Selective Catalytic Methylation of Phloroglucinol with Dimethyl Carbonate in the Presence of Heterogeneous Acids

Article abstract of DOI:10.1002/ejoc.201801112

A facile process for the methylation of phloroglucinol using environmentally friendly dimethyl carbonate as methylating agent and solvent is described. Widely available and inexpensive solid acids have been used as catalysts to promote this transformation. H-Y zeolite proved particularly selective for monomethylation, hence it has been used for the convenient preparation of methoxyresorcinol (MR), with only limited co-production of dimethoxyphenol (DMP). Conversely, the use of tungstosilicic acid on silica easily afforded DMP in excellent isolated yield.

Full text of DOI:10.1002/ejoc.201801112

A Journal of
Accepted Article
Title: Selective Catalytic Methylation of Phloroglucinol with Dimethyl
Carbonate in the Presence of Heterogeneous Acids
Authors: Matthew Lui, Marco Noe, Anthony Masters, and Thomas
Maschmeyer
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201801112
Link to VoR: http://dx.doi.org/10.1002/ejoc.201801112
Supported by

10.1002/ejoc.201801112
European Journal of Organic Chemistry
FULL PAPER
Selective Catalytic Methylation of Phloroglucinol with Dimethyl
Carbonate in the Presence of Heterogeneous Acids
Matthew Y. Lui,[a] Marco Noè,[a] Anthony F. Masters,[a] and Thomas Maschmeyer*[a]
Abstract: A facile process for the methylation of phloroglucinol using
environmentally friendly dimethyl carbonate as methylating agent
and solvent is described. Widely available and inexpensive solid
acids have been used as catalysts to promote this transformation. H-
Y zeolite proved particularly selective for monomethylation, hence it
has been used for the convenient preparation of methoxyresorcinol
(MR), with only limited co-production of dimethoxyphenol (DMP).
Conversely, the use of tungstosilic acid on silica easily afforded DMP
in excellent isolated yield.
phlACBDE gene cluster found in Pseudomonas fluorescens Pf-
5.[8] A decade later, Abdel-Ghany et al. reported the biosynthesis
of phloroglucinols using a transgenic Arabidopsis plant with an
enzyme encoded by phID gene.[9] These findings illustrate the
possibility of producing bio-derived phloroglucinol at scale.
HO
O
OH
OH
HO
O
O
O
HO
OH
Phloroglucinol
OH
Introduction
OH
OH
OH
Eckstolonel
The transition towards a carbon neutral economy, based on the
use of renewable resources is one of the major factors
prompting research in many fields of science.[1] Specifically, the
quest for new processes allowing the transformation and use of
chemicals from renewables, such as biomass, represents one of
the topics gaining considerable attention from both scientists
and policy makers.[2] Several chemical solutions aimed at
exploiting products from renewables have been investigated and
many promising processes and products representing the
foundation of the future biorefining industry have been
described.[3] However, these processes do not easily generate
OH
O
OH
OH
O
O
OH
O
OH
OH
HO
OH
HO
O
Eckol
OH
OH
Triphlorethol A
Figure 1. Phloroglucinol and three examples of phlorotannins (Eckstolonel,
Triphlorethnol A and Eckol)
cheap aromatic building blocks. Hence,
a path for the
exploitation of a bio-based source of aromatics is seen as one of
the main challenges of Green Chemistry.[4] Methods to
depolymerize lignin, the most abundant renewable source of
aromatics, have been intensively researched in the past
decade.[5]
Often, during the processing of phloroglucinol in the preparation
of fine and pharmaceutical chemicals, it is first methylated to
block one or two of its hydroxylic functional groups prior to
further transformations.[10] The mono-methylated derivative
(flamenol, 5-methoxyresorcinol, MR) is particularly valuable, as
reflected in its market price.[11]
Commonly reported methods for PG methylation require the use
of methanol as methylating agent and a Brønsted acid such as
H2SO4 or HCl as the catalyst.[12] This protocol suffers from low
selectivity towards the desired MR derivative since dimethylated
(3,5-dimethoxyphenol, DMP) or even trimethylated (1,3,5-
trimethoxybenzene, TMB) products form well before the reaction
reaches complete conversion. Another undesirable feature of
this procedure is the use of toxic, volatile methanol. Furthermore,
greater than stoichiometric amounts of Brønsted acid need to be
quenched by neutralization with base, leading to the formation of
large amounts of salts to be disposed of or extensive volumes of
aqueous waste. The preparation of methoxyresorcinol via
methylation of phloroglucinol clearly needs a better procedure
that overcomes these issues.
Alternatively, brown algae are known to contain large amounts
(up to 20 % dry weight) of a class of polyphenols, namely
phlorotannins,[6]
oligomers
of
phloroglucinol
(1,3,5
trihydroxybenzene, PG) (Figure 1). PG is a very promising
phenolic compound that is used in the pharmaceutical, cosmetic
and dyeing industries.[7]
Yet, the depolymerization of phlorotannins has not been
investigated extensively. Furthermore, phlorotannins are
currently commercially far less readily available than is lignin. A
promising route for the production of bio-derived phloroglucinol
has been investigated by Frost and co-workers. In 2005 they
described the biosynthesis of phloroglucinols encoded by the
[a]
Dr. M. Y. Lui, Dr. M. Noè, Prof. A. F. Masters, Prof. T. Maschmeyer
Laboratory of Advanced Catalysis for Sustainability, School of
Chemistry F11, The University of Sydney, Sydney, NSW 2006,
Australia.
The use of dimethyl carbonate (DMC) as a Green methylating
agent is well established.[13] It compares favorably with methanol
in terms of their relative toxicities. Methylation of phenols with
DMC using heterogeneous (usually basic) catalysts was studied
in detail and numerous studies can be found in the literature.[14]
E-mail: thomas.maschmeyer@sydney.edu.au
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201801112
European Journal of Organic Chemistry
FULL PAPER
However, the reaction of DMC with phenols in the condensed
phase at lower temperatures is often carried out using
homogeneous catalysts. Indeed, our group and others have
reported the use of base or nucleophilic catalysts for the
methylation of phenols with DMC in condensed phases.[15]
Nonetheless, separation and subsequent recycling of catalysts
are difficult to achieve in these reaction systems.
To the best of our knowledge, no previous investigations on the
methylation of phloroglucinol using heterogeneous catalysis, nor
one using DMC as methylating agent have been reported. In the
present work the methylation of phloroglucinol and other
trihydroxy and dihydroxy benzenes have been investigated
using easily separable, robust and inexpensive solid acid
catalysts (Scheme 1). This work also demonstrates the use of
focused microwave-mediated heating in a batch reactor set-up
that allows accurate control of the reaction temperatures and
times as well as real time monitoring of the reactor pressure.
Modern microwave instruments also enable DMC to be
superheated in a closed vessel, thereby reducing the reaction
time. Using heterogeneous catalysts, in combination with an
“industry-friendly” Green solvent/reactant such as DMC makes
this investigation of interest for future industrial scale preparation
of phloroglucinol derivatives as part of biorefinery strategies.
Entry
Time
(min)
Catalyst[a]
Conv.
(%)[b]
MR
DMP
(%)[b]
TMB
(%)[b]
MR
Sel
(%)[b]
(%)[b]
1
2
40
40
40
40
240
40
240
40
40
40
10
40
40
20
Acidic
Al2O3
-
-
-
-
-
-
-
-
-
-
γ-Al2O3
3
Na-Y
Zeolite
-
-
-
-
-
4
H-Y
Zeolite
6
6
-
-
100
98
100
89
-
5
H-Y
Zeolite
70
11
80
-
68
11
71
-
2
-
6[c]
7[c]
8[d]
9
H-Y
Zeolite
-
-
H-Y
Zeolite
8
-
H-Y
Zeolite
-
-
H-ZSM-5
TS/SiO2
TS/SiO2
1
1
-
-
-
OH
O
O
O
O
10
11
12
13
14
100
84
52
100
85
-
91
21
3
-
-
O
O
+
+
Solid Acid
Catalyst
HO
OH
HO
OH
O
OH
O
O
PG
MR
DMP
TMB
57
48
11
37
-
68
92
11
44
Scheme 1. Methylation of Phloroglucinol (PG) with dimethyl carbonate (DMC)
using solid acid catalysts.
Nafion
SAC13
-
Nafion
NR50
77
40
4
1
Results and Discussion
Our previous study[15b] on the DBU or NHC-catalyzed
methylation of phenols demonstrate that DMC itself is not a
reactive methylating agent and activation of DMC (e.g. by a
nucleophilic catalyst) is desirable for effective methylation. A
simple base is not able to activate DMC to render it more
reactive. Nonetheless, the methylation of phloroglucinol has
been reported to proceed under acidic conditions with
methanol.[12] These considerations prompted us to consider
acidic catalysis, with DMC as methylating agent. With the aim of
developing a truly Green chemical process, solid or solid
supported catalysts were considered the best alternative to
H2SO4 and HCl. For the same reason no additional solvents
were employed and DMC was used in excess as
solvent/reagent.
Nafion
NR50
[a] 200 mg of catalyst was mixed with 200 mg of phloroglucinol and 3 mL of DMC in a 10
mL glass tube. The tube was heated in an Anton Paar Monowave 300 microwave
synthesis reactor with a stirring rate of 600 rpm. [b] conversion carried out at 155 °C
unless stated otherwise; data determined by GC-FID (on derivatized product). [c]
conversion carried out at 165 °C. [d] MeOH was used in place of DMC.
Slightly acidic materials such as acidic alumina, γ-Alumina, Na-Y
zeolite were not able to catalyze the methylation reaction and
not even traces of the desired products were detected (entries
1–3). Only the use of stronger acidic materials like H-Y zeolite
(entries 4–7), tungstosilicic acid (entries 10 and 11) or
sulfonated fluoroethylene polymers (entries 12–14) promoted
the reaction.
Both the silica-supported tungstosilicic acid (TS/SiO2) and the
two forms of Nafion tested proved to be very efficient, leading to
very high conversions in short times. Using H-Y as the catalyst
and conducting the reaction over a longer time (240 min, entry 5
and 7) also afforded high conversions of up to 98 %.
A first screening using different catalysts was conducted to test
the reactivity of PG dissolved in DMC at 155 °C and 165 °C in a
catalyst to substrate ratio of 1:1 by weight. The results obtained
for different catalysts are summarized in Table 1.
Table 1. Catalyst screening for methylation of PG with DMC.
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European Journal of Organic Chemistry
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It is proposed that DMC is activated by the acidic site through its
carbonyl oxygen, a process which renders the methyl group of
DMC more electrophilic.[16] Moreover, PG could be absorbed
onto an adjacent site of the solid acid by hydrogen bonding
(Scheme 2).[17] Alkylation occurs when the oxygen atoms of PG
nucleophilically attacks the methyl group of the activated DMC.
The methylcarbonate moiety, formed as a result of alkylation,
then decomposes[18] to form carbon dioxide and methanol as
byproducts via proton transfers (Scheme 2).
A time-course study with H-Y as catalyst at 165 °C (Figure 2)
reveals that approximately 100% conversion is reached after
300 min. with selectivity remaining well above 80% until 80%
conversion is reached after about 250 min. This observation is
consistent with the relative lack of substrate allowing the more
difficult follow-on methylation to become more prominent.
We also investigated the dependence of MR yield on
temperature and, as expected, the conversion rate of substrate
increased with temperature, peaking at around 70% irrespective
of the temperature employed (Figure S1, Supporting
Information).
OH
OH
This yield limit is further consistent with the previous
interpretation of competing substrate concentrations. To further
investigate the effect of the temperature on selectivity, the same
reaction was carried out for 40 minutes at temperatures of 150,
160, 170, 180 and 190 °C. Conversions of phloroglucinol and
selectivities for MR and DMP are illustrated in Figure 3.
O
O
O
O
H
H
HO
O
HO
O
O
O
H
H
H
H
solid acid
solid acid
- CO2
- CH3OH
OH
100
Conv
HO
O
MR
DMP
80
Sel
Scheme 2. Proposed mechanism for the methylation of phloroglucinol with
DMC over solid acid catalysts; “H”s in italics indicate acid sites on solid acid.
60
40
20
0
As discussed in the introduction, a process for the selective
monomethylation of PG to obtain MR would be very valuable.
Selectivity towards MR was still very high (98%) when H-Y
zeolite was used as the catalyst, even at 70% conversion, while,
in the case of TS/SiO2, when 84% conversion was achieved,
selectivity had already dropped to 68%. SAC13 is even less
selective, i.e. at 85% conversion, the selectivity dropped to 44%.
Methanol was found to be less reactive than DMC for the acid-
catalyzed methylation of PG (entry 8).
140
150
160
170
180
190
200
Temp (° C)
Figure 3. Reactions of phloroglucinol with DMC in the presence of H-Y zeolite
at different temperatures after 40 minutes. “Sel” indicates selectivity to MR.
As expected, at higher temperatures H-Y promoted the second
methylation step and, hence, the formation of DMP. At 190 °C
the GC yield for DMP was approximately 60% after only 40
minutes.
To establish if other active but “less selective” catalysts like
TS/SiO2, Nafion SAC13 and NR50 could be made more
selective toward MR under optimized conditions, similar tests at
different temperatures were conducted using both TS/SiO2 and
Nafion SAC13 (Figures 4 and S2, Supporting Information).
As indicated in Table 1 both NR50 and TS/SiO2 catalysts were
far more active than was H-Y, and high conversions could be
achieved at relatively low temperatures. TS/SiO2 in particular
was so active that the reaction time was reduced to 10 minutes.
100
Conv
MR
DMP
Sel
80
60
40
20
0
0
50
100
150
200
250
300
Time (min)
Figure 2. Reaction profile for the reaction of phloroglucinol with DMC
catalysed by H-Y zeolite at 165 °C. “Sel” indicates selectivity to MR.
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10.1002/ejoc.201801112
European Journal of Organic Chemistry
FULL PAPER
reported to promote the decomposition of DMC into dimethyl
ether and CO2 under the conditions used in our investigation.[21]
The more acidic the catalyst, the higher the rate of this
decomposition pathway. Hence, high-pressures are produced by
activation and decomposition of DMC by the acidic zeolite
catalyst.
100
80
60
40
20
0
Conv
MR
DMP
Sel
Then, conversions of PG were carried out using X and Y zeolites
under similar conditions. Although, the two catalysts possess the
identical solid structures and similar pore sizes, their behaviors
were vastly different for this process. For instance, using a
poorly acidic zeolite like X zeolite (Si/Al: 1.5), the reaction was
so slow that no product formation could be observed at 170 °C
after 40 minutes, while the pressure remained around 12 bar
(Table 2). Conversely, zeolite Y, which has moderate acidity with
Si/Ai ratio (2.6) in between of that of β and X zeolites, gave a
good yield of MR (67 %) but a small amount of DMP (6 %).
Overall, our results demonstrated that the pore size and number
of acid sites of catalysts have neligible effects on the
performance of the process. Acidity of the catalyst has a major
influence on the rate of the process and the yields of MR and
DMP.
120
130
140
150
160
Temp (°C)
Figure 4. Reactions of phloroglucinol with DMC in the presence of TS/SiO2 at
different temperatures after 10 minutes. “Sel” indicates selectivity to MR.
Using either TS/SiO2 or Nafion as catalysts, acceptable yields of
MR could be achieved (57 and 66 % respectively). However, the
selectivity towards MR dropped much more quickly than when
H-Y zeolite was used as the catalyst.
Table 2. Methylation of PG with DMC using different H form zeolites.
The use of TS/SiO2 at lower temperature for longer reaction
times did not improve the outcome of the reaction. Thus, for
example, carrying out the reaction at 130 °C for 40 minutes, the
selectivity remained around 70 % at 81 % conversion.
The formation of the bis-methylated product, DMP, is more rapid
with TS/SiO2 as catalyst than when using HY zeolite as catalyst.
H-Y zeolite not only is inexpensive and readily available, but it
also promotes very high selectivities toward the desired product.
Conversely Nafion NR50 showed the lowest selectivity towards
the desired mono-methylated product. In fact, not only was DMP
produced at relatively low conversion, but also appreciable
amounts of TMB could be detected (Table 1, entries 11–12), in
contrast to the products obtained with the other catalysts tested.
Since TS and Nafion both exhibit extremely strong acidic
behavior: TS being more acidic than p-toluenesulfonic acid[19]
and Nafion being a superacid, the results suggested that
conversion rates of both PG and MR were significantly
dependent on the acidity of the catalysts.
It is well known that Si/Al ratios affect the abundance of active
sites and the acid/base properties of zeolites.[20] To verify that
acidity has the major influence on the outcome of the reactions,
several zeolite of different Si/Ai ratios were prepared and tested
as catalysts.
First, the behavior of a highly acidic zeolite such as H beta
zeolite (Si/Al: 15) was investigated (Figure S3, Supporting
Information).
Catalyst
Si/Ai
Ratio
Pressure
(bar)
Conv.
(%)[a]
MR
DMP
(%)[a]
MR Sel
(%)
(%)[a]
H-X
Zeolite
1.5
2.6
15
12
14
32
-
-
-
6
-
H-Y
Zeolite
75
96
67
44
89
46
H-β
Zeolite
50
[a] determined by GC-FID (on derivatized product) after 40 min at 170 °C.
Catalyst recycling. The recyclability of H-Y zeolite as a catalyst
for the selective mono-methylation of phloroglucinol was tested.
After the reaction was conducted under the best conditions for
the highest methoxyresorcinol yield (i. e. 170 °C for 40 minutes),
the zeolite was separated by centrifugation of the mixture and
successively washed with portions of ethyl acetate (3 x 2 mL).
The zeolite was then washed with DMC (3 x 2 mL) to remove
ethyl acetate and the resulting zeolite impregnated by DMC was
used in the following cycle. The procedure was repeated several
times and the results thus obtained are reported in Figure 5.
Unsurprisingly, excellent conversions were achieved at relatively
low temperatures and low selectivities toward MR were
observed. DMP was obtained as the major product (50 %).
Remarkably, temperatures above 170 °C could not be explored,
since the pressure reached the maximum allowed for our system,
i.e. 32 Bar.
The pressure reached by the vessel furnishes significant
information on the reaction outcome. Faujasites/zeolites are
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10.1002/ejoc.201801112
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FULL PAPER
reported examples of conversion of phloroglucinol. Overall, none
of the catalysts tested was as good as TS/SiO2 for the
preparation of DMP.
To demonstrate the applicability of this protocol for preparative
purposes, the optimized procedures for MR and DMP
preparation were carried out using 1 g of reactant. The products
were purified by column chromatography. As shown in Table 4,
the two target compounds, MR and DMP, could be isolated in
good yields (62 and 85 % respectively).
Table 4. Preparative experiments.
Entry
1
T (°C)
170
Catalyst[a]
MR (%)[c]
62
DMP (%)[c]
2
Figure 5. H-Y zeolite recycling for monomethylation of phloroglucinol with
H-Y Zeolite
DMC (170 °C, 40 min).
2
150
TS/SiO2
5
85
The conversion of phloroglucinol dropped from 75 to 52% after
the H-Y catalyst was reused 3 times. The selectivity towards the
desired mono-methylated product, however, remained
remarkably high after recycling of the catalyst (≥90%).
Preparation of 3,5-dimethoxyphenol. Optimized conditions for
the preparation of DMP were also investigated. Not only were
the most active TS/SiO2 and Nafion based catalysts used, but
H-Y Zeolite was also considered in order to evaluate its ability in
promoting the formation of the dimethylated compound (DMP) at
higher temperature and by performing the reaction for longer
times. The results are summarized in Table 3.
[a] 1.00 g of catalyst was mixed with 1.00 g of PG and 15 mL of DMC in a
30 mL glass tube. The tube was heated for 40 min in an Anton Paar
Monowave 300 microwave synthesis reactor with a stirring rate of 600
rpm. [b] isolated yield.
Different Substrates. To verify the scope of the reaction protocol,
all isomers of mono- di- and trihydroxybenzenes were tested
under the optimized conditions for mono and dimethylation of
phloroglucinol (Table S1, Supporting Information). Surprisingly,
the conversion was much lower when compared to that of PG in
all cases, except for hydroxyquinol (1,2,4 trihydroxybenezene,
Table 3. Conditions for dimethoxyphenol preparation using different catalysts.
Entry
T
(°C)
Catalyst
TS/SiO2
Conv.
(%)[a]
MR
DMP
(%)[a]
TMB
(%)[a]
Others
(%)[a]
entries
3 and 9). Under the conditions for mono and
(%)[a]
dimethylation of PG, high conversions (100 and 89%
respectively), but low selectivities toward O-methylation (less
than 40%) of hydroxyquinol were observed.
This behavior further confirms the particular features of
phloroglucinol as a reactant and therefore justifies the study of
dedicated processes for its chemical upgrading.
1
2
150
190
100
100
-
93
77
-
-
7
H-Y
10
13
Zeolite
3
4
190
150
Nafion
SAC13
100
100
6
88
77
-
6
7
Conclusions
Nafion
NR50
11
4
We unveil an environmentally friendly process for the selective
methylation of phloroglucinol as a strategy to obtain valuable
fine chemicals from a bio-derived aromatic compound. In this
study, phloroglucinol was methylated with environmentally
friendly DMC, which also acted as the solvent, using easily
accessible heterogeneous catalysts such as zeolites,
tungstosilic acid and Nafion based materials in short reaction
times.
[a] determined by GC-FID (on derivatized product) after 40 min.
TS/SiO2 was, as expected, the best performing catalyst. After 40
minutes at a relatively low temperature (150 °C, entry 1), the
desired compound was obtained with excellent selectivity (93%
yield).
The results indicated that monomethylation of phloroglucinol to
yield methylresorcinol can be easily achieved with very high
selectivity (up to 98%) using H-Y zeolite in a straightforward
process of short reaction time, in which the substrate is treated
with DMC as solvent/reagent and the catalyst can be easily
removed once the reaction is completed.
The selectivity was good but lower when using a polymeric
material like Nafion NR50 (entry 4). When Nafion was supported
on silica (entry 3), a very good selectivity was observed (88%
yield), even if a higher temperature (190 °C) was required. Good
selectivity for DMP was also achieved using H-Y zeolite at
190 °C (entry 2). To the best of our knowledge, the yield of DMP
obtained using TS/SiO2 as catalyst is the highest among all the
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Quantification of the reaction products was performed on a Shimadzu
GC-2010 Plus gas chromatograph equipped with Rtx-5MS 0.25 µm × 30
m × 0.25 mm column under the following conditions. The temperature
program had an isothermal period of 5 min at 100 °C, then the
temperature was increased by 15 °C/min to another isothermal period of
15 min at 300 °C.
Using other catalysts, conversions were higher, allowing the
conduct of the reaction at lower temperature and even shorter
times. Unfortunately, this led to a drop in selectivities toward the
desired MR. However, the most active catalyst, i.e. tungstosilic
acid supported on silica, proved highly suitable as catalyst for
the preparation of the dimethylated analogue DMP. Therefore,
two procedures were optimized for the preparation of MR and
DMP using H-Y zeolite and TS/SiO2 respectively. The DMP yield
(93%) obtained using TS/SiO2 is the highest among all the
reported examples of methylation of phloroglucinol. Overall, the
performance of this methylation process is governed largely by
the acidity of the catalysts.
In order to verify the preparative scope of the procedures, the
protocols were also performed on the gram scale, affording the
respective target compounds in good isolated yields.
The interest in a dedicated procedure for the methylation of PG
is demonstrated by its peculiar reactivity. Under similar
conditions, methylation of other phenolic derivatives was
considerably more difficult than phloroglucinol. Poor conversions
were observed for the methylation of mono-, di and other
trihydroxybenzenes under the best conditions for the preparation
of MR and DMP.
Compound identification by GC-MS was performed on a Shimadzu
GCMS-QP2010 equipped with Rtx-5MS 0.25 µm × 30 m × 0.25 mm
column under the following conditions. The temperature program had an
isothermal period of 5 min at 100 °C. Then the temperature was
increased by 15 °C/min to another isothermal period of 15 min at 330 °C.
Compounds were identified by comparing the EI-MS spectrum with the
MS library NIST05.
1H NMR spectra were recorded at 300 MHz at ambient temperature with
(CD3)2CO.13C NMR spectra were recorded at 75 MHz at ambient
temperature with (CD3)2CO.
Conversion of phloroglucinol. A typical procedure for the conversion of
phloroglucinol with DMC using solid acid catalysts is as follows:
Phloroglucinol (200 mg), catalyst (200 mg) and DMC (3 mL, 29 eqv.)
were heated in a 10 mL glass tube, fitted with a pressure cap in an Anton
Paar Monowave 300 microwave synthesis reactor with a stirring rate of
600 rpm. After heating, the reaction tube was removed from the
microwave reactor and cooled to room temperature. The resulting
mixtures were centrifuged to remove the solid catalyst. GC analysis of
the product mixture was carried out after derivatization of the hydroxyl
groups with Ac2O:pyridine (6:1) for better quality of separation.[26] For
isolation of products, the product mixtures were concentrated in vacuo
and separated by column chromatography (eluent: hexane/ethyl acetate
(gradient)). MR: 1H NMR (300MHz, (CD3)2CO) δ 3.67 (3H, s), 5.94 (2H,
m), 5.98 (1H, m). 8.17 (2H, br); 13C NMR (75MHz, (CD3)2CO) δ 55.25
(1C), 93.95 (2C), 96.85 (1C), 159.98 (2C), 162.69 (1C). DMP: 1H NMR
(300MHz, (CD3)2CO) δ 3.71 (6H, s), 6.00 (1H, m), 6.03 (2H, m); 13C NMR
(75MHz, (CD3)2CO) δ 55.38 (2C), 92.69 (1C), 94.89 (2C), 160.00 (1C),
162.67 (2C).
Experimental Section
Materials. Phloroglucinol (C6H3(OH)3.2H2O) was purchased from Fluka
and recrystallised with distilled water before use. DMC was supplied from
Aldrich. Acidic Al2O3 (Condea Vista Co.), γ-Al2O3 (Condea Vista Co.),
Nafion® SAC-13 (Aldrich), Nafion® NR50 (Aldrich), Faujasite Na-Y
(Zeolyst), H-ZSM-5 (Zeolyst) tungstosilicic acid hydrate (Fluka) silica gel
(Grace) and methanol (Redox Chemicals) were used as received. H-
beta was synthesized using a modification of the method reported by
Klomp and co-workers:[22] NaAlO2 (3.316 g) and a 35% TEAOH solution
in water (16 mL) were mixed and stirred for 15 min. To this mixture,
LUDOX HS-40 (30 mL) was added. The thick gel formed was transferred
to Teflon-lined autoclaves and the gel was heated at 170 °C for 4 days.
The autoclaves were quenched with water to room temperature, and the
white powder obtained was centrifuged, washed with water 3 times and
then dried in air overnight. The white powder was calcined at 550 °C for
15 h. After cooling, Na+ was exchanged by H+ by stirring the zeolite for
48 h with a 0.1 M solution of NH4NO3 (500 mL). The zeolite was calcined
at 450 °C for 15 h to yield a white powder.
Acknowledgements
The authors thank the Australian Research Council, Science
and Industry Endowment Fund (SIEF, RP03-028) (M.Y.L.) and
the Australia Awards Endeavour Scholarships and Fellowships
(M.N.) for financial support.
Tungstosilic acid on SiO2, TS/SiO2 catalyst was prepared using a
modification of the method reported by Nasr-Esfahani and co-workers:[23]
silica gel (1.4 g) was mixed with a solution of tungstosilicic acid hydrate
(0.6 g) in distilled water (20 mL). After removal of water in a rotary
evaporator, the resulting solid was dried and calcined in air at 300 °C for
3 h.
Keywords: alkylation • biomass • dimethyl carbonate • green
solvent • solid acids
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The bio-derived platform chemical
phloroglucinol was selectively
methylated with dimethyl carbonate
using readily available solid acids.
Sustainable Synthesis
Matthew Y. Lui, Marco Noè, Anthony F.
Masters, and Thomas Maschmeyer*
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Selective Catalytic Methylation of
Phloroglucinol with Dimethyl
Carbonate in the Presence of
Heterogeneous Acids
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