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

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 2

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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) 4

5. Naming Ethers 5

6. Epoxides (oxiranes) –“epoxy” always preceeds the name of the alkane 6

7. Example 1: Name 7

8. Example 2: Draw 1.Isopropyl methyl ether 2.4-t-butoxy-1-cyclohexene 3.Phenyl propyl ether 4.O- nitro anisole 8

9. Structure, Properties, and Sources of Ethers R–O–R ~ tetrahedral bond angle (112° in dimethyl ether) Oxygen is sp 3 -hybridized Oxygen atom gives ethers a slight dipole moment (diethyl ether 1.2 D) 9

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

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

12. Mechanism 1: Acid catalyzed synthesis of ethers 12

13. Preparation of Ethers Williamson ether synthesis Metal alkoxides react with primary alkyl halides by an S N 2 pathway to yield ethers. Secondary and tertiary substrates react following an E2 mechanism 13

14. Mechanism 2: Williamson Ether Synthesis 14

15. Example 3: Williamson ether synthesis 15

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

17. Example 5: Predict the product: 17

18. Alkoxymercuration of Alkenes React alkene with an alcohol and mercuric acetate or trifluoroacetate Demercuration with NaBH 4 yields an ether Overall Markovnikov addition of alcohol to alkene 18

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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 S N 2 (tertiary ethers undergo S N 1) 21

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

24. Example 6 24

25. Reactions of Ethers: Claisen Rearrangement Specific to allyl aryl ethers, ArOCH 2 CH=CH 2 Heating to 200–250°C leads to an o-allylphenol Result is alkylation of the phenol in an ortho position 25

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

27. Example 7 27

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

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 29

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

32. Mechanism 5: Preparation of Epoxides Using a Peroxyacid 32

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 33

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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) 35

36. Mechanism 6: Acid catalyzed ring-openings 36

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

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

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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 41

42. Mechanism 7: Base-Catalyzed Epoxide Opening 42

43. Mechanism 7: Base-Catalyzed Epoxide Opening 43

44. Addition of Grignards to Ethylene Oxide Adds –CH 2 CH 2 OH to the Grignard reagent’s hydrocarbon chain Acyclic and other larger ring ethers do not react 44

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

46. Example 8: Name 46

47. Example 9: Draw 1.Cyclopentanethiol 2.3-methyl-4-heptanethiol 3.4-ethyl-4-isopropyl-2-methyl-3-hexanethiol 47

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 48

49. Example 10: Name or Draw 49

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 50

51. 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 51