organic reactions susbstitution s - professional...

Organic ReactionsSusbstitution – SN

2

Dr. Sapna Gupta

Kinetics of Nucleophilic Reaction

• Rate law is order of reaction

• 0 order is when rate of reaction is unaffected by change in concentration of the reactants

• 1st order is when rate of reaction doubles when one of the reactants is doubled

• 2nd order is when rate of reaction quadruples when two of the reactants are doubled

• Order of reaction explains the reaction mechanism

Dr. Sapna Gupta/Substitution Reactions 2

• In this reaction a nucleophile is a species with an unshared electron pair which reacts with an electron deficient carbon

• A leaving group is substituted by a nucleophile

• Examples of nucleophilic substitution

Nucleophilic Substitution Reactions


The SN2 Reaction

• 2nd order substitution reaction

• S=substitution

• N (subscript) = nucleophilic

• 2 = (bimolecular) both nucleophile and substrate in characteristic step

• Inversion of stereochemistry occurs


• The initial rate of the following reaction is measured

• The rate is directly proportional to the initial concentrations of both methyl chloride (substrate) and hydroxide (nucleophile)

• The rate equation reflects this dependence

• SN2 reaction: substitution, nucleophilic, 2nd order (bimolecular)

An SN2 Reaction


3

–A transition state is the high energy state of the reaction

• It is an unstable entity with a very brief existence (10-12 s)

– In the transition state of this reaction bonds are partially formed and broken

–Both chloromethane and hydroxide are involved in the transition state and this explains why the reaction is second order

A Mechanism for the SN2 Reaction


SN2 Energy Diagram

• One-step reaction.

• Transition state is highest in energy.


• Negatively charged nucleophiles like HO¯ and HS¯ are used as salts withLi+, Na+, or K+ counterions to balance the charge. Since the identity ofthe counterion is usually inconsequential, it is often omitted from thechemical equation.

Examples of Nucleophilic Substitution

• When a neutral nucleophile is used, the substitution product bears apositive charge.


Uses for SN2 Reactions• Synthesis of other classes of compounds.

• Halogen exchange reaction.


Factors Affecting SN2

1. Nucleophile Strength

2. Size of the nucleophile

3. Substrate (steric effect)

4. Leaving group

5. Effect of solvent


1) Nucleophilic Strength

• Stronger nucleophiles react faster.

• Strong bases are strong nucleophiles, but not all strong nucleophiles are basic*.

• Strength of Nu is based on:

• Charge: In a conjugate acid-base pair, the base (anion) is stronger:

OH- > H2O, NH2- > NH3

• Periodicity: Decreases left to right on the Periodic Table. More electronegative atoms less likely to form new bond:

OH- > F-, NH3 > H2O

• Size: Increases down Periodic Table, as size and polarizabilityincrease: I- > Br- > Cl-

* Bases are characterised by their ability to abstract a proton while nucleophiles reacts with electrophiles.


Nucleophiles

•Some examples


2) Size of Nucleophile

• Larger nucleophiles are not good for SN2 because they will not be able to access the electrophilic carbon.

• E.g. EtO– better than tBuO- even though tBuO- is a stronger base.

Note: Alkoxides as Nucleophiles.

• CH3O-Na+, CH3CH2O-K+ - alkoxides are synthesized as salts – potassium or sodium. They are synthesized by dissolving solid sodium or potassium in the respective alcohol in a moisture and oxygen free environment.

CH3OH + Na CH3O-Na + + H2

• Nomenclature: CH3O-Na+, sodium methoxide, CH3CH2O-K+ potassium ethoxide, (CH3)3CO-Na+ sodium t-butoxide


3) Substrate: Steric Hindrance - 1

• Nucleophile approaches from the back side hence the electrophilic carbon should not be hindered.

• Best substrates for SN2 are primary halides.

1o> 2o>3o


3) Substrate: Steric Hindrance - 2

• The more alkyl groups connected to the reacting carbon, the slower the reaction


4) Leaving Group

• Should be electron-withdrawing to provide an electrophilic carbon

• Stable once it has left (not a strong base)

• Usually halides are good LG.

• Weaker bases make best LG.

• NOTE: weaker base cannot displace stronger base in a SN2 reaction

Examples of leaving groups


5) Solvents3 kinds of solvents

Solvent Polar protic polar aprotic non polar

Examples H2OCH3OH, CH3CH2OH

DMF (dimethylformamide), DMSO (dimethylsulfoxide)Shown below.

HexaneTolueneDiethyl etherDichloromethane

Comments Will form H-bondswith Nu and therefore need more energy to form transition state

Does not form H-bond with Nu butstill helps to solvate ions hence the best kind for SN2

Not good for SN2since they will not stabilize the ions formed.


• Backside attack of nucleophile results in an inversion of configuration

• In cyclic systems a cis compound can react and become trans product

The Stereochemistry of SN2 Reactions


SN1 Reaction

• Unimolecular nucleophilic substitution.

• Two step reaction with carbocation intermediate.

• Rate is first order in the alkyl halide, zero order in the nucleophile.

• Racemization occurs.


The SN1 Reaction Mechanism


SN1 Energy Diagram

• There are three transition states. Step1 crosses the highest energy barrier and is rate determining


Stereochemistry of SN1

Racemization: inversion and retention


Factors Affecting Rates of SN1 Reactions

1. Substrate: 3° > 2° > 1° >> CH3X

2. Leaving group: should be weak base(like SN2)

3. Nucleophile: no effect since its not part of the transition state –but in general weak Nu can also react.

4. Solvent: Polar protic solvent best, it solvates ions strongly with hydrogen bonding.


1) Nature of Substrate

Substrate: 3° > 2° > 1° >> CH3X

a) Order follows stability of carbocations (opposite to SN2)

b) More stable ion requires less energy to form

c) Resonance can also stabilize cation (e.g. allyl cation – C=C-C+)


2) Leaving Group

• Leaving group is key in forming the carbocation intermediate for transition state.

• 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-Toluenesulfonate (TosO-) is excellent leaving group

3) Nucleophile

• Does not matter since nucleophile is not part of the rate determining step.


4) Solvent

Polar solvents help with ionization and stability of the carbocation.


SN2 or SN1?

SN2 SN1

Substrate Primary or methyl Tertiary

Nucleophile Strong nucleophile Weak nucleophile (may also be solvent)

Solvent Polar aprotic solvent Polar protic solvent, silver salts

Kinetics [substrate][Nu] [substrate]

Stereochemistry Inversion Racemic mixture

Rearrangement No Yes


Solved Problems

• Predict mechanism and stereochemistry of each product

• Predict mechanism of the following reaction

• Predict mechanism and stereochemistry of each product

Cl

CH3OH/ H2O

OH OCH3

HCl+

(R)-2-Chlorobutane

+ +

+ +Na+ CN- Na+ Br -

DMSOBr CN

Br

CH3S-Na+

SCH3

Na+Br-+ +acetone

(R)-2- Bromobutane


Key Words/Concepts

•Substitution Reaction•Nucleophile•Electrophile•Leaving group•1st order reaction (unimolecular)•2nd order reaction (bimolecular)•Transition state•Rate determining step•Carbocation

•Polar protic solvent•Polar aprotic solvent•Non polar solvent•Solvolysis

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