BBr3-Assisted Preparation of Aromatic Alkyl Bromides from Lignin and Lignin Model Compounds

Article abstract of DOI:10.1021/acs.joc.8b01628

For the first time, BBr₃-assisted nucleophilic substitution was applied to a variety of β-O-4 and α-O-4 model compounds for the highly effective cleavage of different C-O bonds, including C-O_α-OH, C_β-O/C_α-O and C_Me-O bonds (<0.5 h and >99% conversion for most cases). Without any pretreatment, the substitution proceeds at room temperature in the absence of any catalyst, or additive, selectively affording phenols and important organic synthesis reagents, aromatic alkyl bromides, in high to excellent yields (up to 98%). Preliminary studies also highlight the prospect of this method for the effective cleavage of different types of C-O bonds in real lignin. A total 14 wt % yield of aromatic alkyl bromide, 4-(1,2-dibromo-3-hydroxypropyl)benzene-1,2-diol (10), has been obtained from an extracted lignin through this method.

Full text of DOI:10.1021/acs.joc.8b01628

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Article
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The BBr-Assisted Preparation of Aromatic Alkyl
Bromides from Lignin and Lignin Model Compounds
Xuan Li, Jianghua He, and Yuetao Zhang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01628 • Publication Date (Web): 08 Aug 2018
Downloaded from http://pubs.acs.org on August 8, 2018
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The BBr3ꢀAssisted Preparation of Aromatic Alkyl
Bromides from Lignin and Lignin Model Compounds
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Xuan Li, Jianghua He, and Yuetao Zhang*
State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University,
Changchun, Jilin 130012, China.
KEYWORDS: aromatic alkyl bromide, biomass, CꢀO bond, lignin model compound, nucleophilic
substitution
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ABSTRACT: For the first time, BBr3ꢀassisted nucleophilic substitution was applied to a variety of βꢀOꢀ4 and
αꢀOꢀ4 model compounds for the highly effective cleavage of different CꢀO bonds, including CꢀOαꢀOH, CβꢀO/CαꢀO
and CMeꢀO bonds (< 0.5 h and > 99% conversion for most cases). Without any pretreatment, the substitution
proceeds at room temperature in the absence of any catalyst, or additive, selectively affording phenols and
important organic synthesis reagents, aromatic alkyl bromides, in high to excellent yields (up to 98%). Preliminary
studies also highlight the prospect of this method for the effective cleavage of different types of CꢀO bonds in real
lignin, a total 14 wt% yield of aromatic alkyl bromide, 4ꢀ(1,2ꢀdibromoꢀ3ꢀhydroxypropyl)benzeneꢀ1, 2ꢀdiol (10),
has been obtained from a lignin extracted through this method.
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INTRODUCTION
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With the increasing demand for products derived from petroleumꢀdependent chemicals, finding alternative
renewable energy and valuable chemical resources has become a target that needs to be tackled. As the most
abundant source of renewable aromatics,1 degradation of the highlyꢀfunctionalised lignin exhibits great potential
for the direct preparation of aromatic specialty and fine chemicals, circumventing the requirement for full
defunctionalisation to BTX (benzene, toluene and xylenes) and subsequent refunctionalisation to desired platform
chemicals.2 However, so far lignin is highly underutilized and only less than 2% of lignin is used to deliver
commercial products3 due to its complicated structural characteristic of a variety of distinct and chemically
different bonding motifs, each demanding different conditions for cleavage when selective depolymerization is
targeted. This has greatly stimulated both the academic4 and industrial5 aspirations to develop effective methods for
the degradation and valorization of lignin. Various valueꢀadded products, including aromatic alcohols, 3, 6 phenols,7
aldehydes,8 acid,9 aliphatics,10 etc. have been obtained under oxidizing, 7i, 9a, b, 11 reducing7e, f, 12 or neutral13 reaction
conditions. Generally, a pretreatment strategy is required to achieve the effective cleavage of the CꢀO and/or CꢀC
bonds in different lignin model compounds, either through the oxidation of the αꢀhydroxyl group of lignin models
to a ketone structure with reduced dissociation energy9b, 11 or through a protecting agent14 to stabilize lignin during
extraction. Therefore, more examples and new degradation technologies are still needed for the fundamental
understanding towards the valorization of lignin to generate more renewable aromatic chemicals.
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Organic reactions are closely linked with our life, the application of organic synthetic strategy always opens the
door to solving problems due to its characteristic of easy controllability, forming and breaking chemical bonds
under mild conditions.15 Recently, we successfully applied the classic organic name reaction, BaeyerꢀVilliger (BV)
oxidation, in the effective transformation of inert CꢀC bonds in lignin model compounds into active ester bonds,
followed by alcoholysis reaction to yield esters and phenols in excellent yields.16 As a fundamental class of
reactions occurring at a saturated aliphatic carbon center, nucleophilic substitution has received the greatest
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attention of organic chemists due to its great synthetic utility.17 However, it is seldom reported for the degradation
of lignin, despite that it is wellꢀknown that ether (CꢀO) bonds are abundant in lignin structure, as 50ꢀ65% of all
linkages are βꢀOꢀ4 bond and around 3ꢀ17% are αꢀOꢀ4 bond,1b,18 and ether bonds are prone to nucleophilic
substitution. Herein we successfully applied the BBr3ꢀassisted nucleophilic substitution in the degradation of lignin
model compounds and achieved highly effective cleavage of various types of CꢀO bonds for the first time,
including CꢀOαꢀOH, CβꢀO/CαꢀO and CMeꢀO bonds (< 0.5 h and > 99% conversion for most cases). Unlike the other
degradation strategies, there is no requirement of pretreatment, catalyst or any additives for this method. More
importantly, with strongly Lewis acidic and nucleophilic BBr3, such a method enables us to obtain functionalized
chemical platform, aromatic alkyl bromides, in high to excellent yields (up to 98%) at room temperature. To the
best our knowledge, there has been no such report on the preparation of the useful aromatic alkyl bromides from
lignin so far.
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RESULTS AND DISCUSSION
Figure 1. BBr3ꢀassisted the cleavage CꢀO bonds in αꢀOꢀ4 lignin model compounds. The conversions and yields
were measured by HPLC.
We initiated the study with the reaction of αꢀOꢀ4 (benzylphenylether, A) or βꢀOꢀ4 model
(2ꢀphenoxyethyl)benzene, F) with a series of boron halides, BX3 (X = F, Cl, Br, I) (table S1). We discovered that
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the reactivity is increased with the decrease of the electronegativity: BF3·OEt2 < BCl3 < BBr3 ≈ BI3. BF3·OEt2, is
completely ineffective for both models; BCl3 only works for αꢀOꢀ4 linkage; while BI3 and BBr3 are highly
effective for both models. However, the cost and difficulty in handling of BI3 restrict its application. Therefore, the
less expensive BBr3 was chosen for the reaction. The bromine atom participates in the nucleophilic substitution and
is retained in the final product, and thus we performed the following experiments to investigate the utilization
efficiency of BBr3 since each BBr3 provides 3 equiv. of bromine atoms. It turned out that 0.33 equiv. of BBr3
obtained 71% conversion of A and 0.5 equiv. of BBr3 afforded 90% conversion (table S2), which indicated that at
least two of three bromines of BBr3 are effective for the cleavage of CꢀO bonds. In the presence of 1 equiv. of BBr3,
95% yield of benzyl bromide (1) and 88% yield of phenol (2) was produced within 0.5 h at room temperature. Near
quantitative conversions were obtained for all αꢀOꢀ4 models under optimized conditions (Figure 1). It is noted that
the position of methoxy group also has a significant impact on the reactivity and the BBr3 amount. For B with
orthoꢀmethoxy group, only 1 equiv. of BBr3 is needed to cleave both CαꢀO and CMeꢀO bonds to furnish excellent
yields of 1 in 96% and oꢀbenzenediol (3) in 96%, which also confirmed that at least two of three bromines of BBr3
are in effect. Therefore, the amount of BBr3 was optimized with 0.5 equiv. BBr3 per CꢀO bond in the lignin model
compound for the reaction. It turned out that we could achieve optimal results for most cases with such a feed ratio.
Methyl bromide (CH3Br, Figure S10) is obtained as the bromination product of the methoxy group. However,
the accurate yield of CH3Br was not obtained due to its volatility. For C or D with metaꢀ or paraꢀmethoxy group, 1
equiv. of BBr3 produced 1 in high to excellent yield (80% for C; 97% for D) along with incomplete cleavage
products of CMeꢀO bonds (table S2, entries 5 and 7, 4a, 36% for C; 5a, 47% for D). Therefore, extra BBr3 (2 equiv.)
and extended reaction time (36 h) are needed to obtain high yield of mꢀbenzenediol (4, 85% for C) or
pꢀbenzenediol (5, 97% for D), respectively. It is noted that BBr3 is quite effective for model B with orthoꢀmethoxy
group that needs only 0.5 h to cleave all CꢀO bonds (entry 4, table S2), whereas it took much longer reaction time
(36 h) and more BBr3 (2 equiv. BBr3) to achieve the complete breakdown of all CꢀO bonds for model C with
metaꢀmethoxy group (entry 6, table S2) and model D with paraꢀmethoxy group (entry 8, table S2). For E with
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adjacent electronꢀwithdrawing Cl substituent, only 0.5 equiv. of BBr3 is needed to achieve excellent yield of 1
(94%) and 2ꢀchlorophenol (6, 92%) within 0.5h. Previously, BBr3 was merely reported as a deprotection reagent
for the demethylation19 or depropargylation20 in aryl ethers to afford phenols with a more reactive hydroxyl group
under specific reaction condition. It was noted that such BBr3ꢀassisted demethylation is only effective for the
cleavage of CMeꢀO bond, leaving the other type of CꢀO bonds intact; while BBr3ꢀassisted depropargylation only
works for the cleavage of CpropargylꢀO bond, the methoxy group is notably stable under the reaction conditions,
although BBr3 is known to be an effective reagent for cleaving aryl ethers.21
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Figure 2. BBr3ꢀassisted the cleavage CꢀO bonds in βꢀOꢀ4 lignin model compounds. The conversions and yields
were measured by HPLC.
These results inspired us to apply the BBr3ꢀassisted nucleophilic substitution to βꢀOꢀ4 models, the most
abundant linkage in lignin. To our gratification, BBr3 is highly effective for the cleavage of various CꢀO bonds and
achieves near quantitative conversions for all models, including complex Gꢀtype model M (Figure 2). Excellent
yields of 2ꢀbromoethyl benzene (7, 98%) and phenol (2, 96%) were obtained for F within 0.5h at room temperature,
while G, H, and I with orthoꢀ, metaꢀ and paraꢀmethoxy group all achieved high yields of 7 (G, 95%; H, 93%; I,
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96%), phenols (3 for G, 97%; 4 for H, 93%; 5 for I, 98%) along with CH3Br. To avoid the formation of byproducts,
the experiments were carried out at 5°C for H and I, as it took more than 36h to reach completion. Besides ether
bond, this method is also quite effective for the cleavage of CꢀOαꢀOH bond in J and K with αꢀhydroxyl (OH) group,
affording high yield of 1, 2ꢀdibromoethyl benzene (8) (87% for J; 96% for K) and phenols (2 for J, 85%; 3 for K,
98%). It is noted that the presence of ꢀOH group led to the formation of hydrogen bromide (HBr) (Figure S18).
However, the accurate yield of HBr was not obtained due to its volatility. Interestingly, for L containing both αꢀ
and γꢀOH group, it is effective for the cleavage of CβꢀO and CꢀOαꢀOH bonds but not for CꢀOγꢀOH bond, furnishing
high yield of 2, 3ꢀdibromoꢀ3ꢀphenylpropanꢀ1ꢀol (9) and 2 in 93% and 95%, respectively. Of greater significance is
the effectiveness of this facile method with Gꢀtype βꢀOꢀ4 model (M); excellent yield of
4ꢀ(1,2ꢀdibromoꢀ3ꢀhydroxypropyl)benzeneꢀ1, 2ꢀdiol (10) and oꢀbenzenediol 3 is achieved in 93% and 99% yield,
respectively (Scheme 1), with the requirement of 4 equiv. BBr3.
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Scheme 1. BBr3ꢀassisted the cleavage of CꢀO bonds in Gꢀtype βꢀOꢀ4 model M.
Real lignin structure is quite complex and contains various CꢀO bonds, including CꢀOαꢀOH, CꢀOγꢀOH, CβꢀO/CαꢀO
and CMeꢀO bonds. The investigation of their reactivities would be beneficial to the design and development of
efficient lignin degradation system in the future. Taking βꢀOꢀ4 model as example, we discovered that their
reactivities followed the order in this study: CꢀOαꢀOH > CβꢀO > CMeꢀO >> CꢀOγꢀOH, which was confirmed by the
following experiments. First, model J with both OαꢀOH and CβꢀO bond was chosen for the substrate to react with
BBr3 in different ratios and found that 1 equiv. of BBr3 was needed to achieve near quantitative conversion to the
αꢀOH brominated product, (1ꢀbromoꢀ2ꢀphenoxyethyl)benzene (8'), as the major product along with trace amount
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of cleavage product ((1,2ꢀdibromoethyl)benzene, 8) of CβꢀO bond within one min. Increasing the amount of BBr3
also increased the the yield of 8. With 2 equiv. of BBr3 and 0.5 h reaction time, only negligible amount of 8' was
observed (Figure S25). These results indicated that the cleavage of CꢀOαꢀOH bond is easier than that for CβꢀO bond.
Moreover, increasing the BBr3 amount will speed up the formation of 8. The more BBr3 amounts employed, the
faster reaction activities will be obtained, which was also well demonstrated by the degradation of model F with
different amounts of BBr3 (Figure S29 and S30), which is the characteristic of bimolecular nucleophilic
substitution (SN2) reaction mechanism.22 Second, experimental data revealed that the cleavage of CβꢀO bond is
easier than that for CMeꢀO since only 0.5 h is needed to cleave CβꢀO bond but it took 36 h to complete the cleavage
of CMeꢀO bond for both model H and I (Figure S26 and S27). Third, the BBr3ꢀassisted method is ineffective for the
cleavage of CꢀOγꢀOH bond, which was confirmed by the following experiment: first, BBr3 reacted with
2,3ꢀdibromoꢀ3ꢀphenylpropanꢀ1ol (9) with a γꢀOH to yield dibromo(2,3ꢀdibromoꢀ3ꢀphenylpropoxy)borane (9') after
the elimination of one molecule of HBr. Compound 9' was hydrolyzed back to 9 during the aqueous quenching
process (Figure S28). It is also noted that the dr value of epimerization observed was slightly changed from 67:33
(before reaction for Model L) to 64:36 (after reaction for compound 9') during the inꢀsitu NMR reaction (Figure
S31), which also indicated the BBr3ꢀassisted nucleophilic substitution mainly adopts the SN2 mechanism. Detailed
mechanistic study of this BBr3ꢀassisted nucleophilic substitution remains to be elucidated; however, the
aboveꢀmentioned investigations towards the reactivity of these CꢀO bonds will provide an important foundation for
the future development of lignin depolymerization.
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Scheme 2. Chemical transformation of aromatic alkyl bromide 7 or 8 to useful chemical platform: I) NaN3,
23
DMSO; NaOH, DMSO; a. toluene, reflux; [Cu], DCE, 90°C to 150 °C; 24 b. I2, TBHP, DMA, 100 °C; 25 c.
DBU, DMSO; 26 d. Pd(OAc)2, toluene, 90 °C; 27 II) RNH2, H2O; e. CO2, Cat.; 28 III) cat. base, light; 23 f.
AliBu3/[Ph3C][B(C6F5)4]; 29 IV) K2CO3, allyl amine; g. Acryloyl chloride, Et2N, CH2Cl2, 0 °C to rt;30 V) NaN3,
DMF, 80°C; h. 23 [Ru] dioxane 60°C; 26 i. amide, Tf2O, DCE. 23
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Unlike the other degradation strategies, a key advantage of our method is that there is no need for any
pretreatment, catalyst or additives. Although stoichiometric amount of BBr3 was employed for the nucleophilic
reagent, we achieved not only highly effective cleavage of various CꢀO bonds in lignin model compounds, but also
obtained a variety of aromatic alkyl bromide products at room temperature from the bromination of aryl ether,
which are very important organic synthetic reagents since these reactive Br motifs leave the further derivation
potential to form diverse valueꢀadded aromatic products. The potential relevance of such aromatic alkyl bromides
to the valorization of lignin was confirmed by several chemical transformations starting from monoꢀbromo product
7 or diꢀbromo product 8 (scheme 2). Products includes important heterocyclic compounds,28 polymerizable
monomers, such as styrene,29 allyꢀNꢀalkyl/arylꢀamines,30 etc. Especially, such aromatic alkyl bromides could be
converted to azide compounds,23 which are known to be very important synthetic reagents for a wide range of
chemical transformations, affording Nꢀheterocyclic products of pyrazines,24 imidazoles,25 1,2,3ꢀtriazoles,26 and
isoquinolines.27 These compounds are known to have found vast applications in organic and bioꢀorganic, medicinal
and pharmaceutical, polymer and materials chemistry.
The BBr3ꢀassisted method is highly effective for the cleavage of various types of CꢀO bonds in both αꢀOꢀ4 and
βꢀOꢀ4 models, especially models with orthoꢀmethoxy group, which is commonly observed in the lignin. Therefore,
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we anticipated this method would also exhibit good activity in the lignin depolymerization. Formacell Lignin was
extracted from a native pine tree through a Formacell process, yielding around 5.4 wt% of soluble pineꢀlignin (for
details see SI). The 2D HSQC NMR spectra clearly indicates that the soluble lignin was rich in Guaiacyl (G) units
mainly composed of βꢀOꢀ4 linkage and the absence of Syringyl (S) residues (Figure S32). Therefore, we compared
the inꢀsitu NMR spectrum obtained from the BBr3ꢀassisted degradation of Formacell lignin with that obtained for
Gꢀtype βꢀOꢀ4 model M and observed that major peaks found in the aromatic and aliphatic region of the
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depolymerized lignin products are similar to those for Gꢀtype βꢀOꢀ4 model M as shown in the H NMR spectra
(Figure 3), indicating that this method is also effective for the Formacell lignin and yields similar degradation
products to those obtained for model M. 2D HSQC spectrum of the depolymerized Formacell lignin (Figure 33B)
further revealed that most of the G units were successfully cleaved to produce the same monomeric aromatic alkyl
bromide 10’ as that obtained for Model M (Figure 33B). GPC traces also provide further evidence for the
successful application of BBr3ꢀassisted substitution in the degradation of Formacell lignin at room temperature. As
can be seen from Figure S35, the GPC trace for products obtained after depolymerization shifted to a smaller
molecular weight region with a narrower molecular weight distribution (Đ = 2.12), while the molecular weight (Mw)
value decreased from 1724 g·molꢀ1 for Formacell lignin to 713 g·molꢀ1 for products obtained after
depolymerization. Using Formacell lignin, HPLC analyses indicated that aromatic alkyl bromide 10 is formed in
14 wt% yield after 5 h at room temperature in the presence of 144 wt% BBr3 followed by hydrolysis process
(Scheme S6). In short, preliminary investigation indicates that this BBr3ꢀassisted nucleophilic substitution is also
quite effective for real lignin. Extending investigations on different lignins are under progress.
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Figure 3. Overlay of 1H NMR spectrum of BBr3ꢀassisted depolymerization of Formacell lignin (derived from pine
wood) (above) and Gꢀtype βꢀOꢀ4 model M (below).
CONCLUSIONS
In summary, we have successfully applied the BBr3ꢀassisted nucleophilic substitution to the highly effective
cleavage of various CꢀO bonds in βꢀOꢀ4 and αꢀOꢀ4 lignin model compounds at room temperature for the first time,
affording important organic synthetic reagent, aromatic alkyl bromides along with phenol derivatives in excellent
yields (up to 98% yield). This method is featured with commercial available reagent, simple but highly effective at
room temperature, and no need for pretreatment, catalysts or additives. More importantly, this strategy also exhibits
good activity and chemoselectivity to the real lignin and produced similar monomeric aromatic alkyl bromides and
phenols as that obtained for Gꢀtype lignin model compounds, producing diꢀbromo product 10 as the major product
in a 14 wt% yield from Gꢀtype lignin extracted from native pine tree. Experimental data revealed the BBr3ꢀassisted
method mainly adopted SN2 reaction mechanism and the reactivity for the cleavage of CꢀO bonds followed the
order: CꢀOαꢀOH > CβꢀO > CMeꢀO >> CꢀOγꢀOH. The successful cleavage of different CꢀO bonds in both lignin model
compounds and real lignin extracted from native pine tree achieved by BBr3ꢀassisted substitution reaction provides
the significant important foundation to the depolymerization and valorization of lignin. Relevant work is currently
under way.
EXPERIMENTAL SECTION
General Methods. All syntheses and manipulations of airꢀ and moistureꢀsensitive materials were carried out in
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flamed Schlenkꢀtype glassware on a dualꢀmanifold Schlenk line, a highꢀvacuum line, or a nitrogenꢀfilled glovebox.
Air sensitive NMR samples were conducted in Teflonꢀvalve sealed J. Youngꢀtype NMR tubes. NMR spectra were
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recorded on a Varian Inova 300 (300 MHz, H; 75 MHz, 13C) or Bruker Avance II 500 (500 MHz, 1H; 126 MHz,
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13C) instrument at room temperature. Chemical shifts for H and 13C spectra were referenced to internal solvent
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resonances and are reported as parts per million relative to SiMe4. Fourier transformation infrared (FTIR) spectra
were recorded on a Brucker VERTEX. Mass spectra were recorded on the Bruker MicroTOF Q II.
Boron trifluoride (1.0 M solution in ether), Boron trichloride (1.0 M solution in hexanes), Boron tribromide,
Boron triiodide were purchased from Adamasꢀbeta. Phenethyl alcohol, 2ꢀBromoacetophenone, guaiacol,
diisopropylamine,
nꢀBuLi
(1.6
M
solution
in
hexanes),
3,
4ꢀdimethoxybenzaldehyde,
2ꢀbromoꢀ4'ꢀmethoxyacetophenone, and the standard substances benzyl bromide (1), phenols (2 to 5),
3ꢀmethoxyphenol (4a), 4ꢀmethoxyphenol (5a), (1,2ꢀdibromoethyl) benzene (8) were purchased from J&K.
Solvents were purchased from Titan. All chemicals were used as received unless otherwise specified as follows.
THF was refluxed over sodium/potassium alloy distilled under nitrogen atmosphere and dichloromethane (CH2Cl2)
was dried over CaH2 and distilled before use, then stored over activated 4 Å molecular sieves. CDCl3 was dried
over molecular sieves 4 Å. Standard substances (2ꢀBromoethyl)benzene (7), 2,3ꢀDibromoꢀ3ꢀphenylꢀpropanꢀ1ꢀol (9),
4ꢀ(1,2ꢀDibromoꢀ3ꢀhydroxyꢀpropyl)ꢀbenzeneꢀ1,2ꢀdiol (10) were synthesized in our laboratory as described in the
cleavage of CꢀO bond in βꢀOꢀ4 lignin model compounds. The spectrum of compounds 731 and 932 were in
agreement with those described in the literature. αꢀOꢀ4 and βꢀOꢀ4 lignin model compounds A to I,33 J and K,13b
and M 34 were prepared according to a literature procedure.
L
The reaction mixture was analyzed by using Waters High Performance Liquid Chromatograph (HPLC) system
equipped with autosampler, C18 column (Length: 150mm, Internal diameter: 4.6mm, 35 °C) and UV/Vis detector
(λ = 256 nm). A) CH3OH:H2O (3:1) as a mobile phase with a flow rate of 1mL/min, B) CH3OH:H2O (1:4) as a
mobile phase with a flow rate of 0.8 mL/min, C) CH3CN:H2O (1:1) as a mobile phase with a flow rate of 0.6
mL/min were used for HPLC analysis.
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The Journal of Organic Chemistry
BX3 (X=F, Cl, Br, I) assisted the cleavage of CꢀO bonds in lignin model compounds. The procedure is
detailed for the conversion of lignin model compounds to aryl alkyl halides, using BX3 (X=F, Cl, Br, I) as the
nucleophile. When BBr3 and BI3 were used to cleave the lignin model compounds, near quantitative conversion of
lignin model compound could be obtained (Table S1).
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General procedure: A 10 mL round bottom flask equipped with a magnetic stir bar was charged with lignin
model compounds (0.1 mmol, 1 equiv.) and anhydrous dichloromethane (2 mL), the mixture was stirred until
complete dissolution of the starting materials, then BX3 (n equiv., n is determined by the different models) was
added to the mixture under nitrogen atmosphere at room temperature (RT). The reaction mixture was stirred at RT
for 0.5 h. The following experiments were carried out under the same conditions, unless otherwise specified. After
that the reaction mixture was monitored by High Performance Liquid Chromatograph (HPLC) system. The solvent
was then evaporated under reduced pressure and the crude residue was purified by flash chromatography (using
pentane/ethyl acetate mixture as the eluent). (The inꢀsitu NMR studies were run with a 0.1 mmol scale of substrate
and 0.6 mL CDCl3 in a teflonꢀvalve sealed J. Young type NMR tube).
Typical procedure for the cleavage of CꢀO bonds in lignin model compounds. The procedure is detailed for
the conversion of lignin model compounds to aryl alkyl halides, using BBr3 as the nucleophile. All lignin models,
A to M, could be completely converted to phenols and important organic synthetic reagents, aromatic alkyl
bromides, in high to excellent yields (85% to 99%).
General procedure: A 10 mL round bottom flask equipped with a magnetic stir bar was charged with lignin
model compounds (0.1 mmol, 1 equiv.) and anhydrous dichloromethane (2 mL), the mixture was stirred until
complete dissolution of the starting materials, then BBr3 (n equiv, n is determined by the different models) was
added to the mixture under nitrogen atmosphere at room temperature (RT). The reaction mixture was stirred at RT
for 0.5 h (The reactions of model HꢀI were stirred for 36 h at 5 °C) and then analyzed by High Performance
Liquid Chromatograph (HPLC). The solvent was then evaporated under reduced pressure and the crude residue
was purified by flash chromatography (using pentane/ethyl acetate mixture as the eluent). Inꢀsitu NMR studies
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were carried out with 0.1 mmol scale of substrate and 0.6 mL CDCl3 in a teflonꢀvalve sealed J. Young type NMR
tube and showed the near quantitative conversion of lignin model compounds with BBr3, which is consistent with
the HPLC results (Figure S9ꢀ18 and S20).
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Spectral Data for products. Benzyl bromide (1):1H NMR (500 MHz, CDCl3) δ (ppm) = 7.42 (d, J =7.1Hz, 2H,
Ph), 7.37 (t, J =7.5Hz, 2H, Ph), 7.32 (t, J =7.5Hz, 1H, Ph), 4.52 (s, 2H, PhCH2). 13C NMR (126 MHz, CDCl3) δ
(ppm) = 137.9, 129.1 (2C), 128.9 (2C), 128.5, 33.7.
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Phenol (2): 1H NMR (500 MHz, CDCl3) δ (ppm) = 7.28 (t, J =7.5Hz, 2H, Ph), 6.97 (t, J =7.5Hz, 2H, Ph), 6.87
(d, J =5Hz, 2H, Ph) 4.72 (s, 1H, OH). 13C NMR (126 MHz, CDCl3) δ (ppm) = 155.2, 129.8 (2C), 121.1, 115.5
(2C).
Dibromo(phenoxy)borane(2'): 1H NMR (500 MHz, CDCl3) δ (ppm) = 7.38 (t, J = 5Hz, 2H, Ph), 7.22ꢀ7.27 (t, J
=7.5Hz, 1H, Ph), 7.18 ꢀ 7.01 (d, J =10Hz, 2H, Ph). 13C NMR (126 MHz, CDCl3) δ (ppm) = 154.1, 123.0 (2C),
125.8, 120.1 (2C).
Pyrocatechol (3): 1H NMR (500 MHz, CDCl3) δ (ppm) = 6.90 ꢀ 6.86 (m, 2H, Ph), 6.84 ꢀ 6.80 (m, 2H, Ph), 5.33
(s, 1H, OH). 13C NMR (126 MHz, CDCl3) δ (ppm) = 143.7 (2C), 121.4 (2C), 115.7 (2C).
2ꢀbromobenzo[d][1, 3, 2]dioxaborole (3'): 1H NMR (500 MHz, CDCl3) δ (ppm) = 7.40 ꢀ 7.22 (m, 2H, Ph), 7.22 ꢀ
7.05 (m, 2H, Ph). 13C NMR (126 MHz, CDCl3) δ (ppm) = 148.7 (2C), 123.7 (2C), 112.9 (2C).
Resorcinol (4): 1H NMR (500 MHz, DMSOꢀd6) δ (ppm) = 9.15 (s, 2H, OH), 6.93 (t, J = 7.9 Hz, 1H, Ph), 6.27 ꢀ
6.18 (m, 3H, Ph). 13C NMR (126 MHz, DMSOꢀd6) δ (ppm) = 158.9 (2C), 130.2, 106.7 (2C), 103.0.
3ꢀmethoxyphenol (4a): 1H NMR (500 MHz, CDCl3) δ (ppm) = 7.14 (t, J = 8.0 Hz, 1H, Ph), 6.53 ꢀ 6.48 (m, 1H,
Ph), 6.47 ꢀ 6.41 (m, 2H, Ph), 5.33 (s, 1H, OH), 3.78 (s, 3H, CH3). 13C NMR (126 MHz, CDCl3) δ (ppm) = 161.0,
156.8, 130.3, 108.0, 106.6, 101.7, 55.4.
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1, 3ꢀbis((dibromoboryl)oxy)benzene (4'): H NMR (500 MHz, CDCl3) δ (ppm) = 7.40 (t, J = 8.3 Hz, 1H, Ph),
6.95 (dd, J = 8.3, 2.3 Hz, 2H, Ph), 6.80 (t, J = 2.2 Hz, 1H, Ph). 13C NMR (126 MHz, CDCl3) δ (ppm) = 154.4,
130.7, 117.4, 112.9.
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Hydroquinone (5): 1H NMR (500 MHz, DMSOꢀd6) δ (ppm) = 8.62 (s, 2H, OH), 6.56 (s, 4H, Ph). 13C NMR (126
MHz, DMSOꢀd6) δ (ppm) = 150.19 (2C), 116.12 (4C).
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4ꢀmethoxyphenol (5a): 1H NMR (500 MHz, CDCl3) δ (ppm) = 6.86 ꢀ 6.70 (m, 4H, Ph), 4.86 (s, 1H, OH), 3.77 (s,
3H, CH3). 13C NMR (126 MHz, CDCl3) δ (ppm) = 153.8, 149.6, 116.2 (2C), 115.0 (2C), 56.0.
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1, 4ꢀbis((dibromoboryl)oxy)benzene (5'): H NMR (500 MHz, CDCl3) δ (ppm) = 7.06 (s, 4H, Ph). 13C NMR
(126 MHz, CDCl3) δ (ppm) = 151.3 (2C), 121.4 (4C).
2ꢀChlorophenol (6): 1H NMR (500 MHz, CDCl3) δ (ppm) = 7.33 (dd, J = 8.0, 1.5 Hz, 1H, Ph), 7.19 (td, J = 8.2,
1.6 Hz, 1H, Ph), 7.05 (dd, J = 8.2, 1.6 Hz, 1H, Ph), 6.88 (td, J = 7.7, 1.5 Hz, 1H, Ph), 5.65 (s, 1H, OH). 13C NMR
(126 MHz, CDCl3) δ (ppm) = 151.4, 129.1, 128.5, 121.5, 120.0, 116.4.
(2ꢀbromoethyl)benzene (7): 128 mg, 68% isolated yield. 1H NMR (500 MHz, CDCl3) δ (ppm) = 7.37 (t, J = 7. 5
Hz, 2H, Ph), 7.31 (t, J = 7. 5 Hz, 1H, Ph), 7.26 (d, J = 5.0 Hz, 2H, Ph), 3.61 (t, J = 7.7 Hz, 2H, CH2Br), 3.21 (t, J =
7.7 Hz, 2H, PhCH2). 13C NMR (126MHz, CDCl3) δ (ppm) = 139.0, 128.7 (2C), 128.7 (2C), 127.0, 39.5, 33.0.
(1,2ꢀdibromoethyl)benzene (8): 1H NMR (500 MHz, CDCl3) δ (ppm) = 7.56 ꢀ 7.31 (m, 5H, Ph), 5.16 (dd, J =
10.5, 5.0 Hz, 1H, PhCH), 4.09 (dd, J = 10.5, 5.5 Hz, 1H, CH2Br), 4.04 (dd, J = 10.4, 10.4 Hz, 1H, CH2Br). 13C
NMR (126 MHz, CDCl3) δ (ppm) = 138.7, 129.3, 129.0 (2C), 127.8 (2C), 51.0, 35.2.
(1ꢀbromoꢀ2ꢀphenoxyethyl)benzene (8'): 1H NMR (500 MHz, CDCl3) δ (ppm) = 7.47 (d, J =10 Hz, 2H, Ph), 7.38
(t, J =7.5 Hz, 2H, Ph), 7.33 (t, J =7.5 Hz, 1H, Ph), 7.29 (t, J =7.5 Hz, 2H, Ph), 6.98 (d, J =10 Hz, 1H, Ph), 6.91 (d,
J =10 Hz, 2H, Ph),5.24 (t, J = 7.0 Hz, 1H, PhCHBr), 4.52 (dd, J = 10.5, 7.0 Hz, 1H, CH2O), 4.45 (dd, J = 10.0, 7.0
Hz, 1H, CH2O). 13C NMR (126 MHz, CDCl3) δ (ppm) = 158.1, 138.7, 129.7 (2C), 129.0, 128.9 (2C), 128.0 (2C),
121.7, 115.1 (2C), 72.2, 50.7. GC/MS (EI, m/z [rel. intensity]) 278 [24], 196 [20], 186 [38], 184 [54], 104 [100],
94[16], 78 [38].
dibromo(2,3ꢀdibromoꢀ3ꢀphenylpropoxy)borane (9'): 1H NMR (500 MHz, CDCl3) erythro isomer δ (ppm) = 7.55
ꢀ 7.30 (m, 5H, Ph), 5.22 (d, J = 10.5 Hz, 1H, PhCH), 5.01 (dd, J = 12.0, 4.4 Hz, 1H, CH2), 4.88 (dd, J = 12.0, 3.0
Hz, 1H, CH2), 4.71 ꢀ 4.67 (m, 1H, CHBrCH2). 13C NMR (126 MHz, CDCl3) erythro isomer δ (ppm) = 139.2, 129.4,
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129.0, 128.0, 74.7, 54.9, 52.1. 1H NMR (500 MHz, CDCl3) threo isomer δ (ppm) = 7.55 ꢀ 7.30 (m, 5H, Ph), 5.33
(d, J = 5.7 Hz, 1H, PhCH), 4.62 (dd, J = 11.4, 5.5 Hz, 1H, CH2), 4.53ꢀ4.49 (m, 1H, CHBrCH2), 4.36 (dd, J = 11.5,
5.5 Hz, 1H, CH2). 13C NMR (126 MHz, CDCl3) threo isomer δ (ppm) = 137.4, 129.3, 128.9, 128.4, 73.3, 55.6,
53.2.
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2ꢀbromoꢀ5ꢀ(1,2ꢀdibromoꢀ3ꢀ((dibromoboryl)oxy)propylbenzol[d][1,3,2]dioxaborole (10'): H NMR (500 MHz,
CDCl3) erythro isomer δ (ppm) = 7.36 (d, J = 1.9 Hz, 1H, Ph), 7.28 ꢀ 7.26 (m, 1H, Ph), 7.21 (dd, J = 8.3, 1.9 Hz,
1H, Ph), 5.24 (d, J = 10.8 Hz, 1H, PhCH), 5.01 (dd, J = 12.0, 4.1 Hz, 1H, CH2), 4.87 (dd, J = 12.0, 2.7 Hz, 1H,
CH2), 4.67 ꢀ 4.59 (m, 1H, CHBrCH2). 13C NMR (126 MHz, CDCl3) erythro isomer δ (ppm) = 148.9, 148.5, 135.3,
123.8, 112.7, 112.2, 74.3, 53.2, 51.4. 1H NMR (500 MHz, CDCl3) threo isomer δ (ppm) = 7.49 (t, J = 1.3 Hz, 1H,
Ph), 7.28 ꢀ 7.26 (m, 1H, Ph), 7.21 (dd, J = 8.3, 1.9 Hz, 1H, ph), 5.37 (d, J = 5.2 Hz, 1H, PhCH), 4.67 ꢀ 4.59 (m, 1H,
CH2), 4.45 (q, J = 5.5 Hz, 1H, CHBrCH2), 4.40 (dd, J = 11.1, 5.4 Hz, 1H, CH2). 13C NMR (126 MHz, CDCl3)
threo isomer δ (ppm) = 148.63, 148.52, 133.4, 123.8, 113.2, 112.5, 73.1, 55.3, 53.8.
Typical procedure for the cleavage of L. The procedure is detailed for the conversion of lignin model
compound L to phenol 2 and aromatic alkyl bromide, 2, 3ꢀdibromoꢀ3ꢀphenylpropanꢀ1ꢀol (9) in excellent yields,
using BBr3 as the nucleophile. The inꢀsitu NMR studies showed the near quantitative conversion of lignin model
compound L with BBr3, which is consistent with the HPLC results (Figure S22).
General procedure: A 50 mL round bottom flask equipped with a magnetic stir bar was charged with βꢀOꢀ4
lignin model compound L (200 mg, 1 equiv.) and anhydrous dichloromethane (6 mL), the mixture was stirred until
complete dissolution of the starting materials, then BBr3 (3 equiv.) was added to the mixture under nitrogen
atmosphere. The reaction mixture was stirred at RT for 0.5 h. After that, the reaction was quenched by water, then
the reaction mixture was extracted with dichloromethane (3 × 6 mL). The combined organic layers were dried over
MgSO4, filtered and concentrated under vacuum. Then the mixtures were separated and purified by the fast
chromatographic column (dichloromethane as the eluent) to obtain product 9 as a crystalline white solid (217 mg,
90% isolated yield) and 2 (isolated yield is not obtained due to its volatility). 2,3ꢀdibromoꢀ3ꢀphenylpropanꢀ1ꢀol (9):
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1H NMR (500 MHz, CDCl3) erythro isomer δ (ppm) =7.48 ꢀ 7.31 (m, 5H, Ph), 5.27 (d, J = 11.5 Hz, 1H, PhCH),
4.72 ꢀ 4.68 (m, 1H, CHBrCH2), 4.33 (dd, J = 12.5, 4.5 Hz, 1H, CH2), 4.25 (dd, J = 12.5, 2.6 Hz, 1H, CH2), 2.11 (s,
1H, OH). 13C NMR (126 MHz, CDCl3) erythro isomer δ (ppm) = 140.0, 129.1, 128.9 (2C), 128.0 (2C), 66.0, 59.4,
52.4. 1H NMR (500 MHz, CDCl3) threo isomer δ (ppm) = 7.48 ꢀ 7.31 (m, 5H, Ph), 5.35 (d, J = 6.5 Hz, 1H, PhCH),
4.53 ꢀ 4.49 (m, 1H, CHBrCH2), 3.93 (dd, J = 12.5, 4.5 Hz, 1H, CH2), 3.67 (dd, J = 12.5, 6.5 Hz, 1H, CH2), 2.11 (br
s, 1H, OH). 13C NMR (126 MHz, CDCl3) threo isomer δ (ppm) = 138.1, 129.1, 128.8 (2C), 128.4 (2C), 64.9, 61.9,
59.4, 55.5. GC/MS (EI, m/z [rel. intensity]) 213 [22], 197 [24], 185 [68], 105 [82], 104 [100], 77 [42]. Spectral
data are consistent with that reported in the literature.32 HRMS (ESI) calculated for C9H979Br81BrOꢀ [M ꢀ H]ꢀ
290.9020, found 290.8794.
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Typical procedure for the cleavage of M. The procedure is detailed for the conversion of lignin model
compound M to 4ꢀ(1,2ꢀdibromo)3ꢀhydroxypropyl)benzeneꢀ1,2ꢀol (10), using BBr3 as the nucleophile. Yet, all of
the substrate, M, could completely convert into phenol 3 and aromatic alkyl bromide 10 in excellent yields. The
inꢀsitu NMR studies showed the near quantitative conversion of lignin model compound M with BBr3, which is
consistent with the HPLC results (Figure S24).
General procedure: A 50 mL round bottom flask equipped with a magnetic stir bar was charged with βꢀOꢀ4 lignin
model compound M (200 mg, 1 equiv.) and anhydrous dichloromethane (6 mL), the mixture was stirred until
complete dissolution of the starting materials, then BBr3 (4 equiv.) was added to the mixture under nitrogen
atmosphere, at RT. The reaction mixture was stirred at RT for 0.5 h and such reaction was monitored by HPLC.
The solvent was then evaporated under reduced pressure and the crude residue was purified by flash
chromatography (using pentane/ ethyl acetate (3:1) mixture as the eluent). After solvent removal under reduced
pressure, 10 was obtained as a pale yellow solid (162 mg, 83%). To obtain pure lignin monomer standards, the
resultant product was separated and purified by another silica gel column chromatography. The collected liquid
was dried under reduced pressure in a rotary evaporator under nitrogen atmosphere at RT, and the yielded products
were used for HPLC, IR, high resolution mass spectrometer (ESIꢀHRMS) and NMR analyses.
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4ꢀ(1,2ꢀdibromo)3ꢀhydroxypropyl)benzeneꢀ1,2ꢀol (10): 1H NMR (500 MHz, CD3CN) δ (ppm) = 6.86 (d, J = 2.0 Hz,
1H, Ph), 6.79 (d, J = 8.1 Hz, 1H, Ph), 6.75 (dd, J = 8.1, 2.0 Hz, 1H, Ph), 6.69 (s, 1H, PhꢀOH), 6.67 (s, 1H, PhꢀOH),
4.79 (dd, J = 5.8 Hz, 4.3 HZ, 1H, PhCHBr), 4.26ꢀ4.23 (m, 1H, CHBrCH2), 3.87 ꢀ 3.77 (m, 2H, CH2), 3.22 (t, J =
5.2 Hz, 1H, CH2OH). 13C NMR (126 MHz, CD3CN) δ (ppm) = 145.1 (2C), 134.8, 120.0, 118.3, 115.0, 75.6, 64.5,
61.8.; IR (film) νmax 3383 (br), 2962, 1703, 1609, 1520, 1445, 1375, 1261, 1043, 972, 868, 803 cmꢀ1; HRMS (ESI)
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calculated for C9H979Br81BrO3 [M ꢀ H]ꢀ 322.8924, found 322.8782.
ꢀ
Extraction and characterization of Formacell lignin. Formacell Lignin was extracted using the Formacell
process as described by Delmas etal.35 In a 500 mL roundꢀbottom flask equipped with a magnetic stir bar and a
reflux condenser, 20 g of sawdust was used with a liquor to solid (L/S) ratio of 10.0/0.83. The cooking liquor is a
mixture solution of formic acid/acetic acid/water in a 30/50/20 % volume ratio. The suspension was heated at
107 °C for 10 h (boiling point of water/formic acid azeotrope). After cooling to room temperature, the suspension
was filtered under reduced pressure through G4 funnel and the solids were washed twice with 50 mL of the formic
acid/acetic acid/water mixture solution. The solvents were then evaporated under reduced pressure from the dark
colored solution containing lignin and the hemicellulose derivatives. The solid was washed with 25 mL of distilled
water until the washings were colorless. After that nꢀhexane was used to remove the pine oil and some other
soluble impurities, then the solid was separated into two parts by dichloromethane, the soluble pineꢀlignin (1.07 g,
5.4 wt%) and the insoluble pineꢀlignin (0.29 g, 1.5 wt%). Finally, the soluble lignin was dried overnight under
primary vacuum and then used for 2D HSQC NMR and Gelꢀpermeation chromatography (GPC) analyses. (The
HSQC correlations were in agreement with those described in the literature for organosolv lignin (Figure
S32).11b
)
Depolymerization of Formacell lignin. A 50 mL round bottom flask equipped with a magnetic stir bar was
charged with the soluble Formacell lignin extracted from native pine tree (40 mg, approximatively 0.2 mmol) and
anhydrous dichloromethane (2 mL). The mixture was stirred until complete dissolution of the starting materials,
then BBr3 (144 wt%) was added under nitrogen atmosphere at RT. The reaction mixture was stirred at RT for 5 h
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and then quenched by water, extracted with ethyl acetate (5×3), washed with saltꢀsaturated water and dried over
Na2SO4, The solvent was removed from the combined organic layers under reduced pressure using a rotary
evaporator under nitrogen atmosphere at 20 °C. A total mass yield of 46 mg mixtures was obtained, which is more
than Formacell lignin since Br was introduced into the depolymerization product. HPLC was performed to
determine the yield of aromatic alkyl bromide (10) and GPC was performed to analyze the molecular weight of the
product obtained after depolymerization of extracted Formacell lignin.
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ASSOCIATED CONTENT
Supporting Information Spectroscopic and analytical data as well as the original copy of 1H and 13C NMR spectra
of all compounds. This material is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
* Eꢀmail: ytzhang2009@jlu.edu.cn
ORCID
Yuetao Zhang: 0000ꢀ0002ꢀ6406ꢀ1959
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by the National Natural Science Foundation of China (Grant no. 21422401,
21374040, 21774042), 1000 Young Talent Plan of China funds, the startup funds from Jilin University,
Talents Fund of Jilin, We grateful acknowledge Prof. Xiaopeng Li for the Mass spectrometry
measurements from University of South Florida.
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