elimination reactions – part 1 - chemistry iyc 2011 … reactions – part 1 what is an...
TRANSCRIPT
Elimination Reactions – Part 1
What is an Elimination Reaction? Elimination reaction: A reaction in which a molecule loses atoms or groups from adjacent atoms, resulting in a new pi bond.
• Useful for synthesis of alkenes, alkynes
Alkene Stereoisomer Nomenclature
Cis and Trans • Based on carbon groups bonded to C=C
• Cis/trans nomenclature may be ambiguous or inapplicable:
Carbon groups on same alkene face Cis-but-2-ene
Carbon groups on opposite alkene face Trans-but-2-ene
Alkene Stereoisomer Nomenclature
E and Z • Based on Cahn-Ingold-Prelog priorities at each alkene carbon • Review Cahn-Ingold-Prelog priorities from Chem 14C if necessary
• E/Z never ambiguous and always applicable
Highest priority groups on same face (Z)-1-Bromo-1-chloropropene
Z from German zusammen (together)
Highest priority groups on opposite face (E)-1-Bromo-1-chloropropene
E from German entgegen (against)
Br > Cl CH3 > H
What Influences Alkene Stability? Steric strain Which alkene is more stable?
Cis:
Trans:
General rule: Trans alkene isomer more stable than cis alkene isomer.
• Greater steric strain • Less stable isomer
• Less steric strain • More stable isomer
Steric strain
Steric strain
Space-filling models
Warning: E alkene isomer is not always more stable than Z alkene isomer.
What Influences Alkene Stability? Internal versus Terminal Which alkene is more stable?
Conjugation Which alkene is more stable?
A terminal alkene Less stable isomer
An internal alkene More stable isomer
General rule: Internal alkenes are more stable than terminal alkenes.
General rule: Conjugation increases alkene stability.
Alkene conjugated More stable isomer
Alkene not conjugated Less stable isomer
What Influences Alkene Stability? Degree of Substitution Which alkene is more stable?
Disubstituted alkene Two =C-C bonds
Trisubstituted alkene Three =C-C bonds
Tetrasubstituted alkene Four =C-C bonds
Bond energies (kcal mol-1): Csp3-Csp3 89 Csp3-Csp2 102 Csp3-H 98 Csp2-H 109
Conclusions:
Increasing stability
• Bonds to sp2 carbon are stronger • Changing =C-H to =C-C ↑ stability by 2 kcal mol-1 bond-1
• ↑ number of Csp3-Csp2 bonds ↑ alkene stability
What Influences Alkene Stability? Controlled by: • Strain
• Internal vs. terminal • Conjugation • Degree of substitution
General Alkene Stability Trend
Terminal Monosubstituted
Terminal Disubstituted
Internal Disubstituted
Cis
Internal Disubstituted
Trans
Internal Trisubstituted
Internal Tetrasubstituted
Increasing stability due to degree of substitution
Decreasing stability due to strain
What Influences Alkene Stability? Substitution Versus Strain
Tetra-tert-butyl ethylene
• A tetrasubstituted alkene • Severe steric strain Verify with a model
• Has never been synthesized
General rule For alkene stability, degree of substitution outweighs steric strain, unless strain is severe.
Which Elimination Product is Major?
A B C
Amount produced: 19% 81%
Alkene stability ranking: B > C > A Prediction: Major product is... A B C
Fact: For many reactions major product = most stable product = thermodynamic control
Alkene Stability • Cis alkenes: A B C Trans alkenes: A B C
• Internal alkenes: A B C Terminal alkenes: A B C
• Monosubstituted alkenes: A B C Disubstituted alkenes: A B C
Major elimination product = more stable alkene = Zaitsev’s Rule (1875)
Elimination Reaction Mechanism: E2 Methoxide ion (strong base)
Solvent is often conjugate acid of base
What is the mechanism? • Observed kinetics: Rate = k [R-Cl] [CH3O-]
• Elimination bimolecular
E2 Transition State Geometry Requirement Observation:
Why? • Only difference is Br stereochemistry • How does Br stereochemistry influence reaction?
E2 Transition State Geometry Requirement
No H—C periplanar to C—Br; E2 prevented
E2 requires periplanar H—C—C—LG
Lower energy pathway
Does not occur
Elimination Reactions – Part 2
Summary of Part 1 Elimination reaction: A reaction in which a molecule loses atoms or groups from adjacent atoms, resulting in a new pi bond.
But-1-ene Terminal
Monosubstituted
(Z)-but-2-ene Internal
Disubstituted
More steric strain
(E)-but-2-ene Internal
Disubstituted
Less steric strain
Minor product
Major elimination product = more stable alkene = Zaitsev’s Rule
Major product
+ +
Summary of Part 1 Mechanism:
• H-C-C-LG must be periplanar • Elimination bimolecular → E2
Exceptions to Zaitsev’s Rule
Base = CH3CH2O- Ethoxide
Base = (CH3)3CO- Tert-butoxide
79% 21% Zaitsev
27% 73% Hofmann
Hofmann elimination: Major E2 product is less highly substituted alkene
Conclusion: ↑ steric hindrance at business end of base favors less substituted alkene • Most bases follow Zaitsev's Rule, except for (CH3)3CO-
Exceptions to Zaitsev’s Rule
LG = Br - 31% 51% 18% Zaitsev
LG = N(CH3)3 98% 1% 1% Hofmann
• Hofmann elimination occurs when LG = NR3, SR2, or F- • Other leaving groups give Zaitsev elimination
The E2 Checklist Does my E2 reaction occur at a reasonable rate? • Is Eact low enough?
Base: Usually strong
Leaving group: Moderate or better
Molecular geometry: H-C and C-LG periplanar
Interdependent
• Meeting these requirements indicates the E2 is reasonable • Violating one of these requirements significantly slows or prevents E2
• Often RO-; not ROH • RO- still strong enough base for E2 despite protic solvent (ROH)
• Usually anti-periplanar; rarely syn-periplanar
Additional E2 Examples A nitranion (nitrogen anion) and a strong base Synthesis of an alkyne:
A biological example: In carbohydrate metabolism...
Citrate cis-Aconitate
An Alternate Elimination Mechanism
Consider this elimination reaction:
• Cannot be E2 because...
• Solution: Make HO- into a better leaving group (H2O).
Modified reaction:
LG
An Alternate Elimination Mechanism Mechanism:
H2O is a strong base / poor base E2 is / is not likely
Three carbocation fates
X
An Alternate Elimination Mechanism Mechanism: Three carbocation fates...
• Be deprotonated?
• Capture a nucleophile?
• Rearrange?
Trisubstituted internal alkene More stable alkene
Disubstituted terminal alkene Less stable alkene
An Alternate Elimination Mechanism Kinetics
Kinetics? Multistep mechanism → Identify rate-determining step
rds = formation of carbocation • Same rds as SN1 • Same rate expression as SN1
• Rate = k [R-LG]
• Elimination unimolecular = E1 Notes: • H3O+ is catalyst in this E1 example
• Reaction is reversible:
The E1 Checklist Does my E1 reaction occur at a reasonable rate? • Is Eact low enough?
• Same rds as SN1 → Same requirements as SN1
Leaving group: Moderate or better
Interdependent
• Meeting these requirements indicates the E1 is reasonable • Violating one of these requirements significantly slows or prevents E1
Carbocation: Stability = 2o or better
Solvent: High polarity necessary; protic preferred
Substitution vs. Elimination
Example:
SN2 or SN1? E2 or E1?
and/or
Mechanism choice? Major product? • Carbocation formation is energetically expensive Consider SN2/E2 (no carbocation) before SN1/E1 (have carbocation intermediate)
• Consider E2 before SN2 Exception: 1o alkyl halides - consider SN2 before E2
• SN1 and E1 have same rds SN1 and E1 occur together
Which mechanism operates? What is major product?
Order of Consideration E2 Except for 1o alkyl halide
SN2 SN1/E1