18 - Ethers, Epoxides, Thiols, Sulfides

What is the structure of an ether?

2 organic groups (alkyl, aryl, vinyl) bonded to same O (R-O-R)

What are analogs of alcohols & ethers?

thiols (R-S-H) & sulfides (R-S-R)

How are ethers named?

ID 2 organic substituents & add ether, if other functional groups present, ether is an alkoxy substituent

ex → isopropyl methyl ether

ex → cyclopentyl propyl ether

Properties of Ether

• derivatives of H2O

• R-O-R tetrahedral bond angle (112 for dimethyl ether)

• O is sp3, gives slight dipole

• higher BP than alkanes

• make peroxides R-O-O-R

How are simple ethers prepared?

sulfuric acid-catalyzed dehydration, only SYMMETRICAL ethers & 1o alcohols, sn2

What are the 2 ways ethers are synthesized?

• Williamson Ether

• Alkoxymercuration/Demercuration of Alkenes

What is the best method for preparing ethers?

williamson ether synthesis, involving nucleophilic substitution of alkoxides with primary alkyl halides.

Williamson Ether Synthesis

• alkoxides made by reacting alcohol w/ strong base (NaH)

• metal alkoxide + primary alkyl halide + tosylate → SN2 = ether

• make un/symmetrical ethers

Why must alkyl halide or tosylate be 1o in Williamson Ether synthesis?

for a 1o/tosylate, need a large bulky base to cause E2, so no competition, but in 2/3o base can cause E2 to compete w/ SN2, want alcohol more hindered & alkyl halide less hindered to avoid E2 side rxns

What reagent in the williamson ether reaction can form ether in 1 step?

Ag2O, reacting it with alcohols

Alkoxymercuration/Demercuration of Alkenes

• react alkenes w/ alcohol, mercuric acetate, trifluoroacetate

• demercuration w/ NaBH4 = ether

• Markovnikov of alcohol to alkene

• alcohol can 1, 2,3 , no di/triethers = too much steric hindrance

Acidic Cleavage

• ethers are unreactive, strong acid cleaves at high temp (HI or sometimes HBr)

• makes alkyl halide by attacking less hindered, sn1/2

Cyclic Ether Behavior

cyclic ethers behave like acylic ethers, except if ring is 3 membered due to ring strain

Epoxides

• also oxiranes, 3 membered ring ether

• CH2-O-CH2, triangle

Preparation of Epoxides

• treat an alkane w/ a peroxyacid

• m-chloroperoxybenzoic acid (MCPBA)

• 1 step concerted rxn, syn

Preparation of Epoxides from Halohydrins

• add HO-X to alkene = halohydrin

• treat halohydirde w/ base = epoxide

• intramolecular williamson ether synthesis

• Cl/H = intermediate step

Ring Opening

• cyclic ethers can be cleaved in presence of acid just like acyclic

• easy w/ ring strain → wants to open

• solvents = water, alcohol, HX

Water - Acid Catalyst

• product is a 1,2-diol

• acid protonates O & water adds w/ SN2 w/ backside/trans addition

Alcohol - Acid Catalyst

product is an alkoxy alcohol w/ anti-stereochemistry

HX - Acid Catalyst

• HF, HCl, HBr, HI

• prouct is alkoxy alcohol w/ anti-stereochemistry

What does an epoxide’s structure impact?

• regiochemistry, both C are ½ = nucleophile adds to less hindered (SN2)

• tertiary = attack there due to carbocation character (SN1)

• balancing between ring strain & wanting to open & E to put (+) charge on 1 of C

• Br attacks 3 C has greater carbocation & SN1 character

What makes epoxides unique?

can be cleaved by bases, strain of 3 membered ring is relieve on ring opening, hydroxide cleaves epoxides at elevated temps = trans 1,2 diols, SN2 so attacks less hindered site

How are Grignard Reagents used with epoxides?

• Addition of Grignard reagents can be used to open epoxides

• if ethylene oxide adds CH2CH2OH to grignard reagent’s HC chain

• best if 1 C is unsubstituted

• acyclic & large ring ethers don’t react

Crown Ethers

• large rings with repeating OCH2CH2

• x-crown-y (X= total # of atoms, Y= # of O atoms)

• used as catalyst to help solvate metal cations due to EN- cavity, cations attracted

Thiols & Sulfides

• thiols (RSH), S analogs of alcohols, mercaptans

• SH = mercapto group

Formation & Reaction of Thiols

• from alkyl halids by displacement w/ a S nucleophile (-SH)

• poor reaction unless nucleophile excess, can undergo further reaction w/ another alkyl halide

(O) of Thiols to Disulfides

• alkyl thiol (RSH) reaction w/ Br/I gives disulfide RSSR

• thiol oxidized in process & H is reduced

Sulfides

RSR, S analogs of ethers, sulfide in place of ether & alkylthio in place of alkoxy

Thiolates

(RS), formed by reaction of a thiol w/ base, react w/ ½ alkyl halides to give sulfides (RSR)

excellent nucleophiles & react w/ many electrophiles

Sulfides as Nucleophiles

• S more nucleophilic than O compound analog

Oxidation of Sulfides

• sulfides are easily oxidized w/ H2O2 to sulfoxide (RS2O)

• oxidation of sulfoxide w/ peroxyacid = sulfone (R2SO2)

• DMSO = polar aprotic solvent

Spectroscopy of Ethers

• IR = C-O stretching 1050-1150 overlaps other absorptions

• Proton NMR = H on C next to O shifted downfield to 3.4-3.5

• H NMR = epoxides at 2.5-2.5

• C NMR = downfield shift to 50-80