Aromatic- Electrophilic substitution Flashcards
How does benzene react with strong electrophiles
- In substitution rather than addition
What takes place in an electrophilic substitution reaction
- An atom or group of atoms replaces a hydrogen atom on the benzene ring so that the product retains the stable aromatic ring
Describe the mechanism for an S(E)Ar reaction
- In situ generation of electrophile
- The aromatic ring breaks aromaticity and attacks the very reactive electrophile
- Forms an Wheland intermediate
- Stabilisation of Wheland intermediate by resonance
- The proton at the site of electrophilic attack is lost from this cation intermediate to restore aromaticity
Which is the slow, rate determining step in an SEAr
- The breaking of the aromaticity requires a lot of energy- slow
What position does the charge take in Wheland intermediate resonance
- Either ortho or para never meta
What are the 5 most common substitution reactions of benzene
- Halogenation
- Nitration
- Sulfonation
- Alkylation
- Acylation
Which halogens are accessible and why
- Chlorine
- Bromine
- NOT Fluorine- too reactive/ difficult to handle
- NOT iodine- too unreactive
What is formed when chlorine/bromine reacts with benzene
- Chlorobenzene
2. Bromobenzene
What catalyst is used in bromination/ chlorination of benzene
- FeBr3
2. AlCl3
What are the steps in bromination of benzene
- Bromine atom donates a lone pair of electrons to the Lewis acidic iron centre to give a zwitterion
- This causes the Br-Br bond to become polarised- stronger electrophile
- Benzene acts as a nucleophile and attacks the partially positive bromine atom releasing FeBr4-
- The Wheland intermediate, stabilised by resonance, then rapidly loses a proton to restore aromaticity
- By-products FeBr4- + H+ combine to restore FeBr3 catalyst and HBr
What is needed for the nitration of benzene
- Mixture of concentrated nitric acid and concentrated sulfuric acid
What is the first step in the nitration of benzene
- Generation of NO2+ electrophile
- Sulfuric acid protonates nitric acid to give OH2+ - an excellent leaving group
- Dehydration then occurs to give reactive nitronium ion
What are the uses of nitration
- Synthesis of explosives
- Nitro group can be easily reduced to an amino group to form anilines- found in many pharmaceuticals and natural products
What is used to reduce the nitro group of nitrobenzene
- Small scale Bechamp reduction- Tin in dilute hydrochloric acid
- In industry- hydrogenation using a palladium on carbon catalyst- avoids cost of large amounts of toxic tin waste
What is the product of the sulfonation of benzene
- Benzenesulfonic acid
What is needed for the sulfonation of benzene
- Concentrated sulfuric acid which protonates itself to produce protonated sulfur trioxide HSO3+
Describe the steps of sulfonation of benzene
- H3SO4- produced by H2SO4 protonating itself is dehydrated to produce protonated HSO3+
- HSO3+ is attacked by benzene to form a nonaromatic carbocation Wheland intermediate
- Two electrons move from benzene ring to form new C-S bond and at same time a pair of electrons in S=+OH bond moves to positively charged oxygen
- -OSO3H ion deprotonates the carbocation to form benzene-sulfonic acid and regenerate sulfuric acid.
Describe energy of product in sulfonation of benzene
- Similar energy of product to starting material
- So sulfonation is reversible, the side of the equilibrium the reaction favours depends on the concentration of sulfuric acid used.
What can the reversibility of sulfonation be used for
- Improving regioselectivity of SEAr reactions
What else can be used for sulfonation of benzene
- Oleum- SO3 in H2SO4
How can benzenesulfonic acids be purified
- Easily purified by recrystallisation of their corresponding sodium salts made by treating the sulfonic acid with NaCl
What can chlorosulfuric acid be used for
- Directly synthesise benzenesulfonyl chlorides
2. Valuable intermediates en route to the synthesis of sulfonamides
What is the name for alkylation of benzene using alkyl halides
- Friedel-Crafts alkylation
What is used in Friedel-Crafts alkylation
- Bromoalkane
2. Lewis acid catalyst (AlCl3, FeBr3, FeCl3)
What is the initial step of Friedel-Crafts alkylation e.g.R-Cl + AlCl3
- The chloro or bromoalkane reacts with the Lewis acid to form a strong electrophile
- e.g. Cl joins onto AlCl3 to form AlCl4- and produces a carbocation
What happens once the carbocation electrophile has been formed e.g. R-Cl + AlCl3
- Benzene attacks the C+ to produce a nonaromatic carbocation
- AlCl4- removes a proton from the carbocation to five an alkylbenzene with HCl and AlCl3
Which alkyl halides are most reactive in Friedel-Crafts alkylation
- tertiary>secondary>primary
2. In line with carbocation stability
What else can be used as alkylating agents
- Alkenes and alcohols
2. Bronsted acid has to be used instead of Lewis acid
What are two major limitations of Friedel-Crafts alkylation
- The intermediate carbocation can rearrange to a more stable isomer, if possible- primary–> secondary etc
- The product is typically more reactive than the starting material- as generally more nucleophilic- which can lead to over-alkylation- especially Br
- Lead to production of unwanted and difficult to separate by-products which lowers the efficiency of the reaction and limits its use in synthesis
What did Friedel and Crafts come up with to address the problem with their alkylation reaction
- Developed acylation reaction
2. Using acid chlorides rather than alkyl halides as electrophile
Describe Friedel-Crafts alkylation
- Aluminium trichloride is used as a Lewis acid to help remove chloride to leave behind a cation- acylium ion
- The cation is stabilised by a lone pair on the adjacent oxygen atom- resonance
- Benzene attacks the acylium ion to produce a nonaromatic carbocation
- AlCl4- removes a proton from the nonaromatic carbocation to give an acylbenzene together with HCl and AlCl3
Why does the reaction stop after acylation compared to alkylation
- The addition of the electrophile makes the aromatic ring electron deficient so the reaction stops after a single substitution
What can be formed from the acylbenzene
- Can be reduced so just R chain present
What are the 3 ways an acylbenzene can be reduced
- Wolff-Kishner Reduction
- Clemmensen reduction
- Mozingo Reduction
What is involved in a Wolff-Kishner reduction
- Basic conditions
- H2N-NH2, KOH, EtOH forms intermediate
- Heat added removes N2 to form reduced product
What is involved in the Clemmensen reduction
- Acidic conditions
2. Zn(Hg), HCl reduces straight to product
What is involved in Mozingo reduction
- First add SHCH2CH2CH2SH to form intermediate
2. Then Raney Ni, H2 to form reduced product
