Indium(III) triflate promoted synthesis of alkyl levulinates from furyl alcohols and furyl aldehydes

Article abstract of DOI:10.1016/j.catcom.2014.10.013

A facile protocol for the alcoholysis of furfuryl alcohol into levulinate esters has been developed employing low catalyst loadings of indium(III) triflate. This method provides a rapid and efficient route for the synthesis of these useful materials. The alcoholysis reactions of 5-hydroxymethylfurfural (HMF), furfural and furfural dimethylacetal were also investigated under these reaction conditions.

Full text of DOI:10.1016/j.catcom.2014.10.013

Indium(III) Triflate Promoted Synthesis of Alkyl Levulinates from Furyl
Alcohols and Furyl Aldehydes
Jacqueline R. Kean, Andrew E. Graham
PII:
DOI:
Reference:
S1566-7367(14)00432-4
doi: 10.1016/j.catcom.2014.10.013
CATCOM 4101
To appear in:
Catalysis Communications
Received date:
Revised date:
Accepted date:
21 August 2014
10 October 2014
13 October 2014
Please cite this article as: Jacqueline R. Kean, Andrew E. Graham, Indium(III) Tri-
flate Promoted Synthesis of Alkyl Levulinates from Furyl Alcohols and Furyl Aldehydes,
Catalysis Communications (2014), doi: 10.1016/j.catcom.2014.10.013
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.

ACCEPTED MANUSCRIPT
Indium(III) Triflate Promoted Synthesis of Alkyl Levulinates from
Furyl Alcohols and Furyl Aldehydes
Jacqueline R. Kean and Andrew E. Graham*
School of Applied Sciences
University of South Wales
CF37 4AT, UK
Corresponding author: E-mail: andrew.graham@southwales.ac.uk: Tel: +44 (0)1443 482460
KEYWORDS: biomass valorization· indium(III) triflate · homogeneous catalysis · furan
alcoholysis · alkyl levulinate esters
ABSTRACT: A facile protocol for the alcoholysis of furfuryl alcohol into levulinate esters has
been developed employing low catalyst loadings of indium(III) triflate. This method provides a
rapid and efficient route for the synthesis of these useful materials. The alcoholysis reactions of
5-hydroxymethylfurfural (HMF), furfural and furfural dimethylacetal were also investigated
under these reaction conditions.
1. Introduction
The growing demand for fossil fuel resources comes at a time of diminishing reserves of these
non-renewable resources and an increasing awareness of the influence of greenhouse gases on
global climate change. These factors have led to considerable interest in alternative strategies for
energy production which have reduced environmental impact. Biomass valorization, in
particular, has attracted considerable interest as a sustainable and renewable source of both

ACCEPTED MANUSCRIPT
energy and feedstock chemicals for the chemical industry [1,2]. Initial developments in this area
relied on the use of starch and vegetable oils, however, these resources are valued food
commodities and thus subsequent interest has considered lignocellulose residues, sustainably
sourced from agriculture and forestry activities, as a promising low cost and abundant alternative
[3-5]. One of the most advanced and commercially viable lignocellulosic-fractionating
technologies currently developed is the Biofine Process, which involves the acid catalyzed
hydrolysis of polysaccharides to their monomeric constituents, which are then in turn converted
to furfural 1, levulinic acid and formic acid via 5-hydroxymethyl furfural (HMF) 2 [6]. While
routes for the subsequent conversion of levulinic acid into a wide range of fuel additives, such as
levulinate esters 3 and chemical intermediates are well established [7,8], similar routes for the
valorization of furfural are less well explored.
O
O
O
O
O
+
Biomass
OH
RO
3
O
1
2
O
ROH / H+
+H2
OH
4
Scheme 1. Conversion of carbohydrates into alkyl levulinic esters.
Recent developments have demonstrated that furfural can also be converted into
levulinate esters but must initially be converted to furfuryl alcohol 4 by hydrogenation prior to
hydrolysis. This is an attractive process, since it provides a route for the conversion of furfural,
produced as a minor by-product in biomass hydrolysis, into an additional source of levulinate
products (Scheme 1) [9]. These hydrolysis processes typically employ mineral acids which can
be expensive due to their highly corrosive nature which requires specialist materials for reactor
construction [9,10]. This has led to the development of protocols that employ heterogeneous

ACCEPTED MANUSCRIPT
materials, such as zeolites and solid acid catalysts, as promoters which has alleviated some of
these issues [11,12]. As part of an ongoing programme to develop new catalysts and novel
reaction processes [13-17], we were interested in the potential application of water-tolerant
Lewis acid catalysts as promoters of furan alcoholysis reactions. Of particular interest to us has
been the development of protocols employing indium(III) salts, and in particular indium(III)
triflate (In(OTf)3), which have emerged as highly flexible, non-toxic and chemoselective
catalysts in synthetic chemistry. The recent disclosure by Sun on the indium(III) chloride-
mediated hydrolysis of monosaccharides to levulinic acid prompted us disclose our current
studies in this area [18].
2. Experimental
2.1 Materials
Commercially available materials were used as received except for furfural which was purified
by distillation under reduced pressure prior to use.
2.2 Product Analysis and Quantification
Reaction mixtures were analyzed by GC-MS using a Varian 450GC equipped with a Varian CP-
8410 autoinjector and Varian 300MS. Chromatography was carried out using a VF-5ms capillary
column (30m, 0.25mm i.d. and 0.25m) and a gradient temperature profile with an initial
temperature of 50 °C for 3 minutes rising to 280 °C at a rate of 20 °C/minute. Products were
identified using the NIST library or by comparison with authentic standards in full scan mode.
Levulinate ester quantification was achieved either in full scan mode or using selective ion
monitoring (SIM) of the extracted m/z 99 ion chromatographs. The alkyl levulinate was
quantified using a calibration curve generated by dilution of a standard butyl levulinate solution

ACCEPTED MANUSCRIPT
using the instrument response in either full scan mode or at m/z 99. Where necessary, the
analytical samples were diluted to fall within the calibration curve concentration range, and were
analyzed in duplicate.
2.3 Typical procedure for the alcoholysis of furfuryl alcohol in 1-butanol
Indium triflate (28 mg, 0.05 mmol, 1 mol%) was added to a solution of furfuryl alcohol (490 mg,
5 mmol) in 1-butanol (20 mL) and the mixture heated to reflux and stirred for 1.5 hours. Upon
completion of the reaction, the excess alcohol was removed and the residue purified by
chromatography (hexane) to give n-butyl levulinate 3d as a light orange oil; max (film)/cm-1
(neat) = 1732, 1359, 1310, 1159, 1069, 1027,; 1H NMR (CDCl3; 400 MHz)  = 4.05 (2H, t, J = 7
Hz), 2.75 (2H, t, J = 7 Hz), 2.55 (2H, t, J = 7 Hz), 2.20 (3H, s), 1.60 (2H, pent, J = 7 Hz), 1.35
(2H, hex, J = 7 Hz), 0.95 (3H, t, J = 7 Hz); 13C NMR (CDCl3; 100 MHz)  = 206.6, 172.7, 64.5,
38.0, 30.6, 29.7, 28.1, 19.1, 13.7; MS (EI) m/z 172.
2.4 Typical procedure for the alcoholysis of HMF in 1-butanol
Indium triflate (21 mg, 0.037 mmol, 5 mol%) was added to a solution of 5-hydroxymethylfurfal
(94 mg, 0.75 mmol) in 1-butanol (20 mL) and water (27 mg, 1.50 mmol), and the mixture heated
to reflux and stirred for 4 hour. At this time the reaction was cooled to room temperature and an
additional portion of indium triflate (4 mg, 1 mol%) was added. The reaction was heated to
reflux and stirred for an additional two hours and the conversion to 3d determined by
quantitative GC-MS analysis.

ACCEPTED MANUSCRIPT
2.5 Typical procedure for the alcoholysis of furfural in 1-butanol
Indium triflate (14 mg, 0.025 mmol, 5 mol%) was added to a solution of furfural (48 mg, 0.50
mmol) in 1-butanol (10 mL) and the mixture heated to reflux and stirred for 1 hour. At this time
the reaction was cooled to room temperature and an additional portion of indium triflate (14 mg,
0.025 mmol, 5 mol%) was added. The reaction was heated to reflux and stirred for an additional
two hours and the conversion to 3d determined by quantitative GC-MS analysis.
3. Results and Discussion
3.1 Catalytic Activity of Indium(III) Triflate
Our initial studies considered the alcoholysis reactions of furfuryl alcohol 4 to the corresponding
alkyl levulinate esters in a range of alcohol solvents. Previous studies have demonstrated that
reactions employing low boiling point alcohols, such as methanol and ethanol, proceed slowly
giving low yields of the corresponding alkyl levulinate esters, unless enclosed pressurized
reactors which allow the use of high temperatures are employed [11,12]. In line with these
previous reports, only low conversions of furfuryl alcohol to 3a and 3b were observed when low
catalyst loadings were employed (Table 1, entries 1 and 2). GC-MS analysis of these reactions
did demonstrate, however, the efficient conversion of furfuryl alcohol to the corresponding
intermediate ethers. Previously, this transformation has been shown to only occur at elevated
temperatures [12], and demonstrates the high efficiency of In(OTf)3 in etherification reactions
[19]. In the case of ethanol, extending the reaction time, and increasing the quantity of catalyst
provided significantly improved conversions to 3b. Further improvements were achieved by
adding the catalyst to the reaction in two separate portions, and under these optimized reaction
conditions, moderate conversions of 3b were achieved at comparatively low reaction
temperatures (Table 1, entry 3).

ACCEPTED MANUSCRIPT
Table 1. In(OTf)3 mediated alcoholysis of furfuryl alcohol.a
O
In(OTf)3 (1 mol/%)
O
O
+
OH
OR
OR
ROH, 
O
4
5a R= Me
5b R = Et
5c R = Pr
5d R = Bu
3a R= Me
3b R = Et
3c R = Pr
3d R = Bu
Entry
Alcohol
Time
(h)
1
1
12
1
Temperature
Catalyst
(mol %)
1
Yield 3
(oC)
(%)a
1
2
3
4
5
6
MeOH
EtOH
EtOH
PrOH
PrOH
BuOH
65
78
78
97
97
<5
1
10
1
1
1
10
52
34
83
92
3
1.5
118
a Experimental conditions: indium triflate (1 mol%) was added to a solution of 4
(5 mmol) in 1-butanol (20 mL) and heated to reflux for 1.5 hours.
b Determined by quantitative GC-MS analysis.
Gratifyingly, the use of higher boiling solvents which allow for higher reaction
temperatures, such as 1-propanol, led to a rapid reaction with high yields of 3c being achieved
after only 3 hours even when low catalyst loadings were employed (entry 5). Reactions
employing 1-butanol were even more rapid, and gave near quantitative yields of butyl levulinate
3d in short reaction times, typically less than 1.5 hours (entry 6). In both of these cases,
formation of the corresponding intermediate furyl ether product was again rapid, suggesting that
it is the subsequent temperature dependant ring-opening reaction which is rate limiting. In these
reactions it is noteworthy that only trace quantities of the symmetrical alkyl ether by-products,
produced from the alkyl alcohol, were detected by GC-MS analysis. The production of levulinate
esters from furfuryl alcohol with minimal generation of the corresponding alkyl ether by-product
is highly desirable, as it improves the economic potential of the process. As expected, reactions
containing no catalyst gave no conversion of the starting material to ether or alcoholysis
products, demonstrating the high catalytic activity of In(OTf)3 in these reactions. We next turned

ACCEPTED MANUSCRIPT
our attention to catalyst recovery and recycling using the alcoholysis reaction in 1-butanol. In line
with previous reports [20], the catalyst can be recovered from these reactions by aqueous
extraction of the reaction mixture and subsequent drying which produced a catalyst which
exhibited comparable activity to the fresh material (see Supplementary Information). Finally, to
demonstrate the efficiency of In(OTf)3 in the alcoholysis reaction of furfuryl alcohol, we
undertook a series of experiments employing a small range of heterogeneous catalysts under our
standard reaction conditions (Table 2).
Table 2. Heterogeneous catalyzed alcoholysis reactions of furfuryl alcohol.a
O
catalyst (25 mg)
O
O
+
OBu
OH
OBu
BuOH, 1.5 h
O
3d
5d
Entry
Catalystb
BET Surface Pore Width
Acidity
(mol g-1)f
1450
Yield 3d
Area (m2g-1)c
(nm)e
0.82
1.11
2.44
3.18
24d
(%)g
13
1
2
3
4
ZSM-5-(30)
Zeolite Y-(5)
Al-13-(2.34)
Al-13-(3.18)
AmberlystTM-15
405
763
614
980
45d
300
440
<5
<5
15
95
530
5
4600d
a
Experimental conditions: the catalyst (25 mg) was added to a solution of 4 (1
mmol) in 1-butanol (4 mL) and heated to reflux for 1.5 hours.
b All aluminosilicate catalysts were stored at 120 oC for 12 hours prior to use.
c Obtained by the Brunauer–Emmett–Teller (BET) method.
d Literature value: see reference [21].
e Determined by the non-linear density function theory (NLDFT) method.
f Determined by temperature programmed desorption (TPD) analysis.
g Determined by quantitative GC-MS analysis.
Reactions employing both microporous (entries 1 and 2) and mesoporous aluminosilicate [14-17]
materials (entries 3 and 4) gave the expected low yields of 3d in line with previous literature
reports, where longer reaction times are typically required for generation of significant quantities

ACCEPTED MANUSCRIPT
of the levulinate ester product [11,21,22]. Reactions employing the highly acidic cation exchange
resin AmberlystTM-15 (entry 5) proceeded rapidly as expected to give an excellent yield of 3d
which were comparable to our In(OTf)3 catalyst, although in this case, significant quantities of
the symmetrical alkyl ether by-product were observed [22].
3.2 Catalytic Activity of Metal Triflates
With the potential of this approach established, we carried out a study to identify whether other
commercially available metal triflates or In(III) salts are effective promoters of furfuryl alcohol
alcoholysis (Table 3).
Table 3. Metal triflate-mediated furfuryl alcohol alcoholysis reactions.a
O
catalyst (1 mol/%)
O
O
+
OBu
OH
OBu
BuOH, 1.5 h
O
4
3d
5d
Entry
Catalyst
Yield 3d
(%)b
92
1
2
3
4
5
In(OTf)3
InBr3
Cu(OTf)2
Yb(OTf)3
Gd(OTf)3
<5
66
27
12
a Experimental conditions: the catalyst (1 mol%) was added to
a solution of 4 (5 mmol) in 1-butanol (20 mL) and heated to
reflux for 1.5 hours.
b Determined by quantitative GC-MS analysis.
Interestingly, the alcoholysis of furfuryl alcohol in 1-butanol employing indium(III) tribromide
(InBr3) as catalyst gave no conversion to butyl levulinate, with the starting alcohol being
recovered in near quantitative yield (entry 2). Subtle counterion effects have previously been

ACCEPTED MANUSCRIPT
observed in indium-mediated processes, which are thought to be due to coordination effects
which manifest themselves either in a variation in the activity or selectivity of the catalyst, and
suggests that the physical properties of the counterion are of critical importance [23]. All of the
triflate catalysts studied generated 3d under the reaction conditions, however, only copper(II)
triflate (Cu(OTf)2) showed significant activity, generating moderate yields of butyl levulinate
(entry 3). As expected, gadolinium(III) triflate (Gd(OTf)3) was less active than ytterbium(III)
triflate (Yb(OTf)3) producing low yields of the ester product (entry 5). GC-MS analysis of these
crude reaction mixtures did, however, indicated that all of the catalysts studied were effective in
generating the intermediate alkyl ether suggesting that these catalyst are less efficient in
promoting the subsequent ring-opening reaction.
3.3 Alcoholysis Reactions of 5-Hydroxymethylfurfural
We next turned our attention to the alcoholysis reactions of HMF, an important platform
chemicals for the synthesis of a range of polymer building blocks and biofuels, and another
highly attractive substrate for levulinate ester production given its potential for sustainable
generation from biomass sources (Scheme 2) [3,8]. The alcoholysis reaction proceeds through
initial formation of the corresponding HMF ether 6, which undergoes acid catalyzed ring-opening
to generate the levulinate product and eqimolar quantities of butyl formate [8,22,24].
O
H+
O
O
O
H+
O
O
6
+
OH
OR
RO
OR
ROH
H
OR
H2O
O
2
H+ / H2O
ROH / H+
OR
O
RO
7
Scheme 2. Conversion of HMF into alkyl levulinic esters

ACCEPTED MANUSCRIPT
Under our standard conditions, employing low catalyst loadings in 1-butanol at reflux
temperatures, the alcoholysis reaction proceeded more slowly than the corresponding reaction
with furfuryl alcohol, and extended reaction times were required to achieve moderate
conversions. An added drawback of employing these extended reaction times was the generation
of both polymeric products, and increased quantities of the dibutyl ether by-product. We
therefore undertook a study with the goal of determining optimal catalyst loadings in order to
reduce reaction times and so limit the generation of degradation products.
Fig. 1. Influence of catalyst loading on butyl levulinate formation from In(OTf)3 catalyzed HMF
alcoholysis reactions in 1-butanol
Product formation increased with increasing quantities of catalyst, however, the
generation of 3d slowed over the course of the reaction (Figure 1). Further extending reaction
times led to no tangible improvement in overall conversion, and indeed led to increased
generation of degradation products. Furthermore, in reactions employing higher catalyst loadings,
significant quantities (~20%), of the acetal product, 5-(dibutoxymethyl)-2-furanbutanol 7 (R =

ACCEPTED MANUSCRIPT
OBu) were identified by GC-MS analysis. Acetal products derived from HMF have been
identified as possible intermediates in the formation of levulinate esters from both biomass
sources and HMF [8,22,24-26], although the precise role of these intermediates is currently
unclear. The formation of this product could be suppressed by adding two equivalents of water to
the reaction mixture which led to significantly improved overall conversions to 3d by minimizing
the generation of the acetal product. The addition of additional quantities of water has also
previously been demonstrated to be highly beneficial in the alcoholysis reaction of furfuryl
alcohol in 1-butanol, where it has been proposed to accelerate the ring-opening reaction of the
intermediate ether [12]. In addition to the formation of 3d and 5-(dibutoxymethyl)-2-
furanbutanol 7, quantities of both of the expected hydrolysis products butyl formate and formal
dibutyl acetal were identified by GC-MS analysis of the crude reaction mixture. In line with
previous reports, no levulinic acid formation was observed in these reactions.
3.4 Alcoholysis Reactions of Furfural
Finally, we investigated the alcoholysis reactions of furfural, a substrate which has to date
attracted considerably less attention than furfuryl alcohol or HMF for direct levulinate ester
formation, presumably due to its much greater resistance to alcoholysis. Given that acetal
products have been observed in a number of protocols for levulinate ester formation, we were
intrigued as to the precise role of acetal products in furan alcoholysis reactions, particularly if
their efficient in situ generation could circumvent either the reduced reactivity of substrates such
as furfural or their tendency to undergo acid catalyzed polymerization, and hence lead to the
development of more efficient alcoholysis protocols. We have previously demonstrated that
In(OTf)3, is a highly efficient catalyst for the formation of both cyclic and acyclic acetals [27-29],

ACCEPTED MANUSCRIPT
and the development of such a tandem protocol would be highly attractive, given the recent
interest in this area [30-34].
Our studies initially considered the alcoholysis of furfural in 1-butanol employing 1
mol/% of In(OTf)3 at reflux temperatures. Encouragingly, low conversions to butyl levulinate
were achieved under these conditions if extended reaction times were employed, however,
extensive humin and polymer formation were also observed over the time course of the reaction
(Figure 2).
Fig. 2. Influence of catalyst loading on butyl levulinate formation from In(OTf)3 catalyzed
furfural alcoholysis reactions in 1-butanol
Increasing the quantity of catalyst to 5 mol% or 10 mol% led to very rapid consumption of
the furfural starting material, but did not lead to increased quantities of 3d, with similar
conversions to those obtained with lower catalyst loadings being observed. This may suggest that
once formed, 3d is consumed by competing side-reactions in addition to polymer and humin
formation. It is noteworthy that indium(III) salts have been demonstrated to be highly efficient

ACCEPTED MANUSCRIPT
promoters of a range of carbon-carbon bond forming reactions through the formation of enol
intermediates [35]. A reaction sequence in which 3d, once generated, is consumed by enol
formation followed by aldol reaction with furfural to give 8, followed by subsequent humin
formation can be envisaged [8] (Scheme 3).
O
O
In(OTf)
3
O
O
O
humins
OBu
3d, ROH, 
OH
8
Scheme 3. Aldol reaction of furfural and butyl levulinate
This reaction pathway would not only explain the moderate conversions to 3d but would
also explain the consumption of the aldehyde starting material. Significantly, small quantities
(~5%) of both the aldol product 8 and the corresponding unsaturated ester produced by
elimination were identified by GC-MS analysis of the crude reaction mixtures. No significant
aldol products derived from the self-condensation of 3d were detected, however, and indeed,
GC-MS analysis of test reactions involving 3d in the presence of In(OTf)3 in 1-butanol gave no
identifiable aldol products. Conversions to 3d are also limited by the inherent instability of
furfural in the presence of Lewis acid catalysts, and indeed, heating this material in non-alcoholic
solvents, such as toluene, in the presence of the In(OTf)3 led to significant formation of insoluble
polymeric material.
In addition to aldol and polymeric products, reactions employing high catalyst loadings led
to the production of significant quantities (~ 15%) of a product identified by GC-MS analysis as
2-furancarboxaldehyde dibutyl acetal. This product was present in the early stages of the reaction
and persisted over the time course of the reaction. To determine whether formation of 3d
proceeded through this acetal intermediate, we investigated the alcoholysis reactions employing

ACCEPTED MANUSCRIPT
2-furancarboxaldehyde dimethyl acetal as the starting material. As expected, this substrate
underwent very rapid transacetalization under the reaction conditions to produce the
corresponding dibutyl acetal product [28,29]. This material, however, proved to be resistant to
alcoholysis under the lower reaction temperatures employed in this study, with only trace
quantities of 3d being produced in these reactions.
4. Conclusions
In conclusion, we have demonstrated that low loadings of In(OTf)3 efficiently catalyze the
alcoholysis reactions of furfuryl alcohol to produce alkyl levulinate esters in short reaction times.
The protocol employs a commercially available, water tolerant catalyst, and does not require time
consuming and complicated work-up procedures frequently associated with the use of mineral
acids. Furthermore, this catalyst also catalyzes the efficient alcoholysis reactions of HMF,
although higher catalyst loadings are required to achieve high conversions for this
transformation. In the case of alcoholysis reactions of furfural, extensive degradation of the
starting material and aldol reactions of the alkyl levulinate ester product and acetalization of the
furfural starting material have been identified as potential competing reactions which further
limit conversions. Studies are currently under way to demonstrate the potential of this catalyst in
the transformations of raw biomass sources, and to develop indium containing materials which
can function as heterogeneous catalysts for the alcoholysis reactions.
Supporting Information.
General methods, catalyst recycling data, product characterization and GC-MS product profiles.

ACCEPTED MANUSCRIPT
The authors are grateful to Dr Robert Jenkins (School of Chemistry, Cardiff University) for high
resolution NMR spectra, and the EPSRC National Mass Facility Service, Swansea University for
high resolution mass spectra.
References
[1] J. N. Chheda, G. W. Huber, J. A. Dumesic, Angew Chem. Int. Ed. 46 (2007) 7164–7183.
[2] B. Katryniok, S. Paul, V. Bellière-Baca, P. Rey, F. Dumeignil, Green Chem. 12 (2010)
2079–2098.
[3] G. W. Huber, S. Iborra, A. Corma, Chem. Rev. 106 (2006) 4044–4098.
[4] T. R. Carlson, T. P. Vispute, G.W. Huber, ChemSusChem 1 (2008) 397–400.
[5] J.-P. Lange, in Catalysis for Renewables: From Feedstock to Energy Production, ed. G.
Centi and R. A. van Santen, Wiley-VCH, Weinheim, 2007, pp. 21–51.
[6] D. J. Hayes, S. Fitzpatrick, M. H. B. Hayes, J. R. H. Ross, in Biorefineries-Indusrtial
Processes and Products: Status Quo and Future Directions, ed. B. Kamm, P. R. Gruber and
M. Kamm, Wiley-VCH, Weinheim, 2008, 139–164.
[7] S. Dutta, S. De, B. Saha, M. I. Alam, Catal. Sci. Technol. 2 (2012) 2025–2036.
[8] M. J. Climent, A. Corma, S. Iborra, Green Chem. 16 (2014) 516–547.
[9] J.-P. Lange, E. van der Heide, J. V. Buijtenen, R. Price, ChemSusChem 5 (2012) 150–166.
[10] D. W. Rackemann, W. O. S. Doherty, Biofuels. Bioprod. Bioref. 5 (2011) 198–214.

ACCEPTED MANUSCRIPT
[11] J.-P. Lange, W. D. Van De Graaf, R. J. Haan, ChemSusChem 2 (2009) 437–441.
[12] Z. Zhang, K. Dong, Z. Zhao, ChemSusChem 4 (2011) 112–118.
[13] B. M. Smith, E. J. Skellam, S. J. Oxley, A. E. Graham, Org. Biomol. Chem. 5 (2007)
1979–1982.
[14] T. M. Kubczyk, S. M. Williams, J. R. Kean, T. E. Davies, S. H. Taylor, A. E Graham,
Green Chem. 13 (2011) 2320–2325.
[15] T. E Davies, J. R. Kean, D. C. Apperley, S. H. Taylor, A. E. Graham, ACS Sus. Chem. &
Eng. 2 (2014) 860–866.
[16] M. W. C. Robinson, A. M. Davies, I. Mabbett, T. E. Davies, D. C. Apperley, S. H.
Taylor, A. E. Graham, J. Mol. Catal. A: Chem. 329 (2010) 57–63.
[17] M. W. C. Robinson, A. M. Davies, I. Mabbett, D. C. Apperley, S. H Taylor, A. E.
Graham, J. Mol. Catal. A: Chem. 314 (2009) 10–14.
[18] Y. Shen, J. Sun, Y. Yi, B. Wang, R. Sun, J. Mol. Catal. A: Chem. DOI
10.1016/j.molcata.2014.07.007.
[19] For the use of indium(III) trichloride in etherification reactions see: G. Bhaskar, M.
Solomon, G. Babu, D. Muralidharan, P. T. Perumal, Ind. J. Chem. 49B (2010) 795–801.
[20] R. Ghosh, S. Maiti, A. Chackraborty, R. Halder, J. Mol. Catal. A: Chem. 215 (2004) 49–
53.
[21] P. Neves, S. Lima, M. Pillinger, S. M. Rocha, J. Rocha, A. A. Valente, Catalysis Today
218–219 (2013) 76–84.

ACCEPTED MANUSCRIPT
[22] P. Lanzafame, D. M. Temi, S. Perathoner, G. Centi, A. Macario, A. Aloise, G. Giodarno
Catalysis Today 175 (2011) 435–441.
[23] C. G. Frost, J. P. Hartley, D. Griffin, Tetrahedron Lett. 43 (2002) 4789–4791.
[24] X. Hu, C.-Z. Li, Green Chem. 113 (2011) 1676–1679.
[25] J. Chen, G. Zhao, L. Chen, RSC Adv. 4 (2014) 4194–4202.
[26] M. Balakrishnan, E. R. Sacia, A. T. Bell, Green Chem. 14 (2012) 1626–1634.
[27] B. M. Smith, A. E. Graham, Tetrahedron Lett. 48 (2007) 4891–4894.
[28] B. M. Smith, T. M. Kubczyk, A. E. Graham, Tetrahedron 68 (2012) 7775–7781.
[29] B. M. Smith, A. E. Graham, A. E. Tetrahedron Lett. 52 (2011) 6281–6283.
[30] L. F. Tietze, Chem. Rev. 96 (1996) 115–136.
[31] D. J. Phillips, K. S. Pillinger, L. Wei, A. E. Taylor, A. E.; Graham, Tetrahedron 63 (2007)
10528–10533.
[32] M. C. Bagley, V. Lin, D. J. Phillips, A. E. Graham, Tetrahedron Lett. 50 (2009) 6823–
6825.
[33] G. H. Harris, A. E. Graham, Tetrahedron Lett. 51 (2010) 6890–6892.
[34] D. J. Phillips, A. E. Graham, Synlett 2008 649–652.
[35] A. Dandia, A. K. Jain, S. Sharma, Tetrahedron Lett. 53 (2012) 5270–5274.

ACCEPTED MANUSCRIPT
TOC Entry
Indium(III) Triflate Promoted Synthesis of Alkyl Levulinates from Furyl Alcohols and
Furyl Aldehydes
Jacqueline R. Kean and Andrew E. Graham*
School of Applied Sciences
University of South Wales,
CF37 4AT UK,
O
In(OTf)3 (1 mol/%)
O
OH
OR
R = Me, Et, Pr, Bu
ROH, 
O
*Corresponding author. Email: andrew.graham@southwales.ac.uk
Indium(III) triflate catalyses the alcoholysis of a range of furyl substrates in alcoholic solvents to
produce the corresponding levulinate esters.

ACCEPTED MANUSCRIPT
Indium(III) Triflate Promoted Synthesis of Alkyl Levulinates from Furyl
Alcohols and Furyl Aldehydes
Jacqueline R. Kean[a] and Andrew E. Graham* [a]
School of Applied Sciences
University of South Wales
CF37 4AT, UK
Tel: +44 1443 482460
*Corresponding author. E-mail: andrew.graham@southwales.ac.uk
Highlights
 Low loadings of In(OTf)3 catalyse alcoholysis reactions of furfuryl alcohol.
 HMF alcoholysis reactions proceed efficiently under higher In(OTf)3 loadings.
 Moderate yields of butyl levulinate are also achieved from furfural.
 The catalyst can be recycled without a significant decrease in catalytic activity.