Catalytic etherification of hydroxyl compounds to methyl ethers with 1,2-dimethoxyethane

Article abstract of DOI:10.1039/c4ra15919e

1,2-Dimethoxyethane is explored for the first time as etherification agent for the acid-catalyzed synthesis of methyl ethers from biomass-derived hydroxyl compounds. H₃PW₁₂O₄₀ catalyst can provide the formation of isosorbi

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Communication
Catalytic etherification of hydroxyl compounds to methyl ethers with
1,2-dimethoxyethane
Penghua Che,a,b Fang Lu,*a Xiaoqin Sia,b and Jie Xu*a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
In this work, DMET is explored for the first time as
50 etherification agent for the acid-catalyzed synthesis of methyl
ethers from biomass-derived alcohols. The aliphatic alcohols (n-
butanol and n-hexanol) and isohexides (isosorbide, isomannide
and isoidide) with two hydroxyl groups were chosen as model
compounds. The synthesis in good yields of methyl ethers can be
1,2-Dimethoxyethane is explored for the first time as
etherification agent for the acid-catalyzed synthesis of
methylethers from biomass-derived hydroxyl compounds.
H3PW12O40 catalyst can provide the formation of isosorbide
10 methylethers with 80% GC yield from isosorbide. The acid
catalyst type and acid amount are of critical importance in
improving etherification reactivities of hydroxyl groups with
1,2-dimethoxyethane.
o
55 performed by reaction of the alcohols with DMET at 150 C in
the presence of heteropolyacid as catalyst.
With declining reserves of readily accessible fossil energy,
15 efficient conversion of biomass into fuels and chemicals has
come into the research spotlight worldwide.1 The biomass
polymers, such as cellulose and hemicellulose, usually contain
numerous hydroxyl groups. Therefore, various strategies have
been developed to functionalize hydroxyl groups for efficient
20 utilization of biomass.2
Scheme 1 Etherification of isosorbide with DMET catalyzed by acid.
The reaction of hydroxyl groups in isosorbide with DMET
o
60 took place at 150 C in the presence of acid catalyst. Typically,
three predominant methyl ether products of isosorbide were
observed including dimethyl isosorbide, 5-O-monomethyl
isosorbide and 2-O-monomethyl isosorbide due to the different
configurations of hydroxyl groups (Scheme 1). Pure dimethyl
65 isosorbide, 2-O-monomethyl isosorbide and 5-O-monomethyl
isosorbide were sequentially achieved by separating reaction
mixture through silica-gel column chromatography. They were
identified by NMR spectroscopy, data shown in experimental
section.
Especially, catalytic methylation of hydroxyl groups in
biomass-derived platform chemicals, such as glucose,3 glycerol,4
isosorbide5 and 5-hydroxymethylfurfural,6 has been recognized as
a common and significant approach. These methyl ether products
25 of considerable interest, by themselves or as key chemical
intermediates, are extensively applied as green solvents, biofuels
or oxygenated additives, surfactants, and biopolymers.7 Several
methylating agents with corresponding catalysts have been
explored for etherification of hydroxyl groups. Highly toxic
30 methylating agents, such as dimethyl sulfate and methyl halides,
have been commonly used for methylation reaction in the
presence of strong base as catalyst over the past decades.8
Dimethyl carbonate, due to its low toxicity, has been widely
employed nowadays as a substitute methylating agent catalyzed
35 by base.9 Nevertheless, considering its molecular structure and
the reaction pathway, stoichiometric amount of CO2 is inevitably
formed. Recently, methanol as an alternative agent has been
reported to convert hydroxyl compounds to monoethers using
acid as catalyst.10 However, the consecutive etherification of
40 hydroxyl groups in polyols with methanol can be prevented by
water formed due to equilibrium restrictions.11 Therefore, it is
desirable to develop a new environmental benign etherification
agent which could be efficient and facile for the synthesis of
methyl ethers from mono- and dihydroxyl compounds.
45 Interestingly, 1,2-dimethoxyethane (DMET), as an important
chemical, holds the potential to serve as an efficient etherification
agent for the synthesis of methyl ethers because of its relatively
high boiling point (85 oC), low toxicity and easy availability.12
70
The introduction of different acid catlysts lead to obvious
changes in the catalytic results, as shown in Fig. 1. Surprisingly,
H2SO4 was inert for the etherification reaction with a low
conversion of isosorbide (below 1%) under our reaction
conditions. However, when ion-exchange resins bearing SO3H
75 groups were employed as catalysts, the isosorbide conversions
were increased to 6%, 6% and 34%, for Amberlyst-70,
Amberlyst-15 and Nafion-H, respectively. Interestingly,
heteropolyacids including 12-tungstosilicic acid (H4SiW12O40)
and 12-tungstophosphoric acid (H3PW12O40) exhibited superior
80 activities with the isosorbide conversions of 80% and 87%,
respectively. Furthermore, the mono- and dimethyl ethers of
isosorbide were achieved in excellent total GC yields up to 76%
by using H3PW12O40 as catalyst. Noticeably, H3PW12O40 provides
the highest yield of dimethyl isosorbide among the acid catalysts
85 with the same acid amount. Acid strength is correlated with the
type of acid catalyst. It has been reported that acid strength of
these catalysts is in the order H3PW12O40  H4SiW12O40

Nafion-H  Amberlyst-15  Amberlyst-70  H2SO4.13 The acid
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strength order of these tested catalysts is consistent with the
was consumed rapidly in the initial 30 min, and then slowly
order of their activities for the etherification of isosorbide. 35 reduced with further prolonged reaction time. The yields of both
Therefore, the acid strength of the catalysts plays a vital role in
the etherification of isosorbide with DMET.
5- and 2-O-monomethyl isosorbide ethers increased significantly
and reached 29% and 19% in the first 60 min of reaction,
respectively. With prolonging reaction time, the yield of 5-O-
monomethyl isosorbide decreased apparently while the yield of 2-
40 O-monomethyl isosorbide slightly decreased. Meanwhile, the
yield of dimethyl isosorbide was gradually increased with
increasing reaction time. A slight decrease in the total yields of
isosorbide methyl ethers was noted as reaction time prolonged to
600 min. The different changing trends for isosorbide methyl
45 ethers indicate that the etherification of two hydroxyl groups in
isosorbide takes place sequentially, namely via the isosorbide
monomethyl ethers towards the formation of dimethyl isosorbide.
Additionally, the recyclability of the catalyst, H3PW12O40, was
attempted in the same reaction. After reaction, hexane was added
50 into the reaction mixture to recover the catalyst. As shown in Fig.
S1 (ESI†), although the isosorbide conversion decreased over
three cycles, yields for monomethyl ethers of isosorbide remained.
The loss in reactivity of the recovered catalyst might be caused
by leaching of H3PW12O40 in DMET.
5
Fig. 1 Catalytic performances of different acid catalysts for the
etherification reaction of isosorbide with DMET. Reaction conditions:
Isosorbide (2 mmol), acid catalyst (0.077 mmol H+), DMET (43 mmol),
150 oC, 60 min.
55
10
Fig. 3 Time course of the etherification reaction of isosorbide with
DMET catalyzed by H3PW12O40. Reaction conditions: Isosorbide (2
mmol), H3PW12O40 (0.019 mmol), DMET (43 mmol), 150 oC.
Fig. 2 Effect of acid amount on the etherification reaction of isosorbide
with DMET. Reaction conditions: Isosorbide (2 mmol), DMET (43
mmol), H3PW12O40, 150 oC, 60 min.
The acid amount is expected to influence etherification of
15 isosorbide with DMET. Detailed study was performed to evaluate
the effect of acid amount of H3PW12O40 on its catalytic behaviors
(Fig. 2). Both the conversion of isosorbide and the total yields of
isosorbide methyl ethers increased with increasing the acid
amount of H3PW12O40 from 0.005 to 0.098 mmol. Furthermore,
20 the formation of dimethyl isosrobide increased with an increase
in acid amount, while the total formation of monomethyl ethers
first increased and then decreased. The total yields of isosorbide
methyl ethers were up to 80% including 48% yield of dimethyl
isosorbide at the acid amount of 0.098 mmol. Further increasing
25 the acid amount to 0.147 mmol, no more increase was observed
in both isosorbide conversion and yields of etherified products.
Therefore, the increase in the acid amount of H3PW12O40 could
enhance the etherification activities of hydroxyl groups in
isosorbide and favor the further etherification of the second
30 hydroxyl group towards dimethyl isosorbide.
60 Fig. 4 Catalytic results for the etherification reaction of isosorbide with
different etherification agents (MTBE: methyl tert-butyl ether, NBME: n-
butyl methyl ether, DMET: 1,2-dimethoxyethane). Reaction conditions:
Isosorbide (2 mmol), H3PW12O40 (0.026 mmol), etherification agent (4.5
mL), 150 oC, 60min.
To gain further insights into the reaction of isosorbide with
DMET, experiments were conducted with H3PW12O40 as catalyst
for different reaction time (Fig. 3). Isosorbide as starting material
65
To verify the efficiency of DMET, several reagents with
methoxy substituent were investigated during the etherification of
isosorbide (Fig. 4). When methanol was used, only 1% isosorbide
2
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was converted towards traces of isosorbide monoethers,
indicating that methanol was inactive under our reaction
condition. Methyl tert-butyl ether (MTBE) provided a 17%
ether, which could be mainly formed by self-condensation side-
reactions of DMET. Hence, it indicates that methyl group in the
etherified products may be directly provided by DMET leaving 2-
conversion of isosorbide with 10% yields of isosorbide methyl 55 methoxyethanol as the accompanying byproduct of the
5
ethers. However, the etherified products with tert-butyl
substitutent were meanwhile formed with 5% yields (Table S1,
entry 2, ESI†). Similarly, n-butyl methyl ether (NBME) as
etherification agent afforded a 43% conversion of isosorbide with
etherification reaction (Scheme S1, ESI†).
Furthermore, only three isosorbide methyl ethers were formed
by the etherification of isosorbide with DMET based on their
NMR spectral data shown in experimental section. It suggests
27% yields of isosorbide methyl ethers as well as 11% yields of 60 that all isosorbide-derived methyl ethers can preserve their
10 other isosorbide-derived ethers with butyl substitutent (Fig. 4 and
Table S1, entry 3, ESI†). Hence, the complexity of product
mixture hinders MTBE and NBME as etherification agents.
Notably, DMET exhibits the most promising results with a 87%
conversion and 76% yields of isosorbide methyl ethers among
15 etherification agents examined. Isosorbide-derived ethers with
methoxyethyl group were formed in low yields of 3% (Table S1,
entry 4, ESI†). To further verify the utility of DMET as
etherification agent, the reaction mixture was isolated by using
silica-gel column chromatograph to sequentally obtain dimethyl
20 isosorbide (20% isolated yield), 2-O-monomethyl isosorbide
(18% isolated yield), and 5-O-monomethyl isosorbide (28%
isolated yield). Additionally, it has been reported DMET may be
obtained renewably by oxidative coupling of dimethyl ether,
which can be directly synthesized from biomass syngas.14 This
25 enables the future synthesis of isosorbide methyl ethers
exclusively from renewable feedstocks. Therefore, DMET can be
employed as efficient etherification agent to achieve the selective
formation of isosorbide methyl ethers.
configurations in our synthetic method, which could be ascribed
to the rigid structure of isosorbide. It also indicates that hydroxyl
groups in isosorbide can function as nucleophilic group during
the etherification of isosorbide with DMET.
65 Conclusions
1,2-Dimethoxyethane was explored for the first time as
etherification agent for the acid-catalyzed synthesis of methyl
ethers from biomass-derived hydroxyl compounds. The
etherification activities of hydroxyl groups in isosorbide with
70 DMET strongly depend on the type of acid catalyst and the acid
amount. The successful exploration of DMET as etherification
agent opens up a new etherification approach to functionalize
hydroxyl groups in alcohols. It also provides an efficient route
towards the synthesis of methyl ethers from the readily accessible
75 ether.
Experimental section
To broaden the potential scope of this approach with DMET,
30 several biomass-derived diols and aliphatic alcohols were chosen
as alternative reactants catalyzed by H3PW12O40 (Table 1). Both
isomannide and isoidide, with similar structures to isosorbide,
exhibit good results (Table 1, entries 1 and 2).Furthermore, the
etherification approach is also feasible for the reaction of
35 aliphatic alcohols with DMET (Table 1, entries 3 and 4). Thus,
the hydroxyl groups in alcohols exhibited here present satisfying
reactivities with DMET and achieved the corresponding methyl
ethers in high yields.
General information: All chemicals employed here were
commercially supplied with analytical grade purity unless
otherwise specified. NMR spectra (1H and 13C) were recorded on
80 a Bruker AVANCE III 400 (MHz) spectrometer (1H at 400 MHz,
13C at 101 MHz) in CDCl3 with tetramethylsilane (TMS) as
internal standard. Gas chromatography (GC) analysis was
conducted using an Agilient 7890 GC equipped with a flame
ionization detector (FID) and a HP-INNOWAX capillary column
85 (30 m  0.32 mm  0.25 μm). Gas chromatography-mass
spectrometry (GC-MS) analysis was carried out using an Agilent
7890A GC/5975C MS with a HP-5MS capillary column (30.0 m
× 0.25 mm × 0.25 μm) and electrospray ionization (ESI) mode.
Column chromatography was conducted on silica-gel (200-300
90 mesh).
Table 1 Etherification reactions of alcohols with 1,2-dimethoxyethanea
Conversion
(%)
GC yield of
methyl ether (%)
Entry Substrate
Structure
Isomannide
1
89
72
75 (38)b
61 (13)b
General procedure for the reaction of isosorbide with DMET:
The catalytic etherification of isosorbide with DMET was
performed in a 20 mL stainless steel autoclave reactor equiped
with a manometer, automatic temperature controller and a
95 magnetic stirring bar. In a typical experiment, isosorbide (2
mmol)，DMET (43 mmol) and the given amount of acid catalyst
were charged into the reactor. Then, the sealed reactor was heated
2
Isoidide
3
4
n-Butanol
n-Hexanol
100
98
66
70
40 a Reaction conditions: Alcohol (2 mmol), H3PW12O40 (0.026 mmol),
DMET (43 mmol), 150 oC, 60 min. b GC yields of corresponding
dimethylated ethers of isomannide and isoidide.
o
to 150 C with stirring (900 rpm) for the desired reaction time
To gain further insights into the reaction pathway for the
etherification of hydroxyl groups with DMET, byproducts were
45 further analyzed by GC-MS during the isosorbide conversion. 2-
Methoxyethanol was observed as a major byproduct (Fig. S2,
ESI†). It indicates 2-methoxyethanol can be formed as the
accompanying byproduct in the etherification of hydroxyl groups
with DMET. Additionally, other byproducts were also detected
50 (Fig. S3S8, ESI†), including dimethyl ether, oligomers of
DMET (di- and triglyme) and diethylene glycol monomethyl
under autogenous pressure. After reaction, the autoclave was
100 cooled down. The reaction mixtures were neutralized with
triethylamine prior to GC analysis. Reaction products were
ascertained by GC-MS and by comparison with the GC retention
times of the corresponding authentic samples.
The catalytic results exhibited here were either in terms of
105 conversion or in terms of yields towards desired methyl ethers,
which were determined by GC internal standard method using
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50 b University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
† Electronic Supplementary Information (ESI) available: Experimental
details; additional table, scheme and figures; copies of NMR, GC and MS
spectra. See DOI: 10.1039/b000000x/
naphthalene as internal standard. All results were calculated
based on the initial amount of isosorbide. The conversion of
isosorbide and the yields of monoether (2-O and 5-O-
monomethyl isosorbide) and diether (dimethyl isosorbide)
products, expressed as mol%, were determined as below.
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5
55
60
65
moles of unreacted isosorbide
moles of initial isosorbide



Conversion  1
100%
100%



2
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moles of formed monoether
moles of initial isosorbide




Monoether yield 


moles of formed diether
moles of initial isosorbide



Diether yield 
100%



3
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Separation of the isosorbide methyl ethers: At the end of the
10 reaction, with the addition of hexane, the reaction mixtures were
separated into two layers after centrifugation. The transparent
organic layer was collected, concentrated with a rotary evaporator,
and distilled under vacuum. Then, the enriched distillation
fractions were subjected to silica-gel column chromatography
15 eluted with a gradient mixture of petroleum ether/acetone (15/1 to
5/1, v/v). Thus, isosorbide methyl ethers were isolated as pure
compounds.
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1
2-O-Monomethyl isosorbide: H NMR (400 MHz, CDCl3): 
80
4.60 (t, J = 5.0 Hz, 1H), 4.47 (d, J = 4.5 Hz, 1H), 4.33–4.24 (m,
20 1H), 4.05 (d, J =9.9 Hz, 1H), 3.92 (d, J =3.8 Hz, 1H), 3.90–3.81
(m, 2H), 3.58 (dd, J = 9.5 Hz, J = 5.6 Hz, 1H), 3.39 (s, 3H), 2.68
(d, J =6.7 Hz, 1H) ppm. 13C NMR (101 MHz, CDCl3):  85.94,
85.77, 82.04, 73.95, 73.32, 72.54, 57.53 ppm. ESI-MS (m/z): 160
8
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1
25
5-O-Monomethyl isosorbide: H NMR (400 MHz, CDCl3): 
4.73 (t, J = 4.1 Hz, 1H), 4.46 (d, J = 4.2 Hz, 1H), 4.32 (d, J = 2.8
Hz, 1H), 4.03–3.90 (m, 4H), 3.58 (t, J = 10.8 Hz, 1H), 3.48 (s,
3H), 2.18 (s, 1H) ppm. 13C NMR (101 MHz, CDCl3):  88.69,
82.11, 80.09, 77.07, 76.22, 70.26, 58.60 ppm. ESI-MS (m/z): 160
90
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30 (M+).
1
Dimethyl isosorbide: H NMR (400 MHz, CDCl3):  4.66 (t, J
= 4.3 Hz, 1H), 4.52 (d, J = 4.3 Hz, 1H), 4.043.90 (m, 4H),
3.893.85 (m, 1H), 3.653.54 (m, 1H), 3.47 (s, 3H), 3.38 (s, 3H)
ppm. 13C NMR (101 MHz, CDCl3):  86.23, 86.21, 82.11, 80.22,
35 73.35, 70.07, 58.56, 57.50 ppm. ESI-MS (m/z): 174 (M+). All
spectral features of isosorbide methyl ethers correspond to those
reported in the literature.5 See ESI† for more experimental details.
Acknowledgements
We acknowledge the National Natural Science Foundation of
40 China (Grant No. 21473188, 21233008) and the "Strategic
Priority Research ProgramClimate Change: Carbon Budget and
Related Issues" of the Chinese Academy of Sciences
(XDA05010203) for the financial support. We thank Dr. Y. Z.
Huang, G. S. Feng and S. Chen for their kind help.
45 Notes and references
a State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics,
Chinese Academy of Sciences, Dalian National Laboratory for Clean
Energy, Dalian 116023, P. R. China. Fax: +86-411-8437-9245; Tel:
+86-411-8437-9245; E-mail: xujie@dicp.ac.cn; lufang@dicp.ac.cn.
4
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