Presentation on theme: "Dehydrohalogenation of Alkyl Halides E2 and E1 Reactions in Detail."— Presentation transcript:
Dehydrohalogenation of Alkyl Halides E2 and E1 Reactions in Detail
X Y dehydration of alcohols: X = H; Y = OH dehydrohalogenation of alkyl halides: X = H; Y = Br, etc. C C C C +XY -Elimination Reactions Overview
X Y dehydration of alcohols: acid-catalyzed dehydrohalogenation of alkyl halides: consumes base C C C C +XY -Elimination Reactions Overview
is a useful method for the preparation of alkenes (100 %) likewise, NaOCH 3 in methanol, or KOH in ethanol NaOCH 2 CH 3 ethanol, 55°C Dehydrohalogenation Cl
CH 3 (CH 2 ) 15 CH 2 CH 2 Cl When the alkyl halide is primary, potassium tert-butoxide in dimethyl sulfoxide is the base/solvent system that is normally used. KOC(CH 3 ) 3 dimethyl sulfoxide (86%) CH 2 CH 3 (CH 2 ) 15 CH Dehydrohalogenation
Br 29 % 71 % + Regioselectivity follows Zaitsev's rule More highly substituted double bond predominates = More Stable KOCH 2 CH 3 ethanol, 70°C
Zaitsev’s Rule The more substituted alkene is obtained when a proton is removed from the -carbon that is bonded to the fewest hydrogens
Conjugated alkenes are preferred !
Steric hindrance effects the product distribution
more stable configuration of double bond predominates Stereoselectivity KOCH 2 CH 3 ethanol Br + (23%)(77%)
more stable configuration of double bond predominates Stereoselectivity KOCH 2 CH 3 ethanol + (85%)(15%)Br
Mechanism of the Dehydrohalogenation of Alkyl Halides: The E2 Mechanism
Facts Dehydrohalogenation of alkyl halides exhibits second-order kinetics first order in alkyl halide first order in base rate = k[alkyl halide][base] implies that rate-determining step involves both base and alkyl halide; i.e., it is bimolecular
Facts Rate of elimination depends on halogen weaker C—X bond; faster rate rate: RI > RBr > RCl > RF implies that carbon-halogen bond breaks in the rate-determining step
concerted (one-step) bimolecular process single transition state C—H bond breaks component of double bond forms C—X bond breaks The E2 Mechanism
– O R.... : CCCCCCCCHX.. :: Reactants The E2 Mechanism
– O R.... : CCCCCCCCHX.. :: Reactants The E2 Mechanism
CCCCCCCC –––– OR.... H X..:: –––– Transition state The E2 Mechanism
OR.... H CCCCCCCC–X.. ::.. Products
Stereoelectronic Effects Anti Elimination in E2 Reactions
Stereochemistry of the E2 Reaction Remember: The bonds to the eliminated groups (H and X) must be in the same plane and anti to each other H X More stable conformation than syn-eclipsed
The best orbital overlap of the interacting orbitals is achieved through back side attack of the leaving group X as in an S N 2 displacement.
Configuration of the Reactant
Elimination from Cyclic Compounds Configuration must be trans, which is (anti).
(CH 3 ) 3 C Br Br KOC(CH 3 ) 3 (CH 3 ) 3 COH cis trans Rate constant for dehydrohalogenation of cis is 500 times greater than that of trans Stereoelectronic effect
(CH 3 ) 3 C Br KOC(CH 3 ) 3 (CH 3 ) 3 COH cis H that is removed by base must be anti periplanar to Br Two anti periplanar H atoms in cis stereoisomer H H Stereoelectronic effect
(CH 3 ) 3 C KOC(CH 3 ) 3 (CH 3 ) 3 COH trans H that is removed by base must be anti periplanar to Br No anti periplanar H atoms in trans stereoisomer; all vicinal H atoms are gauche to Br H H (CH 3 ) 3 C BrHH Stereoelectronic effect
cis more reactive trans less reactive Stereoelectronic effect
An effect on reactivity that has its origin in the spatial arrangement of orbitals or bonds is called a stereoelectronic effect. The preference for an anti periplanar arrangement of H and Br in the transition state for E2 dehydrohalogenation is an example of a stereoelectronic effect.
E2 in a cyclohexane ring
Can you predict the products? Cis or trans? Axial or equatorial? a,e e,a e,e a,a Can you explain the products?
Cyclohexane Stereochemistry Revisited l-menthol How many stereoisomers are possible for menthol?
A Different Mechanism for Alkyl Halide Elimination: The E1 Mechanism
CH 3 CH 2 CH 3 Br CH 3 Ethanol, heat + (25%) (75%) C H3CH3CH3CH3C CH 3 C C H3CH3CH3CH3C H CH 2 CH 3 CH 3 C H2CH2CH2CH2C Example
1. Alkyl halides can undergo elimination in absence of base. 2. Carbocation is intermediate 3. Rate-determining step is unimolecular ionization of alkyl halide. The E1 Mechanism
C CH 2 CH 3 CH 3 + C CH 2 CH 3 CH 3 CH 2 + C CHCH 3 CH 3 – H + Step 2 Which alkene is more stable and why?
Reaction coordinate diagram for the E1 reaction of 2-chloro-2-methylbutane
Must consider possible carbocation rearrangement
Stereochemistry of the E1 Reaction
E1 Elimination from Cyclic Compounds E1 mechanism involves both syn and anti elimination
Summary & Applications (Synthesis) S N 1 / E1 vs. S N 2 / E2
E2 and E1 Reactions
Substitution vs. Elimination Alkyl halides can undergo S N 2, S N 1, E2 and E1 Reactions 1) Which reaction conditions favor S N 2/E2 or S N 1/E1? S N 2/E2 reactions are favored by a high concentration of nucleophile/strong base S N 1/E1 reactions are favored by a poor nucleophile/weak base 2) What will be the relative distribution of substitution product vs. elimination product?
Consider S N 1/E1 vs. S N 2/E2 Consider the Substrate
NOTE: a bulky base encourages elimination over substitution
Returning to Sn2 and E2: Considering the differences Can you predict the products? Can you explain the products?
Substitution and Elimination Reactions in Synthesis
A hindered alkyl halide should be used if you want to synthesize an alkene
Which reaction produces an ether?
Consecutive E2 Elimination Reactions: Alkynes
Intermolecular vs. Intramolecular Reactions A low concentration of reactant favors an intramolecular reaction The intramolecular reaction is also favored when a five- or six-membered ring is formed
Three- and four-membered rings are less easily formed Three-membered ring compounds are formed more easily than four-membered ring compounds The likelihood of the reacting groups finding each other decreases sharply when the groups are in compounds that would form seven-membered and larger rings.