disclaimers-space.snu.ac.kr/bitstream/10371/127080/1/000000016919.pdf · 2019-11-14 · leaching of...
TRANSCRIPT
저 시-비 리- 경 지 2.0 한민
는 아래 조건 르는 경 에 한하여 게
l 저 물 복제, 포, 전송, 전시, 공연 송할 수 습니다.
다 과 같 조건 라야 합니다:
l 하는, 저 물 나 포 경 , 저 물에 적 된 허락조건 명확하게 나타내어야 합니다.
l 저 터 허가를 면 러한 조건들 적 되지 않습니다.
저 에 른 리는 내 에 하여 향 지 않습니다.
것 허락규약(Legal Code) 해하 쉽게 약한 것 니다.
Disclaimer
저 시. 하는 원저 를 시하여야 합니다.
비 리. 하는 저 물 리 목적 할 수 없습니다.
경 지. 하는 저 물 개 , 형 또는 가공할 수 없습니다.
공학석사학위논문
Microwave-Assisted C-C Coupling Reaction
using Polymer-supported Electron-Rich
Oxime Palladacycles in Aqueous Condition
전자가 풍부한 옥심 팔라다싸이클 수지를 이용한 수용액상의
마이크로파 탄소-탄소 짝지음 반응
2014년 2월
서울대학교 대학원
화학생물공학부
박 성 준
전자가 풍부한 옥심 팔라다싸이클 수지를 이용한 수용액상의
마이크로파 탄소-탄소 짝지음 반응
Microwave-Assisted C-C Coupling Reaction using
Polymer-supported Electron-Rich Oxime Palladacycles
in Aqueous Condition
지도교수 이 윤 식
이 논문을 공학 석사 학위논문으로 제출함
2014년 2월
서울대학교 대학원
화학생물공학부
박 성 준
박성준의 석사 학위논문을 인준함
2014 년 2 월
위 원 장 김영규 (인)
부 위 원 장 이윤식 (인)
위 원 이종찬 (인)
i
Abstract
Microwave-Assisted C-C Coupling Reaction
using Polymer-supported Electron-Rich
Oxime Palladacycles in Aqueous Condition
Sung Jun Park
Chemical and Biological Engineering
The Graduate School
Seoul National University
Oxime palladacycles are highly active palladium catalysts for C-C
coupling reactions, and possess advantages such as easy preparation,
and air, moisture stability. Previously, electron-rich oxime
palladacycle on polymer support has been prepared to provide
efficient C-C coupling activity and reusability of the catalyst for green
purposes. For water-based Suzuki coupling reaction, microwave
chemistry was applied to polymer-supported oxime palladacycle
system. Suzuki reaction of aryl halide and heterocyclic halide with
phenylboronic acid was successfully performed using polymer-
supported electron-rich oxime palladacyles under the microwave
system to acquire reaction products in water medium.
Keywords : Oxime palladacycle, Microwave, Suzuki-Miyaura
Reaction
Student number : 2012-20944
ii
TABLE OF CONTENTS
Abstract ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• i
List of Abbreviations ••••••••••••••••••••••••••••••••••••••••••••••••••••••••• v
List of Figures ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• vi
List of Tables •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• vii
List of Schemes •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• vii
1. Introduction ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 1
1.1. Electron-rich Oxime Palladacycle •••••••••••••••••••••••••••••••••••••••••••• 1
1.2. Microwave Application for Efficient Catalysis ••••••••••••••••••••••• 4
1.3. C-C Coupling Reactions in Water using Electron-rich Oxime
Palladacycle ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 7
1.4. Research Objectives ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 8
2. Experimental Section •••••••••••••••••••••••••••••••••••••••••••••••••••• 9
2.1. General ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 9
2.1.1. Materials •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 9
2.1.2. Instrument ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 9
2.2. Preparation of Electron-Rich Oxime Palladacycle Resins
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 11
2.2.1. Immobilization of 4′-Hydroxy-3, 5-Dimethoxyacetophenone
iii
Derivatives on CM PS •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 11
2.2.2. Preparation of Oxime Resins••••••••••••••••••••••••••••••••••••••••••••••••••••• 11
2.2.3. Preparation of Palladium Loaded Oxime Resins••••••••••••••••••• 12
2.3. Suzuki Coupling Reactions Catalyzed by Electron-Rich
Oxime Palladacycle Resins •••••••••••••••••••••••••••••••••••••••••••••••••• 13
2.3.1. Optimization of Suzuki Coupling Reactions ••••••••••••••••••••••••• 13
2.3.2. General Experimental Procedure for Suzuki Coupling Reac-
tion of Aryl Halides with Phenylboronic Acid•••••••••••••••••••••• 13
2.3.3. Reaction Profile of Suzuki Coupling Reaction using the
Microwave and Oil Bath••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 14
2.3.4. Reusability Test of Electron-Rich Oxime Palladacycle Resins
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 15
3. Results and Discussion •••••••••••••••••••••••••••••••••••••••••••••••• 16
3.1. Preparation and Characterization of Electron-Rich Oxime
Palladacycle Resins •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 16
3.1.1. Preparation of Oxime Resins ••••••••••••••••••••••••••••••••••••••••••••••••••••• 16
3.1.2. Characterization of Electron-Rich Oxime Palladacycle Resin
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 19
3.2. Suzuki Coupling Reaction Catalyzed by Electron-Rich Oxime
Palladacycle Resins•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 21
3.2.1. Effectes of Solvents and Bases in Suzuki Coupling Reaction
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 21
iv
3.2.2. Reaction Profile Comparison of Suzuki Coupling Reaction
by Microwave Heating and Conventional Heating ••••••••••••• 26
3.2.3. Suzuki Coupling Reaction of Various Aryl Halides with
Phenylboronic Acid ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 28
3.2.4. Suzuki Coupling Reaction of Various Aryl Halides with
Phenylboronic Acid in Water ••••••••••••••••••••••••••••••••••••••••••••••••••••• 31
3.2.5. Reusability Test of Electron-Rich Oxime Palladacycle Resins
for Suzuki Coupling Reaction •••••••••••••••••••••••••••••••••••••••••••••••••••• 35
4. Conclusion •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 37
References •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 38
Abstract in Korean •••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 42
v
List of Abbreviations
CMPS Chloromethyl Polystyrene
DVB Divinylbenzene
DMF N,N -dimethylformamide
EtOH Ethyl Alcohol
EA Elemental Analysis
EDX Energy Dispersive X-ray Spectrometer
FE-SEM Field Emission Scanning Electron Microscopy
FT-IR Fourier Transform-Infrared Spectroscopy
GC-MS Gas Chromatography/Mass Spectroscopy
ICP-AES Inductively Coupled Plasma-Atomic
Emission Spectroscopy
MeOH Methyl Alcohol
NHC N-Heterocyclie Carbene
Pd Palladium
PTC Phase Transfer Catalysis
PVP Polyvinylpyrrolidone
RT Room Temperature
TBAB Tetra-N-Butyl Ammonium Bromide
TEA Triethylamine
THF Tetrahydrofuran
XPS X-ray Photoelectron Spectroscopy
vi
List of Figures
Figure 1. Palladium catalysts on various supports •••••••••••••••••••••••••••••••• 3
Figure 2. Mechanisms and Thermal Gradient of Microwave Heating
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 6
Figure 3. FT-IR spectra of ketone resins and oxime resins (Ketone
group: 1679 cm-1, Hydroxyl group: 3374 cm-1) ••••••••••••••••• 18
Figure 4. FE-SEM Image of CMPS Resins (a) and Oxime
Palladacycle Resins (b) ••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 20
Figure 5. Analysis of Chloro-Bridged, Divalent Palladium on Oxime
Palladacycle Resin by EDX (a) and XPS Analysis (b).
Binding Energy (eV) is shown in (c) •••••••••••••••••••••••••••••••••• 20
Figure 6. Reaction Profile Comparison of the Suzuki Coupling
Reaction of 4-Bromoanisole with Phenylboronic Acid using
the Microwave and Oil Bath ••••••••••••••••••••••••••••••••••••••••••••••••• 27
vii
List of Tables
Table 1. Effect of Solvent Conditions in Suzuki Coupling Reaction of
4-Bromoanisole with Phenylboronic Acid •••••••••••••••••••••••••••• 24
Table 2. Effect of Various Bases in Suzuki Coupling Reaction of 4-
Bromoanisole with Phenylboronic Acid ••••••••••••••••••••••••••••• 25
Table 3. Suzuki Coupling Reaction of various Aryl Halides with
Phenylboronic Acid ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 30
Table 4. Effect of Bases in Suzuki Coupling Reaction of 4-
Bromoanisole with Phenylboronic Acid in Water •••••••••••••• 33
Table 5. Suzuki Coupling Reaction of various Aryl Halides with
Phenylboronic Acid in Water •••••••••••••••••••••••••••••••••••••••••••••••• 34
Table 6. Reusability Test of Electron-Rich Oxime Palladacycle
Resins••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 36
viii
List of Schemes
Scheme 1. Overall Synthesis of Electron-Rich Oxime Palladacycle
Resins •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 17
Scheme 2. Suzuki Coupling Reaction of 4-Bromoanisole and
Phenylboronic Acid in Various Solvent Conditions
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 21
Scheme 3. Suzuki Coupling Reaction of 4-Bromoanisole and
Phenylboronic Acid using Various Bases•••••••••••••••••••••••••• 23
Scheme 4. Suzuki Coupling Reaction of 4-Bromoanisole and
Phenylboronic Acid by Microwave Heating (60W) and Oil
Bath Heating •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 26
Scheme 5. Coupling Reaction of Aryl Halides with Phenylboronic
Acid ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 29
Scheme 6. Effect of Bases in Suzuki Coupling Reaction of 4-
Bromoanisole and Phenylboronic Acid in Water ••••••••••••• 32
Scheme 7. Suzuki Coupling Reaction of Various Aryl Halides and
Phenylboronic Acid in Water, using TBAB (1 mmol)
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 32
Scheme 8. Suzuki Coupling Reaction of 4-Bromoanisole and
Phenylboronic Acid for Reusability Test using Oxime
Palladacycle Resins •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 35
1
1. Introduction
1.1. Developments of Supported Oxime Palladacycle
Catalysts
Oxime palladacycle has been proved to be highly active palladium
catalysts for various coupling reactions such as Mizoroki-Heck,
Suzuki-Miyaura, Stille, Sonogashira, and Ullmann-type reactions by
the pioneering works of the Najera group.1-3 The remarkable features
of ketoxime-derived palladacycles such as stability against heat, air,
and moisture,4-6 led the Najera group to investigate their catalytic
activity in C-C coupling reactions (Figure 1a).7
Nevertheless these highly effective homogeneous catalysts needed
feasible means of easy separation and recycling. For greener chemistry,
the developments of heterogeneous catalytic systems for palladium
have been robustly studied.8-10 Leyva group covalently anchored
oxime-carbapalladacycle on silica supports to create the
heterogeneous catalytic system (Figure 1b).11 Najera group used
polymer support to prepare Kaiser oxime resin, which showed
efficient catalytic activity in Suzuki and Heck reactions (Figure 1c).12-
2
14 These solid-supported oxime palladacycles showed not only
outstanding catalytic activities in coupling reactions, but also low
leaching of palladium in reusability tests. A different approach such as
using PVP for oxime palladacycle support was also demonstrated by
Kirschning group (Figure 1d), which suggested a well suited catalyst
for C-C coupling reactions in continuous flow reactors.15
As mentioned above, various oxime palladacycle catalysts were
designed and developed in order to meet the major concerns in
practicability, which include easy scale-up, work up, recyclability, and
low palladium leaching. With the same concerns, electron-rich oxime
palladacycles were developed by modifying the oxime ligands in our
previous work.16 Considering the fact that catalytic activities could be
controlled by varying the substituents of the oxime containing
aromatic ring,17 alterations in the number of the methoxy groups were
made to adjust the electron-richness of the oxime ligands (Figure 1e).
As a result, oxime palladacycle with dimethoxy substituents showed
highly active catalytic performance in Suzuki reaction.
3
(a) Oxime palladacycle complex used in various C-C coupling reactions
(b) SiO2-OC-Pd Catalyst
(c) Kaiser oxime palladacycle on PS support (d) Oxime palladacycle on PVP support
O
R1
R2
PdN
Cl
OHa: R1=H, R2=Hb: R1=H, R2=OCH3
c: R1=OCH3, R2=OCH3
a-c
(e) Oxime palladacycles with different methoxy substituents
Fig. 1 Palladium catalysts on various supports.
4
1.2. Microwave Application for Efficient Catalysis
Electron-rich oxime palladacycle with dimethoxy-substituted
ligands showed best performance in the C-C coupling reactions.14 For
the purpose of easy separation and recycling, the electron-rich oxime
palladacycle was anchored to chloromethyl polystyrene (CMPS) resin.
To develop full activity of the catalyst, induction time should be
concerned. The induction time of a catalyst refers to the time needed
for reaching a steady state catalytic activity.18 For the Suzuki reaction,
palladium catalysts also require induction time, during which the
palladium precursor complex is converted into the active catalytic
form.19 There are numerous factors that could affect the induction time
of a catalytic system, but in simplicity, the most probable factor that
would be directly influenced is temperature. Microwave is a widely
used tool in organic reactions because of its highly effective heating
ability. Microwave is capable of simultaneous, bulk heating of
dielectric molecules, through the mechanism of the dipolar
polarization and ionic conduction processes (Figure 2a).20
Microwave’s electromagnetic radiation produces an oscillating field,
where the dipoles or ions continuously attempt to realign themselves.
5
Within this electric field, rotation of polar molecules lags behind the
oscillations, producing resistive heating in the medium. In case of ions,
the charged particles oscillate back and forth, collide with neighboring
molecules and produce heat.21 Owing to this phenomenon, microwave
heating shows evident difference with conventional oil bath heating.
While the oil bath heating gradient makes its way from the outside of
the reactor to the inside, microwave heating initiates from within the
medium (Figure 2b).22 By using the microwave, various advantages
are provided, such as increased reaction rates, excellent control of
reaction parameters, selective heating, and higher yields.23-24 Of
course, there exist limitations such as difficulties in scale-up, in situ
monitoring, and high costs,20 but utilizing the robust heating capability
was inevitable.
6
(a) Dipolar Polarization (top), and Ionic Conduction (bottom)
(b) Microwave heating vs. Conventional heating
Fig. 2 Mechanisms and Thermal Gradient of Microwave Heating.
7
1.3. C-C Coupling Reactions in Water using Electron-rich Oxime Palladacycle Catalyst and Microwave Heating
Water is at the very forefront of the solvent replacement research
following the green chemistry principles.25 The focus of using water
as solvent comes from its nontoxic, readily available, nonflammable,
and environmentally friendly characteristics. However, low solubility
of organic substrates in water needs to be overcome for efficient
reactions. Several variations are used to overcome this, which include
organic cosolvents, ionic derivatization, surfactants, or hydrophilic
auxiliaries.26-31 Among the auxiliary reagents, tetrabutylammonium
bromide (TBAB) is one of the most widely used phase transfer
catalyst (PTC) in Suzuki reactions. PTCs are defined as reagents that
facilitate the migration of a reactant in a heterogeneous system from
one phase to another, where the reaction could take place.32 TBAB is a
representative quaternary ammonium salt in PTC, and has shown
excellent catalytic activity in various organic reactions such as Heck,
Suzuki, and Hiyama reactions in neat water.1-3
8
1.4. Research Objectives
In this study, we present the Suzuki coupling reactions of
phenylboronic acid and various aryl halides using the polymer-
supported electron-rich oxime palladacycle catalyst and the
microwave heating. The microwave heating is expected to provide a
shorter induction time for the catalyst, owing to its highly efficient
heating capability. In addition, considering the fact that dipolar
molecules are effectively heated under microwave irradiation,
effective Suzuki reactions in water is also anticipated.
9
2. Experimental Section
2.1. General
2.1.1. Materials
Unless otherwise noted, all solvents and reagents were obtained
from commercial suppliers and used without further purification. CM
PS resin (1% DVB-PS, 100-200 mesh) was obtained from BeadTech,
Inc. (Korea).
2.1.2. Instruments
The CMPS resins were characterized by FT-IR (Bomem,
FTLA2000) and elemental analysis (EA, Leco, CHNS-932). The
morphologies of the resin were investigated by field emission scanning
electron microscopy (FE-SEM, Jeol Inc. JSM-6700F). The loading of
palladium on the resin was detected by energy dispersive X-ray
spectrometer (EDX, Jeol Inc. JSM-6700F) and quantified by
inductively coupled plasma atomic emission spectroscopy (ICP-AES,
10
SHIMADZU, ICPS-1000 IV). Palladium 3d binding energy was
investigated by X-ray photoelectron spectroscopy (XPS, ThermoVG,
SIGMA PROBE). Suzuki reactions were performed under microwave
irradiation with CEM Discover Synthesis Unit (CEM Corp., Matthews,
NC) in sealed glass vessels (10 mL) under magnetic stirring. The
temperature was controlled by a calibrated infrared temperature control
under the reaction vessel. The crude product yield of Suzuki reactions
was measured by gas chromatography/mass spectroscopy (GC-MS,
Hewlett Packard).
11
2.2. Preparation of Electron-Rich Oxime Palladacycle Resins
2.2.1. Immobilization of 4′-Hydroxy-3, 5-Dimethoxyacetophenone
Derivatives on CM PS
CM PS resin (1 g, 2.19 mmol/g) was pre-swollen in DMF (100 mL)
and 4′-hydroxy-3, 5-dimethoxyacetophenone (0.86 g, 4.38 mmol),
sodium methoxide (0.35 g, 6.57 mmol), and potassium iodide (1.09 g,
6.57 mmol) were added to the resin. The mixture was stirred by
overhead stirrer at 70 °C for 12 h. After cooling to room temperature,
the resulting keto resin was washed with H2O, 1N HCl, DMF, CH2Cl2,
and MeOH (×3) and dried in vacuo.
2.2.2. Preparation of Oxime Resins
Excess amount of hydroxylamine hydrochloride (1.14 g, 16.40
mmol) and pyridine (1.30 mL, 16.40 mmol) were added to the keto
resins which were preswollen in absolute EtOH. The mixture was
heated at reflux with stirring for 24 h. After cooling to room
temperature, the resins were washed with EtOH, DMF, CH2Cl2, and
MeOH (×3) and dried in vacuo. The loading level of oxime was
12
determined by elemental analysis (% N, 0.96 mmol/g).
2.2.3. Preparation of Palladium Loaded Oxime Resins
To a suspension of oxime resin (1 g) in dry THF, Li2PdCl4 (78.63
mg, 0.30 mmol) and NaOAc (24.61 mg, 0.30 mmol) and dissolved in
THF were added. The mixture was stirred at room temperature for 12 h.
After the reaction, the resin was washed with THF in a Soxhlet
apparatus and dried in vacuo. The palladium content on palladated
oxime resin was determined by ICP-AES.
For ICP-AES analysis, the resin was treated with HNO3 at 100 °C
for 4 h. After filtration and washing the resin with distilled water, the
filtrate was diluted to 25 mL with distilled water and analyzed by ICP-
AES.
13
2.3. Suzuki Coupling Reaction Catalyzed by Electron-Rich Oxime Palladacycle Resins
2.3.1. Optimization of Suzuki Coupling Reaction
Suzuki coupling reaction of 4-bromoanisole (1 mmol) with
phenylboronic acid (1.2 mmol) was carried out using oxime
palladacycle resin (1 mol% Pd) and K2CO3 (1.5 mmol) as a base in
various solvent systems to investigate the optimal condition. The
following solvent systems (3 mL) were examined; H2O, DMF,
H2O/DMF (1:1), H2O/DMF (2:1), H2O/DMF (1:2), H2O/DMF (2:3),
H2O/DMF (3:2), H2O/DMF (3:1), and H2O/DMF (1:3). The reaction
mixture was microwave-heated under 40W at 50 °C for 15 minutes in a
sealed vessel (10 mL). To identify the effects of bases, Na2CO3, K2CO3,
Cs2CO3, TEA, CH3COONa, KOH, NaOH, K3PO4·H2O, and
Na3PO4·H2O were tested in the H2O/DMF (2:1) system.
2.3.2. General Experimental Procedure for Suzuki Coupling
Reaction of Aryl Halides with Phenylboronic Acid
Aryl halide (1 mmol), phenylboronic acid (1.2 mmol, 1.2 equiv),
and a base (1.5 mmol, 1.5 equiv) dissolved in distilled water and DMF
(3/1, v/v, 3 mL) were added to palladated oxime resins (1 mol% Pd: 16
14
mg). The mixture was microwave-heated under 60W at various
temperatures (50~100 °C) for 30 minutes in a sealed vessel (10 mL).
After filtration and washing the resins with distilled water (1 mL × 5)
and diethyl ether (1 mL × 5), the filtrate was poured into diethyl ether.
The organic layer was washed with water and dried over MgSO4 and
the solvent was evaporated under reduced pressure. The crude product
was identified by gas chromatography/mass spectroscopy (GC-MS).
Suzuki coupling reactions in water was also performed in the same
manner. In this case only water (3 mL) was used in the presence of the
phase transfer catalyst, TBAB.
2.3.3. Reaction Profile of Suzuki Coupling Reaction using the
Microwave and Oil Bath
4-Bromoanisole (31.30 μL, 1 mmol), phenylboronic acid (36.58
mg, 1.2 mmol), and K2CO3 (51.83 mg, 1.5 mmol) dissolved in distilled
water and DMF (3/1, v/v, 3 mL) were added to palladated oxime resins
(1 mol% Pd: 16 mg). The mixture was either microwave-heated
under 60W at 50 °C or heated in an oil bath at 50 °C for a period of 3, 5,
10, 15, 20, 30, 45, 60 minutes in a sealed vessel (10 mL, microwave) or
15
a glass vial (10 mL, oil bath). Each reaction mixture was filtered and
washed with distilled water (1 mL × 5) and diethyl ether (1 mL × 5),
and the filtrate was poured into diethyl ether. The organic layer was
washed with water and dried over MgSO4 and the solvent was
evaporated under reduced pressure. The crude product was identified
by GC-MS.
2.3.4 Reusability Test of Electron-Rich Oxime Palladacycle Resins
4-Bromoanisole (31.30 μL, 1 mmol), phenylboronic acid (36.58
mg, 1.2 mmol), and K2CO3 (51.83 mg, 1.5 mmol) dissolved in distilled
water and DMF (3/1, v/v, 3 mL) were added to palladated oxime resins
(1 mol% Pd: 16 mg). The mixture was microwave-heated under 60W at
50 °C for 30 minutes in a sealed vessel (10 mL). After filtration and
washing the resins with distilled water (1 mL × 5) and diethyl ether (1
mL × 5), the filtrate was poured into diethyl ether. The organic layer
was washed with water and dried over MgSO4 and the solvent was
evaporated under reduced pressure. The crude product was identified
by GC-MS. The filtered resins were reused 5 times for the same
reaction.
16
3. Results and Discussion
3.1. Preparation and Characterization of Electron-Rich Oxime Palladacycle Resins
3.1.1. Preparation of Oxime Resins
First, to prepare oxime ligands on polymer support, dimethoxy
substituted hydroxyacetophenone as oxime precursor was chosen. As
shown in Scheme 1, 4’-hydroxy-3, 5-dimethoxyacetophenone was
immobilized on CM PS in the presence of NaOCH3 and KI. The keto
group was converted to oxime group by reacting with excess
hydroxylamine hydrochloride and pyridine. Loading level of oxime
group, determined by nitrogen analysis was 0.96 mmol/g. The chemical
conversions from CMPS to oxime resin were verified by FT- IR
analysis (Figure 3). As shown in the last step of Scheme 1, the oxime
resins were treated with palladium precursor (Li2PdCl4) in dry THF and
were shaken at RT for 6 h. As demonstrated in previous work,
dimethoxy group-attached oxime ligand was able to catch and stabilize
palladium source efficiently due to the good σ-donor electron-rich
ligand.
17
Scheme 1 Synthesis of Electron-Rich Oxime Palladacycle Resins.
18
Fig 3. FT-IR spectra of keto resins and oxime resins (keto group: 1710 cm-1, oxime
group 1614 cm-1, hydroxyl group: 3349 cm-1).
19
3.1.2. Characterization of Electron-Rich Oxime Palladacycle Resins
The resulting palladated oxime resins were analyzed by FE-SEM
to identify any external morphology changes during the reaction. The
FE-SEM images exhibited the same surface morphology without any
physical damages during the reactions (Figure 4). The existence of Pd
on the resin was verified by EDX analysis. From the existence of Cl
and Pd atoms in EDX spectra (Figure 5a), it was indirectly concluded
that the oxime ligands formed a palladium complex via the chloro
bridge form.7 To support this result, the oxidation state of Pd on the
resins was determined by XPS, and Pd peak (Pd 3d5/2) was found in
337.77 eV which corresponds to Pd (II) (Figure 5c).33 Therefore, it is
demonstrated that Pd atom was immobilized on the oxime palladacycle
resin as a chloro-bridge complex in the divalent state. The amount of
immobilized Pd on the resins was quantified by ICP-AES. The loading
level of Pd was 0.16 mmol/g.
20
(a) (b)
Fig 4. FE-SEM Image of CMPS Resins (a) and oxime palladacycle resins (b).
(a) (b)
(c)
Fig. 5. Analysis of chloro-bridged, divalent palladium on oxime palladacycle resin
by EDX (a) and XPS analysis (b). Binding energy (eV) is shown in (c).
21
3.2. Suzuki Coupling Reaction Catalyzed by Electron-Rich Oxime Palladacycle Resins
3.2.1. Effects of Solvents and Bases on Suzuki Coupling Reaction
A model reaction of 4-bromoanisole with phenylboronic acid was
carried out to optimize the reaction condition using the Pd catalysts. In
our previous work, H2O/DMF (1:1) was the optimum solvent system
for the reaction, but considering the heating mechanism of the
microwave, solvent ratios with higher water proportion were examined.
First, Suzuki coupling reactions were carried out using Cs2CO3 (1.5
mmol) as a base in the following solvent conditions; H2O, DMF,
H2O/DMF (1:1), H2O/DMF (2:1), H2O/DMF (1:2), H2O/DMF (2:3),
H2O/DMF (3:2), H2O/DMF (3:1), and H2O/DMF (1:3), using the Pd
catalysts (1 mol%), (Scheme 2).
Scheme 2. Suzuki coupling reaction of 4-bromoanisole and phenylboronic acid in
various solvent conditions.
22
As expected, solvent conditions with higher water proportion were
more effective to perform the reaction. While H2O/DMF (2:1) system
showed the best result (entry 5 in Table 1), slightly decreased yield
was observed in the H2O/DMF (3:1) condition (entry 8 in Table 1).
This is probably due to the delicate solvent balance required for
Suzuki coupling reaction when inorganic base is used, because
heterogeneous reaction requires both the compatibility of solid support
and the solubility of organic, or inorganic reagents. The heating
mechanism of the microwave would surely be more effective when
there is more water in the solvent system, but the decrease in the
organic solvent could become a drawback for the solubility of organic
substrates.
Base screening test was also performed, applying the new solvent
system (Scheme 3). Inorganic bases generally exhibited moderate
performance except for CH3COONa, and organic base such as TEA
was not suitable, as previously observed. The results with K2CO3,
Cs2CO3 and KOH were analogous, and K2CO3 which showed the best
yield (entry 2 in Table 2) was used in the following Suzuki coupling
reactions.
23
Scheme 3. Suzuki coupling reaction of 4-bromoanisole and phenylboronic acid
using various bases.
24
Table 1. Effect of Solvent Conditions in Suzuki Coupling Reaction of 4-
Bromoanisole with Phenylboronic Acida
Entry Solvent Yield (%)b
1 H2O 2
2 DMF 1
3 H2O/DMF (1:1) 80
4 H2O /DMF (1:2) 20
5 H2O /DMF (2:1) 88
6 H2O /DMF (2:3) 10
7 H2O /DMF (3:2) 74
8 H2O /DMF (3:1) 84
9 H2O /DMF (1:3) 8
aConditions: 4-Bromoanisole (1 mmol), phenylboronic acid (1.2 mmol), oxime
palladacycle resins (1 mol%), Cs2CO3 (1.5 mmol) in various solvent systems (v/v, 3
mL) at 40W and 50ºC for 15 minutes. bGC yields.
25
Table 2. Effect of Various Bases in Suzuki Coupling Reaction of 4-Bromoanisole
with Phenylboronic Acid a
Entry Solvent Temp (°C) Yield (%)b
1 Cs2CO3 50 88
2 K2CO3 50 93
3 Na2CO3 50 69
4 K3PO4 50 74
5 Na3PO4 50 83
6 KOH 50 91
7 NaOH 50 84
8 CH3CHOONa 50 3
9 TEA 50 31
aConditions: 4-Bromoanisole (1 mmol), phenylboronic acid (1.2 mmol), oxime
palladacycle resins (1 mol%), various bases (1.5 mmol) in H2O/DMF (v/v, 2:1, 3 mL),
at 40W and 50ºC for 15 minutes. bGC yields.
26
3.2.2. Comparison of Suzuki Coupling Reaction by Microwave
Heating and Conventional Heating
To compare the effect of conventional heating and microwave
heating on reaction profile of the Suzuki reaction of 4-bromoanisole
with phenylboronic acid, reactions were performed in 3, 5, 10, 15, 20,
30, 45, and 60 minute time intervals (Scheme 5). As expected, the
reaction performed with microwave heating required far less induction
time for the conversion to the product (Figure 6). While the oil bath
heating consumed about 20 minutes for the oxime palladacycle
catalyst to reach its steady catalytic state, microwave heating reduced
the induction period down to 5 minutes and the reaction plateau was
reached in 20 minutes. This result clearly showed that the
instantaneous microwave heating effectively reduced the induction
time of the catalyst, allowing efficient catalytic activity.
Scheme 4. Suzuki coupling reaction of 4-bromoanisole and phenylboronic acid by
microwave heating (60W) and oil bath heating.
27
Fig. 6. Reaction profiles of the Suzuki coupling reaction of 4-bromoanisole with
phenylboronic acid using the microwave and oil bath.
28
3.2.3. Suzuki Coupling Reaction of Various Aryl Halides with
Phenylboronic Acid
Suzuki coupling reaction of various aryl halides with
phenylboronic acid was performed under microwave irradiation in
sealed vessels (Scheme 6). Deactivated aryl bromides as well as aryl
chlorides were converted to the corresponding biaryl compounds. Aryl
bromides were converted to the bromides in excellent yields under mild
conditions. Even at higher temperatures, Suzuki reaction of aryl
chlorides gave not so good yield except for the 4-chloroacetophenone
(entry 10 in Table 3). Further optimization of the reaction condition
will allow improvements in the coupling performance of aryl chlorides.
To extend the substrate variations, Suzuki reaction of heterocyclic aryl
halides with phenylboronic acids was performed. The production of
unsymmetrical biaryl compounds is useful for industrial applications.34-
36 We tested our oxime palladacycle catalysts in the coupling reactions
of 2-bromothiopene, 2-bromopyridine, and 2-bromonaphtalene with
phenylboronic acid, and the biaryls were successfully produced.
29
X BHO
HO Pd catalyst (1 mol%)30 min, 40W
R
1.2 eqX= Br, Cl
1.0 eq
Base (1.5 eq)H2O/DMF (2:1)
R
Scheme 5. Suzuki coupling reaction of aryl halides with phenylboronic acid.
30
Table 3. Suzuki Coupling Reaction of Various Aryl Halides with Phenylboronic
Acid a
Entry Substrate Temp (oC) Yield (%)b
1
50 99
2
50 97
3
50 97
4
50 90
5
50 93
6
70 68
7
70 58
8
100 97
9
100 15
10
100 26
11
100 69
12
100 33
13
100 95
aConditions: 4-Bromoanisole (1 mmol), phenylboronic acid (1.2 mmol), oxime
palladacycle resins (1 mol%), K2CO3 (1.5 mmol) in H2O/DMF (v/v, 2:1, 3 mL) at
60W for 30 minutes. bGC yields.
BrN
Br
BrO
S Br
N Br
Br
31
3.2.4. Suzuki Coupling Reaction of Various Aryl Halides with
Phenylboronic Acid in Water
Suzuki coupling reaction of aryl halides with phenylboronic acid
was performed in water, using TBAB (1 mmol) as an additive under
microwave irradiation. To find out the optimum reaction condition,
effects of bases were tested (Scheme 7). As expected, the high yields
with Cs2CO3 and K2CO3 was noticeable compared to other bases (entry
1, 2 in Table 4). Once again, K2CO3 which showed slightly higher yield
was chosen for further study. Unlike the Suzuki coupling reaction using
DMF as the co-solvent, the reaction did not occur at 50ºC, but at 70ºC.
Using this optimized condition, Suzuki coupling reactions of various
aryl halides with phenylboronic acid were performed (Scheme 8).
Unfortunately, the reactions of aryl chlorides with phenylboronic acid
were not satisfactory. Only 4-chloroacetophenone and 4-
chlorobenzonitrile were able to produce biaryl compounds, while the
others only showed side reactions. One of the reason for this result
could be that quaternary ammonium salts have limitations in their
usage at elevated temperatures (120~150 ºC), where decomposition
could occur.36 Also, the reactivity of aryl chlorides might be too slow
32
for the coupling reaction. Further studies with other phase transfer
catalysts would be necessary.
Br
BHO
HO Pd catalyst (1 mol%)
15 min, 100oC, 40W
O
1.2 eq1.0 eq
O
Base (1.5 mmol), TBAB (1 mmol), H2O
Scheme 6. Effect of bases in Suzuki coupling reaction of 4-bromoanisole and
phenylboronic acid in water.
Scheme 7. Suzuki coupling reaction of various aryl halides and phenylboronic acid in
water, using TBAB (1 mmol).
33
Table 4. Effect of Bases in Suzuki Coupling Reaction of 4-Bromoanisole with
Phenylboronic Acid in Water a
Entry Base Yield (%)b
1 Cs2CO
3 89
2 K2CO
3 91
3 Na2CO
3 73
4 K3PO
4 69
5 Na3PO
4 44
6 KOH 71
7 NaOH 52
8 CH3CHOONa 67
9 TEA 49
aConditions: 4-Bromoanisole (1 mmol), phenylboronic acid (1.2 mmol), oxime
palladacycle resins (1 mol%), and base (1.5 mmol) in H2O (3 mL) at 40W and 100ºC
for 15 minutes. bGC yields.
34
Table 5. Suzuki Coupling Reaction of Various Aryl Halides with Phenylboronic
Acid in Water a
Entry Substrate Temp (ºC) Yield (%)b
1
70 92
2
70 95
3
70 97
4
70 95
5
70 96
6
100 62c
7
120 88
aConditions: Aryl halides (1 mmol), phenylboronic acid (1.2 mmol), oxime
palladacycle resins (1 mol%), and K2CO3 (1.5 mmol) in H2O (3 mL) at 60W for 30
minutes. bGC yields. cCs2CO3 was used as a base.
Br
O
BrN
Br
BrO
ClO
35
3.2.5. Reusability Test of Electron-Rich Oxime Palladacycle Resins
for Suzuki Coupling Reaction
One of the major advantages of heterogeneous catalyst is that the
catalyst can be easily isolated and reused. To evaluate the reusability of
electron-rich oxime palladacycle resins, recycling test was carried out
by using the recovered catalysts in Suzuki coupling reaction of 4-
bromoanisole with phenylboronic acid (Scheme 9). The retrieved
electron-rich oxime palladacycle resins consistently gave the product 4-
bromo-1, 1’-biphenyl in high yield until the fifth cycle, maintaining
good catalytic activity.
Scheme 8. Suzuki coupling reaction of 4-bromoanisole and phenylboronic acid for
reusability test using oxime palladacycle resins.
36
Table 6. Reusability Test of Electron-Rich Oxime Palladacycle Resinsa
Yield (%)b
1st Cycle 2nd Cycle 3rd Cycle 4th Cycle 5th Cycle
94 96 95 95 95
aConditions: 4-Bromoanisole (1 mmol), phenylboronic acid (1.2 mmol), oxime
palladacycle resins (1 mol%), and K2CO3 (1.5 mmol) in H2O/DMF (v/v, 2:1, 3 mL) at
60W and 50ºC for 30 minutes. bGC yields.
37
4. Conclusion
In this study, polymer-supported electron-rich oxime palladacycle
was used as a heterogeneous catalyst for Suzuki coupling reaction
using the microwave heating. The microwave heating allowed
significant reduction in the induction time of the catalyst. The reaction
time of the Suzuki coupling of aryl halides and phenylboronic acid
was effectively decreased, while maintaining high production yields.
To explore further the advantage of our oxime palladacycle catalyst,
Suzuki coupling reaction in water was also attempted. Most of the
reactions were performed well affording excellent yields (92~97%),
except for aryl chloride substrates. In this case, rather harsh reaction
conditions were tried, but failed, probably because the phase transfer
catalyst could not bear the extreme temperature. Finally, our oxime
palladacycle catalysts could be successfully reused up to 5 cycles
without losing its catalytic activity.
38
References
1. D. A. Alonso, L. Botella, C. Nájera, C. Pacheco, Synthesis-Stuttgart
2004, 1713.
2. E. Alacid, D. A. Alonso, L. Botella, C. Nájera, M. C. Pacheco, The
Chem. Rec. 2006, 6, 117.
3. D. A. Alonso, C. Nájera, Chem. Soc. Rev. 2010, 39, 2891.
4. H. Onoue, K. Minami, K. Nakagawa, Bull. Chem. Soc. Jpn.1970, 43,
3480-3485.
5. A. J. Nielson, J. Chem. Soc., Dalton Trans. 1981, 205-211.
6. A. D. Ryabov, G. M. Kazaukov, A. K. Yatsimirsky, L. G. Ku’zmina,
O. Y. Burtseva, M. V. Dvortsova, V. A. Polyakov, Inorg. Chem.
1992, 31, 3083-3090.
7. D. A. Alonso, C. Nájera, M. C. Pacheco, Organic Letters 2000, 2,
1823.
8. P. T. Anastas, M. M. Kirchhoff, Acc. Chem. Res. 2002, 35, 686−694
9. N. E. Leadbeater, M. Marco, Chem. Rev. 2002, 102, 3217−3274;
10. L. Yin, J. Liebscher, Chem. Rev. 2006, 107, 133-173
39
11. A. Corma, D. Das, H. Garcia, A. Leyva, J. Catal. 2005, 229,
322−331.
12. E. Alacid, C. Nájera, Synlett 2006, 18, 2959.
13. E. Alacid, C. Nájera, European Journal of Organic Chemistry
2008, 3102.
14. E. Alacid, C. Nájera, Journal of Organometallic Chemistry 2009,
694, 1658.
15. K. Mennecke, W. Solodenko, A. Kirschning, Synthesis 2008,
1589−1599.
16. H. J. Cho, S. W. Jung, S. R. Kong, S. J. Park, S. M. Lee, Y. S. Lee,
Adv. Synth. Catal. (Under Revision)
17. D. A. Alonso, C. Nájera, M. C. Pacheco, Organic Letters 2000, 2,
1823-1826.
18. A. G. Basrur, S. R. Patwardhan, S. N. Vyas, J. Catal. 1991, 127,
86-95.
19. H. Kosslick, I. Monnich, E. Paetzold, H. Fuhrmann, R.
Fricke, D. Muller, G. Oehme, Microporous and Mesoporous
Materials 2001, 44-45, 537-545.
20. I. Bilecka, M. Niederberger, Nanoscale 2010, 2, 1358-1374.
40
21. P. Lidstrom, J. Tierney, B. Wathey, J. Westman, Tetrahedron 2001,
57, 9225-9283.
22. C. O. Kappe, D. Dallinger, Nature Reviews Drug Discovery 2006,
5, 51-63.
23. C.O. Kappe, Chimia 2006, 60, 308-312.
24. C. Gabriel, S. Gabriel, E. H. Grant, B. S. J. Halstead, D. M. P.
Mingos, Chem. Soc. Rev. 1998, 27, 213-223.
25. C. O. Kappe, D. Dallinger, Chem. Rev. 2007, 107, 2563-2591.
26. P. A. Grieco, Aldrichim. Acta 1991, 24, 59.
27. C. J. Li, Chem. Rev. 1993, 93, 2023.
28. U. M. Lindstrom, Chem. Rev. 2002, 102, 2751.
29. C. J. Li, Chem. Rev. 2005, 105, 3095.
30. R. Breslow, Acc. Chem. Res. 2004, 37, 471.
31. M. C. Pirrung, Chem. Eur. J. 2006, 12, 1312.
32. T. Ooi, K. Maruoka, Angew. Chem. Int. Ed. 2007, 46, 4222-4226.
33. G. Kumar, J. R. Blackburn, R. G. Albridge, W. E. Moddeman, M.
M. Jones, Inorganic Chemistry 1972, 11, 296.
34. M. J. Sharp, V. Snieckus, Tetrahedron Letters, 1985, 26 (49), 5997-
41
6000.
35. M. Mora, C. Jimenez-Sanchidrian, J. R. Ruiz, Appl. Organometal.
Chem. 2008, 22, 122–127.
36. J. C. Bussolari, D. C. Rehborn, Org. Lett. 1999, 1 (7), 965-967.
37. M. Halpern, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim,
2012, 26, 495-501.
42
초 록
옥심 팔라다싸이클은 탄소-탄소 짝지음 반응에 있어서 매우
강력한 팔라듐 촉매이며 쉽게 만들 수 있다는 점과 공기, 수
분에 대해 안정하다는 장점을 지닌다. 이전에, 환경친화적인
화학을 위해서 전자가 풍부한 옥심 팔라다싸이클을 고분자
지지대에 고정시켜서 효과적인 탄소-탄소 짝지음 반응과 재
사용에 대한 성능을 실험했다. 본 연구에서는 물에서의 스즈
키 반응을 위해서 고분자에 고정된 옥심 팔라다싸이클 시스
템에 마이크로파 화학을 적용시켰다. 그 결과, 고분자에 고정
된 전자가 풍부한 옥심 팔라다싸이클과 마이크로파 시스템을
이용하여 할로젠화 벤젠, 헤테로고리 벤젠과 페닐기 붕소산과
의 스즈키 반응을 성공적으로 수분 매체에서 실행할 수 있었
다.
주요어: 옥심 팔라다싸이클, 마이크로파, 스즈키-미야우라 반응
학 번: 2012-20944