Download Conventional Catalytic cycle for hydrogenation with Wilkinson`s

Conventional Catalytic cycle for hydrogenation with Wilkinson’s catalyst
P
P
P
Cl
reductive
elimination
P
Rh
Cl
P
Rh
14e
P
The first step of this
catalytic cycle is the
cleavage of a PPh3 to
generate the active
form of the catalyst
followed by oxidative
addition of dihydrogen.
H2 oxidative
addition
P
RCH2CH3
R
CH2
H2C
H
H
Rh
P
H
P
P
P
Cl
Cl
1, 2 -migratory
insertion
Rh
alkene
coordination
P
H
P
Rh
H
Cl
R
P = PPh3
R
AJELIAS L7-S18
catalytic cycle for hydrogenation
P
Rh
P
P
H2 oxidative
addition
H
H
P
Rh
Cl
P
Cl
P
P
P
P
H
Cl
Rh
P
H2 oxidative
addition
H
Rh
(due to trans
effect of H )
P
P
P
Cl
RCH2CH3
reductive
elimination
R
CH2
H2C
alkene
H
Rh
P
P
Cl
H
P
H
Kinetic studies have
shown that the
dissociation of PPh3
from the distorted
square planar complex
RhCl(PPh3)3 in
benzene occurs only
to a very small extent
(k = 2.3 × 10–7 M at
25°C), and
under an atmosphere
of H2, a solution of
RhCl(PPh3)3 becomes
yellow as a result of
the oxidative addition
of H2 to give cisH2RhCl(PPh3)3.
Rh
1, 2 -migratory
insertion
P
Cl
R
The trans effect is the labilization (making unstable) of ligands that are trans to certain other ligands,
which can thus be regarded as trans-directing ligands. The intensity of the trans effect (as measured
by the increase in rate of substitution of the trans ligand) follows this sequence:
H2O, OH− < NH3 < py < Cl− < Br− < I−, < PR3, CH3− < H−, NO, CO
AJELIAS L7-S19
Relative reactivity of alkenes for homogenous catalytic hydrogenation
• Cis alkenes undergo hydrogenation more readily than trans alkenes
•Internal and branched alkenes undergo hydrogenation more slowly than
terminal ones, and
R
>
>
R
>
R
R
>
R
R
R
R
R
R
R
>
R
R
R
>
AJELIAS L7-S20
Fine tuning of a catalyst:
hydrogenation catalysts which are more efficient than Wilkinsons catalyst
+
+
Ph3P
Ph3P
Rh
PPh3
Rh
PPh3
Cl
Wilkinson's catalyst
PPh3
Ir
PF6
N
PF6
Crabtree's catalyst
Schrock-Osborn's catalyst
Catalyst
25°C, 1 atm H2
PCy3
Turnover frequency (TOF) in h–1 for hydrogenation of
alkenes
Wilkinson’s catalyst
650
700
13
NA
Schrock–Osborn
catalyst
4000
10
NA
NA
Crabtree’s catalyst
6400
4500
3800
4000
The cationic metal center is relatively more electrophilic than neutral metal center
and thus favours alkene coordination.
AJELIAS L7-S21
Hydrogenation with Crabtree’s catalyst
Ir
PCy3
H
PF6
H2
N
Ir
oxidative
addition
16e
π
PCy3
PF6
H
N
18e
migratory
insertion
repeat of
cycle with
cyclooctene
S
Ir
PCy3
Ir
S
PCy3
N
16e
PF6
reductive
elimination
solvent
coordination
Ir
PCy3
PF6
H
σ
N
16e
PF6
N
S
16e
di-solvated
active form
of catalyst
The di-solvated form of the active catalyst generated by the removal of COD [after it gets
hydrogenated and leaves] favors coordination of sterically bulky alkenes as well.
This mechanism is only for understanding not for the exam
AJELIAS L7-S22
Factors which have been found to improve the efficiency (better TOF)
of transition metal catalysts for hydrogenation
• Making a cationic metal center : makes catalyst electrophillic for alkene
coordination
• Use of ligands (eg. Cyclooctadiene) which will leave at the initial stages
of the cycle generating a di-solvated active catalyst : facilitates binding of
even sterically hindered alkenes
• Use of chelating biphosphines: Cis enforcing: reduces steric hindrance at
the metal centre
+
S
Ir
PCy3
N
16e
PF6
Ir
PCy3
PF6
Rh
P
P
N
S
16e
di-solvated
active form
of catalyst
Cis enforcing
PF6
Problem solving- fill in the blanks
Oxidative addition
1,1 Migr. Insertion
1,2 Migr. Insertion
Bio Inorganic chemistry
Study of Inorganic elements in the living systems
11
20
Na
Ca
22.98
40.08
19
12
K
39.09
Mg
24.31
Sodium potassium pump
(1/5th of all the ATP used)
29
27
26
Fe
55.85
Hemoglobin
Myoglobin
Cytochromes
Ferredoxin
Co
58.94
Vit B12
30
Cu
63.55
Hemocyanin
Zn
65.38
Carbonic anhydrase
Carboxypeptidase
Important roles metals play in biochemistry
1. Regulatory Action
Na, K
2. Structural Role
Ca, Mg
3. Electron transfer agents
Fe2+/Fe3+
4. Metalloenzymes
Zn
Sodium potassium channels and pump
Nerve signals and impulses, action potential
muscle contraction
Calcium in bones, teeth
provide strength and rigidity
Cytochromes: redox intermediates
membrane-bound proteins that
contain heme groups and carry out electron
transport in Oxidative phosphorylation
Carbonic anhydrase,
Carboxypeptidase
biocatalysts, CO2 to HCO3−, protein digestion
5. Oxygen carriers and storage
Fe, Cu
Hemoglobin, Myoglobin, Hemocyanin
6. Metallo coenzymes
Co
Vitamin B 12
biomethylation
18 times more energy from glucose in
presence of O2
Structure of a metallo-protein : A metal complex perspective
Spiral - α helix form of protein
Tape - β Pleated sheet form of protein
Prosthetic groups – A metal complex positioned in a crevice. Some of the ligands
for this complex or some times all of the ligands are provided by the side groups
of the amino acid units.
The geometry around the metal and bond distances and angles are decided by the
protein unit
Myoglobin
Carbonic anhydrase
Metalloenzymes and Oxygen carriers =
Protein + Cofactor
A cofactor is a non-protein chemical compound that is bound to a protein and is
required for the protein's biological activity. These proteins are commonly enzymes.
Cofactors are either organic or inorganic. They can also be classified depending on how
tightly they bind to an enzyme, with loosely-bound or protein-free cofactors termed
coenzymes and tightly-bound cofactors termed prosthetic groups.
Porphyrins with
different metals at its
centre are a common
prosthetic group in
bioinorganic chemistry
Coenzyme B12
Cytochrome C
Hemocyanin
Myoglobin
Chlorophyll
Protoporphyrin IX and Heme
15 different ways to arrange the substituents around the porphyrin. Only
one isomer protopophyrin IX is found in the living system. Porphyrins
are planar and aromatic
Proteins –consists of different amino acids in a specific sequence connected by
the peptide bond –
A few important amino acids relevant to the present course
HISTDINE This amino
acid has a pKa of 6.5.
This means that, at
physiologically relevant
pH values, relatively
small shifts in pH will
change its average
charge. Below a pH of 6,
the imidazole ring is
mostly protonated.
VALINE is a branchedchain amino acid having
a hydrophobic isopropyl
R group. In sickle-cell
disease, valine
substitutes for the
hydrophilic amino acid
glutamic acid in
hemoglobin.Valine is
hydrophobic
GLUTAMIC ACID has carboxylic acid
functional group which is hydrophilic,
has pKa of 4.1 and exists in its
negatively charged deprotonated
carboxylate form at physiological pH
ranging from 7.35 to 7.45.
SERINE Serine is an amino acid
having a CH2OH side group. By
virtue of the hydroxyl group, serine
is classified as a polar amino acid.
Serine was first obtained from silk
protein, a particularly rich source, in
1865.
The primary structure of a protein
The four levels of protein structure
H bond between side chains,
hydrophobic interactions,
disulfur linkages,
electrostatic interactions
See youtube video “protein structure” Univ of Surrey ’
Hemoglobin- a quaternary structure of a protein
4 units
Each unit has a
prosthetic group
(heme) embedded
in a crevice and
partly coordinated
by histidine units
Inorganic Active site / Prosthetic group
In molecular biology the
active site (prosthetic
group) is part of an
enzyme where substrates
bind and undergo a
chemical reaction. It can
perform its function only
when it is associated
with the protein unit
Ferredoxin (e transfer)
Heme in Myoglobin (O2
storage)
Carbonic anhydrase
Enzyme)
Nitrogen Fixation
Inorganic Prosthetic group of three well known oxygen carriers
Present in
Vertebrates
Present in
molluscs
Present in some
sea worms
Can the prosthetic unit part of a metalloprotein perform its normal
function without the protein unit around it ?
Fe2+
Fe2+
+ O2
O
O
Free Heme
Fe2+
O +
Fe2+
4+
2 Fe
O
O
Fe4+
O +
Fe2+
Fe3+
O
Fe3+
Reversible binding of O2 is possible on when
protein unit is present around the heme unit
Oxygen : A few Questions
Why do we need oxygen or why do we breathe?
What happens to oxygen in our body and where does
it happen?
How exactly does oxygen change to water ?
What does this reaction produce and how?
How exactly is oxygen carried around and stored in
the body?
How exactly is CO2 removed from the body?
Electron transfer agents
Fe2+/Fe3+
Cytochromes: redox intermediates
membrane-bound proteins that
contain heme groups and carry out
electron transport in Oxidative
phosphorylation
Cytochromes are, in general, membrane-bound (i.e. inner
mitochondrial membrane) heme proteins containing heme groups
and are primarily responsible for the generation of ATP via electron
transport.
They are found bound on the inner mitochondrial membrane either
as monomeric proteins (e.g., cytochrome c) or as subunits of
bigger enzymatic complexes that catalyze redox reactions. These
heme proteins are classified on the basis of the position of their
lowest energy absorption band in the reduced state, as
cytochromes a (605 nm), b (~565 nm), and c (550 nm).
Electron transfer agents; e.g. Cytochrome C
S(Cys) Protein
protein
H
N
S(Cys) Protein
N
N
N
Fe
N
S
CH3
methionine
residue of
protein
N
OH
HO
O
O
Mitochondria: The powerhouse of the Animal Cell
Bio-units of the electron transport chain are present on the inner walls of
the mitochondrion.
Analogous powerhouses on the plant cells are chloroplasts
Glycolysis + Oxidative phosphorylation: How food is converted
into energy
Glucose + 36 ADP + 36 Pi + 36 H+ + 6 O2
6 CO2 + 36 ATP + 42 H2O
Glucose gives 18 times more energy when oxidized
ADP + Pi + H+ + energy
ATP + H2O
Δ G0 = - 7.3 kCal/mole
ATP : Universal currency for energy
Different forms of Cytochromes (except
Cytochrome P-450) are involved in the
electron transfer process leading to ATP
synthesis and conversion of O2 to H2O
in living systems
See youtube video ‘cellular respiration ( electron transfer chain)’
See youtube video ‘gotta get that ATP’ for fun and
learning!
Actual structure of ATP synthase
unit (a molecular machine!)
Cytochromes a and a3
Cytochromes b and c1
Cytochrome c oxidase with electrons
delivered to complex by soluble cytochrome c (hence the
name)
Cytochrome c reductase