Organic and biosynthesis lectures
Lecture 1
23/09/2019
Metoprolol indication used to lower the blood pressure. It is a beta blocker.
Completely new class of compounds much larger structures (antibodies). Antibody drug
conjugate: antibody linked to the drug. What does not change over time chemical properties that
are found in small compounds are also found in large compounds. The basic chemical properties stay
the same.
Chapter 1
Li, Be and B give up electrons. C shares electrons. N, O and F accept electrons.
O, N and C want to be surrounded by 8 electrons. H wants to be surrounded by 2 electrons.
With the loose electrons (lone pairs) it can make a bond by sharing electrons.
Nonpolar covalent bond: bonded atoms are the same or have similar electronegativities.
Polar covalent bond: bonded atoms have different electronegativities.
In the up right corner of the periodic table highest electronegativity.
In the left low corner lowest electronegativity.
Electrostatic potential maps: shows the electron density.
Red is high electron density. Blue is low electron density.
Example: Fluorine has low EN and hydrogen has high EN Hydrogen part will be blue and fluorine
part will be red. Most of the time, hydrogen has the highest EN and the lowest electron density.
The higher the electronegativity the lower the electron density.
Octet rule: 8 electrons around the atom stable configuration. Less than 8 not stable.
When carbon does not form 4 bonds, it has a charge/is a radical:
- Missing a full pair carbocation (positive)
- Missing a bond/having a free lone pair carbanion (negative)
- One free electron (non-paired and highly reactive) radical
Nitrogen forms 3 bonds and has one lone pair in order to have the octet rule. When it forms 2 bonds
negative charge. When it forms 4 bonds positive charge.
Oxygen forms 2 bonds and has 2 lone pairs of electrons. If it does not form 2 bonds, it has charge: 3
bonds positive charge, 1 bond negative charge.
Halogens only make 1 bond, usually to hydrogen. Halogens have 3 lone pairs.
1
,You need to be able to draw a Lewis structure. Count the number of valence electrons that are
available: for example for NO3- : 5+6+6+6+1 = 24 valence electrons. 1 is added because of the
negative charge.
Then make the bonds valence electrons that are over, are lone pairs that need to be added
according to the octet rule.
Then look if there are charges.
Then you can draw resonance structures.
An atomic orbital is the region of space around the nucleus where an electron is most apt to be
found.
If two orbitals overlap you get a new orbital.
You first fill the 1s orbital (1 electron in 1 orbital), in the 2s orbital 2 electrons can be. The electron
density of a 2s orbital is smaller, because the volume is larger than the volume of 1s.
Pi orbitals can go in the x y or z axis.
Hybridization: instead of non-equal orbitals you get equal orbitals.
An sp3 orbital has a large lobe and a small lobe, because the s orbital adds to one lobe of the pi
orbital, and subtracts from the other lobe of the pi orbital to form a hybrid sp3 orbital. Sp3 orbitals
form four bonds to one atom.
Bond angels when 4 atoms are bound: 109.5 degrees.
When 3 atoms are bound: 120 degrees.
When 2 atoms are bound: 180 degrees.
Sp2 hybridization: when carbon bonds to 3 atoms, so it needs to hybridize 3 atomic orbitals. 3 sp2
orbitals are formed and one unhybridized p orbital will remain. Overlapping of the p orbitals results
in a pi bond.
Sp2 hybridization flat compounds, 3 bonds to one atom (120 degrees) double bond between
two carbon atoms.
Sp hybridization three double bond (180 degrees) carbon bonds to 2 atoms, so needs to
hybridize 2 atomic orbitals. The 2 p orbitals both are able to form a pi bond by overlapping.
2
,Chapter 2
Bronsted/Lewis acid: accepts a share in an electron pair. low electron density.
Bronsted/Lewis base: donates a share in an electron pair. high electron density.
An acid is a proton donating acid, while a Lewis acid is a non-proton donating acid. Lewis acids have
an incomplete octet, so a lone pair from the base binds to the Lewis acid to make the octet complete.
A normal acid, donates a proton to the base.
All bases are Lewis bases.
Chapter 5
Electrophiles have:
- Positive charge
- Partial positive charge
- Incomplete octet
Lewis acids are electrophiles.
Nucleophiles have:
- Negative charge
- Lone pair
- Pi bond (double or triple bond)
Nucleophiles react with electrophiles:
In a reaction mechanism you have to draw arrows for each step. Arrows always are drawn from the
nucleophile to the electrophile first you break the bond, then it binds to the electrophile.
You draw curved arrows to show where the electrons start from and where they end up.
You always start an arrow from a bond/lone pair to an atom or bond.
A reaction coordinate diagram that gives you the energy changes most chemical reactions go
down in energy. The Gibbs free energy is negative. This means you make a product that is
thermodynamically stable. If there is high activation energy it is difficult to get over it large
activation energy: reactant is kinetically stable because it reacts slowly.
ΔG*/activation energy is small reactant is kinetically unstable because it reacts rapidly.
ΔG0/Gibbs free energy is negative product is thermodynamically stable compared to the reactant.
This because, to get back to the reactant, the energy to overcome is very high.
When ΔG0 is positive, the product is thermodynamically unstable compared to the reactant.
3
, Rate limiting step is the step with the highest energy barrier.
So the first peak is the rate limiting step, because you have to overcome a much higher activation
energy.
Catalyst: provides a pathway for a reaction with a lower energy barrier. It does not change the
energy of the starting point (reactants) or the energy of the end point (products).
A catalyst only lowers the ΔG*, not the ΔG0 only affects kinetic stability.
Chapter 6
The more R groups, the more stable the compound. R groups decrease the concentration of positive
charge on the carbon the more distribution of charge, the more stable. So that is why a tertiary
carbocation is the most stable.
A carbocation has an empty p orbital that can overlap with the adjacent sp3 orbitals, and thereby you
are stabilizing the carbocation. This process is called hyperconjugation. The more R groups the more
sigma bonds of the sp3 orbitals can engage in hyperconjugation stabilizing the carbocation.
Chapter 8 Delocalized electrons, aromaticity and electronic effects
Localized vs delocalized electrons:
Localized electrons belong to a single atom. Delocalized electrons are shared by 3 or more atoms.
You need to look at the resonance structures to see whether it are localized
or delocalized electrons.
As for in the benzene ring each double bond is partially double. At one time the double bond is
there, at the other time it is not.
4
Lecture 1
23/09/2019
Metoprolol indication used to lower the blood pressure. It is a beta blocker.
Completely new class of compounds much larger structures (antibodies). Antibody drug
conjugate: antibody linked to the drug. What does not change over time chemical properties that
are found in small compounds are also found in large compounds. The basic chemical properties stay
the same.
Chapter 1
Li, Be and B give up electrons. C shares electrons. N, O and F accept electrons.
O, N and C want to be surrounded by 8 electrons. H wants to be surrounded by 2 electrons.
With the loose electrons (lone pairs) it can make a bond by sharing electrons.
Nonpolar covalent bond: bonded atoms are the same or have similar electronegativities.
Polar covalent bond: bonded atoms have different electronegativities.
In the up right corner of the periodic table highest electronegativity.
In the left low corner lowest electronegativity.
Electrostatic potential maps: shows the electron density.
Red is high electron density. Blue is low electron density.
Example: Fluorine has low EN and hydrogen has high EN Hydrogen part will be blue and fluorine
part will be red. Most of the time, hydrogen has the highest EN and the lowest electron density.
The higher the electronegativity the lower the electron density.
Octet rule: 8 electrons around the atom stable configuration. Less than 8 not stable.
When carbon does not form 4 bonds, it has a charge/is a radical:
- Missing a full pair carbocation (positive)
- Missing a bond/having a free lone pair carbanion (negative)
- One free electron (non-paired and highly reactive) radical
Nitrogen forms 3 bonds and has one lone pair in order to have the octet rule. When it forms 2 bonds
negative charge. When it forms 4 bonds positive charge.
Oxygen forms 2 bonds and has 2 lone pairs of electrons. If it does not form 2 bonds, it has charge: 3
bonds positive charge, 1 bond negative charge.
Halogens only make 1 bond, usually to hydrogen. Halogens have 3 lone pairs.
1
,You need to be able to draw a Lewis structure. Count the number of valence electrons that are
available: for example for NO3- : 5+6+6+6+1 = 24 valence electrons. 1 is added because of the
negative charge.
Then make the bonds valence electrons that are over, are lone pairs that need to be added
according to the octet rule.
Then look if there are charges.
Then you can draw resonance structures.
An atomic orbital is the region of space around the nucleus where an electron is most apt to be
found.
If two orbitals overlap you get a new orbital.
You first fill the 1s orbital (1 electron in 1 orbital), in the 2s orbital 2 electrons can be. The electron
density of a 2s orbital is smaller, because the volume is larger than the volume of 1s.
Pi orbitals can go in the x y or z axis.
Hybridization: instead of non-equal orbitals you get equal orbitals.
An sp3 orbital has a large lobe and a small lobe, because the s orbital adds to one lobe of the pi
orbital, and subtracts from the other lobe of the pi orbital to form a hybrid sp3 orbital. Sp3 orbitals
form four bonds to one atom.
Bond angels when 4 atoms are bound: 109.5 degrees.
When 3 atoms are bound: 120 degrees.
When 2 atoms are bound: 180 degrees.
Sp2 hybridization: when carbon bonds to 3 atoms, so it needs to hybridize 3 atomic orbitals. 3 sp2
orbitals are formed and one unhybridized p orbital will remain. Overlapping of the p orbitals results
in a pi bond.
Sp2 hybridization flat compounds, 3 bonds to one atom (120 degrees) double bond between
two carbon atoms.
Sp hybridization three double bond (180 degrees) carbon bonds to 2 atoms, so needs to
hybridize 2 atomic orbitals. The 2 p orbitals both are able to form a pi bond by overlapping.
2
,Chapter 2
Bronsted/Lewis acid: accepts a share in an electron pair. low electron density.
Bronsted/Lewis base: donates a share in an electron pair. high electron density.
An acid is a proton donating acid, while a Lewis acid is a non-proton donating acid. Lewis acids have
an incomplete octet, so a lone pair from the base binds to the Lewis acid to make the octet complete.
A normal acid, donates a proton to the base.
All bases are Lewis bases.
Chapter 5
Electrophiles have:
- Positive charge
- Partial positive charge
- Incomplete octet
Lewis acids are electrophiles.
Nucleophiles have:
- Negative charge
- Lone pair
- Pi bond (double or triple bond)
Nucleophiles react with electrophiles:
In a reaction mechanism you have to draw arrows for each step. Arrows always are drawn from the
nucleophile to the electrophile first you break the bond, then it binds to the electrophile.
You draw curved arrows to show where the electrons start from and where they end up.
You always start an arrow from a bond/lone pair to an atom or bond.
A reaction coordinate diagram that gives you the energy changes most chemical reactions go
down in energy. The Gibbs free energy is negative. This means you make a product that is
thermodynamically stable. If there is high activation energy it is difficult to get over it large
activation energy: reactant is kinetically stable because it reacts slowly.
ΔG*/activation energy is small reactant is kinetically unstable because it reacts rapidly.
ΔG0/Gibbs free energy is negative product is thermodynamically stable compared to the reactant.
This because, to get back to the reactant, the energy to overcome is very high.
When ΔG0 is positive, the product is thermodynamically unstable compared to the reactant.
3
, Rate limiting step is the step with the highest energy barrier.
So the first peak is the rate limiting step, because you have to overcome a much higher activation
energy.
Catalyst: provides a pathway for a reaction with a lower energy barrier. It does not change the
energy of the starting point (reactants) or the energy of the end point (products).
A catalyst only lowers the ΔG*, not the ΔG0 only affects kinetic stability.
Chapter 6
The more R groups, the more stable the compound. R groups decrease the concentration of positive
charge on the carbon the more distribution of charge, the more stable. So that is why a tertiary
carbocation is the most stable.
A carbocation has an empty p orbital that can overlap with the adjacent sp3 orbitals, and thereby you
are stabilizing the carbocation. This process is called hyperconjugation. The more R groups the more
sigma bonds of the sp3 orbitals can engage in hyperconjugation stabilizing the carbocation.
Chapter 8 Delocalized electrons, aromaticity and electronic effects
Localized vs delocalized electrons:
Localized electrons belong to a single atom. Delocalized electrons are shared by 3 or more atoms.
You need to look at the resonance structures to see whether it are localized
or delocalized electrons.
As for in the benzene ring each double bond is partially double. At one time the double bond is
there, at the other time it is not.
4
