DINUCLEAR SILVER(I)-N- HETEROCYCLIC
CARBENE COMPLEXES BASED ON
IMIDAZOLIUM DERIVATIVES: SYNTHESIS
AND BIOLOGICAL ACTIVITIES
PUVANA DEVI A/P SELVARAJOO
UNIVERSITI SAINS MALAYSIA
2018
DINUCLEAR SILVER(I)-N- HETEROCYCLIC
CARBENE COMPLEXES BASED ON
IMIDAZOLIUM DERIVATIVES: SYNTHESIS
AND BIOLOGICAL ACTIVITIES
by
PUVANA DEVI A/P SELVARAJOO
Thesis submitted in fulfilment of the requirements
For the degree of
Master of Science
July 2018
ii
ACKNOWLEDGEMENT
First of foremost, I would like to thank my God for helping those who need
you. So I have deep faith that you will not abandon me.
I would like to thank my supervisors: Dr. Mohd Rizal Razali for his support
and expert leadership and for giving me this opportunity to study under his
supervision. Without his timely guidance I could not have achieved my goals. Assoc
Prof. Dr Rosenani for the assistance, encouragement and valuable suggestions you
have provided to aid me in overcoming the difficulties that I’ve faced during the
course of this work.
I would like to thank Dean of School of Chemical Sciences for providing
such a good research environment and necessary research facilities. I am deeply
thankful to IPS staff who helped me throughout.
A huge thank you to the academic staff in the School of Chemical Science,
particularly Mr. Mohd Nizam, Mr. Azizo and Mdm. Nur Asma for their helps and
supports in completing NMR, FT-IR and CHN analysis studies, respectively. Thank
you to Mr. Mohd Mustaqim from School of Physics for crystal structures
determination. My gratitude goes to Silas Avicor from School of Biological Sciences
for his assistance during larvicidal activities.
A great thank you has to go to everyone past and present who have been in
the inorganic section. Dr Muhammad Adnan Iqbal, Dr Patrick, Dr Tabinda, Umie
Fatihah, Sunusi Yahya and Yeap Choon Wan, making my time during my master so
enjoyable and their sincere support.
iii
I wish to thank my family for their love, kindness and unlimited support, my
brother and sisters for their unconditional encouragement during my study. Without
you all I would not have been able to complete my goals. I would like to give special
thanks to my friends: Ruzaina, Thilaga, Hintumathi, Yamuna, Ghajendran, Kevin
Jason, Ramesh, Ramendirran, Shanmugam, Shanti, Nhivashini, Mohana, and
Sarasvathy.
Puvana Devi a/p Selvarajoo, 2017
iv
TABLE OF CONTENTS
ACKNOWLEDGEMENT
ii
TABLE OF CONTENT
iv
LIST OF TABLES
ix
LIST OF FIGURES
x
LIST OF SCHEMES
xii
LIST OF ABBREVIATIONS AND SYMBOLS
xiii
ABSTRAK
xv
ABSTRACT
xvii
CHAPTER 1: INTRODUCTION
1
1.1
Persistent Carbenes
1
1.2
N-Heterocyclic Carbene
2
1.3
The stability of NHCs
4
1.4
Types of NHC ligands
5
1.5
Synthesis of azolium salts: The NHC precursors
6
1.6
Synthesis of silver(I)-NHC complexes
7
1.6.1
Preparation of the free carbene and reaction with silver
salt 7
1.6.2
In-situ reaction of imidazolium salts
8
1.6.3
Silver base in the basic medium 9
1.7
Applications of silver(I)-NHC complexes 10
1.7.1
Catalytic study
10
v
1.7.2
Carbene transfer chemistry
11
1.7.3
Medicinal chemistry
12
1.8 Research problem 14
1.9
Proposed work
14
1.9.1 The objectives of this project 14
1.9.2 Targeted imidazolium compounds 15
CHAPTER 2: EXPERIMENTAL
17
2.1
Materials
17
2.2
Instruments
17
2.3
Synthesis of non-functionalized compounds
18
2.3.1
Synthesis of N-cyclopentyl imidazole 18
2.3.2
Synthesis of non-functionalized bis-imidazolium salts
(1-4) 18
2.3.2(a) Synthesis of 3,3' [(1,2
phenylenebis(methylene)] bis (1-
cyclopentylimidazolium) bis-
hexaflourophosphate (1)
18
2.3.2(b)
Synthesis of 3,3' [(1,3
phenylenebis(methylene)] bis(1-
cyclopentylimidazolium) bis-
hexaflourophosphate (2) 19
2.3.2(c)
Synthesis of 3,3' [(1,4
phenylenebis(methylene)] bis(1-
cyclopentylimidazolium) bis-
hexaflourophosphate (3) 20
2.3.2(d)
Synthesis of 3,3' [(ethane-1,2-diyl)]
bis(1-cyclopentylimidazolium) bis-
hexaflourophosphate (4) 21
2.3.3
Synthesis of non-functionalized silver(I)-NHC
complexes (5-8) 22
vi
2.3.3(a)
Synthesis of 3,3'-[1,2-
phenylenebis(methylene)] bis(1-
cylopentylimidazolium) disilver(I)
bis(hexaflourophosphate) (5) 22
2.3.3(b)
Synthesis of 3,3'-[1,3-
phenylenebis(methylene)] bis(1-
cylopentylimidazolium) disilver(I)
bis(hexaflourophosphate) (6) 23
2.3.3(c)
Synthesis of 3,3'-[1,4-
phenylenebis(methylene)] bis(1-
cylopentylimidazolium) disilver(I)
bis(hexaflourophosphate) (7) 24
2.3.3(d)
Synthesis of 3,3'-[ethane-1,2-diyl] bis(1-
cylopentylimidazolium) disilver(I)
bis(hexaflourophosphate) (8) 25
2.4
Synthesis of nitrile-functionalized compounds
26
2.4.1
Synthesis of N-(4’-methylbenzyl) imidazole 26
2.4.2
Synthesis of nitrile-functionalized bis-imidazolium salts
(9-12) 26
2.4.2(a)
Synthesis of 3,3' [(1,2
phenylenebis(methylene)] bis(4’-
benzonitrilelimidazolium) bis-
hexaflourophosphate (9) 26
2.4.2(b)
Synthesis of 3,3' [(1,3
phenylenebis(methylene)] bis(4’-
benzonitrilelimidazolium) bis-
hexaflourophosphate (10) 27
2.4.2(c)
Synthesis of 3,3' [(1,4
phenylenebis(methylene)] bis(4’-
benzonitrilelimidazolium) bis-
hexaflourophosphate (11) 28
2.4.2(d)
Synthesis of 3,3' [(ethane-1,2-diyl)]
bis(4’-benzonitrilelimidazolium) bis-
hexaflourophosphate (12) 29
2.4.3
Synthesis of nitrile-functionalized silver(I)-NHC
complexes (13-16) 30
vii
2.4.3(a)
Synthesis of 3,3'-[1,2-
phenylenebis(methylene) bis(1-
cylopentylimidazolium) disilver(I)
bis(hexafluorophosphate) (13) 30
2.4.3(b)
Synthesis of 3,3'-[1,3-
phenylenebis(methylene)] bis(1-
cylopentylimidazolium) disilver(I)
bis(hexafluorophosphate) (14) 31
2.4.3(c)
Synthesis of 3,3'-[1,4-
phenylenebis(methylene)] bis(1-
cylopentylimidazolium) disilver(I)
bis(hexafluorophosphate) (15) 32
2.4.3(d)
Synthesis of 3,3'-[1,4-
phenylenebis(methylene)] bis(1-
cylopentylimidazolium) disilver(I)
bis(hexafluorophosphate) (16) 33
2.5
Single crystal structures analysis
34
2.5.1
Crystallographic details for 3
34
2.5.2
Crystallographic details for 5
34
2.5.3
Crystallographic details for 7
35
2.5.4
Crystallographic details for 10 35
2.6
Application Studies
36
2.6.1
Antimicrobial activities- Disc Diffusion method 36
2.6.2
Larvicidal bioassay
37
CHAPTER 3: SYNTHESIS, CHARACTERISATION AND
MOLECULAR STRUCTURES OF NON-
FUNCTIONALISED BIDENTATE LIGANDS AND
DINUCLEAR SILVER(I)-NHC COMPLEXES
38
3.1
Targeted non-functionalised bis-imidazolium salts 38
3.2
FTIR spectroscopy
39
3.3
NMR spectroscopy
42
viii
3.4
Single crystal X-ray diffraction studies
48
CHAPTER 4: SYNTHESIS, CHARACTERISATION AND
MOLECULAR STRUCTURES OF NITRILE-
FUNCTIONALISED BIDENTATE LIGANDS AND
DINUCLEAR SILVER(I)-NHC COMPLEXES
53
4.1
Targeted nitrile functionalised bis-imidazolium salts 53
4.2
FTIR spectroscopy
56
4.3
NMR spectroscopy
58
4.4
Single crystal X-ray diffraction studies
64
4.5
Proposed structure of nitrile-functionalized dinuclear silver(I)-NHC
complexes (13-16)
66
CHAPTER 5: BIOLOGICAL STUDIES
67
5.1
Introductions
67
5.2
Antimicrobial studies: Disc diffusion method
68
5.3
Larvicidal bioassay
68
CHAPTER 6: CONCLUSIONS AND RECOMMENDATIONS FOR
FUTURE WORKS
75
6.1
Conclusions
75
6.2
Recommendations for future works 77
REFERENCES
79
APPENDICES
LIST OF PUBLICATIONS AND CONFERENCES
ix
LIST OF TABLES
Page
Table 3.1 1H-NMR chemical shifts [δ/ppm] of bis-imidazolium salts
1-4.
44
Table 3.2 1H-NMR chemical shifts [δ/ppm] of bis-imidazolium
complexes 5-8
44
Table 3.3 13
C-NMR chemical shifts [δ/ppm] of bis-imidazolium salts
1-4.
47
Table 3.4 13
C-NMR chemical shifts [δ/ppm] of bis-imidazolium
complexes 5-8.
47
Table 3.5 Selected bond lengths (Ǻ) and angles (°) of salt 3. 49
Table 3.6 Selected bond lengths (Å) and angles (o) of complex 5.
50
Table 3.7 Selected bond lengths (Å) and angles (o) of complex 7.
52
Table 4.1 1H-NMR chemical shifts [δ/ppm] of bis-imidazolium salts 9-
12.
60
Table 4.2 1H-NMR chemical shifts [δ/ppm] of bis-imidazolium
complexes 13-16.
60
Table 4.3 13
C-NMR chemical shifts [δ/ppm] of bis-imidazolium salts
9-12.
63
Table 4.4 13
C-NMR chemical shifts [δ/ppm] of bis-imidazolium
complexes 13-16.
63
Table 4.5 Selected bond lengths (Å) and angles (°) of salt 10. 65
Table 5.1 Larvicidal activity of complexes (9-16) against larvae Ae-
aegypti and Cx.p. quinquefasciatus.
73
x
LIST OF FIGURES
Page
Figure 1.1 A general representation of carbene. 1
Figure 1.2 Electronic states of carbenes, (a) singlet state; (b) triplet
state.
1
Figure 1.3 (a) Electronic and (b) resonance stabilization in N-
heterocyclic carbene.
4
Figure 1.4 Metal bonding to N-heterocyclic carbene.
5
Figure 1.5 Type of N-heterocyclic carbene.
5
Figure 1.6 Structure of silver sulfadiazine [67].
12
Figure 3.1 IR- spectra of imidazolium salt 3 and its respective
complex 7.
40
Figure 3.2 IR- spectra of imidazolium salt 2 and its respective
complex 6.
41
Figure 3.3
1H-NMR (d6-DMSO, 500MHz) spectra for (a) salt 1 and
(b) complex 5.
43
Figure 3.4
13C-NMR (d3-CH3CN, 125MHz) spectra for (a) salt 1 and
(b) complex 5.
46
Figure 3.5 Structure of imidazolium salt 3 with the ellipsoids shown at
50% probability. Symmetry element used, i= 1-x, 1-y, -z.
48
Figure 3.6 Structure of 5 with ellipsoids shown at 50% probability.
Hydrogen atom and PF6- anions in the lattice omitted for
clarity. Symmetry element used: i= 1-x, 1-y, -z.
50
Figure 3.7 Structure of 7 with ellipsoids shown at 50% probability.
Hydrogen atoms and molecules in the lattice omitted for
clarity. Symmetry element used: i= -x, -y, -z-1
51
Figure 4.1 (a) Molecular structure of nitrile functionalized silver(I)-
NHC complex. (b) A cage-like structure that formed by
supramolecular interactions between silver(I)···N(nitrile).
54
Figure 4.2 IR- spectra of imidazolium salt 11 and respective silver(I)-
NHC complex, 15.
57
xi
Figure 4.3 1H-NMR (d6-DMSO, 500MHz) spectra for (a) salt 9 and
(b) complex 13.
59
Figure 4.4 13
C-NMR (d3-CH3CN, 125MHz) spectra for (a) salt 9 and
(b) complex 13.
62
Figure 4.5 Structure of 10 with ellipsoids shown at 50% probability.
Two hexaflurophosphate anions in the lattice omitted for
clarity.
64
Figure 4.6 Proposed structure of complex 13. The structures of the
other complexes (14-16) are similar with the only
difference being the bridging group connecting two N-
heterocyclic moieties.
66
Figure 5.1 Percentage mean mortality of larvae (A) Aedes aegypti and
(B) Culex quinquefasciatus in response to different
concentrations of complexes 9-12.
70
Figure 5.2 Percentage mean mortality of larvae (A) Aedes aegypti and
(B) Culex quinquefasciatus in response to different
concentrations of complexes 13-16.
71
xii
LIST OF SCHEMES
Page
Scheme 1.1 Formation of dimeric entatraamine 2 instead of free NHC
3. 2
Scheme 1.2 Deprotonation of imidazolium salt from 4 to free carbene
5.
3
Scheme 1.3 First isolated carbene ion 7 from azolium salt 6.
3 Scheme 1.4 General representation of syntheses of imidazolium salts
by nucleophilic substitution. 6
Scheme 1.5 General representation of syntheses of imidazolium salts
by multi-components reaction.
7
Scheme 1.6 General representation of multicomponent cyclization and
N-alkylation.
7
Scheme 1.7 Preparation of silver-NHC complexes by free carbene.
8
Scheme 1.8
In-situ reaction of benzimidazolium salts. 9 Scheme 1.9 Synthesis of silver(I)-NHC, 8 using basic phase transfer
catalyst.
9
Scheme 1.10
Active catalytic species of silver(I)-NHC.
10
Scheme 1.11 Transmetalation of silver(I) complexes: (a) Using
Pd(COD)CH3Br [48], (b) Using PdCl2(CH3CN)2 [58].
.
11
Scheme 1.12 General scheme of bis- imidazolium salts (1-4, 9-12) and
their respective silver(I)-NHC complexes (5-8, 1
16
Scheme 3.1 Schematic diagram of 1, 2, 3, and 4.
38
Scheme 4.1 Schematic diagram of 5, 6, 7, and 8.
55
xiii
LIST OF ABBREVIATION AND SYMBOLS
Δ Chemical shift in ppm
° Degrees
°C Degrees Celcius
µg Microgram
µL Microliter
Π Pi
Σ Sigma
Ǻ Angstrom, 1 x 10-10
m
Anal. Analysis
Ar Aromatic Ring
Calc. Calculated
13C NMR Carbon-13 nuclear magnetic resonance
D Doublet
Dc Density
DMSO Dimethylsulfoxide
EtOH Ethanol
FT-IR Fourier transforms infrared
G Gram
1H NMR Proton nuclear magnetic resonance
Hz Hertz
xiv
J Coupling constant
K Kelvin
Kv Kilovolt
LC50 Lethal concentration required to kill 50%
M Molecular mass
M Multiplet
MeCN Acetonitrile
MeOH Methanol
MHz Megahertz
mL Millilitre
Mm Millimeter
Mmol Milimoles
Mol Moles
NHC N-heterocyclic carbenes
OAc Acetate
Ppm Part per millions
RT Room temperature
S Singlet
T Temperature
T Triplet
Tert-BuOK Potassium tertiary butoxide
THF Tetrahydrofuran
V Volume
XRD X-ray single crystal diffraction
xv
KOMPLEKS DINUKLEAR ARGENTUM(I)-N-HETEROSIKLIK KARBENA
BERDASARKAN DERIVATIF IMIDAZOLIUM: SINTESIS DAN AKTIVITI
BIOLOGI
ABSTRAK
Kajian ini menerangkan sintesis dua siri baru, empat garam pelopor baru
dalam siri bukan berfungsi, dinamakan, 3,3' [(1,2 fenilinbis(metilin)] bis(1-
siklopentanaimidazolium bis-heksaflorofosfat (1), 3,3' [(1,3 fenilinbis(metilin)]
bis(1-siklopentanaimidazolium bis-heksaflorofosfat (2), 3,3' [(1,4 fenilinbis(metilin)]
bis(1-siklopentanaimidazolium bis-heksaflorofosfat (3), 3,3' [(etana-1,2-diyl)]
bis(siklopentanaimidazolium) bis heksaflorofosfat (4) dan empat garam sepadan
dalam siri berfungsian nitril, dinamakan, 3,3' [(1,2 fenilinbis(metilin)] bis(4'-
benzonitrilimidazolium) bis-heksaflorofosfat (9), 3,3' [(1,3 fenilinbis(metilin)] bis(4'-
benzonitrilimidazolium) bis-heksaflorofosfat (10), 3,3' [(1,4 fenilinbis(metilin)]
bis(4'-benzonitrilimidazolium) bis-heksaflorofosfat (11) and 3,3' [(etana-1,2-diyl)]
bis(4'-benzonitrilimidazolium) bis-heksaflorofosfat (12). Tindak balas garam
imidazolium dengan argentum(I) oksida menghasilkan pembentukan dua siri baru
kompleks argentum(I)-NHC, masing-masing, (5-8) dan (13-16). Struktur untuk
semua sebatian disahkan dengan spektral (spektroskopi Fourier Transform
Inframerah, spektroskopi 1H dan
13C NMR dan analisis CHN). Struktur molekular
untuk sebatian 3, 5, 7, dan 10 dicapai menggunakan analisis sinaran-X hablur
tunggal. Kajian antibakteria melawan bakteria Gram-positif Staphyococcus aureus
(S. aureus) (ATCC 12600) dan Gram-negatif Escherichia coli (E. coli) (ATCC
xvi
25922) untuk kesemua 16 sebatian dijalankan. Kesemua garam imidazolium
menunjukkan tiada perencatan manakala kesemua kompleks yang menunjukkan
aktiviti antimikrob menunjukkan tiada perbezaan besar dalam diameter zon
perencatan.. Kesemua garam imidazolium menunjukkan tiada perencatan manakala
aktiviti larvisidal untuk kompleks argentum(I)-NHC.
xvii
DINUCLEAR SILVER(I)-N- HETEROCYCLIC CARBENE COMPLEXES
BASED ON IMIDAZOLIUM DERIVATIVES: SYNTHESIS AND
BIOLOGICAL ACTIVITIES
ABSTRACT
This research describes the syntheses of two new series, non-functionalized
series of four new precursor salts , namely 3,3' [(1,2 phenylenebis(methylene)] bis(1-
cyclopentylimidazolium bis-hexaflourophosphate (1), 3,3' [(1,3
phenylenebis(methylene)] bis(1-cyclopentylimidazolium) bis-hexaflourophosphate
(2), 3,3' [(1,4 phenylenebis(methylene)] bis(1-cyclopentylimidazolium) bis-
hexaflourophosphate (3), 3,3' [(ethane-1,2-diyl)] bis(1-cyclopentylimidazolium) bis-
hexaflourophosphate (4) and nitrile functionalized series of four new correspondence
salt, namely 3,3' [(1,2 phenylenebis(methylene)] bis(4'-benzonitrilelimidazolium)
bis-hexaflourophosphate (9), 3,3' [(1,3 phenylenebis(methylene)] bis(4'-
benzonitrilelimidazolium) bis-hexaflourophosphate (10), 3,3' [(1,4
phenylenebis(methylene)] bis(4'-benzonitrilelimidazolium) bis-hexaflourophosphate
(11) and 3,3' [(ethane-1,2-diyl)] bis(4'-benzonitrilelimidazolium) bis-
hexaflourophosphate (12). Reaction of respective imidazolium salts with silver(I)
oxide afforded the formation of two new series of silver(I)-NHC complexes, (5-8)
and (13-16), respectively. The structures of all the compounds were confirmed by the
elemental analysis data, (Fourier Transform Infrared spectroscopy, 1H and
13C NMR
spectroscopy and CHN analysis). Selected molecular structure of compounds 3, 5, 7,
and 10 were established by single crystal X-ray diffraction analysis. The antibacterial
studies against the Gram-positive Staphyococcus aureus (S. aureus) (ATCC 12600)
xviii
and Gram-negative Escherichia coli (E. coli) (ATCC 25922) of all sixteen
compounds were carried out. All the imidazolium salts show no inhibition while all
complexes displayed antimicrobial activity shows no huge difference in the diameter
of the zone of inhibition. On the other hand, larvicidal activities against Ae. aegypti
and Cx. Quinquefasciatus showed no inhibition for imidazolium salts but their
silver(I)-NHC complexes showed larvicidal activity. Therefore, this study quantified
the larvicidal property of silver(I)-NHC complexes, providing information on lethal
concentration that have potential for the control of mosquitoes.
1
CHAPTER 1
INTRODUCTION
1.1 Persistent Carbenes
Carbenes are compound containing a neutral divalent carbon atom with two
non-bonding electrons and six valence electrons, which the two unshared electrons
can be assigned to nonbonding orbitals in different ways [1] (Figure 1.1) .
C
R'
R''
Figure 1.1: A general representation of carbene.
The existences of carbenes are depending on the electronic spins they possess
(singlet or triplet states). Singlet state carbene has two unshared electrons paired spin
adopts sp2-hybridization in the same orbital (Figure 1.2). Triplet state carbene have
unshared electrons arranged in two different orbitals with parallel spins and adopts
the sp-hybridization (Figure 1.2) [2]. Triplet carbenes considered as diradicals
because of their two unpaired electrons [3]. The ground state spin multiplicity can be
determined by the relative energies of σ and pπ orbitals. According to Hoffmann, the
energy differences greater than 2 eV is favored to be a singlet carbenes while the
energy difference below 1.5 eV lead to a triplet ground state [4].
R
R'
Singlet state
(a)
R
R'
Triplet state
(b)
Figure 1.2: Electronic states of carbenes, (a) singlet state; (b) triplet state.
2
The energy difference gap can be increased by the existence of σ-electron
withdrawing substituents adjacent to the divalent carbon atom. Thus, these groups
will stabilize the σ-nonbonding orbital by increasing s orbital character, while
leaving the pπ orbital unchanged [5].
1.2 N-Heterocyclic carbene (NHC)
In early 1960, Wanzlick investigated saturated and unsaturated heterocyclic
carbenes. The focus was first to synthesize C-C saturated molecules of type 3
(Scheme 1.1). However, Wanzlick could never isolate 3 and always obtained 2,
which acquired from the α-elimination reaction of chloroform from 1 [6].
N
C
N H
CCl3
C6H5
C6H5
N
C
N
C
N
N
N
C
N
C6H5 C6H5
C6H5C6H5
C6H5
C6H5
-CHCl3
2
12 3
Scheme 1.1: Formation of dimeric entatraamine 2 instead of free NHC 3.
Later, Wanzlick tried to separate the dimeric entatramine, 2 using cross-
metathesis method, however unsuccessful [7]. In 1970, Wanzlick changed the
starting material to facilitate the formation of free NHC. In his intention to prepare
carbene 5, Wanzlick tried to deprotonate 1,2,3,4,5-tetraphenylimidazolium
perchlorate, 4 with base catalysed medium, KOtBu (Scheme 1.2), but the reaction
could not be isolated as this method was detected as the intermediate product [8].
3
N
CH
N
C6H5
C6H5
C6H5
C6H5
N
C
NC6H5
C6H5
C6H5
C6H5
ClO4-
KOtBu
-KX,-HOtBu
4 5 Scheme 1.2: Deprotonation of imidazolium salt from 4 to free carbene 5.
Various efforts have been applied on synthesis and isolation of carbenes by
researchers until pioneering studies in the late 1980s and early 1990s [9]. In 1991,
Arduengo believed that the intermediate carbenes are unstable as being assumed by
other researchers [10]. Arduengo and co-workers synthesized and isolated the first
crystallogaphically explained NHC, 7 from an azolium salt, 6 in the presence of
sodium hydroxide and DMSO using THF as reaction medium (Scheme 1.3) [11].
This carbene was found to be stable at room temperature in the absence of moisture
and oxygen [12]. Further in 1998, Arduengo prepared, characterized and determine
the single crystal structure of carbene, 5 which Wanzlick could not isolate in 1968
[13].
N N NN
C
HCl- NaH/THF,
Cat, DMSO
,-NaCl, -H2
67
H2(g) NaCl(s)
Scheme 1.3: First isolated carbene ion 7 from azolium salt 6.
4
1.3 The stability of NHCs
Formerly, Arduengo stated that the stability of NHCs is due to the steric
hindrance of the bulky N-adamantyl substituents which prevent the dimerization of
the carbene. Nevertheless, Arduengo’s syntheses of another stable carbene with N-
methyl substituents proved this wrong [14]. Arduengo believed that the electronic
contributions are the main factors in determining the stability of NHC and its
complexes (Figure 1.3). Electronic contributions involve electron donation from the
adjacent nitrogen atoms to the vacant pπ orbital of the carbene carbon. Moreover,
due to higher electronegativity of nitrogen as compare to carbon atom, charge
density is considered to be inductively withdrawn through the σ-framework,
stabilizing the carbene lone pair [14].
e- donation(resonance effect)
vacant p-orbital
unshared electron
e- withdrawal(inductive effect)
(a)
N
N
N
N
N
N
R
R
R
R
R
R
N
N
R
R
N
N
R
R
(b)
Figure 1.3: (a) Electronic and (b) resonance stabilization in N-heterocyclic carbene.
5
Even NHCs are viewed mainly as σ–donor; recent theoretical and structural
studies suggest the existence of some π–backbonding for certain metal centre (Figure
1.4). The electron donation makes NHC as nucleophilic character and gives them
good σ-donors to transition metals in low and high oxidation states. In comparison to
the Fischer and Schrock carbenes, NHCs are stable, capable of independent
existence and can be readily prepared.
M C
N
N
Figure 1.4: Metal bonding to N-heterocyclic carbene.
1.4 Types of NHC ligands
There are several variation of NHC based on their structures. Examples of
NHC are imidazole-2-ylidine, imidazolidin-2-ylidenes, imidazole-5-ylidenes, 1,2,4-
trazolodin-3,5-ylidenes, tetrahydropyramid-2-ylides and benzimidazol-2-ylidene.
Among them, the five membered NHC are the most commonly studied (Figure 1.5).
N NR R
N NR R
N NR R
N NR R
N NR R
R
R
N N
R R
imidazole-2-ylidine imidazolidin-2-ylidenes imidazole-5-ylidenes
1,2,4-trazolodin-3,5-ylidenes tetrahydropyramid-2-ylides benzimidazol-2-ylidene
Figure 1.5: Type of N-heterocyclic carbene.
6
1.5 Synthesis of azolium salts: The NHC precursors
NHC precursors are prepared by two common routes [15]:
a) Nucleophilic substitution starting at the azole heterocycle
This route involves alkylation of azole (imidazole, benzimidazole, triazole
etc) reacted with strong base such as KOH and NaOH. The potassium or sodium
azolide formed is then treated with one equivalent of alkyl or aryl halide in a suitable
solvent to obtain N-alkyl/aryl substituted azole [16]. The N-substituted azole is then
reacted with one equivalent of alkyl or aryl halide to yield disubstituted of
imidazolium salts (Scheme 1.4).
NHN NKN NN NNR' "R R'KOH
DMSO, RT
-H2O
R'-X
DMSO,RT-KX
R"-X
Solvent,reflux
imidazole potassium azolide 1-alkylimidazole1,3-dialkylimidazolium halide
Scheme 1.4: General representation of syntheses of imidazolium salts by
nucleophilic substitution.
b) Multi-components reaction, building up the heterocycle with the appropriate
substituents in one step
This route which involves one pot synthesis using primary amines, glyoxal,
and formaldehyde are reacted in the presence of Brønsted acid [17, 18]. The reaction
starts with coupling between amine and glyoxal to form Schiff base. Further,
condensation with formaldeyde which facilitates the formation of imidazolium salt
(Scheme 1.5).
7
O O
2 R-NH2
N N RR
O
HH
NNR R-2H2O
HX-H2O
X-
Scheme 1.5: General representation of syntheses of imidazolium salts by multi-
components reaction.
The flexible route is suitable for the syntheses of symmetrical 1,3- substituted
azolium salts. Unsymmetrical substituted azolium salts can also be prepared by the
combination of a multicomponent cyclization and follow with an N-alkylation
reaction [19]. After the alkylation, alkyl group (R”) attached at second nitrogen atom
to obtain asymmetrically substituted derivative (Scheme 1.6).
HO OHNN
"R R'
X-
NHNR'
X-+ [R'-NH3]X
+ [NH2]Y
+ CH2O
H+Base"R-X
H-X
Scheme 1.6: General representation of multicomponent cyclization and N-alkylation.
1.6 Synthesis of silver(I)-NHC complexes
NHCs have been extensively used in organometallic and inorganic chemistry
for catalytic study [20] , transmetalation [21] and medicinal studies [22]. Three main
synthetic methods are used to synthesis silver(I)-NHC complexes:
1.6.1 Preparation of the free carbene and reaction with silver salt
The first reported synthesis of silver(I) complex was achieved by this route in
1993. According to this route, deprotonation of imidazolium salt prepared with
strong base and subsequently free carbon reacted with silver triflate to yield silver-
8
NHC complex (Scheme 1.7) [23]. Since then, various silver(I) complexes have been
synthesized using this method [24-26]. A strong base suitable for deprotonation of
imidazolium salts is either potassium hydride, KH or potassium t-butoxide, KOtBu.
As this route in the initial stage of free carbenes, it is limited to those imidazolium
salts which can generate stable carbenes [24, 27-29].
N
N
N
N
N
N
Ag
N
N
KHorKOtBu
CF3SO3-
AgO3SCF3
Scheme 1.7: Preparation of silver(I)-NHC complexes by free carbene.
1.6.2 In-situ reaction of azolium salts
Deprotonation of azolium salt by the use of a silver(I) base such as Ag2O,
AgOAc, and Ag2CO3 [30, 31] has been the most widely used method in the syntheses
of silver(I)-NHC complexes. Lin and co-workers investigated a procedure that using
Ag2O to form silver(I)-NHC complexes of 1, 3 diethylbenzimidazol– 2–ylidene
(Scheme 1.8) [32, 33]. Silver oxide is the most frequently used of the metal bases as
the reaction can easily controlled by removing insoluble silver oxide [34-38].
Different sorts of solvents have been used with Ag2O in the synthesis of silver(I)-
NHC complex such as dimethylformamide, dichloromethane, 1,2-dichloroethane,
dimethyl sulfoxide, acetonitrile, methanol and acetone.
9
N
N
Et
Et
N
N
Et
Et
Ag
N
N
Et
Et
N
N
Et
Et
Ag
N
N
Et
Et
AgBr
Br
X-
PF6-
Ag 2O
X=Br
--
Ag2 O
X=PF6 -
PF6-
Scheme 1.8: In-situ reaction of benzimidazolium salts.
1.6.3 Silver salt in the basic medium
An alternative method to synthesize silver(I)-NHC complexes is through the
deprotonation of imidazolium cations that was first employed by Wang and Lin [32].
These researchers used a basic phase transfer catalyst, tetrabutylammonium bromide
(Bu4N+Br-) to prepare 8 from imidazolium bromide in the presence of silver bromide
(Scheme 1.9). The silver(I)-NHC complexes produced through this method are
sensitive to moisture which leads to decomposition to imidazolium salt. Thus, this
routes have been abandoned due to unsuccessful attempts and the aforementioned
success of silver-based route using silver(I) oxide [39].
Scheme 1.9: Synthesis of silver(I)-NHC, 8 using basic phase transfer catalyst.
10
1.7 Applications of silver(I)-NHC complexes
1.7.1 Catalytic study
In 1996, Fernandez, Peris and co-workers were the first to study silver(I)
NHC as donation from the substituents of the alkene by increasing the conversion
rates of the diboration reaction. Later, they found that increasing the temperature of
the diboration reaction, it slows the conversion of the alkene to the diborane.
However, the active catalytic species of silver(I)-NHCs could not discover as the
nature of silver(I)-NHC in solution.
Later, Waymouth and Hedrich have also studied silver(I)-NHCs for catalytic
purposes [40]. They reported that silver(I)-NHCs, 9 undergoes thermolysis to
produce free NHC (Scheme 1.10), which then used to catalyse the ring opening
polymerization of L-lactide [41]. The thermal stability of 9 was studied by different
scanning calorimetry and thermogravimetric analysis. They attempted to trap the free
NHCs by heating complex 9 in the presence of a trapping reagent, carbon disulphide
to produce zwitterion 10.
N
N
Ag
N
N
N
N S
S-
AgCl2-
CS2,
THF-2AgCl
9 10
Scheme 1.10: Active catalytic species of silver(I)-NHC.
11
1.7.2 Carbene transfer chemistry
One of the most important application of silver(I)-NHC is transmetalation
reaction. Many ligands are unsuccessfully metalate due to degradation under
condition required. Silver(I)-NHC complexes have proven themselves as transfer
agent to other metals such as Au(I), Cu(I), Cu(I), Pd(II), Pt(II), Ni(II), Ir(I), Ir(III),
Rh(I), Rh(III), Ru(II), Ru(III), and Ru(IV). Transmetalation reaction can be carried
out under aerobic conditions, inert atmosphere and presence of water [42].
Transmetallation become more important method in obtaining the NHC complexes
of different metal with interesting biological applications [43].
Transmetalation from silver(I)-NHCs has become a general method for
preparation of Pd(II)-NHCcomplexes where a variety of palladium reagents have
been used for transmetalation including Pd(COD)Cl2 [44-47], Pd(COD)Br2 [48],
Pd(COD)CH3Br [48], Pd(COD)CH3Cl [29, 44, 47-49], PdCl2 [50-52], [Pd(allyl)Cl]2
[53-55], PdCl2(CH3CN)2 [50, 56-59], and PdCl2-(PhCN)2 [44, 60] (Scheme 1.11).
(a)
N N
N
R
R
Ag
Br
NN
N
R
R
Pd
BrBr
CH2Cl2
Pd(COD)CH3Br
(b)
R N N R
Ag
Br
R N N R
Br-
Ag2OPdCl2(MeCN)2
Pd
R R
RR
ClCl
Scheme 1.11: Transmetalation of silver(I) complexes: (a) Using Pd(COD)CH3Br
[48], (b) Using PdCl2(CH3CN)2 [58].
12
1.7.3 Medicinal chemistry
a) The use of silver compounds as antimicrobials
Silver has been used as an antimicrobial in early years. The early civilizations
used silver to store and purify drinking water [61-64]. Antimicrobial properties of
silver nitrate were known in 1800s and it was recognized as an antiseptic in wound
care for more than 200 years. In the late 19th century, it was reported that silver
compounds can kill certain microorganisms at very low concentrations [65]. Créde
began to use of 2% silver nitrate solution to prevent eye infections in new-borns, in
1881.
In 20th century, colloidal silver solutions were introduced to avoid the
irritation associated with silver nitrate. Moyer found a treatment for large human
burns using 0.5% silver nitrate solution [66]. In addition, Fox discovered the use of
silver antibiotics using silver sulfadiazine [67] . Silver sulfadiazine (Figure 1.6) is
designed to combine antibiotic sulphonamide, sulfadiazine, with silver to obtain
wide spectrum antibiotics. It is in solid state, water insoluble complex and exists as
polymer. Besides, it has been shown good biological activities against gram- positive
and gram-negative bacteria [68]. Silver sulfadiazine remains one of most widely
used antimicrobials for infections associated with burns [22].
Figure 1.6: Structure of silver sulfadiazine [67].
13
Silver sulfadiazine have been observed to kill bacteria quickly, but loose their
effect in a short time causing the wound site to be reinfected. The slow release of
silver at the wound sites is essential for faster healing. The strong binding of NHCs
to silver can result in more stable complexes that can slowly release silver ion, thus
retaining the antimicrobial effect over a longer period of time.
b) The use of silver compounds as larvacides
Silver(I)-NHC complexes have been widely tested for their antimicrobial
activities. However, they were rarely studied for their antilarvacidal activity.
At present, different types of metal nanoparticles are being produced
including copper, zinc, titanium, magnesium, gold, alginate and silver [69].Among
these, silver nanoparticles (AgNPs) have received considerable attention due to their
attractive physico-chemical properties, surface plasmon resonance, surface-enhanced
raman scattering (SERS) or biological applications. Biologically synthesised AgNPs
have many applications, including for both in vivo and in vitro biomedical and
industrial research. Addition to this, the AgNPs act as the very good insecticide for
the control of mosquito vectors nowadays [70]. Thus, a novel attempt to test
silver(I)-NHC against mosquito larvae have been reported.
14
1.8 Research Problem
1.8.1 This research problem of this project are to:
i. Evaluate angle and coordination of C-Ag-C geometry upon completion of
silver(I)-NHC complexes using X ray diffraction analysis.
ii. Investigate coordination bond between nitrile groups after formation of
silver(I)-NHC complexes.
iii. Examines the release rate of silver ion towards antimicrobial and larvicidal
activities.
1.9 Proposed work
1.9.1 The objectives of this project are :-
i. To syntheses new N-heterocyclic carbenes (NHC) ligands of xylyl
(ortho/meta/para) linked bis-imidazolium salt with cyclopentyl and 1,4-
bromomethyl benzonitrile.
ii. To syntheses binuclear silver(I)-NHC complexes derives from xylyl
(ortho/meta/para) linked bis-imidazolium salts.
iii. To characterize the ligands and complexes using elemental analysis and
single crystal X ray diffraction analysis for selected compounds.
iv. To evaluate the antimicrobial and larvicidal activities of all synthesized
imidazolium salts and silver(I)-NHC complexes.
1.9.2 Targeted imidazolium compounds
For this research, imidazole was used as a starting material. The targeted
ligands are bidentate consist one substituent of either cyclopentyl or benzonitrile
15
bridged with different xylyl halide and dibromoethane as their halide salts. The
prepared imidazolium salt were then used to produce dinuclear silver(I)-NHC
complexes (Scheme 1.12). The synthesised compounds were characterised using
spectral and analytical methods. Structure of compound 3,5,7 and 10 were confirmed
using single crystal X-ray diffraction techniques. Then, all the compounds were
evaluated for their antimicrobial studies and larvicidal activities.
16
N N R-Br N N R
KOHDM SO
Stir, RT 3 h
a,e
Reflux 24h
N
N
N
N
R
R
MeOHStir, 48h
2Br-
Ag2O
N
N
N
R
R
Ag
AgN
N
N
N
R
R
2PF6-
2+
N
N
N
N
R
R
N
N
N
N
R
R
Ag
Ag
N
N
N
N
R
R
Ag2O
MeOHStir, 48h
2Br-
2PF6-
2+
N NNN
RR
N NNNR R
AgAg
N NN NR
R
b,e Reflux 24h
Ag2O MeOHStir, 48h
2Br-
2PF6-
2+
N NN NR R
d, e
Reflux 24h
NN N N
Ag Ag
N N N N
R
R
R
R
2PF6-
2+
MeOHStir, 48hAg2O
c, e
Reflux 24h
5, 13
6, 14
7,15
8, 16
a = o-xylyl bromideb= m-xylyl bromidec=p-xylyl bromide
d = 1,2 diethane bromidee = 1,4- dioxaneR = Cyclopentyl bromide (1-4)
/4-bromomethyl benzonitrile (9-12)
2Br-
Scheme 1.12: General scheme of bis- imidazolium salts (1-4, 9-12) and their respective silver(I)-NHC complexes (5-8, 13-16).
17
CHAPTER 2
EXPERIMENTAL
2.1 Materials
Imidazole (Merck, for synthesis), 1-bromocyclopentane (Merck, for
synthesis), 1,2-dibromoethane (Sigma Aldrich, 99%), 4-(bromomethyl) benzonitrile
(Sigma Aldrich, 99.0%), potassium hydroxide pellets (R&M chemicals,85%),
potassium hexafluorophosphate (Across Organic, 99.0%), silver(I) oxide (Merck,
99.0%), Celite (Merck, size: 0.02-0.1 mm), dimethyl sulphoxide (QRëC),
chloroform (QRëC), 1,4- dioxane (QRëC), methanol (QRëC), acetonitrile (QRëC),
and diethyl ether (QRëC) were purchased from commercial sources and were used as
received.
2.2 Instruments
The melting point was taken using a Stuart Scientific SMP-1 (UK)
instrument. Elemental analysis was recorded on a Perkin Elmer Series II, 2400
microanalyzer. The Frontier Transforms Infrared (FT-IR) spectra were carried out in
potassium bromide disks using a Perkin Elmer 2000 system spectrometer in the
range of 4000 cm to 400 cm-1. Nuclear Magnetic Resonance (NMR) spectra were
recorded in d6-DMSO d3-acetonitrile using Bruker 500-MHz Ascend spectrometers
at ambient temperature with TMS as an internal standard. The 1H- and 13C-NMR
peaks are labelled as singlet (s), doublet (d), triplet (t), or multiplet (m). Chemical
shifts are assigned with respect to NMR solvent signals.
18
2.3 Synthesis of non-functionalized compounds
2.3.1 Synthesis of N-cyclopentyl imidazole
NN
The N-cyclopentyl imidazole compound was synthesized according to the
reported procedure [71]. The potassium azolide salt of imidazole was obtained by
stirring imidazole with strong base potassium hydroxide in DMSO at room
temperature. Cyclopentyl bromide subsequently was then added dropwise in the
same reaction medium. The synthesized product yields in 84-92%.
2.3.2 Synthesis of non-functionalized bis-imidazolium salts (1-4)
2.3.2(a) Synthesis of 3,3' [(1,2 phenylenebis(methylene)] bis(1-
cyclopentylimidazolium) bis-hexaflourophosphate (1)
The obtained N-cyclopentyl imidazole (1.00 g, 7.30 mmol) was dissolved in
1,4-dioxane (40 mL). 1,2-dibromomethyl benzene (0.96 g, 3.64 mmol) was added to
19
the solution and refluxed at 100 °C for 24 h. The reaction was then cooled to room
temperature. The white precipitates were filtered and washed with fresh 1,4-dioxane
(3 x 5 mL) and diethyl ether (2 x 5 mL) to remove by-product. For further synthesis
procedure, halide salt was used while for characterization purpose, the
hexafluorphosphate salt of the compound was prepared. Bromide salt was directly
converted into its hexafluorophosphate counterpart by metathesis reaction using two
equivalent of KPF6 in methanol (50 mL). The mixture was stirred for 3 h and
filtered, washed with distilled water (3 x 5 mL) and then recrystallized from
acetonitrile. Salt 1 was collected as white powder.
Yield: 2.10 g (86.7 %); MP: 181-183 °C; Anal. Calcd. of C24H32F12N4P2: C, 43.12;
H, 4.80; N, 8.40. Found: C, 43.52; H, 4.69; N, 8.27; FT-IR (KBr, cm-1); 3177 (C-
Haromatic, 1567 (C=C), 1456 (C-N); 1H NMR (500 MHz, d6-DMSO): δ 1.85 (16H, m,
Cyclopentyl 8×CH2), 4.78 (2H, m, Cyclopentyl 2×CHN), 5.56 (4H, d, 2×NCH2,
J=9.5 Hz), 7.44 (4H, m, 4×imid H), 7.81 (4H, m, 4×Ar H), 9.26 (2H, s, 2×NCHN);
13C NMR (125 MHz, d6-DMSO): 23.1, 32.5 (Cyclopentyl 8×CH2), 49.1
(Cyclopentyl 2×CHN), 60.8 (2×NCH2), 121.6, 122.8 (4×imid C), 129.7, 132.7,
(4×Ar C), 135.7 (2×NCHN).
2.3.2.2 Synthesis of 3,3' [(1,3 phenylenebis(methylene)] bis(1-
cyclopentylimidazolium) bis-hexaflourophosphate (2)
20
Compound 2 was prepared in a manner analogous to that resulting 1, but
using 1,3-dibromomethyl benzene (0.96 g, 3.64 mmol) instead of 1,2-dibromomethyl
benzene. Salt 2 was collected as white powder.
Yield: 2.33 g (95.8 %); MP: 178-180 °C; Anal. Calcd. of C24H32F12N4P2: C, 43.12;
H, 4.80; N, 8.40. Found: C, 43.33; H, 4.72; N, 8.24; FT-IR (KBr, cm-1); 3115 (C-
Haromatic, 1561 (C=C), 1456 (C-N); 1H NMR (500 MHz, d6-DMSO): δ 1.97 (16H, m,
Cyclopentyl 8×CH2), 4.77 (2H, m, Cyclopentyl 2×CHN), 5.41 (4H, s, 2×NCH2),
7.49 (4H, m, 4×imid H), 7.82 (4H, m, 4×Ar H), 9.33 (2H, s, 2×NCHN); 13C NMR
(125 MHz, d6-DMSO): 22.0, 31.6 (Cyclopentyl 8×CH2), 50.7 (Cyclopentyl 2×CHN),
59.8 (2×NCH2), 121.6 (4×imid C), 127.1, 127.6, 128.8 (4×Ar C), 134.3 (2×NCHN).
2.3.2.3 Synthesis of 3,3' [(1,4 phenylenebis(methylene)] bis(1-
cyclopentylimidazolium) bis-hexaflourophosphate (3)
Compound 3 was prepared in a manner analogous to that resulting 1, but
using 1,4-dibromomethyl benzene (0.96 g, 3.64 mmol) instead of 1,2-dibromomethyl
benzene. Salt 3 was collected as white powder. Colourless crystals of 3 were
obtained by re-crystallization from acetonitrile.
Yield: 2.23 g (91.6 %); MP: 176–179 °C; Anal. Calcd. of C24H32F12N4P2: C, 43.12;
H, 4.80; N, 8.40. Found: C, 43.32; H, 4.90; N, 8.21; FT-IR (KBr, cm-1); 3170 (C-
Haromatic, 1432 (C=C), 1356 (C-N); 1H NMR (500 MHz, d6-DMSO,): δ 2.10 (16H,
21
m, Cyclopentyl 8×CH2), 4.77 (2H, t, Cyclopentyl 2×CHN, J=7.0 Hz), 5.41 (4H, s,
2×NCH2), 7.50 (4H, s, 4×imid H), 7.8 (2H, s, 2×Ar H), 7.86 (2H, s, 2×Ar H), 9.37
(2H, s, 2×NCHN); 13C NMR (125 MHz, d6-DMSO): 23.1, 32.5 (Cyclopentyl
2×CH2), 51.6 (Cyclopentyl 2×CHN), 60.8 (2×NCH2), 121.7 (4×imid C), 122.6,
128.9, (4×Ar C), 135.3 (2×NCHN).
2.3.2.4 Synthesis of 3,3' [(ethane-1,2-diyl)] bis(1-cyclopentylimidazolium) bis-
hexaflourophosphate (4)
N
N
NN
2PF6-
Compound 4 was prepared in a manner analogous to that resulting 1, but
using 1,2-dibromoethane (0.69 g, 3.64 mmol) instead of 1,2-dibromomethyl
benzene. Salt 4 was collected as brown solid.
Yield: 1.96 g (90.6 %); MP: 190–193. °C; Anal. Calcd. of C18H30F12N4P2: C, 36.21;
H, 5.08; N, 9.49. Found: C, 36.55; H, 5.28; N, 9.22; FT-IR (KBr, cm-1); 3166 (C-
Haromatic, 1565 (C=C), 1463 (C-N); 1H NMR (500 MHz, d6-DMSO): δ 1.95 (16H, m,
Cyclopentyl 8×CH2), 4.65 (4H, s, NCH2CH2N), 4.73 (2H, m, Cyclopentyl 2×CH),
7.60 (2H, s, imid H), 7.85 (2H, s, imid H), 9.11 (2H, s, 2×NCHN); 13C NMR (125
MHz, d6-DMSO): 32.4, 23.0 (Cyclopentyl 8×CH2), 48.5 (Cyclopentyl 4×CHN), 60.9
(NCH2CH2N), 121.7, 122.6, (imid-C), 135.6 (2×NCHN).
22
2.3.3 Synthesis of non-functionalized silver (I)-NHC complexes (5-8)
2.3.3(a) Synthesis of 3,3'-[1,2-phenylenebis(methylene)] bis(1-
cylopentylimidazolium) disilver(I) bis(hexaflourophosphate)(5)
NN
NN
AgAg
NN NN
2 PF6-
2+
A mixture of bromide salt 1 (0.50 g, 0.93 mmol) and Ag2O (0.50 g, 1.86 mmol)
were dissolved in methanol (30 mL) and left to stir at room temperature for 48 h,
covered from light. The reaction mixture was then filtered through Celite and the
clear filtrate was collected. The filtrate was stirred with KPF6 (0.30 g, 1.63 mmol) in
methanol (20 mL), which then facilitated the formation of 5 as white powder. The
product was filtered, washed with distilled water and dried under vacuum. Single
crystals were obtained by recrystalization in a mixture of acetonitrile:1,4-dioxane at
room temperature.
23
Yield: 0.76 g (65.7 %); MP: 179-181 °C; Anal. Calcd. of C48H60Ag2F12N8P2: C,
45.90; H, 4.78; N, 8.93. Found: C, 45.92; H, 4.70; N, 8.80; FT-IR (KBr, cm-1);
3130 (C-Haromatic), 1560 (C=C), 1424 (C-N); 1H NMR (500 MHz, d6-DMSO): δ 1.82
(32H, m, Cyclopentyl 16×CH2), 4.52 (4H, s, Cyclopentyl 4×CHN), 5.37 (8H, s,
4×NCH2), 7.17 (4H, s, 4×Ar H), 7.42 (8H, s, 8×imid H), 7.62 (4H, s, 4×Ar H); 13C
NMR (125 MHz, d6-DMSO): 23.6, 30.6, 33.5 (Cyclopentyl 16×CH2), 51.8
(Cyclopentyl 4×CHN), 62.4 (4×NCH2), 120.0, 122.4 (8×imid C), 128.9, 129.1,
134.4, (8×Ar C), 179.6, 179.6, 178.2, 178.1 (4×NCHN).
2.3.3(b) Synthesis of 3,3'-[1,3-phenylenebis(methylene)] bis(1-
cylopentylimidazolium) disilver(I) bis(hexaflourophosphate) (6)
2PF6-
NN
NN
Ag Ag
N N NN
2+
Complex 6 was prepared in a manner analogous to that resulting 5, but using
compound 2 (0.50 g, 0.93 mmol) instead of 1. The product of 6 was collected as
brown solid.
Yield: 0.85 g (72.8 %); Anal. Calcd. of C48H60Ag2F12N8P2: C, 45.90; H, 4.78; N,
8.93%. Found: C, 45.56; H, 4.60; N, 8.61%; FT-IR (KBr, cm-1); 3144 (C-Haromatic,
24
1452 (C=C), 1422 (C-N); 1H NMR (500 MHz, d6-DMSO): δ 1.98 (32H, m,
Cyclopentyl 16×CH2), 4.77 (4H, s, Cyclopentyl 4×CHN), 5.13 (8H, d, 4×NCH2),
7.08 (4H, s, 4×Ar H), 7.19 (8H, s, 8×imid H), 7.29 (4H, s, 4×Ar H); 13C NMR (125
MHz, d6-DMSO): 33.5, 23.6 (Cyclopentyl 16×CH2), 53.9 (Cyclopentyl 4×CHN),
62.5 (4×NCH2), 119.7, 122.6 (8×imid C), 129.4, 134.6, (8×Ar C), 179.1 (4×NCHN).
2.3.3(c) Synthesis of 3,3'-[1,4-phenylenebis(methylene)] bis(1-
cylopentylimidazolium) disilver(I) bis(hexaflourophosphate) (7)
N NNN
Ag Ag
N N N N
2PF6-
2+
Complex 7 was prepared in a manner analogous to that resulting 5, but using
compound 3 (0.50 g, 0.93 mmol) instead of 1. The product of 7 was collected as a
beige powder. The colorless crystals of 7 were obtained from re-crystallization in
acetonitrile.
Yield: 0.80 g(68.4 %); MP: 171–173 °C; Anal. Calcd. of C48H60Ag2F12N8P2: C,
45.90; H, 4.78; N, 8.93%. Found: C, 45.90; H, 4.72; N, 8.90%; FT-IR (KBr, cm-1);
3168 (C-Haromatic), 1518 (C=C), 1452 (C-N); 1H NMR (500 MHz, d6-DMSO): δ 2.01
(32H, m, Cyclopentyl 16×CH2), 4.85 (4H, s, Cyclopentyl 4×CHN), 5.22 (8H, s,
4×NCH2), 7.13 (8H, s, 8×imid H), 7.26 (4H, s, 4×Ar H), 7.31 (4H, s, 4×Ar H); 13C
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