Fragmentation of structural units of lignin promoted by persulfate through selective C–C cleavage under mild conditions

Abstract

A concise and environmentally benign protocol for lignin model fragmentation was developed by using cheap and commercially available sodium persulfate as an oxidant. The predominant lignin β-O-4 or β-1 model was fragmented into high-value aromatic aldehydes. The other lignin models, such as α-O-4, 4-O-5, and 5–5′, showed good reactivity in this system.

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Energy and environmental issues pose serious threats to humans and urgent solutions to these challenges are required by finding renewable energy sources and sustainable synthetic transformations.¹ Conversion of non-food biomass lignocellulose is a high-potential alternative for the production of valuable chemicals and fuels. Lignin, as the second most abundant biopolymer, constitutes up to 15–30% of the weight and 40% of the energy content of lignocellulosic biomass. However, the conversion of lignin is far behind that of other members of its family, e.g. cellulose and hemicellulose, due to its structural complexity and stability.²

This predicament of lignin is attributed to the complexity of its irregular structure with methoxyl substituted phenyl and phenolic subunits³ (Fig. 1). Indeed, in recent years, much attention has been paid to lignin fragmentation due to its potential as feedstock for high-value chemicals, pharmaceuticals and fuels.⁴ Different oxidative,⁵ reductive,⁶ and redox-neutral⁷ lignin protocols have been demonstrated to fragment lignin, native lignin, and lignin model systems. More encouragingly, beautiful examples of promising catalytic lignin degradation have been recently developed by using transition-metal catalysts. Vanadium complexes showed promising activity on the aerobic oxidative degradation of lignin to afford C–C/C–O cleavage products.^5g,h,k Aerobic oxidation of lignin models with amide bond formation was developed by using Cu catalysts.⁸ Cobalt exhibited a credible ability to catalyze the oxidative conversion of lignin models to benzoquinones in an O₂ atmosphere.⁵ⁱ During preparation of this manuscript, a chemical selective oxidation through C–O bond cleavage of β-O-4 lignin to isolate phenolic monomers was reported.⁹ Under reductive conditions, nickel carbene complexes were effective catalysts for the hydrogenolysis of aryl ether bonds in several lignin model compounds under alkaline conditions in a H₂ atmosphere.^6f Fe catalysts also showed good reductive activity for the hydrogenolysis of aryl ether bonds in lignin models.¹⁰ With a hydrogenation transfer strategy, the Ru-catalyzed C–O cleavage of lignin model compounds under neutral conditions has been developed by Bergman's group^7a and other groups.^7b–f These methods represent diverse strategies toward lignin degradation utilizing transition-metal catalysis.

Fig. 1 Representative structures of a fragment of lignin and some prevalent chemical linkages characterized in lignin from spruce trees.

Other than transition metal catalysis, Stahl and co-workers developed a chemoselective metal-free aerobic secondary alcohol oxidation in lignin models and further converted the generated ketones to corresponding products in two steps.¹¹ Continuous efforts from Stahl's group have been made to explore formic-acid-induced depolymerization of oxidized lignin to aromatics.¹² Interestingly, Stephenson and coworkers developed a photochemical strategy for lignin degradation at room temperature via chemoselective secondary alcohol oxidation and photocatalytic cleavage C–O bond by using an iridium complex photosensitizer.¹³ More recently, a frustrated Lewis pair B(C₆F₅)₃ as catalyst has been applied to the reductive cleavage of C–O bonds of a β-O-4 model.¹⁴ Obviously, the protocols are still facing significant challenges that have yet to be addressed to some extent, such as the step economy and the frequent use of expensive transition-metal catalysts at a high loading. Therefore, new methods to convert the lignin models to valuable chemicals are still appealing. Herein, we report a convenient and transition-metal free protocol for fragmenting lignin models to aromatic aldehydes through selective C–C cleavage in the presence of persulfate.

Persulfates are cheap and commercially available inorganic chemicals, which have been widely applied in the chemical industry and laboratory research as radical initiators and/or oxidants.¹⁵ We envisaged that the electron-rich lignin models probably transferred an electron to persulfate and formed a radical cation, which could further fragment to small molecules through C–C and/or C–O bond cleavage. To examine our hypothesis, we chose and synthesized the predominant lignin β-O-4 model (1a) as the model compound to screen the reaction conditions (Table 1). To our delight, the lignin β-O-4 model reacted with two equivalents of sodium persulfate in a mixture of MeCN/H₂O (3 : 1, v/v) under air at 80 °C and aromatic aldehyde 2a was isolated in 51% yield (entry 1). Unfortunately, the desired phenolic compound guaiacol failed to be isolated, which may be due to over-oxidization to a water-soluble and/or polymeric species. This observation is consistent with previous reported oxidation systems via radical mechanisms using peroxidase^16,17 or Fe/PhI(OAc)₂ ^5e as oxidants. Different persulfates (entries 2–4) were screened and sodium persulfate outperformed the others. Further screening of the reaction temperature found that the best result was obtained at 100 °C (entry 6). Interestingly, air was shown to perform better for this fragmentation than O₂ or N₂ (entry 6 and entries 8 and 9). To our interest, the ratio of the mixed solvent was critical for high efficiency. Decreasing or increasing the amount of water diminished the efficacy (entries 10 and 11, and entries 11–14 in Table S1†). No desired product 2a was obtained at all when only 4.0 equivalents of water was added (entry 11). After carefully screening other parameters in this transformation (Table 1 and S1†), the best conditions were identified in the presence of 2.0 equivalents of sodium persulfate and 1a was fragmented into an aromatic aldehyde in a mixture of MeCN/H₂O (3 : 1, v/v) at 100 °C. Encouragingly, when the reaction was conducted in 2.0 mL of MeCN/H₂O (3 : 1, v/v) with 0.1 mmol of 1a and 0.2 mmol of persulfate at 100 °C for 12 h, the best result was obtained with a 68% isolated yield (entry 16). More importantly, when the product 2a was subjected to the reaction system as substrate, it was successfully recovered in an acceptable isolated yield, accompanied by its oxidized acid product in 7% yield (entry 17). This observation allowed us to conclude that the aldehyde exhibits good compatibility in the oxidation system. Recently, it was reported that lignin, lignin models and hydroxy-aromatics were broken down into C1 and C2 chemicals (mainly methanol, formate, carbonate, and oxalate) via transition-metal free oxidation using persulfate or peroxide as oxidant in alkaline conditions.¹⁸ In contrast to this result, we developed an alternative method to fragment the lignin models to high-value aldehydes using transition-metal free persulfate as oxidant in neutral condition. The difference in the results may be attributed to the solvent and the reaction pH.

Table 1 Optimization Study

Entry^a	[Oxidant]	T (°C)	Solvent (v/v)	Result
a 0.05 mmol of lignin model 1a and 0.1 mmol of Na2S2O8, 0.75 mL of organic solvent and 0.25 mL of H2O, 100 °C, 12 h. NMR yield with using CH2Br2 as internal standard reagent. b DP = decomposed product, no product was identified from the decomposed starting material. c 0.1 mmol of lignin model 1a and 0.2 mmol of Na2S2O8, 1.5 mL of organic solvent and 0.5 mL of H2O, 100 °C, 12 h. d Isolated yield. e 0.2 mmol of 2a and 0.4 mmol of Na2S2O8 in 4.0 mL mixture of MeCN/H2O (v/v = 3 : 1) were reacted at 100 °C for 12 h. f Isolated yield of the recovery of aldehyde 2a. g Isolated yield of the corresponding acid of 2a.
1	Na2S2O8	80	MeCN/H2O (3 : 1)	51%
2	K2S2O8	80	MeCN/H2O (3 : 1)	41%
3	(NH4)2S2O8	80	MeCN/H2O (3 : 1)	42%
4	Oxone	80	MeCN/H2O (3 : 1)	DP^b
5	Na2S2O8	60	MeCN/H2O (3 : 1)	34%
6	Na2S2O8	100	MeCN/H2O (3 : 1)	61%
7	Na2S2O8	120	MeCN/H2O (3 : 1)	50%
8	Na2S2O8/O2	100	MeCN/H2O (3 : 1)	53%
9	Na2S2O8/N2	100	MeCN/H2O (3 : 1)	44%
10	Na2S2O8	100	MeCN/H2O (1 : 1)	36%
11	Na2S2O8	100	MeCN (4 eq. H2O)	DP^b
12	Na2S2O8(1.0 eq.)	100	MeCN/H2O (3 : 1)	29%
13	Na2S2O8(2.5 eq.)	100	MeCN/H2O (3 : 1)	55%
14	Na2S2O8 (9 h)	100	MeCN/H2O (3 : 1)	47%
15	Na2S2O8 (15 h)	100	MeCN/H2O (3 : 1)	55%
16^c	Na2S2O8	100	MeCN/H2O (3 : 1)	65% (68%^d)
17^e	Na2S2O8	100	MeCN/H2O (3 : 1)	55%^f + 7%^g

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With the optimized conditions in hand, we continued to examine other lignin β-O-4 models with different substituents. As shown in Table 2, different substituents on the left phenyl ring A proceeded smoothly to give the corresponding valuable aromatic aldehyde 2 in good yields. A methoxyl group on different positions of ring A exhibited good activities and gave the corresponding aldehydes in good yields (1a–1c). More importantly, the models with other general substituents on lignin, including ethoxyl (1d), benzoxyl (1e), phenoxyl (1f), and phenyl (1g), were fragmented to high-value aromatic aldehydes in good yields. It is worthy of note that the models with benzoxyl (1e), phenoxyl (1f), and phenyl (1g) substituents belong to the α-O-4, 4-O-5 and 5–5′ lignin models, respectively.^2a Our methodology exhibited a high selectivity for β-O-4 lignin models from other structural units of lignin. Unfortunately, the phenolic model (1h) and desired phenol guaiacol decomposed in our system, which is consistent with previously reported results.^5e,16,17 Encouragingly, when a phenyl group was inserted at the para-position of the right phenyl ring B (1i), 19% of 4-phenylphenol and 42% of 2a were successfully isolated, thus providing indirect proof for the formation of the corresponding phenol under this condition. Electron withdrawing groups, such as acetyl (1j) or formyl (1k) at the para-position, affected the efficacy of this fragmentation and 2a was isolated in much lower yields with the recovery of the starting materials. The isolation of vanillin, despite the low yield, further validated the formation of phenol to some extent.

Table 2 Investigation on fragmentation of β-O-4 lignin models

Entry	Substrate (conversion)	Product
a 15% of its deprotected product 1k was recovered.
1
2
3
4
5
6
7
8
9
10^a
11

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Further investigation was focused on the lignin model analogues with different substituents on the β position of the bridge between two aromatic rings (Table 3). Encouragingly, the β-phenyl substituted models (4a–4c), attributed to the β-1 lignin model,^2a,5k were fragmented into two different benzaldehydes in good yields. It was obvious that the β-1 lignin model could be fragmented into different valuable aromatic aldehydes via selective C–C bond cleavage. The β-alkyloxyl substituted models could be also fragmented to aldehydes. The lignin model in which the hydroxymethyl substituent on the β position was replaced with a methoxymethyl group (4e) was converted into aldehyde in 59% yield. Finally, the lignin models with only one substituent on the β position (4f and 4g) were also degraded into 4-methoxy benzaldehyde and 4-methoxy benzoic acid, while the secondary benzyl alcohol (4h) was oxidized to a ketone product in 77% yield.

Table 3 Substrate scope of other lignin models

Entry	Substrate (conversion)	Product
1
2
3
4
5
6
7
8

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To highlight our protocol in real lignin fragmentation, we attempted to subject alkaline lignin and dealkaline lignin to our standard reaction system. Unfortunately, real lignin did not dissolve well in this system. We failed to observe and isolate aldehydes or phenols.

To understand the stability of the products, 3,5-dimethoxy benzaldehyde 2a was submitted to the standard conditions. With increasing amounts of persulfate (from 1 equivalent to 2 equivalents), the recovering yield of 2a was reduced, while, to our interest, the oxidized benzoic acid remained at a very low level. Thus, the relatively lower yields in some cases might arise from the over-oxidation of the products. Moreover, when 2-methoxy phenol was delivered into the flask with a different amount of persulfate, the phenol was completely decomposed, which was consistent with the observed results and previous reports.^5e,16,17 Finally, when 2a and 2-methoxy phenol were added into the same pot, only 86% of 2a was recovered, which further supported our conclusions. Thus, β-O-4 lignin models were fragmented into arylaldehydes in good yields and the phenols were isolated in poor yields due to over-oxidation.

Conclusions

In conclusion, we successfully developed a concise and environmentally benign protocol to fragment lignin models to valuable aldehydes by using sodium persulfate as oxidant. The predominant lignin β-O-4 model was fragmented into high-value aromatic aldehydes in moderate to good yields. The β-1 lignin model was also converted into two different aromatic aldehydes in excellent yields. The other lignin models, such as α-O-4, 4-O-5, and 5–5′, showed good reactivity in this transformation. Further efforts to optimize the reaction conditions for improving the efficacy and using this protocol on real lignin are underway.

Acknowledgements

Support of this work by the “973” Project from the MOST of China (2013CB228102) is acknowledged.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Lignin meodels preparation procedure and their ¹H NMR, ¹³C NMR and FTMS-ESI data. See DOI: 10.1039/c5qo00116a

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