1. Goals for the day: Grignard Reaction Ethers (Naming and reactions)
Epoxides (naming and reactions)
Thiols & sufides (reactions)

2. 17.5 Alcohols from Carbonyl Compounds: Grignard Reagents
Alkyl, aryl, and vinylic halides react with magnesium in ether or tetrahydrofuran to generate Grignard reagents, RMgX
Grignard reagents react with carbonyl compounds to yield alcohols

3. Mechanism of the Addition of a Grignard Reagent
Grignard reagents act as nucleophilic carbon anions (carbanions = : R) in adding to a carbonyl group
The intermediate alkoxide is then protonated to produce the alcohol

4. Try to predict the products…

5. Possible depictions are…

6. Try to fill in the mechanism…

7. Reactions of Grignard Reagents with Carbonyl Compounds

8. Reactions of Esters and Grignard Reagents
Yields tertiary alcohols in which two of the carbon substituents come from the Grignard reagent
Grignard reagents do not add to carboxylic acids – they undergo an acid-base reaction, generating the hydrocarbon of the Grignard reagent

9. Grignard Reagents and Other Functional Groups in the Same Molecule
Cannot be prepared if there are reactive functional groups in the same molecule, including proton donors

10. Predict the product…

11. Remember it goes all the way to the alcohol & two CH3 groups are added…

12. Naming Ethers
Ethers contain the R-O-R bond. Basically, you name the two groups
attached to the oxygen (alphabetically) and add the term ether.
The smallest ether is dimethyl ether

13. Ethers as attachments
Methoxy
Ethoxy
isopropoxy

14. Pick one to try to name & panel submit

15. Pick one to try to name & panel submit
Secbutyl vinyl ether Or
1-secbutoxy ethene
Isopropyl pheny ether Or
Isopropoxy benzene

16. Properties of Ethers R–O–R ~ tetrahedral bond angle
Oxygen is sp3-hybridized
Oxygen atom gives ethers a slight dipole moment
Not very reactive, so they make good solvents (diethyl ether is the “ether” we use in lab all the time). 
Not water soluble (although diethyl ether is slightly…see diagram on the following page)…

17. This is why you have to “dry” the organic layer in your reactions!

18. 18.2 Synthesis of Ethers
Diethyl ether prepared industrially by sulfuric acid–catalyzed dehydration of ethanol – also with other primary alcohols

19. 18.2 Synthesis of Ethers
Works really only if the ether that you want is symmetric….otherwise you can get mixed results..

20. Need for an unsymmetric ether synthesis
Problem is.....propanol reacts with itself and ethanol reacts with itself…

21. Mechanism of ether formation from alcohols…

22. The Williamson Ether Synthesis
Reaction of metal alkoxides and primary alkyl halides and tosylates
Best method for the preparation of unsymmetric ethers
Alkoxides prepared by reaction of an alcohol with a strong base such as sodium hydride, NaH

23. Predict the product...

24. The carbons of the alkyl halide become the “second” group of the ether...

25. An SN2 process…
Note that the second step of the reaction is an SN2 process, so
works best for primary alkyl halides (or methyl bromide)

26. Which is better? (you get phenyl propyl ether either way)…

27. Path “a” is better because the alkyl halide is primary and will react faster in the SN2 reaction

28. Cyclic Ethers
Cyclic ethers behave like acyclic ethers, except if ring is 3-membered
Two common structures are ethylene oxide and THF

29. Epoxides (Oxiranes)
Also called epoxides

30. Preparation of Epoxides Using a Peroxyacid
Treat an alkene with a peroxyacid
Abbreviation for this reagent is MCPBA…

31. What’s the product?

32. Answer…

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

34. 18.6 Reactions of Epoxides: Ring-Opening
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 (trans addition)

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

36. Regiochemistry of Acid-Catalyzed Opening of Epoxides
1) Nucleophile preferably adds to less hindered site if primary and secondary C’s
2) Nucleophile adds to a tertiary carbon because of carbocation character 1) 2)

37. Steps of Acid-Catalyzed Opening of Epoxides
Protonation
Attack of the nucleophile from the backside
Note: check for degree of substitution

38. 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

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

40. 18.7 Crown Ethers
Large rings consisting of repeating (-OCH2CH2-) or similar units
Named as x-crown-y
x is the total number of atoms in the ring
y is the number of oxygen atoms
18-crown-6 ether: 18-membered ring containing 6 oxygen atoms
Central cavity is electronegative and attracts cations

41. 18.8 Thiols and Sulfides
Thiols (RSH), are sulfur analogues of alcohols
Named with the suffix -thiol
SH group is called “mercapto group” (“capturer of mercury”)

42. 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

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

44. Oxidation of Thiols to Disulfides
Reaction of an alkyl thiol (RSH) with bromine or iodine gives a disulfide (RSSR)
The thiol is oxidized in the process and the halogen is reduced
Cysteine amino acid forms cystine bonds

45. 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

46. Have a wonderful day! 

47. 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
Thiols (R–S–H) and sulfides (R–S–R) are sulfur (for oxygen) analogues of alcohols and ethers