11. Reactions of Alkyl Halides:

Nucleophilic Substitutions and

Eliminations

Based on McMurry’s Organic Chemistry, 7th edition

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Alkyl Halides React with

Nucleophiles and Bases

Alkyl halides are polarized at the carbon-halide bond,

making the carbon electrophilic

Nucleophiles will replace the halide in C-X bonds of

many alkyl halides(reaction as Lewis base)

Nucleophiles that are Brønsted bases produce

elimination

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Why this Chapter?

Nucleophilic substitution, base induced

elimination are among most widely occurring

and versatile reaction types in organic

chemistry

Reactions will be examined closely to see:

- How they occur

- What their characteristics are

- How they can be used

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11.2 The SN2 Reaction

Reaction is with inversion at reacting center

Follows second order reaction kinetics

Ingold nomenclature to describe characteristic step:

S=substitution

N (subscript) = nucleophilic

2 = both nucleophile and substrate in

characteristic step (bimolecular)

Mechanism of The SN2 Reaction

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The reaction takes place in

a single step when the

incoming nucleophile

approaches from a

direction 180 away from

the leaving halide ion .

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SN2 Transition State

The transition state of an SN2 reaction has a planar

arrangement of the carbon atom and the remaining

three groups

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11.3 Characteristics of the SN2

Reaction

Sensitive to steric effects

Methyl halides are most reactive

Primary are next most reactive

Secondary might react

Tertiary are unreactive by this path

No reaction at C=C (vinyl halides)

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Reactant and Transition State

Energy Levels Affect Rate

(a) Higher reactant

energy level (red

curve) = faster

reaction (smaller

G‡).

(b) Higher

transition state

energy level (red

curve) = slower

reaction (larger

G‡).

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Energy diagrams showing the effects of (a) substrate, (b) nucleophile, (c) leaving group

And (d)solvent on Sn2 reaction rates. V = k[RX][Nu]

Reactant and Transition State

Energy Levels Affect Rate

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Steric Effects on SN2 Reactions

The carbon atom in (a) bromomethane is readily accessible

resulting in a fast SN2 reaction. The carbon atoms in (b) bromoethane

(primary), (c) 2-bromopropane (secondary), and (d) 2-bromo-2-

methylpropane (tertiary) are successively more hindered, resulting in

successively slower SN2 reactions.

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Order of Reactivity in SN2

The more alkyl groups connected to the reacting

carbon, the slower the reaction

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Vinylic halides and aryl halides are unreactive toward SN2 reaction.

This lack of reactivity is probably due to steric factors.

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The Nucleophile

Neutral or negatively charged Lewis base

Reaction increases coordination at nucleophile

Neutral nucleophile acquires positive charge

Anionic nucleophile becomes neutral

See Table 11-1 for an illustrative list

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Relative Reactivity of Nucleophiles

Depends on reaction and conditions

More basic nucleophiles react faster

Better nucleophiles are lower in a column of the

periodic table

Anions are usually more reactive than neutrals

What product would you expect from SN2

reaction of 1-bromobutane with each of the

following?

a) NaI b) KOH c) H-C≡C-H

Which substance in each of the follwoing pairs

is more reactive as a nucleophile?Explain.

a) (CH3)2N‾ or (CH3)2NH ,b) (CH3)B or (CH3)B

c) H2O or H2S

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The Leaving Group In SN2 reaction the nature of the leaving group displaced by the

incoming nucleophile.

A good leaving group reduces the barrier to a reaction, the best

stabilize the negative charge in the transition state.

Stable anions that are weak bases are usually excellent leaving groups

and can delocalize charge such Cl-,Br-. While strong bases such as

OH-,NH2- are poor leaving groups.

Thionyl chloraide,

Phosphorus tribromid

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Poor Leaving Groups

If a group is very basic or very small, it is prevents reaction

Alkyl fluorides, alcohols, ethers, and amines do not typically undergo SN2 reactions.

Alcohol can be mede more reactive toward nucleophilic substitution by treating with para-toulenesulfonyl chloride to form tosylate.

Tosylate are more reactive reaction than halides in nucleophilic substitutions.

Rank the following compounds in order of

their expected reactivity toward SN2 reaction:

CH3Br, CH3OTos, (CH3)3CCl, (CH3)2CHCl

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The Solvent

The rates of SN2 reaction are strongly affected by solvent.

Solvents that can donate hydrogen bonds (-OH or –NH) slow SN2 reactions by associating with reactants

Energy is required to break interactions between reactant and solvent

Polar a protic solvents form weaker interactions with substrate and permit faster reaction

, Dimethyl sulfoxide,Dimethylformamide

,Acetonitril ,Hexamethylphsphoramide

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11.4 The SN1 Reaction

Tertiary alkyl halides react rapidly in protic solvents by a mechanism that involves departure of the leaving group former to addition of the nucleophile

Called an SN1 reaction – occurs in two distinct steps while SN2 occurs with both events in same step

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SN1 Energy Diagram

Rate-determining step is formation of carbocation

V = k[RX]

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Rate-Limiting Step

Rate-determining step is formation of

carbocation

The general rate of a reaction is controlled by

the rate of the slowest step

The rate depends on the concentration of the

species and the rate constant of the step

The highest energy transition state point on

the diagram is that for the rate determining

step.

V = k[RX]

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11.5 Characteristics of the SN1Reaction

Substrate

Tertiary alkyl halide is most reactive by this mechanism

Controlled by stability of carbocation

Remember Hammond postulate,”Any factor that stabilizes a high-energy intermediate stabilizes transition state leading to that intermediate”

Mechanism of The SN1 Reaction

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The mechanism of the

Sn1 reaction of 2-bromo-2-

Methylpropane with H2O

Involves three steps.

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Allylic and Benzylic Halides

Allylic and benzylic intermediates stabilized by

delocalization of charge

Primary allylic and benzylic are also more reactive in the

SN2 mechanism as well as in SN1

Rank the following substances in order of

their expected SN1 reactivity:

3-Bromobut-1-ene and 1-bromobut-2-ene

undergo SN1 reaction at nearly the same rate

even though one is a secondary halide and

the other is primary. Explain.

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Effect of Leaving Group on SN1

Seriously dependent on leaving group

Reactivity: the larger halides ions are better leaving groups

In acid, OH of an alcohol is protonated and leaving group is H2O, which is still less reactive than halide

p-Toluensulfonate (TosO-) is excellent leaving group

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Nucleophiles in SN1

Since nucleophilic addition occurs afterformation of carbocation, reaction rate is not

normally affected by nature or negatively

charged or concentration of nucleophile

(the nucleophile can't affect the reaction rate)

in Sn2 nucleophile plays a major role .

the reaction occures at the same rate

regardless of wether X is Cl,Br,orI

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The mechanism of the Sn1

reaction of a tertiary

alcohol with HBr to yield an

alkyl halide.

Neutral water is the leaving

group

Nucleophiles in SN1

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Solvent in SN1

Stabilizing carbocation also stabilizes associated transition state and controls rate

Solvent effects in the SN1 reaction are due largely to stabilization or destabilization of the transition state

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Polar Solvents Promote Ionization

Polar, protic and unreactive Lewis base solvents help formation of R+

Sn1 reaction take place much more rapidly in strongly polar solvents, such as water and methanol than in less polar solvent, such as ether and chloroform.

Solvent polarity is measured as dielectric polarization (P)

Nonpolar solvents have low P Polar solvents have high P values

Sn2 reactions are disfavored in protic

solvents because the ground-state energy of

the nucleophile is lowered by solvation.

Sn1 reactions are favored in protic solvents

because the transition-state energy leading to

carbocation intermediate is lowered by

solvation.

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11.7 Elimination Reactions of

Alkyl Halides: Zaitsev’s Rule Elimination is an alternative pathway to substitution

Opposite of addition

Generates an alkene

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Zaitsev’s Rule for Elimination

Reactions Base-induced elimination reaction generally

In the elimination of HX from an alkyl halide, the more

highly substituted alkene product predominates

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Mechanisms of Elimination

Reactions The classification of E – “elimination”

E1: X- leaves first to generate a carbocation

a base abstracts a proton from the carbocation

E2: Concerted transfer of a proton to a base and

departure of leaving group in one step

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11.8 The E2 Reaction

A proton is

transferred to base

as leaving group

begins to depart

Transition state

combines leaving of

X and transfer of H

Product alkene forms

stereospecifically

The E2 reaction is

analogous to the Sn2

reaction

The E1 reaction is analogous to the Sn1

reaction two steps are involved,the first of

which is rate –limiting, and a carbocation

intermediate is present.

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11.9 The E1 Reaction

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E1cB Reaction

Takes place through a carbanion intermediate

Base-induced abstraction of a proton in a slow,

rate-limiting step gives an anion, which expels

a leaving group on the adjacent carbon.

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Comparing E1 and E2

Strong base is needed for E2 but not for E1

E2 is stereospecifc, E1 is not

E1 gives Zaitsev orientation