High yield production of 1,4-cyclohexanediol and 1,4-cyclohexanediamine from high molecular-weight lignin oil

The complete utilization of all lignin depolymerization streams obtained from the reductive catalytic fractionation (RCF) of woody biomass into high-value-added compounds is a timely and challenging objective. Here, we present a catalytic methodology to transform beech lignin-derived dimers and oligomers (DO) into well-defined 1,4-cyclohexanediol and 1,4-cyclohexanediamine. The latter two compounds have vast industrial relevance as monomers for polymer synthesis as well as pharmaceutical building blocks. The proposed two-step catalytic sequence involves the use of the commercially available RANEY® Ni catalyst. Therefore, the first step involves the efficient defunctionalization of lignin-derived 2,6-dimethoxybenzoquinone (DMBQ) into 1,4-cyclohexanediol (14CHDO) in 86.5% molar yield, representing a 10.7 wt% yield calculated on a DO weight basis. The second step concerns the highly selective amination of 1,4-cyclohexanediol with ammonia to give 1,4-cyclohexanediamine (14CHDA) in near quantitative yield. The ability to use RANEY® Ni and ammonia in this process holds great potential for future industrial synthesis of 1,4-cyclohexanediamine from renewable resources.


General information
Column chromatography was performed using Merck silica gel type 9385 230-400 mesh and typically dichloromethane and methanol or EtOAc and pentane as eluent.
Gas Chromatography (GC) was used for product identification as well as determination of conversion and selectivity values. Product identification was performed by GC-MS (5975C MSD) equipped with an HP-5 MS column, and helium as carrier gas. The temperature program started at 50 °C for 5 min, heated by 10 °C•min -1 to 325 °C and held for 5 min. Conversion and products selectivity were determined by GC-FID (Agilent 8890 GC) equipped with an HP-5MS column using nitrogen as carrier gas.
For the analysis of high molecular-weight fraction of lignin oil [1] : A 2mL GC vial was charged with 10 mg of DO, 1 mL anhydrous DCM, 50 µL of anhydrous pyridine and 100 µL of BSTFA. The vial was placed in an oven, and was kept at 60 °C for 1 hour. After that, the mixture was then subjected to GC-FID/MS analysis.

Nuclear Magnetic Resonance (NMR) spectroscopy:
1 H, and 13 C NMR spectra were recorded on a Bruker Avance III 300 MHz (300 and 75 MHz, respectively) and 2D NMR spectra were recorded on a Bruker Avance III 700 MHz with Cryoplatform and a 5mm Triple-Resonance cryoprobe (700 and 175 MHz, respectively). 1 H, 13 a typical procedure, a 100 mL highpressure Parr autoclave was charged with 100 mg Pd/C catalyst, 500 mg 2,6-dimethoxybenzene-1,4diol, 20 mL 2-Me THF, and equipped with mechanical stirring. The reactor was sealed and purged 3 times with H 2 and then pressurized with H 2 (40 bar). The reactor was heated to 140 °C for 6 h under stirring at 400 rpm. After completion of the reaction, the reactor was cooled to RT. Then the product was purified by silica gel column chromatography (gradient elution: methanol: dichloromethane: 0.5: 99.5-2: 98). Finally, 390 mg transparent viscous liquid (3A) containing isomers in a purity of 96 %, characterized by GC was obtained in a yield of 75.6 %.
Preparation of 2-methoxycyclohexane-1,4-diol (4A): In a typical procedure, a 100 mL highpressure Parr autoclave was charged with 100 mg Pd/C catalyst, 500 mg 2-methoxybenzene-1,4-diol, 20 mL 2-Me THF, and equipped with mechanical stirring. The reactor was sealed and purged 3 times with H 2 and then pressurized with H 2 (40 bar). The reactor was heated to 140 °C for 6 h under stirring at 400 rpm. After completion of the reaction, the reactor was cooled to RT. Then the crude product (496 mg) was collected in a yield of 95.2 % after removing the 2-Me THF under reduced pressure.

General experimental procedure
Catalytic demethoxylation and hydrogenation of 2,6-dimethoxybenzoquinone (DMBQ) into 14CHDO: The catalytic demethoxylation/hydrogenation of DMBQ was carried out in a 100 mL highpressure Parr autoclave equipped with an overhead stirrer. Typically, the autoclave was charged with 200 mg Raney Ni catalyst, 1 mmol 2,6-dimethoxybenzoquinone, 20 mL isopropanol and 10 mg dodecane as internal standard. The reactor was sealed and purged 3 times with H 2 and then pressurized with H 2 (30 bar). The reactor was then heated to the desired temperature and stirred at 400 rpm for 4 h. After the reaction was completed, the reactor was cooled down to RT. Then 0.1 mL solution was collected through a syringe and injected to GC-MS or GC-FID after filtration through a PTFE filter (0.45 µm).
The catalytic direct amination of 14CHDO into 14CHDAover Raney Ni catalyst with ammonia gas: The catalytic direct amination of 14CHDO into 14CHDA was performed in 10 mL high-pressure autoclave equipped with magnetic stirring bar. Typically, a 4 mL vial was charged with 100 mg Raney Ni catalyst, 0.5 mmol 14CHDO, 2.5 mL t-amyl alcohol, 5 mg dodecane as an internal standard. Then the vial was sealed inside autoclave and pressurized with 7 bar NH 3 . The reactor was heated to 150 °C and stirred at 400 rpm for 18 h. After completion of the reaction, the reactor was cooled down to RT.
Then, 0.1 mL solution was collected through a syringe and injected to GC-MS or GC-FID after filtration through a PTFE filter (0.45 µm). The crude mixture was then subjected to characterizations d by 1 H and 13 C-NMR.  Considering the assumptions detailed above, the model could be simplified to a power-law model, where k n are the apparent kinetic constants. The resulting system of ordinary differential equations is the following:

 Equations and model prediction
The analytical solution was written in terms of the apparent kinetic constants and concentration of the chemical species.

Compound Expression
[2A] [HQ] The equations described in the table above were used to estimate the concentrations of the chemical species over time. The values of k 1 , k 2 , k 3 and k 4 were adjusted to minimize the standard deviation between the experimental and predicted points, calculated by the following equation: where y measured and y predicted are the measured and predicted concentration for each species, and n is the number of measurements.
Adjustable parameters were determined with σ = 0.004. The graph below shows that the experimental data fit satisfactorily to the first-order pseudo-homogeneous model (dashed line).  Step 1: The mild depolymerization of beech lignocellulose was carried out in a high-pressure Parr autoclave (50 mL), equipped with an overhead stirrer. Typically, the autoclave was charged with 50 mg of Pd/C catalyst, 500 mg of beech lignocellulose and ethanol (12 mL)/water (12 mL) as solvent.
The reactor was sealed and flushed with N 2 at room temperature. Then, the reactor was heated to 200 °C and stirred at 400 rpm for 2 h. After completion of the reaction, the reactor was cooled to room