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Perspective
Vanillin production from lignin and its use as a renewable chemical
Maxence Fache, Bernard Boutevin, and Sylvain Caillol
ACS Sustainable Chem. Eng., Just Accepted Manuscript • DOI: 10.1021/
acssuschemeng.5b01344 • Publication Date (Web): 10 Dec 2015
Downloaded from http://pubs.acs.org on December 14, 2015

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Page 1 of 23 ACS Sustainable Chemistry & Engineering

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4 Vanillin production from lignin and its use as a renewable chemical
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6 Maxence Fache a, Bernard Boutevin a, Sylvain Caillol *a
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9 a
10 Institut Charles Gerhardt Montpellier UMR 5253 - CNRS, Université Montpellier, ENSCM, 8 rue de
11 l’Ecole Normale, 34296 Montpellier, France
12 * Corresponding author: Sylvain Caillol, sylvain.caillol@enscm.fr, +33 4 67144327
13
14 ABSTRACT
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The use of vanillin as building block for the chemical industry is discussed in this article. Vanillin is
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17 currently one of the only molecular phenolic compounds manufactured on an industrial scale from
18 biomass. It has thus the potential to become a key-intermediate for the synthesis of bio-based polymers,
19 for which aromatic monomers are needed to reach good thermo-mechanical properties. After a first part
20 dedicated to the current sourcing of vanillin, this article focuses on the alkaline oxidation lignin-to-
21 vanillin process, reporting advantages and limits, discusses the various post-depolymerization methods
22 for product isolation and finally examines the outlook for the wider use of vanillin as a key-building block
23
for the chemical industry.
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25
26 KEYWORDS
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28 Vanillin; lignin; biobased; phenolic; process
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30
31
32 INTRODUCTION
33 Currently, petro-based resources are raw materials for the vast majority of organic chemicals and
34 polymers. However, the unavoidable shortage of non-renewable resources due to an ever-rising demand
35 will be accompanied by major supply problems and price increases, leading to social repercussions
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37 difficult to predict. Finding alternative solutions from the biomass feedstock is thus a top priority. In this
38 context, the concept of bio-refinery started gaining importance.1 Similar to the crude oil refinery, the
39 idea is to (bio)chemically turn each component of the feedstock into a variety of useful products.
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41 Bio-based chemicals are already industrially available but most of them are aliphatic or cycloaliphatic, for
42 instance derived from cellulose2, starch2 or triglycerides3. However, many key chemicals are aromatic
43 compounds, ultimately derived from petroleum.
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45 The production of shale gas increased massively in recent years. Shale gas is lighter than petroleum,
46 which forced many petro-chemical majors to adapt to this influx of lighter raw material.4 This change
47 drastically decreased the yield of heavier co-products such as aromatics (as well as propylene and
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49 butadiene). Consequently, aromatics availability have decreased and their price have increased.5 Thus,
50 there is a challenge for finding aromatic building-blocks derived from biomass. In Nature, aromatics are
51 found as (poly)phenolics.
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53 The three major classes of phenolics from renewable resources are lignin, tannins, both extracted from
54 wood, and Cashew NutShell Liquid (CNSL).6 Their relative commercial availability is displayed in Figure 1,
55 along with other general sourcing information.
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24 Figure 1: Commercial availability of lignin7, 8, tannins9 and CNSL10, 11
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There is a striking paradox between the enormous amount of (poly)phenolic materials available from
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27 biomass – especially lignin and tannins – and their relatively under-developed industrial use compared to
28 aliphatic resources like vegetable oil.
29 This might be explained by the fact that each of these resources has drawbacks limiting their use. More
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31 precisely, the volume of CNSL available is 125.000 tons per year.10 It makes it an undoubtedly interesting
32 resource for niche applications, but this potential volume might not be sufficient to make it a reliable
33 renewable resource. Also, CNSL is a mixture of phenolics all bearing a C15 alkyl chain on the meta-
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35 position, which gives CNSL-based polymers with low Tg. Lignin and tannins, on the other hand, are
36 available in potentially enormous amounts from biomass. However they are highly complex
37 poly(phenols). Their polymeric nature, difficulty of process, and variability depending on the plant,
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39 method of extraction etc. prevent them from being an industrial reality as raw materials. For the time
40 being, handling molecular compounds isolated from the depolymerization of these feedstocks seems a
41 more viable option. The depolymerization of lignin especially has been intensively studied recently.12, 13
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43 Indeed, the large volumes of lignin produced annually prompted a number of works dealing with its
44 catalytic depolymerization to smaller species.
45 Of specific interest are the molecular compounds ferulic acid and vanillin. Ferulic acid can be obtained by
46
47 alkaline or enzymatic hydrolysis of lignins.14 The main raw materials for its production are rice bran,
48 sugarcane bagasse, and sugar beet pulp. Around 318 tons are produced yearly,15 which makes it the
49 second most available molecular phenolic compound from lignin, far behind vanillin. Indeed, vanillin is
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51 the most available pure mono-aromatic phenol currently produced at an industrial scale from lignin.16
52 Around 20,000 tons of vanillin are produced per year17, 15% of which coming from lignin18 (around 3,000
53 tons/y). Thus, vanillin has the potential to be a key renewable aromatic building-block.
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The advantages of vanillin are numerous: it is a safe compound, aromatic, and it bears two reactive
56 functions that can be chemically modified (the methoxy group being less reactive than the aldehyde and
57 phenol functions). Vanillin can thus be considered as a difunctional compound, which is useful to prepare
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3 thermoplastic polymers. Indeed, raw resources like lignin usually are multifunctional. Preparing
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5 thermoplastics from them is thus more challenging than preparing thermosets. Vanillin is also already
6 produced from lignin which means that it is renewable and does not compete with food sources. It is
7 available on an industrial scale from well-described, ever improving processes.
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9 The aim of this article is to examine in detail the pieces of information available in the literature on the
10 methods of vanillin production, especially on the lignin-to-vanillin processes. From this review, it is
11 possible to highlight the potential of vanillin as a renewable chemical, especially in the field of polymer
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13 science, in which large volumes of raw material are necessary.
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15 DESCRIPTION AND SOURCING
16 Brief history
17
18 Vanillin (4-hydroxy-3-methoxybenzaldehyde, m.p. 81-83°C) is the highest volume aroma chemical
19 produced worldwide.19 It is produced from a variety of sources, namely oil (85%), woody biomass (15%),
20 orchid pods (<1%). It is the chief constituent of natural vanilla flavoring. As such, it is used as a flavoring
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22 and fragrance ingredient in the food or cosmetic industries and the market for vanillin consists mainly of
23 large multinationals in the field of flavor and fragrance (e.g. International Fragrances and Flavors (IFF),
24 Givaudan, Quest, Danisco, Symrise).20 The manufacture of chocolate and ice-cream are especially
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26 demanding in vanillin, as it is used at levels of 0.1 to 0.9%w. in these products.19 Thus, the large
27 producers of ice cream (such as Unilever) and chocolate (Nestle, Cadbury, Suchard) are important
28 players on the vanillin market.20 As far as the aroma and fragrance fields are concerned, the vanillin
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30 produced from lignin is economically competitive because, even if more expensive, it displays an
31 aromatic intensity 1.2 times higher than petro-based vanillin.21 Interestingly, ethyl vanillin is also used
32 commercially as a vanilla flavoring that has about 3.5 times the flavor intensity of vanillin itself, but is
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34 exclusively synthetic.22 Vanillin is also an important intermediate for the synthesis of fine chemicals and
35 pharmaceuticals (for example L-3,4-DihydrOxyPhenylAlanine, L-DOPA).23 Apart from these major
36 applications, examples of other vanillin uses are as a ripening agent to increase the amount of sucrose in
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38 sugarcane, or as a base compound for the preparation of sunscreen.19
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40 The history of vanillin begins with Cortez, the famous Spanish conquistador, who is said to have been
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served a chocolate drink flavored with vanilla by the Aztecs in about 1520. He brought the knowledge of
43 both chocolate and vanilla back to Spain and Europe, where they rapidly became popular.22 Gobley, in
44 1858, was the first to isolate and identify the vanillin constituent of the vanilla bean and to confirm that
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this was the chief flavor component. The vanilla aroma was so popular that in 1875, less than 20 years
47 from its initial isolation, synthetic vanillin prepared from eugenol by its isomerization followed by
48 oxidation became available in France and the United States.22 Eugenol is the main component (ca. 90%)
49
of clove oil, the essential oil extracted of the clove plant. The production of vanillin from the lignin of
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51 waste sulfite liquor began in North America in 1936-1937 based on the works of on the one hand,
52 Sandborn, Salvesen, and Clemens24 and on the other hand of Hibbert and Tomlinson25. This method
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developed rapidly to become the main production process for synthetic vanillin. Even in the 1970’s,
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55 when the use of vanillin dramatically shifted from flavor to chemical intermediate22, this process
56 remained unequalled. The vanillin production of Ontario Pulp and Paper became so profitable that the
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production scale was gradually expanded to 3.4 million kilograms per year by 1981, which was sufficient
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3 to supply 60% of the then current world market22. However, almost all the lignin-to-vanillin plants closed
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5 at the end of the 1990’s due to increased environmental concerns towards the caustic effluents of the
6 process, decreased lignin availability due to the increasing use of the Kraft process for pulping - in which
7 lignin is burnt to produce energy - , and also due to the arising of cheap chemical intermediates from
8
9 petroleum. Since then, the dominant feedstock for vanillin is petroleum.22 Through all these years, the
10 production of natural vanilla extract from vanilla beans remained active as this extract contains, apart
11 from vanillin, many other minor flavoring constituent that makes the natural extract unique, and thus
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13 much appreciated in some food markets where cost is not the top concern.22
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15 Current sourcing
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The worldwide production of natural vanilla extract is only 40 to 50 tonnes per year, which represents
18 less than 1% of the total vanillin production.17 Vanilla beans are harvested from species of the Vanilla
19 orchid, a tropical climbing plant grown in Mexico, Madagascar, Java, Reunion, and Tahiti, and that has to
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be manually pollinized to attain reasonable yields, which is a very laborious task that discourages the
22 cultivation of these plants at a very large scale.20 The vanillin in the green bean is found as vanillin
23 glucoside. During the curing process, the vanillin glucoside is enzymatically hydrolyzed to glucose and
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25 vanillin as shown in Scheme 1 22.
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31 Scheme 1: Vanillin glucoside hydrolysis to vanillin and glucose
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33 When vanillin is produced from vanilla beans by this process, the labeling on the consumer product may
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be indicated as “natural vanilla flavor”, which is a powerful marketing argument. According to EU
36 regulations, vanillin can be sold as ‘‘natural vanilla aroma’’ only if the base material and the process are
37 natural.
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39
However, synthetic vanillin cannot be labeled as such, but rather as "synthetic" or "artificial" vanilla
40 flavor.26 Still, 85% of the world supply is produced from petro-based intermediates, especially guaiacol.23
41 There are different ways to prepare vanillin from guaiacol; however the most employed is the Riedel
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process. The first step of this process involves the condensation of glyoxylic acid onto guaiacol to
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44 produce vanillylmandelic acid as shown in Scheme 2 27:
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54 Scheme 2: Industrial route of vanillin production from phenol
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56 The advantage of this reaction is that the glyoxylic acid condensation is highly region-selective towards
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the para position, which avoids side-products and thus costly separations.28 The preparation of
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3 vanillylmandelic acid has been studied in detail and reported to have a yield of 74% based on glyoxylic
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5 acid.29 The low conversion to product based on glyoxylic acid is probably due to Canizzaro reaction of
6 glyoxylic acid in the presence of alkali, leading to the formation of glycolic acid and oxalic acid.19 In the
7 second step, the vanillylmandelic acid is submitted to an oxidative decarboxylation to form vanillin. This
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9 reaction is usually carried out using a copper(II) hydroxide/oxygen system in an aqueous alkaline
10 medium at a temperature of 80 to 130°C.
11 Rhône Poulenc, now part of the Solvay group, is reported to have developed the process further with the
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13 aim to improve the atom efficiency.28 Their process is reported in Scheme 3:
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21 Scheme 3: Solvay’s route of vanillin production from phenol
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23 The labeling regulation subtlety between "artificial" and "natural" vanillin, and the high price and limited
24 availability of vanillin from vanilla beans led to the development of bio-syntheses of vanillin, which could
25 be labeled as "natural". The most successful strategies are microorganism-based approaches. They have
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27 been extensively reviewed17, 30, 31 and consist in using bio-transformation reactions from native or
28 genetically-modified fungi32, 33, yeast[y] or bacteria[y] to produce vanillin (or a derivative in a different
29 oxidation state) from a structurally close substrate. The most available and promising substrate is ferulic
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31 acid.32, 36, 37 Other promising substrates include glucose38, 39, and lignin fragments31.
32 The Belgian specialty chemical company Solvay, a leading producer of synthetic vanillin after its purchase
33 of Rhodia, makes "natural" vanillin from ferulic acid.17 The process, originally developed by Givaudan and
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35 exclusively licensed to Rhodia, involves the fermentation of this substrate by bacteria.40 Recently, a new
36 enzymatic process for the synthesis of vanillin using D-glucose as the carbon source was reported.38 The
37 Swiss biotech firm Evolva also begins with sugar to produce vanillin by yeast fermentation. Both Evolva
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39 and Solvay are working to scale up their natural vanillin production. Evolva has a partnership with
40 International Flavors & Fragrances to complete development and ready the product for
41 commercialization.17, 39 This small twist in words between "artificial" and "natural" vanillin provided a
42
43 financial drive sufficient to lead to huge investments in bio-technologies. However, when made from
44 petrochemical sources, vanillin costs as little as $10 per kg, whereas vanillin made in a way that can be
45 labeled natural can cost hundreds of dollars per kg.17 The bio-based routes presented are therefore not
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suitable for a use of vanillin in polymer synthesis, in which low prices and large volumes are major
48 requirements. The extraction of vanillin from cow dung in sub-critical water, a method that won the
49 2007 Ig Nobel Prize for chemistry, also has a way to go.[41] Petro-based vanillin is not desirable as it is a
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non-renewable feedstock. However, a last production method, in which vanillin is produced from lignin,
52 would be suitable.
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55
VANILLIN PRODUCTION FROM LIGNIN
56 Lignin depolymerization
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3 The lignin-to-vanillin process is a rather old means of producing vanillin, as presented above. Nowadays,
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5 as mentioned, 15% of the overall vanillin production comes from lignin.18 More precisely, it comes from
6 lignosulfonates, mostly by the Norwegian company Borregaard that has been running a lignin-to-vanillin
7 plant in Sarpsborg, Norway for more than 50 years. For the last 20 years, they have been the only ones
8
9 using this process.17
10 The process starts with the sulfite pulping of wood, which gives the lignosulfonate-rich sulfite liquor as a
11 by-product. This liquor is further processed as shown in Scheme4: 42.
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19 Scheme 4: Schematic process for the production of vanillin from wood
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21 Industrially, only lignin from the sulfite pulping process is used to prepare vanillin, despite the fact that
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this kind of lignin accounts for less than 10% of the total of lignins extracted.23 Kraft lignin, representing
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24 the vast majority of lignins extracted, are usually burned for energy to ensure economical viability of the
25 pulping process.18 However, more and more works investigate the depolymerization of all kinds of
26 lignins, including milled wood lignins, organosolv lignins and lignins obtained from enzymatic
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28 processes.12, 13 This is consistent with the bio-refinery approach, in which lignins are considered as a
29 source of medium-to-high added-value aromatic building-blocks instead of being burned.18, 43 This is also
30 the approach envisaged in this work, which deals with the depolymerization of all kind of lignins under
31
32 alkaline and oxidative conditions to produce vanillin.
33 The process for vanillin production itself consists of treating an aqueous solution of lignin with oxidants,
34 at alkaline pH, and high temperatures and pressures, in order to depolymerize the lignin and obtain
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36 vanillin. Given the complexity and heterogeneity of lignins, establishing a reaction mechanism is
37 extremely challenging. Moreover, there are many parameters influencing the process, which adds even
38 more to the complexity of bringing elementary steps out. Nevertheless, the mechanism shown in
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40 Scheme 5 has been proposed in the literature.44
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24 Scheme 5: Proposed mechanism for lignin depolymerization leading to vanillin
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This mechanism of lignin oxidation to vanillin has been and is still the subject of much debate and
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27 research44-49 and is not fully understood yet. The recent work of Pacek et al.49 pointed out that vanillin
28 can be formed in the absence of O2 by the sole action of lignin alkaline hydrolysis. The authors estimated
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that “overall, approximately 55% of the vanillin was produced by hydrolysis and 45% by oxidation”.
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31
32 Parameters influencing the reaction
33 The main parameters influencing the alkaline oxidative depolymerization of lignin are summarized in
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35 Table 1:
36 Table 1: Main parameters influencing the alkaline oxidative depolymerization of lignin
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38 Lignin natural origin
39 Prior processing (pulping process, isolation, pre-
40
Lignin treatment etc.)
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42 Mw, PDI
43 Impurities
44 Lignin concentration in feed
45 Temperature
46
Pressure
47 Reaction
48 Base nature and concentration
conditions
49 Oxidant nature and concentration
50 Catalyst nature and concentration
51 Duration of reaction
52
Works in which the effect of one or several of these parameters is investigated are numerous. Reviewing
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54 them is a tedious task that has already been accomplished in several papers, especially by Rodrigues and
55 his team at the LSRE laboratory in Porto,18, 23. Therefore, this section is mostly based on the conclusions
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drawn by this team, as well as on several other especially relevant experimental works.
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3 Parameters linked to chemical engineering considerations such as batch or continuous process, shape of
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5 reactor and stirring, or catalyst shape and disposition can also potentially play a major role in the yield of
6 the reaction.20 For instance, in the case of O2 used as the oxidant, its transfer to the solution is of
7 paramount importance.18, 49 Most of the experiments reported in literature have been performed in
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9 batch. However, from an industrial point of view, the continuous process of lignin oxidation is more
10 attractive due to the large liquor volumes to be treated in a pulp industry, to an easier control of the
11 process to attain constant product characteristics, and to lower overall investments and operating
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13 costs.18
14 The oxidation of lignin using alkaline nitrobenzene has been used since the 1940’s to elucidate the
15 structure of lignin: the phenolic products from this oxidation are either derived from hydroxyphenyl (H),
16
17
guaiacyl (G), or syringyl (S) units. Indeed, nitrobenzene is the oxidant that gives the highest yields.[20]
18 However, nitrobenzene is expensive and its reduction products are harmful and difficult to separate,
19 which is why it has not been accepted as an industrial approach.50 Other catalystsoxidants such as CuO
20
are preferred because they can easily be separated and regenerated.20 However, CuO gives lower yields
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22 than nitrobenzene.51 During alkaline CuO oxidation of lignin, vanillin is also slowly converted to vanillic
23 acid.50 O2 is also a possible oxidant for the production of vanillin from lignosulfonates, with CuSO4 as a
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catalyst. Using CuSO4 as a catalyst instead of CuO as a reactant allows a drastic reduction of the amount
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26 of copper that has to be removed after the reaction. O2 is a stronger oxidant than CuO or nitrobenzene,
27 which makes the reaction less selective.50 O2 is an oxidant of choice because of its environmental
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friendliness, high atom economy, and low price (use of air).23 Reaction parameters with this system were
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30 thus finely tuned by statistical experimental design and mathematical modelling to attain good yields.52
31 O2 partial pressure and reaction time have to be balanced in order to avoid vanillin oxidation to vanillic
32 acid and thus increase vanillin yield.
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34 A high pO2 value reduces reaction time but leads to an increased rate of vanillin oxidation.18, 49 A
35 temperature increase can also shorten the reaction times. Overall, short reaction times (30 min - 2 h),
36 high temperatures (130 - 200°C) and severe oxidative conditions seem to work best.51, 53, 54 In their study,
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38 Pacek et al.49 showed that even if usual reaction temperatures are 150-170°C, the alkaline hydrolysis
39 reaction starts around 120°C. They also showed that vanillic acid is not solely due to vanillin oxidation,
40 but comes also from lignin hydrolysis.
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42 The pH is also a crucial parameter for vanillin production. During the lignin oxidation process, the yield of
43 vanillin decreases when the pH value begins to decrease. Indeed, high alkali concentrations (pH > 12)
44 allow to reduce vanillin degradation whereas at lower pH values (< 11.5), vanillin losses by oxidation
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46 become more significant and a sharp decrease in vanillin yield is observed.18, 53 High concentrations of
47 alkaline species are thus necessary. Decrease of pH leads to almost complete suppression of vanillin
48 formation. This phenomenon was attributed to the protonation of reaction intermediates, more basic
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50 than the phenolics produced, (vanillin pKa = 7.4).54
51 Finally, the lignin itself is of course of importance: low molecular weight lignin tends to give better
52 results52, the presence of residual sugars is highly unfavorable55, and the fewer transformations or
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54 chemical treatments lignin suffers, the better the phenolic aldehydes yield.51, 56 The latter point is of
55 importance as the isolation procedure can modify the chemical structure of lignin. More specifically, if
56 lignin separation is performed by acid precipitation, condensation reactions can occur, especially at the
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3 position 5 of the aromatic cycle in G units, which leads to bi-aryl structures56 (Figure 2), and decreases
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5 the yield of vanillin.18, 51
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Figure 2: 5-5’ linkage arising from the condensation of two G lignin fragments
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15 GS lignins tend to give better depolymerization yields since they comprise more S units, more stable to
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17 condensation because of the substitution of the position 5 by a methoxy group.
18 Alternative methods to obtain vanillin are still actively investigated in the literature.57-61
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20
21 Depolymerization products
22 The alkaline oxidative depolymerization of lignin gives a complex mixture of products23, as illustrated by
23 Tables 1 and 2. These products can be classified into oligomeric products, phenolic, and non-phenolic
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25 compounds. Oligomeric products18 are either unreacted lignin fragments or come from condensation
26 reactions as discussed above. The amount of oligomeric residue varies a lot depending on processing
27 conditions and lignin type.
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29 In most studies, authors focus their efforts in detecting specific phenolic compounds of interest. These
30 compounds are usually di-functional and include of course vanillin but also other aldehydes like
31 syringaldehyde, acids, or ketones. The most studied di-functional molecular phenolic compounds
32
33
obtained for G and GS lignins are detailed in Table 2:
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3 Table 2: Products of the alkaline oxidative lignin depolymerization usually studied in the cases of
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softwoods and hardwoods
5
6 Typical yields in Typical yields in
7 Compound Formula softwoods hardwoods
8
9
10 6-12% 1-5%
11 vanillin
52, 53, 62-64 50, 55, 62, 64-70
12
13
14
15
aldehydes

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17 syringaldehyde 0-0.7% 4-16%
18 62 50, 55, 62, 64-70
19
20
21
22
23 p-hydroxy- 0-0.5% 0-0.5%
24 benzaldehyde 62, 64, 71 50, 62, 64-66, 69
25
26
27
28
29 0.5-1.5% 0.2-2.4%
30 vanillic acid
64 55, 64, 67, 68, 70
carboxylic acids

31
32
33
34
35
36 0.5-3.9%
syringic acid N.D. 55, 64, 67, 68, 70
37
38
39
40
41
42 0.6-6.4% 0.3-2.6%
43 acetovanillone
62, 71 50, 62, 65, 66, 68
44
ketones

45
46
47
48
49 1.5-4.2%
acetosyringone N.D. 50, 62, 65, 66, 68
50
51
52
53
54
55 A non-exhaustive list of other compounds found in lignin alkaline oxidative depolymerization mixtures
56 and less often studied in detail is given in Table 3. Interestingly mono-phenolics such as guaiacol or
57 syringol are often mentioned as depolymerization products but their amount is usually not given.
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3 Another compound of interest is the dehydrodivanillin, a by-product of vanillin production formed by
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5 aromatic oxidative coupling of two vanillin molecules. Being an aromatic di-functional phenol, this
6 compound might have many applications, especially in the field of bio-based polymers.72 Given the high
7 pH of the crude mixture, all phenolics are present as phenolates, difficult to extract from water and/or
8
9 isolate. The reaction mixture also contains non-phenolics such as lactones23 or the other compounds
10 shown in Table 3:
11
12
13 Table 3: Other products of the alkaline oxidative lignin depolymerization found in literature
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15 Compound Formula Reference
16
17 Phenol 73
18
19
20 Benzoic acid 65
21
22
23
24 Hydroxybenzoic acid 65
25
26
27
28 Guaiacol 23, 50, 62, 73
29
30
31 Catechol 50, 73
32
33
34
35 3-Methoxy catechol 73
Phenolics
36
37
38 Syringol 23, 50, 62, 73
39
40
41 Pyrogallol 73
42
43
44
45 4-Methyl catechol 73
46
47
48
49 4-Methyl syringol 73
50
51
52
53 4-Ethyl catechol 73
54
55
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2
3
4
5 2-(4-Hydroxy-3-
55
6 methoxyphenyl)acetaldehyde
7
8
9
10 2-(4-Hydroxy-3,5-
55
11 dimethoxyphenyl)acetaldehyde
12
13
14
15
16 Dehydrodivanillin 52
17
18
19
20
21 1,2-Bis(4-hydroxy-3-
52
22 methoxyphenyl)ethane-1,2-dione
23
24
25
26 1,2,3-Trimethoxy benzene 73
27
28
2-Hydroxy-3-methyl-2-
29 62
30 cyclopentenone
31
32 3-Ethyl-2-hydroxy-2-cyclopentenone 62
33
34
35 3,4-Dimethyl maleic anhydride 62
36
37 Butyrolactone 62
38
39 Other Maleic acid 65
40 molecules
41 Fumaric acid 65
42
43
44
Succinic acid 68
45
46 Malonic acid 68
47
48 Propionic acid 65
49
50 Oxalic acid 65, 68
51
52
Acetic acid 65, 68
53
54
Formic acid 65, 68
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2
3 Given the complexity of this mixture, the downstream treatment of the alkaline oxidative lignin
4
5 depolymerization reaction is itself a complex topic that was and is still extensively discussed in both
6 patent and academic literature.
7
8
9 Downstream treatment
10 Finding a way to isolate each of these compounds is currently not possible and even less economically
11 viable. Thus, efforts have been directed to harvest the molecules of interest from this mixture, i.e.
12
13 vanillin and recently syringaldehyde23. The difficulty of isolating pure vanillin from such a mixture is
14 illustrated by the number and variety of processes available in the literature. The two major problems
15 are the acidification of the mixture and the residual lignin removal. One of the oldest process25 performs
16
17
these steps by lignin precipitation in acidic conditions and phenolics are then extracted (Scheme 6). This
18 process requires huge amounts of acid and solvents and the mixture obtained is still difficult to purify.
19
20
21
22
23
24
25
26
27
28 Scheme 6: Lignin-to-vanillin process involving acidification and an extraction step by organic solvents
29 24
30 A process developed at about the same time (Scheme 7) improves the selectivity of the products
31 towards aldehydes.
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51 Scheme 7: Lignin-to-vanillin process involving bisulfitation and an extraction step by organic solvents
52
53 The key step is the bisulfitation of the mixture. Briefly it consists in mixing the crude lignin
54
depolymerization mixture with a solution of NaHSO3 (sodium hydrogen sulfite, or sodium bisulfite) to
55
56 prepare from vanillin a “vanillin bisulfite complex”23, 74, i.e. sodium vanillyl-α-hydroxysulfonate as
57 depicted in Scheme 8:
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2
3 O H HO SO 3 Na
4
5 HSO3 Na
6
7 O O
8 OH OH
9 Scheme 8: Reaction of vanillin with sodium bisulfite to form the “vanillin bisulfite complex”
10
11 The derivatives produced have a good solubility in water, as opposed to the other products from the
12 crude mixture.24 The hydrosulfite anion reacts selectively with the aldehyde moiety, which means that p-
13
14 hydroxybenzaldehyde and syringaldehyde75 are extracted along with vanillin. Products of high molecular
15 weight precipitate during this step, due to the pH increase of the medium.24 Once this precipitate has
16 been removed, the aqueous phase must be further acidified to recover aldehydes and SO2.24
17
18 One major drawback of these two methods is the use of large amounts of organic solvents such as
19 benzene or toluene. Methods have been proposed to circumvent this problem. The first one is based on
20 the replacement of these solvents by supercritical CO2 (Scheme 9).76, 77
21
22
23
24
25
26
27
28
29
30
31
32
33 Scheme 9: Lignin-to-vanillin processes involving an extraction step by supercritical CO2
34
35 Another way to extracts low molecular weight phenolics from the aqueous phase is by adsorbing them.
36
37
Zeolites78 as well as a macroporous resin79 have been proposed as adsorbents (Scheme 10).
38
39
40
41
42
43
44 Scheme 10: Lignin-to-vanillin process involving an extraction step by adsorption
45
46 A major disadvantage of these processes is the requirement of large amounts of acids for neutralization
47
48
and/or acidification prior to the extraction of vanillin.71 In order to reduce this amount, a method of
49 neutralization of the crude lignin depolymerization mixture on a cation exchange resin prior to any other
50 step has been proposed.80
51
Another strategy consists of directly isolating the molecular phenolates from the crude mixture and then
52
53 performing the acidification. The amount of acid necessary and the dilution of the crude liquor is thus
54 greatly reduced.81 A first method described in the literature is the separation of phenolates from higher
55
molecular weight fragments by elution of the crude lignin depolymerization mixture on a strong cation-
56
57 exchange resin in the Na+ form (Scheme 11, top path). Indeed, these two types of species do not have
58
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3 the same retention times and can thus be separated.71 The second method is rather old and consists of
4
5 extracting the phenolates with an appropriate alcoholic solvent81, 82, which can then be distilled off
6 (Scheme 11, middle path). The last method (Scheme 11, bottom path) is more recent and is based on an
7 ultrafiltration step to remove high molecular weight lignin fragments83 followed by an acidification of the
8
9 phenolates in the permeate on an ion-exchange resin.[84] This last method has been proposed in an
10 integrated process that can potentially be adapted in a biorefinery.18 It is worthy to note that the
11 ultrafiltration technology has also been applied to concentrate lignosulfonates in spent sulfite liquor
12
13 prior to the depolymerization reaction.85
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34 Scheme 11: Lignin-to-vanillin processes involving a direct extraction step of phenolates
35
36 The stream of product from all these methods is essentially composed of crude vanillin with varying
37 amounts other phenolics, depending on the process used. Further purification of vanillin to technical
38 grades or food grades is a difficult task. Indeed, the remaining other compounds like acetovanillone or
39
syringaldehyde have very close structures and properties. Separating vanillin from these compounds is
40
41 thus a difficult task, as pointed out by numerous works.23, 75, 86
42 The methods proposed in these works, multistage crystallization for instance, are all tedious and quite
43 difficult to implement on an industrial scale. This is the reason why food-grade vanillin prepared from
44 lignin still displays high amounts of many different impurities, such as syringaldehyde, syringic acid and
45
46 acetovanillone.87 Recently, an original method of purification has been proposed. Briefly, it consists of
47 preparing a vanillin-molecularly imprinted polymer and using it to adsorb with a high selectivity vanillin
48 in the stream to be purified.88
49
50
51 OUTLOOK FOR VANILLIN UTILIZATION
52 Vanillin is currently one of the only molecular phenolic compounds manufactured on an industrial scale
53
54 from biomass. It has thus the potential to become a key-intermediate for the synthesis of bio-based
55 polymers, for which aromatic monomers are needed to reach good thermo-mechanical properties. The
56 amount of research continuously generated on the topic of vanillin production from lignin proves the
57
58
industrial interest of this technique. The fact that the raw material is bio-based, that petroleum price is
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3 on the rise, and the improvements achieved in terms of mechanism understanding, productivity, and
4
5 waste reduction make this vanillin production path more and more attractive from both a green
6 chemistry and economic point of view.
7 However, the current vanillin market as aroma and fragrance is mature and dominated by the low price
8
9 (10 $/kg), petro-based vanillin. Only new markets can stimulate the production on a large scale of the
10 currently more expensive bio-based vanillin (20 $/kg). These emerging markets already exist. Indeed,
11 many recent works deal with the use of vanillin for the synthesis of renewable polymers. These works
12
13 have been summarized in a review article.89 Vanillin, taken as a bio-based building-block90, presents
14 many advantages as mentioned in the introduction. Therefore, it is no surprise that the use of vanillin for
15 the preparation of bio-based polymers attracted that much attention recently.
16
17
In fact, vanillin could provide a solution to the long-standing problem of finding bio-based, aromatic
18 monomers able to replace traditional petro-based, aromatic monomers. The potential of vanillin has
19 been demonstrated in epoxy polymers91-94, as a substitute of bisphenol A. This reprotoxic compound is
20
also used for the synthesis of polycarbonates, and vanillin-derived monomers might also be good
21
22 substitutes in these polymers.95 This potential could be extended to any polymer in which aromatic
23 monomers are needed. Vanillin was used as a base material to prepare polyesters with good thermal
24
properties72, 96, 97, without employing any petro-based terephthalic acid. It was also used to prepare
25
26 reactive diluents or cross-linkers for vinyl ester formulations.98, 99 These vanillin-derived compound
27 advantageously replaced styrene, usually used in such formulations. Styrene needs substitutes as it is a
28
petro-based Volatile Organic Compound (VOC) as well as a Hazardous Air Pollutant (HAP).
29
30 Vanillin is not only able to provide substitutes to problematic petro-based aromatics, it can also be the
31 basis of entirely new polymers possessing interesting properties in areas as diverse as metal ions
32 chelating100, 101, antimicrobial polymer films102, liquid crystalline polymers103, or high performance
33
34 polybenzoxazines thermosets.104
35 In turn, large-scale production of vanillin from biorefineries could lead to a price decrease. The
36 biorefinery concept has gained more and more importance in recent years. Vanillin production can be
37
38 integrated in this concept but cannot be the only aim of a given plant, and the process has to be carefully
39 optimized to be viable. Indeed, the shutting down of the lignin-to-vanillin plants in the 1990’s should
40 serve as an example: producing diverse chemicals and carefully controlling effluents to be economically
41
42 and ecologically viable is necessary to modern biorefineries. Vanillin is a high added-value product but its
43 yield from raw biomass is low because of the difficult purification steps needed to obtain a food-grade
44 compound. This is a first limitation of this process. Thus, vanillin production must be combined with the
45
46 production of large volume, low added-value products such as cellulose, pulp, paper, lignin, etc. In the
47 case of such complementary productions, vanillin is viable in a bio-refinery context.
48 Another limitation of the lignin-to-vanillin process is the various environmentally-damaging steps of the
49
50 process. These problematic steps are mostly needed to purify the mixture obtained after lignin
51 depolymerization. Early processes used large amounts of acids, organic solvents, or energy. As
52 summarized in this work, a great deal of effort has been and is still made to improve these processes or
53
54 find new ones, more environmentally-friendly. These efforts need to be pursued as they are what will
55 make the lignin biorefinery an industrial reality.
56 Lignins are characterized by their composition in hydroxyphenyl (H), guaiacyl (G), and syringyl (S) units.
57
58 There is thus a maximum obtainable vanillin yield from a specific type of lignin. The formation of vanillin
59
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3 or other compounds is strictly related to the available percentage of its precursor in the lignin
4
5 structure18, i.e. in the case of vanillin to the amount of G units. Therefore, in practice, only G lignins from
6 softwoods, containing high amounts of G units, are used in the lignin-to-vanillin process. This is a third
7 limitation of this approach. Importing softwood from the other side of the globe to improve the yield in
8
9 bio-based vanillin is not viable in terms of carbon footprint.
10 These limitations can be dealt with if one considers not only the selective production of vanillin, but the
11 valorization of mixtures of phenolics obtained from lignin depolymerization, either non- or partially
12
13 purified. Indeed, an advantage of the polymer market is that it does not necessarily require pure
14 molecules as raw materials, even if it has been the norm for quite some time with the petro-based
15 refinery. Some polymers can be manufactured from biomass-derived mixtures of compounds. It has
16
17
been recently proven with the synthesis of epoxy thermosets with good thermo-mechanical properties
18 from mixtures of phenolics found as products of the lignin-to-vanillin process.105
19 This approach of using mixtures improves the yield in high value-added products in two ways. Firstly,
20
vanillin is not the sole product, vanillic acid and acetovanillone for instance can also be considered as
21
22 valuable products. Secondly, some of the difficult purification steps that impact the yield are not needed
23 in this approach. In terms of yield improvement, lignins having a structure as close as possible to their
24
native one found in wood seem to be the best. Therefore, lignins from new types of processes such as
25
26 organosolv lignins might be better choices as source of mixtures of bio-based aromatics than the ones
27 from older processes, such as lignosulfonates or Kraft lignins, which structure is heavily altered.
28
Another important positive point of this approach is that all types of wood can then be used, as all types
29
30 of lignin units, H, G, and S, lead to valuable phenolics. For instance, syringaldehyde and syringic acid,
31 obtained from S units of GS lignins from hardwoods, do not have to be considered as impurities and
32 removed. More biomass can thus be processed, and the sourcing of the wood can be local, which is less
33
34 environmentally damaging. Finally, partially or totally removing the purification steps makes the process
35 less demanding in acids, solvents, or energy.
36 The valorization and use of mixtures of products, as would arise from lignin and maybe more generally
37
38 from bio-refineries, will be a great challenge.16 Simply put, “there is a vast difference between a valuable
39 mixture of chemicals and a mixture of valuable chemicals”.43 However, it will be worth it. The advantages
40 of using unrefined mixtures are numerous: more biomass can be used, which means less waste, and the
41
42 difficult purification steps are no longer necessary, improving the overall economic and environmental
43 viability of the bio-refinery concept.
44
45
46 REFERENCES
47 The authors declare no fundings.
48
49
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6 VANILLIN PRODUCTION FROM LIGNIN AND ITS USE AS A RENEWABLE CHEMICAL
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9 Maxence Fache, Bernard Boutevin, Sylvain Caillol*
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11 This manuscript proposes a perspective article on lignin-derived vanillin for further use as an aromatic
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