16 h. Similarly, two more portions of 5 mL piperidine 1 (50 mmol) were added to the same reactor after 16 h. Altogether, the whole procedure was done corresponding to 0.01 mol% of palladium catalyst loading. After all, 98% yield of the desired product was detected by GC analysis using isooctane as the internal standard.
Step 2: THF was removed from 60 mL reaction mixture of step 1 followed by addition of 120 mL toluene. After stirring at room temperature for 20 min, the resulted mixture was filtrated through thin silica gel (2-3 cm). 5 mL toluene was used to wash the residue. The concentration of oxamide 2 in toluene was determined as follows: 1 mL filtrate was taken out followed by addition of 100 L isooctane (internal standard), 94 mg oxamide 2 (0.42 mmol) in 1 mL toluene was observed by GC analysis. Then 12 mL toluene solution of 2 (5 mmol) was added into a 100 mL autoclave which charged with 29 mg Ru-MACHO-BH (0.05 mmol) and 11.2 mg KO t Bu (0.1 mmol) under argon atmosphere. 8 mL toluene was injected by syringe to the autoclave. At room temperature the autoclave was flushed with H 2 three times, and then pressurized with H 2 to 60 bar. The reaction was performed at 160 o C for 12 h. Full conversion of 2 was detected by GC analysis. 96% yield of ethyl glycol was measured by 1 H NMR analysis using tert-butanol as internal standard.