Organic I - elimination reactions

What is the most common type of elimination reactions?

1,2-elimination or a,B-elimination (alpha, beta)

What are three common elimination reactions?

• Base induced elimination of alkyl halides

• Acid catalysed dehydration of alcohols

• Hofmann degradation of quaternary alkylammonium hydroxides

What are the three possible mechanisms for an elimination reaction?

• Concerted (C-X and H-C bonds break simultaneously) - E2

• C-X bond breaks to form a carbocation - E1

• H-C bond breaks to form a carbanion - E1cB

How does a reaction occur under E1?

• Leaving group departs before the proton is removed in a subsequent step

• Rate limiting step = first step to form carbocation

• Rapid elimination (caused by base deprotonation) follows to form neutral alkene

• Can form two eliminated products due to area of attack - will favour the more substituted product

How does the base affect an E1 reaction?

• Base is not involved in the RDS

• Variation in base concentration has no effect on the rate of the E1 reaction

• Usually occurs in the absence of a strong base but in a polar solvent

How does the substrate affect an E1 reaction?

• Factors that stabilise a carbocation favour an E1 mechanism

• Tertiary benzylic and tertiary allylic positions are most stable

• Primary and vinyl positions are least stable

How does the leaving group affect an E1 reaction?

• Iodine is most reactive (longest bond length and least electronegative halide)

• Fluorine is least reactive (shortest bond length and most electronegative halide)

What is Saytzeff’s Rule (determines major product of E1)?

Neutral substrates give predominantly the most substituted alkene (thermodynamically most stable)

What factors increase the stability of a formed alkene?

• Thermodynamic stability increases with increasing substitution

• Pi system of double bonds stabilised by empty pi* orbitals interacting with filled orbitals of parallel C-C and C-H bonds - enables delocalisation through interactions

• More C-H or C-C bonds makes a more stable alkene - increased orbital interactions

What is the requirement for the E1cB mechanism?

Employs a strong base and contains an anion-stabilising group

How does the E1cB mechanism occur?

• Eliminate from the conjugate base of the molecule

• Base deprotonates, stabilising group gains -ve charge

• Rearrangement pushes off the leaving group and changes the location of the double bond

• -OH can be a leaving group in E1cB reactions as already an oxyanion and conjugation assists loss of OH-

How does the E2 mechanism occur?

• One step concerted pathway

• Deprotonation and leaving group occur at the same time

• Base induced - often accompanied by Sn2

How does substrate identity affect an E2 reaction?

• Primary, secondary and tertiary substrates can all react by E2

• Is a case that substrate structure may allow E1 due to carbocation stability

How does the leaving group identity affect an E2 reaction?

• Most common E2 reaction is with alkyl halides

• Iodine is most reactive

• Fluorine is least reactive

How does Hoffman elimination occur?

• Base deprotonates an acidic hydrogen

• Leaving group is a quaternary ammonium salt

• Forms a less substituted alkene due to sterics

What is the stereoselectivity of E2 reactions?

• Elimination conformation must have H, C1, C2 and X all in the same plane

• Due to orbital interactions when breaking/making bonds

• Has two possible conformations: anti-periplanar or syn-periplanar

• Syn-periplanar elimination is not favoured as it is higher energy due to steric interactions (eclipsed substituents)

Why is anti-periplanar elimination favoured?

• Elimination is from a low energy staggered conformation

• Attacking base and leaving group are as far apart as possible in the transition state

• Electron pair from C-H is attacking from opposite the C-X departing pair (such as in Sn2)

• Leads to favouring anti-periplanar elimination and E alkenes

How does the base identity affect E1 vs E2?

• Elimination with a strong base is always via the E2 mechanism

• Size of the base affects regioselectivity - substituted bases give less substituted alkene products due to steric hindrance

How can substrate structure help define substitution vs elimination?

• Sn2 favours a primary alkyl halide most

• E1, E2 and Sn1 favour a tertiary alkyl halide most

• Using a primary substrate will allow substitution to dominate

How can nucleophile/base choices help define substitution vs base?

• Substitution: high concentration of a weak base nucleophile

• Elimination: high concentration of a strong base

• Good nucleophiles are usually good bases - causes competition

• Non-nucleophilic bases can promote elimination

• Favouring Sn2/E2 = strong base/good nucleophile

• Favouring Sn1/E1 = weak base/poor nucleophile

How does the choice of leaving group affect substitution vs elimination?

• Neutral leaving groups favour substitution

• Positively charged leaving groups favour elimination

How does temperature define substitution vs elimination?

High reaction temperatures favour elimination

How does solvent choice define substitution vs elimination?

• Bimolecular reactions (Sn2/E2): polar aprotic solvents

• Unimolecular reactions (Sn1/E1): polar protic solvents