Organic Chemistry

1
Organic Chemistry

• Chapter 8

2
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
3
SN2 and SN1 Reactions

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

SN2
SN1 - CX bond breaks, forming a C then reacts
with a nucleophile
SN1
4
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

5
SN2 Mechanism

• Its a Substitution Reaction (S)
• Its Nucleophilic (N)
• Its rate is second order (2)
• Called bimolecular (rate is dependent on 2
  reactants)
• (Substitution Nucleophilic Bimolecular)

Rate k RX Nu
(Because rate is dependent of BOTH RX and Nu it
is 2nd. order.)
6
SN2 Mechanism

• SN2 Mechanism involves a backside attack

7
SN2 Mechanism

• The backside attack causes an Inversion of
  Configuration

Careful now.. Doesnt mean R becomes S new
atoms are involved
8
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
9
Steric Hindrance

• Activation Energy is higher due to steric
  hindrance..

10
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

11
(No Transcript)
12
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)
13
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)

14
Nucleophiles Strong/Weak Good/Bad

• Stronger base Weaker base
• Better nucleophile poorer nucleophile
• OH- gt H2O
• CH3O- gt CH3OH
• -NH2 gt NH3
• CH3CH2NH- gt CH3CH2NH2

(conjugate acids)
15
Nucleophiles

• The strength of nucleophile depends on reaction
  conditions.
• In the GAS phase (not usually used), direct
  relationship between basicity and nucleophilicity

16
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

17
Protic Solvents

• Protic 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

18
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)

19
Nucleophiles

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

20
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
21
Nucleophiles

• Solvents can solvate the nucleophile

(Methanol is a polar protic solvent.)
22
SN2 Reactions
23
SN2 Reactions
24
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

25
SN2 Reactions

• Compare basicity to see which is a better
  nucleophile.

26
(No Transcript)
27
SN1 Reactions

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

(Maybe not an SN2 reaction!)
28
SN1 Reactions

29
SN1 Mechanism

• Rate determining step does not involve
  nucleophile

Step 1
Step 2
30
SN1 Mechanism
31
SN1 Reactivity

• Relative Reactivities in an SN1 Reaction

1o RX lt 2o RX lt 3o RX
Increasing Reactivity
32
SN1 Stereochemistry

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

33
SN1 Stereochemistry
SN1 should yield racemic mixture but it
doesnt This is due to the steric hindrance of
the leaving group
34
Stereochemistry

• As the leaving group goes (Marvin K) it blocks
  the path of any incoming nucleophiles

35
SN1 vs SN2
Inversion of configuration
racemization with partial inversion
36
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 gt 2o gt 1o gt methyl

Increasing Stability
37
What Doesnt Matter In anSN1 Reactions

• The Nucleophile
• It has NO EFFECT on rate of Rx!!!
• Solvolysis Reactions
• (the nucleophile is also the solvent)

Nu
38
Carbocation Rearrangements

• Since a carbocation is the intermediate, you may
  see rearrangements in an SN1 Rx

No rearrangements in an SN2 Rx
39
Carbocation Rearrangement

• Methyl Shift

40
Benzylic, Allylic, Vinylic,and Aryl Halides

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

41
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!

42
Vinylic,and Aryl Halides

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

43
SN1 vs SN2 Review
44
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

45
Role of the Solvent

• In 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.

46
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.)
47

48
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.)
49
Polar Aprotic Solvents

• Polar Aprotic Solvents include
• DMF N,N-dimethylformamide
• DMSO dimethylsulfoxide
• HMPA hexamethylphosphoramide
• THF Tetrahydrofuran
• And even acetone

50
Polar Aprotic Solvents

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

51
Polar Aprotic Solvents

• DMSO
• DMF
• Acetone
• HMPA

52
Nucleophile Review
53

Problems . . .
54
SN1/SN2 Problems -1

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

55
SN1/SN2 Problems -1

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

56
SN1/SN2 Problems -2

• Predict the mechanism of this reaction

57
SN1/SN2 Problems -2

• Predict the mechanism of this reaction

58
SN1/SN2 Problems -3

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

59
SN1/SN2 Problems -3

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

60
SN1/SN2 Problems -4

• Predict the mechanism

61
SN1/SN2 Problems -4

• Predict the mechanism

62
SN1/SN2 Problems -5

• Predict the mechanism

63
SN1/SN2 Problems -5

• Predict the mechanism

64

• END