Novel synthesis of monoethers of hydroquinone and resorcinol on soluble polymer-supports

Article abstract of DOI:10.1081/SCC-120014979

Monoethers of hydroquinone and resorcinol were easily prepared using PEG as soluble polymer-supports, monoprotection group and phase transfer catalyst with good yields and high selectivity of functionlization in homogenous solution.

Full text of DOI:10.1081/SCC-120014979

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NOVEL SYNTHESIS OF MONOETHERS OF HYDROQUINONE
AND RESORCINOL ON SOLUBLE POLYMER-SUPPORTS
Guichun Yang a , Zuxing Chen a , Zhaojun Zhang a & Xiaoling Qiu a
a Faculty of Chemistry and Material Science , Hubei University , Wuhan, Hubei, 430062, P.R.
China
Published online: 16 Aug 2006.
To cite this article: Guichun Yang , Zuxing Chen , Zhaojun Zhang & Xiaoling Qiu (2002) NOVEL SYNTHESIS OF MONOETHERS OF
HYDROQUINONE AND RESORCINOL ON SOLUBLE POLYMER-SUPPORTS, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 32:23, 3637-3642, DOI: 10.1081/SCC-120014979
To link to this article: http://dx.doi.org/10.1081/SCC-120014979
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 23, pp. 3637–3642, 2002
NOVEL SYNTHESIS OF MONOETHERS
OF HYDROQUINONE AND RESORCINOL
ON SOLUBLE POLYMER-SUPPORTS
*
Guichun Yang, Zuxing Chen, Zhaojun Zhang,
and Xiaoling Qiu
Faculty of Chemistry and Material Science,
Hubei University, Wuhan, Hubei, 430062, P.R. China
ABSTRACT
Monoethers of hydroquinone and resorcinol were easily pre-
pared using PEG as soluble polymer-supports, monoprotec-
tion group and phase transfer catalyst with good yields and
high selectivity of functionlization in homogenous solution.
Key Words: Synthesis; Monoethers; Hydroquinone; Resor-
cinol; Soluble polymer-supports
It is known those monoethers of hydroquinone or resorcinol are useful
synthetic intermediates for the construction of various chemically and bio-
logically significant molecules.[1] Therefore, a general method of the rapid
synthesis of those molecules would be of great value and has been reported.
Such as: reaction of mono or bis salts of hydroquinone with alkyl halide,[2]
demethylation of the bis methyl ether of resorcinol,[3] reaction of trialkyl
phosphites with hydroquinone,[4] reaction of hydroquinone with methanol
using heteropolyacids or other acids as catalyst,[5] reaction of hydroquinone
*Corresponding author. E-mail: ygc33@163.net
3637
DOI: 10.1081/SCC-120014979
Copyright & 2002 by Marcel Dekker, Inc.
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3638
YANG ET AL.
with alkyl halide using Al2O3-supported K2CO3 as a base reagent,[6]
deprotection of benzyloxy using H2/10% Pd-C after reaction of benzyloxy
phenols with alkyl halide.[7] However each of the above methods suffered
from a least one of the following drawbacks: (1) very low yields of mono-
ether, (2) long reaction time, (3) necessary presence of a PTC, (4) expensive
or not readily available reagents, (5) high reaction temperature, or (6)
tedious work up procedures.
Functionalized insoluble polymers for use as protection groups have
been received a great deal of attention in organic synthesis in recent years.[8]
The reaction of hydroquinone or resorcinol on anion exchange resins with
alkyl halide gave mixture of the monoether, diether and hydroquinone or
resorcinol itself.[9] Leznoff reported the synthesis of monoether of symme-
trical dihydroxy aromatic compounds using insoluble polymer as mono-
protection group.[10] However there were drawbacks such as lower
reactivity, extend reaction time and difficulty of monitoring the reaction
progress and configuration of polymer-bound products.
Soluble polymers have been widely applied in organic synthesis, com-
bines the strategical features of solution and solid-phase methods.[11,12]
Poly(ethylene glycol) (PEG) are greatly used as soluble polymers-supports
in organic synthesis, readily functionalized with different spacer and
linker, soluble in many organic solvents and insoluble in poorly polar
solvent. Thus one can carry out a reaction on a modified PEG immobilized
compound in homogenous condition.
Having the above facts in mind and in continuation of our efforts to
utilize soluble polymer-supported systems in organic synthesis.[13] We now
first report in this article the synthesis of monoethers of hydroquinone and
resorcinol using PEG as soluble polymer-supports, monoprotection group
and phase transfer catalyst (Sch. 1).
Considering the balance between loading capacity and the solubility
profile of the resulting polymer derivative, we choose PEG (MW 4000)
as soluble polymer-supports, monoprotection group and phase transfer
Scheme 1.

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MONOETHERS OF HYDROQUINONE AND RESORCINOL
3639
catalyst in synthesis of a monoethers of hydroquinone and resorcinol. PEG
reacted with excess of oxalyl chloride to give PEG-bound acid chloride 1
through ester linkage. The reaction proceed to completion as evidenced by
disappearance of hydroxy, the appearance of ester group and acid chloride
at 1737 and 1785 cmꢀ1 in the IR spectrum. Without further purification, the
PEG-bound acid chloride reacted with excess of 2 to give their respective
PEG-bound phenolic ester 3, in which one of the hydroxy groups was
attached to the PEG through an ester linkage. 3 were easily isolated by
precipitation with cold ether to remove excessive starting materials and
by-products, reacted with R3X in DMF in the presence of K2CO3 to give
PEG-bound monoether 4, meanwhile PEG can act as phase transfer
catalyst.[14,15] Hydrolysis of 4 with 10% NaOH and acidification with
10% HCl until pH ¼ 5 gave monoether 5 which were analyzed on
thin-layer chromatography (CHCl3/ethyl acetate ¼ 4/1 as eluant) to show
containing a little 2 and no diether. Selective functionlization yields have
been improved. Table 1 includes representation examples.
For comparison, we have also investigated the synthesis of monoethers
of hydroquinone and resorcinol using conventional, non-polymeric reagents
methods (Sch. 2).[16] Obtained products were a mixture containing
unreacted starting materials, mono- and di-alkyl ethers, but monoether
was less than 30%. This method proved lower selectivity of functionaliza-
tion and difficult to work up (Table 2).
It is worthy of note that the reaction was easily carried out using PEG
as soluble polymer-supports, monoprotection group and phase transfer cat-
alyst in mild conditions with high selectivity of functionalization, the product
was easily isolated and purified by simply precipitating the polymer by
Table 1. Preparation of Monoether of Hydroquinone and Resorcinol Using PEG
as Soluble Polymer-Supports
5
R1
R2
R3
R4
R5
Yielda,b (%)
a
b
c
d
e
f
OH
OH
OH
OH
H
H
H
H
H
CH3
OCH3
H
H
H
H
OCH3
50.6
53
65
33.7
51.7
50
56
30.5
H
H
H
CH2CH¼CH2 OCH2CH¼CH2
PhCH2
C2H5
OPhCH2
OC2H5
H
H
H
H
OH CH3
OH CH2CH¼CH2
OH PhCH2
OH C2H5
OCH2CH¼CH2
g
h
OPhCH2
OC2H5
b
aIsolated yields; Products were characterised by comparison of their physical data,
1
IR, H NMR spectra with known samples.

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3640
YANG ET AL.
Scheme 2.
Table 2. Preparation of Monoether of Hydroquinone and Resorcinol Using
Conventional, Non-polymeric Reagents Methods
5
R1
R2
R3
R4
R5
Yielda (%)
a
b
c
d
e
f
OH
OH
OH
OH
H
H
H
H
H
CH3
OCH3
H
H
H
H
OCH3
28.5
27.8
29.6
22.5
30.0
25.6
21.9
19.6
H
H
H
CH2CH¼CH2 OCH2CH¼CH2
PhCH2
C2H5
OPhCH2
OC2H5
H
H
H
H
OH CH3
OH CH2CH¼CH2
OH PhCH2
OH C2H5
OCH2CH¼CH2
g
h
OPhCH2
OC2H5
aIsolated yields.
addition of Et2O and removing the unreacted materials and by-product by
filtration, avoiding tedious work up procedures in contrast to using conven-
tional, non-polymeric reagents methods. Isolation purity were easily fol-
lowed by TLC analysis to observe disappearing of lower molecular
reagent by precipitation and washed with cold Et2O, the PEG-bound
1
product configuration was readily analyzed by H NMR and IR without
detaching material from the polymer-supports in each step of the sequences
in contrast to insoluble polymers for use as polymer-supports and
protection groups.
In conclusion, we have developed the new liquid phase combinatorial
synthesis of monoethers of hydroquinone and resorcinol with good yields
and selectivity using modified PEG as soluble polymer-supports, mono-
protection groups and phase transfer catalyst.
EXPERIMENTAL
All organic solvents were dried by standard methods. All PEG samples
were melted at 80ꢁC in vacuum for 30 min before use to remove traces of
moisture. Melting points were determined on a Electrothermal melting point

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MONOETHERS OF HYDROQUINONE AND RESORCINOL
3641
apparatus and are uncorrected. IR spectra were recorded using KBr pellets
1
on a IR-Spectrum One (PE). H NMR spectra were recorded on Brucker
Ac-80 instrument using CDCl3 as solvents and TMS as internal standard.
Synthesis of Monoether of Hydroquinone and Resorcinol
Using PEG as Soluble Polymer-Supports
Preparation of PEG-bound acid chloride 1 and general procedure for
the preparation of PEG-bound monoesters 3. To a ice-cold solution of
oxalyl chloride (1.4 mL, 16 mmol) in CH2Cl2 (250 mL) was added the
solution of PEG 4000 (28 g, 14 mmol-OH), pyridine (2.8 mL, 34 mmol)
and CH2Cl2 (150 mL) with stirring. After 2h, 2 (20 mmol) was added and
the mixture was stirred 18 h at r.t. After precipitation with cold ether, wash-
ing with ether and recrystallization from absolute cold ethanol, white solid
(97%) was obtained. TLC showed that the solid contained no 2 (acetone/
petroleum ether ¼ 1/3 as eluant), which could be illustrated by IR and
1H NMR.
General procedure for the preparation of PEG-bound monoether 4:
K2CO3 (0.8 g, 6 mmol) and alkyl halide (10 mmol) were added to a solution
of 3 (6.0 g) in DMF (60 mL). The mixture was stirred for 18 h at r.t., filtered
to remove K2CO3, concentrated the filter liquor under vacuum until slightly
viscous, purification by precipitation in cold Et2O to give 4.
General procedure for the preparation of 5: 4 (5.6 g) was added to
solution of 1 mol/L NaOH (30 mL). The mixture was stirred for 2h at r.t.,
slowly dropwise added HCl (2mol/L) until pH ¼ 5, extracted with Et2O and
organic layer were washed with saturated brine and dried with dry MgSO4,
evaporated of the solvent under vacuum to give small volume residue, which
was purified by flash chromatography (CHCl3/ethyl acetate ¼ 4/1 as eluant)
to afford 5.
General Procedure for the Preparation of 5 Using Conventional,
Non-polymeric Reagents Methods
To a solution of 2 (20 mmol) and alkyl halide (20 mmol) in C2H5OH
(25 mL), NaOH (20 mmol) in water (3 mL) was added dropwise under reflux
within 60 min and the reaction mixture was further stirred for 7 h under
reflux, evaporated to leave a residue that was dissolved in 30 mL H2O and
further neutralized with dilute aqueous solution of hydrochloric acid until
pH ¼ 5, extracted with Et2O and organic layer were washed with saturated
brine and dried with dry MgSO4, evaporated of the solvent under vacuum to

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3642
YANG ET AL.
give small volume residue, which was purified by flash chromatography
(CHCl3/ethyl acetate ¼ 4/1 as eluant) to afford 5.
ACKNOWLEDGMENTS
This work was financially supported by the education department of
Hubei province and University of Hubei.
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Received in the UK June 26, 2001