Title: Ethers
1Chapter 11
211.1 Structure, Fig. 11-1
- The functional group of an ether is an oxygen
atom bonded to two carbon atoms - in dialkyl ethers, oxygen is sp3 hybridized with
bond angles of approximately 109.5. - in dimethyl ether, the C-O-C bond angle is 110.3
3Structure
- in other ethers, the ether oxygen is bonded to an
sp2 hybridized carbon - in ethyl vinyl ether, for example, the ether
oxygen is bonded to one sp3 hybridized carbon and
one sp2 hybridized carbon
411.2 Nomenclature ethers
- IUPAC the longest carbon chain is the parent
- name the OR group as an alkoxy substituent
- Common names name the groups bonded to oxygen in
alphabetical order followed by the word ether
5Nomenclature cyclic ethers
- Although cyclic ethers have IUPAC names, their
common names are more widely used - IUPAC prefix ox- shows oxygen in the ring
- the suffixes -irane, -etane, -olane, and -ane
show three, four, five, and six atoms in a
saturated ring
611.3 Physical Properties, Fig. 11-2
- Although ethers are polar compounds, only weak
dipole-dipole attractive forces exist between
their molecules in the pure liquid state
7Physical Properties, Fig. 11-3
- Boiling points of ethers are
- lower than alcohols of comparable MW
- close to those of hydrocarbons of comparable MW
- Ethers are hydrogen bond acceptors
- they are more soluble in H2O than are hydrocarbons
811.4 A. Preparation of Ethers
- Williamson ether synthesis SN2 displacement of
halide, tosylate, or mesylate by alkoxide ion
9Preparation of Ethers
- yields are highest with methyl and 1 halides,
- lower with 2 halides (competing ?-elimination)
- reaction fails with 3 halides (?-elimination
only)
10B. Preparation of Ethers
- Acid-catalyzed dehydration of alcohols
- diethyl ether and several other ethers are made
on an industrial scale this way - a specific example of an SN2 reaction in which a
poor leaving group (OH-) is converted to a better
one (H2O)
11Preparation of Ethers
- Step 1 proton transfer gives an oxonium ion
- Step 2 nucleophilic displacement of H2O by the
OH group of the alcohol gives a new oxonium ion
12Preparation of Ethers
- Step 3 proton transfer to solvent completes the
reaction
13C. Preparation of Ethers
- Acid-catalyzed addition of alcohols to alkenes
- yields are highest using an alkene that can form
a stable carbocation - and using methanol or a 1 alcohol that is not
prone to undergo acid-catalyzed dehydration
14Preparation of Ethers
- Step 1 protonation of the alkene gives a
carbocation - Step 2 reaction of the carbocation (an
electrophile) with the alcohol (a nucleophile)
gives an oxonium ion
15Preparation of Ethers
- Step 3 proton transfer to solvent completes the
reaction
1611.4 Reactions, A. Cleavage of Ethers
- Ethers are cleaved by HX to an alcohol and a
haloalkane - cleavage requires both a strong acid and a good
nucleophile therefore, the use of concentrated
HI (57) and HBr (48) - cleavage by concentrated HCl (38) is less
effective, primarily because Cl- is a weaker
nucleophile in water than either I- or Br-
17Cleavage of Ethers
- A dialkyl ether is cleaved to two moles of
haloalkane
18Cleavage of Ethers
- Step 1 proton transfer to the oxygen atom of the
ether gives an oxonium ion - Step 2 nucleophilic displacement on the 1
carbon gives a haloalkane and an alcohol - the alcohol is then converted to an haloalkane by
another SN2 reaction
19Cleavage of Ethers
- 3, allylic, and benzylic ethers are particularly
sensitive to cleavage by HX - tert-butyl ethers are cleaved by HCl at room temp
- in this case, protonation of the ether oxygen is
followed by C-O cleavage to give the tert-butyl
cation
20B. Oxidation of Ethers
- Ethers react with O2 at a C-H bond adjacent to
the ether oxygen to give hydroperoxides - reaction occurs by a radical chain mechanism
- Hydroperoxide a compound containing the OOH group
2111.6 Silyl Ethers as Protecting Groups
- When dealing with compounds containing two or
more functional groups, it is often necessary to
protect one of them (to prevent its reaction)
while reacting at the other - suppose you wish to carry out this transformation
22Silyl Ethers as Protecting Groups
- the new C-C bond can be formed by alkylation of
an alkyne anion - the OH group, however, is more acidic (pKa 16-18)
than the terminal alkyne (pKa 25) - treating the compound with one mole of NaNH2 will
give the alkoxide anion rather than the alkyne
anion
23Silyl Ethers as Protecting Groups
- A protecting group must
- add easily to the sensitive group
- be resistant to the reagents used to transform
the unprotected functional group(s) - be removed easily to regenerate the original
functional group - In this chapter, we discuss trimethylsilyl (TMS)
and other trialkylsilyl ethers as OH protecting
groups
24Silyl Ethers as Protecting Groups
- Silicon is in Group 4A of the Periodic Table,
immediately below carbon - like carbon, it also forms tetravalent compounds
such as the following
25Silyl Ethers as Protecting Groups
- An -OH group can be converted to a silyl ether by
treating it with a trialkylsilyl chloride in the
presence of a 3 amine
26Silyl Ethers as Protecting Groups
- replacement of one of the methyl groups of the
TMS group by tert-butyl gives a
tert-butyldimethylsilyl (TBDMS) group, which is
considerably more stable than the TMS group - other common silyl protecting groups include the
TES and TIPS groups
27Silyl Ethers as Protecting Groups
- silyl ethers are unaffected by most oxidizing and
reducing agents, and are stable to most
nonaqueous acids and bases - the TBDMS group is stable in aqueous solution
within the pH range 2 to 12, which makes it one
of the most widely used -OH protecting groups - silyl blocking groups are most commonly removed
by treatment with fluoride ion, generally in the
form of tetrabutylammonium fluoride
28Silyl Ethers as Protecting Groups
- we can use the TMS group as a protecting group in
the conversion of 4-pentyn-1-ol to 4-heptyn-1-ol
2911.7 Epoxides
- Epoxide a cyclic ether in which oxygen is one
atom of a three-membered ring - simple epoxides are named as derivatives of
oxirane - where the epoxide is part of another ring system,
it is shown by the prefix epoxy- - common names are derived from the name of the
alkene from which the epoxide is formally derived
H
H
1
H
2
3
O
C
C
O
O
2
1
H
3011.8 A. Synthesis of Epoxides
- Ethylene oxide, one of the few epoxides
manufactured on an industrial scale, is prepared
by air oxidation of ethylene
2
O
31B. Synthesis of Epoxides
- The most common laboratory method is oxidation of
an alkene using a peroxycarboxylic acid (a
peracid)
O
O
O
O
2
32Synthesis of Epoxides
- Epoxidation of cyclohexene
33Synthesis of Epoxides
- Epoxidation is stereospecific
- epoxidation of cis-2-butene gives only
cis-2,3-dimethyloxirane - epoxidation of trans-2-butene gives only
trans-2,3-dimethyloxirane
34Synthesis of Epoxides
- A mechanism for alkene epoxidation must take into
account that the reaction - takes place in nonpolar solvents, which means
that no ions are involved - is stereospecific with retention of the alkene
configuration, which means that even though the
pi bond is broken, at no time is there free
rotation about the remaining sigma bond
35Synthesis of Epoxides
- A mechanism for alkene epoxidation
36C. Synthesis of Epoxides
- Epoxides are can also be synthesized via
halohydrins - the second step is an internal SN2 reaction
37Synthesis of Epoxides
- halohydrin formation is both regioselective and
stereoselective for alkenes that show cis,trans
isomerism, it is also stereospecific (Section
6.3F) - conversion of a halohydrin to an epoxide is
stereoselective - Problem account for the fact that conversion of
cis-2-butene to an epoxide by the halohydrin
method gives only cis-2,3-dimethyloxirane
H
H
H
H
C
C
C
C
O
38D. Synthesis of Epoxides
- Sharpless epoxidation
- stereospecific and enantioselective
39Reactions of Epoxides
- Ethers are not normally susceptible to attack by
nucleophiles - Because of the strain associated with the
three-membered ring, epoxides readily undergo a
variety of ring-opening reactions
4011.9 A. Reactions of Epoxides
- Acid-catalyzed ring opening
- in the presence of an acid catalyst, such as
sulfuric acid, epoxides are hydrolyzed to glycols
O
41Reactions of Epoxides
- Step 1 proton transfer to oxygen gives a bridged
oxonium ion intermediate - Step 2 backside attack by water (a nucleophile)
on the oxonium ion (an electrophile) opens the
ring - Step 3proton transfer to solvent completes the
reaction
42Reactions of Epoxides
- Attack of the nucleophile on the protonated
epoxide shows anti stereoselectivity - hydrolysis of an epoxycycloalkane gives a
trans-1,2-diol
43Reactions of Epoxides
- Compare the stereochemistry of the glycols formed
by these two methods
44B. Epoxides
- the value of epoxides is the variety of
nucleophiles that will open the ring and the
combinations of functional groups that can be
prepared from them
45Reactions of Epoxides
- Treatment of an epoxide with lithium aluminum
hydride, LiAlH4, reduces the epoxide to an
alcohol - the nucleophile attacking the epoxide ring is
hydride ion, H-
O
1-Phenylethanol
4611.10 Ethylene Oxide
- ethylene oxide is a valuable building block for
organic synthesis because each of its carbons has
a functional group
47Ethylene Oxide
- part of the local anesthetic procaine is derived
from ethylene oxide - the hydrochloride salt of procaine is marketed
under the trade name Novocaine
48Epichlorohydrin
- The epoxide epichlorohydrin is also a valuable
building block because each of its three carbons
contains a reactive functional group - epichlorohydrin is synthesized from propene
49Epichlorohydrin
- the characteristic structural feature of a
product derived from epichlorohydrin is a
three-carbon unit with -OH on the middle carbon,
and a carbon, nitrogen, oxygen, or sulfur
nucleophile on the two end carbons
50Epichlorohydrin
- an example of a compound containing the
three-carbon skeleton of epichlorohydrin is
nadolol, a b-adrenergic blocker with vasodilating
activity
5111.11 Crown Ethers
- Crown ether a cyclic polyether derived from
ethylene glycol or a substituted ethylene glycol - the parent name is crown, preceded by a number
describing the size of the ring and followed by
the number of oxygen atoms in the ring
52Crown Ethers
- The diameter of the cavity created by the
repeating oxygen atoms is comparable to the
diameter of alkali metal cations - 18-crown-6 provides very effective solvation for
K
5311.12 A. Thioethers
- The sulfur analog of an ether
- IUPAC name select the longest carbon chain as
the parent and name the sulfur-containing
substituent as an alkylsulfanyl group - common name list the groups bonded to sulfur
followed by the word sulfide
54Nomenclature
- Disulfide contains an -S-S- group
- IUPAC name select the longest carbon chain as
the parent and name the disulfide-containing
substituent as an alkyldisulfanyl group - Common name list the groups bonded to sulfur and
add the word disulfide
55B. Preparation of Sulfides
- Symmetrical sulfides treat one mole of Na2S with
two moles of a haloalkane
56Preparation of Sulfides
- Unsymmetrical sulfides convert a thiol to its
sodium salt and then treat this salt with an
alkyl halide (a variation on the Williamson ether
synthesis)
57C. Oxidation Sulfides
- Sulfides can be oxidized to sulfoxides and
sulfones by the proper choice of experimental
conditions
58End of Chapter 11