First preparation of a novel polyol resin for purifying arylboronic acids

Article abstract of DOI:10.1016/j.cclet.2012.06.018

A novel polystyrene-supported triol resin was first prepared by reaction of the Merrifield resin with trometamol. Using this resin, arylboronic acids were efficiently isolated and purified through a capture-release procedure in organic solvents. However, in basic aqueous solvents arylboronic acids were immobilized on the resin only with low yield.

Full text of DOI:10.1016/j.cclet.2012.06.018

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 993–995
www.elsevier.com/locate/cclet
First preparation of a novel polyol resin for
purifying arylboronic acids
*
Fu Long Liu, Sheng Biao Wan, Tao Jiang
Key Laboratory of Marine Drugs, Chinese Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience & Glycotechnology,
School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
Received 6 April 2012
Available online 18 July 2012
Abstract
A novel polystyrene-supported triol resin was first prepared by reaction of the Merrifield resin with trometamol. Using this resin,
arylboronic acids were efficiently isolated and purified through a ‘‘capture-release’’ procedure in organic solvents. However, in
basic aqueous solvents arylboronic acids were immobilized on the resin only with low yield.
# 2012 Tao Jiang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Polystyrene-supported polyol resin; Arylboronic acid; Immobilization
Boronic acids have become an extremely important reagents in organic chemistry and medicinal chemistry. They
are widely used in organic synthesis with the developments in Miyaura–Suzuki couplings, copper-catalyzed
arylboronic acid–heteroatom coupling and the Petasis reactions [1–3]. They are also used as biologically active agents
such as protease enzyme inhibitors, boron neutron capture agents for brain tumors, carbohydrate sensors[4–6].
However, boronic acids are difficultly isolated and purified by conventionals methods due to their polarity and
unstability [7]. Arylboronic acids could form five or six-membered cyclic boronic esters with cis-diol or catechol,
especially in anhydrous organic solvents [8]. Accordingly, many diol-based insoluble resins have been used to isolate
boronic acids, such as the N,N-diethanolaminomethyl polystyrene resin (DEAM-PS), and catechol polystyrene resin
[9,10]. A patent on DEAM-PS resin has been applied because of the excellent property in isolating boronic acids [11].
Boronic acids could be immobilized on these resins quantitatively or with satisfying yield in anhydrous solvents,
particularly in THF. However, these resins were not efficient for the immobilization of boronic acids in water or water–
organic mixed solvents. Matteson reported a useful generalization on the process of the thermodynamic hydrolysis of
boronic esters in 1 mol/L aqueous sodium hydroxide (shown in Fig. 1) [12]. It was indicated that the major species
present was the bicyclic anion 1 by the 1H NMR spectrum. In the present study, we aim to synthesis a novel triol-based
resin to investigate its immobilization effect of arylboronic acids in the organic and basic aqueous solutions.
The Merrifield resin (chloromethyl polystyrene resin) is one of the most popular resin in solid-phase synthesis.
Treatment of the Merrifield resin (loading 1.2 mmol/g, 200À400 mesh) with trometamol in the presence of
* Corresponding author.
E-mail address: jiangtao@ouc.edu.cn (T. Jiang).
1001-8417/$ – see front matter # 2012 Tao Jiang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2012.06.018

994
F.L. Liu et al. / Chinese Chemical Letters 23 (2012) 993–995
Fig. 1. Hydrolysis of phenylboronic esters.
Scheme 1. Preparation of the triol resin.
diisopropylethylamine (DIPEA) in alcohol gave the desired triol resin (Scheme 1). The loading degree was determined
to be about 1.1 mmol/g by elemental analysis of the resin (anal. found C 85.57, H 7.81, N 1.53, Cl 0.05).
This triol resin was found to be efficient in immobilizing arylboronic acids in many organic solvents at room
temperature, which was slightly less efficient than reported DEAM-PS resin (Table 1, entries 1À3). The electron
donating or withdrawing group on phenyl ring had no obvious influence on the immobilizing effect (entries 4, 5).
Cleavage of the boronic acids from the resin was carried out in a THF/water/acetic acid (90/5/5) mixture solvent and
1
gave the pure products which were characterized by their H NMR spectra. The resin could be recycled with no
apparent loss of efficiency after neutralization with base washings (for example, triethylamine/THF 1/8) (entries 6, 7).
Moreover, the immobilization effect of arylboronic acids in aqueous solutions had been investigated (Table 2). The
resin had none effect in neutral aqueous solution (entry 1). Although the bicyclic anion 1 was the major species
present, the resin was not enough efficient in basic aqueous solutions due to the poor swelling of the resin in water
perhaps. The yield in 1 mol/L sodium hydroxide water solution was only 17%, and in the mixture of 4 mol/L sodium
Table 1
The immobilization of boronic acid in organic solventsa.
OH
OH
OH
H
N
O
H
N
B
R
OH
RB(OH)
THF/H O/AcOH
2
2
O
RB(OH)
2
90/5/5
Entry
R (equiv.)
Solvent
Yield (%)
1
4-Me-C6H4 (0.8)
4-Me-C6H4 (0.8)
4-Me-C6H4 (0.8)
C6H4 (0.8)
THF
DCM
EAC
THF
THF
THF
THF
89
75
83
84
90
84
87
2
3
4
5
3-NO2-C6H4 (0.8)
4-Me-C6H4 (0.8)
4-Me-C6H4 (0.8)
6b
7c
a
Immobilizationwascarriedout byshakinga slight excess ofresin1 (1.0 g)withtheboronicacid(0.88 mmol, 0.8 equiv.)inthegivensolvent (10 mL)
at room temperature for 12 h. Release was carried out by shaking the resin-bound boronic acid for 2 h in a THF/H2O/AcOH mixture (90/5/5).
b
The resin had been used for the second time.
c
The resin had been used for the third time.

F.L. Liu et al. / Chinese Chemical Letters 23 (2012) 993–995
995
Table 2
The immobilization of boronic acid in basic aqueous solutionsa.
OH
OH
OH
O
O
Na+
R
Na+
H
N
O
H
N
H
N
B-
B-
R
OH
O
O
OH
RB(OH)
NaOH
THF/H O/AcOH
2
2
RB(OH)
2
90/5/5
Entry
R (equiv.)
Solvent
Yield (%)
1
2
3
4
5
6
4-Me-C6H4 (0.8)
4-Me-C6H4 (0.8)
4-Me-C6H4 (0.8)
C6H4 (0.8)
H2O/MeOH (1/3)
1 N NaOH
<5
17
35
33
44
68
4 mol/L NaOH/MeOH (1/3)
4 mol/L NaOH/MeOH (1/3)
4 mol/L NaOH/MeOH (1/3)
1 mol/L NaOH in MeOH
3-NO2-C6H4 (0.8)
4-Me-C6H4 (0.8)
a
Immobilizationwas carriedoutbyshakinga slightexcess ofresin1(1.0 g)withtheboronicacid(0.88 mmol, 0.8 equiv.)inthegivensolvent (10 mL)
at room temperature for 24 h. Release was carried out by shaking the resin-bound boronic acid for 2 h in a THF/H2O/AcOH mixture (90/5/5).
hydroxide water solution and methanol (1/3) was not satisfying also (entries 2, 3). The yields were 14% and 22%,
respectively using DEAM-PS resin under the same conditions. The yield of 3-nitrophenylboronic acid was higher due
to the stronger acidity perhaps (entry 5). Boronic acid was obtained with 68% yield in basic methanol solution (entry
6), but was obtained with 41% yield using DEAM-PS resin.
In conclusion, a polystyrene-supported triol resin was first prepared conveniently. The resin could fish out the
desired arylboronic acid in organic solvents with satisfying yield. Unluckily, the resin had poor efficiency in aqueous
solutions. The efficiency of the resin was slightly less than DEAM-PS resin in organic solvents, but was slightly higher
in basic conditions. Further work on expanding the use of the resin is under way.
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