1. Chapter 12 Reactions of Alcohols, Ethers, Epoxides, and Sulfur-Containing Compounds Organometallic Compounds Irene Lee Case Western Reserve University Cleveland, OH

2. Reactions of Alcohols reaction with hydrogen halides acid-catalyzed dehydration (E 1 Rxn) reaction with thionyl chloride reaction with phosphorous tribromide & PCl 3 conversion to sulfonate esters

4. Secondary and tertiary alcohols undergo S N 1 reactions with hydrogen halides

5. Primary alcohols undergo S N 2 reactions with hydrogen halides

6. ZnCl 2 can be used to catalyze certain S N 2 reactions

7. Rearrangement of secondary or tertiary alcohols can occur in the S N 1 reaction

8. Amines do not undergo substitution reactions because NH 2 – is a very strong base (a very poor leaving group) RCH 2 F > RCH 2 OH > RCH 2 NH 2 HF H 2 O NH 3 pK a = 3.2 pK a = 15.7pK a = 36

9. Other Methods for Converting Alcohols into Alkyl Halides

10. Activation by SOCl 2

11. Converting Alcohols into Sulfonates (Excellent Leaving Groups)

12. Several sulfonyl chlorides are available to react with -OH group

13. S N 2 Reactions of Activated Sulfonates

14. Dehydration of Alcohols To prevent the rehydration of the alkene product, one needs to remove the product as it is formed

18. Carbocation Rearrangement

19. Ring Expansion

20. Primary Alcohols Undergo Dehydration by an E2 Pathway

21. Stereochemistry of the E1 Dehydration

22. Milder Dehydration

23. Substitution Reactions of Ethers Activation of ether by protonation

25. Reactions of Epoxides Epoxides

26. Nucleophilic attack of hydroxide ion on ethylene oxide and on diethyl ether

27. Ring Opening

28. When a nucleophile attacks an unprotonated epoxide, the reaction is a pure S N 2 reaction

31. Epoxides Are Synthetically Useful Reagents

34. Crown Ethers

36. A crown ether specifically binds certain metal ions or organic molecules to form a host–guest complex, an example of molecular recognition

37. Thiols are sulfur analogs of alcohols They are stronger acids (pK a = 10) than alcohols, but do not exhibit hydrogen-binding ethanethiol 1-propanethiol 3-methyl-1-butanethiol 2-mercaptoethanol

38. In protic solvent, thiolate ions are better nucleophiles than alkoxide ions CH 3 OH

39. The sulfur analogs of ethers are called sulfides or thioethers Sulfur is an excellent nucleophile because its electron cloud is polarized

40. Organometallic Compounds An organic compound containing a carbon–metal bond

41. Preparation of Organolithium Compounds hexane 1-bromobutane butyllithium chlorobenzene phenyllithium

42. Preparation of Organomagnesium Compounds

43. Alkyl halides, vinyl halides, and aryl halides can all be used to form organolithium and organomagnesium compounds However, these organometallic compounds cannot be prepared from compounds containing acidic groups (OH, NH 2, NHR, SH, C=CH, CO 2 H)

45. Coupling Reactions Formation of carbon–carbon bonds