Chapter 9 Ethers, Thiols, and Sulfides
I.
Naming and Physical Properties of Ethers
A.
Nomenclature
1) Name ethers as alkanes with an alkoxy substitutent
2) RO- = alkoxy substitutent
3) Choose the smallest part of the ether as the substituent
4) Common names: name the two R groups, followed by “ether”
CH3CH2
O
CH2CH3
Ethoxyethane
Diethyl ether
5)
O
CH3CH2
O
CH3
2-Ethoxy-2-methylpropane
t-Butyl ethyl ether
O
CH2CH2CH2CH3
1-Methoxybutane
Butyl methyl ether
Cyclic Ethers
a) O group is called an “oxa-” substituent: oxacycloalkanes
b) Common names are prevalent
1
Oxacyclopropane
Epoxide
O
O
1
1
Oxacyclopentane
Tetrahydrofuran (THF)
O
1
4
Oxacyclohexane
Tetrahydropyran
O
1,4-Dioxacyclohexane
1,4-Dioxane
B.
Physical Properties
1) Same molecular formula as Alcohol: CnH2n+2O
2) No Hydrogen Bonding is possible in R—O—R
3) Boiling Points are much lower than alcohols, more like haloalkanes
4) Water solubility much less than alcohols
a) MeOMe and EtOEt have some water solubility
b) Larger ethers are insoluble, very much like alkanes
5) Fairly unreactive, nonpolar solvents for organic reactions
O
C.
O
Metal Complexation by Crown Ethers
O
O
1) Crown Ether is a cyclic polyether: --(CH2CH2O)— 6-crown-2
2) Named as: (# of total atoms in ring)-Crown-(# of oxygens)
O
O
3) Oxygen lone pair can be donated to M+ to form complexes
12-crown-4
4) Allows dissolution of metal salts in organic solvents
5) Size of cavity dictates which metal fits: 18-crown-6 K+ > Rb+ >Na+ etc…
O
O
O
O
O
K+
+ KMnO4
O
O
O
18-crown-6
O
O
+ MnO4O
O
D.
Cryptands and Ionophores
1) Cryptands are topologically complex polyethers
a) Greek kryptos = hidden
b) Even stronger metal binding than crown ethers
c) Nobel prize for crowns/cryptands 1987 Cram, Pederson, Lehn
2) Ionophore = biological polyethers used to transport metal ions
II.
Williamson Ether Synthesis
A.
Alkoxides are good nucleophiles and strong bases
1) Reaction with primary, unhindered electrophile gives SN2
2) Reaction with non-primary or hindered electrophiles gives E2
RCH2I
O-Na+
OCH2R
Ether
Williamson Ether
Synthesis
Alkene
Br
B.
Cyclic Ethers from Intramolecular Reaction
1) Intermolecular reaction is between 2 separate molecules: A + B
2) Intramolecular reaction is between parts of same molecule: A
-
Br
OH
Br
OH
slower
O
O
-
C
C
+ Br-
HO
OH
3)
Ring size effects rate: k3 > k5 > k6 > k4 > k7 > k8
Oa) Ring strain says k3 slow, Entropy makes k3 fast
Br
b) k4 is slow because ring strain > entropy
O
4)
Intramolecular Williamson Ether Synthesis is Stereospecific
a) Like E2 elimination, the leaving group must be anti to nucleophile
b) Gauche leaving group won’t give product
O-
D
H
O-
O
D
H
H
S
anti
Br
H
H
H
R
H
Br
D
gauche
III. Other Ether Syntheses from Alcohols
A.
ROH plus Strong Mineral Acid
1) Remember that ROH plus HBr gives RBr because nucleophile is present
2) Protonation by mineral acid gives good leaving group (H2O) but does not
give an interfering nucleophile
ROH
HBr
H
R O
Br-
RBr + H2O
H
ROH
H2SO4
H
R O
H
H
ROH
-H2O
R O
R
-H+
R O
R
3)
4)
5)
Only makes symmetric ethers
Follows SN2 for primary alcohols, SN1 for 2o and 3o alcohols
Useful for making mixed 3o/1o ethers
H+
B.
CH3OH
OH2+
OH
OCH3
Ether Synthesis through Solvolysis of Haloalkanes or other Electrophiles
1) Solvolysis = nucleophilic substitution by solvent
2) Alcoholysis = solvolysis when solvent = ROH
3) Simple SN1 conditions can give complex ethers by solvolysis
Br
MeOH
MeOH
OMe
OMe
H
IV. Reactions of Ethers
A.
Peroxide formation
1) Ethers open to oxygen can form expolosive peroxide compounds
2) Never use old ethers as solvents or reactants; store ethers properly
2 R O CH
+ O2
2 R O C O O C O R
peroxide (explosive)
B.
Cleavage by Strong Acid
1) Reverse of Ether Synthesis by Strong Acid
2) Tertiary Ethers are most reactive to cleavage
H
+
H
O
3)
O
Secondary Ethers can be cleaved by SN2 or SN1
H
+
H
O
V.
E1
OH +
OH2
O
OH +
+
-H+
OH
OH2
Reactions of Oxacyclopropanes
A.
Nucleophilic Ring Opening
1) Ether Oxygen behaves as an intramolecular leaving group
2) Anionic Nucleophiles can open the oxacyclopropane ring by SN2 attack
O
O
CH3S
-
H2O
HO
-
SCH3
SCH3
3)
4)
5)
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
O-
SN 2
O
CH3SCH3
6)
B.
CH3
CH3S
OH
H2O
CH3S
CH3
Regioselectivity = reaction at only one of multiple sites of a molecule
Alcohols from Oxacyclopropanes
1) LiAlH4 attacks epoxides, but not any other ethers
O
LiAlH4
+
CH3
CH3
CH3
D
2)
SN 2
inverts
CH3 D
H
OH
CH3
CH3
Alkylmetal reagents also react with epoxides only among the ethers
O
CH3CH2MgBr
+
CH3
D
CH3
CH3
SN 2
inverts
CH3 D
CH3CH2
OH
CH3
CH3
C.
Acid Catalyzed Oxacyclopropane Ring Opening
1) Mechanism
O
H
CH3
CH3
H
O
+
2)
3)
4)
5)
H
H
H
H
CH3
CH3
O
=
H
H
H
HO
CH3
CH3
Nu
H
H
Nu
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
VI. Sulfur Analogues of Alcohols and Ethers
A.
CH3
CH3
Nomenclature
1) R—OH = Alcohol
R—SH = Thiol
a) Name as alkanethiol
CH3SH = methanethiol
b) Name as a mercapto- substituent
HSCH2CH2OH =
2-mercaptoethanol
OH > SH priority
2)
R—O—R = Ether
R—S—R = Sulfide (common name = thioether)
a) Name like common names for ethers
i. CH3SCH2CH3 = ethyl methyl sulfide (methylthioethane)
ii. (CH3)3CSCH3 = t-butyl methyl sulfide
iii. H2S = hydrogen sulfide
iv. RS– substituent is called alkylthio
b) RS- anion is called alkanethiolate anion: CH3CH2S- = ethanethiolate
B.
Properties of Thiols and Sulfides
1) RSH doesn’t Hydrogen bond very well (S is too large to match H)
2) Boiling points are lower than the analogous alcohols
3) RS—H bond is weak, so thiols are more acidic than alcohols
C.
Reactivity of Thiols and Sulfides
1) RS- is more nucleophilic than RO- due to larger size
2) Synthesis of thiols and sulfides
-
-
R'SR + X
HS-
RSH + X-
R'S
RX
3)
Use hydroxide to deprotonate RSH
NaOH
CH3CH2Br
CH3SH
CH3S-
4)
Formation of Sulfonium Ion = R3S+ as a good leaving group
CH3SCH3
5)
CH3CH2Br
-
(CH3)2SCH2CH3
sulfonium ion
KMnO4
oxidation
CH3SCH3 + HOCH2CH3
O
CH3
S
OH
sulfonic acid
O
Oxidation of Sulfides
H2O2
RSR
Sulfide
7)
OH
Valence Shell Expansion due to d orbitals is common for S compounds
CH3SH
6)
CH3SCH2CH3 + Br-
O
RSR
Sulfoxide
Disulfide formation
I2
2 RSH
RS
1. Li, NH3
+
2. H , H2O
H2O2
O
RSR
O
Sulfone
SR Disulfide