Hydrogenolysis of a γ-Acetylated Lignin Model Compound with a Ruthenium-Xantphos Catalyst

Article abstract of DOI:10.1007/s10562-014-1401-7

Catalytic hydrogenolysis of a γ-acetylated dimer lignin model compound is effected using a Ru-xantphos catalyst. Mechanistic investigations show mono-aryl degradation products are generated from the β-O-4 substrate as well as a terminal alkene ketone dimer (bis-aryl) that further dimerizes to a tetra-aryl product. Preliminary results using an acetylated kraft lignin as a substrate are also discussed. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s10562-014-1401-7

Catal Lett (2015) 145:511–518
DOI 10.1007/s10562-014-1401-7
Hydrogenolysis of a c-Acetylated Lignin Model Compound
with a Ruthenium–Xantphos Catalyst
Adam Wu
•
Jean Michel Lauzon Brian R. James
•
Received: 2 August 2014 / Accepted: 11 October 2014 / Published online: 30 October 2014
Ó Springer Science+Business Media New York 2014
Abstract Catalytic hydrogenolysis of a c-acetylated
dimer lignin model compound is effected using a Ru–
xantphos catalyst. Mechanistic investigations show mono-
aryl degradation products are generated from the b-O-4
substrate as well as a terminal alkene ketone dimer (bis-
aryl) that further dimerizes to a tetra-aryl product. Pre-
liminary results using an acetylated kraft lignin as a sub-
strate are also discussed.
(Fig. 1). This bond has been identified as a target discon-
nection point for the depolymerisation of lignin using
transition metal catalysts [11–13].
To this end, Bergman, Ellman, and co-workers showed
that an in situ generated Ru(H) (CO)(PPh )(xantphos)
2
3
complex could be used for the catalytic hydrogenolysis of
the b-O-4 linkage in lignin model compounds (LMCs)
[13]. This lead publication inspired our group to investigate
the catalytic system in more detail, culminating in our own
report [12]. During our study, it was discovered that LMCs
containing c-OH functional groups formed catalytically-
inactive ruthenium complexes through a double-dehydro-
genation mechanism. This revelation is of particular con-
cern due to the prevalence of these c-OH groups in lignin
structures [9, 14–17], and this could be important in any
industrial application of such Ru-based technology. Herein
we report that the acetylation of the c-OH groups to c-OAc
groups eliminates the double-dehydrogenation pathway
and allows for hydrogenolysis of the b-O-4 linkage.
Acetylation of lignin in the c-position is seen in several
fibrous plants [18, 19], including a few hardwoods [20];
this results from the presence of acetylated monomers
during biosynthesis [21]. Chemical acetylation of alcohol
groups in lignin [22] has been used to characterize native
lignins by NMR [23–26] and mass spectrometric [27]
methods; similarly prepared samples, when compared to
their unmodified precursors, have increased solubility in
hydrophobic organic solvents [28, 29] and enhanced
photostabilization [30]. Acetylated lignin has been incor-
porated into materials such as welded dowel joints [31],
thin films [32], self-assembled spheres [33], and plastic
blends [34].
Keywords Acetylated lignin ꢀ Hydrogenolysis ꢀ
Ruthenium ꢀ Xantphos ꢀ Lignin degradation
1
Introduction
In the search for a renewable source of biofuel and other
chemical building blocks currently derived from fossil
fuels, lignocellulosic biomass is an attractive proposition.
The intense surge in research in the past decade [1–9] is
particularly significant within the pulp and paper industry,
which generates large quantities that are currently treated
as ‘waste’ [10]. This label is due in part to the irregular,
complex structure of lignin: non-identical phenolic units
interconnected by a series of C–C and C–O bonds [8, 9].
The predominant C–O bond, typically comprising
5
0–60 % of lignin structures, is the so-called b-O-4 linkage
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-014-1401-7) contains supplementary
material, which is available to authorized users.
A. Wu ꢀ J. M. Lauzon ꢀ B. R. James (&)
Department of Chemistry, University of British Columbia, 2036
Main Mall, Vancouver, BC V6T 1Z1, Canada
e-mail: brj@chem.ubc.ca
Herein we report on our study of the catalytic hydrog-
enolysis of a c-acetylated dimer LMC and preliminary
results applying the strategy to acetylated lignin.
123

5
12
A. Wu et al.
O
OR
has been reported on briefly, but characterization involved
13
O
1
only three C{ H} NMR shifts [22]. Acetylated kraft lignin
was kindly donated by Weyerhaeuser Co (Seattle, WA, USA).
RO
OR
2.2 Synthesis of c-Acetylated b-O-4 Ketone Dimer
Fig. 1 Example of a generic, so-called dimeric lignin section
meaning two aromatic rings) with the b-O-4 bond highlighted
Substrate (4)
(
2.2.1 3,4-Dimethoxybromoacetylbenzene (1)
2
Experimental Methods
3,4-Dimethoxyacetophenone (10 g, 55 mmol) in CHCl3
2
.1 General Remarks
(100 mL) was stirred in a round-bottom flask, while Br2
10.6 g, 66 mmol) was added drop-wise over 1 h; the mixture
(
NMR spectra were recorded at room temperature (r.t.,
was then stirred then for 16 h at r.t. The solvent was then
removed in vacuo to give an oil; addition of EtOH (40 mL)
and cooling to -15 °C gave a cream-white precipitate that
*
20 °C), unless otherwise noted, on Bruker spectrometers
300 or 400 MHz for H, 75 or 100 MHz for C{ H}, and
1 13 1
(
3
1
22 MHz for P{ H}). Residual deuterated solvent proton
1
1
was filtered off, washed with EtOH (2 9 20 mL), and dried in
1
vacuo. Yield = 7.0 g (49 %). H NMR (300 MHz, CDCl ):
(
d = 7.16 s, for CDCl or 2.08 qt, for toluene-d ) and
H
3
8
3
solvent carbon (d = 77.16, t, for CDCl ) relative to
d = 3.95, 3.97 (OCH , s, 3H each), 4.42 (CH Br, s, 2H),
C
3
13
H
3
2
1
3
external SiMe4 were used as H and C references,
respectively (s = singlet, d = doublet, t = triplet, q =
quartet, qt = quintet, m = multiplet; coupling constants
6.92(Ar–H, d, 1H, J = 8.7), 7.56(Ar–H, s, 1H), 7.62(Ar–
HH
3
13
H, d, 1H, J = 8.4). C{ H} NMR (75 MHz, CDCl ):
1
HH
3
d = 30.5 (CH Br), 56.1, 56.2 (OCH ), 110.2, 110.9, 123.9
C
2
3
(
J) are given in Hz) [35]. External 85 % H PO (d = 0.0)
(C –H), 127.1 (C C=O), 149.4, 154.1 (C –OCH ), 190.1
Ar Ar Ar 3
3
4
P
3
1
?
(C=O). ESI/MS : 283 [M ? Na] . Anal. Calcd (Found) for
?
was used as a P reference. Deuterated solvents were
purchased from Cambridge Isotope Laboratories, Inc. Gas
chromatography/mass spectrometry (GC/MS) spectra were
recorded on an Agilent 6890 N Network GC System with a
C H O Br: C, 46.36 (46.37); H, 4.28 (4.25).
10 11 3
2.2.2 1-(3,4-Dimethoxyphenyl)-2-(2-
Methoxyphenoxy)Ethanone (2)
5
5
1
975B inert MS detector. The GC column was an HP-5MS
% phenyl(methyl)siloxane capillary column (Agilent
9091 S-433) with 30.0 m 9 250 lm 9 0.25 lm nominal
Compound 1 (6.5 g, 25 mmol) and K CO (5.2 g, 38 mmol)
2
3
dimensions. The initial temperature was set at 50 °C and
held for 1 min, then increased by 20 °C/min for 10 min to
reach 250 °C, which was held for 9 min; a sample of
were stirred in acetone (150 mL) in a round-bottom flask
while guaiacol (3.7 g, 30 mmol) was added drop-wise, and
the reactionmixture was then stirred for 16 h atr.t. Remaining
solid was filtered off, and the filtrate was concentrated in
vacuo to give an oil; addition of EtOH (40 mL) and cooling to
-15 °C gave a cream-coloured precipitate that was filtered
off, washed with EtOH (2 9 20 mL), and dried in vacuo.
*
0.5 lL was injected into the GC column by a 10 lL
microsyringe. Electrospray ionization mass spectra in the
?
positive ion mode (ESI/MS ) were recorded on a Bruker
Esquire-LC ion-trap instrument, with MeOH solution of
samples being infused into the ion-source by a syringe
pump at a flow rate of 200 lL/min. Elemental analyses
were performed using a Carlo Erba EA1108 elemental
analyzer. All solvents and reagents used in the syntheses
were reagent grade and were used as supplied by Aldrich or
Fisher Scientific. Silica gel (SiliaFlashÒ F60, 230–400
mesh) was purchased from Silicycle, and the Praxair gases
1
Yield = 6.0 g (79 %). H NMR (300 MHz, CDCl3):
d = 3.89, 3.93, 3.95 (OCH , s, 3H each), 5.29 (CH , s, 2H),
H
3
2
6.75–7.05 (Ar–H, m, 5H), 7.60 (Ar–H, s, 1H), 7.68 (Ar–H, d,
13
3
1H, JHH = 8.4).
1
C{ H} NMR (75 MHz, CDCl ):
3
d = 56.0, 56.1, 56.2 (OCH ), 72.1 (CH ), 110.2, 110.5,
C
3
2
112.2, 114.8, 120.9, 122.4, 122.9 (C –H), 127.9 (C C=O),
Ar Ar
147.7 (C –OCH ), 149.3, 149.8, 153.9 (C –OCH ), 193.4
Ar
Ar
2
3
?
(C=O). ESI/MS : 325 [M ? Na] . Anal. Calcd (Found) for
?
H (99.995 %, extra dry) and Ar (99.996 %) were used as
2
received. Ru(H) (CO)(PPh )(xantphos) (Ru*) was syn-
3
C H O : C, 67.54 (67.69); H, 6.00 (5.90).
17 18 5
2
thesised as reported [12]. Intermediates (1–3) were syn-
thesised by modification of literature methods [36, 37]. The
modifications involved the use of different solvents during
reactions and modified work-up procedures; our corre-
2.2.3 3-Hydroxy-2-(2-Methoxyphenoxy)-1-(3,4-
Dimethoxyphenyl)-1-Propanone (3)
1
13
1
sponding H and C{ H} NMR data for 1–3 (Figs S1-S3
respectively) are in good agreement with the literature [37].
In a round-bottom flask, 2 (2.2 g, 7.3 mmol), K CO (1.2 g,
2
3
8.7 mmol), and 37 wt% formaldehyde (0.89 g, 11 mmol)
were stirred in a 1:1 EtOH/acetone solution (60 mL) for 2 h
at r.t. The filtrate from this was concentrated in vacuo to
1
13
1
H and C{ H} NMR spectra for novel compounds 4, 9,
and 10 are available in the ESI (Figs S4-S6). Compound 4
1
23

Hydrogenolysis of an Acetylated LMC with a Ru Catalyst
513
give an oil that was subsequently purified by silica gel
chromatography (1:1–1:2 hexanes/EtOAc). The appropriate
fractions were collected and concentrated in vacuo to give
an oil. Addition of CH Cl /hexanes (10 mL/50 mL) pre-
concentration in vacuo gave an oil that was purified by
silica gel chromatography (1:1 EtOAc/hexanes). The
appropriate fractions were collected and concentrated in
vacuo to give an oil, which when scratched with a spatula
in a glass vial yielded a white solid that was collected and
dried in vacuo. Yield = 0.25 g (26 %).
2
2
cipitated a white powder that was filtered off, and dried in
1
vacuo. Yield = 1.2 g (49 %). H NMR (300 MHz, CDCl ):
3
3
d = 3.21 (OH, t, 1H, J = 6.5), 3.85, 3.91, 3.94 (OCH ,
Method 2: A CH Cl solution (15 mL) of 3 (0.50 g,
2
H
HH
3
2
3
s, 3H each), 4.07 (HOCH , d, 2H, JHH = 5.9), 5.40
1.5 mmol) and Et N (441 lL, 3.16 mmol) was stirred at
2
3
3
CHCH , t, 1H, J = 5.3), 6.70–7.10 (Ar–H, m, 5H),
(
30 °C for 10 min. After addition of tosyl chloride (0.34 mg,
1.81 mmol), the mixture was stirred overnight, and then
diluted with 10 mL CH Cl , washed with 15 mL of H O,
2
HH
3
.61 (Ar–H, d, 1H, JHH = 1.5), 7.75 (Ar–H, dd, 1H,
7
2
3
JHH = 8.3, JHH = 1.7).
13
1
C{ H} NMR (75 MHz,
2
2
2
CDCl ): d = 55.9, 56.1, 56.2 (OCH ), 63.9 (CHCH- ),
dried with MgSO , and concentrated in vacuo to give a
4
3
C
3
2
8
1
1
4.6 (CHCH ), 110.2, 111.1, 112.4, 118.4, 121.3, 123.7,
2
yellow oil that was purified by silica gel chromatography
(1:5 EtOAc/hexanes). The appropriate fractions were col-
lected and concentrated in vacuo to give an oil, from which
a white solid was precipitated with hexanes. The solid was
filtered off and dried in vacuo. Yield = 0.38 g (80 %).
23.8 (C –H), 128.2 (C C=O), 147.1 (C –OCH ), 149.3,
Ar
Ar
Ar
2
?
50.5, 154.0 (C –OCH ), 195.1 (C=O). ESI/MS- : 333
Ar
3
?
[
M ? H] . Anal Calcd (Found) for C H O ꢀH O: C,
1
8
20
6
2
6
1.71 (61.56); H, 6.33 (6.20). The H O was detected
2
1
qualitatively in H NMR spectrum (Fig S3).
1
H NMR (400 MHz, CDCl ): d = 3.86, 3.936, 3.942
3
H
2
(
OCH , s, 3H each), 4.70 (C=CHH, d, 1H, J = 2.4),
3 HH
2
5.20 (C=CHH, d, 1H, J = 2.4), 6.87–7.00 (Ar–H, m,
2
.2.4 3-Acetoxy-2-(2-Methoxyphenoxy)-1-(3,4-
Dimethoxyphenyl)-1-Propanone (4)
HH
3H), 7.05–7.17 (Ar–H, m, 2H), 7.64 (Ar–H, d, 1H,
3
2
3
J
3
= 2.4), 7.83 (Ar–H, dd, 1H, J = 8.4, J = 2.0).
HH HH
HH
1
1
Pyridine (0.29 g, 3.7 mmol) and acetyl bromide (1.5 g,
2 mmol) were added step-wise to 3 (1.0 g, 3.0 mmol)
C{ H} NMR (100 MHz, CDCl ): d = 56.0, 56.1, 56.2
3
C
1
(OCH ), 100.0 (C=CH ), 110.0, 112.4, 113.0, 121.3, 121.8,
3 2
dissolved in THF (10 mL), and the reaction mixture was
stirred for 30 min at r.t.; this was filtered, and the filtrate was
concentrated in vacuo to give an oil which was purified by
silica gel chromatography (1:1 EtOAc/hexanes). The
appropriate fractions were collected and concentrated in
vacuo to give an oil. The white powder that precipitated upon
addition of CH Cl /hexanes (5 mL/50 mL) was filtered off,
125.2, 125.9 (C –H), 129.2 (C C=O), 143.4 (C –OC),
Ar Ar Ar
148.8, 151.1, 153.5 (C –OCH ), 158.1 (C=CH ), 189.2
2
Ar
3
?
(C=O). ESI/MS : 315 [M ? H] , 337 [M ? Na] , 353
?
?
?
[M ? K] . Anal. Calcd (Found) for C H O : C, 68.78
1
8 18 5
(68.57); H, 5.77 (5.78).
2.3.2 A Cyclobutyl(diketo)tetramer (10)
2
2
1
and dried in vacuo. Yield = 0.90 g (80 %). H NMR
(
400 MHz, CDCl ): d = 2.04 (C(O)CH , s, 3H), 3.77,
Compound 9 (0.20 g, 0.32 mmol) was dissolved in toluene
(5 mL) in a Schlenk flask which, after three freeze–pump–
thaw cycles, was filled with Ar to 1 atm. The mixture was
heated with stirring at 135 °C for 20 h, and then cooled to r.t.
The solvent was removed in vacuo and the residue was puri-
fied by silica gel chromatography (1:1 hexanes/EtOAc). The
first set of fractions was simply reactant 9 (0.072 g, 36 %).
The second set of fractions when concentrated in vacuo gave
an oil, which on being scratched yielded 10 as a white solid
that was collected and dried in vacuo. Yield = 0.10 g (50 %).
3
H
3
3
2
.92, 3.94 (OCH , s, 3H each), 4.51 (CHCHH, dd, 1H,
3
3
JHH = 11.6, J = 7.2), 4.66 (CHCHH, dd, 1H, J
2
=
HH
HH
3
2
1
3
2.4, JHH = 3.6), 5.61 (CHCH , dd, 1H, JHH = 7.0,
2
JHH = 3.8), 6.76–7.20 (Ar–H, m, 5H), 7.67 (Ar–H, d, 1H,
2
3
1
3
J
3
= 2.0), 7.84 (Ar–H, dd, 1H, J = 8.2, J = 2.2).
HH HH
HH
1
C{ H} NMR (100 MHz, CDCl ): d = 20.9 (C(O)CH ),
3
C
3
5
1
1
5.9, 56.1, 56.2 (OCH ), 64.8 (CHCH- ), 80.4 (CHCH ),
3 2 2
10.3, 111.2, 112.7, 118.1, 121.1, 123.5, 123.9 (C –H),
Ar
28.1 (C C=O), 147.0 (C –OCH ), 149.2, 150.4, 154.0
Ar
Ar
2
1
0
(
C –OCH ), 171.1 (C(O)CH ), 194.2 (C(O)CH). ESI/
3
H NMR (400 MHz, CDCl ): d = 2.32–2.48 (CHH, C HH,
Ar
3
3
H
?
MS- : 397 [M ? Na] , 413 [M ? K] . Anal Calcd (Found)
?
?
0
m, 2H), 2.58–2.71 (C HH, m, 1H), 2.80–2.95 (CHH, m, 1H),
for C H O : C, 64.16 (63.92); H, 5.92 (5.92).
22
3.63, 3.73, 3.80, 3.83, 3.87, 3.91 (OCH , s, 3H each),
3
2
0
7
6
.66–7.00 (Ar–H, m, 9H), 7.16–7.22 (Ar–H, m, 3H), 7.78
3
2
2
.3 Synthesis of Catalysis By-products
(Ar–H, d, 1H, J = 2.0), 8.05 (Ar–H, dd, 1H, J = 8.8,
HH HH
3
13
1
JHH = 2.0). C{ H} NMR (100 MHz, CDCl ): d = 20.7
3
C
0
(CH ), 29.5 (C H ), 55.6, 55.7, 55.8, 56.0, 56.0, 56.1 (OCH ),
2 2 3
2
.3.1 2-(2-Methoxyphenoxy)-1-(3,4-Dimethoxyphenyl)-1-
Oxo-2-Propene (9)
101.9, 110.1 (CC=O), 110.5, 110.6, 112.2, 112.4, 112.9,
15.1, 119.9, 120.6, 120.7, 121.0, 122.4, 123.9, 125.5, 127.0
(C –H), 131.3, 140.3 (C C=O), 143.0, 145.8 (C –OC),
1
Method 1: A THF solution (20 mL) of 3 (1.0 g, 3.0 mmol)
and KOH (0.34 g, 6.1 mmol) was stirred for 1 h at r.t.;
Ar
Ar
Ar
148.2, 148.6, 148.7, 149.6, 151.2, 153.5 (C –OCH ), 192.7
Ar 3
123

5
14
A. Wu et al.
?
C=O). ESI/MS : 651 [M ? Na] , 667 [M ? K] . Anal.
?
?
(
O
O
O
1
.2 guaiacol
Br
Calcd (Found) for C H O ꢀ0.5H O: C, 67.81 (67.97); H,
1.2 Br2
CHCl3
1.5 K2CO3
acetone
3
6
36 10
2
1
5
.85 (5.71). The H O was detected qualitatively in the H
2
MeO
MeO
MeO
NMR spectrum (Fig S6). 10 (20 mg) was also dissolved in
1
C D (0.6 mL) in a J-Young NMR tube, and the H NMR
OMe
OMe
OMe
1
, 49% yield
6
6
spectra recorded from 25–90 °C, and then again at 25 °C (Fig
S7, Table S1).
OMe
O
OMe
1
1
.5 HCHO
.2 K2CO3
O
O
EtOH/
acetone
MeO
OH
2
.4 Procedure for Catalytic Hydrogenolysis
OMe
3
, 49% yield
2, 79% yield
The lignin model substrate 4 (0.10 mmol), 9 (0.10 mmol),
or acetylated kraft lignin (15 mg) and the catalyst
O
OMe
4 AcBr
.2 pyridine
THF
O
1
(
5 mol % of Ru*) were dissolved in toluene-d (0.5 mL)
8
and transferred to a J-Young NMR tube. After three
MeO
OAc
, 80% yield
OMe
freeze–pump–thaw cycles, the tube was filled with 1 atm of
1
H or Ar. The H NMR spectrum was recorded at r.t., and
4
2
the tube was then placed in a 135 °C oil-bath for 20 h. The
reaction mixture was then cooled to r.t., and pivalic acid
Scheme 1 Synthesis of the c-acetylated b-O-4 ketone dimer lignin
model compound 4
(
5–15 mg, 0.05–0.15 mmol) was added as an external
standard for determination of product yields and substrate
conversions. The relevant dH values used in toluene-d8
solutions are: for 4 (5.67, CHCH , dd), 5 (1.15, CH , t), 6
Compound 4 (0.20 M), on treatment with 5 mol %
)(xantphos) (Ru*) in toluene-d
is converted completely to hydrog-
Ru(H) (CO)(PPh
2
at 135 °C
3
8
for 20 h under Ar or H
2
3
2
(
3.19, OCH , s), 7 (2.22, CH , s), 8 (1.91, CH C(O), s), 9
3
enolysisproducts: 3,4-dimethoxypropiophenone (5), guaiacol
(6), 3,4-dimethoxyacetophenone (7), 2-methoxyphenyl ace-
tate (8), 2-(2-methoxyphenoxy)-1-(3,4-dimethoxyphenyl)-1-
oxo-2-propene (9), and the cyclobutyl(diketo)tetramer (10)
(Scheme 2); mono-aryl product yields up to 42 % were
observed (Table 1: Entry II). All of the products except 10
3
3
(5.26, C=CHH, d), 10 (2.70–2.88, CHH, m), and pivalic
acid (1.07, (CH ) , s). To confirm the presences of all
3
3
species, *0.5 lL of the reaction mixture (prior to the
addition of pivalic acid) was injected into the GC/MS
instrument, and their m/z values observed: for 5 (194), 6
(
124), 7 (180), 8 (166), 9 (314), and PPh (262).
3
were identified (as well as PPh ) using GC/MS; presumably,
3
the larger molecular size of 10 prevents its elution through the
GC column. The findings contrast sharply with our previous
results using non-acetylated substrates where the c-hydroxyl
group interacted to form catalytically inactive Ru complexes
that were fully characterized [12]. Of note, just prior to the
submissionofourpaper, Liandco-workers, whohadfollowed
upstudiesbyour group [12] and those ofBergman and Ellman
[13], reported that a ‘dimer’ (bis-aryl) LMC containing a c-
OH group could be degraded in toluene at 125 °C over
3
Results and Discussion
3
.1 Synthesis and Catalytic Hydrogenolysis of 4
The synthesis of c-acetylated b-O-4 ketone dimer lignin
model compound 3-acetoxy-2-(2-methoxyphenoxy)-1-(3,4-
dimethoxyphenyl)-1-propanone (4) is outlined in Scheme 1.
First, 3,4-(dimethoxy)acetophenone is reacted with Br in
2
12–48 h under Ar using RuHCl(CO)(PPh ) and KOH in the
3 3
CHCl to produce 3,4-dimethoxy(bromoacetyl)benzene (1) in
3
absence of xantphos [38]. As with our acetylated substrate
(Table 1), consumption of the dimer LMC approached
100 %, with one mono-aryl product being formed in 26 %
over 24 h (others were present in\10 %), and the fate of most
of the substrate was unaccounted for; dimerized products akin
to 10 were not mentioned. Although not discussed, the con-
ditions suggest a heterogeneously catalyzed system, and
deeper insight into the mechanism of this KOH promoted
method is needed.
moderate yield (49 %). Reaction of 1 with K CO and guai-
2
3
acol in acetone gives the b-O-4 ketone dimer 1-(3,4-dime-
thoxyphenyl)-2-(2-methoxyphenoxy)ethanone (2, 79 %). The
c-OH moiety is then incorporated using K CO and HCHO in
2
3
acetone/EtOH to give 3-hydroxy-2-(2-methoxyphenoxy)-1-
(3,4-dimethoxyphenyl)-1-propanone (3, 49 %). The synthe-
ses of intermediates 1–3 described in the experimental section
involve modifications of literature methods [36, 37]. Pro-
duction of 4 (in 80 % yield) from 3 was accomplished using
AcBr and pyridine for the acetylation; on previous smaller
scale syntheses (0.05–0.2 mmol) in the absence of pyridine,
the yield was only 21 % [22]. The pyridine neutralizes the
HBr byproduct and prevents its reaction with 4.
The yields of 5 and 6 are significantly higher under H
(vs. under Ar), a consequence of the two equivalents of H
2
2
necessary for their formation from 9 (vide infra). Yields of
7 and 8 are comparable under either atmosphere. The
yields of 10 could not be determined because of
1
23

Hydrogenolysis of an Acetylated LMC with a Ru Catalyst
515
O
OMe
O
OMe
HO
AcO
+
+
+
MeO
MeO
OMe
OMe
5
6
7
8
O
OMe
O
5
1
mol% Ru*
35 °C, 20 h
O
OMe
MeO
toluene-d
OAc
8
O
OMe
1
0
+
+
4
(
dimer of 9)
MeO
OMe
9
Scheme 2 Products of the catalytic hydrogenolysis of 4. See Scheme 5 for a representation of 10
Table 1 Catalytic hydrogenolysis of 4 (Scheme 2) and 9 (Scheme 5) after 20 h
a
b
c
c
c
c
c
c
c
Entry
Substrate
Catalyst
Gas
Ar
Consumpn.
5
6
7
8
9
10
d
I
4
4
9
9
9
9
Ru*
Ru*
Ru*
Ru*
None
None
100
100
85
9
20
42
25
19
0
24
18
0
17
9
B39
d
II
H
2
27
8
B31
III
IV
V
VI
a
Ar
13
–
72
d
H
2
86
15
0
23
0
0
–
B63
Ar
81
\2
\2
0
0
–
75
77
H
2
82
0
0
0
–
0
.20 M
b
c
d
1
atm
1
Average consumption and yield (average of duplicate experiments) determined by H NMR integration
Overlapping signals prevent determination of yield; the upper limit is given, based on mass balance
1
overlapping H NMR signals for the ‘bridging’ cylcobutyl
protons but, based on mass balance, the upper limits are
H or Ar (Table 1) suggest they are formed from one
2
molecule in an H -free process; the mass balance by-
2
3
9 % under Ar and 31 % under H . In the absence of the
2
product for such a process is CO, via a net catalytic de-
carbonylation. This is a well-known Ru-catalyzed reaction
[39–41] that has been reported for acetic acid [41], but to
our knowledge not for an acetyl group. A reviewer sug-
gested other pathways, both involving formation of 3 as an
intermediate: one involved acetyl transfer from 4 to 6 to
give 8 and 3, which then undergoes a retro-aldehyde
reaction to form 2 and HCHO (Scheme 1); the aldehyde
Ru–xantphos catalyst, no reaction of 4 is observed under
H or Ar.
2
1
The solution H NMR spectrum at the end of a Ru-
catalyzed reaction of 4 under Ar or H shows no high-field
2
3
Ru-hydride signals, and, consistent with this, the P NMR
1
spectrum shows no P–H coupling patterns. Free PPh
1
3
3
1
(dP =-4.7) is seen in the P{ H} NMR spectrum, in
agreement with the GC/MS data; seen also are unassigned
could decompose into CO and H , the latter reacting with 2
2
diamagnetic signals at d = 22.1, 26.9, 33.5, 39.8, 42.8,
and 49.4, presumably of new Ru–xantphos non-hydride
to give 7 and 6, which then picks up the acetyl again to
form 8; the second suggestion hinged on an initial dehy-
drogenation of the CH OH group of 3, followed by de-
P
species.
2
carbonylation of the aldehyde product. We thus exposed
equimolar amounts of 6 and 4 to the ‘standard’ catalysis
conditions, and found that 3 was not formed, while 4 was
totally consumed according to the observed catalysis pro-
file (Table 1, Entry I); pathways involving 3 thus look
unlikely, and indeed we have established that such c-OH
functional groups lead to formation of catalytically inactive
3
.2 Proposed Pathway for the Hydrogenolysis
The catalyzed hydrogenolysis of 4 yields multiple pro-
ducts, implying complex mechanistic pathways. Cleavage
of 4 to give mono-aryl products 7 and 8 occurs in the
presence of Ru* (Scheme 3). The yields of 7 and 8 under
123

5
16
A. Wu et al.
O
O
OMe
AcO
-
"CO"
+
MeO
MeO
O
OMe
OMe
7
O
5
mol% Ru*
35 °C, 20 h
toluene-d
8
1
MeO
8
OAc
O
OMe
HO
OMe
OMe
O
+
2 H2
4
- "AcOH"
+
MeO
OMe
OMe
9
1
5
6
Δ
0
Scheme 3 Proposed mechanistic pathways for hydrogenolysis of 4
Ru species (see Introduction). Some key mechanistic
details of Scheme 3 thus remain unclear.
O
OMe
O
OMe
O
O
2
KOH
Control experiments also showed that 6 does not react
with AcOH to yield 8 (under the catalytic conditions with
Ar or H ), but does react quantitatively with AcBr to give
THF
MeO
MeO
OH
OMe
OMe
9, 26% yield
3
2
8. Thus, the formation of 8 requires C–O cleavage and
intramolecular transfer of the acetyl group to the guaiacol
Scheme 4 Synthesis of 9 (26 % yield) from intermediate 3
oxygen; the formation of 7 requires the cleavage of the
C -C bond.
b
c
procedure was unsuccessful because isolation via silica gel
chromatography could not be effected.
Formation of 9 was surprising (Scheme 3). A mono-aryl
species featuring a terminal alkene group has been formed
as a final product in the degradation of a dimer LMC using
a vanadium catalyst, and a radical mechanism was sug-
gested [36]. In our system, 9 is an intermediate, as evi-
Under the catalysis conditions for 20 h under Ar or H , 9
2
is 85–86 % consumed to give hydrogenolysis products 5
and 6, and 10 (abbreviated as the ‘tetramer’); see Scheme 5
and Table 1: Entries III and IV. The 5 and 6 yields are low
denced by the higher 4 h yields (40 and 50 % for H and
2
(\25 %), being best under the H conditions. No 7 and 8
2
1
products (cf. Scheme 3, top) were observed by H NMR or
Ar, respectively) compared to the 20 h yields (9 and 17 %,
respectively; Table 1). The mass balance by-product of the
GC/MS. Most of 9 was converted into 10 under either Ar or
H2 (72 and 63 % yield respectively) but, even in the
absence of catalyst under otherwise identical conditions,
similar conversion is seen, and with no hydrogenolysis
products (5 and 6, Table 1: Entries V and VI). Thus, 9
mainly dimerizes to give 10.
4–9 conversion is AcOH, but this could not be confirmed
1
by H NMR spectroscopy because of overlapping signals
for the CH groups of both species (d = 1.6 in toluene-
3
H
d8). Hydrogenolysis of 9 via C–O cleavage at the b-O-4
linkage, involving two equivalents of H , would generate 5
2
1
and 6; indirect support for this mechanism is the higher
yields of 5 and 6 observed when the reaction is performed
under H . In addition, 9 can dimerize to give 10.
The H NMR spectrum for the reaction of 9 (like that of
4) under catalytic conditions shows no Ru-hydride signals,
and is similar to that observed for the reaction of 4, while
2
3
the P{ H} NMR spectrum again shows free PPh and a
1
1
These mechanistic pathways have been supported by an
3
independent synthesis of 9 from 3 (Scheme 4), followed by
1
its exposure to catalytic conditions. The H NMR spectrum
similar set of unidentified resonances (at d = 14.7, 31.9,
44.7, and 47.4).
P
of 9 in CDCl shows coupled doublets for the two inequiv-
3
Compound 10 was isolated in 50 % yield by heating 9 in
toluene at 135 °C for 20 h under Ar, with unconverted 9
being recovered in 36 % yield. The H NMR spectrum of
2
alent C=CH protons (d = 4.70 and 5.20, J = 2.4 Hz).
2
H
HH
1
This type of dehydration reaction has been reported for the
synthesis of an analogous compound, 1-(4-ethoxy-3-
methoxyphenyl)-2-(2-methoxyphenoxy)-1-oxo-2-propene,
by treatment of the corresponding c-OH species with POCl3
in pyridine [42]. However, the synthesis of 9 using this
10 in CDCl shows multiplets at d = 2.32–2.48 (2H),
3
H
2.58–2.71 (1H), and 2.80–2.95 (1H) for four coupled pro-
tons, and these signals are assigned to the two ‘bridging’
cylcobutyl CH /CH groups. The OCH protons appear as
2
2
3
1
23

Hydrogenolysis of an Acetylated LMC with a Ru Catalyst
517
O
O
O
OMe
O
OMe
O
HO
O
5
1
mol% Ru*
35 °C, 20 h
toluene-d
+
+
O
O
MeO
MeO
O
8
O
O
OMe
OMe
O
9
5
6
10
O
Scheme 5 Products of the catalytic hydrogenolysis of 9
six singlets (d = 3.63, 3.73, 3.80, 3.83, 3.87, and 3.91),
conditions noted above. Despite the increased solubility of
lignins upon acetylation [28, 29], 15 mg of acetylated
lignin was not totally dissolved in 0.5 mL of toluene-d8
even at elevated temperatures (135 °C). However, a sig-
H
1
3
1
and there are twice as many C{ H} NMR signals than are
present in the monomer unit 9. These data support a
structure such as that proposed in Scheme 5—any dimer
structure allows for the calculated yields of 10 (Table 1).
Despite numerous attempts, no X-ray quality crystals of 10
could be grown to confirm this structure. A variable tem-
1
nificant change is observed in the H NMR spectrum with
an increase in the number of signals observed from
dH = 3.2–3.6 (Fig S9), suggesting that more species with
OCH groups are in solution, presumably from a degra-
1
perature H NMR study (25–90 °C) was undertaken to see
3
if the six OCH signals would coalesce to three due to
dation process. Other qualitative differences appear in the
3
symmetry at elevated temperatures (Fig S7, Table S1).
aromatic region (d = 6.5–9.0); however, the identities of
H
Repeat 25 °C data showed that no decomposition occurred
these new species are impossible to discern due to over-
lapping NMR signals. A control experiment performed in
the absence of the Ru catalyst did not show an increase of
up to 90 °C. In contrast to the six OCH signals observed in
3
CDCl , only five signals were seen at 25 °C, but one of
3
1
them (d = 3.40) had a double integration value for six
signals in this region (Fig S10). While H NMR does not
H
protons, due to two overlapping signals. The signals shift
downfield with increasing temperature, but at different
rates, causing two signals to appear as one at 70 °C;
however, above this temperature, these revert to two sig-
nals. The non-coalescence is consistent with a non-sym-
metrical structure, as exemplified in Scheme 5. Preliminary
calculations were also performed to explore the lack of
symmetry in 10. Two geometries possessing C2 symmetry,
and two with no symmetry, were optimized using density
functional theory (B3LYP/6-31G*); optimization to local
energy minima revealed that none of the structures con-
tained symmetry elements, the lowest relative energy
structure (3.3–5.8 kcal/mol lower than the other minima)
being shown in Scheme 5 (see also Fig S8). This structure
identify reaction products, the qualitative data in concert
with GC/MS fragmentation patterns assist in determining
the types of degradation products. Figure 2 outlines major
fragments present in the chromatogram (Fig S11, Table
S2), and in addition there are two higher mass fragments
(m/z 171, 295) that may correspond to a highly substituted
mono-aryl species and a dimeric (bis-aryl) compound.
To increase the solubility of the acetylated lignin,
varying amounts of N,N-dimethylformamide (DMF) were
added to the J-Young tube as a co-solvent with the toluene-
d8. A previous screening of non-protic, high-boiling, polar
solvents, all of which are capable of dissolving a range of
lignins, has shown that neat DMF promoted the highest
substrate conversion of dimer LMCs [43]. Unfortunately,
this conversion is typically 50 % lower than when toluene-
d8 is used as the solvent [43]. This decrease in activity,
perhaps due to competitive binding of the amide to the Ru,
is mirrored in the current study: with increasing percent of
DMF, catalytic reactivity decreases. This decline is evi-
is one of many orientations that do not possess C2 sym-
1
metry, and is consistent with six OCH signals in the H
3
NMR spectrum. The mechanism of the net dimerization of
9
? 10 is unclear but, because 2 ? 2 cycloadditions are
thermally forbidden, reaction between two molecules of 9
behaving differently, for example, one more nucleophilic
and one more electrophilic, must be involved; this is
indirectly consistent with 10 having no C2 symmetry.
1
denced by almost identical H NMR spectra before and
after the reaction when neat DMF is used with further
qualitative data from GC/MS experiments.
Though preliminary, these initial studies with acetylated
lignin seem promising. When native lignin is exposed to
1
these reaction conditions, no change in the H NMR
3
.3 Catalytic Hydrogenolysis of Acetylated Lignin
Having established the successful hydrogenolysis of 4, we
subjected an acetylated kraft lignin to the catalytic
spectrum is observed, probably due to the complete lack of
solubility in toluene-d . Current research is focused on the
8
123

5
18
A. Wu et al.
9
. Zakzeski J, Bruijnincx PCA, Jongerius AL, Weckhuysen BM
(
O
O
OH
2010) Chem Rev 110:3552
O
O
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HO
O
1
1
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1
1
2. Wu A, Patrick BO, Chung E, James BR (2012) Dalton Trans
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7
59
73
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4
Fig. 2 Mass fragments corresponding to signals observed in GC/MS
chromatogram
1
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(
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´
Reported here is the first catalytic hydrogenolysis of a c-
acetylated lignin model compound (4) with a Ru–xantphos
catalyst; this contrasts with the noted non-acetylated (c-
OH) models that form catalytically inactive Ru species
(
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24. Capanema EA, Balakshin MY, Kadla JF (2005) J Agric Food
Chem 53:9639
terminal alkene group (9) that can undergo further catalysis
to yield two mono-aryl products (5 and 6) and a dimer-
ization product (10). The formation of 5, 6, and 10 from 9
was confirmed by using an independently synthesised 9 as
a substrate. This finding also proved that 7 and 8 are cat-
alytic hydrogenolysis products formed directly from the c-
OAc substrate 4. The catalytic methodology was also
applied to an acetylated kraft lignin with promising pre-
liminary results, including detection of mono-aryl frag-
ments using GC/MS.
2
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Acknowledgments We thank the NSERC Lignoworks Network for
funding, Weyerhaeuser Co (Seattle, WA, USA) for supplying the
acetylated lignin, and a reviewer for constructive comments.
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