ACTAUNIVERSITATIS

UPSALIENSISUPPSALA

2015

Digital Comprehensive Summaries of Uppsala Dissertationsfrom the Faculty of Science and Technology 1310

Palladium-catalyzed ligninvalorization: Towards a lignin-basedbiorefinery.

MAXIM GALKIN

ISSN 1651-6214ISBN 978-91-554-9393-6urn:nbn:se:uu:diva-265315

Dissertation presented at Uppsala University to be publicly examined in B:22, UppsalaBiomedical Centre (BMC), Husargatan 3, Uppsala, Monday, 14 December 2015 at 09:30 forthe degree of Doctor of Philosophy. The examination will be conducted in English. Facultyexaminer: Professor Rafael Luque (Universidad de Cordoba, Departamento de QuimicaOrganica).

AbstractGalkin, M. 2015. Palladium-catalyzed lignin valorization. Towards a lignin-based biorefinery.Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science andTechnology 1310. 56 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-9393-6.

The work described in this thesis focuses on the cleavage of the β-O-4′ bond, which is the mostabundant interunit linkage in the lignin polymer.

In the first part, three methods based on palladium catalysis have been developed and theirapplicability has been verified using lignin model compounds. A transfer hydrogenolysis ofthe β-O-4′ bond using formic acid as a mild hydrogen donor together with a base. An aerobicoxidation of the benzylic alcohol motif in the β-O-4′ linkage to generate a key intermediatein the cleavage reaction was performed. A redox neutral cleavage of the β-O-4′ bond wasaccomplished in which no stoichiometric reducing or oxidizing agents were added.

In the second part of the thesis, a mechanistic study is presented. The corresponding ketonefrom a dehydrogenation reaction of the benzylic alcohol motif was identified to be the keyintermediate. This ketone and its enol tautomer was found to be responsible for the β-O-4′ bondcleavage reaction under the employed reaction conditions.

In the final part of this thesis, the methodologies have been applied to native lignin.The depolymerization reaction was combined with organosolv pulping. This approach wassuccessful, and together with cellulose and hemicellulose, propenyl aryls were generated inexcellent yields directly from wood. In this transformation, the lignin derived molecules havebeen reduced by an endogenous hydrogen donor from the wood.

Keywords: Lignin, Heterogeneous Catalysis, Palladium, Biomass, Depolymerization,Reduction, Oxidation, Biorefinery, Transfer Hydrogenolysis

Maxim Galkin, Department of Chemistry - BMC, Synthetical Organic Chemistry, Box 576,Uppsala University, SE-75123 Uppsala, Sweden.

© Maxim Galkin 2015

ISSN 1651-6214ISBN 978-91-554-9393-6urn:nbn:se:uu:diva-265315 (http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-265315)

Now, here, you see, it takes all the run-ning you can do, to keep in the sameplace. If you want to get somewhere else,you must run at least twice as fast as that!

—Lewis Carroll Dedicated to my dear wife Aleksandra,my parents, and relatives, who always supported me, whatever I did.

List of Papers

This thesis is based on the following papers, which are referred to in the text by their Roman numerals.

I M. V. Galkin†, S. Sawadjoon†, V. Rohde, M. Dawange, J. S. M.

Samec, “Mild Heterogeneous Palladium-Catalyzed Cleavage of β-O-4′-Ether Linkages of Lignin Model Compounds and Native Lignin in Air”, ChemCatChem 2014, 6, 179–184.

II M. Dawange, M. V. Galkin, J. S. M. Samec, “Selective Aerobic Benzylic Alcohol Oxidation of Lignin Model Compounds: Route to Aryl Ketones”, ChemCatChem 2015, 7, 401–404.

III M. V. Galkin, C. Dahlstrand, J. S. M. Samec, “Mild and Robust Redox-Neutral Pd/C-Catalyzed Lignol β-O-4′ Bond Cleavage Through a Low-Energy-Barrier Pathway”, ChemSusChem 2015, 8, 2187–2192.

IV M. V. Galkin, J. S. M. Samec, “Selective Route to 2-Propenyl Aryls Directly from Wood by a Tandem Organosolv and Palla-dium-Catalysed Transfer Hydrogenolysis”, ChemSusChem 2014, 7, 2154–2158.

Reprints were made with permission from the respective publishers.

† Authors contributed equally to the publication.

Publications not included in This Thesis

V J. Samec, M. V. Galkin, J. Löfstedt, (KAT2BIZAB) “Catalytic reductive Cleavage of a β-O-4 Bond of Ethers or Polyethers such as Lignin”, WO2014039002 A1, 2014.

VI J. Samec, M. V. Galkin, (KAT2BIZAB), “Depolymerization of Lignin in Biomass”, WO2015080660 A1, 2015.

VII M. V. Galkin†, A. T. Smit†, E. Subbotina, K. A. Artemenko, J. Bergquist, W. J. J. Hujgen, J. S. M. Samec, “Toward a lignin-based biorefinery” (Manuscript).

VIII J. Löfstedt, C. Dahlstrand, A. Orebom, G. Meuzelaar, S. Sawad-joon, M. V. Galkin, P. Agback, Å. Håkansson, M. Wimby, E. Corresa, Y. Mathieu, L. Sauvanaud, S. Eriksson, A. Corma, J. S. M. Samec, “EN590 Road Diesel from Black Liquor in 4 steps” (Manuscript).

Contents

1 Introduction .................................................................................................. 9 1.1 Importance of Organic Chemistry ........................................................ 9 1.2 Green Chemistry for Sustainable Development ................................... 9 

1.2.1 Catalysis ...................................................................................... 10 1.2.2 Renewable feedstock .................................................................. 11 

1.3 Lignocellulosic Biomass .................................................................... 12 1.3.1 Lignin .......................................................................................... 13 1.3.2 Lignin isolation ........................................................................... 16 1.3.3 Challenges and applications of technical lignins ........................ 20 

1.4 Lignin depolymerisation strategies .................................................... 21 1.4.1 Catalytic hydrogenolysis of lignin .............................................. 21 1.4.2 Reductive approaches utilizing hydrogen donors ....................... 22 1.4.3 Hydrogen neutral approaches ..................................................... 23 

1.6 The aim of this thesis ......................................................................... 24 

2 Cleavage of Lignin Model Compounds β-O-4′ Ether bond (Paper I-III) ... 25 2.1 Solvent selection ................................................................................ 25 2.2 Substrate scope–modelling the lignin linkages .................................. 26 2.3 Pd/C cleavage of β-O-4′ ether linkages .............................................. 27 

3 Elucidation of the reaction mechanism (Paper I and III) ........................... 34 

4 Lignin depolymerisation (Paper I and IV) ................................................. 39 

5 Concluding remarks and outlook ............................................................... 45 

Summary in Swedish .................................................................................... 46 

Acknowledgements ....................................................................................... 47 

References ..................................................................................................... 49 

Abbreviations

The abbreviations are used in agreement with standards of the subject.i Only non-standard and unconventional abbreviations that appear in the thesis are listed here.

4CL 4-Coumarate: CoA ligase C2-β-O-4′ 2-Aryloxy-1-arylethan-1ol models C3-β-O-4′ 2-Aryloxy-1-arylpropane-1,3-diol models C3H para-Coumarate 3-hydroxylase C4H Cinnamate 4-hydroxylase CAD Cinnamyl alcohol dehydrogenase CCoA-OMT Caffeoyl-CoA o-methyltransferase CCR Cinnamoyl-CoA reductase COD Cycloocta-1,5-diene F5H Ferulate 5-hydroxylase HCT para-Hydroxycinnamoyl-CoA:

para-hydroxycinnamoyltransferase PAL Phenylalanine ammonial-lyase PD Polydispersity PMO Porous metal oxide PMHS Polymethylhydrosiloxane POD Peroxidases

i The ACS Style Guide, 3rd ed. (Eds.: A. M. Coghill, L. R. Garson), American Chemical Society, Washington, DC, 2006.

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1 Introduction

1.1 Importance of Organic Chemistry Organic chemistry is a chemistry sub-discipline involving the scientific study of the structure, properties, composition, reactions, and preparation of organic compounds and materials. The range of applications of organic compounds is enormous and is central to the function of the modern society. The quality of life is largely dependent on the sophistication level of the chemical technol-ogy, for example, in polymeric engineering, construction materials, transpor-tation fuels, synthetic textiles, dyes, pharmaceuticals, and a wide diversity of other chemical products.

The last few decades of the 20th century witnessed growing concerns over the impact of industry on the global environment. This has sparked an interest in efficient, clean, and environmentally friendly methods for producing or-ganic compounds. The use of such methods has been summarized and named Green Chemistry.

1.2 Green Chemistry for Sustainable Development

A traditional approach in industrial chemistry has been the optimization of the time space yield. From a modern perspective, this limited viewpoint should be enlarged. There are a number of drivers, including: a) the depletion of finite oil, gas, and mineral resources, b) the generation of waste, some of which is harmful to living organisms and the environment, and c) the manufacturing of products that do not degrade when disposed. This aspiration can be summed up in one word–sustainability. Sustainability can be defined as the develop-ment that meets the needs of the present generation without compromising the ability of future generations to meet their own needs. In the early 1990s, the term Green Chemistry was coined by Paul Anastas. Later on, the twelve prin-ciples of Green Chemistry1 were formulated by Paul Anastas and John Warner, which have become the generally accepted guidelines for scientists and industry (Table 1).

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1.2.1 Catalysis

In the early 19th century, a number of observations from several laboratories indicated that certain substances influenced the progress of a chemical reac-tion without being consumed. The decomposition of ammonia on metals (L. J. Thenard, 1813),4 the conversion of starch into glucose (G. S. C. Kirchhoff, 1814),5 and platinum catalyzed oxidation of methane (H. Davy, 1817)6 are important examples. The term catalysis was coined by Jöns Jacob Berzelius, who defined and summarized the observed phenomena. In his report to the Swedish Academy of Science from 1835, Berzelius introduced catalysis in order to propose a classification, rather than to offer a possible explanation.7,8 Throughout the rest of 19th century, the term remained heavily debated, until W. Ostwald defined it in terms of the chemical kinetics: “A catalyst is a sub-stance which affects the rate of a chemical reaction without being part of its end products.”9,10 Today a catalyst is officially defined by IUPAC as: “A sub-stance that increases the rate of a reaction without modifying the overall stand-ard Gibbs energy change in the reaction”11 (Figure 1). As a catalyst remains unchanged after the reaction, it can be used in substoichiometric amounts, re-

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covered and reused. Application of catalysis enables reactions to occur in rea-sonable time frames with higher selectivity and productivity. Thus, catalysis is essential in Green Chemistry.

Figure 1. A schematic diagram showing the free energy profile of the course of a hypothetical chemical reaction. The presence of the catalyst opens a different reac-tion pathway (shown in grey) with a lower activation energy.

1.2.2 Renewable feedstock

One of the main principles of Green Chemistry is to use a renewable feed-stock. Our modern society is based on geologically derived supplies. We cur-rently extract fossil fuels, coal, oil, natural gas, and minerals from ground until they are exhausted. The main fraction of worldwide energy carriers and mate-rial products come from fossil fuel refineries. Besides the inevitable fossil fuels depletion, there are a number of drivers including environmental con-cerns, energy security, and rural development; combined, these lead to a global effort to find a replacement for fossil fuels.

One alternative to fossil fuels is biomass.12-14 Biomass is a collective term for plants (trees, grasses, algae, etc.) that are able to absorb carbon dioxide from air and fix it in their tissues, utilizing sun energy by photosynthetic pro-cesses. Renewable carbon is produced at a high rate in the biosphere; about 77·109 tons are fixed annually as biomass, of which we currently use 3.5% for human needs. It is estimated that roughly a quarter of the annual production could supply almost all domestic organic chemical demands.15-19

Thus, an economy based on the biorefinery concept is foreseeing. ”Biore-fineries are facilities that convert biomass–biological materials from living or recently living organisms–into fuels, energy, chemicals, and materials”.20 The first generation biorefineries for production of fuels are focused on edible bi-omass feeds. Vegetable oils (rapeseed, palm, soybean, etc.) are used to pro-duce biodiesel, carbohydrate syrups (extracts from corn, sugarcane, sugar

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beet, etc.) are used in bioethanol production.20,21 However, use of such bio-mass in the production of chemicals and fuels is not sustainable, as its produc-tion competes with food, consumes large amounts of fertilizers and water, and is often accompanied by deforestation. The second generation biorefineries utilize biomass consisting of the residual non-food parts of current crops or other non-food sources, e.g. timber. Non-edible biomass and especially ligno-cellulose is advantageous, being one of the most abundant, having lower water and energy consumption, and do not compete with food supplies.22

1.3 Lignocellulosic Biomass

Biomass of higher (vascular) plants consists of cellulose, hemicellulose, and lignin. The amount of each of these components varies depending on the origin of the biomass.23,24 Cellulose is a linear polymer consisting of hundreds to thousands of β-1,4-linked glucose units. During biosynthesis the cellulose chains self-assemble into microfibrils through inter- and intra-chain hydrogen bonding and van der Waal’s interactions (Figure 2). These microfibrils are packed into fibers, making the cellulose more crystalline and insoluble. Cel-lulose shows both well-ordered crystalline and disordered amorphous regions. Complete depolymerization of cellulose yield glucose as the sole product. Hemicellulose is a short, highly branched hetero-polymer composed of pen-toses, hexoses and sugar acids. Hemicelluloses are referred to as mannans, xylans or galactans depends on the predominant types of sugar present in the polymer. The pentoses and hexoses are linked through 1,3-, 1,6- and 1,4-gly-cosidic bonds and can be partially acetylated. Hemicellulose acts as a binder between cellulose and lignin. Lignin is a macromolecular constituent of wood, composed of phenolic propylbenzene skeletal units, linked at various sites and apparently randomly.25 Lignin is located in the layers of the cell walls where it operates as a glue, forming an amorphous matrix together with hemicellu-loses, in which cellulose fibrils are embedded (Figure 2).

Figure 2. Schematic structure of lignocellulose.

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1.3.1 Lignin

Lignin (from Latin lignum–wood, timber) is the second most abundant terres-trial organic matter on Earth after cellulose. Lignin was first mentioned in 1813 by the Swiss botanist A. P. de Candolle, who has also created the term.26 Lignin is a chemical and morphological component characteristic for tissues of vascular plants such as pteridophytes and spermatophytes (gymnosperms and angiosperms). Its presence is typical for tissues with liquid-conduction, such as xylem, and is fundamental in the water and mineral transport in a plant. It is commonly accepted that lignin evolved together with the adaptation of plants to a terrestrial life to provide structural support needed for an erect growth. It has a rigidity-enhancing function contributing to the shearing and compressive strength of plant tissues. Lignin also protects the cell wall from biodegradation.27,28

The abundance of lignin depends heavily upon the type of plant and its organs. The lignin content in wood shows rather broad variations e.g., it makes up 25 to 30 weight percent (wt %) in softwoodii and 9 to 23 wt % in hard-woodiii.29 For grasses, the amount varies from 10 to 30 wt %. The protective tissues of plants, like nut shells, contain more lignin (from 30 to 40 wt %) than other tissues. Vice versa, there is almost no lignin presents in soft tissues such as leaves and cotton seed hairs.30 Examination of the wood structural arrange-ment at a cellular level has shown that lignin largely concentrates in the middle lamella and in the cell wall (about 25 wt %). Its concentration is governed not only by the plant species, but also by many other factors, such as climate, soil characteristics, age of the tree, stresses caused by weather and pests.31,32

The formation of the lignin macromolecule–lignification–in plants consists of a system of complex biological, biochemical, and chemical processes.33,34 The main building blocks of lignin are the hydroxycinnamyl alcohols: co-niferyl, sinapyl, and p-coumaryl. The biosynthesis of these hydroxycinnamyl alcohols, known as monolignols, (Scheme 1) begins with the glucose genera-tion during the photosynthesis. Glucose transforms to shikimic acid and by the “shikimic acid” pathway yields aromatic amino acids: L-phenyl alanine and L-tyrosine. L-phenyl alanine serve as starting substance for the enzymatic syn-thesis of phenyl-propanoid compounds. This synthesis proceeds through acti-vated intermediates of cinnamic acid to give off three cinnamyl alcohols.35

ii Hardwood is wood from dicot angiosperm trees such as birch, poplar, eucalyptus, etc. iii Softwood is wood from gymnosperm trees such as pine, spruce, etc.

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Scheme 1. Simplified metabolic grid of monolignol biosynthetic reactions, including the primary lignin monomers and the monolignols, exemplified by coniferyl alcohol biosynthesis. The lignin polymer units are denoted based on the methoxyl substitu-tion on the aromatic ring as H, S and G units.

Once the monolignols are formed (Scheme 1) and transported36-38 to ligni-fication sites, they undergo radicalization catalyzed by enzymes, such as pe-roxidases, phenol oxidases, and laccases, or by radical exchange reactions.39-41 The resulting radicals are relatively stable due to delocalization of the un-paired electron in the conjugated system (Scheme 2).24

Scheme 2. Formation of resonance-stabilized phenoxyl radicals by enzymatic dehy-drogenation of cinnamyl alcohols. Coniferyl alcohol used as an example.

The generation of polymeric lignin starts with a random combination of two radical monomers (end-wise polymerization) yielding dilignols (dimeric

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structures). A simplified overall reaction mechanism of the radical coupling of two coniferyl alcohols, forming the β-O-4′ linkage, is shown in Scheme 3.

Scheme 3. Simplified reaction of a hydroxycinnamyl alcohol at its favored β-posi-tion results in formation of quinone methide intermediate. Quinone methides add water to form the arylglycerol-β-aryl ethers (A). Water can add from either face of the planar quinone methide, producing two isomers, the threo- (or syn-, or RR/SS-) and the erythro- (or anti- or RS/SR-) isomers.

Monolignol radicals favour reaction at their β-positions, resulting in the β-O-4′ (A), β-β′ (B), and β-5′ (C) dimers (Figure 3).42

Figure 3. Major structural units in lignin and their abundance.24 The bolded bonds are formed via radical coupling reactions.

The process of lignin formation is often referred to as statistically random. The ratio of products is governed primarily by the reactivity of the coupling partners, the nature of stabilizing post-coupling reactions, the matrix, and sol-vent, as well as physical conditions such as temperature and pressure.36 Since all the possible combinations are available, but with different probability, such processes are essentially combinatorial.41,43 In addition to radical polymeriza-tion, ionic reactions occur with the participation of quinone methide interme-diates. Nucleophilic attack by alcohols or phenolic hydroxyl groups on the benzylic carbon of the quinone methide intermediate (Scheme 3) will result in branching of the polymer. The dilignols formed undergo further end-wise polymerization, instead of combining with one another.

The most abundant phenylpropane linkage in softwood and hardwood lig-nins is the β-O-4′ bond (50–70%). Other linkages of lignin include α-O-4′, β-5′, β-β′, β-1′, 4-O-5′, 5-5′ and dibenzodioxocin44 of which the last three are serving as branching points.45 More than twenty different linkage types have been identified and it is proposed that several more will be discovered with the progression of lignin structure analyses.43,46 A number of approaches exist

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to make a schematic representation of a lignin polymer.41,44,47 The purpose of such lignin representations is to depict the general features of the polymer and accommodate the main linkage types and their approximate relative frequen-cies without taking primary structure or sequencing into account. Such models serve as a tool to visualize the linkages and functional groups in lignin.48 In Figure 4, a schematic model of a lignin polymer is presented.

Figure 4. A proposed structural model for a poplar lignin polymer (adapted from Boerjan et al.).49 Some of the common structural units are marked; the bold bonds are formed via radical coupling reactions.

1.3.2 Lignin isolation To isolate lignin from the rest of lignocellulose biomass, the biomass needs to be fractionated. The properties and structure of lignin strongly depends on the isolation method from the lignocellulosic feedstock.50 There are four main processes–the Sulphite, Kraft, Soda and Organosolv–that generate 40–50 mil-lion tons per annum of lignin worldwide.51,52 Usually, the lignin undergoes intensive chemical modification during these processes. The goal of pulping is to liberate cellulosic fibers from the lignocellulose matrix by removing the majority of lignin. This can be achieved by depolymerizing the lignin, break-ing bonds between lignin and polysaccharides, and making the lignin more soluble.53

During biomass fractionation lignin can participate in two categories of re-actions, nucleophilic reactions (delignifying reagent supplies an electron pair) and electrophilic reactions (delignifying reagent accepts an electron pair). The pulping processes are exclusively governed by nucleophilic reactions, whereas the bleaching step is initiated by electrophilic reactions and followed by a combination of both.54

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One of the most important intermediates during delignification processes are quinone methide intermediates or their protonated forms, which are readily formed during the initial stage of the pulping processes. These intermediates are able to participate in two types of reaction, both governed by rearomatisa-tion as the driving force. The first type is the addition of a nucleophile (AdN) from the pulping liquor (Nu = RO-, S2-, SO3

2-) or from lignin itself (internal nucleophile). A reaction with lignin will lead to condensation reactions. The second reaction type is elimination of the terminal hydroxymethyl group, as formaldehyde, resulting in the formation of unsaturated conjugated structures (styrenes and stilbenes) (Scheme 4).

Scheme 4. Sites of electrophilic (δ-) and nucleophilic (δ+) attack in arylalkane units. The nature of the leaving group depends on the pH of the reaction media. The addi-tion of a nucleophile to quinone methide intermediates and the elimination of for-maldehyde are competing pathways.

After the addition of a nucleophile to the quinone methide intermediates, a second nucleophilic attack is possible. The introduced substituent at the α-po-sition may attack the β-carbon. This synartetic acceleration (neighbouring group participation) constitutes the second important mode of lignin fragmen-tation during pulping (Scheme 5).

Scheme 5. Generalized scheme showing the neighboring group participation in the β-O-4′ bond cleavage reaction.

1.3.2.1 Kraft pulping The dominant fractionation process of lignocellulose is kraft pulping, which corresponds to about 85% (43·106 tons per annum) of the lignin generated worldwide.29,55 The kraft process is conducted in a high pH water solution containing considerable amount of sulphide and at temperatures between 150

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and 180 °C. During pulping, the lignin polymer is solubilized by cleavage of the interunit ether linkages in order to obtain and separate it from insoluble cellulose fibers used for pulp production. The majority of lignin and the most of the hemicellulose are dissolved in the spent pulping liquor. Dissolved or-ganic matter serves as a fuel for the operation of a kraft mill and is used to regenerate process chemicals. In a kraft process, lignin may be recovered from the black liquor by lowering the pH that will result in its precipitation.56,57 The molecular weight average (Mw) of technical kraft lignin varies from 1000 to 3000 Da (up to 15000 Da, PD = 2.5–3.5).58 The high Mw values are due to the lignin condensation reactions, where new C–C bonds have formed as a result of the quinone methide reactions at the α-position with different lignin derived carbon nucleophiles (Scheme 4).59-63 As a result, the molecular structure of kraft lignin differs from the native lignin. A significant decrease in the β-O-4′ and β-5′ bond abundance has been observed.63 Besides change in the interunit linkages of lignin and the introduction of new bonds, kraft lignin is heavily contaminated with carbohydrates from hemicellulose (in a form of lignin car-bohydrate complexes)53,64 and fatty acids (Figure 5).

Figure 5. Two-dimensional (2-D) NMR spectrum (heteronuclear single quantum co-herence (HSQC) experiment; DMSO-D6, 25 °C) of industrial Lignoboost lignin from Kraft black liquor. The lignin structures identified are: (A) β-O-4′ substructure; (A′) A motif with a conjugated carbonyl or carboxyl group; (D) β-1′ substructure; (B) resinol substructure; (G) guaiacyl unit; (S) syringyl unit; (S′) Cα-oxidized S unit; (G′) Cα-oxidized G unit; (X) β-xylan units; (F and uF) saturated and unsatu-rated fatty acids or esters residues (Paper VIII).

1.3.2.2 Sulphite pulping In sulphite pulping, the biomass is heated in aqueous solution of HSO3

- or SO3

2- at 125–150 °C.65 The sulphite process does not degrade lignin to the

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same extent as the kraft process does.66 The molecular weight of the generated lignosulphonates varies between 1000 Da and 50000 Da (PD = 4.2–7.0). The β-O-4′ and α-O-4′ linkages are prone to undergo cleavage by several types of reactions giving raise to partially sulphonated oligolignols.67,68 Introduction of polar groups into the lignin skeleton facilitate its solubilization in the cooking liquor. In addition, a number of condensation reactions take place leading to the formation of new C–C bonds.67-70 Lignosulphonates can contain up to 30 wt % of carbohydrate, ash and other impurities.

Figure 6. 2-D NMR spectrum (HSQC experiment; D2O, 50 °C) of lignosulfonates. The lignin structures identified are: (A′′) sulfonated β-O-4′ substructure; (D′) sul-fonated β-1′ substructure; (X) β-xylan units. Reprinted from67 A. Prates et al., 2009. Reprinted by permission of Taylor & Francis LLC.

1.3.2.3 Organosolv pulping Organosolv pulping was developed to give a more environmentally benign alternative to kraft and sulphite pulping.71 The organosolv process is based on the treatment of biomass with organic solvents, such as methanol, ethanol, acetic acid or peroxyformic acid, at temperatures ranging from 180 to 200 °C.72 A number of full scale and pilot plants were operating based on organosolv pulping: Organocell and ASAM (methanol), Acetosolv (acetic acid), Avideliv (formic and acetic acids), Milox (peroxyformic acid) and Al-cellv (ethanol).71,73,74 The Alcell process, in which biomass is treated with an ethanol–water mixture, was shown to be the one of the most promising.75 The dominant reaction in the lignin molecule breakdown during organosolv pulp-ing is the cleavage of α-O-4′ bonds. Cleavage of β-O-4′ linkages occurs to a smaller extent in comparison to other pulping processes and likely takes place in the pulping liquor when the lignin oligomers are liberated from the ligno-cellulose matrix.72,76,77 When alcohols are used as a co-solvent they can act as

iv Currently the process is operated by CIMV, France. See www.cimv.fr. v The last owner of technology is The Lignol Innovations Corp. Canada.

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an external nucleophile (Scheme 4) and perform alkoxylation at the α-posi-tions (Figure 14).53,78 In total, these reactions lead to the dissolution of lignin in the pulping media. The organosolv process produces low molecular weight lignin (500–5000 Da, PD = 1.5).

Figure 7. 2-D NMR spectra (HSQC experiment; DMSO-D6, 25 °C) of the organo-solv isolated lignins. From M. giganteus (on the left). Reprinted with permission from,78 D. E. Wemmer et al., 2012. Copyright 2012 American Chemical Society. And from Pinus sylvestris (on the right). Reprinted from Paper I. Copyright 2014 by John Wiley Sons, Inc. Reprinted by permission of John Wiley & Sons, Inc. The lig-nin structures identified are: (A) β-O-4′ substructure; (A′′′) α-ethoxylated β-O-4′ substructure, (B) resinol substructure, (C) phenylcoumaran substructure.

1.3.3 Challenges and applications of technical lignins Most of the biorefineries dealing with lignocellulose currently focus on valor-izing the carbohydrate part of biomass. Unlike cellulose and hemicellulose, which have a more homogeneous composition and can be released as mono-meric sugars, lignin naturally is a complex and polydispers substance. The process applied for biomass fractionation significantly changes the chemical structure by introducing new bonds and cleaving existing ones; as a result, the physical properties of lignin, such as solubility and polydispersity, are altered. Therefore, lignins possess a non-uniform structure, show unique chemical re-activity, and contain impurities, depending on the processing method. The common denominator is that lignins are mostly non-commercialized waste products. In the pulping mills, lignin is incinerated to produce heat and energy to a low value, with only 40% needed to maintain the pulping process. Only 2% of the generated lignin is used in commercial applications such as produc-tion of synthetic vanillin, dispersants, emulsifiers, and binders.50,79

Lignin has great potential as a renewable feedstock in the production of transportation fuels and fine chemicals. It is the only large-volume renewable feedstock that is composed of aromatics.80,81 Therefore, there is a need to de-velop new and efficient methods to valorize lignin.82

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1.4 Lignin depolymerisation strategies A plethora of strategies has been developed for lignin valorization. Different scientific disciplines have been involved to reach this goal.83-86 A very im-portant classical approach is thermal degradation of lignin, including pyrolysis and hydrothermal treatment. The outcome depends on the applied conditions and can result in smaller aromatic fragments (pyrolytic oils) or lead to full cleavage of the carbon framework generating syngas.87-92

A number of new methods have been developed for lignin depolymerisa-tion including enzymatic,93-96 mechanochemical,97 electrochemical,98-100 mi-crowave assisted,101,102 and photochemical103 based techniques. Recent pro-gress has been made in the field of chemical catalysis. Application of organ-catalysis and transition metal catalysis (homogenous86 and heterogene-ous13,83,104) have shown to be promising for lignin depolymerisation.

This PhD thesis will deal with transition metal catalyzed depolymerisation of lignin. Methods based on the catalytic depolymerisation of lignin are re-viewed in this thesis. The thermal, enzymatic, mechanical, etc. degradation of lignin are out of the scope of this work and, thus, will not be highlighted.vi

1.4.1 Catalytic hydrogenolysis of lignin Hydrogenolysis of lignin has been studied thoroughly since “it was one of the most effective methods of obtaining valuable information about the chemical structure of lignin” and was reviewed in great depth.83,86,105 One of the first studies on the catalytic hydrogenolysis of lignin was conducted by Harris in 1938.106 Hydrogenolysis of aspen lignin catalyzed by copper chromite resulted in 40% yield of propyl cyclohexanols. This pioneering work promoted further studies by a number of investigators. Significant contributions to the area were made by Pepper and co-workers.107-110 From 1948 to 1978 they reported a number of very effective catalytic systems for native lignin depolymerisation using Pd/C, Raney Nickel, Rh/C, Ru/C. Using Raney Nickel the correspond-ing n-propyl phenols were obtained in approximately 50% yield based on Kla-son lignin content.107-110

In summary, these path breaking studies (1930–1990) revealed that most of the ether bonds undergo hydrogenolysis. Carbon–carbon linkages may also be cleaved trough hydrocracking or retro aldol reactions, depending on the reaction conditions. It was shown that hydrogenolysis and hydrogenation re-actions compete, and when the hydrogenation of the aromatic rings occurred first led to a lower efficiency in the ether bond cleavage. Polymerization and condensation reactions of cleaved lignin fragments are possible if the catalyst is omitted or not active enough. The yield of monomeric units depends on the lignin origin. Poor yields were usually reported when process lignin liquors

vi The reader is kindly asked to refer to appropriate reviews listed in the section 1.4.

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were used in comparison with native lignin. Also yields of monomers from hardwood lignin generally exceed softwood ones. Sakakibara proposed that this could depend on the abundancy of the β-O-4′ ether bond.105

A few industrial scale processes of lignin hydrogenolysis to phenols and aromatic hydrocarbons were in use, namely, Noguchi process 1959–1966,111,112 Crown-Zellerbach process 1966,112,113 Lignol process 1960–1983.114 All of them have been discontinued due to a number of drawbacks making them cost-ineffective. Most of the methodologies of this period suf-fered from a number of limitations including high hydrogen pressure, near stoichiometric or over stoichiometric catalyst loadings, specific solvents, and high reaction temperatures. Harsh reaction conditions and the utilization of very active catalysts led to full hydrogenation of lignin and this gave a lower yield of desired aromatic monomers.

In recent decades, the focus in catalytic hydrogenolysis of lignin moved towards sustainability (milder conditions, more effective catalytic systems), the search for alternatives to replace hydrogen, and studies of the reactions mechanisms.

1.4.2 Reductive approaches utilizing hydrogen donors The vast majority of hydrogen gas is currently produced from fossil fuels: es-timated at 49% from natural gas, 29% from liquid hydrocarbons, directly from naphtha or related feedstocks, 18% from coal, and only 4% from electroly-sis.115 Lowering hydrogen demands or even omitting the use of hydrogen will enable a biorefinery independence from fossil fuels usage. Furthermore, it will significantly mitigate eventual costs for a factory construction, as there will be no need to operate under hydrogen pressure.

Hydrogenolysis and hydrogenation of lignin via hydrogen transfer from al-cohols is a highly attractive approach. Especially, considering that alcohols, which can serve as a hydrogen donor, can be produced from biomass by fer-mentation.116,117 In 2009 Ford and co-workers described a selective aromatic ether bond cleavage in the lignin model compound–dihydrobenzofurane.118 The reaction was catalyzed by copper doped porous metal oxides (Cu-PMO) and was carried out at 300 °C. Hydrogen was generated through methanol reforming. With a designed catalytic system, a quantitative conversion of or-ganosolv lignin and lignocellulosic biomass was observed. A mixture of C2–C9 alcohols were obtained, remarkably without the formation of char.119-121

The limitation to non-aromatic compounds has been overcome by other in-vestigators utilizing Cu-PMO catalyst family.122,123 Also ethanol has been shown as a promising hydrogen donor and capping agent which can prevent repolymerisation of phenolic intermediates by C- and O-alkylation.124,125 Xu et al. reported an elegant method of lignin depolymerisation catalyzed by Ni/C in the presence of methanol as the hydrogen donor. Propyl guaiacol and propyl

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syringol products were obtained in remarkable selectivity and 54% yield start-ing from birch sawdust.126,127 A method combining deoxygenation and lignin depolymerisation was reported by Rinaldi producing a mixture of simple al-kanes and arenes from organosolv lignin. Combination of Raney Ni, solid acid catalyst, and isopropanol, as the hydrogen donor, allowed to perform the pro-cesses under low severity conditions and with high selectivity towards aro-matics.128-131

The studies by Hartwig et al. focused on cleavage of ether 4-O-5′ and α-O-4′ bonds in lignin model compounds. The catalytic system prepared from Ni(COD)2 and a N-heterocyclic carbene ligand in the presence of strong base was efficient to cleave these bonds already at 120 °C, with high conversion. However, the most representative β-O-4' glycerol-aryl ether model compound decomposed at the stated conditions resulting in complex mixture. It was showed that base alone was efficient enough to perform this reaction. Remark-ably, different hydride donors such as Et3SiH and aluminum hydride can be applied, and the catalyst can operate at hydrogen pressure as low as 1 bar.132,133 Grubbs’ group reported a transition metal free system that successfully cleaved 4-O-5′ and α-O-4′ bonds with Et3SiH and a strong base at 75–165 °C.134 A number of studies on silanes use in lignin depolymerisation has been reported.135-137 Using inexpensive polymethylhydrosiloxane (PMHS) and tetramethyldisiloxane as reductants and a Lewis acid catalyst, ether link-ages in model compounds and lignin were reduced to primary alcohols and phenols under mild reaction conditions and in excellent yields. Importantly, PMHS is cheap and available in large quantities as a by-product of the silicone industry.

1.4.3 Hydrogen neutral approaches From the perspective of atom economy and sustainability, even the cheapest hydrogen donors are inferior to using no hydrogen donors. Lignin contains a plethora of aliphatic alcohol moieties. It is well known that secondary and especially benzylic alcohols can act as a very mild hydrogen source for bond cleavage reactions enabling a hydrogen neutral approach.

Ellman, Bergman, and co-workers reported a method for the selective β-O-4′ ethanol-aryl bond cleavage catalyzed by xantphos-based ruthenium complex.138 The reaction proceeds through initial dehydrogenation of the ben-zylic alcohol in the β-O-4′ model compound yielding a hydrogen equivalent and a ketone, which undergo ether bond cleavage with hydrogen liberated.139 James and co-workers made an unsuccessful attempt to adapt a similar catalyst system for a β-O-4′ glycerol-aryl ether bond cleavage. The presence of a γ-OH function inhibits the hydrogenolysis by formation of a chelate complex with the active catalyst.140 Results obtained by Bergman and Ellman promoted fur-ther studies involving ruthenium complexes.141-143 These studies have revealed

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the importance of an oxidized dimeric model compound as the key intermedi-ate in the reaction. In a following reports it was demonstrated that selective oxidation of the α-hydroxyl to the corresponding ketone in the common β-O-4′ lignin motif will lead to significant weakening of the ether bond, making it more labile and prone to cleavage.144-147

Another hydrogen neutral approach was reported by Toste and Son where vanadium based catalysts were used. The β-O-4′ glycerol-aryl ether model compound utilized in these studies underwent a redox-neutral cleavage to give very good yields of monomers.148 However, degradation experiments with more challenging organosolv lignin resulted in only a moderate shift toward lower molecular weight of the polymer.149-153

1.6 The aim of this thesis The overall aim of this thesis is to develop benign methods for the transition metal-catalyzed depolymerization of native lignin based on mechanistic un-derstanding of the transformations.

More specific goals include to elucidate: Which parts of the most abundant β-O-4′ motif is important for the

reactivity. What reducing or oxidizing agents are most efficient for the cleav-

age of the β-O-4′ bond. What intermediates are generated in the overall reaction. The nature of the catalyst. The difference in reactivity between model compounds and native

lignin. How to depolymerize lignin avoiding recondensation reactions.

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2 Cleavage of Lignin Model Compounds β-O-4′ Ether bond (Paper I-III)

Lignin depolymerisation, by means of catalysis, is a key for efficient utiliza-tion of lignin (Chapter1.4). Palladium-based catalysts have been used success-fully for lignin depolymerisation. In earlier reports severe reaction conditions have been employed. Typically, such reactions are conducted at high hydro-gen pressures (above 30 bars) and high temperatures (above 200 °C) or both,154-159 which limits their application in an industrial process.120,121

One possibility to overcome the use of hydrogen gas is to use hydrogen donors. Hydrogen donors include hydrazine, dihydronaphthalene, silanes, di-hydroanthracene, isopropanol, and formic acid, etc. The advantage of formic acid is that it can be produced from lignocellulose biomass (or generated as a side product)13,160,161 and by selective decomposition can be a source of hydro-gen gas. Thus, formic acid offers a mild and sustainable way for hydrogen storage and releasing when needed.162 Formic acid is compatible with lignin and was applied for its disassembly.102,145,163-166 In our group it was previously shown that Pd/C is reactive in the transfer hydrogenolysis of benzyl alcohols with formates as hydrogen equivalents.167 Hydrodeoxygenation of C–O bonds, relevant to lignin substrates, was achieved in good yields and under mild conditions (80 °C). A better and more representative substrate scope is required in order to develop a depolymerization method applicable to lignin.

2.1 Solvent selection In the presented contributions vide infra, water and a co-solvent were required to obtain the desired reactivity. The choice of co-solvents was based on green solvent guidelines.168-171 An important factor is the availability of such sol-vents from the biorefinery. Therefore, we have selected the following solvents for evaluation: methanol, ethanol, 2-propanol, ethyl acetate, 2-methyltetrahy-drofuran, cyclopentyl methyl ether. Ethanol is used in organosolv pulping and can be generated from carbohydrates, derived from biomass, as it was dis-cussed in Chapter 1.3.3, hence, is particularly interesting for further applica-tions. Ethyl acetate and methyl tert-butyl ether were used to simplify analysis and allowing for fast separation of products and starting material from the re-action media.

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2.2 Substrate scope–modelling the lignin linkages

Due to the difficulties associated with the lignin and products characteriza-tion,172 the majority of researchers use well-defined model compounds that mimic the representative interunit linkage in lignin, especially, when in-depth understanding of the processes is needed. It is worth to choose a model that represents the most abundant interunit linkage. The β-O-4′ ether bond com-prises above 50% of the monomer linkages in lignin and is significantly weaker than other bonds.173,174 Thus, most research has targeted the β-O-4′ structural motif (Figure 8).

Figure 8. Widely accepted examples of β-O-4′ bond model compounds (1 and 2) and estimated BDE values for some of the commonly studied interunit linkages.

A range of β-O-4′ bond model compounds was prepared following a synthetic route shown in Scheme 6. Besides simple models representing the minimized β-O-4′ bond pattern, models containing arylglycerol-β-aryl ether bond were synthesized in good yields. It is crucial to include models that can participate in the formation of quinone methide intermediates (Scheme 4). We have syn-thesized a number of compounds with a free phenolic groups. In order to mimic physical properties of lignin, such as polymeric nature, polydispersity, and solubility, a model lignin polymer was included.

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Scheme 6. Synthesis of lignin model compounds. Rn = H, OMe or OH. To obtain models 8 and 9, where R4 = OH, protection and deprotection steps were needed (see supporting information Papers I–III).

2.3 Pd/C cleavage of β-O-4′ ether linkages 2-phenoxy-1-phenylethan-1-ol (10) was used as a benchmark model substrate in our studies. The reaction was carried out in the presence of 5 mol % Pd/C varying the amount of hydrogen donor and base. The reactivity and selectivity of the reaction depended significantly on the amount of the base and the hy-drogen donor used (Scheme 7).

Scheme 7. Transfer hydrogenolysis of 2-phenoxy-1-phenylethan-1-ol (10) at differ-ent amount of base and formic acid added.

The cleavage of the β-O-4′ bond was minor reaction when 0.25 equivalents of base were used. Under these reaction conditions, a transfer hydrogenolysis of the α-C–O bond was performed to generate compound 11.167 When the amounts of the base was increased to 1 equivalent a cleavage reaction occurs and acetophenone was isolated in 98% yield. Equimolar amounts of formic acid and ammonia were found to be superior for cleavage of the β-O-4′ ether

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bond. An increase of formic acid and base (2.5 equiv.) resulted in the cleavage and a subsequent reduction of the acetophenone to the corresponding benzylic alcohol 14. Performing the reaction in two steps lead to the full deoxygenation product–ethylbenzene (15), which was isolated in 95% yield. The optimized reaction conditions were applied to different β-O-4′ ethanol-aryl ethers. The degree of methoxy substitution or presence of unprotected phenols did not affect the catalysis. In all cases the products from β-O-4′ bond hydrogenolysis were isolated in excellent yields (95% in average; see Paper I, Table 2). With-out modification of the reaction conditions the poorly soluble polymer (16) resulted in full conversion to the desired monomeric acetophenone derivative (Scheme 8).

Scheme 8. Transfer hydrogenolysis of model polymer.

Encouraged by these results the more challenging glycerol-aryl ether model compound (1) was tested. Due to the more complicated structure, these model compounds could undergo a number of transformations that are not viable for the simplified model compounds (Figure 9). With increased temperature and equivalents of hydrogen donor we were able to obtained two products from the cleavage reaction. Phenylpropanol (23) and propyl benzene (22) were iso-lated in overall 71% yield (Scheme 9).

Figure 9. Reaction centers of β-O-4′ glycerol-aryl model compounds.

Scheme 9. Hydrogenolysis of the glycerol-aryl ether model compound 1 and prod-ucts obtained. Conditions: Pd/C 5 mol %, EtOAc/H2O, 120 °C; 1) HCOONH4 4 equiv. 24 h; 2) HCOOH 2 equiv. 12 h.

A number of important findings have been made from these initial studies. Accurate analysis of reaction mixtures revealed the presence of the oxidized dimeric lignin model, that was not observed when reaction was completed.

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Based on this, we assumed that the oxidized dimeric lignin model could be a key intermediate in the cleavage reaction. Also, when the reaction was quenched fast enough and without access of extra oxygen from the air, we observed the presence of the corresponding phenylethanols in the reaction mixtures; whereas exposing these reaction mixtures to air before quenching resulted solely in acetophenones. We assumed that rapid oxidation of the ben-zylic alcohols took place and that the excess of hydrogen donor used was not required (second is evident from the hydrogen balance of the reaction).

Bergman and co-workers also reported that the β-O-4′ ketone was a key intermediate in their reaction.138 Theoretical studies on the bond dissociation energies of the lignin linkages showed that the C–O bond in the oxidized β-O-4′ ketone has a lower BDE then the corresponding native β-O-4′ bond (Figure 8).173 Weakening of the bond makes this motif far more susceptible to cleavage. Several recent reports demonstrated the benefits of the selective ox-idation of benzylic alcohol in the β-O-4′ motif. 103,143-147,175-177

It was shown that the addition of catalytic amount of sodium borohydride and excess of the base could prevent deactivation of palladium in the oxidation of benzylic alcohols.178,179 It was suggested by An et al. that sodium borohy-dride has two functions in the reaction: to clean palladium surface from an oxide layer and to quench the over-oxidized sites that could form during the reaction.178-179 We found that these reaction conditions could be employed in the cleavage of the β-O-4′ ether bond. Initial screening, using β-O-4′ glycerol-aryl ether lignin model, revealed that a number of hydrogen donors promoted the formation of the corresponding ketone in moderate yields (40–60%). This was significantly higher than the results obtain in the absence of a hydrogen donor (18%). Surprisingly, the reaction was productive as well in the presence of carbohydrates (glucose, sorbitol and sucrose). The best result was obtained when glucose (0.4 equiv.) was used. The model compound 1 was dehydrogen-ated in 68% yield (see Paper II, Table 1). The optimized conditions were em-ployed on different C2-β-O-4′ ethers model compounds. The dehydrogenation products were obtained in moderate to good yields (Table 2).

The oxidation of lignin model compounds is more challenging than the ox-idation of benzylic alcohols, due to the retro-aldol reaction that leads to the fragmentation of the propyl chain (Figure 8).146,180 Gratifyingly, no fragmen-tation was observed, when β-O-4′ glycerol-aryl ethers were used as substrates, the corresponding ketones were isolated in 60–80% yield.

Also, we have studied the role of glucose. The absence of any product of glucose oxidation and similar reactivity with pinacol, that cannot act as a hy-drogen donor, suggests that polyols stabilizes palladium on support and pre-vent it from morphological changes. Palladium catalyst particles growth by different processes181-184 is one of the reasons for catalyst deactivation.185 Sim-ilar observations have been reported by other research groups.186-189

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To demonstrate the distinctive benefits of the selective oxidation of the sec-ondary alcohol in the C3-β-O-4′ motif, we performed a sequential transfor-mation of compound 1 (Scheme 10). An aerobic oxidation resulted in the for-mation of ketone 30 in 68% yield. This ketone was subsequently reacted to generate the propylarylketone 32 as the final product under mild reaction con-ditions (80 °C, 4h). We have demonstrated that oxidized β-O-4′ motif was far more susceptible to cleavage under hydrogenation conditions (Scheme 10, step C) than the corresponding alcoholic β-O-4′ motif (Scheme 9).

Scheme 10. Selective oxidation of the benzylic alcohol followed by β-O-4′ bond cleavage. I) Pd/C 5 mol %, glucose 0.4 equiv., 80 °C, 12 h. II) K2CO3 2.5 equiv., 4 h. 80 °C. III) Pd/C from the first step, HCOONH4 2 equiv., HCOOH 1 equiv., 80 °C, 4 h.

The use of carbohydrates as additives in lignin chemistry should be straight forward, because lignin generated in a pulping process contains carbohydrates (Chapter 1.3.2).

Results obtained in Paper I and Paper II in combination with Bergman and co-workers report138 revealed the importance of controlling the amount of re-ducing agent. This suggest a possibility of applying a redox-neutral cleavage method for arylethanol-β-aryl ethers.

Initial attempts to perform the cleavage reaction under inert atmosphere failed. Therefore, we have evaluated the ability of different hydrogen donors to operate at sub stoichiometric amounts (Paper III, Table 1). Among the

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screened additives, sodium borohydride led to a full conversion of the C2-β-O-4′ model compound. We have found that the amount of hydrogen do-nor used equals the amount of oxygen from air present in the reaction vessel (Paper III). An interesting result was obtained when the amount of sodium borohydride was varied (Figure 10). When more than 0.2 equivalents were used, the cleavage reaction was significantly slowed down and phenylethanol was observed in less than 20% yield. This inhibition could be rationalized in the view that the keto-dimer is an intermediate in the cleavage reaction. If deoxygenation is essential for cleavage to take place, an excess of hydrogen in the system will suppress the equilibrium towards starting material accord-ing to Le Châtelier's principle.

Figure 10. Effect of sodium borohydride amount on the reactivity and product distri-bution. Reprinted from Paper III. Copyright 2015 by John Wiley Sons, Inc. Re-printed by permission of John Wiley & Sons, Inc.

Similar suppression of the desired cleavage reaction was observed in Paper I when hydrogen gas was used. To study the effect of the hydrogen atmosphere, two reactions were performed. One reaction was performed at 50 bars hydro-gen pressure, where the other reaction was purged with hydrogen (Scheme 11). When the reaction was performed with an excess of hydrogen, the chemoselectivity changed towards hydrogenolysis of the benzylic alcohol. The C–O bond hydrogenolysis led to that the ether bond cleavage reaction was suppressed, and undesired hydrogenation of the aromatic rings took place. The main product of the reaction–compound 11–was found to be stable at hydro-genolysis conditions, even when the time was prolonged to 12 hours. Phen-ethoxybenzene (11) has previously been reported to be cumbersome to trans-form at various conditions,190-192 and elevated temperatures are needed for C–O bond cleavage to occur.193 However, when hydrogen amount was low, the reaction led to the full conversion in 6 hours to yield the acetophenone and phenol. The outcome of these experiments revealed one of the problems of earlier reported procedures (Chapter 1.4.2), where use of high hydrogen pres-sure results in the formation of less reactive species (like phenethoxybenzene) that conversely needs higher temperature to undergo cleavage.

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Scheme 11. The effect of hydrogen gas amount used on the hydrogenolysis of β-O-4′ bond model compound 10.

With the optimized reaction conditions (5 mol % Pd/C and 10 mol % of so-dium borohydride with ethyl acetate and water as a solvent) a wide range of C2-β-O-4′ model compounds were examined (Table 3). The products of the cleavage reaction were obtained in good isolated yields regardless of the sub-stituents on the aromatic rings.

Not all interunit bond patterns presented in lignin could undergo redox neutral bond cleavage. Three more models that have not been included into Papers I-IV were studied using the same reaction conditions, but in the presence of a stoichiometric amount of sodium borohydride (Scheme 12). Interestingly, phenylcoumaran and dibenzodioxocin model compounds undergo cleavage of ether bonds and the corresponding products were isolated in excellent yields without the need to modify the reaction conditions. Resinol model compound showed to be very resistant to hydrogenolysis even under higher temperatures and longer reaction time.

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Scheme 12. Transformation of various lignin models. Phenylcoumaran (α-O-4′) model 34, dibenzodioxocin model compound 37 and resinol (β-β′) model compound 36.

A Pd/C catalyzed C–O ether bond cleavage at reducing, oxidizing and redox-neutral conditions was demonstrated. The reactions were carried out at mild reaction conditions and do not need Schlenk techniques or inert atmosphere. The reactions were tolerant to the presence of water, which is beneficial for transformations of native lignin.

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3 Elucidation of the reaction mechanism (Paper I and III)

There is a lack of in-depth studies in earlier reports on the mechanisms of lignin hydrogenolysis (Chapter 1.4.2). Recently, a significant effort has been made to elucidate the reaction mechanism of lignin depolymerization. The pi-oneering work of Bergman and Ellman on the redox neutral transformation of lignin model compounds has led to a several mechanistic studies.138 Beck-ham’s group employed density functional theory calculations and kinetics to study the reaction mechanism of ruthenium catalyzed ethanol-aryl ether bond cleavage reaction.139 James’ group performed mechanistic studies with a sim-ilar ruthenium based catalyst, as well as Jameel’s group.194,195

Scheme 13. Proposed mechanism for Ru catalyzed ether bond cleavage in model C2-β-O-4′ compounds.195

These mechanistic studies resulted in the following proposed reaction mecha-nism. The first step is the dehydrogenation of 2-aryloxy-1-arylethanol 8. An equilibrium between keto and enol forms of the aryloxy-1-arylethanone is es-tablished more rapidly with base assistance, followed by ruthenium enolate 40 formation. The insertion into C–O ether bond lead to intermediate 41. Follow-ing hydrogen addition yields a Ru-monohydride 42 and releases phenol. The cycle closes by reductive elimination of the ketone 3 with regeneration of the active catalyst 43.

Rauchfuss’ group proposed a reaction mechanism for the Pd/C catalyzed transfer hydrogenolysis of β-O-4′ ethanol-aryl ethers utilizing dioxane as hy-drogen donor.193 The reaction was suggested to proceed through an insertion

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of palladium into the α-C–H bond of 8 (Scheme 14). The formed phenoxyalkyl palladium (II) hydride 44 could eliminate phenol and the enol form of aceto-phenone.

Scheme 14. Proposed mechanism for Pd/C catalyzed ether bond cleavage in model C2-β-O-4′ compounds.193

Due to the similarity of the mechanisms proposed in our studies, the results of the studies discussed in Paper I will not be presented here.

As it was previously mentioned, we have proposed a reaction mechanism in which the dehydrogenated β-O-4′ ketone is a key intermediate (both for Paper I and III). To verify this, we performed an experiment where the hydro-gen atoms, essential for the reactivity, were substituted by methyl groups (Scheme 15). When hydrogen at the α-position or in the hydroxyl group were substituted by methyl group no reactivity was observed.

Scheme 15. Reaction on model β-O-4′ compounds 46 and 47 that could not undergo dehydrogenation of the benzylic alcohol.

To verify the higher reactivity of the keto dimer versus alcoholic model com-pound a cross-experiment was performed (Scheme 16). First we measured the cleavage reaction rate for compounds 10 and 50 independently. Then reaction of 48 with 10 a as hydrogen donor was studied. It resulted in formation of 12 in 57% conversion and 2-fluorophenol in 55% conversion.

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Scheme 16. Comparison of dimeric ketones reactivity versus dimeric alcohols.

The selectivity towards C–O cleavage reaction of 48 was 96% and this is much higher than what is expected (70%) based on the rate difference. Then we in-terchanged the position of ketone and alcohol. Under identical conditions 33 with 50 were converted to 12 in 27% and 49 in 15% yield. Selectivity towards the ketone was found to be 44%. Again it was much higher than the expected (30%) from rate difference. From these experiments, we have concluded that the oxidation of the benzylic alcohol group is essential for the reaction. Fur-thermore, the oxidized species formed are more reactive then corresponding alcohols. Also in a time-dependent experiment, the reaction curves displayed a steady state type concentration dependence on 33.

Figure 11. Time dependent experiment. Formation of 33 and 12 thought the reac-tion. Reprinted from Paper III. Copyright 2015 by John Wiley Sons, Inc. Reprinted by permission of John Wiley & Sons, Inc.

To determine if the hydrogen in the β-position participates in the overall trans-formation, we exchanged the hydrogen atoms at the β-position with two me-thyl groups (Scheme 17). The reaction resulted in a low dehydrogenation re-action and no β-O-4′ bond cleavage was observed. However, at elevated tem-perature (160 °C) full conversion of 51 to yield cleaved products 53 and phe-nol was observed.

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Scheme 17. Reaction of model β-O-4′ bond compounds that could not undergo enol formation.

The experiments revealed that the enol formation is crucial for reactivity. The mechanism proposed by Bergman, Ellman and co-workers suggest a direct insertion of ruthenium species into C–O ether bond. This was not observed with substrate 51, vide supra, which would be expected if the reaction fol-lowed stated reaction mechanism. The reaction mechanism suggested by Rauchfuss et al. where a direct insertion of the catalyst to the α-C–H bond followed by cleavage has a higher energy barrier and only take place at ele-vated temperatures.

The following reaction mechanism is proposed for the redox neutral reac-tion performed at 80 °C (Scheme 18).

Scheme 18. Proposed reaction mechanisms for the redox neutral transfer hydrogen-olysis of 8. Metal atoms are depicted by surface for clarity.

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The reaction starts with a reversible dehydrogenation of 8 to generate 7 and hydrogen chemically adsorbed on Pd/C. The base (most of our reactions per-formed in the presence of the base) facilitate the keto-enol tautomerisation and this enhances the adsorption of the substrate. It was shown that a number of ketones undergo hydrogenation in the presence of platinum group based cata-lysts in which the enol tautomer is the reactive species.196-198 Two different modes of addition is proposed. The enol could be added across the double bond (2,3-addition) or in a 1,3-addition fashion forming new bonds both through oxygen and carbon center. Following a Horiuti–Polanyi-like mecha-nism,199,200 the hydrogen atom could be added into either α- or β-bonds of in-termediates B and D. In route I, atomic hydrogen inserts into the β-position to generate intermediate A and G. The formation of G is unproductive and lead back to the starting material. However, intermediate A could undergo C–O bond cleavage that will generate intermediate E. A new formed intermediate E decomposes to product 3 and corresponding phenol. The key intermediate of this route is similar to the one proposed by Rauchfuss, however, the overall pathway is distinctly different. In route II, atomic hydrogen inserts into the α-position to give intermediate C. Through a C–O bond cleavage a carbene and aryloxide is formed (F). Reductive elimination of aryloxide and the carbene tautomerization will lead to the final products.

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4 Lignin depolymerisation (Paper I and IV)

With a successful ether bond cleavage method obtained for C2-β-O-4′ and C3-β-O-4′ model compounds in Paper I, we decided to test the depolymerisa-tion method on organosolv lignin. As a bench mark substance, dioxanosolv lignin was prepared from Pine sawdust (Pinus sylvestris) according to the method reported by Wemmer and co-workers.78 This approach utilizes diox-ane and a mineral acid in a catalytic amount for biomass fractionation. We used reaction conditions that were previously optimized for the arylglycerol-β-aryl ether model compound. In a two-step one pot reaction lignin, Pd/C and ammonium formate were heated in ethyl acetate and water for 24 hours after which formic acid was added to the reaction mixture and the reaction was continued for 12 hours. A blank reaction, where the catalyst was omitted was performed as well. All samples from the reactions were subjected to in-depth analysis. Reaction mixtures were analyzed by a size exclusion chromatog-raphy (SEC), NMR, and GC/MS. SEC analysis showed a moderate change towards lower molecular weight fragments (Figure 12). The “blank” experi-ment displayed similar GPC chromatograms. However, a number of draw-backs of this technique should be taken into account: SEC only display the soluble fractions of the polymer, preparation of the sample may alter it, and the detection method and calibration are not straight forward.201

Figure 12. Overlay of (SEC) chromatograms of organosolv lignin before and after treatment with Pd/C and after treatment when catalyst was omitted. Reprinted from Paper I. Copyright 2014 by John Wiley Sons, Inc. Reprinted by permission of John Wiley & Sons, Inc.

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The NMR data showed that most of the lignin interunit linkages were de-graded (Figure 15). Nevertheless, the yield of monomeric fraction was negli-gible. The following compounds were identified using GC/MS spectrometry: coniferyl dihydro alcohol, coumaryl dihydro alcohol, and derivatives thereof. None of these compounds were observed in the control experiment.

Figure 15. 2-D NMR spectra (HSQC experiment) of organosolv lignin before (on the left) and after transfer hydrogenolysis (on the right). The lignin structures identi-fied are: (A) β-O-4′ substructure; (B) β-β′ resinol substructure; (C) β-5′, α-O-4′ phe-nylcoumaran substructure. Reprinted from Paper I. Copyright 2014 by John Wiley Sons, Inc. Reprinted by permission of John Wiley & Sons, Inc.

The main outcome of this experiment was that the nature of the products was similar with compounds obtained from the model studies (Scheme 19). That suggests that the method developed on model compounds is transferable to real lignin samples.

Scheme 19. Comparison of products obtained from transfer hydrogenolysis of the model compound 1 and monomers obtained from organosolv lignin transfer hydro-genolysis.

The moderate results need to be interpreted. Certain bonds in the native lignin polymer were cleaved. However, insignificant changes in the molecular weight of the polymer were observed due to the formation of new bonds. It was proposed by a number of investigators Daima et al.,202 Sarkanen,203 and

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Argyropoulos204,205 that simultaneous recondensation take place when the del-ignification process is carried out under acidic conditions and solvent can not prevent recondensation, by acting as an internal nucleophile.206 Also Wemmer et al. suggested that the method developed for lignin isolation could lead to condensation reactions. Data obtained from 2-D NMR experiments suggested that dioxanosolv lignin underwent recondensation reactions during the frac-tionation processes (Paper I, Supporting Information).207

Recondensation of lignin during pulping is a well-known problem. All cur-rent biomass fractionation processes generated lignin with altered structure where new C–C bonds have been introduced.208,209 Even under relatively mild reaction conditions, such as organosolv pulping, the lignin structure is al-tered.78,210 It would be advantageous to prevent lignin recondensation directly during the fractionation processes. A method to depolymerize lignin would increase its solubility and simplify the separation, and also generate valorized compounds. Organosolv pulping seems to be more applicable for the chemis-try processes we developed. Integration of the lignin depolymerization into organosolv pulping could lead to a better economic calculation. The crucial advantage for the organosolv technique is the formation of formic acid through the carbohydrates piling reaction. This method could be auto cata-lyzed by the organic acids released from wood. 71,211,212 Thereby, the use of formic acid formed from wood could potentially replace exogenous reducing agents.

Recently, similar ideas have been discussed by a number of research-ers.127,156,213,214 All of these studies have one common disadvantage in gener-ating complex mixture of products. A contrast to these studies is the method presented by Song et al.127 In their report, wood sawdust was subjected to pulping in supercritical methanol. The solvent was serving as a reaction media and a hydrogen donor. In the presence of Ni/C, lignin was selectively trans-formed into 4-n-propylguaiacol and 4-n-propylsyringol in excellent selectivity and yields.

We have examined the possibility of a palladium-catalyzed transfer hydro-genolysis of the lignin during pulping process. Untreated pine (Pinus syl-vestris) sawdust was subjected to organosolv conditions: 195 °C, in a 1:1 (v/v) ethanol–water. After the reaction the biomass components were easily sepa-rated. Insoluble cellulose was filtered off to give a homogeneous solution of hemicellulose and lignin. Subjecting this solution to evaporation resulted in a biphasic mixture, where hemicellulose was dissolved in the water phase and oily lignin residue was floating on the top. For accuracy of the quantification and ease of analysis, the lignin fraction was extracted. However, a more be-nign method of separation, such as direct decantation, is possible.

The lignin derived bio-oil was isolated in 54% yield (w/w) based on the original Klason lignin content in the sample. HSQC experiment showed that the corresponding signals from β-O-4′ bond had significantly decreased in in-tensity. The bio-oil was analyzed by GC–MS spectrometry, the analysis

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showed one major compound. After purification by column chromatography a 10:1 ratio of E and Z isomers of 2-methoxy-4-(prop-1-enyl)phenol (57) in a 21% yield (based on Klason lignin content) was isolated.vii

Figure 16. Two-dimensional NMR spectra (HSQC experiment) of organosolv lignin from pine (on the left) and product mixture (on the right). The lignin structures iden-tified are: (A) β-O-4′ substructure; (B) β-β′ resinol substructure; (C) β-5′, α-O-4′ phenylcoumaran substructure. Reprinted from Paper IV. Copyright 2015 by John Wiley Sons, Inc. Reprinted by permission of John Wiley & Sons, Inc.

Scheme 20. Pine wood transfer hydrogenolysis at organosolv pulping conditions and main product obtained.

All our methods were designed to perform cleavage of the β-O-4′ bond. It would be rational to have a starting material that is rich in its content. The β-O-4′ motif is more abundant in birch (Betula pendula) lignin than it is in pine. Transfer hydrogenolysis was performed using the same reaction condi-tions. Purification of the bio-oil by column chromatography lead to a number of products with the 2,6-dimethoxy-4-(prop-1-enyl)phenol (58) as a main product in a 10:1 ratio of E and Z isomers. The compound was isolated in a 49% yield of the total Klason lignin. The monomeric bio-oil components could easily be separated by strait distillation.

vii There is a miscalculation in Paper IV, which we have noticed while working on the thesis. However, in the SI the values to calculate the yield are correct. Also, there is a misprint in the SI the amount of the solvent used in the experiments with biomass should be 200 mL instead of 100 mL.

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Figure 17. Two-dimensional NMR spectra (HSQC experiment) of organosolv lignin from birch (on the left) and transfer hydrogenolysis products mixture (on the right). The lignin structures identified are: (A) β-O-4′ substructure; (B) β-β′ resinol sub-structure; (C) β-5′, α-O-4′ phenylcoumaran substructure. Reprinted from Paper IV. Copyright 2015 by John Wiley Sons, Inc. Reprinted by permission of John Wiley & Sons, Inc.

Scheme 21. Birch wood transfer hydrogenolysis at organosolv pulping conditions and main product obtained.

Figure 18. Schematic depiction of the designed processes. Photos of main biomass components after fractionation and transfer hydrogenolysis. Cellulose, hemicellu-lose, and distilled lignin bio-oil.

We have performed additional experiments on wood lignin transfer hydrogen-olysis that has not be included into the Paper IV. We have demonstrated that flashing the reaction mixture with hydrogen gas prior to heating is not neces-sary and can be omitted without affecting the yield. If oxygen from the air was present in the reaction mixture, formation of vanillin and syringyl aldehyde was observed.

Another interesting observation was that changing the type of the birch used even within the same plant species but from different places and ages could significantly affect the yield of monomeric compounds. The average yield observed was 38±9%. The same observation was reported recently by

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Abu-Omar et al. when his group made an attempt to reproduce Song’s group results utilizing different wood samples than Song did.215

A number of similar approaches to our own have been published re-cently.216-220 Interestingly, palladium on charcoal has been utilized in three of them. Based on the results obtained in these publications and our mechanistic investigation the following mechanism has been proposed (Scheme 22). Sels and co-workers have showed that a palladium-catalyzed hydrogenolysis of wood lignin under hydrogen atmosphere will give 4-n-propanalsyringol and 4-n-propanguaiacol in excellent selectivity and yield. These results are in agreement with our mechanistic studies, vide supra, in which a hydrogenoly-sis of α-C–O bond will dominate under hydrogen atmosphere. Under condi-tions when the system lacks hydrogen at the beginning of the reaction (before formic acid or another hydrogen equivalent has not been released from the biomass) dehydrogenation will take place forming a very reactive ketone. Ap-plying acidic conditions during organosolv pulping, water will be eliminated to give the α,β-unsaturated ketone. This intermediate is reduced to the corre-sponding isoeugenols.

Scheme 22. Comparison of two main pathways observed in Pd/C catalyzed lignin hydrogenolysis.

We have demonstrated a tandem organosolv and palladium-catalyzed transfer hydrogenolysis of lignin from pine and birch wood, using only an endogenous hydrogen source. Lignin was transformed into a bio-oil in high selectivity to-wards a few monomeric products.

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5 Concluding remarks and outlook

This thesis describes the development of a new palladium-catalyzed oxidation of the lignin model compounds and transfer hydrogenolysis under reductive and redox-neutral conditions of the lignin model compounds as well as lignin.

The first part focuses mainly on the method development utilizing model compounds mimicking the native lignin bond patterns. Efficient methods for the transfer hydrogenolysis of model compounds resulted in excellent yields of cleaved products under both reductive and redox-neutral conditions. Also a selective method for the oxidation of model compounds was developed to obtain the key intermediate–dimeric ketones–in good yields.

In the second part, an in-depth mechanistic study has been performed. This led to the understanding of what structural motif of lignin that were important for reactivity, and the nature of the reactive intermediates. Also, the nature of the active catalyst was studied, where we found that if the metal surface could be controlled, a low energy pathway for the depolymerization could be achieved.

In the third part, lignin depolymerization under organosolv pulping condi-tions was developed. Combining the palladium-catalyzed transfer hydrogen-olysis with a biomass fractionation process allowed the formation of lignin bio-oil, hemicellulose and cellulose in one step. The obtained bio-oil was com-posed of monomeric molecules to a large extend, from which propenyl aryls were isolated in good yields. An advantage, compared to other lignocellulose fractionation techniques, was that the valorization of both carbohydrate and lignin part of biomass could take place in one process.

In my opinion, further development of methods for biomass fractionation, which can enable the parallel valorization of three main components of bio-mass is needed. Such new pulping techniques, that would take into account lignin and hemicellulose valorization in addition to cellulose, can become a core technology for second generation biorefineries.

The lignin part of the biomass can answer the need for green aromatic building blocks in the manufacture of materials, pharmaceuticals, transporta-tions fuels, etc.

In these perspectives, results presented in this thesis are very promising. Still a robust and recyclable catalysts based on abundant and cheap metals are needed, control and conversation of all three streams: cellulose, hemicellulose, lignin should be studied and economically evaluated.

Thus, an economy based on the biorefinery concept is foreseeing.

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Summary in Swedish

Idag kan kemister syntetisera väldigt komplexa molekyler med hjälp av tek-niker som är utvecklade för oljebaserade kolkällor. I en framtid kommer detta sakteligen ändras då flera nackdelar av den oljebaserade ekonomin har blivit uppenbara. Även om elektricitet kan substituera energianvändningen i flera applikationer så kommer det att behövas kolkällor för att kunna tillverka avan-cerade material, läkemedel, transportbränsle, finkemikalier osv. För ett nor-diskt land som Sverige finns det stora möjligheter att använda växtriket som billig kolkälla. För att kunna göra detta så måste de kemiska metoderna ändras i grunden då växtriket är uppbyggt av alkoholer och etrar till skillnad från oljan som är uppbyggd av kolväten.

I den här avhandlingen så har katalytiska transformationer av lignin stude-rats. Lignin är en biopolymer som finns i lignocellulosa (ej ätbara delar av växtriket). Ett träd består ungefär till 30% av lignin viktmässigt, men energi-värdet är ungefär 50% av trädet. Lignin är en oregelbunden polymer med en hög andel aromater som sitter ihop med eterbindningar. Idag så genereras det lignin vid pappersmassatillverkning. En väldigt liten del av detta lignin an-vänds som bindemedel i olika applikationer. Till största delen så förbränns ligninet till ett lågt värde för att producera elektricitet. Då lignin är en av de få källor till växtbaserade aromater och idag en lågvärdesprodukt, så finns det ett intresse att utveckla gröna kemiska metoder att förädla den.

Nyckeln till att kunna använda lignin som startmaterial inom kemin är att kunna depolymerisera ligninpolymeren till monomera aromatiska enheter. I denna avhandling så presenteras en studie på hur en specifik övergångsmetall ”Palladium” klyver en specifik bindning i lignin. Β-O-4′ bindningen är den vanligaste kemiska bindningen mellan de monomera aromatiska enheterna i ligninpolymeren. Dels har en reduktiv, en oxidativ och en redox neutral metod utvecklats för att klyva modellsubstanser av lignin. Dessutom, har en mekan-istisk studie utförts där en lågenergi-reaktionsväg för att klyva β-O-4′ bind-ningen funnits. Dessa studier har utmynnat i utvecklingen av ett helt nytt kon-cept kring att transformera lignin. I denna transformation så använder vi trä som startmaterial och får fram isoeugenol, en högvärdesprodukt från lignin, tillsammans med cellulosa och hemicellulosa.

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Acknowledgements

There ain't no surer way to find out whether you like people or hate them than to travel with them.

—Mark Twain

First of all, I would like to express my sincere gratitude to my supervisor Dr. Joseph S. M. Samec for the opportunity to perform Ph. D. studies in your group. Thank you for your patience, wise guidance and support. I appreciate the freedom you gave me to manage this research. It was a wonderful four-year trip to the lignin chemistry. A special thanks to my co-supervisor Prof. Pher G. Andersson. I’m grateful for all your kind help and expertise.

I would like to thank past and present members of Joseph’s group and RenFuel Company: Dr. Alexander P. for being my guide and fume hood neighbor from the first days in Uppsala, and for the all fun and crazy things we’ve done. Alban C. for nice talks, proof reading of all, what I believed was written in English, and for introducing me to whiskey. Dr. Supaporn S., we had a hard time with our “first baby”, but I have learned a lot from you and it was a pleasure to work together. Dr. Srijit B. for all fruitful discussions regardless was it about chemistry or life, looking forward your first independent publi-cation. Monali D., it was nice to work together and good luck with your de-fense! Dr. Christian D., being patient with me and Alex chatting Russian all the time. Dr. Joakim L., for being almost a co-supervisor to me. Anon B., Dr. Sunisa A. and Pemikar (Cherry) S., Volker R., Dr. Beliram H., Sandra K. O. and Dr. Rahul W. for making this lab alive 7-eleven fashion (not local version) and for all nice fikas and chatting. Elena S., cleave it and carry on!

This thesis would probably never be published without your combined ef-fort. Carina S., Dr. Lukasz P., Dr. Joakim L., Prof. Helena G., Dr. Christian D., Alexey V., Aleksandra D. Thank you for proofreading and wise sugges-tions.

Many thanks to people at BMC: The 14th group elements team: Kjell J., Dr. Rafaello P., Aleksandra D., Rabia A. and Prof. Henrik O. for keeping us excited and for discussions on DFT calculations and photochemistry. Good luck to all of you! Moving right the periodic table and the corridor: Jia-Fei P. for not let me burn out at work, literally, and the rest of the oxygen family members–Jia-Jie Y. and Dr. Vijay P. S–providing me kugelrohr and fancy

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chemicals and there spiritual leader–Prof. Lars E. Prof. Olle M. for help and excellent discussions on chemical kinetics. Your talk on poisons in fine liter-ature is inspiring; hope the book will be available in English soon. AGHG group: Anna L., Xiao H., Magnus B. and Michael N., Hao H. Thank you for making my day and being helpful with NMR. Special thanks to Prof. Adolf G.–our NMR-guru and best Santa ever, for all your help with NMR. Prof. Lars B. and his nice group: Aleksandra B. and Jie Y. Also, many thanks to Dr Eszter B. and her group: Dr. Anna A., Ruisheng X., and Daniel K. Special thanks to Prof. Mikael W., Emil H., Prof. Jan K., Lina L. for all the lectures and talks they gave making our department more Bio. Dr Tobias A. whose yoke-fellow I was in our war with the GC–MS system. Special thanks to Inger H. and Johanna J. providing me with all types of documents for Swedish officials. And our technicians: Gunnar S. for supplying us and Bo F. for making our PCs running.

Many thanks to people who have fulfilled my life: Huan M., Carina S., Karthik D., Dr. Lukasz P., Dr. Emilien D., Alban C., Dr. Xu Q. and Dr. Byron P. Thank you for all great nights at O'Connor's, for all trips we have made and barbecues we have burned, and for other after work activities. Also, thanks go to our small Russian-speaking community, here in Uppsala: Dr. Alexander P., Michael N., Dr. Konstantin A., Dr. Irina S., Vladimir T. and Dr. Eldar A.; in Lund: Mikhail V. K. and in Stockholm: Alexey V., Olga K. and Maria V. Thank you for excellent time we have. Alexey, good luck with your defense!

Everything has its start. I would like to express my sincere gratitude to my first mentor in chemistry Aleksej A. Sjomkin; my Alma Mater and people who were leading me by the hand through the world of chemistry: Prof. Vladimir I. Terenin for being my mentor for eight years, and supervise me both in sci-ence and life–thank you, and Prof. Mikhail A. Proskurnin for teaching me to shoot a laser, and at SSNAB: Dr. Elena P. Rusanova for introducing me the world of food chemistry and biopolymers.

I would like to acknowledge Swedish Energy Agency for financial support of this work and C. F. Liljevalch J:ors stipendiefond, Stiftelsen ÅForsk, Helge Ax:son Johnsons stiftelse and Kungl Vetenskaps Akademi (The Royal Swe-dish Academy of Science) for their generous financial support in providing travelling grants.

Other things may change us, but we start and end with family.

—Anthony Brandt

Thanks to my dear wife Aleksandra D. and my parents and relatives. Спасибо вам - Юля и Вадим, мои дорогие бабушки - Лида и Нина, и конечно, Надя. Спасибо вам большое за помощь и поддержку. Спасибо, Саша, за терпение. Я вас всех очень люблю!

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