Effect of side-chain length in lignin model compound on MnO2 oxidation: comparison of oxidations between C6-C2- and C6-C1-type compounds

Monomeric C6-C2-type lignin model compounds with a p-hydroxyphenyl (H), guaiacyl (G), syringyl (S), or p-ethylphenyl (E) nucleus (1-phenylethanol derivatives) were individually oxidized by MnO2 at a pH of 1.5 and room temperature. The results were compared with those of the corresponding C6-C1-type benzyl alcohol derivatives obtained in our recent report to examine the effect of the presence of the β-methyl group on the oxidation. The presence decelerated the oxidation regardless of the type of aromatic nucleus, although it did not change the order of the oxidation rates: G > S >> H > E. This deceleration results from the steric factor of the β-methyl group in the C6-C2-type compounds. The MnO2 oxidations of the corresponding C6-C2-type compounds deuterated at their α-(benzyl)positions showed that the magnitudes of the kinetic isotope effects are smaller than those observed in the oxidations of the corresponding C6-C1-type compounds, regardless of the type of aromatic nucleus. These smaller magnitudes suggest that the presence of the β-methyl group shifts the initial oxidation mode of MnO2 from direct oxidation of the benzyl position to one-electron oxidation of the aromatic nucleus. Only the S-type compounds afforded products via degradation of the aromatic nuclei.


Introduction
Oxidation, together with acidic and alkaline reactions, is a common method for chemical treatment in biomass conversion where delignification is targeted. We have focused on manganese dioxide (MnO 2 ) as an oxidant of lignin, owing to its easy handling and recyclability. MnO 2 is reduced to divalent manganese ion (Mn 2+ ) when used as an oxidant under acidic conditions, and Mn 2+ can be reconverted to MnO 2 by oxygen oxidation under alkaline conditions. However, MnO 2 oxidation of lignin from a pure chemistry viewpoint has been examined in only a few studies [1,2].
Our previous report showed that MnO 2 is a good delignifying agent and is appropriate for introduction at the prebleaching stage (oxygen delignification) [3]. When an oxygen delignification process is substituted with MnO 2 oxidation at a temperature of 70 ºC and pH of 2.0 in a sulfate buffer solution after the middle stage, the delignification of hardwood unbleached kraft pulp progresses more than in the process without the substitution, while carbohydrates are damaged only slightly.
A common mode of MnO 2 oxidation is to oxidize a conjugated hydroxy group, such as allyl or benzyl alcohol, to the corresponding carbonyl group. This does not seem to contribute to depolymerization of lignin and delignification, and therefore the mechanism of MnO 2 oxidation was subsequently examined using various non-phenolic lignin model compounds with a p-hydroxyphenyl (H), guaiacyl (G), or syringyl (S) nucleus as well as p-ethylphenyl (E) nucleus, benzene derivatives (H-type (I H ), G-type (I G ), S-type (I S ), and E-type (I E ), Fig. 1), benzyl alcohol derivatives (H-type (II H ), G-type (II G ), S-type (II S ), and E-type (II E ), Fig. 1), and the corresponding benzyl alcohol derivatives deuterated at the benzyl positions (H-type (III H ), G-type (III G ), S-type (III S ), and E-type (III E ), Fig. 1) at a pH of 1.5 and room temperature in our recent report [4]. Compound I G or I S is oxidized by MnO 2 to afford the corresponding benzoquinone derivative (B G or B S , respectively, Fig. 1) as the only exclusive major product, while compound I H or I E is stable. This oxidation mode of MnO 2 was not previously known. Compound II or III (indistinguishably showing all the types of aromatic nucleus) except for the S-type compound is oxidized almost quantitatively to the corresponding benzaldehyde derivatives (H-type (A H or A H ', respectively), G-type (A G or A G ', respectively), and E-type (A E or A E ', respectively), Fig. 1). Compound II S or III S affords not only product A S or A S ', respectively, but also product B S as the exclusive major reaction product. The rates are dependent on the type of the aromatic nucleus (G-> S->> H-> E-type). On the basis of these observations, three reaction modes are proposed for the MnO 2 oxidation of compound II (or III) (Fig. 2). Mode 1 is the direct oxidation of their benzyl alcohols to the aldehydes, product A (or A'). Mode 2 begins with the oxidation of their aromatic nuclei to afford the aromatic cation radical, but ultimately results in the oxidation of the benzyl alcohol to product A (or A'). Mode 3 begins the same as mode 2, but results in the oxidative degradation of the aromatic nuclei to form product B as well as many minor unidentified aliphatic reaction products. The magnitude of the kinetic isotope effect, which is estimated from the ratio of the pseudofirst-order rate constant (k obs ) of compound II to that of compound III observed for their disappearances (H-type: 4.7, G-type: 4.0, S-type: 2.7, and E-type: 8.6), can be an index of the degree of the contribution of mode 1. On the basis of these magnitudes, compounds II H and II G are suggested to undergo both modes 1 and 2, with the contribution of mode 2 to the oxidation of the compound II G generally being slightly greater than to that of compound II H , although mode 1 is almost exclusive for compound II E . Compound II S undergoes all three modes to further decrease the magnitude. In contrast to modes 1 and 2, progress to mode 3 can contribute to delignification in actual pulp bleaching where MnO 2 oxidation is introduced.
In this paper, monomeric C 6 -C 2 -type non-phenolic compounds including lignin models, 1-phenylethanol derivatives . The obtained results were compared with those in our recent report to examine the effect of the presence of the β-methyl groups and whether the contribution of each reaction mode differs in the MnO 2 oxidations between the C 6 -C 1 -(II and III) and C 6 -C 2 -type (IV and V) compounds.
Although our recent report describes why the E-type compounds, which are not lignin models, were applied [4], this reason is included again here. The Hammett's substituent constant (σ value) of the ethyl group present at the para-positions of the benzyl carbons in the E-type compounds, − 0.151, is almost the same as the sum of those of the two methoxy groups present at the  Fig. 1 Structure of monomeric C 6 -C 1 -type compounds used as starting materials and quantified exclusive major reaction products in our recent report [4] meta-and para-positions of the benzyl carbons in the G-type compounds: + 0.115-0.268 = -0.153. Therefore, the rates of the E-and G-types in compound II, III, IV, or V will be similar in chemical reactions at the benzyl positions when these reactions are affected only by the electronic effects of these ethyl and methoxy groups locally appearing only at the benzyl positions. When the reactions are also affected, for instance, by the electron density of the π-electron systems of the compounds, the rates will be different. The application of the E-type compounds thus makes the discussion deeper than for that lacking this application.

1-Phenylethanol derivatives D euterated 1-phenylethanol derivatives
Structure of monomeric C 6 -C 2 -type compounds used as starting materials and quantified exclusive major reaction products in this study Sun and Yokoyama J Wood Sci (2021) 67:29

Materials
All chemicals used in this study except for the compounds synthesized as described below were purchased from FUJIFILM Wako Pure Chemical Industries, Ltd.
(Tokyo, Japan), or Sigma-Aldrich Japan K. K. (Tokyo, Japan), and used without further purification. Ultrapure water used in all the experiments was prepared by a generator, Puric-Z (Organo Co., Tokyo, Japan). Compounds IV were commercially available and purified by flash chromatography (Isolera ™ , Biotage Japan Ltd., Tokyo, Japan) before use. Compounds V were synthesized from the corresponding commercially available acetophenone (acetylbenzene) derivatives by reduction with sodium borodeuteride (NaBD 4 ) in ethanol, and purified by flash chromatography before use.

Preparation of MnO 2 for reaction
MnO 2 was prepared from Mn 2+ by oxygen oxidation under alkaline conditions. The detailed procedures were as described in our previous and recent reports [3,4]. The prepared MnO 2 was ground into powder in a mortar. The oxidation power of the MnO 2 was 84.9% of the theoretical value.

MnO 2 oxidation reaction
Although the detailed procedures were as described in our previous report [4], the major portions are included below.
All reactions were conducted in a round-bottom glass flask (200 mL) equipped with a magnetic stirrer. A sulfate buffer (0.50 mol/L, pH 1.5) was prepared in advance by mixing sodium sulfate and sulfuric acid solutions (0.50 mol/L each).
The powdered MnO 2 (1.2 mmol: oven-dry basis (oxidation power basis: 1.02 mmol)) was aged in a sulfate buffer solution (50 mL, 0.50 mol/L, pH 1.5) for 120 min in a glass flask at room temperature. Another sulfate buffer solution (10 mL) consisting of the same sulfate components and containing one of the compounds shown in Fig. 2 (60 μmol) as a starting material was added to the sulfate buffer solution containing the MnO 2 powder to initiate the reaction at room temperature. The initial concentrations of the compound and MnO 2 (insoluble solid) were 0.20 and 20 mmol/L, respectively. Each reaction was conducted three times to confirm reproducibility.

Quantification
A specific amount of the reaction solution was withdrawn at prescribed reaction times to quantify the residual starting material and reaction products. The withdrawn solution was rapidly neutralized with an excess amount of a saturated sodium hydrogen carbonate solution, and mixed with methanol containing an internal standard compound (1,2,3-trimethoxybenzene or 3,4-dimethoxybenzaldehyde). The mixture was filtrated with a membrane filter and injected into an HPLC instrument equipped with an ultraviolet-visible (UV-VIS) absorption detector (LC-2010C HT , Shimadzu Co., Ltd., Kyoto, Japan) using the absorbance at 280 nm for quantification.

Results and discussion
Compounds IV and V were individually oxidized by MnO 2 under the above-described conditions, which were the same as those employed in our recent report [4]. The disappearance of each type of compounds IV and formation of all the exclusive major reaction products are illustrated in Fig. 4. The disappearance of each compound approximated to a pseudo-first-order reaction, although the deviations were not very small in the approximations of several compounds. Table 1 lists the pseudo-first-order reaction rate constants (k obs ) observed for these disappearances and, as references, for those of compounds II and III from our recent report [4], with the squares of the correlation coefficients (R 2 ) in these approximations. Table 1 also lists the ratios between two values of k obs s (k obs (II)/k obs (III)); this is explained in the "Introduction" section, and will be used in discussing the oxidation mechanism below.

MnO 2 oxidation of 1-phenylethanol derivatives (compound IV)
Compounds IV were oxidized at rates in the order of compound IV G > IV S > > IV H > IV E . A possible explanation for this order is described in our recent report [4]. The disappearance of compound IV H , IV G , or IV E was, respectively, accompanied by the almost quantitative formation of product C H , C G , or C E (Fig. 3). The oxidation of compound IV S afforded not only product C S , but also B S (Fig. 3) as the only major reaction products, although their formations did not quantitatively accompany the disappearance. The HPLC chromatogram did not show any peak other than those of products C S and B S , which indicates that the S-nucleus of compound IV S is degraded to afford ring-opening products. Various types of ring-opening product commonly form without formation of any major product when aromatic nucleus is oxidized and degraded. The S-nucleus tends to undergo oxidation to afford ring-opening products more strongly than the other nuclei, owing to high electron density of its aromatic π-electron system. Thus, these results show that oxidation of the benzyl alcohol quantitatively affords product C irrespective of whether mode 1 or 2 is followed (Fig. 2), while the aromatic nucleus is degraded and hence unidentified aliphatic reaction products form to deviate the amounts of the detected products from being quantitative in mode 3. The contribution of mode 3 in the MnO 2 oxidation of compound IV S can be calculated by dividing total yield of products via mode 3 by conversion of compound IV S . The total yield of products via mode 3 can be calculated by subtracting yield of product C S from conversion of compound IV S . Thus, the contribution can be calculated to be 49% at a reaction time of 480 min.
These observed phenomena mostly reflect the same tendencies as those in the MnO 2 oxidation of compound II in our recent report [4] except that compound IV was oxidized more slowly than the corresponding type of compound II. This slower rate confirms that the presence of the β-methyl group in compound IV decelerates the oxidation owing to the steric factor being larger than that of compound II, although the β-methyl group also has an electron-donating inductive effect to accelerate the oxidation. The ratios of the k obs values between compounds IV and II (k obs (IV)/k obs (II)) were 0.25, 0.34, 0.16, or 0.23 Circles, triangles, and stars indicate the 1st, 2nd, and 3rd trials, respectively, for compounds IV and products C. Squares, inverted triangles, and diamonds indicate the 1st, 2nd, and 3rd trials, respectively, for products B for the H-, G-, S-, or E-types, respectively, which can be an index of the rate-decreasing effect of the presence of the β-methyl group on the disappearance of compound IV. The degree of the rate-decreasing effect of the methyl group in compounds IV is thus dependent on the type of aromatic nucleus, although the degrees are not large enough for the order of the disappearance rates of compounds IV to differ from that of compounds II. This large steric factor of compounds IV must affect their reaction modes (Fig. 2), because mode 1 seems most sensitive to the steric factor. The dependence of the reaction modes on the steric factor will be discussed later.

MnO 2 oxidation of deuterated 1-phenylethanol derivatives (compound V)
The observed phenomena were all almost the same as those of compounds IV except for the slower disappearances of compounds V, which show kinetic isotope effects owing to the presence of the α-deuteriums, and for another phenomenon observed in the oxidation of compound V S described below. In the oxidation of compound IV H , the recovery yield and yield of product C H were 94.3 ± 0.3% and 5.3 ± 0.1%, respectively, at a reaction time of 660 min (± standard deviation calculated from three duplicated runs). The total of these was 99.6%. In the oxidation of compound V G , the recovery yield and product C G were 31.8 ± 0.5% and 67.2 ± 0.4%, respectively, at a reaction time of 120 min. The total of these was 99.0%. In the oxidation of compound V S , products C S and B S formed as the exclusive major and secondary prominent reaction products, respectively. The recovery yield and yields of products C S and B S were 27.7 ± 1.3%, 8.2 ± 0.2%, and 5.3 ± 0.1%, respectively, at a reaction time of 480 min. The total of these was 41.2%. In the oxidation of compound V E , the recovery yield and yield of product C E were 98.2 ± 0.1% and 1.5 ± 0.0%, respectively, at a reaction time of 2880 min. The total of these was 99.7%. The oxidation of compound V S showed a significant difference from that of compound IV S . The amount of afforded product C S was about 1.5 times larger than that of product B S in the oxidation of compound V S , while it was about 5 times that of product B S in the oxidation of compound IV S (yields of products C S and B S at a reaction time of 480 min: 46.8 ± 1.2% and 9.3 ± 0.2%, respectively, Fig. 4). This difference suggests that the oxidation of the S-nucleus in compound V S is competitively and alternatively enhanced by suppressing the oxidation of the benzyl position due to the presence of the deuterium decelerating its abstraction. Table 1 lists the ratios of the k obs values between compounds IV and V with a specific type of aromatic nucleus (k obs (IV)/k obs (V)) or between compounds II and III (k obs (II)/k obs (III)) observed in our recent report [4], which is an index of the magnitude of the observed kinetic isotope effect. The magnitude of the kinetic isotope effect is large when the contribution of mode 1, the direct oxidation of the benzyl alcohol, is large.

Effect of the presence of the β-methyl group on reaction mode
The ratio between compounds IV and V (k obs (IV)/k obs (V)) is always smaller than that between compounds II and III (k obs (II)/k obs (III)), regardless of the type of aromatic nucleus, indicating that the presence of the β-methyl group decreases the contribution of mode 1. The presence of the β-methyl group not only suppresses mode 1, owing to its steric factor, but also must have the reverse effect to enhance the contribution of mode 1, as described above. The former effect thus appears more clearly regardless of the type of aromatic nucleus.
Although the ratio between the E-type compounds (k obs (IV E )/k obs (V E )), 7.6, seems large enough to say that these compounds exclusively undergo mode 1, it is smaller than the ratio of k obs (II E )/k obs (III E )), 8.6. Therefore, mode 2 contributes at least slightly to the oxidations of compounds IV E and V E . The exclusive contribution of mode 1 was presumed for the oxidations of compounds II E and III E in our recent report [4], although a slight contribution of mode 2 to the oxidations of these compounds cannot completely be denied.

Conclusions
The disappearance of compound IV was in the order of: IV G > IV S > > IV H > IV E in MnO 2 oxidation. That of compound IV H , IV G , or IV E was accompanied by almost quantitative formation of product C H , C G , or C E , respectively. In contrast, not only product C S , but also B S was produced from compound IV S as the exclusive major reaction products, but their formation was not quantitative. These phenomena were exactly the same as observed in the same MnO 2 oxidation of compound II in our recent report, although the disappearance of a specific type of compound IV was slower than that of the corresponding type of compound II. It was thus confirmed that the presence of the β-methyl group in compound IV decelerates the oxidation owing to the steric factor, although the group should also have an accelerating effect on the oxidation due to the electron-donating inductive effect on the α-carbon.