1. Ethers and Epoxides

2. Ethers and Their Relatives
An ether has 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. Ethers are named two ways:
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. Epoxides (oxiranes) “epoxy” always preceeds the name of the alkane
Naming Ethers
Epoxides (oxiranes)
“epoxy” always preceeds the name of the alkane

7. Example 1: Name

8. Isopropyl methyl ether 4-t-butoxy-1-cyclohexene Phenyl propyl ether
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. Acid catalyzed synthesis of ethers:
Preparation of Ethers
Acid catalyzed synthesis of ethers:
Limited to symmetrical ethers. WHY?

12. Mechanism 1: Acid catalyzed synthesis of ethers

13. Williamson ether synthesis
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. Anisole (methyl phenyl ether)
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. 1,2-ethanediol from acid catalyzed hydration of ethylene
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 (RSH), are sulfur analogs of alcohols
Named with the suffix -thiol
SH group is called “mercapto group”

46. Example 8: Name

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

48. 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

51. Thiolates (RS) are formed by the reaction of a thiol with a base
Sulfides
Thiolates (RS) are formed by the reaction of a thiol with a base
Thiolates react with primary or secondary alkyl halide to give sulfides (RSR’)
Thiolates are excellent nucleophiles and react with many electrophiles