Aromatic Chemistry Amines Dr Fawaz Aldabbagh NUI Galway

Aromatic Chemistry & Amines Dr. Fawaz Aldabbagh NUI, Galway Fawaz. Aldabbagh@nuigalway. ie Recommended Text: Organic Chemistry by Paula Y. Bruice 4 th or 5 th Edition

Benzene First isolated by Michael Faraday in 1825 General Formula: C 6 H 6 Aromatic originally referred to the smell, as opposed to aliphatic Test for Aromatic: High Carbon content – burn with a smoky flame

Structure of Benzene 1. Each Carbon atom is sp 2 -hybridised : Making three σ-bonds with two adjacent carbons and one hydrogen atom: bond angles = 120º This is the σ-Framework 2. The p-orbital on each carbon atom overlaps above and below the σ-framework with the p-orbital on the adjacent carbon atom

1856: Friedrich Kekulé Resonance Structures Resonance arrow indicates structures are electronically equivalent The problem is that C-C single and double bonds would be different lengths and molecule would be a distorted hexagon 1930 s: X-ray crystal structures showed benzene is planar and six carbon bonds have the same length (C-C 1. 39 A), which is shorter than C-C single bond at 1. 54 A. But longer than a C=C. Thus, benzene does not have alternating bonds!

• Kekulé resonance structures • Neither canonical form is correct structure • Resonant Hybrid is correct structure

Another Problem with the Kekulé Model: Extra Stability than 1, 3, 5 -Cyclohexatriene Structure Would Suggest! Experimental ∆Hº = 50 kcalmol-1 Benzene is more stable than expected, and cannot be cyclohexatriene. The six π-electrons must be delocalised and not localised 37 kcalmol-1 of resonance stabilization

Delocalisation of the six π-electrons A resonance hybrid is more stable than the predicted stability of its resonance contributor, and the more resonance contributors there are, the greater the stability p-orbitals must be aligned!

When Is A Molecule Aromatic? • For a molecule to be aromatic it must: ØBe cyclic ØHave a p-orbital on every atom in ring ØBe planar ØPosses 4 n+2 p electrons (n = number of rings) Erich Hückel

Huckel’s Rule Planar Monocyclic Ring; (4 n + 2) = 2, 6, 10, 14 π electrons are aromatic

Aromatic Hydrocarbons Aromatic Molecules? • Are the following structures aromatic? ØCyclic? P-Orbital? Planar? 4 n+2 p electrons?

Which is Aromatic? Draw Resonance Structures if so! Homework: Try Problem 4 : page 645 of Bruice (5 th Ed) or Problem 2 : page 597 of Bruice (5 th Ed)

Aromatic Hydrocarbons: Nomenclature • Substituent plus benzene ØHowever, there are exceptions

Nomenclature • Two identical substituents: di- (3: tri- etc. ) • Numbering of C atoms in ring Kekule structures are the most important for writing mechanisms

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

Fast Step is the loss of a proton ---rapid re-aromatization E. g. Nitration of benzene + H+ Sir Christopher Ingold's ideas (1930 s), terminology and nomenclature for reaction mechanisms (e. g. electrophilic, nucleophilic, inductive, mesomeric, SN 1, SN 2 etc) were generally accepted and employed everywhere.

Derive the Lewis Structure of NO 2+, which is the electrophile (E+) for nitration Generating NO 2+ Sulfuric acid is a stronger acid than nitric acid

The Nitration of Benzene

Label the parts of the Electrophilic Aromatic Substitution Profile Formation of the intermediate is the RDS

Some Reactions of Benzene You should be able to write mechanisms for all the transformations below. All reactions will be described in your lectures Sulfonation is the only reversible electrophilic aromatic substitution

Friedel-Crafts Charles Friedel James Mason Crafts Homework: Give a mechanism and rationalise the substitution pattern

Mechanism for Acylation Mechanism for Alkylation Water is required here

Carbonyl Group can complex with Lewis acid (e. g. Al. Cl 3), thus more than one equivalent of Al. Cl 3 is required for the reaction & water is added at the end of the reaction to liberate the product from the complex

Reactions of Substituted Benzenes toluene R (alkyl) groups are weakly activating at ortho- & para. Toluene reacts 25 times faster than benzene in nitration aniline phenol Note – no catalyst -NH 2, -OH, -OMe, Me. CONH- are all powerful activating groups Ortho- and para- directing + R, - I

Alkyl groups (e. g. CH 3) inductively donate electrons (+I) (through σ-bonds) + I + R +R activate through π-bonds Activates o & p towards E+ attack + R, - I The strongest activator wins out NHCOCH 3 directs para, but makes benzene less reactive compared to aniline

Strong –R Deactivators: NO 2, CHO, COOH, CO 2 R, CN Deactivates o & p towards E+ attack; Thus, strong meta-directors Undergoes nitration 10, 000 times slower than benzene - R, -I

Two Reasons For Substituent Directing Effects 1. Activation by electron with-drawl or donation by Substituent 2. Stability of the Wheland Intermediate Carbocation Favoured Not Favoured

directors reinforce each other Halogens are weak deactivators – directing ortho- and para- I, +R The halo groups are the only o- and p-directors that are deactivating groups o-bromochlorobenzene p-bromochlorobenzene

Tutorial Questions 1. Write a mechanism for the generation of the nitronium ion (NO 2+) from concentrated nitric and sulfuric acid. 2. Write a mechanism for the nitration of benzene. 3. Draw dinitrobenzenes A-C. 4. Predict the ratio of isomeric products A-C from the nitration of nitrobenzene, and comment on the rate of nitration of benzene compared to nitrobenzene. Rationalize your answers with resonance structures. 5. Draw the structure of an aromatic that undergoes electrophilic aromatic substitution faster than benzene. Briefly give reasons for your answer.

Tutorial Questions 1. What are the four rules of aromaticity? 2. Draw one aromatic molecule, which does not contain a benzene ring. 3. Draw the following molecules; 4. 4. ortho-dibromobenzene, para-nitroaniline, phenol, meta-nitroanisole and 2, 4, 6 -trinitrotoluene (T Predict the major product for the following reaction, and name the product. 5. Provide a brief synthesis for TNT starting from toluene 6. Provide a mechanism for the following reaction;

Synthesis of Substituted Benzenes Using Arenediazonium Salts Benzenediazonium chloride 0 ºC Nitrous acid made on ice

Arenediazonium Ion as an Electrophile Aryl diazonium salts undergo coupling reactions with activated aromatic rings, such as phenols and anilines to yield brightly coloured azo compounds (Ar-N=N-Ar) Diazonium coupling is a typical electrophilic aromatic substitution, where the phenol or aniline is the electron-rich aromatic and the diazonium salt is the electrophile. Electrophilic aromatic substitution occurs at the para-position to the electron-rich aromatic William Perkin

Examples of Azo-Dyes Yellow of margarine Orange solid The mechanism formation of an azo-dye will be described in your lectures

Tutorial Questions 1. Draw the chemical structure of A, and give a full reaction mechanism for the formation of yellow azo-compound B (Scheme 1). Scheme 1 Scheme 2 2. Draw structures A, C and E, and give reagents & brief conditions X and Y. 3. Give a mechanism for the formation of C (Scheme 2).

Amines are derivatives of Ammonia & amines are bases by virtue of their lone pair of electrons R = alkyl groups Ammonia NH 3 Methylamine NH 2 Me 1º amine Dimethylamine NHMe 2 2º amine Triethylamine NMe 3 3º amine

Amines are bases because of the lone pair on the nitrogen atom - red litmus paper to blue

Aniline is a weaker base than aliphatic amines due to the resonance delocalisation of the lone pair of electrons in the free amine This delocalisation of the lone pair of electrons makes it less available to H + The delocalisation is lost upon formation of the salt

Reactions of Amines with Nitrous Acid - Revisited 1º aliphatic amines form very unstable diazonium salts 1º aromatic amines form stable diazonium salts at 0 ºC of great synthetic utility Secondary Amines with nitrous acid N-Nitrosoamines N-Nitrosodimethylamine (yellow oil) N-Nitoso-N-methylaniline (yellow oil) Tertiary Amines with nitrous acid Nitrous acid reacts to give salts with 3º aliphatic amines (not useful), with 3º aromatic amines NO+ becomes an electrophile in electrophilic aromatic substitution p-Nitoso-N, N-dimethylaniline (exclusive product)

Tutorial Questions 1. Draw the structure of a primary, a secondary and a tertiary aliphatic amine, and name all three amines. 2. Give a mechanism for the reaction of triethylamine with HCl. 3. Explain the origin of amine basicity and how does the basicity of aniline compare with that of a primary aliphatic amine. Draw resonance structures to explain your answer. 4. Describe the reactions of nitrous acid (HNO 2) with primary, secondary and tertiary aromatic amines.