Chapter 9 Ethers, Thiols, and Sulfides

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. 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. 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. 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. 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