Chapter 5: Study of Reaction Mechanisms in Organic Chemistry

I/ Introduction :

The writing of a reaction equation does not provide information about the different steps
involved in transforming reactants into products. There may be multiple elementary steps and
several reaction intermediates formed during the reaction.
A reaction mechanism corresponds to the sequence of elementary steps occurring as reactants
are converted into products.
Reaction intermediates are chemical species formed between two elementary steps; they are
highly unstable and have very short lifetimes. The study of reaction mechanisms aims to
account for the electronic, geometric, energetic, and kinetic changes in the evolving system.

II/ Classification of Reactions:

From a stoichiometric perspective, chemical reactions can be classified into four groups:
1) Substitution Reactions: A σ bond is replaced by another σ bond.

Example:

2) Addition Reactions: 1 π bond is broken, and 2 σ bonds are formed.

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Example :

3) Elimination Reactions: Formation of a π bond.

Example :

4) Transposition (or Rearrangement) Reactions: Movement of atoms (tautomerism).

Examples :

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III/ Energy aspects of reactions

III-1/ Molecular-scale reaction sequence

A reaction occurs as a result of effective shocks between substrate A and reagent B.

Substrate: the main molecule undergoing a transformation.

A reactant: the chemical agent capable of causing a reaction.
An effective shock is one whose energy is sufficient for the reaction to take place.

If the reaction takes place :

- in a single stage (a single shock), it is an ELEMENTARY REACTION,

- in two or more stages, i.e. a succession of elementary reactions: COMPLEX REACTION.

III-2/ Elementary reaction

When A and B collide, a highly unstable transition state is formed, which then rapidly evolves
towards C. The evolution of the reaction, on a molecular scale, is represented by the following
energy diagram:

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III-3/ Complex reaction

The reaction takes place in several stages, which are a succession of elementary processes. It
passes through one (or more) reaction intermediate (s) before arriving at product C.

Each intermediate is preceded and followed by a transition state.

Reaction intermediates are not very stable entities (very short lifetimes), and are therefore very
reactive. The step with the highest activation energy is the slowest, and therefore kinetically
decisive.

IV/ Electronic aspect. Reaction intermediates

Substrate (reagent) intermediate product

A substrate can undergo two types of cleavage: heterolytic cleavage and homolytic cleavage.

IV-1/ Breaking σ-bonds

There are 2 types of mechanism, depending on the intermediates involved:

- Homolytic mechanism: symmetrical breakage of the covalent bond (formation of radicals).

This break is usually initiated by U.V. radiation.

- Heterolytic mechanism: asymmetric breaking of the covalent bond (passage through ionic
intermediates: cations and anions).

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In this course, we will focus on heterolytic reactions.

IV-2/ The role of solvents in organic synthesis reactions

A solvent is a non-reactive liquid, capable of dissolving the reagents and products formed, on
the one hand; on the other, it can promote or inhibit certain reactions by solvating reagents or
products. There are 2 classes of solvent:

- Non-polar solvents: These solvents are characterized by a zero dipole moment: benzene
(C6H6), toluene (C6H5-CH3), carbon tetrachloride (CCl4), hydrocarbons (hexane,
cyclohexane...)... Being uncharged, they do not solvate ions from the reaction medium.

- Polar solvents: these are divided into 2 groups :

1) Protic solvents: these have at least one hydrogen atom linked to a heteroatom (O, N, S...),
as in water (H-O-H) and alcohols (R-O-H).

Due to the polarization of the bonds (H-O, H-N, H-S...), these mobile protons are able to form
hydrogen bonds with molecules carrying free doublets or negative charges.

- A protic solvent increases the polarity of the substrate's C-X bond, facilitating the departure
of the leaving group (X).
- A protic solvent will solvate the nucleophile by forming hydrogen bonds, and reduce its
nucleophilic power: the protic solvent cages the nucleophile and slows down its attack.

2) Aprotic solvents: they contain atoms with free doublets but no mobile hydrogen: hydrogen
atoms are bonded exclusively to carbon atoms:

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These solvents dissolve ionic compounds by solvation of the cations: the steric effect prevents
the solvation of anions, which cannot approach the positive charge inside the solvent molecule;
the unencumbered anions are then highly reactive.

IV-3/ Reaction intermediates

Between the initial and final stages of a chemical reaction, reaction intermediates are formed,
which are not very stable and have very short lifetimes. These chemical species are entirely
consumed at the end of the reaction, so they do not figure in the stoichiometric equation.

a) Free radicals: These are neutral atoms with a single electron in an atomic orbital (•CH3).
Radicals result from the homolytic (symmetrical) breaking of a covalent bond. They are easily
broken by heating in the presence of peroxides, or by irradiation (photochemical radiation).

The stability of carbon radicals is analogous to that of carbocations, i.e. inductive or mesomeric
donor effects (+I, +M) can stabilize them by reducing their electronic deficit.

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b) Carbocations: These are cations whose positive electronic charge is carried by a carbon
atom. They have a planar geometry, so sp2 hybridization.

As the carbocation is electrophilic (positive charge), a nucleophile can attack it from either side
of the plane, which can influence the stereochemistry of the resulting product.

Carbocations result from a heterolytic break between a carbon and a more electronegative atom:

With their electron deficiency, these species are highly reactive and have a high energy content.
Inductive effects or donor mesomers (+I, +M) can stabilize them by reducing their electronic
deficit, but they are unstable and non-isolable species.

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c) Carbanions: these are anions whose negative charge is carried by a carbon atom. They
have a tetrahedral geometry, so sp3 hybridization.

Carbanions result from a heterolytic bond between a carbon and an atom less electronegative
than the carbon.

Carbanions are highly unstable, high-energy species that cannot be isolated. They have an
electron surplus and a negative charge; one of their orbitals has an electron doublet.

The donor effect of alkyl groups (+I) increases the electronic excess and destabilizes the
species. Attractor effects (I-) stabilize carbanions. The delocalization of the negative charge by
mesomerism is a stabilizing factor, as it is for carbocations.

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IV-4/ Electrophilic and nucleophilic reagents

a) Electrophilic reagents: these are electron-poor reagents.

- They can be electrically neutral: molecules whose central atom has an electron gap (e.g.
Lewis acids: AlCl3, BF3, FeCl3...).

- They may be charged, in the form of cations:

- They may be polar :

- They may be polarizable:

During a reaction, the electrophile (electron-deficient) is attacked by an electron-rich center

(nucleophile).

b) Nucleophilic reagents: electron-rich reagents.

- They may be electrically neutral: molecules whose central atom has one (or more) free
doublet(s):

- They may be negatively charged (anions):

- They may contain a multiple bond:

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Note: Anions are more nucleophilic than the corresponding neutral molecules.

Application exercise:
Classify the following series by increasing stability:

Response :

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