A new protocol for O-methylation of phenolic compounds with trimethyl phosphite or trimethyl phosphate under solvent-free condition and microwave irradiation

Article abstract of DOI:10.1080/714040947

A simple method for the preparation of industrially important alkyl aryl ethers is reported. Several phenolic compounds such as phenols, naphthols, and hydroxy coumarins were O-methylated with trimethyl phosphite or trimethyl phosphate under microwave irradiation and solvent-free condition in almost quantitative yields. Reaction of 2-naphthol with trimethyl phosphate gave mixture of 2-methoxynaphthalene and 1-methyl-2-methoxynaphthalene while the reaction with trimethyl phosphite gave mostly 2-methoxynaphthalene. This method is highly efficient for the methylating of phenolic compounds with very easy experimental procedure and environmental friendly conditions.

Full text of DOI:10.1080/714040947

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A New Protocol for O-Methylation of Phenolic
Compounds with Trimethyl Phosphite or Trimethyl
Phosphate Under Solvent-Free Condition and
Microwave Irradiation
Mohammad R. Saidi a & Fatemeh Rajabi a
a Sharif University of Technology, Tehran, Iran
Version of record first published: 18 Jun 2010.
To cite this article: Mohammad R. Saidi & Fatemeh Rajabi (2003): A New Protocol for O-Methylation of Phenolic Compounds
with Trimethyl Phosphite or Trimethyl Phosphate Under Solvent-Free Condition and Microwave Irradiation, Phosphorus, Sulfur,
and Silicon and the Related Elements, 178:11, 2343-2348
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Phosphorus, Sulfur, and Silicon, 178:2343–2348, 2003
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500390234740
A NEW PROTOCOL FOR O-METHYLATION
OF PHENOLIC COMPOUNDS WITH TRIMETHYL
PHOSPHITE OR TRIMETHYL PHOSPHATE UNDER
SOLVENT-FREE CONDITION AND MICROWAVE
IRRADIATION
Mohammad R. Saidi and Fatemeh Rajabi
Sharif University of Technology, Tehran, Iran
(Received April 23, 2003; accepted May 15, 2003)
A simple method for the preparation of industrially important alkyl aryl
ethers is reported. Several phenolic compounds such as phenols, naph-
thols, and hydroxy coumarins were O-methylated with trimethyl phos-
phite or trimethyl phosphate under microwave irradiation and solvent-
free condition in almost quantitative yields. Reaction of 2-naphthol
with trimethyl phosphate gave mixture of 2-methoxynaphthalene and
1-methyl-2-methoxynaphthalene while the reaction with trimethyl
phosphite gave mostly 2-methoxynaphthalene. This method is highly
efficient for the methylating of phenolic compounds with very easy ex-
perimental procedure and environmental friendly conditions.
Keywords: Alkyl aryl ethers; microwave irradiation; solvent-free;
trimethyl phosphite
Alkyl aryl ethers are an industrially important class of compounds.1 In
particular, methyl aryl ethers have various usages in different chemical
processes.2 Methyl aryl ethers are useful as starting materials for the
preparation of fragrances, dyes, and pesticides, as antioxidants in oils
and fats or as stabilizers of plastics.3
There have been several approaches for the methylation of phe-
nolic compounds. Dimethyl carbonate was used for O-methylation of
phenols in the presence of potassium or cesium carbonate and phase
transfer catalysts such as tertiary amines and pentaalkylguanidines at
temperatures between 120 and 200◦C under autogenous pressure for
We are grateful to the Research Council of Sharif University of Technology for
financial support.
Address correspondence to Mohammad R. Saidi, Department of Chemistry, Sharif
University of Technology, P.O. Box 11365-9516, Tehran, Iran. E-mail: saidi@sharif.edu
2343

2344
M. R. Saidi and F. Rajabi
several hours.4 Methyl aryl ethers, such as anisole, also were prepared
from aryl bromides and concentrated sodium methoxide solutions in
dimethyl formamide and methanol.2 Alkyl methyl carbonates, methyl
iodide, orthoesters, and dimethyl sulfate also were used to accomplish
the O-methylation of phenolic compounds in the presence of alkaline
base or potassium carbonate in polar solvents and in an autoclave or
reflux conditions.5 Gas solid phase transfer method was also reported
for such a process using polyethyleneglycol (PEG) or crown ethers as
phase transfer catalyst.6
Solvent-free media coupled with microwave promoted reactions are
gaining more widespread use in organic chemistry. The published ex-
amples clearly show that microwave energy significantly reduces re-
action time for a diverse selection of chemical processes traditionally
performed under external heating.7 In continuation of our work on
solvent-free and microwave-assisted organic reactions,8 we now report
a very simple, fast, and general method for the O-methylation of phe-
nolic compounds without using a solvent with trimethyl phosphit or
trimethyl phosphate under microwave irradiation with almost quanti-
tative yields.
Although trimethyl phosphite has been used in the conversion of car-
boxylic acids to the corresponding methyl ester under neutral condition,
but to the best of our knowledge, there is not any report in the litera-
ture for using trimethyl phosphite as methylating agents for phenols
and naphthols.
RESULTS AND DISCUSSION
O-Methylation of phenolic compounds with other methylating agents
can be carried out under conventional conditions after several hours,
which is cumbersome and time consuming. By using trimethyl phos-
phite or trimethyl phosphate under microwave irradiation and solvent-
free and environmentally benign conditions, the reaction time is signifi-
cantly reduced from several hours to a few minutes, with improvement
in the isolated yields. In addition trimethyl phosphite and specially
trimethyl phosphate is a readily available and cheap reagent in com-
parison with other reported methylating agents. Thus when phenol and
1.1 equivalent of trimethyl phosphite or trimethyl phosphate were ir-
radiated for about 1.0 min in a conventional microwave oven in the
presence of 1.0 mL solution of BF3 in ether, anisole was produced with
more than 99% yield. The same reaction was performed for naphthols
and several phenolic compounds. In all cases the corresponding methyl
aryl ethers were produced with high yields (Scheme 1, Table I). In the

Alkyl Aryl Ethers
2345
TABLE I Methylation of Phenolic Compounds with Trimethyl Phosphite
Entry
1
Substrate
Product
Time (s)
65
Yield (%)a
85
2
3
35
40
99b
92
4
5
6
7
8
9
55
90
93
88
86
85
84
74
120
180
180
150
10
11
150
180
76
72
aIsolated yields.
bTotal yield for the mixture of 2-methoxynaphthalene and 1-methyl-2-methoxyna-
phthalene.
case of 2-naphthol, a mixture of 2-methoxynaphthalene and 1-methyl-
2-methoxynaphthalene was produced with the ratio of 2 to 1 (Table I,
entry 2).
SCHEME 1
When trimethyl phosphate was used for the methylation of 2-
naphthol, 7-hydroxycoumarin and 4-methyl-7-hydroxycoumarin,
a mixture of C- and O-methylating products was obtained. Since

2346
M. R. Saidi and F. Rajabi
TABLE II C- and O-Methylation of Phenolic Compounds with Trimethyl
Phosphate
Entry
1
Substrate
2-naphthol
Product
Time (s) Yield (%)a
45
99
2
3
4-methyl-7-hydroxy
coumarin
100
90
84
81
7-hydroxy coumarin
aIsolated yields.
C-methylation of 2-naphthol is difficult and very time consuming,9
this process can be used for the preparation of 1-methyl-2-methoxy-
naphthalene, 8-methyl-7-methoxycoumarin and 4,8-dimethyl-7-
methoxycoumarin and two other phenolic compounds (Table II). By
changing the irradiation time or microwave power, the ratio of C-
to O-methylated products was not changed. Under these conditions
1-naphthol and other phenolic compounds gave only O-methylating
products.
CONCLUSION
In conclusion, we report a mild and efficient method for the methyla-
tion of phenolic compounds by using trimethyl phosphite or trimethyl
phosphate as the methylating agent under microwave irradiation and
environmentally benign solvent-free condition with good to excellent
yields.
EXPERIMENTAL
General
All yields refer to isolated products. The products were identified by
comparison of their physical and spectral data (IR, NMR, and MS) with
those obtained for known samples. The purity of the products was deter-
mined with TLC and GC. NMR spectra were recorded on a Bruker ACF

Alkyl Aryl Ethers
2347
500. IR spectra were measured with the Perkin Elmer 1600 FTIR spec-
trometer. Mass spectra were obtained on Fisson 800 Trio, and GC-Mass
HP 5973 MSD.
General Procedure for O-Methylation of Phenolic
Compounds
A mixture of phenol (1.5 mmol), trimethyl phosphite or trimethyl
phosphate (1.6 mmol), and BF3/ether (1.0 mL) were placed in a closed
glass container and subjected to microwave irradiation in a conven-
tional oven with high power for 30 s to 3 min. After cooling, the mixture
was diluted with CH2Cl2 (20 mL) and washed with a 5% solution of
sodium hydroxide (2 × 20 ml) and then with water (2 × 20 ml), dried
over MgSO4, and evaporated to get the pure products.
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2348
M. R. Saidi and F. Rajabi
APPENDIX 1
Selected spectroscopic data: 2-Methoxy naphthalene, 1, Solid, m.p.,
69–72◦C (lit., m.p. 70–73◦C);10a 1H NMR (500 MHz, CDCl3), δ 3.98 (s,
3H), 7.30–7.32 (m, 1H), 7.39–7.41 (m, 1H), 7.53–7.56 (m, 1H), 7.64–7.67
(m, 1H), 7.90–7.98 (m, 3H); 13C NMR (125 MHz, CDCl3), δ 55.7 (CH3),
106.4 (CH), 119.4 (CH), 124.1 (CH), 126.9 (CH), 127.8 (CH), 128.4 (CH),
129.6 (C), 130.1 (CH), 135.3 (C), 158.3 (C). IR (KBr), ν 3059.5, 3030.7,
3000.0, 2953.2, 1600.3, 1498.6, 1247.6, 1040.4, 784.6, 690.1 cm−1
.
7-Methoxy 4-methyl coumarin, 4, Solid, m.p. 159–161◦C (lit. m.p.
161–162◦C),10b 1H NMR (500 MHz, CDCl3), δ 2.36 (s, 3H), 3.87 (s, 3H),
6.11 (s, 1H), 6.78 (d, J = 2.3 Hz), 6.84 (m, 1H) , 7.47 (d, J = 8.7 Hz);
13C NMR (125 MHz, CDCl3), δ 19.0 (CH3), 56.0 (CH3), 96.5 (CH), 101.2
(CH), 112.4 (C), 113.9 (CH), 152.6 (C), 155.7 (C), 161.3 (C), 163.0 (C);
MS, 190 (M+), 162, 147 (base peak), 91, 77; IR (KBr), ν, 3356.6, 3097.2,
2961.2, 1730.5, 1523.1, 1445.3, 1392.3, 1261.3, 1051.5 cm−1
.