Lignol cleavage by Pd/C under mild conditions and without hydrogen: A role for benzylic C=H activation?

Article abstract of DOI:10.1002/cssc.201301253

The cleavage of C=O bonds in lignin model compounds without hydrogen was developed using the commercially available Pd/C. Hydrogen donor solvents are helpful for this reaction through transfer hydrogenation, but not necessary. A redox neutral process that utilizes the internal hydrogen source for the cleavage is also possible. An initial mechanistic study indicates that the β-benzylic-H atom in the substrate plays a critical role and that the present system undergoes a process different from previous reports. Cleavage within: The selective cleavage of β-O-4 bond linkage in lignin has received great attention. We developed a method using the commercially available heterogeneous catalyst, Pd/C, to cleave the C=O bond in β-O-4 linkage model compound without hydrogen. A mechanistic study shows that the present catalytic system undergoes a process different from previous reports, in which the β-benzylic-H atom in the substrates plays a critical role.

Full text of DOI:10.1002/cssc.201301253

CHEMSUSCHEM
COMMUNICATIONS
DOI: 10.1002/cssc.201301253
Lignol Cleavage by Pd/C Under Mild Conditions and
Without Hydrogen: A Role for Benzylic CÀH Activation?
Xiaoyuan Zhou, Joyee Mitra, and Thomas B. Rauchfuss*[a]
The cleavage of CÀO bonds in lignin model compounds with-
out hydrogen was developed using the commercially available
Pd/C. Hydrogen donor solvents are helpful for this reaction
through transfer hydrogenation, but not necessary. A redox
neutral process that utilizes the internal hydrogen source for
the cleavage is also possible. An initial mechanistic study indi-
cates that the b-benzylic-H atom in the substrate plays a critical
role and that the present system undergoes a process different
from previous reports.
this problem entails heterogeneous catalysts. Indeed, hetero-
geneous Pd-,[9] Ni-,[10] and Cu-based[11] systems have been
shown to catalyze the hydrogenolysis of b-O-4 linkages in
lignin model compounds, but such reactions require hydrogen
at high pressure. Hydrogen consumption is problematic be-
cause hydrogen production facilities are probably incompatible
with biorefineries, which will operate at a smaller scale than
traditional petroleum refineries.[12]
In this paper, we show that one of the most common heter-
ogeneous catalysts, palladium on carbon (Pd/C), activates li-
gnols. Although palladium-based catalysts have been widely
applied to the degradation of lignin,[3a] demanding conditions,
especially high hydrogen pressure, are usually required. This
system addresses disadvantages of previous processes—ex-
pensive ligands, problematic product separation, and the need
for hydrogen in particular. On the latter point we were mindful
of the potential value of “internal hydrogen”, available from
abundant benzylic hydroxy groups, ArCH(R)OH, within lignin.[4]
We were attracted to Pd/C because it is widely available com-
mercially with a well-established activity for the hydrogenolysis
and dehydrogenation of benzylic ethers and alcohols, which
are abundant in lignin. As we describe below, not only is Pd/C
highly effective but also gives rise to a new hydrogenolysis
mechanism.
Intense interest is focused on lignocellulosic biomass as a po-
tential source of liquid fuels and chemicals to replace petrole-
um-derived products.[1] Work on saccharide components of
lignocellulose is rather advanced, but the utilization of lignin is
still in its formative stages despite the fact that this fraction ac-
counts for up to 40% of the energy content of typical plant
matter.[2]
Lignin can be viewed as an irregular polymer derived from
cinnamyl alcohols.[3] Owing to the strength of the ether linkag-
es and the high degree of crosslinking, lignin is recalcitrant to
mild reaction conditions. Indeed, natural selection requires
that lignin resists mild hydrolytic or redox conditions. Lignin is,
however, not evolutionarily adapted to organometallic routes
for its deconstruction, which is the focus of our work.
It is accepted that degradation pathways should target CÀO
bonds as these are typically weaker than CÀC linkages.
Because of the abundance of b-O-4 linkages within lignin
(Figure 1), the selective cleavage of this CÀO bond has re-
ceived the greatest attention.[4–8]
Initial tests focused on 2-phenoxy-1-phenylethanol (1a),
a commonly used lignin model substrate that contains the key
b-O-4 linkage (Scheme 1).[4,11c,13] Heating this substrate with 5%
Although homogeneous catalytic systems cleave b-O-4 ether
linkages, their use is complicated by the classic problem of
separating catalysts from products. The obvious solution to
Scheme 1. Cleavage of b-O-4 lignin model compound.
Pd/C in dioxane resulted in complete conversion to C8 cleav-
age products and phenols. Three major products resulted: ace-
tophenone (ACP), ethylbenzene (PhEt), and phenol (PhOH). A
small amount (5%) of the dehydrogenation product
PhC(O)CH2OPh (1b) also forms (Table 1, entry 1).The ratio of
PhOH to C8 products (ACP+PhEt) was close to 1:1 in all experi-
ments. Also observed, to our surprise, was dioxene, indicating
that dioxane functions as a hydrogen donor.[14] Further tests
showed that a variety of hydrogen transfer solvents, for exam-
ple, alcohols, could be used in place of dioxane (see the Sup-
porting Information, Table B). Dioxane is as effective as any al-
ternative and was the focus of the remaining studies described
below. Notably, reducing the catalyst loading from 20 to
5 mol% leads to a much lower yield of C8 species and a higher
Figure 1. b-O-4 linkage of lignin.
[a] Dr. X. Zhou, Dr. J. Mitra, Prof. T. B. Rauchfuss
Department of Chemistry
University of Illinois at Urbana-Champaign
600 South Mathews Avenue, Urbana, IL 61801 (USA)
Fax: (+1)217-244-3186
E-mail: rauchfuz@illinois.edu
Supporting Information for this article is available on the WWW under
http://dx.doi.org/10.1002/cssc.201301253.
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 0000, 00, 1 – 4
&
1
&
ÞÞ
These are not the final page numbers!

CHEMSUSCHEM
COMMUNICATIONS
www.chemsuschem.org
Table 1. Cleavage of b-O-4 lignin model compound under various condi-
tions.[a]
Entry Solvent
([mL])
Pd/C
T
Yield[b] [%]
[mol%] [8C] ACP PhEt PhOH 1b dioxene
1[c]
2[c]
3[c]
4[c]
5[c]
6[c]
7[e]
8[e]
dioxane (5) 20
160
160
160
81 18
>95
26 46
69 30
>95
80 19
37 61 N/A[d]
71 21 N/A[d]
77 22 N/A[d]
0
130
20
22
66
13
dioxane (5)
dioxane (1)
dioxane (5)
dioxane (1)
5
5
5
1
25
64
0
5
0
0
0
0
0
180 >95
0
180
160
160
180
77
34
74
76
toluene (5) 20
toluene (5) 20
toluene (1)
1
Scheme 3. Two possible pathways for the CÀO bond cleavage of b-O-4
lignin model compound.
[a] Reaction conditions: 1a (0.25 mmol), 5 wt% Pd/C, 15 h. [b] Yields were
determined by 1H NMR vs. an internal standard. [c] Run in a sealed reactor
under air. [d] Not available. [e] Run in a sealed reactor under N2.
genolysis. We found that in an open system to allow evolution
of hydrogen, Pd/C in toluene rapidly dehydrogenates 1a to
ketone 1b (see the Supporting Information). Mechanism A has
been implicated in the homogeneously catalyzed hydrogenoly-
sis of 1a.[4,15] In contrast, mechanism B begins with ether hy-
drogenolysis, as has been proposed for other heterogeneous
systems.[10a,11c]
yield of 1b (entry 2). The selectivity, however, could be im-
proved by elevated reaction concentration and temperature
(entries 3 and 4). By combining these two beneficial factors,
catalyst loading could be minimized (1 mol%), with decent
yield of cleaved products (entry 5).
Rates of ether cleavage decreased when the reaction was
carried out in non-hydrogen donor solvents. For example, the
rate of conversion of 1a dropped by 50% when dioxane was
replaced by toluene (Table 1, entry 6 vs. entry 1). It is notewor-
thy that we can alleviate the loss of activity by conducting the
reaction under nitrogen atmosphere instead of air (entry 6 vs.
entry 7). This is probably due to the consumption of in situ
generated hydrogen by oxygen in air, driving the reaction to-
wards the formation of 1b. Again, the best result was obtained
at increased reaction concentration and temperature (entry 8).
Furthermore, in toluene the major products were ACP and
PhOH as well as the dehydrogenation product 1b. PhEt was
not observed in the absence of a hydrogen donor.
For the Pd/C-catalyzed route in dioxane, one argument
against mechanism A is that keto-ether 1b is a less reactive
substrate than 1a (Figure 2). Under identical conditions, 1a is
cleaved quantitatively to yield C8 species (ACP and PhEt) and
PhOH, whereas only ca. 50% of 1b is cleaved. Computational
results show that the ether bond is weaker in 1b [bond disso-
ciation energy (BDE)=227 kJmolÀ1] than in 1a (BDE=
303 kJmolÀ1). Therefore, 1b is expected to be a more reactive
substrate than 1a towards cleavage if the reaction follows
mechanism A, which is just the opposite of experimental
results.
Also arguing against mechanism A is the fact that replacing
ÀOH with ÀOMe (1c vs. 1a) has little effect on the cleavage
rate and yield (Figure 2). This results shows that the reactivity
difference between 1a and 1b is not due to the benzylic ÀOH
group. In this conversion, a-methoxy-ethylbenzene, PhCH-
A series of experiments were conducted to clarify the path-
ways leading to PhEt and ACP in dioxane.
Pathway to PhEt. Our results indicate that PhEt is formed via
the intermediate PhCH2CH2OPh (1d). Thus, in dioxane solution
1d is rapidly consumed at 1608C by Pd/C to a 1:1 mixture of
PhEt and PhOH. Consistent with its high reactivity toward Pd/
C/dioxane, 1d is not detected as an intermediate in reactions
involving 1a (Scheme 2). We had anticipated that PhEt arises
from ACP or styrene, but control experiments showed other-
wise: ACP and styrene are unreactive towards Pd/C in dioxane.
Pathway to ACP. Two pathways are apparent for the conver-
sion of 1a into ACP and phenol, depending on the sequence
of (i) the dehydrogenation of the alcohol and (ii) the hydroge-
nolysis of the ether (Scheme 3). In mechanism A, dehydrogena-
tion converts 1a into keto-ether 1b, which undergoes hydro-
Figure 2. Comparison of reactivities among 1a, 1b, and 1c. Reaction condi-
tions: substrate (0.25 mmol), 5 wt% Pd/C (20 mol%), 1,4-dioxane (5 mL),
1608C, 15 h.
Scheme 2. Mechanism for formation of ethylbenzene.
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 0000, 00, 1 – 4
&
2
&
ÞÞ
These are not the final page numbers!

CHEMSUSCHEM
COMMUNICATIONS
www.chemsuschem.org
(OMe)Me, was identified as the major intermediate (Figure 3,
Scheme 4).
Table 2. Cleavage of b-O-4 lignin model compounds with different ali-
phatic chain lengths. Ar=3,5-dimethylphenyl.
Benzylic vs. homobenzylic reactivity. One of the more striking
results from this work is the greater lability of the
ArCH(OMe)CH2ÀOPh bond versus the benzylic ether ArCH(À
OMe)CH2OPh bond. Conventionally, Pd/C is used for the hydro-
genolysis of benzylic ethers, but such deprotections rely on hy-
Chain length n
DH
[kJmolÀ1
BDE
[kJmolÀ1
]
Product yield
[%]
]
1
2
3
À133.11
À124.19
À128.91
243.12
296.16
293.79
<5
>95
<5
when the benzylic hydrogen atom in 1c is replaced by methyl
as in PhCMe(OMe)CH2OPh (1e, Scheme 5). Compound 1e con-
verts to PhCHMe2 and PhOH via PhCH(Me)CH2OPh at less than
half the rate for 1c (40% vs. 90% conversion in 8 h), presum-
ably due to the slow cleavage of the CÀOMe bond to install
a b-benzylic-H atom.
Figure 3. Products versus time for the conversion of 1c.
Scheme 5. b-benzylic-H atom facilitates CÀO cleavage.
Regarding the overall pathway for cleavage of phenyl
ethers, our experiments point to a role for the benzylic CÀH
bond. Oxidative addition across this bond by palladium(0)
would yield a b-phenoxyalkyl palladium(II) hydride (Scheme 6).
Such a species would be poised to eliminate PhOH and the
enol acetophenone.
Scheme 4. Hydrogenolysis of the b-phenoxyether precedes hydrogenolysis
of the benzylic ether.
In conclusion, Pd/C is shown to be a simple and effective
catalyst for the cleavage of b-O-4 ether bonds in lignin model
compounds. Transfer hydrogenation proceeds both from
donor solvents and internal hydroxyl groups. The b-benzylic-H
atom in the substrate appears to facilitate ether cleavage.
These results indicate the promise of Pd/C for upgrading lignin
and its derivatives without the need of hydrogen.
drogen.[16] Using hydrogen donors, such as dioxane, the rela-
tive reactivity of benzylic versus homobenzylic ethers is re-
versed. Thus, in dioxane, the lignol-derived substrates
ArCH(R)CH2OAr are “privileged”. This point is reinforced by re-
actions of the homologous series Ph(CH2)nOAr (n=1–3), where
Ar=C6H3-3,5-Me2. Of this series, only Ph(CH2)2OAr undergoes
significant cleavage under our standard conditions. The tri-
methylene and benzylic substrates are untouched in spite of
their relatively weak CÀO bond strength (Table 2).
The results for Ph(CH2)nOAr can be rationalized if the benzyl-
ic CÀH bonds participate in the hydrogenolysis process. In this
scenario, mechanism B in Scheme 1 could be envisioned to
proceed via a direct route (no neighboring group participation)
or one in which the neighboring benzylic CH moiety partici-
pates in the reaction. Otherwise, PhCH2ÀOPh would be expect-
ed to be the most reactive substrate.
Relevant to the privileged nature of the homobenzylic
ethers, an important role is implicated for the benzylic CÀH
center. The rate of conversion of PhCH(Me)CH2OPh and its deu-
terated analogue PhCD(Me)CH2OPh is about 1.5:1. In addition
to this isotope effect, the rate of ether cleavage decreased
Scheme 6. Proposed b-O-4 bond cleavage mechanism.
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 0000, 00, 1 – 4
&
3
&
ÞÞ
These are not the final page numbers!

CHEMSUSCHEM
COMMUNICATIONS
www.chemsuschem.org
Sreekumar, K. Wang, F. D. Toste, ACS Catal. 2013, 3, 1369–1377; c) B.
Sedai, C. Diaz-Urrutia, R. T. Baker, R. L. Wu, L. A. Silks, S. K. Hanson, ACS
Catal. 2011, 1, 794–804; d) S. K. Hanson, R. L. Wu, L. A. Silks, Angew.
Chem. Int. Ed. 2012, 51, 3410–3413; Angew. Chem. 2012, 124, 3466–
3469; e) G. Q. Zhang, B. L. Scott, R. L. Wu, L. A. Silks, S. K. Hanson, Inorg.
Chem. 2012, 51, 7354–7361; f) R. G. Harms, I. I. E. Markovits, M. Drees,
W. A. Herrmann, M. Cokoja, F. E. Kꢁhn, ChemSusChem 2014, 7, 429–434.
[6] a) J. Zakzeski, P. C. A. Bruijnincx, B. M. Weckhuysen, Green Chem. 2011,
13, 671–680; b) B. Biannic, J. J. Bozell, Org. Lett. 2013, 15, 2730–2733.
[7] A. N. Desnoyer, B. Fartel, K. C. MacLeod, B. O. Patrick, K. M. Smith, Orga-
nometallics 2012, 31, 7625–7628.
Experimental Section
Representative procedure for CÀO bond cleavage: In a typical
experiment, a 15 mL pressure reactor was charged with Pd/C
(100 mg), substrate (0.25 mmol), and solvent (5 mL). The suspen-
sion was stirred at 1608C (oil bath temperature). After the desired
reaction time, the reactor was quenched in an ice bath and
charged with a known amount of MeNO2 (internal standard). A
1
portion of the reaction mixture was mixed with [D6]DMSO. H NMR
spectrum was recorded.
[8] A. G. Sergeev, J. F. Hartwig, Science 2011, 332, 1263–1263.
[9] a) T. H. Parsell, B. C. Owen, I. Klein, T. M. Jarrell, C. L. Marcum, L. J. Hau-
pert, L. M. Amundson, H. I. Kenttamaa, F. Ribeiro, J. T. Miller, M. M. Abu-
Omar, Chem. Sci. 2013, 4, 806–813; b) C. Zhao, J. A. Lercher, Chem-
CatChem 2012, 4, 64–68.
[10] a) J. Y. He, C. Zhao, J. A. Lercher, J. Am. Chem. Soc. 2012, 134, 20768–
20775; b) Q. Song, F. Wang, J. Xu, Chem. Commun. 2012, 48, 7019–
7021.
[11] a) Z. Strassberger, A. H. Alberts, M. J. Louwerse, S. Tanase, G. Rothen-
berg, Green Chem. 2013, 15, 768–774; b) G. S. Macala, T. D. Matson, C. L.
Johnson, R. S. Lewis, A. V. Iretskii, P. C. Ford, ChemSusChem 2009, 2,
215–217; c) T. D. Matson, K. Barta, A. V. Iretskii, P. C. Ford, J. Am. Chem.
Soc. 2011, 133, 14090–14097.
[12] a) A. Kazmi, J. Clark in Renewable Raw Materials: New Feedstocks for the
Chemical Industry, (Eds.: R. Ulber, D. Sell, T. Hirth), Wiley-VCH, Weinheim,
2011; b) http://www.hydrogen.energy.gov/pdfs/12024_h2_production_
cost_natural_gas.pdf.
[13] a) A. Wu, B. O. Patrick, E. Chung, B. R. James, Dalton Trans. 2012, 41,
11093–11106; b) T. vom Stein, T. Weigand, C. Merkens, J. Klankermayer,
W. Leitner, ChemCatChem 2013, 5, 439–441.
[14] T. Nishiguchi, K. Fukuzumi, J. Am. Chem. Soc. 1974, 96, 1893–1897.
[15] S. C. Chmely, S. Kim, P. N. Ciesielski, G. Jimenez-Oses, R. S. Paton, G. T.
Beckham, ACS Catal. 2013, 3, 963–974.
[16] W. H. Hartung, R. Simonoff, Hydrogenolysis of Benzyl Groups Attached to
Oxygen, Nitrogen, or Sulfur in Organic Reactions, Wiley-VCH, Weinheim,
2011, pp. 263–326.
Acknowledgements
This research was supported by BP through the Energy Biosci-
ences Institute and in part under contract DEFG02–90ER14146
with the U.S. Department of Energy by its Division of Chemical
Sciences, Office of Basic Energy Sciences.
Keywords: biomass
· heterogeneous catalysis · lignin ·
palladium · reaction mechanisms
[1] a) A. J. Ragauskas, C. K. Williams, B. H. Davison, G. Britovsek, J. Cairney,
C. A. Eckert, W. J. Frederick, J. P. Hallett, D. J. Leak, C. L. Liotta, J. R. Mie-
lenz, R. Murphy, R. Templer, T. Tschaplinski, Science 2006, 311, 484–489;
b) G. W. Huber, S. Iborra, A. Corma, Chem. Rev. 2006, 106, 4044–4098;
c) A. Corma, S. Iborra, A. Velty, Chem. Rev. 2007, 107, 2411–2502; d) J.
Ohlrogge, D. Allen, B. Berguson, D. DellaPenna, Y. Shachar-Hill, S.
Stymne, Science 2009, 324, 1019–1020; e) P. Gallezot, Chem. Soc. Rev.
2012, 41, 1538–1558.
[2] J. R. Regalbuto, Science 2009, 325, 822–824.
[3] a) J. Zakzeski, P. C. A. Bruijnincx, A. L. Jongerius, B. M. Weckhuysen,
Chem. Rev. 2010, 110, 3552–3599; b) J. C. Hicks, J. Phys. Chem. Lett.
2011, 2, 2280–2287; c) M. Stçcker, Angew. Chem. Int. Ed. 2008, 47,
9200–9211; Angew. Chem. 2008, 120, 9340–9351.
[4] J. M. Nichols, L. M. Bishop, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc.
2010, 132, 12554–12555.
[5] a) S. Son, F. D. Toste, Angew. Chem. Int. Ed. 2010, 49, 3791–3794; Angew.
Chem. 2010, 122, 3879–3882; b) J. M. W. Chan, S. Bauer, H. Sorek, S.
Received: November 21, 2013
Revised: February 17, 2014
Published online on && &&, 0000
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 0000, 00, 1 – 4
&
4
&
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
Cleavage within: The selective cleavage
of b-O-4 bond linkage in lignin has re-
ceived great attention. We developed
a method using the commercially avail-
able heterogeneous catalyst, Pd/C, to
cleave the CÀO bond in b-O-4 linkage
model compound without hydrogen. A
mechanistic study shows that the pres-
ent catalytic system undergoes a process
different from previous reports, in
X. Zhou, J. Mitra, T. B. Rauchfuss*
&& – &&
Lignol Cleavage by Pd/C Under Mild
Conditions and Without Hydrogen: A
Role for Benzylic CÀH Activation?
which the b-benzylic-H atom in the sub-
strates plays a critical role.
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 0000, 00, 1 – 4
&
5
&
ÞÞ
These are not the final page numbers!