General chemistry

–
Introduction to
Organic & Inorganic Chemistry

Electronic effects, aromaticity

acids and bases
Dr. Armen Panossian
Part 3, 2023
1
 Part 3 – Topics

1. Covalent bonds and electronic effects

2. Covalent bonds and aromaticity

3. Covalent bonds and hyperconjugation

4. Electronic effects of substituents

5. Electronic effects and intermediates

6. Acids and bases

2
 Covalent bonds – Electronic effects

Increasing DEN

M+ X:– d+Y :Xd– X:X

Ionic bond Polarized covalent bond Unpolarized covalent
bond

Red =
Electron-rich region.

Blue =
Electron-poor region.

3
(Electrosta+c poten+al plots of CH3Cl and CH3Li)
 Covalent bonds – Electronic effects
Induc@ve effects
Dissymmetry of electronic repar@@on of a covalent bond can be prolonged to
neighbouring atoms along several s bonds. These effects, called induc@ve effects, become
weaker along the chain.
H2 Polariza@on of the C-Cl bond induces a polarisa@on of
H3C > C >> Cl
the neighboring C-C bond: This is the induc,ve effect.
𝛅 𝛅 𝛅

Increasing –I effect
effet -I croissant Increasing +I effect
effet +I croissant
H
+ NHR
NR3 NO2 X CR3 Metal
OR
F>Cl>Br>I CR3> CHR2>CH2R> CH3 4
SR
 Covalent bonds – Electronic effects
Resonance and mesomeric effect

Displacement of p electrons or lone pairs leads to electron-rich or electron-poor sites within

the molecule. This is the mesomeric effect.

+
O O + O

Increasing –M effect Increasing +M effect

NO2 SO2R COR, CO2R CONHR CN X OCOR NHR, OR O⊖

5
 Covalent bonds – Electronic effects
Resonance and mesomeric effect

Resonance forms of the phenolate anion (+M effect of the nega@vely charged oxygen atom)

O O O The negative charge is

delocalized on the
whole molecule (atoms
marked in red)

not the same! O

O O

etc.

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 Covalent bonds – Electronic effects
Resonance and mesomeric effect

Resonance forms of the benzylic cation (–M effect of the positively charged carbon atom)

CH2 CH2 CH2 The posi@ve charge is

delocalized on the
whole molecule (atoms
marked in blue)

not the same! O

CH2 CH2

etc.

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 Covalent bonds – Electronic effects
Inductive and mesomeric effects of common functional groups
Inductive effect Mesomer effect
+I -I +M -M
F SH O– NO2
O– NR3+
S– SO2R
COO– SR2 + Cl SR
NHR COR
CR3 NH3+ Br OH
NHCOR COOR
CHR2 NO2 I C ≡ CR
OR CONHR
CH2R SO2Ar OAr Ar OCOR CN
CH3 CN COOR CH = CHR SR
D SOR OR X (F, Cl,
Br, I)
COOH COR
NO
Remarks Ar
- Halogens (X) have an aTrac@ng induc@ve effect but a donor CH = CHR
mesomeric effect. C ≡ CR
- Some groups can be mesomeric donors or aTractors depending
on the circumstances. 8
 Covalent bonds – Aromaticity
Molecular formula of benzene: C6H6

Resonance in Benzene

not the same!

etc.

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 Covalent bonds – Aromaticity
The s system for benzene

C=C : 1.34 < C-C benzene < C-C : 1.470

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 Covalent bonds – Aromaticity
The p system for benzene

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 Covalent bonds – Aromaticity
Aroma@c Requirements

Hückel’s Rule
• If the compound has a continuous ring of overlapping p
orbitals which are occupied by 4N + 2 electrons, it is aromatic
(with N = 0, 1, 2, 3…).
👉 Note that these p orbitals can be used in double bonds, or
be occupied by lone pairs, or be vacant!
6 (= 4x1 + 2) electrons (⚠ not 4N+2 electron pairs!!!)
in con,guous and parallel p orbitals on a ring => cyclic p system

• If the compound has a continuous ring of overlapping p

orbitals occupied by 4N electrons, it is antiaromatic.

B
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 Covalent bonds – Aromaticity
Aromatic Requirements

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 Covalent bonds – Aromaticity
Aromatic Requirements

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 Covalent bonds – Aromaticity
Aromatic Requirements

Pyridine
• Heterocyclic aromaFc compound.
• Nonbonding pair of electrons in sp2 orbital, so weak base,
pKb = 8.8.

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 Covalent bonds – Aromaticity
Aroma@c Requirements
Pyrrole
Also aromatic, but lone pair of e- is delocalized, so much weaker base.
H
N H + H 2O N + HO
H

looks like sp3 sp3

but is in fact sp2
pyrrole N-protonated pyrrole
pKb = 13.6 pKa = 0.4
(weak base) (strong acid)

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 Covalent bonds – Aromaticity
Aromatic Requirements

Other Heterocyclics

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 Covalent bonds – Aromaticity
Aromatic Requirements

Fused Ring Hydrocarbons

• Naphthalene — 10e– (not 12e–) in two separate rings

• Anthracene

• Phenanthrene 24
 Covalent bonds – Hyperconjugation
Carbocation stabilization via hyperconjugation

Hyperconjugation in a carbocation is an overlapping between a vacant p orbital of a carbon

atom with a neighbouring s molecular orbital (C-H bond).

sp2

The charge of the tert-butyl ca@on

F is delocalized on the 3 methyl
groups (blue color is less intense
on the central carbon atom)

The positive charge of the methyl cation C is localized

Carboca,on
on the carbon atom (deep blue on the carbon atom).
stabiliza,on 25
 Electronic effects and reacHon intermediates
Carboca@ons

Structure
R3
R1 C C is sp2 hybridized, with a vacant p orbital
R2

Stability
Carbocations are stabilized when their electronic deficiency is compensated by some
donor inductive (+I) or donor mesomer (+M) effects or by positive hyperconjugation.

H3C H3C +
+ + + +
H3C C > CH > CH CH > CH3 R O C + R O C
3 2

H3C H3C

+ +
C C C + +C C C RO C RO C

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 Electronic effects and reacHon intermediates
Radicals

Formation
Radicals are formed by homolytic cleavage of a covalent bond. Heteroatomic bonds are
easily cleaved by heating or irradiation.
O O O O
D Ph + CO2
R 2
R O O R O Ph O

hn C C
Cl 2 Cl C C + R
Cl
R

Structure, stability and reactivity

C is sp2 hybridized, with a single

R3
electron occupying the p orbital The same rules of stability
R1 C
(other C radicals with different than for carbocations
R2
hybridization or occupation of
orbitals also exist)

Radicals are generally electrophilic intermediates. 28

 Electronic effects and reaction intermediates
Radical stabilization via hyperconjugation

H3C-H ® CH3. + H. DH = 438 kJ

CH3CH2-H ® CH3CH2. + H. DH = 420 kJ

(CH3)2CH-H ® (CH3)2CH. + H. DH = 401 kJ

(CH3)3C-H ® (CH3)3C. + H. DH = 390 kJ

Stability order of radicals:

ter@ary > secondary > primary > methyl

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 Electronic effects and reacHon intermediates
Radical stabiliza@on via hyperconjuga@on

Overlapping between a p orbital occupied by one electron and a C–H s bond of the
neighbouring alkyl group leads to a delocalization of electrons

H H H
H
H
H H H
H H
H H
Ethyl radical iso-Propyl radical
H H
H

H H
H
H H
tert-Butyl radical 30
 Electronic effects and reacHon intermediates
Carbanions
R2
Structure R1 C C
C C C
R3 R1 R3
R1
R2

sp3 carbanion sp2 carbanion sp carbanion

Stability
- Carbanions are stabilized by aTrac@ve induc@ve effect -I (Cl3C), aTrac@ve mesomer
effect -M (PhCH2-, CH2=CH-CH2- ...) and/or by nega@ve hyperconjuga@on.

- Carbanions are also stabilized when the percentage of s character of the orbital
containing the lone pair of e– increases: The s orbital is lower in energy than the p orbital,
consequently the sp hybrid orbital is more stable than hybrid sp2, which is itself more
stable than hybrid orbital sp3.
E

2p 2p 2p Hybridization 2p 2p 2p

sp3 sp3 sp3 sp3

sp2 sp2 sp2
sp sp
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2s
 Covalent bonds – Hyperconjugation
Stabilization via hyperconjugation

In fact, there are more than one type of hyperconjugation.

Hyperconjuga@on in a carboca@on is an example of posi6ve hyperconjuga6on, where an
empty (or par@ally empty) p orbital or p* orbital overlaps with a neighbouring filled bonding
s molecular orbital. σ→p σ→π*
overlap overlap

unfilled p orbital filled σ orbital unfilled π* orbital filled σ orbital

But there is also nega6ve hyperconjuga6on, where a filled non-bonding or p orbital

overlaps with a neighbouring an,bonding s* molecular orbital.
n→σ* π→σ*
overlap overlap
filled n orbital unfilled σ* orbital filled π orbital unfilled σ* orbital

But there is also neutral hyperconjugation, which blends positive and negative
hyperconjugations. 34
 So what with all these
orbitals and
electronic effects
⁉

Prediction of the properties of molecules

Example: acid-base behavior

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 Acids and bases
Brønsted-Lowry Acids and Bases

• A Brønsted-Lowry acid is a proton donor.

• A Brønsted-Lowry base is a proton acceptor.
• H+ = proton

Examples of Brønsted–Lowry acids and bases

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 Acids and bases
Brønsted-Lowry Acids and Bases

Some molecules contain both hydrogen atoms and lone pairs and thus, can act either as
acids or bases, depending on the particular reaction. An example is the addictive pain
reliever morphine.

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 Acids and bases
Brønsted-Lowry acid-base reactions

• A Brønsted-Lowry acid-base reac@on consists in the transfer of a proton from an acid to

a base.
• In an acid-base reac@on, one bond is broken, and another one is formed.
• The electron pair of the base B: forms a new bond with the proton of the acid.
• The acid H—A loses a proton, leaving the electron pair in the H—A bond on A.

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 Acids and bases
Brønsted-Lowry acid-base reac@ons

• The movement of electrons in reactions can be illustrated using the curved arrow
notation. Because 2 electron pairs are involved in this reaction, two curved arrows are
needed.
• Loss of a proton from an acid forms its conjugate base.
• Gain of a proton by a base forms its conjugate acid.
• A double reaction arrow is used between starting materials and products to indicate that
the reaction can proceed in the forward and reverse directions. These are equilibrium
arrows.
Examples

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 Acids and bases
Acid strength and pKa

• Acid strength is the tendency of an acid to donate a proton.

• The more readily a compound donates a proton, the stronger an acid it is.
• Acidity is measured by an equilibrium constant.
• When a Brønsted-Lowry acid H—A is dissolved in water, an acid-base reaction occurs, and
an equilibrium constant can be written for the reaction.

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 Acids and bases
Acid strength and pKa

Because the concentration of the solvent H2O is essentially constant, the equation can be
rearranged and a new equilibrium constant, called the acidity constant, Ka, can be defined.

It is generally more convenient when describing acid strength to use “pKa” values rather
than Ka values.

E O
R1
O

O R2CO2H is more acidic than R1CO2H

R2
O

👉 The more stable the conjugate base, the more acidic the acid.
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 Acids and bases
Acid strength and pKa

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 Acids and bases
Factors that determine acid strength

• Anything that stabilizes a conjugate base A:(–) makes the starting acid H—A more
acidic.
• Four factors affect the acidity of H—A. These are:
A) Element effects
B) Inductive effects
C) Resonance effects
D) Hybridization effects
• No matter which factor is discussed, the same procedure is always followed. To
compare the acidity of any two acids:
o Always draw the conjugate bases and compare them!!!
o Determine which conjugate base is more stable.
o The more stable the conjugate base, the more acidic the acid.

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 Acids and bases
Factors that determine acid strength

A) Element effects—Trends in the Periodic Table.

A-1) • Across a row of the periodic table, the acidity of H—A increases as the
electronega@vity of A increases.
This is due to the beTer stabiliza@on of the nega@ve charge on the conjugate base by a
more electronega@ve atom.

A-2) • Positive or negative charge is stabilized when it is spread over a larger volume.

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 Acids and bases
Factors that determine acid strength

A) Element effects—Trends in the Periodic Table.

A-2) (continued)
• Down a column of the periodic table, the acidity of H—A increases as the size of A
increases. Size, and not electronega@vity, determines acidity down a column.

A) Element effects—Summary

• The acidity of H—A increases both left-to-right across a row and down a column of the
periodic table.
• Although four factors determine the overall acidity of a particular hydrogen atom,
element effects—the identity of A—is the single most important factor in determining
the acidity of the H—A bond.
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 Acids and bases
Factors that determine acid strength

B) Induc,ve effects
• An induc@ve effect is the pull of electron density through s bonds caused by
electronega@vity differences between atoms.

In the example below, we note that 2,2,2-trifluoroethanol is more acidic than ethanol.

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 Acids and bases
Factors that determine acid strength

B) Inductive effects
B-1) Donor inductive effect (+I)

R— H— H3C— H3C-CH2-CH2—
R—CO2H
pKa 3.75 4.76 4.82

👉 The alkyl group exerts a +I effect which diminishes acidity

B-2) ATrac,ve induc,ve effect (–I)

O
R— I— Br— Cl— F– N
R—CH2-CO2H O
pKa 3.17 2.90 2.87 2.59 1.68

👉 The –I effect leads to an increase of acidity

👉 The –I effect increases with the electronega6vity of the atom or with its charge
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 Acids and bases
Factors that determine acid strength

B) Induc,ve effects
B-3) Influence of the number of electronegative atoms

x 1 2 3
ClxH3-xC—CO2H
pKa 2.87 1.26 0.63

👉 The –I effect increases with the number of electronegative atoms

B-4) Propaga,on of the induc,ve effect

H2 H H H2 H2 H2
R— H 3C C C H 3C C C H 2C C C
R—CO2H Cl Cl Cl
pKa 2.86 4.05 4.53

👉 The inductive effect fades out with the number of sC–C bonds
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 Acids and bases
Factors that determine acid strength

C) Resonance effects
• In the following example,
we note that acetic acid is
more acidic than ethanol.

• Comparison of conjugate bases

• The acidity of H—A

increases when the
conjugate base A:¯ is
stabilized by resonance. 49
 Acids and bases
Factors that determine acid strength

C) Resonance effects
• Electrostatic potential plots of CH3CH2O¯ and CH3COO¯ below indicate that the
negative charge is concentrated on a single O in CH3CH2O¯, but delocalized over both
of the O atoms in CH3COO¯.

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 Acids and bases
Factors that determine acid strength

C) Resonance effects
O O O
H H
CH2
H3C H
O
O H
pKa 16 4,8 18 10

The conjugated base is stabilized by resonance in the case of ace@c acid and phenol.

OH O O O O

B
+ BH

R R R R R

NH2 OMe CH3 H COCH3 CN NO2 +

R N(CH3)3
pKa 11,28 10,86 10,25 9,89 8,79 8,56 8,24 8,08

+M +M +I -M -M -M -I

The attractive effect of the para substituent increases the acidity of phenol. The donating
effect decreases it.
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 Acids and bases
Factors that determine acid strength

D) Hybridiza,on effects

Let us consider the rela@ve acidi@es of three different compounds containing C—H bonds.

• The higher the percent of s-character of the hybrid orbital, the closer the lone pair is
held to the nucleus, and the more stable the conjugate base.

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 Acids and bases
Factors that determine acid strength

D) Hybridization effects

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 Acids and bases
Factors that determine acid strength

Summary of the factors that determine acidity

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 Acids and bases
Lewis acids and bases

• The Lewis definition of acids and bases is more general than the Brønsted-
Lowry definition.
• A Lewis acid is an electron pair acceptor.
• A Lewis base is an electron pair donor.

• Lewis bases are structurally the same as Brønsted-Lowry bases. Both have an
available electron pair—a lone pair or an electron pair in a p bond.
• A Brønsted-Lowry base always donates this electron pair to a proton, but a
Lewis base donates this electron pair to anything that is electron deficient.

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 Acids and bases
Lewis acids and bases

• A Lewis acid must be able to accept an electron pair, but there are many ways
for this to occur.
• All Brønsted-Lowry acids are also Lewis acids, but the reverse is not necessarily
true.
o Any species that is electron deficient and capable of accepting an electron
pair is also a Lewis acid.
• Common examples of Lewis acids (which are not Brønsted-Lowry acids) include
BF3 and AlCl3. These compounds contain elements in group 3A of the periodic
table that can accept an electron pair because they do not have filled valence
shells of electrons.

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 Acids and bases
Lewis acids and bases

• Any reaction in which one species donates an electron pair to another species
is a Lewis acid-base reaction.
• In a Lewis acid-base reaction, a Lewis base donates an electron pair to a Lewis
acid.
• Lewis acid-base reactions illustrate a general pattern in organic chemistry.
Electron-rich species react with electron-poor species.
• In the simplest Lewis acid-base reaction one bond is formed and no bonds are
broken. This is illustrated in the reaction of BF3 with H2O. H2O donates an
electron pair to BF3 to form a new bond.

59
 Acids and bases
Lewis acids and bases

• A Lewis acid is also called an electrophile.

• When a Lewis base reacts with an electrophile other than a proton, the Lewis
base is also called a nucleophile. In this example, BF3 is the electrophile and
H2O is the nucleophile.

electrophile nucleophile

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 Acids and bases
Lewis acids and bases

61
 Acids and bases
Lewis acids and bases in biology

• The heme group of hemoglobin can

interact with O2 and CO.

• The Fen+ ion in hemoglobin is a Lewis acid.

• O2 and CO can act as Lewis bases.

Heme group

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