Overview of Types of Organic Reactions

Chapter Four

Kinds of Reactions
Can be classified based on their Mechanisms
a)polar,
b) non-polar pathway)
 Organic Reactions
 A chemical reaction is the transformation of one chemical or collection of chemicals into
another chemical or collection of chemicals.
 A chemical reaction involves making new chemical bonds and breaking old chemical
bonds.
The major types of organic reactions is divided into four categories;
 Substitution – an atom (group) of the molecule is replaced by another atom (group).
parts from two molecules exchange.
 Addition –π-bond of a compound serves to create two new covalent bonds that join the
two reactants together. two molecules combine to form a single product.
 Elimination – two atoms (groups) are removed from a molecule which is thus cleft into
two products. one molecule splits into two.
 Rearrangement – atoms and bonds are rearranged within the molecule; thus, isomeric
compound is formed.
Note: Other organic reactions like Redox reaction, pericyclic and photochemical
reactions are also available. 2
Types of organic reactions

3
Types of Reactions

4
 Types of bonding breaking
A reaction can proceed by:
 homolytic pathway: each fragment possesses one of the bonding electrons; thus,
radicals are formed. A–B  A• + B•
 Free radical intermediates are therefore involved and these transformations are
consequently called radical reactions.

 heterolytic pathway: one of the fragments retains both the bonding electrons; thus, ions
are formed: A–B  A+ + :B–
 These reactions are also called ionic reactions, since ionic reactants, products, or
intermediates are usually involved.

 Pericyclic: no ionic or radical intermediates are fromed during this reaction. Proceed in a
single concerted step, with no intermediates, characterized by a cyclic transition state.
Being cyclic transition states involved these reactions are called
pericyclic. 5
 Arrow notation in organic reaction Mechanisms
Reaction arrows
 Curved arrows indicate breaking and forming
of bonds Equilibrium arrows (reversible reactions,
usually used when significant fraction of both
 Arrowheads with a “half” head (“fish-hook”) reactant and products are present at
indicate homolytic and homogenic steps equilibrium)
(called ‘radical processes’)
lopsided equilibrium

Resonance arrows

Retrosynthetic arrows (reverse of reaction

Arrowheads with a complete head indicate
arrow - used in planning a synthesis)
heterolytic and heterogenic steps (called
‘polar processes’)
Examples

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 Bond Breaking: Non-polar

Bond Forming:
Polar

Note: The positively charge cation generated after heterolysis is called a carbocation
(earlier called carbonium ion). Carbocations are classified as primary, secondary or
tertiary depending on whether one, two or three carbons are directly attached to the
positively charged carbon. More substituted carbocations are more stable
 Chemical Species involved polar and non-polar reaction path way

 Radical – possess an unpaired electron (Cl•)-occur in non-polar pathway

Polar pathway
 Ionic:
A) nucleophilic – possess an electron pair that can be introduced into an electron-
deficient substrate:
• i) anions (H–, OH–)
• ii) neutral molecules (NH3, H2O)
B) electrophilic – electron-deficient  bind to substrate centres with a higher electron
density:
• i) cations (C(CH3)3+)
• ii) neutral molecules (for example Lewis acids: AlCl3)
Electrophiles Nucleophiles
Electrophiles are electron deficient species Nucleophiles are electron rich species
They electron loving species They are nucleus loving species
They are electron pair acceptor from any donor They are electron pair done species
They behave as Lewis acid They behave as Lewis acid
They do have vacant p/d orbital
Types of electrophiles Types of nucleophiles
Type I: positively charged species Type I: negatively charged species
Examples, all cations except cation of IA, IIA, NH4+ and Examples, OH-, NH2-, N3-, H-, CH3- etc.
H3O+
Type II: neutral electrophile with Type II: neutral nucleophiles
1) Vacant p orbital 1)compound with at least one lone pairs
Examples BF3, BeCl2 AlCl3 etc. Examples, H2O, NH3, CH3-NH2, etc.
1) Vacant d orbital 2)compound with Pi bond
Examples SnCl4, ZnCl2, FeBr3, SbCl5 etc. Alkene and alkyne compounds
Type III: Type III: all organometallic compounds
Examples halogen molecules like Br-Br, Cl-Cl, I-I Examples, RMgX (Grignard reagent,
Type IV: Ambident nucleophiles(two or more nucleophilic
site in a molecule)
Example, C=N, NH2OH, enolate anions , etc 9
 Substitution Reaction
 Nucleophilic substitution is a fundamental class of substitution reaction in which an
"electron rich" nucleophile selectively bonds with or attacks the positive or partially
positive charge of an atom attached to a group or atom called the leaving group; the
positive or partially positive atom is referred to as an electrophile.

 Nucleophilic substitution reactions can be broadly classified as

 Nucleophilic substitution at saturated carbon centres (SN1 or SN2 )
 Nucleophilic substitution at unsaturated carbon centres (carbonyl reactions)
 When the substitution occurs at the carbonyl group, the acyl group may undergo
nucleophilic acyl substitution. This is the normal mode of substitution with carboxylic
acid derivatives such as acyl chlorides, esters and amides. 10
 Types of halides
 Alkyl halides are organic molecules containing a halogen atom bonded to an sp3
hybridized carbon atom. Alkyl halides are classified as primary (1°), secondary (2°), or
tertiary (3°), depending on the number of carbons bonded to the carbon with the halogen
atom.
 Vinyl halides have a halogen atom (X) bonded to a C—C double bond.
 Aryl halides have a halogen atom bonded to a benzene ring.
 Allylic halides have X bonded to the carbon atom adjacent to a C—C double bond.
 Benzylic halides have X bonded to the carbon atom adjacent to a benzene ring.

 Nucleophilic substitution via the SN1 or SN2 mechanism does not generally occur with
vinyl or aryl halides or related compounds.

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 Substitution via polar pathway
 Substitution reaction can be divided into two categories depending upon the mechanistic
pathway.
1. The Bimolecular Nucleophilic Substitution (SN2) Reaction
• SN2 is a concerted reaction-it takes place in a single step, so no intermediates are formed.
The nucleophile attacks the carbon bearing the leaving group and displaces the leaving
group.
• SN2 reaction takes place in a single step.
• The Nu–C bond forms at the same time the C–L bond breaks.

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 Nucleophilic Substitution Reaction (SN2)
 For example, the reaction of methyl bromide with hydroxide ion is an example of an
reaction, where “S” stands for substitution, “N” for nucleophilic, and “2” for
bimolecular. Bimolecular means that two molecules are involved in the rate-
determining step.

mechanism of the SN2 reaction

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A wide array of structures can be synthesized from sulfonates and alkyl halides through
nucleophilic substitution of X = OSO2R, I, Br, Cl in C–C bond forming reactions.

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 Example of Nucleophilic Substitution Reaction (SN2)
Mechanism

The stability order of the carbocations is as follows

1°alkyl < 2° alkyl = 1° allylic < 1° benzylic < 3° alkyl < 2° Allylic= 2° Benzylic < 3°
Allylic= 3° Benzylic.
Example
2° allylic, Totally it has seven resonating
structures that contributes its stability
SN2 Reactivity

Methyl hailde > 1°alkyl halide > 2° alkyl halide > 3° alkyl halide
Why: The pattern reflects the relative stability of the transition states. In the case of 3˚ versus 2˚ versus 1˚, the
issue is steric congestion in the transition state. The transition states for the more highly substituted halides are
destabilized. In the case of allylic halides, the transition state is stabilized for orbital reasons, not steric reasons.
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 The rate of an reaction depends not only on the number of alkyl groups attached to the carbon that is
undergoing nucleophilic attack, but also on their size. For example, while ethyl bromide and propyl bromide
are both primary alkyl halides, ethyl bromide is more than twice as reactive in an reaction because the bulkier
propyl group provides more steric hindrance to back-side attack. Also, although
neopentyl bromide is a primary alkyl halide, it undergoes reactions very slowly because its single alkyl group
is unusually bulky.

Reaction coordinate diagrams for (a) the SN2 reaction of methyl bromide with hydroxide ion; (b) an SN2 reaction of
a sterically hindered alkyl bromide with hydroxide ion. 16
 Factors Affecting SN2 Reactions
1. The Leaving Group
 The leaving group is usually
displaced with a negative charge
The best leaving groups are
those with atoms or groups that
can best stabilize a negative
charge.
 relative leaving abilities of the halide ions

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 2. The Nucleophile
 In the case of an reaction, nucleophilicity is a measure of how readily the nucleophile
attacks an sp3 hybridized carbon bonded to a leaving group.

3. Structure of Substrate

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 4. Solvent
Solvation: solvent molecules form “shells” around reactants and dramatically influence their
reactivity.
protic: acidic hydrogens that can
form hydrogen bonds
(water, alcohols).

aprotic: no acidic hydrogens.

Polar protic solvents stabilize the nucleophile, thereby lowering its energy. This will raise
the activation energy of the reactions. SN2 reactions are not favored by polar protic solvents.

Polar aprotic solvents selectively solvate cations. This raises the energy of the anion
(nucleophile), thus making it more reactive. SN2 reactions are favored by polar aprotic
solvents.
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 2. Unimolecular Nucleophilic Substitution Reaction(SN1)
 SN1 reaction, where “S” stands for substitution, “N” stands for nucleophilic, and “1”
stands for unimolecular.
 Unimolecular means that only one molecule is involved in the rate-determining step.
 A nucleophilic substitution reaction taking place in two steps is an example of a
unimolecular nucleophilic substitution (SN1) mechanism.

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1. The rate law shows that the rate of the reaction depends only on the concentration of the
alkyl halide. This means that we must be observing a reaction whose rate-determining step
involves only the alkyl halide.

2. When the methyl groups of tert-butyl bromide are successively replaced by hydrogens, the
rate of the reaction decreases progressively.

mechanism of the SN1 reaction

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Bond breaking and bond formation occur in stepwise manner in SN1 reaction
Note: However, Vinylic and aryl halides,
however, are virtually inert to the
conditions that promote SN2, SN1 or E1,
and E2 reactions of alkyl halides.

More example Major product

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 Examples of Nucleophilic Substitution Reaction (SN1)

Mechanism

relative reactivity of alkyl halides in an SN1 reaction

Why: Because as the stability of the

cation produced in the rate-
determining step increases, the
reactivity of the parent halide
increases as well

30 allylic cation
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 Factors Affecting SN1 Reactions
3. The Nucleophile
1. The Leaving Group
Because the nucleophile comes
 relative reactivities of alkyl halides in an SN1
reaction into play after the rate-
determining step, the reactivity
of the nucleophile has no effect
on the rate of an SN1 reaction
 relative leaving abilities of the halide ions
4. Solvent
 Solvent polarity is measured by
dielectric constant (ꜫ)

2. Structure of Substrate

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The role of the solvent in
SN1 reactions:
polar solvents are favored over non-
polar for the SN1 reaction.
protic solvents are favored over
aprotic for the SN1 reaction.

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 Substitution Reaction via radical pathway

Radical pathway has three steps: Initiation, propagation and termination steps. examples

Initiation. Initiation generates a reactive intermediate. A

chlorine atom is highly reactive because of the presence
of an unpaired electron in its valence shell. It is
electrophilic, seeking a single electron to complete the
octet. It acquires this electron by abstracting a hydrogen
atom from methane. 26
 Propagation. In this step, the intermediate reacts
with a stable molecule to produce another reactive
intermediate and a product molecule.

 The propagation step yields a new electrophilic

species, the methyl radical, which has an unpaired
electron. In a second propagation step, the methyl
radical abstracts a chlorine atom from a
chloromethane molecule, and generates a chlorine
radical.
Termination. Various reactions between the
possible pairs of radicals allow for the formation of
ethane, Cl2 or the methyl chloride. In this step, the
reactive particles are consumed, but not generated.
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Comparing SN2 vs SN1

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 Addition Reactions
 Electrophilic addition reactions
 Nucleophilic addition reactions
 Radical addition reactions
 Addition reactions occur when two starting materials add together to form only one
product with no atoms left over.
 In an addition all parts of the adding reagent appear in the product; two molecules
become one.
Examples

H H Br
H
C=C + HBr C C
H H
H H
H H 29
 Addition of hydrogen
Addition halides and water to
reactions alkenes

Addition of bromine
to alkenes polar and
free radical pathway

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Map of Alkene reaction

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 Electrophilic addition to symmetrical and unsymmetrical pi bonds
 When the same substituents are at each end of the double or triple bond, it
is called symmetrical.
 Unsymmetrical means different substituents are at each end of the double or triple
bond. Electrophilic addition of unsymmetrical reagents to unsymmetrical double or
triple bonds follows Markovnikov’s rule.
 According to Markovnikov’s rule, addition of unsymmetrical reagents, e.g. HX, H2O
or ROH, to an unsymmetrical alkene proceeds in a way that the hydrogen atom adds to
the carbon that already has the most hydrogen atoms.

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33
Predict the major product(s) for each of the following reactions.

Solution for b

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 Nucleophilic Addition to carbon-carbon double bonds
Nucleophilic Addition to carbon-hetero double bonds
 Addition reactions of a nucleophile to carbon – hetero double bonds such as C=O or
CN triple bond show a wide variety.

 These bonds are polar (have a large difference in electronegativity between the two
atoms) consequently carbon carries a partial positive charge. This makes this atom the
primary target for the nucleophile. This type of reaction is also called a 1, 2
nucleophilic addition.

Conjugate Addition vs Direct Addition: What is Conjugate Addition?

 Conjugate addition refers to nucleophilic addition directed to the electrophilic carbon

of the C=C (double bond) in α,β-unsaturated systems.

 It is the alternative to direct nucleophilic addition in reactions of a,b-unsaturated

systems. 35
 1,4-addition or
conjugate addition
or Michael addition

1, 2-addition 1, 4-addition 36
Direct Addition vs Conjugate Addition
The Nature of the Nucleophile

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 Other reactions of double bonds
Ozonization, Diels-alder, glycol formation and polymerization
Ozonolysis
 Electrophilic addition of ozone to alkene produces a cyclic peroxide known as ozonide;
the reaction results in the cleavage of C=C double bond. The ozonide being explosive is
not isolated; rather further decomposition of ozonide is carried out by reduction (known
as reductive ozonolysis) or by oxidation (called oxidative ozonolysis).

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 The reductive ozonolysis with Zn/H2O forms aldehydes and/or ketone;
 The oxidative ozonolysis with H2O2 produces carboxylic acid and /or ketones.
Carboxylic acids are formed instead of aldehydes because any aldehyde that is initially
formed will be immediately oxidized to a carboxylic acid by hydrogen peroxide.

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 Diels-Alder reaction
 The general Diels-Alder reaction forms a cylohexene product
 Two new s bonds are formed at the expense of two p bonds
 The conjugated diene is a 4p-electron system
 The dienophile (“diene lover”) is a 2p-electron system
 The product is called an adduct
The simplest possible example of a Diels-Alder
reaction goes at very low yield and requires high
temperatures

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 To proceed in good yield and at low temperature the dienophile should have electron-
withdrawing groups
 The Diels-Alder reaction is favored by electron withdrawing groups on the dienophile
and electron donating groups on the diene.

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 Glycol formation
With cold alkaline KMnO4 (Baeyer’s reagent): The aqueous alkaline solution of
potassium permanganate oxidizes alkenes and results to the formation of cis-diols;
hydroxylation occurs at the double bond position. The permanganate adds to the alkene
double bond to form a cyclic ester which is hydrolyzed by the base to form diol.

With osmium tetroxide (OsO4): Reaction of alkene with osmium tetroxide is same as with
potassium permanganate; alkene reacts with OsO4 to form an osmate ester which on
hydrolysis produces cis-diols.

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 Addition Polymerization
 In addition polymerization (sometimes called chain-growth polymerization), a chain
reaction adds new monomer units to the growing polymer molecule one at a time
through double or triple bonds in the monomer.
 Addition polymerization proceed through two types of mechanism
A) Free radical mechanism
B) Ionic mechanism.
A) Ionic mechanism are two type
i) Cationic mechanism ii) Anionic mechanism
 Every polymerization reaction proceeds through three steps
1) Chain initiation
2) Chain propagation
3) Chain termination

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 Alkene Stability
More substituted alkenes are more stable
- Trans alkenes are more stable than cis alkenes

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 Elimination reactions
 Elimination reactions are the opposite of addition reactions.
 Elimination reactions involve the loss of fragments or groups from a molecule to generate
multiple bonds.
 A generalized equation is shown below for 1,2-elimination wherein the X and Y from two
adjacent carbon atoms are removed.
 Elimination reactions give us a method for preparing compounds with double and triple
bonds. Two sigma bonds are broken, and a pi bond is formed between adjacent atoms.

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Classification of Elimination reactions

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 Three major types of elimination reactions are:
1. α-elimination: two atoms or groups are removed from the same atom. It is also known as
1,1-elimination.

2. β-elimination: loss of atoms or groups on adjacent atoms. It is also known as 1,2-

elimination.

3. γ-elimination (1, 3-elimination reaction): loss of atoms or groups from the 1st and
3rd positions as shown below. Generally such elimination reactions result in cyclic
compounds.

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 More details on β-eliminations
 β-eliminations can be further subdivided into three categories
depending upon the mechanistic pathway. The important aspect is to establish the
number of molecules taking part in the elimination step (molecularity of the reaction)
The types of β-eliminations are 1) E2, 2) E1, 3) E1cB

E2 Eliminations
Key mechanistic features in this family are
• two groups depart simultaneously and Involves one step (in other words, no intermediates
are involved)
• bimolecular reaction i.e., both substrate and nucleophile participate in a single step
• The base abstracts the β hydrogen and leaving group simultaneously leaves such that it
forms a multiple bond between α and β carbon atoms.

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An illustration of a common elimination reaction is given below, or mechanism

Dehydrohalogenation

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 The Regioselectivity of the E2 Reaction
Zaitsev’s rule is an empirical rule used to predict the major products of elimination reactions.
It states that in an elimination reaction the major product is the more stable alkene with the
more highly substituted double bond.

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 According to Zaitsev’s rule, the more substituted alkene will be the one formed by
removing a proton from the -carbon that is bonded to two hydrogens, rather than from
the -carbon that is bonded to three hydrogens.

 Therefore, 2-pentene (a disubstituted alkene) is the major product, and 1-pentene (a

monosubstituted alkene) is the minor product.

Alkene Stability Pattern

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 The E1 Reaction

Elimination reactions can also take place

in two steps, via a unimolecular
elimination- The Unimolecular
Elimination (E1) Reaction. The reaction
of tert-butyl bromide with water to form
2-methylpropene is an example of an E1
reaction; “E” stands for elimination and
“1” stands for unimolecular.

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 Competition Between E2 and E1 Reactions

 Primary alkyl halides undergo only E2 elimination reactions. They cannot undergo E1
reactions because of the difficulty encountered in forming primary carbocations.
Secondary and tertiary alkyl halides undergo both E2 and E1 reactions (Table 11.3).
 For those alkyl halides that can undergo both E2 and E1 reactions, the E2 reaction
is favored by the same factors that favor an reaction and the E1 reaction is favored
by the same factors that favor an reaction.
 Thus, an E2 reaction is favored by a high concentration of a strong base and an
aprotic polar solvent (e.g., DMSO or DMF), whereas an E1 reaction is favored by a
weak base and a protic polar solvent (e.g., or ROH).

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Comparing E2 vs E1

54
Note: Often times, E2 elimination competes with SN2 reactions. This is due to the inherent
propensity of the incoming nucleophile also to attack the carbon atom bearing the leaving
group. Such situations will lead to substitution products.

Examples of E2 elimination :

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 Predicting Reaction Mechanisms

Strong bulky bases like t-butoxide are hindered. They have difficulty
hitting the alpha-carbon in a 1° alkyl halide. As a result, they favor E2 over
SN2 products.
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 Rearrangement via carbocation intermediates

 Wagner-Meerwein rearrangement : Rearrangements that occur with elimination of w

ater in the dehydration of an alcohol, of hydrogen halide in the dehydrohalogenation of
an alkyl halide,...etc., are commonly referred to as Wagner-Meerwein rearrangement.

 The driving force for the rearrangement resides in the greater stability of a tertiary
carbocation compared to that of primary carbocation.

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 Pinacole-pinacolone rearrangement: acid-catalyzed conversion of diols to ketones.
The pinacol rearrangement or pinacol–pinacolone rearrangement is a method for
converting a 1,2-diol to a carbonyl compound in organic chemistry.

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 Rearrangements on Heteroatoms
 Baeyer-villiger rearrangement: The acid-catalyzed reaction of ketones with
hydroperoxide derivatives is known as the Baeyer-Villiger reaction. organic reaction that
forms an ester from a ketone or a lactone from a cyclic ketone
Rearrangement

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The End

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