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ALKIL HALIDA
1. Manfaat (Pestisida, Bahan Dasar Sintesis Alkohol, Alkena)
2. Struktur (Metil, Primer, Sekunder, Tersier, Benzil dan Vinil)
3. Reaksi (SN-2, SN-1, E-2 dan E-1)
PETA REAKSI ALKIL HALIDA
1. Metil Halida2. Alkil halida Primer3. Alkil Halida Sekunder4. Alkil Halida Tersier
5. Alil Halida6. Benzil Halida
SN-2
SN-2SN-2, SN-1 dan E-2
SN-2, SN-1 dan E-2
SN-2, SN-1
SN-2, SN-1
7. Vinil Halida8. Aril Halida
Dalam Pembahasan Tersendiri
-Organic compounds with an electronegative atom or an electron-withdrawing group bonded to a sp3 carbon undergo substitution or elimination reactions
Organic compounds with an electronegative atom or an electron-withdrawing group bonded to a sp3 carbon undergo substitution or elimination reactions
Substitution
Elimination
Halide ions are good leaving groups. Substitution reaction on these compounds are easy
and are used to get a wide variety of compounds
Halide ions are good leaving groups. Substitution reaction on these compounds are easy
and are used to get a wide variety of compounds
alkyl fluoride alkyl chloride alkyl bromide alkyl iodide
Substitution Reaction with Halides
If concentration of (1) is doubled, the rate of the
reaction is doubled.
If concentration of (1) is doubled, the rate of the
reaction is doubled.
bromomethane
(1) (2)
If concentration of (2) is doubled, the rate of the
reaction is doubled.
If concentration of (2) is doubled, the rate of the
reaction is doubled.
If concentration of (1) and (2) is doubled, the rate of the reaction quadruples.
If concentration of (1) and (2) is doubled, the rate of the reaction quadruples.
methanol
Substitution Reaction with Halides
bromomethane
(1) (2)
methanol
Rate law:
rate = k [bromoethane][OH-]
this reaction is an example of a SN2 reaction.S stands for substitutionN stands for nucleophilic 2 stands for bimolecular
Rate law:
rate = k [bromoethane][OH-]
this reaction is an example of a SN2 reaction.S stands for substitutionN stands for nucleophilic 2 stands for bimolecular
Mechanism of SN2 Reactions
The rate of reaction depends on the concentrations of both reactants.The rate of reaction depends on the concentrations of both reactants.
When the hydrogens of bromomethane are replaced with methyl groups the reaction rate slow down.
When the hydrogens of bromomethane are replaced with methyl groups the reaction rate slow down.
The reaction of an alkyl halide in which the halogen is bonded to an asymetric center leads to the formation of only one stereoisomer
The reaction of an alkyl halide in which the halogen is bonded to an asymetric center leads to the formation of only one stereoisomer
Alkyl halide Relative rate
1200
40
1
≈ 0
Mechanism of SN2 Reactions
Hughes and Ingold proposed the following mechanism:Hughes and Ingold proposed the following mechanism:
Transition state
Increasing the concentration of either of the reactant makes their collision more probable.Increasing the concentration of either of the reactant makes their collision more probable.
Mechanism of SN2 Reactions
activationenergy: G1
activationenergy: G2
Steric effectSteric effect
Inversion of configurationInversion of configuration
(S)-2-bromobutane (R)-2-butanol
Ener
gy
reaction coordinate reaction coordinate
Factor Affecting SN2 Reactions
relative rates of reaction pKa HX
HO- + RCH2I RCH2OH + I- 30 000 -10
HO- + RCH2Br RCH2OH + Br- 10 000 -9
HO- + RCH2Cl RCH2OH + Cl- 200 -7
HO- + RCH2F RCH2OH + F- 1 3.2
relative rates of reaction pKa HX
HO- + RCH2I RCH2OH + I- 30 000 -10
HO- + RCH2Br RCH2OH + Br- 10 000 -9
HO- + RCH2Cl RCH2OH + Cl- 200 -7
HO- + RCH2F RCH2OH + F- 1 3.2
The leaving group
The nucleophile
In general, for halogen substitution the strongest the base the better the
nucleophile.
In general, for halogen substitution the strongest the base the better the
nucleophile.
pKa Nuclephilicity
SN2 Reactions With Alkyl Halidesan alcohol
a thiol
an ether
a thioether
an amine
an alkyne
a nitrile
Substitution Reactions With Halides
If concentration of (1) is doubled, the rate of the
reaction is doubled.
If concentration of (1) is doubled, the rate of the
reaction is doubled.
If concentration of (2) is doubled, the rate of the reaction is not doubled.
If concentration of (2) is doubled, the rate of the reaction is not doubled.
Rate law:
rate = k [1-bromo-1,1-dimethylethane]
this reaction is an example of a SN1 reaction.
S stands for substitutionN stands for nucleophilic 1 stands for unimolecular
Rate law:
rate = k [1-bromo-1,1-dimethylethane]
this reaction is an example of a SN1 reaction.
S stands for substitutionN stands for nucleophilic 1 stands for unimolecular
1-bromo-1,1-dimethylethane 1,1-dimethylethanol
Mechanism of SN1 Reactions
The rate of reaction depends on the concentrations of the alkyl halide only.The rate of reaction depends on the concentrations of the alkyl halide only.
When the methyl groups of 1-bromo-1,1-dimethylethane are replaced with hydrogens the reaction rate slow down.
When the methyl groups of 1-bromo-1,1-dimethylethane are replaced with hydrogens the reaction rate slow down.
The reaction of an alkyl halide in which the halogen is bonded to an asymetric center leads to the formation of two stereoisomers
The reaction of an alkyl halide in which the halogen is bonded to an asymetric center leads to the formation of two stereoisomers
Alkyl halide Relative rate
≈ 0 *
≈ 0 *
12
1 200 000
* a small rate is actually observed as a result of a SN2
Mechanism of SN1 Reactions
C-Br bond breaksC-Br bond breaks
nucleophile attacks the carbocation
nucleophile attacks the carbocation
Proton dissociationProton dissociation
slow
fast
Mechanism of SN1 Reactions
G
Rate determining stepRate determining stepCarbocation intermediateCarbocation intermediate
R++ X-
R-OH2
+
R-OH
Mechanism of SN1 Reactions
Same configuration as the alkyl halide
Same configuration as the alkyl halide
Inverted configuration
relative the alkyl halide
Inverted configuration
relative the alkyl halide
Factor Affecting SN1 reaction
Two factors affect the rate of a SN1 reaction:• The ease with which the leaving group dissociate from the carbon• The stability of the carbocation
Two factors affect the rate of a SN1 reaction:• The ease with which the leaving group dissociate from the carbon• The stability of the carbocation
The more the substituted the carbocation is, the more
stable it is and therefore the easier it is to form.
The more the substituted the carbocation is, the more
stable it is and therefore the easier it is to form.
As in the case of SN2, the weaker base is the leaving group, the less tightly it is
bonded to the carbon and the easier it is to break the bond
As in the case of SN2, the weaker base is the leaving group, the less tightly it is
bonded to the carbon and the easier it is to break the bond
The reactivity of the nucleophile has no effect on the rate of a SN1 reaction
The reactivity of the nucleophile has no effect on the rate of a SN1 reaction
Comparison SN1 – SN2
SN1 SN2
A two-step mechanism A one-step mechanism
A unimolecular rate-determining step A bimolecular rate-determining step
Products have both retained and inverted configuration relative to the reactant
Product has inverted configuration relative to the reactant
Reactivity order:3o > 2o > 1o > methyl
Reactivity order:methyl > 1o > 2o > 3o
Elimination Reactions
1-bromo-1,1-dimethylethane 2-methylpropene
Rate law:
rate = k [1-bromo-1,1-dimethylethane][OH-]
this reaction is an example of a E2 reaction.E stands for elimination2 stands for bimolecular
Rate law:
rate = k [1-bromo-1,1-dimethylethane][OH-]
this reaction is an example of a E2 reaction.E stands for elimination2 stands for bimolecular
The E2 Reaction
A proton is removed
A proton is removed
Br- is eliminatedBr- is eliminatedThe mechanism shows that an E2
reaction is a one-step reactionThe mechanism shows that an E2
reaction is a one-step reaction
Elimination Reactions
If concentration of (1) is doubled, the rate of the
reaction is doubled.
If concentration of (1) is doubled, the rate of the
reaction is doubled.
If concentration of (2) is doubled, the rate of the reaction is not doubled.
If concentration of (2) is doubled, the rate of the reaction is not doubled.
Rate law:
rate = k [1-bromo-1,1-dimethylethane]
this reaction is an example of a E1 reaction.
E stands for elimination1 stands for unimolecular
Rate law:
rate = k [1-bromo-1,1-dimethylethane]
this reaction is an example of a E1 reaction.
E stands for elimination1 stands for unimolecular
1-bromo-1,1-dimethylethane 2-methylpropene
The E1 Reaction
The alkyl halide dissociate, forming a
carbocation
The alkyl halide dissociate, forming a
carbocation
The base removes a
proton
The base removes a
proton
The mechanism shows that an E1 reaction is a two-step reaction
The mechanism shows that an E1 reaction is a two-step reaction
Products of Elimination Reaction
2-bromobutane
2-butene
1-butene
80%
20%
The most stable alkene is the major product of the reaction
for both E1 and E2 reaction
The most stable alkene is the major product of the reaction
for both E1 and E2 reaction
The greater the number of alkyl substituent the more
stable is the alkene
The greater the number of alkyl substituent the more
stable is the alkeneFor both E1 and E2 reactions, tertiary alkyl halides
are the most reactive and primary alkyl halides are the least reactive
For both E1 and E2 reactions, tertiary alkyl halides are the most reactive and primary alkyl halides
are the least reactive
30% 50%
Elimination Reactions
C C
X Y
C C + X Y
Dehydrohalogenation (-HX) and Dehydration (-H2O) are the main types of elimination reactions.
The E2 mechanism
..:..
__
+
+ Br_
..:
concerted mechanism
H O
C C
Br
H
H O
H
C C
This reaction is done in strong base at high concentration, such as 1 M NaOH in water.
_
Kinetics
• The reaction in strong base at high concentration is second order (bimolecular):
Rate law: rate = k[OH-]1[R-Br]1
The E1 mechanism
1)
++ Br
_slow
+
2)..
:
+fast
O.. +O
C C
Br
C C
H
C C
HC C
H
H H
H
H
H
rate determining step
This reaction is done in strong base such as 0.01 M NaOH in water!! Actually, the base solution is weak!
Kinetics
• The reaction in weak base or under neutral conditions will be first order (unimolecular):
• Rate law: rate = k [R-Br]1
• The first step (slow step) is rate determining!
The E2 mechanism• Mechanism• Kinetics• Stereochemistry of reactants• Orientation of elimination (Zaitsev’s rule)• Stereochemistry of products• Competing reactions
E2 mechanism
..:..
__
+
+ Br_
..:
concerted mechanism
H O
C C
Br
H
H O
H
C C
This reaction is done in strong base at high concentration, such as 1 M NaOH in water.
Kinetics of an E2 reaction• The reactions are second order (bimolecular
reactions).
• Rate = k [R-Br]1[Base]1
second order reaction (1 + 1 = 2)High powered math!!
Stereochemistry of reactants
• E2 reactions must go by an anti elimination• This means that the hydrogen atom and
halogen atom must be 180o (coplanar) with respect to each other!!
• Draw a Newman projection formula and place the H and X on opposite sides.
Stereochemistry of E2 Reaction
KOH
AlcoholSolventH
Br
H
HH
CCH3
CH3
CH3
C
H
CH3
CH3
CH3H
H
H and Br are anti structure in conformation!!!!!!!!!
(S,S)-diastereomer
KOHethanolheat
(E)-isomer (Z)-isomer
??? ???
C C
Br
HCH3
CH3
H
C C
CH3 CH3
H t-butyl
C C
H CH3
CH3 t-butyl
t-butyl
(R,S)-diastereomer
KOHethanolheat
(E)-isomer (Z)-isomer
??? ???
C C
Br
HH
CH3
CH3
t-butyl
C C
CH3 CH3
H T-butyl
C C
H CH3
CH3 t-butyl
Orientation of elimination: regiochemistry/ Zaitsev’s Rule• In reactions of removal of hydrogen halides from
alkyl halides or the removal of water from alcohols, the hydrogen which is lost will come from the more highly-branched -carbon.
A. N. Zaitsev -- 1875 C C C C
H
H
H H
X
H
H
HH
CH3
Less branchedMore branched
Product formed from previous slide
C
C CC
H
HH
H
HCH3
HH
More substituted alkene is more stable!!!!!!!!
Typical bases used in E2 reactions
High concentration of the following >1MIf the concentration isn’t given, assumethat it is high concentration!• Na+ -OH• K+ -OH• Na+ -OR• Na+ -NH2
Orientation of elimination: regiochemistry/ Zaitsev’s Rule
Explaination of Zaitsev’s rule:When you remove a hydrogen atom from the more branched position, you are forming a more highly substituted alkene.
Stereochemistry of products• The H and X must be anti with respect to each
other in an E2 reaction!• You take what you get, especially with
diastereomers! See the previous slides of the reaction of diastereomers.
Competing reactions• The substitution reaction (SN2) competes with
the elimination reaction (E2).• Both reactions follow second order kinetics!
The E1 mechanism• Mechanism• Kinetics• Stereochemistry of reactants• Orientation of elimination (Zaitsev’s rule)
• Stereochemistry of products• Competing reactions
E1 mechanism
1)
++ Br
_slow
+
2)..
:
+fast
O..+O
C C
Br
C C
H
C C
HC C
H
H H
H
H
H
water helpsto stabilizecarbocation
This reaction is done in strong base at low concentration, such as 0.01 M NaOH in water)
E1 Reactions • These reactions proceed under neutral
conditions where a polar solvent helps to stabilize the carbocation intermediate.
• This solvent also acts as a weak base and removes a proton in the fast step.
• These types of reactions are referred to as solvolysis reactions.
• tertiary substrates go by E1 in polar solvents, with little or no base present!
• typical polar solvents are water, ethanol, methanol and acetic acid
• These polar solvents help stabilize carbocations
• E1 reactions also occur in a low concentration of base (i.e. 0.01M NaOH).
Carbocation stability order
Tertiary (3o) > secondary (2o) > primary (1o)
It is hard (but not impossible) to get primary compounds to go by E1. The reason for this is that primary carbocations are not stable!
Kinetics of an E1 reaction• E1 reactions follow first order (unimolecular)
kinetics:Rate = k [R-X]1
• The solvent helps to stabilize the carbocation, but it doesn’t appear in the rate law!!
Stereochemistry of the reactants• E1 reactions do not require an anti coplanar
orientation of H and X. • Diastereomers give the same products with E1
reactions, including cis- and trans products.• Remember, E2 reactions usually give different
products with diastereomers.
Orientation of elimination• E1 reactions faithfully follow Zaitsev’s rule!• This means that the major product should be
the product that is the most highly substituted.
Stereochemistry of productsE1 reactions usually give the thermodynamically most stable product as the major product. This usually means that the largest groups should be on opposite sides of the double bond. Usually this means that the trans product is obtained.
Competing reactions
• The substitution reaction (SN1) competes with the elimination reaction (E1).
• Both reactions follow first order kinetics!
Whenever there are carbocations…• They can undergo elimination (E1)• They can undergo substitution (SN1)
• They can rearrange– and then undergo elimination– or substituion
Rearrangements• Alkyl groups and hydrogen can migrate in
rearrangement reactions to give more stable intermediate carbocations.
• You shouldn’t assume that rearrangements always occur in all E1 reactions, otherwise paranoia will set in!!
Comparison of E2 / E1• E1 reactions occur under essentially neutral
conditions with polar solvents, such as water, ethyl alcohol or acetic acid.
• E1 reactions can also occur with strong bases, but only at low concentration, about 0.01 to 0.1 M or below.
• E2 reactions require strong base in high concentration, about 1 M or above.
Comparison of E2 / E1• E1 is a stepwise mechanism (two or more);
Carbocation intermediate!• E2 is a concerted mechanism (one step)
No intermediate!• E1 reactions may give rearranged products• E2 reactions don’t give rearrangement• Alcohol dehydration reactions are E1
Bulky leaving groupsHofmann Elimination
+
OH_
heat
+
6%
94%
CH3 CH2 CH2 CH CH3
N
CH3
CH3CH3
CH3 CH2 CH CH CH3
CH3 CH2 CH2 CH CH2
This give the anti-Zaitsev product (least substituted product is formed)!
Orientation of elimination: regiochemistry/ Hofmann’s Rule • In bimolecular elimination reactions in the presence
of either a bulky leaving group or a bulky base, the hydrogen that is lost will come from the LEAST LEAST highly-branched -carbon.
C C C C
H
H
H H
X
H
H
HH
CH3
Less branchedMore branched
Elimination with bulky bases
• Non-bulky bases, such as hydroxide and ethoxide, give Zaitsev products.
• Bulky bases, such as potassium tert-butoxide, give larger amounts of the least substituted alkene (Hoffmann) than with simple bases.
Comparing Ordinary and Bulky Bases
CH3 C CH CH3
Br
NaOC2H5
C2H5OHheat
C CHCH3 CH3
CH3 C CH CH3
Br
KOC(CH3)3
(CH3)3COHheat
C CHCH3 CH2
Major
H
CH3 CH3
CH3
H
CH3
Major
H
1-butene: watch out for competing reactions!
H3C CH2 CH2 CH2 Br
KOCH3
Non-bulky
SN2
H3C CH2 CH2 CH2 O-CH3
H3C CH2 CH CH2
bulky baseKO-t-butyl
E2
Highlights• Dehydrohalogenation -- E2 Mechanism• Zaitsev’s Rule• Dehydrohalogenation -- E1 Mechanism• Carbocation Rearrangements -- E1• Elimination with Bulky Leaving Groups and Bulky
Bases -- Hofmann Rule -- E2
Competition Between SN2/E2 and SN1/E1
rate = k1[alkyl halide] + k2[alkyl halide][nucleo.] + k3[alkyl halide] + k2[alkyl halide][base] rate = k1[alkyl halide] + k2[alkyl halide][nucleo.] + k3[alkyl halide] + k2[alkyl halide][base]
SN1SN1 SN2SN2 E1E1 E2E2
• SN2 and E2 are favoured by a high concentration of a good nucleophile/strong base• SN1 and E1 are favoured by a poor nucleophile/weak base, because a poor nucleophile/weak base disfavours SN2 and E2 reactions
• SN2 and E2 are favoured by a high concentration of a good nucleophile/strong base• SN1 and E1 are favoured by a poor nucleophile/weak base, because a poor nucleophile/weak base disfavours SN2 and E2 reactions
Competition Between Substitution and Elimination
• SN2/E2 conditions:In a SN2 reaction: 1o > 2o > 3o
In a E2 reaction: 3o > 2o > 1o In a SN2 reaction: 1o > 2o > 3o
In a E2 reaction: 3o > 2o > 1o
90% 10%
25% 75%
100%
Competition Between Substitution and Elimination
• SN1/E1 conditions:
All alkyl halides that react under SN1/E1 conditions will give both substitution and elimination products (≈50%/50%)
All alkyl halides that react under SN1/E1 conditions will give both substitution and elimination products (≈50%/50%)
Summary
• Alkyl halides undergo two kinds of nucleophilic subtitutions: SN1 and SN2, and two kinds of elimination: E1 and E2.
• SN2 and E2 are bimolecular one-step reactions• SN1 and E1 are unimolecular two step reactions• SN1 lead to a mixture of stereoisomers• SN2 inverts the configuration od an asymmetric carbon• The major product of a elimination is the most stable alkene• SN2 are E2 are favoured by strong nucleophile/strong base• SN2 reactions are favoured by primary alkyl halides• E2 reactions are favoured by tertiary alkyl halides