Terms and Terminologies in

Mechanistic Organic Chemistry

Key words: Acids, bases, nucleophiles, electrophiles,

Hardness-Softness (HSAB) concepts
Introduction

In this module, some very basic terms and terminologies are described.
Historical perspectives and origin of some of the concepts are presented.
Concepts such as electrophiles, nucleophiles, hardness and softness etc., are discussed.

These concepts are of high significance to the following modules under reaction
Mechanisms.
The term acid • It comes from the Latin root ac,
was first used in
the seventeenth meaning sharp, as in acetum i.e.
century. vinegar.

• a characteristic sour taste

Acids have long
been recognized • ability to change the color of
as a distinctive litmus from blue to red
class of
compounds • react with certain metals to
whose aqueous
solutions exhibit produce gaseous H2
the following
properties. • react with bases to form a salt
and water.

First definition • According to his definition, acids

of acid was are substances containing common
given by element which gives that
Antoine compound the acidic nature.
Lavoisier, in • And he postulated that element to
1787.
be oxygen.
In 1811, • By 1830, dozens of oxygen free
Humphrey Davy acids had been discovered.
showed that
muriatic acid • But it was only after 1840, the
(HCl) does not hydrogen theory of acid became
contain oxygen. generally accepted.

In 1890, the • According to his theory, acid is a

Swedish chemist substance containing hydrogen
Svante atom, that can dissociate or ionize,
Arrhenius
formulated the when dissolved in water,
first important producing hydrated hydrogen ion
theory of acids. and an anion.

However, there
are substances • Hence, definition of acid was
which do not modified to “a substance that
contain H, but
still yield H+ yields an excess of hydrogen ions
ions when when dissolved in water.”
dissolved in
water.
 • HCl is a strong acid, it
dissociates completely in water.

H 2O
HCl H3O+ + Cl-

• H2SO4 is a polyprotic acid, it

dissociates completely in water in
two stages.

HCl H2SO4
H2O
H3O+ + HSO4-
H2O
HSO4- H3O+ + SO42-

• Acetic acid is a weak acid, it does

not dissociate completely in water.

H2O
CH3COOH H3O+ + CH3COO-
‘Base’ , as • The word alkali is synonymous
defined by
Arrhenius, is with base. It is of Arabic origin, but
substance that the root word comes from the same
yields excess of Latin kalium i.e., potash
OH- ions when
dissolved in • Alkali more specifically used for
water. those containing OH- ions.

• a bitter taste
The name base • a soapy feeling when applied to the
has long been
associated with a skin
class of • ability to restore the original blue
compounds color of litmus that has been turned
whose aqueous
solutions are red by acids
characterized by • ability to react with acids to form
salts.

NaOH, KOH, H2O

oxides of certain NaOH Na + + OH-
metal and
hydrogen H2O
compound of CaO Ca2+ + 2OH-
certain nonmetals
are classified as H2O
Arrhenius bases. NH3 NH4+ + OH-
Although
Arrhenius gave
useful definition
of acid and base, • acidic nature of FeCl3
he could not • basic nature of NH3, Na2S
justify nature of
certain
substances.

In 1923, a • Danish chemist J.N. Bronsted

theory that is and English Chemist T.M.Lowry,
both simple and put forward, independently, the
more general
was proposed by proton donor-acceptor concept.
two chemists.

According to
this concept,
acid is a proton • Definition makes no reference to
donor whereas the environment in which proton
base is a proton transfer takes place, so that it
acceptor. applies to all kinds of reaction.
Reaction • If the acid is denoted by AH and
between acid
and base is thus the base by B, then we can write a
a proton generalized acid-base reaction as
exchange
reaction. AH + B A - + BH +

• It gives rise to a very important

concept of conjugate acid-base
In this reaction, pair.
the protonated
base formed is • Conjugate pair differ by one
capable of proton.
losing H+ ions in • Conjugate acid and base are in
the solvent. equilibrium in solution.
acid1 + base2 base1 + acid2

Some common conjugate acid-base pairs

Substance Acid Conjugate
base
Thus, the Hydrochloric acid HCl Cl-
protonated base
is another Acetic acid CH3COOH CH3COO-
potential acid Nitric acid HNO3 NO3-
and anion of
first acid is Ammonium NH4+ NH3
another potential chloride
base. Water H2O OH-
Hydronium ion H3O+ H2O
 The stronger an
acid is, the • Table showing examples of
weaker its
strong and week conjugate acid
conjugate base
will be and vice base pairs.
versa.

Many • For example water is a Bronsted-

substances can Lowry base in its reaction with
Proton Acid act as an acid in
one reaction and HCl and an acid in its reaction
as a base in with NH3.
Base another are
called HCl + H2O -----> H3O+ + Cl-
amphoteric. H2O + NH3 -----> NH4+ + OH-

Another • In fact the amino acids usually

important group of
amphoteric species exist in zwitterion form, where the
is the amino acids. proton has transferred from
Each amino acid the carboxyl to the amino group.
molecule contains
an acidic carboxyl NH2
NH 3
group and a basic
amino group. R CH COOH
R CH COO
The Bronsted- • But still it fails to explain
Lowry theory is reactions between substances that
more general show similar features but no
than any that protons are transferred in the
preceded it. reaction.

This deficiency
was overcome by
more general • According to this concept, acid is
concept
proposed by an electron pair acceptor while
American base is an electron pair donor.
chemist, G N
Lewis in 1923.

The acid-base • If acid is denoted by A and base

reaction is by B:, then acid-base reaction
sharing of between them is formation of
electrons
between the adduct A-B.
two. A + B: A B
The principal
advantage of the • Therefore the number of acid-
Lewis theory is
the way it base reactions are also in majority
expands the in relation to this theory.
number of acids.

Various
molecules, ions, • A classical example is formation
etc., can be of adduct between molecules BH3
grouped as acid and NH3.
according to this
theory. BH 3 + :NH3 H3B-NH3

Like BH3, acidic • Al3+, thus exhibits acidic

properties of
various other properties as it can accept lone pair
molecules and of electrons from water molecule
ions can be in the hydration reaction.
explained using
Lewis theory. Al3+ + 6H2O: [Al(H2O) 6]3+
The Lewis acid-
base theory can • In the course of the reaction,
also be used to water molecule acts as a base
explain why donating a pair of electrons to
nonmetal oxides
such as CO2 carbon in CO2 molecule.
dissolve in water CO2 (g) + H2 O H2 CO 3(aq)
to form acids.

The proton (H+) • Ignoring the fact that H+ is

is one of the solvated, acid-base reactions of H+
strongest but can be viewed as formation of
also one of the adduct.
most H+ + OH-
complicated H2O
Lewis acids.
H+ + NH3 NH4+

Nearly all
compounds of • Many Lewis bases are
transition metals multidentate, i.e., they can form
can be viewed several bonds to the Lewis acid.
as a collections These multidentate Lewis bases
of the Lewis
bases. are called chelating agents.
 The acid-base • Reactions like,
nomenclature FeCl3 + Cl- ------> FeCl4-
can create are a little confusing viewed as the
confusion with acid (FeCl3) being a species
Bronsted lacking an octet, (Fe3+) is a neutral
nomenclature.
species.

Molecular orbital The reactions can

• a filled atomic or molecular
be viewed as
interpretation involving the orbital on the base
interaction of
molecular orbitals • an empty atomic or molecular
on the base and the orbital on the acid.
acid.

The filled orbital • Then we refer to the reaction

would be the highest
energy occupied simply as a filled-empty
molecular orbital, interaction or a HOMO-LUMO
the HOMO, and the
empty orbital will be interaction.
the lowest energy H
unoccupied
H H B
molecular orbital,
the LUMO. H
HOMO 1s LUMO 2p
 Substance that yields H+ ACID is a proton donor. ACID is an electron pair
ARRHENIUS THEORY

LEWIS THEORY
BRONSTED-LOWRY THEORY
(H3O+) in solution is an BASE is a proton acceptor.
ACID. acceptor. BASE is an electron pair
donor.
Substance that yields OH- 1. Acid1 ----> H+ + Base1
in solution is a BASE. A + B: -----> A-B
2. Base2 + H+ -----> Acid2
Acid1 + Base2 -----> BF3 + F- -----> BF4-
AH ------> H+ + A- Base1 + Acid2 I2 + I- -----> I3-
BOH ------> B+ + OH- HCl -----> H+ + Cl-
NH3 + H+ -----> NH4+ Acid: species lacking an
HCl + NaOH These are called octet: BH3, CH3+, etc.
is actually conjugate acid-base Base: species with an
H+ + OH- -----> H2O pairs. unshared pair of
electrons: H2O, NH3, H-,
Cl-, etc.
ACID BASE
Hydrogen halides : NaOH, KOH, LiOH
HCl, HBr, HI
Halogen oxyacids : Ba(OH)2, Ca(OH)2,
HClO, HClO2, Mg(OH)2
HClO3, HClO4
H2SO4, HSO3F Al(OH)3
HNO3, H3PO4
Acetic acid,
Benzenesulfonic
acid, PTSA
Oxalic acid
In 1965, Ralph
Pearson • He introduced the hard and soft
attempted to
explain the acid-base (HSAB) principle.
differential
affinity of Lewis • He classified Lewis acids and
bases towards bases as hard, borderline or soft.
Lewis acids.

According to
him, hard acids • This statement is neither an
prefer to explanation or a theory. It is
coordinate to simply a guideline that helps one
hard bases and to qualitatively predict the relative
soft acids to soft
stability of acid-base adducts.
bases.

• The adjectives hard and soft

doesn't mean strong and weak.
Ralph G • Classification in the original
Pearson, JACS, work was mostly based on
85, 3533(1963) equilibrium constants for reaction
of two Lewis bases competing for
a Lewis acid.
In 1968, G.
Klopman • Hard acids bind to hard bases to
quantified give charge controlled ionic
Pearson's HSAB
principle using complexes.
frontier • Soft acids bind to soft bases to
molecular
orbital theory. give FMO controlled covalent
complexes.

In 1983, the
qualitative • A less polarizable atom or ion is
definition of
HSAB was hard.
converted to a
quantitative one • A more easily polarized atom or
by using the idea ion is soft.
of polarizability.

• High positive charge

With these • Small size
modifications, • Not easily polarizable
hard acid is
• High energy LUMO
supposed to be
associated with • No electron pairs in their valence
properties such shells
as • Low electron affinity
• Strongly solvated
 • Low or partial positive charge
• Large size
On the other • Easily oxidized
hand soft acids • Highly polarizable
have properties • Low energy LUMO and large
such as LUMO coefficients
• Electron pairs in their valence
shells

• Low polarizability
Hard bases have • High electronegativity
properties such • Not easily oxidized
as • Low energy HOMO
• Highly solvated

• High polarizability
• Diffuse donor orbital
Soft bases have • Low electronegativity
properties as • Easily oxidized
• High energy HOMO and large
HOMO coefficients
 Characteristic Properties of Hard and Soft acids and bases

Properties Hard Acids Soft Acids Soft Bases Hard Bases

Electronegativity 0.7 – 1.6 1.9 – 2.5 2.1 – 3.0 3.4 – 4.0

Ionic radius (pm) < 90 > 90 > 170 ~ 120

Ionic charges ≥ +3 ≤ +2

Borderline species have intermediate properties. It is not necessary for species to possess all properties.
 HARD SOFT
BORDERLINE
H+, Na+, K+, Li+ Cu+, Ag+, Au+, Tl+, Hg+, Cs+,
Bi2+, Mg2+, Ca2+, Mn2+, Sr2+ Co+
Fe2+, Co2+, Ni2+, Sn2+,
Al3+, Se3+, Ga3+, Gd3+, In3+, Ru2+, Rh3+, Cu2+, Zn2+, Pd2+, Cd2+, Pt2+, Hg2+
La3+ Pb2+, B(CH3)3, SO2, CH3Hg+
Cr3+, Co3+, Fe3+, As3+, Ir3+ NO+, C6H5+ Tl3+, Ti(CH3)3, RH3, InCl3
Si4+, Ti4+, Zr4+, Tb4+, Pu4+, RS+, RSe+, RTe+, BH3
VO2+
2+,
I+, Br+, HO+, RO+
UO2 (CH3)2Sn2+
I2, Br2, INC, etc.
BeMe2, BF3, BCl3, B(OR)3
Trinitrochlorobenzene, etc.
Al(CH3)3, Ga(CH3)3,
In(CH3)3 Chloranil, Quinones, etc.
RPO2+, ROPO2+ Tetracyanoethylene
RSO2+, ROSO2+, SO3 Carbenes

I7+, I5+, Cl7+ M0 (Metal atoms)

Bulk Metals
R3C+, RCO+, CO2, NC+ ACID
HX (Hydrogen bonding
molecules)
 BORDERLINE

Aniline, Pyridine, N3-,

HARD Br- NO2-, SO32-, N2 SOFT

H2O, HO-, F- R2S, RSH, RS-

CH3CO2-, PO43-, SO42- I-, SCN-, S2O32-
Cl-, CO32-, ClO4-, NO3- R3P, R3As, (RO)3P
ROH, RO-, R2O CN-, RNC, CO
NH3, RNH2, N2H4 Ethylene, Benzene
H-, R-

BASE
 The HSAB Principle for Organic and Main Group Chemists

For our purposes main group and organic reaction chemistry the Pearson approach is very
successful when comparing pairs of species:

 Sodium ion, Na+, is harder than the silver ion Ag+

 Copper(II) ion is harder than copper(I) ion

 Alkoxide ions, RO–, are harder than thioanions, RS–

 The nitrogen anion end of the ambidentate cyanide ion, CN–, is harder than the carbon
anion end, NC-

 The ambidentate enolate ion, has a hard oxyanion centre while the carbanion centre is
softer and more nucleophilic

This type of analysis can be very useful in explaining reaction selectivity.

For example, in ring opening reaction of β-propiolactone by nucleophilic Lewis bases, attack
can occur at two positions and nucleophiles exhibit regioselectivity.
 O

O -
Nu(soft) Nu (soft) O

O
(hard)Nu O

-O
Nu (hard)

O O
Harder nucleophiles like alkoxide
ion (RO–) attack the carbonyl carbon. - O
-
O OR
RO

O O
-
Softer nucleophiles like a cyanide NC

ion (NC–) or a thiolate (RS–), -

O NC O
attack the β-alkyl carbon.

O O
-
RS

-
O RS O
In a nucleophilic substitution reaction in which one Lewis base replaces another, for
example, if the acid site is hard, then soft nucleophile will not provide a high rate of
reaction. If the acid is soft, then a soft nucleophile will react more quickly. [Pearson R. G.
and Songstad J, JACS, 1967, 89, 1827.]

Although, it certainly does not say that soft acids do not ever complex with hard bases, or
that hard acids do not form stable complexes with any soft bases.
ELECTROPHILES
AND NUCLEOPHILES
 History
 Terminology
 Examples
 Types
 Key Facts
 • The terms nucleophile and electrophile were introduced
by Christopher Kelk Ingold in 1929, replacing the
terms cationoid and anionoid proposed earlier by A. J. Lapworth in
HISTROY 1925.
• The word nucleophile is derived from nucleus and the Greek
word phile for affinity, while electrophile is derived from electros
meaning electron.

• Electron loving
• electron deficient molecules
Electrophile • attracted to negative charge i.e. high electron density

(E / E+) • bear partial or full positive charge or an open octet

• accepts pair of electrons
• similar to Lewis acid

• deficiency in valence electron shell

Examples O

Positively charged ions H

C
N

O
 H
Polar molecules O δ-
O
valence saturated but contain an atom C δ+ Hδ+ Clδ-
O
from which bonding electron pair can C δ+ O
Brδ− H
be removed as leaving group
H

Polarizable molecules
# easily polarizable bond • Br Br Cl Cl I I
# generates electrophilic end

Neutral molecules with incomplete • Carbenes AlCl3 BF3

octet

• for same electrophilic atom, greater degree of positive charge

Key Facts gives stronger electrophile
e.g. H3C+ > H3Cδ+-Brδ─
 • Nucleus loving
• abundance of electrons i.e. electron rich molecules
Nucleophile • attracted to positive charge i.e. low electron density
• bear partial or full negative charge or pi bond or lone pair of electrons
(Nu: / Nuc)
• donates pair of electrons
• similar to Lewis base

• easily available non-bonding electron pair

Examples Br OH C N
Anions Cl OR HC C
I SR

H H H C H
pi bonds C C
H C C H
C C
H H H C H

H
 Molecules with lone pairs H O
O N
bonding electron pair that can be
H H
donated from bond involved H
H

δ- δ+
Polar molecules H 3C MgBr

• Carbon nucleophiles: alkyl metal halides such as Grignard reagent,

organolithium, organozinc reagents, and anions of a terminal alkyne.
Enolates are also carbon nucleophiles. Enolates are commonly used in
Types of nucleophiles condensation reactions such as Claisen condensation, Aldol
condensation reactions, etc.
• Nitrogen nucleophile: NH3, RNH2, RCN, H2N─, etc.

• Oxygen nucleophiles: H2O, HO─, ROH, RO─, H2O2, COO─, etc.

• Sulfur nucleophiles: hydrogen sulfide and its salts (HS), thiols (RSH),
Types of nucleophiles thiolate anion (RS─), thiocarboxylic acids (RCOSH), dithiocarbonates
(ROCSS─), dithiocarbamates (R2NCSS─), etc.
In general, sulfur is very nucleophilic. Due to its large size, it is
polarizable and its lone pair of electrons are easily accessible.
 • all nucleophiles are bases but not all bases can act as nucleophiles
e.g. lithium diisopropylamide is a very strong base but a very poor
nucleophile
Key Facts • stronger base is stronger nucleophile (same nucleophilic atom)
e.g. HO─ is better nucleophile than H2O
RO─ > HO─ > phenoxide > carboxylate >> alcohol, H2O >>> RSO3─

• nucleophile with negative charge is more powerful than its conjugate

acid
e.g. H2N─ >NH3, HO─ >H2O
Key Facts • nucleophilicity decreases with increasing electronegativity of the
attacking atom (within same period)
e.g. R3C─ > R2N─ > RO─ > F─
H2N─ > RO─ > R2HN─ > ArO─ > NH3 > Py > F─ > H2O > ClO4─

• going down in a group nucleophilicity increases

e.g. I─ >Br─ > Cl─ >> F─
RS─ > RO─
Key Facts • more free nucleophile, more nucleophilicity
e.g. NaOHDMSO >NaOHwater
In water Na+ and HO ─ both are solvated while in DMSO Na+ is
solvated preferably than HO ─, leaving HO ─ as free nucleophile.
 • Steric effect is also important in deciding strength of nucleophile. Less
basic but sterically unhindered nucleophiles have higher nucleophilicity.
e.g. RCH2O─ > R2CHO─ > R3CO─
Key Facts • Nucleophilicity is increased by attached heteroatom that possess free
electron pair (α-effect).
e.g. HO-O─ > H-O─ , H2N-NH2 > H-NH2

• Sometimes not whole molecule, but small region on large molecules

can function as nucleophile or electrophile.
• Some molecules have both electrophilic and nucleophilic regions
Key Facts within them. They often go hand-by-hand.
• More electronegative atom functions as nucleophilic region. It may be
partially negatively charged.

• Similarly, less electronegative atom functions as electrophilic region. It

may be partially positively charged.
e.g. C=O bond
Key Facts • Flow of electrons, in a reaction, is always from nucleophile to
electrophile.
Nu E+
Electrophilic moiety Nucleophilic moiety
H Cl
H Br
H I
H OSO 3H

H OH2
Cl Cl
Br Br
Cl OH
Br OH
RS Cl
Hg (OAc)2

R 2B H