A comparison of the oxidation of lignin model compounds in conventional and ionic liquid solvents and application to the oxidation of lignin

Abstract

The oxidation of lignin model compounds was studied in conventional solvents in parallel with oxidations in ionic liquid solvents. Catalyst systems were investigated in ionic liquid solvents to determine how reaction rates and the selectivity for benzylic carbon oxidation were affected. Oxidation rates were often lower in ionic liquids than in conventional solvents – as indicated by lower conversion in a standard reaction time – likely due, at least in part, to the higher viscosity of ionic liquids. Selectivity of the TPPFeCl/t-BuOOH catalyst system for oxidation of the benzylic C–OH versus benzylic C–H was higher in the ionic liquids tested than in conventional solvents.

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Introduction

Lignin is a complex polymer found in vascular plants and is one of the most abundant organic compounds on earth.^1,2 As a plentiful and renewable material, lignin represents a significant resource as a fuel³ and as a potential source of chemical feedstocks. The production of high value compounds from lignin requires deconstruction of the polymer, and this has proven to be problematic.⁴ Methods for lignin processing in bio-refineries have recently been reviewed.⁵ Different depolymerization strategies have been developed, and reviews have recently been published.^6,7

Recently, a two-step approach, involving oxidation of benzylic C–OH groups to ketones, followed by C–C/C–O bond cleavage, has been shown to be an effective strategy for lignin depolymerization. For example, in previous work we used a two-step oxidation approach to selectively cleave the C_α–C_β bond in β-O-4 lignin model compounds by first oxidizing the benzylic alcohol of the compounds, then further oxidizing the resulting ketones to esters by Baeyer–Villiger reaction.⁸ Cleavage of the C_α–C_β bond was achieved by hydrolysis of the ester, yielding carboxylic acids and phenols. Very recently, Wang described the selective cleavage of the C–C bond in the β-O-4 linkage by first oxidation of the β-O-4 alcohol to a ketone over a VOSO₄/TEMPO catalyst, followed by oxidation over a Cu/1,10-phenanthroline catalyst.⁹

Initial oxidation of alcohols to ketones is particularly useful when breaking a C–O bond. Calculations have shown that this oxidation step weakens β-O-4 linkages, specifically the C_β–O bond, by lowering its bond energy from 247.9 kJ mol⁻¹ to 161.1 kJ mol⁻¹.^9,10 Lancefield applied this oxidation strategy in a one-pot depolymerization of birch lignin to phenolic monomers by first oxidizing the β-O-4 benzylic alcohols to ketones using a DDQ catalyst, followed by reductive cleavage of the C–O aryl bond with Zn.¹¹ A similar oxidation-reduction strategy was applied by Nguyen and Rahimi, who both used TEMPO-based catalyst for chemoselective oxidation of benzylic alcohols to ketones, then employed an iridium photocatalyst and aqueous formic acid, respectively, for the reductive cleavage of the C–O bond.^12,13

Over the years, oxidation of an alcohol to ketone has found increasing applications in lignin depolymerization approaches.^14–16 A notable example is the work by Rahimi et al. where a TEMPO derivative was used for chemo-selective aerobic oxidation of secondary benzylic alcohols in lignin.¹⁷ Other related studies employed catalysts based on transition metals such as vanadium,^18–20 palladium,²¹ copper,^22,23 and cobalt²⁴ to achieve oxidation for the purpose of selective C–C/C–OH bond cleavage and for lignin conversion to aromatic compounds. Studies using DDQ-based catalyst systems for cleavage and modification of certain lignin linkages^11,25 and for selective benzylic/allylic oxidation,^26–28 have also been reported. Of late, dehydrogenative oxidation²⁹ and heterogeneous catalytic oxidations have been investigated as well.³⁰

One of the significant barriers to the application of these methods in lignin is the notoriously poor solubility of the native polymer. Ionic liquids (ILs; salts that are liquid below 100 °C) are one of the few classes of solvents in which biomass, including lignin³¹ and cellulose,³² has significant solubility. Studies on the various applications of ILs in lignocellulosic biomass processing (pretreatment, deconstruction/fractionation),^33–37 as well as ILs' usefulness as solvent for catalysis (promotion of high conversion rates and selectivity; facilitation of catalyst and IL recycling)^37–43 and the origin of their positive solvent effects⁴⁴ have been the subject of extensive reviews by several groups. The use of ILs in studies on oxidation of lignin and lignin-like compounds,^30,45–50 cleavage of lignin β-O-4 linkage⁵¹ and lignin depolymerization^52,53 has also been described.

In the current work, we present a study of oxidation of alcohols to ketones in ionic liquid solvents in an effort to determine if such liquids are useful in lignin deconstruction. We investigated the oxidation of the benzylic C–H and C–OH groups in model compounds using catalysts based on iron tetraphenylporphyrin, DDQ, and TEMPO under mild and practical conditions with either molecular oxygen or peroxides as the ultimate oxidant. These oxidants were selected because of literature precedent⁸ and because each catalyst is ultimately regenerated with inexpensive peroxide or molecular oxygen. The oxidations were carried out in a conventional solvent in parallel with oxidations in the ionic liquids 1-butyl-3-methylimidazolium chloride ([C4C1im]Cl) and tetrabutylphosphonium chloride ([P4444]Cl). Utilization of [C4C1im]Cl in the investigation of lignocellulosic biomass has been well documented, while the use of [P4444]Cl is based on its higher thermal stability and resistance to oxidation.

Results and discussion

Preparation of lignin model compounds

The monomeric units of lignin, small phenylpropanoid units known as monolignols, are linked together in a number of ways, with the most common linkage involving the β-carbon of one monolignol and a phenolic hydroxyl on another. The β-O-4 linkage, as this is known, makes up about 45–60% of the linkages in softwood and hardwood lignin.¹⁴

Five β-O-4 model compounds (1–5), analogous to a set that has previously been studied by our group,⁸ were synthesized and used in this study, permitting comparisons to our prior work in conventional solvents. These model compounds include a benzylic hydroxyl group and a β-phenethyl phenyl ether unit, and are functionalized at various positions in the aryl and alkyl groups, affording them different reactivity toward oxidants. Compounds 2, 3, 4, and 5 include a γ-carbon with a hydroxyl group in 4 and 5 but none in 2 and 3. Additionally, compounds 3 and 5 have unprotected phenols, which is characteristic of the monolignols that make up lignin, while the rest (2 and 4) have methoxy groups (Fig. 1).

Fig. 1 Some of the lignin model compounds used in this study.

Model compounds 1–3 were prepared by literature methods^54–56 while 4 and 5 were prepared based on a procedure similar to that in the literature,⁸ but using a different phenol reagent (Scheme 1).

Scheme 1 Preparation of 4 and 5.

Benzylic oxidation of lignin model compounds

Lignin model compounds 1–5 were subjected to oxidation reactions in two ionic liquid solvents ([C4C1im]Cl and [P4444]Cl), in parallel with the same oxidation carried out in a conventional organic solvent.

Oxidation with TPPFeCl/t-BuOOH

One of the catalyst systems we investigated consists of tetraphenylporphyrin iron chloride (TPPFeCl) and tert-butylhydroperoxide (t-BuOOH). An iron porphyrin has been identified as one of the components of the oxidases that were isolated from ligninolytic cultures of the white rot fungus Phanerochaete chrysosporium,^57,58 which, in the presence of H₂O₂, was found to be accountable for natural biodegradation of lignin.⁵⁹ We carried out the oxidation of compounds 1–5 by treating 100 mg of each compound with TPPFeCl (0.01 eq.) and t-BuOOH (70% aq. soln, 1 eq.) in the appropriate solvent (1.0 mL MeCN or 1.05 g [C4C1im]Cl/0.9 g [P4444]Cl) and 3.0 mL phosphate buffer (0.1 N, pH 3) at 25 °C for 14 h.⁸ We observed that the catalyst system selectively oxidized the benzylic hydroxyl group of 1, 2, and 4 in both the conventional and ionic liquid solvents, with corresponding products as shown in Scheme 2. Oxidation of 3 and 5 did not produce isolable products (see below).

Scheme 2 Oxidation of 1, 2, and 4 with TPPFeCl/t-BuOOH.

The formation of the products shown (10–12) was confirmed by the ¹³C NMR chemical shift for the carbonyl group at 194.5, 197.6, and 195.3 ppm for ketones 10, 11, and 12, respectively. The structural assignments were further confirmed by changes in the ¹H NMR spectra, including complete disappearance of the signal for the α_C–H (multiplets at 5.13–5.06 ppm for 1, at 4.93–4.87 and at 4.63–4.56 ppm for the two diastereomers of 2, and at 4.98–4.93 ppm for 4). In addition, the multiplet signal for the β_C–H in each was changed (to a singlet for 1, to a quartet for 2, and to a doublet of doublets for 4), and shifted downfield to around 5.0 ppm.

The comparison of porphyrin oxidation of 1, 2, and 4 in MeCN to the same oxidation in ILs is given in Table 1. Under the experimental conditions, there appears to be no significant difference in the rates of benzylic hydroxyl oxidation in MeCN and in [P4444]Cl, although the rates in [C4C1im]Cl are lower, as indicated by lower conversion in a standard reaction time. The lower rate is likely due, at least in part, to the high viscosity of [C4C1im]Cl (142 cP at 80 °C).⁶⁰ It is possible that the presence of a substantial amount of phosphate buffer (3 mL) reduced the viscosity of [P4444]Cl (120 cP at 80 °C)⁶¹ enough to allow oxidation to proceed as in the conventional solvent.

Table 1 Oxidation of 1, 2, and 4 with TPPFeCl/t-BuOOH

Starting mat.^a	Prod.^b	MeCN	[C4C1im]Cl	[P4444]Cl
		(A)	(B)	(C)
a Reactions were carried out for 14 hours using 0.01 eq. TPPFeCl and 1 eq. t-BuOOH.b Yields are for purified, isolated products. Recovered starting material is given in parentheses.
1	10	41%	28%	47%
		(58%)	(67%)	(50%)
2	11	22%	9.5%	25%
		(68%)	(72%)	(58%)
4	12	38%	22%	30%
		(55%)	(69%)	(64%)

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Oxidation of model compounds 3 and 5, which contain unprotected phenolic groups, failed to produce the expected ketone products, consistent with what was observed previously for analogous models under similar conditions.⁸ We suspect that the starting material and/or the products undergo polymerization through phenolic oxidative coupling, which can occur in processes where free radical species are present.⁶² In oxidation with TPPFeCl and peroxide, radical species are present resulting from H atom abstraction, this being the first step in the proposed reaction mechanism.⁶³

In earlier work, we investigated the use of this porphyrin catalyst system to oxidize benzylic C–H and C–OH bonds in conventional solvent systems.⁸ In the current study, we investigated how the TPPFeCl oxidation of 13 and 14 (Fig. 2) performed in ionic liquid solvents. These models include an unfunctionalized alkyl chain, and the degree of oxidation of this side chain provides an additional measure of the selectivity of this fairly vigorous oxidant.

Fig. 2 Ring-alkylated lignin model compounds.

The oxidation of 13 and 14 was carried out by treating 50 mg of each compound with TPPFeCl (0.01 eq.) and 70% aq. soln of t-BuOOH (2 eq.) in the appropriate solvent (0.5 mL MeCN/0.2–0.3 g [C4C1im]Cl/0.2–0.3 g [P4444]Cl) and 1.5 mL phosphate buffer (0.1 N, pH 3) at 25 °C for 14 h.⁸ We observed that under these conditions, 13 was oxidized at the benzylic C–OH and C–H positions in both the conventional and ionic liquid solvents, giving three different products (15, 16, and 17) as shown in Scheme 3, where 15 was the result of oxidation of the benzylic C–OH only, 16 was from oxidation of the benzylic C–H only, and 17 was from oxidation of both groups.

Scheme 3 Oxidation of 13 with TPPFeCl/t-BuOOH.

In the case of the more highly functionalized model compound 14, we did not observe in the IL solvents a product that was oxidized solely at the benzylic C–H (19), although we were able to isolate a product that was consistent with a doubly oxidized species (20), along with the benzylic ketone resulting from C–OH oxidation (18) (Scheme 4).

Scheme 4 Oxidation of 14 with TPPFeCl/t-BuOOH.

The porphyrin-catalyzed oxidation of 13 and 14 is summarized in Table 2. This data shows that in all three solvents, oxidation of the benzylic C–OH (40–44% yield for 13; 23–36% for 14) generally occurs faster than that of the benzylic C–H group (8–10% yield for 13; 0–13% for 14). This observation is consistent with bond dissociation energies (BDE), indicating that the C–H bond in benzylic alcohol is weaker than that in a benzylic alkyl group: average of 347.5 kJ mol⁻¹ in 4-MeOC₆H₄CH₂OH and 360 kJ mol⁻¹ in 4-MeOC₆H₄CH₂CH₃.⁶⁴ The doubly oxidized product – oxidized at both benzylic positions – was isolated at 9–18% for 13 and 3–14% for 14.

Table 2 Oxidation of 13 and 14 with TPPFeCl/t-BuOOH

Starting mat.^a	Prod.^b	MeCN	[C4C1im]Cl	[P4444]Cl
		(A)	(B)	(C)
a Reactions were carried out for 14 hours using 0.01 eq. TPPFeCl and 1 eq. t-BuOOH.b Yields are for purified, isolated products. Yield of recovered starting material is given in parentheses.
13	15	41%	40%	44%
		(36%)	(30%)	(26%)
	16	8%	9%	10%
	17	9%	17%	18%
14	18	36%	34%	23%
		(46%)	(51%)	(59%)
	19	13%	0%	0%
	20	3%	12%	14%

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Dissociation of the benzylic C–H bond through hydrogen atom transfer (HAT) is the slow step in the proposed mechanism for the porphyrin-catalyzed oxidation of both the C–OH and C–H groups.^63,65 For this oxidation, an iron-oxo intermediate is believed to abstract a hydrogen atom from the substrate. In the case of C–OH oxidation, this step results in the formation of an α-hydroxycarbinyl radical, which subsequently transfers an electron and a proton to the oxidant to yield the corresponding carbonyl product.⁶³ For the C–H bond oxidation, formation of the carbon radical is followed by oxygen rebound (alkyl rebound in some reports) forming an alcohol,⁶⁵ which may be oxidized further to a carbonyl compound.

It is worth noting that in this reaction, the reactivity to benzylic C–OH oxidation is similar in all three solvents. This may reflect the fact that the presence of the pH 3 buffer rendered the three reaction mixtures essentially aqueous, hence the similarity in reactivity. In order to determine if the presence of water has any effect on the porphyrin-mediated oxidation under aqueous condition, we conducted parallel experiments on 13, omitting the pH 3 buffer and using tert-butylhydroperoxide in decane instead of 70% aqueous solution (Table 3). We noticed that under non-aqueous conditions, the conversion to products decreased in the IL solvents, and the yield of all the products decreased significantly in all three solvents, especially 16 and 17.

Table 3 Oxidation of 13 in non-aqueous solution

Prod.^a	MeCN	[C4C1im]Cl	[P4444]Cl
	(A)	(B)	(C)
a Reaction was carried out for 14 hours using 0.01 eq. TPPFeCl and 1 eq. t-BuOOH. Yields are for purified isolated products; yield of recovered starting material is given in parentheses.
15	14%	11%	12%
	(36%)	(56%)	(34%)
16	1%	trace	0%
17	3%	1%	2%

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At this point, it has become evident that the presence of water plays a significant role in the porphyrin-catalyzed oxidation, where dramatic decreases in yields were obtained in going from aqueous to non-aqueous conditions. This may primarily be due to the elimination of the pH 3 reaction conditions, but the water component of the buffer might have a significant effect as well. For example, water may contribute to the enhanced reaction rate in acetonitrile when the aqueous buffer is used.⁶⁶ It is believed that H atom transfer from a C–H bond to an O-centered radical involves a polar transition state (TS) in which a negative charge develops on the oxygen center while a positive charge is acquired by the incipient carbon radical.^67–69 As such, hydrogen bonding interactions with water molecules may stabilize the polar TS more than it stabilizes the reactants, causing the free energy of activation to decrease in the slow step.⁶⁶

In the oxidations carried out in ILs, the low conversion and yields under non-aqueous conditions may possibly be due in part to the high viscosity of the IL reaction mixtures. Low reaction rates in some reactions carried out in ILs have been attributed to the high viscosity of the solvent.^70,71 In these reactions, significant rate enhancement was achieved when a co-solvent was added, decreasing the viscosity of the reaction medium.

The enhanced selectivity in the IL medium may also be due – at least in part – to high solvent viscosity (Table 4), which is known to produce solvent cage effects.^72–74 It has been observed that as the viscosity increases the solvent cage lifetime increases, affording trapped reactive species more time to recombine.^74,75 It is possible that in this oxidation, radical intermediates react with the iron-oxo species again reforming the starting material. In a reversible situation, hydrogen atoms would most likely be abstracted from the PhCH(OH) (BDE 347 kJ mol⁻¹) rather than from the PhCH₂– (BDE 360 kJ mol⁻¹). The result is an enhanced preference for the formation of either the C–OH oxidation products (15, 18) or the diketone products (17, 20) or both, at the expense of the C–H oxidation products 16 and 19.

Table 4 Viscosities of the solvents used in this study

Solvent^a	Viscosity (η, cP)
a [C4C1im]Cl and [P4444]Cl are solid at rt, thus values can not be measured at this temp.
MeCN	0.334 (25 °C); 0.38 (15 °C)
[C4C1im]Cl	142 (80 °C)^60
[P4444]Cl	120 (80 °C)^61
Water	0.89 (25 °C); 0.354 (15 °C)
MeCN–water mixture (1 : 3 v/v)	0.96 (25 °C)^77
[C4C1im]Cl–water mixture (1 : 8 w/w)	1.16 (25 °C)^78

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Oxidation with DDQ/NaNO₂/O₂

Very recently, Westwood's group reported that the DDQ/t-BuONO/O₂ system promoted the chemo-selective oxidation of the β-O-4 linkage in model compounds and in real lignin.¹⁷ Earlier, the DDQ/NaNO₂/O₂ combination was used by Wang and co-workers to selectively oxidize benzylic hydroxyl groups,⁷⁶ and we have investigated the oxidation of β-O-4 lignin model compounds in conventional solvents using this system.⁸ We observed that in DCM the functionalized models 2–5 were selectively oxidized at the benzylic hydroxyl group, giving corresponding ketone products (Scheme 5) in moderate yields (27–61%, Table 5). However, no reaction was observed with the least electron-rich model compound (1). We moved the same combination to ionic liquid solvents to see if the selectivity changes.

Scheme 5 Oxidation of 2–5 with DDQ/NaNO₂/O₂.

Table 5 Oxidation of 2–5 with DDQ/NaNO₂/O₂

Starting mat.^a	Prod.^b	DCM	[C4C1im]Cl	[P4444]Cl
		(A)	(B)	(C)
a Reactions were carried out for 19 hours using 0.1 eq. DDQ and 0.1 eq. NaNO2.b Yields are for purified, isolated products. Recovered starting material is given in parentheses.
2	11	61%	10%	7%
		(38%)	(60%)	(85%)
3	21	57%	6%	0%
		(2%)	(93%)	(0%)
4	12	27%	5%	Trace
		(65%)	(89%)	(75%)
5	22	48%	1%	0%
		(0%)	(67%)	(0%)

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In applying the DDQ/NaNO₂/O₂ system, we treated 100 mg each of 1–5 with DDQ (0.1 eq.) and NaNO₂ (0.1 eq.) in 9 : 1 solvent/acetic acid mixture (solvent = CH₂Cl₂/[C4C1im]Cl/[P4444]Cl) under an O₂ atmosphere (1 atm) at 25 °C for 19 h.

In the IL solvents, we observed the same selectivity as in the conventional solvent (Table 5), although reaction rates were much lower, again likely due to the high viscosity of the solvents. Additionally, the [P4444]Cl system appears to be incompatible with substrates bearing phenolic groups. DDQ-catalyzed oxidation can proceed through several different routes, including by hydride transfer⁷⁶ and by a quick series of steps involving transfer of electrons and protons.⁷⁹ The routes may be different in [C4C1im]Cl and in [P4444]Cl.

Oxidation with TEMPO/NaNO₂/O₂

In view of recent successes in the use of TEMPO to oxidize alcohols,^80–84 lignin model compounds,^8,17,85 and lignin itself,¹⁷ it is important to determine how these oxidations proceed in ionic liquid solvents. So far, some of the studies that have employed ILs in TEMPO-catalyzed oxidations involve immobilization of the catalyst to the IL in order to improve efficiency and facilitate recycling of the catalyst and the IL.^80,81 Other reports have used ILs as solvent in the oxidation of alcohols to aldehydes and ketones, and a high selectivity for the aldehyde product was noted with primary and benzylic alcohols.^81,86 An improved selectivity has also been noted in the case of oxidation of allylic alcohols using a functionalized TEMPO in the presence of [C4C1im]Br.⁸² Several TEMPO-based catalysts have been investigated, but for this study we used the TEMPO/NaNO₂/HCl/NaCl combination^87,88 which we have observed to give good results on model compounds.

Oxidation of 1–5 was carried out by treating 100 mg of each compound with TEMPO (0.15 eq.), NaNO₂ (0.25 eq.), 36% aq. HCl (0.5 eq.), and NaCl (0.5 eq.) in the different solvents (0.6 mL DCM/0.63 g [C4C1im]Cl/0.54 g [P4444]Cl) under an O₂ atmosphere.⁸⁸ Under these conditions, compounds 1, 2, and 4 were selectively oxidized to corresponding ketones in the conventional solvent as shown in Scheme 6. As in the porphyrin-catalyzed oxidation, TEMPO oxidation of phenols 3 and 5 failed to produce any identifiable products in either the conventional or ionic liquid solvents.

Scheme 6 Oxidation of 1, 2, and 4 with TEMPO/NaNO₂/O₂.

The TEMPO-catalyzed oxidation gave moderate to excellent yields in DCM (Table 6), but in the ionic liquid solvents, however, oxidation rates were so slow that conversion was not observed within the standard 19 hour reaction time. TEMPO oxidation of alcohols could be slowed down in ILs as a result of their high viscosity.⁸⁹

Table 6 Oxidation of 1, 2, and 4 with TEMPO/NaNO₂/O₂

Starting mat.^a	Prod.^b	DCM	[C4C1im]Cl	[P4444]Cl
		(A)	(B)	(C)
a Reactions were carried out for 19 hours using 0.15 eq. TEMPO and 0.25 eq. NaNO2.b Yields are for purified, isolated products. Recovered starting material is given in parentheses.
1	10	96%	Trace	Trace
		(0%)	(98%)	(93%)
2	11	88%	0%	0%
		(0%)	(90%)	(75%)
4	12	53%	0%	0%
		(0%)	(53%)	(80%)

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In view of low conversion and yield in IL solvents, optimization experiments were performed using DDQ oxidation of 3 in [C4C1im]Cl as a test case. When higher concentrations were used (by decreasing the volume of the solvent), the yield increased, as expected, from 6% to 24%. When higher temperatures were used, however, no improvement in yield was noted. Unfortunately, the reaction temperature could not be increased significantly above 120 °C, as [C4C1im]Cl has been shown to start decomposing at about 140 °C.⁹⁰ Finally, the reaction was run for a longer period of time, but yields did not improve (Table 7).

Table 7 Optimization of DDQ oxidation in [C4C1im]Cl

	1	2	3	4	5	6	7
AcOH (mL)	0.4	0.4	0.2	0.4	0.2	0.2	0.4
[C4C1im]Cl (g)	3.78	0.4	0.2	3.78	1.9	1.9	0.4
Temp (°C)	rt	rt	rt	50	100	120	rt
% yield	6	24	23	4	5	2	23
% SM	9	69	69	93	61	66	40
Recovered							(2 weeks)

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Oxidation of indulin kraft lignin

Having demonstrated that the TPPFeCl/t-BuOOH catalyst system oxidizes non-phenolic lignin model compounds, we then applied the system to kraft lignin for possible oxidation of the polymer. This reaction was carried out by treating 0.5 g of lignin with TPPFeCl (0.01 eq.) and t-BuOOH (70% aq. soln, 1 eq.) in the appropriate solvent (2.5 mL MeCN or 2.63 g [C4C1im]Cl/2.25 g [P4444]Cl) and 7.5 mL phosphate buffer (0.1 N, pH 3) at 25 °C for 14 h.⁸ Initial results, based on KBr-FTIR absorption spectra, showed evidence of lignin oxidation in both the conventional and ionic liquid solvents, as shown by the appearance of additional absorption bands/shoulders in the carbonyl region, ∼1707–1713 cm⁻¹, coupled with an increase in intensity of the absorption bands in the same region (Fig. 3). The new bands fall within the range of the spectral window where lignin carbonyl bands have been observed.^91–106 Additional results based on ¹H NMR experiment showed a signal at around 7.8 ppm in the post-oxidation spectra in ILs, consistent with benzylic OH group oxidation to ketone in β-O-4 model compounds (Fig. 4; see ESI† for ¹H NMR spectra of oxidized model compounds). This signal was not observed, though, in the post-oxidation spectrum in the conventional solvent, possibly due to the lower solubility of lignin in said solvent. In both the conventional and IL solvents, the extent of oxidation is not sufficient to show in a low-sensitivity measurement such as ¹³C-NMR and HSQC NMR spectroscopy.

Fig. 3 KBr-FTIR spectra of kraft lignin before and after oxidation with TPPFeCl/t-BuOOH in different solvents. The carbonyl region is shown with an arrow.

Fig. 4 ¹H NMR spectra of kraft lignin before and after oxidation with TPPFeCl/t-BuOOH in different solvents. Resonances at 7.8 ppm (circled) are consistent with the formation of benzylic ketones.

Conclusions

The TPPFeCl/t-BuOOH catalyst system selectively oxidized the benzylic C–OH group in the non-phenolic lignin model compounds, in both conventional and ionic liquid solvents. In the case of the non-phenolic, ring alkylated compounds (13 and 14), the catalyst system oxidized both the benzylic C–H and C– OH groups in the conventional solvent but in the ionic liquid solvents there was an increased selectivity for oxidation of the benzylic C–OH. Under these conditions, phenolic models 3 and 5 were consumed but no identifiable, chromatographically mobile products were obtained, and we believe that oxidation of these compounds results in insoluble polymeric products. The DDQ/NaNO₂/O₂ combination selectively oxidized the benzylic hydroxyl group of the functionalized models (both phenolic and non-phenolic), in the conventional solvent and in the ionic liquid [C4C1im]Cl. Under these conditions, the compounds with unprotected phenolic groups (3 and 5) were not lost to polymerization in either the conventional solvent or ionic liquid [C4C1im]Cl. The aerobic TEMPO/NaNO₂ system effectively oxidized the benzylic hydroxyl group in the non-phenolic models with good to excellent yields in the conventional solvent, but we find that in ionic liquids this reaction was very slow and, as was the case in conventional solvent, unprotected phenolic groups were not tolerated.

Oxidation rates were often lower in ionic liquids than in conventional solvents, as indicated by lower conversion in a standard reaction time, likely due in part to the higher viscosity of ionic liquids. Using the DDQ/NaNO₂ system, it was shown that oxidation in [C4C1im]Cl could be enhanced by increasing the concentration of the reaction mixture, as expected, although the reduction in rate could not be overcome by increasing the temperature. In the case of the iron porphyrin-mediated oxidation in ILs, the oxidation rate was significantly higher under aqueous, relative to non-aqueous conditions, suggesting a possible role of water (as a co-solvent) in enhancing the rate of this oxidation.

Of particular significance was the observed increase in selectivity of the benzylic carbon towards oxidation (C–OH vs. C–H) when the reaction was carried out in ionic liquid solvents. This selectivity is indicated by a change in the product distribution in the oxidization of 13 and 14 using the TPPFeCl/t-BuOOH system as catalyst. In the ionic liquid solvents, the product resulting from oxidation of both the C–OH and C–H groups was significantly enhanced in both 13 and 14, while the product arising from sole oxidation of the C–H bond was not observed in the more functionalized compound (14).

The TPPFeCl/t-BuOOH catalyst system brought about partial oxidation of kraft lignin in both the conventional and ionic liquid solvents. The extent of oxidation was enough to be observable in an KBr-FTIR experiment but not enough to be detected in the less sensitive HSQC technique. In the IL solvents, the extent of oxidation was sufficient to be seen under ¹H NMR experiment.

Considering their capacity to dissolve lignin, ionic liquids have characteristics that make them obvious candidates as solvents in reactions on lignin (including deconstruction, by any chemical method). The use of an ionic liquid appears to enhance selectivity in some cases – as exemplified by porphyrin oxidation – and to provide a medium where both phenolic and nonphenolic compounds can be oxidized, like when DDQ is used, but reaction rates drop significantly. Hence, additional optimization work will be needed in order to identify solvent/reagent combinations, possibly including the addition of a co-solvent, that produce efficient deconstruction of lignin.

Experimental section

Anhydrous solvents were purchased from commercial sources, dispensed with syringe techniques and used as received. Column chromatography was performed using silica gel-60 (Supelco).

Synthesis of [C4C1im]Cl

1-Chlorobutane (116.60 g, 1259.6 mmol) was slowly added to 1-methyl imidazole (94.00 g, 1145.0 mmol). Stirring was maintained throughout. The solution was then heated to 50 °C and allowed to stir at this temperature for 3 days. The resulting mixture was then purified by subjecting it to rotary evaporation for three eight-hour periods at less than 10 mbar. The bath temperature was initially set to 50 °C, then increased to 60 °C, and then to 75 °C, during the subsequent intervals. Finally, the IL was evacuated on a Schlenk apparatus at 75 °C and less than 1 mbar of pressure for 5 days, yielding a viscous, pale yellow liquid, which is pure (other than a trace of water) as observed in NMR.

Synthesis of [P4444]Cl

1-Chlorobutane (69.86 g, 754.7 mmol) was added via cannula to tributyl phosphine (162.76 g, 611.2 mmol) under an atmosphere of dry nitrogen. Stirring was maintained throughout. The solution was then heated to 50 °C and allowed to stir at this temperature for 3 days. The resulting mixture was purified by subjecting it to rotary evaporation for three eight-hour periods at less than 10 mbar. The bath temperature was initially set to 70 °C, then increased to 80 °C, then to 95 °C, during the subsequent intervals. Finally, the IL was evacuated on a schlenk apparatus at 150 °C and less than 1 mbar of pressure for 5 days, yielding a waxy, white solid at room temperature, which is pure (other than a trace of water) as observed in NMR.

Preparation of 4

β-Keto ester 8 (44.2 mg, 0.12 mmol) was stirred in THF (1.6 mL) and H₂O (0.16 mL) at room temperature.⁴³ Sodium borohydride (44.9 mg, 1.2 mmol) was added over 3 h and the solution was further stirred for 24 h at room temperature. The mixture was quenched with saturated aqueous NH₄Cl (5 mL) and concentrated under vacuum. The residue was diluted with water (15 mL) and extracted with EtOAc (3 × 10 mL). The solvent was evaporated under vacuum and the residue was subjected to column chromatography on silica gel (EtOAc : hexane 1 : 1) to yield 4 (16.2 mg, 0.05 mmol, 41%). ¹H NMR (400 MHz, CDCl₃, mixture of diastereomers): δ 7.0–6.72 (m, 7H), δ 4.98–4.93 (m, 1H, C_α), δ 4.25–4.16 (m, 1H, C_β), δ 3.96–3.5 (m, 2H, C_γ), δ 3.85, 3.84, 3.83, 3.74, 3.73 (s, 9H). ¹³C NMR (400 MHz, CDCl₃, mixture of diastereomers): δ 154.7, 154.7, 152.1, 151.7, 149.0, 148.9, 148.8, 148.5, 133.2, 132.4, 119.3, 118.7, 118.3, 118.1, 114.7, 114.6, 111.0, 109.9, 109.5, 84.4, 83.4, 73.8, 73.6, 61.4, 61.0, 55.9, 55.7, 55.6. GC-MS m/z (relative intensity): major diastereomer: 376(M⁺ − 18, 3), 298(4), 286(100), 271(24), 257(16), 238 (2), 226(8), 207(10), 193(8), 183(3), 165(5), 151(15), 135(5), 123(15), 107(10), 92(8), 77(15), 63(5), 51(4). HRMS (ESI) m/z [M + Na]⁺ calcd for C₁₈H₂₂O₆Na 357.1309, found 357.1308.

Preparation of 8

In three separate one-neck round bottom flasks were placed NaH (60% dispersion in mineral oil) (0.662 g, 16.54 mmol), 6 (4.37 g, 13.2 mmol) and 4-methoxyphenol (2.053 g, 16.54 mmol).⁴³ The flasks were purged with N₂ for 15 min, after which 4.6 mL THF and 17.2 mL DMF were added to each. The solution of NaH in THF/DMF was cooled to 0 °C and the solution of 4-methoxyphenol was added. The mixture was stirred at room temperature for 1 h and then cooled to 0 °C again. The solution of 6 was added and the resulting mixture was stirred at room temperature for 8 h, then poured onto ice water (200 mL). The resulting aqueous layer was extracted with EtOAc (3 × 100 mL). The extract was washed with water, dried over MgSO₄, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel (EtOAc : hexane 3 : 7) to yield 8 (3.64 g, 9.7 mmol, 74%). ¹H NMR (400 MHz, CDCl₃): δ 7.83 (dd, J₁ = 8.5, J₂ = 2.2 Hz, 1H), δ 7.62 (d, J = 2.1 Hz, 1H), δ 6.94–6.87 (m, 3H), δ 6.83–6.77 (m, 2H), δ 5.63 (s, 1H, C_β), δ 4.28 (q, J = 6.9 Hz, 2H), δ 3.94 (s, 3H), δ 3.91 (s, 3H), δ 3.74 (s, 3H), δ 1.24 (t, J = 7.3 Hz, 3H). ¹³C NMR (400 MHz, CDCl₃): δ 190.0 (C_α), 167.1 (C_γ), 155.0, 154.2, 151.0, 149.0, 126.9, 124.8, 116.8, 114.7, 111.3, 110.1, 82.3 (C_β), 62.2, 56.0, 55.9, 55.6, 14.0. GC-MS m/z (relative intensity): 374(M⁺, 8), 301(1) 273 (2), 165 (100), 151(2), 137(4), 123(5), 107(2), 92(4), 77(5), 64(1), 51(1).

Preparation of 5

A solution of 9 (1.0 g, 2.78 mmol) in THF (25 mL) and H₂O (2.5 mL) was stirred at room temperature.⁴³ Sodium borohydride (1.06 g, 27.8 mmol) was added over 3 h and the solution was further stirred for 24 h at room temperature. The reaction mixture was quenched with a saturated solution of ammonium chloride, (15 mL) and was then concentrated under vacuum. The residue was diluted with water (100 mL) and extracted with dichloromethane (3 × 50 mL). The solvent was evaporated under vacuum, and the residue was subjected to column chromatography on silica gel (EtOAc : hexane 1 : 1) to produce 5 (0.683 g, 2.13 mmol, 77%). ¹H NMR (400 MHz, CDCl₃, mixture of diastereomers): δ 7.0–6.76 (m, 7H), δ 4.99–4.92 (m, 1H, C_α), δ 4.25–4.19 (m, 1H, C_β), δ 3.95–3.51 (m, 2H, C_γ), δ 3.87, 3.86, 3.77, 3.75 (s, 6H). ¹³C NMR (400 MHz, CDCl₃, mixture of diastereomers): δ 154.7, 152.1, 151.7, 151.6, 146.7, 146.6, 145.5, 145.2, 132.5, 131.8, 119.9, 119.3, 118.3, 118.1, 114.8, 114.7, 114.4, 114.3, 109.5, 109.0, 84.4, 83.5, 73.8, 73.7, 61.4, 61.0, 55.9, 55.7. GC-MS m/z (relative intensity): major diastereomer: 302(M⁺ − 18, 0.4), 284(2), 272(100), 255(0.8), 243(2.8), 211(1.3), 183(1.7), 149(1.3), 133(1.5), 124(1.6), 109(1.5), 89(1.0), 77(1.4), 63(0.6), 51(0.6). Minor diastereomer: 302(M⁺ − 18, 0.4), 284(84), 272(87), 253(18), 243(51), 225(14), 207(45), 197(11), 183(13), 169(3), 161(29), 149(33), 137(34), 124(100), 109(79), 89(24), 77(39), 63(19), 53(16). HRMS (ESI) m/z [M + Na]⁺ calcd for C₁₇H₂₀O₆Na 343.1152, found 343.1152.

Preparation of 9

In three separate one-neck round bottom flasks were placed NaH 60% dispersion in mineral oil (1.12 g, 28.12 mmol), 7 (4.95 g, 15.62 mmol) and 4-methoxyphenol (3.96 g, 31.24 mmol).⁴³ The flasks were purged with N₂ for 15 min after which 5.5 mL THF and 20.5 mL DMF were added to each. The solution of NaH in THF/DMF was cooled to 0 °C and the solution of 4-methoxyphenol was added. The mixture was stirred at room temperature for 1 h and then cooled to 0 °C again. The solution of 7 was added, and the resulting mixture was stirred at room temperature for 8 h, then poured onto ice water (120 mL). The resulting aqueous layer was extracted with EtOAc (3 × 60 mL). The extract was washed with water, dried over MgSO₄, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel (EtOAc : hexane 3 : 7) to yield 9 (1.0 g, 2.8 mmol, 18%). ¹H NMR (400 MHz, CDCl₃): δ 7.76 (dd, J₁ = 8.4, J₂ = 2.0 Hz, 1H), δ 7.63 (d, J = 2.0 Hz, 1H), δ 6.94 (d, J = 8.5 Hz, 1H), δ 6.93–6.88 (m, 2H), δ 6.83–6.76 (m, 2H), 5.62 (s, 1H, C_β), δ 4.28 (q, J = 7.2 Hz, 2H), δ 3.92 (s, 3H), δ 3.74 (s, 3H), δ 1.23 (t, J = 7.1 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃): δ 189.8(C_α), 167.0(C_γ), 160.7, 157.8, 151.6, 146.7, 145.4, 126.6, 125.4, 114.2, 114.2, 111.3, 108.5, 107.4, 99.0, 80.9, 62.3, 56.0, 55.2, 38.2, 24.1, 13.99, 13.7. GC-MS m/z (relative intensity): 360(M⁺, 0.9), 281(0.2), 259(0.1), 207(0.7), 151(100), 135(0.2), 123(0.9), 109(0.6), 92(0.2), 77(0.3), 65(0.2), 52(0.1).

Oxidation reactions

Oxidation of 1 withTPPFeCl. Mixtures of 1 (100 mg, 0.47 mmol), TPPFeCl (4.3 mg, 0.0047 mmol), t-BuOOH (70% aq. solution, 64 μL, 0.47 mmol), and 0.1 N phosphate buffer, pH 3 (3 mL) in three different solvents [1.0 mL CH₃CN (A), 1.05 g [C4C1im]Cl (B), and 0.9 g [P4444]Cl (C)] were stirred at 25 °C for 14 h. The mixtures were extracted separately with EtOAc (3 × 10 mL) and each set of combined extracts was washed with saturated aq. NaCl solution, then dried over MgSO₄. After evaporating the solvent under vacuum, each of the resulting residues was subjected to column chromatography on silica gel (EtOAc : hexanes 1 : 5) to give 1A (58.2 mg, 0.27 mmol, 58%) and 10A (40.2 mg, 0.19 mmol, 41%); 1B (67 mg, 0.31 mmol, 67%) and 10B (28 mg, 0.13 mmol, 28%) and 1C (50 mg, 0.23 mmol, 50%) and 10C (46.5 mg, 0.22 mmol, 47%).

Oxidation of 2 withTPPFeCl. Mixtures of 2 (100 mg, 0.31 mmol), TPPFeCl (2.9 mg, 0.0031 mmol), t-BuOOH (70% aq. solution, 43 μL, 0.31 mmol), and 0.1 N phosphate buffer, pH 3 (3 mL) in three different solvents [1.0 mL CH₃CN (A), 1.05 g [C4C1im]Cl (B), and 0.9 g [P4444]Cl (C)] were stirred at 25 °C for 14 h. The mixtures were extracted separately with ethyl acetate (3 × 10 mL) and each set of combined extracts was washed with saturated aq. NaCl solution, then dried over MgSO₄. After evaporating the solvent under vacuum, each of the resulting residues was subjected to column chromatography on silica gel (EtOAc : hexanes 1 : 3) to give 2A (68 mg, 0.22 mmol, 68%) and 11A (22 mg, 0.07 mmol, 22%); 2B (72 mg, 0.23 mmol, 72%) and 11B (9.4 mg, 0.03 mmol, 9.5%); and 2C (58 mg, 0.18 mmol, 58%) and 11C (25.2 mg, 0.08 mmol, 25%).

Oxidation of 4 withTPPFeCl. Mixtures of 4 (100 mg, 0.47 mmol), TPPFeCl (4.3 mg, 0.0047 mmol), t-BuOOH (70% aq. solution, 64 μL, 0.47 mmol), and 0.1 N phosphate buffer, pH 3 (3 mL) in three different solvents [1.0 mL CH₃CN (A), 1.05 g [C4C1im]Cl (B), and 0.9 g [P4444]Cl (C)] were stirred at 25 °C for 14 h. The mixtures were extracted separately with ethyl acetate (3 × 10 mL) and each set of combined extracts was washed with saturated aq. NaCl solution, then dried over MgSO₄. After evaporating the solvent under vacuum, each of the resulting residues was subjected to column chromatography on silica gel (EtOAc : hexanes 1 : 5) to give 4A (55 mg, 0.16 mmol, 55%) and 12A (37 mg, 0.11 mmol, 38%); 4B(69 mg, 0.21 mmol, 69%) and 12B (21.5 mg, 0.07 mmol; 22%) and 4C (64 mg, 0.19 mmol, 64%) and 12C(30 mg, 0.09 mmol, 30%). ¹H NMR (400 MHz, CDCl₃): δ 7.75 (dd, J₁ = 8.4, J₂ = 2.0 Hz, 1H), δ 7.57 (d, J = 2.0 Hz, 1H), δ 6.88 (d, J = 8.5 Hz, 1H), δ 6.87–6.75 (m, 4H), δ 5.43 (dd, J₁ = 6.1, J₂ = 4.2 Hz, 1H), δ 4.17–4.04 (m, 2H)), δ 3.94 (s, 3H), δ 3.89 (s, 3H), δ 3.73 (s, 3H). ¹³C NMR (400 MHz, CDCl₃): δ 195.3, 154.6, 154.1, 151.4, 149.2, 127.9, 123.6, 116.6, 114.8, 110.8, 110.1, 82.0, 63.6, 56.1, 55.9, 55.6. GC-MS m/z (relative intensity): 314(M⁺ − 18, 1.0), 302(25), 284(1.0), 207(0.5), 165(100), 151(8), 137(5), 123(5), 107(5), 92(4), 77(7), 65(2), 51(2). HRMS (ESI) m/z [M + H]⁺ calcd for C₁₈H₂₁O₆ 333.1333, found 333.1332.

Oxidation of 13 with TPPFeCl. Mixtures of 13 (50 mg, 0.195 mmol), TPPFeCl (5 mg, 0.005 mmol), t-BuOOH (70% aq. solution, 27 μL, 0.47 mmol), and 0.1 N phosphate buffer, pH 3 (1.5 mL) in three different solvents [0.5 mL CH₃CN (A), 0.2 g [C4C1im]Cl (B), and 0.2 g [P4444]Cl (C)] were stirred at 25 °C for 14 h. The mixtures were extracted separately with EtOAc (3 × 5 mL) and each set of combined extracts was washed with saturated aq. NaCl solution, then dried over MgSO₄. After evaporating the solvent under vacuum, each of the resulting residues was subjected to column chromatography on silica gel (EtOAc : hexanes 1 : 9) to give 13A (18 mg, 0.07 mmol, 36%), 15A (20.4 mg, 0.08 mmol, 41%), 16A (4.2 mg, 0.016 mmol, 8%), and 17A (4.7 mg, 0.017 mmol, 9%); 13B (15 mg, 0.06 mmol, 30%), 15B (20 mg, 0.08 mmol, 40%), 16B (4.7 mg, 0.017 mmol, 9%), and 17B (8.9 mg, 0.033 mmol, 17%); 13C (13 mg, 0.05 mmol, 26%), 15C (22 mg, 0.09 mmol, 44%), 16C (5.3 mg, 0.019 mmol, 10%), and 17C (9.4 mg, 0.035 mmol, 18%).

Oxidation of 14 withTPPFeCl. Mixtures of 14 (70 mg, 0.186 mmol), TPPFeCl (6 mg, 0.006 mmol), t-BuOOH (70% aq. solution, 51 μL, 0.37 mmol), and 0.1 N phosphate buffer, pH 3 (2 mL) in three different solvents [0.6 mL CH₃CN (A), 0.3 g [C4C1im]Cl (B), and 0.3 g [P4444]Cl (C)] were stirred at 25 °C for 14 h. The mixtures were extracted separately with ethyl acetate (3 × 10 mL) and each set of combined extracts was washed with saturated aq. NaCl solution, then dried over MgSO₄. After evaporating the solvent under vacuum, each of the resulting residues was subjected to column chromatography on silica gel (EtOAc : CH₂Cl₂ 1 : 14) to give 14A (32 mg, 0.085 mmol, 46%), 18A (25 mg, 0.07 mmol, 36%), 19A (9.4 mg, 0.024 mmol, 13%), and 20A (2.1 mg, 0.005 mmol, 3%); 14B (35.7 mg, 0.09 mmol, 51%), 18B (24 mg, 0.06 mmol, 34%) and 20B (8.7 mg, 0.023 mmol, 12%); 14C (41 mg, 0.11 mmol, 59%), 18C (16 mg, 0.04 mmol, 23%) and 20C (10.1 mg, 0.026 mmol, 14%).

Oxidation of 2 with DDQ/NaNO₂/O₂. Mixtures of 2 (100 mg, 0.314 mmol), DDQ (7.14 mg, 0.031 mmol), NaNO₂ (2.17 mg, 0.031 mmol), and acetic acid (0.4 mL) in three different solvents [3.6 mL CH₂Cl₂ (A), 3.78 g [C4C1im]Cl (B), and 3.24 g [P4444]Cl (C)] were stirred under an O₂ atmosphere (1 atm) at 25 °C for 19 h. The mixtures were extracted separately with ethyl acetate (3 × 10 mL) and each set of combined extracts was washed with saturated aq. NaCl solution, then dried over MgSO₄. After evaporating the solvent under vacuum, each of the resulting residues was subjected to column chromatography on silica gel (EtOAc : hexanes 1 : 3) to give 2A (38 mg, 0.12 mmol, 38%) and 11A (60 mg, 0.19 mmol, 61%); 2B (60 mg, 0.19 mmol, 60%) and 11B (10.2 mg, 0.032 mmol, 10%); and 2C (85 mg, 0.27 mmol, 85%) and 11C (7 mg, 0.02 mmol, 7%).

Oxidation of 3 with DDQ/NaNO₂/O₂. Mixtures of 3 (100 mg, 0.329 mmol), DDQ (7.5 mg, 0.033 mmol), NaNO₂ (2.27 mg, 0.033 mmol), and acetic acid (0.4 mL) in three different solvents [3.6 mL CH₂Cl₂ (A), 3.78 g [C4C1im]Cl (B), and 3.24 g [P4444]Cl (C)] were stirred under an O₂ atmosphere (1 atm) at 25 °C for 19 h. The mixtures were extracted separately with ethyl acetate (3 × 10 mL) and each set of combined extracts was washed with saturated aq. NaCl solution, then dried over MgSO₄. After evaporating the solvent under vacuum, each of the resulting residues was subjected to column chromatography on silica gel 1 : 3) to give 3A (1.9 mg, 0.006 mmol, 2%), 21A (56.6 mg, 0.19 mmol, 57%); 3B (93 mg, 0.31 mmol, 93%) and 21B (5.6 mg, 0.019 mmol, 6%).

Oxidation of 4 with DDQ/NaNO₂/O₂. Mixtures of 4 (100 mg, 0.3 mmol), DDQ (6.81 mg, 0.03 mmol), NaNO₂ (2.07 mg, 0.03 mmol), and acetic acid (0.4 mL) in three different solvents [3.6 mL CH₂Cl₂ (A), 3.78 g [C4C1im]Cl (B), and 3.24 g [P4444]Cl (C)] were stirred under an O₂ atmosphere (1 atm) at 25 °C for 19 h. The mixtures were extracted separately with ethyl acetate (3 × 10 mL) and each set of combined extracts was washed with saturated aq. NaCl solution, then dried over MgSO₄. After evaporating the solvent under vacuum, each of the resulting residues was subjected to column chromatography on silica gel (EtOAc : hexanes 1 : 1) to give 4A (65 mg, 0.195 mmol, 65%), 12A (27 mg, 0.08 mmol, 27%); 4B (89 mg, 0.27 mmol, 89%) and 12B (4.7 mg, 0.014 mmol, 5%); and 4C (75 mg, 0.225 mmol, 75%) and 12C (trace).

Oxidation of 5 with DDQ/NaNO₂/O₂. Mixtures of 5 (100 mg, 0.313 mmol), DDQ (7.1 mg, 0.0313 mmol), NaNO₂ (2.16 mg, 0.0313 mmol), and acetic acid (0.4 mL) in three different solvents [3.6 mL CH₂Cl₂ (A), 3.78 g [C4C1im]Cl (B), and 3.24 g [P4444]Cl (C)] were stirred under an O₂ atmosphere (1 atm) at 25 °C for 19 h. The mixtures were extracted separately with ethyl acetate (3 × 10 mL) and each set of combined extracts was washed with saturated aq. NaCl solution, then dried over MgSO₄. After evaporating the solvent under vacuum, each of the resulting residues was subjected to column chromatography on silica gel (EtOAc : hexanes 1 : 1) to give 22A (47.2 mg, 0.148 mmol, 48%); 5B (67 mg, 0.21 mmol, 67%) and 22B (1.3 mg, 0.004 mmol, 1%). ¹H NMR (400 MHz, CDCl₃): δ 7.75 (dd, J₁ = 8.4, J₂ = 2.0 Hz, 1H), δ 7.69 (dd, J₁ = 8.5, J₂ = 2.0 Hz, 1H), δ 7.57 (d, J = 2.0 Hz, 1H), δ 6.94 (d, J = 8.3 Hz, 1H) δ 6.87–6.75 (m, 4H), δ 5.43 (dd, J₁ = 6.4, J₂ = 4.1 Hz, 1H), δ 4.17–4.03 (m, 2H), δ 3.9 (s, 3H), δ 3.73 (s, 3H). ¹³C NMR (400 MHz, CDCl₃): δ 195.2, 154.6, 154.4, 151.2, 146.8, 127.6, 124.2, 116.6, 114.8, 114.1, 110.7, 81.8, 63.5, 56.1, 55.7. GC-MS m/z (relative intensity): 300(M⁺ − 18, 2.0), 288(34), 165(0.5), 151(100), 137(9), 123(14), 108(4), 92(4), 77(6), 65(3), 52(3). HRMS (ESI) m/z [M + H]⁺ calcd for C₁₇H₁₉O₆ 319.1176, found 319.1176.

Oxidation of 1 with TEMPO/NaNO₂/O₂. Mixtures of 1 (100 mg, 0.47 mmol), TEMPO (11.2 mg, 0.07 mmol), NaNO₂ (8.1 mg, 0.12 mmol), 36% aq. HCl (7 μL, 0.23 mmol), and NaCl (13.7 mg 0.23 mmol) in three different solvents [0.6 mL CH₂Cl₂ (A), 0.63 g [C4C1im]Cl (B), and 0.54 g [P4444]Cl (C)] were stirred under an O₂ atmosphere (1 atm) at 25 °C for 19 h. The mixtures were extracted separately with dichloromethane (3 × 10 mL) and each set of combined extracts was washed successively with 30% aq. Na₂S₂O₃ solution, saturated aq. NaHCO₃ solution, and water. The extracts were dried separately over MgSO₄ and after evaporating the solvent under vacuum, each of the resulting residues was subjected to column chromatography on silica gel (EtOAc : hexanes 1 : 5) to give 10A (95 mg, 0.45 mmol, 96%); 1B (98 mg, 0.46 mmol, 98%), 10B (trace) and 1C (93 mg, 0.43 mmol, 93%), 10C (trace).

Oxidation of 2 with TEMPO/NaNO₂/O₂. Mixtures of 2 (100 mg, 0.314 mmol), TEMPO (7.5 mg, 0.047 mmol), NaNO₂ (5.4 mg, 0.08 mmol), 36% aq. HCl (5 μL, 0.16 mmol), and NaCl (9.2 mg, 0.16 mmol) in three different solvents [0.6 mL CH₂Cl₂ (A), 0.63 g [C4C1im]Cl (B), and 0.54 g [P4444]Cl (C)] were stirred under an O₂ atmosphere (1 atm) at 25 °C for 19 h. The mixtures were extracted separately with dichloromethane (3 × 10 mL) and each set of combined extracts was washed successively with 30% aq. Na₂S₂O₃ solution, saturated aq. NaHCO₃ solution, and water. The extracts were dried separately over MgSO₄ and after evaporating the solvent under vacuum, each of the resulting residues was subjected to column chromatography on silica gel (EtOAc : hexanes 1 : 3) to give 11A (86.8 mg, 0.275 mmol, 88%); 2B (90 mg, 0.283 mmol, 90%) and 2C (75 mg, 0.24 mmol, 75%).

Oxidation of 4 with TEMPO/NaNO₂/O₂. Mixtures of 4 (100 mg, 0.3 mmol), TEMPO (7.2 mg, 0.045 mmol), NaNO₂ (5.2 mg, 0.075 mmol), 36% aq. HCl (5 μL, 0.15 mmol), and NaCl (8.8 mg, 0.15 mmol) in three different solvents [0.6 mL CH₂Cl₂ (A), 0.63 g [C4C1im]Cl (B), and 0.54 g [P4444]Cl (C)] were stirred under an O₂ atmosphere (1 atm) at 25 °C for 19 h. The mixtures were extracted separately with dichloromethane (3 × 10 mL) and each set of combined extracts was washed successively with 30% aq. Na₂S₂O₃ solution, saturated aq. NaHCO₃ solution, and water. The extracts were dried separately over MgSO₄ and after evaporating the solvent under vacuum, each of the resulting residues was subjected to column chromatography on silica gel (EtOAc : hexanes 1 : 1) to give 12A (52 mg, 0.16 mmol, 53%); 4B (53 mg, 0.16 mmol, 53%) and 4C (80 mg, 0.24 mmol, 80%).

Acknowledgements

This work was financially supported by the National Science Foundation under awards NSF-EFRI-0937657 and NSF-IIA-1355438. We would like to thank Dr Bert Lynn and Dr Marcelo Guzman for sharing valuable insights in the processing and interpretation of our IR spectra.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: NMR spectra of 1–5, 8–12, 21–22, kraft lignin pre-oxidation, kraft lignin post-oxidation in MeCN, in [C4C1im]Cl, in [P4444]Cl; IR spectra of kraft lignin pre-oxidation, kraft lignin post-oxidation in MeCN, in [C4C1im]Cl, in [P4444]Cl. See DOI: 10.1039/c6ra18806k

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