1. Sulfur-Containing Compounds
Organic Chemistry
4th Edition
Paula Yurkanis Bruice
Chapter 12
Reactions of Alcohols,
Ethers, Epoxides, and
Sulfur-Containing Compounds
Organometallic
Compounds
Irene Lee
Case Western Reserve University
Cleveland, OH
©2004, Prentice Hall

2. Alcohols and ethers have to be activated before they can undergo a substitution or an elimination reaction
Convert the strongly basic leaving group (OH–) into a
good leaving group
Only weakly basic nucleophiles can be used

4. Secondary and tertiary alcohols undergo SN1 reactions
with hydrogen halides

5. Primary alcohols undergo SN2 reactions with hydrogen
halides

6. ZnCl can be used to catalyze certain SN2 reactions

7. Look out for rearrangement product in the SN1 reaction
of the secondary or tertiary alcohol

8. Amines do not undergo substitution reactions because
NH2– is a very strong base (a very poor leaving group)
RCH2F > RCH2OH > RCH2NH2
HF H2O NH3
pKa = 3.2
pKa = 15.7
pKa = 36
Protonation of the amine moiety does not solve the
problem

9. Other Methods for Converting Alcohols
into Alkyl Halides

10. Activation by SOCl2

11. Converting Alcohols into Sulfonates

12. Several sulfonyl chlorides are available to activate OH
groups

13. SN2 of the 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. Look out for carbocation rearrangement

19. Ring Expansion

20. Primary Alcohols Undergo Dehydration by an E2 Pathway

21. The Stereochemical Outcome of the E1 Dehydration

22. A Milder Way to Dehydrate an Alcohol

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 SN2 reaction

31. Epoxides Are Synthetically Useful Reagents

34. Crown Ethers

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

36. Thiols are sulfur analogs of alcohols
ethanethiol
1-propanethiol
3-methyl-1-butanethiol
2-mercaptoethanol
are stronger acids (pKa = 10) than alcohols
are not good at hydrogen-binding

37. In protic solvent, thiolate ions are better nucleophiles
than alkoxide ions
CH3OH

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

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

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

41. Preparation of Organomagnesium Compounds

42. 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, NH2, NHR, SH, C=CH, CO2H)

44. A Grignard reagent will undergo transmetallation if it is added to a metal halide whose metal is more electropositive than magnesium

45. Coupling Reactions
Formation of carbon–carbon bonds

48. The Heck Reaction
Pd(PPh3)4
(CH3CH2)3N
Pd(PPh3)4
(CH3CH2)3N

49. The Stille Reaction
Pd(Ph3)4
THF
Pd(Ph3)4
THF

50. The Suzuki Coupling
Pd(PPh3)4
NaOH
Pd(PPh3)4
NaOH