Electrophilic Aromatic Substitution Reactions

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Electrophilic Aromatic Substitution Reactions

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hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 1 of 16 Electrophilic Aromatic Substitution eactions Benzene (discovered 1825 by a (Physical!) chemist, Michael Faraday) is special! ückel ule: any aromatic molecule is planar with 4N + 2 π electrons

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 2 of 16 Graph theory can be used to rationalize aromaticity of monocyclic hydrocarbons π orbital energies charge / # π electrons consequence The 4N + 2 rule also applies to polycylic aromatic systems also (but no easy graph theory)

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 3 of 16 Aromaticity assessed using empirical resonance energy Benzene is more thermodynamically stable than predicted from the degree of unsaturation Benzene undergoes electrophilic subsitution rather than electrophilic addition vs.

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 4 of 16 esonance energy is thought to drive the choice of substitution over addition The general mechanism of all electrophilic subsitution reactons is given by: The σ-complex is a very important intermediate; stabilized by delocalization of the positive charge.

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 5 of 16 Nomenclature of Aromatic compounds: some examples Some benzene derivatives are simply name by the substituent followed by benzene Many older benzene derivatives have well-entrenched historical names that are now officially accepted as valid root name for further substitution Polycyclic aromatic compounds also have many trivial names that have stuck

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 6 of 16

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 7 of 16 Specific Examples of Electrophilic Aromatic Substitution: Generation of Electrophiles Key to most EAS reactions is the generation of the electrophiles under specific conditions

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 8 of 16 Alkylation: the Friedel-rafts eaction Lewis Acid activation is the original F- condition Mechanism: the normal EAS process Brønsted Acid Activation is also possible, and usually grouped with F

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 9 of 16 aution: carbocation rearrangement may occur during the Friedel-rafts Alkylation! earrangement is always a concern when carbocations are involved and alkyl or hydride shift is possible. Acylation: another EAS reaction enabled by Friedel-rafts conditions. Mechanism

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 10 of 16 Friedel-rafts acylation can be used to circumvent the problem of carbocation rearrangement What is an acid chloride? A primer on the carboxylic acid family The following are all members of the family related to the carboxylic acids You need to know all of them to excel in organic chemistry The parent carboxylic acid The ester The amides N N N " ' ' 1 amide 2 amide 3 amide The acid halides The anhydrides l Br acid chloride acid bromide

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 11 of 16 Electrophilic Aromatic Substitution on Substituted Benzenes In practice, some unusual results are encountered. onsider the following:

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 12 of 16 We consider two cases to explain these observations: #1 direction via activation #2 direction via deactivation

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 13 of 16 Substituents with adjacent lone pairs are a special case Groups that count as o,p directors and are activating are: Groups that count as o,p-directors, but are deactivating are: Meta directing groups include the following:

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 14 of 16 A Summary of Directing Effects for Electrophilic Aromatic Subsitution

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 15 of 16 Some additional considerations

hemistry 2600 Lecture Notes hapter 12 Electrophilic Aromatic Subsitution Page 16 of 16 Important non-eas eactions that are Utilized in onjunction with EAS reactions Include the protection/deprotection sequence for anilines Include the reversibility of sulfonation (also a protecting/deptrotecting sequence) Alkyl groups on aromatic rings are more susceptible to oxidation to carboxylic acids Anilene is synthesized via reduction of nitro groups (no other method!) Anilene can itself easily be replaced by other groups Propose syntheses for: