07 lecture

© 2013 Pearson Education, Inc.

Chapter 7Lecture

Alkyl Halides:Nucleophilic Substitution

and Elimination



Classes of Alkyl Halides

• ___________ halides: Halogen is directly bonded to sp3 carbon.

• Vinyl halides: Halogen is bonded to ____ carbon of alkene.

• ______halides: Halogen is bonded to sp2 carbon on _______ ring.

C CH

H

H

Cl

C

H

H

H

C

H

H

Br

I

Chapter 6 2


IUPAC NomenclatureCH3CH2CH2CHCH2CH2CH3

CH2CH2F

4-(2-fluoroethyl)heptane

CH3CHCH2CH3

Cl

Chapter 6 3

CH3CHCH2CH2CH2CHCH2CH2CH3

BrCH3Br

F H

H


Common Names

CH3CHCH2

CH3

Br CH3CH2CH

CH3

Br CH3C

CH3

Br

CH3

Chapter 6 4

CH2X2 is called methylene halide.CHX3 is a haloform.CX4 is carbon tetrahalide.

Common halogenated solvents: ________ is methylene chloride.

_______ is chloroform.

________is carbon tetrachloride.

© 2013 Pearson Education, Inc. Chapter 6 5

Compare classification to alcohols and amines


Uses of Alkyl Halides• Industrial and household cleaners.• Anesthetics:

• CHCl3 used originally as general anesthetic but it is toxic and carcinogenic.

• CF3CHClBr is a mixed halide sold as Halothane. • Freons are used as refrigerants and foaming agents.

• Freons can harm the ozone layer, so they have been replaced by low-boiling hydrocarbons or carbon dioxide.

• Pesticides such as DDT are extremely toxic to insects but not as toxic to mammals. • Haloalkanes can not be destroyed by bacteria, so

they accumulate in the soil to a level that can be toxic to mammals, especially humans.

Chapter 6 6


Dipole Moments depends on electronegativity and bond length

• Electronegativities of the halides:

• > > > > • Bond lengths increase as the size of

the halogen increases:

• > > > >• Bond dipoles:

C—Cl > C—F > C—Br > C—I 1.56 D 1.51 D 1.48 D 1.29 D

Chapter 6 7

Carbon—halogen bond is polar, carbon has partial _______ charge and can be attacked by ____________


Boiling Points and Densities• Greater intermolecular forces, higher b.p.

• Dipole-dipole attractions not significantly different for different halides.

• London forces greater for larger atoms.• Greater mass, higher b.p.• Spherical shape decreases b.p.

(CH3)3CBr CH3(CH2)3Br 73 C 102 C

• Alkyl fluorides and alkyl chlorides (those with just one chlorine atom) are less dense than water (1.00 g/mL).

• Alkyl chlorides with two or more chlorine atoms are denser than water.

• All alkyl bromides and alkyl iodides are denser than water.•

Chapter 6 8


Preparation (synthesis) of Alkyl Halides

• Free radical halogenation• _________________more selective than

__________________

• Free radical allylic halogenation• Halogen is placed on a carbon

________________to the double bond (allylic).

Chapter 6 9


Write the mechanism for the free radical bromination of propane

Chapter 2 11


Synthesis of alkyl halides by allylic bromination

• Allylic radicals are resonance stabilized.• Bromination occurs with good yield at the

allylic position (sp3 C next to C C).

Chapter 6 12


Mechanism of allylic bromination• N-Bromosuccinimide (NBS) is an allylic brominating agent.• Reacts close to room temperature.

• The mechanism involves an ___________stabilized by ____________. Both allylic radicals can react with bromine.

Chapter 6 13

© 2013 Pearson Education, Inc. Chapter 6 14

Major Write mechanism


Reactions of Alkyl Halides

Chapter 6 15


The SN2 Reaction: Substitution Nucleophilic Bimolecular

• The___________atom on the alkyl halide is replaced with the ____________(HO-).

• Since the halogen is more electronegative than carbon, the C—I bond breaks ________________ and the iodide ion leaves.

Chapter 6 16


Back-Side Attack in the SN2 Reaction

Chapter 6 17

SN2 Energy Diagrama_) Exergonic

b) ____________

c) Transition state resembles ____hybridizationd) _____species participate in rds

e) Rate law

f) Stereochemistry ______________


New functional groups synthesized with the SN2 Reaction or RX

Chapter 6 18


SN2 requires a _______ nucleophileStronger nucleophiles give fast SN2

Chapter 6 19

A negatively charged nucleophile is ___________ than its neutral counterpart:

In the same period, nucleophilicity ____________ from left to right: __________down periodic table, as size and polarizability increase:


The more polarizable, the better Nu

Electrons in a larger atom are not as tightly held as the electrons in a smaller atom and can be used to form a bond much easier

Chapter 6 20


The solventDielectric constant: A measure of a solvent’s ability to insulate opposite charges from one another: The greater the value of the dielectric constant of a solvent, the smaller the interaction between ions of opposite charge dissolved in that solvent.


SN2 reactions proceed faster in aprotic solvents that “free” the Nu

• Polar protic solvents ________ acidic hydrogens (O—H or N—H) that can solvate the nucleophile, _________ their nucleophilicity.

• Nucleophilicity in protic solvents increases as the size of the atom increases

Chapter 6 22

Polar aprotic solvents ________have acidic protons and therefore ________ hydrogen bond and Nu is “free” to attack


Crown ethers solvate the cation, so the nucleophilic strength of the anion

increases (“Free” to attack) • Fluoride becomes a

good nucleophile.

Chapter 6 23


A good leaving group is required in substitution and elimination

reactionsThe best leaving groups are:• Electron-withdrawing, to polarize the carbon atom.• Stable (not a strong base) once they have left.• Polarizable, to stabilize the transition state.

Chapter 6 24


Relative rates for SN2 depends on structure of substrate (RX, electrophile)

Nucleophile approaches fromthe back side; It must overlapthe back lobe of the C—X sp3

orbital.

Chapter 6 25

CH3X 1° 2° 3°• Tertiary halides do not react via the SN2 mechanism,

due to _________________hindrance.


Stereochemistry of SN2 SN2 reactions will result in an inversion of

configuration also called a Walden inversion.

Chapter 6 26

The SN2 reaction is a ___________ nucleophilic substitution.

It is a ______________ reaction

Rate = ____________________

_____________ of configuration occurs.


Write the mechanism for the reaction or (S)-2-Chlorobutane with iodide ion

Chapter 6 27


The SN1 Reaction• The SN1 reaction is a ______________

nucleophilic substitution.

• _____________It has a ____________ intermediate.

• Racemization ___________

• Rate = ____________Chapter 6 28


SN1 Mechanism

If the nucleophile is an uncharged molecule like water or an alcohol, the positively charged product must lose a proton to give the final uncharged product.

Step 1: Formation of the carbocation (rate-determining step)

Step 2: Attack of the nucleophile.

Chapter 6 29


Step 3: If the nucleophile was neutral, a third step (deprotonation) will be needed.

Chapter 6 30

SN1 Energy Diagram______________

Forming the carbocation is ______________

Step 2 is _______ with a ______activation energy.If the product is chiral a _____________is obtainedRate =


Stereochemistry of SN1enantiotopic phases of the carbocation

• Carbocations are _______hybridized and have ________ geometry. The lobes of the empty p orbital are perpendicular to the trigonal plane above and below.

• Nucleophilic attack can occur from either side, producing mixtures of retention and inversion of configuration if the carbon is chiral.

Chapter 6 31


Stereochemistry of SN1

The SN1 reaction produces mixtures of enantiomers. There is usually slightly _______inversion than retention of configuration.

Chapter 6 32


examples of complete racemization have been observed, but partial racemization with a slight excess of inversion is more

common.


Factors that favor SN1 reactionsa) Nature of the electrophile (RX)

b) A better leaving group will increase the rate of the reaction.

c) Polar protic solvent is best because it can solvate both ions strongly through hydrogen bonding stabilizing the carbocation. This reactions usually are solvolysis.

Chapter 6 34


Rearrangements can occur

• Carbocations can rearrange to form a more stable carbocation: 1,2 Hydride shift: H-, 1,2- Methyl shifts: CH3

- or phenyl Ph- shifts.

Chapter 6 35


Write mechanism for the following reaction

Chapter 6 36


SN1 or SN2 Mechanism?SN2 SN1

CH3X > 1º > 2º 3º > 2º

Strong nucleophile Weak nucleophile (may also be used as solvent)

Polar aprotic solvent Polar protic solvent

Rate = k[alkyl halide][Nuc] Rate = k[alkyl halide]

Inversion at chiral carbon Racemization

No rearrangements Rearranged products

Chapter 6 37


Exercises


In general, strong bases are strong nucleophiles,

but not all strong nucleophiles are basic.

• Basicity is defined by the equilibrium constant for abstracting a proton.

• Nucleophilicity is defined by the rate of attack on the electrophilic carbon atom

Chapter 6 41


Elimination Reactions

• Elimination reactions produce double bonds.• Also called dehydrohalogenation (-HX).

Chapter 6 42


The E1 Reaction “Nucleophile” acts as base.• __________ elimination.• Stepwise. ___________ intermediate.• Solvolysis reaction • Rate = • The E1 and SN1 reactions have the same conditions so a

mixture of products will be obtained.

Chapter 6 43


E1 MechanismStep 1: The leaving group leaves to form a ____________

Step 2: Solvent abstracts a proton to form an __________

Chapter 6 44


In elimination reactions, the major product of the reaction is the more stable, more

substituted double bond: Zaitsev’s rule.

tetrasubstituted trisubstituted disubstituted monosubstituted

Chapter 6 45


E1 and SN1occur in solvolysis

• Substitution results from _________attack on the carbocation • Ethanol serves as a ___________ in the elimination and as a

______________ in the substitution.

A carbocation can:React with its own leaving group to return to the reactant.React with a nucleophile to form a substitution product (SN1).Lose a proton to form an elimination product (E1).Rearrange to give a more stable carbocation, then react further.

Chapter 6 46


The E2 Reaction

• ___________________.• Requires a __________ base.• This is a _________________ reaction: The proton

is abstracted, the double bond forms, and the leaving group leaves, all in one step.

Chapter 6 47


The E2 Reaction• Reactivity for alkyl halides:

3° > 2 ° > 1°• Mixture may form, but

Zaitsev product predominates

• The halide and the proton to be abstracted must be anti-coplanar ( = 180º) (orbitals aligned so they can begin to form a pi bond in the transition state and

steric hindrance between the base and the leaving group is minimized) Chapter 6 48


E1 or E2 Mechanism?• Tertiary > secondary• Base strength usually

weak. Solvolysis• Good ionizing solvent

(polar protic)• Rate = k[alkyl halide]• Zaitsev product

• No required geometry

• Rearranged products

• Tertiary > secondary• Strong base required

• Polar aprotic solvent

• Rate = k[alkylhalide][base]• Zaitsev product

• Coplanar leaving groups (usually anti)

• No rearrangements

Chapter 6 49


Substitution or Elimination?• Strength of the nucleophile determines

order: Strong nucleophiles or bases promote bimolecular reactions.

• 10 halides usually undergo SN2.• 30 halides are a mixture of SN1, E1, or

E2. They cannot undergo SN2.• High temperature and bulky bases favor

elimination.

Chapter 6 50


20 halides: strong nucleophiles will promote SN2/ Strong bases E2.Weak nucleophiles/ bases promote SN1/E1.

• Bromide and iodide are good examples of strong nucleophiles, weak bases

• Ethoxide/ethanol is a better base than a nucleophile• Terbutoxide/terbutyl alcohol can not act as a

nucleophile• Ethanol (polar protic solvent solvolysis

Chapter 6 51


.

Predict the mechanisms and products of the following reaction

Chapter 6 52


Predict the mechanisms and products of the following reaction.

Chapter 6 53