1. Chapter 9 Ethers, Thiols, and Sulfides
Naming and Physical Properties of Ethers
Nomenclature
Name ethers as alkanes with an alkoxy substitutent
RO- = alkoxy substitutent
Choose the smallest part of the ether as the substituent
Common names: name the two R groups, followed by “ether”
Cyclic Ethers
O group is called an “oxa-” substituent: oxacycloalkanes
Common names are prevalent

2. Physical Properties
Same molecular formula as Alcohol: CnH2n+2O
No Hydrogen Bonding is possible in R—O—R
Boiling Points are much lower than alcohols, more like haloalkanes
Water solubility much less than alcohols
MeOMe and EtOEt have some water solubility
Larger ethers are insoluble, very much like alkanes
Fairly unreactive, nonpolar solvents for organic reactions
Metal Complexation by Crown Ethers
Crown Ether is a cyclic polyether: --(CH2CH2O)—
Named as: (# of total atoms in ring)-Crown-(# of oxygens)
Oxygen lone pair can be donated to M+ to form complexes
Allows dissolution of metal salts in organic solvents
Size of cavity dictates which metal fits: 18-crown-6 K+ > Rb+ >Na+ etc…

3. Cryptands and Ionophores
Cryptands are topologically complex polyethers
Greek kryptos = hidden
Even stronger metal binding than crown ethers
Nobel prize for crowns/cryptands 1987 Cram, Pederson, Lehn
Ionophore = biological polyethers used to transport metal ions

4. Williamson Ether Synthesis
Alkoxides are good nucleophiles and strong bases
Reaction with primary, unhindered electrophile gives SN2
Reaction with non-primary or hindered electrophiles gives E2
Cyclic Ethers from Intramolecular Reaction
Intermolecular reaction is between 2 separate molecules: A + B C
Intramolecular reaction is between parts of same molecule: A C
Ring size effects rate: k3 > k5 > k6 > k4 > k7 > k8
Ring strain says k3 slow, Entropy makes k3 fast
k4 is slow because ring strain > entropy

5. Other Ether Syntheses from Alcohols
Intramolecular Williamson Ether Synthesis is Stereospecific
Like E2 elimination, the leaving group must be anti to nucleophile
Gauche leaving group won’t give product
Other Ether Syntheses from Alcohols
ROH plus Strong Mineral Acid
Remember that ROH plus HBr gives RBr because nucleophile is present
Protonation by mineral acid gives good leaving group (H2O) but does not give an interfering nucleophile

6. Reactions of Ethers Only makes symmetric ethers
Follows SN2 for primary alcohols, SN1 for 2o and 3o alcohols
Useful for making mixed 3o/1o ethers
Ether Synthesis through Solvolysis of Haloalkanes or other Electrophiles
Solvolysis = nucleophilic substitution by solvent
Alcoholysis = solvolysis when solvent = ROH
Simple SN1 conditions can give complex ethers by solvolysis
Reactions of Ethers
Peroxide formation
Ethers open to oxygen can form expolosive peroxide compounds
Never use old ethers as solvents or reactants; store ethers properly

7. Reactions of Oxacyclopropanes
Cleavage by Strong Acid
Reverse of Ether Synthesis by Strong Acid
Tertiary Ethers are most reactive to cleavage
Secondary Ethers can be cleaved by SN2 or SN1
Reactions of Oxacyclopropanes
Nucleophilic Ring Opening
Ether Oxygen behaves as an intramolecular leaving group
Anionic Nucleophiles can open the oxacyclopropane ring by SN2 attack

8. Alkoxide usually a poor leaving group (but it doesn’t really leave here)
Driving force is opening of the strained 3-membered ring
For unsymmetric oxacyclopropanes, the Nu attacks at the least subst. C
Regioselectivity = reaction at only one of multiple sites of a molecule
B. Alcohols from Oxacyclopropanes
LiAlH4 attacks epoxides, but not any other ethers
Alkylmetal reagents also react with epoxides only among the ethers

9. Sulfur Analogues of Alcohols and Ethers
Acid Catalyzed Oxacyclopropane Ring Opening
Mechanism
Regioselective and Stereospecific for Nu- attack at the Most Hindered C
Partial C+ forms only on most hindered carbon
Not a full carbocation, because we see stereospecific inversion
(SN2, not SN1)
Now we have tools to add Nu at most (H+, Nu) or least (Nu-) carbon of an epoxide
Sulfur Analogues of Alcohols and Ethers
Nomenclature
R—OH = Alcohol R—SH = Thiol
Name as alkanethiol CH3SH = methanethiol
Name as a mercapto- substituent HSCH2CH2OH =
2-mercaptoethanol
OH > SH priority

10. R—O—R = Ether R—S—R = Sulfide (common name = thioether)
Name like common names for ethers
CH3SCH2CH3 = ethyl methyl sulfide (methylthioethane)
(CH3)3CSCH3 = t-butyl methyl sulfide
H2S = hydrogen sulfide
RS– substituent is called alkylthio
RS- anion is called alkanethiolate anion: CH3CH2S- = ethanethiolate
Properties of Thiols and Sulfides
RSH doesn’t Hydrogen bond very well (S is too large to match H)
Boiling points are lower than the analogous alcohols
RS—H bond is weak, so thiols are more acidic than alcohols
Reactivity of Thiols and Sulfides
RS- is more nucleophilic than RO- due to larger size
Synthesis of thiols and sulfides
hydrosulfide

11. Use hydroxide to deprotonate RSH
Formation of Sulfonium Ion = R3S+ as a good leaving group
Valence Shell Expansion due to d orbitals is common for S compounds
Oxidation of Sulfides
Disulfide formation
sulfonic acid