Organic Chemistry II with Dr Roche

Lecture Notes

http://crab.rutgers.edu/~alroche

Email

alroche@crab.rutgers.edu

Room
Phone

Sci 311
225-6166

Text

(a) Organic Chemistry Wade, 4/5th Editions

(b) Solution Manual, 4/5th Ed

(labs: Sci 328F/309/304A/318/319)

(organic model kit)

Do the problems in the book

Learn as you go along
Aim for understanding, not memorization

Ch14 Ethers and Epoxides

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Ethers and Epoxides

Ethers are a class of compound of the general formula R-O-R.
R and R can be alkyl or aryl.
Structure
Ethers can be thought of as alkyl analogues of water.
H O H

R O R

Uses
Since ethers are relatively unreactive and are strongly polar (due to the lone
pairs on the oxygen), they are commonly used as solvents for organic
reactions. (Diethyl ether and THF, the Grignard reaction).
Ethers will often form complexes with molecules that have vacant orbitals,
enabling unstable molecules to be used as reagents.
E.g. Hydroboration uses BH3.THF
H

H
B

H
B

H
+ _
O B H
H

Crown ethers are macrocyclic ethers, which help to solvate metal cations,
and thus allow inorganic salts to dissolve in organic solvents.
O
O

K
O

O
O

18-Crown-6

18-Crown-6 is the ideal size to incorporate a potassium ion, and allows

organic solutions of ionic potassium salts to be prepared (purple benzene).

Ch14 Ethers and Epoxides

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Nomenclature of ethers
Common names of ethers add the suffix ether after naming the groups on
either side of the oxygen.
IUPAC names ethers by taking the more complex alkyl group as the root
name, and naming the remaining part as an alkoxy group.
E.g.
H
OCH3

H3C O-CH2CH3
methoxyethane

methoxycyclohexane

Cl
H
H
OCH3
trans-1-chloro-2-methoxycyclobutane

H2C O-H
H2C O-CH2CH3
2-ethoxyethanol

Cyclic Ethers
Naming these heterocyclic compounds depends on the ring size and number
of oxygens.
(It can be confusing at first)
Epoxides
These 3 membered rings are named using the term epoxy as a substituent.
H

H
H3C

CH-CH2CH3

OCH3
cis-2,3-epoxy-4-methoxyhexane

(cis refers to the substituents, not the epoxide which must be cis/syn).
Epoxides have considerable ring strain.

Ch14 Ethers and Epoxides

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Oxetanes
These are four membered rings with one oxygen.
O

O
H3C

CH2CH3
CH3 H

oxetane

2-ethyl-3,3-dimethyloxetane

Oxetanes have ring strain, but not as much as epoxides.

Furans
These are five membered rings with one oxygen and two double bonds.
(Furan is an aromatic molecule).
O

OCH3
furan

tetrahydrofuran
(THF)

3-methoxyfuran

Pyrans
These are six membered rings with one oxygen and two double bonds.
H
H

O
pyran

CH3
H
O

4-methylpyran

O
tetrahydropyran
(THP)

Ch14 Ethers and Epoxides

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Dioxanes
These are six membered rings with two oxygens.
O

O
O

O
1,4-dioxane

CH3

4-methyl-1,3-dioxane

Ether Synthesis (Recap)

Williamson synthesis
OH 1) Na

O-CH2CH3

2) CH3-CH2-OTs
ethoxycyclohexane

Alkoxymercuration-Demercuration

CH3(CH2)3 CH CH2

1) Hg(OAc)2, CH3OH
2) NaBH4

CH3(CH2)3 CH CH3
OCH3
2-methoxyhexane
(Markovnikov product)

Bimolecular dehydration of Alcohols

2 CH3 OH

H2SO4, 140oC

CH3-O-CH3

Ch14 Ethers and Epoxides

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Reactions of Ethers
Typically ethers are stable and chemically inert, although they can undergo
two types of reaction (cleavage, oxidation).
Cleavage
Ethers are cleaved by H-Br and H-I, generating the corresponding alkyl
halides.
R-O-R + excess H-X R-X + R-X
Ethers are stable to bases, but acidic conditions leads to the protonation of
the ether oxygen, which then can undergo substitution reactions.

CH3CH2-O-CH2CH3

H Br

CH3CH2

:Br
H
O CH2CH3
+

CH3CH2-Br
CH3CH2-OH
H-Br
Br:

CH3CH2-Br

CH3CH2

H
O H
+

The alcohol produced reacts to generate a second molecule of alkyl halide.

Phenyl ethers are slightly different, and cleave to give alkyl halides and
phenols.

O CH2CH3

H I

H
O CH2CH3
+

OH
:I

phenol
CH3CH2-I

Ch14 Ethers and Epoxides

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The reaction stops at the phenol stage since the sp2 carbon of the C-OH bond
does not allow the required SN1 or SN2 reactions to generate the second
molecule of aryl halide.
Oxidation of Ethers
Ethers may auto-oxidize if left in the presence of oxygen for extended
periods of time (Dangerous in the laboratory).

CH3
H

CH3

O
CH3

CH3

excess O2

H
CH3

H
months

O
CH3

CH3

CH3

O-O-H + H
CH3

hydroperoxide

O O
CH3

CH3
H
CH3

dialkylperoxide

The peroxides and hydroperoxides are unstable and explosive.

Epoxides
Unlike straight chain ethers, epoxides are very reactive (release of ring
strain), and are useful intermediates because of their chemical versatility.
Synthesis
Recall alkene and peroxyacid epoxide and carboxylic acid
E.g.
H

MCPBA

H
O
H
epoxycyclohexane

O
Cl

O-O-H

MCPBA

MCPBA is one of the most common epoxidising reagents.

Ch14 Ethers and Epoxides

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Epoxidations work better for electron rich double bonds.

CH3

CH3

MCPBA

O
CH3

CH3

Synthesis from Halohydrins

When halohydrins are treated with base, an intramolecular cyclisation
occurs, and epoxides are formed.
O-H

O-

:OH

X-

Recall that halohydrins are produced from alkenes by reaction with halogens
in the presence of water. (Chlorine water or related reagents).
Cl2, H2O

NaOH

H
Cl
HO H

Acid Catalyzed ring Opening

Epoxides react to release their considerable (25kcal/mol) strain energy.
Recall that the acidic hydrolysis of epoxides gives anti diols.
H
O

H
H O H
+

-H+
+
O H

H
OH
H
OH

H2O:
trans-cyclopentane-1,2-diol

Ch14 Ethers and Epoxides

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This overall transformation (alkene anti 1,2-diol) can be achieved in one

step by reaction with aqueous peroxyacids.
H
OH
H
OH

CH3CO3H
H+, H2O

Epoxides can be ring opened by alcohols with acidic catalysis to generate

alkoxy alcohols with anti stereochemistry.
H
O

H
H O H
+

H
OH
H
OR

-H+
+
O H

H
RO-H

Hydrohalic Acids
Epoxides react with H-X to produce halohydrins, which react further with
H-X to generate 1,2-dihalides.

H Br

H
OH
H
Br

O+ H

O
H
Br:

H-Br

mixture of
cis and trans

Br
H
H
Br

(However it is synthetically easier just to add X2 to an alkene).

Ch14 Ethers and Epoxides

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Base Catalyzed Ring Opening

Normal ethers do not undergo nucleophilic substitution or eliminations
because the alkoxide anion is not a good leaving group. (That is why acid
catalysis is required).
Epoxides are different though. The release of strain when an epoxide is
opened more than compensates for the poor leaving group ability, and so
epoxides will open under nucleophilic conditions.

Figure 14-8

The strained epoxide has a lower Ea than the corresponding straight chain
ether.

Ch14 Ethers and Epoxides

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The reaction of hydroxide (or alkoxide) with a symmetric epoxide generates

anti diols (or alkoxy alcohols) identical to those produced under acidic
conditions.
H
OH
OH

H
O
H
HO:

H2O

H
OH
H
OH

H
O
H

H3CO-+Na
CH3OH

H
OH
H
OCH3

Orientation of Ring Opening

Unsymmetrical epoxides give products with different regiochemistry with
basic opening compared to acidic opening.

H+, CH3CH2-OH
H3C

CH3 OH
H
H3C
CH3CH2O H

CH2
H3C

O
CH3CH2O- +Na
CH3OH

CH3 OCH2CH3
H
H3C
HO H

Ch14 Ethers and Epoxides

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Under basic conditions, the alkoxide simply attacks the least sterically
hindered epoxide carbon in an SN2 displacement.

H3C

CH3 OCH2CH3
H3C
H
HO H

CH3 OCH2CH3
CH3CH2OCH3OH
CH2
H
H3C
H3C
O
O- H

Under acidic conditions, the alcohol seems to attack the more hindered
carbon, but it is more complicated.
The protonated epoxide has several resonance structures.

H3C

H3C
CH2

H3C O
+
H

+ CH
2

H3C O
H

(I)

H3C

+
CH2

H3C O
H

(II)

(III)

Structure II is a major contributor since the cation is more highly substituted

and therefore more stable.
H3C
H3COH

H3C
+O
H

CH2

-H+

CH3O H
H3C
H
H3C OH

The nucleophile attacks the carbon with greatest positive partial charge.

Ch14 Ethers and Epoxides

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Organometallic Reagents
H3C
CH2
H3C

CH3 Ph

Ph-MgBr
H3C

Ether

H3O

CH3 Ph

H3C

O- H

OH H

MgBr

Grignard and organolithium reagents also attack epoxides at the least

hindered carbon to generate alcohols (after acidic workup).

Ch14 Ethers and Epoxides

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