Chapter 11: Reactions of Alkyl Halides: Nucleophilic Substitutions and Eliminations

Goals

•     After this chapter, you should be able to:

–    Determine the stereochemistry of SN2 reactions

–    Determine Products of SN2 vs SN1 reactions

–    Determine whether SN2, SN1, E1 or E2 will occur

 

 

 

Review

•     http://www.chem.monash.edu.au/Docs/DGHewitt/Powerpnt/Lect5/sld001.htm

Walden Inversion

 

 

What is an SN2 Reaction?

•     SN2 mechanism; S for substitution, N for nucleophilic and 2 because two molecules collide at the critical point in the reaction.

An SN2 Reaction

•     From CD

–    D:\OCOL_HTM\OCOL\MECH\MOVIE\11_03.MOV

–    E:\OCOL_HTM\OCOL\MECH\MOVIE\11_03.MOV

•     From Zip

–    Ch11files\11_03.MOV

Stereochemistry of Inversion

•     If the nucleophile and the leaving group are both high in the R/S priority order, this means that an R alkyl halide gives an S product, and vice-versa

 

Energy of Inversion

Energy of Inversion

With SN2, Size of Substituent Groups Matters

Kinetics of Nucleophilic Substitution

•     Rate = k[RBr][Nu-]

•     Second order kinetics

Effect of Bond Strength of the Leaving Group on SN2 Reactivity

•     Since the carbon-halogen bond strength increases up the periodic table the relative SN2 reactivity of the alkyl halide is:

 RF < RCl < RBr < RI

TosO- is a better leaving group than I-

OH-, NH2-, and RO- are worse than F-

Nucleophilicity:

CH3CO2 (-) < Cl(-) < Br(-) < N3(-) < CH3O(-) < CN(-) < I(-) < SCN(-) < CH3S(-) 

 

•    

Parallels basicity

–    H2O < C2H3O2- < OH-

•     Increases down the periodic table

–    I- < Cl- < F-

•     Anions are more nucleophilic than neutral compounds

•     The solvent matters!

Solvent Effects

Consider KBr as a nucleophile source

•     Protic solvents with –OH, -NH slow SN2 rxn

–    These solvents cluster around the nucleophile lowering the effective nucleophilicity

•     Polar aprotic solvents speed SN2

–    These solvents cluster around the metal ion of the salt freeing the nucleophile to be nucleophilic.

 

Characteristics of SN2 Reactions

•     Single Step Mechanism

•     Inversion of configuration

•     SN2 reactions are generally reliable only when the alkyl halide is primary

•     Halogen is generally Cl or Br since

–    C-F bond is too strong

–    C-I bond is weak and compounds are unstable

An SN2 Reaction

•     From CD

–    D:\OCOL_HTM\OCOL\MECH\MOVIE\11_03.MOV

–    E:\OCOL_HTM\OCOL\MECH\MOVIE\11_03.MOV

•     From Zip

–    Ch11files\11_03.MOV

Test Your Knowledge

•     Quiz Type Quiestions:

–    http://www.cem.msu.edu/~reusch/OrgPage/VirtualText/alhalrx2.htm

 

 

SN1 Reactions

•     SN1 reactions proceed by a two step mechanism

–    First: Leaving group leaves giving a carbocation


 

 

 


–    Second: Nucleophile attacks carbocation


 


An SN1 Reaction

•     From CD

•     D:\OCOL_HTM\OCOL\MECH\MOVIE\11_09.MOV

•     E:\OCOL_HTM\OCOL\MECH\MOVIE\11_09.MOV

•     From Zip

•     Ch11files\11_09.MOV

SN1 Reactions


Leaving Groups

OH- < NH2 -<RO- F - < Cl - < Br - <  I < TosO-

 

Susceptibility to leaving

Evidence for SN1 Kinetics

•     The reaction rate is only dependent upon the concentration of the substance with the leaving group

–    R-X ΰ R+ + X- is a slow = rate determining

•     Racemic mixtures are usual

–    Carbocation formation

•     Rate = k[R-X] where X is leaving group

SN1 Reaction Rates

•     Depend on stability of the carbocation

–    More stable carbocation=faster reaction

-CH3 < 1° <                                                   » 2° < 3°

 

       Relative Stability of Carbocation

 


The Nucleohile has no effect on rate of  SN1


Energy for SN1

Solvent Effects on SN1

•    

Polar solvents stabilize the intermediate carbocation.

Summary SN1

•     Fastest with

–    Compounds that form stable carbocation

–    Good leaving group

–    Nucleophiles that are not basic to prevent competing elimination reactions

–    Polar solvents

An SN1 Reaction

•     From CD

•     D:\OCOL_HTM\OCOL\MECH\MOVIE\11_09.MOV

•     E:\OCOL_HTM\OCOL\MECH\MOVIE\11_09.MOV

•     From Zip

•     Ch11files\11_09.MOV

Elimination Reactions

•     Zaitsev’s Rule:

–   

Base induced elimination reactions generally give the more highly substituted double bond alkene product

An E2 Reactions

•     From CD

–    D:\OCOL_HTM\OCOL\MECH\MOVIE\11_17.MOV

–    E:\OCOL_HTM\OCOL\MECH\MOVIE\11_17.MOV

•     From Zip

–    Ch11files\11_17.MOV

E2 Reactions

•    

Single step attack of nucleophile on hydrogen on carbon adjacent to the carbon containing the leaving group.

E2 Kinetics

•     The rate of the reaction is dependent upon the concentration of the compound containing the leaving group and the nucleophile base.

•     Rate = k[RX][Base]

Geometry of E2

 

•     All atoms involved are in same plane

•    

The hydrogen and leaving group are anti

 

 



Cycloalkane E2:
 What do you expect?

E2 Reaction

An E2 Reactions

•     From CD

–    D:\OCOL_HTM\OCOL\MECH\MOVIE\11_17.MOV

–    E:\OCOL_HTM\OCOL\MECH\MOVIE\11_17.MOV

•     From Zip

–    Ch11files\11_17.MOV

The E1 Reaction

•     From CD

–    D:\OCOL_HTM\OCOL\MECH\MOVIE\11_21.MOV

–    E:\OCOL_HTM\OCOL\MECH\MOVIE\11_21.MOV

•     From Zip

–    Ch11files\11_21.MOV

E1 Reactions

•     First step is identical to SN1 – Elimination of the leaving group giving a carbocation

•     First step is slow and rate determining

•     Second step is the attack of a hydrogen on a carbon adjacent to the carbocation

•     Racemic mixtures are usual

 

 

 

 

E1 Kinetics

•    
Rate = k[R-X]


Substitutions in Synthesis

•     See Text