Biological ChemistryFIRST YEAR ORGANIC CHEMISTRY
Lecture Five
Aromatics, Heterocycles
Amines and Alkaloids
Convenor : Dr. Fawaz Aldabbagh
BenzeneC
CC
C
CC
H
H
H
H
HH
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.
C6H6
Resonance Structure- Rearrange the bonding electrons
Delocalised or Conjugated System – -bonding electrons can move within the molecule
Delocalisation, Resonance-Stabilise molecules, so make them less reactive
High Carbon content – burn with a smoky flame
In aromatic compounds the C atoms are sp2 hybrids, so that each C atom has one remaining p-electron involved in -bonding
C
CC
C
CC
H
H
H
H
HH
Kekul said that he dreamt the structure of benzene – so called Kekul structure of benzene
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 sigma bonds with two other carbons and one hydrogen atom.
Each carbon atom uses the sp2 hybrids to form -bonds with two other carbons and one hydrogen atom.
This extensive sideways overlap produces a system of -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.
= Flat (Planar) MoleculeRegular Hexagon
-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 carcinogenBenzene 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
Electrophilic Aromatic SubstitutionH
H
H
H
H
H
E
H
H
H
H
HE X+ H X
E EH
EH
EH
Electrophilic attack – Slow Rate Determining Step
E
H
sp3
Delocalised Cyclohexadienyl cation
Transition State
Loss of a proton – fast step
EH
E
Hor
fast E
- H+
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.
e.g. The Nitration of benzene
HNO3(c), H2SO4(c)NO2
NO2
H
NO2 NO2
Nitrobenzene
Mechanism
Friedel-Crafts Alkylation
RX+AlCl3 or FeCl3 R
+ HX
Lewis Acid Catalyst is used to activate the alkyl halideA 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
Friedl-Crafts Alkylation
CH3CH2Cl +AlCl3
CH2CH3
AlCl4
H
CH2CH3H
Al Cl
Cl
Cl
ClCH2CH3
+ HCl
+ AlCl3
Professor Charles Friedeland Professor James Crafts
Cl
BrBr2, FeBr3
Cl2, AlCl3
HALOGENATION
BrFeBr4Br Br FeBr3 H +
The Halogen is polarised
Naming Aromatic HydrocarbonsF CH2CH3 CH3 NH2
OH COH
OCl
Cl
Cl
Cl
Cl
Cl
CH3
NO2
NO2
CH3
CH3O2N
Br
Fluorobenzene
EthylbenzeneToluene Aniline
Phenol
Benzoic Acid1,2-Dichlorobenzene1,3-Dichlorobenzene
-meta
-ortho
-para
1,4-Dichlorobenzene 2,4,6-Trinitrotoluene (TNT)
o-Xylene m-Bromostyrene
1. Must be cyclic 2. Must be planar 3. Each atom of the ring must have a p orbital and these p orbitals must
be perpendicular to the plane of the ring 4. Must contain 4n+2 electrons (where n = 0, 1, 2, ...) –Hückel Rule
Rules for Aromaticity
Naphthalene Anthracene Phenanthrene
n = 1 , 6electrons
10 -electrons 14 -electrons
sp3-carbon NOT Aromatic 6electrons
HETEROCYCLES
N N
H
N
N
H
N
N
S N
H
PyridinePyrrole Imidazole
PyrimidineThiophene
Indole
ALL ARE AROMATIC1. Planar2. Uninterrupted Cycle of p-
orbitals3. All Atoms are sp2 hybridized4. Obey Hückel’s Rule
Most Pharmaceutical compounds are Heterocycles and derivatives
Aromatics with one non-carbon or Heteroatom
N atom in Pyridine, one of the N atoms in Imidazole and both N atoms in Pyrimidine possess a basic lone pair of electrons
Amines are organic bases
H N H
H
R N H
H
R N H
R
R N R
R
Ammonia Primary (1o) Amine
Secondary (2o) Amine Tertiary (3o) Amine
NH2
H Cl
N
H
H
H Cl
Base + Acid = Ammonium Salt
NH Cl
N H Cl
Pyridinium Salt
Aromatic Amine
Aliphatic AminesH2N
NH2
Putrescine(found in decaying meat) NH2
Amphetamine(dangerous stimulant)
N
H Piperidine
N
Triethylamine NH2
Isopropylamine
Alkaloids
Extractions from bark, leaves, berries and fruits yields nitrogen containing bases called alkaloidsName 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.
N
N
CH3H
NicotineN
C
O
OH
Nicotinic Acid
small doses its a stimulantlarger doses its a poisonNicotine salts are insecticides
incoperated into NAD+
nicotinamide adenine dinucleotide
N
HH
CH2CH2CH3
Coniine (conium maculatum)poison from hemlock
N
H3C
HOC
O
CPh
H
HOH2C
AtropineIntense Poison0.5-1% solutions are used to dilute the pupilsderivatives used against the common-cold
N
H3C
OH
Cocainesmall doses - stimulantcauses physical addiction and depressionwas used medically as an anesthetic
C
O
Ph
H
OOCH3
Erythroxylum coca1% is cocaine
Professor Marshall Gates – In 1952First Synthesis + Conformation of the structure of morphine
Papaver somniferum (opium poppy)
N
Isoquinoline
N
H3CO
H3CO
H3CO
H3CO
Papaverine
O
HO
RO
NH
H
CH3
Morphine, R = HCodeine, R = CH3
Morphine is a potent analgesicUsed in medicine to relieve “deep” painAddiction + depression + respiratory falure
Alkaloids containing Indole or Reduced Indole Ring
N
O
O
N
H
H
H
H
HN
CH2 N
CH3
CH3
H
GramineStrychnine
Strychnos nuxvomica
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