1. 1
Introduction

2. Mechanisms of Reactions
Since there are enormous numbers of possible reactions of
organic molecules, understanding organic chemistry would
be an enormous difficult task.
However, the all varied reactions result from a relatively
small number of basic processes.
(Mysterious or even impossible)
Consider three things in this book
- meaning of the “mechanism’ of a reaction
- “Proposing” or “writing” a mechanism means
- a mechanism is “reasonable”
Reaction mechanism
- Description everything that happens as the starting
materials for the reaction are converted into the products

3. Mechanisms of Reactions
If reaction proceed by a sequence of several consecutive
reactions, the proposal should include equations for every
step in the overall mechanism.
- Intermediate identification is a crucial part of any
proposal for the reaction mechanism
- Description of changes in the electronic structures of
molecules (use of curved arrows which show the change
in position of a pair of electrons)

4. Mechanisms of Reactions
In free radical reaction
Transition state (rate-limiting step) – no isolation
- the point of highest energy in a reaction or in each step
of a reaction involving more than one step

5. Mechanisms of Reactions
Knowledge of the transition state(TS) for organic reaction is
important to understand the mechanism, but description of
transition state as part of proposed reaction mechanism is
impossible.
- TS always involve partially formed or partially broken
bonds (representation of dotted lines)

6. Mechanisms of Reactions
Microscopic reversibility
The reverse of any reaction must proceed along exactly
the same route as the forward reaction (the lowest energy
route in one diraction in a reaction equilibrium must also
be the lowest energy route in the other)
- Application of this concept in the case of identical
condition for both reactions
Reasonable mechanism
- Basic principle
Each step in the reaction of any compound should be a
well-known reaction of that type of compound under the
conditions of the reaction. Nearly all chemical changes
that appear extraordinary are simple the result of well-
known routine reactions (combination of reactions you
studied)

7. Mechanisms of Reactions
Proposing reaction mechanisms
Rejecting an unreasonable mechanism
Nucleophilic substitution Reaction (SN2)?
-OC2H5 is good leaving group?

8. Mechanisms of Reactions
Proposing reaction mechanisms
Rejecting an unreasonable mechanism
Anions, all the conjugate bases of strong acids, can act
as leaving group in SN2 reactions
- Cl-, Br-, I-, RSO3- (benzenesulfonate anions)
Neutral molecules (H2O, ROH, ROR’) can act as leaving
groups in acid-catalyzed SN1 and E1 reactions

9. Mechanisms of Reactions
Proposing reaction mechanisms
Proposing a reasonable mechanism
- Focus on the starting materials instead of the product,
and select the reaction they are most likely to undergo
under the reaction conditions
- When there are several reasonable alternatives at each
mechanism, check the product formation from the each
alternative. If this not reasonable, go back to other
alternative and check again.
Above reaction has only one reasonable pathway

10. Mechanisms of Reactions
Proposing reaction mechanisms
Proposing a reasonable mechanism
The mechanism is reasonable, because each step is
very common, routine reaction

11. Mechanisms of Reactions
Proposing reaction mechanisms
Another example
Reaction (8) can be accounted for by a retro-cyanohydrin
reaction

12. Mechanisms of Reactions
Proposing reaction mechanisms
Another example
Mechanism in (9b) is reasonable because each step is a
common reaction, with many precedents.

13. Mechanisms of Reactions
Proposing reaction mechanisms
More about leaving groups
Actually, CN- and C2H5O- are not good leaving groups.
Why CN- and C2H5O- can be ejected from Eq (7b) and
(9b)?
The leaving group and a negatively charged atom are
both bonded to the same atom, so that ejection of the
leaving group resulted in the formation of a new p bond.
- This type of reactions occur much more easily than do
substitution by external nucleophiles or elimination by
external bases. (Common anions : CN-, OH-, RO-, C=C-O-)
- However, hydrocarbon anions and hydride anions can
not act as leaving group.

14. Electron Delocalization and Resonance
The Theory of resonance
Hybrid structures
Most primary halides and ethers are quite unreactive
under the same conditions. However, above reaction
is a rapid. How can you explain about this?
The theory of resonance provides a simple explanation
for the formation of the reaction products as well as for
the rapid of the reaction.

15. Electron Delocalization and Resonance
The Theory of resonance
Hybrid structures
Changing the positions of p electrons or unshared
electrons
The actual structure is ‘a hybrid’ of all the individual
resonance forms. The lower in energy a particular
resonance form would be, the more closely the actual
structure will resemble that resonance form.

16. Electron Delocalization and Resonance
The theory of resonance
Hybrid structures
Delocalized bonds are sometimes represented by dotted
lines.

17. Electron Delocalization and Resonance
The theory of resonance
Significant and insignificant forms
Resonance forms that would be a great deal higher in
energy than other forms may be considered ‘insignificant’
How to figure out which form is ‘significant’ or which form
is ‘insignificant’?
Resonance forms that have the maximum number of
bonds that may be drawn for a particular structure.
Significant form

18. Electron Delocalization and Resonance
The theory of resonance
Significant and insignificant forms
(2) Every resonance form that can be drawn without
losing one or more bonds must be considered
significant
Nonpolar form
More significant
Dipolar form
Less significant

19. Electron Delocalization and Resonance
The theory of resonance
Significant and insignificant forms
(3) Hyperconjugation resonance forms, involving the
delocalization of s bonds rather than p bonds, are
not usually included among the significant forms.
However, the appreciable stabilization of carbocations
by alkyl groups is usually attributed to hyperconjuga-
tion rather than to inductive effects.
More important form is resonance with s bonds rather
than p bonds (No-bond resonance)

20. Electron Delocalization and Resonance
The theory of resonance
Using resonance structure
There are two basic rules to follow in using resonance
structures to predict possible products of organic
reactions and to propose reasonable mechanisms
Draw all significant resonance structures for ions and
molecules taking part in a reaction.
(2) Imagine that each resonance form has an individual
existence, with localized bonds and charges, and
draw the reaction products arising from each form.
Each product is a possible product of the actual ion
or molecule.

21. Electron Delocalization and Resonance
The theory of resonance
Using resonance structure
All resonance forms after dissociation of C-Cl bond (Rule 1)

22. Electron Delocalization and Resonance
The theory of resonance
Using resonance structure
Possible reactions of the individual resonance forms
(1) Resonance form 3a

23. Electron Delocalization and Resonance
The theory of resonance
Using resonance structure
(2) Resonance form 3b
Hemiacetal form
(unstable)

24. Electron Delocalization and Resonance
The theory of resonance
Using resonance structure
(2) Resonance form 3b
Hemiacetal is rapidly converted to carbonyl compound
in acid solution.

25. Electron Delocalization and Resonance
The theory of resonance
Which products are actually formed?
There is no simple set of rules that will reliably predict
which products will be obtained from the reactions of
a molecule or ion with several significant resonance
structures.

26. Electron Delocalization and Resonance
The theory of resonance
(less stable)
Kinetic product
Thermodynamic product
(more stable)
The relative amounts of each depend on the reaction time
and reaction condition

27. Electron Delocalization and Resonance
The theory of resonance
Alkylation at a-carbon to the carbonyl group
No alkylation at g carbon
Acylation at oxygen atom of the carbonyl group
Thereare no general rules that can reliably predict the
relatively yields of products from reaction of molecules
or ions with delocalized bonds.

28. Electron Delocalization and Resonance
Resonance stabilization
A molecule or ion with delocalized bonds is always more
stable than its lowest energy resonance form.
Resonance stabilization energy
The difference in energy between the actual structure
and the lowest energy form.
Dependance of the number of possible resonance forms

29. Electron Delocalization and Resonance
Resonance stabilization
The value of the resonance stabilization energy also
depends on the relative stabilities of the various
resonance forms.
“The closer in energy the different resonance forms are,
the greater the degree of delocalization of the electrons
and the higher the resonance energy”
8 is less effective than allyl radical (high resonance energy)

30. Electron Delocalization and Resonance
Resonance stabilization
Resonance is a general term applied to the phenomenon
of bond delocalization.
Aromaticity (or antiaromaticity) is special properties of
rings composed entirely of conjugated p bonds, empty
orbitals, or unshared pairs of electrons.

31. Electron Delocalization and Resonance
Nonplanar p systems
The orbitals should be lined up parallel to several p
orbitals in order for electrons to be delocalization.
However, if one or more orbitals are twisted away from
the parallel arrangement, the energy of the system will
be increased.
- no possibility in open p systems
- possibility in cyclic molecules
- Steric inhibition of resonance

32. Electron Delocalization and Resonance
Nonplanar p systems

33. Electron Delocalization and Resonance
Nonplanar p systems
Not undergo ionic dissociation even when heated with
strong Lewis acids.

34. Electron Delocalization and Resonance
Nonplanar p systems
Compound (12) is more than 104 times less basic than
Compound (13) even though alkyl substitution usually
has only a slight effect on the basicity of anilines.
- Unshared electrons on the amino group in 12 could
interact effectively with p systems of the ring and
the nitro group.