Chapter Four

Alkyl Halides

6/26/2024 By: Fikadu Girma

 Introduction
 Halo-alkane (alkyl halide): A compound containing a
halogen atom covalently bonded to an sp3 hybridized carbon
atom.
 The general symbol for a halo-alkane is R-X, where X may be
-F, -Cl, -Br, or -I.
 If a halogen is bonded to a doubly bonded carbon of an
alkene, the compound belongs to a class called halo-alkenes.
 If it is bonded to a benzene ring, the compound belongs to a
class called halo-arenes, which have the general symbol Ar-X

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 Nomenclature
 The parent chain is numbered from the direction that gives
the first substituent encountered the lowest number.
 Halogen substituents are indicated by the prefixes fluoro-,
chloro-, bromo-, and iodo and are listed in alphabetical order
with other substituents.
 Compounds of the type CHX3 are called halo-forms.
 The common name for CHCl3, for example, is chloroform.
 Hydrocarbons in which all hydrogen's are replaced by
halogens are commonly called per-halo-alkanes

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 Substitution Reactions
 In nucleophilic substitution reaction of alkyl halides, one
atom /group of atoms is replaced by another atom /group of
atoms) at SP3 hybridized carbon bonded to a leaving group .
 The atom or group that is lost is called the leaving group and
the atom or group that is added is a nucleophile.
 Nucleophilic substitution reactions can occur via two distinct
mechanisms. Those are SN 1 and SN 2 substitution reaction:
 Example: a nucleophile substitution reaction is carried out
between 2-bromopropane and the hydroxide ion. In this
reaction, bromide is the leaving group and hydroxide is the
nucleophile.

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 SN2 Mechanism:
 Bond breaking and bond forming occur simultaneously.
 Thus, departure of the leaving group is assisted by the
incoming nucleophile.
 The SN2 reaction is said to be a concerted reaction through a
single transition state
 This mechanism is designated SN2, where S stands for
substitution, N for nucleophilic, and 2 for a bimolecular
reaction.
 This type of substitution reaction is classified as bimolecular
because both the alkyl-halide and nucleophile are involved in
the rate-determining step.

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 Cont.….
 The nucleophile attacks the reactive center from the side
opposite to the leaving group.
 So, SN2 reaction involves backside attack of the nucleophile.
 B/C the leaving group blocks the approach of the nucleophile
to the front side of the molecule.
 As a result there is inversion of configuration.
 In this diagram, the dashed lines in the transition state
represent partially formed or broken bonds.

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 Factors Affecting Reactions SN2 reaction
 The Leaving Group:
 We would find that the alkyl iodide is the most reactive and the
alkyl fluoride is the least reactive.
 Iodide ion is the best leaving group and the fluoride ion is the
worst.
 The weaker the basicity of a group, the better is its leaving
ability.
 In fact, the fluoride ion is such a strong base that alkyl
fluorides essentially do not undergo SN2 reactions.

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 Cont.….
 The Nucleophile
 When we talk about atoms or molecules that have lone-pair
electrons, sometimes we call them bases and sometimes we
call them nucleophiles.
 Basicity is a measure of how well a compound (a base) shares
its lone pair with a proton. The stronger the base, the better it
shares its electrons.
 Nucleophilicity is a measure of how readily a compound (a
nucleophile) is able to attack an electron-deficient atom.
 There is a direct relationship b/n basicity and nucleophilicity.
 Stronger bases are better nucleophiles.

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 Cont.….
 A species with a negative charge is a stronger base and a
better nucleophile than a species with the same attacking
atom that is neutral.

 Molecules with attacking atoms of approximately the same

size, the stronger bases are again the better nucleophiles.

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 Cont.….
 Steric Hindrance
 The ability of groups, because of their size, to hinder access to
a reaction site within a molecule is called steric hindrance.
 If we compare the ease of approach to the substitution center
of a 1° halo-alkane with that of a 3° halo-alkane, we see that
the approach is considerably easier for bromo-ethane than
for tert-butyl bromide.
 Two hydrogen atoms and one alkyl group screen the backside
of the substitution center of a 1° halo-alkane. In contrast,
three alkyl groups screen the backside of the 3° halo-alkane.

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 Cont.….
 In fact, 3° halo-alkanes are never observed to react by an SN2
mechanism.
 In contrast, halo-methanes and 1° halo-alkane are observed to
react by an SN2 mechanism.

 We see a similar effect of steric hindrance on SN2 reactions in

molecules with branching at the beta-carbon.
 The carbon bearing the halogen in a halo-alkane is called the
alpha-carbon, and the next carbon is called the beta-carbon.

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 Cont.….
• Examples

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 Cont.….
 Steric effects, on the other hand, do affect nucleophilicity.
 A bulky nucleophile cannot approach the back side of a
carbon as easily as a less sterically hindered nucleophile can.
 Bulky tert-butoxide ion is a poorer nucleophile than Ethoxide
ion even though tert-butoxide ion is a stronger base.

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 Cont.….
 Solvent Effect
 A molecule of a solvent such as water or an alcohol called a
protic solvent.
 Molecules of protic solvents can, therefore, form hydrogen
bonds to nucleophiles.
 Hydrogen bonding encumbers a nucleophile and hinders its
reactivity in a substitution reaction.
 Aprotic solvents do not have a hydrogen atom bonded to an
electronegative atom, and therefore do not hinder
nucleophiles through hydrogen bonding.
 A number of polar aprotic solvents have come into wide use
by chemists because they are especially useful in SN2
reactions.

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 Cont.….
 Examples of aprotic solvent

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 SN1 Mechanism
 SN1 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.
 The leaving group in reaction departs before the nucleophile
approaches.
 The rate of the reaction dependent to the concentration of the
alkyl halide.
 Changing the concentration of the nucleophile has no effect
on the rate of the reaction.
 Not all steric effects decrease reaction rates.

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 Cont.….
 The rates of SN1 reactions are governed mainly by electronic
factors, namely the relative stabilities of carbocation
intermediates.
 Two distinct intermediates are formed. The first step is the
slow step, that is the rate-determining step.
 Molecule of tert-butyl bromide ionizes and becomes a tert-
butylcation and a bromide ion.
 In the transition state for this step the carbon–bromine bond of
tert-butyl chloride is largely broken and ions are develop.

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 Cont.….
 The rate of an reaction decreases as the methyl groups of tert-
butyl bromide are successively replaced by hydrogen.
 Actually, 1o carbocation's and methyl cations are so unstable
that primary alkyl halides and methyl halides do not undergo
SN1 reactions.
 An reaction of an alkyl halide in which the leaving group is
attached to an asymmetric carbon forms two stereoisomers.

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 Factors Affecting SN1 Reactions
 The Leaving Group: Because the rate-determining step of an
reaction is the dissociation of the alkyl halide to form a
carbocation, two factors affect the rate of an reaction.
 The ease with which the leaving group dissociates from the
carbon and the stability of the carbocation that is formed.
 Tertiary alkyl halides are more reactive than secondary alkyl
halides, which are more reactive than primary alkyl halides.
 This is because the more substituted the carbocation is, the
more stable it is and therefore the easier it is to form.
 The weaker the base, the less tightly it is bonded to the carbon
and the easier it is to break the carbon–halogen bond.

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 Cont.….
 As a result, an alkyl iodide is the most reactive and an alkyl
fluoride is the least reactive of the alkyl halides in both
SN1and SN2 reactions.

 The Nucleophile
 The nucleophile reacts with the carbocation that is formed in
the rate-determining step of an reaction. Because the
nucleophile comes into play after the rate determining step,
the reactivity of the nucleophile has no effect on the rate of an
SN1 reaction
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 Cont.….
 In most reactions, the solvent is the nucleophile.
 Water serves as both the nucleophile and the solvent.
 Reaction with a solvent is called solvolysis.
 Carbocation Rearrangements
 A carbocation intermediate is formed in an reaction.
 If the carbocation formed in an reaction can rearrange, and
reactions of the same alkyl halide can produce different
constitutional isomers as products.
 since a carbocation is not formed in an SN2 reaction and
therefore the carbon skeleton cannot rearrange.

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 Cont.….
 Here is example

 Benzylic and allylic halides readily undergo SN2 reactions

unless they are tertiary.
 Tertiary benzylic and tertiary allylic halides, like other tertiary
halides, are unreactive in SN2 reactions because of steric
hindrance.

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 Cont.….

 Primary benzylic and primary allylic halides readily undergo

SN1 reactions because their carbo-cations are stabilized by
electron delocalization.
 While primary alkyl halides cannot undergo SN1 reactions
because their carbo-cations are too unstable.

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 Cont.….
 If the resonance contributors of the allylic carbocation
intermediate have different groups bonded to their carbons,
two substitution products will be obtained.

 Vinylic halides and aryl halides do not undergo SN2 or SN1

reactions.
 They do not undergo SN2 reactions because, as the
nucleophile approaches the back side of the sp2 carbon, it is
repelled by the electron cloud of the double bond or the
aromatic ring.
.
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 Cont.….
 Here is Vinylic and aryl halide

 Solvent effect:
 An SN1 reaction of an alkyl halide is favored by a in a protic
polar solvent.
Example: water, methanol, ethanol

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 Elimination reaction
 Elimination reactions are those reactions in which hydrogen
along with a leaving group will be eliminated.
 Elimination reactions are used for the generation of double
and triple bonds from a saturated compounds.
 Alkyl halides undergo elimination of HX when treated with
base. The products are Alkenes.
 Elimination reactions usually require forcing conditions, i.e.
heat and strong base.
 The elimination reactions which alkyl halides undergo are
known as 1,2-eliminations or β -eliminations.
 β -elimination reactions that lead to formation of carbon-
carbon double bonds.
 β -elimination reactions can be E1 and E2.
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 Cont.….
 E1 mechanism:
 These reactions proceed under neutral conditions where a
polar solvent helps to stabilize the carbocation intermediate.
 This solvent also acts as a weak base and removes a proton in
the fast step. The mechanism shows that an E1 reaction is a
two-step reaction.
 First step is similar to that of SN1 reaction that generate
carbocation intermediate. subsequently, hydrogen is
abstracted by the base rather than attack on the carbocation as
in SN1.

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 Cont.….
 E2 mechanism:
 Two groups depart simultaneously.
 Involves one step (in other words, no intermediates are
involved.
 The base abstracts the β-hydrogen and leaving group
simultaneously leaves such that it forms a multiple bond
between α and β-carbon atoms.
 It is favored by strong base with negatively charged. Like
OH-, RO-, NH2-

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 Factors Affecting the Rate of an E1 Reaction
 The rate of an E1 reaction increases as the number of R
groups on the carbon with the leaving group increases.

 The strength of the base usually determines whether a

reaction follows the E1 or E2 mechanism.
 Strong bases like OH− and OR− favor E2 reactions, whereas
weaker bases like H2O and ROH favor E1 reactions.
 Better leaving group leads to faster reaction rates.

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 How to Favor an E2 Mechanism
1. Use a secondary or tertiary alkyl halide if possible.
 Because steric hindrance in the substrate will inhibit
substitution.
2. When a synthesis must begin with a primary alkyl halide, use a
bulky base.
 Because the steric bulk of the base will inhibit substitution.
[Link] tert-butoxide in tertbutyl alcohol (t-BuOK/t-BuOH)
are bases typically used to promote E2 reactions.

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 E1 Vs E2 mechanism
Here is summary

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 Saytzef rules
 An alkyl halide such as 2-bromopropane has two carbons from
which a proton can be removed in an E2 reaction.
 Because the two carbons are identical, the proton can be
removed with equal ease from either one.
 The product of this elimination reaction is propene.

 In contrast, 2-bromobutane has two structurally different

carbons from which a proton can be removed.
 So when 2-bromobutane reacts with a base, two elimination
products are formed: 2-butene and 1-butene.

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 Cont.….

 The stability of an alkene depends on the number of alkyl

substituents bonded to its carbons.
 The greater the number of substituents, the more stable is the
alkene.
 The major product of an E2 reaction is the most stable alkene.

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 Cont.….
 Zaitsev, devised a shortcut to predict the more substituted
alkene product.
 He pointed out that the more substituted alkene product is
obtained when a proton is removed from the carbon that is
bonded to the fewest hydrogen.

 Keep in mind that the major product of an E2 reaction is the

more stable alkene, which is more substituted alkene

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 Cont.….
 The more substituted alkene is not always the more stable
alkene.
 The conjugated alkene is the more stable alkene even though
it is not the most substituted alkene.
 The major product of each reaction is, therefore, the
conjugated alkene because, being more stable, it is more
easily formed.

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 Cont.….
 Zaitsev’s rule does not take into account the fact that
conjugated are more stable than isolated double bonds.
 So, if there is a double bond or a benzene ring in the alkyl
halide, do not use Zaitsev’s rule to predict stable product.
 In some elimination reactions, the less stable alkene is the
major product. If the base in an E2 reaction is sterically bulky,
the base will preferentially remove the most accessible
hydrogen.

End
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