4.8 Preparation of Alkyl Halides from Alcohols and Hydrogen Halides

1. 4.8Preparation of Alkyl Halides fromAlcohols and Hydrogen Halides ROH + HX  RX + H2O

2. Reaction of Alcohols with Hydrogen Halides ROH + HX  RX + HOH Hydrogen halide reactivity HI HBr HCl HFmost reactiveleast reactive

3. Reaction of Alcohols with Hydrogen Halides ROH + HX  RX + HOH Alcohol reactivityR3COH R2CHOH RCH2OH CH3OHTertiary Secondary Primary Methanolmost reactiveleast reactive

4. OH + HBr Br Preparation of Alkyl Halides 25°C (CH3)3CCl + H2O 78-88% (CH3)3COH + HCl 80-100°C + H2O 73% 120°C CH3(CH2)5CH2OH + HBr CH3(CH2)5CH2Br + H2O 87-90%

5. Preparation of Alkyl Halides A mixture of sodium bromide and sulfuric acid may be used in place of HBr. NaBrH2SO4 CH3CH2CH2CH2Br CH3CH2CH2CH2OH heat 70-83%

6. 4.9Mechanism of the Reaction of Alcohols with Hydrogen Halides

7. + R R C R Carbocation The key intermediate in reaction of secondary and tertiary alcohols with hydrogen halides is a carbocation. A carbocation is a cation in which carbon has6 valence electrons and a positive charge.

8. + R R C R Carbocation The key intermediate in reaction of secondary and tertiary alcohols with hydrogen halides is a carbocation. The overall reaction mechanism involves threeelementary steps; the first two steps lead to thecarbocation intermediate, the third step is the conversion of this carbocation to the alkyl halide.

9. + H3C CH3 C CH3 Example 25°C (CH3)3CCl + H2O (CH3)3COH + HCl tert-Butyl alcohol tert-Butyl chloride Carbocation intermediate is: tert-Butyl cation

10. .. + : H Cl .. H .. – + + : : : O Cl (CH3)3C .. H Mechanism Step 1: Proton transfer from HCl to tert-butyl alcohol .. : O (CH3)3C H fast, bimolecular tert-Butyloxonium ion

11. H + : O (CH3)3C H H : : O H Mechanism Step 2: Dissociation of tert-butyloxonium ion slow, unimolecular + + (CH3)3C tert-Butyl cation

12. .. – : : Cl .. .. : Cl (CH3)3C .. Mechanism Step 3: Capture of tert-butyl cation by chloride ion. + + (CH3)3C fast, bimolecular tert-Butyl chloride

13. 4.10Structure, Bonding, andStability of Carbocations

14. Figure 4.8 Structure of methyl cation. Carbon is sp2 hybridized.All four atoms lie in same plane.

15. Figure 4.8 Structure of methyl cation. Empty 2p orbital. Axis of 2p orbital is perpendicular to plane of atoms.

16. + R R C R Carbocations Most carbocations are too unstable to beisolated. When R is an alkyl group, the carbocation isstabilized compared to R = H.

17. + H H C H Carbocations Methyl cationleast stable

18. Carbocations + H H3C C H Ethyl cation(a primary carbocation) is more stable than CH3+

19. Carbocations + CH3 H3C C H Isopropyl cation(a secondary carbocation) is more stable than CH3CH2+

20. Carbocations + CH3 H3C C CH3 tert-Butyl cation(a tertiary carbocation) is more stable than (CH3)2CH+

21. Figure 4.9 Stabilization of carbocationsvia the inductive effect positively chargedcarbon pullselectrons in  bondscloser to itself +

22. Figure 4.9 Stabilization of carbocationsvia the inductive effect positive charge is"dispersed ", i.e., sharedby carbon and thethree atoms attachedto it    

23. Figure 4.9 Stabilization of carbocationsvia the inductive effect electrons in C—Cbonds are more polarizable than thosein C—H bonds; therefore, alkyl groupsstabilize carbocationsbetter than H. Electronic effects transmitted through bonds are called "inductive effects."    

24. Figure 4.10 Stabilization of carbocationsvia hyperconjugation electrons in this bond can be sharedby positively chargedcarbon because thes orbital can overlap with the empty 2porbital of positivelycharged carbon +

25. Figure 4.10 Stabilization of carbocationsvia hyperconjugation electrons in this bond can be sharedby positively chargedcarbon because thes orbital can overlap with the empty 2porbital of positivelycharged carbon  

26. Figure 4.10 Stabilization of carbocationsvia hyperconjugation Notice that an occupiedorbital of this type isavailable when sp3hybridized carbon is attached to C+, but is not availabe when His attached to C+. Therefore,alkyl groupsstabilize carbocationsbetter than H does.  

27. + R R C R Carbocations The more stable a carbocation is, the faster it isformed. Reactions involving tertiary carbocations occurat faster rates than those proceeding via secondarycarbocations. Reactions involving primary carbocations or CH3+ are rare.

28. + R R C R Carbocations Carbocations are Lewis acids (electron-pairacceptors). Carbocations are electrophiles (electron-seekers). Lewis bases (electron-pair donors) exhibit just theopposite behavior. Lewis bases are nucleophiles(nucleus-seekers).

29. .. – : : Cl .. .. : Cl (CH3)3C .. Mechanism Step 3: Capture of tert-butyl cation by chloride ion. + + (CH3)3C fast, bimolecular tert-Butyl chloride

30. .. .. – : Cl : : Cl (CH3)3C .. .. Carbocations + + (CH3)3C The last step in the mechanism of the reaction oftert-butyl alcohol with hydrogen chloride is the reaction between an electrophile and a nucleophile. tert-Butyl cation is the electrophile. Chloride ionis the nucleophile.

31. + – Fig. 4.11 Combination of tert-butyl cation andchloride ion to give tert-butyl chloride nucleophile (Lewis base) electrophile (Lewis acid)

32. 4.11Potential Energy Diagrams forMultistep Reactions:The SN1 Mechanism

33. H2O H Br + H2O—H + Br – Recall...   the potential energy diagram for proton transfer from HBr to water Potentialenergy H2O + H—Br Reaction coordinate

34. 25°C (CH3)3CCl + H2O (CH3)3COH + HCl Extension The potential energy diagram for a multistep mechanism is simply a collection of the potential energy diagrams for the individual steps. Consider the mechanism for the reaction oftert-butyl alcohol with HCl.

35. .. + : H Cl .. H .. – + + : : : O Cl (CH3)3C .. H Mechanism Step 1: Proton transfer from HCl to tert-butyl alcohol .. : O (CH3)3C H fast, bimolecular tert-butyloxonium ion

36. H + : O (CH3)3C H H : : O H Mechanism Step 2: Dissociation of tert-butyloxonium ion slow, unimolecular + + (CH3)3C tert-Butyl cation

37. .. – : : Cl .. .. : Cl (CH3)3C .. Mechanism Step 3: Capture of tert-butyl cation by chloride ion. + + (CH3)3C fast, bimolecular tert-Butyl chloride

38. + ROH2 carbocation formation carbocation capture R+ proton transfer ROH RX

39. – + O H Cl (CH3)3C H + ROH2 carbocation formation carbocation capture R+ ROH RX

40. H + + O (CH3)3C H + ROH2 carbocation capture R+ proton transfer ROH RX

41. + – Cl (CH3)3C + ROH2 carbocation formation R+ proton transfer ROH RX

42. Mechanistic notation The mechanism just described is an example of an SN1 process. SN1 stands for substitution-nucleophilic-unimolecular. The molecularity of the rate-determining step defines the molecularity of theoverall reaction.

43. H + + O (CH3)3C H Mechanistic notation The molecularity of the rate-determining step defines the molecularity of theoverall reaction. Rate-determining step is unimoleculardissociation of alkyloxonium ion.

44. 4.12Effect of Alcohol Structureon Reaction Rate

45. slow step is: ROH2+  R+ + H2O The more stable the carbocation, the fasterit is formed. Tertiary carbocations are more stable thansecondary, which are more stable than primary,which are more stable than methyl. Tertiary alcohols react faster than secondary, which react faster than primary, which react fasterthan methanol.

46. Hammond's Postulate If two succeeding states (such as a transition state and an unstable intermediate)are similar in energy, they are similar in structure. Hammond's postulate permits us to infer the structure of something we can't study (transition state) from something we can study (reactive intermediate).

47. + ROH2 carbocation formation carbocation capture R+ proton transfer ROH RX

48. + ROH2 carbocation formation Rate is governed by energy of this transition state. Infer structure of this transition state from structure of state of closest energy; in this case the nearest state is the carbocation. carbocation capture R+ proton transfer ROH RX

49. 4.13Reaction of Primary Alcohols withHydrogen Halides.The SN2 Mechanism

50. OH + HBr Br Preparation of Alkyl Halides 25°C (CH3)3CCl + H2O 78-88% (CH3)3COH + HCl 80-100°C + H2O 73% 120°C CH3(CH2)5CH2OH + HBr CH3(CH2)5CH2Br + H2O 87-90%