Professional Documents
Culture Documents
Alkyl Halide and Nucleophilic Substitution
Alkyl Halide and Nucleophilic Substitution
2
Introduction to Alkyl Halides
Figure 7.2 Four types of organic halides (RX) having X near a π bond
4
Nomenclature
5
Nomenclature
Common names are often used for simple alkyl halides.
To assign a common name:
Name all the carbon atoms of the molecule as a single
alkyl group.
Name the halogen bonded to the alkyl group.
Combine the names of the alkyl group and halide,
separating the words with a space.
6
Physical Properties
7
Physical Properties
8
The Polar Carbon-Halogen Bond
9
The Polar Carbon-Halogen Bond
10
General Features of Nucleophilic Substitution
• Three components are necessary in any substitution reaction.
11
General Features of Nucleophilic Substitution
• Negatively charged nucleophiles like HO¯ and HS¯ are used as
salts with Li+, Na+, or K+ counterions to balance the charge.
Since the identity of the counterion is usually inconsequential, it
is often omitted from the chemical equation.
12
General Features of Nucleophilic Substitution
15
The Leaving Group
16
The Leaving Group
17
The Nucleophile
18
The Nucleophile
19
The Nucleophile
• Nucleophilicity parallels basicity in three instances:
1. For two nucleophiles with the same nucleophilic atom, the
stronger base is the stronger nucleophile.
The relative nucleophilicity of HO¯ and CH3COO¯, two oxygen
nucleophiles, is determined by comparing the pKa values of
their conjugate acids (H2O = 15.7, and CH3COOH = 4.8). HO¯ is
a stronger base and stronger nucleophile than CH3COO¯.
2. A negatively charged nucleophile is always a stronger
nucleophile than its conjugate acid.
HO¯ is a stronger base and stronger nucleophile than H2O.
3. Right-to-left-across a row of the periodic table,
nucleophilicity increases as basicity increases:
20
The Nucleophile
• Nucleophilicity does not parallel basicity when steric hindrance
becomes important.
• Steric hindrance is a decrease in reactivity resulting from the
presence of bulky groups at the site of a reaction.
• Steric hindrance decreases nucleophilicity but not basicity.
• Sterically hindered bases that are poor nucleophiles are called
nonnucleophilic bases.
21
The Nucleophile
• If the salt NaBr is used as a source of the nucleophile Br¯ in H2O,
the Na+ cations are solvated by ion-dipole interactions with H2O
molecules, and the Br¯ anions are solvated by strong hydrogen
bonding interactions.
22
The Nucleophile
24
The Nucleophile
• Polar aprotic solvents solvate cations by ion—dipole
interactions.
• Anions are not well solvated because the solvent. These anions
are said to be “naked”.
25
The Nucleophile
26
The Nucleophile
27
Mechanisms of Nucleophilic Substitution
In a nucleophilic substitution:
28
Mechanisms of Nucleophilic Substitution
[1] Bond making and bond breaking occur at the same time.
29
Mechanisms of Nucleophilic Substitution
33
Mechanisms of Nucleophilic Substitution
34
Mechanisms of Nucleophilic Substitution
35
Mechanisms of Nucleophilic Substitution—Stereochemistry
• All SN2 reactions proceed with backside attack of the
nucleophile, resulting in inversion of configuration at a
stereogenic center.
Figure 7.9 Stereochemistry of the SN2 reaction
36
Mechanisms of Nucleophilic Substitution—Stereochemistry
Figure 7.10
Two examples of inversion
of configuration in
the SN2 reaction
37
Mechanisms of Nucleophilic Substitution
39
Mechanisms of Nucleophilic Substitution
40
Mechanisms of Nucleophilic Substitution
41
Mechanisms of Nucleophilic Substitution
The mechanism of an SN1 reaction would be drawn as follows:
Note the curved arrow formalism that is used to show the flow
of electrons.
Key features of the SN1 mechanism are that it has two steps,
and carbocations are formed as reactive intermediates. 42
Mechanisms of Nucleophilic Substitution
Figure 7.15
An energy diagram
for the SN1 reaction:
43
Mechanisms of Nucleophilic Substitution—Stereochemistry
44
Mechanisms of Nucleophilic Substitution—Stereochemistry
• Loss of the leaving group in Step [1] generates a planar
carbocation that is achiral. In Step [2], attack of the nucleophile
can occur on either side to afford two products which are a pair
of enantiomers.
• Because there is no preference for nucleophilic attack from
either direction, an equal amount of the two enantiomers is
formed—a racemic mixture. We say that racemization has
occurred.
45
Mechanisms of Nucleophilic Substitution—Stereochemistry
Figure 7.16
Two examples of racemization
in the SN1 reaction
46
Mechanisms for Nucleophilic Substitution
• The rate of an SN1 reaction is affected by the type of alkyl halide
involved.
48
Carbocation Stability
49
Carbocation Stability
Figure 7.17
Electrostatic
potential maps
for differerent
carbocations
51
Carbocation Stability
• The order of carbocation stability is also a consequence of
hyperconjugation.
• Hyperconjugation is the spreading out of charge by the
overlap of an empty p orbital with an adjacent bond. This
overlap (hyperconjugation) delocalizes the positive charge
on the carbocation, spreading it over a larger volume, and
this stabilizes the carbocation.
• Example: CH3+ cannot be stabilized by hyperconjugation, but
(CH3)2CH+ can.
52
Alcohols, Ethers and Epoxides
Carbocation Rearrangements:
• Often, when carbocations are intermediates, a less stable
carbocation will be converted into a more stable carbocation
by a shift of a hydrogen or an alkyl group. This is called a
rearrangement.
• Because the migrating group in a 1,2-shift moves with two
bonding electrons, the carbon it leaves behind now has only
three bonds (six electrons), giving it a net positive (+) charge.
53
Alcohols, Ethers and Epoxides
Carbocation Rearrangements:
• A 1,2-shift can convert a less stable carbocation into
a more stable carbocation.
• Rearrangements are not unique to dehydration
reactions. Rearrangements can occur whenever a
carbocation is formed as a reactive intermediate.
Consider the example below: 2° Carbocation A
rearranges to the more stable 3° carbocation by a 1,2-
hydride shift, whereas carbocation B does not rearrange
because it is already 3°.
54
Predicting the Likely Mechanism of a Substitution Reaction
• Four factors are relevant in predicting whether a given reaction
is likely to proceed by an SN1 or an SN2 reaction—The most
important is the identity of the alkyl halide.
55
Predicting the Likely Mechanism of a Substitution Reaction
• The nature of the nucleophile is another factor.
• Strong nucleophiles (which usually bear a negative charge)
present in high concentrations favor SN2 reactions.
• Weak nucleophiles, such as H2O and ROH favor SN1 reactions
by decreasing the rate of any competing SN2 reaction.
• Let us compare the substitution products formed when the 2°
alkyl halide A is treated with either the strong nucleophile HO¯
or the weak nucleophile H2O. Because a 2° alkyl halide can react
by either mechanism, the strength of the nucleophile
determines which mechanism takes place.
56
Predicting the Likely Mechanism of a Substitution Reaction
57
Predicting the Likely Mechanism of a Substitution Reaction
• A better leaving group increases the rate of both SN1 and SN2
reactions.
58
Predicting the Likely Mechanism of a Substitution Reaction
59
Predicting the Likely Mechanism of a Substitution Reaction
60
61
Nucleophilic Substitution and Organic Synthesis
62
Nucleophilic Substitution and Organic Synthesis
63
Oxidation and Reduction
Reduction of Polar C—X Bonds:
• Alkyl halides can be reduced to alkanes with LiAlH4.
• Epoxide rings can be opened with LiAlH4 to form alcohols.
64
Oxidation and Reduction