Cleavage of Organosolv Lignin to Phenols Using Nitrogen Monoxide and Hydrazine

From the variety of methods known for the depolymerization of organosolv lignin, a broad range of diversely substituted aromatic compounds are available today. In the present work, a novel two-step reaction sequence is reported, which is focused on the formation of phenols. While the first step of the depolymerization strategy comprises the 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-catalyzed oxidation of organosolv lignin with nitrogen monoxide so that two waste materials are combined, cleavage to the phenolic target compounds is achieved in the second step employing hydrazine and potassium hydroxide under Wolff–Kishner-type conditions. Besides the fact that the novel strategy proceeds via an untypical form of oxidized organosolv lignin, the two-step sequence is further able to provide phenols as cleavage products, which bear no substituent at the 4-position.


General Remarks
Solvents and reagents were obtained from commercial sources and were used as received. NMR spectra were recorded on Bruker Avance 600 (  The yields were calculated on the basis of the mass of the organosolv lignin used with a rounded average mass of 200 g/mol per monomer. According to this, a 1 g experiment (= mass of organosolv lignin) corresponds to 5 mmol of lignin monomers, and the amount of 5 mmol was used as basis (= 100%) for the calculation of the yields of the finally obtained phenols. Also the amounts of reagents used were calculated on these 5 mmol (as an example).

General procedure for oxidation
To a solution of organosolv lignin (M = ø 200 g/mol) in acetonitrile (60 ml/g) in a round bottom flask with a reflux condenser and a balloon for pressure compensation on top, DDQ was added and the mixture was heated up to 80 °C. In the meantime, nitrogen monoxide was synthesized according general procedure for nitrogen monoxide production. At 80 °C, nitrogen monoxide was added to the reaction via a syringe. The reaction mixture was stirred for 18-24 h at 80°C.
Afterwards, the solvent was removed under reduced pressure and the oxidized lignin was further used without processing. For detailed reaction conditions, e.g. the amounts of organosolv lignin and DDQ, see Figure 2 in the article.

General procedure for nitrogen monoxide production 2
Nitrogen monoxide was synthesized using sodium nitrite (6.8 g) and potassium iodide (2.6 g) in a 500 mL three-necked flask. A funnel was plugged into the middle neck of the flask and the connection between flask and funnel was closed airtight. One of the other two necks was also closed with a septum. 1M H2SO4 was filled into the flask until it was free from air, sodium nitrite was added, and the mixture was stirred. The third neck was then closed with a septum (see Figure   S3 of empty setup (left) below). Potassium iodide was dissolved in water (10 mL   , the yields were determined by 1 H NMR spectroscopy using maleic acid as internal standard. For detailed reaction conditions and yields see Tables S1, S2 and S3. Figure 4) General procedure: oxidized organosolv lignin (22)   General procedure: oxidized organosolv lignin (22)   General procedure: oxidized organosolv lignin (22) (1.0 equiv), KOH (2.0 equiv), H2NNH2 (20 equiv), ethylene glycol (10-20 mL), 150 °C, 16 h in an air-filled closed reaction vessel. Yields determined after flash column chromatography by 1 H-NMR spectroscopy using maleic acid as internal standard. Yields based on lignin.

Calculation of E factor and process mass intensity (PMI)
The E factor and the process mass intensity were calculated as shown in Figure S8 according to ref. 3 Solvents are not included in the calculation as they are recoverable. S11 Figure S8. Calculation of E factor and PMI using the optimized conditions (see experimental section of the manuscript) For comparison, the E factor and the PMI were also calculated for the related two-step process by Westwood 4 ( Figure S9).

Procedure for organosolv lignin oxidation with TBN/DDQ
In a round-bottom flask organosolv lignin (21)

Procedure for organosolv lignin oxidation with NO/DDQ
To a solution of 21 (1.0 g, 1.0 equiv) in acetonitrile (60 ml) in a round bottom flask with a reflux condenser and a balloon for pressure compensation on top of it, DDQ (227 mg, 0.20 equiv) was added and the mixture was heated up to 80 °C. In the meantime, nitrogen monoxide was synthesized according general procedure for nitrogen monoxide production. At 80 °C selfsynthesized nitrogen monoxide (44.8 mL, 0.40 equiv) was added to the reaction via a syringe. The S12 reaction was stirred for 24 h. Afterwards, the solvent was removed under reduced pressure and the oxidized organosolv lignin was further used without any processing. (Table 1, entries 1 and

Procedure for hydrazine-induced cleavage of oxidized organosolv lignin (Table 1, entry 4)
By NO/DDQ oxidized organosolv lignin (22) (1.20 g, 1.0 equiv), hydrazine monohydrate (5.90 mL, 20.0 equiv) and potassium hydroxide (680 mg, 2.00 equiv) were dissolved in ethylene glycol (10 mL) and the mixture was stirred for 16 h at 150 °C under air in a closed reaction vessel with a balloon on top for pressure compensation. Afterwards, the reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate neutral (pH=7) and acidic (pH=3-4). The pH value was adjusted with 5M HCl. The organic phase was washed with saturated sodium chloride solution, dried over sodium sulfate and the solvent was removed under reduced pressure not lower than 200 mbar. After flash column chromatography (hexane : ethyl acetate = 4:1), the yields of the products 17a (2.08%), 17b (2.36%), 17c (1.67%) and 17d (0.79%) were determined by 1 H-NMR spectroscopy using maleic acid as internal standard.
To a solution containing both octyl 2-(4-formyl-2-methoxyphenoxy)acetate (1, 10 g, 31 mmol, 0.5 eq.) and octyl 2-(4-formyl-2,6-dimethoxyphenoxy)acetate (2, 10.9 g, 31 mmol, 0.5 eq.) in THF (400 mL) was added dropwise a freshly prepared solution of LDA (74.4 mmol, 1.2 eq.) in THF S14 (60 mL) at -20 °C. The reaction mixture was stirred at -20 °C for 1.5 hour. Then the reaction was quenched by adding sat. NH4Cl solution (100 mL). The reaction mixture was allowed to warm to room temperature. The reaction mixture was diluted with H2O (100 mL) and ethyl acetate (200 mL). The phases were separated, and the aqueous layer was extracted with ethyl acetate (3 x 200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to yield the crude polyester 3. The crude product 3 was then dissolved in ethanol (300 mL). To this solution was added sodium borohydride (11.7 g, 310 mmol, 5 eq.) and the reaction mixture heated to 50 °C. Methanol (37.6 mL, 930 mmol, 15 eq.) was then added dropwise over 15 mins and the reaction maintained at 50 °C overnight. The reaction mixture was then concentrated in vacuo and the residue was taken up in water (400 mL) and the crude polymer precipitated by acidification with conc. HCl. The product was collected as a light-yellow gum and dried in vacuo.
The crude polymer was then taken up in acetone/methanol (9:1, 30 mL), filtered and precipitated by dropwise addition to diethyl ether (400 mL). The polymer 4 was collected by filtration and dried in vacuo to give a white powder (4 g, ~20%). A section of the 2D HSQC analysis of 4 is shown in Figure S10 below. Figure S10. 2D HSQC NMR spectrum of polymer 4.

S15
The polymer 4 (500 mg) was dissolved in 1,4-dioxane/MeOH (9 mL/1 mL) and DDQ (600 mg) was added. The reaction was heated at 50 °C overnight. The reaction mixture was cooled to room temperature and precipitated into diether ether. The precipitated oxidized polymer 5 was collected by filtration and dried in vacuo. Yield of polymer 5: ~ 100 wt%. A section of the 2D HSQC analysis of 5 is shown in Figure S11 below. Figure S11. 2D HSQC NMR spectrum of polymer 5. The reaction resulted in a complex mixture of unidentifiable substances. No traces of 23b could be identified.

Control reactions C-D under reductive cleavage conditions
Scheme S4. Control reaction C.

Extraction of air-dried birch lignin 4
Air-dried birch sawdust (200.0 g) was mixed with 1,4-dioxane (1.44 L) and 2N HCl (160.0 mL), placed under N2, heated to a gentle reflux and stirred for 1 h. The reaction mixture was allowed to cool, the liquor was collected by filtration and concentrated in vacuo until a gummy residue was obtained. The residue was taken up in acetone/water (9:1, 500 mL) and poured into rapidly stirring water (2.50 L). The crude lignin was filtered off and dried under vacuum. Next, the dried lignin was taken up in acetone/methanol (9:1) and poured into rapidly stirring diethyl ether (2.00 L). The precipitated lignin was filtered off and dried under vacuum to give purified birch lignin (15.3 g).
The experimental results obtained with birch lignin as starting material are summarized in Table   S4. For reaction conditions and procedures, see section 3.3.