Switching the hydrogenation selectivity of urea derivatives via subtly tuning the amount and type of additive in the catalyst system

Catalytic hydrogenation of urea derivatives is considered to be one of the most feasible methods for indirect reduction functionalization of CO2 and synthesis of valuable chemicals and fuels. Among value-added products, methylamines, formamides and methanol are highly attractive as important industrial raw materials. Herein, we report the highly selective catalytic hydrogenation of urea derivatives to N-monomethylamines for the first time. More importantly, two- and six-electron reduction products can be switched on/off by subtly tuning 0.5 mol% KOtBu (2% to 1.5%): when the molar ratio of KOtBu/(PPh3)3RuCl2 exceeds 2.0, it is favorable for the formation of two-electron reduction products (N-formamides), while when it is below 2.0, the two-electron reduction products are further hydrogenated to six-electron reduction products (N-monomethylamines and methanol). Furthermore, changing the type of additive can also regulate this interesting selectivity. Control experiments showed that this selectivity is achieved by regulating the acid-base environment of the reaction to control the fate of the common hemiaminal intermediate. A feasible mechanism is proposed based on mechanistic experiments and characterization. This method has the advantages of being simple, universal and highly efficient, and opens up a new synthesis strategy for the utilization of renewable carbon sources.


General Experimental
All experiments were carried out under an atmosphere of purified nitrogen in a Vacuum Atmospheres glove box.All solvents were reagent grade or better.Deuterated solvents were used as received.All solvents were degassed with argon and kept in the glove box over 4Å molecular sieves.All the chemicals used in the catalytic reactions and authentic samples of the product (N-methylamines and amines) are commercially available.NMR spectra were recorded using Bruker-500 instrument. 1 H NMR chemical shifts are reported in ppm downfield from tetramethylsilane and referenced to the residual signals of an appropriate deuterated solvent.Mass spectra were recorded on Agilent 6545 Q-TOF, using Electro Spray Ionization (ESI) mode.GC-MS was carried out on a Shimadzu GC/MS-QP2010 system (Shimadzu, Germany), carried out using a DB-5 column (30 m × 0.25 mm × 0.25 μm film thickness), and helium as carrier gas.GC analysis were obtained on GC-2010 (Shimadzu, Japan) and carried out using a HP-1 column (30 m × 0.25 mm × 0.25 μm film thickness) using biphenyl as an internal standard.The quantitative analysis of the products (formamides and amines) was performed by comparison with the corresponding authentic samples (commercially purchased).Inlets: 280 o C; Detector: FID 300 o C; Carrier Gas: N 2 ; Flow: 1 mL/min; Oven: 40 o C, hold 7 min; 5 o C/min to 80 o C, hold 3 min; 2 o C/min to 100 o C, hold 3 min; 20 o C/min to 300 o C, hold 3 min.

Procedure for the catalytic hydrogenation of urea derivatives
In a N 2 glove box, 0.01 mmol of the ruthenium precursor, 0.015 mmol of 1,1,1tris(diphenylphosphinomethyl)ethane and 0.0025 mmol of KO t Bu were added in 4 mL of THF to a 50 mL autoclave (Anhui CHEM N Instrument Co., Ltd).This mixture was stirred for 5 min, then 2 mmol urea derivative was added to it.Remove the sealed autoclave from the glove box, rinse it four times with hydrogen gas (Pressure to 50 bar, release to 2 bar, cycle four times) and pressurize it to the specified pressure, and heat it with stirring at the specified temperature.After the reaction, the steel autoclave was cooled in an ice-bath for 30 min and slowly depressurized.The biphenyl (internal standard) was added to the cold solution and then filtered through Celite, and the solution was analyzed by GC/GC-MS and 1 H NMR spectroscopy.S4

Further experimental data (a) Hydrogenation experiment
In a N 2 glove box, 2 mmol chlorophenylisocyanate was added in 4 mL of THF to a 50 mL autoclave.Remove the sealed autoclave from the glove box, rinse it four times with H 2 (Pressure to 50 bar, release to 2 bar, cycle four times) and pressurize it to the specified pressure, and heat it with stirring at the specified temperature.After the reaction, the steel autoclave was cooled in an ice-bath for 30 min and slowly depressurized.The biphenyl (internal standard) was added to the cold solution and then filtered through Celite, and the solution was analyzed by GC.In a N 2 glove box, 0.01 mmol of the ruthenium precursor, 0.015 mmol of 1,1,1tris(diphenylphosphinomethyl)ethane and 0.025 mmol of KO t Bu were added in 4 mL of THF to a 50 mL autoclave.Remove the sealed autoclave from the glove box, rinse it four times with hydrogen gas (Pressure to 50 bar, release to 2 bar, cycle four times) and pressurize it to the specified pressure, and heat it with stirring at the specified temperature.After reaction 2h, the steel autoclave was cooled in an ice-bath for 30 min.Then, 0.01 mmol of HNTf 2 was added to it were added in catalyst solution in a N 2 glove box.This mixture was stirred for 5 min, then 2 mmol of 1,3-bis(4-chlorophenyl)urea was added to it.Remove the sealed autoclave from the glove box, rinse it four times with hydrogen gas (Pressure to 50 bar, release to 2 bar, cycle four times) and pressurize it to the specified pressure, and heat it with stirring at the specified temperature.After reaction 12h, the steel autoclave was cooled in an ice-bath for 30 min and slowly depressurized.The biphenyl (internal standard) was added to the cold solution and then filtered through Celite, and the solution was analyzed by GC.In a N 2 glove box, 0.01 mmol of the ruthenium precursor and 0.01 mmol of KO t Bu were added in 4 mL of THF to a 50 mL autoclave.This mixture was stirred for 5 min, then 2 mmol N-(4chlorophenyl)formamide was added to it.Remove the sealed autoclave from the glove box, rinse it four times with hydrogen gas (Pressure to 50 bar, release to 2 bar, cycle four times) and pressurize it to the specified pressure, and heat it with stirring at the specified temperature.After reaction 8h, the steel autoclave was cooled in an ice-bath for 30 min and slowly depressurized.The biphenyl (internal standard) was added to the cold solution and then filtered through Celite, and the solution was analyzed by GC.A 50 mL autoclave was charged with a solution of 1,1,1-tris(diphenylphosphinomethyl)ethane (0.03 mmol), (PPh 3 ) 3 RuCl 2 (0.02 mmol) and t BuOK (0.05 mmol) in 4.0 mL THF.The autoclave was pressurized with 50 bar H 2 and heated for 4 h at 140 °C.After the reaction, the autoclave was cooled in an ice-bath for 30 min and vented in a glove box.0.1 mL of the solution filtered with Celite was sealed in a vial for ESI-MS test.A 50 mL autoclave was charged with a solution of 1,1,1-tris(diphenylphosphinomethyl)ethane (0.03 mmol), (PPh 3 ) 3 RuCl 2 (0.02 mmol) and t BuOK (0.02 mmol) in 4.0 mL THF.The autoclave was pressurized with 50 bar H 2 and heated for 4 h at 140 °C.After the reaction, the autoclave was cooled in an ice-bath for 30 min and vented in a glove box.0.1 mL of the solution filtered with Celite was sealed in a vial for ESI-MS test.In a N 2 glove box, 0.01 mmol of the ruthenium precursor, 0.015 mmol of 1,1,1tris(diphenylphosphinomethyl)ethane and 0.025 mmol of KO t Bu were added in 4 mL of THF to a 50 mL autoclave.Remove the sealed autoclave from the glove box, rinse it four times with hydrogen gas (Pressure to 50 bar, release to 2 bar, cycle four times) and pressurize it to the specified pressure, and heat it with stirring at the specified temperature.After reaction 2h, the steel autoclave was cooled in an ice-bath for 30 min.Then, 0.01 mmol of HNTf 2 was added to it were added in catalyst solution in a N 2 glove box.Remove the sealed autoclave from the glove box, rinse it four times with hydrogen gas (Pressure to 50 bar, release to 2 bar, cycle four times) and pressurize it to the specified pressure, and heat it with stirring at the specified temperature.After reaction 12h, the autoclave was cooled in an icebath for 30 min and vented in a glove box.0.1 mL of the solution filtered with Celite was sealed in a vial for ESI-MS test.In a N 2 glove box, 0.01 mmol of the ruthenium precursor and 0.015 mmol of 1,1,1tris(diphenylphosphinomethyl)ethane were added in 4 mL of THF to a 50 mL autoclave.This mixture was stirred for 5 min, then 2 mmol 1,3-bis(4-chlorophenyl)urea was added to it.Remove the sealed autoclave from the glove box, and heated for 12 h at 140 °C.After the reaction, the autoclave was cooled in an ice-bath for 30 min and vented in a glove box.0.1 mL of the solution filtered with Celite was sealed in a vial for ESI-MS test.In a N 2 glove box, 0.01 mmol of the ruthenium precursor, 0.015 mmol of 1,1,1tris(diphenylphosphinomethyl)ethane and 0.025 mmol of t BuOK were added in 4 mL of THF to a 50 mL autoclave.This mixture was stirred for 5 min, then 2 mmol 1,3-bis(4-chlorophenyl)urea was added to it.Remove the sealed autoclave from the glove box, rinse it four times with hydrogen gas (Pressure to 50 bar, release to 2 bar, cycle four times) and pressurize it to the specified pressure, and heat it with stirring at the specified temperature.After the reaction, the steel autoclave was cooled in an ice-bath for 30 min and slowly depressurized.Afterwards, THF was slowly evaporated and the product precipitated form the concentrated reaction mixture which was analysed by NMR.[3]   In a N 2 glove box, 0.01 mmol of the ruthenium precursor, 0.015 mmol of 1,1,1tris(diphenylphosphinomethyl)ethane and 0.01 mmol of t BuOK were added in 4 mL of THF to a 50 mL autoclave.This mixture was stirred for 5 min, then 2 mmol 1,3-bis(4-chlorophenyl)urea was added to it.Remove the sealed autoclave from the glove box, rinse it four times with hydrogen gas (Pressure to 50 bar, release to 2 bar, cycle four times) and pressurize it to the specified pressure, and heat it with stirring at the specified temperature.After the reaction, the autoclave was cooled in an ice-bath for 30 min and vented in a glove box. 1 mL of the solution filtered with Celite was sealed in a vial for ESI-MS test.In a N 2 glove box, 0.01 mmol of (PPh 3 ) 3 Ru(CO)(H) 2 , 0.015 mmol of 1,1,1tris(diphenylphosphinomethyl)ethane and 0.01 mmol of t BuOK were added in 4 mL of THF to a 50 mL autoclave.This mixture was stirred for 5 min, then 2 mmol 1,3-bis(4-chlorophenyl)urea was added to it.Remove the sealed autoclave from the glove box, rinse it four times with hydrogen gas (Pressure to 50 bar, release to 2 bar, cycle four times) and pressurize it to the specified pressure, and heat it with stirring at the specified temperature.After reaction 12h, the autoclave was cooled in an ice-bath for 30 min and vented in a glove box. 1 mL of the solution filtered with Celite was sealed in a vial for ESI-MS test.In a N 2 glove box, 0.01 mmol of (PPh 3 ) 3 Ru(CO)(H) 2 and 0.015 mmol of 1,1,1tris(diphenylphosphinomethyl)ethane were added in 4 mL of THF to a 50 mL autoclave.This mixture was stirred for 5 min, then 2 mmol 1,3-bis(4-chlorophenyl)urea was added to it.Remove the sealed autoclave from the glove box, rinse it four times with hydrogen gas (Pressure to 50 bar, release to 2 bar, cycle four times) and pressurize it to the specified pressure, and heat it with stirring at the specified temperature.After reaction 12h, the autoclave was cooled in an ice-bath for 30 min and vented in a glove box. 1 mL of the solution filtered with Celite was sealed in a vial for ESI-MS test.In a N 2 glove box, 0.01 mmol of (PPh 3 ) 3 RuCl 2 and 0.015 mmol of 1,1,1tris(diphenylphosphinomethyl)ethane were added in 4 mL of THF to a 50 mL autoclave.This mixture was stirred for 5 min, then 2 mmol 1,3-bis(4-chlorophenyl)urea was added to it.Remove the sealed autoclave from the glove box, rinse it four times with hydrogen gas (Pressure to 50 bar, release to 2 bar, cycle four times) and pressurize it to the specified pressure, and heat it with stirring at the specified temperature.After reaction 12h, the autoclave was cooled in an ice-bath for 30 min and vented in a glove box. 1 mL of the solution filtered with Celite was sealed in a vial for ESI-MS test.

Figure S3 .
Figure S3.The control experiment was carried out at 160 °C.
HNTf 2 was used to neutralize excess KO t Bu in the reaction solution.