STRUCTURE and

REACTIVITY
Types of Chemical Reactions
Elements of Reaction Mechanisms – Substrates, Conditions, Transition States, Intermediates
Bond Cleavage Mechanisms
Structure and Reactivity of Organic Compounds
Prominent Rules in Reaction Mechanism
Recall: Chemical Reactions
 A chemical reaction is a transformation process which involves the following:
• Bond-breaking (endothermic process, requires energy)
• Bond-forming (exothermic process, releases energy)

 In general, chemical reactions can be classified into 4 different types:

• Combination reactions: bond-formation is dominant over bond-breaking
• Decomposition reactions: bond-breaking is dominant over bond-formation
• Displacement/Substitution reactions: equal bond-breaking and bond-forming processes
• Rearrangement reactions: processes involving changes in the bonding of atoms in a compound

 Chemical reactions can also be classified into these 2 types:

• Exothermic reactions: reactions that release heat
• Endothermic reactions: reactions that absorb heat
Reaction Mechanisms in Organic Chemistry
Term Example
Substrate The chemical of interest
Reagent Interacts with the substrate to produce the desired product
Intermediate A short-lived but observable species that exists only during the reaction
Carbocation A positively-charged carbon center of an intermediate
Carbanion A negatively-charged carbon center of an intermediate
Transition State A theoretical, high-energy state through effective collision of molecules
Product The final form of the chemical of interest after the reaction
Major Product The product that has the highest relative amount after the reaction
Side Product An unwanted product brought about by a side reaction
Reaction Mechanisms in Organic Chemistry
Type Example Subtype
Free-Radical
Addition Electrophilic
Nucleophilic
Bimolecular (E2)
Elimination
Unimolecular (E1)
Nucleophilic (SN1, SN2, SNAr)
Substitution Electrophilic
Free-radical
Alkyl/Methyl Shifts
Rearrangement
Tautomerization
Reaction Mechanisms in Organic Chemistry
Type Example

Oxidation

Reduction

Condensation
Reaction Mechanisms in Organic Chemistry
Bond Cleavage Mechanisms
Type Definition Example

The electron pair is divided between the

Homolysis atoms.
Usually driven by light (radiation)

The electron pair is drawn to one of the

Heterolysis atoms.
Driven by many other factors
Reaction Mechanisms in Organic Chemistry
Type Example

Overall
Reaction

Mechanism
Structure and Reactivity of Organic Compounds
Stability of Alkyl Carbocations and Carbanions
Hyperconjugation is the ability of a certain sigma bond to interact with an adjacent empty
orbital to increase the delocalization of its electron. It provides extra stability for the
compound.
EXAMPLE

Primary carbocations are Secondary carbocations are Tertiary carbocations are

stabilized by only one stabilized by 2 adjacent sp3 stabilized by 3 adjacent sp3
adjacent sp3 orbital orbitals orbitals
Note that hyperconjugation decreases the stability of carbanions.
Structure and Reactivity of Organic Compounds
The following are a result of the effects of hyperconjugation:
1. In order of increasing carbocation stability, CH3+ < R-CH2+ < R2CH+ < R3C+
2. In order of increasing carbanion stability, R3C- < R2CH- < RCH2- < CH3-
3. In order of increasing carbon radical stability, CH3• < R-CH2 • < R2CH • < R3C •
EXAMPLE
The major product is based on the more stable Sometimes, the intermediate rearranges to
intermediate. increase its stability.
Structure and Reactivity of Organic Compounds
Resonance and Inductive Effect:
RESONANCE EFFECT: Stability brought about by an increase in possible resonance forms
INDUCTIVE EFFECT: Stability brought about by presence of electron-withdrawing and
electron-releasing Groups.
EXAMPLE

< <

Phenols are acidic because of the enhanced

The proximity of the chloride to the acidic
stability brought about by the increase in its
hydrogen increases the acidity of the carboxylic
resonance forms after dissociation (increased
acid.
resonance stabilization)
Structure and Reactivity of Organic Compounds
Electron-withdrawing and electron-releasing groups
Electron-withdrawing groups (EWG) draws the electron density towards them, either
inductively or by virtue of resonance. This creates an electron-poor region.
Electron-releasing groups (EWG) draws electron density towards the electron-poor regions of
the structure, either inductively or by virtue of resonance.

EXAMPLE

The carboxyl group in benzoic acid draws Aniline donates its electron pair to the ring
electrons from the benzene ring through through resonance. The –NH2 group is an EDG.
resonance. The –COOH group is an EWG.
Structure and Reactivity of Organic Compounds
Acidity of Hydrogens
Both inductive and resonance effects are criteria for determining if a hydrogen would react to
a base during a chemical reaction.
An important note: Acidic hydrogens are usually exchangeable (can be attacked by a base) if it
does not result to a relatively unstable carbanion (a negatively-charged carbon), or would not
result to a production of very unstable anions (hydrides, alkylides, etc.)
EXAMPLE

>

In this compound, HB is more acidic than HA. The nitrogen in pyridine is more basic than the
(resonance and inductive effects) nitrogen in aniline (resonance effect)
Structure and Reactivity of Organic Compounds
Nucleophilicity and Basicity
Nucleophiles tend to attach to the electron-deficient center, while Bases tend to accept an
acidic hydrogen.
EXAMPLE

In this mechanism, the hydroxide acts as a In this mechanism, the hydroxide acts as a
nucleophile attacking an electron-deficient base attacking an acidic hydrogen from the
carbon. compound.
Structure and Reactivity of Organic Compounds
1. Nucleophilicity is inversely proportional to the electronegativity of the species.
2. Weak nucleophiles are also weak bases.
3. Large e--rich groups tend to act more as a base than as a nucleophile.
4. Stronger nucleophiles can easily replace weaker nucleophiles in a substitution reaction.
EXAMPLE

Br- is a stronger nucleophile than Cl-. It can In some cases, the substitution reaction can
easily substitute alkyl chlorides. be forced by adding an excess amount of the
weaker nucleophile to shift the reaction
forward.
Drawing the Reaction Mechanism
A whole arrow is used if an electron pair is being “transported” in the step, while a half-arrow
is used for a single electron transport.
EXAMPLE

In this mechanism, electron pairs are In this mechanism, a single electron from each
transported from the e--rich compound atom is shared to form a bond, while
(nucleophile) to the electron-deficient producing radical species.
compound (electrophile)
Drawing the Reaction Mechanism
Octet rule is observed as much as possible, except if the mechanism allows for the production
of a carbocation or a carbanion.
EXAMPLE

Notice that oxygen in H2O had a +1 charge after bonding with the carbonyl carbon, while the
carbonyl oxygen immediately withdraws its electrons to preserve the tetravalent bonding of C.
Addition Reactions
EXAMPLE

Electrophilic Addition
on Alkenes

Nucleophilic Addition
on Aldehydes

Free-radical Addition
Addition : Markovnikov’s Rule
EXAMPLE
Substitution Reactions
EXAMPLE

Bimolecular
Nucleophilic
Substitution
(SN2)

Unimolecular
Nucleophilic
Substitution
(SN1)
Substitution Reactions
EXAMPLE

Electrophilic
Aromatic
Substitution

Nucleophilic
Acyl
Substitution
Elimination Reactions
EXAMPLE

Bimolecular
Elimination
(E2)

Unimolecular
Elimination
(E1)
Elimination : Zaitsev’s Rule
EXAMPLE
Rearrangement Reactions
EXAMPLE

Keto-enol
tautomerization

Autocyclization
Mechanism of Chemical Reactions
Chemical reactions are influenced by two main factors:
• Thermodynamic Control: Temperature, stability of intermediates, amount of reactants
• Kinetic Control: Collision frequency, stereochemistry of contact, activation energy of reaction

Two theories are used to explain the control of chemical reactions:

• Collision Theory – the frequency, energy, and orientation of the collisions affect reaction rates
• Transition State Theory – the energy of the activated complex (transition state) affect reaction rates

Both factors distinguish the type of products and the speed in which the reaction occurs
• Labile compounds – compounds that are kinetically favored
• Inert compounds – compounds that are thermodynamically favored
The Collision Theory
Collision Theory is a model that describes the effects of kinetics and thermodynamics of reactions.
In this model:
The kinetic energy of the particles are directly proportional to its temperature.
The frequency of the collisions depends on the temperature and the mass of the particles.
The efficiency of collision depends on both the energy of the collision and its orientation.
Changing the reaction conditions (Temperature, time, and concentration of substrates) can lead to
either of the controls

The products that have the shortest mechanistic paths are favored.
Kinetic Control
The collisions will form products that are fast-forming, regardless of the stability.
Kinetic Control: shorter time, lower temperature, lower concentration

The products that have the greatest stability

Thermodynamic
Control The collisions will form products that are more stable and inert, regardless of the mechanistic path.
Thermodynamic Control: longer time, higher temperature, higher concentration.
Kinetic vs. Thermodynamic Control
Kinetic vs. Thermodynamic Control of Reactions
The substrate may react differently with the reagent depending on the reaction conditions.
EXAMPLE

The secondary carbocation

forms faster (kinetically-
favored) but the tertiary
carbocation is more stable
(thermodynamically-favored)

The 1,2-addition intermediate

is fast-forming (kinetically-
favored) but the allylic
carbocation intermediate is
more stable
(thermodynamically-favored)
The Transition State
Transition states are compounds that have states that are so unstable that their lifetimes are very short.
These compounds are postulated to exist but are never directly observed.
The transition state is estimated through Valence Shell Electron – Pair Repulsion Theory (VSEPR) and
Valence Bond Theory (VBT). The transition state is noted through the double cross (‡) sign.

𝐴 + 𝐵 ⇌ 𝐴𝐵 ‡
𝐴𝐵 ‡ → 𝑝𝑟𝑜𝑑𝑢𝑐𝑡𝑠
The energy associated with the collision of A and B to form the transition state AB is called the
Activation Energy (Ea) of the step. The value of Eact is determined using the Arrhenius model
−𝐸𝑎ൗ
𝑘= 𝐴𝑒 𝑅𝑇

The Arrhenius equation can be linearized to a form that is used for non – isothermal analysis of
collision frequencies, called the kinetic compensation effect.
𝐸𝑎
ln 𝑘 = ln 𝐴 −
𝑅𝑇
 𝐺‡
The Transition State
In some textbooks, the energy profile is
represented by Gibbs energies (G), while some are
represented in other books as enthalpy (H).
The difference is in the formulation of the
Transition – State Theory.
The derivation of the TST, which treats the 𝐺𝑝𝑟𝑜𝑑𝑢𝑐𝑡𝑠
activation energy as a Gibbs function, leads to the
formulation of the Eyring Equation, ∆𝐸𝑎𝑐𝑡 𝐺𝐴+𝐵 ∆𝐺𝑟𝑒𝑎𝑐𝑡𝑖𝑜𝑛

∆𝐺 ‡ = −𝑅𝑇 ln 𝐾 ‡
∆𝐺 ‡ 𝐴 + 𝐵 ⇌ 𝐴𝐵 ‡
= − ln 𝐾 ‡
𝑅𝑇 𝐴𝐵 ‡ → 𝑝𝑟𝑜𝑑𝑢𝑐𝑡𝑠
∆𝐻‡ − 𝑇∆𝑆 ‡ 𝐴𝐵 ‡
= − ln 𝐾 ‡
𝑅𝑇 𝐾‡ =
𝐴 𝐵
∆𝑆 ‡ −∆𝐻 ‡
𝐾 ‡ = 𝑒 𝑅 𝑒 𝑅𝑇
A Case Study: SN1 reactions
In 1924, Ronald Bell, Meredith Evans and Michael Polanyi developed a model to describe the
relative rates of different SN1 reactions by looking at the different carbocation intermediates.

𝐶𝐻3 𝐶𝐻2 𝐶𝐻2 𝐶𝑙 ⇌ 𝐶𝐻3 𝐶𝐻2 𝐶𝐻2 + + 𝐶𝑙 − 2nd TS

𝐶𝐻3 𝐶𝐻2 𝐶𝐻2 + + 𝐶𝑁 − → 𝐶𝐻3 𝐶𝐻2 𝐶𝐻2 𝐶𝑁
𝐶𝐻3 𝐶𝐻2 𝐶𝐻2 +

𝐶𝐻3 2 𝐶𝐻𝐶𝑙 ⇌ 𝐶𝐻3 2 𝐶𝐻+ + 𝐶𝑙−

𝐶𝐻3 2 𝐶𝐻+ + 𝐶𝑁 − → 𝐶𝐻3 2 𝐶𝐻𝐶𝑁 𝐶𝐻3 2 𝐶𝐻+

𝐶𝐻3 3 𝐶𝐶𝑙 ⇌ 𝐶𝐻3 3 𝐶 + + 𝐶𝑙 − 𝐶𝐻3 3 𝐶 +

𝐶𝐻3 3 𝐶 + + 𝐶𝑁 − → 𝐶𝐻3 3 𝐶𝐶𝑁 1st TS
A Case Study: SN1 reactions
They realized that there is something similar with the 3 reactions:

𝐻 𝐻 ‡ 𝐻
𝑅 𝐶 𝐶𝑙 𝑅 𝐶 𝐶𝑙 𝑅 𝐶
+
𝐻 𝐻 𝐻

Tetrahedral reactant Tetrahedral Trigonal planar

transition state intermediate

𝐻 ‡ 𝐻
𝐻
𝐶𝑁
𝑅 𝐶 𝑅 𝐶 𝑅 𝐶 𝐶𝑁
+
𝐻
𝐻 𝐻

Trigonal planar Trigonal planar Tetrahedral

intermediate transition state product
A Case Study: SN1 reactions
The differences in the energy is determined by the similarity in structural geometry
𝐻 ‡
𝑅 𝐶 𝐶𝑙

𝐻 𝐻
‡
𝐶𝑁
𝑅 𝐶

𝐻 𝐻
𝑅 𝐶 𝐶𝑙

𝐻 𝐻
𝐻
𝑅 𝐶
+ 𝑅 𝐶 𝐶𝑁
𝐻
𝐻
The Hammond - Leffler Postulate
𝐴 + 𝐵 ⇌ 𝐴𝐵 ‡
𝐴𝐵 ‡ → 𝑝𝑟𝑜𝑑𝑢𝑐𝑡𝑠 𝐺‡
𝐺‡

𝐺𝐴+𝐵 𝐺𝑝𝑟𝑜𝑑𝑢𝑐𝑡𝑠

𝐸𝑎𝑐𝑡 𝐺𝑝𝑟𝑜𝑑𝑢𝑐𝑡𝑠 ∆𝐺𝑝𝑟𝑜𝑑𝑢𝑐𝑡𝑠 𝐸𝑎𝑐𝑡 𝐺𝐴+𝐵 ∆𝐺𝑝𝑟𝑜𝑑𝑢𝑐𝑡𝑠

In the Arrhenius model, endothermic reactions have transition states that resemble the products,
while exothermic reactions have transition states that resemble the reactants.
There are many interpretations to this reaction energy plot, but the common practice is to consider
the energy differences