11 Lecture

© 2014 Pearson Education, Inc.

Reactions of Alcohols, Ethers,

Epoxides, Amines, and Thiols

Paula Yurkanis BruiceUniversity of California,

Santa Barbara

Chapter 11


More About the Families in Group II

The families in Group II all have an electronegative atom or groupthat is attached to an sp3 carbon.


Strongly Basic Leaving Groups Cannot Be Displaced


Acid Converts the Poor Leaving Group into a Good Leaving Group

Alcohols have to be “activated” before they can react.

Only weakly basic nucleophiles can be used.Strongly basic nucleophiles would react with the proton.


Converting Alcohols to Alkyl Halides

Primary and Secondary alcohols require heat; tertiary alcohols do not.


The Reactions of Secondary and Tertiary Alcohols with Hydrogen Halides are SN1 Reactions


An SN1 Reaction Creates a Carbocation Intermediate, So Watch Out for Carbocation Rearrangements


The Reactions of Primary Alcoholswith Hydrogen Halides are SN2 Reactions

Recall that Br– is a good nucleophile in a protic solvent.

Alcohols undergo SN1 reactions unless they would have to form a primary carbocation.


Cl– is the Poorest Nucleophile of the Halide Ions

ZnCl2 increases the rate of the reaction by creating a better leaving group than water.


Why is It Important to Be Able to Convert Alcohols to Alkyl Halides?

Alcohols are readily available but unreactive.Alkyl halides are less available but reactive and can be used to synthesized a wide variety of compounds.


Other Methods to Convert Alcohols into Alkyl Halides

phosphorus tribromide, phosphorus trichloride, thionyl chloride


The Mechanism for the Reaction with PBr3 or PCl3

A bromophosphite (chlorophosphite) group is a better leaving group than a halide ion.

Pyridine is the solvent and acts as a base.


The Mechanism for the Reaction with SOCl2

A chlorosulfite group is a better leaving group than a halide ion.

Pyridine is the solvent and acts as a base.


Converting Alcohols to Alkyl Halides


Primary and Secondary Alcohols Can Be Activated by Being Converted to Sulfonate Esters


A Sulfonic Acid is a Strong Acid


Common Sulfonyl Chlorides

tosyl chloride = TsCl


The Mechanism


A Sulfonate Ester Reacts with Nucleophiles


Activating an Alcohol


Two SN2 Reactions or One SN2 Reaction?


Dehydration of an Alcohol

Dehydration of an alcohol is an elimination reaction.


Dehydration is a Reversible Reaction

To prevent the alkene from adding water and reforming the alcohol,the water is removed as it is formed.


Dehydration of Secondary and Tertiary Alcohols are E1 Reactions


Dehydration is a Regioselective Reaction

The major product is the more stable alkene.


The More Stable Alkene Has the More Stable Transition State Leading to Its Formation


Tertiary Alcohols are the Easiest to Dehydrate

The rate of dehydration reflects the ease of carbocation formation.


An E1 Reaction Creates a Carbocation Intermediate, So Watch Out for Carbocation Rearrangements


Dehydration of a Primary Alcohol is an E2 Reaction

Both E2 and SN2 products are obtained.

Alcohols undergo E1 reactions unless they would have to form a primary carbocation.


The Major Product is 2-Butene


Dehydration is Stereoselective

The major product is the stereoisomer with the largest groups on opposite sides of the double bond.


Dehydration Under Mild Conditions


The Mechanism

The E1 dehydration has been changed to an E2 dehydration.


Another Way to Do an E2 Dehydration


Oxidation of Secondary Alcohols


Oxidation of Primary Alcohols


Tertiary Alcohols Cannot Be Oxidized to a Carbonyl Compound


Oxidation by Hypochlorous Acid (HOCl)


The Mechanism


Alcohols and Ethers Have Similar Leaving Groups

Alcohols and ethers have to be “activated” before the compounds can react.


The Leaving Group of an Ether Can Be Activated by Protonation


The Mechanism

If a relatively stable carbocation is formed when ROH leaves, it will be an SN1 reaction.


If a relatively stable carbocation would not be formed when ROH leaves,it will be an SN2 reaction.

The Mechanism

Ethers undergo SN1 reactions unless they would have to form a primary carbocation.


Ethers Cannot Be Activated by Other Methods

An alcohol forms an intermediate that can lose a proton.

An ether forms an intermediate that cannot lose a proton.


Ethers Are Common Solvents Because They React Only with Hydrogen Halides


Synthesis of an Epoxide


Synthesis of an Epoxide


Epoxides are More Reactive Than Ethers Because of Ring Strain


The Acid-Catalyzed Mechanism


If the Epoxide is Not Symmetrical, Which Carbon Does the Nucleophile Attack?

The nucleophile attacks the more substituted ring carbon.


Under Acidic Conditions the Nucleophile Attacks the More Substituted Ring Carbon


Under Neutral or Basic Conditions the Nucleophile Attacks the Less Substituted Carbon


The Conditions Determine the Site of Nucleophilic Attack


Using Epoxides in Synthesis


The Addition of Water to an Alkene

Carbocation rearrangements can occur during the acid-catalyzed addition of water.


Adding Water to an Alkene Without a Carbocation Rearrangement

The regioselectivity is the same as the acid-catalyzed addition of waterbecause the hydride ion adds to the sp2 carbon bonded to the most hydrogens.


Forming a trans-1,2-Diol


Forming a cis-1,2-Diol


The Mechanism


Arene Oxides


Two Pathways for Reaction


Mechanism for Formation of Phenol


The Epoxide Opens Preferentially in the Direction That Forms the More Stable Carbocation


Addition Products Can Be Carcinogenic

If formation of the addition products is faster than formation of the phenol, the arene oxide can be carcinogenic.


Relative Reactivities


Protonating an Amine Does Not Form a Compound with a Good Leaving Group

Amines cannot undergo substitution and elimination reactions.


Amines are Common Organic Bases


Amines are Common Nucleophiles


The Hofmann Elimination Reaction

A quaternary ammonium ion can undergo an elimination reactionwith a strong base such as hydroxide ion.


The Hofmann Elimination is an E2 Reaction


The Base Removes the H from the -Carbon Bonded to the Most Hydrogens


Because the Leaving Group is Poor,the Transition State Is Carbanion-Like

Recall that alkyl fluorides have carbanion-like transition states because the leaving group is poor.


It Must Be a Quaternary Hydroxide

Aqueous silver oxide converts a quaternary ammonium halide to a quaternary ammonium hydroxide.


Thiols

Thiols used to be called mercaptans because they capture mercury.


Nomenclature of Thiols


Thiols are Good Nucleophiles in a Protic Solvent

The product is a sulfur analogue of an ether (thioether or a disulfide).

Thiolate ions are better nucleophiles in a protic solvent than alkoxide ions.


Thioethers are Also Nucleophiles


A Sulfonium Salt is an Alkylating Agent


The Families in Group II

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11 Lecture