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CHAPTER 9
Further Reactions of Alcohols and
the Chemistry of Ethers
A variety of reaction modes are available to alcohols.
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9-1
Reactions of Alcohols with Base: Alkoxides
Strong bases are needed to deprotonate alcohols completely.
Base strength must be stronger than that of the alkoxide.
Alkali metals also deprotonate alcohols, but by reduction of H+.
Vigorous:
Less Vigorous:
Relative reactivities:
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Uses for alkoxides:
Hindered alkoxides
E2 reactions with haloalkanes to form alkenes.
Less hindered alkoxides
SN2 reactions with haloalkanes to form ethers.
9-2
Reactions of Alcohols with Strong Acids:
Alkyloxonium Ions in Substitution and
Elimination Reactions of Alcohols
Water has a high pKa (15.7) which means that its conjugate base,
OH- is an exceedingly poor leaving group.
The –OH group of an alcohol must be converted into a
better leaving group for alcohols to participate in substitution
or elimination reactions.
Protonation of the hydroxy substituent
of an alcohol to form an alkyloxonium
ion converts the –OH from the poor
leaving group, OH-, to the good
leaving group, H2O.
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Primary bromoalkanes and iodoalkanes can be prepared by
the reaction with HBr and HI. Chloroalkanes cannot be prepared
by this method because Cl- is too poor a nucleophile.
Secondary and tertiary alcohols undergo
carbocation reactions with acids: SN1 and E1.
Primary alkyloxonium ions undergo only SN2 reactions with acid.
Their carbocation transition state energies are too high to allow
SN1 and E1 reactions under ordinary laboratory conditions.
Secondary and tertiary alkyloxonium ions lose water when treated
with acid to form a carbocation.
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When good nucleophiles are present, the SN1 mechanism
predominates.
Here the tertiary carbocation is generated at a relatively low
temperature, which prevents the competing E1 reaction.
At higher temperatures, or in the absence of good nucleophiles,
elimination becomes dominant.
Secondary alcohols show complex behavior when treated with
HX, following SN2, SN1, and E1 pathways.
Relatively hindered (compared to primary alcohols):
Retarded SN2 reactivity
Slow to form carbocations (compared to tertiary alcohols):
Retarded SN1 reactivity.
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E1 reactions of alcohols (dehydrations) result in the formation of
alkenes. Non-nucleophilic acids, such as H3PO4 or H2SO4, are
used in this case, rather than the nucleophilic acids, HBr and HI.
Dehydrations of tertiary alcohols often occur just above room
temperature.
Summary
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9-3
Carbocation Rearrangements
Hydride shifts give new SN1 products.
Treatment of substituted secondary alcohols produces
unexpected results:
Rearrangement of an initial secondary carbocation to the more
stable tertiary carbocation by a hydride shift results in a
rearranged product.
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Hydride shifts are very fast (faster than SN1 or E1) which is
partially due to hyperconjugation in the carbocation weakening
the C-H bond):
1o carbocations are too unstable to be formed by rearrangement.
2o or 3o carbocations equilibrate readily, leading to a
mixture of products when trapped by a nucleophile.
Carbocation rearrangement takes place regardless of the
precursor leading to the carbocation.
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Carbocation rearrangements also give new E1 products.
Under conditions favoring elimination (elevated
temperatures and non-nucleophilic media), carbocations can
also rearrange to give rearranged products.
Other carbocation rearrangements are due to alkyl shifts.
Alkyl shifts, rather than hydride shifts, can occur when a
carbocation lacks a suitable secondary or tertiary hydrogen next
to the positively charged carbon.
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Alkyl and hydride shifts are faster when leading to a tertiary
carbocation than when leading to a secondary carbocation.
In the previous haloalkane rearrangement, movement of an ethyl
group rather than a hydride would result in a secondary rather
than a tertiary carbocation.
Exceptions to this general rule can occur as a result of electronic
stabilization or steric relief.
Primary alcohols may undergo rearrangement.
Alkyl and hydride shifts to primary carbons bearing leaving
groups can occur without the formation of primary carbocations.
Steric hindrance interferes with direct attack by the bromide
ion. Instead, water leaves at the same time as the methyl group
migrates, bypassing the formation of a primary carbocation.
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9-4
Organic and Inorganic Esters from Alcohols
Organic esters are derivatives of carboxylic acids.
Inorganic esters are the analogous derivatives of inorganic acids.
9-4
Organic and Inorganic Esters from Alcohols
Alcohols react with carboxylic acids to give organic esters.
Esterification is the reaction of alcohols with carboxylic acids in
the presence of catalytic amounts of a strong inorganic acid
(H2SO4 or HCl) which yields esters and water.
This is an equilibrium process which can be shifted in either
direction.
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Haloalkanes can be made from alcohols through inorganic esters.
As an alternative to the acid-catalyzed conversions of alcohols into
haloalkanes, a number of inorganic reagents can convert the
alcoholic hydroxyl group into a good leaving group under milder
conditions.
Reaction of PBr3 with a secondary alcohol yields a bromoalkane
and phosphorous acid (all three bromine atoms can be utilized).
Iodoalkanes can be prepared using PI3,
which, because of its reactivity, is
generated from red phosphorous and
iodine in the reaction mixture itself.
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Chloroalkanes are commonly prepared using thionyl chloride
by warming an alcohol in its presence.
An amine such as triethyl amine is usually added to consume
the generated HCl.
Alkyl sulfonates are versatile substrates for substitution
reactions.
Alkyl sulfonates are excellent leaving groups, generated by
the reaction of an alcohol with sulfonyl chloride.
Pyridine or a tertiary amine is used to remove the HCl formed.
Alkyl sulfonates are often crystalline solids and can be isolated
and purified before further reaction.
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The sulfonate group can be displaced by halide ions
(particularly in primary and secondary systems).
The sulfonate group can also be displaced by any good
nucleophile, not just by halide ions as was the case for hydrogen,
phosphorous, and thionyl halides.
9-5
Names and Physical Properties of Ethers
In the IUPAC system, ethers are alkoxyalkanes.
IUPAC:
Ethers are alkanes bearing an alkoxy substituent.
The larger substituent is the stem and the smaller substituent
is the alkoxy group (methoxyethane).
Common Names:
The names of the two alkyl groups are followed by the word
“ether” (ethylmethylether).
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Except for strained cyclical derivatives, ethers are fairly
unreactive and are often used as solvents in organic reactions.
Cyclic ethers are members of cycloalkanes called heterocycles:
one or more carbon atoms have been replaced by a heteroatom.
Cyclic ethers’ names are based on the oxacycloalkane stem:
Oxacyclopropane (oxiranes, epoxides, ethylene oxides)
Oxacyclobutane, Oxacyclopentane (tetrahydrofurans)
Oxacyclohexanes (tetrahydropyrans)
Ring numbering starts on the oxygen atom.
Cyclic polyethers based on the 1,2-ethanediol unit are called
crown ethers. The crown ether 18-crown-6 contains 18 total
atoms and 6 oxygen atoms.
Note that the inside of the ring is electron rich.
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Simple alkoxyalkanes have the same molecular formula as the
equivalent alkanols, CnH2n+2O, but have much lower boiling points
due to the absence of hydrogen bonding.
The smaller alkoxyalkanes are water soluble, however
solubility decreases with increasing hydrocarbon size.
Methoxymethane — completely water soluble
Ethoxyethane —
10% aqueous solution
Polyethers solvate metal ions: crown ethers and ionophores.
Crown ethers can render salts soluble in organic solvents by
chelating the metal cations. This allows reagents such as KMnO4
to act as an oxidizing agent in the organic solvents.
The size of the central cavity can be tailored to selectively bind
cations of differing ionic radii.
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Three-dimensional analogs of crown ethers are polyethers called
cryptands. These are highly selective in alkali and other metal
cation binding.