Thesis Submission

Department of Pure and Applied Chemistry
Synthesis of a Novel Palladium Catalyst System and its
Application in the Heck Reaction
By
Callum Maxwell

2
Acknowledgements
Firstly, I would like to thank Prof. Billy Kerr and Dr. Siddharth Patwardhan for
allowing me to undertake such an interesting and challenging project and for
advising me throughout its progress. I would also like to thank Dr. Laura
Paterson for her help throughout the duration of this project.
My special thanks to Malcolm Gordon and Rachael Dunn, for all their efforts and
for the enthusiasm and attitude they brought to the lab every day, as well as the
patience and guidance they offered.
Finally I would like to thank the rest of the Kerr Group - Calum, Natalie, Laura
“Goldie”, Marc, Murali, Richard, Andy, and my fellow undergraduates, Tim and
Amelia, for all their help throughout my time in the lab.

3
Contents
Acknowledgements.......................................................................................................2
Contents.........................................................................................................................3
List of abbreviations......................................................................................................6
1. Abstract......................................................................................................................7
2. Aims and objectives ..................................................................................................8
3. Introduction.............................................................................................................10
3.1 Cross-coupling reactions .......................................................................................................................10
3.1.1 Palladium-catalyzed cross-coupling..........................................................................................10
3.2 Heck Reaction.............................................................................................................................................12
3.2.1 Mechanism...........................................................................................................................................12
3.2.2 Regioselectivity...................................................................................................................................14
3.3 Homogeneous catalysis..........................................................................................................................15
3.4 Heterogeneous catalysis ........................................................................................................................16
3.5 Nanoparticle catalysis.............................................................................................................................17
3.6 Formation of silica....................................................................................................................................18
3.5 Biosilification..............................................................................................................................................20
3.5.1 Controlling effects on porosity and surface area..................................................................20
3.5.2 Alternative supports.........................................................................................................................22
3.6 Analysis of heterogeneous catalysts.................................................................................................23
3.6.1 Thermogravimetric analysis.........................................................................................................23
3.6.2 Transmission electronic microscopy..........................................................................................24
3.6.2 BET analysis.........................................................................................................................................25
3.6.3 BJH analysis.........................................................................................................................................28
4.Previous work...........................................................................................................29
5. Results and discussion.............................................................................................34
5.1 Objectives.....................................................................................................................................................34
5.1.1 Synthesisof the silica support.......................................................................................................35
5.1.2 Preparationof palladium nanoparticles on silica................................................................37
5.1.3 Synthesisof palladium catalysts..................................................................................................38
5.1.3 Calcination...........................................................................................................................................40
5.2 Investigating the physical properties of the catalyst.................................................................41

4
5.2.1 BET testing...........................................................................................................................................42
5.2.3 ICP testing.............................................................................................................................................43
5.2.4 BJH analysis.........................................................................................................................................46
5.2.5 Conclusions ..............................................................................................................................................47
5.3 Catalyst Testing..........................................................................................................................................48
5.3.1 Objectives..................................................................................................................................................48
5.3.2 Test of uncalcinated catalyst........................................................................................................52
5.3.3 Test of calcinated catalyst..............................................................................................................53
5.3.3 Substrate scope...................................................................................................................................54
5.3.4 Electronic effects on the Heck reaction.....................................................................................55
5.3.5 Steric effects on the Heck reaction..............................................................................................57
5.3.6 Investigation into the effects of catalyst loading..................................................................58
5.4 Conclusions..................................................................................................................................................60
6. Future work .............................................................................................................61
7. Experimental............................................................................................................62
7.1 General...........................................................................................................................................................62
7.2 General Procedures..................................................................................................................................62
7.2.1 General Procedure A: Preparation of silica catalyst support...........................................62
7.2.2 General Procedure B: Preparation of catalyst .......................................................................63
7.2.3 General Procedure C: Calcinationof the prepared catalyst..............................................64
7.2.3 General Procedure D: Standard Reaction for testing..........................................................64
7.2.4 General ProcedureE: Standard Reaction with additive PPh3..........................................64
7.3 Synthesis of silica support.....................................................................................................................65
7.4 Synthesis of palladium catalyst...........................................................................................................66
7.5 Calcination of prepared catalyst.........................................................................................................67
7.6 Determination of standard reaction conditions..........................................................................68
7.6.1 Synthesisof methyl 3-(4-acetylphenyl)acrylate....................................................................68
7.7 Testing of uncalcinated catalyst .........................................................................................................70
7.8 Test of Calcinated catalyst.....................................................................................................................71
7.9 Investigation into the effects of electronics on the Heck reaction.......................................72
7.9.1 Synthesisof methyl 3-(4-(trifluoromethyl)phenyl)acrylate.............................................72
7.9.3 Synthesisof methyl 3-(p-tolyl)acrylate.....................................................................................74

5
7.9.5 Investigation into the effect of steric hindrance on the Heck reaction..........................76
7.10 Investigation into the effects of catalyst loading......................................................................76
7.10.1 Synthesis of methyl 3-(4-(trifluoromethyl)phenyl)acrylate...........................................76
8. Appendix 1...............................................................................................................78
8.1 Calculating the molar loading of the catalyst................................................................................78
8.2 Calculating loading of the catalyst (% w/w).................................................................................81
9. Appendix 2...............................................................................................................83
10. Bibliography...........................................................................................................86

6
List of Abbreviations
amu Atomic mass units
BET Brunauer-Emmett-Teller
BJH Barrett-Joyner-Halenda
[bmim][BF4] 1-Butyl-3-methylimidazolium
tetrafluoroborate
cm Centimetres
DCM Dichloromethane
DMF Dimethylformamide
DMSO Dimethyl sulfoxide
Et3N Triethylamine
h Hours
ICP-MS Inductive coupled plasma - Mass
Spectroscopy
J Coupling Constant
m Metres
MHz Megaherts
min Minutes
mg Milligrams
ml Millilitres
mmol Millimol
Pd(OAc)2 Palladium Acetate
PEHA Pentaethylenehexamine
PVP Polyvinylpyrrolidone
S.M. Sodium metasilicate
TGA Thermogravimetric Analysis
TEM Transmission Electronic Microscopy
TEOS Tetraethyl orthosilicate

7
1. Abstract
The following work details a method developed for the bioinspired preparation
of a palladium catalyst and the preliminary investigations into its use in metal
heterogeneous catalysis.
Inspired by biosilification and replicated in the laboratory, silica aggregations
were prepared using pentaethylenehexamine (PEHA) in aqueous solution. The
method used was extended to incorporate palladium nanoparticles onto the
silica prepared creating a low energy, low cost preparation of a heterogeneous
palladium catalyst.
The preliminary investigations into the stability and activity of the catalyst have
focused on the cross-coupling Mizoroki-Heck reaction between methyl acrylate
and a range of aryl halides.
The range of aryl halides available were used to investigate how the electronic
effect experienced by the halide affected the overall efficiency of the catalyst in
the system.

8
2. Aims and Objectives
In the present economic climate, energy costs are rising, fossil fuels are running
out and the impact is being felt across all industries. Recently in America, Forbes
reported on a major movement indicating that it is time for universities to divest
their investments in fossil fuels.[1] This is a major sign that the environmental
and moral costs of fossil fuels are catching up with the economic value associated
with them. As a result of the rising cost of energy from fossil fuels it is of
paramount importance to find low energy methods to prepare effective catalysts
that are active and cheap to produce.
Taking inspiration from biology, where plants and grasses are able to synthesise
silica naturally to strengthen their cell walls, bioinspired silica has been
produced whilst replicating the mild conditions associated with its natural
synthesis.[2] The green routes associated with biosilification represent an
opportunity to reduce the cost, both economically and environmentally, of
nanoparticle catalysis.
The applications of bioinspired silica are numerous, however this project will
focus on the use of the silica as a system for catalyst support. With this in mind,
gaining an understanding of the overall process, and synthesising a silica support
using a bioinspired method under mild conditions was the first aim of the
project.
In this project, pentaethylenehexamine (PEHA) was used in the preparation of
the modified-silica due to its ability to control the particle size of the silica and
the physical properties of the overall support prepared, such as the surface area
and pore size.
The second aim of this project was to prepare a palladium catalyst by
incorporating palladium nanoparticles into the bioinspired silica during its
preparation. The novel approach to the preparation of this catalyst aimed to be
environmentally friendly with little chemical waste and a low energy cost. By

9
preparing the catalyst at room temperature, with mild pH, and using water as a
main solvent, it was hoped that this low cost preparation could be scaled up as a
method to produce highly active and alternative catalyst systems for cross-
coupling reactions at a far reduced cost.
Since the morphology of the silica prepared was controllable, this project aimed
to prove the robustness of the reaction by keeping the physical properties of the
silica supports consistent during separate catalyst preparations. To investigate
the physical properties of the catalyst prepared Brunauer-Emmett-Teller (BET)
and Barrett-Joyner-Halenda (BJH) analysis were both used, as they would allow
the surface area and specific pore size of the catalyst to be examined.
To investigate the activity and versatility of the catalyst system prepared, the
Heck reaction was identified as a suitable reaction candidate. By using a range of
substrates the transformational capabilities of this catalyst system were hoped
to be identified, as well as where its limitations appear.
Currently heterogeneous catalysts do not have a particularly high turnover
number, and poor reusability is a trait common due to leaching of the catalyst
from its support into the respective reaction mixtures. The final objective of the
project was therefore to investigate the reusability of the catalyst. If the catalysts
prepared using the green route are as recyclable as the current catalyst systems
available, they will represent a significant drop in cost.

10
3. Introduction
3.1 Cross-coupling reactions
Cross-coupling reactions are some of the most important reactions used in
chemistry today. The cross coupling reaction has the sole aim of generating a
new carbon to carbon bond, and palladium is the most widely chosen metal to
act as the catalyst for the reactions.[3] Scheme 1 shows the general form of a
cross coupling reaction; R1 is an organic fragment of a molecule, X is a good
halide or triflate, and R2 is a different organic fragment, usually attatched to a
metal species. In the presence of a metal catalyst and a base, the reaction will
bond the two organic fragments.
Scheme 1
3.1.1 Palladium-catalyzed cross-coupling
Palladium has been utilised as a catalyst in many different cross-coupling
reactions, for example, the Suzuki-Miyaura reaction, Hiyama-coupling, Negishi
coupling and the Heck reaction.
The Suzuki-Miyaura reaction (Scheme 2) was first published in 1979 and
involves the coupling of an aryl or vinyl borane with an aryl or vinyl halide or
pseudo-halide (e.g. triflate).[4],[5] Palladium (0) is used to catalyse the reaction,
with the desired product being obtained in an excellent 98% yield.

11
Scheme 2
Scheme 3 shows the Hiyama-coupling, first discovered in 1988, which is a cross
coupling reaction of an organosilane with an organohalide or triflate in the
presence of a fluoride source.[6],[7] Scheme 3 indicates that the Hiyama-coupling
can be carried out at room temperature.
Scheme 3
The Negishi-coupling was first published in 1977 and involves the coupling of an
organozinc compound with an organic halide or triflate.[8] The reaction is
commonly carried out using either palladium or nickel as the catalyst (Scheme
4).[9] In the case of the Negishi coupling, the metal incorporated into the second
organic fragment is Zinc. Similarly with the Hiyama-coupling, the Negishi-
coupling can be carried out at room temperature.
Scheme 4

12
3.2 Heck Reaction
The Heck reaction was first reported in the late 1960’s and involves the reaction
between an unsaturated organohalide and an olefin, to produce a new
unsaturated product as illustrated in Scheme 5.[10],[11],[12]
Scheme 5
3.2.1 Mechanism
The general mechanism for the Heck reaction and the catalytic cycle can be seen
in Scheme 6. When the reaction is carried out under a palladium (II) source, it is
first reduced from Pd(II) to Pd(0) to allow the palladium to initiate the catalytic
cycle. Such reduction of Pd (II) to Pd (0), can be carried out using, for example,
PPh3. The first step of the catalytic cycle is oxidative addition, in which palladium
inserts into the carbon – halide bond which results in the palladium (II) species.
Following oxidative addition, carbometallation occurs which involves the
insertion of the olefin into the carbon-palladium bond. β-hydride elimination
then occurs to produce the product, before the palladium (0) is reformed via
reductive elimination.[12] The catalytic cycle is completed at this stage and, as
shown in Scheme 6, the reformation of palladium (0) allows the reaction to be
naturally catalytic in palladium (0). The number of catalytic cycles able to be
completed before reactants run out is known as the turnover.

13
Scheme 6
The Heck coupling mechanism shown above indicates the group X is initially
connected to an unsaturated organic molecule (e.g. R=Ar). The X group, as in the
previously discussed cross-coupling reactions can be an iodide, bromide,
chloride or triflate. The alkene can be mono, di, tri or tetrasubstituted.
Within the catalytic cycle, attaching phosphine ligands can further stabilise the
palladium catalyst. Under these conditions, the palladium (0) complex will be
more stable and therefore the risk of palladium black formation, which is
catalytically inactive, will be significantly reduced. Another method to reduce the
formation of palladium black is to lower the catalyst loading. This can also
encourage ligandless systems to succeed.Error! Reference sourcenot found.

14
3.2.2 Regioselectivity
Within the Heck reaction, attaching an electron-withdrawing group to the alkene
results in the arylation or vinylation selectively occurring at the β-position of the
alkene as shown in Scheme 7.[15] Additionally, when more electron rich alkenes
are employed, a reversal in regioselectivity is observed.
Scheme 7
Where less electronically bias alkenes are used as reactants in the Heck reaction,
regioselectivity is not as pronounced, with a mixture of α- and β-substituted
alkenes forming. Following the same procedure as Scheme 7, examples of
reactants that will produce a mixture of and products are shown in Figure 1.
Figure 1

15
3.3 Homogeneous Catalysis
Homogeneous catalysis refers to a catalytic system in which the catalyst and the
substrates are in the same phase in the reaction mixture. In most cases this will
be the liquid phase. Under these conditions some problems occur when
separating out the products from the reaction mixture, especially when working
with nanoparticles.
Within industry, homogenously catalyzed reactions are of a smaller significance
than most heterogeneously catalyzed reactions, since heterogeneous catalysis
creates all the raw materials and building blocks for chemicals.[16] Perhaps the
most important reaction from a homogenous standpoint is hydrogenation, such
as the hydrogenation of alkenes using Wilkinson catalyst (RhCl(PPh3)3),
(Scheme 8). The yield of product observed in the reaction was 80%.[17]
Scheme 8
The selectivity of the hydrogenation is controllable using different reactants and
alternative catalysts. In industry asymmetric hydrogenation is used in the large-
scale synthesis of the precursor to L-Dopa (Scheme 9), which is widely used in
the pharmaceutical industry. L-Dopa is then synthesised by acid catalysed
hydrolysis.[18]
Scheme 9

16
3.4 Heterogeneous Catalysis
In contrast to homogeneous catalysis, heterogeneous catalysis refers to a
catalytic system in which the catalyst is in a different phase to the reaction
mixture. There has been significant research into heterogeneous catalysis, and in
particular, the concept of attaching metal nanoparticles into a solid support has
been a successful idea through recent history. Placing a catalyst, such as
palladium metal in the Heck reaction, into a stable support allows the
opportunity to create new reactive catalysts for industry.[19], [20]
Since the recovery of a heterogeneous catalyst is both easy and cheap, this serves
as main advantage over homogeneous catalysis. Reusability of catalysts is
extremely important when trying to reduce the costs of industrial scale
reactions.
The main physical properties associated with a successful catalyst are pore
volume and surface area.[21] The support chosen will differ from reaction to
reaction but the support chosen must be completely inert to the reaction
conditions it finds itself in. Three commonly used support materials used for
heterogeneous catalysis are alumina, silica, and carbon. These materials all have
high melting points as well as high decomposition temperatures. The
characteristics of the catalyst support such as pore size, surface area and pore
distribution, can be characterised for these materials using BET and BJH
analysis.[21]
The support network used can also have an effect on the reactivity of the
catalyst. As well as preventing the build up of palladium molecules congregating
and creating palladium black, chemicals such as bismuth have been shown to
improve the activity of heterogeneous catalysts in cross-coupling reactions. The
support structure shown in Figure 2 ([BiPd(O2CCF3)5(HO2CCF3)]2) gives an
indication of how complex the chemistry of the support network has become.

17
Figure 2
Mesoporous silica is extremely stable both thermally, as well as chemically and
has the bonus of a relatively simple synthesis. As far as the desired
characteristics of a support go, silica is an excellent choice from a catalytic point
of view. Its high thermal and chemical stability mean that it will not change form
and increase leaching during a reaction.[22] Silica’s stability will prevent the
catalyst support decomposing under reaction conditions, and allow the catalyst
to be long living.
3.5 Nanoparticle catalysis
As previously noted (Section 3.4), generally the higher the surface area of a
catalyst the more effective it will be. Therefore, making the particles of your
catalyst as small as possible will generate the largest surface area and in turn, the
most effective catalyst. Generally, a nanoparticle is any particle between 1 and
100 nm in size.[23] As well as the ability to generate catalysts with high surface
areas, nanoparticle technology has also resulted in a few chemicals such as gold,
which is usually considered chemically inert, to be effective as a catalyst.[11],[24]
As a result of this, nanoparticles have become a major interest to the catalyst
industry. In Figure 3, the graph shown indicates the decrease in activity of gold
nanoparticles on different catalyst supports, as the diameter of the gold
nanoparticles increases.

18
Figure 3
3.6 Formation of silica
Passing oxygen over the surface of elemental silicon traditionally forms Silicon
Dioxide, (silica). At high temperatures (between 600 and 1200oC) and using
either dry or wet oxidation techniques, multiple layers of silica can be formed
whilst maintaining control of the physical properties of the product. The reaction
for the wet oxidation technique is shown in Scheme 10.[25]
Scheme 10
At higher temperatures, the layer of oxide produced increases in thickness from
1 micron at 920oC to around 1.08 microns at 1200oC (Figure 4).[25]
Si 2H2O2 SiO2 2H2
920 - 1200oC,
10 h.

19
Figure 4
The dry oxidation technique is carried out under similar conditions although
oxidation can occur at temperatures as low as 700oC, (Scheme 11).[25]
Scheme 11
In the experiment carried out by Deal et al., at 700oC an oxide thickness of 0.05
microns was observed, whilst at 1200oC an oxide thickness of 1 micron was
recorded (Figure 5). This correlates well with the information from the wet
oxidation of silicon, where the same pattern was recorded.
Figure 5
Si O2 SiO2
700 - 1200oC,
30 - 100 h

20
Traditional methods of forming silica such as wet and dry oxidation require high-
energy input to produce the product. Another method of forming silica is by the
sol-gel method, which is a type chemical solution deposition.[26] The most
common reaction for the sol-gel preparation of silica involves the hydrolysis of
tetraalkoxysilanes, Si(OR)4, (Scheme 12).[27]
Scheme 12
One of the most common precursors for sol-gel preparation of silica is tetraethyl
orthosilicate (TEOS).[28],[29] To obtain nanoscale silicon dioxide powder, the
crude product is required to be calcinated in a furnace, which requires a high
energy input. This is the main disadvantage to the preparation of silica using the
sol–gel method.[30]
3.5 Biosilification
Biosilicification is the synthesis of silica in vivo, that is, in a natural environment.
For catalysis this could be a very important process used to build structural
supports for nanoparticles. The biological silica formation brings with it some
very interesting features, including the fact that it occurs at mild pH and ambient
temperatures.[31] This environmentally friendly technique is also controllable,
something sought after in synthetic synthesis. Biologically inspired silica has
seen the use of additives in an effort to try and manage the characteristics of the
silica formed. For example the pore size and surface area of the catalyst can be
controlled depending on which substrate is used in the bioinspired silica
synthesis.
3.5.1 Controlling effects on porosity and surface area
One advantage of biosilification is the ability to influence and change the pore
size of the support for a catalyst, and hence can improve the catalyst’s efficiency.
Si(OC2H5)4 H2O
catalyst
SiO2 4C2H5OH

21
As one of the most important factors affecting the efficiency of a catalyst the
ability to influence the pore size of the catalytic support is an important
advantage of biosilification. By using different substrates in the initial synthesis
of the silica, the pore size of the support, as well as the surface area, can be
tailored to suit the properties required of each individual catalyst.
The range of surface area tailored can range from <10 up to 1030 m2 g-1 with
pore sizes ranging from <2 up to 60 nm, with the advantage of having a fast
preparation and mild conditions associated with biosilification.[32-37] In contrast,
using non-bioinspired routes of synthesis such as sol-gel processing, high surface
areas and high porosity silica can be synthesised but only using methods and
commonly harsher conditions than biosilification required.[38], [39]
Coradin et al., were able to produce a silica support containing 2 distinctive pore
sizes, mesopores of diameter 2.5-3.5 nm and meso-to-micropores with a
diameter span of 10-100 nm, using surfactants derived from amino acids. The
resulting support also had a high surface area (>500 m2 g-1).[40] Conversely,
propylamines, such as the amines found in the diatom algae, have been shown to
influence the surface area of the silica precipitating to a surface area of
<10 m2 g.[41]
Through implementing biosilification into synthetic chemistry, it is possible to
replicate the mild conditions associated with the silica production. By eventually
understanding its process, biosilification could be scaled up to be used in
biotechnological processes, for example, bioimplants (the materials used from
human or animal origin to replace or support biological systems), and enzyme
immobilisation (the process of placing an enzyme onto an insoluble solid).[42], [43]
Metal oxides can also support catalysts and these have been employed in
numerous areas, for example Suzuki coupling reactions. For example, M. Kantam
et al., synthesised a catalyst using palladium nanoparticles that had been
synthesised by counter ion stabilisation of [PdCl4]2- with nanocrystalline
magnesium oxide, followed by a reduction.[44] The catalyst synthesised showed

22
good reactivity for aryl bromides and aryl iodides. For a 0.5 % loading of this
catalyst, the Suzuki coupling was carried out in 6 hours at room temperature.
However, in the experimentation, the loading of the catalyst was reduced to
0.01% and was effective. The high surface area of the magnesium oxide support
(≈ 600 m2 g-1) was attributed to the activity of the catalyst.
3.5.2 Alternative Supports
Carbon nanotubes have also been used to support palladium catalysts.[45]
Alternative methods of encapsulating the palladium on the surface of the tubes
have been employed such as impregnation, [46] supercritical fluid attatchment,[47]
and pyrolysis.[48] Pyrolysis is a type of thermolysis carried out at increased
temperature without the presence of oxygen, and is one of the simplest methods
of placing the palladium onto carbon nanotubes such as in Scheme 13, where
the palladium particles become trapped within the carboxylic acid
functionality.[48]
Scheme 13
Recently, more organic materials such as functionalised polymers have been
used to support metal catalysts in coupling reactions.[49] Polymers can be
extremely versatile when used as supports, they allow for the recycling of the
catalysts, as well as the high efficiency normally associated with homogeneous
catalysts. Sayed et al. used PVP polymers as a support for palladium catalysed
al nanoparticles on the surface of carbon
al nanoparticle–nanotube heterogeneous
n employed in fuel cells,25
electrocatalytic
as sensors27
and only a few reports include
in Heck, Suzuki, Stille, and Sonogashira
However, the catalytic application of
particle composites in acyl Sonogashira
s been missing till to date. In the present
hetic process was adopted to anchor
es (PdNPs) onto the surface of carboxylic
WNTs following our recent approach to
eous PdNPs anchored in a polymer
he SWNT–PdNPs as a catalyst in acyl
under copper free condition to synthesize a
he ‘‘ynones’’ are multipurpose isolable
synthesis of pharmaceutically prominent
ve N-heterocyclic compounds, such as
1
isoxazoles,32
pyrimidines,33
quinolines,34
olines.35
Synthetic methods for the pre-
ilize well defined palladium catalysts for
alkynes with an acid chloride (acyl
29,36
or with organic halides in thepresence
carbonylative Sonogashira reaction).37
A
ey unveils that most of these studies
pper as a co-catalyst, which in turn makes
products more tedious, generating alkyne
ucts. Nevertheless, the acyl Sonogashira
more straightforward process for the
avoiding poisonous carbon monoxide
extended to design sequential reactions in
eading to pharmaceutically important
e embellish the carboxylic acid functiona-
In the current strategy, SWNT–PdNPs nanocomposite can be
accomplished after mixing carboxylic acid functionalized
SWNTs and palladium acetate in dry DM F followed by one
hour sonication and thermal treatment at 95 uC for four hours.
The as-synthesized SWNT–PdNPs were characterized by trans-
mission electron microscopy (TEM ), energy dispersive X-ray
spectrum (EDX), scanning electron microscopy (SEM ), atomic
force microscopy (AFM ), ICP-AES, X-ray photoelectron
spectroscopy (XPS), UV-vis-NIR spectroscopy, and resonance
Raman spectroscopy.
TEM images, recorded on a carbon–copper grid following a
drop-cast method from a very dilute sample in DM F, revealed
the presence of palladium particles having nanospheric dimen-
sion (Fig. 1A,B) in between the range 5 to 14 nm (Fig. 1C) and
EDX spectrum collected from TEM confirmed the presence of
palladium in the SWNT–PdNPs sample (see ESI{ ). The SEM
Scheme 2 A schematicrepresentation for thesynthesisof SWNT–PdNPs
considering a small part of the nanotube–nanoparticle architectures.
View Article Online

23
Suzuki cross coupling reactions.[50] By varying the size of the palladium
nanoparticles they were able to investigate the effect that particle size had on the
turnover frequency of the Suzuki reaction. The results they obtained showed
that as the particle size increased, the turnover frequency decreased, suggesting
that the Suzuki reaction was structure sensitive. They also observed low activity
with very small particles, which could be attributed to the poisoning effect by the
intermediates formed.
3.6 Analysis of heterogeneous catalysts
After selecting an efficient method of synthesising the catalyst it is important to
select a method to analyse its physical composition. Different techniques can be
used to investigate the physical and chemical characteristics of a catalyst.
3.6.1 Thermogravimetric Analysis
Thermogravimetric analysis (TGA) is one such method of analysis.[51] In TGA
the rate of change in the weight of a substance is plotted as a function of the
temperature, as percentage residue. The changes in mass as the temperature
increases give an indication of the composition of elements within the
material. This allows an understanding of the thermal stability and chemical
make up of a catalyst. Figure 6, from Davar et al., indicates that as
temperature increases, the weight of the structure decreases as fragments are
removed from the molecule.[52]

24
Figure 6
3.6.2 Transmission Electronic Microscopy
Transmission electron microscopy (TEM) is a method of microscopy that uses a
focused beam of electrons travelling through a sample of a material to generate
an image of the material in the same way as a light microscope. When de Broglie
released his paper on the de Broglie hypothesis (the proposal that all matter
exhibits wave-like properties, as photons do),[53] a group working at the
Technological University of Berlin believed that using electrons rather than light
would allow for an image of much higher resolution to be produced.[54] This
effect is due to electrons having a much lower de Broglie wavelength than light.
In Figure 7, shown below, nanosheets of palladium metal have been
photographed using TEM, and the structure of the palladium on the sheet in
shells is clear. [55]

25
Figure 7
3.6.2 BET analysis
BET analysis was based on the BET theory developed and first published in
1938.[56] Based initially on Langmuir’s theory for monolayer molecular
adsorption, BET theory is an extension of molecular adsorption to incorporate
multilayer adsorption.[57]
Irvine Langmuir, who won a Noble prize based on his work, first derived the
Langmuir adsorption model in 1916. The model is based on single-layered
adsorption and can easily be applied to catalysts. In Figure 8, the model is
shown as a gas next to a planar surface, with gas molecules being adsorbed onto
this surface.
Figure 8
CP302 Part 3 9
Type II isotherms correspond to strong adhesion at low pressure, hence the steep
initial slope, and either very wide pores or an isolated surface. After the initial
monolayer is formed the isotherm becomes nearly horizontal, but then begins to
curve upwards again as the saturation pressure is approached. This upturn
corresponds to the formation of multilayers and ultimately a layer of liquid starts to
form on the surface, called a wetting layer, whose thickness is unbounded as the
saturation pressure is approached.
Type III isotherms are similar to type II isotherms, except gas adhesion to the
surface is much weaker.
Type IV isotherms are characteristic of adsorption in mesoporous materials where
gas adhesion to the surface is strong. Initially, monolayer or multilayer adsorption
occurs at low pressure. The hysterisis loop occurs because of capillary
condensation, whereby gas condenses to liquid within the mesopores at a pressure
lower than the bulk saturation pressure.
Type V isotherms are similar to type IV isotherms, except that gas adhesion to the
surface is weak.
3.4. Langmuir isotherm
Microporous adsorbents are usually used to separate mixtures of gases. So we will
mostly be concerned with type I isotherms. It is useful to be able to represent these
kinds of isotherm in terms of an adjustable function, and the Langmuir isotherm is
the simplest example. Much more sophisticated modelling techniques, such as those
based on ‘statistical mechanics‘(which is the physical theory that lies behind
thermodynamics), are able to reproduce all these isotherms as well as other
adsorption effects.
Irvine Langmuir, who received the Noble Prize for chemistry in 1932, derived his
eponymous equation in 1916, as well as a simple method for fitting it to experimental
data. It must have been a short paper, because we can easily re-derive both the
equation and fitting method! Consider Figure 3.
S surface
sites
only F are
filled
gas nextto
surfacewith
concentration C
Figure 3 –illustrating Langmuir–s model for surface adsorption

26
The planar surface, shown above, has a maximum number of surface sites, S. Of
these sites, only the amount, F, are filled. Irvine Langmuir based his model on
assumptions he made which are listed below;
 The surface of the adsorbing site is perfectly planar,
 the gas is stationary when adsorbed onto the surface,
 all sites are equivalent,
 one molecule can only be adsorbed to one site at a time,
 there are no interactions between adjacent sites.
From these assumptions Langmuir derived an equation to calculate the
fractional coverage of the surface by the gas (Equation 1) where 𝜃 is the
fractional coverage of the surface, 𝛼 is the Langmuir constant, which varies
depending on the substrate, and P is the gas pressure or concentration.
𝜃 =
𝛼 . 𝑃
1 + 𝛼 . 𝑃
Equation 1
BET theory uses the same assumptions as Langmuir theory, but it also includes
three more to address some problems with Langmuir theory. The first is that gas
molecules will physically adsorb on a solid in layers infinitely, the second
assumes the different adsorption layers do not interact and the third assumes
that the theory can be applied to each layer.[58] Equation 2 is the accepted form
of the BET equation, where vm is the monolayer absorbed gas volume, v is the
measured volume of gas adsorbed, x is equal to
𝑝
𝑝0
and c is the BET constant.
𝑣 =
𝑣 𝑚. 𝑐. 𝑥
(1 − 𝑥)(1 − 𝑥 + 𝑐𝑥)
Equation 2

27
Rearranging Equation 2 gives the graphical representation of the BET isotherm,
Equation 3;
𝑥
𝑣(1 − 𝑥)
=
1
𝑣 𝑚 𝑐
+
𝑥(𝑐 − 1)
𝑣 𝑚 𝑐
Equation 3
From the values obtained for
𝑥
𝑣.(1−𝑥)
and from experimental data, a graph can be
plotted with
𝑝0
𝑝
on the x-axis to create a BET plot. The gradient of the slope of the
linear line is used to calculate the monolayer adsorbed gas quantity (vm) as
shown in Equation 4, where A is the slope of the BET curve and I is the y-
intercept;
𝑣 𝑚 =
1
𝐴 + 𝐼
Equation 4
vm is then used to calculate the total surface area in Equation 5, where SBET,total is
equal to the total surface area, N is Avogadro’s number, s is the cross section for
adsorption and V is molar volume of adsorbate gas;
𝑆 𝐵𝐸𝑇,𝑡𝑜𝑡𝑎𝑙 =
(𝑣 𝑚 𝑁𝑠)
𝑉
Equation 5
From total surface area of material the specific surface area, SBET and 𝑎 is equal to
the mass of adsorbent;
𝑆 𝐵𝐸𝑇 =
𝑆 𝐵𝐸𝑇,𝑡𝑜𝑡𝑎𝑙
𝑎
Equation 6

28
3.6.3 BJH Analysis
Another method of analysing the physical characteristics of catalysts is the
Barrett-Joyner-Halenda (BJH) analysis, which is used to calculate pore area and
specific pore volume. This method of analysis uses a modification to the Kelvin
equation to incorporate condensation occurring with in the pores of a
material.[59] The Kelvin equation is used to calculate pore size distribution and is
shown in equation 7, where d is pore size distribution, p is vapour pressure, p0
is the saturated vapour pressure and the surface tension is .
𝑑 =
2. 𝛾. 𝑉𝐿
𝑅𝑇𝑙𝑛(
𝑝0
𝑝
)
Equation 7
The modified form of the Kelvin equation incorporates the thickness of the
multilayers of condensation occurring in the pore walls, t, (Equation 8).
𝑑 =
2. 𝛾. 𝑉𝐿
𝑅𝑇𝑙𝑛(
𝑝0
𝑝
)
+ 2𝑡
Equation 8
Having stated all of the above, it is clear that there are many different catalytic
systems widely in use. As energy supplies appear to dwindle, the interest in
synthesising efficient catalysts and their subsequent systems increases. Although
the number of systems is numerous, the investment into research continues. The
latest breakthroughs in the chemistry of catalysts are likely to come from our
ability to replicate nature, reducing the cost of building highly efficient catalyst
systems. With this in mind, this project will attempt to use the process of bio-
inspired silica as a support for palladium, in the hope of proving that catalysts
synthesised this way can be efficient and cost efficient. The Heck reaction will be
used as a means to test the effectiveness of the catalyst, while BET and BJH
testing will be used to investigate the physical properties of the catalyst.

29
4.Previous work
Previously within the University, Javier Barral undertook a project that aimed to
investigate the use of bioinspired synthesis of silica as a catalyst support. A
reaction system was identified to prepare the silica produced on a consistent
scale with consistent properties.[60]
The reaction system for the preparation of the silica was adapted as a support
system for a catalyst, and accordingly, palladium nanoparticles were
incorporated into its structure. Each batch of catalyst was prepared and analysis
of physical properties using BET and ICP analysis were carried out to determine
the loading of the catalyst. BJH analysis was also used to investigate the pore
area and specific pore volume of the catalyst support. Table 2 shows the results
obtained during physical characterisation of the silica prepared. In this case the
results reflect the characteristics of a catalyst on a 9.3 and 7.0 mmol scale
(sodium metasilicate).
Entry
Scale S.M.
(mmol)
BET surfacearea
(m2/g)
PoreVolume
(cm3/g)
BJH adsorption:
AveragePore
Diameter (4V/A)
/nm
BJH desorption:
AveragePore
Diameter (4V/A)
/nm
1 9.3 20.772 0.03803 14.1127 10.4392
2 7.0 20.397 0.05707 12.8096 12.4274
Table 2
From Table 2 it is clear that the previous work carried out obtained silica with
very consistent physical conditions. Although there was some variance between
the scale of Entry 1 and 2, the BET surface area for both entries varied only
slightly (20.772 m2/g and 20.397 m2/g). This trend continued across pore
volume associated with each entry (0.03803 cm3/g and 0.05707 cm3/g). There
was a larger difference between BJH adsorption pore diameters, with Entry 1

30
having a pore diameter of 14.1127 nm compared to 12.8096 nm in Entry 2. This
difference is continued in BJH desorption pore diameter, where the Entry 1 has a
pore diameter of 10.4392 nm whilst Entry 2 was ≈ 2 nm larger. No comment was
made on the reasons for these minor differences, however it may have been
down to experimental error.
Having investigated the physical properties of the catalyst, the chemical
properties of the catalyst were then investigated using the Suzuki-Miyaura cross
coupling reaction. By selecting a range of substrates with varying electron
densities, it was hoped that the transformational limitations of the prepared
catalyst would be identified. A substrate scope was identified tending from using
substrates with a low electron density at the position of palladium insertion
(4-bromoacetophenone and 4-bromobenzotrifluoride) towards a substrate with
a higher electron density (4-bromoanisole).
Following a literature search a standard reaction was identified for the reaction.
To determine a comparison towards standard catalyst systems such as
palladium acetate, an initial reaction was used using palladium acetate as the
catalyst. The substrate chosen for the first reaction was 4-bromoacetophenone
whilst phenylboronic was used as the aryl boronic acid in all subsequent
reactions. The results from the experiment are shown below, and 1H NMR
spectroscopy was used to investigate the conversion and yield of the products
formed (Table 3).

31
Scheme 14
Run Base Solvent Yield (%)
1 K2CO3 EtOH 82
2 K2CO3 EtOH 79
Table 3
Using 4-bromoacetophenone, the anticipated yield using palladium acetate was
expected to be high. The low electron density around the halide would
encourage palladium insertion and the yields observed reflect this. Between
Entries 1 and 2 the yield achieved was relatively high with 82 and 79%,
respectively. Following the results of the standard reaction using palladium
acetate, the catalyst prepared in the lab was used to catalyse the same reaction,
however no product conversions were detailed Having said this, it was reported
that the desired product was obtained for approximately 25% of the runs.
Continuing the investigation into the effects of electron withdrawing groups on
the yield for the Suzuki reaction, 4-bromobenzotrifluoride was selected as the
cross-coupling partner with phenylboronic acid. Table 4 indicates the reported
yield when using palladium acetate as the catalyst.

32
Scheme 15
Table 4
From Table 4, the product yield appeared to fluctuate between the two Entries.
Entry 1 resulted in a significantly lower yield (69%), than Entry 2 (87%). The
strong electron withdrawing effect of the trifluoromethyl function group meant
that the oxidative addition, and palladium insertion steps to the Heck reaction
should have been favourable in this reaction system. It was assumed that the
reduced yield in Entry 1 was a result of experimental error.
When the catalyst prepared in the labaratory was used in the reaction system,
products were identified for 1 reaction out of the 31 carried out, though no
yields were reported.
The reaction between 4-bromoanisole and phenylboronic acid was used to
investigate how the yield observed with palladium acetate as the catalyst would
reduce based on the reduced electron withdrawing effect experienced by the
halide. Table 5 indicates the reported yield when using palladium acetate as the
catalyst.
1 K2CO3 EtOH 69
2 K2CO3 EtOH 87

33
Scheme 16
1 K2CO3 EtOH 43
2 K2CO3 EtOH 48
Table 5
Using 4-bromoanisole as the selected substrate, it was anticipated that the yields
obtained would be lower than had been previously recorded using
4-bromoacetophenone and 4-bromobenzotrifluoride. From the results in Table
5, it is clear that the product yield for Entries 1 and 2 (43 and 48%) is
significantly lower than when 4-bromoacetophenone was used (82 and 79%)
and also lower than the when 4-bromobenzotrifluoride was used (69 and 87%).
The increased electron density within 4-bromoanisole resulted in a drop of in
yield as oxidative addition became more difficult for the catalyst to carry out.
When the catalyst was used the more challenging conditions appeared to affect
the success of the catalyst prepared and none of the expected product was
obtained in any of the runs.
While experiencing difficulty in obtaining products, Javier was able to recover
the catalyst easily after each reaction by filtering off the product, which was an
aim of the project.

34
5. Results and Discussion
The following section shows the results obtained throughout the project.
5.1 Objectives
The objective of this project was to further develop the:
i. synthesis of a novel silica supported heterogeneous palladium catalyst,
and
ii. use the catalyst system in a series of Heck reactions to highlight its
potential as an alternative catalyst system in organometallic
transformations to traditional homogeneous reagents.
The following section will contain first a description of how the synthesis of the
catalyst was carried out and analysed, and secondly, provide details on the
catalysts performance.
However, before attempting the preparation of the palladium catalyst, an
understanding into the formation of the silica support was required. By
approaching the project in this way, it provided an opportunity for
familiarisation of the required experimental procedures and to obtain consistent
results before attempting to incorporate the metal in the catalyst system.

35
5.1.1 Synthesis of the silica support
All attempts at the synthesis of the silica support were achieved following a
bioinspired approach developed from within the laboratories of Dr. Siddharth
Partwardhan, as shown in Scheme 17. A 1:1 ratio of sodium metasilicate and
PEHA were combined and dissolved in water, resulting in a basic solution (pH
13). Upon complete dissolution of the reagents, 1M aq. HCl was slowly titrated
into the solution until a consistent pH of 7 was achieved. At pH 7 the silica
precipitates out of solution as a result of the interaction between the PEHA and
the silica itself. Throughout the neutralisation, the reaction mixture was stirred
using a magnetic stirrer, and having obtained the correct final pH (6.9-7.1), the
silica support was isolated from the reaction mixture by centrifuge. Following
this, the product was washed with water to remove excess PEHA. From analysis
of previous results from within the group, the rough volume of HCl required to
reduce the solution to the correct pH was already known. It was with this
knowledge that a series of titrations were carried out to investigate the
formation of the desired silica support. Towards this aim, the reaction sequence
was repeated until three consistent results were obtained.
Scheme 17
The results shown in Table 6 indicate that when the synthesis was attempted on
a small scale (0.5 mmol), that a relatively constant mass output of ≈ 20 mg could
be achieved, with only minor variances observed (Entries 1-4). It should also be
noted that although the final pH values fluctuated slightly (between 6.91 in Entry
1 to 7.03 in Entry 2) this did not appear to affect the mass of silica isolated
significantly.
sodium metasilicate
PEHA
crude silica support silica support
1) dissolve reactants
2) mix reactants
3) reduce pH 3) oven dry
1) Centrifuge
2) 3 x H2O washes

36
Table 6
Whilst working on this very small scale provided confidence that the described
procedure was in fact robust and reproducible, it unfortunately did not deliver a
realistic mass of catalyst support to provide the required material to complete a
project of this nature. At this stage, the scale of the silica produced was increased
ten-fold, and the results obtained are shown in (Table 7).
Entry
Sodium
metasilicate
(mg)
PEHA (mg) Initial pH Final pH HCl (μl)
Mass silica
support (mg)
1 636.0 116.0 12.58 6.91 6634 289.1
2 635.6 117.5 12.36 6.94 6615 201.6
3 636.2 116.4 12.42 6.92 6625 285.3
Table 7
The results shown in Table 7 indicate that upon increasing the scale of the
reaction, the mass of silica output varied from between 201.6 mg in Entry 2 to
289.1 mg in Entry 1. Comparing these results to that of the smaller scale
reactions, shown in Table 6, highlights the differences in isolated mass of silica
support upon scale up. In Table 6 the average mass of catalyst was ≈20 mg,
therefore by scaling up ten-fold, a mass of ≈ 200 mg was expected. From this
perspective, Entry 2 would appear to have produced an isolated mass of silica,
consistent with previous results, with 201.6 mg produced. However, Entries 1
and 3 produced significantly higher amounts of silica support (285.3 and 289.1
mg). At this stage, it is unclear if the increase in isolated mass observed was a
Entry
Sodium
metasilicate
(mg)
PEHA
(mg)
Initial pH Final pH HCl (μl)
Mass silica
support
(mg)
1 63.9 11.9 12.99 6.91 630 19
2 63.7 12.4 13.30 7.03 663 20
3 63.6 12.2 13.21 6.93 662 21
4 63.6 12.1 13.17 6.90 664 18

37
result of greater reaction efficiency at scale, or if simply more of the PEHA was
present in the final silica residue, having not been washed out as effectively as
with Entry 2. These results do however highlight that the reaction appeared to
be much more sensitive at an increased scale, with yields varying significantly
despite following an identical protocol. Unfortunately, due to time constraints
further optimisation of the procedure was suspended at this time.
Having successfully prepared silica in a controlled method, the first aim of the
project had been completed, and the preparation of palladium catalyst was the
next objective.
5.1.2 Preparation of palladium nanoparticles on silica
Preliminary work from within the laboratories of Dr. Siddharth Partwardhan had
previously identified a method to prepare the palladium catalyst as shown
(Scheme 18).
Scheme 18
The main difference in protocol between the preparation of the silica support
(Scheme 17) and the silica supported palladium catalyst (Scheme 18) was that
in the latter case, the procedure required the addition of a preformed solution of
palladium acetate (Pd(OAc)2) and sodium metasilicate, to a solution of PEHA in
water, before neutralising to pH 7. Towards this aim, the palladium acetate was
initially dissolved in 5 cm3 of acetone, before combining with an aqueous
solution of sodium metasilicate. Acetone was chosen as the eluent of preference,
since previous results from within the group had indicated that Pd(OAc)2
sodium metasilicate
PEHA
Crude Product
Palladium
Catalyst
1) dissolve reactants
2) mix reactants
3) reduce pH 3) oven dry
1) Centrifuge
2) 3 x H2O washes
Pd(OAc)2 / (CH3)2CO

38
dissolved in acetone formed a more homogeneous solution, compared to when
dissolved in ethanol.[31,54]
5.1.3 Synthesis of palladium catalysts
With regards to the palladium catalyst itself, it was decided at an early stage that
a relatively low loading of metal would be used in order to allow for easy
handling of the resultant product. Towards this aim, the loading that was aspired
to was 10 mol % of palladium. In an attempt to try to achieve this, 10-mol % of
palladium was added comparative to the initial amount of sodium metasilicate.
Additionally, it was recognised that although the initial loading of the metal
would be calculated using a basic molar ratio between sodium metasilicate and
palladium, that the final metal loading would be calculated retrospectively using
ICP analysis of the wastewater generated from each batch of catalyst. From
previous work, it was noted that while aspiring to a 10 mol % catalyst, the
percentage loading (% w/w) achieved was actually closer to 35% w/w. With this
knowledge in mind, catalyst preparation could be initiated.
Since a procedure was already established, the only decision to be made was the
scale at which to prepare the first batches of catalyst. Finally settling on a 5 mmol
scale with respect to sodium metasilicate, an initial set of reactions was
attempted (Table 8).
Catalyst
Batch
Sodium
metasilicate
(mmols)
PEHA
(mmol)
Palladium
(mmol)
Initial pH Final pH HCl (μl)
Mass of
catalyst
(mg)
1 5.26 0.50 0.45 12.39 6.98 6129 324.8
2 5.21 0.51 0.44 12.36 7.01 6150 298.4
3 15.64 1.50 1.56 12.67 7.08 18000 873.8
4 15.64 1.51 1.56 12.68 7.03 17900 935.6
Table 8

39
From the table above, it can be seen that the differences between Catalyst 1 and
2 are relatively small. The initial pH of the reaction mixtures were very similar,
with a difference of only 0.03 between both attempts. The final pH of the reaction
mixture was also very similar between Entries 1 and 2 with 6.98 in comparison
to 7.01, respectively. Surprisingly, however, the mass of catalyst produced in
each of the reactions did vary slightly, with Entry 1 affording 324.8 mg of catalyst
compared to an isolated mass of 298.4 mg in Entry 2. Again, the reasons for this
variation in isolated mass were not clear, but it was recognised that the
differences in mass were not different enough to justify a lengthy optimisation
sequence. Due to time constraints, it was decided to scale up the reaction to
provide the required volume of material to screen the subsequent Heck
reactions. Additionally, it was also recognised that should there be any
significant differences between the batches of catalyst produced, that this would
be discovered when further investigating the physical properties of the catalyst.
Having successfully synthesised 2 batches of catalyst, the reaction was scaled up
to prepare enough catalyst to carry out all the subsequent Heck reactions.
Hence, Batches 3 and 4 of the catalyst reflect a three-fold increases in scale of
catalyst preparation, to 15 mmol sodium metasilicate. The results shown above
compare favourably with Batches 1 and 2, with very similar initial pH values
associated with each system, 12.67 and 12.68 respectively for Batches 3 and 4.
The final pH was also similar (7.03 – 7.08) between the two. In accordance with
the scale up, the mass of catalyst isolated has increased by around three times
(298.4 - 324.8 mg for Batches 1 and 2, and 873.8 – 935.6 mg for 3 and 4).
However, a variation in the mass of catalyst isolated in Batches 3 and 4 was
observed. It should be noted, however, that similar variances were observed
from Batches 1 and 2. With time constraints in place, it was decided that having
produced enough catalyst to begin testing the reactivity of the system, we would
move on.

40
5.1.3 Calcination
Calcination is the heat treatment of a material as a method to remove volatile
fractions from a material or result in a thermal deposition, or phase change of a
material. Prior to investigating the physical properties of the catalysts prepared,
they were first subjected to calcination in an air furnace. This was necessary,
since the unreacted PEHA left in the reaction mixture has a tendency to remain
in pores after oven drying, and only the increased temperature within the
furnace has the ability to evaporate the amine from the silica. This heat
treatment meant that the catalyst should result in an increase to both surface
area and pore size.[15] As a result of the calcination the mass of each catalyst
reduced as the PEHA was evaporated, the results pre and post calcination are
shown in Table 9.
Catalyst
Batch
Pre-Calcination mass
(mg)
Post-calcination mass
(mg)
Change in mass
(mg)
Change in mass
(%)
1 324.8 275.4 49.4 15.21
2 298.4 247.5 50.9 17.06
3 873.8 736.8 137.0 15.68
4 935.6 804.9 130.7 13.97
Table 9
Each catalyst was subjected to the same conditions throughout the calcination,
with the furnace set to 5500C for five hours. This was to ensure that all of the
PEHA was removed from the pores of the catalysts, and Table 9 indicates the
change of mass of the catalyst due to this process. Although Catalyst 3 and 4
were prepared in a larger scale (three-fold) to Catalysts 1 and 2, the percentage
change in mass from the original pre-calcination mass is relatively constant,
scaling from 13.97% in Catalyst 4 to a maximum of 17.06% in Catalyst 2.
Catalysts 1 and 2 showed a similar change in mass (49.40 mg and 50.90 mg)
however, since the pre-calcination mass of catalyst was larger for catalyst 1, the

41
change in mass represented a smaller overall change of 15.21%, while for
Catalyst 2, having a significantly lower pre-calcination mass meant that the
change in mass had a greater overall difference to the mass of catalyst and a
larger percentage change in mass of 17.06%,
Catalysts 3 and 4 experienced a similar percentage change in mass (15.68% and
13.97%) indicating that there was a similar mass of PEHA trapped in the
structure of the catalyst. Although there is a larger change in mass between
Catalysts 3 and 4 than between 1 and 2, this represents a lower percentage
difference since the catalysts prepared are on a larger scale.
These results might also indicate that the variances observed in the masses of
catalyst produced cannot be due to residual PEHA, since a consistent amount
was removed from each of the catalyst batches prepared.
It should be noted that a small amount of the catalyst prepared was not
calcinated in an effort to test the effect of the uncalcinated catalyst in direct
comparison to the calcinated catalyst, to determine if this step is necessary.
5.2 Investigating the physical properties of the catalyst
Before proceeding to investigate the overall reactivity of the final catalyst system
in organometallic transformations, one final piece of information was required,
namely, its physical properties. Towards this aim, three methods were identified
as crucial. The first of these was BET testing, as this would show the total surface
area of the catalyst as well as the specific surface area, (Equations 5-6 in Section
3.6.2). Secondly, BJH analysis would be used to investigate pore size, for both
adsorption and desorption, (Equation 8 in Section 3.6.3). Finally, ICP testing
would be carried out to estimate the quantity of the metal present within the
catalyst system. From these results we should be able to determine if the catalyst
preparation provides consistent physical properties and loading to further

42
identify if the procedure is suitable or if further optimisation is required to
obtain a reliable synthesis.
5.2.1 BET testing
The first method used to investigate the physical properties of the catalyst was
BET testing. Having numbered each batch of catalyst as they were was prepared,
the batches were submitted for BET testing individually. The results obtained are
shown below in Table 10.
Catalyst Batch 1 2 3 4
Scale (mmol S.M.) 5 5 15 15
BET surface Area (m2/g) 60.3187 64.8807 120.1755 170.7142
Pore Volume (cm3/g) 0.06401 0.06976 0.03803 0.02103
Table 10
The batches of catalyst in Table 10 can be looked at separately according to the
scale at which they were synthesised. As can be seen in Table 10, Batches 1 and
2 were physically very similar to one another. Their total surface area compare
favourably, with the surface area for Batch 1 equal to 60.32 m2/g, while for Batch
2 the calculated surface area was equal to 64.88 m2/g. The difference in pore
volume between the two batches is also very small, with Batch 1 having a pore
diameter for adsorption of just 0.06401 cm3/g, while Batch 2 has a pore volume
of 0.06976 cm3/g. These results would seem to suggest that on a 5 mmol scale
for sodium metasilicate the described method allows for a relatively consistent
mass of catalyst prepared (see Table 8).
However, Batches 3 and 4 (15 mmol scale synthesis) of the catalyst appear to be
significantly different in physical properties to the smaller scale Batches of 1 and
2 (5 mmol). Firstly, in general the surface area appears to be much larger with

43
120-170 m2/g observed in Batches 3 and 4 compared to 60-65 m2/ g associated
with Batches 1 and 2 of the catalyst. As a larger structure of silica had been
produced, it was expected that the surface area of Batches 3 and 4 would be
greater than the surface area of Batches 1 and 2. Additionally, the pore volumes
of the catalysts appear to be significantly different, having decreased from
around 0.064 - 0.069 cm3/g in Batches 1 and 2, to between 0.038 – 0.02103
cm3/g in Batches 3 and 4. Importantly, when taking a closer look at just Batches
3 and 4 of the catalyst, it quickly becomes clear that the present method does not
seem suitable to produce a consistent catalyst at increased scale. Notably,
despite Batches 3 and 4 having been synthesised on the same scale, the large
difference in surface area between the two is relatively striking. Hence, Batch 3
had a surface area of 120.1755 m2/g while Batch 4 had a surface area of
170.7142 m2/g. The pore volume also experiences a similar discontinuity
between observed results; with the pore volume of Batch 3 was equal to 0.03803
cm3/g, whilst, for Batch 4, the pore volume was equal to 0.02103 cm3/g.
It should be noted that, at this time, it is unclear why these physical properties
vary so widely upon increasing the scale of the reaction, resulting in an overall
increase in pore volume and surface area. There results were rather surprising
since each of the smaller scale (5 mmol) batches appeared to be very similar
both in terms of mass produced and physical properties. These results would
indicate that further investigation is required to develop a protocol that would
allow a reproducible catalyst both in terms of mass of catalyst and physical
properties. It is also unclear what the overall effect on the reactivity of the
catalyst these clear changes in physical properties would have. Unfortunately,
due to time constraints further investigation into catalyst synthesis was not
pursued.
5.2.3 ICP testing
In an effort to investigate the amount of palladium contained within the silica
support, ICP testing of the wastewater generated from each catalyst preparation
was obtained. The assumption made during testing was that any palladium that

44
was not discovered in the wastewater would instead be attached to the catalyst
support. By calculating how much palladium remained in the wastewater, it
would be possible to calculate how much palladium could be found in the silica
support. The results obtained by the ICP testing are shown below in Table 11.
Table 11
The results in Table 11 show that for Batch 1 and 2 (5 mmol) that a similar
amount of palladium was found in the wastewater, Batch 1 contained 239.52
mg/l while Batch 2 contained 237.69 mg/l. This indicates that on the smaller
scale, the loading is similar and appears to be reproducible. In Batches 3 and 4
(15 mmol) the results are also fairly similar, though there is more variance
between the final two batches than the first two, Batch 4 containing 639.03 mg/l
compared with 584.73 mg/l in Catalyst 3. It should be noted however that the
significant difference in palladium values between Batches 1-2 and 3-4 is due to
the increased scale from 5 mmol to 15 mmol. Furthermore, Table 12 shows the
results after calculating the estimated percentage loading by mole of the catalyst
having calculated the palladium remaining in the silica support.
Catalyst 1 2 3 4
Scale
(mmol
S.M.)
5 5 15 15
Conc.
palladium
(mg/l)
239.52 237.69 584.73 639.03

45
Catalyst
Batch
Concentration Pd
in sample (mg/l)
Sample
Volume (cm3)
Palladium in
silica (mmol)
Percentage
loading
(mol %)
1 239.52 50 0.45 10.844
2 237.69 50 0.44 12.073
3 548.73 50 1.56 15.507
4 639.02 50 1.56 13.188
Table 12
As mentioned previously (Section 5.1.3), preparation of the catalyst was
designed to produce a metal loading of 10 mol %. From Table 12 it can be seen
that the estimated percentage loading appears to be fairly close to the desired
value of 10 mol%, with Catalysts 1 – 4 showing a loading range of between
10.844% and 15.509 mol%. Looking more specifically at the results it can be
seen that some variance in loading is observed in each of the various batches
with loadings slightly higher in 3 and 4 (15 mmol) with 15.507% and 13.188%
respectively. Compared to Batch 1 and 2, with loadings calculated at 10.844%
and 12.073% respectively. However, the protocol does appear to be suitable to
provide the catalyst at the desired loading, although further optimisation is
required. The methodology for the calculation for the estimated molar loading of
the catalyst is shown in appendix 1 (Section 8).

46
5.2.4 BJH analysis
The final type of analysis carried out on the prepared catalyst was BJH testing.
Used in conjunction with BET testing, BJH analysis specifically looks at the pore
diameters of a catalyst for adsorption and desorption.
Catalyst Batch 1 2 3 4
BET surface area
(m2/g)
60.3187 64.8807 120.1755 170.7142
BJH adsorption (nm) 16.2253 15.6309 22.9997 17.2249
BJH desorption (nm) 20.4723 19.9013 31.4944 23.5811
Table 13
From the results presented in Table 13, it can be seen that in the smaller scale
reactions (Batches 1 and 2, 5 mmol), the pore size does appear to be relatively
similar, with a diameter for adsorption of 16.23 nm observed for Catalyst 1,
whilst a diameter of 15.63 nm was observed for Catalyst 2. This indicates that
the synthesis of the catalyst does appear robust when on the small scale (5
mmol). Importantly, for the larger scale synthesis (Catches 3 and 4, 15 mmol),
the difference in adsorption diameter was significantly different, having values of
22.9997 nm and 17.2249 nm, compared to ≈ 16 nm in Batches 1 and 2. These
results would seem to confirm that when the reaction is scaled up from 5 mmol,
to a 15 mmol scale, that significant differences in physical characteristics of the
catalyst are occurring.

47
5.2.5 Conclusions
Overall, the results suggest that the current procedure for the preparation of the
catalyst is robust at a small scale (5 mmol), but less so at a larger scale (15
mmol). Further investigation is required to obtain a protocol to synthesise the
catalyst on a larger scale.
As a final comment, this project is focused on the proof of concept of bioinspired
silica and its use as a catalyst support. To avoid any variances in reactivity due to
the differences in physical properties of the catalysts, all four batches of catalyst
prepared were combined together to form a homogenised catalyst system,
before reacting them under the conditions identified in the next section.

48
5.3 Catalyst Testing
5.3.1 Objectives
With the silica-supported catalyst now in hand, the second objective of the
project could now be started. Towards this aim, the catalyst would be introduced
as the active catalytic ingredient to mediate an organotransition metal coupling.
More specifically, palladium has become the most versatile of transition metal
catalysts mediating a range of cross coupling reactions including Suzuki, Heck
and Negishi couplings, amongst the most commonly used in industry. As
previously mentioned, research from the group had analysed the effectiveness of
the catalyst in a series of Suzuki reactions as shown.
Scheme 19
Although some moderate success had been achieved to date, the catalyst system
was still at an early stage of development and further optimisation was required
to attain results competitive with other systems currently in the recent scientific
literature, (see Section 4).[34]
In an effort to extend the substrate scope and further illustrate the versatility of
the novel catalyst system under investigation, the Heck reaction was identified
as a suitable reaction candidate. From the outset of this project, the aim had been
to test the limits of its transformational capability. Due to the time constraints
surrounding the project, the substrate of choice had to be commercially available
and easy to purify. With this in mind, methyl acrylate was identified as an
excellent candidate, since it is well known as a reagent in Heck reactions, is

49
commercially available and has a low boiling point (80oC). The final of these
qualities was off the upmost importance since, upon reaction completion, any
unreacted methyl acrylate could be easily removed at reduced pressure, leaving
only starting bromide and products. From the remaining product mixture 1H
NMR analysis should allow a ratio of product to starting materials to be
determined to give an estimation of conversions.
It was from this point, that a comprehensive literature search identified a set of
standard conditions that provided a suitable basis to test the reactivity of our
catalyst system comparative to a known system as shown in Scheme 20, Table
14. [35]
Scheme 20
Entry Catalyst
Percentage
conversion (%)
1 Pd(OAc)2 85
2 Pd2(dba)3.CHCl3 75
3 Pd(OAc)2/2PPh3 100
4 Pd(OAc)2/2PPh3 97
5 Pd(OAc)2/dppe 85
6 Pd(OAc)2/dppp 86
7 Pd(OAc)2/dppf 96
Table 14

50
Although the literature example was concerned with the effect of ligands on
conversions within homogeneous catalysis it did provide a standard reaction
protocol to compare the reactivity of our catalysts system to. It is from this point
that the chemical analysis of the catalyst was initiated.
In the following section the results are presented as % conversion, for clarity
these are not determined using a standard, but rather are a ratio of the
diagnostic peaks for starting material against the product peaks obtained in the
1H NMR spectrum.
4-bromoacetophenone
In their paper relating to the activity of various palladium catalysts in the Heck
reactions, the Qadir group identified that 4-bromoacetophenone could be readily
transformed under Heck conditions, using Pd(OAc)2 and Et3N in DMF at 140oC
(Scheme 21).[61] In this specific example the reaction was deemed an excellent
place to initiate the testing of our catalyst due to the simplicity of the system.
Before beginning the analysis of the novel catalyst system, a standard set of
reactions was performed. This allowed not only the identification of an optimal
set of conditions to provide high conversions, but also allow a familiarisation of
both the experimental procedure and the 1H NMR analysis of the resultant
product mixture. The results obtained from the experiments are shown in Table
15 below.
Scheme 21

51
Entry
Palladium
source
Additive Reaction Time (h) Conversion (%)
1 Pd(OAc)2 - 24 80
2 Pd(OAc)2 - 24 100
3 Pd(OAc)2 PPh3 24 80
4 Pd(OAc)2 PPh3 24 90
5 Pd(OAc)2 - 24 95
6 Pd(OAc)2 - 24 100
Table 15
Table 15 represents an attempt to find a standard set of reaction conditions that
would allow high levels of conversions combined with simple analysis. All
reactions were carried out in a sealed vessel, heating to 140oC, for 24 hours.
Entries 1-2 represent the simplest conditions identified from the Qadis group
paper. In this case, Et3N converts the Pd(II) to Pd(0) in situ to provide the active
catalyst. Upon reaction completion Et3N is also of sufficiently low boiling point
(89oC) to allow simple removal at reduced pressure so as not to complicate the
final 1H NMR spectra. As can be seen from the results this very simple system
proved extremely successful with conversions of 80-100% observed.
Entries 3-4 represent identical reaction conditions only with the inclusion of
PPh3 as an additive. PPh3 was added for two reasons: firstly PPh3 is widely used
to reduce Pd(II) to Pd(0) under the reaction conditions. The paper by Qadis also
identified phosphine ligands as beneficial to reaction conversions hence it was
hoped that the inclusion of PPh3 would increase the efficiency of the system. The
results show that although conversions of 80-90 % were observed, no obvious
advantage was gained from the addition of phosphine additives. Furthermore,

52
PPh3 has a high boiling point (3600C) and proved detrimental to 1H NMR analysis
by further complicating the resultant spectra.
From these results it was decided that the conditions to be used going forward
would be: DMF, 1400C, 24 h, Et3N, Pd(OAc)2 (10 mol %).
With these results in hand, Entries 5-6 represent further repeats of entries 1 and
2. These experiments were carried out to provide confidence that the identified
conditions were roust and reproducible. This was confirmed by conversions of
95-100 %.
5.3.2 Test of uncalcinated catalyst
To determine the effect of any PEHA remaining in the pores of the uncalcinated
catalyst, two reactions were carried out under standard conditions. These
reactions were designed specifically to determine if calcinations of the catalyst
system were necessary before deployment in organometallic reactions (Scheme
20, Table 16).
Scheme 22
Entry
Palladium
source
1 Pd/SiO2 - 24 95
2 Pd/SiO2 PPh3 24 <10
Table 16

53
From the results it can be seen that the uncalcinated catalyst is extremely active
under certain conditions (Table 16). More specifically, Entry 1 represents the
reaction of the uncalcinated catalyst using the identified standard conditions.
Under these reaction conditions a conversion of 95% was obtained showing that
an effective catalytic system can be achieved using an uncalcinated catalyst.
However, at present it is unclear if calcination is necessary but it will be revisited
once it can be compared to calcinated results.
Entry 2 represents the effect of PPh3 on the catalyst system. From the results
obtained from the standard reactions (Table 15) it was unclear if the PPh3
would promote the reaction, have little or no effect on the reaction, or potentially
block the pores of the catalyst and slow the reaction. As can be seen from the
results in Table 16, a conversion of <10% was observed. From the results of
Entry 2, it is clear that to adding PPh3 is completely detrimental and shuts down
the catalyst system.
5.3.3 Test of calcinated catalyst
Following investigation into the activity of the uncalcinated catalyst, two
reactions were set up to directly compare the reactivity of the calcinated catalyst
under standard conditions. The results are shown below in Table 17.
Scheme 23
Entry
Palladium
source
1 Pd/SiO2 - 24 100
2 Pd/SiO2 - 24 100

54
Table 17
It can be seen from the results that the calcinated catalyst is active under
standard conditions (Table 17). Both Entries 1 and 2 achieved extremely high
levels of conversion with 100% observed for both entries. Comparing these
results to the reactivity of the uncalcinated catalyst (Table 16), it was observed
that the level of conversion was only marginally better than the uncalcinated
catalyst (95%, Entry 1, Table 16).
The results obtained in Table 17 can also be compared to the standard reactions
using unsupported palladium acetate. With this in mind, conversions obtained in
Table 17 for both Entries 1 and 2 (100%) compared favourably to the results
obtained in Table 14 with unsupported palladium acetate (80-100%). These
results also indicate that the catalyst prepared in the laboratory is at least as
effective as unsupported palladium acetate in the conversion of 4-
bromoacetophenone.
Having successfully concluded that the calcinated catalyst prepared in the
laboratory was effective within the Heck reaction system, it was decided to
investigate whether different substrates would affect the level of conversion, and
ultimately, the effectiveness of the catalyst within the Heck reaction.
5.3.3 Substrate Scope
Having proven that the catalyst system is reactive under standard reaction
conditions, a range of alternative coupling partners were examined. To begin this
expansion of substrate scope, a variety of aryl halides were examined, beginning
with electron deficient and tending towards more difficult, electron rich
substrates. By changing the electronics of the coupling partner a relative
examination of the activity of the catalyst could be determined.

55
From this point of view electron deficient systems are known to be highly
reactive systems since the oxidative addition step of the Heck reaction occurs
readily in these substrates. As the aryl halide becomes increasing electron rich or
sterically encumbered, the oxidative insertion step should become more difficult
and hence only a highly reactive catalyst will succeed in catalysing these
reactions.
5.3.4 Electronic Effects on the Heck Reaction
Table 18 represents the relative product conversions associated with the
various aryl halides when the calcinated catalyst was reacted under standard
conditions, (Scheme 24).
Scheme 24
Entry R1 R2 Reaction time Conversion
1 -CF3 Br 24 > 95
2 -CF3 Br 24 100
3 -COCH3 Br 24 100
4 -COCH3 Br 24 100
5 -CH3 Br 24 50
6 -CH3 Br 24 40
7 -COCH3 Cl 24 < 10
8 -COCH3 Cl 24 0
Table 18

56
Entries 1 and 2 represent the results obtained whilst using
4-bromobenzotriflouride as the substrate. With the three fluorine atoms at the
same end of the benzene ring, an area of electron density will occur as a result of
the dipole caused by the highly electronegative fluorine atoms. As a result of the
dipole the oxidative addition step of the Heck reaction should become easier,
making the substrate more reactive compared to electron rich substrates. From
Table 18, the results indicate that the catalyst activity was high with product
conversions of 95% and 100% observed. Comparing these results to Entries 3
and 4 (4-bromoacetophenone), it can be seen that in a slightly more electron rich
system, the catalyst also performed well, obtaining 100% conversion for both
attempts. It was anticipated from the outset that the overall conversion of
Entries 1-4 would be relatively high, and the results between these substrates
endorse the hypothesis.
In Entries 5 and 6 the substrate used was 4-bromotoluene. Having used strongly
electron-withdrawing groups up to this point it was anticipated that this
coupling partner would represent a more difficult test for the catalyst.
Accordingly, the product conversions were reduced to 40 and 50% for Entries 5
and 6 with this coupling partner. With regards to the level of product
conversion, the catalyst was successful in transforming some of the substrate to
the desired product, under standard conditions. This result indicates that the
catalyst prepared is robust enough that it is not restricted to substrates
containing beneficial electron withdrawing groups, however it appears that
optimisation of the reaction is required to improve conversions further. With
this in mind, conversions may improve with prolonged reaction times.
The final substrate used was 4-chloroacetophenone (Entries 7 and 8), which
represented a different type of challenge for the palladium catalyst. As
previously mentioned the carbonyl group is an electron-withdrawing group,
however, the chlorine atom is not as effective a leaving group as bromine in
4-bromoacetophenone. Bromine is an excellent leaving group because it does not
form particularly strong bonds with carbon (288 kJ/mol) and has a longer bond

57
length (194 pm) than the equivalent chlorine-carbon bond (177 pm).
Accordingly, the shorter bond length associated with the chlorine-carbon bond is
indicative that the overlap of the bonding orbitals between the two atoms is
better than that of the bromine-carbon bond, and hence the overall bond energy
for the chlorine-carbon bond is higher (330 kJ/mol) than that of the bromine-
carbon bond. Taking this information into account, the oxidative addition step
would be expected to be more difficult and hence a lower reactivity was
expected to be observed.
From Table 18, it can be seen that as expected a lower level of conversion was
achieved for Entries 7 and 8 (< 10% and 0 respectively). Although expected, the
low conversion figures achieved by the palladium catalyst for 4-
chloroacetophenone were nonetheless slightly disappointing. However, A.C.
Hillier et al., discovered that while using aryl chloride substrates in the Heck
reaction, “no activity was observed”.[62] With this in mind, and understanding
that aryl chlorides are tough cross-coupling partners, we decided to move on to
allow sufficient time to investigate the effect of steric hindrance and catalyst
loading to the reaction.
5.3.5 Steric effects on the Heck reaction
Having investigated if varying the electronics on the aryl halide affects product
conversions, it was decided that the steric effects should also be analysed. Since
4-bromoacetophenone was known to be a highly effective substrate, it was
decided that 2-bromoacetophenone would be used to investigate how steric
hindrance would affect performance of the catalyst under standard conditions.
From the investigation into the electronic effects on the Heck reaction the
observed conversions would allow a direct comparison between the substrate
chosen (2-bromoacetophenone) and the previous results obtained (Scheme 25).

58
Scheme 25
Entry Substrate Reaction Time Conversion
1 2-bromoacetophenone 24 0
Table 19
From Table 19 we can see that there was no reaction was observed with 2-
bromoacetophenone. This result can be directly compared to the conversion
associated with 4-bromoacetophenone (100 %, Table 17, Entry 1) From this
result it can be determined that increased steric hindrance around the carbon-
halide bond would appear to inhibit reaction progress. Due to the complete
failure of this reaction further investigations were suspended at this time.
Having investigated the difference in percentage conversion between two
sterically different regioisomers, and under time constraints, it was decided that
it was important to move on to an investigation into the loading of the catalyst
before the supply of the prepared catalyst was exhausted.
5.3.6 Investigation intothe effects of catalyst loading
From the outset of this project, it was hoped that the catalyst could be recyclable
for multiple reactions as had been possible in the previous investigations
involving Suzuki reactions (see section 4). However, when using DMF as a
solvent it immediately became clear that recycling the catalyst was not going to
be a facile process. With this in mind, it was decided to investigate if the loading

59
of the catalyst could be decreased significantly for the purposes of reducing cost
and chemical waste of the system, but without reducing overall activity.
Furthermore, throughout the investigations, the presence of the catalytically
inactive palladium black was suspected. With this in mind, it seemed of
paramount importance for future work to attempt to reduce or prevent its
formation. A literature search indicated that high catalyst loadings can
encourage the formation of palladium black, and also that the leaching of
palladium into reaction mixtures results in its formation.[37] In an attempt to
address this problem, it was hoped that by reducing the loading of the catalyst, a
reduction in palladium black formation would occur. Towards this aim, two
separate catalyst loadings were used, 2.5 mol% and 1.25 mol% (Table 20,
Scheme 26).
Scheme 26
Entry
Catalyst Loading
(mol%)
Reaction
Time
Conversion
1 2.50% 24 100
2 1.25% 24 100
Table 20
From the results shown in Table 20, it is clear that reducing the loading of the
catalyst had little or no effect on the overall conversion to the products. Prior to
starting this experiment, it had been thought that to achieve similar conversions
at a lower catalyst loading, the reaction times may have had to be increased.
However, TLC analysis of the reaction mixture indicated that after 24 hours both

60
reactions had gone to completion. Importantly, within the reaction mixture there
was no visible palladium black. This was of paramount importance since in all
previous reactions the mixture had to be filtered through celite before
separating. The success of the reduced loading may suggest that while testing the
effects of electronics and steric hindrance of the substrates on the catalyst, the
reaction mixtures could have been slightly saturated by palladium. To confirm
this, further investigation into the effects of catalyst loading is required.
5.4 Conclusions
Overall, the novel palladium doped catalyst prepared has proven to be very
active both at higher and lower loadings. Using substrates with electron-
withdrawing substituents such as 4-bromoacetophenone and 4-
bromobenzotrifluoride resulted in the highest conversions to products. As the
substrate scope moved into increasingly electron-rich systems, such as 4-
bromotoluene, moderate levels of conversion were achieved (40-50%). It would
also appear that this catalyst system is not applicable to aryl chlorides, or
sterically congested substrates. Under the current standard conditions, it would
appear that recycling the catalyst is not a viable option without further
modifications of either the catalyst or the reaction conditions.
This project was undertaken in an effort to prove that a cheap, reliable,
palladium catalyst could be prepared under mild conditions and be effective in
the cross-coupling Heck reaction, and to this end the experimentation has been
successful.

61
6. Future work
This project aimed to prove the concept that a bioinspired silica based palladium
catalyst could be used efficiently to catalyse the Heck reaction. However,
throughout the project there were certain areas that could not be optimized
effectively. The preparation of silica, and the variances between physical
properties of the batches of catalyst prepared throughout this project in
particular should be thoroughly reinvestigated to identify a protocol that
produces a consistent form of catalyst at increased scale. From this standpoint, it
is clear that until consistent batches of catalyst can be produced gaining
consistent results in chemical transformations is always going to be difficult.
A significant difficulty in this project was the inability to recycle the catalyst after
each experiment. Perhaps future work could involve the screening of several
solvent systems that may allow easier recycling of the catalyst. Significantly, it
also appeared that the formation of palladium black may be an issue. Further
investigation should involve loading studies that includes the addition of both
less catalyst to the reaction mixture, and also having a significantly lower metal
loading within the silica support. By developing a catalyst that can be recycled,
future studies should involve ICP analysis of the products to determine the levels
of palladium leaching.

62
7. Experimental
7.1 General
All reagents used were obtained from commercial suppliers and were used with
no further purification.
Calcination of the catalyst was carried out in an open-air tube furnace at 5500C
for 8 hours with a variation of 100C per minute when warming up and cooling
down.
ICP analysis was carried out using an Agilent Technologies 7700 Series ICP-MS.
50 ml of the reaction mixture and wastewater were submitted for analysis.
BET and BJH analysis were carried out using a micromeritics ASAP 2520. For
each batch of catalyst, a 25 mg sample was submitted for analysis.
Thin layer chromatography was carried out using Camlab silica plates coated
with fluorescent indicator UV254. The plates were analysed using a Mineralight
UVGL-25 lamp and further developed using vanillin solution.
1H NMR spectra were recorded using either a Bruker DPX-500 at 500 MHz, or a
Bruker DPX-400 at 400 MHz. The chemical shifts are reported in ppm, whilst the
coupling constants are reported in Hz and refer to 3JH-H interactions unless
otherwise specified.
7.2 General Procedures
7.2.1 General Procedure A: Preparation of silica catalyst support

63
Into a centrifuge tube, sodium metasilicate was dissolved in water (Solution A).
In a separate sample tube, pentaethylenehexamine was dissolved in water
(Solution B). Solution B was mixed with solution A, and a magnetic stirrer bar
was added. The pH was recorded and the mixture was then neutralised using
HCl. By a process of co-precipitation the silica crashed out of the reaction
mixture and having reached a pH of 6.9 – 7.1 the reaction mixture was
centrifuged at 8000 rpm for 15 minutes. The silica recovered was removed from
the centrifuge and rinsed with distilled water. The reaction mixture was
centrifuged again at 8000 rpm for 15 minutes to allow all silica to be recovered.
This process was carried out a further two times. The wastewater and reaction
mixture were collected for ICP analysis. The silica prepared was dried in an oven
at 800C for 3 hours.
7.2.2 General Procedure B: Preparation of catalyst
In a beaker, sodium metasilicate was dissolved in distilled water (Solution A). In
a separate beaker, pentaethylenehexamine was dissolved in distilled water
(Solution B). At the same time, palladium acetate was dissolved in acetone in a
sample tube, before being added to Solution A. Solution B was then mixed with
Solution A, and a magnetic stirrer was added. Noting the initial pH of the reaction
mixture, HCl was then pipetted drop wise into the mixture to neutralise the pH.
By a process of co-precipitation the silica crashed out of the reaction mixture
with the palladium nanoparticles incorporated within the structure of the silica.
When the pH had reduced to between 6.9 and 7.1, the reaction mixture was
centrifuged at 8000 rpm for 15 minutes. The catalyst recovered was removed
from the centrifuge and rinsed with distilled water. The reaction mixture was
centrifuged again at 8000 rpm for 15 minutes to allow all catalyst to be
recovered. This process was carried out a further two times. The wastewater and
reaction mixture were collected for ICP analysis. The catalyst recovered was
dried in an over for 3 hours at 1400C. The mass of the dried catalyst was then
recorded.

64
7.2.3 General Procedure C: Calcination of the prepared catalyst
The prepared catalyst was spread evenly in a rectangular crucible. The crucible
was then calcinated in an open-air furnace for 8 hours at 5500C. The temperature
was increased at a rate of 100C per min, and the furnace was cooled at the same
rate. The final calcinated mass of the catalyst was recorded.
7.2.3 General Procedure D: Standard Reaction for testing
In a 10 ml microwave tube, palladium was added with triethylamine for 10
minutes and heated gently to 400C using an oil bath. Following this, the chosen
substrate was added with methyl acrylate and DMF before sealing the
microwave tube for 24 hours and increasing the temperature to 1400C. When
working up the products, the reaction mixture was filtered through celite and
washed through using DCM, before washing the DMF from the mixture by
separating with brine in a separator funnel. A rotavapor was then used to
evaporate off the methyl acrylate and DCM. The product obtained was dissolved
in chloroform before being submitted for 1H NMR analysis.
7.2.4 General Procedure E: Standard Reaction with additive PPh3
In a 10 ml microwave tube, palladium acetate was added to PPh3 and DMF. The
solution was then heated gently to 400C for 10 minutes using an oil bath.
Following this, the chosen substrate was added with methyl acrylate, Et3N and
before sealing the microwave tube for 24 hours and increasing the temperature
to 1400C. The reaction mixture was filtered through celite and washed through
using DCM, before washing the DMF from the mixture by separating with brine
in a separating funnel. A rotavapor was then used to evaporate the unreacted
methyl acrylate and DCM. The product obtained was dissolved in deuterated
chloroform before being submitted for 1H NMR analysis.

65
7.3 Synthesis of silica support
Following General Procedure A, results are reported as a) amount of sodium
metasilicate, b) volume of distilled water in Solution A, c) amount of PEHA, d)
volume of distilled water Solution B, e) volume of HCl, f) reaction time, g) mass of
product.
Table 6, Entry 1:
a) 63.6 mg, 0.5 mmol, b) 5ml, c) 11.9 mg, 0.05 mmol, d) 4ml, e) 630 μl,
f) 10 minutes, g) 19 mg.
Table 6, Entry 2:
Table 6, Entry 3:
Table 6, Entry 4:
Table 7, Entry 1:
a) 636.0 mg, 5 mmol, b) 50 ml, c) 116.0 mg, 0.5 mmol, d) 40 ml, e) 6634 μl,
f) 10 minutes, g) 289.1 mg.

66
Table 7, Entry 2:
f) 10 minutes, g) 201.6 mg.
Table 7, Entry 3:
f) 10 minutes, g) 285.3 mg
7.4 Synthesis of palladium catalyst
Following General Procedure B, results are reported as a) amount of sodium
metasilicate, b) volume of distilled water in Solution A, c) amount of PEHA, d)
volume of distilled water Solution B, e) amount of palladium acetate, f) volume of
acetone, g) volume of HCl required, h) reaction time, i) uncalcinated mass, j)
calcinated mass
Table 8, Entry 1
a) 642.0 mg, 5.26 mmol, b) 50 ml c) 117.9 mg, 0.507 mmol, d) 40 ml
e) 100.1 mg, 0.4459 mmol f) 5 ml g) 6129 μl, h) 10 min, i) 324.8 mg,
j) 298.4 mg.
Table 8, Entry 2
e) 99 mg, 0.4409 mmol f) 5 ml g) 6150 μl, h) 10 min, i) 298.4 mg,
j) 247.5 mg.

67
Table 8, Entry 3
e) 351.1 mg, 1.56 mmol f) 15 ml g) 18000 μl, h) 10 min, i) 873.8 mg,
j) 735.8 mg.
Table 8, Entry 4
a) 1909.1 mg, 15.64 mmol, b) 150 ml c) 350.22 mg, 1.507 mmol, d) 120
ml, e) 351.1 mg, 1.56 mmol f) 15 ml g) 18000 μl, h) 10 min, i) 935.6 mg,
j) 804.9 mg.
7.5 Calcination of prepared catalyst
Following General procedure D, the results were reported as a) pre-calcination
mass, b) post-calcination mass, c) change in mass, d) percentage change in mass.
Table 9, Entry 1
a) 324.8 mg, b) 275.4 mg, c) 49.4 mg, d) 15.21 %
Table 9, Entry 2
a) 298.4 mg, b) 247.5 mg, c) 50.9 mg, d) 17.06 %
Table 9, Entry 3
a) 873.8 mg, b) 736.8 mg, c) 137.0 mg, d) 15.68 %
Table 9, Entry 4
a) 935.6 mg, b) 804.9 mg, c) 130.7 mg, d) 13.97 %

68
7.6 Determination of Standard reaction conditions
7.6.1 Synthesis of methyl 3-(4-acetylphenyl)acrylate
1H NMR (500 MHz, CDCL3):
δ 7.88 (d, 2H, J = 8.3 Hz, ArH), 7.63 (d, 1H, J = 16.1 Hz) 7.50 (d, 2H, J = 8.3 Hz,
ArH), 6.40 (d, 1H, J = 16.1 Hz, CH), 3.75 (s, 3H, CH3), 2.53 (s, 3H, OCH3).
Following General Procedure D, results are reported as; a) amount of palladium
acetate, b) amount of 4-bromoacetophenone, c) volume of methyl acrylate, d)
volume of Et3N, e) volume of DMF, f) reaction time, g) reaction temperature, h)
substrate conversion.
Table 15: Entry 1
a) 0.01122 g, 0.5 mmol, b) 0.1099 g, 1 mmol, c) 0.418 ml, 3 mmol,
d) 0.272 ml, 3 mmol, e) 3 ml f) 24 hours, g) 1400C, h) 80 %.
Table 15: Entry 2
a) 0.01122 g, 0.5 mmol, b) 0.1099 g, 1 mmol, c) 0.418 ml, 3 mmol,
d) 0.272 ml, 3 mmol, e) 3 ml, f) 24 hours, g) 1400C , h) 100 %.
Following General Procedure E, the results are reported as; a) amount of
palladium acetate, b) amount of 4-bromoacetophenone, c) amount of PPh3, d)
volume of methyl acrylate, e) volume of Et3N, f) volume of DMF, g) reaction time
h) reaction temperature, i) substrate conversion.

Thesis Submission

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