394 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 394^395y
Demethylation of Methyl Aryl Ethers using
Pyridine Hydrochloride in Solvent-free
Conditions under Microwave Irradiationy
P. P. Kulkarni,a A. J. Kadam,a R. B. Mane,a Uday V. Desai*a
and P. P. Wadgaonkarb
aDepartment of Chemistry, Shivaji University, Kolhapur-416004, Maharashtra, India
bNational Chemical Laboratory, Pune-8, India
Methyl aryl ethers are deprotected in high yields using pyridine hydrochloride in the absence of solvent under
microwave irradiation
Table 1 MW assisted demethylation of methyl aryl ethers
Ethers are the most useful protective groups in synthetic
organic chemistry.1 Methylation of phenolic hydroxy
moieties is considered to be the most e¡ective protection
OMe
OH
py•HCl
methodology owing to its high stability under a variety
of reaction conditions and easy regeneration via
demethylation. There are several reagents for the
deprotection of methyl aryl ethers. Some of the classical
reagents developed for this purpose include Lewis acids such
MW 14–16 min.
R
R
MW
heating
time/min (%)
2f
as BBr3,2a AlI3,2a BeCl2,2c, AlCl3,2d AlH2Cl,2e Py HBr3
Yielda
as well as trimethylsilyliodide,2g L-selectride,2h lithium
diphenylphosphide,2i KF^alumina,2j
pyridine hydro-
Entry
R
H
o-Me
m-Me
Mp/8C Bp/8C Lit./8C
chloride2k and CeTab with HCl.2l Most of these reagents
are expensive and require the use of solvents. Their use
has been reviewed earlier,3 and amongst these, pyridine
hydrochloride is the most favourable owing to its low cost,
ready availability and the fact that no solvent is required.
Methyl aryl ethers are generally di¤cult to demethylate
under mild reaction conditions and the drastic reaction con-
ditions required usually brings about structural and
stereochemical changes along with the formation of
by-products. We came across this di¤culty during
1
2
3
4
5
6
7
8
14
14
14
14
16
16
16
16
16
14
87
82
82
81
78
74
78
82
65
95
76
ö
ö
ö
ö
113
106
ö
ö
43
178
187
196
197
ö
182
191
202
202
116
109^111
235
217
45
p-Me
p-CHO
p-MeCO
p-Br
p-Cl
o-NO2
ö
232
214
ö
9
10
11
b-Naphthyl
118
110
ö
ö
122
ö
4,5-Dimethyl- 16
7-hydroxy-1-
tetralone
demethylation of 4,5-dimethyl-7-methoxy-1-tetralone
I
aYields refer to pure isolated products.
(Scheme 1) an important intermediate in the synthesis of
cacalol. The demethylation of I was achieved in 3 h using
pyridine hydrochloride,4;2k at 180^190 8C. During this, apart
from the desired phenolic tetralone II several by-products
were obtained which caused di¤culties in the isolation of
pure tetralone.
microwave irradiation (215 W) for 2 min. After each 2
min irradiation, the reaction mixture was cooled to room
temperature and reirradiated. Demethylation in most cases
was complete within 16 min. (2 Â 8 pulses).
In conclusion, we have presented here a simple, quick and
highly e¤cient method for demethylation of methyl aryl
ethers using pyridine hydrochloride, an easily available
reagent, in absence of solvent using microwave irradiation.
O
O
MeO
HO
py•HCl
185–190 ˚C 3 h
Experimental
I
II
General.öMicrowave irradiation was carried out using a commer-
cial microwave oven (BPL-Sanyo, BMO-700 T) operating at variable
frequency and the products obtained were analyzed by IR and
NMR spectroscopy.
Scheme 1
Methyl aryl ethers and pyridine hydrochloride were prepared by
Microwave dielectric heating has become an important
technique in organic syntheses and many classical organic
reactions are now carried out using it.5 This led us to
attempt the demethylation of tetralone I with pyridine
hydrochloride under microwave irradiation and the success-
ful demethylation prompted us to undertake the
demethylation of various methyl aryl ethers under similar
conditions.
standard methods.6
Microwave Assisted Demethylation of Methyl Aryl Ethers.öA
mixture of methyl aryl ether (0.01 mol) and pyridine hydrochloride
(0.05 mol) were placed in a stoppered round bottom £ask and
subjected to microwave irradiation at 215 W for various time
intervals. After complete conversion the reaction mixture was
decomposed using ice-water and extracted with diethyl ether. The
ether extract was repeatedly washed with water, dried over anhydrous
sodium sulfate and the ether removed to obtain the product.
Various methyl aryl ethers were deprotected (Table 1) by
heating a mixture of a methyl aryl ether and pyridine hydro-
Received, 16th February 1999; Accepted, 12th March 1999
Paper E/9/01278H
chloride in
a stoppered round bottom £ask, under
* To receive any correspondence.
References
y This is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).
1
T. W. Green and P. G. M. Wutz, Protective Groups in Organic
Synthesis, John Wiley, New York, 2nd edn., 1991.
Kulkarni
