Biological Chemistry FIRST YEAR ORGANIC CHEMISTRY

1
Biological ChemistryFIRST YEAR ORGANIC CHEMISTRY
Lecture Five Aromatics, Heterocycles Amines and
Alkaloids
Convenor Dr. Fawaz Aldabbagh
2
An Aromatic Hydrocarbon is a cyclic compound that
does not readily undergo addition reactions
Reactivity is different to other unsaturated
compounds-Substitution rather than Addition is
favoured.
Benzene
C6H6
High Carbon content burn with a smoky flame
Delocalisation, Resonance -Stabilise molecules,
so make them less reactive
Resonance Structure - Rearrange the bonding
electrons
Delocalised or Conjugated System p-bonding
electrons can move within the molecule
3
Kekul? said that he dreamt the structure of
benzene so called Kekul? structure of benzene
Each carbon atom uses the sp2 hybrids to form
sigma bonds with two other carbons and one
hydrogen atom.
In aromatic compounds the C atoms are sp2
hybrids, so that each C atom has one remaining
p-electron involved in p-bonding
Three sp2 hybrid orbitals arrange themselves as
far apart as possible - which is at 120 to each
other in a plane. The remaining p orbital is at
right angles to them.
Each carbon atom uses the sp2 hybrids to form
s-bonds with two other carbons and one hydrogen
atom.
This extensive sideways overlap produces a system
of p-bonds which are spread out over the whole
carbon ring. Because the electrons are no longer
held between just two carbon atoms, but are
spread over the whole ring, the electrons are
said to be delocalised.
4
Flat (Planar) Molecule Regular Hexagon
p-Electron Density Rings above and below the
plane of the ring Susceptible to electrophilic
attack
Benzene is a colourless odourless liquid that is
a suspected carcinogen
Benzene and its derivatives are said to be
aromatic - a term coined because of the strong
fragrance of some of the derivatives of benzene
Non-aromatic compounds are said to be aliphatic
Michael Faraday first isolated benzene in 1825
5
Electrophilic Aromatic Substitution
Electrophilic attack Slow Rate Determining Step
Transition State
Delocalised Cyclohexadienyl cation
6
Loss of a proton fast step
e.g. The Nitration of benzene
Sir Christopher Ingold's ideas (1930s),
terminology and nomenclature for reaction
mechanisms (e.g. electrophilic, nucleophilic,
inductive, mesomeric, SN1, SN2 etc) were
generally accepted and employed everywhere.
7
Mechanism
Friedel-Crafts Alkylation
Lewis Acid Catalyst is used to activate the alkyl
halide
A catalyst is usually a molecule which speeds up
a reaction, and is required in only a small
amount. It is regenerated at the end of the
reaction
8
Friedl-Crafts Alkylation
9
HALOGENATION
Professor Charles Friedel and Professor James
Crafts
The Halogen is polarised
10
Naming Aromatic Hydrocarbons
Fluorobenzene
Ethylbenzene
Toluene
Aniline
-ortho
-meta
Phenol
Benzoic Acid
1,2-Dichlorobenzene
1,3-Dichlorobenzene
-para
o-Xylene
m-Bromostyrene
1,4-Dichlorobenzene
2,4,6-Trinitrotoluene (TNT)
11
Rules for Aromaticity

• Must be cyclic
• Must be planar
• Each atom of the ring must have a p orbital and
  these p orbitals must be perpendicular to the
  plane of the ring
• Must contain 4n2 p-electrons (where n 0, 1, 2,
  ...) Hückel Rule

10 p-electrons
14 p-electrons
12
HETEROCYCLES
Aromatics with one non-carbon or Heteroatom
Pyridine
Pyrrole
Imidazole
N atom in Pyridine, one of the N atoms in
Imidazole and both N atoms in Pyrimidine possess
a basic lone pair of electrons
Thiophene
Pyrimidine
Indole
Most Pharmaceutical compounds are Heterocycles
and derivatives

• ALL ARE AROMATIC
• Planar
• Uninterrupted Cycle of p-orbitals
• All Atoms are sp2 hybridized
• Obey Hückels Rule

13
Amines are organic bases
Aromatic Amine
Aliphatic Amines
14
Alkaloids
Extractions from bark, leaves, berries and fruits
yields nitrogen containing bases called
alkaloids Name comes from alkali or base-like
most react with acids to give soluble
salts. Common ending ine, reflecting the fact
they are all amines. The names are all
non-systematic. Most produce striking
physiological effects that vary from alkaloid to
alkaloid.
15
Erythroxylum coca 1 is cocaine
16
Papaver somniferum (opium poppy)
Morphine is a potent analgesic Used in medicine
to relieve deep pain Addiction depression
respiratory falure
Professor Marshall Gates In 1952 First
Synthesis Conformation of the structure of
morphine
17
Alkaloids containing Indole or Reduced Indole Ring
Gramine
Strychnine
Death results from paralysis of the respiratory
muscles
Small doses stimulate the respiratory centre,
larger doses paralyse it. Juice of the fresh bark
is used in cholera and dysentery. The dried bark
is given either as a decoction or as a paste. A
poultice made of leaves is used for chronic
ulcers. The seeds boiled in milk, are pounded
into a paste and given to opium addicts this is
believed to be effective in curing addiction
Strychnos nuxvomica