Added-Value Chemicals from Lignin Oxidation

molecules

Review Added-Value Chemicals from Lignin Oxidation

Carina A. Esteves Costa 1, Carlos A. Vega-Aguilar 1,2 and Alírio E. Rodrigues 1,*

1 Laboratory of Separation and Reaction Engineering—Laboratory of Catalysis and Materials (LSRE-LCM), Department of Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal; [email protected] (C.A.E.C.); [email protected] (C.A.V.-A.) 2 Centro de Investigação de Montanha−CIMO, Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal * Correspondence: [email protected]

Abstract: Lignin is the second most abundant component, next to cellulose, in lignocellulosic biomass. Large amounts of this polymer are produced annually in the pulp and paper industries as a co- product from the cooking process—most of it burned as fuel for energy. Strategies regarding lignin valorization have attracted significant attention over the recent decades due to lignin’s aromatic structure. Oxidative depolymerization allows converting lignin into added-value compounds, as phenolic monomers and/or dicarboxylic acids, which could be an excellent alternative to aromatic petrochemicals. However, the major challenge is to enhance the reactivity and selectivity of the lignin structure towards depolymerization and prevent condensation reactions. This review includes a comprehensive overview of the main contributions of lignin valorization through oxidative depolymerization to produce added-value compounds (vanillin and syringaldehyde) that have been developed over the recent decades in the LSRE group. An evaluation of the valuable products obtained from oxidation in an alkaline medium with oxygen of lignins and liquors from different sources and delignification processes is also provided. A review of C4 dicarboxylic acids obtained from lignin oxidation is also included, emphasizing catalytic conversion by O2 or H2O2 oxidation. Citation: Costa, C.A.E.; Vega-Aguilar, C.A.; Rodrigues, A.E. Keywords: biorefineries; lignocellulosic biomass; lignin; depolymerization; oxidation; phenolic Added-Value Chemicals from Lignin monomers; vanillin and syringaldehyde; dicarboxylic acids Oxidation. Molecules 2021, 26, 4602. https://doi.org/10.3390/ molecules26154602

Academic Editor: Mara G. Freire 1. Introduction Lignocellulosic biomass, including hardwood, softwood, and herbaceous crops, is an Received: 30 June 2021 abundant renewable resource mainly composed of cellulose, hemicellulose, and lignin [1,2]. Accepted: 27 July 2021 The typical lignin content may vary from 18 to 33% in softwoods, 15 to 30% in hardwoods, Published: 29 July 2021 and 5 to 30% in herbaceous crops [2,3]. However, most biorefineries are currently focused on the valorization of cellulose and hemicellulose, a so-called sugar-based platform. In this Publisher’s Note: MDPI stays neutral context, lignin is usually considered as a low-value residual product and has significant with regard to jurisdictional claims in potential as a renewable resource to produce bio-based materials, fuels, and valuable published maps and institutional affil- chemicals [4]. iations. In the literature, the main lignin valorization strategies are focused on the depolymerization of lignin into valuable compounds that could be used as platform molecules for industry. The oxidative depolymerization of lignin could be performed through different types of oxidants, and the characteristics of each oxidant determine their activity Copyright: © 2021 by the authors. and selectivity in the oxidation reaction [5]. Therefore, oxidant selection is based on the Licensee MDPI, Basel, Switzerland. properties that allow obtaining the maximum yields of the required products. Valuable This article is an open access article low molecular weight phenolic compounds, such as vanillin and syringaldehyde, are fre- distributed under the terms and quently obtained as the main depolymerization products from lignin oxidation in alkaline conditions of the Creative Commons medium using oxygen as an oxidant and are the focus of many research works. Vanillin Attribution (CC BY) license (https:// (V, 4-hydroxy-3-methoxybenzaldehyde) is the most commonly produced aroma compound creativecommons.org/licenses/by/ worldwide, with an annual production of 20,000 tons, 15% of which comes from lignin, 4.0/).

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and only 40 to 50 tons per year are produced from natural vanilla extract [6]. Around 85% of the world supply is produced from petro-based intermediates, especially guaiacol [7]. Vanillin is used as a flavoring and fragrance ingredient in the food or cosmetic industries. It is also an essential intermediate for synthesizing fine chemicals such as pharmaceuticals, e.g., L-DOPA (L-3,4-dihydroxyphenylalanine) [3,8]. Syringaldehyde (S, 4-hydroxy-3,5- dimethoxybenzaldehyde) is a valuable starting material for the chemical and pharmaceutical industries, being a precursor for the synthesis of 3,4,5-trimethoxybenzaldehyde [3,9]. This aromatic aldehyde is also a precursor for the food and cosmetic industry, and it has been synthesized from gallic acid, pyrogallol, and V itself [8,10]. In addition to the phenolic product conversion, dicarboxylic acids have also been obtained from the aromatic ring cleavage of lignin or its fragments using more potent oxidants and/or more severe reaction conditions [11]. Dicarboxylic acids such as muconic acid, maleic acid, succinic acid, and malonic acid are valuable platform chemicals and intermediates used in the polymer, pharmaceutical, and food industries [12–14]. C4 dicarboxylic acids were selected as one of the 12 building blocks for a future bio-based economy, receiving particular attention in recent years [15]. Commercial dicarboxylic acids are all produced from petroleum-based feedstocks or fermentation of edible biomass [12,14]. Usu- ally, severe oxidations have low selectivity, requiring further purification steps. However, their yields show a significant dependence on the type of lignin, extraction techniques, and operating conditions (e.g., pressure, temperature, lignin concentration, and stirring rate). Catalyst presence is also essential to achieve a high yield of a specific acid [12,16,17]. The development of a producing pathway of C4 dicarboxylic acids from lignin will arouse interest in chemical industries and biorefineries. This work provides a brief overview of lignin oxidation research, emphasizing the work performed by the research group in the Laboratory of Separation and Reaction Engineering (LSRE), University of Porto, Portugal. A strong emphasis is given to lignin oxidation under an alkaline medium with oxygen to produce aromatic compounds, such as aldehydes and acids, comparing different lignin sources, delignification processes, and oxidation technologies. It also includes recent advances on lignin depolymerization towards C4 dicarboxylic acids, mainly by catalytic oxidation.

2. Lignin: Valorization, Structure, and Classification Lignin, along with cellulose and hemicellulose, is one of the principal components of the lignocellulosic biomass, accounting for up to 40% of dry biomass weight. A biorefinery concept that integrates processes and technologies for biomass conversion demands an efficient utilization of all three components. Since lignin is the largest non-carbohydrate component in biomass and composed of aromatic compounds, its utilization can significantly enhance the cost competitiveness of the biomass biorefinery. For effective lignin applications, recent biorefinery and lignin valorization developments have tried to fractionate lignin selectively from other components with minimal structural modifications. A new strategy has emerged in the past few years, named the “lignin-first” approach [18,19]. This strategy considers lignin disassembly prior to carbohydrate valorization, through the com- bination of lignocellulose fractionation with integrated lignin depolymerization [18–21]. However, a lack of information still exists between the selective and efficient application of this approach in native lignin and the utilization of the obtained compounds in the production of value-added products, thereby influencing the overall economic feasibil- ity of lignocellulosic biorefineries. Consequently, most of the biorefinery schemes are focused on the utilization of easily convertible fractions, while lignin remains relatively under-valorized concerning its potential [22]. Nowadays, it has been estimated that 0.5–3.6 billion tons of lignin are produced annually in nature [23]. As the largest chemical process that utilizes plant biomass as raw material, the pulp and paper industry generates 60 million tons of lignin each year [23]. More than 98% of the generated lignin is burned as a source of energy, primarily in the paper and pulp industry, and only 2% of the produced lignin is utilized for commercial Molecules 2021, 26, x FOR PEER REVIEW 3 of 21

More than 98% of the generated lignin is burned as a source of energy, primarily in the paper and pulp industry, and only 2% of the produced lignin is utilized for commercial macromolecular applications (polyurethane foams, epoxy resins, dispersing or emulsi-

Molecules 2021, 26, 4602 fying agents, and as an additive for concrete and rubber) [24,25].3 ofApart 21 from its valorization as a polymer or material, lignin can undergo depolymerization reactions towards valuable low molecular weight compounds. However, lignin depolymerization and val- macromolecularorization remain applications a challenge. (polyurethane foams, epoxy resins, dispersing or emulsifying agents,The and as lack an additive of established for concrete processes and rubber) [that24,25 ].add Apart value from itsto valorizationlignin can as be a attributed mainly to polymer or material, lignin can undergo depolymerization reactions towards valuable low molecularits chemical weight compounds.recalcitrance However, and lignincomplex depolymerization and heterogeneous and valorization composition remain and structure. aAdding challenge. to this complexity, the lignin structure is highly dependent on the type of plant andThe species, lack of establishedthe delignification processes that process, add value an tod lignin the depolymerization can be attributed mainly method applied [2,26]. to its chemical recalcitrance and complex and heterogeneous composition and structure. AddingLignin to is this a complexity,complex thethree-dimensional lignin structure is highly amorphous dependent onand the highly type of plantbranched aromatic poly- andmer species, constituted the deligniﬁcation of methoxylated process, and the phenylprop depolymerizationane methodunits.applied Its crucial [2,26]. function in woody Ligninbiomass is a complex is to provide three-dimensional strength, amorphous rigidity, and and highly resistance branched aromatic to degradation polymer [2]. There are three constituted of methoxylated phenylpropane units. Its crucial function in woody biomass isprimary to provide monomers, strength, rigidity, syringyl and resistance (S), guaiacyl to degradation (G), and [2]. Therep-hydroxyphenyl are three pri- (H), derived from marythe monolignols monomers, syringyl p-coumaryl, (S), guaiacyl coniferyl, (G), and p-hydroxyphenyl and sinapyl (H), alcohols derived (Figure from the 1). Depending on the monolignolsbiomass source,p-coumaryl, ligninconiferyl, varies and in sinapyl the monomer alcohols (Figure composition.1). Depending Herbaceous on the crops contain all biomass source, lignin varies in the monomer composition. Herbaceous crops contain all threethree monomers monomers and are and relatively are relatively rich in H units. rich Gymnosperm in H units. lignins, Gymnosperm isolated from lignins, isolated from softwoods,softwoods, lack Slack units, S whileunits, angiosperm while angiosperm lignins, isolated lignins, from hardwoods, isolated are from rich inhardwoods, G are rich in G andand S. S.

FigureFigure 1. Sinapyl, 1. Sinapyl, coniferyl, coniferyl, and p-coumaryl and p-coumaryl alcohols, precursors alcohols, of S, G, precursors and H units, respectively.of S, G, and H units, respectively.

The lignin polymerization process leads to a variety of inter-unit linkages, including arylThe ether lignin bonds polymerization (β-O-4, α-O-4, 4-O-5) process and carbon-carbon leads to a linkagesvariety (5-5 of0 ,inter-unitβ-5, β-1, linkages, including βaryl–β)[25 ether,27]. The bonds frequency (β-O of-4, each α- typeO-4, of 4- linkageO-5) inand lignin’s carbon-carbon structure depends linkages on the (5-5′, β-5, β-1, β–β) relative[25,27]. contribution The frequency of each monomer of each to type the polymerization of linkage in process. lignin’s In native structure lignin, thedepends on the relative most abundant dilignol linkage is the β-O-4 type (structure A, Figure2), accounting for morecontribution than 50% of of the each interunit monomer linkages into lignin the structurepolymeri [8,zation28]. Therefore, process. the βIn-O -4native lignin, the most contentabundant of isolated dilignol lignins stronglylinkage depends is the on β- theO-4 separation type (structure method used A, and Figure the severity 2), accounting for more ofthan the applied 50% of process the conditions.interunit linkages in lignin structure [8,28]. Therefore, the β-O-4 content The existence of various interunit linkages, high propensity for the formation of condensedof isolated structures lignins when strongly thermochemically depends processed, on the poor separation product selectivity, method and easeused and the severity of ofthe use applied as a solid fuelprocess are the conditions. major barriers to the development of lignin-based bioreﬁning technologiesThe [existence28]. For these of reasons,various valorization interunit of technicallinkages, lignins high requires propensity detailed for the formation of insight into the structure and composition impact of the type of plant and species, the deligniﬁcationcondensed process,structures and the when isolation thermochemically method applied [2]. processed, poor product selectivity, and ease of use as a solid fuel are the major barriers to the development of lignin-based biorefining technologies [28]. For these reasons, valorization of technical lignins requires detailed insight into the structure and composition impact of the type of plant and species, the delignification process, and the isolation method applied [2].

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Figure 2. Main structural moieties in lignin structure: (A) β-O-4, (B) 5-5, (C) α-O-4, (D) β-5, (E) β-β, Figure(F) 4-O-5, 2. and Main (G) structuralβ-1. (Reprinted moieties from [22 in] Copyrightlignin structure: 2011, with ( permissionA) β-O-4, from (B) John5-5, Wiley(C) α-O-4, (D) β-5, (E) β-β, (andF) 4- Sons.)O-5, and (G) β-1. (Reprinted from [22] Copyright 2011, with permission from John Wiley and Sons.) The LSRE lignin research group established a classification tool for lignins based on the major structural characteristics of lignin that allows evaluating lignin relative to its viability as a sourceThe LSRE of added-value lignin lowresearch molecular group phenolic established compounds, a suchclassification as vanillin and/or tool for lignins based on thesyringaldehyde major structural [26,29,30]. characteristics Radar plots represent of anlignin effective that classification allows evaluating technique for lignin relative to its viabilitylignins and as are a asource useful approach of added-value for assessing low their molecular characteristics phenolic to maximize compounds, lignin such as vanillin valorization [26]. This classification tool combines the assessment of crucial structural and/orcharacteristics syringaldehyde such as H:G:S ratio, [26,29,30]. condensation, Radar and β -plotsO-4 content represent and allows an a qualitativeeffective classification tech- niqueprediction for of lignins the yield and expected are a by useful oxidative approach depolymerization for assessing of different their lignins characteristics under to maximize ligninsimilar reactionvalorization conditions. [26]. These This characteristics classification are the descriptorstool combines used to buildthe assessment the radar of crucial struc- plot for each studied lignin, reducing the unavoidable complexity of lignin structure to turalits key characteristics aspects while maintaining such as the H:G:S scientific ratio, basis condensation, of the data sets with and quantitative β-O-4 content and allows a qualitativeinformation [ 26prediction]. In the works of developedthe yield in expected LSRE, the radar by oxidative plot was built depolymerization to describe of different ligninsand compare under the potentialsimilar ofreaction different conditions. lignins to produce These vanillin characteristics and/or syringaldehyde are the descriptors used to by oxidative depolymerization with oxygen in an alkaline medium [26,29,30]. The key buildcharacteristics the radar selected plot are for the each contents studied in β-O -4lignin, structures, reducing non-condensed the unavoidable structures complexity of lignin(NCS), structure S and G units, to its and key the yield aspects of vanillin while and maintaining syringaldehyde obtainedthe scientific by nitrobenzene basis of the data sets with quantitativeoxidation (Figure information3). [26]. In the works developed in LSRE, the radar plot was built to The radar classification presented allows the screening of lignins resulting from in- describedustrial or and preindustrial compare processes the potential for their potentialof different as a source lignins of valuable to produce phenolic vanillin and/or syrin- galdehydecompounds. Considering by oxidative lignin’s depolymerization current availability in with the side oxygen streams ofin pulp an industriesalkaline medium [26,29,30]. Theand biorefineries,key characteristics this could be anselected important are approach the contents given lignin in exploitation β-O-4 structures, for high non-condensed added-value applications, improving the economic viability of the plant. structures (NCS), S and G units, and the yield of vanillin and syringaldehyde obtained by nitrobenzene oxidation (Figure 3).

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Figure 3.FigureRadar classification3. Radar classification for eucalyptus bole for lignins eucalyptus produced bole by different lignins processes produced (LKEgbole—lignin by different from processes industrial (LKEg- Kraft liquorbole—lignin of eucalyptus from bole; industrial LOEgbole—lignin Kraft produced liquor byof ethanol eucalyptus organosolv bole; process LOEgbole—lignin of eucalyptus bole; LAEgbole— produced by etha- lignin isolatednol organosolv by mild acidolysis process from of eucalyptus eucalyptus bole). bole; (Reprinted LAEgbole—lignin with permission from isolated [26]. Copyright by mild 2015 acidolysis American from eu- Chemical Society.) calyptus bole). (Reprinted with permission from [26]. Copyright 2015 American Chemical Society.) 3. Oxidative Depolymerization of Lignin The radar classificationConsidering the presented vast literature allows about ligninthe screening valorization, of the lignins major challenge resulting for from converting lignin into value-added compounds is the selective bond cleavage during the industrial or preindustrialdepolymerization processes process. While for native their lignin potential is highly reactiveas a source towards of depolymerization, valuable phenolic compounds. Consideringlignin streams isolatedlignin’s from current biorefinery avai processeslability suchin the as kraft,side sulfite,streams or organosolvof pulp industries and biorefineries,pulping are muchthis could more recalcitrant be an important as a consequence approach of the structural given condensationlignin exploitation and/or for degradation that takes place during the biorefinery process [4,26]. Structural degradation high added-valueinvolves applications, cleavage of labile improving ether and the ester economic linkages (mainly viability the β of-O -4the ether plant. bond) and formation of stable carbon-carbon linkages through condensation [25,28,31]. The cleavage 3. Oxidative Depolymerizationof carbon-carbon linkages of Lignin is the big challenge of lignin depolymerization. This type of linkage is significantly more resistant and most of them remain in lignin’s structure Consideringregardless the vast of the depolymerizationliterature about process, lign havingin valorization, a strong influence the onmajor lignin reactivity.challenge for converting ligninConsequently, into value-a productsdded derived compounds from lignin is depolymerization the selective bond strongly cleavage depend on during the the depolymerizationdepolymerization process. While method native itself but lignin also onis thehighly lignin reactive isolation processtowards and depolymeriza- the lignin source [2,23,26]. tion, lignin streamsVarious isolated thermal- from and biorefinery chemical-based processes lignin depolymerization such as kraft, processes sulfite, have or been organosolv pulping areproposed much and more applied recalcitrant in the literature as a [1 consequence,22,32–40]. Pyrolysis of the (thermolysis), structural gasification, condensation and/or degradationhydrogenolysis, that takes hydrolysis place under during supercritical the conditions,biorefinery and oxidationprocess reactions [4,26]. are Structural the major depolymerization methods studied (Figure4). degradation involves cleavage of labile ether and ester linkages (mainly the β-O-4 ether bond) and formation of stable carbon-carbon linkages through condensation [25,28,31]. The cleavage of carbon-carbon linkages is the big challenge of lignin depolymerization. This type of linkage is significantly more resistant and most of them remain in lignin’s structure regardless of the depolymerization process, having a strong influence on lignin reactivity. Consequently, products derived from lignin depolymerization strongly depend on the depolymerization method itself but also on the lignin isolation process and the lignin source [2,23,26]. Various thermal- and chemical-based lignin depolymerization processes have been proposed and applied in the literature [1,22,32–40]. Pyrolysis (thermolysis), gasification, hydrogenolysis, hydrolysis under supercritical conditions, and oxidation reactions are the major depolymerization methods studied (Figure 4).

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FigureFigure 4. Processes 4. Processes for thefor conversionthe conversion of lignin of lignin (the (the abscissa abscissa represents represents the typicalthe typical temperature temperature range range of the of ligninthe lignin conversion conversion processes) (reprinted with permission [36]. Copyright 2015 American Chemical Society). processes) (reprinted with permission [36]. Copyright 2015 American Chemical Society).

DespiteDespite all all the the depolymerizationdepolymerization methods, oxidation oxidation aroused aroused great great interest interest in inthe the fieldfield of of lignin lignin valorization valorization sincesince it represents an an effective effective method method for for added-value added-value com- com- poundpound production production from from differentdifferent sourcessources of li ligningnin [35,40–46]. [35,40–46]. Oxidative Oxidative conversion conversion gives gives a complex mixture of products highly dependent on the nature of the raw material and a complex mixture of products highly dependent on the nature of the raw material and the selected reaction conditions. Among them, it is possible to find oligomeric products, the selected reaction conditions. Among them, it is possible to find oligomeric products, phenolic, and non-phenolic compounds. In most studies, the authors focused their at- phenolic, and non-phenolic compounds. In most studies, the authors focused their atten- tention on producing valuable platform chemicals, including low molecular weight tion on producing valuable platform chemicals, including low molecular weight phenolic phenolic compounds, with high selectivity and yields. Moreover, the formation of di- compounds, with high selectivity and yields. Moreover, the formation of dicarboxylic acids carboxylic acids and quinone structures have also been commonly observed as products andfrom quinone the oxidative structures depolymerization have also been of commonly lignin or observedits fragments as products [42]. The from activity the and oxidative se- depolymerizationlectivity of the oxidative of lignin depolymerization or its fragments [ 42of ].lignin The activitydepend andon the selectivity type and of characteris- the oxidative depolymerizationtics of the oxidant of and lignin the depend severity on of the the type reaction and characteristicsconditions [5]. ofNitrobenzene, the oxidant andsome the severitymetal oxides of the reaction(copper (II) conditions oxide), and [5]. oxygen Nitrobenzene, (with or some without metal catalyst), oxides all (copper of them (II) in oxide), al- andkaline oxygen medium, (with orare without mild oxidants catalyst), that all preserve of them inlignin’s alkaline aromatic medium, ring are and mild produce oxidants thatmainly preserve aldehydes lignin’s [22,45]. aromatic Nitrobenzene ring and produce is an effective mainly aldehydesoxidant that [22 gives,45]. Nitrobenzenethe highest isproduct an effective yield. oxidant Still, it is that an givesexpensive the highestand harmful product chemical, yield. and Still, its it reduction is an expensive products and harmfulare difficult chemical, to separate and its from reduction the reaction products medium are difficult [47]. However, to separate nitrobenzene from the reactionis fre- mediumquently [ 47employed]. However, for nitrobenzenecharacterization is frequentlypurposes and employed as a reference for characterization in lignin oxidation purposes andsince as ait referenceallows one in ligninto estimate oxidation the maximum since it allows conversion one to estimateof lignin theinto maximum functionalized conver- sionphenolics of lignin [39,48,49]. into functionalized In this perspective, phenolics some [39 ,48authors,49]. Inhave this suggested perspective, that some the yields authors haveobtained suggested by NO that are the about yields 40–50% obtained of the by yield NO areof oxidation about 40–50% with ofO2 the in yieldan alkaline of oxidation me- withdium O 2[39,50].in an alkalineThe use mediumof oxygen [39 in, 50lignin]. The depolymerization use of oxygen inis ligninadvantageous depolymerization when eco- is advantageousnomic and environmental when economic questions and environmentalare considered [48]. questions This is arean inexpensive considered and [48]. green This is anoxidant, inexpensive which and preserves green oxidant,the lignin which aromatic preserves rings theduring lignin the aromatic oxidation rings reaction during and the oxidationpresents reactiona high efficiency and presents per weight a high of efficiency oxidant [8,51]. per weight of oxidant [8,51]. LigninLignin oxidation oxidation usingusing oxygenoxygen has been extensively extensively studied studied in in the the recent recent decades decades concerningconcerning depolymerization depolymerization ofof condensedcondensed lignin lignin substrates substrates such such as as lignosulfonates lignosulfonates and and kraftkraft lignins. lignins. Oxygen Oxygen delignification delignification proceedsproceeds predominantlypredominantly through a radical chemis- chemistry mechanismtry mechanism that that plays plays anessential an essential role role in producingin producing functionalized functionalized aromatics aromatics (Figure(Figure5 ) . Since5). Since oxygen oxygen is a is weak a weak oxidizing oxidizing agent agent in in its its normalnormal state, the the reaction reaction requires requires basic basic conditionsconditions to to ionize ionize freefree phenolicphenolic hydroxyl groups groups in in lignin lignin units units [1,42]. [1,42 ].Consequently, Consequently, whenwhen aromatic aromatic products products areare targeted,targeted, the oxidation is is mainly mainly performed performed aerobically aerobically in in aqueous alkaline (usually NaOH) medium since this enables the selectivity production of phenolic aldehydes such as vanillin and syringaldehyde [40].

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Molecules 2021, 26, 4602 7 of 21 aqueous alkaline (usually NaOH) medium since this enables the selectivity production of phenolic aldehydes such as vanillin and syringaldehyde [40].

FigureFigure 5. 5. OxygenOxygen oxidation oxidation of lignin mechanisms: ((AA)) conjugatedconjugated side-chainside-chain oxidation, oxidation, ( B(B) aromatic) aromatic ring ring cleavage, cleavage, and and (C) oxidative condensation. (Reprinted from [42] Copyright 2015, with permission from John Wiley and Sons.) (C) oxidative condensation. (Reprinted from [42] Copyright 2015, with permission from John Wiley and Sons.)

3.1.3.1. Phenolic Phenolic Compounds Compounds from LigninLignin OxidationOxidation TheThe history history behind utilizingutilizing ligninlignin asas aa source source of of valuable valuable phenolic phenolic compounds compounds can can bebe dated dated back back to the mid-twentieth centurycentury asas part part of of the the paper paper industry’s industry’s search search for for new new valorizationvalorization pathways for ligninlignin [[52,53].52,53]. However,However, itit is is well well known known that that the the structural structural transformationstransformations and chemical treatmentstreatments suffered suffered by by lignin lignin have have a a considerable considerable influence influence onon the the formation of phenolicphenolic compoundscompounds sincesince modifiedmodified lignin lignin has has less less availability availability of of phenolicphenolic precursors in itsits structure.structure. AlkalineAlkaline oxidationoxidation converts converts lignin lignin into into a complexa complex mixturemixture of of products that couldcould bebe phenolicphenolic monomers, monomers, dimers, dimers, and and oligomers. oligomers. As As already already stated, the selectivity and efficiency of oxidative depolymerization depend strongly on stated, the selectivity and efficiency of oxidative depolymerization depend strongly on processing conditions and lignin origin. Alkaline oxidation of softwood lignins produces processing conditions and lignin origin. Alkaline oxidation of softwood lignins produces mainly vanillin and vanillic acid, while syringaldehyde and syringic acid are obtained mainly vanillin and vanillic acid, while syringaldehyde and syringic acid are obtained from hardwood lignins. A literature overview of some representative works about alkaline from hardwood lignins. A literature overview of some representative works about alka- oxidations of lignin using oxygen shows values in the range of 4–12% w/w lignin for linevanillin oxidations and 5–20% of ligninw/w usinglignin oxygen for syringaldehyde, shows values depending in the range on of the 4–12% origin, w/ type,w lignin and for vanillinprocessing and of 5–20% each lignin w/w [lignin8,22,39 for,43 ,44syringaldehyde,,48,49,54]. depending on the origin, type, and processingLignin of valorization each lignin is [8,22,39,43,44,48,49,54]. a solid research field, of more than 30 years, at the Laboratory of SeparationLignin valorization and Reaction is a solid Engineering research (LSRE) field, of (Figure more6 than). The 30 LSREyears, groupat the hasLaboratory vast ofexperience Separation in studyingand Reaction alkaline Engineering oxidation (LSRE) using oxygen (Figure to 6). produce The LSRE added-value group has phenolic vast ex- periencecompounds in studying from lignin, alkaline namely oxidation vanillin using and syringaldehyde.oxygen to produce The added-value potential of severalphenolic compoundslignins and liquorsfrom lignin, from differentnamely vanillin sources ofan biomassd syringaldehyde. and delignification The potential processes of several was ligninsevaluated and through liquorsbatch from [26different,39,41,43 sources,44,48,55 of] and/orbiomass continuous and delignification experiments processes [56–58]. was evaluatedThe batch through oxidation batch experiments[26,39,41,43,44,48,55] were performed and/or in continuous a jacketed reactorexperiments with a [56–58]. capacity of 1The L with batch initial oxidation temperature experiments and pressure were performed control at in the a beginningjacketed reactor of the with reaction. a ca- pacityDuring of the 1 oxidation,L with initial the system’stemperature total pressureand pressure was kept control constant at the through beginning the continuous of the reaction.feeding During of oxygen the oxidation, to the reactor, the and system’s the reaction total mixturepressure (solution was kept of ligninconstant in NaOH through with the continuousa selected concentration) feeding of oxygen was maintained to the reactor, under and stirring. the reaction The experimental mixture (solution setup used of lignin for inbatch NaOH oxidation with a experimentsselected concentration) at LSRE is presented was maintained in Figure under7. stirring. The experimental setup used for batch oxidation experiments at LSRE is presented in Figure 7.

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Figure 6. Research in lignin valorization started by Professor Alírio Rodrigues at LSRE (* thesis supervised by Prof. M. Filomena Barreiro (IPB, Portugal)). (a) Álvaro Luiz Figure 6. ResearchMathias in lignin(UF Paraná, valorization Brazil), “Production started by Professorof vanillin from Alírio kraft Rodrigues lignin: Kinetics at LSRE and (* processes”, thesis supervised 1993; (b) Daniel by Prof. Araújo, M. Filomena “Production Barreiro of vanillin (IPB, from Portugal)). lignin present (a) Á inlvaro the Luiz Mathias (UF Paraná, Brazil),Kraft black “Production liquor of ofthe vanillin pulp and from paper kraft industry”, lignin: 2008; Kinetics (c) Miriam and processes”,Zabkova (Slovakia), 1993; (b “Clean) Daniel technologies Araújo, “Production for the purification of vanillin of wastewaters: from lignin adsorptive present parametric in the Kraft black liquor of the pulp andpumping”, paper industry”, 2007; (d) 2008;Carolina (c) Cateto, Miriam “Lignin-based Zabkova (Slovakia), polyurethanes: “Clean synt technologieshesis, characterization for the purification and applications”, of wastewaters: 2008; (e) Carina adsorptive Costa, “Vanillin parametric and pumping”,syringaldehyde 2007; (d) Carolina Cateto, “Lignin-basedfrom side polyurethanes: streams of pulp synthesis, & paper in characterizationdustries and biorefineries”, and applications”, 2017; (f) Inês 2008; Mota, (e) “Fractionation Carina Costa, of “Vanillin syringaldehyde and syringaldehyde and vanillin from from oxidation side streams of lignin”, of pulp 2017; & (g paper) industries Elson Gomes, “Development of a continuous process for the production of vanillin and syringaldehyde from kraft black liquor”, 2019; (h) João Pinto (IPB), “Development and biorefineries”,of sustainable 2017; (f) polymer Inês Mota, solutions”, “Fractionation 2019; (i) Carlos of syringaldehyde Alberto Vega-Aguilar and vanillin (Costa from Rica), oxidation “Dicarboxylic of lignin”, acids from 2017; lignin”, (g) Elson 2021; Gomes,(j) Filipa “DevelopmentCasimiro (IPB), “Studies of a continuous on lignin process for the production of vanillinoxidation and and syringaldehyde degradation of phenolic from kraft products”, black liquor”,2022; (k) 2019;Eduarda (h) Baptista, João Pinto “Ultrafiltração (IPB), “Development de extrato de of casca sustainable de Eucalyptus polymer globulus solutions”, para recuperação 2019; (i) Carlos de compostos Alberto Vega-Aguilar (Costa Rica), “Dicarboxylicpolifenólicos”, acids 2013; from (l) CYTED lignin”, IV.2—“Transformación 2021; (j) Filipa Casimiro de lignina (IPB), “Studies en produtos on lignin de alto oxidation valor agregado”; and degradation (m) POCTI/1999/EQU/33198—“Development of phenolic products”, 2022; (k) Eduarda of an integrated Baptista, “Ultrafiltração de extrato de cascaprocess de for Eucalyptus the production globulus of vanillin para from recuperaç the blackão deliquor compostos of the pulp polifen industry”;ólicos”, (n) POCI/EQU/61738/2004—“Purification 2013; (l) CYTED IV.2—“Transformaci of vanillinón de ligninafrom theen lignin produtos oxidation de broth”, alto valor agregado”; 2007; (o) BIIPP (SI IDT—11551/2010)—“Biorefinaria Integrada na Indústria da Pasta e Papel”; (p) BIOBLOCKS—“Concepção de produtos de base biológica como (m) POCTI/1999/EQU/33198—“Developmentprecursores para a bioindústria de of síntese an integrated química processe de biomateriais for the production a partir de of fontes vanillin lenhocelulósicas”; from the black ( liquorq) FEUP/RJR/2014/01—Production of the pulp industry”; (n) POCI/EQU/61738/2004—“Purification of Vanillin from tobacco of vanillin frombiomass the lignin lignin oxidation (R. J. Reynolds broth”, Tobacco 2007; ( oCompany,) BIIPP (SI USA); IDT—11551/2010)—“Biorefinaria (r) Collaboration with SAPPI—“Lignosul Integradaphonate’s na Ind úcharacterization”,stria da Pasta e 2020. Papel”; (p) BIOBLOCKS—“Concepção de produtos de base biológica como precursores para a bioindústria de síntese química e de biomateriais a partir de fontes lenhocelulósicas”; (q) FEUP/RJR/2014/01—Production of Vanillin from tobacco biomass lignin (R. J. Reynolds Tobacco Company, USA); (r) Collaboration with SAPPI—“Lignosulphonate’s characterization”, 2020.

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Figure 7. Experimental setup used in batch oxidation experiments at LSRE. (Reprinted with per- Figure 7. Experimental setup used in batch oxidation experiments at LSRE. (Reprinted with permis- mission from [59]. Copyright 2019 American Chemical Society.) sion from [59]. Copyright 2019 American Chemical Society.)

TheThe effect effect of of one one or or several several process process parameters parameters on on lignin lignin oxidative oxidative depolymerization depolymerization performedperformed through through batch batch experiments experiments have have been b intensivelyeen intensively investigated investigated with the with primary the pri- objectivemary objective of achieving of achieving the ideal conditionsthe ideal conditions for obtaining for theobtaining maximum the conversionmaximum conversion of lignin whileof avoidinglignin while the oxidation avoiding of thethe phenolic oxidation monomers of theproduced phenolic [8 ,41monomers,43,47,48, 54produced,55,59]. The[8,41,43,47,48,54,55,59]. origin, composition, The and origin, processing composition, of lignin and (pulping processing process, of lignin isolation (pulping method, pro- pretreatment,cess, isolation etc.), method, the oxygen pretreatment, partial pressure, etc.), the theoxygen initial partial temperature, pressure, and the the initial lignin tem- andperature, sodium and hydroxide the lignin concentration and sodium in hydroxide the reaction concentration solution were in studied,the reaction and solution its ef- fectwere on thestudied, selectivity and its and effect efficiency on the of selectivity alkaline oxidativeand efficiency depolymerization of alkaline oxidative process wasdepol- evaluatedymerization [8,48 ,process51,56,59 ,was60]. Itevaluated was found [8,48,51,56,59,60]. that a high partial It was pressure found of that oxygen a high reduces partial reactionpressure time of butoxygen leads reduces to an increased reaction time rate but of vanillin leads to oxidation. an increased Increasing rate of vanillin the oxygen oxida- pressuretion. Increasing accelerated the both oxygen product pressure formation accelerated and degradation, both product and formation therefore and shortened degrada- thetion, time and needed therefore to reach shortened the maximum the time product need yieldsed to [reach43,61]. the In similarmaximum works, product Schutyser yields and[43,61]. coworkers In similar found works, that lignin Schutyser oxidation and cowo underrkers an inertfound atmosphere that lignin producedoxidation mainlyunder an oligomericinert atmosphere products, produced while thesame mainly reaction oligomeric under oxygenproducts, primarily while the generated same reaction monomeric under productsoxygen [primarily46]. Concerning generated the monomeric effect of pH products of the mixture, [46]. Concerning it was concluded the effect that of duringpH of the themixture, lignin oxidation it was concluded process, thethat yield during of vanillinthe lignin decreased oxidation when process, the pH the value yield beganof vanillin to decrease.decreased Moreover, when the there pH was value a smaller began vanillinto decrea degradationse. Moreover, for strongthere was alkaline a smaller conditions vanillin thatdegradation increased significantlyfor strong alkali whenne pH conditions was smaller that than increase 11.5d [41 significantly,47]. Consequently, when pH high was alkalismaller concentrations than 11.5 [41,47]. (pH > 12) Consequently, are needed to high reduce alkali vanillin concentrations degradation. (pH For > temperature,12) are needed it wasto reduce found vanillin that an increasedegradation. in this For reaction temperature, condition it was can found shorten that the an reaction increase time in this but, re- onaction the other condition hand, can results shorten in faster the reaction degradation timeof but, the on aldehydes the other produced. hand, results However, in faster ◦ Pacekdegradation and coworkers of the verifiedaldehydes that produced. even if usual However, reaction Pacek temperatures and coworkers were 150–170 verified C,that theeven alkaline if usual hydrolysis reaction reaction, temperatures caused were by the 150–170 high temperature°C, the alkaline and hydrolysis strongly alkaline reaction, ◦ conditions,caused by started the high at around temperature 120 C[ and62]. strongly These authors alkaline also conditions, argued that started hydrolysis at around started 120 ◦ at°C just [62]. above These 100 authorsC, and also it produced argued that not onlyhydrolysis vanillin started but also at just vanillic above acid, 100 traces °C, and of it acetovanillone,produced not and only other vanillin compounds. but also Finally, vanillic the acid, lignin traces itself isof aacetovanillone, variable with a hugeand other in- fluencecompounds. on the final Finally, yields the of lignin oxidation itself products. is a variable Considering with a huge lignin influence content on in the the final reaction yields medium,of oxidation Fargues products. et al. found Considering that the vanillin lignin content yield only in the increased reaction for medium, lignin concentration Fargues et al. offound up to 60 that g/L, the decreasing vanillin yield for higher only increased values [48 for]. Moreover, lignin concentration a lignin with of a up low to molecular 60 g/L, de- weightcreasing and for a less higher condensed values structure[48]. Moreover, tends to a givelignin better with oxidation a low molecular results, theweight presence and a of less residualcondensed sugars structure is highly tends unfavorable, to give better and the oxidatio fewern structural results, the transformations presence of residual or chemical sugars treatmentsis highly ligninunfavorable, suffers, theand better the fewer the reactivity structural toward transformations oxidation andor chemical consequently treatments the betterlignin the suffers, yields ofthe phenolic better the compounds reactivity obtainedtoward oxidation [39,45,47]. and consequently the better the yieldsUsing of thephenolic experimental compounds results obtained from evaluating[39,45,47]. the main reaction conditions’ effect in the alkalineUsing the oxidation experimental with oxygen results infrom a batch evaluating reactor, the the main authors reaction developed conditions’ a kinetic effect in the alkaline oxidation with oxygen in a batch reactor, the authors developed a kinetic

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study ofof vanillinvanillin production production [ 48[48,56,59,61].,56,59,61]. The The objective objective was was to to measure measure the the reaction reaction orders or- regardingders regarding lignin, lignin, oxygen, oxygen, and and vanillin vanillin species, spec asies, well as well as the as influencethe influence of temperature of tempera- onture the on kinetic the kinetic rate constantsrate constants to discuss to discu thess overall the overall process process of lignin of lignin oxidation oxidation [48]. [48]. The mathematicalThe mathematical model model proposed proposed by the by authors the authors showed showed to be able to be to predictable to thepredict behavior the be- of vanillinhavior of oxidation vanillin foroxidation the different for the operating different conditions operating tested.conditions Since tested. the vanillin Since producedthe vanil- bylin ligninproduced oxidation by lignin is also oxidation oxidized is also and dependsoxidized onand the depends pH and on the the temperature pH and the of tem- the solution,perature theof the influence solution, of the these influence two parameters of these ontwo the parameters kinetics of on vanillin the kinetics degradation of vanillin had beendegradation studied had on vanillin been studied alone. Theon vanillin validation alone. of a The kinetic validation model for of vanillina kinetic degradation model for separatelyvanillin degradation confirmed separately that its degradation confirmed canthat beits welldegradation predicted can in be the well lignin predicted oxidation in experimentsthe lignin oxidation [56]. More experiments recently, the [56]. kinetic More model recently, developed the kinetic for vanillin model degradation developed was for improvedvanillin degradation by evaluating was theimproved degradation by evaluating of all the the main degradation phenolic monomers of all the main produced phe- fromnolic ligninmonomers oxidation: produced vanillin, from vanillic lignin acid, oxidatio acetovanillone,n: vanillin, syringaldehyde,vanillic acid, acetovanillone, syringic acid, andsyringaldehyde, acetosyringone syringic [59]. Theacid, kinetic and acetosyringone study considering [59]. theseThe kinetic individual study products considering is of greatthese interestindividual since; products during is oxidation, of great interest their formation since; during can be oxidation, simultaneously their formation accompanied can bybe simultaneously their degradation accompanied process that by is their dependent degradation on the process applied that oxidation is dependent conditions. on the In Figureapplied8 ,oxidation the effect conditions. of initial concentration, In Figure 8, the oxygen effect partial of initial pressure, concentration, and temperature oxygen par- on thetial degradationpressure, and as temperature a function of on reaction the degradation time for vanillin as a function (V) and of syringaldehyde reaction time for (Sy) van- is shownillin (V) [ 59and]. syringaldehyde (Sy) is shown [59].

Figure 8. Effect of initial concentration, oxygen partial pressure, and temperature on the degradation as a function of reaction time for V and Sy. The lines represent the ﬁtted kinetic model (experimental conditions: [NaOH] = 80 g/L; pt = 9.8 bar) (reprinted with permission from [59]. Copyright 2019 American Chemical Society).

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All the performed studies allowed us to confirm that a trade-off between enhancing the phenolics conversion and minimizing oxidation is achieved for a temperature of around 120 ◦C, oxygen partial pressure around 3 bar, and lignin concentration of 60 g/L, prepared in a solution of 2 N NaOH [2,8,43,48]. Having these conditions as a starting point for the oxidative depolymerization of lignin, the LSRE team studied the potential of a wide variety of lignins from different origins and delignification processes. The yields of vanillin and syringaldehyde achieved for each lignin by nitrobenzene oxidation and alkaline oxidation with oxygen in the batch reactor are summarized in Table1. In addition to vanillin and syringaldehyde, other phenolics such as vanillic acid, acetovanillone, syringic acid, and acetosyringone were also identified in minor quantities; their occurrence also has a significant role in the study of reaction efficiency. Moreover, the presented data allow the evaluation of the benefit of lignin source and isolation on product yields.

Table 1. Yields of vanillin and syringaldehyde obtained by nitrobenzene oxidation (NO) and alkaline

oxidation using O2 of lignins studied at LSRE (experimental conditions of alkaline oxidation using ◦ O2 and performed in reactor batch: Ti = 120 C; [lignin] = 60 g/L; [NaOH] = 80 g/L; pO2 = 3 bar; pt = 9.8 bar).

Vanillin, % w/w lignin * Syringaldehyde, % w/w lignin * NO ** Alkaline Oxid. NO ** Alkaline Oxid. LInAT 1,2 9.3 3.4 - - LWest 1 12.1 4.4 - - LBoostS 1 11.1 3.1 - - LOrgs 1 4.8 1.2 13.2 2.5 KL 3 2.9 0.73 12.5 1.9 KLlig 3 3.4 1.2 13.6 2.8 EKL 3 2.2 0.71 9.2 1.4 EKLlig 3 2.5 0.82 9.5 2.0 HTEKL 3 3.4 0.54 9.8 1.5 HTEKLlig 3 2.6 0.94 9.8 2.0 SL 3 2.5 1.5 11.3 3.3 4 LTobObut 2.8 0.74 2.5 0.34 4 LTobOethan 7.2 1.2 4.8 0.94 LCelbi 1.7 0.81 9.5 2.1 * Values reported on dry weight and corrected to non-volatile solid weight after deducting ashes and carbohydrates; ** NO conditions detailed in the literature [63]. 1 [39]; 2 [56]; 3 [44]; 4 [26]. (LInAT—lignin Indulin AT, industrial pine kraft lignin from Westvăjco; LWest—kraft lignin from southern pine (Pinus spp.), supplied by Westvăjco; LBoostS—kraft lignin from softwood (mainly spruce) isolated by LignoBoost process; LOrgs—lignin extracted from beech wood by organosolv process using aqueous ethanol, supplied by Fraunhofer (Germany); KL, EKL, and HTEKL—Eucalyptus globulus kraft liquor collected at different stages of a Portuguese bleached kraft pulp plant: at the outlet of kraft digester (KL), after the evaporation stage (EKL), and after heat treatment just before the recovery furnace (HTEKL); KLlig, EKLlig, and HTEKLlig—lignins isolated from kraft liquors KL, EKL, and HTEKL, respectively; SL—industrial spent liquor from magnesium-based acidic sulﬁte pulping of E. globulus collected after the evaporation step in a Portuguese sulﬁte pulp mill; LTobObut and LTobOethan—lignin from tobacco stalks produced by organosolv process using butanol and ethanol, respectively; LCelbi—kraft lignin from hardwood (eucalyptus), supplied by Celbi.).

Most of the works focused on lignin oxidation have been performed in batch mode. However, from an industrial point of view, the continuous process of lignin oxidation presents more advantages due to the large volumes of liquor generated, the easier control of the process, and the lower overall investments and operating costs [55]. Araújo [56] built an experimental pilot setup to promote lignin oxidation in a continuous operating mode. The schematic diagram of the pilot installation is shown in Figure9. The bubble column reactor was made in 316L stainless steel with 8 L capacity, and the gas–liquid reaction takes place in the cylindrical body of the reactor. It has a 10 cm internal diameter and 70 cm height and is ﬁlled with three modules of Mellapak 750.Y structured packing (Sulzer Chemtech, Switzerland) that enhance the system’s overall mass transfer performance. Molecules 2021, 26, x FOR PEER REVIEW 12 of 21

Molecules 2021, 26, 4602 12 of 21 (Sulzer Chemtech, Switzerland) that enhance the system’s overall mass transfer performance.

FigureFigure 9. Schematic 9. Schematic diagram diagram of the of the pilot pilot setup setup for thefor continuousthe continuous production production of phenolic of phenolic monomers mono- frommers lignin: from (1) lignin: safety (1) valve; safety (2) valve; on–off (2) valve; on–off (3) valv electromagnetice; (3) electromagnetic valve; (4) valve; needle (4) valve;needle (5) valve; safety (5) valve;safety (6) valve; three-way (6) three-way valve; (7) valve; mass ﬂow(7) mass controller; flow controller; PT—pressure PT—pressure transducer; transducer; TT—thermocouple. (ReprintedTT—thermocouple. from [55] Copyright (Reprinted 2009, from with [55] permission Copyright from 2009, Elsevier.) with permission from Elsevier.)

However,However, oxidation oxidation in in the the continuous continuous reactor reactor showedshowed that the the lignin lignin conversion conversion was wassubstantially substantially lower lower than than that that obtained forfor thethe batchbatch process process [ 56[56–58].–58]. To To improve improve the the performanceperformance of theof the continuous continuous reactor reactor and and reach reac theh the production production yields yields obtained obtained in bathin bath mode,mode, some some studies studies focused focused on the on inﬂuence the influenc of the maine of reactionthe main were reaction performed were [55 performed,56,60]. The[55,56,60]. results showed The results that the showed oxygen that mass the transfer oxyge fromn mass the gastransfer phase from to the the reaction gas phase medium to the of sodiumreaction hydroxidemedium of and sodium lignin hydroxide was the limiting and lignin step was to vanillin the limiting formation, step to and vanillin the use for- of puremation, oxygen and the in the use gas of pure feed wasoxygen considered. in the gas In feed this was case, considered. the liquid residenceIn this case, time the was liquid decreasedresidence as time the oxygen was decreased mass transfer as the rate oxygen increased mass to transfer avoid excessiverate increased vanillin to oxidation.avoid exces- A valuesive vanillin of vanillin oxidation. yield, in A thevalue exit of stream, vanillin of yield, approximately in the exit 85%stream, of the of maximumapproximately value 85% obtainedof the inmaximum the batch value reactor obtained was achieved in the considering batch reactor the improvementswas achieved inconsidering the continuous the im- reactionprovements [56,60]. in the continuous reaction [56,60].

3.2.3.2. Dicarboxylic Dicarboxylic Acids Acids from from Lignin Lignin Oxidation Oxidation A harshA harsh depolymerization depolymerization causes causes cleavage cleavage of of the the remaining remaining bonds bonds that that were were not not broken in mild depolymerization [11]. When the aromatic ring is cleaved (Figure 10), C broken in mild depolymerization [11]. When the aromatic ring is cleaved (Figure 10),6 C6 acidsacids are are obtained obtained (mainly (mainly muconic muconic acid), acid), which which are quickly are quickly degraded degraded to lower to lower carbon- car- content acids (C -C acids) [12]. The products can be completely mineralized to CO and bon-content acids2 4 (C2-C4 acids) [12]. The products can be completely mineralized2 to CO2 H O under very harsh conditions. Even though C acids have important industrial uses, 2and H2O under very harsh conditions. Even though6 C6 acids have important industrial they are very unstable and are swiftly converted to C4 dicarboxylic acids (C4-DCA), which uses, they are very unstable and are swiftly converted to C4 dicarboxylic acids (C4-DCA), are relatively stable and can be easily separated at the end of the reaction. which are relatively stable and can be easily separated at the end of the reaction.

Molecules 2021, 26, 4602 13 of 21 Molecules 2021, 26, x FOR PEER REVIEW 13 of 21

Figure 10. Oxidation of lignin through ring-opening reactions to yield C4 dicarboxylic acids. (Re- Figure 10. Oxidation of lignin through ring-opening reactions to yield C4 dicarboxylic acids. (Reprintedprinted from from [64] [64 Copyright] Copyright 2018, 2018, wi withth permission permission from from Elsevier.) Elsevier.)

TheThe acids acids with with a highera higher prevalence prevalence in lignin in lignin oxidation oxidation are succinic are succinic (SA), malic (SA), (MAL), malic and(MAL), maleic and acids maleic (MA), acids with (MA), small amountswith small of fumaricamounts (FA) of fumaric and tartaric (FA) (TA) and acids. tartaric Most (TA) of theseacids. acids Most are of currently these acids used are in currently food, pharmaceutical used in food,, and pharmaceutical, polymer industries, and polymer as well asin- chemicaldustries, precursors as well foras 1,4-butanediol,chemical precursors tetrahydrofuran for 1,4-butanediol,, and γ-butyrolactone tetrahydrofuran, [13–15,65– 70and]. Inγ-butyrolactone the last 15 years, [13–15,65–70]. several authors In the have last studied 15 years, C 4several-DCA fromauthors lignin have and studied lignin C model4-DCA compoundsfrom lignin underand lignin catalytic model and compounds non-catalytic under conditions, catalytic using and different non-catalytic strong conditions, oxidants, i.e.,using O2 ,Odifferent3,H2O strong2, and oxidants, peracetic i.e., acid. O2, Some O3, H of2O2, these and peracetic works were acid. focused Some of on these lignin works de- polymerizationwere focused on towards lignin depolymerization aromatic monomers towards and reported aromatic the monomers C4-DCA asand a degradation reported the product.C4-DCA Yet,as athis degradation information product. is valuable Yet, this to identify information possible is valuable research to lines identify and optimalpossible conditionsresearch lines for ligninand optimal depolymerization. conditions for lignin depolymerization.

3.2.1.3.2.1. Non-Catalytic Non-Catalytic Harsh Harsh Oxidation Oxidation

EvenEven though though O O22is is widely widely used used for for lignin lignin depolymerization depolymerization to to phenolics, phenolics, it it can can cause cause ring-openingring-opening reactions.reactions. However,However, itsits oxidantoxidant power power is is lower lower than than other other oxidants, oxidants, being being less effective towards C -DCA [16,36,71,72]. Demesa et al. [71] performed alkali lignin less effective towards C4 4-DCA [16,36,71,72]. Demesa et al. [71] performed alkali lignin oxidation using O , achieving up to 3 wt% of succinic acid (SA). Ozone, a stronger oxidant, oxidation using O2 2, achieving up to 3 wt% of succinic acid (SA). Ozone, a stronger oxi- wasdant, used was on used pyrolytic on pyrolytic lignin, lignin, obtaining obtaining a small a amountsmall amount of SA (2.0of SA wt%) (2.0 andwt%) maleic and maleic acid (MA)acid (2.3(MA) wt%) (2.3 [73wt%)]. Comparatively, [73]. Comparatively, previous previous works from works other from research other groupsresearch using groups O3 on technical lignins showed low yields of C4-DCA [74,75]. using O3 on technical lignins showed low yields of C4-DCA [74,75]. Hydrogen peroxide has received a strong focus when ring-opening reactions are the Hydrogen peroxide has received a strong focus when ring-opening reactions are the objective because it is more reactive than O2, with the beneﬁt of being environmentally be- objective because it is more reactive than O2, with the benefit of being environmentally nign, allowing milder conditions, and avoiding mass transfer barriers that appear between benign, allowing milder conditions, and avoiding mass transfer barriers that appear liquid and gas phases [22,76–78]. However, given that H2O2 is a weak acid, its reactivity between liquid and gas phases [22,76–78]. However, given that H2O2 is a weak acid, its is strongly associated with the pH, being stable at acidic conditions but decomposing in reactivity is strongly associated with the pH, being stable at acidic conditions but de- alkaline conditions [79,80]. Lignin model compounds (guaiacol, syringol, and phenol) were composing in alkaline conditions◦ [79,80]. Lignin model compounds (guaiacol, syringol, oxidized using H2O2 at 300 C and short times, obtaining different C1-C6 dicarboxylic and phenol) were oxidized using H2O2 at 300 °C and short times, obtaining different acids [81]. Catechol oxidation reached very high yields of TA, FA, and MAL, with up C1-C6 dicarboxylic acids [81]. Catechol oxidation reached very high yields of TA, FA, and to 41% C4-DCA [79]. Both studies concluded that the oxidation of the phenolic model MAL, with up to 41% C4-DCA [79]. Both studies concluded that the oxidation of the compounds goes through o-benzoquinones and p-benzoquinones, yielding muconic and phenolic model compounds goes through o-benzoquinones and p-benzoquinones, 2,5-dioxo-3-hexenoic acids, which are highly unstable and are degraded to C4-DCA. Some yielding muconic and 2,5-dioxo-3-hexenoic acids, which are highly unstable and are de- C4-DCA were identiﬁed in hardwood kraft lignin oxidation using peracetic acid [82]. Flow graded to C4-DCA. Some C4-DCA were identified in hardwood kraft lignin oxidation using peracetic acid [82]. Flow reactor oxidation of alkali lignin using H2O2 showed up to

Molecules 2021, 26, 4602 14 of 21

reactor oxidation of alkali lignin using H2O2 showed up to 13 wt% SA [83] when using very high temperatures and short times. SA was formed above 150 ◦C, confirming that harsh conditions are required to achieve valuable yields, at least in a non-catalyzed reaction. Following the interest in the C4-DCA obtained from lignin, the LSRE group analyzed the peroxide oxidation of lignin and lignin model compounds [84], studying the effect of the methoxy substituents in the lignin aromatic ring on the production of C4-DCA. It was found that methoxy substituents increased reactivity toward peroxide oxidation, causing lignin model compounds with more methoxy substituents (syringic acid) to be degraded easily, while p-hydroxybenzoic acid (without methoxy substituents) was more resistant to oxidation. Compounds with lower methoxy substituents (p-hydroxybenzoic and vanillic acid) showed higher overall C4-DCA yield and higher succinic acid (SA) yield than syringic acid. Interestingly, when two lignins with different S:G ratios were compared, the hardwood lignin (higher S:G ratio) not only showed a better lignin conversion but also achieved a higher SA yield (3.2 wt%). The softwood lignin achieved a lower SA yield (2.5 wt%) but a higher MAL yield in the first minutes of the reaction. This study demonstrated that even though the methoxy substituent can reduce C4-DCA production from model compounds, they boost lignin reactivity towards peroxide oxidation, making it easier to depolymerize lignin into smaller fragments that will be converted to C4-DCA, increasing their final yield.

3.2.2. Catalytic Lignin Harsh Oxidation

Peroxide oxidation of lignin towards C4-DCA can be performed using different types of catalyst, which can vary from expensive noble metals, cheaper zeolites, or even homogeneous metal ions, such as Fenton’s reagent [71]. More than 65% of the latest publications on lignin conversion to C4-DCA use catalytic conversion, and those works were focused on two oxidants: O2 and H2O2, with the latter having a higher amount of research. Homogeneous catalysts are mainly transition metal ions with at least two oxidation states, e.g., Cu+/2+ and Fe2+/3+. Oxygen oxidation with these catalysts produced very low C4-DCA yields [85,86]. With H2O2 in Fenton’s conditions, phenol oxidation yielded 8% of MA [87], and other model compounds produced small amounts of MA and FA (<2%) [88]. However, no C4-DCA was obtained when lignin was oxidized [89], concluding that Fenton’s catalyst approach is not efficient for depolymerization towards C4-DCA. Different heterogeneous catalysts have been used with distinct outcomes. Perovskite- type oxides (such as chalcopyrite) have in their structures transition metals with at least two different oxidation states, which catalyzes H2O2 oxidation [42,90]. Chalcopyrite (CuFeS2) presented promising results in model compounds [12] and biorefinery lignins (diluted- acid corn stover lignin: 7% SA, 1% MAL), but with low SA yields for bagasse lignin [91]. Chalcopyrite nanoparticles used on lignin at acidic pH produced high yields of SA (12%) with low yields of FA and MA (1%, each) [92]. Other catalysts, such as sodium percarbonate in alkaline conditions, yielded ~1% SA and MA/FA traces for bagasse oxidation [91]. Gas-phase O2 oxidation using aluminium-vanadium-molybdenum oxide and vanadium pyrophosphate in a fluidized bed only produced small amounts of MA (1.5 wt%) [93], while eight supported metal catalysts (involving V, Mo, Mg, and W) produced a small amount of C4-DCA (SA and/or MA/FA) [94]. It was V-W/HZSM-5 that produced the highest yields (nearly 2% SA and 12% MA/FA), confirming that V5+ activates the aromatic rings in monomeric units. Titanium silicalite 1 (TS-1), a zeolite with an MFI structure and no more than 3% of TiO2 in its structure, has hydrophobic properties that permit peroxide oxidation of non-polar compounds in an aqueous medium. The H2O2 is adsorbed in the Ti tetrahedral sites to form Ti-OOH groups that act as the active species, increasing the overall reactivity. Currently, it is used for cyclohexanone ammoximation to caprolactam and the production of propylene oxide [95–97]. Guaiacol peroxide oxidation using TS-1 in mild alkaline conditions achieved high percentages of MA and oxalic acid, with small percentages of FA and MAL [98]. Other works oxidizing furfural reported good yields on MA [99,100]. Following these promising Molecules 2021, 26, x FOR PEER REVIEW 15 of 21

ages of FA and MAL [98]. Other works oxidizing furfural reported good yields on MA Molecules 2021, 26, 4602 [99,100]. Following these promising results, the LSRE research group15 of 21selected this catalyst to evaluate the conversion of lignin and lignin model compounds into C4-DCA, with particular attention on SA yield, due to its high value to polymer production and chem- results,ical theprecursor LSRE research [13,65]. group An selected initial thisapproach catalyst toby evaluate Vega-Aguilar the conversion et al. of [101] lignin used vanillic acid and lignin model compounds into C4-DCA, with particular attention on SA yield, due to as a lignin model compound to evaluate different operating conditions under H2O2 oxi- its high value to polymer production and chemical precursor [13,65]. An initial approach bydation. Vega-Aguilar Specific et al. C [1014-DCA] used type vanillic and acid yield as a ligninwere modelaffected compound by pH, to achieving evaluate more hydrox- differentylated operating acids in conditions alkaline pH, under while H2O2 SAoxidation. was the Speciﬁc primary C4-DCA acid typein acidic and yieldpH (Figure 11). After werethe affected optimum by pH, reaction achieving moretime, hydroxylated the acid yields acids in were alkaline slowly pH, while degraded SA was the to low molecular primaryweight acid compounds, in acidic pH (Figure e.g., 11formic,). After acetic, the optimum and oxal reactionic acids. time, the Additional acid yields weremodifications of TS-1 slowly degraded to low molecular weight compounds, e.g., formic, acetic, and oxalic acids. Additionalcatalyst modiﬁcations were made ofwith TS-1 Fe, catalyst Cu, wereand Co made oxides with Fe,by Cu, wet and impregnation Co oxides by wetdue to the observed impregnationcatalytic effects due to theof observedthese transition catalytic effects metal of ox theseides. transition Only the metal Fe/TS-1 oxides. catalyst Only increased SA theyield Fe/TS-1 slightly catalyst in increased acidic pH. SA yield Oxygen slightly oxidation in acidic pH. of vanillic Oxygen oxidationacid was of also vanillic tested using TS-1 in acida wasBüchi also reactor, tested using but TS-1no promising in a Büchi reactor, results but were no promising obtained. results were obtained.

FigureFigure 11. Effect11. Effect of TS-1 of andTS-1 modified and modified TS-1 catalysts TS-1 incatalysts the C4-DCA in the yields C4-DCA for the yields wet peroxide for the wet peroxide oxidationoxidation of vanillic of vanillic acid. (Modified acid. (Modif from [ied101]. from Copyright [101]. 2020, Copyright with permission 2020, wi fromth Elsevier.)permission from Elsevier.) The TS-1 catalyst was used for oxidation of different industrial lignins (Indulin AT (IAT), AlkalineThe TS-1 lignin catalyst (ALK), Lignol was (usedEOL) lignin,for oxidation and E. globulus of differentkraft lignin industrial (EKL)). In thislignins (Indulin AT work,(IAT Vega-Aguilar), Alkaline et lignin al. [102 (]ALK evaluated), Lignol different (EOL operating) lignin, conditions and E. andglobulus the catalyst kraft lignin (EKL)). In reusabilitythis work, in several Vega-Aguilar cycles. The C et4-DCA al. [102] showed evaluated a strong dependence different onoperating pH, temperature, conditions and the cat- reaction time, catalyst load, and H2O2 load. The main C4-DCA were MAL and SA, and alyst reusability in several cycles. The C4-DCA showed a strong dependence on pH, there was an increase in the SA yield between the non-catalyzed and the catalyzed reactions, uptemperature, to four times for reaction indulin ATtime, and catalyst alkaline ligninsload, (Tableand H2).2O High2 load. temperatures The main were C4-DCA were MAL neededand toSA, achieve and athere good ligninwas conversionan increase and in C 4the-DCA SA yields, yield but between acid degradation the non-catalyzed also and the happenedcatalyzed at these reactions, temperatures. up to Acidic four andtimes neutral for pHsindulin showed AT the and best alkaline yields, with lignins the (Table 2). High neutral pH being the best operating condition since lignin shows a poor solubility at acidic temperatures were needed to achieve a good lignin conversion and C4-DCA yields, but pH. A 10 wt% H2O2 loading was the optimum amount; a higher amount over-oxidized the products,acid degradation while a lower onealso avoided happened complete at these conversion. temperatures. Interestingly, Acidic the best and reaction neutral pHs showed parametersthe best were yields, similar with to vanillic the neutral acid oxidation. pH being The catalystthe best showed operating stability condition and a slight since lignin shows C4-DCAa poor yield solubility decrease at after acidic five cycles, pH. A due 10 to wt% catalyst H2 lossO2 loading during the was centrifugation the optimum steps, amount; a higher associatedamount with over-oxidized the small particle the size, products, and not contamination while a lower or catalyst one degradation.avoided complete This conversion. study showed that TS-1 can be a valuable catalyst to improve SA as the main C -DCA after Interestingly, the best reaction parameters were similar to vanillic4 acid oxidation. The lignin oxidation, and further studies can be conducted to enhance its use on larger scales. catalyst showed stability and a slight C4-DCA yield decrease after five cycles, due to catalyst loss during the centrifugation steps, associated with the small particle size, and not contamination or catalyst degradation. This study showed that TS-1 can be a valuable catalyst to improve SA as the main C4-DCA after lignin oxidation, and further studies can be conducted to enhance its use on larger scales.

Molecules 2021, 26, 4602 16 of 21

Table 2. Best C4-DCA yields for four industrial lignin oxidations for catalyzed and non-catalyzed wet peroxide oxidations using TS-1 catalyst [102].

Acid Yields (wt%) Lignin Catalyst Succinic Malic Maleic Fumaric Tartaric No 1.6 1.0 n.d. n.d. n.d. ALK TS-1 5.8 6.6 0.1 0.04 0.9 No 2.4 4.8 n.d. n.d. n.d. IAT TS-1 11.3 10.1 0.1 0.06 n.d. No 6.9 22.6 n.d. n.d. n.d. EOL TS-1 9.7 19.5 0.1 0.04 n.d. No 0.6 3.6 n.d. n.d. n.d. EKL TS-1 7.6 5.5 n.d. n.d. n.d. n.d.: not detected.

As mentioned before, this research line has not only recently been followed in the LSRE, but also worldwide. Therefore, as results are relatively new and the process has not the maturity of the lignin oxidation process for aromatic monomers, this topic has not been included yet in the integrated process developed by Prof. Rodrigues’s research group.

4. Integrated Process In addition to all the work developed regarding lignin oxidation, the LSRE team has been working on a general concept of an integrated process that combines reaction engineering and efficient separation processes for converting lignin from pulping spent liquors into value-added aldehydes, such as vanillin and syringaldehyde. The integrated concept proposed starts with the oxidation of a portion of the by- product streams generated in biorefineries. The pulping liquors or isolated lignins, obtained by acidification/precipitation or ultrafiltration, will be depolymerized through alkaline oxidation with oxygen [41,43,44,48,57]. Then, the oxidized stream continues to an ultrafiltration process, leading to the separation of high molecular weight fraction of degraded lignin from the lower molecular weight species [58,103,104]. Vanillin and syringaldehyde go preferentially to the permeate stream due to their low molecular weights, while the oxidized high molecular weight fraction of lignin remains in the retentate. The fraction retained by the membrane during the ultrafiltration process, the retentate, can be considered as a raw material for lignin-based polyurethanes. The production of polymers from lignin is an attractive approach since it can take advantage of its functional groups and macromolecular proprieties. This application has been the topic of intense research in the Polytechnic Institute of Bragança (IPB), and materials with quite promising properties were already obtained [105–107]. After a membrane separation step, the permeate, containing the low molecular weight phenolates and excess NaOH, flows through a packed bed with a polymeric resin [58,108]. The separation of the different species will be achieved by adsorption, which can fractionate the permeate solution in families of chemicals, namely phenolic acids, aldehydes, and ketones [109,110]. In the end, the phenolic compounds of interest, aldehydes in this case, that are present in the enriched desorbed fraction will be recovered by crystallization [60]. This complete process (reaction and separation steps), represented in Figure 12, could be integrated into a pulp and paper industrial plant, considering the possibility of part of the lignin from side streams (spent liquor) to be deviated to produce high added- value chemicals instead of only being burned to generate energy. Moreover, this process perfectly fits into the scope of new emerging lignocellulosic-based biorefineries concerning lignin valorization. Molecules 2021, 26, 4602 17 of 21 Molecules 2021, 26, x FOR PEER REVIEW 17 of 21

Figure 12. IntegratedFigure 12. Integrated process to process produce to value-added produce value-added phenolics ph andenolics polymers and polymers from lignin from inlignin a bioreﬁnery in a bi- concept. orefinery concept. (Modified from [55] Copyright 2009, with permission from Elsevier.) (Modiﬁed from [55] Copyright 2009, with permission from Elsevier.)

Author Contributions:Author Contributions: The manuscriptThe was manuscript written wasthrough written the through contributions the contributions of all au- of all authors— thors—C.A.E.C.,C.A.E.C., C.A.V.-A. C.A.V.-A. and A.E.R. and All A.E.R. authors All authorshave read have and read agreed and to agreed the published to the published version version of the of the manuscript.manuscript. All authors All contributed authors contributed equally. equally. Funding: This Funding:work was Thisfinancially work supported was financially by Base supported Funding—UIDB/50020/2020 by Base Funding—UIDB/50020/2020 and Pro- and grammatic-UIDP/50020/2020Programmatic-UIDP/50020/2020 Funding of the Associat Fundinge Laboratory of the AssociateLSRE-LCM—funded Laboratory by LSRE-LCM—funded nation- by al funds through FCT/MCTES (PIDDAC) and Base Funding—UIDB/00690/2020 of CIMO—Centro national funds through FCT/MCTES (PIDDAC) and Base Funding—UIDB/00690/2020 of CIMO— de Investigação de Montanha—funded by national funds through FCT/MCTES (PIDDAC). COST Centro de Investigação de Montanha—funded by national funds through FCT/MCTES (PIDDAC). Action LignoCOST (CA17128). Carlos Vega-Aguilar thanks the Costa Rican Science, Technology COST Action LignoCOST (CA17128). Carlos Vega-Aguilar thanks the Costa Rican Science, Technol- and Telecommunications Ministry for the PhD. Scholarship MICITT-PINN-CON-2-1-4-17-1-002. ogy and Telecommunications Ministry for the PhD. Scholarship MICITT-PINN-CON-2-1-4-17-1-002. Conflicts of Interest: The authors declare no conflict of interest. Conflicts of Interest: The authors declare no conflict of interest.

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