CHAPTER 14: ETHERS, EPOXIDES AND SULFIDES

- Ethers

o Polarity of Ethers

§ What dissolves in ether

§ Boiling points of ethers

o Naming ethers

o Mass spectroscopy

§ α carbons

o Synthesis

§ Williamson

· Substrate must be primary, unhindered

· To get your alkoxide…

1. Add Na, K or NaH to an alcohol

2. Add a substrate

· If you’re getting your alkoxide from a phenol, just add NaOH, because the phenol is acidic enough to lose its proton and form the alkoxide. Then add substrate

§ Alkoxymercuration-Demercurization

· Start with an alkene

· Add Hg(OAc)₂ to make a mercuric ion

· Bust it open with the OR of your choice

· Clean up the HgOAc with NaBH₄

§ Bimolecular Dehydration (industrial)

· Fuse two primary alcohols with heat and acid

· Issues:

o Can’t be too hindered

o Equilibrium must favor products

o General conditions for reacting ethers

§ You need an acid to protonate the O, then you have an alcohol as a leaving group

§ You need a strong nucleophile to kick out the alcohol

o REACTION 1: Chopping up ethers with HBr

§ HBr protonates the ether

§ The Br- nucleophile kicks out the alcohol

§ The alcohol gets protonated

§ The Br- nucleophile kicks out water via S_N2

· Since a phenol can’t do S_N2, it will not get brominated. It will stay as an alcohol

o REACTION 2: Autoxidation

§ It’s very simple, people: Ether + oxygen = peroxides. Peroxides + flame = EXPLOSION

- Sulfides

o Synthesis

§ Make a thiolate ion by reacting a thiol (like an alcohol but with an S) with NaOH

§ Have that thiol attack a primary halide (or other good leaving group)

o Oxidizing them

§ You add hydrogen peroxide in acetic acid to oxidize a sulfide once. That makes a sulfoxide. Then you do it again and you get a sulfone.

§ Sulfides are good reducing agents, because it’s very easy to oxidize them.

o Having them do nucleophilic attacks

§ They can attack unhindered alkyl halides to produce sulfonium salts

§ Once you have this sulfonium salt, another nucleophile can attack it and knock out the sulfide as a leaving group

- Epoxides

o Synthesis

§ Using peroxyacids

· Alkene + peroxyacid = expoxide

· However, you can’t have lots of strong acid around, or else it will bust open the epoxide ring before you even get started

· So, you use a weakly acidic peroxyacid called MCPBA

· And you do it in CH₂Cl₂ to keep it aprotic

· The mechanism is concerted, so you retain stereochemistry about the double bond (cis/trans stuff)

§ Making a halohydrin attack itself

· Make a halohydrin

o Take an alkene and add halogen water (bromine water, chlorine water)

o The double bond attacks one of the chlorines and makes a halonium ion (+)

o The water attacks the +

o The water loses a H, leaving you with a halohydrin

· Add a base to the halohydrin

o The base rips the proton off the OH group

o The OH turns into an O-

o The O- knocks out the halogen via S_N2

o It’s good to use bulky bases so that they take the proton from the OH but don’t knock out the halogen via S_N2

o Busting epoxides open: Acids

§ Acid + water

· The acid protonates the O, the water attacks the vulnerable + charge on one of the carbons

§ Acid + alcohol

· Same concept, just OR instead of OH, so you get OR stuck on the former epoxide

§ HCl, HBr, HI

· The H protonates and the Cl- or Br- opens the ring.

· Then, the OH is protonated and bumped out via another Cl-, Br-, etc.

o Busting open epoxides: Bases

§ To go from ether to alcohol using a base is thermodynamically unfavorable and has a high activation energy. However, going from epoxide to alcohol has a lower activation energy and is thermodynamically favorable

§ The base attacks the carbon and pops out the O from the epoxide. The O then gets protonated by water

§ Again, you can use an alkoxide ion (CH₃O-) to put something on one of the carbons besides OH

§ You can use ammonia as your base

· Ammonia can pair up with three epoxides on the same N

o Where stuff attacks when you’re opening an epoxide ring

§ Acids: When there’s an acid around, the epoxide gets protonated and there’s a partial + on one of the carbons, which will be on the more highly substituted one. The acid goes for that one.

§ Bases: The base attacks the less hindered carbon. This includes Grignards.