Ethers & Epoxides

1. Ethers & Epoxides Uses Galore

2. General Anesthesia • Starter Fluid • Antibiotics • Pheromones • Marijuana • Gasoline additives • Antifreeze • Polyesters Ethers & Epoxides

3. R-O-R’ • Epoxides—cyclic 3-membered ring ethers Ethers & Epoxides

4. Name each alkyl or aryl group in alphabetical order, followed by ether Nomenclature of Ethers

5. More complex structures require the naming of the –OR group as an alkoxy group. Smaller alkoxy is named as substituent Nomenclature of Ethers

6. Colorless • Relatively pleasant odors • Lower bp than ROH with equal C’s • Almost same bp as equivalent HC • Cannot form H-bonds with itself • Can form H-bonds with ROH • Low MW soluble in H2O • Less dense than H2O Physical Properties of Ethers

7. Relatively inert • Makes ethers excellent solvents • Used to extract organic cpds from natural sources • May oxidize over time to peroxides • Test papers detect peroxides • Shaken with FeSO4 reduces peroxides CH3CH2OCH2CH3 + O2CH3CH2OCHCH3 OOH Ethers as Solvents

8. Victor Grignard—1912 Nobel in Chemistry • When Mg turnings (pieces) are stirred with an ether soln of either alkyl or aryl halide, exothermic rxn occurs • Mg bonds to halogen as does carbon R—X + Mg R—MgX dry ether The Grignard Reagent: an organometallic compound

9. Though ethers are not normally shown as part of the Grignard reagent, they do play an important role as Lewis bases and stabilize the Mg with lone pairs R—Mg—X The Grignard Reagent: an organometallic compound

10. 2 most common ethers used in Grignard preparation • diethyl ether • tetrahydrofuran (THF) • Ether must be perfectly dry…no H2O or ROH CH3—I + Mg  CH3MgI ether The Grignard Reagent: an organometallic compound

11. Alkyl or aryl group is usually negatively charged and Mg is positively charged R—MgX • Carbanion is formed • Strong base • Conjugate base of HC(weak acids) • Grignard reagents react vigorously with weak acids like H2O or with any cpd with OH, SH, or NH The Grignard Reagent: an organometallic compound

12. R—MgX + H—OH  R—H + Mg2+(OH)-X- • This is why the ether must be perfectly dry stronger base stronger acid weaker acid weaker base The Grignard Reagent: an organometallic compound

13. Rxn of Grignard with H2O can be useful in making a radiolabeled cpd • If heavy water (deuterium oxide), D2O, is used, then D can be substituted for X The Grignard Reagent: an organometallic compound

14. Prepare CH3CHDCH3 from CH2=CHCH3 The Grignard Reagent: an organometallic compound

15. Organometallic cpds contain a C-metal bond • Acetylides (R-C=C-) act similarly to Grignard reagents • Organolithiumcpds are also useful in synthesis rxns R—X + 2 Li  R—Li + Li+X- The Grignard Reagent: an organometallic compound

16. Most important ether is diethyl ether • Made from ethanol and sulfuric acid at 140˚C • If at 180˚C, ethene is made • Conditions are important Preparation of Ethers

17. The preparation of ethene occurs by E2 • By what mechanism does the preparation of diethyl ether occur? Preparation of Ethers

18. t-butyl methyl ether (MTBE) • Octane # enhancer • Use has declined due to health concerns Preparation of Ethers

19. Write the mechanism of the preparation of MTBE. Preparation of Ethers

20. Williamson Synthesis • 1st step—ROH is converted to alkoxide by treatment with reactive metal like Na or K or metal hydride • 2nd step—SN2 displacement btw alkoxide and alkyl halide 2ROH + 2Na  2RO-Na+ + H2 RO-Na+ + R’—X  ROR’ + Na+X- Preparation of Ethers

21. Williamson Synthesis • Write an equation for the synthesis of CH3OCH2CH2CH3 using Williamson method Preparation of Ethers

22. With lone pair on O, ethers are Lewis bases • React with strong acids, Lewis acids, and boron halides H R—O—R’ + H+ R—O—R’ R—O—R’ + Br—B—Br R—O—R’ Br Br—B—Br Br Cleavage of Ethers

23. Similar to rxn of ROH and strong acids • If R and R’ are 1˚or 2˚, bond to O can be broken by strong nucleophile like I- or Br- via SN2 Cleavage of Ethers

24. If R or R’ is 3˚, a strong nucleophile is not required since rxn will occur by SN1 (or E1) mechanism Cleavage of Ethers

25. Write the steps of the mechanism for the first rxn on slide 29: Cleavage of Ethers

26. Prior to 1846, asphyxiation, pressure on nerves, narcotics, ROH • William T.G. Morton in 1846 removed tumor from jaw using diethyl ether as general anesthetic • Ceased being used due to flammability, side effects, slow action Ether & Anesthetics

27. Also known as oxiranes • 3-membered rings containing 1 oxygen atom • Most important is ethylene oxide • Used as raw material for production of ethylene glycol Epoxides

28. Defoliate hardwood trees in NE • Pheromone disparlure • Synthesized to lure male moths to traps • Alternative to pesticide Gypsy Moth’s Epoxide

29. Much more reactive than ordinary ethers due to the strain on the 3-membered ring • Products will show that ring opens • ~8.2 billion lbs of (CH2)2(OH)2 are produced annually in this manner Reactions of Epoxides

30. Show mechanism of previous rxn: Reactions of Epoxides

31. Other nucelophiles add in a similar way Reactions of Epoxides

32. Most common other than epoxides are 5- and 6-membered rings tetrahydrofurantetrahydropyran 1,4-dioxane Cyclic Ethers

33. THF • Useful solvent • Miscible in H2O • Often superior to diethyl ether for preparation of Grignard reagents Cyclic Ethers

34. Macrocyclicpolyethers • Crowns • Form complexes with Na+, K+etc • Antibiotics are often crown cpds [18]crown-6 Cyclic Ethers

35. Nonactin • Selectively binds to K+ in presence of Na+ • Allows for transport of K+ but not Na+ Cyclic Ethers