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

A Final Thought Concerning E1 and SN1

Rate data: kArctic ~ kAntarctica >>> kequator

Explanation? • Rate controlled by rds = ionization of carbon-leaving group bond...

Answer:

End of exam 1 coverage