MBMB 1212: General Chemistry

Chapter 6

Nomenclature, physical and chemical properties of

Alcohols, ethers and thiols

September – December 2022

Alcohols
 Did you ever wonder…
Veisalgia, the medical term for a
hangover, refers to the unpleasant
physiological effects that result from
drinking too much alcohol. These
effects include headache, nausea,
vomiting, fatigue, and a heightened
sensitivity to light and noise. Hangovers
are caused by a multitude of factors.
These factors include (but are not
limited to) dehydration caused by the
stimulation of urine production, the loss
of vitamin B, and the production of
acetaldehyde in the body. Acetaldehyde
is a product of the oxidation of ethanol.
Oxidation is just one of the many
reactions that alcohols undergo

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 Structure and properties of alcohols
Alcohols are compounds that possess a hydroxyl group (OH) and
are characterized by names ending in “ol”:

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 Alcohols
A vast number of naturally occurring compounds contain the
hydroxyl group. Here are just a few examples

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 Phenols
Phenol is a special kind of alcohol. It is comprised of a hydroxyl
group attached directly to a phenyl ring. Substituted phenols are
extremely common in nature and exhibit a wide variety of
properties and functions, as seen in the following examples

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 Nomenclature of alcohols
Recall that four discrete steps are required to name alkanes,
alkenes, and alkynes.
1. Identify and name the parent
2. Identify and name the substituents
3. Assign a locant to each substituent
4. Assemble the substituents alphabetically
Alcohols are named using the same four steps and applying the
following rules.
• When naming the parent, replace the suffix “e” with “ol” to
indicate the presence of a hydroxyl group:

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 Nomenclature of alcohols
• When choosing the parent of an alcohol, identify the longest
chain that includes the carbon atom connected to the hydroxyl
group:

• When numbering the parent chain of an alcohol, the hydroxyl

group should receive the lowest number possible, despite the
presence of alkyl substituents or π bonds:

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 Nomenclature of alcohols
• The position of the hydroxyl group is indicated using a locant. The
IUPAC rules published in 1979 dictate that this locant be placed
immediately before the parent, while the IUPAC
recommendations released in 1993 and 2004 allow for the locant
to be placed before the suffix “ol.” Both names are acceptable
IUPAC names:

• When a chirality center is present, the configuration must be

indicated at the beginning of the name; for example:

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 Nomenclature of alcohols
• Cyclic alcohols are numbered starting at the position bearing the
hydroxyl group, so there is no need to indicate the position of the
hydroxyl group; it is understood to be at C–1:

• IUPAC nomenclature recognizes the common names of many

alcohols, such as the following three examples:

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 Nomenclature of alcohols
Alcohols are also designated as primary, secondary, or tertiary,
depending on the number of alkyl groups attached directly to the
alpha (α) position (the carbon atom bearing the hydroxyl group).

The word “phenol” is used to describe a specific compound

(hydroxybenzene) but is also used as the parent name when
substituents are attached

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 Skill builder
1. Provide an IUPAC name for each of the following alcohols:

2. Draw the structure of each of the following compounds:

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 Commercially important alcohols
Methanol
Methanol (CH3OH) is the simplest alcohol. It is toxic, and ingestion
can cause blindness and death, even in small quantities. Methanol
can be obtained from heating wood in the absence of air and has
therefore been called “wood alcohol.” Industrially, methanol is
prepared by the reaction between carbon dioxide (CO2) and
hydrogen gas (H2) in the presence of suitable catalysts.
Each year, the United States produces approximately 2 billion
gallons of methanol, which is used as a solvent and as a precursor in
the production of other commercially important compounds.
Methanol can also be used as a fuel to power combustion engines

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 Commercially important alcohols
Ethanol
Ethanol (CH3CH2OH), also called grain alcohol, is obtained from the
fermentation of grains or fruits, a process that has been widely used
for thousands of years. Industrially, ethanol is prepared via the acid-
catalyzed hydration of ethylene. Each year, the United States
produces approximately 5 billion gallons of ethanol, used as a
solvent and as a precursor for the production of other commercially
important compounds. Ethanol that is suitable for drinking is highly
taxed by most governments. To avoid these taxes, industrial-grade
ethanol is contaminated with small quantities of toxic compounds
(such as methanol) that render the mixture unfit for human
consumption. The resulting solution is called “denatured alcohol.”

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 Commercially important alcohols
Isopropanol
Isopropanol, also called rubbing alcohol, is prepared industrially via
the acid-catalyzed hydration of propylene. Isopropanol has
antibacterial properties and is used as a local antiseptic.
Sterilizing pads typically contain a solution of isopropanol in water.
Isopropanol is also used as an industrial solvent and as a gasoline
additive.

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 Physical properties of alcohols
Boiling point

The boiling point of ethanol is much higher than the other two
compounds as a result of the hydrogen-bonding interactions that
occur between molecules of ethanol

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 Commercially important alcohols
Solubility in water
These interactions are fairly strong intermolecular forces, and they
are also critical in understanding how alcohols interact with water

As the size of the hydrophobic region increases, solubility in water

decreases. For example, octanol exhibits extremely low solubility in
water at room temperature. Alcohols with more than eight carbon
atoms, such as nonanol and decanol, are considered to be insoluble
in water

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Chain length as a factor in drug Design

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 Acidity of the hydroxyl functional group

The conjugate base of an alcohol is called an alkoxide ion, and it

exhibits a negative charge on an oxygen atom. A negative charge on
an oxygen atom is more stable than a negative charge on a
carbon or nitrogen atom but less stable than a negative charge on a
halogen, X

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 Acidity of the hydroxyl functional group
Therefore, alcohols are more acidic than amines and alkanes but
less acidic than hydrogen halides (Figure 13.3). The pKa for most
alcohols falls in the range of 15–18.

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Factors affecting the acidity of alcohols and phenols

The factors help us predict the more acidic from a given number of
alcohols.

1. Resonance.
Resonance is a very significant factor affecting the acidity of
alcohols. As a striking example, compare the pKa values of
cyclohexanol and phenol:

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 Factors affecting the acidity of alcohols and phenols
When phenol is deprotonated, the conjugate base is stabilized by
resonance.

This resonance-stabilized anion is called a phenolate, or a phenoxide

ion. Resonance stabilization of the phenoxide ion explains why
phenol is eight orders of magnitude (100,000,000 times) more acidic
than cyclohexanol. As a result, phenol does not need to be
deprotonated with a very strong base like sodium hydride. Instead, it
can be deprotonated by hydroxide.

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 Factors affecting the acidity of alcohols and phenols

The acidity of phenols is one of the reasons that phenols are a special category of
alcohols.

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Factors affecting the acidity of alcohols and phenols

2. Induction
Another factor in comparing the acidity of alcohols is induction. As an
example, compare the pKa values of ethanol and trichloroethanol.

Trichloroethanol is four orders of magnitude (10,000 times) more

acidic than ethanol, because the conjugate base of trichloroethanol
is stabilized by the electron-withdrawing effects of the nearby
chlorine atoms.

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Factors affecting the acidity of alcohols and phenols

3. Solvation effects. To explore the effect of alkyl branching, compare

the acidity of ethanol and tert-butanol.

The pKa values indicate that tert-butanol is less acidic than ethanol,
by two orders of magnitude. This difference in acidity is best
explained by a steric effect. The ethoxide ion is not sterically
hindered and is therefore easily solvated (stabilized) by the solvent,
while tert-butoxide is sterically hindered and is less easily solvated.
The conjugate base of tert-butanol is less stabilized than the
conjugate base of ethanol, rendering tert-butanol less acidic.

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 Factors affecting the acidity of alcohols and phenols
The conjugate base of tert-butanol is less stabilized than the conjugate
base of ethanol, rendering tert-butanol less acidic.

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 Skill builder
For each of the following pairs of alcohols, identify the one that is
more acidic, and explain your choice:

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 Skill builder
Consider the structures of 2-nitrophenol and 3-nitrophenol. These
compounds have very different pKa values. Predict which one has the
lower pKa, and explain why. (Hint: In order to solve this problem, you
must draw the structure of each nitro group.)

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 Oxidation states
• To calculate the formal charge on an atom, we treat all bonds to
that atom as if they were purely covalent, and we break them
homolytically

• For calculating oxidation states, we will take another extreme

approach. We treat all bonds as if they were purely ionic, and we
break them heterolytically, giving each pair of electrons to the
more electronegative atom in each case. Formal charges and
oxidation

• States therefore represent two extreme methods of electron

bookkeeping.

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 Oxidation states

In the figure above, the formal charge of the carbon atom is zero,
because we count four electrons on the central carbon atom,
which is equivalent to the number of valence electrons a carbon
atom is supposed to have. In contrast, the same carbon atom has
an oxidation state of −2, because we count six electrons on the
carbon atom, which is two more electrons than it is supposed to
have 30
 Oxidation states
A carbon atom with four bonds will always have no formal
charge, but its oxidation state can range anywhere from
−4 to +4

A reaction involving an increase in oxidation state is called an oxidation. For

example, when methanol is converted into formaldehyde, we say that methanol
was oxidized. In contrast, a reaction involving a decrease in oxidation state is
called a reduction. For example, when formaldehyde is converted into methanol,
we say that formaldehyde was reduced. Let’s get some practice identifying
oxidations and reductions
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 Skill builder
In each of the following transformations, identify whether the
starting material has been oxidized, reduced, or neither. Try to
determine the answer without calculating oxidation states, and then
use the calculations to see if your intuition was correct.

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 Diols
Diols are compounds with two hydroxyl groups, and the following
additional rules are used to name them:
1. The positions of both hydroxyl groups are identified with numbers
placed before the parent
2. The suffix “diol” is added to the end of the name:

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 Diols
Notice that an “e” appears in between the parent and the suffix. In a
regular alcohol, the “e” is dropped (i.e., propanol or hexanol). A few
simple diols have common names that are accepted by IUPAC
nomenclature

The term glycol indicates the presence of two hydroxyl groups

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35
Reactions of alcohols

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Reactions of alcohols

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Reactions of alcohols

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Ethers
 Ethers
• Ethers are compounds that exhibit an oxygen atom bonded to two
R groups, where each R group can be an alkyl, aryl, or vinyl group.

• The ether moiety is a common structural feature of many natural

compounds, for example:

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 Ethers
Many pharmaceuticals also exhibit an ether moiety, for example:

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 Nomenclature of ethers
IUPAC rules allow two different methods for naming ethers.
1. A common name is constructed by identifying each R group,
arranging them in alphabetical order, and then adding the word
“ether”, for example:

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 Nomenclature of ethers
When the two alkyl groups are identical, the compound is
called a symmetrical ether and is named as a dialkyl
ether.

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 Nomenclature of ethers
A systematic name is constructed by choosing the larger group to
be the parent alkane and naming the smaller group as an alkoxy
substituent.

Systematic names must be used for complex ethers that exhibit

multiple substituents and/or chirality centers

(R)-1,1-Dichloro-3-ethoxycyclopentane
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 Skill builder
1. Provide an IUPAC name for each of the following compounds:

2. Draw the structure of each of the following compounds:

(a) (R)-2-Ethoxy-1,1-dimethylcyclobutane
(b) Cyclopropyl isopropyl ether

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 Structure and properties of ethers
The geometry of an oxygen atom is similar for water, alcohols, and
ethers. In all three cases, the oxygen atom is sp3 hybridized, and
the orbitals are arranged in a nearly tetrahedral shape. The exact
bond angle depends on the groups attached to the oxygen atom,
with ethers having the largest bond angles

However, ethers cannot function as hydrogen bond donors, and

therefore, ethers cannot form hydrogen bonds with each other. As a
result, the boiling points of ethers are significantly lower than their
isomeric alcohols.

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 Structure and properties of ethers

Ethers therefore exhibit dipole-dipole interactions, which slightly

elevate the boiling point relative to propane. Ethers with larger alkyl
groups have higher boiling points due to London dispersion forces
between the alkyl groups on different molecules. This trend is
significant.

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 Structure and properties of ethers
Ethers are often used as solvents for organic reactions, because they
are fairly unreactive, they dissolve a wide variety of organic
compounds, and their low boiling points allow them to be readily
evaporated after a reaction is complete. Below are three common
solvents.

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49
 Cyclic ethers
Cyclic ethers are compounds that contain an oxygen atom
incorporated in a ring. Special parent names are used to indicate the
ring size

We will focus on oxiranes, cyclic ethers containing a three-

membered ring system. This ring system is more reactive than
other ethers because it has significant ring strain. Substituted
oxiranes, which are also called epoxides, can have up to four R
groups. The simplest epoxide (no R groups) is often called by its
common name, ethylene oxide.
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 Cyclic ethers
Epoxides, although strained, are commonly found in nature. The
following are two examples.

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 Naming epoxides
2 ways:
1. The oxygen atom is considered to be a substituent on the parent
chain, and the exact location of the epoxide moiety is identified
with two numbers followed by the term “epoxy.”

2. The parent is considered to be the epoxide (parent = oxirane),

and any groups connected to the epoxide are listed as
substituents

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Thiols
 Thiols
Sulfur is directly below oxygen in the periodic table (in the same
column), and therefore, many oxygen-containing compounds have
sulfur analogs. Sulfur analogs of alcohols contain an SH group in
place of an OH group and are called thiols. The nomenclature of
thiols is similar to that of alcohols, but the suffix of the name is
“thiol” instead of “ol”:

Notice that the “e” is kept before the suffix “thiol.” When another
functional group is present in the compound, the SH group is
named as a substituent and is called a mercapto group:
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 Thiols
Notice that the “e” is kept before the suffix “thiol.” When another
functional group is present in the compound, the SH group is
named as a substituent and is called a mercapto group:

The term “mercapto” is derived from the fact that thiols were once
called mercaptans derived from the Latin mercurium captans
(capturing mercury) and describes the ability of thiols to form
complexes with mercury as well as other metals. This ability is put to
good use by the drug called dimercaprol, which is used to
treat mercury and lead poisoning.
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 Thiols
This ability is put to good use by the drug called dimercaprol, which is
used to treat mercury and lead poisoning

Thiols are most notorious for their pungent, unpleasant odors. Skunks
use thiols as a defense mechanism to ward off predators by spraying a
mixture that delivers a mighty stench. Methanethiol is added to
natural gas so that gas leaks can be easily detected. If you have ever
smelled a gas leak, you were smelling the methanethiol (CH3SH) in the
natural gas, as natural gas is odorless. Surprisingly, scientists who have
worked with thiols report that the nasty odor actually becomes
pleasant after prolonged exposure. The author of this textbook can
attest to this fact.
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 Sulfides
The sulfur analogs of ethers are called sulfides, or thioethers

Nomenclature of sulfides is similar to that of ethers. Common

names are assigned using the suffix “sulfide” instead of “ether.”

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 Sulfides
More complex sulfides are named systematically, much the way ethers
are named, with the alkoxy group being replaced by an alkylthio
group

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