Dehydrohalogenation of Alkyl Halides E2 and E1 Reactions in Detail

1. Dehydrohalogenation of Alkyl Halides E2 and E1 Reactions in Detail

2. X Y C C C C b-Elimination Reactions Overview • dehydration of alcohols: X = H; Y = OH • dehydrohalogenation of alkyl halides: X = H; Y = Br, etc. + Y X a b

3. X Y C C C C b-Elimination Reactions Overview • dehydration of alcohols:acid-catalyzed • dehydrohalogenation of alkyl halides:consumes base + Y X a b

4. Cl Dehydrohalogenation • is a useful method for the preparation of alkenes NaOCH2CH3 ethanol, 55°C (100 %) likewise, NaOCH3 in methanol, or KOH in ethanol

5. CH3(CH2)15CH CH2 Dehydrohalogenation • When the alkyl halide is primary, potassiumtert-butoxide in dimethyl sulfoxide is the base/solvent system that is normally used. KOC(CH3)3 CH3(CH2)15CH2CH2Cl dimethyl sulfoxide (86%)

6. KOCH2CH3 Br ethanol, 70°C Regioselectivity • follows Zaitsev's rule • More highly substituted double bond predominates = More Stable + 71 % 29 %

7. Zaitsev’s Rule The more substituted alkene is obtained when a proton is removed from the b-carbon that is bonded to the fewest hydrogens

9. Conjugated alkenes are preferred !

10. Steric hindrance effects the product distribution

12. KOCH2CH3 ethanol Stereoselectivity • more stable configurationof double bond predominates Br + (23%) (77%)

13. Br KOCH2CH3 ethanol Stereoselectivity • more stable configurationof double bond predominates + (85%) (15%)

14. Mechanism of theDehydrohalogenation of Alkyl Halides:The E2 Mechanism

15. 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

16. 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

17. The E2 Mechanism • concerted (one-step) bimolecular process • single transition state • C—H bond breaks • p component of double bond forms • C—X bond breaks

18. The E2 Mechanism

19. .. : R .. H C C : : X .. The E2 Mechanism – O Reactants

20. .. : R .. H C C : : X .. The E2 Mechanism – O Reactants

21. : : X .. The E2 Mechanism d– .. H R O .. Transition state C C d–

22. – .. : : X .. The E2 Mechanism .. H R O .. C C Products

23. Anti Elimination in E2 Reactions • Stereoelectronic Effects

24. Stereochemistry of the E2 Reaction H X Remember: The bonds to the eliminated groups (H and X) must be in the same plane and anti to each other More stable conformation than syn-eclipsed

25. The best orbital overlap of the interacting orbitals is achieved through back side attack of the leaving group X as in an SN2 displacement.

26. Regioselectivity

29. Configuration of the Reactant

30. Elimination from Cyclic Compounds Configuration must be trans, which is (anti).

35. Br (CH3)3C (CH3)3C Stereoelectronic effect KOC(CH3)3(CH3)3COH cis-1-Bromo-4-tert- butylcyclohexane

36. (CH3)3C Br (CH3)3C Stereoelectronic effect trans-1-Bromo-4-tert- butylcyclohexane KOC(CH3)3(CH3)3COH

37. Br (CH3)3C (CH3)3C Br (CH3)3C Stereoelectronic effect cis KOC(CH3)3(CH3)3COH • Rate constant for dehydrohalogenation of cis is 500 times greater than that of trans KOC(CH3)3(CH3)3COH trans

38. Br (CH3)3C (CH3)3C Stereoelectronic effect cis KOC(CH3)3(CH3)3COH • H that is removed by base must be anti periplanar to Br • Two anti periplanar H atoms in cis stereoisomer H H

39. H Br H (CH3)3C H H (CH3)3C Stereoelectronic effect trans KOC(CH3)3(CH3)3COH • 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

40. Stereoelectronic effect cis more reactive trans less reactive

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.

42. E2 in a cyclohexane ring

43. E2 in a cyclohexane ring Cis or trans? Axial or equatorial? a,e  e,a e,e  a,a Can you predict the products? Can you explain the products?

44. Cyclohexane Stereochemistry Revisited http://www.csir.co.za/biochemtek/newsletter/aug/menthol.html How many stereoisomers are possible for menthol? l-menthol http://www.library.ucsf.edu/tobacco/batco/html/9000/9036/

45. A Different Mechanism for Alkyl Halide Elimination:The E1 Mechanism

46. C H3C CH3 H C H2C C C CH3 CH2CH3 H3C Example CH3 CH2CH3 CH3 Br Ethanol, heat + (75%) (25%)

47. The E1 Mechanism • 1. Alkyl halides can undergo elimination in absence of base. • 2. Carbocation is intermediate • 3. Rate-determining step is unimolecular ionization of alkyl halide.

48. CH3 CH2CH3 C CH3 : : Br .. CH3 C + CH2CH3 CH3 .. – : : Br .. Step 1 slow, unimolecular

49. CH3 C + CH2CH3 CH3 Step 2 – H+ CH3 CH2 + C C CHCH3 CH3 CH2CH3 CH3 Which alkene is more stable and why?