chapter 81 substitution reactions of alkyl halides: chapter 8
TRANSCRIPT
Chapter 8 1
Substitution Reactions of Alkyl Substitution Reactions of Alkyl Halides:Halides:Chapter 8Chapter 8
Chapter 8 2
Contents of Chapter 8 Reactivity Considerations
The SN2 Reaction
Reversibility of the SN2 Reaction
The SN1 Reaction
Stereochemistry of SN2 and SN1 Reactions
Benzylic, Allylic, Vinylic & Aryl Halides
Competition between SN2 and SN1 Reactions
Role of the Solvent No Biological Methylating Reagents
Chapter 8 3
Substitution and Elimination A compound with an sp3 hybridized carbon
bonded to a halogen can undergo two types of reactions
Two different mechanisms for substitution are SN1 and SN2 mechanisms
These result in diff prods under diff conditions
Chapter 8 4
SN2 Mechanism
SN2 mechanism: C–X bond weakens as nucleophile approaches all in one step
Chapter 8 5
SN1 Mechanism
SN1 mechanism: C–X bond breaks first without any help from nucleophile
This is a two-step process
slow step
fast step
Chapter 8 6
Substitution Reactions
Both mechanisms are called nucleophilic substitutions
Which one takes place depends on the structure of the alkyl halide the reactivity and structure of the nucleophile the concentration of the nucleophile, and the solvent in which reaction is carried out
Chapter 8 7
The SN2 Reaction Bimolecular nucleophilic substitution
rate = k [alkyl halide][nucleophile]
Chapter 8 8
The SN2 Reaction
The inversion of configuration resembles the way an umbrella turns inside out in the wind
If a single chiral enantiomer reacts a single chiral product (inverted) results.
Chapter 8 9
Steric Accessibility in the SN2 Reaction
Chapter 8 10
The SN2 Reaction: Leaving Group Stability
Chapter 8 11
The SN2 Reaction: Nucleophile Basicity
stronger base weaker base better nucleophile poorer nucleophile
HO– > H2O
CH3O– > CH3OH
–NH2 > NH3
CH3CH2NH– > CH3CH2NH2
Chapter 8 12
The SN2 Reaction: Nucleophile Basicity
Comparing nucleophiles with attacking atoms of approximately the same size, the stronger base is also the stronger nucleophile
Chapter 8 13
The SN2 Reaction: Nucleophile SizeIn nonpolar solvents nucleophilicity order same as basicity order- size doesn’t matter
Chapter 8 14
The SN2 Reaction: Nucleophile SizeSize is related to polarizability
Chapter 8 15
The SN2 Reaction: Nucleophile Size and Type
Nucleophilicity ~ both size and basicity
Chapter 8 16
The SN2 Reaction: Nucleophile Bulkiness
Nucleophilicity is affected by steric effects A bulky nucleophile has difficulty getting near
the back side of a sp3 carbon
CH3CH2O CH3CO
CH3
CH3
ethoxide ion tert-butoxide ion
better nucleophile stronger base
Chapter 8 17
The SN1 Reaction
The more stable the C+ the lower the G‡, and the faster the rxn
Chapter 8 18
The SN1 Reaction
Chapter 8 19
The SN1 ReactionThe SN1 reaction leads to a mixture of stereoisomers
Chapter 8 20
The SN1 Reaction: Factors Affecting the Rate
increasing reactivity
RI > RBr > RCl > RF
Two factors affect the rate of formation of the carbocation ease with which the leaving group leaves
stability of the carbocation
increasing reactivity
3º alkyl halide > 2º alkyl halide > 1º alkyl halide
Chapter 8 21
The SN1 Reaction: Carbocation Rearrangements
Chapter 8 22
Stereochemistry of SN2 and SN1 Reactions
inversion
both enantiomers
Chapter 8 23
Competition Between SN2 and SN1 Reactions
Chapter 8 24
Competition Between SN2 and SN1 Reactions
TABLE 9.6 Summary of the Reactivity of Alkyl Halides in Nucleophilic Substitution Reactions
methyl & 1o alkyl halides SN2 only
2o alkyl halides SN2 & SN1
3o alkyl halides SN1 only
benzylic & allylic halides SN2 & SN1 vinylic & aryl halides neither SN2 nor SN1
3o benzylic & allylic halides SN1 only
Chapter 8 25
Competition Between SN2 and SN1 ReactionsWhat are the factors that determine which What are the factors that determine which mechanism operates?mechanism operates? concentration of the nucleophileconcentration of the nucleophile reactivity of the nucleophilereactivity of the nucleophile solvent in which the reaction is carried outsolvent in which the reaction is carried out
For SN2 rate = k2 [alkyl halide][nucleophile]
For SN1 rate = k1 [alkyl halide]
Chapter 8 26
Competition Between SN2 and SN1 Reactions
An increase in the concentration of the nucleophile increases the rate of the SN2 reaction but has no effect on rate of SN1 reaction
An increase in the reactivity of nucleophile also speeds up an SN2 rxn but not an SN1 rxn
Chapter 8 27
Role of the Solvent The solvent in which a nucleophilic
substitution reaction is carried out has an influence on whether the reaction proceeds via an SN2 or an SN1 mechanism
Two important solvent aspects include solvent polarity whether it is protic or aprotic
Chapter 8 28
Solvent PolarityThe dielectric constant is a measure of how well the solvent can insulate opposite charges from each other
Chapter 8 29
Role of the Solvent Polar solvents have a high dielectric constant
Water Alcohols Dimethylsulfoxide (DMSO)
Solvents having O–H or N–H bonds are called protic solvents
Polar solvents without O-H or N-H bonds called polar aprotic solvents
Chapter 8 30
Role of the Solvent If charge on reactants(s) in slow step is
greater than the charge on the transition state, a polar solvent will slow down rxn (by stabilizing reactants)
If all reactant(s) involved in slow step are neutral polar solvent will speed up rxn
If reactant(s) involved in slow step are charged polar solvent slows down rxn
Chapter 8 31
SN1 Reaction: Effect of Solvent
Most SN1 reactions involve a neutral alkyl halide which needs to produce a C+
Consequently a polar solvent stabilizes the transition state more than the reactant
Increasing the polarity of the solvent speeds up such an SN1 reaction
Protic solvents stabilize the leaving group by H-bonding and thus stabilize the transition state
Chapter 8 32
SN2 Reaction: Effect of Solvent
Most SN2 reactions involve a neutral alkyl halide and a charged nucleophile
Consequently a polar solvent stabilizes the nucleophile more than the transition state and slows rxn
The nucleophiles used in SN2 reactions however are generally insoluble in nonpolar solvents - some solvent polarity is needed, but it’s best to use an aprotic solvent to avoid overstabilizing nucleophile reactant
Chapter 8 33
Competition Between SN2 and SN1 Reactions
When a halide can undergo both an SSNN2 2
and Sand SNN1 1 reaction:: SSNN2 will be favored by a high concentration 2 will be favored by a high concentration
of a good (negatively charged) nucleophileof a good (negatively charged) nucleophile SSNN2 will be favored in a polar aprotic solvent2 will be favored in a polar aprotic solvent
SSNN1 will be favored by a poor (neutral) 1 will be favored by a poor (neutral)
nucleophile in a polar protic solventnucleophile in a polar protic solvent
Chapter 8 34
Problem-solving Info Nucleophile strength
Protic solvent Size most important Look at basicity if same row of periodic table
Aprotic solvent- look at basicity only Strength in aprotic solvent > protic solvent First two points not strictly true but will work
in this course
Chapter 8 35
Problem-solving Info Electrophile strength
SN2 reactions Steric accessibility Electron withdrawing group (EWG) attached to C
reaction site Good leaving group
SN1 reactions Carbocation stability EWG not attached to reaction site Good leaving group
Chapter 8 36
Problem-solving Info Solvent polarity
Reduces rate with charged reactants Charge on both nucleophile and electrophile
important in SN2
Only electrophile important in SN1
Increases rate with uncharged reactants Reduces nucleophilicity Stabilizes leaving group for SN1
Chapter 8 37
Problem-solving Info Reaction speed comparisons
Increasing speed in SN1 reaction Polar solv/uncharged electrophile, vice-versa Relief of steric strain making C+ More stable carbocation formed Anything which destabilizes electrophile Increased leaving group stability (less basic)
Increasing speed in SN2 reaction Charge on electrophile & nuc vs. solv polarity
Chapter 8 38
Problem-solving Info Increased leaving group stability Less steric hindrance (both nuc & electrophile) Switch from protic to aprotic solvent Higher concentration of nucleophile More basic nucleophile Larger size of nucleophile’s attacking atom Anything which destabilizes nuc or electrophile
Stereochemistry SN1 reactions give both isomers at chiral C
SN2 reactions give only inversion at chiral C
Chapter 8 39
Problem-solving Info Carbocation rearrangements
Will occur if posible with SN1 Will not occur with SN2
SN1 vs SN2 chemistry Conditions which give SN1
Tertiary C reaction center C+ stability 2 & weak nuc (H-nuc pKa <7)
Carboxylates and sulfonates Neutral O nucleophiles Halides Neutral large-atom (row >2) nucleophiles
Chapter 8 40
Problem-solving Info Conditions which give SN2
C+ stability index = 1 and unhindered rxn site C+ stability 2, not 3°, strong nucleophile
Any nuc with conj acid pKa 7 (Table 10.3 pg 373) Alkoxides and hydroxide Ammonia and amines Carbanions Sulfides Hydride Nitrogen anions
In this text “high conc” of nuc is code for SN2 Other conditions give SN1/SN2 mixture