Dimethyl Carbonate and Phenols To Alkyl Aryl Ethers Via Clean Synthesis
Dimethyl Carbonate and Phenols To Alkyl Aryl Ethers Via Clean Synthesis
Dimethyl Carbonate and Phenols To Alkyl Aryl Ethers Via Clean Synthesis
synthesis
Samedy Ouk,a Sophie Thibaud,*a Elisabeth Borredona and Pierre Le Garsb
a
The industrially important alkyl aryl ethers (ArOR) were selectively obtained in good yields from the O-alkylation
of the corresponding phenols with the environmentally benign reagents, dimethyl carbonate or diethyl carbonate.
The reactions were carried out under atmospheric pressure, in a homogenous process, without solvent and in the
presence of potassium carbonate as catalyst.
Introduction
The development of sciences and technologies have resulted in
a substantial improvement of our lifestyles. These almost
unbelievable achievements have, however, led to some impacts
on the global environment and public awareness. In particular,
chemistry has been contributing to this evolution. Through the
combination of knowledge on molecular reactivity, design and
other subdisciplines of chemistry and chemical engineering,
green chemistry has been looked upon as a sustainable science
which accomplishes both economical and environmental goals,
simultaneously. With this objective, we developed an alternative process to obtain the industrially important aryl methyl
ethers by O-methylation of phenols with dimethyl carbonate
(DMC).
Alkyl methyl ethers are useful for the preparation of
fragrances, pesticides, cosmetic products, dyes, etc.1 By far the
most common method of production is the O-methylation of
phenols with dimethyl sulfate25 or methyl halides.611 These
reagents are very harmful, and the need for a stoichiometric
amount of base to neutralise the acid by-product results in large
amounts of inorganic salts to be disposed of. Methanol has also
been used as the methylating agent. However, the reaction
needs a strong acid catalyst1214 or to be carried out at very high
temperature (200400 C) using zeolite as catalyst.1525
Furthermore, the reaction was not selective. Due to these
problems, DMC has been emerging as a potential methylating
agent.2629
The O-methylation of phenols with DMC can be carried out
in an autoclave at a temperature between 120 and 200 C, in the
presence of catalysts such as alkali or organic bases in
combination with an iodide,30 tertiary amines or phosphines,31
nitrogen-containing heterocyclic compounds (e.g. 4-(dimethylamino)pyridine),32 pentaalkylguanidines33 or cesium carbonate.34
Basic zeolites, aluminas or alumina-silica were described as
good catalysts in a continuous-flow process. The reactions were
conducted at a temperature range from 180 to 300 C in the
vapour phase. Although high yields of aryl methyl ethers were
obtained, by-products of C-methylation were also observed.35,36 Guaiacol and veratrole were synthesised by Omethylation of catechol over modified aluminas in a continuous-flow process at a temperature between 250 and 300
C.3739 Selectivity towards either guaiacol38 or veratrole39 was
obtained over alumina loaded with alkali hydroxide or alumina
DOI: 10.1039/b203353b
Green Context
The replacement of salt-forming reagents with more efficient systems is exemplified by the use of dimethyl carbonate
(DMC) in place of e.g. methyl chloride. Here, DMC is
successfully used to methylate phenols in good yield and
with only (recyclable) methanol and CO2 as co-products.
DJM
Separation is relatively simple.
431
Scheme 1
The reaction medium was homogeneous since during the preheating period, K2CO3 was progressively dissolved in p-cresol.
While nearly total conversion of pC was attained, the base
reappeared in the solid state. This phenomena can be explained
by the formation of CH3(C6H4)OK which is miscible with pcresol. The formation of this potassium salt was confirmed by
FTIR spectra (Fig. 3). The spectrum of the mixture of p-cresol
and K2CO3, after heating to 160 C, shows a decrease of
intensity of a broad band characteristic of OH of p-cresol at
3338 cm21. The degree of solubility depends on temperature as
shown in Fig. 4. Therefore at 160 C, the pC/K2CO3 molar ratio
should be > 23 (or K2CO3/pC molar ratio < 0.043) to ensure
that the medium is homogeneous.
To reduce the reaction time, the pC/K2CO3 molar ratio was
decreased from 120 to 25. In the investigation of the effect of
solvent, we found that the solvent does not influence the
MHSV[4MA] (Table 1 entries 510). Meanwhile, the pC/
K2CO3 molar ratio has a slight influence on MHSV[4MA],
because when the reaction medium is too concentrated in pcresol (entries 1 and 4), MHSV[4MA] is slightly decreased.
Hydrogen-bonding among molecules of p-cresol might disturb
phenolate anion formation, and consequently the reaction
kinetics are slowed down.
432
Entry
K2CO3/
pC/mol mol
1
1.2
2
0
3
0.3
4
1.2
5
0.5
6
0.5
7
0.5
8
0.5
9
0.5
10
0.5
a Over 15 h
0.01
0.01
0.01
0.01
0.02
0.02
0.02
0.02
0.02
0.02
DMC
(t0)/mol
Solvent
Identity
Wt/g
T/C
0.277
0
0.1
0.277
0.133
0.133
0.133
0.133
0.133
0.133
None
4MA
4MA
4MA
4MA
4MA
4MA
4MA
4MA
None
0
50
50
50
50
25
12
6
3
0
160
160
160
160
160
160
160
160
160
160
Time/h
DMC
Total pC/ Yield
flow/mol pC flow/ Total
mol h21 DMC/mol mol
(%)
h21
Average
MSHV[4MA]/
h21
30
26
24
26
5
5
5
5
5
5
0.072
0.096
0.072
0.072
0.120
0.120
0.120
0.120
0.120
0.120
3.92
4.57
4.97
4.55
4.85
4.8
4.9
4.85
4.9
4.85
0
0.08a
0.06a
0
0
0
0
0
0
0
2.437
2.496
1.728
2.149
0.733
0.733
0.733
0.733
0.733
0.733
1.2
1.2
1.2
1.2
0.5
0.5
0.5
0.5
0.5
0.5
98
99
99
99
97
96
98
97
98
97
KOH
47
69
KHCO3
KNO3
0
90
K2CO3
Na2CO3
21
63
Cs2CO3
CaCO3
0
No catalyst
0
Reaction conditions: p-cresol = 0.5 mol, K2CO3 = 0.02 mol, DMC (t0) =
0.13 mol; DMC continuous flow rate = 0.15 mol h21; temperature = 160
C time = 4 h.
Process generalisation
Table 3 shows the results of O-alkylation of various phenols
with dialkyl carbonate by using the same procedure as for Omethylation of p-cresol with DMC. Therefore, the generalisation can easily be adopted to other phenols (entries 1119) as
well as to other alkyl carbonates (entries 20 and 21). Total
conversion would be obtained if the reaction time is adequately
extended. The reaction is totally O-selective except in the case
of catechol in which various by-products were detected by gas
chromatography analysis (entries 19).
Conclusion
The combination of the use of dimethyl carbonate as reagent
and potassium carbonate as recyclable catalyst avoids the use of
conventional methylating agents. DMC is obviously more atom
economic than MeI, MeBr or dimethyl sulfate (DMS). Furthermore, when DMC is used as the methylating agent, it only
leads to methanol and carbon dioxide. These by-products can
easily be separated from the alkyl aryl ethers and methanol can
be re-used according to the principle of life cycle assessment.
Compared with methanol, DMC is a better methylating agent
Green Chemistry, 2002, 4, 431435
433
Entry
Substrate Identity
Mol
Reaction conditions
K2CO3/ DMC (t0)/
mol
mol
T/C
Time/h
DMC flow/
mol h21
DMC
total/mol
Yield
(%)
Residual
substrate
(%)
11
Phenol
0.5
0.02
0.1
150
5
0.13
0.75
70
26
12
4-Chlorophenol
0.5
0.02
0.135
160
4.5
0.15
0.81
99
0
13
4-Hydroxybenzophenone
0.5
0.02
0.175
160
5
0.13
0.82
52
44
14
4A-Acetophenone
0.5
0.04
0.145
160
9
0.88
0.94
86
14
15
2-Naphthol
0.5
0.04
0.2
160
6
0.1
0.80
96
3
16
4-Hydroxyphenylacetic acid
0.5
0.04
0.15
160
11
0.1
1.25
29
65
17
Eugenol
0.5
0.04
0.145
170
6
0.12
0.86
93
5
15
18
2,4-Dihydroxybenzophenone
0.5
0.02
0.15
160
10
0.1
1.15
80a
31
19
Catechol
0.5
0.04
0.15
160
3
0.2
0.75
48b
20
p-Cresolc
0.5
0.02
0.17
160
12
0.08
1.13
94d
0
0.5
0.02
0.1
155
8
0.08
0.74
90e
8
21
Phenolc
a Yield of 2-hydroxy-4-methoxybenzophenone. b Yield of guaiacol. c O-Ethylation with diethyl carbonate (DEC). d Yield of 4-ethoxytoluene.
phenetole.
Experimental
The reaction was conducted in a 250 ml reactor equipped with
a mechanical stirrer, a thermocouple linked to heater by an
automatic regulator and a distillation column. The top of
distillation column was equipped with a reflux system, enabling
adjustment of the outlet flow rate of by-product. The reagents
were fed into the reactor by a peristaltic pump (Scheme 2). At
the end of the reaction, residual DMC can be separated from the
product by distillation.
Dimethyl carbonate and diethyl carbonate were obtained
from SNPE. Other reagents were commercially available in a
purity of at least 97%.
The yield of each reaction was determined by gas chromatography on a Hewlett Packard 5890 with monochlorobenzene
used as internal standard. The capillary column (BP1, 50 m 3
0.25 mm 3 0.25 mm) was temperature-programmed from 50 to
220 C with a heating rate of 20 C min21. The injector and
detector temperature were 240 and 260 C, respectively. The
column head pressure was 20 psi.
The products obtained were purified before being identified
by 13C and 1H NMR on NMR Brucker AC 200 equipment
Acknowledgement
Dr F. Violleau, (Senior researcher at Laboratoire de Chimie
Agro-industielle) is gratefully acknowledged for his contribution. We also thank SNPE-Toulouse for their financial support.
References
1
2
3
4
5
8
9
10
11
12
13
14
15
16
17
18
434
3.5
5.5
2.6
1.2
2.0
0.33
1.9
2.0
2.0
1.9
2.8
e Yield of
(CDCl3 as solvent, 200 MHz for 1H NMR and 50 MHz for 13C
NMR).
FT-IR spectra analysis: the mixture of p-cresol and K2CO3
(4% molar of K2CO3) was heated to 160 C with stirring and the
mixture became homogeneous. After cooling down to room
temperature, a brown solid was obtained which was analysed
using a PERKIN ELMER Spectrum BX II FT-IR system.
6
7
Average
MSHV/
h21
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
435