Date post: | 17-Dec-2015 |
Category: |
Documents |
Upload: | elizabeth-briggs |
View: | 227 times |
Download: | 3 times |
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
example
SN1 - CX bond breaks, forming a C+ then reacts with a nucleophile
XC+
C + + X-
NuCC + + Nu:
SN1
SN2
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)
CH3Br + HO - CH3OH + Br-
methyl bromide methyl alcohol
Rate = k [RX] [Nu:]
(Because rate is dependent of BOTH RX and Nu: it is 2nd. order.)
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
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 Weaker baseBetter nucleophile poorer nucleophile
OH- > H2O
CH3O- > CH3OH-NH2> NH3
CH3CH2NH- > 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 SolventsProtic 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)
acetone
CH3CCH3
O
dimethyl sulfoxide
CH3SCH3
O
DMSON,N-dimethylformamide
HC N
O
CH3
CH3
DMF
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
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
CH2CH3 Br + I- CH2CH3 I + Br-CH2CH3 Br + I- CH2CH3 I + Br-
SN1 Reactions
• Reaction of t-butyl bromide with water should be slow– water is a poor nucleophile– t-butyl bromide is sterically hinderedHowever– Reaction is a million times faster than with CH3Br
t-butyl bromide
CCH3
CH3
Br
CH3
+ H2O
t-butyl alcohol
CCH3
CH3
OH
CH3
+ HBr
t-butyl bromide
CCH3
CH3
Br
CH3
+ H2O
t-butyl alcohol
CCH3
CH3
OH
CH3
+ HBr
(Maybe not an SN2 reaction!)
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’tThis 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
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 anSN1 Reactions
• The Nucleophile• It has NO EFFECT on rate of Rx!!!
• Solvolysis Reactions • (the nucleophile is also the solvent)
Carbocation RearrangementsSince a carbocation is the intermediate, you may see
rearrangements in an SN1 Rx
No rearrangements in an SN2 Rx
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
BrBr
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
Role of the SolventIn 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 N,N-dimethylformamide
– DMSO dimethylsulfoxide
– HMPA hexamethylphosphoramide
– THF Tetrahydrofuran– And even… 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
Nucleophile Review
strong
weak
Br-, I-
HO-, CH3O-, RO-
CH3S-, RS -
CH3CO2-, RCO2
-
H2OCH3OH, ROHCH3CO2H, RCO2H
NH3, RNH2, R2NH, R3NCH3SH, RSH, R2S
EffectivenessNucleophile
moderate
CN-, N3-
SN1/SN2 Problems -1
• Predict the type of mechanism for this reaction, and the stereochemistry of each product
+
+ +
OH
Cl
OCH3
CH3CHCH2CH3
CH3CHCH2CH3
CH3CHCH2CH3
CH3OH/H2O
HCl(R)-enantiomer
SN1/SN2 Problems -1
• Predict the type of mechanism for this reaction, and the stereochemistry of each product
+
+ +
OH
Cl
OCH3
CH3CHCH2CH3
CH3CHCH2CH3
CH3CHCH2CH3
CH3OH/H2O
HCl(R)-enantiomer
SN1/SN2 Problems -2
• Predict the mechanism of this reaction
+
+
DMSOCH3
CH3
CH3CHCH2CN
CH3CHCH2Br Na+CN-
Na+Br-
SN1/SN2 Problems -2
• Predict the mechanism of this reaction
+
+
DMSOCH3
CH3
CH3CHCH2CN
CH3CHCH2Br Na+CN-
Na+Br-
SN1/SN2 Problems -3
• Predict the mechanism. If the starting material has the R configuration, predict the configuration of product
+
+
acetone
Br
SCH3
CH3CHCH2CH3 CH3S-Na+
CH3CHCH2CH3 Na+Br-
SN1/SN2 Problems -3
• Predict the mechanism. If the starting material has the R configuration, predict the configuration of product
+
+
acetone
Br
SCH3
CH3CHCH2CH3 CH3S-Na+
CH3CHCH2CH3 Na+Br-
SN1/SN2 Problems -5
• Predict the mechanism
+ toluene
Br-
(CH3)3PCH3(CH2)5CH2Br
CH3(CH2)5CH2-P(CH3)3
+
SN1/SN2 Problems -5
• Predict the mechanism
+ toluene
Br-
(CH3)3PCH3(CH2)5CH2Br
CH3(CH2)5CH2-P(CH3)3
+