Module 2: Acids and Bases

Substances that taste sour have long been known as acids. Ethanoic (acetic) acid is the essential ingredient
of vinegar, and citric acid contributes to the sour taste of lemons, limes, and other citrus fruit (hence
its name). Citric acid is produced industrially by fermentation of sugar and used on a massive scale as a
flavouring agent and preservative in soft drinks. Bases are compounds which counteract or neutralize acids
and an acid–base reaction is most widely understood simply to involve transfer of a proton from the acid
to the base. The base sodium hydrogencarbonate (bicarbonate) is a familiar domestic item which is taken
orally to relieve the discomfort of ‘acid indigestion’. With tartaric acid (which occurs naturally in various
fruit, especially grapes), sodium bicarbonate is a component of baking powder; the tartaric acid transfers
a proton to the bicarbonate anion, which leads to the liberation of carbon dioxide as tiny bubbles within
the dough and makes it lighter.

The strength of an acid is measured by the equilibrium constant for the reversible proton transfer to the
solvent (usually water) and, since the deprotonated acid is a base, the same equilibrium constant is a
measure of base strength. Factors which affect acid and base strengths are largely the same as those which
affect equilibrium and rate constants of other organic reactions.

Bronsted-Lowry Concept of Acid and Base

As defined by Bronsted in Denmark in the early part of the twentieth century, an acid is a compound which donates a proton (H
+ ) and a base is a compound which can accept a proton. As shown in the reaction below,gaseous hydrogen chloride, HCl,
dissolves in water and immediately reacts by proton transfer in a typical Bronsted acid–base reaction, to give hydrochloric acid.
In this acid dissociation reaction , HCl donates a proton to a water molecule so HCl is an acid and H 2 O is a base. In principle, this
reaction is reversible and, in the reverse direction, the chloride accepts a proton from the oxonium ion H 3 O + (also called
hydronium ion); Cl − is now a base (the conjugate base of HCl) and H 3 O + is an acid (the conjugate acid of H 2 O). In practice,
however, no covalent HCl molecules can be detected at equilibrium in dilute aqueous solution (it is an example of a strong acid.

In another example, ammonia dissolves in water with proton transfer from H 2 O to NH 3 , i.e. the solute ammonia acts as a base
with water acting as solvent and as an acid. The reaction does not dissociate completely since ammonia is a weak base.

Gaseous hydrogen cyanide, HCN, also dissolves in water and reacts as an acid, but the reaction does not proceed to completion;
HCN (the solute) is a weak acid and covalent HCN molecules coexist in aqueous solution with the dissociated acid.

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Lewis Concept of Acid and Base
A more general definition of acids and bases was proposed by Lewis in 1923 with the focus on the electron pair of the base
rather than the proton of the acid; a Lewis base is an electron pair donor and a Lewis acid is an electron pair acceptor . The
central atom in a Lewis acid is able to accept the lone pair of a base into its valence shell and thereby form
a covalent bond between them. Typical Lewis acids include AlCl3 , FeBr3 , ZnCl2 , and BF3 . For example, BF3 with only six valence
electrons on the boron reacts with ammonia, which has a lone pair on the nitrogen, to form an adduct, as shown below. In this
way, the valence needs of both B and N are satisfied when a covalent bond is formed between
them. The shared electron pair of the bond, however, comes wholly from the N, so there is a transfer of charge and the adduct
is dipolar.

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Acid Dissociation Constant and pKa
Dissociation of a Bronsted acid in aqueous solution is an acid–base reaction with a solvent water molecule acting as the base as
shown below for a generic acid, AH. A proton transfers from acid AH to H 2 O to give the conjugate base A − and H 3 O +
(oxonium ion).

The extent of proton transfer when the system achieves equilibrium is expressed by an equilibrium constant, K a , defined in the
conventional way where [AH], [A − ],and [H 3 O + ] stand for the equilibrium concentrations of AH, A − , and H 3 O +. The
equilibrium constant, K a , is called the acid dissociation constant (or acidity constant ), and provides a measure of the acid
strength (or acidity) of a compound, i.e. its effectiveness as a proton donor.

Organic acids are generally weak and K a is correspondingly small. In order to deal conveniently with a wide range of very small
numbers, a logarithmic scale is used and p K a is defined as the negative logarithm of the numerical value of K a . It follows that
the stronger an acid, the smaller its pK a (acids as strong as HCl or H 2 SO 4 have negative p K a values). For the dissociation of
ethanoic (acetic) acid, a typical weak organic acid, K a = 1.74 × 10 –5 mol dm –3 .

Equilibrium in Acid-Base Reactions

Hydrogen chloride dissociates completely in aqueous solution so, expressed rather loosely, equilibrium in the acid–base
reaction of HCl with H 2 O lies far to the right hand side. In other words, HCl is a stronger acid than H 3 O + ,
p K a (HCl) < p K a (H3 O + ),and Cl − is a weaker base than H 2 O.

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On the other hand, ethanoic acid is a weak acid; p K a (CH 3 CO 2 H) > p K a (H 3 O + ) and ethanoate (acetate) is a stronger base
than H 2 O. It dissociates in aqueous solution to only a very small extent; equilibrium lies well over to the left hand side, and
most of the ethanoic acid molecules in aqueous solution are undissociated.

Factors Affecting Acidity and Basicity

1. Electronegativity of the element bearing the acidic Hydrogen
Dissociation of an acid in aqueous solution involves transfer of a proton from the acidic site of the acid to a water molecule to
give the conjugate base of the acid and H 3 O + . However, since H 3 O + is generated in all acid dissociations in aqueous solution,
we can ignore its formation when considering the relative strengths of different acids. The strength of the bond to the
dissociable H in the acidic site, therefore, is a principal factor when considering relative acidities. The p K a values of hydrogen
halides HX decrease (the acidity increases) in the order shown:

The bond strength of H–X decreases as the size of the atom X increases owing to the increasingly poor overlap between the
orbital on X which is involved and the smaller 1s orbital of hydrogen. This trend is also seen in the relative acidities of
H 2 O (p K a = 15.7) and H 2 S (p K a = 7.0).
The conjugate base of any neutral acid XH is an anion, and the stability of the anion, X − , is also a major factor in affecting the
acidity of XH. The more electronegative the atom to which the proton is bonded, the better able it will be to accommodate a
negative charge following dissociation. This trend is illustrated by the increasing acidities of the hydrides of the elements as we
proceed across the second period from left to right.

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In the particular case of carbon, the acidities of ethane, ethene, and ethyne increase in the order shown:

The negative charge of the conjugate bases resides as a lone pair in sp 3 , sp 2 , and sp hybrid orbitals of the carbon, respectively.
As the s character of the orbital increases, the energy level of the hybrid orbital becomes lower and the anion becomes more
stable (electrons are held closer to the nucleus). In other words, the electronegativity of the carbon increases in the
hybridization order: sp 3 -C < sp 2 -C < sp-C as the s character increases from 25 to 33 to 50% along the series, and this leads to
increasing acidity.

2. Charge Delocalization or Resonance Effect

Anions are stabilized by dispersion (delocalization) of negative charge (or electrons). The relative acidities of the oxy-acids of
chlorines are typical:

The higher acidity of carboxylic acids (p K a of AcOH = 4.76) compared with alcohols (p K a of ethanol = 15.9) is also explained
by electron delocalization in the conjugate base of the acid. The negative charge of ethoxide, EtO − is localized on a single O
atom whereas the charge of the carboxylate anion is delocalized symmetrically, and the two oxygen atoms
become equivalent.

Similarly, phenol is more acidic than cyclohexanol because of resonance stabilization of the conjugate base (the phenoxide).

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3. Substituent Effects
When a hydrogen atom on a carbon in a molecule is replaced by another atom or group, the atom or group introduced is called
a substituent and its effects on properties of other parts of the molecule, especially a functional group, are called substituent
effects .
a. Inductive Effects
When a proton is abstracted from an acidic functional group of an uncharged molecule, the conjugate base becomes an anion
and, in the absence of any special effect, the charge resides as a lone pair localized on the functional group. An electron-
withdrawing ( electron- attracting ) group elsewhere in the molecule will stabilize the anion by dispersing the negative charge
and thereby enhance the acidity of the molecule. The highly electronegative chlorine, for example, is a substituent which
stabilizes an anion by attracting electron density.
The p K a values of chloroethanoic acids given below illustrate this effect:

When the methyl hydrogen atoms of ethanoic acid are replaced by chlorine atoms one by one, the acid becomes increasingly
stronger. The origin of this inductive effect is the strong polarization of the C–Cl σ bond.
Inductive effects are transmitted through the σ bonds of a molecule and weaken rapidly as the number of σ bonds between
a substituent and the reaction site increases. This tendency can be seen in a series of chlorobutanoic acids:

Methyl and other alkyl groups are electron donating ( electron releasing ), although the effect is small, so ethanoic acid is less
acidic than methanoic (formic) acid.

b. Resonance Effect or Conjugative Effect

Substituents can also affect the electron distribution within a molecule, and hence its properties, by conjugation. Such effects
of substituents are known as conjugative (or resonance ) effects and are found in molecules (or ions) containing π electron
systems; they can be represented by drawing the contributing resonance forms. The effect is exemplified by the acidity of
nitrophenols. A m -nitro group enhances the acidity of phenol through its inductive effect but a p -nitro group enhances the
acidity even more strongly even though it is further away from the reaction site.

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The negative charge of p -nitrophenoxide ion is delocalized over the molecule as illustrated by a resonance contributor with
direct conjugation between the anionic oxygen and the nitro group through the π system of the benzene ring. Although a lone
pair on the OH of un-ionized p -nitrophenol can also be delocalized by resonance into the NO 2 , this leads to charge separation
which is absent in the corresponding delocalization in the p -nitrophenoxide. Consequently, resonance stabilization is greater in
p -nitrophenoxide than in the p -nitrophenol, and p -nitrophenol is a stronger acid than phenol. For the m -nitro derivative, such
direct conjugation is impossible, and only the inductive electron- withdrawing effect of the nitro group stabilizes the m
nitrophenoxide ion relative to the un-ionized m -nitrophenol.

A p -methoxy substituent is an example of an electron-donating group (EDG) by resonance, in contrast to the electron-
withdrawing inductive effect of the methoxy group (oxygen is an electronegative element). These opposing properties of the
methoxy group are illustrated by the acidities of the methoxybenzoic acids: p -methoxybenzoic acid is weaker than the
unsubstituted benzoic acid, whereas the m -methoxy analogue is stronger than both.

The m -methoxy group can only attract electrons through σ bonds, and this effect is stronger in the anionic conjugate base than
in the carboxylic acid. In contrast, a p -methoxy group can conjugate with the carboxy group of benzoic acid through the π
system of the benzene ring (a lone pair of the methoxy is delocalized to some degree into the carbonyl of the carboxy group).
And because this resonance effect is greater in the carboxylic acid than in the carboxylate anion, the acid is stabilized with
respect to its conjugate base so the acidity is decreased by the p -methoxy substituent.

Carbon Acids and Carbanions

Hydrocarbons in general are extremely weak acids because of the strength and low polarity of the C–H bond. Nonetheless, an
acetylenic hydrogen bonded to an sp-hybridized carbon has a p K a of about 25: ethyne is a stronger acid than ammonia (p K a =
35). Acids which release a proton by heterolysis of the C–H bond are called carbon acids , and the conjugate bases are known as
carbanions which carry a formal negative charge on the carbon. Carbon acids become stronger as the conjugate carbanion
bases are stabilized by electron-withdrawing substituents or by resonance.

Toluene is somewhat more acidic than propene. The conjugate base of toluene is the benzyl anion, which is stabilized by
extensive delocalization of its negative charge.

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The stabilizing conjugative effect of a phenyl attached to a carbanionic centre is cumulative so, if there is an additional phenyl
group, it will further enhance the acidity of the C–H. However, the third phenyl group in the triphenylmethyl (trityl) anion
shows only a small additional effect when the p K a values of diphenylmethane and triphenylmethane are compared.

For greatest stabilization of a π system by conjugation, all the p orbitals involved need to be parallel for maximal sideways
overlap. Consequently, the phenyl group should be coplanar with the sp 2 -hybridized carbon of the carbanionic centre in order
to achieve the highest possible conjugative stabilization (delocalization of electrons). However, a perfectly planar trityl anion
would involve very close proximity of pairs of the six ortho hydrogen atoms of the three phenyl groups; this severe steric strain
is avoided by the three phenyl groups being twisted to give a propeller shape as shown below. Because of this non-planarity,
however, sideways orbital overlap is less than maximal and the additional resonance stabilization arising from the third phenyl
group is weak; triphenylmethane is not as acidic as expected for a planar structure.

The cyclopentadienide anion consists of a five-membered ring with six π electrons. A cyclic six π electron system is aromatic
and this stabilizes the conjugate base, making cyclopentadiene, acidic.

4. Effects of Electron-Withdrawing Group on C-H acidity

When a conjugatively electron-withdrawing group (EWG) is attached to a hydrogen-bearing carbon, the acidity increases
tremendously; examples of such groups include nitro, carbonyl, and cyano. The nitro group is especially effective, and the p K a
of nitromethane is similar to that of phenol. The conjugate base of propanone is an enolate anion, previously encountered as
an allyl anion analogue.

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Carbon acids become stronger (i.e. their conjugate bases become more stable) if two or even three EWGs are bonded to the C
bearing the acidic H.

Basicity of Organic Compounds’

A Bronsted base is always related to its conjugate acid, so the p K a of the conjugate acid can be used as a quantitative measure
of the basicity of a base. If the acid is strong its conjugate base is weak or stable. However, when a compound (B) is uncharged
and the focus is on its base strength with the reaction written below, we usually refer to the p K BH+ of B rather than the p K a of
BH +, but the numerical value is, of course, the same. We see, therefore, that the
larger the value of the p K BH+ , the more basic compound B is.

Nitrogen Bases

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Amines are the most commonly encountered organic bases. For most typical alkylamines, p K BH+ is about 10 , but arylamines
are much weaker (p K BH+ = 4.6 for aniline). This relationship is similar to the one between an alcohol and a phenol except that
some degree of delocalization is possible for the phenol as well as phenoxide.

Aniline is isoelectronic with phenoxide and the benzyl anion. The lone pair on the nitrogen of aniline is delocalized into the
benzene ring as the resonance forms below show. But this is not possible for the protonated form, the anilinium ion, so
appreciable resonance stabilization is lost upon protonation.

Amines are often used as bases in synthetic reactions and, when a simple alkylamine is not suffi ciently basic, modifi ed versions
are available. The p K BH+ values of acetamidine and guanidine are 12.4 and 13.6, respectively, so they are quite strong as
neutral bases in spite of the hybridization of the nitrogen (sp 2 compared with sp 3 of the N in simple alkylamines). The high
basicity of these amines compared with the analogous imines is attributable to the extra resonance stabilization of their
conjugate acids.

Weakly Basic Organic Compounds

Neutral organic compounds which contain heteroatoms such as nitrogen or oxygen have lone pairs capable of being
protonated, and p K BH+ values of representative compounds are given below:

Carbonyl compounds are less basic than alcohols but (very usefully) protonation makes them more electrophilic, i.e. susceptible
to nucleophilic attack; this is the basis of acid catalysis in many reactions of carbonyl compounds with nucleophiles.
The lower basicity of carbonyl oxygens in ketones and esters compared with alcohols and ethers is attributable to the lone pair
on the carbonyl oxygen being in an sp 2 – rather than sp 3 -hybridized orbital—the orbital with the greater s-character holds the
lone pair closer to the nucleus (see Sub-section 6.3.1 for hybridization effects). However, the carbonyl and ether oxygens in an
ester are not independent; protonation of the carbonyl oxygen gives a structure which is resonance stabilized to a degree not
possible following protonation of the ether oxygen. Also, the electron-withdrawing effect of the carbonyl group reduces the
basicity of the ether oxygen of the ester. Consequently, the carbonyl oxygen of an ester is the more basic site.

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Polyfunctional Acids and Bases
Some acids have two or more acidic hydrogens—sulfuric and phosphoric acid are familiar examples.
Dicarboxylic acids are typical diprotic organic acids; some examples and their p K a values are shown below:

When one of the two acidic groups dissociates, the other group acts as a substituent and modifi es the acidity of the fi rst. The
carboxy group –CO 2 H is electron withdrawing, which causes the dissociation of the other to be more favourable than that of
an isolated carboxy group. Dissociation of the second carboxy group is affected by the (slightly) electron- donating carboxylate.
More important, however, this second dissociation involves removal of a proton from an anion, which is more diffi cult than
proton abstraction from a neutral molecule. Consequently, p K a1 <p K a2 and the difference between the two p K a
values is greater when the two acidic groups are closer together. However, proximate carboxy groups can sometimes form an
intramolecular hydrogen bond, especially in the mono-dissociated state. In this event, the fi rst dissociation is further enhanced
and the second is further inhibited because of the strongly stabilized cyclic hydrogen-bonded structure of the mono-dissociated
ion. Scheme 6.1 shows the dissociations of ( E )- and ( Z )-butenedioic acid.

Compounds with two basic groups can be considered in the same way starting with their diprotonated conjugate acids. The p K
a values for conjugate acids of some diamines are shown:

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The ammonio group with a positive charge is strongly electron withdrawing, while the amino group is only weakly so; this
accounts for the large difference between the p K a1 and p K a2 values of the conjugate acids of ethanediamine. The difference
diminishes with the increasing number of intervening CH 2 groups. Some organic compounds have both acidic and basic groups,
and are said to be amphoteric . Amino acids, which are important as constituents of proteins, are typical and glycine is the
simplest example.

In acidic aqueous solution, glycine exists in its protonated form: this is a diprotic acid, and the fi rst dissociation (p K a1 = 2.3) is
of the carboxy group whose acidity is enhanced by the ammonio group. This dissociation gives a zwitterion (or dipolar ion). The
second dissociation (p K a2 = 9.6) is of the ammonio group, which is hardly affected by the carboxylate group. An amino acid as
crystals, or in aqueous solution in the absence of additional acids or bases, is in the zwitterion form.

Carboxylic acids are widespread in nature, often combined with other functional groups. Simple alkyl carboxylic
acids, composed of four to ten carbon atoms, are liquids or low melting solids having very unpleasant odors.
The fatty acids are important components of the biomolecules known as lipids, especially fats and oils.

Saturated Fatty Acids

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Unsaturated Fatty Acids

Naturally Occurring Carboxylic Acids

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Naturally Occurring Amines

Methyl amine (rotten fish); Pyridine (coal tar); Putrescine (rotten meat); Cadaverine (rotten flesh); Amphetamine
(diet aids)

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