CH 18: Ethers and Epoxides

1. CH 18: Ethers and Epoxides Renee Y. Becker Valencia Community College CHM 2211

2. Ethers and Their Relatives • An etherhas two organic groups (alkyl, aryl, or vinyl) bonded to the same oxygen atom, R–O–R • Diethyl ether is used industrially as a solvent • Tetrahydrofuran (THF) is a solvent that is a cyclic ether • Epoxides contain a C-O-C unit which make-up a three membered ring • Thiols (R–S–H) and sulfides (R–S–R) are sulfur (for oxygen) analogs of alcohols and ethers

4. Naming Ethers • Ethers are named two ways: • As alkoxy derivatives of alkanes • Derived by listing the two alkyl groups in the general structure of ROR’ in alphabetical order as separate words and adding the word ether • When both alkyl groups are the same, the prefix di- precedes the name of the alkyl group • (Ethers can be described as symmetrical or unsymmetrical)

5. Naming Ethers

6. Naming Ethers • Epoxides (oxiranes) • “epoxy” always preceeds the name of the alkane

7. Example 1: Name

8. Example 2: Draw • Isopropyl methyl ether • 4-t-butoxy-1-cyclohexene • Phenyl propyl ether • O- nitro anisole

9. Structure, Properties, and Sources of Ethers • R–O–R ~ tetrahedral bond angle (112° in dimethyl ether) • Oxygen is sp3-hybridized • Oxygen atom gives ethers a slight dipole moment (diethyl ether 1.2 D)

10. Structure, Properties, and Sources of Ethers (comparative boiling points)

11. Preparation of Ethers • Acid catalyzed synthesis of ethers: Limited to symmetrical ethers. WHY?

12. Mechanism 1: Acid catalyzed synthesis of ethers

13. Preparation of Ethers • Williamson ether synthesis • Metal alkoxides react with primary alkyl halides by an SN2 pathway to yield ethers. • Secondary and tertiary substrates react following an E2 mechanism

14. Mechanism 2: Williamson Ether Synthesis

15. Example 3: Williamson ether synthesis

16. Example 4 How would you prepare the following compounds using a Williamson synthesis? • Methyl propyl ether • Anisole (methyl phenyl ether)

17. Example 5: Predict the product:

18. Alkoxymercuration of Alkenes • React alkene with an alcohol and mercuric acetate or trifluoroacetate • Demercuration with NaBH4 yields an ether • Overall Markovnikov addition of alcohol to alkene

21. Reactions of Ethers: Acidic Cleavage • Ethers are generally unreactive • Strong acid will cleave an ether at elevated temperature • HI, HBr produce an alkyl halide from less hindered component by SN2 (tertiary ethers undergo SN1)

23. Mechanism 3: Acidic Cleavage Note that the halide attacks the protonated ether at the less highly substituted site.

24. Example 6

25. Reactions of Ethers: Claisen Rearrangement • Specific to allyl aryl ethers, ArOCH2CH=CH2 • Heating to 200–250°C leads to an o-allylphenol • Result is alkylation of the phenol in an ortho position

26. Mechanism 4: Claisen Rearrangement • Concerted pericyclic 6-electron, 6-membered ring transition state • Mechanism consistent with 14C labeling

27. Example 7

28. Cyclic Ethers: Epoxides • Cyclic ethers behave like acyclic ethers, except if ring is 3-membered • Dioxane and tetrahydrofuran are used as solvents

29. Epoxides (Oxiranes) • Three membered ring ether is called an oxirane (root “ir” from “tri” for 3-membered; prefix “ox” for oxygen; “ane” for saturated) • Also called epoxides • Ethylene oxide (oxirane; 1,2-epoxyethane) is industrially important as an intermediate • Prepared by reaction of ethylene with oxygen at 300 °C and silver oxide catalyst

31. Preparation of Epoxides Using a Peroxyacid • Treat an alkene with a peroxyacid

32. Mechanism 5: Preparation of Epoxides Using a Peroxyacid

33. Epoxides from Halohydrins • Addition of HO-X to an alkene gives a halohydrin • Treatment of a halohydrin with base gives an epoxide • Intramolecular Williamson ether synthesis

35. Ring-Opening Reactions of Epoxides • Water adds to epoxides with dilute acid at room temperature • Product is a 1,2-diol (on adjacent C’s: vicinal) • Mechanism: acid protonates oxygen and water adds to opposite side (anti-addition)

36. Mechanism 6: Acid catalyzed ring-openings

37. Ethylene Glycol • 1,2-ethanediol from acid catalyzed hydration of ethylene • Widely used as automobile antifreeze (lowers freezing point of water solutions)

38. Halohydrins from Epoxides • Anhydrous HF, HBr, HCl, or HI combines with an epoxide • Gives trans product

41. Base-Catalyzed Epoxide Opening • Strain of the three-membered ring is relieved on ring-opening • Hydroxide cleaves epoxides at elevated temperatures to give trans 1,2-diols • Complete the reaction

42. Mechanism 7: Base-Catalyzed Epoxide Opening

43. Mechanism 7: Base-Catalyzed Epoxide Opening

44. Addition of Grignards to Ethylene Oxide • Adds –CH2CH2OH to the Grignard reagent’s hydrocarbon chain • Acyclic and other larger ring ethers do not react

45. Thiols • Thiols (RSH), are sulfur analogs of alcohols • Named with the suffix -thiol • SH group is called “mercapto group”

46. Example 8: Name

47. Example 9: Draw • Cyclopentanethiol • 3-methyl-4-heptanethiol • 4-ethyl-4-isopropyl-2-methyl-3-hexanethiol

48. Sulfides • Sulfides (RSR), are sulfur analogs of ethers • Named by rules used for ethers, with sulfide in place of ether for simple compounds and alkylthio in place of alkoxy

49. Example 10: Name or Draw

50. Thiols: Formation and Reaction • From alkyl halides by displacement with a sulfur nucleophile such as SH • The alkylthiol product can undergo further reaction with the alkyl halide to give a symmetrical sulfide, giving a poorer yield of the thiol