Electronic and steric factors for enhanced selective synthesis of 2-ethyl-1-hexanol in the Ir-complex-catalyzed Guerbet reaction of 1-butanol

Article abstract of DOI:10.1016/S1872-2067(20)63772-X

1-Butanol is a potential bio-based fermentation product obtained from cellulosic biomass. As a value-added chemical, 2-ethyl-1-hexanol (2-EH) can be produced by Guerbet conversion from 1-butanol. This work reports the enhanced catalytic Guerbet reaction of 1-butanol to 2-EH by a series of Cp*Ir complexes (Cp*: 1,2,3,4,5-pentamethylcyclopenta-1,3-diene) coordinated to bipyridine-type ligands bearing an ortho-hydroxypyridine group with an electron-donating group and a Cl^? anion. The catalytic activity of the Cp*Ir complex increased by increasing the electron density of the bipyridine ligand when functionalized with the para-NMe₂ and ortho-hydroxypyridine groups. A record turnover number of 14047 was attained. A mechanistic study indicated that the steric effect of the ethyl group on the α-C of 2-ethylhexanal (2-EHA) and the conjugation effect of C=C–C=O in 2-ethylhex-2-enal (2-EEA) benefits the high selectivity of 2-EH from 1-butanol by inhibiting the cross-aldol reaction of 2-EHA and 2-EEA with butyraldehyde. Nuclear magnetic resonance study revealed the formation of a carbonyl group in the bipyridine-type ligand via the reaction of the Cp*Ir complex with KOH.

Full text of DOI:10.1016/S1872-2067(20)63772-X

Chinese Journal of Catalysis 42 (2021) 1586–1592
a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m
journal homepage: www.sciencedirect.com/journal/chinese‐journal‐of‐catalysis
Article
Electronic and steric factors for enhanced selective synthesis of
2‐ethyl‐1‐hexanol in the Ir‐complex‐catalyzed Guerbet reaction of
1‐butanol
Zhanwei Xu a, Peifang Yan a,Changhui Liang a,b, Songyan Jia c, Xiumei Liu a, Z. Conrad Zhang a,*
a State Key Laboratory of Catalysis, Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences,
Dalian 116023, Liaoning, China
b University of Chinese Academy of Sciences, Beijing 100049, China
c College of Chemical Engineering, Shenyang University of Chemical Technology, Shenyang 110142, Liaoning, China
A R T I C L E I N F O
A B S T R A C T
Article history:
1‐Butanol is a potential bio‐based fermentation product obtained from cellulosic biomass. As a
value‐added chemical, 2‐ethyl‐1‐hexanol (2‐EH) can be produced by Guerbet conversion from
1‐butanol. This work reports the enhanced catalytic Guerbet reaction of 1‐butanol to 2‐EH by a
series of Cp*Ir complexes (Cp*: 1,2,3,4,5‐pentamethylcyclopenta‐1,3‐diene) coordinated to bipyri‐
dine‐type ligands bearing an ortho‐hydroxypyridine group with an electron‐donating group and a
Cl− anion. The catalytic activity of the Cp*Ir complex increased by increasing the electron density of
the bipyridine ligand when functionalized with the para‐NMe2 and ortho‐hydroxypyridine groups. A
record turnover number of 14047 was attained. A mechanistic study indicated that the steric effect
of the ethyl group on the α‐C of 2‐ethylhexanal (2‐EHA) and the conjugation effect of C=C–C=O in
2‐ethylhex‐2‐enal (2‐EEA) benefits the high selectivity of 2‐EH from 1‐butanol by inhibiting the
cross‐aldol reaction of 2‐EHA and 2‐EEA with butyraldehyde. Nuclear magnetic resonance study
revealed the formation of a carbonyl group in the bipyridine‐type ligand via the reaction of the Cp*Ir
complex with KOH.
Received 25 December 2020
Accepted 22 January 2021
Available online 5 May 2021
Keywords:
2‐Ethyl‐1‐hexanol
Guerbet reaction
1‐Butanol
Iridium
Hydrogenation
© 2021, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
1. Introduction
hydrogen gas to butyraldehyde, and base‐catalyzed aldol con‐
densation of butyraldehyde to 2‐ethyl‐2‐hexenal, followed by
The development of renewable chemicals from biomass
remains one of the most important objectives for attaining
global sustainability. 2‐Ethyl‐1‐hexanol (2‐EH), one of the
“plasticizer alcohols,” has been used in polyvinyl chloride man‐
ufacturing [1]. Moreover, 2‐EH has been extensively applied in
the production of soaps, surfactants, solvents, adhesives, diesel,
and lube additives. The industrial three‐step production of
2‐EH involves the hydroformylation of propylene with CO and
hydrogenation of 2‐ethyl‐2‐hexenal with hydrogen gas
(Scheme 1) [2–4]. Recent progress has been made to integrate
the aldol condensation of butyraldehyde and hydrogenation of
2‐ethyl‐2‐hexenal into a one‐pot reaction [5,6]. However, in‐
dustrial processes still depend on unsustainable fossil carbon
resources, and external CO and hydrogen gas are required.
The abundance of cellulosic biomass provides an environ‐
mentally beneficial, renewable feedstock as an alternative to
* Corresponding author. Tel/Fax: +86‐411‐84379462; E‐mail: zczhang@yahoo.com
This work was supported by the National Natural Science Foundation of China (21706255, 21932005, 21690084).
DOI: 10.1016/S1872‐2067(20)63772‐X | http://www.sciencedirect.com/journal/chinese‐journal‐of‐catalysis | Chin. J. Catal., Vol. 42, No. 9, September 2021

Zhanwei Xu et al. / Chinese Journal of Catalysis 42 (2021) 1586–1592
1587
1‐butanol, the reported catalytic performance measured by
TON was less than 1000 [30,31]. Developing an efficient metal
catalyst with superior performance for both dehydrogenation
and hydrogenation is critical for enhanced performance in the
Guerbet reaction of 1‐butanol to 2‐EH. The Cp*Ir complexes
coordinated by pyridine‐type ligands bearing an or‐
tho‐hydroxypyridine group (a proton‐response ligand) are a
class of excellent catalysts for hydrogenation/dehydrogenation,
such as the hydrogenation of CO2 and 5‐hydroxymethylfurfural
(5‐HMF), and the dehydrogenation of alcohol and formic acid
[35–48]. We previously demonstrated the excellent perfor‐
mance of a series of Cp*Ir complexes coordinated with bipyri‐
dine‐type ligands bearing an ortho‐hydroxypyridine group for
the hydrogenation of 5‐HMF to 1‐hydroxyhexane‐2,5‐dione
(HHD) with a turnover frequency (TOF) of 31560 h–1[39,40].
The equilibrium reaction of ortho‐hydroxypyridine to or‐
tho‐oxyanion was found to assist H2 heterolytic dissociation.
The strong electron‐donating NMe2 group on the bipyri‐
dine‐type ligand was found to further enhance the high catalyt‐
ic performance for hydrogenating aldehyde and olefin inter‐
mediates, resulting in the TOF of hydrogenating 5‐HMF to HHD
[40]. In this work, the in situ formed ortho‐oxyanion as a base is
expected to assist the deprotonation of 1‐butanol, as well as to
enhance the performance of the subsequent hydrogenation of
the in situ generated aldol condensation intermediate, leading
to an enhanced catalytic performance of the Guerbet reaction of
1‐butanol catalyzed by the Cp*Ir complex. Based on the above
hypothesis, we synthesized Cp*Ir complexes bearing an or‐
tho‐hydroxypyridine group, which are electron‐donating
groups targeted for Guerbet catalysis in this work (Scheme 2).
The Cp*Ir complex bearing an electron‐donating group, or‐
tho‐hydroxypyridine, and a Cl– anion, is favorable for the Guer‐
bet reaction of 1‐butanol to 2‐EH under mild conditions. A
mechanism for the Cp*Ir complex‐catalyzed Guerbet reaction of
1‐butanol to 2‐EH is proposed.
Scheme 1. Alternative route for the synthesis of 2‐ethyl‐1‐hexanol.
fossil carbon resources to produce chemicals and fuels. The
Guerbet reaction has been used for upgrading biomass‐based
light alcohols to value‐added higher alcohols. For example, the
Guerbet reaction of ethanol, a fermentation product of sug‐
ar‐containing crops, has been studied to produce 1‐butanol as
an “advanced biofuel.” Heterogeneously and homogeneously
catalyzed Guerbet reactions of ethanol to 1‐butanol have been
reported [7–20]. 1‐Butanol is also a potential fermentation
product obtained via the acetone‐butanol‐ethanol fermentation
process [21–24].
The synthesis of 2‐EH from the Guerbet reaction of
1‐butanol is a green alternative process (Scheme 1). The hy‐
drogen required for the Guerbet reaction is borrowed in situ
from the dehydrogenation of 1‐butanol and does not involve
the typical H2 dissociation step [15,25,26]. Compared with the
conventional three‐step process in the production of 2‐EH from
fossil resources, the synthesis of 2‐EH through the Guerbet
reaction offers technical and potentially economic advantages,
as it is a one‐step process that eliminates the need for opera‐
tions under pressurized CO and H2. Heterogeneous catalysts,
such as Ir on N‐doped carbon and Pd on metal oxides, have
been applied for the Guerbet reaction of 1‐butanol to 2‐EH un‐
der a high temperature (> 170 °C) with byproducts including
olefins, ethers, and higher alcohols [27–29]. Homogeneous
catalysts, such as Ir complexes, have been reported to exhibit
good catalytic dehydrogenation/hydrogenation functions in‐
volved in the Guerbet reaction of 1‐butanol. Ishii et al. [30] re‐
ported that [Cp*IrCl2]2 or [IrCl(COD)]2 (Cp* for
1,2,3,4,5‐pentamethylcyclopenta‐1,3‐diene, and COD for cy‐
cloocta‐1,5‐diene) complex catalyzed the Guerbet reaction of
2. Experimental
t
1‐butanol to 2‐EH in the presence of a BuOK base catalyst in
All the reagents used were of analytical grade, purchased
locally and used without any purification unless otherwise
specified. NMR spectra were measured in CDCl3, or CD3OD on a
400 MHz instrument and recorded at the following frequencies:
proton (1H, 400 MHz), carbon (13C, 100 MHz).
xylene at 120 °C. However, the performance of the Ir complex
measured by the turnover number (TON) was less than 100. Xu
et al. [31] reported that IrCl3 combined with a functionalized
1,10‐phenanthroline ligand in the presence of the required
stoichiometric KOH/NaOAc base‐catalyzed Guerbet reaction of
1‐butanol yielded a TON of approximately 250 in water at 150
°C. Given the current state of progress, developing an efficient
catalyst with high activity and selectivity is an important but
highly challenging research goal for enhanced productivity for
the Guerbet reaction of 1‐butanol to 2‐EH. This work aims to
identify the critical structural and functional factors of ligands
in the catalyst design for enhanced performances of Ir com‐
plexes in the Guerbet reaction of 1‐butanol to 2‐EH.
Synthesis of [Cp*IrClL4]Cl: a mixture of Cp*IrCl2 (100 mg),
L4 (64.3 mg) was stirred in methanol (20 mL) under N2 at‐
The Guerbet reaction of 1‐butanol involves the following
catalytic sequence: (1) metal‐catalyzed dehydrogenation of
1‐butanol to butyraldehyde, (2) base‐catalyzed aldol condensa‐
tion of butyraldehyde, and (3) metal‐catalyzed hydrogenation
of the aldol condensation product [32–34]. Although Ir com‐
plexes exhibited the potential for Guerbet catalysis of
Scheme 2. Chemical structures of Cp*Ir complexes in this work.

1588
Zhanwei Xu et al. / Chinese Journal of Catalysis 42 (2021) 1586–1592
mosphere at room temperature for 12 h. The methanol solution
was removed under vacuum to give the product as a yellow
solid. The yellow solid was used for Guerbet catalysis without
further purification. 1H NMR (400 MHz, CD3OD) δ 1.64 (s, 15H),
3.60–3.62 (m, 4H), 3.82–3.84 (m, 4H), 7.07–7.11 (m, 2H), 7.65
(d, J = 2.8 , 1H), 7.88–7.99 (m, 2H), 8.36 (d, J = 6.92, 1H); 13C
NMR (100 MHz, CD3OD) δ 8.0, 65.9, 88.5, 106.2, 110.6, 112.7,
114.4, 141.8, 150.1, 153.9, 155.9, 156.2, 164.0.
Guerbet reaction of 1‐butanol: As shown in Table 1, a mix‐
ture of Cp*Ir complex, 1‐butanol (2.0 g), and KOH was stirred
under N2 atmosphere. The final reaction mixture was diluted
by CH3CN, and dioxane was added as an internal standard for
GC analysis. The TON was calculated based on converted
1‐butanol in the products.
We previously reported that the hydrogenation perfor‐
mance of the Cp*Ir complex was enhanced when ligand L2 was
tuned to produce a more electron‐rich variation [40]. Consid‐
ering that the hydrogenation step is also involved in the Guer‐
bet reaction, a Cp*Ir complex bearing a stronger elec‐
tron‐donating group on ligand L2 may be expected to increase
the activity of the Guerbet reaction of 1‐butanol by enhancing
the hydrogenation activity. Therefore, we studied the catalytic
performance of the [Cp*IrClL3]Cl and [Cp*IrClL4]Cl complexes
bearing the electron‐donating groups, para‐NMe2, and pa‐
ra‐morpholine, respectively (Table 1, entries 4 and 5). Com‐
pared with the [Cp*IrClL2]Cl complex (Table 1, entry 3), both
the yield and selectivity of 2‐EH were significantly increased. As
a
result, the [Cp*IrClL3]Cl complex bearing an elec‐
tron‐donating para‐NMe2 group exhibited higher catalytic ac‐
tivity (Table 1, entry 4). Upon further increasing the reaction
temperature to 130 °C, the TON of the [Cp*IrClL3]Cl complex
reached a maximum of 3492 (Table 1, entry 6).
3. Results and discussion
We first tested the [Cp*IrCl2]2 complex without a bipyri‐
dine‐type ligand as the catalyst for the Guerbet reaction of
1‐butanol with KOH as the base catalyst. The TON reached 411
in 6 h, and the desired 2‐EH product was obtained with a selec‐
tivity of 74.3% (Table 1, entry 1). 2‐Ethylhexanal (2‐EHA),
2‐ethylhex‐2‐enal (2‐EEA), and 2‐ethylhex‐2‐en‐1‐ol (2‐EHE)
were also detected with selectivities of 4.1%, 2.9%, and 18.7%,
respectively. In comparison, the [Cp*IrClL1]Cl complex
achieved a TON of 629, indicating that the bipyridine ligand L1
significantly enhanced the catalytic activity of the Cp*Ir com‐
plex (Table 1, entry 2). To assess the effect of the or‐
tho‐hydroxypyridine group, the catalytic activity of
[Cp*IrClL2]Cl with an ortho‐hydroxypyridine group was tested
for comparison (Table 1, entry 3). The TON of the [Cp*IrClL2]Cl
complex nearly doubled that of the [Cp*IrClL1]Cl complex, in‐
dicating that the ortho‐hydroxypyridine group of the bipyri‐
dine‐type ligand played an important role in the formation of
2‐EH, probably because the ortho‐hydroxypyridine group as‐
sisted the dehydrogenation of 1‐butanol and the subsequent
hydrogenation step. The ortho‐hydroxypyridine group is
known to form an ortho‐oxyanion that may serve as a base to
trap the proton of 1‐butanol to accelerate the dehydrogenation
step [47]. The Cp*Ir complex with a strong electron‐donating
ortho‐oxyanion generated in situ may favor the hydrogenation
step involved in the Guerbet reaction of 1‐butanol [40].
The Guerbet reaction of 1‐butanol to 2‐EH was then carried
out by prolonging the reaction time to 48 h at 130 °C, resulting
in a 2‐EH yield of 23.9% and a 2‐EH selectivity of 89.5% (Sup‐
porting Information). A TOF of 564 h–1 was achieved using the
[Cp*IrClL3]Cl complex as the catalyst after half an hour. Signif‐
icantly, the catalytic performance of the [Cp*IrClL3]Cl complex
was further tested at a catalyst charge as low as 1.6 × 10–5
mol%, and a record TON of 14047 was reached (Supporting
Information). The results indicate that the catalyst is highly
active, while maintaining a high stability under the reaction
conditions to achieve a high TON.
We studied the effect of the base amount on the Guerbet re‐
action of 1‐butanol with the [Cp*IrClL3]Cl complex as a cata‐
lyst. As shown in Fig. 1(a), upon increasing the amount of KOH
from approximately 1.0 to 6.6 mol%, the TON first increased to
a maximum value of 2900 and then decreased steadily. As
shown in Fig. 1(b), the selectivity of the desired product 2‐EH
followed a similar trend to the TON curve, suggesting that ap‐
proximately 1.7 mol% of KOH is the optimum base amount for
producing 2‐EH from 1‐butanol with the maximum TON and
selectivity. The selectivity of 2‐EHA and 2‐EEA remained at a
plateau of approximately 2% and 8%, respectively. The selec‐
tivity of 2‐EHE followed a trend that first decreased and then
increased, probably because the hydrogenation of 2‐EHE to
2‐EH was suppressed with increasing amounts of KOH.
We propose a Guerbet reaction pathway for 1‐butanol to
2‐EH, as shown in Scheme 3 [30–32]. 1‐Butanol is dehydrogen‐
ated to butyraldehyde by [Cp*IrClL3]Cl and KOH, followed by
the KOH‐catalyzed aldol condensation of butyraldehyde to an
unsaturated aldehyde, 2‐EEA. 2‐EEA may first undergo hydro‐
genation of the C=O bond to 2‐EHE (Scheme 3, path a) or hy‐
drogenation of the C=C bond to 2‐EHA (Scheme 3, path b). Fur‐
ther hydrogenation of 2‐EHE or 2‐EHA produces the final
product 2‐EH. The detection of 2‐EHA, 2‐EEA, and 2‐EHE, as
shown in Table 1, demonstrates that 2‐EHA, 2‐EEA, and 2‐EHE
are intermediates.
Table 1
Guerbet reaction of 1‐butanol to 2‐EH by using a Cp*Ir complex as cat‐
alyst.
Selectivity (%)
2‐EHA 2‐EEA 2‐EHE 2‐EH
Entry
Catalyst
T (°C ) TON
1
2
3
4
5
6
[Cp*IrCl2]2
[Cp*IrClL1]Cl 120
[Cp*IrClL2]Cl 120 1124
[Cp*IrClL3]Cl 120 2900
[Cp*IrClL4]Cl 120 2192
[Cp*IrClL3]Cl 130 3492
120
411
629
4.1
3.8
3.5
1.1
1.3
0.7
2.9
7.6
6.9
6.1
5.4
4.5
18.7
26.6
27.6
15.0
17.7
8.4
74.3
62.0
62.0
77.8
75.6
86.4
To understand the factors that determine the pathway and
product selectivity involving the observed intermediates as
shown in Scheme 3, the multiple potentially competing aldol
Reaction conditions: Cp*Ir complex (0.5 μmol), 1‐butanol (2 g), and
KOH (30 mg) under N2 atmosphere (10 bar) for 6 h.

Zhanwei Xu et al. / Chinese Journal of Catalysis 42 (2021) 1586–1592
1589
(A)
3200
2800
2400
2000
1600
1200
800
(a)
1
2
3
4
5
6
7
Scheme 4. Steric and conjugation effects on product selectivity in the
aldol reactions of butyraldehyde, 2‐EHA, and 2‐EEA. Reaction condi‐
tions: butyraldehyde (1 mmol), 2‐EHA (0.5 mmol), 2‐EEA (0.5 mmol),
KOH (30 mg), 1‐butanol (2 g), at 25 °C for 5 min.
KOH (mol%)
100
90
80
70
60
50
40
30
20
10
0
2-EHA
2-EEA
2-EHE
2-EH
(B)
(b)
To verify the rate‐determining factor in the hydrogenation
pathway of the unsaturated aldehyde, 2‐EEA, the selective hy‐
drogenation of 2‐EEA catalyzed by the Cp*Ir complex was
studied as a model (Supporting Information). The hydrogena‐
tion products, 2‐EHA, 2‐EHE, and 2‐EH were obtained with
selectivities of 20.0%, 31.5%, and 39.7%, respectively. The
results of hydrogenation of 2‐EHA and 2‐EHE to 2‐EH are
shown in Table 2. The blank reaction exhibited no Guerbet
product generated from 1‐butanol under the reaction condi‐
tions (Table 2, entry 1). The reaction rate measured by the TOF
of 2‐EHA hydrogenation to 2‐EH (1409 h–1, entry 2, Table 2)
was much higher than that of 2‐EHE hydrogenation to 2‐EH (56
h–1, entry 3, Table 2). The rates of TOF on 2‐EHA and 2‐EHE
hydrogenations, as shown in Table 2, indicate that the hydro‐
genation of –C=O is kinetically favored over that of –C=C– by
the [Cp*IrClL3]Cl catalyst. The kinetics of the hydrogenation of
these model compounds help to explain the intermediates ob‐
served in Fig. 1. As a result, for the Guerbet reaction of
1‐butanol to 2‐EH shown in Table 1, the selectivity of 2‐EHE is
generally higher than that of 2‐EHA because the consumption
rate of 2‐EHE to 2‐EH is much slower than that of 2‐EHA to
2‐EH.
1
2
3
4
5
6
7
KOH (mol%)
Fig. 1. (a) Effect of the amount of KOH on TON by using the
[Cp*IrClL3]Cl complex as the catalyst (conditions: 0.5 μmol of
[Cp*IrClL3]Cl, and 2 g of 1‐butanol under 10 bar of N2 atmosphere at
120 °C for 6 h); (b) The effect of the amount of KOH on the selectivity by
using [Cp*IrClL3]Cl as the catalyst (conditions: 0.5 μmol of
[Cp*IrClL3]Cl and 2 g of 1‐butanol under 10 bar of N2 atmosphere at
120 °C for 6 h).
reactions of butyraldehyde, 2‐EHA, and 2‐EEA were studied
(Scheme 4). The self‐aldol reaction of butyraldehyde produced
2‐EEA as a major product with a conversion of 73.7% and yield
of 72.6%. In the presence of 2‐EHA, the self‐aldol product,
2‐EEA, from butyraldehyde was still obtained with a yield of
68.7%, while the cross‐aldol product, 2,4‐diethyloct‐2‐enal, was
only obtained with a yield of 3.2%. The reduced cross‐aldol
reaction of 2‐EHA with butyraldehyde was probably due to the
steric effect of the ethyl group on the α‐C. In the presence of
2‐EEA, the self‐aldol reaction of butyraldehyde to 2‐EEA was
not influenced. The cross‐aldol product, 2,4‐diethylocta‐
2,4‐dienal, was not detected, indicating that the C=C–C=O con‐
jugation effect suppressed the cross‐aldol reaction of 2‐EEA
with butyraldehyde. As a result, for the Guerbet catalysis of
1‐butanol, the conjugation effect and steric hindrance on the
α‐C of aldehyde intermediates enhanced the selectivity of the
Guerbet alcohol, 2‐EH, by suppressing the cross‐aldol reaction
of 2‐EHA and 2‐EEA with butyraldehyde.
The [Cp*IrClL3]Cl complex is proposed to react with KOH,
forming the [Cp*IrClL3'] complex that bears an ortho‐oxyanion
group driven by the neutralization of HCl with a strong base,
OH− (Scheme 5) [36,49]. Further ligand exchange between OH−
and Cl− in the [Cp*IrClL3'] complex led to the formation of the
[Cp*Ir(OH)L3'] complex [36]. As the [Cp*Ir(OH)L3'] complex
Table 2
Control experiments for the hydrogenation of 2‐EHA and 2‐EHE.
Entry
1
Substrate
—
TOF (h–1)
—
Selectivity (%)
—
2
3
1409
56
92.6
> 99
OH
path a
O
OH
2-EHE
Ir complex
KOH
KOH
OH
O
2-EH
2-EEA
O
Reaction conditions: [Cp*IrClL3]Cl (0.4 μmol ), 1‐butanol (1 g), sub‐
strate (1 mmol), and KOH (1 mg) under H2 atmosphere (10 bar) at 120
°C for 20 min.
path b
2-EHA
Scheme 3. Proposed pathways of the Guerbet reaction of 1‐butanol to
2‐EH.

1590
Zhanwei Xu et al. / Chinese Journal of Catalysis 42 (2021) 1586–1592
+
Me2N
Cl
N
Ir
OH
Cl
N
[Cp*IrClL3]Cl
Cp*
KOH
Scheme 5. The proposed reaction of [Cp*IrClL3]Cl complex with KOH.
Me2N
could be rearranged to form a [Cp*Ir(OH)L3’] complex that
bears an ortho‐carbonyl group, we studied the reaction of the
[Cp*IrClL3]Cl complex with KOH by 1H NMR and 13C NMR
(Supporting Information). In Fig. 2(a), the peaks (6.3 < δ < 8.5)
are assigned to the bipyridine ring of the [Cp*IrClL3]Cl com‐
plex. In the presence of KOH, a significant change in the 1H NMR
spectrum from that of the [Cp*IrClL3]Cl complex was observed,
indicating that a [Cp*Ir(OH)L3''] complex with a carbonyl
group on the bipyridine ring (Fig. 2(b)) is generated from the
reaction of the [Cp*IrClL3]Cl complex with KOH. For the corre‐
sponding 13C NMR spectrum, as shown in Fig. 2(c), the peaks
(100 < δ < 175) are assigned to the bipyridine ring of the
[Cp*IrClL3]Cl complex, and the peak (δ = 164.0, Fig. 2(c)) is
assigned to C2 of the bipyridine ring [34,47]. In the presence of
KOH, a significant change in the position of C2 in the 13C NMR
spectrum (δ = 171.6, Fig. 2(d)) supported the formation of a
carbonyl group in the [Cp*Ir(OH)L3''] complex [36,49].
N
Ir
O
1-butanol
N
OH
OH
Cp*
[Cp*Ir(OH)L3'']
Me2N
N
Ir
O
2-EH
N
H
Cp*
Ir-H, OH
Ir-H
O
O
OH
+
butyraldehyde
2-EHA
2-EHE
KOH
Ir-H
O
2-EEA
Scheme 6. The proposed mechanism of the Guerbet reaction of
1‐butanol to 2‐EH.
Based on the above experimental results, we further pro‐
pose a mechanism for the Cp*Ir complex‐catalyzed Guerbet
reaction of 1‐butanol to 2‐EH (Scheme 6). The [Cp*IrClL3]Cl
complex may first react with KOH to form the active catalyst,
[Cp*Ir(OH)L3''] (Scheme 5) [36,49], followed by the dehydro‐
genation of 1‐butanol to form the catalyst, Ir‐H, and butyralde‐
hyde [35]. The KOH‐catalyzed aldol reaction of butyraldehyde
produces an unsaturated aldehyde, 2‐EEA. The aldehyde
(2‐EEA) is hydrogenated with the catalyst, Ir‐H, to intermediate
products, 2‐EHA and 2‐EHE, and further to 2‐EH with the re‐
generated [Cp*Ir(OH)L3'']‐catalyst. The hydrogenation activity
of the catalyst (Ir‐H) was significantly enhanced with ligand L3,
bearing a strong electron‐rich para‐NMe2 group and an or‐
tho‐hydroxypyridine group. The ethyl group on the α‐C and the
conjugation effect of the C=C double bond inhibits the further
cross‐aldol reaction of 2‐EHA and 2‐EEA with butyraldehyde,
resulting in an increase in selectivity in the Guerbet reaction of
1‐butanol to produce 2‐EH.
4. Conclusions
We have demonstrated an efficient homogeneous system
for the catalytic Guerbet reaction of 1‐butanol to produce
2‐ethyl‐1‐hexanol. The catalytic activity of the Cp*Ir complex
increased when the electron density of the ligand was in‐
creased by introducing
a
para‐NMe2 group, an or‐
tho‐hydroxypyridine group, and a Cl− anion. A record TON of
14047 was attained. The ethyl group on the α‐C of 2‐EHA and
the conjugation effect of the C=C double bond of 2‐EEA are
found to benefit the high selectivity of 2‐EH from 1‐butanol by
inhibiting the cross‐aldol reaction of 2‐EHA and 2‐EEA with
butyraldehyde. The NMR study revealed the formation of a
carbonyl group in the bipyridine‐type ligand via the reaction of
the Cp*Ir complex with KOH. The new mechanistic under‐
standing represents an important addition to the suite of
Guerbet catalysis and hydrogen‐borrowing chemistry. Further
Fig. 2. The 1H NMR and 13C NMR spectra of the [Cp*IrClL3]Cl complex
with/without KOH. (a) The 1H NMR spectrum of [Cp*IrClL3]Cl without
KOH; (b) The 1H NMR spectrum of [Cp*IrClL3]Cl with KOH; (c) The 13
C
NMR spectrum of [Cp*IrClL3]Cl without KOH; (d) The 13C NMR spec‐
trum of [Cp*IrClL3]Cl with KOH.

Zhanwei Xu et al. / Chinese Journal of Catalysis 42 (2021) 1586–1592
1591
Eng. Chem. Res., 2017, 56, 13310−13321.
[10] G. R. M. Dowson, M. F. Haddow, J. Lee, R. L. Wingad, D. F. Wass,
Angew. Chem. Int. Ed., 2013, 52, 9005–9008.
[11] R. L. Wingad, E. J. E. Bergström, M. Everett, K. J. Pellow, D. F. Wass,
improvement of the catalyst efficiency based on the mechanis‐
tic understanding and development of a homogeneous catalytic
process for the economic production of higher alcohols from
1‐butanol or ethanol is underway.
Chem. Commun., 2016, 52, 5202–5204.
[12] T. Moteki, D. W. Flaherty, ACS Catal., 2016, 6, 4170−4183.
[13] C. N. Neumann, S. J. Rozeveld, M. Yu, A. J. Rieth, M. Dincă, J. Am.
Chem. Soc., 2019, 141, 17477−17481.
[14] K.‐N. T. Tseng, S. Lin, J. W. Kampf, N. K. Szymczak, Chem. Commun.,
2016, 52, 2901−2904.
Electronic supporting information.
Supporting information is available in the online version of
this article
[15] H. Aitchison, R. L. Wingad, D. F. Wass, ACS Catal., 2016, 6,
7125−7132.
Notes
[16] Y. Xie, Y. Ben‐David, L. J. W. Shimon, D. Milstein, J. Am. Chem. Soc.,
2016, 138, 9077−9080.
The authors declare no competing financial interest.
[17] H. Li, A. Riisager, S. Saravanamurugan, A. Pandey, R. S. Sangwan, S.
Yang, R. Luque, ACS Catal., 2018, 8, 148–187.
[18] Q. Liu, G. Xu, X. Wang, X. Liu, X. Mu, ChemSusChem, 2016, 9,
3465–3472.
[19] G. Xu, T. Lammens, Q. Liu, X. Wang, L. Dong, A. Caiazzo, N. Ashraf, J.
Guana, X. Mu, Green Chem., 2014, 16, 3971–3977.
[20] S. Chakraborty, P. E. Piszel, C. E. Hayes, R. T. Baker, W. D. Jones, J.
Am. Chem. Soc., 2015, 137, 14264−14267.
[21] E. M. Green, Curr. Opin. Biotechnol., 2011, 22, 337−343.
[22] C. Jin, M. Yao, H. Liu, C.‐F. Lee, J. Ji, Renew. Sust. Energy Rev., 2011,
15, 4080−4106.
[23] A. Prakash, R. Dhabhai, V. Sharma, Curr. Biochem. Eng., 2015, 3,
37−46.
[24] J. C. Liao, L. Mi, S. Pontrelli, S. Luo, Nat. Rev. Microbiol., 2016, 14,
288−304.
[25] M. H. S. A. Hamid, P. A. Slatford, J. M. J. Williams, Adv. Synth. Catal.,
2007, 349, 1555−1575.
[26] G. E. Dobereiner, R. H. Crabtree, Chem. Rev., 2010, 110,
681–703.
[27] D. Liu, X. Chen, G. Xu, J. Guan, Q. Cao, B. Dong, Y. Qi, C. Li, X. Mu, Sci.
Rep., 2016, 6, 21365.
References
[1] J. Ma, L. Xu, L. Xu, H. Wang, S. Xu, H. Li, S. Xie, H. Li, ACS Catal.,
2013, 3, 985−992.
[2] S. K. Sharma, R. V. Jasra, Ind. Eng. Chem. Res., 2011, 50,
2815–2821.
[3] L. Zhao, Y. Wang, H. An, X. Zhao, Y. Wang, Catal. Commun., 2018,
103, 74–77.
[4] G. M. Torres, R. Frauenlob, R. Franke, A. Bo
̈rner, Catal. Sci. Technol.,
2015, 5, 34−54.
[5] Y. Li, X. Liu, H. An, X. Zhao, Y. Wang, Ind. Eng. Chem. Res., 2016, 55,
6293−6299.
[6] N. Liang, X. Zhang, H. An, X. Zhao, Y. Wang, Green Chem., 2015, 17,
2959–2972.
[7] R. L. Wingad, P. J. Gates, S. T. G. Street, D. F. Wass, ACS Catal., 2015,
5, 5822−5826.
[8] R. Mazzoni, C. Cesari, V. Zanotti, C. Lucarelli, T. Tabanelli, F. Puzzo,
F. Passarini, E. Neri, G. Marani, R. Prati, F. Viganò, A. Conversano, F.
Cavani, ACS Sustainable Chem. Eng., 2019, 7, 224−237.
[9] V. N. Panchenko, E. A. Paukshtis, D. Y. Murzin, I. L. Simakova, Ind.
[28] C. Carlini, A. Macinai, A. M. R. Galletti, G. Sbrana, J. Mol. Catal. A,
Graphical Abstract
Chin. J. Catal., 2021, 42: 1586–1592 doi: 10.1016/S1872‐2067(20)63772‐X
Electronic and steric factors for enhanced selective synthesis of 2‐ethyl‐1‐hexanol in the Ir‐complex‐catalyzed Guerbet reaction
of 1‐butanol
Zhanwei Xu, Peifang Yan,Changhui Liang, Songyan Jia, Xiumei Liu, Z. Conrad Zhang *
Dalian Institute of Chemical Physics, Chinese Academy of Sciences; University of Chinese Academy of Sciences;
Shenyang University of Chemical Technology
An enhanced catalytic Guerbet reaction of 1‐butanol to 2‐ethyl‐1‐hexanol by a Cp*Ir complex was reported.

1592
Zhanwei Xu et al. / Chinese Journal of Catalysis 42 (2021) 1586–1592
2004, 212, 65–70.
Catal., 2015, 5, 788–792.
[29] V. N. Panchenko, E. A. Paukshtis, D. Yu. Murzin, I. L. Simakova, Ind.
Eng. Chem. Res., 2017, 56, 13310−13321.
[40] Z. Xu, P. Yan, H. Li, K. Liu, X. Liu, S. Jia, Z. C. Zhang, ACS Catal., 2016,
6, 3784–3788.
[30] T. Matsu‐ura, S. Sakaguchi, Y. Obora, Y. Ishii, J. Org. Chem., 2006,
71, 8306−8308.
[31] G. Xu, T. Lammens, Q. Liu, X. Wang, L. Dong, A. Caiazzo, N. Ashraf, J.
Guana, X. Mu, Green Chem., 2014, 16, 3971–3977.
[32] S. Hanspal, Z. D. Young, J. T. Prillaman, R. J. Davis, J. Catal., 2017,
352, 182−190.
[41] N. Onishi, S. Xu, Y. Manaka, Y. Suna, W.‐H. Wang, J. T. Muckerman,
E. Fujita, Y. Himeda, Inorg. Chem., 2015, 54, 5114−5123.
[42] J. F. Hull, Y. Himeda, W.‐H. Wang, B. Hashiguchi, R. Periana, D. J.
Szalda, J. T. Muckerman, E. Fujita, Nat. Chem., 2012, 4, 383−388.
[43] W.‐H. Wang, S. Xu, Y. Manaka, Y. Suna, H. Kambayashi, J. T. Muck‐
erman, E. Fujita, Y. Himeda, ChemSusChem, 2014, 7, 1976−1983.
[44] W.‐H. Wang, J. F. Hull, J. T. Muckerman, E. Fujita, Y. Himeda, Energy
Environ. Sci., 2012, 5, 7923−7926.
[33] A. V. Chistyakov, P. A. Zharova, S. A. Nikolaev, M. V. Tsodikov, Catal.
Today, 2017, 279, 124−132;
[34] W. Y. Hernández, K. De Vlieger, S. Clerick, P. Van Der Voort, A.
Verberckmoes, Catal. Commun., 2017, 98, 94−97.
[35] K. Sordakis, C. Tang, L. K. Vogt, H. Junge, P. J. Dyson, M. Beller, G.
Laurenczy, Chem. Rev., 2018, 118, 372−433.
[36] K. Fujita, R. Kawahara, T. Aikawa, R. Yamaguchi, Angew. Chem. Int.
Ed., 2015, 54, 9057–9060.
[45] Y. Suna, M. Z. Ertem, W.‐H. Wang, H. Kambayashi, Y. Manaka, J. T.
Muckerman, E. Fujita, Y. Himeda, Organometallics, 2014, 33,
6519−6530.
[46] W.‐H. Wang, M. Z. Ertem, S. Xu, N. Onishi, Y. Manaka, Y. Suna, H.
Kambayashi, J. T. Muckerman, E. Fujita, Y. Himeda, ACS Catal.,
2015, 5, 5496−5504.
[37] K. Fujita, Y. Tanaka, M. Kobayashi, R. Yamaguchi, J. Am. Chem. Soc.,
2014, 136, 4829−4832.
[47] W.‐H. Wang, J. T. Muckerman, E. Fujita, Y. Himeda, ACS Catal.,
2013, 3, 856−860.
[38] W. P. Wu, Y. J. Xu, R. Zhu, M. S. Cui, X. L. Li, J. Deng, Y. Fu, ChemSus‐
Chem, 2016, 9, 1209–1215.
[48] W.‐H. Wang, Y. Himeda, J. T. Muckerman, G. F. Manbeck, E. Fujita,
Chem. Rev., 2015, 115, 12936−12973.
[39] Z. Xu, P. Yan, W. Xu, X. Liu, Z. Xia, B. Chung, S. Jia, Z. C. Zhang, ACS
[49] K.‐I. Fujita, N. Tanino, R. Yamaguchi, Org. Lett., 2007, 9, 109−111.
电子和空间位阻效应促进铱配合物催化1-丁醇经Guerbet反应选择制备2-乙基己醇
许占威a, 颜佩芳a, 梁长慧a,b, 贾松岩c, 刘秀梅a, 张宗超a,*
a中国科学院大连化学物理研究所, 洁净能源国家实验室(筹), 催化国家重点实验室, 辽宁大连110623
b中国科学院大学, 北京100049
c沈阳化工大学化工学院, 辽宁沈阳110142
摘要: 2-乙基己醇是一种增塑剂醇, 可用于合成增塑剂、表面活性剂和溶剂等诸多化工领域. 目前工业上2-乙基己醇的合成
是以化石资源丙烯为原料,与氢气和一氧化碳通过氢甲酰化反应制备1-丁醛, 后者经羟醛缩合和催化加氢反应生成2-乙基
己醇. 由生物质发酵产生的1-丁醇为原料, 只需要经Guerbet反应可一步直接生成2-乙基己醇. 比较而言, Guerbet反应路线
步骤更少, 且1-丁醇原位脱氢产生的氢为氢源, 无需额外氢, 因此比化石资源丙烯路线对环境友好. 目前, 文献报道的非均
相催化1-丁醇Guerbet反应条件苛刻(如温度 > 170 oC), 副产物多(如烯烃、醚和高碳醇等), 且均相催化剂的活性低.
本文报道了一类Cp*Ir(Cp*为1,2,3,4,5-五甲基环戊二烯基)配合物用于该Guerbet反应. 当Cp*Ir配合物的配体上修饰给
电子基N,N-二甲基氨基和邻羟基时, Cp*Ir配合物的催化活性增强, 催化剂的转化数最高达到了14047. 当氢氧化钾和
Cp*Ir配合物(配体上修饰了N,N-二甲基氨基和邻羟基官能团)在1-丁醇中的浓度分别为1.7 mol%和0.04 wt%时, 在130 oC反
应48 h, 产物2-乙基己醇收率为23.9%, 选择性为89.5%. 核磁(NMR)研究结果表明, Cp*Ir配合物配体上的邻羟基与氢氧化
钾反应脱除质子, 生成了羰基结构配体配位的Cp*Ir配合物, 继续催化1-丁醇脱氢反应. 机理研究表明, 中间产物2-乙基己
醛α-碳上乙基的位阻效应和2-乙基己烯醛本身的共轭效应抑制了其继续发生羟醛反应, 从而提高了目标产物的选择性.
关键词: 2-乙基己醇; Guerbet反应; 1-丁醇; 铱; 加氢
收稿日期: 2020-12-25. 接受日期: 2021-01-22. 上网时间: 2021-05-05.
*通讯联系人. 电话/传真: (0411)84379462; 电子信箱: zczhang@yahoo.com
基金来源: 国家自然科学基金(21706255, 21932005, 21690084).
本文的电子版全文由Elsevier出版社在ScienceDirect上出版(http://www.sciencedirect.com/journal/chinese-journal-of-catalysis).