Presentation on theme: "Dehydrohalogenation of Alkyl Halides E2 and E1 Reactions in Detail"— Presentation transcript:
1 Dehydrohalogenation of Alkyl Halides E2 and E1 Reactions in Detail
2 b-Elimination Reactions Overview dehydration of alcohols: X = H; Y = OHdehydrohalogenation of alkyl halides: X = H; Y = Br, etc.CC+XYXYab2
3 b-Elimination Reactions Overview dehydration of alcohols: acid-catalyzeddehydrohalogenation of alkyl halides: consumes baseCC+XYXYab2
4 is a useful method for the preparation of alkenes Dehydrohalogenationis a useful method for the preparation of alkenesClNaOCH2CH3ethanol, 55°C(100 %)likewise, NaOCH3 in methanol, or KOH in ethanol4
5 DehydrohalogenationWhen the alkyl halide is primary, potassium tert-butoxide in dimethyl sulfoxide is the base/solvent system that is normally used.KOC(CH3)3CH3(CH2)15CH2CH2Cldimethyl sulfoxideCH2CH3(CH2)15CH(86%)5
6 More highly substituted double bond predominates = More Stable RegioselectivityBrKOCH2CH3ethanol, 70°C+29 %71 %follows Zaitsev's ruleMore highly substituted double bond predominates = More Stable10
7 Zaitsev’s RuleThe more substituted alkene is obtained when a proton is removed from the b-carbon that is bonded to the fewest hydrogens
12 more stable configuration of double bond predominates StereoselectivityKOCH2CH3ethanolBr+(23%)(77%)more stable configuration of double bond predominates11
13 more stable configuration of double bond predominates StereoselectivityBrKOCH2CH3ethanol+(85%)(15%)more stable configuration of double bond predominates11
14 Mechanism of the Dehydrohalogenation of Alkyl Halides: The E2 Mechanism 13
15 Dehydrohalogenation of alkyl halides exhibits second-order kinetics FactsDehydrohalogenation of alkyl halides exhibits second-order kineticsfirst 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 bimolecular14
16 Rate of elimination depends on halogen FactsRate of elimination depends on halogenweaker C—X bond; faster rate rate: RI > RBr > RCl > RFimplies that carbon-halogen bond breaks in the rate-determining step14
17 concerted (one-step) bimolecular process single transition state The E2 Mechanismconcerted (one-step) bimolecular processsingle transition stateC—H bond breaksp component of double bond formsC—X bond breaks16
18 The E2 Mechanism Figure: 07-07-13UN Caption: Second-order elimination is a reliable synthetic reaction, especially if the alkyl halide is a poor SN2 substrate. E2 dehydrohalogenation takes place in one step, in which a strong base abstracts a proton from one carbon atom as the leaving group leaves the adjacent carbon.
37 Stereoelectronic effect (CH3)3CBrcisKOC(CH3)3 (CH3)3COH(CH3)3CRate constant for dehydrohalogenation of cis is 500 times greater than that of trans(CH3)3CBrKOC(CH3)3 (CH3)3COHtrans21
38 Stereoelectronic effect (CH3)3CBrcisKOC(CH3)3 (CH3)3COHH(CH3)3CHH that is removed by base must be anti periplanar to BrTwo anti periplanar H atoms in cis stereoisomer21
39 Stereoelectronic effect transH(CH3)3CBrKOC(CH3)3 (CH3)3COH(CH3)3CH that is removed by base must be anti periplanar to BrNo anti periplanar H atoms in trans stereoisomer; all vicinal H atoms are gauche to Br21
41 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.22
43 Can you predict the products? Can you explain the products? E2 in a cyclohexane ringCis or trans?Axial or equatorial?a,e e,ae,e a,aCan you predict the products?Can you explain the products?21
44 Cyclohexane Stereochemistry Revisited How many stereoisomers are possible for menthol?l-menthol21
45 A Different Mechanism for Alkyl Halide Elimination: The E1 Mechanism 23
46 Example CH3 C CH3 CH2CH3 Br Ethanol, heat CH2CH3 CH3 C H2C H3C CH3 C H +(25%)(75%)25
47 1. Alkyl halides can undergo elimination in absence of base. The E1 Mechanism1. Alkyl halides can undergo elimination in absence of base.2. Carbocation is intermediate3. Rate-determining step is unimolecular ionization of alkyl halide.24
48 Step 1 CH3 C CH2CH3 Br : .. slow, unimolecular C + CH2CH3 CH3 – : Br 25
49 Which alkene is more stable and why? Step 2CCH2CH3CH3+– H+CH3CH2+CCCH3CHCH3CH3CH2CH3Which alkene is more stable and why?27
50 Figure: 07-05Caption:Figure 7-5trans-2-Butene is more stable than 1-butene by 2.7 kcal/mol (11 kJ/mol).
51 Figure: 07-06Caption:Figure 7-6The isomer with the more highly substituted double bond has a larger angular separation between the bulky alkyl groups.
52 Figure: 07-07Caption:Figure 7-7Relative energies of typical p bonds compared with ethylene. (The numbers are approximate.)
53 Reaction coordinate diagram for the E1 reaction of 2-chloro-2-methylbutane
64 Substitution vs. Elimination Alkyl halides can undergo SN2, SN1, E2 and E1 Reactions1) Which reaction conditions favor SN2/E2 or SN1/E1?SN2/E2 reactions are favored by a highconcentration of nucleophile/strong baseSN1/E1 reactions are favored by a poornucleophile/weak base2) What will be the relative distribution of substitution productvs. elimination product?
65 Consider SN1/E1 vs. SN2/E2Consider the Substrate
66 NOTE: a bulky base encourages elimination over substitution
67 Returning to Sn2 and E2: Considering the differences Can you explain the products?Can you predict the products?21
68 Substitution and Elimination Reactions in Synthesis
69 A hindered alkyl halide should be used if you want to synthesize an alkene
72 Intermolecular vs. Intramolecular Reactions A low concentration of reactant favors an intramolecularreactionThe intramolecular reaction is also favored when a five-or six-membered ring is formed
73 Three- and four-membered rings are less easily formed Three-membered ring compounds are formed moreeasily than four-membered ring compoundsThe likelihood of the reacting groups finding each otherdecreases sharply when the groups are in compoundsthat would form seven-membered and larger rings.