Download Chapter One: Molecular Structure

CHEM 12B
FOOTHILL COLLEGE
ARMSTRONG
OUTLINE TO KLEIN CHAPTER FOURTEEN
CHAPTER FOURTEEN: ETHERS AND EPOXIDES
1. Structure/ Properties
 Relative Boiling points: hydrogen bonding
 Ethers as Solvents/ Crown Ethers
 Nomenclature
2. Preparation of Ethers
 The Williamson Ether synthesis (review; p 642)
o Alkoxide + 1° RX
 From Alkenes with alkoxymercuration-demercuration (review; p653)
 From self-condensation of alcohols (limitations)
3. Preparation of Thioethers
4. Preparation of Epoxides (review; Section 4.8)
 Epoxides from Alkenes with peroxyacids RCO3H
 via intra-molecular Williamson
Enantioselective Sharpless Epoxidation (p653)
5. Reactivity of Ethers
 Inert under Basic Conditions
 Cleavage under highly Acidic conditions ( SN1 for 2° and 3°)
o Mechanism: alkonium ion as leaving group
o Rearrangement
ii. With HX (HBr, HI) :
iii. With H2SO4, H2O or H2SO4, ROH
Note: Book omits hydrolysis of ether with hydronium ion generated by
sulfuric acid in water- you must know this reaction!
 Autooxidation to form explosive hydroperoxides (p646)
 Ethers as Protecting groups for alcohols
i. Tert-butyl ethers
ii. Benzyl ethers
iii. Silyl ethers 14-10B
Preparation with TIPSCl (i-Pr)3SiCl, deprotection with Bu4NF
6. Epoxide Reactivity
i. Cleavage in Acid: “SN1 like”: Cleavage with weak nucleophiles under
acidic conditions: Nucleophile to more substituted carbon with
inversion (examples: HBr, H3O+, CH3OH2+) (p660)
ii. Cleavage with highly basic or highly nucleophilic nucleophiles: “SN2
like” Nucleophile to less crowded carbon with inversion (examples:
CH3NH2, CH3O–, HO–, SH–, CN–) (p 654)
iii. Nucleophilic Substitution with Grignard and Organolithium Reagents
(“SN2” like) (p669)
iv. Reduction with hydride reducing agent LiAlH4 : Omitted in text
CHEM 12B
FOOTHILL COLLEGE
ARMSTRONG
OUTLINE TO KLEIN CHAPTER FOURTEEN
LEARNING OUTCOMES:
 Use knowledge about nucleophilic substitution reactions to predict products of
reaction between ethers and epoxides with nucleophiles under acidic and basic
conditions.
 Predict the stereochemistry and optical activity of a product from an understanding of
its mechanism of formation.
 Propose a reaction or sequence of reactions to produce a target ether or epoxide in
high yield.
 Predict the products of reactions involving ethers and epoxides with common
reagents.
 Predict the likelihood of carbon skeleton rearrangement under a given set of
conditions.
 Predict the stereochemistry and optical activity of a product from an understanding of
its mechanism of formation.
 Recognize structural features of a molecule that are key to its stability and reactivity.
 Propose a reaction or sequence of reactions to produce a target organic compound in
high yield.
1. Consider the reaction below and tell why it DOES NOT provide high yields of the
products shown. Draw alternative products, if any are formed.
2. Give the step-wise mechanism of the following chemical transformation using curved
arrow formalism. Show every step in sequence, including proton transfers and draw
all non-bonded electrons and formal charges.
3. Give the major organic product of the following reaction and include all
stereoisomers formed:
4. Consider the reaction below and answer the following:
A. Why doesn’t it provide high yields of the product shown?
B. Propose an alternative synthesis of the product (i.e How might the product be
synthesized in high yield via a different reaction).