Chemistry

Chapter 11: Alcohols and Ethers
Alcohols and Ethers: Structure and Properties (Sections 11.1-2)

Important Alcohols and Ethers (Section 11.3)
Synthesis of Alcohols from Alkenes (Section 11.4; Chapter 8)
Reactions of Alcohols (Section 11.5)
Old Acid Base Stuff (Section 11.6, Chapter 3)
Alcohols into Alkyl Halides (Section 11.7)
Alcohol Reactions w/ HX (Section 11.8)
Alcohol Reactions w/ PBr3, SOCl2 (Section 11.9)
Alcohol Derivatives as Leaving Groups (Section 11.10)
Synthesis of Ethers (Section 11.11)
Reactions of Ethers (Section 11.12)
Epoxides: Synthesis and Opening (Sections 11.13 and 11.14)
Anti 1,2 Dihydroxylation of Alkenes (Section 11.15)
Alcohols: General Nomenclature

OH
OH
OH
Ethanol
Methanol
OH
2-Propanol
2-methyl-2-propanol
OH
OH
2-Propynol
2-Propenol
Benzyl alcohol
OH
OH
Phenol
OH
m-Ethylphenol
Bu
OH
p-tert-Butylphenol
Naming Cyclic Ethers
Can Use Replacement Nomenclature (oxa O replaces CH2)

Also Many Common Name (Acceptable to Use)
Alcohols and Ethers: Physical Properties

Properties of Ethers Similar to Alkanes of Like Masses
Diethyl ether (MW=74); Pentane (MW=72)
Diethyl ether (BP=34.6 C); Pentane (BP=36 C)
Alcohols Boil Much Higher than Comparable Ethers/Alkanes
Related to Hydrogen Bonding of Alcohols (See Chapter 4)
Alcohols form Hydrogen Bonding Networks w/ one Another
Ethers Cannot Hydrogen Bond w/ one Another
Ethers CAN H-Bond w/ H2O and Alcohols (Soluble in These)
Properties of Some Alcohols/Ethers in Tables 11.1 and 11.2
Important Alcohols and Ethers

Methanol (CH3OH)
Often Called Wood Alcohol (Distilled From Wood)
Prepared Now via Catalytic Hydrogenation Reactions
Ethanol (CH3CH2OH)
Made Through Fermentation of Sugars, in Alcoholic Drinks
Common Solvent in Organic Labs (Absolute Ethanol)
Ethylene Glycol (HOCH2CH2OH)
Good Antifreeze: Low MW, High Boiling Point (197 C)
Diethyl Ether (CH3CH2OCH2CH3)
Low Boiling Point, Volatile, Highly Flammable Liquid
One of First Uses was as Surgical Anesthetic
Watch Out for Old Ether Containers (Peroxides!!)
Synthesizing Alcohols from Alkenes

Weve Looked at Several OH Synthesis Reactions in Ch. 8
Acid-Catalyzed Hydration (Markovnikov)
H3O+/H2O OR warm, dilute H2SO4, H2O
Oxymercuration/Demercuration (Markovnikov)
1. Hg(OAc)2 THF/H2O 2. NaBH4, NaOH
Hydroboration/Oxidation (Anti-Markovnikov)
1. BH3 : THF 2. H2O2, NaOH
Now Lets Consider Some Reactions of Alcohols
Reactions of Alcohols
H
O
H
Alcohol
(Lewis Base,
Nucleophile)
Strong Acid
+ A
H
Protonated
Alcohol
Lone Pairs on Alcohols: Lewis Bases, Nucleophiles

Note Bond Polarizations: C, H are + and O is
Alcohol Carbon Not Particularly Electrophilic (HO Bad LG)
Protonation of Alcohol H2O; Good Leaving Group

Presence of Good Leaving Group Makes COH Electrophilic
OH2+ More Electron Withdrawing than OH; More Polarized
Can Observe SN1 or SN2 Reactions (Depends on Alcohol Class)
O
H
Alcohol
(Lewis Base,
Nucleophile)
H
O
H
Protonated
Alcohol
SN 2
Reaction
O
H
Protonated Ether
H2O

Another Alcohol Moleculae Can React, Get Protonated Ether
Subsequent Deprotonation Ether Product (Symmetric Here)
Reaction is CONDENSATION of Two Alcohols
Converting Alcohols into Alkyl Halides

conc. HCl
OH
Cl
25 C
+ H 2O
conc. HBr
OH
Reflux
PBr3
OH
Br
Br
-10 to 0 C
Cl
OH
SOCl2
pyridine
OCH3
+ H3PO3
+ SO2 + HCl
OCH3
HX Reactions with Alcohols (3, 2)

Step 1
OH
OH2
H
Step 2
+
OH2
H2O
Step 3
Cl
Cl
H2O
HX Reactions with Alcohols (1, MeOH)

H
OH
Br
H
OH2
OH2
Br
+ H2O
H2O
As Seen Previously, Protonation Makes Good Leaving Group

Presence of Nucleophile (Br) Allows for Substitution Reaction
Can also Add Lewis Acid to Help (esp. ZnCl2 w/ Cl)
Leaving Groups: OH Derivatives

O
H3 C
O
H3 C
O
Mesyl Group
(Ms)
O
F3C
O
Tosyl Group
(Ts)
O
Trifyl
(Tf)
Make OH Better as Leaving Group (Replace H, Bond to O)

This General Class is Called the Sulfonate Ester Class
Prepared By Reacting Alcohol w/ a Sulfonyl Chloride and Base
Formation of Derivatives does not Alter CO Stereochemistry
Leaving Groups: OH Derivatives

O
H3C
Cl
OH
OTs
Pyridine
O
Ts
O
F3C
OTf
OH
Cl
Pyridine
O
Tf
Sample Derivatizations. Note Retention of Stereochemistry in 2 nd
Synthesis of Ethers
Weve Already Seen Ether Synthesis by Alcohol Dehydration:
O
H
Alcohol
(Lewis Base,
Nucleophile)
H
O
H
Protonated
Alcohol
SN 2
Reaction
O
H
Protonated Ether
+ H2 O
Utility of this Reaction is Limited in its Scope:

Mixture of Ether/Alkenes with 2 Alkyl Groups
Exclusively Alkenes with 3 Alkyl Groups
Only Useful for Synthesis of Symmetric Ethers
ROH + ROH ROR + ROR + ROR
Williamson Synthesis of Ethers

Unsymmetrical Ethers From RONa + Halide, Sulfonate, etc.
Na
LG
O
Asymmetric Ether
Utility of this Reaction is Much Greater Than Condensation:

Works with 1 and 2 Halides, Sulfonates, etc.
Still Exclusively Alkenes with 3 Alkyl Groups
Lower Temperatures Favor Substitution over Elimination
SN2 Conditions Apply Prefer Unhindered Substrate
Alkoxymercuration-Demercuration
This Reaction is Analogous to Oxymercuration-Demercuration
Using New Hg Salt Here (Triflate) Can Use Hg(OAc)2 Also

Instead of H2O in First Step, We Use an Alcohol
Carbocation is Captured by Alcohol Molecule
After Loss of Proton, Alkoxide is Added Instead of Alcohol
See Chapter 8 for Mechanistic Details (Completely Parallel)
Protecting Groups: Alcohol Alkylation

OH
H2SO4
Alcohol Groups do not Survive Many Organic Reactions

Alkylation (Ether Formation) Protects OHs During Synthesis
Can Remove the Protecting Group w/ Dilute Aqueous Acid
Generally Dissolve Alcohol in Acid, THEN add Isobutylene
Addition in this Manner Minimizes Isobutylene Dimerization
Lets See Why We Might Want to Use a Protecting Group
Protecting Groups: How They Work

OH
Target Molecule:
Na
Reagents:
and
Br
OH
We can't simply mix the reagents here: deprotonation occurs faster

than alkylation (acid base reaction, think about pKa differences)
Na
+ Br
+ Br
OH
ONa
So, we protect the alcohol as an ether first, and we can successfully alkylate:
Br
1. H2SO4
OH 2. CH =C(CH )
2
3 2
OtBu
H3O+/H2O
Na
Br
OtBu
OH
+
BuOH
Protecting Groups: Silyl Ethers
Silyl Ethers Stable Over a 4-12 pH Range (Acidic and Basic)

Can Survive Conditions of Many Organic Reactions
Typically Removed w/ Flouride Source (NBu4F; aka TBAF)
Silyl Ethers More Volatile Than Alcohols (GC Applications)
Ether Reactions w/ Strong Acids
Ethers Can be Protonated by Strong Acids (Oxonium Ions)

w/ 2 Equivalents of Acid (HX), Cleaved to 2 Eq. Alkyl Halide
Protonation, SN2, Protonation, SN2
Ether Cleavage by HBr: Mechanism

Br
O
Br
H
-
Br
Br
Br
Br
-H2O
H2 O
HO
Two Equivalents of Ethyl bromide Produced (+ H2O)
Synthesis of Epoxides
Three-Membered Oxygen Containing Ring; Use Peroxy Acid
Some Peroxyacids
Reactive, Often Unstable Species: Chemists use More Stable
Epoxide Opening: Acid-Catalyzed

H
O
OH
-H+
HO
Trans 1,2 Diol
H2O
Epoxides Are Reactive to Opening Due to Ring Strain

After Protonation, Opening is SN2 Like Reaction (Anti)
Desire to Relieve Ring Strain Good Electrophiles
Epoxide Opening: Base-Catalyzed

H
OR
OH
O
HO
HO
Trans 1,2 Diol
OH
Epoxides Are Ethers That Can be Attacked by Bases

Reactivity is Due to Ring Strain (Increases Electrophilicity)
As in Acid Case, Opening is an SN2 Reaction
Can Open With Strong Base, Hydroxide and Alkoxide Usual

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Chapter 11: Alcohols and Ethers

Alcohols and Ethers: Structure and Properties (Sections 11.1-2)

Alcohols: General Nomenclature

Naming Cyclic Ethers

Can Use Replacement Nomenclature (oxa O replaces CH2)

Alcohols and Ethers: Physical Properties

Important Alcohols and Ethers

Synthesizing Alcohols from Alkenes

Lone Pairs on Alcohols: Lewis Bases, Nucleophiles

Protonation of Alcohol H2O; Good Leaving Group

Protonation of Alcohol H2O; Good Leaving Group

Converting Alcohols into Alkyl Halides

HX Reactions with Alcohols (3, 2)

HX Reactions with Alcohols (1, MeOH)

As Seen Previously, Protonation Makes Good Leaving Group

Leaving Groups: OH Derivatives

Make OH Better as Leaving Group (Replace H, Bond to O)

Leaving Groups: OH Derivatives

Sample Derivatizations. Note Retention of Stereochemistry in 2 nd

Utility of this Reaction is Limited in its Scope:

Williamson Synthesis of Ethers

Utility of this Reaction is Much Greater Than Condensation:

Using New Hg Salt Here (Triflate) Can Use Hg(OAc)2 Also

Protecting Groups: Alcohol Alkylation

Alcohol Groups do not Survive Many Organic Reactions

Protecting Groups: How They Work

We can't simply mix the reagents here: deprotonation occurs faster

Protecting Groups: Silyl Ethers

Silyl Ethers Stable Over a 4-12 pH Range (Acidic and Basic)

Ether Reactions w/ Strong Acids

Ethers Can be Protonated by Strong Acids (Oxonium Ions)

Ether Cleavage by HBr: Mechanism

Two Equivalents of Ethyl bromide Produced (+ H2O)

Three-Membered Oxygen Containing Ring; Use Peroxy Acid

Reactive, Often Unstable Species: Chemists use More Stable

Epoxide Opening: Acid-Catalyzed

Epoxides Are Reactive to Opening Due to Ring Strain

Epoxide Opening: Base-Catalyzed

Epoxides Are Ethers That Can be Attacked by Bases

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