Depolymerization of Native Lignin into Vanillin, Vanillic Acid, and Other Related Compounds via Alkaline Aerobic Oxidation: Reaction Mechanisms and Process Control Using Organic Cations

Abstract

Vanillin is one of the platform chemicals in industry, which is used not only as a traditional fragrance but also as a raw material for medicines and polymer materials. Industrial vanillin production by alkaline aerobic oxidation of lignin is carried out with degradation of lignosulfonate at temperatures around 170°C under pressurized air in the presence of Cu2+ as a catalyst. However, this method has problems such as low vanillin yields and by production of sulfur-containing wastewater, and various studies have been conducted to solve them. Research on the mechanism of the vanillin formation reaction by aerobic oxidation of lignin and the search for a method to control this reaction has also been conducted. In this chapter, we review relevant studies from the above perspective, mainly those conducted by the authors’ research group.

1. Introduction

Currently, environmental issues, such as the depletion of fossil resources and global warming, are of worldwide concern, which has raised growing interest in renewable and environmentally friendly biomass resources as an alternative to fossil resources. Among the various types of biomasses, wood is a promising resource because of its huge stocks and inedibility. Wood is composed mainly of three components: cellulose, hemicellulose, and lignin. Among these, lignin constitutes 20–35% of the wood [1]. Because of its aromatic nature, lignin is expected as bio-based source of low molecular weight (MW) aromatics that are indispensable in the chemical industry [2, 3, 4, 5, 6, 7, 8].

The production of low MW aromatics from lignin requires conversion methods that facilitate effective cleavage of interunit linkages in lignin polymer. Among many methods currently suggested, alkaline aerobic oxidation is a promising way from the viewpoint that lignin is effectively degraded by nontoxic molecular oxygen [9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21]. Aerobic oxidation of lignosulfonate in waste liquor from sulfite pulping of softwood has been put into practical use as industrial vanillin (4-hydroxy-3-methoxybenzaldehyde) production [22, 23, 24, 25, 26, 27].

Vanillin is a versatile compound that is useful as a source of medicines and polymer materials, as well as a traditional fragrance [24, 25, 26, 27, 28, 29, 30]. The vanillin production from lignosulfonate is usually carried out in aqueous alkali, that is, aqueous NaOH solution, under compressed air in the presence of a Cu²⁺-based catalyst. This method was a major industrial vanillin production method until 1990s. However, the yield of vanillin is usually less than 10% based on the original sodium lignosulfonate [25, 31]. In addition to this relatively low yield of the target compound, high temperature and air pressure, typically 160–200°C/0.5–2.0 MPa, required for the process and management of wastewater containing sulfur compounds are drawbacks of this biomass-based vanillin production [25]. Recent vanillin production is, therefore, substituted almost with petrol-based ones, that is, formylation of guaiacol [27].

In light of recent environmental concerns, however, the production method of vanillin derived from biomass should be continuously studied and improved as it could be a breakthrough in establishing a method to produce low MW aromatic compounds from wood. To promote the adoption of the lignin-based vanillin production method in the chemical industry, it is necessary to address some of the shortcomings of this method described above. One solution to the sulfur-containing waste problem is to use native lignin in wood, as well as lignosulfonate as raw material for vanillin. Developing methods that provide the target product in good yield without the use of transition metals or high-temperature and high-pressure conditions would be another issue to tackle. Furthermore, mechanistic knowledge of alkaline aerobic oxidation as the foundation of the process development is essential for realizing these goals.

This chapter presents the results of fundamental and applied studies on vanillin production from lignin, conducted mainly in the authors’ research group, from the above perspective. In addition to vanillin, other related oxidation products, for example, vanillic acid, are also produced in the aerobic oxidation of lignin. The formation of these compounds will also be briefly summarized.

2. Alkaline aerobic oxidation of lignin in the presence of organic cations

In vanillin production via alkaline aerobic oxidation of lignin, simple alkaline solution, such as aqueous NaOH solution, is generally employed as a reaction medium. Alternatively, our research group developed a new alkaline medium, that is, tetrabutylammonium hydroxide (TBAH) for lignin degradation. The chemical structure of tetrabutylammonium ion, Bu₄N⁺, is presented in Figure 1. TBAH is a salt of Bu₄N⁺ and OH⁻ and its aqueous solution exhibits strongly alkaline nature, as aqueous NaOH solution does. In this respect, TBAH is similar to NaOH, but a distinguishing characteristic of TBAH is that it possesses the bulky organic cation.

Figure 1.

Organic cations employed in our studies [32, 33]. ^a) In the case of 12C4-Na⁺, a complex cation in which Na⁺ is bound by two molecules of 12C4 is also reported [34].

Figure 2 shows the changes with time in yields of vanillin and its related substance, vanillic acid (4-hydroxy-3-methoxybenzoic acid); when sodium lignosulfonate or Japanese cedar (Cryptomeria japonica) wood flour is oxidatively degraded at 120°C under air in the aqueous NaOH solution or aqueous TBAH solution with their concentration being 1.25 mol/L. In the vanillin production from the sodium lignosulfonate, the raw material for current lignin-based vanillin production [33], it has been indicated that the -SO₃⁻ moieties in the raw material play important roles in the vanillin formation [35, 36]. This point can be confirmed by comparing the yield of vanillin in the NaOH medium in Figure 2 between wood flour and sodium lignosulfonate. In other words, in the case of the NaOH medium, the yields of vanillin and vanillic acid are comparable between sodium lignosulfonate and the wood flour (vanillin yield: 3–5 wt%; vanillic acid yield: 1–3 wt%). Considering significant degradation of the original lignin structures during its isolation process, it can be concluded that sodium lignosulfonate gives the target compounds in relatively high yields. This result would be attributed to the presence and the positive effect of the -SO₃⁻ moiety.

Figure 2.

Formation behavior of vanillin (⬧) and vanillic acid (◾) from Japanese cedar wood flour (A) and sodium lignosulfonate (B), during their alkaline aerobic oxidation under air in a sealed system (volume of the gas phase: 8 mL). Reaction conditions: sample 14 mg/ reaction solution (1.25 mol/L aqueous TBAH solution or aqueous NaOH solution 2.0 mL)/ 120°C. ^a) Yield from the wood flour is based on its Klason lignin amount [33].

On the other hand, higher yields of vanillin and vanillic acid are obtained in the TBAH medium, regardless of the presence of the -SO₃⁻ moiety, as shown in Figure 2. Also, the wood flour exhibited much higher vanillin yield in TBAH than sodium lignosulfonate did in the same medium. This result is interesting from the perspective of reducing sulfur-containing waste during the vanillin production; efficient vanillin production from the wood flour, an originally sulfur-free material, was achieved in TBAH, which leads to the establishment of processes that are not bothered by the sulfur-containing waste. It should be also emphasized that the vanillin production was carried out without any transition metal additives. The employed reaction temperature, 120°C, was much lower than those generally adapted in current vanillin production processes.

The vanillin production shown in Figure 2 takes a long reaction time, over 43 h, to reach the maximum product yield. The current process solves this problem by using pressurized air and high temperatures to promote the oxidation. Table 1 summarizes the maximum yields of vanillin and vanillic acid and the time to reach them for the oxidation of Japanese cedar wood flour in various reaction media. It becomes clear that the addition of NaOH(s) to the reaction system and replacing the air in the reaction system with pure O₂ significantly shortens the reaction time and increases the yields of the products [16, 20]. Finally, the yields of vanillin and vanillic acid under optimum conditions are 23.2, 1.2 wt%, respectively, and the time to reach of this yield is 4.0 h. Thus, in the TBAH media, it is possible to improve the reaction efficiency at low temperature of 120°C without pressurizing the reaction system, which is advantageous compared to the current process with harsh reaction conditions. For vanillic acid, on the other hand, the compound tends to form in relatively low yields under the conditions in which vanillin production is facilitated. This may suggest that the production pathways of vanillin and vanillic acid are in trade-off relationship.

Medium/oxidant	[OH^−] (mol/L)	Time (h)b	Temperature (°C)	Yield (wt %)a
				Vanillin	Vanillic acid	Total
NaOH/air	4.0	96	120	6.2	2.4	8.6
NaOH/nitrobenzenec	2.0	2.5	170	27.2	1.2	28.4
TBAH/air	1.25	43	120	15.4	3.9	19.3
TBAH+NaOHd/air	3.75	20	120	18.9	2.2	21.1
TBAH+NaOH/oxygene	3.75	4.0	120	23.2	1.2	24.4
NaOH +18C6f/air	4.0	96	120	16.1	2.3	18.4
NaOH +15C5f/air	4.0	96	120	15.2	2.3	17.5
NaOH +12C4f/air	4.0	72	120	16.1	2.3	18.4
NaOH +1,4-dioxanef/air	4.0	96	120	5.5	3.4	8.9
NaOH + TEGf/air	4.0	96	120	8.9	5.0	13.9
NaOH + TRGf/air	4.0	96	120	5.4	9.2	14.6

Table 1.

The yield of vanillin and vanillic acid from Japanese cedar wood flour after its oxidation in several oxidation systems [16, 32, 33].

^a

The yield is based on the Klason lignin content of the wood flour.

^b

The reaction time is the one in which the yield of vanillin becomes maximum.

^c

The alkaline nitrobenzene oxidation (AN oxidation) was carried out under the established conditions.

^d

In the TBAH+NaOH medium, [Bu₄N⁺] is set to 1.25 mol/L with [OH⁻] being adjusted to the presented value by adding NaOH(s) to the TBAH solution.

^e

“Oxygen” means the experiment is carried out under pure O_2.

^f

The reaction medium is prepared by adding the ether compounds to the NaOH solution, where 18C6, 15C5, and 12C4 are the polycyclic ethers with different cavity sizes (see Figure 1), and TEG and TRG are tetraglyme and triglyme (non-cyclic polyethers with different chain lengths), respectively.

The above yields of vanillin and vanillic acid are remarkable in the history of lignin chemistry. One of the most important reactions in lignin chemistry is alkaline nitrobenzene oxidation (AN oxidation). This is an oxidative degradation of a lignin-containing sample such as wood and isolated lignin by nitrobenzene to give p-hydroxybenzaldehydes reflecting the substitution pattern of the lignin sample, mostly vanillin in the case of softwood lignin. Despite its more than 60-year history, AN oxidation has been one of the most efficient lignin degradation methods in use today and the product yield in the AN oxidation has been employed as a benchmark to measure the efficiency of other oxidation methods. Table 1 shows that the yields of vanillin and vanillic acid in the TBAH+NaOH/O₂ system are comparable to those of AN oxidation. These results indicate that the TBAH-based alkaline aerobic oxidation is a highly efficient oxidation method and exploit the potential of the raw material to produce the target compounds.

The high yield of vanillin achieved in the aforementioned TBAH is clearly due to the presence of the bulky tetrabutylammonium ion, compared to Na⁺. This led us to the idea of producing vanillin under the presence of various bulky organic cations. Namely, we added polycyclic ethers, that is, 18-Crown-6 (1,4,7,10,13,16-hexaoxacyclooctadecane, 18C6), 15-Crown-5 (1,4,7,10,13-pentaoxacyclopentadecane, 15C5), and 12-Crown-4 (1,4,7,10-tetraoxacyclododecane, 12C4) to an aqueous NaOH solution and studied the alkaline aerobic oxidation behaviors of Japanese cedar wood flour in these reaction media. These crown ethers capture Na⁺ in the aqueous NaOH solution, forming three types of complex cations 18C6-Na⁺, 15C5-Na⁺, and 12C4-Na⁺ as shown in Figure 1 [37]. It is expected that these organic cations would exhibit enhancing effects on the vanillin production, which is similar to those observed for Bu₄N⁺.

The aerobic oxidation of Japanese cedar wood flour was conducted in a 4.0 mol/L aqueous NaOH solution in the presence of 2.0 mol/L of the three crown ethers. As shown in Table 1, the vanillin yield under the three crown ethers (18C6, 15C5, 12C4) is 15.2–16.1 wt%, which is clearly higher than that in the pure NaOH system. In contrast, in the aerobic oxidation using equimolar amounts of tetraglyme (TEG) and triglyme (TRG) and non-cyclic analogs of 15C5 and 12C4 respectively, the vanillin yields are 8.9 and 5.4 wt%, nearly the same as that obtained in the pure NaOH system. This can be explained by the fact that cyclic polyethers generally exhibit much stronger complexing ability toward metal cations than their corresponding non-cyclic polyethers [38], suggesting that the increased vanillin yield due to the addition of the crown ethers results from the formation of the complex cations in Figure 1. Moreover, the increase in vanillin yield by cyclic polyethers seems to depend highly on their Na⁺ accommodation ability. For instance, the addition of 1,4-dioxane, which has a considerably smaller ring size than the three crown ethers, results in a vanillin yield of 5.5 wt% (Table 1). This is likely because the cavity size of 1,4-dioxane is too small to accommodate Na⁺.

For vanillic acid, another major product, the yield from Japanese cedar wood flour in the presence of complex cations is 2.3 wt%, regardless of the types of the crown ethers. This value is nearly identical to that obtained in the absence of the complex cations (2.4 wt%). This phenomenon of minimal influence of the complex cations on the production of vanillic acid is also observed in the aforementioned aerobic oxidation of Japanese cedar wood flour in the presence of Bu₄N⁺. Thus, it can be stated that the complex cations formed from Na⁺ and the crown ethers and Bu₄N⁺ exert quite similar effects, significantly increasing the yield of vanillin while having little impact on the formation of vanillic acid. In the following section, we will elaborate on this issue from the perspective of reaction mechanisms. Moreover, the addition of TEG and TRG, which are non-cyclic polyethers, does not substantially increase the vanillin yield, but it increases the yield of vanillic acid. For instance, the addition of TRG significantly increases the yield of vanillic acid from 2.4 to 9.2 wt% (Table 1). Although there are few clues to explain these results rationally at this point, they represent intriguing phenomena when considering the potential for further reaction control by complex cations.

3. Mechanism of vanillin formation from lignin and the roles of organic cations

Bu₄N⁺ and the complex cations between Na⁺ and the polycyclic ethers are found to facilitate the vanillin production by alkaline aerobic oxidation of lignin. However, the mechanisms underlying the improved vanillin yield caused by the presence of the organic cations are not clear. We, thus, investigated the role of organic cations (Bu₄N⁺ and the crown ether-based complex cations) in the vanillin formation mechanisms, by analyzing the behaviors of lignin model compounds LM1 and LM2 shown in Figure 3 under the alkaline aerobic oxidation conditions. These models carry a β-O-4 linkage, which is the most abundant linkage in lignin, but are different in that LM1 has the phenolic OH group, while LM2 does not.

Figure 3.

Reaction pathways involved in alkaline aerobic oxidation of LM1 (A) and LM2 (B) [16, 33, 39].

LM1 with the phenolic OH group was examined as a model for the phenolic end group of lignin [16]. As shown in Figure 3, an enol ether intermediate EE is formed in the initial stage of the oxidation via the formation of a quinone methide QM structure from LM1 and the following elimination of C_γ position as HCHO (Pathway A1 and A2). The second step involves the oxidation of the C_α = C_β moiety of EE finally leading to vanillin (Pathway A3). The mechanisms in the oxidation of EE are not clear at the moment, but vanillin formation from EE via a dioxetane intermediate was suggested in several studies on O₂ pulp bleaching conditions [40, 41]. For the effect of Bu₄N⁺ in the TBAH medium, Bu₄N⁺ stabilizes EE probably by coordinating with the side chain of EE, which results in slower vanillin formation from LM1 in TBAH compared to that in NaOH. It is, therefore, likely that Bu₄N⁺ does not have positive effects on the vanillin production from the phenolic end of lignin.

Experiments using LM2, a model for the middle β-O-4 phenylpropane unit of lignin, have suggested the following reaction mechanisms [16, 39]. First, the cleavage of the β-ether of LM2 via the neighboring group participation of C_α-OH occurs to give a veratryl glycerol intermediate VGL (Pathway B1). This intermediate is then oxidized to an α-carbonyl compound, which is in equilibrium with the corresponding γ-carbonyl compound through the keto-enol tautomerization (Pathway B2). A retro-aldol reaction proceeds from the γ-carbonyl compound, leading to the formation of veratraldehyde (VAld) via Pathway B3. On the other hand, another retro-aldol pathway starting from the α-carbonyl is less significant [39]. There are two possible fates of VAld with one being disproportionation to produce veratric acid (VAcid) and veratryl alcohol (VAlc) (Pathway B4) and the other being conversion of the 4-OMe group to OH to produce vanillin (Pathway B5).

Comparison of the degradation behaviors of LM2 in the TBAH and NaOH system revealed that TBAH promoted the cleavage of the β-ether in the initial stage of the reaction (Pathway B1) and increased the selectivity of the vanillin production from VAld in the final stage (Pathway B5). The former promotion of the β-ether cleavage can be explained by the fact that the OH⁻ activity in the aqueous TBAH solution is higher than that of the aqueous NaOH solution, even when their OH⁻ concentration is the same. On the other hand, the latter promotion of vanillin formation from VAld is due to the interaction of Bu₄N⁺ with VAld in the aqueous TBAH solution, as indicated by the ¹H NMR analysis of VAld in the presence of Bu₄N⁺ salt [16]. In other words, VAld is in the cage made of Bu₄N⁺ in the aqueous TBAH solution, which inhibits the progress of the disproportionation (Pathway B4). This results in relative increase in the selectivity of the vanillin forming pathway B5.

The influence of the complex cations on the reactivity of LM2 is confirmed by evaluating the additive effect of crown ethers (18C6, 15C5, and 12C4) on the reactivity of LM2 in the aqueous NaOH solution. When the complex cations are present in the reaction system, a decrease in the yields of VAcid and VAlc is observed, along with an increase in vanillin yield, similar to the previously confirmed Bu₄N⁺ system. Thus, it is inferred that both complex cations and Bu₄N⁺ essentially increase the vanillin yield through the same mechanism, namely, the suppression of the disproportionation pathway of VAld due to the cage effect. Interestingly, in the case of the non-cyclic ethers such as TEG and TRG, and 1,4-dioxane, a cyclic ether with a much smaller ring size, no significant increase in vanillin yield is observed in the model experiments using LM2. This suggests that the formation of complex cations shown in Figure 1, and the suppression of the disproportionation pathway (Pathway B4) are closely related. In addition to the similar effects of Bu₄N⁺ and the complex cations as mentioned above, the complex cations exhibit several specific effects that are not observed with Bu₄N⁺ [32]. For instance, in the case of the complex cation systems, the inhibition of the oxidative degradation of the VGL side chain to the aldehyde group is observed probably by the stabilization of VGL by its interaction with the complex cation.

The above phenomena observed for LM1 and LM2 suggest that vanillin formation from middle phenylpropane units in lignin is promoted in the presence of the organic cations, with the reaction at the phenolic end being rather suppressed. In other words, the formation of vanillin from the middle unit plays an important role in the formation of vanillin under the alkaline aerobic oxidation conditions. Figure 4 shows a possible pathway for vanillin formation from the middle unit of lignin based on the study of the reaction mechanisms of LM2. First, the β-ether of the middle β-O-4 unit undergoes alkaline hydrolysis to form the glycerol end (pathway І). The glycerol end is oxidized to a C_α-aldehyde end (pathway Π), and finally, vanillin is released from this end (pathway Ш). In an actual lignin molecule, the middle units are considered to be more abundant than the phenolic ends. It is, thus, likely that the suppressing effect of Bu₄N⁺ on the vanillin production from the phenolic end is canceled out, and the overall vanillin yield was increased in the organic cation-containing media.

Figure 4.

Vanillin formation from a β-O-4 middle unit of lignin polymer [16].

The model compounds LM1 and LM2 discussed so far are designed to mimic the β-O-4 structure in lignin. However, the compound has a much more simplified structure than the actual lignin. Therefore, when applying the reaction pathway based on the degradation behavior of LM2 (Figure 3) to actual lignin molecules, careful consideration is required. When comparing the vanillin production behavior from LM2 and wood flour, a certain correspondence can be recognized between the oxidation behaviors of actual lignin and the model compounds in that the increase in vanillin yield from the wood flour observed in the presence of organic cations is reproduced even in the case of the model compound. Thus, it is likely that the suppression of the disproportionation by the cage effect of the organic cations plays a certain role also in the vanillin production from actual lignin. In the case of actual lignin, however, VAld, which was produced from LM2, never forms, and instead the C_α-aldehyde end group shown in Figure 4 is formed as a vanillin precursor. The rates of vanillin elimination from this C_α-aldehyde end and the conversion reaction of VAld to vanillin (conversion of the 4-position methoxy group to a hydroxy group) are expected to differ significantly, which may affect the degree of suppression of disproportionation by the cage effect. Also, in the C_α-aldehyde end linked to the actual lignin side chain, more complex side reactions not observed with VAld might proceed. According to these ideas, future studies using model compounds that more accurately mimic the actual C_α-aldehyde end are needed to more precisely elucidate the mechanism of increased vanillin yield by the cage effect.

4. Conclusions

This chapter presented high-yield vanillin production from lignin (mainly native softwood lignin) by the alkaline aerobic oxidation in the presence of organic cations. When conducting alkaline aerobic oxidation of lignin in the presence of bulky organic cations such as Bu₄N⁺ and the complex cations formed between the crown ethers and Na⁺, a significant increase in the yield of vanillin from the lignin samples is observed. In this organic cation-containing system, the alkaline aerobic oxidation allows for the efficient production of vanillin at a temperature of 120°C, employing native lignin in the wood flour as the starting material. This vanillin production process is more advantageous than the current process using lignosulfonate in that it can achieve a high vanillin yield comparable to that of AN oxidation and does not produce sulfur-containing effluent.

One of the vanillin production pathways in the alkaline aerobic oxidation of lignin involves the elimination of vanillin from the C_α-aldehyde structure, which is produced by the oxidative degradation of non-phenolic intermediate units in lignin. It has been found that the aforementioned organic cations improve the selectivity of this vanillin elimination reaction. Research on such reaction mechanisms and further mechanistic insights into the function of the organic cations are expected to lead to the development of more rational reaction control methods to improve the efficiency of the vanillin production processes.

Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research (C) (No. 21K05715 and 23K05343) from the Japan Society for the Promotion of Science.