CHEM10009 Study Guide - Final Guide: Nucleophilic Substitution, Racemic Mixture, Leaving Group
10 Jun 2018
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Department
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Professor
Substitution reactions
Atom (or group) on a molecule is replaced by a diff atom (or group) to form a
new molecule
-
Elimination reactions
Loss of atom to form a multiple bond (C=C)
-
Requires reagents that are STRONG BASES and relatively WEAK NUCLEOPHILES
Eg. NaH, Potassium tert-butoide
○
-
Nucleophile (e-rich)
Molecule containing an electron rich atom that can form a bond by donating a
pair of e- to an electron poor atom on another molecule
-
Strength
Strongest base = best
○
Has a weak conjugate acid
○
-
Electrophile (e-poor)
Molecule containing e- poor atom that can form a bond by accepting a pair of e-
from another molecule
-
Leaving group
Group replaced in a nucleophilic substitution reaction
-
Best form most stable, least basic anions (ie. Weakest bases)
Eg. Halides (I-, Br-, Cl-), water
○
Better ability of base to stabilize negative charge, better leaving group
○
-
NUCLEOPHILIC SUBSTIUTION
Sn1 Reactions
2 steps
Carbocation intermediate formation (RDS)
1)
Rapid nucleophilic attack of carbocation
2)
-
Favoured for tertiary
Faster and easier - most stable carbocation
○
-
Rate dependent only on carbocation formation - rate = k(substrate)
-
Chiral substrate gives rise to racemic mixture
-
Sn2 Reactions
1 step
Making and breaking of bonds is simultaneous
○
-
Entering nucleophile attacks carbon from 180 degrees from leaving group ->
inversion of stereochemistry
-
Rate depends on [substrate] and [nucleophile] - rate = k[substrate][nucleophile]
-
Transition state, but no carbocation intermediate
-
Favoured for primary and secondary
Steric hindrance - groups interact w/ each other -> primary fastest
○
-
Secondary substrates
Either Sn1 or Sn2
-
Eg. Inversion of stereochemistry (S-> R) = Sn2 reaction
-
E1 reactions
2 step
IONIZATION: Substrate spontaneously dissociates to give carbocation ie.
Loss of leaving group (RDS)
1)
DEPROTONATION: rapid deprotonation of neighbouring carbon by a base 2)
-
Carbocation intermediate - implications for geometrical isomers of product - can
get E AND Z
-
Rate = k[substrate]
-
Example
-
Loss of leaving group precedes loss of proton
○
Loss of leaving group is RDS
○
E2 reactions
1 step
Making and breaking bonds simultaneous
○
-
Base attacks hydrogen on carbon neighbouring carbon on which the leaving
group (Y) is attached and starts to remove the H at the same time as double bond
begins to form + leaving group starts to leave (transition state)
-
Alkene produced when both C-H and C-Y bonds are broken
-
Hydrogen and leaving group must be in ANTIPERIPLANAR GEOMETRY
Antiperiplanar: H and leaving group are 180 degrees to form double bond -
orbital overlap is crucial
○
-
Rate = k[substrate][base]
-
Alkanes are terrible acids - carbon cant hold negative charge -> double bond
formed -> leaving group takes negative charge
-
Doesn’t matter If base is bulky - no steric effect
-
EXAMPLE:
-
Loss of proton and loss of leaving group same time
-
Very bulky -> Sn2 can't occur
-
Strong base -> E2 is good
-
Comparing E1 and Sn1
First step is identical
-
Harder to control competition b/w E1 and Sn1
Carbocation wants electrons
○
How many hydrogens available?
○
-
Zaitsev's Rule
In elimination of H-X from an alkyl halide, the more highly substituted (and less
sterically hindered) alkene product predominates
-
More substituted and less sterically crowded alkene predominates:
(E)-2-butene > (Z)-2-butene > 1-butene
§
○
Summary of Sn1, Sn2, E1, E2
Primary alkyl halides
Sn2 if good nucleophile used (eg. RS-, I-, Cn-, Br-, NH3)
○
E2 if strong, bulky base used (eg. Tert-butoxide)
○
-
Secondary alkyl halides
Sn2 and E2 occur in competition, thus mixture of products
○
Sn2 favoured for strong bases (eg. HO-, H2N-, CH3CH2O-) in polar aprotic
solents
○
E2 favoured for strong bases (eg. HO- H2N-, CH3CH2O-)
○
Allylic and benzylic secondary alkyl halids can undergo Sn1/E1 if a weak
basic nucleophile is used in protic solvents (eg. EtOH or CH3COOH)
○
-
Tertiary alkyl halides
E2 if base used (eg. HO- or RO)
○
Non basic (eg. EtOH), then mixture of Sn1 and E1 products
○
-
Examples:
Example 1
Mixture of Sn2 and E2 produced
○
Primary carbocation -> Sn1 and E1 suck
○
Not bulky nucleophile
○
90% ether (Sn2)
○
10% alkene (E2)
○
-
Example 2
Tertiary carbocation
○
Very strong base
○
Only elimination - E2
○
100% alkene
○
-
Example 3
Secondary
○
Elimination
○
75% alkene - more stable
More highly substituted
§
Less sterically hindered
§
○
25% alkene
○
-
Regiochemistry of elimination
Transition state for E2 reactions dictates stereochemical outcome
-
Need to use newman projections to predict outcome
-
Using Newman projections to predict outcome of elimination reaction
Make sure they are antiperiplanar
-
For drawing:
-
SUMMARY:
Tuesday, 29 May 2018
11:24 am
Substitution reactions
Atom (or group) on a molecule is replaced by a diff atom (or group) to form a
new molecule
-
Elimination reactions
Loss of atom to form a multiple bond (C=C)
-
Requires reagents that are STRONG BASES and relatively WEAK NUCLEOPHILES
Eg. NaH, Potassium tert-butoide
○
-
Nucleophile (e-rich)
Molecule containing an electron rich atom that can form a bond by donating a
pair of e- to an electron poor atom on another molecule
-
Strength
Strongest base = best
○
Has a weak conjugate acid
○
-
Electrophile (e-poor)
Molecule containing e- poor atom that can form a bond by accepting a pair of e-
from another molecule
-
Leaving group
Group replaced in a nucleophilic substitution reaction
-
Best form most stable, least basic anions (ie. Weakest bases)
Eg. Halides (I-, Br-, Cl-), water
○
Better ability of base to stabilize negative charge, better leaving group
○
-
NUCLEOPHILIC SUBSTIUTION
Sn1 Reactions
2 steps
Carbocation intermediate formation (RDS)
1)
Rapid nucleophilic attack of carbocation
2)
-
Favoured for tertiary
Faster and easier - most stable carbocation
○
-
Rate dependent only on carbocation formation - rate = k(substrate)
-
Chiral substrate gives rise to racemic mixture
-
Sn2 Reactions
1 step
Making and breaking of bonds is simultaneous
○
-
Entering nucleophile attacks carbon from 180 degrees from leaving group ->
inversion of stereochemistry
-
Rate depends on [substrate] and [nucleophile] - rate = k[substrate][nucleophile]
-
Transition state, but no carbocation intermediate
-
Favoured for primary and secondary
Steric hindrance - groups interact w/ each other -> primary fastest
○
-
Secondary substrates
Either Sn1 or Sn2
-
Eg. Inversion of stereochemistry (S-> R) = Sn2 reaction
-
E1 reactions
2 step
IONIZATION: Substrate spontaneously dissociates to give carbocation ie.
Loss of leaving group (RDS)
1)
DEPROTONATION: rapid deprotonation of neighbouring carbon by a base 2)
-
Carbocation intermediate - implications for geometrical isomers of product - can
get E AND Z
-
Rate = k[substrate]
-
Example
-
Loss of leaving group precedes loss of proton
○
Loss of leaving group is RDS
○
E2 reactions
1 step
Making and breaking bonds simultaneous
○
-
Base attacks hydrogen on carbon neighbouring carbon on which the leaving
group (Y) is attached and starts to remove the H at the same time as double bond
begins to form + leaving group starts to leave (transition state)
-
Alkene produced when both C-H and C-Y bonds are broken
-
Hydrogen and leaving group must be in ANTIPERIPLANAR GEOMETRY
Antiperiplanar: H and leaving group are 180 degrees to form double bond -
orbital overlap is crucial
○
-
Rate = k[substrate][base]
-
Alkanes are terrible acids - carbon cant hold negative charge -> double bond
formed -> leaving group takes negative charge
-
Doesn’t matter If base is bulky - no steric effect
-
EXAMPLE:
-
Loss of proton and loss of leaving group same time
-
Very bulky -> Sn2 can't occur
-
Strong base -> E2 is good
-
Comparing E1 and Sn1
First step is identical
-
Harder to control competition b/w E1 and Sn1
Carbocation wants electrons
○
How many hydrogens available?
○
-
Zaitsev's Rule
In elimination of H-X from an alkyl halide, the more highly substituted (and less
sterically hindered) alkene product predominates
-
More substituted and less sterically crowded alkene predominates:
(E)-2-butene > (Z)-2-butene > 1-butene
§
○
Summary of Sn1, Sn2, E1, E2
Primary alkyl halides
Sn2 if good nucleophile used (eg. RS-, I-, Cn-, Br-, NH3)
○
E2 if strong, bulky base used (eg. Tert-butoxide)
○
-
Secondary alkyl halides
Sn2 and E2 occur in competition, thus mixture of products
○
Sn2 favoured for strong bases (eg. HO-, H2N-, CH3CH2O-) in polar aprotic
solents
○
E2 favoured for strong bases (eg. HO- H2N-, CH3CH2O-)
○
Allylic and benzylic secondary alkyl halids can undergo Sn1/E1 if a weak
basic nucleophile is used in protic solvents (eg. EtOH or CH3COOH)
○
-
Tertiary alkyl halides
E2 if base used (eg. HO- or RO)
○
Non basic (eg. EtOH), then mixture of Sn1 and E1 products
○
-
Examples:
Example 1
Mixture of Sn2 and E2 produced
○
Primary carbocation -> Sn1 and E1 suck
○
Not bulky nucleophile
○
90% ether (Sn2)
○
10% alkene (E2)
○
-
Example 2
Tertiary carbocation
○
Very strong base
○
Only elimination - E2
○
100% alkene
○
-
Example 3
Secondary
○
Elimination
○
75% alkene - more stable
More highly substituted
§
Less sterically hindered
§
○
25% alkene
○
-
Regiochemistry of elimination
Transition state for E2 reactions dictates stereochemical outcome
-
Need to use newman projections to predict outcome
-
Using Newman projections to predict outcome of elimination reaction
Make sure they are antiperiplanar
-
For drawing:
-
SUMMARY:
Tuesday, 29 May 2018
11:24 am
Substitution reactions
Atom (or group) on a molecule is replaced by a diff atom (or group) to form a
new molecule
-
Elimination reactions
Loss of atom to form a multiple bond (C=C)
-
Requires reagents that are STRONG BASES and relatively WEAK NUCLEOPHILES
Eg. NaH, Potassium tert-butoide
○
-
Nucleophile (e-rich)
Molecule containing an electron rich atom that can form a bond by donating a
pair of e- to an electron poor atom on another molecule
-
Strength
Strongest base = best
○
Has a weak conjugate acid
○
-
Electrophile (e-poor)
Molecule containing e- poor atom that can form a bond by accepting a pair of e-
from another molecule
-
Leaving group
Group replaced in a nucleophilic substitution reaction
-
Best form most stable, least basic anions (ie. Weakest bases)
Eg. Halides (I-, Br-, Cl-), water
○
Better ability of base to stabilize negative charge, better leaving group
○
-
NUCLEOPHILIC SUBSTIUTION
Sn1 Reactions
2 steps
Carbocation intermediate formation (RDS)1)
Rapid nucleophilic attack of carbocation 2)
-
Favoured for tertiary
Faster and easier - most stable carbocation
○
-
Rate dependent only on carbocation formation - rate = k(substrate)
-
Chiral substrate gives rise to racemic mixture
-
Sn2 Reactions
1 step
Making and breaking of bonds is simultaneous
○
-
Entering nucleophile attacks carbon from 180 degrees from leaving group ->
inversion of stereochemistry
-
Rate depends on [substrate] and [nucleophile] - rate = k[substrate][nucleophile]
-
Transition state, but no carbocation intermediate
-
Favoured for primary and secondary
Steric hindrance - groups interact w/ each other -> primary fastest
○
-
Secondary substrates
Either Sn1 or Sn2
-
Eg. Inversion of stereochemistry (S-> R) = Sn2 reaction
-
E1 reactions
2 step
IONIZATION: Substrate spontaneously dissociates to give carbocation ie.
Loss of leaving group (RDS)
1)
DEPROTONATION: rapid deprotonation of neighbouring carbon by a base
2)
-
Carbocation intermediate - implications for geometrical isomers of product - can
get E AND Z
-
Rate = k[substrate]
-
Example
-
Loss of leaving group precedes loss of proton
○
Loss of leaving group is RDS
○
E2 reactions
1 step
Making and breaking bonds simultaneous
○
-
Base attacks hydrogen on carbon neighbouring carbon on which the leaving
group (Y) is attached and starts to remove the H at the same time as double bond
begins to form + leaving group starts to leave (transition state)
-
Alkene produced when both C-H and C-Y bonds are broken
-
Hydrogen and leaving group must be in ANTIPERIPLANAR GEOMETRY
Antiperiplanar: H and leaving group are 180 degrees to form double bond -
orbital overlap is crucial
○
-
Rate = k[substrate][base]
-
Alkanes are terrible acids - carbon cant hold negative charge -> double bond
formed -> leaving group takes negative charge
-
Doesn’t matter If base is bulky - no steric effect
-
EXAMPLE:
-
Loss of proton and loss of leaving group same time
-
Very bulky -> Sn2 can't occur
-
Strong base -> E2 is good
-
Comparing E1 and Sn1
First step is identical
-
Harder to control competition b/w E1 and Sn1
Carbocation wants electrons
○
How many hydrogens available?
○
-
Zaitsev's Rule
In elimination of H-X from an alkyl halide, the more highly substituted (and less
sterically hindered) alkene product predominates
-
More substituted and less sterically crowded alkene predominates:
(E)-2-butene > (Z)-2-butene > 1-butene
§
○
Summary of Sn1, Sn2, E1, E2
Primary alkyl halides
Sn2 if good nucleophile used (eg. RS-, I-, Cn-, Br-, NH3)
○
E2 if strong, bulky base used (eg. Tert-butoxide)
○
-
Secondary alkyl halides
Sn2 and E2 occur in competition, thus mixture of products
○
Sn2 favoured for strong bases (eg. HO-, H2N-, CH3CH2O-) in polar aprotic
solents
○
E2 favoured for strong bases (eg. HO- H2N-, CH3CH2O-)
○
Allylic and benzylic secondary alkyl halids can undergo Sn1/E1 if a weak
basic nucleophile is used in protic solvents (eg. EtOH or CH3COOH)
○
-
Tertiary alkyl halides
E2 if base used (eg. HO- or RO)
○
Non basic (eg. EtOH), then mixture of Sn1 and E1 products
○
-
Examples:
Example 1
Mixture of Sn2 and E2 produced
○
Primary carbocation -> Sn1 and E1 suck
○
Not bulky nucleophile
○
90% ether (Sn2)
○
10% alkene (E2)
○
-
Example 2
Tertiary carbocation
○
Very strong base
○
Only elimination - E2
○
100% alkene
○
-
Example 3
Secondary
○
Elimination
○
75% alkene - more stable
More highly substituted
§
Less sterically hindered
§
○
25% alkene
○
-
Regiochemistry of elimination
Transition state for E2 reactions dictates stereochemical outcome
-
Need to use newman projections to predict outcome
-
Using Newman projections to predict outcome of elimination reaction
Make sure they are antiperiplanar
-
For drawing:
-
SUMMARY:
Tuesday, 29 May 2018 11:24 am
Document Summary
Atom (or group) on a molecule is replaced by a diff atom (or group) to form a new molecule. Loss of atom to form a multiple bond (c=c) Requires reagents that are strong bases and relatively weak nucleophiles. Molecule containing an electron rich atom that can form a bond by donating a pair of e- to an electron poor atom on another molecule. Molecule containing e- poor atom that can form a bond by accepting a pair of e- from another molecule. Best form most stable, least basic anions (ie. weakest bases) Better ability of base to stabilize negative charge, better leaving group. Rate dependent only on carbocation formation - rate = k(substrate) Entering nucleophile attacks carbon from 180 degrees from leaving group -> inversion of stereochemistry. Rate depends on [substrate] and [nucleophile] - rate = k[substrate][nucleophile] Steric hindrance - groups interact w/ each other -> primary fastest. Inversion of stereochemistry (s-> r) = sn2 reaction.
