Biological Chemistry FIRST YEAR ORGANIC CHEMISTRY Lecture Five Aromatics, Heterocycles Amines and Alkaloids Convenor : Dr. Fawaz Aldabbagh

Benzene 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. C6H6C6H6 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 sp 2 hybrids, so that each C atom has one remaining p-electron involved in  -bonding Kekul  said that he dreamt the structure of benzene – so called Kekul  structure of benzene Three sp 2 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 sp 2 hybrids to form sigma bonds with two other carbons and one hydrogen atom. Each carbon atom uses the sp 2 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) Molecule Regular 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 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

Electrophilic Aromatic Substitution Electrophilic attack – Slow Rate Determining Step Delocalised Cyclohexadienyl cation Transition State

Loss of a proton – fast step Sir Christopher Ingold's ideas (1930s), terminology and nomenclature for reaction mechanisms (e.g. electrophilic, nucleophilic, inductive, mesomeric, S N 1, S N 2 etc) were generally accepted and employed everywhere. e.g. The Nitration of benzene

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

Friedl-Crafts Alkylation

Professor Charles Friedel and Professor James Crafts HALOGENATION The Halogen is polarised

Naming Aromatic Hydrocarbons FluorobenzeneEthylbenzene TolueneAniline Phenol Benzoic Acid1,2-Dichlorobenzene1,3-Dichlorobenzene -meta -ortho -para 1,4-Dichlorobenzene2,4,6-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 10  -electrons14  -electrons

HETEROCYCLES Pyridine PyrroleImidazole Pyrimidine Thiophene Indole ALL ARE AROMATIC 1.Planar 2.Uninterrupted Cycle of p-orbitals 3.All Atoms are sp 2 hybridized 4.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 Aromatic Amine Aliphatic Amines

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.

Erythroxylum coca 1% is cocaine

Professor Marshall Gates – In 1952 First Synthesis + Conformation of the structure of morphine Papaver somniferum (opium poppy) Morphine is a potent analgesic Used in medicine to relieve “deep” pain Addiction + depression + respiratory falure

Alkaloids containing Indole or Reduced Indole Ring Gramine Strychnine 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