4.S: Ethers and Epoxides; Thiols and Sulfides (Summary)
Concepts & Vocabulary
4.0 Introduction
- Ethers are molecules containing oxygen which is bonded to two carbon groups.
- Thiols are sulfur analogues of alcohols with an SH group instead of OH.
- Sulfides are sulfur analogues of ethers with sulfur bonded to two carbon groups instead of oxygen.
4.1 Names and Properties of Ethers
- Ether groups are named as alkoxy groups.
- Ethers do not have intramolecular hydrogen bonding (unlike alcohols), therefore ethers have significantly reduced intermolecular forces causing boiling points that are much lower than similar sized alcohols.
4.2 Preparing Ethers
- Alkoxymercuration can be used to prepare an ether from an alkene.
4.3 Reactions of Ethers: Acidic Cleavage
- The carbon-oxygen bonds of ethers can be cleaved with strong acids through either nucleophilic substitution or elimination reactions.
4.4 Reactions of Ethers: Claisen Rearrangement
- The Claisen rearrangement is a [3, 3] sigmatropic rearrangement reaction that converts aryl or enol ethers into carbonyl compounds (though the aromatic version rearranges into a phenol to re-establish aromaticity.
4.5 Cyclic Ethers: Epoxides
- Epoxides, also called oxiranes, have a three-membered ring structure with one oxygen and two carbon atoms.
- Epoxides can be formed from alkenes by reaction with peroxy acids (MCPBA for example).
- Epoxides can be formed from halohydrin molecules by reaction with a base, which causes an intramolecular Williamson ether synthesis.
4.6 Reactions of Epoxides: Ring Opening
- When epoxides are ring opened under basic conditions, they follow S N 2 mechanism leading to the nucleophile adding to the less substituted side of the epoxide.
- When epoxides are ring opened under acidic conditions, they follow S N 1 mechanism leading to the nucleophile adding to the more substituted side of the epoxide.
- When epoxides are ring opened in aqueous reactions, the result is an anti-diol.
- Halo acids can be added to epoxides to form anti-halohydrins.
4.7 Crown Ethers
- Crown ethers are cyclic ethers containing several oxygen atoms.
- Crown ethers are named by the number of total atoms in the ring, followed by the word crown and finally the number of oxygen atoms (18-crown-6 for example).
4.8 Thiols and Sulfides
- Thiols can be prepared from alkyl halides through reaction with hydrosulfide ion (SH - ) or through a more complicated series of reactions including thiourea.
- Thiols can be oxidized with mild oxidizing agents to form disulfides.
- Disulfide bridges link cysteine residues in protein structures.
- Sulfides are sulfur analogues of ether, though are much better nucleophiles with sulfur in place of oxygen.
4.9 Spectroscopy of Ethers
- Ethers show standard C-H stretches and bends in IR along with a strong C-O stretch around 1000 cm -1 .
- In 1 H NMR, hydrogens on carbons adjacent to the oxygen typically appear between 3.4-4.5 ppm.
- Hydrogens on carbons of an epoxide ring typically appear between 2.5-3.5 ppm in 1 H NMR.
4.10 Interchapter: A Preview of Carbonyl Chemistry
- Carbonyl groups are one of the most important features in organic chemistry and consist of a sp 2 carbon double-bonded to oxygen.
- Carbonyl groups are present in ~10 different functional groups.
- Carbonyl groups are polarized with a partial positive charge on carbon and partial negative charge on oxygen. This makes the carbon atom an electrophile, while the oxygen can act as a nucleophile.
- Carbonyl groups can react through several mechanisms including nucleophilic addition and nucleophilic acyl substitution, alpha substitution and condensation.
Skills to Master
- Skill 1 Name ethers using common naming and IUPAC.
- Skill 2 Write reaction equations for preparation of ethers.
- Skill 3 Write mechanisms for reactions of ethers with strong halogen acids.
- Skill 4 Draw mechanisms for Cope and Claisen rearrangements.
- Skill 5 Draw mechanisms for ring-opening epoxides under acidic and basic conditions.
- Skill 6 Draw and name crown ethers.
- Skill 7 Explain how disulfide bridges contribute to protein structure.
- Skill 8 Give an example of S-adenosyl methionine activity in biological systems.
- Skill 9 Use IR and NMR spectra to identify ethers.
Summary of Reactions
Ether and Epoxide Preparation
Ether Reactions
Claisen Rearrangement
Epoxide Reactions
Sulfur Compound Reactions