Reactions of Alcohols

Because alcohols are easily synthesized and easily transformed into other compounds, the
y serve as important intermediates in organic synthesis. A multistep synthesis may use G
rignard-like reactions to form an alcohol with the desired carbon structure, followed by r
eactions to convert the hydroxyl group of the alcohol to the desired functionality. The m
ost common reactions of alcohols can be classified as oxidation, dehydration, substitution
, esterification, and reactions of alkoxides.

Oxidation
Alcohols may be oxidized to give ketones, aldehydes, and carboxylic acids. These functi
onal groups are useful for further reactions; for example, ketones and aldehydes can be
used in subsequent Grignard reactions, and carboxylic acids can be used for esterification
. Oxidation of organic compounds generally increases the number of bonds from carbon
to oxygen (or another electronegative element, such as a halogen), and it may decrease t
he number of bonds to hydrogen.

Oxidizing a primary alcohol only as far as the aldehyde stage is more difficult because
of the ease with which aldehydes are oxidized to acids. Special reagents have been devel
oped to convert primary alcohols to aldehydes. Pyridinium chlorochromate, often abbrevi
ated PCC, is a milder oxidant than chromic acid and oxidizes most primary alcohols to
aldehydes. PCC is a complex of chromium trioxide (CrO3) with pyridine (C5H5N) and h
ydrogen chloride (HCl), written as pyridine ∙ CrO3 ∙ HCl.

Biological oxidation
All substances are toxic if taken in large enough quantities, and alcohols are no exceptio
n. Although ethanol is less toxic than methanol, it is nonetheless a poisonous substance,
and many people die each year from ethanol poisoning. When someone is suffering from
mild ethanol poisoning, the person is said to be intoxicated. Because animals often cons
ume food that has fermented and contains ethanol, their bodies have developed methods
to remove or detoxify ethanol before it can accumulate and poison the brain. One way t
he body detoxifies ethanol is to oxidize it, using an enzyme produced by the liver, alcoh
ol dehydrogenase, or ADH. Alcohol dehydrogenase catalyzes the oxidation of ethanol to
acetaldehyde, which is further oxidized to acetic acid (as the acetate ion), a normal meta
bolite. The actual oxidizing agent is the oxidized form of nicotinamide adenine dinucleot
ide, NAD+.
A
d
The body’s vresponse to simple alcohols is to oxidize them. This strategy works well wit
h ethanol, because
e the product is acetate, a normal metabolite. When other alcohols are i
ngested, however,
r oxidation may lead to other toxic products. For example, oxidation of
methanol produces
t formaldehyde and subsequently formic acid (as the formate ion); both
i
s
e
m
e
 of these products are more toxic than methanol itself. Ethylene glycol (automotive antifr
eeze) is oxidized to oxalic acid (as the oxalate ion), the toxic compound found in rhubar
b leaves and many other plants. Ethylene glycol has a sweet taste, and many dogs and c
ats are poisoned each year by drinking automotive antifreeze that has been carelessly dis
carded.

One common treatment for methanol or ethylene glycol poisoning is to give the patient i
ntravenous infusions of diluted ethanol. The ADH enzyme is kept occupied by oxidizing
ethanol to acetic acid, giving the kidneys time to excrete most of the methanol or ethyle
ne glycol before it is oxidized to more toxic compounds. This is an example of competit
ive inhibition of an enzyme.

Dehydration to alkenes
Converting an alcohol to an alkene requires removal of the hydroxyl group and a hydrog
en atom on the neighbouring carbon atom. Because the elements of water are removed, t
his reaction is called a dehydration. Dehydrations are most commonly carried out by war
ming the alcohol in the presence of a strong dehydrating acid, such as concentrated sulfu
ric acid.
A
d
Most alcohol
v
dehydrations take place by the mechanism shown below. Protonation of the
hydroxyle group allows it to leave as a water molecule. The species that remains has a c
arbon atom
r with only three bonds and a positive charge and is called a carbocation. This
intermediate
t species can be stabilized by loss of a proton from a carbon atom adjacent
i
to the positively charged carbon ion, giving the alkene.
s
Because ethey involve carbocation intermediates, alcohol dehydrations go more quickly an
m
d easily eif they form relatively stable carbocations. More highly substituted carbocations
are moren stable (3° > 2° > 1°); therefore, more highly substituted alcohols undergo dehy
dration more
t readily than less highly substituted alcohols (3° > 2° > 1°). Carbocations c
an undergo rearrangements in which an alkyl group, aryl group, or hydrogen atom, along
with its bonding electrons, shifts to the positively charged carbon atom to form a more
stable species. Rearrangements are thus a common nuisance in alcohol dehydrations. If
more than one alkene can be formed in a dehydration, the major product is usually the p
roduct with the most highly substituted double bond (Saytzeff’s rule).

Dehydration to ethers
Under carefully controlled conditions, simple alcohols can undergo intermolecular dehydr
ation to give ethers. This reaction is effective only with methanol, ethanol, and other sim
ple primary alcohols, but it is the most economical method for making ethyl ether (also
known as diethyl ether), an important industrial solvent.
Substitution to form alkyl halides
Alkyl halides are often synthesized from alcohols, in effect substituting a halogen atom f
or the hydroxyl group. Hydrochloric (HCl), hydrobromic (HBr), and hydroiodic (HI) acid
s are useful reagents for this substitution, giving their best yields with tertiary alcohols.
Thionyl chloride (SOCl2), phosphorus tribromide (PBr3), and phosphorus triiodide (genera
ted from phosphorus, P, and molecular iodine, I2) are also useful for making alkyl chlori
des, bromides, and iodides, respectively.

Esterification
Alcohols can combine with many kinds of acids to form esters. When no type of acid is
specified, the word ester is assumed to mean a carboxylic ester, the ester of an alcohol
and a carboxylic acid. The reaction, called Fischer esterification, is characterized by the
combining of an alcohol and an acid (with acid catalysis) to yield an ester plus water.

Under appropriate conditions, inorganic acids also react with alcohols to form esters. To
form these esters, a wide variety of specialized reagents and conditions can be used.

Acidity of alcohols: formation of alkoxides

Alcohols are weak acids. The most acidic simple alcohols (methanol and ethanol) are ab
out as acidic as water, and most other alcohols are somewhat less acidic.

A strong base can deprotonate an alcohol to yield an alkoxide ion (R―O−). For example
, sodamide (NaNH2), a very strong base, abstracts the hydrogen atom of an alcohol. Met
allic sodium (Na) or potassium (K) is often used to form an alkoxide by reducing the pr
oton to hydrogen gas.

Alkoxides can be useful reagents. For example, the most common synthesis of ethers inv
olves the attack of an alkoxide ion on an alkyl halide. This method is called Williamson
ether synthesis.