Orgo Ch 18

Flashcard maker : Ember Wagner
What happens in a electrophilic substitution Reaction
a hydrogen atom is replaced by an electrophile.
Characteristic Reactions of Benzene
electrophilic aromatic substitution

Benzene has six ? electrons delocalized in six p orbitals that overlap above and below the plane of the ring.
These loosely held ? electrons make the benzene ring electron rich, and so it reacts with electrophiles.

Why doesn’t Benzene undergo Addition reactions
Because addition would yield a product that is not aromatic. It likes to keep its aromatic ring intact.
Electrophilic aromatic substitution: basic steps
two-step mechanism:
1. addition of the electrophile E? to form a resonance-stabilized carbocation
2. deprotonation with a base
Electrophilic Aromatic Substitution: Mechanism
electrophilic aromatic substitution forms what intermediary?
A carbocation, for which three resonance structures can be drawn:
• Always draw in the H atom on the carbon bonded to E. This serves as a reminder that it is the only sp³ hybridized carbon in the carbocation intermediate.
• Notice that the positive charge in a given resonance structure is always located ortho or para to the new C-E bond. In the hybrid, therefore, the charge is delocalized over three atoms of the ring.
Energies of electrophilic aromatic substitution RXNs
• The mechanism has two steps, so there are two energy barriers.
• Step [1] is rate-determining; its transition state is at higher energy.
Types of Electrophilic Aromatic Substitution RXNS
How to the different electrophilic aromatic substitution reactions differ?
how the electrophile is generated. Then the electrophile reacts with the aromatic compound with the same two step process
Halogenation of an aromatic compound
Benzene reacts with Cl? or Br? in the presence of a Lewis acid catalyst, such as FeCl? or FeBr?, to give the aryl halides chlorobenzene or bromobenzene, respectively.

Reactions with I? and F? aren’t possible because I? is too unreactive and F? reacts too violently.

Bromination of Benzene (Mechanism)
Generation of the electrophile in both nitration and sulfonation requires What?
A strong acid
Formation of the Nitronium Ion (+NO?) for Nitration
The electrophile is NO?? (the nitronium ion), formed by protonation of HNO? followed by loss
of water
Formation of the Electrophile +SO?H for Sulfonation
In sulfonation, protonation of sulfur trioxide, SO?, forms a positively charged sulfur species (?SO?H) that acts as an electrophile
What is the step-wise mechanism for the nitration of a benzene ring
transfer of an alkyl group from one atom to another (from Cl to benzene ).
Friedel-Crafts alkylation
The transfer of an acyl group from one atom to another
Friedel-Crafts acylation,
A benzene ring is treated with an acid chloride (RCOCl) and AlCl? to form a ketone.
Unique feature of each Electrophilic Aromatic Substitution Reactions
How the electrophile is generated. The rest is the same
Formation of the Electrophile in Friedel-Crafts Alkylation—Two Possibilities (Mechanism)
• For CH?Cl and 1° RCl, the Lewis acid-base complex itself serves as the electrophile for electrophilic aromatic substitution.
• With 2° and 3° RCl, the Lewis acid-base complex reacts further to give a 2° or 3° carbocation, which serves as the electrophile. Carbocation formation occurs only with 2° and 3° alkyl chlorides, because they afford more stable carbocations.
Friedel-Crafts Alkylation Using a 3° Carbocation (Mechanism)
• Addition of the electrophile (a 3° carbocation) forms a new carbon-carbon bond in Step [1].
• AlCl?- removes a proton on the carbon bearing the new substituent, thus re-forming the aromatic ring in Step [2].
Formation of the Electrophile in Friedel-Crafts Acylation (Mechanism)
Other Facts About Friedel-Crafts Alkylation (3)
[1] Vinyl halides and aryl halides do not react in Friedel-Crafts alkylation
[2] Rearrangements can occur.
[3] Other functional groups that form carbocations can also be used as starting materials.
Do Vinyl halides and aryl halides react in Friedel-Crafts alkylation?
Most Friedel-Crafts reactions involve carbocation electrophiles. Because the carbocations derived from vinyl halides and aryl halides are highly unstable and do not readily form, these organic halides do not undergo Friedel-Crafts alkylation.
Friedel-Crafts Alkylation Involving Carbocation Rearrangement (Mechanism)
A Rearrangement Reaction Beginning with a 1° Alkyl Chloride (Mechanism)
Rearrangements can occur even when no free carbocation is formed initially.
a 1,2-hydride shift forms a 2° carbocation, which then serves as the electrophile in the two-step mechanism for electrophilic aromatic substitution
What other functional groups that form carbocations can also be used as starting materials in Friedel-Crafts Alkylation/Acylation?
any compound that readily forms a carbocation can be used instead. The two most common alternatives are alkenes and alcohols, both of which afford carbocations in the presence of strong acid.
How do you use an alkene for Alkylation?
Protonation of an alkene forms a carbocation, which can then serve as an electrophile in a Friedel-Crafts alkylation.
How do you use an alcohol for Alkylation?
Protonation of an alcohol (From an acid), followed by loss of water, likewise forms a carbocation
Intramolecular Friedel-Crafts Reactions
Starting materials that contain both a benzene ring and an electrophile are capable of intramolecular reaction, and this forms a new ring
Inductive Effects
• Atoms more electronegative than carbon—including N, O, and X—pull electron density away from carbon and thus exhibit an electron-withdrawing inductive effect.
• Polarizable alkyl groups donate electron density, and thus exhibit an electron-donating
inductive effect.
Resonance Effects
• A resonance effect is electron donating when resonance structures place a negative charge on carbons of the benzene ring.
• A resonance effect is electron withdrawing when resonance structures place a positive charge on carbons of the benzene ring.
When is electron-donating resonance effect seen?
whenever an atom Z having a lone pair of electrons is directly bonded to a benzene ring (general structure—(C?H? – Z:) atoms: N, O, and halogen.
When is electron-withdrawing resonance effect seen?
in substituted benzenes having the general structure C?H? -Y=Z, where Z is more electronegative than Y
Is an alkyl group electron-donating group or withdrawing?
An alkyl group is an electron-donating group and an alkyl benzene is more electron rich than benzene.
Common Electron Donating groups
Alkyl groups or groups with an N or O atom
(with a lone pair) bonded to the benzene ring.
Common Electron withdrawing groups
Common electron-withdrawing groups are halogens or groups with an atom Y bearing a full or partial positive charge (+ or ??) bonded to the benzene ring.

Also, C6H5 -Y=Z (with Z more electronegative than Y) are electron withdrawing

Considering Both Inductive and Resonance Effects
• When a neutral O or N atom is bonded directly to a benzene ring, the resonance effect dominates and the net effect is electron donation.
• When a halogen X is bonded to a benzene ring, the inductive effect dominates and the net effect is electron withdrawal.
Ortho, para directors and activators
Ortho, para deactivators
Meta directors
All ortho, para directors are what?
R groups or have a nonbonded electron pair on the atom bonded to the benzene ring.
All meta directors are what?
All meta directors have a full or partial positive charge on the atom bonded to the benzene ring.
make a benzene ring react faster than benzene itself

All activators are either R groups or they have an N or O atom with a lone pair bondeddirectly to the benzene ring. These are the electron-donor groups

Make a benzene ring react slower than by itself.

All deactivators are either halogens or they have an atom with a partial or full positive charge bonded directly to the benzene ring. These are the electron-withdrawing groups

Why is the CH? Group—An ortho, para Director?
attack ortho or para to CH? generates a resonance structure that places a positive charge on a carbon atom with the CH? group. The electron-donating CH? group stabilizes the adjacent positive charge.
Why is The NH? Group—An ortho, para Director?
Because of the lone pair on the N atom, attack at the ortho and para positions generates a fourth resonance structure, which is stabilized because every atom has an octet of electrons. This additional resonance structure can be drawn for all substituents that have an N, O, or halogen atom bonded directly to the benzene ring.
The NO? Group—A meta Director
The reactivity and directing effects of common substituted benzenes
Halogenation of Activated Benzenes
benzene rings activated by strong electron-donating groups—OH, NH?, and their alkyl derivatives (OR, NHR, and NR?)—undergo polyhalogenation when treated with X? and FeX?.
Monosubstitution of H by Br in Benzene
occurs with Br? alone without added catalyst to form a mixture of ortho and para products.
Friedel-Crafts reactions with NH? groups
Doesn’t occur. NH? groups are strong Lewis bases (due to the nonbonded electron pair on N), so they react with AlCl?, the Lewis acid needed for alkylation or acylation. The resulting product contains a positive
charge adjacent to the benzene ring, so the ring is now strongly deactivated and therefore unreactive in Friedel-Crafts reactions.
Friedel-Crafts reactions with NO? groups
No Reaction. A benzene ring deactivated by a strong electron-withdrawing group—that is, any of the meta directors—is not electron rich enough to undergo Friedel-Crafts reactions.
Treatment of benzene with an alkyl halide and AlCl?
places an electron-donor R group on the ring. Because
R groups activate a ring, the alkylated product (C?H?R) is now more reactive than benzene itself towards further substitution, and it reacts again with RCl to give products of polyalkylation.
Polysubstitution with Friedel-Crafts acylation
does not occur because the product now has an electron-withdrawing group that deactivates the ring towards another electrophilic substitution.
What happens when the directing effects of two groups REINFORCE each other on Disubstituted Benzenes
the new substituent is located on the position
directed by both groups.
What happens when the directing effects of two groups OPPOSE each other on Disubstituted Benzenes?
the more powerful activator “wins out.”
What happens with the directing effects of two meta substituents on Disubstituted Benzenes?
No substitution occurs BETWEEN two meta substituents because of crowding
How would you synthesize
the Br group is an ortho, para director and the NO? group is a meta director. Because the two substituents are para to each other, the ortho, para director
must be introduced first
Benzylic Bromination (Mechanism)
alkyl benzene undergoes two different reactions with Br?, depending on the reaction
Oxidation of Alkyl Benzenes
Arenes containing at least one benzylic C- H bond are oxidized with KMnO? to benzoic acid,
Oxidation of Substrates with more than one alkyl group or no benzylic C-H bonds?
Reduction of Aryl Ketones
Ketones formed as products in Friedel-Crafts acylation can be reduced to alkyl benzenes by two different methods
Clemmensen reduction
uses zinc and mercury in the presence of strong acid to reduce an aryl ketone to a alkyl benzene
Wolff-Kishner reduction
uses hydrazine (NH?NH?) and strong base (KOH) to reduce an aryl ketone to a alkyl benzene
two different ways to introduce an alkyl group on a benzene ring
• A one-step method using Friedel-Crafts alkylation
• A two-step method using Friedel-Crafts acylation to form a ketone, followed by reduction
How do you prepare propylbenzene?
propylbenzene cannot be prepared by a Friedel-Crafts alkylation. Instead, when benzene is treated with 1-chloropropane and AlCl?, isopropylbenzene is formed
by a rearrangement reaction. Propylbenzene can be made, however, by a two-step procedure using Friedel-Crafts acylation followed by reduction.
Reduction of Nitro Groups
the nitro group is readily reduced to an amino group (NH?) under a variety of conditions. The most common methods use H? and a catalyst, or a metal (such as Fe or Sn) and a strong acid like HCl
Design a synthesis of m-bromoaniline from benzene.
Design a synthesis of styrene from ethylbenzene.
What can you use to Reduce Aryl Ketones to Alkyl Benzenes?
What can you use to Reduce Nitro Groups?
What can you use to oxidize an Alkyl Benzene?
To be reactive in Friedel Crafts alkylation the halogen must be bonded to what?
An SpÂł hybridized carbon. If its connected to a double bond its unreactive. Vinyl halides (CH?=CHCl) and aryl halides (Ph-Cl)

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