organic chemistry chapter 8. substitution and elimination if an sp 3 c is bonded to electronegative...

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Organic Chemistry Chapter 8

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Organic Chemistry

Chapter 8

Substitution and Elimination

• If an sp3 C is bonded to electronegative atom Substitution reactions and

Elimination reactions are possible

This chapter is all about substitution

SN2 and SN1 Reactions

SN2 - Reaction – bonds break and form at the same time

example

SN1 - CX bond breaks, forming a C+ then reacts with a nucleophile

XC+

C + + X-

NuCC + + Nu:

SN1

SN2

Nucleophilic Substitution Reactions

Either mechanism depends on the:• structure of the alkyl halide• reactivity of the nucleophile• concentration of the nucleophile• The solvent in which the Rx is carried out• The leaving group

SN2 Mechanism

• It’s a Substitution Reaction (S)

• It’s Nucleophilic (N)

• It’s rate is second order (2)– Called bimolecular (rate is dependent on 2 reactants)

• (Substitution Nucleophilic Bimolecular)

CH3Br + HO - CH3OH + Br-

methyl bromide methyl alcohol

Rate = k [RX] [Nu:]

(Because rate is dependent of BOTH RX and Nu: it is 2nd. order.)

SN2 Mechanism

• SN2 Mechanism involves a “backside attack”

SN2 Mechanism

The “backside attack” causes an Inversion of Configuration

Careful now….. Doesn’t mean R becomes S – new atoms are involved

Steric Hindrance

• Groups that block the path from the nucleophile to the electrophilic atom produce steric hindrance

• This results in a rate differences or no reaction at all

methyl halide ethyl halide isopropyl halide t-butyl halide

Steric Hindrance

• Activation Energy is higher due to steric hindrance…..

Substitution Reactions Depend on a Good Leaving Group

• R-F alkyl fluorides• R-Cl alkyl chlorides• R-Br alkyl bromides• R-I alkyl iodides• Alkyl Halides make good “leaving groups”

– They are easily displaced by another atom– They allow the Conversion of alkyl halides to other functional

groups

SN2 Mechanism

• The Leaving Groups also affects rate• RI reacts fastest, RF slowest

– Iodide is the best “leaving group”– Fluoride is the worst “leaving group”

(…reacting with the same alkyl halide under the same conditions)

Basicity

• The weaker the basicity of a group, the better the leaving ability.

(Lewis base = e- pair donor)

– Leaving ability depends on basicity because a weak base does not SHARE its e- as well as a strong base.

– Weak bases are not strongly bonded to a carbon

(weak bases are GOOD leaving groups)

Nucleophiles – Strong/Weak Good/Bad

Stronger base Weaker baseBetter nucleophile poorer nucleophile

OH- > H2O

CH3O- > CH3OH-NH2> NH3

CH3CH2NH- > CH3CH2NH2 (conjugate acids)

Nucleophiles

• The strength of nucleophile depends on reaction conditions.

• In the GAS phase (not usually used), direct relationship between basicity and nucleophilicity

Solvent Effects

• In a solution phase reaction, the solvent plays a large role in how the reaction will occur

• Solvent effects can cause just the opposite of what might be the expected behavior of the nucleophile

• Solvents are categorized as either protic or aprotic

Protic SolventsProtic solvents has a H bonded to a N or O

– It is a H bonder

– Examples: H2O, CH3OH, NH3, etc

– Solvent is attracted to the Nucleophile and hinders its ability to attack the electrophile

Aprotic Solvents• Use an aprotic solvent

• Solvates cations • Does not H bond with anions (nucleophile free)• Partial + charge is on inside of molecule• Negative charge on surface of molecule (solvates

cation)• Examples include:

– DMSO (dimethyl sulfoxide)– DMF (dimethyl formamide)

– Acetone (CH3COCH3)

acetone

CH3CCH3

O

dimethyl sulfoxide

CH3SCH3

O

DMSON,N-dimethylformamide

HC N

O

CH3

CH3

DMF

Nucleophiles

• In the organic solvent phase, INVERSE relationship between basicity and nucleophilicity with a protic solvent

Question…

Nucleophiles• Solvents can solvate the nucleophile

– Usually this is NOT good because the nucleophile is “tied up” in the solvent and LESS REACTIVE.

Ion-dipole interactions

Nucleophiles• Solvents can solvate the nucleophile

(Methanol is a polar protic solvent.)

SN2 Reactions

SN2 Reactions

SN2 Reactions• SN2 reactions might be reversible

• Leaving group would become the nucleophile

• Compare basicity (nucleophile strength) to see which is a better leaving group.

• The stronger base will displace the weaker base– If basicity is similar, the Rx will be reversible

CH2CH3 Br + I- CH2CH3 I + Br-CH2CH3 Br + I- CH2CH3 I + Br-

SN2 Reactions

Compare basicity to see which is a better nucleophile.

SN1 Reactions

• Reaction of t-butyl bromide with water should be slow– water is a poor nucleophile– t-butyl bromide is sterically hinderedHowever– Reaction is a million times faster than with CH3Br

t-butyl bromide

CCH3

CH3

Br

CH3

+ H2O

t-butyl alcohol

CCH3

CH3

OH

CH3

+ HBr

t-butyl bromide

CCH3

CH3

Br

CH3

+ H2O

t-butyl alcohol

CCH3

CH3

OH

CH3

+ HBr

(Maybe not an SN2 reaction!)

SN1 Reactions•

SN1 Mechanism• Rate determining step does not involve

nucleophile

Step 2

Step 1

SN1 Mechanism

SN1 Reactivity

• Relative Reactivities in an SN1 Reaction

1o RX < 2o RX < 3o RX

Increasing Reactivity

SN1 Stereochemistry

• Because a planer carbocation is formed, nucleophilic attack is possible on both sides, so both isomers are possible

SN1 Stereochemistry

SN1 should yield racemic mixture but it doesn’tThis is due to the steric hindrance of the leaving group

Stereochemistry• As the leaving group goes (Marvin K) it

blocks the path of any incoming nucleophiles

SN1 vs SN2

Inversion of configuration

racemization withpartial inversion

What Makes SN1 Reactions work the best

• Good Leaving Group– The weaker the base, the less tightly it is held

(I- and Br- are weak bases)

• Carbocation– How stable is the resulting carbocation?

• 3o > 2o > 1o > methyl

Increasing Stability

What Doesn’t Matter In anSN1 Reactions

• The Nucleophile• It has NO EFFECT on rate of Rx!!!

• Solvolysis Reactions • (the nucleophile is also the solvent)

Carbocation RearrangementsSince a carbocation is the intermediate, you may see

rearrangements in an SN1 Rx

No rearrangements in an SN2 Rx

Carbocation Rearrangement

• Methyl Shift

Benzylic, Allylic, Vinylic,and Aryl Halides

• Benzylic and allylic halides can readily undergo SN2 unless they are 3o – (steric hindrance)

Benzylic, Allylic, Vinylic,and Aryl Halides

• Benzylic and allylic halides can also undergo SN1 (they form stable carbocations)

• Even though 1o RX do not go SN1, 1o benzylic and 1o allylic CAN react SN1!

Vinylic,and Aryl Halides

• Vinylic halides and aryl halides– do not undergo SN1 or SN2 reactions! e- repel incoming Nucleophile

BrBr

SN1 vs SN2 Review

SN1 vs SN2

Methyl, 1o RX …2o RX …3o RX …

Vinylic, aryl RX …1o, 2o benzylic, allylic RX …

3o benzylic, allylic RX …

SN2 only

SN1 and SN2

SN1 only

neither SN1 nor SN2

SN1 and SN2

SN1 only

Role of the SolventIn an SN1, a carbocation and halide ion are formed

– Solvation provides the energy for X- being formed– In SN1 the solvent “pulls apart” the alkyl halide– SN1 cannot take place in a nonpolar solvent or in

the gas phase– Increasing the polarity of the solvent will

INCREASE the rate of Rx if none of the REACTANTS are charged.

– If reactants are charged it will DECREASE the rate.

Role of the Solvent

• So….• In an SN1 reaction, the reactant is RX. The

intermediate is charged and is STABILIZED by a POLAR solvent

A POLAR solvent increases the rate of reaction for an SN1 reaction.

(However, this is true only if the reactant is uncharged.)

*

Role of the Solvent In SN2

• In an SN2 reaction, one of the reactants is the nucleophile (usually charged).

• The POLAR solvent will usually stabilize the nucleophile.

A POLAR solvent decreases the rate of reaction for an SN2 reaction.

(However, this is true only if the nucleophile is charged.)

Polar Aprotic Solvents

• Polar Aprotic Solvents include:– DMF N,N-dimethylformamide

– DMSO dimethylsulfoxide

– HMPA hexamethylphosphoramide

– THF Tetrahydrofuran– And even… acetone

Polar Aprotic Solvents

Polar Aprotic Solvents – do not H bond– solvate cations well– do NOT solvate anions (nucleophiles) well– good solvents for SN2 reactions

Polar Aprotic Solvents

• DMSO• DMF• Acetone• HMPA

Nucleophile Review

strong

weak

Br-, I-

HO-, CH3O-, RO-

CH3S-, RS -

CH3CO2-, RCO2

-

H2OCH3OH, ROHCH3CO2H, RCO2H

NH3, RNH2, R2NH, R3NCH3SH, RSH, R2S

EffectivenessNucleophile

moderate

CN-, N3-

SN1/SN2 Problems -1

• Predict the type of mechanism for this reaction, and the stereochemistry of each product

+

+ +

OH

Cl

OCH3

CH3CHCH2CH3

CH3CHCH2CH3

CH3CHCH2CH3

CH3OH/H2O

HCl(R)-enantiomer

SN1/SN2 Problems -1

• Predict the type of mechanism for this reaction, and the stereochemistry of each product

+

+ +

OH

Cl

OCH3

CH3CHCH2CH3

CH3CHCH2CH3

CH3CHCH2CH3

CH3OH/H2O

HCl(R)-enantiomer

SN1/SN2 Problems -2

• Predict the mechanism of this reaction

+

+

DMSOCH3

CH3

CH3CHCH2CN

CH3CHCH2Br Na+CN-

Na+Br-

SN1/SN2 Problems -2

• Predict the mechanism of this reaction

+

+

DMSOCH3

CH3

CH3CHCH2CN

CH3CHCH2Br Na+CN-

Na+Br-

SN1/SN2 Problems -3

• Predict the mechanism. If the starting material has the R configuration, predict the configuration of product

+

+

acetone

Br

SCH3

CH3CHCH2CH3 CH3S-Na+

CH3CHCH2CH3 Na+Br-

SN1/SN2 Problems -3

• Predict the mechanism. If the starting material has the R configuration, predict the configuration of product

+

+

acetone

Br

SCH3

CH3CHCH2CH3 CH3S-Na+

CH3CHCH2CH3 Na+Br-

SN1/SN2 Problems -4

• Predict the mechanism

+ acetic acidBr

OCCH 3

O

O

CH 3 COH

+ HBr

SN1/SN2 Problems -4

• Predict the mechanism

+ acetic acidBr

OCCH 3

O

O

CH 3 COH

+ HBr

SN1/SN2 Problems -5

• Predict the mechanism

+ toluene

Br-

(CH3)3PCH3(CH2)5CH2Br

CH3(CH2)5CH2-P(CH3)3

+

SN1/SN2 Problems -5

• Predict the mechanism

+ toluene

Br-

(CH3)3PCH3(CH2)5CH2Br

CH3(CH2)5CH2-P(CH3)3

+

END