Chapter 9 Ethers, Thiols, and Sulfides

I. Naming and Physical Properties of EthersA. 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”

5) Cyclic Ethers

a) O group is called and “oxa-” substituent: oxacycloalkanes

b) Common names are prevalent

CH3CH2O

CH2CH3

EthoxyethaneDiethyl ether

CH3CH2O

2-Ethoxy-2-methylpropanet-Butyl ethyl ether

CH3O

CH2CH2CH2CH3

1-MethoxybutaneButyl methyl ether

O

OxacyclopropaneEpoxide

O

OxacyclopentaneTetrahydrofuran (THF)

O

OxacyclohexaneTetrahydropyran

O

O

1,4-Dioxacyclohexane1,4-Dioxane

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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

C. Metal Complexation by Crown Ethers

1) Crown Ether is a cyclic polyether: --(CH2CH2O)—

2) Named as: (# of total atoms in ring)-Crown-(# of oxygens)

3) Oxygen lone pair can be donated to M+ to form complexes

4) Allows dissolution of metal salts in organic solvents

5) Size of cavity dictates which metal fits: 18-crown-6 K+ > Rb+ >Na+ etc…

OO

6-crown-2

OO

O O

12-crown-4

O

O

O

OO

O

18-crown-6

+ KMnO4

O

O

O

OO

O

K++ MnO4

-

II. Williamson Ether SynthesisA. 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

B. Cyclic Ethers from Intramolecular Reaction

1) Intermolecular reaction is between 2 separate molecules: A + B C

2) Intramolecular reaction is between parts of same molecule: A C

3) Ring size effects rate: k3 > k5 > k6 > k4 > k7 > k8

a) Ring strain says k3 slow, Entropy makes k3 fast

b) k4 is slow because ring strain > entropy

O-Na+ RCH2IOCH2R Ether

BrAlkene

Williamson EtherSynthesis

O-Br

OHBr OH- O

+ Br-

slowerOH

HO

Br

O-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

III. Other Ether Syntheses from AlcoholsA. 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

O-

BrH

HD

H

O

D

HS R

O-

DH

BrH

H

antigauche

RBr + H2OBr-

R OH

H

HBrROH

R OH

H

H2SO4ROHROH R O

H

RR O R

-H2O

-H+

3) Only makes symmetric ethers

4) Follows SN2 for primary alcohols, SN1 for 2o and 3o alcohols

5) Useful for making mixed 3o/1o ethers

B. 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

IV. Reactions of EthersA. Peroxide formation

1) Ethers open to oxygen can form expolosive peroxide compounds

2) Never use old ethers as solvents or reactants; store ethers properly

OHH+

OH2+ CH3OH

OCH3

BrMeOH MeOH

OMe

H

OMe

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

3) Secondary Ethers can be cleaved by SN2 or SN1

V. Reactions of OxacyclopropanesA. Nucleophilic Ring Opening

1) Ether Oxygen behaves as an intramolecular leaving group

2) Anionic Nucleophiles can open the oxacyclopropane ring by SN2 attack

OH+

O

HOH + E1

OH+

O

HOH + OH2

+ OHOH2-H+

O

CH3S-

H2O O-

SCH3

HO

SCH3

3) Alkoxide usually a poor leaving group (but it doesn’t really leave here)

4) Driving force is opening of the strained 3-membered ring

5) For unsymmetric oxacyclopropanes, the Nu attacks at the least subst. C

6) Regioselectivity = reaction at only one of multiple sites of a molecule

B. Alcohols from Oxacyclopropanes

1) LiAlH4 attacks epoxides, but not any other ethers

2) Alkylmetal reagents also react with epoxides only among the ethers

O

CH3

CH3S-

H2O SN2

CH3CH3S

O-

CH3CH3S

OH

O

D

CH3

CH3

CH3LiAlH4 +

OH

H

CH3D

CH3CH3

SN2

inverts

inverts

SN2 OH

CH3CH2

CH3D

CH3CH3

O

D

CH3

CH3

CH3CH3CH2MgBr +

C. Acid Catalyzed Oxacyclopropane Ring Opening

1) Mechanism

2) Regioselective and Stereospecific for Nu- attack at the Most Hindered C

3) Partial C+ forms only on most hindered carbon

4) Not a full carbocation, because we see stereospecific inversion

(SN2, not SN1)

5) Now we have tools to add Nu at most (H+, Nu) or least (Nu-) carbon of an epoxide

VI. Sulfur Analogues of Alcohols and EthersA. Nomenclature

1) R—OH = Alcohol R—SH = Thiol

a) Name as alkanethiol CH3SH = methanethiol

b) Name as a mercapto- substituent HSCH2CH2OH =

2-mercaptoethanol

O

H

H

CH3

CH3

O

H

H

CH3

CH3

H

H+

H

HCH3

CH3HO

NuNu

O

H

H

CH3

CH3

H

=

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 alkythio

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

RXR'S-

HS-

R'SR + X-

RSH + X-

3) Use hydroxide to deprotonate RSH

4) Formation of Sulfonium Ion = R3S+ as a good leaving group

5) Valence Shell Expansion due to d orbitals is common for S compounds

6) Oxidation of Sulfides

7) Disulfide formation

CH3SHNaOH

CH3S- CH3CH2BrCH3SCH2CH3 + Br-

CH3SCH3CH3CH2Br

(CH3)2SCH2CH3 sulfonium ion

OH-

CH3SCH3 + HOCH2CH3

CH3SHKMnO4

CH3 S OH

O

Ooxidation

2 RSHI2 RS SR Disulfide

1. Li, NH3

2. H+, H2O

RSR RSR

O

RSR

O

O

H2O2 H2O2

Sulfide SulfoxideSulfone