Manganese-Catalyzed Selective Upgrading of Ethanol with Methanol into Isobutanol

Article abstract of DOI:10.1002/cssc.201802689

Isobutanol serves as an ideal gasoline additive owing to its good compatibility with current engine technology, high energy density, and high octane number. Herein, an efficient and selective Mn-catalyzed upgrading of ethanol with methanol into isobutanol is reported. This is the first example of deoxygenative coupling of lower alcohols to isobutanol by using a homogeneous non-noble-metal catalyst. This transformation proceeded at very low catalyst loading with a high turnover number (9233) and up to 96 % isobutanol selectivity.

Full text of DOI:10.1002/cssc.201802689

Accepted Article
Title: Manganese-Catalyzed Selective Upgrading of Ethanol with
Methanol into Isobutanol
Authors: Yaqian Liu, Zhihui Shao, Yujie Wang, Lijin Xu, Zhiyong Yu,
and Qiang Liu
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: ChemSusChem 10.1002/cssc.201802689
Link to VoR: http://dx.doi.org/10.1002/cssc.201802689
A Journal of
www.chemsuschem.org

ChemSusChem
10.1002/cssc.201802689
COMMUNICATION
Manganese-Catalyzed Selective Upgrading of Ethanol with
Methanol into Isobutanol
Yaqian Liu‡,[a,b] Zhihui Shao , Yujie Wang, Lijin Xu,* Zhiyong Yu,* and Qiang Liu*
‡ [b]
[b]
[a]
[a]
[b]
Abstract: Isobutanol serves as an ideal gasoline additive due to its
good compatibility with current engine technology, high energy
density and high octane number. Herein, we report an efficient and
selective Mn-catalyzed upgrading of ethanol with methanol into
isobutanol. This is the first example of deoxgenative coupling of lower
alcohols to isobutanol by using a homogeneous non-noble-metal
catalyst. This transformation could proceed at very low catalyst
loading with high turnover number (9233) and up to 96% isobutanol
selectivity was also reached.
it is challenging to achieve high selectivity towards isobutanol
rather than various other higher alcohol products. This
transformation was firstly realized via heterogeneous catalysis, in
which high conversion of alcohols could be obtained but suffered
from ether low selectivity, high reaction temperature or high
catalysts loading.[
10]
With respect to homogeneous catalytic
systems, to the best of our knowledge, only a handful of catalysts
based on precious metals have been applied for this
transformation (Figure 1).[11]
Sustainable production of liquid fuels from renewable biomass
are receiving increasing industrial and scientific attention, driven
by the diminishing crude oil reserves and ongoing climate
change.[1] Bio-ethanol, mainly obtained by the fermentation of
sugar-containing crops, is utilized currently as a blend additive
with conventional gasoline in internal combustion engines.[2]
However, ethanol is not an ideal alternative to gasoline due to its
low energy density, water solubility and corrosivity to the engine.
Higher alcohols, such as 1-butanol, can alleviate these problems
caused by ethanol, because of their fuel characteristics more
closer to conventional gasoline.[3] The most known approach to
production of 1-butanol from bio-feedstocks, ABE fermentation
process, suffers from low conversion and poor selectivity.[4] In this
context, an attractive alternative method is to direct upgrading of
easily available (bio)ethanol into higher alcohols. A number of
homogeneous catalysts based on precious metals (Ru[5] and Ir[6])
with good performances for the upgrading of ethanol into 1-
butanol have been developed. Notably, we recently reported a
more sustainable version of the same transformation by using a
manganese catalyst , in which high selectivity (92%) and a record
Scheme 1. Proposed route for the co-condensation of ethanol
with methanol into isobutanol.
[7]
The replacement of expensive noble-metal catalysts by first-
row base-metals is highly appreciated in terms of sustainability.
Encouraged by the significant achievements in Mn-catalyzed
alcohol dehydrogenation reactions,[12] we disclose herein the first
turnover number (>110 000) were reached .
Despite significant advances in upgrading of ethanol into 1-
butanol mentioned above, the synthesis of its branched isomer
isobutanol, as an advanced liquid fuel possessing improved
octane number over 1-butanol,[8] was seldom explored. The co-
condensation of (bio)ethanol and widely available methanol
provides an attractive route for the synthesis of isobutanol. Using
this strategy, ethanol and methanol undergo sequential
dehydrogenation, aldol coupling, and re-hydrogenation cycle to
yield n-propanol, which occurs the same consecutive coupling
process with methanol to produce isobutanol (Scheme 1). Clearly,
[9]
[
a]
b]
Miss Y. Liu, Prof. Z. Yu and Prof. L. Xu
Department of Chemistry
Renmin University of China
Beijing,100872, China
[
Miss Y. Liu, Mr. Z. Shao, Mr. Y. Wang, Prof. Q. Liu
Center of Basic Molecular Science (CBMS), Department of
Chemistry
Tsinghua University
Beijing 100084, China
E-mail: qiang_liu@mail.tsinghua.edu.cn.
Y. Liu and Z. Shao contributed equally to this work.
Firgure 1. Homogeneous metal catalysts for the upgrading of
ethanol with methanol into isobutanol.
‡
This article is protected by copyright. All rights reserved.

ChemSusChem
10.1002/cssc.201802689
COMMUNICATION
non-noble metal catalyzed upgrading of ethanol with methanol
into isobutanol by using a well-defined manganese catalyst
[Mn]-1 and tricarbonyl iPrPNP-Mn(I) complex [Mn]-2 gave similar
results due to the conversion of the tricarbonyl complex [Mn]-2
to dicarbonyl species [Mn]-1 at high temperature (table1, entries
(
Figure 1). Notably, this robust pincer Mn-catalyst achieved the
-1
[7] Ph
Cy
highest turnover number (9233) and turnover frequency (833 h )
among all these homogeneous catalysts for the synthesis of
isobutanol.
1 and 2).
PNP-Mn(I) complex [Mn]-3 and
PNP-Mn(I)
complex [Mn]-4 displayed comparable ethanol conversion but
lower selectivity of isobutanol than [Mn]-1 (entries 1, 3 and 4).
There was no reaction in the absence of Mn-catalysts or
5
employing commercially available Mn(CO) Br as the catalyst,
Table 1. Mn-catalyzed upgrading of ethanol with methanol to
isobutanol
a
indicating the importance of the Mn-catalysts and the supporting
pincer ligands (entries 7 and 8). Besides, the N-methylated
complexes [Mn]-5 and [Mn]-6 showed much lower reactivity,
revealing the essential role of the “N-H moiety” for the hydrogen
transfer process (entries 5 and 6). Further increase or decrease
of base loading could neither improve ethanol conversion nor
yield and selectivity of isobutanol for this transformation (entry 9
and 10). In these Mn-catalyzed reactions for the synthesis of
isobutanol, the selectivity was significantly influenced with bases
(
Table S1). n-Propanol along with C5, C6 aliphatic alcohols and
C8, C9, C10 aromatic alcohols were also detected in the liquid
fraction as side products when using other strong bases, such as
t
NaOEt, NaO Bu or NaOH (Table S1, entries 2, 3 and 4). The
proposed reaction pathways for the generation of these higher
alcohols were discussed in detail in the supporting information
(
2 3
Scheme S1). Using weaker base, Na CO , could not promote
this transformation (Table S1, entry 5). Acceptorless alcohol
dehydrogenative coupling (ADC) products, such as ethyl acetate
and methyl formate, were not detected in any of these reactions.
HCOONa and NaOAc could be formed in the solid-phase verified
by NMR analysis, indicating
a process of Mn-catalyzed
dehydrogenative coupling of alcohols with hydroxides into
carboxylates was involved.[14]
We then examined different reaction parameters to improve the
efficiency of this transformation (Table 2 and Table S3). The
choice of bases is of great importance for this Guerbet reaction
process. NaOMe was found to be the optimal base likely because
its protonation product MeOH could be used as the excessive
component for this transformation (Table S1, entry 1). It is
envisioned that the ratio of ethanol and methanol would play a
key role for the selectivity of isobutanol.[10d] Specifically, increase
of the amount ethanol from 1 mL to 1.25 mL in combination with
1
0.4 mL of methanol gave lower yield, conversion and TON for
aReaction conditions: 1 mL (17.13 mmol) ethanol, 10.4 mL (256.95 mmol)
methanol, [Mn] (0.00857 mmol, 0.05 mol%), and NaOMe (51.39-68.52
mmol, 300-400 mol%) at 160 oC for 16 h under Ar in 25 mL autoclave.
isobutanol production (table 2, entries 1 and 2). An increase of
methanol amount to 15 mL resulted in lower selectivity of
isobutanol as well (entry 3), in which n-propanol was obtained with
37% selectivity (for more details, see Table S3). Higher TON and
selectivity were observed by increasing reaction temperature
(entries 1, 4, 5 and 6), which could be resulted from more efficient
dehydrogenation of n-propanol and methanol at high temperature.
Notably, increasing reaction time to 48 h could be beneficial to the
conversion, yield as well as selectivity (entry 7).To our delight, up
to 40% yield and 96% selectivity could be acquired under 0.1 mol%
catalysts loading in 48 hours (entry 9). In order to boost the
efficiency of the catalyst, we further investigated the performance
of this Mn-catalytic system at lower catalyst loading. Notably, an
obvious improvement of TON was realized as the decrease of
catalyst loadings without any loss of the selectivity (entries 10 and
b
c
Total conversion of ethanol to all alcohol products. Yield was determined
d
by GC. Selectivity was determined by mmol of isobutanol per mmol of
higher alcohol products. eTON based on mmol of EtOH converted to
isobutanol per mmol of [Mn] catalysts.
We initially evaluated the reactivity of different Mn-pincer
catalysts in this transformation by reacting 1 mL of ethanol, 10.4
mL of methanol, 0.05 mol% Mn catalysts, and 350 mol% NaOMe
o
(
mol% based on ethanol substrate) at 160 C for 16 h (Table 1).
It is worth mentioning that the TON, conversion, yield, and
selectivity of these Mn-catalyzed upgrading reactions of ethanol
with methanol were calculated in the same manner as previous
reports for comparison (see SI for more detail). All the manganese
catalysts shown in Table 1 were prepared as reported in our
11). A synergetic increase of the amount of ethanol and methanol
previous work.[7,
13]
Isolated dicarbonyl iPrPNP-Mn(I)complex
along with the use of 0.031 mol% of [Mn]-1 resulted in a
remarkable TON of 9233 after 48 hours (entry 13). Moreover, the
This article is protected by copyright. All rights reserved.

ChemSusChem
10.1002/cssc.201802689
COMMUNICATION
TOF of catalyst [Mn]-1 in this reaction could reach up to 833 h-1
[1]
a) M. Poliakoff, J. M. Fitzpatrick, T. R. Farren, P. T. Anastas, Science 2002,
297, 807-810; b) D. R. Dodds, R. A. Gross, Science 2007, 318, 1250-1251;
for the first 7 hours (entry 12). However, the selectivity for
isobutanol was decreased to 75% along with 25% n-propanol
selectivity.
c) D. M. Alonso, J. Q. Bond, J. A. Dumesic, Green Chem. 2010, 12, 1493-
1513; d) C. O. Tuck, E. Pérez, I. T. Horváth, R. A. Sheldon, M. Poliakoff,
Science 2012, 337, 695-699.
[
[
2] J. Goldemberg, Science 2007, 315, 808-810.
3] a) P. Durre, Biotechnol. J. 2007, 2, 1525-1534; b) S. Atsumi, A. F. Cann,
M. R. Connor, C. R. Shen, K. M. Smith, M. P. Brynildsen, K. J. Chou, T.
Hanai, J. C. Liao, Metab Eng 2008, 10, 305-311; c) B. G. Harvey, H. A.
Meylemans, J. Chem. Technol. Biotechnol. 2011, 86, 2-9.
Table 2. Optimization of the reaction conditions.a
[
[
4] C. Jin, M. Yao, H. Liu, C.-f. F. Lee, J. Ji, Renew. Sust. Energy Rev. 2011,
15, 4080-4106.
5] a) G. R. Dowson, M. F. Haddow, J. Lee, R. L. Wingad, D. F. Wass, Angew.
Chem. Int. Ed. 2013, 52, 9005-9008; b) R. L. Wingad, P. J. Gates, S. T. G.
Street, D. F. Wass, ACS Catal. 2015, 5, 5822-5826; c) K. N. Tseng, S. Lin,
J. W. Kampf, N. K. Szymczak, Chem. Commun. 2016, 52, 2901-2904; d)
Y. Xie, Y. Ben-David, L. J. Shimon, D. Milstein, J. Am. Chem. Soc. 2016,
1
38, 9077-9080.
6] a) K. Koda, T. Matsu-ura, Y. Obora, Y. Ishii, Chem. Lett. 2009, 38, 838-
39; b) S. Chakraborty, P. E. Piszel, C. E. Hayes, R. T. Baker, W. D. Jones,
[
8
J. Am. Chem. Soc. 2015, 137, 14264-14267.
[
[
7] S. Fu, Z. Shao, Y. Wang, Q. Liu, J. Am. Chem. Soc. 2017, 139, 11941-
11948.
8] A. M. Brownstein, in Renewable Moto Fuels: The Past, the Present and the
Uncertain Future, Vol. 5, Butterworth-Heinemann, Oxford, 2014, p. 47.
9] H. Aitchison, R. L. Wingad, D. F. Wass, ACS Catal. 2016, 6, 7125-7132.
10] a) W. Ueda, T. Kuwabara, T. Ohshida, Y. Morikawa, J. Chem. Soc., Chem.
Commun. 1990, 1558-1559; b) C. Carlini, M. Di Girolamo, A. Macinai, M.
Marchionna, M. Noviello, A. M. Raspolli Galletti, G. Sbrana, J. Mol.Catal.
A: Chem. 2003, 200, 137-146; c) E. S. Olson, R. K. Sharma, T. R. Aulich,
Appl. Biochem. Biotechnol. 2004, 115, 913-932; d) Q. Liu, G. Xu, X. Wang,
X. Mu, Green Chem. 2016, 18, 2811-2818; e) Q. Liu, G. Xu, Z. Wang, X.
Liu, X. Wang, L. Dong, X. Mu, H. Liu, ChemSusChem 2017, 10, 4748-4755.
11] a) R. L. Wingad, E. J. Bergstrom, M. Everett, K. J. Pellow, D. F. Wass,
Chem. Commun. 2016, 52, 5202-5204; b) R. J. Newland, M. F. Wyatt, R.
L. Wingad, S. M. Mansell, Dalton Trans. 2017, 46, 6172-6176; c) K. J.
Pellow, R. L. Wingad, D. F. Wass, Catal. Sci. Technol. 2017, 7, 5128-5134.
12] a) S. Elangovan, J. Neumann, J.-B. Sortais, K. Junge, C. Darcel, M. Beller,
Nat. Commun. 2016, 7, 12641; b) M. Mastalir, M. Glatz, E. Pittenauer, G.
Allmaier, K. Kirchner, J. Am. Chem. Soc. 2016, 138, 15543-15546; c) A.
Mukherjee, A. Nerush, G. Leitus, L. J. W. Shimon, Y. Ben David, N. A.
Espinosa Jalapa, D. Milstein, J. Am. Chem. Soc. 2016, 138, 4298-4301; d)
M. Peña‐López, P. Piehl, S. Elangovan, H. Neumann, M. Beller, Angew.
Chem. Int. Ed. 2016, 55, 14967-14971; e) M. Andérez-Fernández, L. K.
Vogt, S. Fischer, W. Zhou, H. Jiao, M. Garbe, S. Elangovan, K. Junge, H.
Junge, R. Ludwig, M. Beller, Angew. Chem. Int. Ed. 2017, 56, 559-562; f)
A. Bruneau-Voisine, D. Wang, V. Dorcet, T. Roisnel, C. Darcel, J.-B.
Sortais, J. Catal. 2017, 347, 57-62; g) A. Bruneau-Voisine, D. Wang, V.
Dorcet, T. Roisnel, C. Darcel, J.-B. Sortais, Org. Lett. 2017, 19, 3656-3659;
h) F. Kallmeier, B. Dudziec, T. Irrgang, R. Kempe, Angew. Chem. Int. Ed.
[
[
[
[
aReaction conditions: 1 mL (17.13 mmol) ethanol, 10.4 mL (256.95 mmol)
methanol, 0.05 mol% [Mn]-1, and 350 mol% NaOMe at given temperature
and reaction time under Ar in 25 mL autoclave. Conversion, yield,
b
selectivity and TON were determined in the same way as in Table 1. 1.25
c
d
mL (21.41 mmol) ethanol, 280 mol% NaOMe. 15 mL MeOH. In 60 mL
autoclave, using 4 mL ethanol, 41.6 mL methanol.
In summary, we have developed an effective and sustainable
synthesis of advanced biofuel isobutanol via upgrading of
2
017, 56, 7261-7265; i) M. Mastalir, E. Pittenauer, G. Allmaier, K. Kirchner,
J. Am. Chem. Soc. 2017, 139, 8812-8815; j) D. H. Nguyen, Y. Morin, L.
Zhang, X. Trivelli, F. Capet, S. Paul, S. Desset, F. Dumeignil, R. M. Gauvin,
ChemCatChem 2017, 9, 2652-2660; k) D. H. Nguyen, X. Trivelli, F. Capet,
J.-F. Paul, F. Dumeignil, R. M. Gauvin, ACS Catal. 2017, 7, 2022-2032; l)
U. K. Das, Y. Ben-David, Y. Diskin-Posner, D. Milstein, Angew. Chem. Int.
Ed. 2018, 57, 2179-2182; m) U. K. Das, S. Chakraborty, Y. Diskin-Posner,
D. Milstein, Angew. Chem. Int. Ed. 2018, 57, 13444-13448; n) F. Kallmeier,
R. Kempe, Angew. Chem. Int. Ed. 2018, 57, 46-60; o) N. Gorgas, K.
Kirchner, Acc. Chem. Res. 2018, 51, 1558-1569; p) G. Zhang, T. Irrgang,
T. Dietel, F. Kallmeier, R. Kempe, Angew. Chem. Int. Ed. 2018, 57, 9131-
(
bio)ethanol with methanol. This transformation was realized by
using well-defined pincer PNP Mn-catalyst, reaching
remarkable turnover number (9233) and turnover frequency (833
a
a
-1
h ).
Acknowledgements
9
135.
13] Y. Wang, Z. Shao, K. Zhang, Q. Liu, Angew. Chem. Int. Ed. 2018, 57,
5143-15147.
[
[
1
We are grateful for the financial supports from National Program
for the National Natural Science Foundation of China (91845107,
14] Z. Shao, Y. Wang, Y. Liu, Q. Wang, X. Fu, Q. Liu, Org. Chem. Front. 2018,
5, 1248-1256.
21822106) and the 111 project.
Keywords: Methanol • Ethanol • Isobutanol • Manganese •
Guerbet reaction
This article is protected by copyright. All rights reserved.

ChemSusChem
10.1002/cssc.201802689
COMMUNICATION
COMMUNICATION
Yaqian Liu, Zhihui Shao, Yujie Wang,
Lijin Xu*, Zhiyong Yu*, Qiang Liu*
Page No. – Page No.
Manganese-Catalyzed Selective
Upgrading of Ethanol with Methanol
into Isobutanol
Isobutanol is currently an desired gasoline alternative because of its compatibility with modern engine technology, high energy density
and octane number. In this work, we disclosed here the first homogeneous non-noble metal catalyst for a sustainable production of
isobutanol by upgrading of (bio)ethanol and widely availble methanol. This transformation could proceed at an very low catalyst loading
with remarkable turnover number (9233) and up to 96% isobutanol selectivity was also reached.
This article is protected by copyright. All rights reserved.