Summary

This chapter has finished the coverage of functional groups with C–O and C–S single bonds, focusing primarily on ethers, epoxides, thiols, and sulfides. Ethers are compounds that have two organic groups bonded to the same oxygen atom, ROR′. The organic groups can be alkyl, vinylic, or aryl, and the oxygen atom can be in a ring or in an open chain. Ethers are prepared by either Williamson ether synthesis, which involves S_N2 reaction of an alkoxide ion with a primary alkyl halide, or the alkoxymercuration reaction, which involves Markovnikov addition of an alcohol to an alkene.

Ethers are inert to most reagents but react with strong acids to give cleavage products. Both HI and HBr are often used. The cleavage reaction takes place by an S_N2 mechanism at the less highly substituted site if only primary and secondary alkyl groups are bonded to the ether oxygen, but by an S_N1 or E1 mechanism if one of the alkyl groups bonded to oxygen is tertiary.

Epoxides are cyclic ethers with a three-membered, oxygen-containing ring. Because of the strain in the ring, epoxides undergo a cleavage reaction with both acids and bases. Acid-catalyzed ring-opening occurs with a regiochemistry that depends on the structure of the epoxide. Cleavage of the C–O bond at the less highly substituted site occurs if both epoxide carbons are primary or secondary, but cleavage of the C–O bond to the more highly substituted site occurs if one of the epoxide carbons is tertiary. Base-catalyzed epoxide ring-opening occurs by S_N2 reaction of a nucleophile at the less hindered epoxide carbon.

Thiols, the sulfur analogs of alcohols, are usually prepared by S_N2 reaction of an alkyl halide with thiourea. Mild oxidation of a thiol yields a disulfide, and mild reduction of a disulfide returns the thiol. Sulfides, the sulfur analogs of ethers, are prepared by an S_N2 reaction between a thiolate anion and a primary or secondary alkyl halide. Sulfides are more nucleophilic than ethers and can be alkylated by reaction with a primary alkyl halide to yield a sulfonium ion. Sulfides can also be oxidized to sulfoxides and to sulfones.