Chapter 10 Alkyl Halide

SN2 Mechanism

SN2 Process

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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

• Hybridization is sp2

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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• Unhindered secondary halides react und

er some conditions• Tertiary are unreactive by this path• No reaction at C=C (vinyl or aryl halides)

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Reactant and Transition-state Energy Levels Affect Rate

Higher reactant energy level (red curve) = faster reaction (smaller G‡).

Higher transition-state energy level (red curve) = slower reaction (larger G‡).

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Steric Effects on SN2 Reactions

The carbon atom in (a) bromomethane is readily accessibleresulting 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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Steric Hindrance Raises Transition State Energy

• Steric effects destabilize transition states• Severe steric effects can also destabilize

ground state

Very hindered

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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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Kinetics of Nucleophilic Substitution

Rate = d[CH3Br]/dt = k[CH3Br][OH-1]

This reaction is second order: two concentrations appear in the rate law

SN2: Substitution Nucleophilic 2nd order

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The Leaving Group

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Poor Leaving Groups

• If a group is very basic or very small, it does not undergo nucleophilic substitution.

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The Solvent

• Protic solvents (which can donate hydrogen bonds; -OH or –NH) slow SN2 reactions by associating with reactants (anions).

• Energy is required to break interactions between reactant and solvent• Polar aprotic solvents (no NH, OH, SH) form weaker interactions with

substrate and permit faster reaction

SN1 Mechanism

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Some Polar Aprotic Solvents极性的非质子溶剂

S

O

CH3

H3C

dimethylsulfoxide (DMSO)

CH

O N

CH3

CH3

dimethylformamide(DMF)

PO

N

N

N

H3C CH3

CH3

CH3

CH3H3C

hexamethylphosphoramide(HMPT)

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Summary of SN2 Characteristics:

• Substrate: CH3->1o>2o>>3o (Steric effect)• Nucleophile: Strong, basic nucleophiles favor th

e reaction• Leaving Groups: Good leaving groups (weak ba

ses) favor the reaction• Solvent: Aprotic solvents favor the reaction; proti

c reactions slow it down by solvating the nucleophile

• Stereochemistry: 100% inversion

SN1 Reactivity:

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SN1 Energy Diagram

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Rate-Limiting Step

• The overall 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 step with the largest energy of activation is the rate-limiting or rate-determining step.

• See Figure 11.9 – the same step is rate-determining in both directions)

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Stereochemistry of SN1 Reaction

• The planar carbocation intermediate leads to loss of chirality• Product is racemic or has some inversion

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Effects of Ion Pair Formation

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Relative Reactivity of Halides:

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Effect of Solvent

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Effects of Solvent on Energies

• Polar solvent stabilizes transition state and intermediate more than reactant and product

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11.7 Alkyl Halides: Elimination

• Elimination is an alternative pathway to substitution

• Elimination is formally the opposite of addition, and generates an alkene

• It can compete with substitution and decrease yield, especially for SN1 processes

亲核取代反应

消除反应

• Nucleophiles that are Brønsted bases produce elimination

• Alkyl halides are polarized at the carbon-halide bond, making the carbon electrophilic

• Nucleophiles will replace the halide

Alkyl halides which have a proton attached to a neighboring β-carbon atom can undergo an elimination reaction to produce an alkene plus a hydrogen halide.

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Zaitsev’s Rule ( 扎依采夫规则） for EliminationReactions

（消除反应 ） (1875)• In the elimination of HX from an alkyl halide, the more

highly substituted alkene product predominates

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Mechanisms of Elimination Reactions 消除反应机理

• Ingold nomenclature: E – “elimination”• E1 (1st order): X- leaves first to generate a

carbocation– a base abstracts a proton from the

carbocation• E2 (2nd order): Concerted transfer of a proton to

a base and departure of leaving group

E1 mechanism: starts out like SN1

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E1 SN1

E1

E1 Mechanism

E2 mechanism: concerted

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E2 Mechanism

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Reactivity Summary: SN1, SN2, E1, E2

1o

2o

3o

reaction conditionsthe nature of the nucleophile the nature of the alkyl halide.

RX

E

SN

E1 E2

SN1 SN2

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The Nature of Substitution

• Substitution requires that a "leaving group", which is also a Lewis base, departs from the reacting molecule.

• A nucleophile is a reactant that can be expected to participate as a Lewis base in a substitution reaction.

RX1o

nucleophiles (e.g. RS, I, CN, NH3, or Br)

in polar aprotic solvents hexamethylphosphoramide(HMPA; [(CH3)2N]3PO).

strong bases HO- or EtO-. bulky basetert-butoxide [(CH3)3C–O].

E2

SN2

Increasing the temperature SN2 higher activation energy due to more bonds being broken.

E2E2

sodium tert-butoxide

RX

2o

SN2 and E2 reactions to give a mixture of products.

a polar aprotic solvent SN2a strong base E2Increasing the temperature E2 If weakly basic or nonbasic nucleophiles are used in protic solvents, eliminationand substitution may occur by the SN1 and E1 mechanisms to give mixtures.

RX

3o

SN1( 极性溶剂） and E1 （强碱） reactions