1. Dr. Wolf's CHM 201 & 202 5-1 5.14 Dehydrohalogenation of Alkyl Halides

2. Dr. Wolf's CHM 201 & 202 5-2 H Y dehydrogenation of alkanes:  H; Y = H dehydration of alcohols:  H; Y = OH dehydrohalogenation of alkyl halides:  H; Y = Br, etc.    -Elimination Reactions Overview C C C C +HY

3. Dr. Wolf's CHM 201 & 202 5-3 H Y dehydrogenation of alkanes: industrial process; not regioselective dehydration of alcohols: acid-catalyzed dehydrohalogenation of alkyl halides: consumes base    -Elimination Reactions Overview C C C C +HY

4. Dr. Wolf's CHM 201 & 202 5-4 DehydrohalogenationDehydrohalogenation A useful method for the preparation of alkenes Cl (100 %) likewise, NaOCH 3 in methanol, or KOH in ethanol NaOCH 2 CH 3 ethanol, 55°C

5. Dr. Wolf's CHM 201 & 202 5-5 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%) DehydrohalogenationDehydrohalogenation CH 2 CH 3 (CH 2 ) 15 CH

6. Dr. Wolf's CHM 201 & 202 5-6 Br 29 % 71 % + Regioselectivity follows Zaitsev's rule: more highly substituted double bond predominates KOCH 2 CH 3 ethanol, 70°C

7. Dr. Wolf's CHM 201 & 202 5-7 more stable configuration of double bond predominates Stereoselectivity KOCH 2 CH 3 ethanol Br + (23%) (77%)

8. Dr. Wolf's CHM 201 & 202 5-8 more stable configuration of double bond predominates Stereoselectivity KOCH 2 CH 3 ethanol + (85%) (15%)Br

9. Dr. Wolf's CHM 201 & 202 5-9 5.15 Mechanism of the Dehydrohalogenation of Alkyl Halides: The E2 Mechanism

10. Dr. Wolf's CHM 201 & 202 5-10 Facts (1)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 (second-order)

11. Dr. Wolf's CHM 201 & 202 5-11 Facts (2)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

12. Dr. Wolf's CHM 201 & 202 5-12 The E2 Mechanism concerted (one-step) bimolecular process single transition state C—H bond breaks  component of double bond forms C—X bond breaks

13. Dr. Wolf's CHM 201 & 202 5-13 The E2 Mechanism – O R.... : CCCCCCCCHX.. :: Reactants

14. Dr. Wolf's CHM 201 & 202 5-14 The E2 Mechanism – O R.... : CCCCCCCCHX.. :: Reactants

15. Dr. Wolf's CHM 201 & 202 5-15 CCCCCCCC The E2 Mechanism –––– OR.... H X..:: –––– Transition state

16. Dr. Wolf's CHM 201 & 202 5-16 The E2 Mechanism OR.... H CCCCCCCC–X.. ::.. Products

17. Dr. Wolf's CHM 201 & 202 5-17 5.16 & 5.17 Anti Elimination in E2 Reactions Stereoelectronic Effects Isotope Effects

18. Dr. Wolf's CHM 201 & 202 5-18 (CH 3 ) 3 C Br KOC(CH 3 ) 3 (CH 3 ) 3 COH cis-1-Bromo-4-tert- butylcyclohexane Stereoelectronic effect

19. Dr. Wolf's CHM 201 & 202 5-19 (CH 3 ) 3 C Br KOC(CH 3 ) 3 (CH 3 ) 3 COH trans-1-Bromo-4-tert- butylcyclohexane Stereoelectronic effect

20. Dr. Wolf's CHM 201 & 202 5-20 (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

21. Dr. Wolf's CHM 201 & 202 5-21 (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

22. Dr. Wolf's CHM 201 & 202 5-22 (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

23. Dr. Wolf's CHM 201 & 202 5-23 cis more reactive trans less reactive Stereoelectronic effect

24. Dr. Wolf's CHM 201 & 202 5-24 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.

25. Dr. Wolf's CHM 201 & 202 5-25 Isotope effect Deuterium,D, is a heavy isotope of hydrogen but will undergo the same reactions. But the C-D bond is stronger so a reaction where the rate involves breaking a C-H (C-D) bond, the deuterated sample will have a reaction rate 3-8 times slower. In other words comparing the two rates, i.e. k H /k D = 3-8 WHEN the rate determining step involves breaking the C-H bond.

26. Dr. Wolf's CHM 201 & 202 5-26 5.18 A Different Mechanism for Alkyl Halide Elimination: The E1 Mechanism

27. Dr. Wolf's CHM 201 & 202 5-27 ExampleExample 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

28. Dr. Wolf's CHM 201 & 202 5-28 1. Alkyl halides can undergo elimination in absence of base. 2. Carbocation is intermediate 3. Rate-determining step is unimolecular ionization of alkyl halide. 4.Generally with tertiary halide, base is weak and at low concentration. The E1 Mechanism

29. Dr. Wolf's CHM 201 & 202 5-29 Step 1 slow, unimolecular C CH 2 CH 3 CH 3 + CH 2 CH 3 Br CH 3 C :.. : :.. : Br..–

30. Dr. Wolf's CHM 201 & 202 5-30 Step 2 C CH 2 CH 3 CH 3 + C CH 2 CH 3 CH 3 CH 2 + C CHCH 3 CH 3 – H +

31. Dr. Wolf's CHM 201 & 202 5-31 End of Chapter 5