1, 2-Elimination: E1 & E2 i. ii. iii. iv. v. vi. vii. viii. ix. Overview Reactivity: 1 vs. 2 vs.

3 Regioselectivity: Stability of alkenes, Saytzev orientation Stereochemistry of Elimination E1 vs. E2 Elimination vs. Substitution SUMMARY Other 1,2-eliminations The E1CB mechanism Elimination from chromate esters: oxidation of alcohols

i.

Overview 1. E1: Elimination, Unimolecular 3>2>1 Rate = k[Reagent] Carbocation intermediate Most substituted alkene is formed (Saytzev orientation) 2. E2: Elimination, Bimolecular Anti-periplanar arrangement of the two leaving groups, H and X 3>2>1 Rate = k[Reagent][Base-] Usually, the most substituted alkene is formed (Saytzev orientation) 3. Kinetic Isotope Effects: Isotope effects are useful in determining r.d.s If C-H bond is broken in the r.d.s, we can determine it is an E2 reaction Deuterium is used to identify important C-H bond

ii.

Reactivity 1. For E1 elimination, the tertiary carbocation is more stable than the secondary, which is more stable than the primary The same factors that control reactivity in SN1 will also control E1 The more orbital overlap, the more stable the carbocation 2. The rate for E2 elimination is fastest for tertiary, then secondary then primary carbocations The more -hydrogens available, the higher the probability of attack A more substituted alkene is formed more quickly through a stabilised TS

iii.

Regioselectivity: Stability of alkenes, Saytzev Orientation 1. E1 exhibits Saytzev Orientation In dehydrohalogenation, the preserved product is the alkene that has the greatest number of alkyl groups attached to the doubly bonded carbon atoms More substituted alkenes are more stable as there more possible overlaps: bonds can overlap with the alkene * orbital The first step is rate determining The second step is product determining: the more stable the alkene, the faster it is formed (kinetic product) 2. E2 elimination may see more than one alkene (also known as an olefin) being produced The more substituted alkene is favoured 3. Hofmann Elimination An amine is reacted to form a tertiary amine and then finally converted into an alkene. The least substituted alkene is known as the Hofmann product: Amine + CH3I (Anything that makes it a good leaving group)Tertiary amine+ + H2O + Ag2O + heat Least substituted alkene (Hofmann product) Hofmann product favoured when its TS is more stable than TS for most substituted alkene

iv.

Stereochemistry of -elimination: E1 and E2 1. E1 eliminations can be stereoselective A stereoselective reaction is one in which the reaction can choose to afford predominately one of the two possible stereoisomerislly different products A carbocation intermediate is formed The TS with the lower energy (i.e. more stable) will have its final product dominate 2. E2 elimination occurs via stereospecific anti-periplanar arrangement of the two leaving groups, H and X Anti-periplanar arrangement allows for good orbital overlap in TS of C-H orbital and C-X * orbital If the leaving group is not very bulky, the most substituted alkene is favoured (Saytzev) For E2 elimination in cyclohexanes, both C-H and C-X must be in the axial position: elimination can only occur if leaving group is in the axial position

v.

E1 vs. E2 1. Rate of both E1 and E2 elimination reactions increase from 1 to 2 to 3 They increase for different reasons for E1 and E2: For E1, the rate is fastest for 3 carbocation as it is the TS that is more stable For E2, anti-periplanar arrangement allows for orbital overlap and stabilisation

vi.

Elimination vs. Substitution SUMMARY E.g. Me-X 1 2 3 Poor nucleophile H2O No reaction No reaction SN1, E1 SN1, E1 Weakly basic nucleophile ISN2 SN2 SN2 SN1, E1 Strongly basic unhindered nucleophile EtOSN2 SN2 E2 E2 Strongly basic hindered nucleophile tBuOSN2 E2 E2 E2

E1 and SN1 involve carbocation intermediates and are prone to rearrangements

vii.

Other 1,2-eliminations 1. 1,2-dehalogenation Rate=k[I-][RBr] 2. 1,2-dehalogenation from vinyl halides: Synthesis of Alkynes Haloalkenes are reacted to form alkynes. H and X are anti-periplanar to each other

viii.

The E1CB Mechanism: A third mechanism for elimination 1. E1CB mechanism involves initial deprotonation by a base to form a carbanion The second step is the r.d.s The mechanism can occur only if the carbanion can be stabilised (often as an enolate when dealing with carbonyls and alcohols as side groups) 2. Regioselective: Fixed by position of leaving group and acidic H Intermediate carbanion is planar due to resonance 3. E1CB is the reverse of conjugate addition 4. E1CB commonly occurs when the product formed is a conjugate carbonyl

ix.

Elimination from chromate esters: oxidation of alcohols 1. Elimination is a key step in the oxidation of alcohols The oxidation product of alcohols depends on if they are 1, 2 or 3 1 oxidised to aldehyde, then carboxylic acid 2 oxidised to ketone 3 will not oxidise 2. Jones reagent of Na2Cr2O7 with H2SO4, H2O and acetone can oxidise 1 and 2 alcohols The elimination step where the chromate ester is broken is the r.d.s

Preparation of Haloalkanes From alcohols ROH + PX3 RX Free radical halogenation of certain hydrocarbons RH + X2RX + HX Addition of hydrogen halides to alkenes Alkene +HXAlkane with H and X both attached Addition of halogens to alkenes Alkene + X2RX2 Halide Exchange (Finkelstein reaction) RX+Y-RY + X-

Preparation of Alcohols Hydration of alkenes Alkene + H++H2OMarkovnikov alcohol Hydroboration-oxidation of alkenes Alkene+(i)BH3+(ii)OH +H2O2Anti Markovnikov alcohol Addition of a nucleophile to a carbonyl Carbonyl +RMgBrAlcohol Hydrolysis of alkyl halides RX+H2OROH Reduction of carbonyl and carboxylic acid derivatives Carbonyl+NaBH4Alcohol
-

Preparation of Aliphatic Amines Reductive amination NEXT YEAR Alkylation of NH3 or amines NH3+RXRNH2+RXR2NH+RXR3NX Reduction of nitriles RCN+H2+LiAlH4RNH2 Gabriel Synthesis/Use of Azide Anion Potassium phthalimide+ (i)RX + (ii)hydrazineRNH2 RX+(i)NaN3+(ii)LiAlH4RNH2