Orgo Quiz 3

Chapter 16/17, Chapter 18, & Chapter 19

Mechanism

Electrophilic Aromatic Substitution

1) Benzene ring attacks electrophile, carbocation forms

2) Base attacks H, aromaticity regained

Steps for Electrophilic Aromatic Substitution

Mechanism

Bromination of Benzene

1) Form a stronger electrophile using FeBr₃

2) Benzene ring attacks electrophile, carbocation forms

3) Base attacks H, aromaticity regained

Steps for Bromination of Benzene

Mechanism

Iodination of Toluene

Pre-steps) Form electrophile (I⁺ ion)

1) Toluene attacks electrophile, carbocation forms

2) Deprotonation, aromaticity regained

Steps for Iodination of Toluene

Mechanism

Chlorination of Benzene

1) Form stronger electrophile using AlCl₃

2) Benzene attacks electrophile, carbocation

3) Base attacks H, aromaticity regained

Steps for Chlorination of Benzene

Mechanism

Nitration of Benzene

Pre-steps) Form electrophile (⁺NO₂)

1) Benzene attacks electrophile, carbocation forms

2) Base attacks H, aromaticity regained

Steps for Nitration of Benzene

Mechanism

Sulfonation of Benzene

1) Benzene attacks electrophile (SO₃), carbocation forms

2) Base attacks H

3) Protonation

Steps for Sulfonation of Benzene

Mechanism

Desulfonation of Benzene

Activating Groups do what?

Speed Up Reactions

Activating groups are what?

Electron Donating Groups

Example of What?

Ortho and Para Directing Substituents

Deactivating Groups do what?

Slows Reaction

Deactivating Groups are what?

Electron Withdrawing Groups

Examples of What?

Meta Directing Substituents

Halobenzenes are what?

Ortho and Para directing BUT deactivating

Activating Groups in relation to Deactivating Groups

Stronger Directing Effect

Mechanism

Friedel-Crafts Alkylation

1) Form carbocation using AlCl₃ or HF or BF₃

2) Benzene ring attacks carbocation, sigma complex forms

3) Base attacks H, aromaticity regained

Steps for Friedel-Crafts Alkylation

Limitations of Friedel-Crafts Alkylation

Only works with benzene, activated benzenes, and halobenzenes; rearrangements are common; polyalkylation is possible

Mechanism

Friedel-Crafts Acylation

1) Form electrophile (R-C⁺=O)

2) Benzene attacks electrophile, carbocation forms

3) Base attacks H, aromaticity regained

Steps for Friedel-Crafts Acylation

Mechanism

Clemmensen Reduction

1) Reduces acylbenzene using Zn (Hg) and aq HCl

2) Produces alkylbenzene

Steps for Clemmensen Reduction

Mechanism

Gatterman-Koch Formylation

1) Form electrophile (H-C⁺=O)

2) Benzene ring attacks electrophile

Steps for Gatterman-Koch Formylation

Mechanism

Addition-Elimination

1) Nucleophile attacks benzene ring, sigma complex

2) Loss of leaving group, aromaticity regained

Steps for Addition-Elimination

Condition for Addition-Elimination Reaction

Requires benzene ring with strong electron withdrawing group

Mechanism

Elimination-Addition: Benzyne

1) Nucleophile deprotonates benzene > carbanion > benzyne

2) Nucleophile attacks benzyne > carbanion > protonate

Steps for Elimination-Addition: Benzyne

Conditions for Elimination-Addition: Benzyne

Requires benzene with no strong electron withdrawing groups

Mechanism

(Total) Chlorination of Benzene

1) Add 3Cl₂

2) Add heat, pressure, or hv

Steps for (Total) Chlorination of Benzene

Mechanism

Catalytic Hydrogenation

1) Add 3H₂, 1000 psi

2) Add Pt, Pd, Ni, Ru, or Rh

Steps for Catalytic Hydrogenation

Mechanism

Permanganate Oxidation

1) Add hot KMnO₄ and H₂O

2) Protonate

Steps for Permanganate Oxidation

Mechanism

Side-Chain Chlorination

1) Add Cl radical, resonance

2) Add Cl-Cl to form benzene halide

Steps for Side-Chain Chlorination

Mechanism

Side-Chain Bromination

1) Add Br radical, resonance

2) Add Br-Br to form benzene halide

Steps for Side-Chain Bromination

Mechanism

SN1: Benzylic Halides

Mechanism

SN2: Benzylic Halides

Mechanism

Acylation of Phenols

1) Phenol + Acetic Acid = Ester

Steps for Acylation of Phenols

Mechanism

Formation of Phenoxide Ions

1) Phenol + NaOH = Phenoxide Ion

Steps for Formation of Phenoxide Ion

Mechanism

Phenol Substitution

1) Phenol + NaOH = Phenoxide Ion

2) Phenoxide Ion + excess Br₂

3) ^-OH attacks H

4) Use Br₂ to add more bromines

Steps for Phenol Substitution

Mechanism

Oxidation of Alcohols (into Ketones & Aldehydes)

Mechanism

Ozonolysis (Alkene into Ketones & Aldehydes)

Mechanism

Friedel-Crafts Acylation (forms ketones)

Mechanism

Hydration of Alkynes

1) Alkyne + Hg²⁺, H₂SO₄, H₂O = Enol Intermediate (Markovnikov)

2) Enol Intermediate + Tautomerization = Methyl Ketone

Steps for Hydration of Alkynes

Mechanism

Hydroboration of Alkynes

1) Alkyne + Sia₂BH + H₂O₂, NaOH = Enol Intermediate (Anti-Markovnikov)

2) Enol Intermediate + Tautomerization = Aldehyde

Steps for Hydroboration of Alkynes

Mechanism

Carboxylic Acids into Ketones

1) Carboxylic Acid + LiOH = Lithium Carboxylate + R’-Li = Dianion

2) Dianion + H₃O⁺ = Hydrate - H₂O = Ketone

Steps for Carboxylic Acids into Ketones

Mechanism

Carboxylic Acids into Aldehydes

1) Carboxylic Acid + SOCl₂ = Acid Chloride

2) Acid Chloride + LiAlH(O-t-Bu)₃ = Aldehyde

Steps for Carboxylic Acids into Aldehydes

Mechanism

Carboxylic Acids into Ketones with R₂CuLi

Pre) Carboxylic Acid + SOCl₂ = Acid Chloride

1) R-X + Li = R-Li + CuI = R₂CuLi

2) R₂CuLi + Acid Chloride = Ketone

Steps for Carboxylic Acids into Ketones with R₂CuLi

Mechanism

Nitriles into Ketones

1) Nitrile + R’-Mg-X = Mg salt of Imine + H⁺ = Imine

2) Imine + H₃O⁺ = Ketone

Steps for Nitriles into Ketones

Mechanism

Nitriles into Aldehydes

1) Nitrile + DIBAL-H = Aluminum Complex

2) Aluminum Complex + H₃O⁺ = Aldehyde

Steps for Nitriles into Aldehydes

Mechanism

Esters into Aldehydes

1) Ester + DIBAL-H (-78°C) = Aluminum Complex

2) Aluminum Complex + H₂O = Aldehyde

Steps for Esters into Aldehydes

Mechanism

Acid-Catalyzed Hydration

1) Protonate Ketone/Aldehyde

2) Water nucleophile attack on carbon, lose double bond

3) Deprotonate = Geminal Diol/Hydrate

Steps for Acid-Catalyzed Hydration

Mechanism

Base-Catalyzed Hydration

1) ^-OH nucleophile attacks carbon, forms alkoxide

2) Protonate = Geminal Diol/Hydrate

Steps for Base-Catalyzed Hydration

Mechanism

Cyanohydrin

1) HCN: + H₂O = ^- :CN:

2) Aldehyde + ^- :CN: = Alkoxide + HCN: = Aldehyde Cyanohydrin

Steps for Cyanohydrin

Mechanism

Imines

1) Protonate Aldehyde, NH₂CH₃ attacks carbon, lose double bond

2) Use NH₂CH₃ to deprotonate N = Hemiaminal Intermediate

3) Protonate OH to make good leaving group, N forms double bond

4) Deprotonate N = Imine

Steps for Imines

Mechanism

Acetals

1) Protonate Ketone using H-OTs, lose double bond, carbocation

2) CH₃OH nucleophilic attack, deprotonate = Hemiacetal Intermediate

3) Protonate OH to make good leaving group, carbocation

4) CH₃OH nucleophilic attack, deprotonate = Acetal

Steps for Acetals

Mechanism

Cyclic Acetals

1) Ketone/Aldehyde + Ethylene Glycol/Diol

2) Add H⁺ = Cyclic Acetal

Steps for Cyclic Acetals

Purpose of Cyclic Acetals?

Protects ketones/aldehydes from unwanted reactions

Mechanism

Wittig Reaction

1) Ph₃P: + Br-CH₂-R = ⁺PPh₃-CH₂-R + Bu-Li = ⁺PPh₃- ^- :CH-R (Ylide)

2) Ketone/Aldehyde + Ylide = Alkene

Steps for Wittig Reaction

Mechanism

Oxidation of Aldehydes

1) Aldehyde + Ag₂O, THF/H₂O = Carboxylic Acid

(Can use Na₂Cr₂O₇ with H₂SO₄ OR KMnO₄ OR excess NaOCl/TEMPO)

Steps for Oxidation of Aldehydes

Mechanism

Hydride Reductions

1) Ketone/Aldehyde + NaBH₄, CH₃OH = Alcohol

> NaBH(OAc)₃ reduces aldehydes ONLY

Steps for Hydride Reductions

Mechanism

Catalytic Hydrogenation (of Ketone/Aldehyde)

Mechanism

Clemmensen Reduction (of Ketone/Aldehyde)