Transcript Organic Chemistry - Snow College | It's SNOWing

Organic Chemistry
Chapter 8
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
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
+
C X

C+
-
+ X
SN1
C+
+ Nu:
C Nu
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
SN2 Mechanism
• It’s a Substitution Reaction (S)
• It’s Nucleophilic (N)
• It’s rate is second order (2)
– Called bimolecular (rate is dependent on 2 reactants)
• (Substitution Nucleophilic Bimolecular)
CH 3Br
+ HO-
methyl bromide
CH 3OH + Br methyl alcohol
Rate = k [RX] [Nu:]
(Because rate is dependent of BOTH RX and Nu: it is 2nd. order.)
SN2 Mechanism
• SN2 Mechanism involves a “backside attack”
SN2 Mechanism
The “backside attack” causes an Inversion of Configuration
Careful now….. Doesn’t mean R becomes S – new atoms are involved
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
Steric Hindrance
• Activation Energy is higher due to
steric hindrance…..
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
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)
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)
Nucleophiles – Strong/Weak
Good/Bad
Stronger base
Better nucleophile
OHCH3O-NH
2
CH3CH2NH-
>
>
>
>
Weaker base
poorer nucleophile
H2O
CH3OH
NH3
CH3CH2NH2
(conjugate acids)
Nucleophiles
• The strength of nucleophile depends
on reaction conditions.
• In the GAS phase (not usually used), direct
relationship between basicity and
nucleophilicity
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
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
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)
O
CH 3 S CH 3
dimethyl sulfoxide
DMSO
O CH 3
HC N CH 3
N,N-dimethylformamide
DMF
O
CH 3 C CH 3
acetone
Nucleophiles
• In the organic solvent phase,
INVERSE relationship between basicity and
nucleophilicity with a protic solvent
Question…
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
Nucleophiles
• Solvents can solvate the nucleophile
(Methanol is a polar protic solvent.)
SN2 Reactions
SN2 Reactions
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
CH 3 CH 2 Br
+
I-
CH 3 CH 2 I
+ Br -
SN2 Reactions
Compare basicity to see which is a better nucleophile.
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
CH 3
CH 3
CH 3 C Br
+
CH 3
t-butyl bromide
H2 O
CH 3 C OH
CH 3
t-butyl alcohol
(Maybe not an SN2 reaction!)
+ HBr
SN1 Reactions
•
SN1 Mechanism
• Rate determining step does not involve
nucleophile
Step 1
Step 2
SN1 Mechanism
SN1 Reactivity
• Relative Reactivities in an SN1 Reaction
1o RX <
2o RX < 3o RX
Increasing Reactivity
SN1 Stereochemistry
• Because a planer carbocation is formed,
nucleophilic attack is possible on both sides,
so both isomers are possible
SN1 Stereochemistry
SN1 should yield racemic mixture but it doesn’t
This is due to the steric hindrance of the leaving group
Stereochemistry
• As the leaving group goes (Marvin K) it
blocks the path of any incoming
nucleophiles
SN1 vs SN2
Inversion of
configuration
racemization with
partial inversion
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 > 2o > 1o > methyl
Increasing Stability
What Doesn’t Matter In an
SN1 Reactions
• The Nucleophile
• It has NO EFFECT on rate of Rx!!!
• Solvolysis Reactions
• (the nucleophile is also the solvent)
Carbocation Rearrangements
Since a carbocation is the intermediate, you may see
rearrangements in an SN1 Rx
No rearrangements in an SN2 Rx
Carbocation Rearrangement
• Methyl Shift
Benzylic, Allylic, Vinylic,
and Aryl Halides
• Benzylic and allylic halides can readily
undergo SN2 unless they are 3o
– (steric hindrance)
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!
Vinylic,and Aryl Halides
• Vinylic halides and aryl halides
– do not undergo SN1 or SN2 reactions!
e- repel incoming Nucleophile
p
Br
Br
SN1 vs SN2 Review
SN1 vs SN2
…
2o RX …
3o RX …
Vinylic, aryl RX …
1o, 2o benzylic, allylic RX …
3o benzylic, allylic RX …
Methyl, 1o
RX
SN2 only
SN1 and SN2
SN1 only
neither SN1 nor SN2
SN1 and SN2
SN1 only
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.
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.)
*
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.)
Polar Aprotic Solvents
• Polar Aprotic Solvents include:
– DMF
– DMSO
– HMPA
– THF
– And even…
N,N-dimethylformamide
dimethylsulfoxide
hexamethylphosphoramide
Tetrahydrofuran
acetone
Polar Aprotic Solvents
Polar Aprotic Solvents
– do not H bond
– solvate cations well
– do NOT solvate anions (nucleophiles) well
– good solvents for SN2 reactions
Polar Aprotic Solvents
•
•
•
•
DMSO
DMF
Acetone
HMPA
Nucleophile Review
Effe ctive n e ss Nu cle oph il e
Br - , I HO - , CH 3 O- , RO
s tron g
CN- , N 3 CH3 S - , RS CH3 CO2 - , RCO
2
-
-
mode rate CH3 SH, RSH, R 2 S
NH 3 , RNH 2 , R 2 NH, R
H2 O
we ak CH3 OH, ROH
CH3 CO2 H, RCO 2 H
3N
SN1/SN2 Problems -1
• Predict the type of mechanism for this
reaction, and the stereochemistry of each
product
CH3 CHCH 2 CH3 + CH3 OH/H 2 O
Cl
(R)-en an tiome r
CH3 CHCH 2 CH3 + CH3 CHCH 2 CH3 + HCl
OH
OCH3
SN1/SN2 Problems -1
• Predict the type of mechanism for this
reaction, and the stereochemistry of each
product
CH3 CHCH 2 CH3 + CH3 OH/H 2 O
Cl
(R)-en an tiome r
CH3 CHCH 2 CH3 + CH3 CHCH 2 CH3 + HCl
OH
OCH3
SN1/SN2 Problems -2
• Predict the mechanism of this reaction
CH3
CH3 CHCH 2 Br +
+
Na CN
-
DMS O
CH 3
CH 3 CHCH 2 CN + Na + Br -
SN1/SN2 Problems -2
• Predict the mechanism of this reaction
CH3
CH3 CHCH 2 Br +
+
Na CN
-
DMS O
CH 3
CH 3 CHCH 2 CN + Na + Br -
SN1/SN2 Problems -3
• Predict the mechanism. If the starting
material has the R configuration, predict
the configuration of product
Br
CH3 CHCH 2 CH3 + CH3 S - Na +
ace ton e
SCH 3
CH3 CHCH 2 CH3 +
Na + Br -
SN1/SN2 Problems -3
• Predict the mechanism. If the starting
material has the R configuration, predict
the configuration of product
Br
CH3 CHCH 2 CH3 + CH3 S - Na +
ace ton e
SCH 3
CH3 CHCH 2 CH3 +
Na + Br -
SN1/SN2 Problems -4
• Predict the mechanism
O
Br +
CH 3 COH
acetic acid
O
OCCH 3 + HBr
SN1/SN2 Problems -4
• Predict the mechanism
O
Br +
CH 3 COH
acetic acid
O
OCCH 3 + HBr
SN1/SN2 Problems -5
• Predict the mechanism
CH3 (CH 2 ) 5 CH2 Br
+ (CH 3 ) 3 P
tol ue ne
+
CH3 (CH 2 ) 5 CH2 -P(CH 3 ) 3 Br -
SN1/SN2 Problems -5
• Predict the mechanism
CH3 (CH 2 ) 5 CH2 Br
+ (CH 3 ) 3 P
tol ue ne
+
CH3 (CH 2 ) 5 CH2 -P(CH 3 ) 3 Br -
END