Microwave-assisted methylation of carboxylic acids and phenolic compounds with dimethyl-carbonate under solvent-free condition

Article abstract of DOI:10.1081/SCC-200036622

Phenolic compounds and carboxylic acids are methylated with dimethyl carbonate in the presence of a catalytic amount of BF₃· OEt₂, DBU, or KOH, in good to excellent yields under microwave irradiation and solvent-free conditions.

Full text of DOI:10.1081/SCC-200036622

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Microwave‐Assisted
Methylation of Carboxylic
Acids and Phenolic
Compounds with
Dimethyl‐Carbonate Under
Solvent‐Free Condition
a
a
Fatemeh Rajabi & Mohammad R. Saidi
a
Department of Chemistry, Sharif University of
Technology, PO Box 11365‐9516, Tehran, Iran
Version of record first published: 10 Jan 2011.
To cite this article: Fatemeh Rajabi & Mohammad R. Saidi (2004):
Microwave‐Assisted Methylation of Carboxylic Acids and Phenolic Compounds with
Dimethyl‐Carbonate Under Solvent‐Free Condition, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry,
34:22, 4179-4188
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w
SYNTHETIC COMMUNICATIONS
Vol. 34, No. 22, pp. 4179–4188, 2004
Microwave-Assisted Methylation of
Carboxylic Acids and Phenolic Compounds
with Dimethyl-Carbonate Under
Solvent-Free Condition
*
Fatemeh Rajabi and Mohammad R. Saidi
Department of Chemistry, Sharif University of Technology, Tehran, Iran
ABSTRACT
Phenolic compounds and carboxylic acids are methylated with dimethyl
.
carbonate in the presence of a catalytic amount of BF3 OEt , DBU, or
2
KOH, in good to excellent yields under microwave irradiation and
solvent-free conditions.
Key Words: Carboxylic acid; Dimethyl carbonate; Methylation; Micro-
wave irradiation; Phenolic compounds.
Methylation of carboxylic acids and phenolic compounds are industrially
[
1]
important process in chemistry. Although many effective and reliable
protocols for the synthesis of methyl esters and methyl aryl ethers have
*
Correspondence: Mohammad R. Saidi, Department of Chemistry, Sharif University
of Technology, PO Box 11365-9516, Tehran, Iran; E-mail: saidi@sharif.edu.
4
179
DOI: 10.1081/SCC-200036622
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

4
180
Rajabi and Saidi
been reported in the literature, the common approaches to the synthesis of
these compounds are methylating with hazardous reagents such as methyl
iodide, dimethyl sulfate, orthoesters, and diazomethane, or methylating with
[2]
nontoxic reagents under harsh condition, using a solvent such as DMF.
Furthermore, the development of an environmentally friendly process for
[3]
synthesis of these compounds has also attracted extensive attention.
More recently, methylation of phenols and NH-containing heteroaromatic
compounds have been reported with dimethyl carbonate using a tertiary amine
base such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or DABCO under
conventional thermal heating with long reaction time. The rate enhancement
was accomplished by applying microwave irradiation using CH CN or
3
DMF as solvent. The same microwave reaction further accelerated by
charging one equiv. of expensive phase-transfer catalyst such as tetrabutyl-
[
4]
ammonium iodide (TBAI) to the reaction mixture.
Solvent-free media under microwave irradiation are gaining more
widespread use in organic chemistry. The published examples clearly show
that microwave energy significantly reduces reaction time for a diverse
selection of chemical processes traditionally performed under external
[5]
heating. In continuation of our work on solvent-free and microwave-assisted
[6]
organic reactions, we now report a very simple, fast, and general method for
the O-methylation of carboxylic acids and phenolic compounds without
using a first solvent with dimethyl carbonate (DMC) in the presence of
.
BF3 OEt as a catalyst, under microwave irradiation with excellent yields.
2
DMC is a green reagent and generates methanol and CO as by-products
2
after reaction. The methylating activity of DMC has been widely studied in
[7,8]
recent years.
When phenolic compounds were reacted with DMC in the presence of
.
catalytic amounts of BF3 OEt (ca. 0.2 equiv.) under microwave irradiation
2
and solvent-free conditions, the corresponding O-methylated compounds
were obtained in good yields (Scheme 1, Table 1). The same results were
obtained when carboxylic acids or phenolic compounds were reacted with
DMC in the presence of 0.1 equiv. of 1,8-diazabicyclo[5.4.0]undec-7-ene
(
DBU) under microwave irradiation in about 1 min (Tables 1 and 2). We
also studied methylation of carboxylic acids in the presence of potassium
hydroxide as a base under solvent-free conditions and microwave irradiation.
Although KOH is very cheap reagent and methylation reaction was carried out
under solvent-free conditions, comparison of the yields and the reaction times
in Table 1 clearly shows that by using DBU, better yields of methylating
products were obtained with shorter reaction times. It should be pointed out
that the methylation of carboxylic acids did not proceed without using DBU
or KOH as a base. Thus, methylation reaction of 2-hydroxy benzoic acid
(
salicylic acid) with DMC in the presence of 0.1 equiv. of DBU in DMF

Methylation of Carboxylic Acids and Phenolic Compounds
4181
Scheme 1.
(
Table 2, entry 7) gave methyl 2-methoxybenzoate in high yield. All products
were known and identified by comparison with the literature known NMR
data.
In conclusion, the results obtained in this study reveal that a clean, fast,
efficient, environmentally benign and solvent-free O-methylation of phenolic
compounds can be carried out with dimethyl carbonate (DMC) as a methy-
.
lating agent in the presence of catalytic amounts of BF3 OEt under micro-
2
wave irradiation with good to excellent yields. Methylation of carboxylic
acids was carried out in the presence of catalytic amounts of DBU or KOH.
Although, by using KOH, lower yields of methylating products were obtained
with longer reaction time compared with DBU, no solvent was used in this
method.
EXPERIMENTAL
NMR spectra were recorded on a Bruker ACF 500. IR spectra were
measured with Perkin–Elmer 1600 FTIR and on Matt Son 1000 Unicam
FTIR spectrophotometers.
General Procedure for O-Methylation of Phenolic Compounds
with DMC Under Solvent-Free Condition.
A mixture of phenol (5 mmol), dimethyl carbonate (10 mmol) and
.
BF3 OEt (1 mmol) was placed in a sealed teflon container (screw cap type,
2
5
0 mL) and subjected to microwave irradiation in a conventional microwave

4
182
Rajabi and Saidi

Methylation of Carboxylic Acids and Phenolic Compounds
4183

4
184
Rajabi and Saidi

Methylation of Carboxylic Acids and Phenolic Compounds
4185

4
186
Rajabi and Saidi
oven with high power for 1–5 min (Table 2). After cooling, the mixture
was diluted with CH Cl (20 mL) and washed with 5% solution of sodium
2
2
hydroxide (2 ꢀ 20 mL) and then with water (2 ꢀ 20 mL), dried over
MgSO4, and evaporated to give the pure products. Further purification was
carried out by column chromatography on basic alumina eluting with ethyl
acetate/hexane, if needed. All compounds were characterized on the basis
of spectroscopic data (IR, NMR, and MS) and by comparison with those
reported in the literature.
General Procedure for O-Methylation Carboxylic Acids or
O-Methylation of Phenolic Compounds with DMC in the
Presence of DBU
A mixture of phenol or carboxylic acid (5 mmol), DMC (10 mmol), DBU
0.5 mmol), and DMF (5 mL) was placed in a sealed teflon container (screw
(
cap type, 50 mL) and subjected to microwave irradiation in a conventional
microwave oven with high power for 30 sec to 4.0 min. After cooling, the
mixture was diluted with CH Cl (20 mL), washed with 5% solution of
2
2
sodium hydroxide (2 ꢀ 20 mL), washed with 5% solution of HCl
(
2 ꢀ 20 mL), and with water (2 ꢀ 20 mL), dried over MgSO4, and evaporated
to give the pure products. Further purification was carried out by column
chromatography on basic alumina eluting with ethyl acetate/hexane, if
needed. All compounds were characterized on the basis of spectroscopic
data (IR, NMR, and MS) and by comparison with those reported in the
literature.
General Procedure for O-Methylation Carboxylic Acids with
DMC in the Presence of KOH
A mixture of phenol or carboxylic acid (5 mmol), DMC (10 mmol), and
KOH (5 mmol) was placed in a sealed teflon container (screw cap type,
50 mL) and subjected to microwave irradiation in a conventional microwave
oven with high power for 30 sec to 4.0 min. After cooling, the mixture was
diluted with CH Cl (20 mL) and washed with water (2 ꢀ 20 mL), dried
2
2
over MgSO , and evaporated to give the pure products. Further purification
4
was carried out by column chromatography on basic alumina eluting with
ethyl acetate/hexane, if needed. All compounds were characterized on the
basis of spectroscopic data (IR, NMR, and MS) and by comparison with
those reported in the literature.

Methylation of Carboxylic Acids and Phenolic Compounds
4187
Methoxy Naphthalene, 4b
1
Solid, mp, 69–728C (lit., mp 70–738C); H NMR (500 MHz, CDCl ): d
3
3
7
.98 (s, 3H), 7.30–7.32 (m, 1H), 7.39–7.41 (m, 1H), 7.53–7.56 (m, 1H),
1
.64–7.67 (m, 1H), 7.90–7.98 (m, 3H); C NMR (125 MHz, CDCl ): d 5.7
3
3
(CH ), 106.4 (CH), 119.4 (CH), 124.1 (CH), 126.9 (CH), 127.8 (CH), 128.4
3
(
CH), 129.6 (C), 130.1 (CH), 135.3 (C), 158.3 (C); IR: (KBr), y, 3059.5,
2
1
3
030.7, 3000.0, 2953.2, 1600.3, 1498.6, 247.6, 1040.4, 784.6, 690.1 cm
.
7-Methoxy 4-Methyl Coumarin, 4c
1
Solid, mp 159–1618C (lit., mp 161–1628C), H NMR (500 MHz,
CDCl ), d 2.36 (s, 3H), 3.87 (s, 3H), 6.11 (s, 1H), 6.78 (d, J ¼ 2.3 Hz), 6.84
3
1
3
(
m, 1H), 7.47 (d, J ¼ 8.7 Hz); C NMR (125 MHz, CDCl ): d 19.0 (CH ),
3
3
5
1
7
1
6.0 (CH3), 96.5 (CH), 101.2 (CH), 112.4 (C), 113.9 (CH), 152.6 (C),
55.7 (C), 161.3 (C), 163.0 (C); MS, 190 (Mþ), 162, 147 (base peak), 91,
7; IR: (KBr), y, 3356.6, 3097.2, 2961.2, 1730.5, 1523.1, 1445.3, 1392.3,
2
1
261.3, 1051.5 cm
.
ACKNOWLEDGMENT
We are grateful to the Sharif University of Technology Research Council
for financial support of this research.
REFERENCES
. (a) Henk, L.; Aalten, H.L.; Koten, G.; Grove, D.; Kuilman, M.T.;
1
Piekstra, O.G.; Lumbertus, A.; Hulshof, L.A.; Roger, A.; Sheldon, R.A.
Tetrahedron 1989, 45, 5565; (b) Grinev, A.N.; Ryabova, S.Yu. Chem.
Heterocycl. Compd., Engl. Transl. 1982, 18, 153; (c) Kotake, Y.;
Okauchi, T.; Jijima, A.; Yoshimatsu, K.; Nomura, H. Chem. Pharm.
Bull. 1995, 43, 829.
2
. (a) Minisci, F.; Vismara, E.; Fontana, F. J. Org. Chem. 1989, 54, 5224;
(b) Zabirov, N.G.; Shamsevaleev, F.M.; Cherkasov, R.A. J. Gen. Chem.
USSR, Engl. Transl. 1990, 60, 464; (c) Mizrakh, L.I.; Polonskaya, L.Yu.;
Gvozdetskii, A.N.; Ivanova, T.M.L.; Karpunina, B. Chem. Heterocycl.
Compd., Engl. Transl. 1990, 26, 482; (d) Jursic, B.; Bregant, N. Synth.
Commun. 1989, 19, 2087; (e) Leggio, A.; Liguori, A.; Napoli, A.;
Siciliano, C.; Sindona, G. J. Org. Chem. 2001, 66, 2246; (f) Sulko, J.
J. Acta Pol. Pharm. 2000, 57, 79.

4
188
Rajabi and Saidi
3
. (a) Green, T.W.; Wuts, P.G.M. Protective Groups In Organic Synthesis,
nd ed.; John Wiley & Sons, Inc.: New York, 1991; 224–276;
b) Lee, A.S.; Yang, H.; Su, F. Tetrahedron Lett. 2001, 42, 301.
2
(
4. Shieh, W.; Dell, S.; Bach, A.; Repic, O. Org. Lett. 2001, 3, 4279.
5. Shieh, W.; Dell, S.; Bach, A.; Repic, O. Tetrahedron Lett. 2002, 43, 5607.
6. (a) Saidi, M.R.; Bigdeli, K. J. Chem. Res. (S) 1998, 800; (b) Sharifi, A.;
Mojtahedi, M.M.; Saidi, M.R. Tetrahedron Lett. 1999, 40, 2661;
(
c) Mojtahedi, M.M.; Saidi, M.R.; Heravi, M.M.; Bolourtchian, M.
Monash. Chem. 1999, 130, 1175; (d) Mojtahedi, M.M.; Saidi, M.R.;
Bolourtchian, M.; Heravi, M.M. Phosphorus, Sulfur, and Silicon 2002,
177, 289; (e) Saidi, M.R. Indian J. Chem. 1982, 21B, 474; (f) Saidi, M.R.;
Rajabi, F. Heterocycles 2001, 55, 1805.
. (a) Katritzky, A.R.; Singh, S.K. J. Org. Chem. 2002, 67, 9077;
7
(
b) Pottorof, R.S.; Chadha, N.K.; Katkevics, M.; Ozola, V.; Suna, E.;
Ghane, H.; Regberg, T.; Player, M.R. Tetrahedron Lett. 2003, 44, 175;
c) Ferret, R.R.; Hyde, M.J.; Lahti, K.A.; Friebe, T.L. Tetrahedron Lett.
(
2
6
003, 44, 2573; (d) Villemin, D.; Caillot, F. Tetrahedron Lett. 2001, 42,
39; (e) Ouk, S.; Thiebaud, S.; Borredon, E.; Legars, P.; Lecomte, L.
Tetrahedron Lett. 2002, 43, 2661; (f) He, H.; Wu, Y.-J. Tetrahedron
Lett. 2003, 44, 3445.
. (a) Shieh, W.; Dell, S.; Bach, A.; Repic, O. J. Org. Chem. 2002, 67, 2188;
8
(b) Selva, M.; Tundo, P.; Pesora, A. J. Org. Chem. 2002, 67, 9238;
(c) Perosa, A.; Selva, M.; Tundo, P.; Zordan, F. Synlett 2000, 272;
(d) Kirumakki, S.R.; Nagaraju, N.; Murthy, K.V.V.S.B.S.R.;
Narayanan, S. Applied Catal. 2002, 226, 175; (e) Lee, Y.; Shimizu, I.
Synlett. 1998, 1063; (f) Bomben, A.; Marques, C.A.; Selva, M.;
Tundo, P. Tetrahedron 1995, 51, 11573; (g) Bomben, A.; Selva, M.;
Tundo, P. J. Chem. Res. (S) 1997, 2688.
Received in the UK December 12, 2003