BAHAGIAN A – Pengesahan Kerjasama *
Adalah disahkan bahawa projek penyelidikan tesis ini telah dilaksanakan melalui
kerjasama antara _____________________ dengan _________________________
Disahkan oleh:
Tandatangan : ..........................................................
Nama
: ..........................................................
Jawatan
:...........................................................
Tarikh : ..........................
(Cop rasmi)
* Jika penyediaan tesis/projek melibatkan kerjasama.
BAHAGIAN B – Untuk Kegunaan Pejabat Sekolah Pengajian Siswazah
Tesis in telah diperiksa dan diakui oleh:
Nama dan Alamat
Pemeriksa Luar
:
Dr. Shafida Binti Abd Hamid
School of Chemical Sciences
Universiti Sains Malaysia
11800 MINDEN
Pulau Pinang
Nama dan Alamat
Pemeriksa Dalam I
:
Prof. Madya Dr. Farediah Binti Ahmad
Fakulti Sains
UTM, Skudai
Pemeriksa Dalam II
:
Nama Penyelia Lain :
(jika ada)
Prof. Dr. Hasnah Binti Mohd Sirat
Prof. Madya Dr. Zakaria Bin Bahari
Disahkan oleh Penolong Pendaftar di SPS:
Tandatangan : ..........................................................
Nama
: GANESAN A/L ANDIMUTHU
Tarikh : ..........................
THE HECK REACTIONS OF ARYL BROMIDES IN IONIC LIQUIDS MEDIUM
OF N-BUTYL-N-METHYLPYRROLIDINIUM
TRIFLUOROMETHANESULFONATE
MOHAMAD HAFIZ BIN AHMAD TAJUDIN
A thesis submitted in fulfilment of the
requirements for the award of the degree of
Master of Science (Chemistry)
Faculty of Science
Universiti Teknologi Malaysia
FEBRUARY 2006
iii
to my beloved family…
abah, mama, ashah, yati, eda
hadi and harith
and to someone special…
shazira sheikh said
thank you for waiting all this while.
iv
ACKNOWLEDGEMENT
All praise to God Almighty, for His mercy that has given me the strength,
blessings and the time to complete this thesis.
Firstly, I would like to take this opportunity to express my sincere thanks to
my supervisors; Assoc. Prof. Dr Mustaffa Shamsuddin, Prof. Dr. Hasnah Mohd Sirat
and Assoc. Prof. Dr Zakaria Bahari for their patience, endless efforts in guidance and
comfort while imparting their vast knowledge to me. This thesis is a sign of
remarkable accomplishment, thanks to the ever constant advices from them.
I am also indebted to Universiti Teknologi Malaysia (UTM) and Institute of
Ibnu Sina (IIS) for funding my M.Sc. study and providing the CHN and NMR
facilities. Laboratory assistant, librarian and support staff also deserve special thanks
for their full friendliness and assistance in supplying relevant literatures and
information.
Also, to my friends; Sofian, Abdul Malik, Murshid, Irwandi, Najib, Asyraf,
Hasbullah, Syazril, Nizam, Asrul, Hoon Loong and fellow colleagues who have
given me support, mentally and physically. Finally, I would like to acknowledge all
individuals who have provided assistance in various occasions. Your views and ideas
are useful indeed. Thank you.
v
ABSTRACT
The application of the ionic liquids in the palladium catalyzed Heck reactions
have been reported extensively, however, without proper evidence addressing the
role of ionic liquids in the catalytic process. In this thesis, a new series of N-alkyl-Nmethylpyrrolidinium trifluoromethanesulfonate salts (46-52) have been synthesized
to study their potential as the alternative solvents for the Heck reaction, instead of
using conventional molecular solvents. These salts were synthesized through
quaternization reaction between N-methylpyrrolidine (38) with several alkyl iodides,
followed by metathesis reaction with silver trifluoromethanesulfonate, to give the
desired products (46-52) (yield: 72-96%) with melting points ranging from room
temperature to 300°C. All the salts obtained were characterized by using 1H and 13CNMR spectroscopies, CHN elemental analysis, melting point, density and molar
conductivity. The effects of alkyl chains towards the melting points and molar
conductivities of these salts (46-52) have been investigated. The N-butyl-Nmethylpyrrolidinium trifluoromethanesulfonate, [Bmplim]CF3SO3 (49), has been
chosen as the solvent in the Heck reactions between methyl acrylate (61) and several
types of aryl bromides (56-60) to give Heck adducts (62-66) with satisfactory yield
between 37 to 97%. Parameters such as the types of bases, the amount of Pd catalyst
loadings and the reaction temperatures were also studied in order to optimize the
percentage conversion of respective Heck adducts (62-66). Results show that, the
optimum condition to enhance the percentage conversion for this catalytic system is
by using Et3N as base, Pd catalysts loading at 1.5mmol% and reaction temperature at
120°C, to achieve the calculated TONs of ~6667. With these conditions, the Heck
adducts of reactive aryl bromides; 4-bromonitrobenzene (56), 4-bromoacetophenone
(57) and bromobenzene (58) have achieved an extremely high percentage conversion
(~100%). As for the unreactive aryl bromides; 4-bromoanisole (59) and 4bromoaniline (60), the addition of PPh3 was proved to be useful; however, leads to
contamination from the by-product which results to problematical separation of the
desired products (62-66). The ionic liquid of [Bmplim]CF3SO3 (49), can be recycled
up to three runs, without showing any distinct losses in its activities.
vi
ABSTRAK
Penggunaan cecair ionik dalam tindak balas Heck bermangkinkan paladium
telah dilaporkan secara meluas, namun ianya tidak disertakan dengan bukti yang
jelas tentang peranan cecair ionik dalam proses tindak balas pemangkinan ini. Tesis
ini melaporkan sintesis garam ionik baru bagi siri N-alkil-N-metilpirolidinium
triflorometanasulfonat (46-52) untuk dikaji potensinya sebagai pelarut alternatif di
dalam tindak balas Heck, selain daripada penggunaan pelarut molekul konvensional.
Garam-garam ini disintesis melalui tindak balas pengkuateneran antara sebatian Nmetilpirolidina (38) dengan beberapa alkil halida, diikuti dengan tindak balas
metatesis dengan argentum triflorometanasulfonat, untuk memberikan hasil yang
dikehendaki (46-52) (hasil: 72-96%), dengan takat lebur dalam julat suhu bilik ke
300°C. Kesemua garam ini kemudiannya dicirikan dengan menggunakan
spektroskopi RMN 1H and 13C, analisis unsur CHN, takat lebur, ketumpatan dan
kekonduksian molar. Kesan panjang rantai alkil terhadap takat lebur dan
kekonduksian molar bagi garam-garam ini telah dikaji. Cecair ionik N-butil-Nmetilpirolidinium triflorometanasulfonat [Bmplim]CF3SO3 (49), telah dipilih sebagai
pelarut dalam tindak balas Heck di antara metil akrilat (61) dengan beberapa jenis
aril bromida (56-60) untuk memberikan aduk Heck (62-66) dengan perolehan hasil
yang memuaskan, berjulat di antara 37 hingga 97%. Parameter seperti jenis bes,
amaun mangkin Pd yang digunakan, dan suhu tindak balas turut dikaji bagi
mengoptimumkan peratusan pertukaran bagi aduk Heck (62-66) terbabit. Keputusan
menunjukkan bahawa keadaan paling optimum bagi meningkatkan peratusan
pertukaran dalam sistem pemangkinan bagi tindakbalas ini adalah dengan
penggunaan Et3N sebagai bes, amaun Pd sebanyak 1.5mmol% dan suhu tindak balas
pada 120°C bagi mencapai kiraan TONs sebanyak ~6667. Dengan menggunakan
parameter-parameter ini, kesemua aduk Heck bagi aril bromida yang reaktif; 4bromonitrobenzena (56), 4-bromoasetofenon (57) dan bromobenzena (58) telah
berjaya mencapai peratusan pertukaran yang sangat tinggi (~100%). Bagi sebatian
aril bromida yang tidak reaktif pula; 4-bromoanisol (59) dan 4-bromoanilina (60),
penambahan PPh3 didapati membantu meningkatkan peratusan pertukaran hasil,
tetapi, pada masa yang sama, ia menyebabkan kehadiran bendasing yang membawa
kepada masalah pengasingan aduk-aduk Heck (62-66) yang dikehendaki. Cecair
ionik [Bmplim]CF3SO3 (49) didapati boleh dikitar semula sehingga tiga kali
penggunaan tanpa menunjukkan kehilangan yang jelas dalam aktivitinya.
vii
TABLE OF CONTENTS
CHAPTER
TITLE
PAGE
TITLE PAGE
DECLARATION
ii
DEDICATION
iii
ACKNOWLEDGEMENT
iv
ABSTRACT
v
ABSTRAK
vi
TABLE OF CONTENTS
vii
LIST OF TABLES
xi
LIST OF FIGURES
xii
LIST OF SCHEMES
xiii
LIST OF SYMBOLS / ABBREVIATIONS /
1
NOTATION / TERMINOLOGY
xiv
LIST OF APPENDICES
xv
INTRODUCTION
1.1
General Introduction
1
1.2
Background of Research and Problem Statement
2
1.3
Objectives of Research
4
1.4
Scope of Research
5
1.5
Thesis Outline
6
viii
2
LITERATURE REVIEWS
2.1
Ionic Liquids
7
2.2
Combination of Cations and Anions
8
2.2.1 Cations
8
2.2.2 Anions
10
2.2.3 Zwitterionic-Type Ionic Liquids
12
The Unique Properties of Ionic Liquids
13
2.3.1 High stability
13
2.3.2 Environmental Friendly
13
2.3.3 Liquid-Crystalline Properties
14
2.3
2.4
2.5
3
Ionic Liquids as Solvent in Organic and Catalytic
Reactions
14
The Heck Reactions
20
2.5.1 Components of the Heck Reaction Medium
20
2.5.2 Mechanism of the Heck Reaction
22
RESULTS AND DISCUSSION
3.1
The Synthesis of Ionic Liquids Derived from Nalkyl-N-methylpyrrolidinium Trifluoromethane
sulfonate Series (46-52)
25
3.1.1 Quaternization and Metathesis Reactions
25
3.1.2 Synthesis of N-alkyl-N-methyl
pyrrolidinium Trifluoromethanesulfonate
Salts (46-52) from N-alkyl-N-methyl
pyrrolidinium Iodide Salts (39-45)
27
3.1.3 Characterization of N-alkyl-N-methyl
pyrrolidinium Trifluoromethanesulfonate
Salts (46-52)
33
3.1.3.1 1H-NMR Spectroscopy Analysis
33
3.1.3.2 13C-NMR Spectroscopy Analysis
35
ix
3.1.3.3 CHN Elemental Analysis
3.2
The Heck Reactions
38
39
3.2.1 Characterization of the Heck Adducts (6241
66)
3.2.1.1 1H-NMR Spectroscopy Analysis
13
41
3.2.1.2 C-NMR Spectroscopy Analysis
43
3.2.1.3 CHN Elemental Analysis
45
3.2.2 Studies on the Heck Reaction Parameters
46
3.2.2.1 The Effect of Bases
46
3.2.2.2 The Effect of Pd(OAc)2 Catalysts
Loadings
47
3.2.2.3 The Effect of Reaction
3.3
4
Temperatures
48
3.2.2.4 Addition of Co-ligand
49
Recyclability of Ionic Liquids
50
EXPERIMENTAL
4.1
General Experimental Procedures
51
4.2
Chemicals
52
4.3
Preparation of Ionic Liquids
52
4.3.1 Preparation of N-alkyl-N-methyl
pyrrolidinium Iodide Salts (39-45)
52
4.3.2 Preparation of N-alkyl-N-methyl
pyrrolidinium Trifluoromethanesulfonate
Salts (46-52)
4.4
Preparation of the Heck Adducts
53
55
4.4.1 Catalytic Reactions of Aryl Bromides (5660) in Different Bases
57
4.4.2 Catalytic Reactions of Aryl Bromides (5660) in Different Palladium Loadings
58
x
4.4.3 Catalytic Reactions of Aryl Bromides (5660) at Different Temperatures
4.5
5
Recyclability of Ionic Liquids
59
60
CONCLUSION AND SUGGESTION
5.1
Conclusion
62
5.2
Suggestion
65
SEMINARS AND PUBLICATIONS
66
REFERENCES
67
APPENDIX
74
xi
LIST OF TABLES
TABLE NO.
3.1
TITLE
Physical characterization of N-alkyl-N-methyl
pyrrolidinium trifluoromethanesulfonate salts (46-52)
3.2
1
33
13
C-NMR data of the N-alkyl-N-methylpyrrolidinium
trifluoromethanesulfonate salts (46-52)
3.4
28
H-NMR data of the N-alkyl-N-methylpyrrolidinium
trifluoromethanesulfonate salts (46-52)
3.3
PAGE
36
CHN elemental analysis of the N-alkyl-N-methyl
pyrrolidinium trifluoromethanesulfonate salts (46-52)
38
3.5
1
41
3.6
13
43
3.7
CHN elemental analysis of the Heck adducts (62-66)
45
4.1
Catalytic reactions of aryl bromides (56-60) in different
H-NMR data of the Heck adducts (62-66)
C-NMR data of the Heck adducts (62-66)
bases
4.2
Catalytic reactions of aryl bromides (56-60) in different
palladium loadings
4.3
4.4
58
59
Catalytic reactions of aryl bromides (56-60) at different
temperatures
60
Recyclability test for ionic liquid of [Bmplim]CF3SO3 (49)
61
xii
LIST OF FIGURES
FIGURE NO.
1.1
TITLE
General structure of the N-alkyl-N-methylpyrrolidinium
trifluoromethanesulfonate salts
2.1
4
Some examples of the cations used in the preparation of
ionic liquids
3.1
PAGE
8
The effect of alkyl chains lengths towards the melting
points of the N-alkyl-N-methylpyrrolidinium trifluoro
methanesulfonate salts (46-52)
3.2
29
The effect of alkyl chains lengths towards the molar
conductivities (ȁM) of the N-alkyl-N-methyl
pyrrolidinium trifluoromethanesulfonate salts (46-52)
3.3
The effect of different bases towards the Heck adducts
(62-66)
3.4
46
The effect of different Pd loadings towards the Heck
adducts (62-66)
3.5
30
47
The effect of different reaction temperatures towards the
Heck adducts (62-66)
48
xiii
LIST OF SCHEMES
SCHEME NO.
2.1
TITLE
PAGE
The dimerization of propene (20) in ionic liquid of
[Bmim]Cl via the Dimersol / Difasol process
2.2
16
The polymerization of propene (20) in ionic liquid of
[Emim]Cl via the Z
iegler-Natta reaction
2.3
17
The Diels-Alder reaction betw
een cyclopentadiene (23)
and ethyl acrylate (24) in ionic liquid of [Bmim]PF6
2.4
The hydrogenation of pentene (27) to pentane (28) in
18
ionic liquid of [Bmim]SbF6
2.5
The hydroformylation of 1-octene (29) in ionic liquid
19
[Bmim]Cl-SnCl2
2.6
The Friedel-Crafts alkylation of benzene (32) iwth
ethylene (33) in ionic liquid of [Emim]Cl
2.7
18
19
The reduction of Pd(OAc)2 (35) to the active Pd(0) (36)
Heckcatalyst
23
2.8
G
eneral mechanism of the Heckreaction
24
3.1
G
eneral method of quatern ization and metathesis
reactions for preparing N-alkyl-N -methylpyrrolidinium
trifluoromethanesulfonate salts (46-52)
3.2
26
Synthesis of N-alkyl- N-methylpyrrolidinium
trifluoromethanesulfonate salts (46-52)
3.3
The Heckreactions betw
een methyl acrylate
several types of aryl bromides (56-60)
27
(61) and
39
xiv
LIST OF SYMBOLS / ABBREVIATIONS / NOTATION / TERMINOLOGY
[Bmplim]CF3SO3
-
N-butyl-N-methylpyrrolidinium trifluoro
methanesulfonate
13
C-NMR
-
Carbon nuclear magnetic resonance
1
H-NMR
-
Proton nuclear magnetic resonance
BINAP
-
2,2'-bis(diphenylphosphino)-1,1'-binaphthyl
BMI / Bmim
-
1-butyl-3-methylimidazolium
Bu4NCl
-
Tetrabutylammonium chloride
C20MIM
-
N-isocane-N’-methylimidazolium
CDCl3
-
Chloroform-d6
CHN
-
Carbon-Hydrogen-Nitrogen
DMF
-
N,N’-dimethylformamide
DMSO
-
Dimethylsulfoxide-d6
EMI / Emim
-
1-ethyl-3-methylimidazolium
Et3N
-
Triethylamine
NaHCO3
-
Sodium hydrogen carbonate
Na2CO3
-
Sodium carbonate
NaOAc
-
Sodium acetate
NTf2¯
-
Bis(trifluoromethylsulfonyl)imide
RTIL
-
Room temperature ionic liquid
ScCO2
-
Supercritical carbon dioxide
TFSA(III)
-
Bis(trifluoromethanesulfonyl)amide
TONs
-
Turnover numbers
xv
LIST OF APPENDICES
APPENDIX
1
TITLE
1
H-NMR spectrum of N,N-dimethylpyrrolidinium
trifluoromethanesulfonate (46)
2
PAGE
74
13
C-NMR spectra of N,N-dimethylpyrrolidinium
trifluoromethanesulfonate (46); (a) 13C–{H},(b)
DEPT135 and (c) DEPT90
3
1
H-NMR spectrum of N-ethyl-N-methyl
pyrrolidinium trifluoromethanesulfonate (47)
4
75
76
13
C-NMR spectra of N-ethyl-N-methyl
pyrrolidinium trifluoromethanesulfonate (47); (a)
13
C–{H},(b) DEPT135 and (c) DEPT90
5
1
H-NMR spectrum of N-methyl-N-propyl
pyrrolidinium trifluoromethanesulfonate (48)
6
77
78
13
C-NMR spectra of N-methyl-N-propyl
pyrrolidinium trifluoromethanesulfonate (48); (a)
13
C–{H},(b) DEPT135 and (c) DEPT90
7
1
H-NMR spectrum of N-butyl-N-methyl
pyrrolidinium trifluoromethanesulfonate (49)
8
79
80
13
C-NMR spectra of N-butyl-N-methyl
pyrrolidinium trifluoromethanesulfonate (49); (a)
13
C–{H},(b) DEPT135 and (c) DEPT90
81
xvi
9
1
H-NMR spectrum of N-methyl-N-pentyl
pyrrolidinium trifluoromethanesulfonate (50)
10
82
13
C-NMR spectra of N-methyl-N-pentyl
pyrrolidinium trifluoromethanesulfonate (50); (a)
13
C–{H},(b) DEPT135 and (c) DEPT90
11
1
H-NMR spectrum of N-hexyl-N-methyl
pyrrolidinium trifluoromethanesulfonate (51)
12
83
84
13
C-NMR spectra of N-hexyl-N-methyl
pyrrolidinium trifluoromethanesulfonate (51); (a)
13
C–{H},(b) DEPT135 and (c) DEPT90
13
1
H-NMR spectrum of N-heptyl-N-methyl
pyrrolidinium trifluoromethanesulfonate (52)
14
85
86
13
C-NMR spectra of N-heptyl-N-methyl
pyrrolidinium trifluoromethanesulfonate (52); (a)
13
C–{H},(b) DEPT135 and (c) DEPT90
15
1
H-NMR spectrum of methyl 4-nitrocinnamate
(62)
16
C-NMR spectra of methyl 4-nitrocinnamate (62);
1
89
H-NMR spectrum of methyl 4-acetoxycinnamate
(63)
18
88
13
(a) 13C–{H},(b) DEPT135 and (c) DEPT90
17
87
90
13
C-NMR spectra of methyl 4-acetoxycinnamate
(63); (a) 13C–{H},(b) DEPT135 and (c) DEPT90
91
19
1
92
20
13
H-NMR spectrum of methyl cinnamate (64)
C-NMR spectra of methyl cinnamate (64); (a)
13
C–{H},(b) DEPT135 and (c) DEPT90
21
1
H-NMR spectrum of methyl 4-methoxycinnamate
(65)
22
94
13
C-NMR spectra of methyl 4-methoxycinnamate
(65); (a) 13C—
{H},(b) DEPT135 and (c) DEPT90
23
93
1
95
H-NMR spectrum of methyl 4-aminocinnamate
(66)
96
xvii
24
13
C-NMR spectra of methyl 4-aminocinnamate
{H},(b) DEPT135 and (c) DEPT90
(66); (a) 13C—
25
The Heck reaction between 4-bromoanisole (59)
with methyl acrylate (61) in [B
mplim]CF
3SO3
(49); (a) without PPh3 and (b) with PPh3
26
97
98
The Heck reaction between 4-bromoaniline (60)
with methyl acrylate (61) in [B
mplim]CF
(49); (a) without PPh3 and (b) with PPh3
3SO3
99
CHAPTER 1
INTRODUCTION
1.1
General Introduction
The design of chemical products and processes that reduce or eliminate the
use and generation of hazardous substances is the main goal of green chemistry [1].
The identification of environmentally benign solvents and separation processes is
one of the most active research areas in this field today. Most traditional chemical
processes use large quantities of organic solvents, because of their volatility,
flammability and toxicity are incompatible with the aims of green chemistry. An
ideal solvent for green chemistry should have low volatility, be chemically and
physically stable, easy to handle, recyclable and reusable. Recently, possible
replacements for traditional solvents that are more compatible with the aims of green
chemistry are ionic liquids.
Ionic liquids are simply liquids composed entirely of ions [2]. They have
garnered increasing interest in the last few years as novel solvents for synthesis,
separations, electrochemistry and process chemistry. Organic ionic liquids were
known for almost a century, but it was only during the last decade or so that they
2
emerged as important materials with a growing application base sufficient to sustain
interest in their development.
1.2
Background of Research and Problem Statement
The Heck reaction has been studied intensively and numerous excellent
surveys on a wide variety of different aspects of this reaction have been published
[3], including; i) the development of ligands for this reaction, ii) advances in
mechanistic studies, iii) the reactivity and the selectivity of the reactions, and iv)
application in natural products synthesis. This thesis will discuss the latter topic, in
which the use of ionic liquids as the solvent in the Heck reactions of aryl bromides.
Although there have been numerous reports on the use of ionic liquids in the
Heck reactions [4-6], the fundamental studies of the relationship between the
properties of ionic liquids and the improved performance compared to the
conventional solvents are still rare. For example, many studies have found that the
reaction rates, conversions and selectivities are enhanced to different degrees, though
the reason why the ionic liquids show higher efficiency or specificity in the reaction
is still an open question.
Moreover, there appears to be some confusion concerning the reactivity of
aryl halides. In many studies, reactive aryl iodides substrates are routinely used to
test the efficiency of a novel catalytic system, when it has been clearly demonstrated
that even unliganted palladium precursors can easily achieved extremely high
turnover numbers (TONs), where most of them were up to millions [7]. Furthermore,
the couplings of different types of aryl halides with methyl acrylate have very
different rate-determining steps. This has important implication for the development
of catalysts for the activation of unreactive aryl halides such as bromides and
3
chlorides. Despite numerous reports of catalytic systems with impressive TONs, the
majority of these studies were performed using electron-poor aryl halides, typically
4-bromoacetophenone and electron-poor olefins such as acrylates and styrenes.
The current challenge lies in the development of catalytic systems that will
activate unreactive aryl halides towards Heck catalysis, especially aryl bromides and
chlorides where the TONs still remain in the lower hundreds. Although certain
aspects of this thesis have been covered by previous researchers [8, 9], a study
addressing the Heck reactions of aryl bromides is considered to be particularly
timely.
Homogeneous catalysis offers many advantages such as high selectivity, low
investment cost and flexible operations under mild condition with easy mixing and
heat removal. The quests for new catalyst immobilization or recovery strategies to
facilitate its reuse are incessant. An approach which has been industrially applied is
the use of liquid-liquid two-phase systems wherein the catalyst is immobilized in a
polar liquid phase, and water operates as the second phase [10]. This approach is
effective towards organic products, which are poorly miscible. Although the use of
water has been largely developed, it still has some limitations; it may be coordinating
towards the active metal centre, react with the metal-carbon bond or low solubility
for some reactants [11]. Moreover, the high consumption of the expensive palladium
catalyst makes it a relatively impractical process on an industrial scale. Therefore,
recycling the catalyst is a key objective.
To overcome these problems, this research is intended to answer some
curiosities, if not all, regarding the application of ionic liquids in the Heck reaction
by introducing a new series of ionic liquids of N-alkyl-N-methylpyrrolidinium
trifluoromethanesulfonate salts, R[Mplim]CF3SO3 (Figure 1.1), as the solvent for this
fascinating reaction. Furthermore, the discussion will be based on the optimization of
the ionic liquids system rather than modification of the complicated catalyst
precursors. The purpose of this thesis is therefore to present the underlying principles
4
and outcomes of the latest efforts to activate these more difficult substrates for Heck
catalysis, thus highlighting the challenges in this highly competitive area.
3
4
H 3C
5
Figure 1.1
2
1
+
N
CF3SO3¯
R
General structure of the N-alkyl-N-methylpyrrolidinium trifluoro
methanesulfonate salts
1.3
Objectives of Research
There are three key objectives of this research. Firstly, to synthesize a new
series of room temperature ionic liquids (RTILs) derived from the N-alkyl-N-methyl
pyrrolidinium cation, R[Mplim]+ and the trifluoromethanesulfonate anion, CF3SO3¯ .
Secondly, to apply these ionic liquids as the solvents to replace the conventional
organic solvent in the Heck reactions of several aryl bromides with different
reactivities. Finally, to determine the optimum conditions for the reaction to proceed
in the ionic liquid mediums by varying the parameters of the reaction; the bases,
palladium catalyst loadings, reaction temperatures and addition of co-ligand.
5
1.4
Scope of Research
The first objective was achieved by reacting N-methylpyrrolidine (38) with
several alkyl iodides through the quaternization process to produce a series of iodide
salts (39-45). Next, these iodide salts (39-45) underwent anion-exchange with silver
trifluoromethanesulfonate through the metathesis reaction to obtain the desired ionic
liquids (46-52). These ionic liquids (46-52) were then characterized by using the
digital melting point apparatus, the conductivity meter, the proton and carbon NMR
spectroscopies and the CHN elemental analysis.
For the second objective, the ionic liquid which gave the highest yield and
purity was chosen as the solvent in the palladium-catalyzed Heck reactions. In this
reaction, methyl acrylate (61) was reacted with five aryl bromides with different
reactivity; 4-bromonitrobenzene (56), 4-bromoacetophenone (57), bromobenzene
(58), 4-bromoanisole (59) and 4-bromoaniline (60), respectively. The Heck adducts
(62-66) were then characterized by using the digital melting point apparatus, the
proton and carbon NMR spectroscopies and the CHN elemental analysis.
Finally, the third objective was achieved by conducting all the experiments in
various combination of the reaction components; bases (Et3N, NaHCO3, Na2CO3 and
NaOAc), Pd catalyst loadings (1.0, 1.5 and 2.0 mmol%) and reaction temperatures
(80, 100 and 120°C). The percentage conversion rate of the Heck adducts (62-66)
were determined from the proton NMR spectra. The system which gave the highest
conversion rate for the entire Heck adducts (62-66) was considered as the optimum
reaction conditions.
6
1.5
Thesis Outline
This thesis is divided into 5 main chapters. The main idea and objectives of
this thesis are described in Chapter 1, followed by a concise discussion on literature
reviews in Chapter 2. Chapter 3 provides the discussion on the findings of the
experiments, while the experimental methods were described in Chapter 4. Finally,
Chapter 5 provides the summary of all the chapters and suggestions for the future
works.
CHAPTER 2
LITERATURE REVIEWS
2.1
Ionic Liquids
To date, most of our understandings of chemistry have been based upon the
behavior of molecules in the solution phase in the molecular solvents [12]. However,
a new class of solvent, named ionic liquids has emerged.
Ionic liquids can be defined as any material containing only ionic species
without any neutral molecules and having a melting point of lower than 298 K [13].
First discovered by Frank Hurley and Tom Weir in 1951 [14], ionic liquids have now
been utilized as the green solvents; primarily as replacements for the conventional
media in chemical processes. As they are made up of at least two components which
can be varied (the cation and anion), the solvents can be designed with a particular
end use in mind, or to possess a particular set of properties. Hence, the term
“designer solvents” has come into common use [15]. They feature unique properties
such as possess low vapour pressure, chemically and physically stable, recyclable
and easy handling.
8
2.2
Combination of Cations and Anions
By a judicious combination of cations and anions, a number of potential ionic
liquids can be prepared. Moreover, the physical and chemical properties for these
salts can be modified by fine-tuning the types of cations or anios used [16, 17].
2.2.1
Cations
The most commonly used cations are generally bulk, organic with low
symmetrical structure. Those described until now are based on ammonium (1),
sulfonium (2), phosphonium (3), lithium (4), imidazolium (5), pyridinium (6),
picolinium (7), pyrrolidinium (8), thiazolium (9), triazolium (10), oxazolium (11),
and pyrazolium (12) differently substituted. The structures for these cations are
shown in Figure 2.1.
[NRXH(4-X)]+
[SRXH(3-X)]+
[PRXH(4-X)]+
Li+
(1)
(2)
(3)
(4)
R1
R1
+
N
R
2
R
(6)
R1
R2
R
4
Figure 2.1
N
+
N
O
R2
N
N
+
(9)
R1
R2
N
N
R4
R2
R1
(8)
R
(7)
R1
N
R3
+
N
NH
+
N
(5)
+
S
+
N
R2
N
+
R
3
R
5
R3
R3
R4
R4
(10)
(11)
(12)
Some examples of the cations used in the preparation of ionic liquids
9
Of particular interest are the salts based on the N,N’-dialkylimidazolium
cation (5) due to its wide spectrum of physico-chemical properties available in that
class. Although it has been assumed that the non-symmetrical N,N’dialkylimidazolium cations give lower melting point salts, certain symmetrical
derivaties such as 1,3-dialkylimidazolium hexafluorophosphate with the dibutyl,
dipentyl, dioctyl, dinonyl and didecyl substituents are found to be liquid at the room
temperature.
Besides the N,N’-dialkylimidazolium cation, pyrrolidinium cations (8) have
gained attention first as the plastic crystal former with anions such as
tetrafluoroborate, BF4¯ or bis(trifluoromethylsulfonyl)imide, NTf2¯ [18]. These low
melting salts exhibit interesting ionic conductivities and, therefore, have received
attention for use as electrolytes in a wide range of applications including solar cells
and batteries.
Other recently developed cations are the planar trialkylsulfonium ones such
as 2. When combined with the NTf2¯ anion, they give low melting salts with very
high conductivity and the lowest viscosity of all the NTf2¯ based room temperature
ionic liquids of triethylsulfonium bis(trifluoromethylsulfonyl)imide, [SEt3][NTf2]
(m.p. -35°C and 30 mPas at 25°C). Their high conductivities can be ascribed to a
little stronger degree of association between SEt3+ and NTf2¯ than of 1-ethyl-3methylimidazolium, EMI+ and NTf2¯ salts [19].
Organic polycations such as 13 and 14 have also been envisioned. Associated
with the bromide anions, the dictation 14 (m = 4, R1 = R2 = methyl) gives a salt
melting at 67-69°C [20]. Based on these polycations, new category of phosphate
ionic liquids was described and presented as good candidates for organic
electrochemical processes.
10
H3C
+N
N+
H3C
CH3
CH3
(13)
R1
N
+
N
(CH2)m
N
+
N
R2
(14)
Besides the organic cations based ionic liquids, the lithium salts are
increasingly developed particularly for secondary batteries and storage of energy.
They often possessed lower lattice energy and, therefore, lower melting points than
their neighbouring elements of the periodic table. As an example, a mixture of LiCl
and EtAlCl2 gives a liquid, on a large range of composition, at temperatures lower
than 0°C [21].
Generally, most of the chemical applications regarding ionic liquids were
influence by the cations, which controlled the physical properties of the medium.
However, a chemical effect of the cation is also possible. For example, in the
hydrovinylation of styrene catalyzed by Ni-organometallic complexes, 4methylpyridinium salts proved to give higher enantioselectivity than their 1-ethyl-3butylimidazolium homologue [22]. On the other hand, when used as solvents for the
regioselective alkylation of indole, 1,3-dialkyl or 1,2,3-trialkylimidazolium base salts
proved to be superior to the alkylpyridinium base salts [23].
2.2.2
Anions
The anions can be classified into two parts; polynuclear and mononuclear
anions [24]. The polynuclear anions are generally formed by the reaction of
corresponding Lewis acid with the mononuclear anion, for example AlCl3 with
AlCl4¯. They are particularly air and water sensitive. Other examples of the
polynuclear anions are Al2Cl7¯, Al3Cl10¯, Au2Cl7¯, Fe2Cl7¯ and Sb2Cl11¯. The
second class of anions corresponded to the mononuclear anions, which lead to
11
neutral, stoichiometric ionic liquids. The examples for this type of anions are BF4¯,
PF6¯, CF3SO3¯, ZnCl3¯, SbF6¯ and N(CF3SO2)2¯. More recently, NTf2¯ anion (15)
and carborane-based salts such as carborane anions, CB11H12¯ (16) have become the
particular interest.
..
SO2CF3
..
¯N
O
O
O
SO2CF3
(15)
O
O
O
O
O
O
O
¯
O
O CH
O BH
O
(16)
The NTf2¯ anion was expected to produce particularly thermally stable salts
up to 400°C [25]. Salts based on this anion can be easily prepared by anion exchange
reactions using the commercially available lithium trifluoromethylsufonylamide. Due
to the delocalization of the negative charge, the anion is probably less associated
with the cation and then more mobile than the triflate ones such as CF3SO3¯. There is
also a theory suggesting that the imide anion strongly lower the melting point of
salts, such as quaternary ammonium salts, even for symmetrical ammonium such as
tetraethylammonium bis(trifluoromethylsulfonyl)imide, [Et4N][NTf2] (m.p. =
105°C). Moreover, other NTf2¯ salts derivatives such as LiNTf2 and lithium LiCTf3
were used as alternatives to LiPF6 in the high voltage ion cells due to the hydrolytic
instability of LiPF6.
The carborane anion, CB11H12¯ (16), is one of the inert anion in modern
B
chemistry [26]. Nevertheless, despite their great stability, the position one of the
CB11H12¯ ion can be alkylated to produce new derivatives with melting points just
above room temperature, such as [Emim][1-C3H7-CB11H11], which melts at 45°C. It
is also possible to substitute the B–H bond with strong electrophiles which allows a
systematic variation of the properties of the anion which is unavailable in most
conventional anions. Furthermore, their very weak nucleophilicity and redox
12
inertness allowed the exploration of new extreme cation reactivity and the isolation
of new superacids.
Driven by the need to construct an ionic liquid with low viscosity,
dicyanamide anions, N(CN)2¯ have recently been utilized [27]. The viscosity for the
[EMI]N(CN)2 liquid salt is only 21 mPas at 25°C compared to 34 mPas for
[EMI]NTf2 at 20°C. Moreover, this anion, when associated with [Bmplim],
tetraalkylammonium (N6444) or with [Emim], gives the ionic compounds with
melting point below -10°C.
2.2.3
Zwitterionic-Type Ionic Liquids
Another series of ionic liquids were the zwitterionic-type, which consist of
imidazolium cations containing a covalently bound counter anionic site, such as
sulfonate (17) or sulfonamides such as (18) and (19) [28].
Et
N
+
N
(CH2)3SO3–
1
R
N
+
N
O
(CH2)m
O
S
–
NCH2CF3
R2
(17)
(18)
R1 = Et, R2 = H, m = 3
(19)
R1 = Me, R2 = Me, m = 2
Initially, compound 17 is a white powder which melts at 150°C. However, by
adding an equimolar amounts of LiNTf2, the mixture presents a glass transition
temperature of -16°C. The zwitterionic imidazolium salts such as 18 and 19 exhibit
an excellent ion conductive matrix, eventhough their components ion cannot migrate.
13
2.3
The Unique Properties of Ionic Liquids
Application of ionic liquids in chemical processes has blossomed only within
the last decade. Comprehensive information regarding the development of this field
may be found in a number of reports by previous researchers [29, 30]. These reports
provide an excellent and essential source of the physico-chemical properties of ionic
liquids. Listed below are the significant properties of the ionic liquids which
fascinated its application in numerous task-specific application in which the
conventional solvents are non-applicable or insufficiently effective.
2.3.1
High Stability
The stability of ionic liquids is crucial for the optimum process performances.
Several studies have indicated that certain ionic liquids incorporating 1,3dialkylimidazolium cations (5) are generally more resistant than the conventional
solvents under problematical process conditions, such as those occurring in
oxidation, photolysis and radiation processes.
2.3.2
Environmental Friendly
Although any liquid may be used as the solvents, relatively few are in general
use. However, as the introduction of cleaner technologies has become a major
concern throughout both industry and academia, the search for alternatives to the
most damaging solvents has become a high priority. Organic solvents are high on the
list of unfriendly chemicals for two simple reasons; 1) they are used in huge
amounts, and 2) they are usually volatile liquids that are difficult to contain.
Therefore, ionic liquids are the solution for these drawbacks due to their fascinating
properties in preserving the environment.
14
2.3.3
Liquid-Crystalline Properties
Long-chain ionic liquids have attracted some interest due to their liquid
crystalline (LC) properties. The origin for these can be found in the formation of
domains; the “Coulombic” layers in which the ionic head-groups interact with the
counterions, and the “van der Waals” layer which is formed by the anti-parallel
stacking of the alkyl chains. Hexafluorophosphate salts with cations such as
C20MIM have been investigated by differential thermal analysis (DTA) and show
one or more LC transitions. Melting to isotropic liquids occurs at rather high
temperatures up to >100°C.
Moreover, by fine-tuning the structure, these properties can be tailor-designed
to satisfy the specific application requirements. As a result, the ionic liquids are very
popular materials and they enjoy an abundance of applications in various domains of
physical sciences.
2.4
Ionic Liquids as Solvent in Organic and Catalytic Reactions
In today’s environmentally conscious world, the organic reactions, catalytic
and separation processes require the development of alternative solvents and
advanced technologies [31]. Although water has emerged as a useful reaction
medium for the past 20 years, its application is still limited due to the low miscibility
of organic substrates, which often resulted in low reaction rates. Moreover, water is a
protic coordinating solvent so it can react with organometallic complexes by halidecarbon bond protolysis or metal-carbon bond split, contaminating the desired yield.
Therefore, if water represents a very interesting solvent for two-phase catalysis, it
cannot be used for all catalysts and substrates without modifications.
15
The usage of conventional molecular organic solvents such as acetonitrile,
DMF and chlorinated hydrocarbons, to name a few, proved to be constructive;
however, they were hazardous to the health and the environment. Furthermore, in
transition metal catalyzed reactions, the toxic and air sensitive phosphanes have been
used as ligands.
More recently, perfluorinated solvents have come to interest, nevertheless,
specific ligands must be designed to solubilize catalyst in the perfluorinated phase.
Moreover, decomposition of fluorous solvents at high temperature also yields toxic
compounds, and fluorous derivatives are often detected in the organic phase.
Supercritical fluids such as ScCO2 were also described as the new solvents
for organic and catalytic reactions. Their physical and chemical stability made them
described as particularly green solvents. Unfortunately, critical conditions needed for
their use is still a limitation.
Due to the above reasons, most of the industrial organic synthesis needs
rethinking. An approach to resolve these drawbacks is most probably the use of nonaqueous ionic liquids to replace the conventional solvents. Some simple properties of
these ionic liquids that make them interesting as potential solvents for synthesize are
the following [32]; 1) they are good solvents for a wide range of organic and
inorganic materials, and unusual combination of reagents can be brought into the
same phase, 2) they are often composed of poorly coordinating ions, so they have the
potential to be highly polar yet non-coordinating solvents, 3) they are immiscible
with a number of organic solvents and provide a non-aqueous, polar alternative for
two phase systems, while in other cases, hydrophobic ionic liquids can be used as
immiscible polar phases with water and 4) ionic liquids are non-volatile, hence they
may be used in high-vacuum systems without evaporating and eliminating many
containment problems.
16
One of the most distinct advantages of the ionic liquids that have been
rationale for their characterization as the “green solvents” is their negligible
volatility. This characteristic made them as potential candidates to replace the
volatile organic compounds that have been widely used in large quantities in
chemical and engineering industries, which is a source of major environmental
problems. Moreover, many ionic liquids can be recycled and reused repeatedly.
Based on the unique properties of ionic liquids, they have been successfully
employed in many organic and catalytic reactions [33], including the Dimersol /
Difasol process, Ziegler-Natta polymerization, Diels-Alder reactions, hydrogenation
and hydroformylation, Friedel-Crafts chemistry and the topic of interest in this thesis,
the Heck reaction.
The Dimersol / Difasol process was developed and commercialized by the
Institut Français du Pétrole (IFP) [34]. This Ni-catalyzed process is widely used
industrially for the dimerization of alkenes, typically propene and butanes, to
produce more valuable branched hexenes and octenes. This process used acidic
chloroaluminate ionic liquids with small amounts of alkylaluminiums as the solvent
for the catalytic Ni centre. In addition to the ease of product / catalyst separation are
the increased activity of the catalyst, better selectivity to desirable dimers and the
efficient use of valuable catalysts through simple recycling of the ionic liquid. An
example of this reaction is the dimerization of propene (20) to 2,3-dimethylbutene
(21) in ionic liquid of [Bmim]Cl (Scheme 2.1)
Ni
2
[Bmim]Cl / AlCl3 / AlEtCl2
83%
(20)
Scheme 2.1
(21)
The dimerization of propene (20) in ionic liquid of [Bmim]Cl via the
Dimersol / Difasol process
17
The Ziegler-Natta polymerization produced Į-olefins from the
polymerization of ethylene. It has been reported that the reaction of ethylene in an
acidic [Emim]Cl-AlCl3 ionic liquid while using dichloro-bis(Ș5-cyclopentadienyl)
titanium(IV) with an alkyl-chloroaluminium(III) as the co-catalyst [35]. The ionic
liquid system was proved to be more superior to analogous zirconium and hafnium
complexes which were failed to show catalytic activity. The general reaction scheme
for this reaction is the polymerization of propene (20) to polypropane (22) as shown
in Scheme 2.2.
Ti
[Emim]Cl / AlCl3
n
(20)
Scheme 2.2
(22)
The polymerization of propene (20) in ionic liquid of [Emim]Cl via
the Ziegler-Natta reaction
Neutral ionic liquids have been demonstrated as effective solvents for DielsAlder reactions [36]. The use of ionic liquids leads to significant rate enhancements
and high yields and selectivities based on the endo / exo ratios, comparable with the
best results obtained in conventional solvents. An additional benefit is that the ionic
liquid can be recycled and reused after solvent extraction or direct distillation of the
product from the ionic liquid. An example of a Diels-Alder reaction in an ionic liquid
is the reaction between cyclopentadiene (23) and ethyl acrylate (24) in [Bmim]PF6,
to obtain the product isomer of (25) and (26) (Scheme 2.3).
18
O
[Bmim]PF6
+
O
+
AlCl3
CO2C2H5
CO2C2H5
(23)
(24)
endo
exo
(25)
(26)
The Diels-Alder reaction between cyclopentadiene (23) and ethyl
Scheme 2.3
acrylate (24) in ionic liquid of [Bmim]PF6
Hydrogenation is an addition of hydrogen into alkenes, usually catalyzed by
Rh, Ru or Co-based catalysts. The hydrogenation of olefins catalyzed by transition
metal complexes dissolved in ionic liquid of solvent have been reported using Rhcatalyst, where the hydrogenation rates have shown to be up to five times higher than
the comparable reactions in propanone, or in analogous two-phase aqueous-organic
systems [37]. In this example (Scheme 2.4), pentene (27) was hydrogenated to
pentane (28) using the Osborn rhodium catalyst [Rh(norbornadiene)(PPh3)2]PF6 in
ionic liquids of [Bmim]SbF6.
[Rh(nbd)(PPh3)2]PF6
[Bmim]SbF6
(27)
Scheme 2.4
(28)
The hydrogenation of pentene (27) to pentane (28) in ionic liquid of
[Bmim]SbF6
For hydroformylations in ionic liquids, biphasic catalysis is a well-established
method for effective catalyst separation and recycling [38]. Most hydroformylations
are rhodium-catalyzed, however, platinum, cobalt and ruthenium can serve as
catalyst. The catalyst is dissolved in the ionic liquid phase. Scheme 2.5 showed an
example of a biphasic hydroformylation of the Pt-catalyzed hydroformylation of 1-
19
octene (29) in [Bmim]Cl-SnCl2, with a remarkable n (30) / iso (31) selectivity of
20:1 .
PtCl2(PPh3)2
O
H
[Bmim]Cl-SnCl2
+
O
H
iso-product
n-product
(29)
(30)
Scheme 2.5
(31)
The hydroformylation of 1-octene (29) in ionic liquid [Bmim]Cl-
SnCl2
Friedel-Crafts alkylation places an alkyl group on a benzene ring. It involves
the interaction of an alkylation agent, such as an alkyl halide, alcohol or alkene with
an aromatic compound. Friedel-Crafts alkylation has been demonstrated using
chloroaluminate(III) ionic liquids as both solvent and catalyst [39]. Reaction rates are
much faster, where in certain cases are often essentially instantaneous, with total
reagent conversion. Typically, alkylation reactions with alkenes are performed
between 80-200 °C using 0.5% ionic liquid catalyst. Scheme 2.6 showed an example
of the Friedel-Crafts alkylation of benzene (32) with ethylene (33) in [Emim]ClAlCl3 to obtained ethylbenzene (34).
+
(32)
Scheme 2.6
[Emim]Cl / AlCl3
(33)
(34)
The Friedel-Crafts alkylation of benzene (32) with ethylene (33) in
ionic liquid of [Emim]Cl
20
2.5
The Heck Reactions
In the early 1970’s, Richard Heck from the Hercules Co. and later at the
University of Delaware discovered a palladium-catalyzed reaction in which the
carbon group of haloalkenes and haloarenes is substituted for a hydrogen on the
vinylic carbon of an alkene [40]. This reaction, now known as the Heck reaction, is
particularly valuable in synthetic organic chemistry because it is the only general
method yet discovered for this type of substitution.
Substitution for a vinylic hydrogen by the Heck reaction is highly
regioselective; formation of the new carbon-carbon bond most commonly occurs at
the less substituted carbon of the double bond. In addition, where a cis or trans
configuration is possible at the new carbon-carbon double bond of the product, the
Heck reaction is highly stereoselective, often giving almost exclusively the Econfiguration of the resulting alkene. Moreover, the Heck reaction is stereospesific
with regard to the haloalkene; the configuration of the double bond in the haloalkene
is preserved.
The Heck reaction has been extensively utilized in preparing a wide variety
of olefinic compounds. One major transformation in the Heck reaction is the
synthesis of cinnamic acid and its derivatives, which are very versatile compounds as
the flavour substances and UV absorbents [41].
2.5.1
Components of the Heck Reaction Medium
The most commonly used palladium catalyst in the reaction medium is in the
form of palladium(II) acetate, Pd(OAc)2. This compound and others of the same
oxidation state are better termed precatalysts because the catalytically active form of
the metal is a complex zero-valent metal, Pd(0), formed in situ by reduction of Pd(II)
21
to Pd(0). However, most of previous reports used additional ligands, L, to give the
actual catalyst, Pd(0)L2 [42]. This catalyst then reacts with the organic halide to
begin the catalytic cycle. Since palladium is very expensive, only a small amount of
the catalyst is required.
The most commonly used halides are the aryl, heterocyclic, benzylic and
vinylic iodides, which are known to be more reactive than the bromides and the
chloride derivatives [43]. Alkyl halides which contain ȕ-hydrogen are rarely used
because they are easily undergoing ȕ-elimination under condition of the Heck
reaction to form alkenes. A particular advantage of the Heck reaction is the wide
range of the functional groups including alcohols, ethers, aldehydes, ketones and
esters that may be occur elsewhere in the organo-halogenated compound or alkene,
do not affect the Heck reaction.
The types of alkenes used are based on its reactivities [44]. The reactivity of
the alkenes is a function of steric crowding about the carbon-carbon double bond.
The greater the degree of substitution on the double bond, the slower the reaction and
the lower yield of the product. Thus, ethylene and mono-substituted alkenes are the
most reactive.
Other components of the reaction medium are the bases, solvents and the
ligands. Commonly used bases are triethylamine, sodium or potassium acetate, and
sodium hydrogen carbonate, while polar aprotic solvent such as DMF, acetonitrile,
dimethylsulfoxide are normally used. However, in some cases it is possible to carry
out the Heck reaction in aqueous ethanol [45]. Finally, ligands which are used to
coordinate with Pd(0) are normally triphenylphosphine, PPh3, and BINAP. Many
other ligands can be used as well, including asymmetric ones which lead to chiral
products [46].
22
Recently, it has been discovered that the Heck reaction proceeds more
rapidly, with higher yields by the addition of a quaternary ammonium salt such as
tetrabutylammonium chloride, Bu4NCl [47]. This type of salt belongs to a class of
compounds called phase-transfer catalysts. Due to this reason that some Heck
reactions take place in a single homogenous phase, the function of this salt is most
probably to increase the polarity of the medium.
In this thesis, the Heck reactions between several aryl bromides with different
substituted groups (56-60) with methyl acrylate (61) have been conducted in ionic
liquids medium of N-butyl-N-methyl trifluoromethanesulfonate, [Bmplim]CF3SO3
(49). The effects of the bases, palladium catalysts loadings and reaction temperatures
have been studied to determine the best condition for this reaction to proceed in ionic
liquids. The effect of phosphine ligands is also being studied in certain cases when
dealing with unreactive aryl bromides derivatives such as 4-bromoanisole (59) and 4bromoaniline (60).
2.5.2 Mechanism of the Heck Reaction
The mechanism of the Heck reaction is divided into two stages [48]. The
preliminary stage is the reduction of Pd(II) (35) to Pd(0) (36), followed by the
complexation of Pd(0) with other ligands, L (in cases where liganted-Pd catalyst are
involved). This Pd(0) or PdL2 complex is the actual Heck catalyst. As illustrated in
Scheme 2.7, conversion of Pd(II) to Pd(0) requires a tetraamine (37) such as
triethylamine to function as the reducing agent. The amine also assists in the final
hydrogen halide elimination step in Scheme 2.8.
23
R2NCH2R'
+
Pd
OAc
R2N
Pd
OAc
(37)
HPdOAc
+
R2N
reductive
elimination
+
+
—
OAc
H
OAc
(35)
ȕ elimination
CHR'
—
CHR' OAc
+ HPdOAc
Pd0 + HOAc
(36)
Scheme 2.7
The reduction of Pd(OAc)2 (35) to the active Pd(0) (36) Heck catalyst
Then, the catalytic cycle begins. There are four key steps in the catalytic
cycle of the Heck reaction; oxidative addition, alkene insertion, ȕ-hydride
elimination and reductive elimination. However, the catalytic cycle of liganted-Pd
precursors are suggested to be more complicated [49]. Scheme 2.8 shows the general
mechanism which occurred during the Heck reaction catalytic cycle. In this example,
an oxidative addition reaction between Pd(0) (36) and aryl halide with methyl
acrylate produces a ı-arylpalladium(II) complex. This complex undergoes an alkene
insertion reaction with the methyl acrylate. Internal rotation around the CʊC bond
as indicated position of the ı-arylpalladium(II) intermediate for subsequent ȕhydride syn elimination which produces the alkene-aryl halide coupling product and
palladium hydride halide. The Pd(0) (36) catalyst regenerated from this complex by
reductive elimination of hydrogen halide by the base.
24
R1
Ar
R1
oxidative
+ Pd(0) addition
(36)
X
X
Pd
Ar
H
Ar
Pd
X
H
H
H
COOCH3
alkene
insertion
H
H
R1
COOCH3
rotation
R1
Pd
H
Ar
H
H
H
H
COOCH3
X
ȕ-hydride
R1
Ar
elimination
(Product)
COOCH3
+
H
Pd
X
(Catalyst)
H
Pd
X
+
Scheme 2.8
base
reductive
elim ination
P d0
+
(36)
General mechanism of the Heck reaction
ʊ
+
E t 3 N H ,I
CHAPTER 3
RESULTS AND DISCUSSION
3.1
The Synthesis of Ionic Liquids Derived from N-alkyl-N-methyl
pyrrolidinium Trifluoromethanesulfonate Series (46-52)
3.1.1
Quaternization and Metathesis Reactions
In general, the preparative method of the ionic compound is a two-step
process. The first step is known as the quaternization reaction, followed by the
metathesis reaction in the second step. All reactions were conducted in an inert and
dry atmosphere of nitrogen in order to avoid the hydrolysis of N-alkyl-Nmethylpyrrolidinium iodide salts (39-45) [50]. The general method for this process is
shown in Scheme 3.1.
26
(quaternization)
(metathesis)
+ RI
N
CH3
(38)
Scheme 3.1
+
N
ether
H3C
(39) R = CH3
(40) R = C2H5
(41) R = C3H7
(42) R = C4H9
I-
AgCF3SO3
R
(43) R = C5H11
(44) R = C6H13
(45) R = C7H15
CF3SO3-
+
N
EtOH
H3C
R
(46) R = CH3
(47) R = C2H5
(48) R = C3H7
(49) R = C4H9
(50) R = C5H11
(51) R = C6H13
(52) R = C7H15
General method of quaternization and metathesis reactions for
preparing N-alkyl-N-methylpyrrolidinium trifluoromethanesulfonate salts (46-52)
In previous reports, the potential of N-heterocyclic compounds has been
studied as an alternative replacement for the conventional organic solvents due to the
high nucleophilicity of the ring nitrogen atom [51]. In this thesis, N-alkyl-N-methyl
pyrrolidinium trifluoromethanesulfonate salts (46-52) have been synthesized to
explore their potential usage as the room temperature ionic liquids, for the
application as the solvent in the Heck reactions.
In the quaternization step, N-methylpyrrolidine (38) was reacted with several
types of linear alkyl iodides, ranging from methyl to heptyl derivatives. Due to the
presence of the nitrogen atom from the cation, which is basic and nucleophilic, this
reaction involved the attacking of the isolated electron from the nitrogen atom
towards the carbon atom of the alkyl iodides. Time taken for a complete reaction
depends on the lengths of the alkyl chains of the iodides. The longer the carbon
chains, the longer the time required for completion. This is due to the mesomeric
effects caused by the alkyl chains lengths [52]. As for longer chain, the localization
of electrons made the structure more stable than the shorter chain; therefore, the
structure is more reluctant to undergo reaction compared to the shorter chain.
27
However, the N-alkyl-N-methylpyrrolidinium iodide salts (39-45), with
melting point ranging from 79 to 300°C [53], were air and moisture-sensitive, thus
limiting the potential of these salts to be used as an ideal solvent. In order to
overcome this problem, these salts are anion exchanged through the metathesis
reaction, with the trifluoromethanesulfonate anion, which are known to lower the
melting point values and made these salts more stable towards air and moisture [54].
This process, however, was very rapid due to the fact that the lengths of alkyl chains
have no effect on this step. In each case, the yellow precipitate of silver iodide, AgI,
was produced immediately and observed during this process. This precipitate is
easily separated since these salts (46-52) exist as liquid in the ethanol solution,
therefore enabling a facile separation from the solid by-product of AgI. These salts
(46-52) were collected by reducing the volume of the filtrate to a quarter of its
original volume. These salts (46-52) which are predicted to be thermally stable up to
400°C [55], will remain as a pure, isolated products.
3.1.2
Synthesis of N-alkyl-N-methylpyrrolidinium Trifluoromethanesulfonate
Salts (46-52) from N-alkyl-N-methylpyrrolidinium Iodide Salts (39-45)
I-
+
N
H3C
(39) - (45)
Scheme 3.2
R
AgCF3SO3
CF3SO3-
+
N
EtOH
H3C
R
(46) R = CH3
(47) R = C2H5
(48) R = C3H7
(49) R = C4H9
(50) R = C5H11
(51) R = C6H13
(52) R = C7H15
Synthesis of N-alkyl-N-methylpyrrolidinium trifluoromethane
sulfonate salts (46-52)
28
A series of salts derived from the N-alkyl-N-methylpyrrolidinium
trifluoromethanesulfonate (46-52) have been successfully synthesized with
moderately high yield, ranging between 72 to 96%. Among this series, three salts
were observed to exist as oily yellow liquids at room temperature (~25°C); the butyl
(49), the pentyl (50) and the heptyl (52) derivatives, while the other derivatives;
methyl (46), ethyl (47), propyl (48) and hexyl (51), exist as yellow / white solid
compounds with melting points ranging from 62 to 302°C. These salts were
characterized by their physical data, such as densities, solubilities and molar
conductivities. The data for each salt is tabulated in Table 3.1.
Table 3.1: Physical characterization of N-alkyl-N-methylpyrrolidinium trifluoro
methanesulfonate salts (46-52)
R[mplim]CF3SO3
m.p.
*Molar Conductivity (ȁM)
Density
S cm2mol-1
(g/mL)
(28°C)
(28°C)
Solubility
Yield
in Water
(%)
Alkyl chain, R
(°C)
Methyl (46)
300-302
8100
0.08
Yes
95.7
Ethyl (47)
87-89
7480
0.17
Yes
88.5
Propyl (48)
77-78
5400
0.22
Yes
78.4
Butyl (49)
<25
2700
1.03
Yes
80.8
Pentyl (50)
<25
2530
1.14
Yes
75.0
Hexyl (51)
62-64
2270
1.38
Yes
72.1
Heptyl (52)
<25
1980
1.57
Yes
78.7
*NaCl 1 x 10-2 M = 1568 S cm2mol-1
The study of the effect of alkyl chains lengths towards the melting points of
the N-alkyl-N-methylpyrrolidinium trifluoromethanesulfonate salts (46-52) was
carried out to determine the required molecular structure of the substances used in
order to produce the low melting points ionic compounds. Furthermore, the changes
in molecular structure will affect other properties such as viscosities, densities and
hydrophobicity of respective salts [56].
29
350
300
m.p. (°C)
250
200
150
100
50
Solid
25°C
Liquid
0
0
1
2
3
4
5
6
7
8
Alkyl Chain Length, n
R
Figure 3.1
The effect of alkyl chains lengths towards the melting points of the N-
alkyl-N-methylpyrrolidinium trifluoromethanesulfonate salts (46-52)
As can be observed from Figure 3.1, the melting points fall sharply from the
methyl derivatives of the series to the propyl analogue (n = 1 to n = 3). All these
three derivatives were obtained as the solid adducts at room temperature. However,
from the butyl to heptyl derivatives (n = 4 to n = 7), the products were obtained as
liquid at room temperature, except for the hexyl derivative (n = 6) which exists as
solid. Therefore, it can be concluded that there is no correlation between the lengths
of alkyl chains towards the melting points of these salts (46-52) and it is difficult to
predict the precise pattern of the melting points for these materials. These
observations are in full agreement with other ionic liquids derived from the Nheterocyclic compounds such as 1,3-dialkylimidazolium hexafluorophosphate series
(53), reported by Dzyuba et al. [57].
1
R
N
+
N
(53)
2
R
PF6
ʊ
30
However, it has been proposed that the use of diffuse negative charge and
low-symmetry anion such as bis(trifluoromethanesulfonyl)amide, TFSA(III), and
triflate compounds were accounted for the low-melting points ionic liquids [58]. Due
to the weak interaction between these types of anions with the organic cations, the
ionic compounds with low lattice energy will be produced.
Figure 3.2 shows the effect of alkyl chains lengths towards the molar
conductivities of the obtained N-alkyl-N-methylpyrrolidinium trifluoromethane
sulfonate salts (46-52). The purpose of this study is to determine the electrochemical
properties of these respective salts in order to prove their existence as ionic
compounds. Moreover, this study provides a major contribution to electrochemists in
developing future potential electrolytes derived from ionic compounds [59].
9000
8000
6000
(S cm2mol-1)
*Molar Conductivity (ȁM)
7000
5000
4000
3000
2000
1000
0
0
1
2
3
4
5
6
7
8
Alkyl Chain Length, R
Figure 3.2
The effect of alkyl chains lengths towards the molar conductivities
(ȁM) of the N-alkyl-N-methylpyrrolidinium trifluoromethanesulfonate salts (46-52)
The molar conductivities for these salts were measured by dissolving 1x10-2
M solution of each salt in ethanol. Figure 3.2 shows that as the size of cation
increases, the molar conductivities for these salts decreases. This condition can be
explained by observing the size of the cation and the mobility of the anion [60]. For
31
instance, the value of the molar conductivity is initially high due to the size of the
anion which was bigger than the cation. This difference in size enabled the anion to
move freely in the solution. However, as the size of the cations increases and
surpassed the size of the anion, the cation will increases the electrostatic force
towards the anion, thus limiting the anion movement, resulting the molar
conductivity to decrease. A similar observation was reported by previous researchers
for [Emim]BF4 (54) [61] and [Emim]F(HF)n (55) [62].
R1
N
+
N
(54)
ʊ
R2
BF4
1
R
N
+
N
ʊ
2
R
F(HF)n
(55)
The densities of all the salts were determined by weighing a measured
volume of these materials. As can be seen in Table 3.1, the densities for the N-alkylN-methylpyrrolidinium trifluoromethanesulfonate salts (46-52) increases as the size
of the cation increases. This is due to the packing of the ionic molecules in its lattice,
as for a bulky compound, the density will be higher and vice versa. Furthermore,
there is an interesting tendency that the compounds of bulky, and therefore, weakly
coordinating anions possess relatively high densities regardless of the counter cations
[63].
The miscibility of ionic liquids with water is particularly interesting. Most of
the ionic liquids described to date are hygroscopic, in which some will mix with
water in all compositions, whereas others eventually saturated and then form two
layers [64, 65]. However, all the N-alkyl-N-methylpyrrolidinium trifluoromethane
sulfonate salts (46-52) discussed in this study dissolved in water and other common
polar solvents such as methanol and ethanol. This behavior is principally controlled
by the anion of the ionic liquid, with the cation having a secondary effect [66]. The
mutual solubilities of ionic liquids in water and organic solvents depend on the
ability of ionic liquids to form hydrogen bonds or other possible interactions with the
32
potential solvents. These interactions depend on the capability for hydrogen-bond
donation from the cation to polar or dipolar compounds, hydrogen-bond accepting
functionality of the anion and ʌ-ʌ interactions, which enhance aromatic solubility
[67]. For example, 1-ethyl-3-methyl-imidazolium hexafluorophosphate can act both
as hydrogen-bond acceptor (PF6¯) and donor (Emim+) and would be expected to
interact with solvents which have both accepting and donating sites. There are also
some reports which claimed that the miscibility of ionic liquids in water can be
manipulated through addition of short chain alcohol to biphasic systems to increase
mixing [68], adding salts to separate otherwise water miscible ionic liquids [69], or
varying the alkyl chain lengths of the respective cation or the nature of the anion
[70].
In terms of stability, the N-alkyl-N-methylpyrrolidinium trifluoromethane
sulfonate salts (46-52) are more stable towards air and moisture compared to the
iodide salts (39-45). It has been reported that there are two types of anions;
polynuclear and mononuclear anions [71]. Polynuclear anions such as Al2Cl7¯,
Al3Cl10¯, Au2Cl7¯, Fe2Cl7¯ and Sb2Cl11¯ are formed by the reaction of the
corresponding Lewis acid with the mononuclear anion, for example AlCl3 with
AlCl4¯. These types of anions are particularly air and moisture sensitive. The
mononuclear anions such as BF4¯, PF6¯, CF3SO3¯, ZnCl3¯, SbF6¯ and N(CF3SO2)2¯,
which are the weakly complexing anion, on the other hand, lead to neutral,
stoichiometric and stable ionic liquids. Therefore, it can be concluded that the
stability of these salts were determined by the types of the anions used in the
compounds.
33
3.1.3
Characterization of N-alkyl-N-methylpyrrolidinium Trifluoromethane
sulfonate Salts (46-52)
3.1.3.1 1H-NMR Spectroscopy Analysis
The 1H-NMR spectra of the N-alkyl-N-methylpyrrolidinium trifluoromethane
sulfonate salts series (46-52) are shown in Appendices 1, 3, 5, 7, 9, 11 and 13. The
data are tabulated in Table 3.2.
Table 3.2: 1H-NMR data of the N-alkyl-N-methylpyrrolidinium trifluoromethane
sulfonate salts (46-52)
3
4
2
1
+
N
5
H3C
CF3SO3-
(46) R = CH3
(47) R = C2H5
(48) R = C3H7
(49) R = C4H9
(50) R = C5H11
(51) R = C6H13
(52) R = C7H15
R
Chemical shift, į (ppm)
Alkyl Chain, R
H-6
H-7
H-8
H-9
H-10
H-11
H-12
-6CH3-
(46)
3.08
-
-
-
-
-
-
-6CH2-7CH3-
(47)
3.37
1.26
-
-
-
-
-
-6,7(CH2)2-8CH3-
(48)
3.25
1.72
0.91
-
-
-
-
-6,7,8(CH2)3-9CH3-
(49)
3.28
1.66
1.30
0.91
-
-
-
-6,7,8,9(CH2)2-10CH3-
(50)
3.26
1.67
0.85
-
-
-6,7,8,9,10(CH2)2-11CH3-
(51)
3.29
1.68
0.86
-
-6,7,8,9,10,11(CH2)2-12CH3-
(52)
3.28
1.68
1.28
1.28
1.27
0.87
34
The 1H-NMR spectrum for N,N-dimethylpyrrolidinium trifluoromethane
sulfonate (46) (Appendix 1) showed the presence of an unresolved triplet at į 2.09
ppm which corresponded to 4 protons of the methylene groups at C-2 and C-3.
Presumably, this phenomenon occurred due to the properties of methylene protons at
C-1 and C-4 which were suggested to be chemically but not magnetically equivalent.
Therefore, the coupling of the protons at C-2 and C-3 with protons at C-1 and C-4
made the peaks observable yet not resolved. Moreover, the H-1 and H-4 protons
resonances were observed at į 3.44 ppm – at a higher chemical shift than usual. This
is due to the deshielding effect of N+ ion. The six’s C-5 and C-6 methyl protons are
also being deshielded by the N+ ion and are observed to be chemically equivalent,
thus appeared as a singlet peak at į 3.08 ppm. Additional peaks were observed at į
2.50 and 3.39 ppm were resulted from water and DMSO respectively.
The 1H-NMR spectrum for N-ethyl-N-methylpyrrolidinium trifluoromethane
sulfonate (47) (Appendix 3) showed a triplet signal at į 1.26 ppm, corresponded to 3
protons at C-7 methyl group. The methyl protons at C-5 which was deshielded by the
N+ ion, were observed as a singlet signal at į 2.95 ppm. The methylene protons at C6 which were also being deshielded by the N+ ion resonated as a multiplet at į 3.37
ppm. This peak was observed at the same chemical shift with the multiplet of
methylene protons at C-1 and C-4. The methylene protons at C-2 and C-3 which
coupled with the methylene protons at C-1 and C-4 were observed as a broad singlet
at į 2.08 ppm. Again, the signal for water and DMSO were observed at į 2.50 and
3.49 ppm respectively.
The 1H-NMR spectrum for N-methyl-N-propylpyrrolidinium trifluoro
methanesulfonate (48) (Appendix 5) showed similar signals for protons at C-1, C-2,
C-3, C-4 and C-5 as in compound 47. A triplet peak was also observed at į 0.91
ppm, corresponded to 3 protons at C-8 methyl group. The methylene protons at C-6,
which were coupled with the protons at C-7 and being deshielded by the N+ ion, was
observed as a multiplet at į 3.25 ppm.
35
The 1H-NMR spectrum for N-butyl-N-methylpyrrolidinium trifluoromethane
sulfonate (49) (Appendix 7), also showed similar pattern as in compound 48, the only
different is that there was an additional multiplet signal at į 1.30 ppm, corresponded
to the methylene protons at C-8, which was coupled with both of the methylene and
methyl protons at C-7 and C-9. Other signals at į 2.50 and 3.80 ppm were resulted
from water and DMSO respectively.
As for the other compounds, namely; N-methyl-N-pentylpyrrolidinium
trifluoromethanesulfonate (50) (Appendix 9), N-hexyl-N-methylpyrrolidinium
trifluoromethanesulfonate (51) (Appendix 11) and N-heptyl-N-methylpyrrolidinium
trifluoromethanesulfonate (52) (Appendix 13), the 1H-NMR spectra for these salts
were similar to compound 49, but with an addition of methylene protons at; C-9 for
pentyl derivative (50), C-10 for hexyl derivative (51) and C-11 for heptyl derivative
(52) during the homologues addition of alkyl chains which was directly bonded to
the N+ ion. These signals were observed around į 1.27 to 1.28 ppm as a multiplet or
a broad singlet peak. Again, other signals at į 2.50 and ~3.68 ppm in these spectra
were corresponded to water and DMSO respectively.
In conclusion, the N-alkyl-N-methylpyrrolidinium trifluoromethanesulfonate
salts (46-52) have been successfully synthesized and the 1H-NMR spectral data for
these salts were consistent with their proposed structure.
3.1.3.2 13C-NMR Spectroscopy Analysis
The ionic liquids synthesized in this work have also been characterized using
the 13C-NMR spectroscopy. In this thesis, three types of 13C-NMR analysis have
been conducted. Instead of the normal 13C–{H} analysis which determine all types of
13
C nuclei, the DEPT90 and DEPT135 experiments were also employed to further
aid in the 13C-NMR analysis. As in the 1H-NMR data, the 13C-NMR data were also
varied by the alkyl chain groups, R. The 13C-NMR spectra of the N-alkyl-N-
36
methylpyrrolidinium trifluoromethanesulfonate salts (46-52) are shown in
Appendices 2, 4, 6, 8, 10, 12 and 14. The data are tabulated in Table 3.3.
Table 3.3: 13C-NMR data of the N-alkyl-N-methylpyrrolidinium trifluoromethane
sulfonate salts (46-52)
3
4
2
1 CF SO 3
3
+
N
5
H3C
Alkyl Chain, R
(46) R = CH3
(47) R = C2H5
(48) R = C3H7
(49) R = C4H9
(50) R = C5H11
(51) R = C6H13
(52) R = C7H15
R
Chemical shift, į (ppm)
C-6
C-7
C-8
C-9
C-10
C-11
C-12
-6CH3-
(46) 51.99
-
-
-
-
-
-
-6CH2-7CH3-
(47) 59.30
9.06
-
-
-
-
-
-6,7(CH2)2-8CH3-
(48) 65.56
16.97
10.96
-
-
-
-
-6,7,8(CH2)3-9CH3-
(49) 64.00
25.35
19.62
13.36
-
-
-
-6,7,8,9(CH2)2-10CH3-
(50) 64.00
23.05
28.08
21.53
13.14
-
-
-6,7,8,9,10(CH2)2-11CH3-
(51) 64.00
25.94
30.92
23.32
22.08
13.81
-
-6,7,8,9,10,11(CH2)2-12CH3-
(52) 64.00
26.28
31.31
28.36
23.37
22.18
13.91
The 13C-NMR spectra of the N,N-dimethylpyrrolidinium trifluoromethane
sulfonate (46) (Appendix 2) showed a signal at į 22.10 ppm which was assigned to
the two methylene carbons at C-2 and C-3. A signal resonated at į 65.76 ppm was
attributed to the other two methylene carbons at C-1 and C-4 which were deshielded
by the N+ ion. Meanwhile, the methyl carbons at C-5 and C-6, which were also
deshielded by the N+ ion, resonated at į 51.99 ppm.
37
The other N-alkyl-N-methylpyrrolidinium trifluoromethanesulfonate salts
derivatives; the ethyl (47) (Appendix 4), propyl (48) (Appendix 6), butyl (49)
(Appendix 8), pentyl (50) (Appendix 10), hexyl (51) (Appendix 12) and heptyl (52)
(Appendix 14), showed four typical signals between; į 21.60-21.84 ppm were
corresponded to the methylene carbons at C-2 and C-3, į 63.78-64.44 ppm were
corresponded to the methylene carbons at C-1 and C-4 and the deshielded methyl
carbon at C-5 was observed at į 48.15-48.99 ppm. Lastly, the methylene carbon at C6, which was also being deshielded by the N+ ion, was observed around į 59.3065.56 ppm. The C-6 signal, which sometimes was not observed in the spectra, was
found to be overlapping with the C-1 and C-4 signals. However, through the
DEPT135 and DEPT90 analysis, this signal was successfully identified.
Another methyl carbon located at the end of the alkyl chains of these
compounds; C-7 of the ethyl derivative (47) (Appendix 4), C-8 of the propyl
derivative (48) (Appendix 6), C-9 of the butyl derivative (49) (Appendix 8), C-10 of
the pentyl derivative (50) (Appendix 10), C-11 of the hexyl derivative (51)
(Appendix 12) and C-12 of the heptyl derivative (52) (Appendix 14), were observed
between į 9.06-13.91 ppm, depending on the length of the alkyl chain. The value
was shifted to a higher chemical shift, for longer alkyl chains.
Finally, all the methylene carbons for compounds 48 to 52 which involved in
the homologues addition in the alkyl chains were observed between į 16.97 to 31.31
ppm. Although some signals could not be observed in the 13C–{1H} spectra, the
DEPT135 and DEPT90 analysis confirmed those peaks to be identified.
In conclusion, all the 13C-NMR spectra for these salts (46-52) were consistent
with their respective 1H-NMR spectral data.
38
3.1.3.3 CHN Elemental Analysis
The NMR spectra of the N-alkyl-N-methylpyrrolidinium trifluoromethane
sulfonate salts (46-52) which were recorded in DMSO-d6 solvent showed very
similar pattern with the N-alkyl-N-methylpyrrolidinium iodide salts series (39-45).
This is because the ion exchange step between the iodide and the trifluoromethane
sulfonate did not affect the molecular structure of these respective salts. Therefore,
CHN elemental analysis has been carried out to determine the purity of these salts.
The CHN data analysis of N-alkyl-N-methylpyrrolidinium trifluoromethanesulfonate
salts series (46-52) are shown in Table 3.4.
Table 3.4: CHN elemental analysis of the N-alkyl-N-methylpyrrolidinium trifluoro
methanesulfonate salts (46-52)
Anion
Alkyl, R
Methyl (46)
Ethyl (47)
Propyl (48)
Butyl (49)
Pentyl (50)
Hexyl (51)
Heptyl (52)
CF3SO3¯
%C
%H
%N
33.53
5.45
5.48
(33.73)
(5.66)
(5.62)
36.65
6.30
5.41
(36.50)
(6.13)
(5.32)
39.00
6.66
5.25
(38.98)
(6.54)
(5.05)
41.15
6.89
4.78
(41.23)
(6.92)
(4.81)
43.36
7.33
4.62
(43.27)
(7.26)
(4.59)
45.22
7.60
4.45
(45.13)
(7.57)
(4.39)
46.84
7.76
4.24
(46.83)
(7.86)
(4.20)
*Numbers in parenthesis are the calculated values
39
Although the relative molecular weight for the iodide (39-45) and the
trifluoromethanesulfonate salts series (46-52) differs for only 22.17 g/mol for each
derivatives, their differences in elemental analysis were very clear. From the results,
it was observed that the experimental value is in close proximity to the calculated
value, with the standard deviations of ± 0.50%. This shows that the purity of the
synthesized N-alkyl-N-methylpyrrolidinium trifluoromethanesulfonate salts (46-52)
were considerably high.
In conclusion, all the molecular formula of the N-alkyl-N-methyl
pyrrolidinium trifluoromethanesulfonate salts series (46-52) were consistent with
their molecular structures.
From the results, the N-butyl-N-methylpyrrolidinium trifluoromethane
sulfonate, [Bmplim]CF3SO3 (49), has been chosen as the solvent in the Pd-catalyzed
Heck reactions of aryl bromides based on its existence as an oily yellow substrate
and giving the highest yield of product (80.8%) compared to other derivatives.
3.2
The Heck Reactions
O
Br
O
Pd(OAc)2 (35)
OMe
R1
1
1
(59) R = OCH3
(56) R = NO2
(57) R1 = COCH3 (60) R1 = NH2
(58) R1 = H
Scheme 3.3
OMe
[Bmplim]CF3SO3 (49)
+
(61)
R1
(62) R1 = NO2
1
(63) R = COCH3
(64) R1 = H
(65) R1 =OCH3
1
(66) R = NH2
The Heck reactions between methyl acrylate (61) and several types of
aryl bromides (56-60)
40
This thesis aims to draw attention to the future challenges in the area of
organic synthesis by highlighting advances concerning the Heck coupling reactions
using aryl bromides in the ionic liquids medium. This type of halide is more reluctant
to undergo catalytic reactions due to its stronger C–X bonds, a problem made worse
if the aryl group carries electron-rich substituents [72]. Aryl bromides, however, are
much more useful substrates to synthetic chemists, as they are cheaper and readily
available.
In this study, five aryl bromides with different substituents groups have been
used; 4-bromonitrobenzene (56), 4-bromoacetophenone (57), bromobenzene (58), 4bromoanisole (59) and 4-bromoaniline (60) to study the effects of using the ionic
liquids of [Bmplim]CF3SO3 (49) towards the reaction yield. The experiments were
conducted by dissolving the aryl bromides and methyl acrylate in the ionic liquids of
[Bmplim]CF3SO3 (49), in the presence of Pd(OAC)2 (35) catalysts. Other reaction
parameters such as types of bases, amount of Pd catalysts loading and reaction
temperature were controlled to optimize the catalytic systems.
This study has an important implication for the development of the activation
of aryl bromides. Although there have been numerous papers reported on the
catalytic systems with impressive turnover numbers (TONs), the majority of these
studies were, however, performed using only the electron-poor aryl halides such as
4-bromoacetophenone (57) [73]. The purpose of this thesis is therefore to present the
underlying principles and outcomes of the latest efforts to activate these more
difficult substrates, especially when the reaction is carried out in ionic liquid medium
as compared to the conventional organic solvent.
Other variable such as types of bases, palladium loadings and reaction
temperatures were also being studied to investigate the role of these parameters
towards the yield of the Heck adducts (62-66).
41
3.2.1
Characterization of the Heck Adducts (62-66)
3.2.1.1 1H-NMR Spectroscopy Analysis
The 1H-NMR spectra for the Heck adducts (62-66) are shown in Appendices
15, 17, 19, 21 and 23. The data are tabulated in Table 3.5.
Table 3.5: 1H-NMR data of the Heck adducts (62-66)
H
5
7
R
O
4
2
6
H
1
H
8
7
6
3
1
OCH3
1
1
(62) R = NO2
(63) R1 = COCH3
(65) R = OCH3
(66) R1 = NH2
1
(64) R = H
H
H
H
Substitute Group, 1R
Chemical shift, į (ppm)
H-1
H-2
H-3
H-4
H-5
H-6
H-7
H-8
H-9
H-10
(62)
3.83
-
6.58
7.74
-
7.69
8.27
-
-
-
(63)
3.84
-
6.54
7.73
-
7.62
8.00
-
-
2.63
H
(64)
3.82
-
6.46
7.72
-
7.39
7.53
7.39
-
-
O-9CH3
(65)
3.78
-
6.46
7.65
-
7.39
6.78
-
3.85
-
NH2
(66)
3.65
-
6.34
7.56
-
7.15
6.52
-
-
-
NO2
9
10
C-O- CH3
The 1H-NMR spectrum of methyl 4-nitrocinnamate (62) (Appendix 15)
showed a set of doublets at į 6.58 and 7.74 ppm, corresponded to the vinylic protons
at C-3 and C-4 respectively. These protons, with the coupling constants of J 16.2 Hz,
suggesting that both H-3 and H-4 are in trans-configuration. The other set of
doublets with coupling constants of J 9.0 Hz, resonated at į 7.69 and 8.27 ppm were
assigned to four aromatic protons at C-6 and C-7 respectively.
42
For other compounds, namely methyl 4-acetoxycinnamate (63) (Appendix
17), methyl cinnamate (64) (Appendix 19), methyl 4-methoxycinnamate (65)
(Appendix 21) and methyl 4-aminocinnamate (66) (Appendix 23), a similar set of
doublets for the vinylic protons at C-3 and C-4 with the coupling constants of J ~16.0
Hz, were observed around į 6.44 ppm and 7.65 ppm respectively, which also
suggested that both vinylic protons are in a trans-orientation. The aromatic protons
showed some varieties from one compound to another due to the differences in
electronegativity of the substituents groups carried by the halide compounds.
The 1H-NMR spectrum of methyl 4-acetoxycinnamate (63) (Appendix 17),
showed a set of AB pattern at į 7.62 and 8.00 ppm, corresponded to the two C-6 and
C-7 protons respectively, with the coupling constants of J 8.4 Hz. The aromatic
protons of methyl cinnamate (64) (Appendix 19) were observed as a multiplet at į
7.39 ppm and assigned to both C-6 and C-8 protons. The other aromatic protons at C7 for compound 64 were observed as multiplet at 7.53 ppm.
The remaining compounds which contain an electron donating group (EDG);
showed a different value of chemical shift for C-6 and C-7 protons compared to the
previous compounds carrying electron withdrawing groups (EWG). The 1H-NMR
spectrum of methyl 4-methoxycinnamate (65) (Appendix 21) showed a set of
doublets with the coupling constants of J 8.4 Hz at į 6.78 and 7.39 ppm, were
assigned to aromatic protons at C-7 and C-6 respectively. As for methyl 4aminocinnamate (66) (Appendix 23), the aromatic protons at C-6 and C-7 were
observed as a set of doublets at į 7.15 and 6.52 ppm respectively, with the coupling
constants of J 7.8 Hz. This was because the electron donating substituents had
shielded the protons at C-7, thus increased the electron densities around the protons
and finally made the doublet signal of the C-7 protons to resonate at lower chemical
shift than the aromatic protons at C-6. The electron withdrawing substituents, on the
other hand, had deshielded the protons at C-7, lowering the electron densities around
the protons and therefore, made the signal observed at higher chemical shift than the
C-6 protons.
43
In conclusion, the Heck reactions (62-66) have been successfully carried out
in ionic liquids medium of [Bmplim]CF3SO3 (49) with considerably high yield of
products. The 1H-NMR spectra for these salts were consistent with their suggested
molecular structures.
3.2.1.2 13C-NMR Spectroscopy Analysis
13
C-NMR spectra for the Heck adducts (62-66) are shown in Appendix 16,
18, 20, 22 and 24. All the 13C-NMR data are tabulated in Table 3.6
Table 3.6: 13C-NMR data of the Heck adducts (62-66)
H
5
7
R
O
4
2
6
H
1
H
8
7
6
3
1
OCH3
1
(62) R = NO2
(63) R1 = COCH3
1
1
(65) R = OCH3
(66) R1 = NH2
(64) R = H
H
H
H
Substitute Group, 1R
Chemical shift, į (ppm)
C-1
C-2
C-3
C-4
C-5
C-6 C-7
C-8
C-9
C-10
NO2
(62)
50
164
119
143
141
129
124
148
196
-
9
(63)
51
166
119
143
139
128
128
135
196
26
H
(64)
50
169
119
146
134
129
127
130
-
-
O-9CH3
(65)
51
170
119
143
127
127
114
162
57
-
NH2
(66)
52
167
121
142
126
128
117
147
-
-
C-O-10CH3
The 13C-NMR spectrum of methyl 4-nitrocinnamate (62) (Appendix 16)
showed a signal resonated at į 50.00 ppm, corresponded to the methyl carbon at C-1.
The resonances at į 119.21 and 141.90 ppm were attributed to the methylene carbon
at C-3 and C-4 respectively. An additional signal of the quaternary carbons at C-5
44
and C-8 resonated at į 141.07 and į 148.05 ppm respectively. The carbon at C-8 was
deshielded by the N atom, thus made the signal shifted at higher chemical shift than
the carbon at C-5. The carbonyl group at C-2 was observed at į 164.23 ppm.
The 13C-NMR spectra of each compound of the methyl 4-acetoxycinnamate
(63) (Appendix 18), methyl cinnamate (64) (Appendix 20), methyl 4-methoxy
cinnamate (65) (Appendix 22) and methyl 4-aminocinnamate (66) (Appendix 24),
showed a similar signal of the methyl carbon at C-1 as in compound 62, at around į
~50 ppm. Signals for vinylic carbons at C-3 and C-4 were observed at į ~120 ppm
and į ~144 ppm respectively.
As for methyl 4-acetoxycinnamate (63) (Appendix 18), a signal for another
methyl group was observed at į 25.93 ppm and assigned to the carbon at C-10.
Signals observed at downfield region at į 196.01 and 165.52 ppm, were assigned to
the carbonyl group at C-9 and the ester group at C-2 respectively.
The 13C-NMR spectrum of methyl cinnamate (64) (Appendix 20) showed a
similar spectrum as in compound 62. However, both of them can be distinguished by
observing the chemical shift for both protonated aromatic carbons of C-6 and C-7.
The differences in value were due to the electronegativity effect of the aromatic
substituents. The other quaternary carbons at C-5 and C-8 were observed at į 134.03
and 130.26 ppm respectively and confirmed by the DEPT135 and DEPT90.
A similar 13C-NMR spectra was also observed for methyl 4-methoxy
cinnamate (65) (Appendix 22) and methyl 4-aminocinnamate (66) (Appendix 24),
the only different is that the compound 65 contains an extra methoxy group,
observed at į 57.11 ppm and bonded to the quaternary carbon at C-8. Moreover, the
signal for quaternary C-5 in compound 65, unlike in compound 66, was overlapping
with the aromatic carbon at C-6, thus made the intensity of the C-6 signal stronger
than the C-7 signal. The chemical shift for the quaternary carbon at C-8 also varies
45
for both compounds, in which the signal for the C-8 atom in compound 65 was
observed at higher chemical shift than in the compound 66.
Based on the data, the 13C-NMR spectra for the Heck adducts (62-66) were
consistent with their proposed structures.
3.2.1.3 CHN Elemental Analysis
The CHN elemental analysis data of the Heck adducts (62-66) are tabulated
in Table 3.7.
Table 3.7: CHN elemental analysis of the Heck adducts (62-66)
1
R —C6H4(CH)2CO2CH3
Substitute Group, R1
NO2
(62)
COCH3 (63)
H
(64)
OCH3
(65)
NH2
(66)
Elemental Analysis (%)
C
H
N
58.01
4.44
6.81
(57.97)
(4.38)
(6.76)
70.63
5.99
-
(70.57)
(5.92)
-
74.22
6.30
-
(74.06)
(6.21)
-
68.43
6.15
-
(68.74)
(6.29)
-
68.08
6.50
8.30
(67.78)
(6.26)
(7.90)
*Numbers in parenthesis are the calculated values
46
From the results, it was observed that the experimental value is in close
proximity to the calculated value, with the standard deviations of ± 0.50%. This
shows that the purity of the entire Heck adducts (62-66) were considerably high. In
conclusion, all the molecular formula of the Heck adducts (62-66) were consistent
with their suggested molecular structures.
3.2.2
Studies on the Heck Reaction Parameters
3.2.2.1 The Effect of Bases
The function of base in the Heck reactions is to reduce the Pd(OAc)2 catalyst
from unreactive Pd2+ to activated Pd0 intermediate [74]. The base is also assists in the
final hydrogen halide reductive elimination step. In this study, four types of bases
have been used; Et3N, Na2CO3, NaHCO3 and NaOAc, in order to study the effect of
bases towards the percentage conversion of the Heck adducts (62-66). The results of
the bases effect are summarized in Figure 3.3.
120
Et3N
Et3N
Na2CO3
Na2CO3
NaHCO3
NaHCO3
NaOAc
NaOAc
100
%Conversion
80
60
40
20
0
NO
NO22
COCH
COCH33
HH
OCH
3
OCH3
NH2
NH2
1
Aryl Bromide Substituents, R
Figure 3.3
The effect of different bases towards the Heck adducts (62-66)
47
From our studies, it was found that the best base was Et3N, giving at least
three times more conversion than any other type of bases after 40 hours of reactions.
This may be due to the higher bulkiness of the Et3N compared to the other bases
[75]. Although NaHCO3 gave a quite comparable result, the product separation from
the solvent system is quite difficult, thus limiting the advantages of ionic liquid of
[Bmplim]CF3SO3 (49) as a facile separation medium.
3.2.2.2 The Effect of Pd(OAc)2 Catalysts Loadings
The Pd catalysts are important in the oxidative addition and the alkene
insertion steps, which were the rate-determining steps in the Heck reactions [76]. By
controlling the amount (mmol%) of the Pd catalysts, higher TONs can be achieved to
maximize the percentage conversion of the desired products. The Pd(OAc)2 had been
chosen as the catalyst precursor due to its high solubility in the ionic liquids medium
of [Bmplim]CF3SO3 (49). The effect of the catalysts loadings is shown in Figure 3.4
120
100
1.0 mmol%
1.5 mmol%
2.0 mmol%
% Conversion
80
60
40
20
0
NO2
NO2
COCH3
COCH3
H
H
OCH
3
OCH3
NH
2
NH2
Aryl Bromide Substituents, R1
Figure 3.4
The effect of different Pd loadings towards the Heck adducts (62-66)
48
The results from Figure 3.4 shows that the best amount of Pd loading must be
kept between 1.0 to 1.5 mmol% in order to obtain the theoretical turnover numbers
(TONs) of 10,000 and 6667 respectively – if 100% conversion of aryl bromides were
achieved. The increase of Pd-catalysts loading, however, will inhibit the reactions
and as a result to no conversion to form the desired adducts, especially for aryl
bromides compounds with an electron donating substituents.
3.2.2.3 The Effect of Reaction Temperatures
Reaction temperatures assist in the activation of the aryl bromides. This
parameter, however, must be carefully controlled due to; a) if the temperature is too
low, the activation of aryl bromides could not be achieved, b) if the temperature is
too high, the formation of Pd black will occur and inhibit the Heck reactions catalytic
cycle and c) in cases where phosphine ligands / additives are involved, the P–C bond
cleavage will occur, thus lead to contamination of the Heck adducts [77]. The effect
of the reaction temperatures is shown in Figure 3.5
120
80°C
80C
100°C
100C
120°C
120C
100
% Conversion
80
60
40
20
0
NO2
NO2
COCH
COCH33
H
H
OCH3
OCH3
NH2
NH2
Aryl Bromide Substituents, R1
Figure 3.5
The effect of different reaction temperatures towards the Heck
adducts (62-66)
49
In Figure 3.5, the best reaction temperature was found to be 120żC, which is
suitable for the activation of aryl bromides. However, the temperatures should be
carefully monitored to avoid the formation of Pd black, which usually occurs at
100żC, and lead to the decomposition of the catalyst. Moreover, reactions which
involve additives containing phosphine should be strictly controlled due to the
possibilities of the formation of side product which will then contaminate the Heck
adducts (62-66). From our observation, the Heck reaction using temperature greater
than 120żC were avoided due to the decomposition of the Pd catalysts, which
therefore terminated the Heck catalytic cycle immediately.
3.2.2.4 Addition of Co-ligand
It is observed that ligandless-Pd reaction for reactive aryl bromides; 4bromonitrobenzene (56), 4-bromoacetophenone (57) and bromobenzene (58)
resulting in high conversion of reactants. This is due to the presence of electron
withdrawing group (EWG) in the compound which allows a more convenience
condition for the reaction to accelerate [78]. Unreactive aryl bromides; 4bromoanisole (59) and 4-bromoaniline (60), on the other hand, carry an electron
donating substituents (EDG) which made the oxidative addition more difficult, thus
lead to a poor conversion of reactants.
Although the addition of PPh3 gave a better rate of conversion, it is suggested
that the aryl scrambling occurred, generating by-products, thus resulting in
problematical separation of the ionic liquids solvent system and the desired product.
The existence of suggested by-product (67) was observed in Appendix 25 (b) and
Appendix 26 (b). A doublet at į 6.30 ppm with the coupling constants calculated as
16.0 Hz and a singlet at į ~3.70 ppm represent extra trans-vinylic protons and a
methyl group from the by-product. This may be caused by the reaction between PPh3
and methyl acrylate to form the 67 species during the catalytic cycle which lead to
contamination of the desired products.
50
H
Ph3P
4
O
3
1
2
O
H
(67)
3.3
Recyclability of Ionic Liquids
The recyclability test is carried out to study the ability of respective ionic
liquid, [Bmplim]CF3SO3 (49), to sustain its performances in continuous runs, and
thus, to determine whether it has the potential as an environmetal-friendly solvents in
the Pd-catalyzed Heck reactions. This study is carried out by recovering the
[Bmplim]CF3SO3 (49) solvents from the first experiment, and then reused it for
another run continuously, while observing the percentage conversion of the Heck
adducts (62-66). The recovering and reusing processes of the [Bmplim]CF3SO3 (49)
solvent were repeated twice.
From the results shown in Table 4.4, it is observed that the Heck adducts of
the reactive aryl bromides; 4-bromonitrobenzene (56), 4-bromoacetophenone (57)
and bromobenzene (58) gave a satisfactory yield of 96-98% after the third run.
However, for unreactive aryl bromides reactants such as 4-bromoanisole (59) and 4bromoaniline (60), the percentage conversion for their Heck adducts (62-66)
respectively, show in decreased of activities. This may be due to the incomplete
recovery of pure ionic liquids from previous run caused by the contamination of
reactants, co-ligand or Pd black species. Therefore, during the second and the third
run of the Heck reactions catalytic cycle, the decreased in catalytic activities has been
observed for the compounds 59 and 60.
CHAPTER 4
EXPERIMENTAL
4.1
General Experimental Procedures
All the experiments were conducted in an inert atmosphere of N2 gas flow.
Melting points were measured on an Electrothermal digital melting point apparatus
and were uncorrected. Molar conductivities were measured on a WPA CMD630
digital conductivity meter. The protons (1H) and carbons (13C) nuclear magnetic
resonance (NMR) spectra were recorded in CDCl3 or DMSO solvent on a Bruker
AVANCE 300 NMR spectrometer which operates at 300 MHz with TMS used as the
standard references. Elemental analysis were determined by using the Thermo
Finnigan Flash 1112 EA CHN-O analyzer.
52
4.2
Chemicals
For the preparation of ionic liquids, N-methylpyrrolidine (38), iodomethane,
iodoethane, iodopropane, iodobutane, iodopentane, iodohexane and iodoheptane
were obtained from Aldrich while silver trifluoromethanesulfonate was obtained
from Fluka. In the preparation of the Heck adducts, 4-bromonitrobenzene (56), 4bromoacetophenone (57), bromobenzene (58), 4-bromoanisole (59), and methyl
acrylate (61) were obtained from Fluka while 4-bromoaniline (60) and palladium
acetate, Pd(OAc)2 (35), were obtained from Aldrich. All chemicals were used as
received without further purification.
4.3
Preparation of Ionic Liquids
Generally, the ionic compounds were prepared by a two-step process, in
which the N-alkyl-N-methylpyrrolidinium iodide (39-45) was initially prepared, and
then methathesized with silver trifluoromethanesulfonate.
4.3.1
Preparation of N-alkyl-N-methylpyrrolidinium Iodide Salts (39-45)
N-methylpyrrolidine (38) (1.04 mL, 0.01 mol) was dissolved in ethanol (15
mL) and stirred under nitrogen for 15 minutes. Alkyl iodides (0.01 mol) was then
added slowly into the solution by using additional funnel and the mixture was let
stirred overnight. A white precipitate which had formed was filtered off from the
solution. The white precipitate was collected as the expected N-alkyl-Nmethylpyrrolidinium iodide salts (39-45).This preparative method of N-alkyl-Nmethylpyrrolidinium iodide salts (39-45) has been described and characterized in
detailed by Sofian et al. [79].
53
4.3.2
Preparation of N-alkyl-N-methylpyrrolidinium Trifluoromethane
sulfonate Salts (46-52)
N-alkyl-N-methylpyrrolidinium iodide (39-45) (0.001 mol) was dissolved in
ethanol (10 mL) and stirred under nitrogen for 0.5 h. Silver trifloromethane sulfonate
(0.001 mol) was then added into the solution and the mixture was further stirred for
another 0.5 h. A yellow precipitate which had formed was filtered off from the
solution. The filtrate volume was reduced and the residue was collected as the
expected N-alkyl-N-methylpyrrolidinium trifluoromethanesulfonate salts (46-52). All
products were characterized as follows: -
From compound 39, N,N-dimethylpyrrolidinium trifluoromethanesulfonate (46) was
obtained as a white solid (0.2385 g, 95.7%, m.p. 300-302°C), CHN elemental
analysis: [C6H14N]+[CF3SO3]Ǧ; Experiment: C 33.53%, H 5.45%, N 5.48%
(Calculated: C 33.73%, H 5.66%, N 5.62%); 1H-NMR (Appendix 1): į (DMSO-d6)
2.09 (4H, s, -2,3CH2-), 3.08 (6H, s, -5,6CH3-), 3.44 (4H, m, -1,4CH2-). 13C-NMR
(Appendix 2): į (DMSO-d6) 22.10 (2,3C–H2), 51.99 (5,6C–H3), 65.76 (1,4C–H2).
From compound 40, N-ethyl-N-methylpyrrolidinium trifluoromethanesulfonate (47)
was obtained as a white solid (0.2330 g, 88.5%, m.p. 87-89°C), CHN elemental
analysis: [C7H16N]+[CF3SO3]Ǧ; Experiment: C 36.65%, H 6.30%, N 5.41%
(Calculated: C 36.50%, H 6.13%, N 5.32%); 1H-NMR (Appendix 3): į (DMSO-d6)
1.26 (3H, t, J 7.8 Hz, -7CH3-), 2.08 (4H, s, -2,3CH2-), 2.95 (3H, s, -5CH3-), 3.37 (6H,
m, -1,4,6CH2-). 13C-NMR (Appendix 4): į (DMSO-d6) 9.06 (7C–H3), 21.83 (2,3C–H2),
48.15 (5C–H3), 59.30 (6C–H2), 63.78 (1,4C–H2).
From compound 41, N-methyl-N-propylpyrrolidinium trifluoromethanesulfonate (48)
was obtained as a white solid (0.2174 g, 78.4%, m.p. 77-78°C), CHN elemental
analysis: [C8H18N]+[CF3SO3]Ǧ; Experiment: C 39.00%, H 6.66%, N 5.25%
(Calculated: C 38.98%, H 6.54%, N 5.05%); 1H-NMR (Appendix 5): į (DMSO-d6)
54
0.91 (3H, t, J 7.5 Hz, -8CH3-), 1.72 (2H, m, -7CH2-), 2.08 (4H, s, -2,3CH2-), 2.97 (3H,
s, -5CH3-), 3.25 (2H, m, -6CH2-), 3.45 (4H, m, -1,4CH2-). 13C-NMR (Appendix 6): į
(DMSO-d6) 10.96 (8C–H3), 16.97 (7C–H2), 21.84 (2,3C–H2), 48.78 (5C–H3), 64.32
(1,4C–H2), 65.56 (6C–H2).
From compound 42, N-butyl-N-methylpyrrolidinium trifluoromethanesulfonate (49)
was obtained as an oily yellow substrate (0.2354 g, d20°C 1.03 g/mL, 80.8%), CHN
elemental analysis: [C9H20N]+[CF3SO3]Ǧ; Experiment: C 41.15%, H 6.89%, N 4.78%
(Calculated: C 41.23%, H 6.92%, N 4.81%); 1H-NMR (Appendix 7): į (DMSO-d6)
0.91 (3H, t, J 7.5 Hz, -9CH3-), 1.30 (2H, m, -8CH2-), 1.66 (2H, m, -7CH2-), 2.07 (4H,
s, -2,3CH2-), 2.96 (3H, s, -5CH3-), 3.28 (2H, m, -6CH2-), 3.45 (4H, m, -1,4CH2-). 13CNMR (Appendix 8): į (DMSO-d6) 13.36 (9C–H3), 19.62 (8C–H2), 21.80 (2,3C–H2),
25.35 (7C–H2), 48.99 (5C–H3), 64.00 (6C–H2), 64.32 (1,4C–H2).
From compound 43, N-methyl-N-pentylpyrrolidinium trifluoromethanesulfonate (50)
was obtained as an oily yellow substrate (0.2290 g, d20°C 1.14 g/mL 75.0%), CHN
elemental analysis: [C10H22N]+[CF3SO3]Ǧ; Experiment: C 43.36%, H 7.33%, N 4.62%
(Calculated: C 43.27%, H 7.26%, N 4.59%); 1H-NMR (Appendix 9): į (DMSO-d6)
0.85 (3H, t, J 7.5 Hz, -10CH3-), 1.28 (4H, m, -8,9CH2-), 1.67 (2H, m, -7CH2-), 2.06
(4H, s, -2,3CH2-), 2.94 (3H, s, -5CH3-), 3.26 (2H, m, -6CH2-), 3.42 (4H, m, -1,4CH2-).
13
C-NMR (Appendix 10): į (DMSO-d6) 13.14 (10C–H3), 21.53 (9C–H2), 21.60 (2,3C–
H2), 23.05 (7C–H2), 28.08 (8C–H2), 48.62 (5C–H3), 64.00 (6C–H2), 64.44 (1,4C–H2).
From compound 44, N-hexyl-N-methylpyrrolidiniumtrifluoromethane sulfonate (51)
was obtained as a white solid (0.2303 g, 72.1%, m.p. 62-64°C), CHN elemental
analysis: [C11H24N]+[CF3SO3]Ǧ; Experiment: C 45.22%, H 7.60%, N 4.45%
(Calculated: C 45.13%, H 7.57%, N 4.39%); 1H-NMR (Appendix 11): į (DMSO-d6)
0.86 (3H, t, J 6.0 Hz, -11CH3-), 1.28 (6H, s, -8,9,10CH2-), 1.68 (2H, m, -7CH2-), 2.08
(4H, s, -2,3CH2-), 2.97 (3H, s, -5CH3-), 3.29 (2H, m, -6CH2-), 3.43 (4H, m, -1,4CH2-).
13
C-NMR (Appendix 12): į (DMSO-d6) 13.81 (11C–H3), 21.80 (2,3C–H2), 22.08 (10C–
55
H2), 23.32 (9C–H2), 25.94 (7C–H2), 30.92 (8C–H2), 48.70 (5C–H3), 64.00 (6C–H2),
64.27 (1,4C–H2).
From compound 45, N-heptyl-N-methylpyrrolidinium trifluoromethanesulfonate (52)
was obtained as an oily yellow substrate (0.2624 g, d20°C 1.57 g/mL 78.7%), CHN
elemental analysis: [C12H26N]+ [CF3SO3]Ǧ; Experiment: C 46.84%, H 7.76%, N
4.24% (Calculated: C 46.83%, H 7.86%, N 4.20%); 1H-NMR (Appendix 13): į
(DMSO-d6) 0.87 (3H, s, -12CH3-), 1.27 (8H, s, -8,9,10,11CH2-), 1.68 (2H, m, -7CH2-),
2.07 (4H, s, -2,3CH2-), 2.96 (3H, s, -5CH3-), 3.28 (2H, m, -6CH2-), 3.45 (4H, m, 1,4
CH2-). 13C-NMR (Appendix 14): į (DMSO-d6) 13.91 (12C–H3), 21.79 (2,3C–H2),
22.18 (11C–H2), 23.37 (10C–H2), 26.28 (7C–H2), 28.36 (9C–H2), 31.31 (8C–H2), 48.67
(5C–H3), 64.00 (6C–H2), 64.26 (1,4C–H2).
4.4
Preparation of the Heck Adducts
The ionic liquid of N-butyl-N-methylpyrrolidinium trifluoromethane
sulfonate, [Bmplim]CF3SO3 (49), which was obtained from previous experiments,
was used as the solvent. For each preparation, aryl bromide (56-60) (10 mmol) was
reacted with methyl acrylate (61) in ionic liquid medium of [Bmplim] CF3SO3 (49)
(3 mL). These following reaction parameters were used; Pd(OAc)2 (35) (0.0337g, 1.0
mmol%) as the catalyst and Et3N (2.4 molar equiv.) as the base. All substances were
mixed together in a reaction flask whilst purging with nitrogen and the mixture was
then heated at 120°C for 40 hours. After the reaction period, ether (3 mL) was added
to the reaction mixture and the organic layer was isolated by separation funnel. The
filtrate volume was reduced and the residue was recrystallized in hot ether (5 ml) to
give the pure desired products. All products obtained (62-66) were characterized as
follows: -
56
From compound 56, methyl 4-nitrocinnamate (62) was obtained as a yellow solid
(1.9806 g, 95.6%, m.p. 162-163°C), CHN elemental analysis: C10H9NO4;
Experiment: C 58.01%, H 4.44%, N 6.81% (Calculated: C 57.97%, H 4.38%, N
6.76%); 1H-NMR (Appendix 15): į (CDCl3) 3.83 (3H, s, -1CH3-), 6.58 (1H, d, J 16.2
Hz, -3CH-), 7.69 (2H, d, J 9.0 Hz, -6CH-), 7.74 (1H, d, J 16.2 Hz, -4CH-), 8.27 (2H,
d, J 9.0 Hz, -7CH-) 13C-NMR (Appendix 16): į (CDCl3) 50.33 (1C–H3), 119.21 (3C–
H), 123.91 (7C–H), 128.53 (6C–H), 141.07 (5C–H), 141.90 (4C–H), 148.05 (8C–N),
164.23 (2C=O).
From compound 57, methyl 4-acetoxycinnamate (63) was obtained as a yellow solid
(1.9340 g, 94.7%, m.p. 123-124°C), CHN elemental analysis: C12H12O3; Experiment:
C 70.63%, H 5.99% (Calculated: C 70.57%, H 5.92%); 1H-NMR (Appendix 17): į
(CDCl3) 2.63 (3H, s, -10CH3-), 3.84 (3H, s, -1CH3-), 6.54 (1H, d, J 16.0 Hz, -3CH-),
7.62 (2H, d, J 8.4 Hz, -6CH-), 7.73 (1H, d, J 16.0 Hz, -4CH-), 8.00 (2H, d, J 8.4 Hz, 7
CH-) 13C-NMR (Appendix 18): į (CDCl3) 25.93 (10C–H3), 50.91 (1C–H3), 119.42
(3C–H), 127.94 (6C–H), 128.41 (7C–H), 134.84 (8C–C), 138.60 (5C–C), 142.55 (4C–
H), 165.52 (2C=O), 196.01 (9C=O).
From compound 58, methyl cinnamate (64) was obtained as a yellow solid (1.5732 g,
97.0%, m.p. 36-38°C), CHN elemental analysis: C10H10O2; Experiment: C 74.22%,
H 6.30% (Calculated: C 74.06%, H 6.21%); 1H-NMR (Appendix 19): į (CDCl3) 3.82
(3H, s, -1CH3-), 6.46 (1H, d, J 16.2 Hz, -3CH-), 7.39 (3H, m, -6,8CH-), 7.53 (2H, m, 7
CH-), 7.72 (1H, d, J 16.2 Hz, -4CH-) 13C-NMR (Appendix 20): į (CDCl3) 50.21
(1C–H3), 118.82 (3C–H), 126.82 (7C–H), 128.57 (6C–H), 130.26 (8C–H), 134.03 (5C–
C), 145.91 (4C–H), 168.53 (2C=O).
From compound 59, methyl 4-methoxycinnamate (65) was obtained as a yellow solid
(0.6477 g, 33.7%, m.p. 88-89°C), CHN elemental analysis: C11H12O3; Experiment: C
68.43%, H 6.15% (Calculated: C 68.74%, H 6.29%); 1H-NMR (Appendix 21): į
(CDCl3) 3.78 (3H, s, -1CH3-), 3.85 (3H, s, -9CH3-), 6.46 (1H, d, J 16.0 Hz, -3CH-),
6.78 (2H, d, J 8.4 Hz, -7CH-), 7.39 (2H, d, J 8.4 Hz, -6CH-), 7.65 (1H, d, J 16.0 Hz, -
57
4
CH-) 13C-NMR (Appendix 22): į (CDCl3) 51.23 (1C–H3), 57.11 (9C–H3), 114.38
(7C–H), 119.40 (3C–H), 127.27 (6C–H), 127.27 (5C–C), 143.03 (4C–H), 161.91 (8C–
O), 169.97 (2C=O).
From compound 60, methyl 4-aminocinnamate (66) was obtained as a yellow solid
(0.5121 g, 28.9%, m.p. 73-74°C), CHN elemental analysis: C10H11NO2; Experiment:
C 68.08%, H 6.50%, N 8.30% (Calculated: C 67.78%, H 6.26%, N 7.90%); 1H-NMR
(Appendix 23): į (CDCl3) 3.65 (3H, s, -1CH3-), 4.08 (2H, s, -NH2-), 6.34 (1H, d, J
16.2 Hz, -3CH-), 6.52 (2H, d, J 7.8 Hz, -7CH-), 7.15 (2H, d, J 7.8 Hz, -6CH-), 7.56
(1H, d, J 16.2 Hz, -4CH-) 13C-NMR (Appendix 24): į (CDCl3) 52.20 (1C–H3), 117.0
(7C–H), 121.27 (3C–H), 125.59 (5C–H), 128.11 (6C–H), 142.40 (4C–H), 147.15 (8C–
N), 167.29 (2C=O).
These reactions were repeated under different parameters; i) different types of
bases, ii) different Pd catalysts loadings and iii) different reaction temperatures in
order to study the effects of these parameters towards the percentage conversion of
the Heck adducts (62-66).
4.4.1 Catalytic Reactions of Aryl Bromides (56-60) in Different Bases
Different bases, namely Et3N, NaHCO3, Na2CO3 and NaOAc were used to
study the effect of bases towards the Heck reaction in [Bmplim]CF3SO3 (49) as
tabulated in Table 4.1. In each catalytic run, aryl bromide (56-60) (10 mmol),
[Bmplim] CF3SO3 (49) (3 mL), Pd(OAc)2 (35) (0.0337g, 1.0 mmol%) and base (2.4
molar equiv.) were mixed together in a Radley’s 12-placed reaction carousel whilst
purging with nitrogen. The reaction carousel was then heated at 120°C with the
temperature carefully controlled by a contact thermometer ( 1°C) for 40 hours.
After the reaction period, ether (3 mL) was added to the reaction mixture and the
organic layer was isolated by separation funnel. The filtrate volume was reduced and
the residue was collected as the crude product. A 50 mg portion of the crude dried
58
product was dissolved in hot ether (5 ml) and the pure product was isolated from the
cooled mixture.
As for 4-bromoanisole (59) and 4-bromoaniline (60), PPh3 (2.0 mmol) were
added into the mixture to study the effects of co-ligands towards the convertion rate
of the Heck adducts for unreactive aryl bromides. The percentage conversion was
calculated from 1H-NMR spectra by measuring the integral value of the reactants and
the end products peaks. The results of each product are shown in Table 4.1.
Table 4.1: Catalytic reactions of aryl bromides (56-60) in different bases
Entrya
R1
Additive
1
NO2
2
COCH3 (57)
3
H
(58)
4
OCH3
(59)
5
NH2
(60)
(56)
Time
Base / % conversion
(h)
Et3N
-
40
95.3
27.0
88.6
30.5
-
16
23.0
-
-
-
-
40
91.0
25.2
86.0
25.8
-
40
89.0
23.0
44.1
25.2
-
40
12.5
0
14.8
0
PPh3
40
40.0
28.9
29.6
19.7
-
40
11.0
0
10.3
0
PPh3
40
31.9
25.5
27.6
18.3
Na2CO3 NaHCO3
NaOAc
a
Catalysts loading: 1.0% mmol of Pd(OAc)2, temperature: 120żC
4.4.2 Catalytic Reactions of Aryl Bromides (56-60) in Different Palladium
Loadings
The same procedure as in 4.4.1 was followed, only the amount of Pd(OAc)2
(35) loading were varied at 1.0, 1.5 and 2.0 mmol% respectively, while aryl
bromides (56-60) (10 mmol), base (2.4 molar equiv.) and reaction temperature of
120°C were kept as constant. The results of each product are shown in Table 4.2
59
Table 4.2: Catalytic reactions of aryl bromides (56-60) in different palladium
loadings
Entrya
a
R1
Additive
Time
Pd loading (mmol%) / % conversion
(h)
1.0
1.5
2.0
1
NO2
(56)
-
40
95.3
100.0
100.0
2
COCH3 (57)
-
40
91.0
100.0
88.1
3
H
(58)
-
40
100.0
100.0
84.3
4
OCH3
(59)
-
40
12.5
23.4
0
PPh3
40
40.0
56.4
0
5
NH2
(60)
-
40
11.0
21.1
0
PPh3
40
31.9
42.2
0
ż
Base: Et3N, temperature: 120 C
4.4.3 Catalytic Reactions of Aryl Bromides (56-60) at Different Temperatures
The same procedure as in 4.4.1 was followed, only the reactions temperature
were varied at 80, 100 and 120°C respectively, while aryl bromides (56-60) (10
mmol), Pd(OAc)2 (35) (0.0505g, 1.5 mmol%) and base (2.4 molar equiv.) were kept
as constant. The results of each product are shown in Table 4.3
60
Table 4.3: Catalytic reactions of aryl bromides (56-60) at different temperatures
a
1
Entry
R
Additive
Time
Temperature (żC) / % conversion
(h)
80
100
120
40
43.6
100.0
100.0
16
-
-
100.0
40
39.6
88.2
100.0
1
NO2
(56)
-
2
COCH3 (57)
-
3
H
(58)
-
40
30.1
80.0
100.0
4
OCH3
(59)
-
40
0
6.6
22.5
PPh3
40
19.5
28.3
40.0
5
NH2
(60)
-
40
0
4.8
20.0
PPh3
40
15.6
25.1
31.9
a
Base: Et3N, catalysts loading: 1.5 mmol% Pd(OAc)2 (35)
4.5
Recyclability of Ionic Liquids
The study of the recyclability of ionic liquid was carried as follows. After the
reaction finished, the organic layer was isolated from the reaction mixture and
ethanol (10 mL) was added into the remaining residue to extract the ionic liquids.
The ionic liquids-ethanolic solution, was then filtered and the volume was reduced to
recover the ionic liquid of [Bmplim]CF3SO3 (49). This ionic liquid was re-used in
4.4 to study its potential for recyclability. These following reaction parameters were
used; Et3N (2.4 molar equiv.) as the base, Pd(OAc)2 (35) catalyst loading at 1.5
mmol% and reaction temperature at 120żC. The experimental and recovering process
of this ionic liquid were repeated twice. The results are shown in Table 4.4.
61
Table 4.4: Recyclability test for ionic liquid of [Bmplim]CF3SO3 (49)
Entrya
a
R1
Additive
Time
No. of run / % conversion
(h)
1
2
3
1
NO2
(56)
-
40
100.0
100.0
98.3
2
COCH3 (57)
-
40
100.0
98.0
96.0
3
H
(58)
-
40
100.0
99.2
95.6
4
OCH3
(59)
PPh3
40
56.4
10.9
2.2
5
NH2
(60)
PPh3
40
42.2
8.1
1.3
Base: Et3N, catalysts loading: 1.5 mmol% Pd(OAc)2 (35), temperature: 120żC
CHAPTER 5
CONCLUSION AND SUGGESTIONS
5.1
Conclusion
In this thesis, new series of ionic compounds derived from the Nmethylpyrrolidine (38) have been successfully synthesized through a two-step
process. The first step is the quaternization reaction, in which the Nmethylpyrrolidine (38) is reacted with several alkyl iodides with different alkyl chain
lengths to produce a series of N-alkyl-N-methylpyrrolidinium iodide salts (39-45).
The second steps involved the anion-exchanged between the N-alkyl-Nmethylpyrrolidinium iodide salts (39-45) with silver trifluoromethanesulfonate
through the metathesis reaction to produce a new series of N-alkyl-N-methyl
pyrrolidinium trifluoromethanesulfonate salts (46-52) which are the desired products
in this study. All these salts were fully characterized by using NMR spectroscopies,
CHN elemental analysis, melting points and molar conductivities determination.
63
Among this series, three derivatives exist as liquids at room temperature
(<25°C); N-butyl-N-methylpyrrolidinium trifluoromethanesulfonate (49), N-methylN-pentylpyrrolidinium trifluoromethanesulfonate (50) and N-heptyl-N-methyl
pyrrolidinium trifluoromethanesulfonate (52). Based on the highest yield (80.8%)
and purity, [Bmplim]CF3SO3 (49) has been chosen as the solvent in the palladiumcatalyzed Heck reaction between methyl acrylate (61) and five different-substituted
aryl bromides (56-60). These aryl bromides which are classified into two groups;
reactive and unreactive aryl bromides, were expected to react differently in the ionic
liquids medium.
Instead of the effect of using ionic liquids as solvent in the Heck reaction,
other reaction components such as types of bases, Pd catalysts loadings and reaction
temperatures were also studied to determine the optimum conditions for this reaction
to proceed in the ionic liquids medium. Both Et3N and NaHCO3 are found to be the
excellent bases, however, Et3N is more preferable due to its easy separation from the
solvent phase. The Pd catalysts loading is kept at 1.5 mmol%, as for lower or higher
concentration will inhibit the reaction cycle and hamper the conversion rate of the
Heck adducts (62-66). The best reaction temperature is at 120°C, which is the most
appropriate temperature for the activation for aryl bromides compounds, although for
some reactive aryl bromide compounds such as 4-bromonitrobenzene (56), 4bromoacetophenone (57) and bromobenzene (58) require less heat than the
unreactive ones.
The usage of PPh3 in the Heck reaction involving unreactive aryl bromides
such as 4-bromoanisole (59) and 4-bromoaniline (60) was found to be useful since it
enchanced the conversion rate up to four times better than the regular reaction
conditions. However, separation and contamination of by-products are inevitable.
64
By using these conditions in the Heck reaction of aryl bromides (56-60), a
total of 32-100% conversion of the Heck adducts (62-66) have been achieved.
Therefore, it can be concluded that the best combination of reaction parameters for
the Heck reaction in ionic liquids medium are; Et3N as base, 1.5 mmol% of
Pd(OAc)2 catalyst and reaction temperature at 120°C. Furthermore, in certain cases
regarding the use of unreactive aryl bromides such as 4-bromoanisole (59) and 4bromoaniline (60), the addition of PPh3 was proved to be necessary.
In terms of recyclability, for reactive aryl bromides reactants; 4-bromonitro
benzene (56), 4-bromoacetophenone (57) and bromobenzene (58), the ionic liquid of
[Bmplim]CF3SO3 (49) can be re-used up to three times, giving a satisfactory yield
between 96-98% after the third run. However, unreactive aryl bromides; 4bromoanisole (59) and 4-bromoaniline (60) show a decrease in percentage
conversion of their Heck adducts of 65 and 66 respectively. This may be due to the
decrease in purity of the recovered ionic liquid caused by the contamination of byproducts from previous runs. Therefore, for recovery and recyclability purpose, ionic
liquid of [Bmplim]CF3SO3 (49) were effective towards reactive aryl bromides
substrates, in contrast to the unreactive aryl bromides substrates.
In conclusion, the Heck reactions of aryl bromides (56-60) have been
successfully conducted in ionic liquids medium. Although the yield for all adducts
(62-66) were satisfactory, there are still room for improvement for unreactive aryl
bromides compounds. The addition of PPh3 are proved to be constructive, however,
led to separation problems and contamination of by-products.
65
5.2
Suggestions
For future works, the mechanistic studies on the mechanism of ionic liquids
in the Heck reaction catalytic cycle should be studied intensively to understand the
behavior of the ionic liquid in stabilizing the Pd catalysts precursors. This has a
major impact towards the enhancement of the percentage conversion of the Heck
adducts, especially in cases involving unreactive aryl bromides or chlorides
substrates.
The application of the ionic liquids can be extended to other organic synthesis
reaction, such as the Suzuki cross-coupling reaction. The Suzuki reaction is by far
the most versatile and useful synthetic reaction for the assembly of biaryl systems,
such as kuropensamine A and hippadine, which are popular in natural product
synthesis [80].
66
SEMINARS AND PUBLICATIONS
1. Sofian Ibrahim, Mustaffa Shamsuddin, Mohamad Hafiz Ahmad Tajudin,
Hasnah Mohd Sirat and Zakaria Bahari (2003). Ionic Liquids: New Solvent
for Organic Reaction. Proceedings of Annual Fundamental Science Seminar
(AFSS). May 20-21. Johor Bahru, Johor: Institut Ibnu Sina (IIS), 87-91.
2. Sofian Ibrahim, Mohamad Hafiz Ahmad Tajudin (Oral Presenter), Mustaffa
Shamsuddin, Hasnah Mohd Sirat and Zakaria Bahari (2003). Ionic Liquids:
New Solvent for the Diels-Alder Reaction. Proceedings of International
Conference on Advancement in Science and Technology (iCAST). Aug 5-7.
Kuala Lumpur: Universiti Islam Antarabangsa (UIA), 124-126.
3. Mohamad Hafiz Ahmad Tajudin (Oral Presenter), Sofian Ibrahim, Mustaffa
Shamsuddin, Hasnah Mohd Sirat and Zakaria Bahari (2003). N-methyl-Npropylpyrrolidinium Tetrafluoroborate: New Solvent for Organic Reaction.
Book of Abstracts of 16th Malaysian Analytical Chemistry Symposium
(SKAM-16). Sept 9-11, 2003. Kuching, Sarawak: Universiti Malaysia
Sarawak (UNIMAS), 50.
4. Sofian Ibrahim, Mohamad Hafiz Ahmad Tajudin, Mustaffa Shamsuddin,
Hasnah Mohd Sirat and Zakaria Bahari (2003). Cecair Ion: Pelarut Alternatif
dalam Sintesis Organik. Poster presentation of 16th Malaysian Analytical
Chemistry Symposium (SKAM-16). Sept 9-11. Kuching, Sarawak: Universiti
Malaysia Sarawak (UNIMAS).
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74
APPENDIX 1
1
H-NMR spectrum of N,N-dimethylpyrrolidinium trifluoromethanesulfonate
(46)
3
4
2
1 CF3SO3-
+
N
H3C
5
CH3
6
DMSO
-5,6CH3-
-1,4CH2-
-2,3CH2Water
4.0
3.5
3.0
2.5
2.0
1.5
ppm
75
APPENDIX 2
13
C-NMR spectra of N,N-dimethylpyrrolidinium trifluoromethanesulfonate
(46); (a) 13C–{H}, (b) DEPT135 and (c) DEPT90
2,3
1,4
5,6
C-H2
DMSO
C-H3
C-H2
(a)
70
65
60
55
50
45
40
35
30
25
20
ppm
(b)
70
65
60
55
50
45
40
35
30
25
20
ppm
70
65
60
55
50
45
40
35
30
25
20
ppm
(c)
76
APPENDIX 3
1
H-NMR spectrum of N-ethyl-N-methylpyrrolidinium trifluoromethane
sulfonate (47)
DMSO
3
4
2
1 CF3SO3-
+
N
H3C
5
CH2CH3
6 7
-5CH3-
-1,4,6CH2-
-2,3CH2-
-7CH3-
Water
3.5
3.0
2.5
2.0
1.5
1.0
ppm
77
APPENDIX 4
13
C-NMR spectra of N-ethyl-N-methylpyrrolidinium trifluoromethanesulfonate
(47); (a) 13C–{H}, (b) DEPT135 and (c) DEPT90
1,4
C-H2
2,3
6
C-H2
5
DMSO
7
C-H2
C-H3
C-H3
(a)
65
60
55
50
45
40
35
30
25
20
15
10
5
ppm
(b)
65
60
55
50
45
40
35
30
25
20
15
10
5
ppm
60
55
50
45
40
35
30
25
20
15
10
5
ppm
(c)
65
78
APPENDIX 5
1
H-NMR spectrum of N-methyl-N-propylpyrrolidinium trifluoromethane
sulfonate (48)
3
4
2
1 CF3SO3-
+
N
H3C
5
CH2CH2CH3
6 7 8
-5CH3-
-2,3CH2-
-1,4CH2-
-8CH3-
-6CH2-7CH2Water
3.5
3.0
2.5
2.0
1.5
1.0
ppm
79
APPENDIX 6
13
C-NMR spectra of N-methyl-N-propylpyrrolidinium trifluoromethane
sulfonate (48); (a) 13C–{H}, (b) DEPT135 and (c) DEPT90
7
2,3
(a)
1,4
DMSO
C-H2
5
6
C-H2
65
60
55
C-H2
C-H2
8
C-H3
C-H3
50
45
40
35
30
25
20
15
10
5
ppm
(b)
65
60
55
50
45
40
35
30
25
20
15
10
5
ppm
65
60
55
50
45
40
35
30
25
20
15
10
5
ppm
(c)
80
APPENDIX 7
1
H-NMR Spectrum of N-butyl-N-methylpyrrolidinium trifluoromethane
sulfonate (49)
3
4
2
1 CF3SO3-
+
N
H3C
5
DMSO
CH2CH2CH2CH3
6 7 8 9
-5CH3-9CH3-2,3CH2-1,4CH2-6CH2-
-8CH2-
-7CH2Water
4.0
3.5
3.0
2.5
2.0
1.5
1.0
ppm
81
APPENDIX 8
13
C-NMR spectra of N-butyl-N-methylpyrrolidinium trifluoromethanesulfonate
(49); (a) 13C–{H}, (b) DEPT135 and (c) DEPT90
2,3
C-H2
9
7
DMSO
8
1,4
C-H2
5
6
C-H2
C-H3
C-H2
C-H2
C-H3
(a)
65
60
55
50
45
40
35
30
25
20
15
ppm
65
60
55
50
45
40
35
30
25
20
15
ppm
(b)
(c)
65
60
55
50
45
40
35
30
25
20
15
10
5
ppm
82
APPENDIX 9
1
H-NMR spectrum of N-methyl-N-pentylpyrrolidinium trifluoromethane
sulfonate (50)
3
DMSO
4
2
+
1 CF3SO3-
N
H3C
5
CH2CH2CH2CH2CH3
6 7 8 9 10
-5CH3-
-10CH3-
-2,3CH2-1,4CH2-8,9CH2-6CH2-
-7CH2Water
3.5
3.0
2.5
2.0
1.5
1.0
ppm
83
APPENDIX 10
13
C-NMR spectra of N-methyl-N-pentylpyrrolidinium trifluoromethane
sulfonate (50); (a) 13C–{H}, (b) DEPT135 and (c) DEPT90
9
7
6
8
C-H2 &1,4C-H2
C-H2
C-H2
C-H2
&
2,3
C-H2
9
C-H3
DMSO
5
(a)
65
60
55
C-H3
50
45
40
35
30
25
20
15
ppm
(b)
2,3
6
1,4
C-H2
9
C-H2
C-H2
C-H2
65
60
55
50
45
40
35
30
25
20
15
ppm
65
60
55
50
45
40
35
30
25
20
15
ppm
(c)
84
APPENDIX 11
1
H-NMR spectrum of N-hexyl-N-methylpyrrolidinium trifluoromethane
sulfonate (51)
3
4
2
+
1 CF3SO3-
N
H3C
5
CH2CH2CH2CH2CH2CH3
6 7 8 9 10 11
8 9 10
-
-5CH3-1,4CH2-2,3CH2-
-11CH3-
-6CH2-7CH2Water
3.5
3.0
2.5
2.0
1.5
1.0
ppm
85
APPENDIX 12
13
C-NMR spectra of N-hexyl-N-methylpyrrolidinium trifluoromethanesulfonate
(51); (a) 13C–H}, (b) DEPT135 and (c) DEPT90
10
8
6
C-H2 &1,4C-H2
(a)
60
9
C-H2
C-H2
2,3
DMSO
5
65
C-H2
7
C-H2
C-H2
11
C-H3
C-H3
55
50
45
40
35
30
25
20
15
ppm
(b)
6
1,4
C-H2
C-H2
65
60
55
50
45
40
35
30
25
20
15
ppm
65
60
55
50
45
40
35
30
25
20
15
ppm
(c)
86
APPENDIX 13
1
H-NMR spectrum of N-heptyl-N-methylpyrrolidinium trifluoromethane
sulfonate (52)
3
4
2
1 CF3SO3-
+
N
H3C
5
CH2CH2CH2CH2CH2CH2CH3
6 7 8 9 10 11 12
DMSO
-5CH3-
-12CH3-
2,3
- CH2-1,4CH2-6CH2-7CH2Water
4.0
3.5
3.0
2.5
2.0
1.5
1.0
ppm
87
APPENDIX 14
13
C-NMR spectra of N-heptyl-N-methylpyrrolidinium trifluoromethane
sulfonate (52); (a) 13C–{H}, (b) DEPT135 and (c) DEPT90
10
C-H2
6
8
DMSO
1,4
C-H2 & C-H2
C-H2 9C-H2
7
2,3
C-H2
C-H2
12
C-H3
5
C-H3
11
C-H2
(a)
65
60
55
50
45
40
35
30
25
20
15
ppm
(b)
1,4
C-H26C-H2
65
60
55
50
45
40
35
30
25
20
15
ppm
65
60
55
50
45
40
35
30
25
20
15
ppm
(c)
88
APPENDIX 15
1
H-NMR spectrum of methyl 4-nitrocinnamate (62)
-6CH-
6
H
-7CH-
O
H
H
5
4
1
OCH3
2
7
3
CDCl3
3
- CH-
-4CH-
O2N
8
6
7
H
H
H
8.5
8.0
7.5
7.0
6.5 ppm
-1CH3-
-6CH-3CHCDCl3
-7CH-
-4CH-
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
ppm
89
APPENDIX 16
13
C-NMR spectra of methyl 4-nitrocinnamate (62); (a) 13C–{H}, (b) DEPT135
and (c) DEPT90
6
4
2
(a)
C=O
8
C-N
C-H5
C-H
C-H
7
C-H
3
C-H
CDCl3
1
C-H3
180 175 170 165 160 155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40
ppm
(b)
180 175 170 165 160 155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40
ppm
(c)
180 175 170 165 160 155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40
ppm
90
APPENDIX 17
1
H-NMR spectrum of methyl 4-acetoxycinnamate (63)
-6CH-
-7CH-
-3CH-4CHCDCl3
8.2
8.0
7.8
7.6
7.4
7.2
7.0
6.8
6.6
6.4 ppm
H
-1CH3H
5
4
7
7
- CH-
9
8
6
7
O
2
3
-6CH-3CH-
O
6
H
10
H3C
-10CH3-
1
OCH3
H
H
H
4
- CHCDCl3
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
ppm
91
APPENDIX 18
13
C-NMR spectra of methyl 4-acetoxycinnamate (63); (a) 13C–{H}, (b) DEPT135
and (c) DEPT90
7
(a)
9
4
2
C=O
C-H
8
C-C
3
CDCl3
C-H
1
C-H3
10
C=O
C-H3
5
190
C-H6C-H
C-C
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
ppm
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
ppm
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
ppm
(b)
(c)
92
APPENDIX 19
1
H-NMR spectrum of methyl cinnamate (64)
-6,8CH-3CH-4CH-
-7CH-
CDCl3
-1CH37.8
7.6
7.4
7.2
7.0
6.8
6.6
6.4
ppm
H
O
4
2
6
H
-3CH-
H
5
7
-6,8CHH
4
- CH-7
- CH-
3
8
6
7
1
OCH3
H
H
H
CDCl3
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
ppm
93
APPENDIX 20
13
C-NMR spectra of methyl cinnamate (64); (a) 13C–{H}, (b) DEPT135 and (c)
DEPT90
6
4
2
(a)
C=O
C-H
8
5
CDCl3
C-H 7C-H
3
C-H
C-H
1
C-H3
C-C
180 175 170 165 160 155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40
ppm
(b)
180 175 170 165 160 155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40
ppm
(c)
180 175 170 165 160 155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40
ppm
94
APPENDIX 21
1
-4CH-
H-NMR spectrum of methyl 4-methoxycinnamate (65)
-6CH-
-7CH-
-3CH-
CDCl3
-9CH3- -1CH3-
7.8
7.6
7.4
7.2
7.0
6.8
6.4 ppm
6.6
H
H
6
H
4
5
7
-6CH-
9
H3C
-7CH-
O
O
8
1
OCH3
H
6
H
7
-3CH-
2
3
H
-4CHCDCl3
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
ppm
95
APPENDIX 22
13
C-NMR spectra of methyl 4-methoxycinnamate (65); (a) 13C–{H}, (b)
DEPT135 and (c) DEPT90
CDCl3
6
C-H
&
5
C-C
4
2
C=O
(a)
180
8
C-H
7
3
C-H
C-H
9
C-O
C-H3
1
C-H3
170
160
150
140
130
120
110
100
90
80
70
60
50
40
ppm
170
160
150
140
130
120
110
100
90
80
70
60
50
40
ppm
170
160
150
140
130
120
110
100
90
80
70
60
50
40
ppm
(b)
180
(c)
180
96
APPENDIX 23
1
H-NMR spectrum of methyl 4-aminocinnamate (66)
-3CH-4CH-
-6CH-7CH-1CH3-
7.8
7.6
7.4
7.2
7.0
6.8
6.6
6.4 ppm
H
-4CH-
-3CH-
H
O
6
H
5
4
2
7
-6CH-
H2N
-7CH-
3
8
6
7
1
OCH3
H
H
-NH2-
H
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
ppm
97
APPENDIX 24
13
C-NMR spectra of methyl 4-aminocinnamate (66); (a) 13C–{H}, (b) DEPT135
and (c) DEPT90
CDCl3
6
4
8
(a)
2
C=O
3
C-H
C-H
C-H
1
C-N
5
180
7
C-H
C-H3
C-C
170
160
150
140
130
120
110
100
90
80
70
60
50
40
ppm
170
160
150
140
130
120
110
100
90
80
70
60
50
40
ppm
170
160
150
140
130
120
110
100
90
80
70
60
50
40
ppm
(b)
180
(c)
180
98
APPENDIX 25
The Heck reaction between 4-bromoanisole (59) with methyl acrylate (61) in
[Bmplim]CF3SO3 (49); (a) without PPh3 and (b) with PPh3
(a)
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
ppm
4.5
4.0
3.5
ppm
(b)
7.5
7.0
6.5
6.0
5.5
5.0
99
APPENDIX 26
The Heck reaction between 4-bromoaniline (60) with methyl acrylate (61) in
[Bmplim]CF3SO3 (49); (a) without PPh3 and (b) with PPh3
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
ppm
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
ppm