wwu -- chemistry chapter 10 nucleophilic substitution: the s n 1 and s n 2 mechanisms
TRANSCRIPT
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Chapter 10Chapter 10
Nucleophilic Substitution:
The SN1 and SN2Mechanisms
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Assignment for Chapter Assignment for Chapter 1010
• We will cover all the sections in this chapter, except Sections 10.12 and 10.13
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Problem Assignment Problem Assignment for Chapter 10for Chapter 10
In-Text Problems1 - 15 17, 18 19 (SN2 react)
20 (SN1 reaction), 21, 22, 24, 25, 26,27, 28
End-of-Chapter Problems30 - 37 39 - 42 44 – 49
51 - 55
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Sect. 10.1: Sect. 10.1: Nomenclature of alkyl Nomenclature of alkyl
halides -- common halides -- common namesnames
methylene chloride CH2Cl2chloroform CHCl3carbon tetrachloride CCl4
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More common and IUPAC More common and IUPAC namesnamesisopropyl chloride (2-chloropropane)sec-butyl chloride (2-chlorobutane)isobutyl chloride (1-chloro-2-methylpropane)tert-butyl chloride (2-chloro-2-methylpropane)allyl chloride (3-chloro-1-propene)vinyl chloride (chloroethene)
benzyl chloride (chloromethylbenzene)phenyl chloride (chlorobenzene)
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Sect. 10.2: Overview of Sect. 10.2: Overview of nucleophilic nucleophilic substitutionsubstitution
• The substitution reaction: SN1 and SN2• Primary halides = SN2 • Secondary halides = both mechanisms!• Tertiary halides = SN1• Leaving groups: halogens most
common• There are a number of different
nucleophiles!!
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Nucleophilic Substitution Nucleophilic Substitution (S(SNN2)2)
R-CH2-X + Nu_
R-CH2-Nu + X_
substrate nucleophile product leaving group
Oxygen Nucleophiles (SN2)
O-H_
R-CH2-O-Halcoholhydroxide
R-CH2-X +_
+ X
O-R_
R-CH2-O-RR-CH2-X +_
+ X
etheralkoxide
O-C-R_
R-CH2-R-CH2-X +_
+ X
estercarboxylateO
O-C-R
O
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Nitrogen as a nucleophile Nitrogen as a nucleophile (S(SNN2)2)
R-CH2-X + Nu_
R-CH2-Nu + X_
substrate nucleophile product leaving group
NH3 R-CH2-NH3ammonia
R-CH2-X ++
X_
R-CH2-NH3
+X
_
R-CH2-NH2 + H-Xprimaryamine
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Carbon as a nucleophile Carbon as a nucleophile (S(SNN2)2)
R-CH2-X + Nu_
R-CH2-Nu + X_
substrate nucleophile product leaving group
C_
nitrilecyanideR-CH2-X +
_+ X
R-CH2-R-CH2-X +_
+ Xalkyne
CH2-C-R_
R-CH2-X +
O
N C NR-CH2
C_
C-H
CH2-C-R
O
R-CH2 + X_
ketone
C C-H
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energy
Reaction coordinate
CH
H
Br-
OH
R
..:..
__H O
C H
H
Br
R
Br
H O
CH
HR
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The SThe SNN1 Mechanism1 Mechanism1)
2)
: :..
slow
++ : Br :
..
..
_
++ :
fast
CH3 C CH3
CH3
Br
CH3 C CH3
CH3
CH3 C CH3
CH3
CH3 C CH3
CH3
Nu
Nu_
carbocation
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energy
Reaction coordinate
C
R
Br
RR
R CRR
Br
R CR
R
R CR
R
Nu
CR
R
Nu
R
intermediate
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Sect. 10.3: SSect. 10.3: SNN2 2 MechanismMechanism
•reaction and mechanism•kinetics•stereochemistry•substrate structure•nucleophiles• leaving groups•solvents
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The SThe SNN2 Reaction2 Reaction
+ + Br: :..
..
_
:..
..
_ ..
..CH3 Br O H CH3 OH
Sterically accessible compounds reactby this mechanism!!
Methyl group is small
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SSNN2 Mechanism: 2 Mechanism: kineticskinetics
•The reactions follows second order (bimolecular) kinetics
•Rate = k [R-Br]1 [OH-]1
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energy
Reaction coordinate
CH
H
Br-
OH
R
..:..
__H O
C H
H
Br
R
Br
H O
CH
HR
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.. _
:..
3
C BrH
Et
CHH O
(R)- enantiomer
H O C
CH
EtH
Br
3
..
..H O C
CH
HEt
Br_
+3
(S) enantiomer
SSNN2 Reaction: 2 Reaction: stereochemistrystereochemistry
Inversion of configuration
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For an SFor an SNN2 Reaction:2 Reaction:
EVERY REACTION EVENT ALWAYS LEADS TO
INVERSION OF CONFIGURATION
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SSNN2 Reaction: substrate 2 Reaction: substrate structure (Table 10-5)structure (Table 10-5)
KI in Acetone at 25°
krel
150
1
0.008
unreactive!
CH3 Br
CH3 CH2 Br
CH3 CH Br
CH3
CH3 C Br
CH3
CH3
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Chloromethane + Chloromethane + Iodide as the Iodide as the NucleophileNucleophile
I-
Fast
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terttert-Butyl Chloride + -Butyl Chloride + Iodide as the Iodide as the NucleophileNucleophile
I-
No reaction
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SSNN2 Reaction: 2 Reaction: substrate structuresubstrate structure
> > C
primary secondary tertiary
CH3-Br CH3-CH2-Br CH3 CH
CH3
Br > CH3
CH3
CH3
Br
Reactivity order---- fastest to slowest!
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SSNN2 Reaction: 2 Reaction: nucleophilicitynucleophilicity
Basicity Nucleophilicity
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Predict which is more Predict which is more nucleophilicnucleophilic
CH3-O- or CH3-S-
CH3-S-is more nucleophilic!
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Relative NucleophilicityRelative Nucleophilicity
Increasing Nucleophilicty
H2O
CH3OH_ _
OCH3
_I_ _
SH
_
C N
OH_
CH3 C O
O
O
1) In general, stronger bases are better nucleophiles
2) However, iodide doesn’t fit that pattern (weak base, but great
nucleophile!)
3) Cyanide is an excellent nucleophile because of its linear
structure
4) Sulfur is better than oxygen as a nucleophile
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SSNN2 Reaction: Leaving 2 Reaction: Leaving GroupsGroups
• Best leaving groups leave to form weak Lewis bases.
• Good leaving groups:– Br, I, Cl, OTs, OH2
+
• “Lousy” leaving groups:– OH, OR, NH2,, F
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Sulfonate Leaving Sulfonate Leaving GroupsGroups
S CH3OR
O
O
S BrOR
O
O
para-Toluenesulfonate Tosylate
para-Bromobenzenesulfonate Brosylate
R OTs
R OBs
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Tosylate leaving groupTosylate leaving group
(S)-(+)-1-Phenyl-2-propanol
(S)-(+)-1-Methyl-2-phenylethyl tosylate
C2H5O
2-Ethoxy-1-phenylpropaneIs this ether (R) or (S)?
C OH
CH2
CH3
H
CH3 S Cl
O
O
C O
CH2
CH3
H Ts
C O
CH2
CH3
H Ts
CH2 CH O CH2 CH3
CH3_
+ H-Cl
Retention of configuration
Retention or inversion?
[Ts-Cl]
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Inversion of Inversion of ConfigurationConfiguration
CH2
CH
CH3
O S
O
O
CH3 CH2
CH3 CH2 O C
CH2
HCH3
+ CH3 S O
O
O
(S)
(R)
_
O_ CH3
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SSNN2 Reaction: solvents2 Reaction: solventsSN2 reactions are accelerated in polar, aprotic solvents. Consider Na+ -OEt as an example of a nucleophile.
Why are reactions accelerated? The Na+ cation is complexed by the negative part of the aprotic solvent molecule pulling it away from –OEt.Now that the sodium ion is complexed, the oxygen in the nucleophile –OEt is more available for attack.
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Aprotic solventsAprotic solvents• These solvents do not have OH bonds in them.
They complex the cation through the lone pairs on oxygen or nitrogen:
AcetoneH3C
O
CH3
Dimethyl sulfoxide (DMSO)H3C
S
O
CH3
Dimethylformamide (DMF) H
O
NCH3
CH3
Acetonitrile C NH3C
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How cations are How cations are complexed with aprotic complexed with aprotic
solventssolvents
H3CS
O
CH3
Na
H3C S CH3
O
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Now that the NaNow that the Na++ is is complexed, the complexed, the ––OEt can OEt can
react more easilyreact more easily
Et O H3C Br Et O CH3 Br
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SSNN2 Reaction: solvents2 Reaction: solventsSN2 reactions are retarded (slowed) in polar, protic solvents. Protic solvents have O-H groups.
Why are reactions retarded? Nucleophile is hydrogen bonded to solvent!
Et O H OEt
The nucleophile ishydrogen bondedto ethanol - reducesnucleophilicity
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Protic solventsProtic solvents Typical protic solvents:
WaterH
OH
Methanol HO
CH3
HO
CH2CH3
HOEtEthanol
HO
C
O
CH3Acetic acid HOAc
HO
C
O
HFormic acid
HOMe
abbreviations
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Sect. 10.4: SSect. 10.4: SNN1 1 MechanismMechanism
•reaction and mechanism•kinetics•stereochemistry•substrate structure•nucleophiles•leaving groups•solvents
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Solvolysis of Solvolysis of terttert-Butyl -Butyl BromideBromide
+ H2O +
+ other products
acetoneCH3 C CH3
CH3
Br
CH3 C CH3
CH3
OH
H Br
Acetone is used to dissolve everything! Water is the Acetone is used to dissolve everything! Water is the
solvent and nucleophile (solvolysis). solvent and nucleophile (solvolysis).
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The SThe SNN1 Mechanism1 Mechanism1)
2)
3)
: :..
slow
++ : Br :
..
..
_
++ : :
fast
:+
:+
fast
:..
+ H+
CH3 C CH3
CH3
Br
CH3 C CH3
CH3
CH3 C CH3
CH3
CH3 C CH3
CH3
O H
H
O
H
H
CH3 C CH3
CH3
O H
H
CH3 C CH3
CH3
O H
1935: Hughes & Ingold
carbocation
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energy
Reaction coordinate
C
R
Br
RR
R CRR
Br
R CR
R
R C
R
O
R
H H
CR
R
OH
R
intermediate
intermediate
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SSNN1 Reaction: kinetics1 Reaction: kinetics
•The reactions follows first order (unimolecular) kinetics
•Rate = k [R-Br]1
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SSNN1 Reaction: 1 Reaction: stereochemistrystereochemistry
With chiral R-X compounds, the product will be racemic (50% of
each enantiomer).
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Stereochemistry in SStereochemistry in SNN1 1 reactions – racemic reactions – racemic
productproduct
CH3
H
CH3C
Et
BrPr CH3-O-H
CH3C
Et
OPr
3o substrate
polarproticsolvent!
C
Pr
H3C Et
(S) enantiomerplanar carbocation
C
Pr
H3C Et
front sideattack
back sideattack
CH3-O-H
CH3-O-H
Slow
Pr
CH3Et
OH3C
H
Pr
CH3Et
OH3C
CHEt
OPr CH3H
H
50% (S)
50% (R)
Fast fast
fast
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energy
Reaction coordinate
C
R
Br
RR
R CRR
Br
R CR
R
R C
R
O
R
H3C H
CR
R
O-CH3
R
intermediate
intermediate
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SSNN1 Reaction: substrate 1 Reaction: substrate structurestructure
krel
no reaction
1.00
11.6
61.2 x 10
CH3 Br
CH3 CH2 Br
CH3 CH Br
CH3
CH3 C Br
CH3
CH3
Solvolysis in water at 50°C
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SSNN1 Reaction: 1 Reaction: substrate structuresubstrate structure
tertiary>secondary>primary > methyl
Primary and methyl halides are very unreactive! They don’t go by SN1 reactions.
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C
tertiary
C
tertiary secondary
>
primary
+
carbocation (very stable)
secondarycarbocation
+
CH3
>Br
CH3
CH3
CH3 CH
CH3
Br
CH3 CH
CH3
CH3CH3-CH2-Br
CH3
+
primarycarboc
CH3
carbocation(unstable)
CH3
+
CH3-Br>
very unstable carbocation
three methyl groups
two methyl groups
one methyl group
no methyl groups
CH3 CH2
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NucleophilesNucleophiles
• Usually SN1 reactions are run in polar protic solvents; compounds with O-H groups.
• The polar protic solvent acts as BOTH nucleophile as well as the solvent.
• Common solvent/nucleophiles include:water, ethanol, methanol, acetic acid, and formic acid.
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A protic solvent acts as both a A protic solvent acts as both a solvent and nucleophile in Ssolvent and nucleophile in SNN1 1
reactions - solvolysis:reactions - solvolysis:Water
HO
H
Methanol HO
CH3
HO
CH2CH3
HOEtEthanol
HO
C
O
CH3Acetic acid HOAc
HO
C
O
HFormic acid
HOMe
abbreviations
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Typical solvolysis Typical solvolysis reaction reaction
CH3
H
CH3C
Et
BrPr CH3-O-H
CH3C
Et
OPr
3o substrate
polarproticsolvent!
C
Pr
H3C Et
(S) enantiomerplanar carbocation
C
Pr
H3C Et
front sideattack
back sideattack
CH3-O-H
CH3-O-H
Slow
Pr
CH3Et
OH3C
H
Pr
CH3Et
OH3C
CHEt
OPr CH3H
H
50% (S)
50% (R)
Fast fast
fast
Polar solvent
stabilizes
the carbocation!Solvent is the
nucleophile
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Leaving groupsLeaving groups
• Leaving groups are the same as in SN2 reactions:
• Cl, Br, I, OTs are the usual ones.
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SSNN1 Reaction: solvent 1 Reaction: solvent polaritypolarity
• SN1 solvolysis reactions go much faster in trifluoroacetic acid and water (high ionizing power).
• SN1 solvolysis reactions go slower in ethanol and acetic acid (lower ionizing power).
• See table 10-9.
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SSNN2 2 versusversus S SNN1 1 ReactionsReactions
• A primary alkyl halide or a methyl halide should react by an SN2 process. Look for a good nucleophile, such as hydroxide, methoxide, etc. in an polar aprotic solvent.
• A tertiary alkyl halide should react by an SN1 mechanism. Make sure to run the reaction under solvolysis (polar protic solvent) conditions! Don’t use strong base conditions -- it will give you nothing but E2 elimination!
• A secondary alkyl halide can go by either mechanism. Look at the solvent/nucleophile conditions!!
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SSNN2 2 versusversus S SNN1 Reactions 1 Reactions (continued)(continued)
• If the reaction medium is KI or NaI in acetone, this demands an SN2 mechanism.
• If the reaction medium is AgNO3 in ethanol, this demands an SN1 mechanism.
• If the medium is basic, look for SN2.
• If the medium is acidic or neutral, expect SN1.
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Comparison of SComparison of SNN1 and 1 and SSNN2 Reactions2 Reactions
• See Table 10-10 on page 936. Great table!!
• Section 10-5: Solvent effects; been there done that!!
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Sect. 10.6: Sect. 10.6: classification tests classification tests
• Sodium iodide and potassium iodide in acetone are typical SN2 reagents!!
• Silver nitrate in ethanol is a typical SN1 reagent!!
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Sect. 10.7: Special Sect. 10.7: Special CasesCases
Neopentyl compounds are very unreactive in SN2 reactions.
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Effect Effect of of -substitution-substitution on S on SNN2 reactivity (Table 10-2 reactivity (Table 10-
11)11)
KI in Acetone at 25°
krel
1.0
0.65
0.15
0.000026
CH2 CH2 Br
CH2 CH2 Br
CH3 C CH2 Br
CH3
CH3
Neopentyl bromide
CH3
CH3 CH CH2 Br
CH3
H
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Neopentyl Transition Neopentyl Transition StateState
C C
Y
Nu
R1
R2
R3
Nu
YR1
H
H
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Allylic and Benzylic Allylic and Benzylic compoundscompounds
Allylic and benzylic compounds are especially reactive in SN1 reactions.Even though they are primary substrates, they are more reactive most other halides! They form resonance stabilized carbocations.
CH2-Br CH2=CH-CH2-Br
benzyl bromide allyl bromide
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Solvolysis Rates: SSolvolysis Rates: SNN11Table 10-13Table 10-13
krel
Ethyl chlorideIsopropyl chlorideAllyl chlorideBenzyl chloridetert-Butyl chloride
very small 1 74 140 12,000
80% Ethanol-water at 50°
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Allylic and Benzylic Allylic and Benzylic compounds compounds
Allylic and benzylic compounds are especially reactive in SN2 reactions.They are more reactive than typical primary compounds!
CH2-Br CH2=CH-CH2-Br
benzyl bromide allyl bromide
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Reaction with KI in Reaction with KI in Acetone: SAcetone: SNN22Table 10-14Table 10-14
krel
Ethyl chlorideAllyl chlorideMethyl chlorideBenzyl chloride
1 33 93 93
60° C
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Vinyl and Phenyl Vinyl and Phenyl CompoundsCompounds
Vinyl and Phenyl compounds are completely inert in both
SN1 and SN2 reactions!!
vinyl phenyl
CCH2
Cl
H Cl
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Reactivity order for SReactivity order for SNN11
RC
R R
Br>
CH2Br
C CCH2
Br
HH
H
>
3o
BenzylAllyl
RCH
RBr
2o
>
1o
R CH2 Br> >> CH3-Br
methyl
>> Br
CBr
R
R
H
phenylvinyl
Inert!!No reaction
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Reactivity order for SReactivity order for SNN22
RC
R R
Br
CH2Br
C CCH2
Br
HH
H
3o
BenzylAllyl
RCH
RBr
2o1o
R CH2 BrCH3-Br
methyl
>> Br
CBr
R
R
H
phenylvinyl
Inert!!No reaction!!
>> >
Can not undergoSN2
= >> >
About same reactivity
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Sect. 10.8: Cyclic Sect. 10.8: Cyclic SystemsSystems
• Cyclopropyl and cyclobutyl halides are very unreactive in both SN1 and SN2 reactions
• Cyclopentyl halides are more reactive than cyclohexyl halides in SN1 and SN2 reactions.
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Bicyclic systems: Bredt’s Bicyclic systems: Bredt’s RuleRule
You can’t have p orbitals on a bridgehead position in a rigid bicyclic molecule.
-- You cannot form a carbocation at a bridgehead position.
--You cannot have a double bond at a bridgehead position.
+
bridgehead
bridgehead
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Cl
AgNO3
Ethanol
No reaction!
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Sect. 10.9: Sect. 10.9: Carbocation Carbocation RearrangementRearrangement
1)
slow
++ Br
_
2)
+ +
3)
++ ROH + H
+
CH3 C CH CH3
CH3
CH3 Br
CH3 C CH CH3
CH3
CH3
CH3 C CH CH3
CH3
CH3
CH3 C CH CH3
CH3
CH3
CH3 C CH CH3
CH3
CH3
CH3 C CH CH3
CH3
CH3OR
a carbocation
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A Closer Look...A Closer Look...
+ +
+
CH3 C CH CH3
CH3
CH3
CH3 C CH CH3
CH3
CH3
CH3 C CH CH3
CH3
CH3
transition state
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Carbocation Carbocation RearrangementRearrangement
CH3 C CH CH3
CH3
CH3
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Carbocation Carbocation RearrangementRearrangement
CH3 C CH CH3
CH3
CH3
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Carbocation Carbocation RearrangementRearrangement
CH3 C CH CH3
CH3
CH3
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Carbocation Carbocation RearrangementRearrangement
CH3 C CH CH3
CH3
CH3
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Carbocation Carbocation RearrangementRearrangement
CH3 C CH CH3
CH3
CH3
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Carbocation Carbocation RearrangementRearrangement
CH3 C CH CH3
CH3
CH3
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Carbocation Carbocation RearrangementRearrangement
CH3 C CH CH3
CH3
CH3
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Carbocation Carbocation RearrangementRearrangement
CH3 C CH CH3
CH3
CH3
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Sir Christopher IngoldSir Christopher Ingold
Source: Michigan State University, Department of Chemistry
http://www.chemistry.msu.edu/Portraits/PortraitsHH_collection.shtml
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Saul WinsteinSaul Winstein
Source: Michigan State University, Department of Chemistry
http://www.chemistry.msu.edu/Portraits/PortraitsHH_collection.shtml
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Sect. 10.10 Competing Sect. 10.10 Competing Reactions: Elimination Reactions: Elimination
-- Table 10-16-- Table 10-16• Lower temperatures favor substitution; higher
temperatures give more elimination. • Highly branched compounds (secondary and
tertiary compounds) give mostly elimination with strong bases. Weaker bases give more substitution. A basic medium favors E2; a more nucleophilic medium favors SN2.
• Primary compounds give mostly substitution with non-bulky nucleophiles. A bulky base (tert-butoxide) gives elimination.
• Tertiary compounds should be reacted under solvolysis conditions to give substitution!!!
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Sect. 10.11: Sect. 10.11: Neighboring group Neighboring group
participationparticipation+ CH3O
_
> 0.5 M
_ _
+ CH3O_
< 0.1 M
_ _
(R)-(+) (S)-(-)
(R)-(+)(R)-(+)
+ Br_
+ Br_
CH3OH
CH3OH
!!!
CH3 CH C O
Br
O
CH3 CH C O
OCH3
O
CH3 CH C O
Br
O
CH3 CH C O
OCH3
O
inversion
retention
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Under SUnder SNN2 Conditions2 Conditions
_
_
(R)
..:..
- -
_
+ Br_
_
(S)
Inversion of configuration
C Br
CH3
HC
OO
CH3 OCH3
C
H C
BrO
OO
CH3
CH3 O C
CH3
HC
OO
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Internal SInternal SNN2 reaction 2 reaction followed by an external followed by an external
SSNN2 reaction2 reaction
.._
:..
(R)
slow
: :
_ ..:
..
..
..
+ H+
+ Br_
(R)
Retention of Configuration
C Br
CH3
HC
O
O
C
C
O
CH3H
O
OCH3 H
C O CH3
CH3
CH
OO
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Neighboring Group Neighboring Group ParticipationParticipation
slow+ : X :
..
..
_
fast
Nu :
1)
2)
C C
G:
X
C C
G
C C
G
C C
G:
Nu
G:
X
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Neighboring group Neighboring group participation: Summaryparticipation: Summary•Retention of configuration•Enhanced rate of reaction
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Mustard gasMustard gas• Mustard gas is a substance that causes tissue blistering (a
vesicant). It is highly reactive compound that combines with proteins and DNA and results in cellular changes immediately after exposure. Mustard gas was used as a chemical warfare agent in World War I by both sides.
S
ClCl
S
Cl
Neighboringgroup participationInternal SN2
S
Cl O-Enzyme
External SN2S
O-EnzymeCl
Cl
ClCl
Mustard gas
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Sect. 10.13: Ion-pair Sect. 10.13: Ion-pair mechanisms (skip!!)mechanisms (skip!!)
• SN1 reactions are “expected” to give a 50-50 (racemic) mixture of the two enantiomers!!
• But, if the leaving group doesn’t get out of the way, you will get more inversion than retention, which makes it “look like” SN2.
• In the extreme, you could have a carbocation give only inversion of configuration by an SN1 mechanism!!
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In-Class ProblemIn-Class Problem
For the following reaction,
CH3 CH CH CH2 OTs H2O
acetone
A) Identify the mechanism of this reaction.
B) Predict the product(s) of this reaction, and identifythem as major or minor, if appropriate.
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The following table may The following table may be helpful as a review be helpful as a review
WWU -- ChemistryWWU -- Chemistry
Substitution Substitution versusversus EliminationElimination
SN1 SN2 E1 E2
Substrate Strong effect; reaction favored by tertiary halide
Strong effect; reaction favored by methyl or primary halide
Strong effect; reaction favored by tertiary halide
Strong effect; reaction favored by tertiary halide
Reactivity – primary
Does not occur Highly favored Does not occur Occurs with strong base!
Reactivity – tertiary
Favored when nucleophile is the solvent – solvolysis
Does not occur Occurs under solvolysis conditions or with strong acids
Highly favored when strong bases (OH-, OR-) are used
Reactivity – secondary
Can occur in polar, protic solvents
Favored by good nucleophile in polar, aprotic solvents
Can occur in polar, protic solvents
Favored when strong bases are used
Solvent Very strong effect; reaction favored by polar, protic solvents
Strong effect; reaction favored by polar, aprotic solvents
Very strong effect; reaction favored by polar, protic solvents
Strong effect; reaction favored by polar, aprotic solvent
Nucleophile/Base Weak effect; reaction favored by good nucleophile/weak base
Strong effect; reaction favored by good nucleophile/weak base
Weak effect; reaction favored by weak base
Strong effect; reaction favored by strong base
Leaving Group Strong effect; reaction favored by good leaving group
Strong effect; reaction favored by good leaving group
Strong effect; reaction favored by good leaving group
Strong effect; reaction favored by good leaving group