1. Ethers & Epoxides
Uses Galore

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

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

6. Physical Properties of Ethers
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. Ethers as Solvents 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. The Grignard Reagent: an organometallic compound
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. The Grignard Reagent: an organometallic compound
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. The Grignard Reagent: an organometallic compound
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. The Grignard Reagent: an organometallic compound
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. The Grignard Reagent: an organometallic compound
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. The Grignard Reagent: an organometallic compound
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. The Grignard Reagent: an organometallic compound
Prepare CH3CHDCH3 from CH2=CHCH3
The Grignard Reagent: an organometallic compound

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

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

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

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

28. Gypsy Moth’s Epoxide 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
tetrahydrofuran tetrahydropyran 1,4-dioxane
Cyclic Ethers

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

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

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