Mechanochemical Oxidation and Cleavage of Lignin Î²-O-4 Model

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Mechanochemical Oxidation and Cleavage of Lignin #-O-4 Model Compounds and Lignin Saumya Dabral, Hermann Wotruba, Jose G. Hernandez, and Carsten Bolm ACS Sustainable Chem. Eng., Just Accepted Manuscript • DOI: 10.1021/ acssuschemeng.7b03418 • Publication Date (Web): 17 Jan 2018 Downloaded from http://pubs.acs.org on January 18, 2018

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ACS Sustainable Chemistry & Engineering

Mechanochemical Oxidation and Cleavage of Lignin

β-O-4 Model Compounds and Lignin Saumya Dabral,a Hermann Wotruba,b José G. Hernández,a* and Carsten Bolma* a) Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany b) Mineral Processing Unit (AMR), RWTH Aachen University, Lochnerstraße 4-20, 52064 Aachen, Germany *E-mail: [email protected]

[email protected]

KEYWORDS: Mechanochemistry, mechanical milling, oxidation, lignin.

ABSTRACT

A mechanochemically oxidation and cleavage reaction in lignin β-O-4 model compounds and lignin catalyzed by HO–TEMPO/KBr/Oxone® has been developed under milling conditions. The studies on non-phenolic lignin β-O-4 model compounds led to selective oxidations of the benzylic hydroxyl groups. Complementary, subjecting phenolic lignin model compounds to the oxidative conditions in a ball mill initiated aryl–C bond cleavage reactions leading to the α

formation of the corresponding quinones and phenol derivatives. Transferring the

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mechanochemical protocol to lignin resulted in the simultaneous oxidation and cleavage of bonds with varied selectivity for monomeric products. Finally, a scale-up approach of the oxidative procedure by using vibrating disc mill technology enabled the mechanochemical protocol to be applied in gram-scale batch reactions under reduced milling time, while affording similar extent of oxidation.

INTRODUCTION

In recent years, notable attempts have been made to tailor mechanical energy in order to facilitate the synthesis of advanced molecules and materials by inducing the formation of new covalent, coordination,

ionic

mechanochemistry

bonds allowed

as the

well

as

non-covalent

development

of

interactions.1

sustainable

and

In

this

efficient

context, chemical

transformations, along with the discovery of new chemical reactivity.2,3 This includes several areas of chemistry such as organic,4-9 inorganic,10,11 organometallic,12 polymer,13,14 enzyme,15-17 photo-,18 supramolecular,19 coordination,20-21 nanomaterial,22-23 medicinal chemistry,24 catalysis,25 and many others. However, besides promoting the formation of new bonds and non-covalent interactions, mechanochemical activation also has an enormous potential to enable the selective cleavage of specific chemical bonds. This aspect of mechanochemistry can be foreseen to be highly valuable, for example, in biomass valorization. Indeed, milling techniques, that were in principle utilized for the purpose of comminution (minerals, stones, wood, cellulose, polymers, among others), have now gained recognition as efficient alternatives to bypass the solubility concerns faced when working with lignocellulosic materials, reagents, and catalysts of different solubility profiles. In particular, previous attempts on the mechanochemical transformation of


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lignin model compounds and lignin have highlighted the possibility to initiate selective cleavage reactions under requisite milling conditions.26-32 Today, mechanocatalytic depolymerization of cellulose has been achieved by milling the biopolymer in the presence of heterogeneous catalysts such as clays,33 or by pre-impregnating the lignocelullosic biomass with Brønsted acids before proceeding to grinding.34-37 A recent article by Yan and co-workers also highlighted a more efficient solvent-free milling of chitin to lower molecular weight chitosan in the presence of catalytic amounts of base.38 In the year 2013, our group pioneered the development of lignin depolymerization in ball mills in the presence of solid bases.39 Lignin is one of the three principle components of the lignocellulosic biomass constituting a fraction of around 15–30% on weight basis and 40% on the basis of energy content.40-41 Structurally, lignin is a complex and amorphous threedimensional biomacromolecule due to the random repetition of methoxylated hydroxy cinnamyl alcohol building blocks which are bonded together through different types of C–O–C and C–C inter-unit linkages.40-41 The solubility limitations associated with wood42-44 along with the structural complexity found in the lignin biomacromolecule poses difficulty in catalytic processes, thereby making the valorization technologies challenging. Despite this, the large amounts of lignin that are now available in the paper mills and in the upcoming biorefineries makes it extremely important to circumvent these issues and to establish routes for effective lignin valorization. Our recent findings on base,45 metal46-48 and specially organocatalytic-oxidative depolymerization of lignin via primary alcohol oxidation in solution,49 made us wonder about the possibility to develop a mechanochemical protocol for the oxidation of lignin model compounds and lignin,


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with the potential to induce simultaneously structural changes in the biomacromolecule and to trigger a mechanically-induced lignin depolymerization route (Scheme 1). The aliphatic hydroxyl groups represent a major inter-unit functionality while linking the aromatics by ether bond in the biopolymer. A potential selective benzylic oxidation followed by subsequent cleavage50-57 or direct oxidative cleavage reactions46-48,58-65 are alternative pathways for procuring a range of monomeric-aromatic aldehydes and quinone products that are useful precursors in agrochemical and fine chemical industries. Along this direction of research and to avoid the solubility issues, we envisioned a system to carry out oxidative transformations on both lignin β-O-4 model compounds and the lignin itself under milling conditions. As a starting point, we chose 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) as a catalyst in combination with Oxone® (potassium peroxymonosulfate, 2KHSO5·KHSO4·K2SO4) as the oxidizing agent, which has been extensively used in solution chemistry.66 In fact, in the past our group reported on several supported-TEMPO catalyzed oxidation of alcohols in combination with a secondary oxidant.67-69 Of particular mention is the TEMPO-catalyzed oxidation of alcohols with Oxone® in the solution chemistry.70 More recently, this solid oxidant has proven to perform well in the ball mill for the oxidative halogenation of organic molecules71-72 and organometallic complexes.73-74 as well as for the direct oxidative amidation of aryl aldehydes with anilines to synthesize amides.75 In addition to this, Oxone®, TEMPO and its substituted derivatives are readily available, non-toxic and most importantly shock-stable, making them ideal for our high speed oxidative-milling experiments.


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Experimental Materials Lignin β-O-4 model compounds 1a-g (Table 1-2 and Scheme 2) were synthesized following previous literature procedures.39,76 Organosolv beechwood lignin (OS-BWL) was extracted from beechwood chips with aqueous ethanol (50% w/w) without the addition of an acid catalyst. Lignin was then precipitated with water and afterwards washed with more water to remove the residual carbohydrates. The precipitate was recovered by centrifugation, and the liquor above decanted. Finally, the lignin was dried and pulverized. All other reagents were acquired from commercial suppliers and used without further purification. Small scale ball milling experiments were conducted in a RETSCH MM400 mixer mill using 10 mL milling jars made of either zirconium oxide (ZrO2), stainless steel (SS) or tungsten carbide (WC) with a milling ball of 10 mm in diameter (Supporting Information, Figure S1). The 10 g milling reactions were conducted in two different mills: (a) a SIEBTECHNIK vibrating disc mill using a WC 250 mL milling vessel and a WC disc weighing 1.2 kg; (b) a LAARMANN LMM6-100 mortar mill with a WC mortar vessel of 250 mL in volume (Supporting Information, Figure S5). Methods General procedure for the oxidative transformation of lignin β -O-4 model compounds in a mixer mill. A 10 mL milling jar made of ZrO2, SS or WC was charged with model compounds 1a-g (0.25 mmol, 1.0 equiv) along with the requisite amounts of oxidation catalysts in the presence of the atmospheric oxygen available in the jars from the start of the process. The reaction mixture


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was then milled at either 25 Hz or 30 Hz for 60 min to 180 min. After milling, the mixture was extracted with ethyl acetate (EtOAc). Unless otherwise specified, the conversion and product quantification was done by quantitative 1H NMR spectroscopy with respect to 2,4 dinitrobenzene (7.0 mg) as an internal standard. The conversion and product yields for the phenolic model compounds 1f and 1g were calculated after pre-calibrated GC analysis with respect to a standard solution of n-octadecane (1.0 mL of n-octadecane in acetonitrile c = 0.2 mol·L–1), added to the reaction mixture. Procedure for the HO–TEMPO/KBr/Oxone® catalyzed oxidative transformations of OSBWL under milling conditions. Oxidative treatment in the mixer mill (MM) A 10 mL milling jar made of tungsten carbide (WC) was charged with the lignin sample (OS-BWL, 100 mg), 4-hydroxy-TEMPO (HO–TEMPO, 10.3 mg, 0.2 equiv), KBr (7.1 mg, 0.2 equiv) and Oxone® (137 mg, 1.5 equiv). The loadings for HO–TEMPO, KBr and Oxone® were calculated by dividing the mass of the OS-BWL sample by the molar mass of 1d to approximately estimate the maximum amount of diol fragments. The mixture was then milled at 30 Hz for either 90 or 180 min followed by filtration over a sintered funnel using water (2 × 10 mL) to remove the inorganic salts. The residue was then washed with distilled Et2O (2 × 10 mL). The resulting liquid phases (water and Et2O) were separated using an extraction funnel to obtain the low molecular weight organics (oil) from the solid residual lignin.


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Oxidative treatment in a LAARMANN LMM6-100 mortar and pestle mill (MPM). A 250 mL milling vessel was charged with lignin sample (OS-BWL, 10 g), HO–TEMPO (1 g, 0.2 equiv), KBr (0.7 g, 0.2 equiv) and Oxone® (13.7 g, 1.5 equiv). The loadings for HO– TEMPO, KBr and Oxone® were calculated by dividing the mass of the OS-BWL sample by the molar mass of 1d to roughly estimate the amount of diol fragments. The mixture was then milled at 120 rpm in a cyclic fashion (10 min × 3 times; 10 min brake). After the milling was complete, 100 mg of the solid reaction mixture was collected and filtered over a sintered funnel using water (2 × 10 mL) to remove the inorganic salts followed by Et2O (2 × 10 mL) wash. The resulting phases (water and Et2O) were separated using an extraction funnel to obtain the low molecular weight organics (oil) from the solid residual lignin. This oily filtrate was then subjected to further characterizations (Supporting Information, Scheme S1). Oxidative treatment in a SIEBTECHNIK vibrating disc mill. A 250 mL milling vessel was charged with lignin sample (OS-BWL, 10 g), HO–TEMPO (1 g, 0.2 equiv), KBr (0.7 g, 0.2 equiv) and Oxone® (13.7 g, 1.5 equiv). The loadings for HO– TEMPO, KBr and Oxone® were calculated by dividing the mass of the OS-BWL sample by the molar mass of 1d to roughly estimate the amount of diol fragments. The mixture was then milled at 50 Hz in a cyclic fashion (10 min × 3 times; 10 min brake), followed by a similar work-up and product analysis procedures as described before. (For details also see, Supporting Information, Scheme S1).


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Characterization NMR spectroscopy 1

H NMR and 13C NMR spectra for lignin model compounds and the 2D-HSQC NMR analysis of

OS-BWL were recorded on a Varian Inova 400 (1H NMR: 400 MHz, 13C NMR: 101 MHz) or an Agilent VNMRS 600 (1H NMR: 600 MHz, 13C NMR: 151 MHz) spectrometer. The 31P NMR analysis was conducted on a Bruker 300 MHz spectrometer. Abbreviations are as follows: s (singlet), d (doublet), t (triplet), m (multiplet), dd (doublet of doublets), br.s (broad singlet). Chemical shifts (δ) are given in ppm relative to the residual solvent peak (CDCl3: δ = 7.26 ppm, DMSO-d6: δ = 2.50 ppm). Spin-spin coupling constants (J) are given in Hz. Mass spectrometry Mass spectra were recorded on a Finnigan SSQ 7000 spectrometer (EI) and HRMS on a Finnigan MAT 95 spectrometer (ESI). Melting point Melting points were measured with a Büchi melting point B-540 apparatus. Gas chromatography-mass spectrometry (GC-MS): analysis of the organic-soluble fractions from the mechanochemical oxidation of lignin. After the mechanochemical oxidation of the lignin was stopped, the solid reaction mixture was washed first with deionized water followed by diethyl ether. These two phases were separated to afford an organic-soluble fraction (ethereal extract). Then the ethereal phase was evaporated, and a known amount of n-octadecane (1.0 mL of n-octadecane in acetonitrile c = 0.2 mol·L–1) was


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added into the resulting oil as an internal standard. The solution was then diluted with EtOAc and subjected to GC-MS analysis using an Agilent 7890A series GC system equipped with an Agilent 5975C inert XL EI/CI MSD with triple axis detector and an Agilent DB-5ms column (30 m x 0.25 mm x 0.25 µm) with helium as the carrier gas. The standard method of analysis consisted of a 1 µL injection volume at a split ratio of 50:1, having a flow of 1.2 mL·min–1 with a temperature profile that started at 60 °C with a 5 min isotherm followed by a 10 °C·min–1 ramp for 20 min which finished at 260 °C. Finally, this temperature was held for 5 min. NIST 08 standard reference database was used for characterizing the peaks. 31

P NMR, IR, GPC and TGA analyses of the solid oxidized lignin.

The residual solid recovered after filtration of the reaction mixture with deionized water and diethyl ether, hereinafter referred as oxidized OS-BWL, was transferred into a pre-weighed round bottom flask. This solid was dried overnight under high vacuum in an oil bath at 40 °C. The dry solid was then subjected to various analytical procedures to determine the changes in the lignin structure and existing functionalities. Quantitative

31

P NMR spectroscopy of the OS-BWL sample before and after the

mechanochemical oxidative treatment. The quantitative 31P NMR analysis for the phenolic and the aliphatic hydroxyl groups in the lignin OS-BWL both before and after the oxidation were conducted on a Bruker 300 MHz spectrometer following previous literature reports.77 A weighed amount of vacuum dried lignin sample (30 mg) was dissolved in 700 µL of an anhydrous solvent mixture (pyridine : CDCl3, 1.6:1, v/v). To this, 100 µL of cyclohexanol solution (pyridine : CDCl3, 1.6:1, v/v;) (10.8


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mg·mL–1), was added as an internal standard along with 100 µL of chromium (III) acetylacetonate solution (pyridine : CDCl3, 1.6:1, v/v;) (5.2 mg·mL–1), as the relaxation reagent. Finally,

100

µL

of

the

phosphitylating

agent

(2-chloro-4,4,5,5-tetramethyl-1,2,3-

dioxaphospholane) was added and the mixture was transferred into a 5 mm in diameter NMR tube for NMR acquisition. Acquisition parameters: 512 scans, 250 ppm sweep width and a relaxation delay of 10 sec. Infrared spectroscopy (IR). The IR spectra for the lignin samples were recorded on a Perkin Elmer Spectrum 100 FT-IR spectrometer. The wavenumbers are given in reciprocal centimeters (cm–1) and only absorption bands with intensity greater than 35% are reported. Gel permeation chromatography (GPC). GPC analysis of the OS-BWL samples before and after the oxidative depolymerization in the ball mills was performed on an Agilent 1200 series instrument equipped with a refractive index (RI) detector (DawnEOS, Wyatt Technology). The eluent solution consisted of 0.1 M sodium hydroxide (NaOH, 99%, Sigma Aldrich) and 0.01 wt % sodium azide (NaN3, extra pure, Merck KGaA), prepared using HPLC grade water. A solution of 12.5 mg·mL–1 glucose monohydrate in water (Merck KGaA) was used as the internal standard for all the measurements. One precolumn (8 × 50 mm) and three MCX gel columns (8 × 300 mm, particle diameter: 5 μm, nominal pore width: 1000 Å) were used at a flow rate of 1.0 mL·min–1 at 40 °C. The molecular weights were determined using narrowly distributed polystyrene sulfonate standards of known molecular weight distribution.


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Thermogravimetric analysis (TGA). The thermal characterization of the OS-BWL samples before and after the mechanochemical oxidative depolymerization was carried out through thermal gravimetric analysis on a Mettler Toledo TGA instrument operating under argon. In each measurement, approximately 20 mg of lignin sample was weighed in a 70 µL alumina crucible and scanned from 20 °C to 800 °C, at a rate of 10 °C·min–1. Results and discussion Oxidative transformations of lignin β -O-4 model compounds in a mixer mill. To commence, monolignol 1a was selected as the lignin β-O-4 model compound for the screening and optimization of the mechanochemically induced oxidation reactions. The initial experiments were carried out in a mixer mill operated at a milling frequency of 25 Hz for 180 min. Control reactions performed with 1a in the absence of external oxidants showed that the atmospheric oxygen present in the vessel did not lead to any observable change in the structure of 1a (Supporting Information, Table S1, entry 1). Then, preliminary attempts to oxidize 1a were conducted using various oxidizing agents (Supporting Information, Table S1). Amongst the oxidants tested, 2-iodoxybenzoic acid (IBX), Dess–Martin periodinane (DMP), Oxone®, trichloroisocyanuric acid (TCCA), and bleach resulted in the benzylic oxidation of 1a to 2a in the ball mill, albeit low conversions were observed (Supporting Information, Table S1). Alongside these experiments, mechanochemical oxidations using 2,2,6,6-tetramethylpiperidineN-oxyl (TEMPO)/additive/oxidant combinations were also carried out for the oxidation of 1a. For example, milling 1a for 3 h at 25 Hz in the presence of TEMPO/KBr/Oxone® (0.2:0.2:1.5)


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afforded the ketone 2a in 45% yield (Table 1, entry 1. For other additives and oxidants, see Table S1). Keeping in mind the availability and the cost of the catalysts, two other relatively economical TEMPO derivatives, 4-acetamido-TEMPO (AcNH-TEMPO) and HO–TEMPO, were tested as catalysts in the above reaction system (Table 1, entries 2 and 3). Oxidation of model compound 1a in solution has been reported using similar oxidants.50,51 Here, both TEMPO derivatives proved active under the mechanochemical reaction conditions. In particular, the HO– TEMPO showed similar reactivity compared to the TEMPO catalyst and even afforded the oxidized product 2a in higher yield (Table 1, entries 1 and 3). An increase in the milling frequency from 25 Hz to 30 Hz had a positive effect on the oxidation of 1a in the ball mill, yielding 2a in 86% after the same reaction time (Table 1, entry 4). Under these adjusted reaction conditions, reducing the amount of Oxone® was possible although the yield of 2a dropped to 79% (Table 1, entry 5). To further improve the conversion of 1a and with the goal to shorten the milling time, different milling media having a higher material density than ZrO2 (ZrO2; 5.7 g/cm3, SS; 7.8 g/cm3, WC; 15.6 g/cm3) were employed (Table 1, entries 6-9). Pleasingly, the use of stainless steel (SS) and tungsten carbide (WC) milling jar and balls had a positive effect on the reaction (Table 1, entries 6 and 7). Not only the formation of 2a was favored using denser milling media but also the milling time of the mechanochemical oxidation could be reduced (Table 1, entries 6-9). After this fine tuning of the milling parameters the lignin β-O-4 model compound 1a could be fully converted into ketone 2a in the presence of HO– TEMPO/KBr/Oxone® after just 90 min of milling (Table 1, entry 8). Expanding the above mechanochemical oxidation protocol to methoxy-substituted monolignol derivatives 1b and 1c proved successful. Milling a mixture of model compounds 1b and 1c in the presence of HO–TEMPO/KBr/Oxone® afforded the corresponding ketones 2b and 2c in 93% and


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87%, respectively, after purification by column chromatography (Scheme 2). The excellent results on the mechanochemical oxidation of lignin β-O-4 model compound 1a-c, motivated us to widen the scope of the reaction to more challenging non-phenolic and phenolic lignin model compounds bearing both benzylic as well as primary alcoholic groups (Table 2). Both nonphenolic dilignol model compounds erythro 1d and threo 1e resulted in the selective benzylic oxidation to ketone 2d in 95% and 94% yields, respectively (Table 2, entries 1 and 2). Moreover, performing the oxidation reaction of 1d under argon (glove-box technique) resulted in a similar product yield (2d = 96%). This results rules out a major participation of atmospheric oxygen in the mechanochemical oxidation of 1d. Interestingly, employing guaiacyl phenolic dilignol (1f; G-type) under the same reaction conditions, resulted in the direct formation of cleavage products. After only 90 min of milling 1f gave 2-methoxybenzoquinone (3a) in 82% yield and guaiacol (4) in 76% yield (Table 2, entry 3). On the contrary, carrying out the same oxidation reaction in acetonitrile using HO-TEMPO (0.2 equiv), KBr (0.2 equiv) and Oxone® (1.5 equiv) for 3 h in an oil bath at room temperature resulted in 70% conversion of 1f. The reaction afforded 3a and 4 in 35 and 41% yields respectively. The yields for the corresponding cleavage products increased with the syringyl model compound (1g; S-type), which afforded 2,6dimethoxybenzoquinone (3b) and 4 in 91% and 82% yields, respectively (Table 2, entry 4). Such changes in product composition using the lignin model compounds 1f and 1g could be attributed to the presence of the reactive phenolic functionalities. Along these lines, the formation of quinones 3a and 3b could be related to the previous observation by Anastas, Crabtree, Hazari, and co-workers, who reported that simple lignin-like methoxylated aromatic compounds such as trimethoxybenzene led to the formation the corresponding quinones after treatment with Oxone®.78


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Oxidative transformations of beechwood lignin in a mixer mill. Motivated by the aforementioned results obtained using lignin model compounds, we decided to advance our studies on mechanochemical oxidations by applying the ball milling protocol to organosolv beechwood lignin (OS-BWL). Characterization of OS-BWL by 2D-HSQC NMR spectroscopy revealed the presence of β-O-4, β-5 and β-β linkage content in the lignin sample (for details, see Table S2 in the Supporting Information). The initial experiments with the lignin sample were carried out under the optimized reaction conditions established for β-O-4 lignin model compounds in a mixer mill. The oxidative transformations taking place in the OS-BWL samples monitored by comparing the 2D-HSQC NMR, IR, GPC, and GC-MS spectra for the OS-BWL samples before and after the transformations. Structural changes in OS-BWL by 2D-HSQC NMR studies. To compare structural changes in the OS-BWL and OS-BWL samples subjected to mechanochemical oxidative transformations, two-dimensional 1H-13C correlation (HSQC) NMR spectroscopy was used. To begin with, 100 mg of OS-BWL sample was loaded in a 10 mL WC milling jar together with a 10 mm in diameter WC ball. Then, the OS-BWL sample was milled for 90 min at 30 Hz. In the absence of the oxidative system, the HSQC spectrum of the resulting milled OS-BWL residue (MM-WC-90 min-no catalyst) showed negligible oxidative changes in its aliphatic (δC/δH 50−90/2.5−5.8) as well as in the aromatic regions (δC/δH 100−124/7.2−7.6) when compared with the unreacted OS-BWL sample (Figure 1a and 1b). These results highlighted the stability of the bulk biomacromolecule and of its individual β-O-4’ aryl ether linkages A as well as the resinol B and the phenylcoumaran C substructures under the milling conditions (90 min at 30 Hz). On the other hand, the negligible changes observed in the OS-


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BWL upon milling could have been a consequence of structural changes suffered by the OSBWL simple during its isolation process. Next, an identical experiment was performed, this time in the presence of HO–TEMPO (0.2 equiv), KBr (0.2 equiv) and Oxone® (1.5 equiv) (Figure 1c). After 90 min of milling, the analysis by 2D-NMR spectroscopy of the residual solids recovered after the filtration step, showed major changes in the structure of the OS-BWL (Figure 1c). For example, substantial differences were observed in the aliphatic regions of the spectrum, including diminished integrals values corresponding to the β-O-4’ aryl ether linkages and phenylcoumaran substructures. Additionally, the aromatic region of the oxidized OS-BWL spectra also accounted for 40% benzylic oxidation in the biomacromolecule, with increased integrals for the cross peaks corresponding to oxidized syringyl S’ and guaiacyl G’ units (Figure 1c and Table 3, entry 3). To enhance the oxidative effect, the reaction was milled for an additional 90 min (MM-WC-180 min). This change in the milling parameters indeed increased the degree of oxidation to 84% (Figure 1d and, Table 3, entry 4). Lengthening the milling time beyond 180 min did not lead to further oxidation of the OS-BWL sample. Similarly, subjecting the residual oxidized OS-BWL to an additional milling cycle (90 min; 30 Hz), in the presence of fresh HO–TEMPO/KBr/Oxone®, could not promote extra oxidative transformations in the original residual oxidized lignin.

Structural changes in OS-BWL by IR spectroscopy. Analysis of the untreated OS-BWL, the ball milled OS-BWL and the oxidized residual solid from OS-BWL was conducted by comparing the IR spectra of these samples (Supporting Information, Figure S4). Pleasingly, the corresponding IR spectrum of the oxidized OS-BWL


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(MM-WC-90 min) showed the appearance of a new carbonyl band (C=O) at 1721 cm–1. Such band was observed to be have higher intensity for the oxidized residual solid from OS-BWL for 180 min (MM-WC-180 min).43 Simultaneously, a relative decrease in the hydroxyl group region (3439 cm–1) was observed in the oxidized residual solid from OS-BWL. These structural changes observed by IR spectra showed a good correlation with the outcome of the 2D-HSQC analysis confirming the oxidative transformations that had taken place in the presence of spectra HO–TEMPO/KBr/Oxone® in the mixer mill. GPC analysis of the OS-BWL, milled OS-BWL and the oxidized residual solid from OSBWL. Samples of the untreated OS-BWL and ball milled OS-BWL were analyzed by GPC. Both exhibited similar average molecular weights and elution volumes, excluding major structural changes occurring in the structure of the biomacromolecule upon ball milling in the absence of oxidants (Figure 2 and Table 4). Subsequently, the residual solids recovered after the filtration of the mechanochemical oxidation reaction mixtures, were also analyzed by GPC (Figure 2). The average molecular weights (Mw) and the elution volumes of the oxidized residual solid from OSBWL were found to differ considerable from the sample before the reaction in the ball mill. Specifically, a progressive shift in the Mw of the OS-BWL samples towards lower values, when increasing of the milling time, was observed. Grinding a mixture of OS-BWL and HO– TEMPO/KBr/Oxone® for 90 min and 180 min led a 30% and 40% decrease in the Mw values of OS-BWL, respectively (Figure 2 and Table 4). Such results not only evidence the structural modification undergone by the lignin upon the oxidative mechanical treatment but also correlate well with the previously observed changes in the OS-BWL sample by NMR and IR spectroscopy.


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Analysis of the organic-soluble fraction by GC-MS. Intrigued by the shift in the molecular weight values (Mw) of the oxidized OS-BWL after the reaction in the mixer mill, the corresponding ether-extracted fractions of the experiments were subjected to GC-MS analysis (Figure 3). The analysis of the organic-soluble phase collected after the 180 min of milling highlighted the formation of 3,5-dimethoxyquinone as the major monomer (2.5 wt % with respect to the starting OS-BWL), along with 2-methoxybenzoquinone (0.5 wt %). Both monomers were formed possibly due to the oxidation of terminal phenolic groups present in the lignin sample. This observation is well in line with the product distribution obtained after the mechanochemical oxidation of the model compounds 1f and 1g. Scaled up oxidative transformations of OS-BWL in a mortar and pestle mill (MPM) and in a vibrating disc mill (DM). The positive results obtained for the oxidative transformations in the mixer mill (100 mg lignin scale), prompted us to investigate scaling-up alternatives for the mechanochemical oxidation reaction. Currently, mechanochemical transformations are often scaled up by using large-size planetary ball mills and attrition mills79 or extrusion techniques such as twin-screw extruders.80-81 Here, we decided to proceed in a different manner for performing a 100-fold scaled up experiment (10 g of lignin) and changed the milling device from the mixer mill to a 250 mL tungsten carbide LAARMANN LMM6-100 mortar and pestle mill (MPM). Grinding of an OSBWL sample with the oxidant mixture (HO–TEMPO/KBr/Oxone®) for 30 min at 120 rpm afforded a homogenous solid mixture. However, analysis of the organic soluble fraction and oxidized OS-BWL revealed negligible changes in the structure of the OS-BWL sample (Supporting Information, Figure S6 and Table S3). Challenged by this result, 10 g of OS-BWL


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was milled in the presence of the oxidant in a 250 mL tungsten carbide SIEBTECHNIK vibrating disc mill (DM). Considering the high-energy input due to both the WC milling media and the rotation speed (50 Hz), the reaction time was restricted to 30 min. After the mechanochemical reaction was stopped, 100 mg of the reaction mixture was weighed out and subjected to the standard workup procedure (for a flowchart see Scheme S1 in the Supporting Information). This time, the 2D-HSQC NMR analysis done on the oxidized OS-BWL revealed significant structural changes in the biomacromolecule (Figure 4). For example, a drastic modification in the aliphatic region for lignin (δC/δH 50−90/2.5−5.8) was observed, involving the disappearance of the cross peaks corresponding to β-O-4’ aryl ether and phenylcoumaran substructures. Furthermore, a comparative study of the integrals in the aromatic region of the spectra (δC/δH 100−124/7.2−7.6) afforded 24% oxidation of the OS-BWL sample obtained after the reaction in the vibrating disc mill (Table S3, entry 3). This moderate value could be reasoned by taking into consideration that the decrease in the integrals corresponding to the S and G units of the OS-BWL could only be directly correlated to the S’ and G’ values of a selectively oxidized OS-BWL, which did not undergo any depolymerization reactions. Moreover, the GPC analysis of the residual oxidized OS-BWL in the vibrating disc mill showed a drop of 48% in its Mw value compared to the untreated OS-BWL. Such reduction in the average molecular weight was comparable to the small-scale experiments carried out for 180 min in a mixer mill (Figure 5). Complementary, the organic-soluble fraction obtained after filtration of the reaction mixture with water and extraction with diethyl ether was further subjected to GC-MS analysis. Pleasingly, the GC-FID chromatogram of the ether extract displayed the presence of a range of monomeric products, confirming structural cleavage occurred in the biomacromolecule (Figure 6 and


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Supporting Information, Table S5). In addition to the previously identified quinone derivatives (Figure 3), the oxidative treatment of lignin in the vibrating disc mill led to the formation of phenolic compounds such as guaiacol and aldehydes (e.g., vanillin), among others. In total, the identified cleavage monomers accounted for 16 wt % of with respect to initial lignin sample. Additional milling experiments of lignin without the oxidants in the vibrating disc mill ruled out a direct mechanical cleavage of the biomacromolecule in the absence of the oxidative conditions (Supporting Information, Figure S8). This experimental observation is in agreement with previous DFT calculation studies, which revealed the increased susceptibility of oxidized lignin samples to undergo C–O bond cleavage reactions in comparison to untreated lignins due to the decrease in the C–O bond dissociation energies in the former ones.82-83 Analysis of the oxidized OS-BWL by 31P NMR spectroscopy. Quantitative 31P NMR studies were performed on the OS-BWL samples before and after the mechanochemical oxidative transformations to determine changes in the hydroxylic group content in the biomacromolecule (Figure 7). Quantification of the aliphatic hydroxyl, phenolic and carboxylic groups in the samples is summarized in the Table 5. Out of the four lignins analyzed, the OS-BWL samples oxidized for 180 min in the mixer mill and the residual oxidized OS-BWL from the vibrating disc mill accounted for the least remain -OH group content. Such decrease in the hydroxyl content in the oxidized residual OS-BWL confirmed the structural changes induced in the biomacromolecule by lignin oxidation and depolymerization reactions (Table 5).


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TGA of OS-BWL before and after the mechanochemical oxidation. To complement the characterization of the oxidized OS-BWL samples, both vacuum dried OSBWL residues from the reactions carried out in the mixer mill (30 Hz, 180 min) and in the vibrating disc mill (50 Hz, 30 min) were analyzed by TGA, and compared to the untreated OSBWL. Thermal stability of the oxidized OS-BWL residues can be correlated with the degree of structural condensation of the depolymerized residual samples. As depicted in the Figure 8, although all OS-BWL samples followed a similar thermal degradation tendency, the thermal weight loss for both oxidized OS-BWL samples started at lower temperature (110 °C), than the unreacted OS-BWL sample (165 °C). Furthermore the 20% weight loss (T20%) for the oxidized OS-BWL samples occurred at much lower temperatures of 273 °C and 247 °C, compared to the unreacted OS-BWL at 343 °C (Table 6). These changes in thermal stability of the samples could be associated with the oxidation reactions underwent by OS-BWL in the ball mill. The above analysis by GC-MS evidenced that the mechanochemical oxidation promoted the release monomers from the terminal phenolic group ends in the case of a mixer mill, as well as to initiate the inter-unit cleavage after the more energetic mechanical treatment in the vibrating disc mill. In both cases, this structure modification could have resulted in lowering of thermal stability of the residual biomacromolecule. Furthermore, the oxidized OS-BWL samples underwent pyrolysis more rapidly than the unreacted OS-BWL. The char content at 800 °C was found to be 36% for the OS-BWL oxidized in the vibrating disc mill and 20% for oxidized sample ground in the mixer mill, which demonstrated some degree of condensation in the oxidized OS-BWL sample during the pyrolysis process.


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CONCLUSION A route towards the oxidative transformations of lignin model compounds and lignin has been developed under mechanochemical conditions. The reaction of β-O-4 lignin model compounds with catalytic amounts of HO–TEMPO/KBr in the presence of Oxone® as terminal oxidant led to a selective benzylic oxidation in non-phenolic model compounds. On the other hand, milling phenolic model compounds under similar reaction conditions, resulted in the formation of cleavage products quinones (3) and guaiacol (4) in good yields. Moreover, the reaction scope was further expanded by employing an organosolv lignin sample extracted from beechwood. Applying the best reaction conditions to this lignin sample confirmed the benzylic alcohol oxidation, along with the cleavage of terminal phenolic groups as analyzed. Additionally, 100fold scale-up oxidation experiments proved possible by using a larger disc mill. Analysis of the oxidized OS-BWL by 2D-HSQC, IR, GPC, and 31P NMR spectroscopy evidenced the structural changes in the structure of lignin upon the oxidative milling treatment. Similarly, analysis of the organic-soluble fraction by GC-MS techniques revealed the formation of monomeric products along with the oxidation of the residual OS-BWL. From a more general perspective, the results of this investigation highlight one more time not only the versatility of mechanochemistry to facilitate the work with solid substrates and reagents of limited or different solubility. In addition to improving the mixing of the reaction partners, the mechanical treatment of the oxidized lignin resulted in the partial cleavage of the C–C/C–O bonds in the biomacromolecule. Along these lines, the differences in reactivity using various automated milling equipment (i.e., vibrating disc mill, mixer mill, mortar mill), can be rationalized taking into account the impact, pressure and friction experienced in these apparatuses (Table 7). Short milling times and a considerable extent of the oxidative depolymerization in lignin when treated in the vibrating disc mill clearly points


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at the importance of having highly energetic mechanochemical activation by friction, where the shearing forces applied in opposite directions by the disc could have been beneficial to cleavage the bonds of the oxidized OS-BWL.

With regard to the energy efficiency of the

mechanochemical reaction, it has been demonstrated that ball milling techniques have lower energy consumption compared to alternative approaches such as microwave irradiation.84 Importantly, this energy consumption was reported to decrease with upscaling of the reactions making mechanochemistry a reasonable strategy for biomass valorization.36 Further studies using molecular oxygen as an oxidant for the oxidation of lignin in the ball mill are currently underway in our group. ASSOCIATED CONTENT The Supporting Information is available free of charge on the ACS Publications website. Full procedures and analytical data for the synthesized lignin model compounds and products obtained after the oxidation reactions along with the associated spectra, and lignin characterization (2D HSQC NMR analysis) (PDF) AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]

[email protected]


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ORCID Saumya Dabral: 0000-0002-1860-1109 José G. Hernández: 0000-0001-9064-4456 Carsten Bolm: 0000-0001-9415-9917 Notes The authors declare no competing financial interest. ACKNOWLEDGMENT This work was supported by the European Union (Marie Curie ITN ‘SuBiCat’ PITN-GA-2013607044, S.D.) and by the Distinguished Professorship Program at RWTH Aachen University funded by the Excellence Initiative of the German federal and state governments. JGH thanks the RWTH Start-up grant StUpPD_221-16 funded by the Excellence Initiative of the German federal and state governments. We thank Davide De Marino (RWTH Aachen University) for the GPC measurements. Prof. Dr. Andrea Wanninger (University of Applied Sciences, Krefeld) is acknowledged for supplying organosolv beechwood lignin (OS-BWL). Dr. J. Langanke, Dr. C. Rosorius, M.Sc. A. Ernst (CAT Catalytic Center Aachen) are acknowledge for the access to TGA and for their technical assistance.

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Scheme 1. Chemoselective Oxidation of Lignin β -O-4 Model Compounds

Table 1. Mechanochemical Oxidation of Lignin Model Compound 1a in a Mixer Milla OH O

catalyst, KBr, Oxone

OMe 1a

O O

OMe

ball milling

OMe

OMe

2a

milling media ZrO2

milling conditions

conv [%]b

2a [%]b

1

catalyst TEMPO derivative TEMPO

25 Hz, 180 min

50

45

2

AcNH-TEMPO

ZrO2

25 Hz, 180 min

33

26

3

HO–TEMPO

ZrO2

25 Hz, 180 min

49

49

4

HO–TEMPO

ZrO2

30 Hz, 180 min

90

86

5c

HO–TEMPO

ZrO2

30 Hz, 180 min

79

79

6

HO–TEMPO

SS

30 Hz, 180 min

95

90

7

HO–TEMPO

WC

30 Hz, 180 min

99

96

8

HO–TEMPO

WC

30 Hz, 90 min

99

97(92)d

9

HO–TEMPO

WC

30 Hz, 60 min

85

82

entry

a

Reaction conditions: 1a (68.5 mg, 0.25 mmol, 1.0 equiv), catalyst (0.2 equiv), KBr (0.2 equiv), Oxone® (1.5 equiv) were ball milled in a mixer mill. b The conversion of 1a and the yield of 2a were determined by 1H NMR spectroscopy with 1,4-dinitrobenzene as internal standard. c Use of 1.0 equiv of Oxone®. d After column chromatography.


37


Page 38 of 50

Scheme 2. Oxidation of Lignin Model Compounds 1b and 1c in the Ball Mill using WC Milling Media; Yields after Column Chromatography OMe OMe

OH O

OMe HO–TEMPO, KBr, Oxone (0.2:0.2:1.5 equiv)

R

OMe

90 min, 25 Hz

O O

OMe

2b, (93%)

OMe

OMe

1b, R = H 1c, R = OMe

O O

OMe

OMe

OMe

2c, (87%)


38

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Table 2. Mechanochemical Oxidation of Lignin Model Compounds 1d-g in a Mixer Mill Using WC Milling Media OMe

OMe

OH HO–TEMPO (0.2 equiv) KBr (0.2 equiv) Oxone (1.5 equiv)

O HO

R

OH O

R R

90 min, 25 Hz

1d-g

2d

OH

+

+

O

OMe

O

O 4

3a, 3b

products [%]b entry

substrate

conv[%]a

ketone [%]b

quinone [%]c

guaiacol [%]c

1

>99

-

-

2

>99

-

-

3

>99

-

4

>99

-

a

Percentage values calculated based on the converted starting material 1d-g and determined by 1H NMR spectroscopy. b Yield after column chromatography. c Yield determined by GC calibrations with respect to n-octadecane as an internal standard.


39


Page 40 of 50

Figure 1. Analysis of the mechanochemical oxidation reaction of OS-BWL by 2D-HSQC NMR spectroscopy (left: aliphatic region; right: aromatic region in DMSO-d6). (a) Untreated OSBWL; (b) OS-BWL milled for 90 min at 30 Hz in the absence of oxidants; (c) residual oxidized OS-BWL after 90 min of milling at 30 Hz in the presence of (HO–TEMPO/KBr/Oxone®); (d)


40

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residual oxidized OS-BWL after 180 min of milling at 30 Hz in the presence of (HO– TEMPO/KBr/Oxone®). A: β-O-4’ aryl ether linkages with a free-OH at the α-carbon; B: resinol substructures formed by β−β’-, α-O-γ’-, and γ-O-α’- linkages; C: phenyl coumaran substructures formed by β-5’- and α-O-4’-linkages; S: syringyl units; S’: syringyl unit with oxidized benzylic position; G: guaiacyl units; G’: guaiacyl unit with oxidized benzylic position. Table 3. Extent of the Benzylic Oxidation of OS-BWL by Milling entry beechwood lignin ratio of areas integrated

degree of oxidation

[OS-BWL]

[oxidized/untreated]a

[%]

1

before reaction

0.06

6

2

MM-WC-90 min-no catalyst; 30 Hz

0.09

8

3

MM-WC-90 min; 30 Hz

0.66

40

4

MM-WC-180 min; 30 Hz

5.47

84

a

Ratios determined by comparing the integrals of the aromatic cross-peak characteristic of oxidized and untreated OS-BWL samples in the 2D-HSQC NMR.


41


Page 42 of 50

Figure 2. GPC measurements for OS-BWL (in 0.1M NaOH, RI response): before the reaction (black line); OS-BWL milled without catalyst for 90 min at 30 Hz in a mixer mill (green line), OS-BWL milled with oxidant (HO–TEMPO/KBr/Oxone®) for 90 min at 30 Hz in a mixer mill (blue line), OS-BWL milled with oxidant (HO–TEMPO/KBr/Oxone®) for 180 min at 30 Hz in a mixer mill (red line). Left: mass distribution with respect to sulfonated polystyrene standards calibration. Right: elugram.

Table 4. Changes in the Average Lignin Molecular Weight Before and After the Mechanochemical Oxidation Reactions (Reaction Conditions: MM = Mixer Mill, 30 Hz, 90180 min) Mw (Da) lignin

before reaction

MM-WC-90 min-blank

MM-WC-90 min

MM-WC-180 min

OS-BWL

3.131·103

3.126·103

2.164·103

1.855·103


42

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Figure 3. GC-FID trace of the organic-soluble fraction (diethyl ether filtration) after the mechanochemical oxidation of OS-BWL with HO–TEMPO/KBr/Oxone® in a WC jar at 30 Hz for 90 min in a mixer mill (MM). Quantification done using n-octadecane as an internal standard (SI). Identification of the major products was done by comparison of the major products with commercial samples.


43


Page 44 of 50

Figure 4. Analysis of the mechanochemical oxidation reaction of OS-BWL by 2D-HSQC NMR spectroscopy (left: aliphatic region; right: aromatic region in DMSO-d6). (a) Untreated OSBWL; (b) residual oxidized OS-BWL after 30 min of milling at 50 Hz in the presence of the oxidant (HO–TEMPO/KBr/Oxone®) in the disc mill; A: β-O-4’ aryl ether linkages with a freeOH at the α-carbon; B: resinol substructures formed by β−β’-, α-O-γ’-, and γ-O-α’- linkages; C: phenyl coumaran substructures formed by β-5’- and α-O-4’-linkages; S: syringyl units; S’: syringyl unit with oxidized benzylic position; G: guaiacyl units; G’: guaiacyl unit with oxidized benzylic position.


44

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Figure 5. GPC measurements for OS-BWL (in 0.1M NaOH, RI response): before the reaction (black line); OS-BWL milled with oxidant (HO–TEMPO/KBr/Oxone®) for 180 min at 30 Hz in a mixer mill (red line); OS-BWL milled with oxidant (HO–TEMPO/KBr/Oxone®) for 30 min in a vibrating disc mill at 50 Hz (blue line). Left: mass distribution with respect to sulfonated polystyrene standards calibration. Right: elugram.


45


Page 46 of 50

Figure 6. GC-FID trace for the ether soluble monomeric products obtained from the scaled-up oxidative transformation of OS-BWL in a vibrating disc mill (DM-WC-30 min). A detailed list of the products identified and quantified by GC-MS have been include in the supporting information (Table S5).


46

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Figure 7. Quantitative 31P NMR spectra of beechwood lignin samples using cyclohexanol as the internal standard (IS). Red: untreated OS-BWL; black: residual oxidized OS-BWL after 90 min of milling at 30 Hz in the mixer mill; green: residual oxidized OS-BWL after 180 min of milling at 30 Hz in the mixer mill; blue: residual oxidized OS-BWL after 30 min of milling at 50 Hz in the vibrating disc mill.


47


Table 5. OS-BWL Hydroxyl Groups Quantified by Internal Standard

31

Page 48 of 50

P NMR Using Cyclohexanol as an

OH (mmol·g-1)a OS-BWL

aliphatic OH

5-substituted + syringyl OH (S)

guaiacyl

p-hydroxyphenyl

carboxyl

OH (G)

OH (H)

OH

before reaction

1.36

2.47

0.86

0.17

-

MM-WC-90 min

0.97

0.86

0.72

-

0.56

MM-WC-180 min

0.24

0.55

0.03

-

0.47

DM-WC-30 min

0.16

0.24

0.01

-

0.39

a

Amounts displayed with respect to a known amount of cyclohexanol.


48

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Figure 8. Thermogravimetric analysis for untreated OS-BWL: before reaction, (black line), OSBWL oxidized in a mixer mill (MM-WC-180 min, red line) and OS-BWL oxidized in a vibrating disc mill (DM-WC-30 min, green line). Table 6. Degradation Temperature at 20 and 50% Fiber Degradation, Obtained by TGA of Untreated OS-BWL and Oxidized OS-BWL by Milling in the Mixer Mill and Vibrating Disc Mill OS-BWL T20% T50% Residue at 800 °C [%] before reaction

343.5

517.5

20.66

WC-MM-180 min

273.16

534.66

29.40

WC-DM-30 min

247.83

422.83

36.66

Tp% represents the onset decomposition temperature of 20 and 50% weight loss.


49


Page 50 of 50

Table 7. Principal Mechanochemical Activation Modes in the Milling Equipment Utilized for the Oxidative Transformations of OS-BWL Equipment

Impact

Pressure

Friction

Mixer mill

High

Low

Medium

Mortar mill

None

High

Low

Vibrating disc mill

None

Medium

High

GRAPHICAL ABSTRACT (TOC) A solvent-free mechanochemical oxidation of lignin provides a simple, effective a scalable alternative for the cleavage of this important biomacromolecule.


50

Mechanochemical Oxidation and Cleavage of Lignin Î²-O-4 Model

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