Selective electrochemical C[sbnd]O bond cleavage of β-O-4 lignin model compounds mediated by iodide ion

Article abstract of DOI:10.1016/j.tet.2017.03.027

The electrochemically oxidative cleavage of lignin β-O-4 model compounds mediated by iodide ion has been studied. The results indicate that electrolytic conditions play a predominant role in determining the distribution of cleavage products. The preparative-scale electrolysis proceeds in a simple undivided cell, employing a catalytic amount of NaI as the redox mediator and supporting electrolyte in methanol. Under these conditions, the C_β[sbnd]O bond is selectively cleaved with 2,2-dimethoxy-2-arylacetaldehyde being the main product. In some cases, the reaction gives a good yield of cleavaged products. The results further demonstrate that the indirect electrolysis mediated by halide is a versatile approach for chemical transformation.

Full text of DOI:10.1016/j.tet.2017.03.027

Accepted Manuscript
Selective electrochemical C-O bond cleavage of β-O-4 lignin model compounds
mediated by iodide ion
Wei-Jing Gao, Chiu Marco Lam, Bao-Guo Sun, R. Daniel Little, Cheng-Chu Zeng
PII:
S0040-4020(17)30264-8
10.1016/j.tet.2017.03.027
TET 28533
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 16 January 2017
Revised Date: 9 March 2017
Accepted Date: 10 March 2017
Please cite this article as: Gao W-J, Lam CM, Sun B-G, Little RD, Zeng C-C, Selective electrochemical
C-O bond cleavage of β-O-4 lignin model compounds mediated by iodide ion, Tetrahedron (2017), doi:
10.1016/j.tet.2017.03.027.
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ACCEPTED MANUSCRIPT
Graphical Abstract:

ACCEPTED MANUSCRIPT
Selective electrochemical C-O bond cleavage of β-O-4 lignin model compounds
mediated by iodide ion
a,b
c
a,
c
Wei-Jing Gao, Chiu Marco Lam, Bao-Guo Sun, * R. Daniel Little , Cheng-Chu
a,b,
Zeng
*
a
Beijing Advanced Innovation Center for Food Nutrition and Human Health, School
of Food and Chemical Engineering, Beijing Technology and Business University,
Beijing 100048, China
Tel.: 0086-10-67396211; Fax: 0086-10-67396211, E-mail: zengcc@bjut.edu.cn,
sunbg@btbu.edu.cn
b
College of Life Science & Bioengineering, Beijing University of Technology, Beijing
1
00124, China
c
Department of Chemistry & Biochemistry, University of California, Santa Barbara,
California 93106-9510, USA
Graphical Abstract:
Abstract
The electrochemically oxidative cleavage of lignin β-O-4 model compounds
mediated by iodide ion has been studied. The results indicate that electrolytic
conditions play a predominant role in determining the distribution of cleavage
products. The preparative-scale electrolysis proceeds in a simple undivided cell,
employing a catalytic amount of NaI as the redox mediator and supporting electrolyte
in methanol. Under these conditions, the C -O bond is selectively cleaved with
β
2
,2-dimethoxy-2-arylacetaldehyde being the main product. In some cases, the reaction
gives a good yield of cleavaged products. The results further demonstrate that the
indirect electrolysis mediated by halide is a versatile approach for chemical
1

ACCEPTED MANUSCRIPT
transformation.
Key words: β-O-4 lignin model compounds; C-O bond cleavage; electrochemical
cleavage; indirect electrolysis.
1
. Introduction
Lignin, the second most abundant natural polymer, consists of an oxygenated
phenylpropane subunit connected via C-O and C-C bonds with the β-O-4 ether bond
being the most common linkage and comprising approximately 50% of all subunit
1
bonds of this type. Due to its abundance in nature and potential of providing
high-valued aromatics with low molecular weight, selective decomposition of lignin
is considered as a longstanding aim in sustainable development and green chemistry.
In principal, the decomposition and fragmentation of lignin can be achieved via
1
cracking, hydrolysis, catalytic reduction and catalytic oxidation. Among them,
catalytic oxidation has attracted most of the attention since oxidation reactions tend to
form more structurally complex platform of aromatic subunits, and possess
functionality that could be used to convert lignin directly to fine chemicals. In the
2
context, metal oxides, nitrobenzenes and CoCrO have been used for catalytic
4
3
oxidative cleavage of lignin. Recently, new catalytic methods have also been
4
developed, including biocatalysis, organometallic catalysis, biomimetic catalysis,
5
6
7
photocatalysis, the use of mesoporous materials and vanadium-based catalysis.
Electrochemistry provides an alternative approach for the decomposition of lignin
and lignin model compounds by proposing direct electron transfer between the lignin
component and the working electrode, or an indirect process using a redox catalyst.
For example, Kraft lignin was degraded electrochemically using a Ti/TiO NT/PhO
2
2
electrode, leading to a 13% reduction in the C-O-C group content and a 44% increase
8
in C=O groups. Hempelmann and coworkers studied electro-catalytic oxidative
cleavage of lignin in protic ionic liquid (triethylammonium methanesulfonate) by
using a working electrode coated with ruthenium-vanadium-titanium alloy oxide. The
authors observed that the applied potential powerfully influenced the product portfolio;
2

ACCEPTED MANUSCRIPT
9
higher potentials resulted the formation of molecules with smaller molecular weights.
Recently, Chen and Wan et al. carried out electrochemical depolymerization of lignin
in an undivided cell using a RuO -IrO /Ti mesh anode and an alkaline electrolyte. The
2
2
linkage among C9 units (such as p-hydroxybenzene, guaiacyl, and syringyl
phenylpropane units) in lignin was found being cleaved; more than 20 kinds of
low-molecular weight aromatics were produced and identified by GC-MS and
10
ESI-MS/MS measurements.
Because of the complexity of lignin, especially its low solubility in most of the
common solvents, most of studies of the electrochemical oxidative cleavage of lignin
have been performed based on the model compounds. Utley and coworkers
investigated the direct electrooxidative cleavage of non-phenolic lignin model dimers
I (bearing a secondary benzylic hydroxyl unit – see structure I) and dimers II (a
carbonyl unit conjugated with one of the aromatic rings – see structure II) in an
alkaline electrolyte using a nickel anode (Figure 1). It was observed that
polymerization was predominant, although aldehydes are formed together with larger
11
amounts of the corresponding carboxylic acids. When the anodic oxidation of dimer
I compound was performed in methanol containing 0.2 M NaClO , preparative scale
4
electrolysis gave 3,4-dimethoxybenzaldehyde as the major product, corresponding to
cleavage of C -C bonds, whereas, model II analogues were not cleaved under the
α
β
1
2
identical conditions.
Electrochemical cleavages of lignin model compounds in the presence of redox
catalysts have also investigated. Employing triarylamine as an electron carrier, the
anodic oxidation of model I compounds in acetonitrile afforded aldehydes (vanillin or
11
syringaldehyde derivatives) as the major products. In addition, Takano et al. carried
out systematic studies of electro-oxidative reactions of non-phenolic lignin model
compounds in the presence of laccase mediators (such as N-hydroxyphthalimide
(
NHPI),
1-hydroxybenzotriazole
(HBT),
violuric
acid
(VLA),
and
2
2
,2,6,6-tetramethylpiperidine-N-oxyl
(TEMPO)
,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS)). The authors found that
3

ACCEPTED MANUSCRIPT
the oxidation of dimers I with NHPI, HBT, VLA, and TEMPO as mediators gave
exclusively dimers II, the corresponding C =O products, in high yield, whereas ABTS
α
1
3
resulted in C -C cleavage.
α
β
Figure 1. Representation of the structure of lignin and lignin model compounds,
highlighting the β-O-4 linkage.
It has been reported that the β-O-4 linkage (see the subunit in the frame in Fig. 1)
is significantly weakened upon oxidation of either the secondary benzylic or the
1
4
primary hydroxyl unit to a carbonyl group. In addition, the dehydrogenative cross
coupling of propiophenone derivatives and secondary amines could be achieved
1
5
chemically and electrochemically (Scheme 1). Based on these observations, we
envisioned that the electrochemical oxidation of model II type structures (e.g.,
2
-phenoxy-1-arylethanone, III), mediated by halide in the presence of an amine,
where it may produce an N,O-ketal such as IV. This structure of intermediate IV is
oxidation intact and readily undergoes cleavage of the C -O bond. In such a two-step
β
pattern, the resulting fragmental products, such as 2-oxo-2-arylacetaldehyde and
phenols, may avoid of being over-oxidized electrochemically and therefore lead to a
higher yield (Scheme 1). Herein, we describe our findings in electro-oxidative
cleavage of lignin model compounds III in the presence of an iodide mediator.
4

ACCEPTED MANUSCRIPT
Scheme 1. Our working hypothesis
. Results and discussion
To demonstrate the feasibility of our idea, we initially carried out constant current
2
electrolysis (CCE) of o-methoxyphenoxy phenylethanone, 1d, in the presence of a
secondary amine with graphite plate as the working electrode. Despite much effort
screening amines (Et NH, morpholine), redox catalysts (n-Bu NI, Et NBr, NaBr) and
2
4
4
solvents (CH CN and NMP), we invariably obtained complex reaction mixtures from
3
which it proved difficult to isolate and identify the products.
In order to clarify any possible products, the aforementioned reaction mixture
was analyzed by GC-MS. The presence of acetophenone, 4c, and o-methoxyphenol
were confirmed. This result indicates that C -O bond cleavage of 1d did occur (Table
β
1
, entry 1). The C -O bond cleavage of 1d was further confirmed by electrochemical
β
oxidation of 1d in the presence of morpholine; after 7 F/mol of charge was consumed,
d is completely consumed and 4c was isolated in 10% yield, along with unidentified
1
product mixtures after column chromatography (Scheme 2 and entry 2).
5

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O
O
2
equiv morpholine
O
0
.2 equiv Bu NI/CH CN
4
3
+
complex mixture
graphite anode
MeO
Fe plate cathode
CCE at 3 mA/cm2
4
c (10%)
1d
Scheme 2. Electrochemical cleavage of 1d in the presence of morpholine
In order to obtain a better identification of the product structures and a deeper
insight of the reaction mechanism, we decided to choose 1a as the model substrate. It
was observed that the results of the electrochemical oxidation of 1a was affected by
different 1) bases and 2) redox mediators. For example, when 1a was subjected to
2
electrolysis at a constant current of 6 mA/cm in methanol in the presence of
morpholine (1.2 equiv) with KI as mediator, 4-methoxyacetophenone, 4a, and methyl
2
-(4-methoxyphenyl)-2-oxoacetate, 7a, were isolated in 35% and 18% yields,
respectively, along with other unidentified mixture (Scheme 3 and Entry 3). These
results suggest that morpholine functioned only as a base rather than being
incorporated in the manner portrayed in Scheme 1. That means, in order to avoid
possible side reactions, secondary amines should not be added in subsequent
experiments.
Scheme 3. Electrochemical cleavage of 1a in the presence of morpholine
Next, the electrochemical oxidation of 1a using inorganic bases was performed;
once again, product mixtures were obtained. For example, in the presence of NaOH
(0.4 equiv), the electrochemical oxidation of 1a in MeOH using NaI (0.6 equiv) as
redox mediator afforded compounds 5a, 6a and 7a with isolated yields of 34%, 13%
and 13%, respectively (Scheme 4 and entry 4). When the reaction mixture was treated
with acetic acid, products 5a and 6a disappeared and the yield of 7a increased to 31%.
In addition, when NaHCO was employed as a base, a different product distribution
3
6

ACCEPTED MANUSCRIPT
1
was observed, with 2a, 3a and 4a being determined as 28%, 9% and 5% ( H NMR
yield using 1,3,5-trimethoxybenzne as an internal standard) (Scheme 5 and entry 5).
1
Notably, we found that 2a and 3a were produced in 46% and 27% H NMR yield,
respectively, with a combined 73% yield after 4 F/mol of charge was consumed when
the reaction was performed in MeOH without any base (Scheme 6 and entry 6).
Therefore, the presence of base is dispensable for the electro-oxidative cleavage of
β-O-4 lignin compounds.
Scheme 4. Electrochemical cleavage of 1a in the presence of NaOH
Scheme 5. Electrochemical cleavage of 1a in the presence of NaHCO3
Scheme 6. Electrochemical cleavage of 1a in neutral MeOH.
The nature of the redox catalyst also influenced the cleavage-product distribution.
For example, replacing NaI by NaBr, the anodic oxidation of 1a in the presence of
NaOH gave a 40% yield of 4a and a 16% yield of 7a (entry 7). When n-Bu NI was
4
used as a redox catalyst, complex mixtures were observed based on TLC monitoring
7

ACCEPTED MANUSCRIPT
(entry 8).
Table 1. Screening of base, redox catalysts and solvent for the selective cleavage of
a
C -O bond of lignin model compound 1d and 1a
β
b
Entry
substrate Base (equiv)
mediator
equiv.)
n-Bu NI
solvent
Product (yield)
(
c
1
1d
1d
1a
1a
1a
Et NH (2.0)
CH CN
Complex mixture
2
4
3
(0.2)
2
3
4
morpholine
n-Bu NI
CH CN
4c (10%) + other mixture
4a (35%) + 7a (18%)
5a (13%) + 6a (34%) + 7a
4
3
(
2.0)
morpholine
1.2)
(0.2)
KI (1.0)
MeOH
MeOH
MeOH
(
NaOH (0.4)
NaI (0.6)
NaI (0.6)
(13%)
d
5
NaHCO3
2a (28%) + 3a (9%) +
4a (5%)
(0.6)
d
6
1a
1a
-
NaI (0.6)
NaBr
MeOH
MeOH
2a (46%) + 3a (27%)
4a (40%) + 7a (16%)
7
8
NaOH (0.4)
NaOH (0.4)
(0.6)
1a
n-Bu NI
4
MeOH
Complex mixture
(0.6)
a
Conditions: starting 1d or 1a (0.5 mmol), redox catalyst (0.6 mmol) in 12 mL
2
solvent, graphite anode, iron plate cathode, undivided cell, 6 mA/cm .
b
Isolated yield from column chromatography
c
The presence of acetophenone, 4c, and o-methoxyphenol were confirmed by
GC-MS.
d
1
Yield determined by H NMR using 1,3,5-trimethoxybenzne as an internal
8

ACCEPTED MANUSCRIPT
standard.
Based on the preliminary results described above, we concluded that the efficient
anodic cleavage of model compound 1a calls for using NaI as the mediator and
neutral methanol as the solvent. With these results in hand, we further optimized the
reaction conditions. By using NaI as the redox catalyst and MeOH as solvent, the
o
charge consumption was first screened at 0 C. When 6 F/mol of charge passed, an 84 %
yield was observed, consisting of 66% of 2a, and 18 % of 3a. After passing 8 F/mol
and 10 F/mol of charge, 3a was not detected in either case, and 2a was isolated with a
lower yield of 46% and 37%, respectively (Table 2, Entry 1-4). In addition,
monitoring the reaction mixture using HPLC-MS showed that o-methoxyphenol
appeared after passing 2 F/mol of charge; its integration area reached a maximum at 6
F /mol, and dropped to 0 after 10 F/mol of charge was passed. A similar tendency was
observed for product 2a. The results indicate that the use of excess charge is not
compatible for the generation of 2a.
Temperature also influenced the reaction selectivity. When the electrolysis of 1a
o
was performed at room temperature (~ 25 C), a total yield of 78 % resulted, but with
lower reaction selectivity (Table 2，Entry 5). Thus, two additional compounds, 5a and
6
a, were detected and identified in 11% and 14% yields, respectively, along with the
formation of 2a (29%) and 3a (24%). A further increase of the reaction temperature to
o
4
0 C decreased the yield of 2a to 15%, whereas 5a and 6a were isolated in 12 % and
2
3% yield, respectively, in addition to 23% of 3a (Table 1, Entry 6). Therefore, we
concluded that the use of a lower temperature proves beneficial and leads to higher
chemical selectivity.
9

ACCEPTED MANUSCRIPT
a
Table 2: Further conditional optimization
b
Q
T
Anode
Yield
Yield
(%)
73
84
46
37
78
73
29
67
45
45
73
81
57
73
71
55
79
Entry
o
(
F/mol) ( C) /cathode 2a 3a 4a 5a 6a
1
2
3
4
5
6
4
6
8
10
6
6
6
6
6
6
6
6
6
6
6
6
6
0
0
C /Fe
C /Fe
C /Fe
C /Fe
C /Fe
C /Fe
C /Fe
C /Fe
C /Fe
GC/Fe
46 27
0
0
0
0
0
0
0
0
0
0
66 18
0
46
37
0
0
0
0
0
25
40
0
29 24
15 23
0
11 14
12 23
0
c
7
18
45 22
45
0
11
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
d
8
0
e
9
0
0
0
1
0
1
0
17 10 18
1
0
DSA/Fe 36 32
5
5
1
1
1
1
1
1
2
3
4
5
6
7
0
Pt/Fe
C/Sn
C/Al
C/Ni
C/C
53 23
0
27 13 17
44 24
0
5
0
45 12 14
25 10 20
0
0
C/Pt
57 22
9
a
Conditions: substrate 1a (0.5 mmol) in MeOH (10 mL) containing NaI (0.6 equiv), 6
2
mA/cm
b
H NM yield
c
0.3 equiv of NaI was used
d
e
0
.9 equiv of NaI was used
LiClO (0.1 M)/CH OH as supporting electrolyte
4
3
The product distribution was also effected by the amount of redox catalyst. As
1
0

ACCEPTED MANUSCRIPT
shown in Table 2, when the amount of NaI decreased to 0.3 equiv from the initial
value of 0.6 equiv, a different product distribution was observed, and products 2a and
4
a were identified and isolated in 18% and 11% yields respectively (Table 2, Entry 7).
In contrast, 2a (45%) and 3a (22%) were obtained in a total yield of 67% when the
loading of NaI increased to 0.9 equiv. (Table 2，Entry 8). We conclude that 0.6 equiv.
of NaI constitutes the best loading. Notably, when the reaction was repeated in the
presence of LiClO (0.1 M) as conducting salt, 2a was generated exclusively, while
4
the yield was not improve (Table 2, Entry 9).
Since the nature of the electrode can play an important role in an electrolysis,
electrode material screening was also carried out. It was observed that both the anode
and the cathode effect the reaction. For example, when the graphite working electrode
was replaced by a glassy carbon electrode, reaction selectivity decreased and three
products (2a, 3a and 4a) with a total yield of 45% were isolated (Table 2, Entry 10).
In the cases of dimension stable anode (DSA) and Pt, the total yield increased to 73%
and 81%, respectively, with 2a and 3a being predominate products (Table 2, entries 11
and 12). On the other hand, when Sn, Al, Ni and graphite were used as the cathode, 2a,
3
a and 4a were identified, while their yields were dependent upon the cathode (Table
, entries 13-15).
2
Based on the results described above, we conclude that the optimal reaction
conditions call for using NaI as the redox catalyst and also as the supporting
electrolyte (60 mol%), a graphite plate as the working electrode and an Fe plate as the
o
cathode. The reaction is best performed at 0 C in an undivided cell using methanol as
the solvent without additional conducting salt or added base, and with 6 F/mol of
charge.
With the optimal conditions in hand, we then studied the scope and the generality
of the protocol by examining other β-O-4 lignin model compounds. As shown in
Table 3, when phenol ether 1b was subjected to electrolysis under the standard
conditions, only 2a was obtained albeit in a 36% yield (Entry 2). Comparison of this
outcome with that obtained using the o-methoxy substituted substrate 1a, reveals that
1
1

ACCEPTED MANUSCRIPT
the presence of electron-donating substituents on the phenol ether subunit may benefit
the C-O cleavage. This assumption is further verified when one compare the results of
1
c with 1d, in which higher yield was obtained from 1d, the methoxy substituted
analog of 1c. Appending two electron donating groups proved either beneficial or
deleterious, depending upon their location. For instance, 3,4-dimethoxy phenol ether
1
f provided a 68% yield of 2a, along with 9a in 9% yield. In contrast, 2,5-dimethoxy
phenol ether 1e, led to only a 14% yield of 2a. The results imply that that the nature of
the substituent, as well as its position influences the efficiency of selective C-O bond
cleavage.
For alkyl-substituted phenol ethers 1g and 1h, several yields of cleavage product
2
a were obtained. However, when 1i was subjected to anodic oxidation under
standard conditions, a precipitate formed at the anodic surface and only 9% yield of
b was detected from the reaction mixture. Eventually, when 1j was used as the
4
substrate, only a trace amount of 2b was found.
a
Table 3. Electrochemical C-O bond cleavage of β-O-4 lignin model compounds
1
2

ACCEPTED MANUSCRIPT
Substrates
O
Products (yield)
MeO
MeO
OMe
MeO
H
O
H
O
+
+ others
O
O
MeO
MeO
MeO
MeO
MeO
MeO
1a
2a (66%)
3a (18%)
O
MeO OMe
O
O
H
+
others
O
1b
2a (36%)
2b (38%)
2b (68%)
O
MeO OMe
H
+
+
others
others
1c
O
O
OMe
OMe
MeO
O
H
O
1d
O
OMe
MeO OMe
O
H
+
others
MeO
MeO
O
O
MeO
1
e
2a (14%)
2a (66%)
O
O
MeO OMe
OMe
OMe
H
+
+
others
MeO
O
MeO
1f
4a (9%)
MeO
O
MeO
OMe
H
O
O
+
others
others
O
1g
MeO
2a (36%)
MeO
MeO
O
MeO OMe
H
+
O
MeO
2a (30%)
4b (9%)
1
h
O
O
O
+
others
others
OMe
OMe 1i
OH
O
MeO OMe
H
+
O
1j
2b (trace)
a
o
Reaction conditions: substrates (0.25 mmol), 0 C, Q = 6 F/mol, NaI (60 mol%),
2
and 10 mL of CH OH, 6 mA/cm , graphite anode and Fe plate cathode. Yields of
3
products were determined by H NMR using 1,3,5-trimethoxybenzene as the internal
standard.
1
3

ACCEPTED MANUSCRIPT
On the basis of these results and the well-known electrochemical α-hydroxylation
1
6
of ketones, a possible mechanism for the formation of the various cleavage products
is proposed and illustrated in Scheme 7. The chemistry starts with the anodic
⊕
oxidation of iodide ion to form its oxidation state, I ; meanwhile, the solvent
-
methanol is reduced at the cathode to generate methoxide anion, MeO . The
electrochemically generated methoxide serves as a base to deprotonate the starting
2
-aryloxyarylethanone 1 followed by the subsequent reaction with electrochemically
⊕
in situ generated I to generate α-iodoketone 8. Addition of the methoxide anion to
the carbonyl group of intermediate 8, followed by an intramolecular cyclization leads
to intermediate epoxide 9. Subsequent ring-opening of 9 induced by the second
equivalent of methoxide anion results in the formation of α-hydroxy ketals 10. Once
2
the key intermediate 10 is generated, it undergoes hydrolysis, removing the Ar OH
unit to form α,α-dimethoxy aryl acetoaldehyde 2. On the other hand, oxidation of
intermediate 10 to corresponding ester 5, followed by trans-esterification and
hydrolysis affords product 7; alternatively, ester 5 first undergoes hydrolysis to give
intermediate 11, followed by a trans-esterification to generate methyl α-oxo
arylacetate 7.
cathode
anode
MeOH
O
MeO
I
I
O
O
Ar1
O
O
9
Ar1
Ar2
O
Ar1
Ar2
O
O
Ar1
Ar2
Ar2
MeO
1
1'
I
MeO
8
OMe
OMe
O
OMe
MeO
Ar1
[O]
MeO
Ar1
MeOH
MeO
Ar1
MeOH
O
O
OMe
Ar2
Ar2
2
-
Ar -OH
OH
O
10
5
6
2
-
Ar -OH
H
3
O
3
H O
OMe
O
MeO
Ar1
O
MeOH
H
Ar1
O
Ar2
OMe
2
Ar
O
O
- Ar -OH
O
2
11
7
Scheme 7. Proposed mechanism for the electrochemical formation of 2, 5, 6 and
7
.
1
4

ACCEPTED MANUSCRIPT
To account for the formation of compound 3a, we propose that the epoxide 9a
initially undergoes a ring-opening process in the presence of methanol to form
intermediate 12a, which then loses methanol and undergoes a 1,2-H~ and aryl transfer
to form intermediate 15a and finally generate 3a.
H
MeO
OMe
O OMe
O
OMe
OMe
OMe
H
O
+H
O
MeOH
OH
O
MeOH
OMe
2a
H
H
MeO
MeO
MeO
9
a
13a
1
MeO
O
H
H
H
H
O OMe
O
OMe
O OMe
O
OMe
MeO
- H
H
O
MeO
MeO
3
a
15a
14a
OMe
Scheme 8. Proposed mechanism for the electrochemical formation of 3a.
3
. Conclusions
In summary, the study of electrochemical oxidative cleavage of lignin β-O-4
model compounds was conducted. Various electrolytic parameters, including solvent,
additive, mediator, charge, temperature and electrode material, were investigated to
optimize the reaction conditions. Constant current electrolysis of a series of lignin
β-O-4 model compounds was achieved in a simple undivided cell, employing
catalytic amount of NaI as the redox mediator and supporting electrolyte in methanol.
It was found that addition of an amine or an inorganic base as additives was not
necessary for this electro-oxidative cleavage. In addition, complicated reaction
mixtures of cleavage products were invariably obtained, the distribution being
dependent upon electrolytic parameters while 2,2-dimethoxy-2-arylacetaldehyde was
concluded as the main product. Finally, a plausible reaction mechanism was proposed.
4
. Experimental
4
.1 Instruments and Reagents.
Analytical thin-layer chromatography was carried out using silica gel 60 F254
precoated plates. Silica gel (600 mesh) was used for flash column chromatography
using the combination of ethyl acetate and petroleum ether as eluent. All commercial
1
5

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reagents were used as received. All melting points were measured by an
electrothermal melting point apparatus, and are uncorrected. IR spectra were recorded
1
as neat samples for liquid and in KBr for solids. H NMR spectra were recorded with a
1
13
4
00 M spectrometer (400 MHz H frequency and 100 MHz C frequency). Chemical
shifts are given in ppm, and coupling constants are in Hertz. All starting materials
1
7
were synthesized according to known procedures.
4
.2 Typical Procedure for the electrochemical cleavage of lignin model compounds
A 50 mL beaker-type undivided cell was equipped with a carbon anode and a Fe
plate cathode and connected to a DC regulated power supply. Lignin model substrates
0.25 mmol), NaI (0.15mmol) and 15 mL of CH OH were added to the cell. The
(
3
2
o
mixture was electrolyzed using constant current conditions (∼ 6 mA/cm ) at 0 C
−
1
while stirring. The electrolysis was terminated when 6 F mol of charge had been
consumed. After the electrolysis, the solvent was removed under reduced pressure.
Then the residue was extracted by CH Cl (20 mL×3). The combined organic phase
2
2
was washed with water (15 mL×3) and dried with Na SO . After filtration to remove
2
4
Na SO and evaporation to remove solvent, the residue was subjected to column
2
4
chromatography to give the desired products. Alternatively, to the residue was added
,3,5-trimethoxybenzene as well as 15 mL CH Cl . When CH Cl was removed under
1
2
2
2
2
reduced pressure, the residue was placed into a vacuum drying oven for over 10 h.
1
The yields of products were calculated by H NMR measurement.
2
,2-Dimethoxy-2-(4-methoxyphenyl)acetaldehyde (2a). Isolated as a colorless oil.
1
H NMR (400 MHz, CDCl ): δ 3.33 (s, 6H), 3.83 (s, 3H), 6.95 (d, J = 8.8 Hz, 2H),
3
1
3
7
1
1
+
.45 (d, J = 8.8 Hz, 2H), 9.32 (s, 1H); C NMR (400 MHz, CDCl ): δ 50.3, 55.3,
3
-1
03.0, 113.6, 125.5，129.0, 160.5, 195.3; IR (KBr) (cm ): 2954, 2360, 1716, 1607,
512, 1435, 1257, 1170, 1031, 848, 771; HRMS (ESI) m/z calcd for C H O Na (M
11
14
4
+
Na) 233.0784, found 233.0780.
,2-Dimethoxy-2-phenylacetaldehyde (2b). Isolated as an oil. H NMR (400 MHz,
CDCl ): δ 3.35 (s, 6H), 7.40-7.46 (m, 3H), 7.55 (d, J = 7.2 Hz, 2H), 9.37 (s, 1H).
1
7
1
2
3
2
-Methoxy-2-(2-methoxyphenoxy)-2-(4-methoxyphenyl)acetaldehyde
(3a).
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6

ACCEPTED MANUSCRIPT
1
Isolated as a colorless oil. H NMR (400 MHz, CDCl ): δ 3.45 (s, 3H), 3.83 (s, 3H),
3
3
8
.94 (s, 3H), 6.79-6.83 (m, 1H), 6.93-7.04 (m, 4H), 7.24-7.27 (m, 1H), 7.64 (d, J =
1
3
.8 Hz, 2H), 9.34 (s, 1H); C NMR (400 MHz, CDCl ): δ 50.9, 55.3, 55.9, 104.8,
3
112.2, 114.4, 119.5, 120.8, 123.6, 125.5, 129.3, 143.6, 150.7, 160.7, 193.3; IR (KBr)
-1
(
cm ): 3445, 2960, 1726, 1681, 1600, 1503, 1261, 1174, 835, 746; HRMS (ESI) m/z
+
calcd for C H O (M -H) 301.1076, found 301.1080.
1
7
17
5
18
o
1
-(4-Methoxyphenyl)ethanone (4a). Isolated as a colorless solid, m.p.: 37-39 C.
1
H NMR (400 MHz, CDCl ): δ 2.58 (s, 3H), 3.89 (s, 3H), 6.95 (d, J = 9.2 Hz, 2H),
3
7
.96 (d, J = 9.2 Hz, 2H).
-(2-Methoxyphenyl)ethanone (4b). Isolated as a colorless oil, H NMR (400 MHz,
CDCl ): δ 2.63 (s, 3H), 3.91 (s, 3H), 6.97-7.03 (m, 2H), 7.46-7.50 (m, 1H), 7.74-7.76
1
9
1
1
3
(m, 1H).
2
-Methoxyphenyl 2,2-dimethoxy-2-(4-methoxyphenyl)acetate (5a) Isolated as a
1
colorless oil. H NMR (400 MHz, CDCl ): δ 3.37 (s, 3H), 3.63 (s, 3H), 3.83 (s, 3H),
3
3
8
.95 (s, 3H), 6.77-6.81 (m, 1H), 6.91-7.00 (m, 4H), 7.23-7.27 (m, 1H), 7.71 (d, J =
1
3
.8 Hz, 2H); C NMR (400 MHz, CDCl ): δ 50.7, 53.0, 55.2, 56.1, 102.3, 112.1,
3
-1
1
13.8, 117.4, 120.7, 122.7, 128.2, 128.6, 144.1, 150.2, 160.2, 168.9; IR (KBr) (cm ):
3
002, 2952, 2838, 2603, 1753, 1610, 1504, 1457, 1253, 1173, 1106, 749; HRMS (ESI)
+
m/z calcd for C H O (M-H) 331.1182, found 331.1183.
1
8
19
6
2
0
Methyl 2,2-dimethoxy-2-(4-methoxyphenyl)acetate (6a). Isolated as a white oil.
1
H NMR (400 MHz, CDCl ): δ 3.27 (s, 6H), 3.74 (s, 3H), 3.83 (s, 3H), 6.91 (d, J =
3
1
3
8
1
.8 Hz, 2H), 7.53 (d, J = 8.8 Hz, 2H); C NMR (400 MHz, CDCl ): δ 50.3, 52.9, 55.2,
3
01.5, 114.3, 128.1, 128.6, 160.1, 169.6.
2
1
Methyl 2-(4-methoxyphenyl)-2-oxoacetate (7a). Isolated as a colorless solid, m.p.:
o
1
5
2
1
4 C. H NMR (400 MHz, CDCl ): δ 3.88 (s, 3H), 3.91 (s, 3H), 6.93 (d, J = 8.8 Hz,
3
1
3
H), 8.01 (d, J = 8.8 Hz, 2H); C NMR (400 MHz, CDCl ): δ 51.9, 55.4, 113.6, 122.6,
3
31.6, 163.3, 166.9.
Acknowledgements
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This work was supported by grants from the National Natural Science Foundation
of China (No. 21472011) and the National Key Research and Development Program
(
2016YFD0400801). ZCC and SBG are grateful to the Beijing Advanced Innovation
Center for Food Nutrition and Human Health for fostering our collaboration
(SPFWHX-2016-ZD)).
(
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