Ethers, Epoxides, Sulfides

Ethers are organic compounds with an oxygen atom bonded to two groups. Those groups may be the same or different, and they can be alkyl, aryl, or vinyl groups. In dimethyl ether, the simplest ether, the C–O–C link has an angle of about 110.3 degrees. The oxygen is sp3-hybridized, and the C–O distance is about 140 pm.

Ethers are classified by the groups attached to the oxygen atom. Symmetrical ethers have identical groups on both sides, such as dipropyl ether and diphenyl ether. Unsymmetrical...

Ethers have a net dipole moment because the C-O bonds are polar. This polarity helps explain why their boiling points are lower than alcohols with similar molecular weight and slightly higher than hydrocarbons with similar molecular weight.

Ethers can also accept hydrogen bonds, which makes them more water-soluble than hydrocarbons. However, they cannot donate hydrogen bonds, so they are much less soluble in water than alcohols. Their mix of hydrogen bonding with other molecules and London...

Ethers can be made from alcohols by dehydration and by Williamson ether synthesis. These two routes show how alcohols can act in different roles during ether formation. The first method uses a protic acid, while the second method uses an alkoxide ion and an alkyl halide.

In alcohol dehydration, the alcohol loses water in the presence of a protic acid such as sulfuric acid. Ethanol gives ethoxyethane at 413 K, but it gives ethene at 443 K. This reaction is a nucleophilic substitution reaction,...

Ethers can be made from alkenes by adding alcohols under acidic or organomercury conditions. The two routes shown here are acid-catalyzed addition of alcohol to an alkene and alkoxymercuration-demercuration. Both methods start with an alkene and an alcohol and end with an ether.

In acid-catalyzed addition, the alkene reacts with an excess of alcohol in the presence of an acid catalyst. Under the right conditions, the hydrogen adds to the less substituted carbon. This lets the alcohol group...

Ethers can be cleaved into alkyl halides when heated with strong acids such as HBr and HI. This reaction is useful because ethers are usually unreactive in direct nucleophilic substitution. Their alkoxy groups are strong bases, so they are poor leaving groups.

The acid cleavage happens in two substitution steps. First, the ether is converted into one alkyl halide and one alcohol. Then the alcohol reacts with excess HX acid to form a second alkyl halide.

The reaction pathway depends on the...

Stored ethers can slowly turn dangerous because they react with oxygen in air and form peroxides. This process is called autoxidation, which means a compound oxidizes on its own while standing in air. Over time, ethers can produce hydroperoxides and dialkyl peroxides.

These peroxide products can be explosive if they become concentrated or are heated. For that reason, ethers should be bought in small amounts, kept in tightly sealed containers, and used soon after opening. Careful storage helps...

Crown ethers are cyclic polyethers with several oxygen atoms arranged in a ring. Their ring shape gives them a crown-like form. Charles Pederson first synthesized the first crown ether at DuPont in 1967, and he later shared the 1987 Nobel Prize in Chemistry for that work.

Crown ethers are named with the format x-crown-y. In this name, x is the total number of atoms in the ring, and y is the number of ether oxygen atoms. A common example is 18-crown-6.

These molecules can bind specific alkali...

Epoxides are three-membered cyclic ethers that contain two carbon atoms and one oxygen atom in the ring. Cyclic ethers are heterocyclic compounds, which means the ring includes atoms other than carbon. Their names depend on the number of carbon atoms in the ring.

A three-membered cyclic ether is called an oxirane. Four-membered rings are called oxetane, five-membered rings are called oxolane, and six-membered rings are called oxane. Smaller rings have more angle strain, and the three-membered...

Alkenes can form epoxides through oxidation. This reaction can happen with air, peroxy acids, hypochlorous acids, or halohydrin cyclization. Epoxides are three-membered oxygen rings, and they are common products in alkene chemistry.

A common lab method uses a peroxy acid such as meta-chloroperoxybenzoic acid, or MCPBA. In this reaction, the carbon-carbon double bond is converted into an epoxide by adding electrophilic oxygen. Because the O-O bond in a peroxy acid is very weak, the oxygen adds...

Sharpless epoxidation is a chiral reaction that converts allylic alcohols into epoxides. It was discovered by K. Barry Sharpless. The reaction is useful because it can favor one enantiomer, or mirror-image product, over the other.

The key to this selectivity is a chiral catalyst. It is mainly a complex of titanium tetraisopropoxide and a tartrate ester with a specific stereoisomer, or 3D arrangement. The stereoisomer in the catalyst controls which enantiomer forms in excess.

Using...

Epoxide ring strain makes these three-membered ethers highly reactive. Because the ring is so strained, epoxides can open in reactions with halogen acids or with weak nucleophiles when a mild acid is present.

The acid catalyst changes the epoxide oxygen into an oxonium ion, which is a better leaving group. This makes the ring-opening reaction possible. The reaction follows an S N 2 mechanism, and the protonated oxygen does not leave the molecule on its own.

The product pattern depends on the...

Epoxide ring opening by strong nucleophiles happens because epoxides have a highly strained three-membered ring. This strain makes them ready for nucleophilic substitution in either acid or base. In the base-catalyzed pathway, a strong nucleophile or base attacks the ring and opens it.

Common nucleophiles for this reaction include sodium hydroxide, sodium alkoxide, sodium hydrosulfide, sodium cyanide, lithium aluminum hydride, and Grignard reagents. The attack follows an SN2 mechanism and...

Thiols and sulfides are sulfur-based organic compounds. Thiols are sulfur analogs of alcohols, and sulfides are sulfur analogs of ethers. In thiols, the sulfur atom is written as RSH, where R is an alkyl group and SH is the functional group.

Sulfides have a central sulfur atom bonded to two hydrocarbon groups, one on each side. These compounds can be symmetrical or asymmetrical, depending on the groups attached. Both thiols and sulfides have a bent shape, much like alcohols and ethers.

The...

Thiols are sulfur compounds that can be made by nucleophilic substitution with alkyl halides. In one route, the hydrosulfide anion acts as the nucleophile. For example, bromobutane reacts with sodium hydrosulfide to form butanethiol.

That direct method has a limitation. If excess alkyl halide is present, the thiol product can react again and form a sulfide as a by-product. A better route uses thiourea as the nucleophile. This reaction first gives an alkyl isothiourea salt as an intermediate.

Sulfides are sulfur compounds that contain two hydrocarbon groups attached to one sulfur atom. They are the sulfur analog of ethers, just as thiols are the sulfur analog of alcohols. Depending on the groups attached, sulfides may be symmetrical or asymmetrical.

Symmetrical sulfides can be made by an S N 2 reaction. In this method, two equivalents of an alkyl halide react with one equivalent of sodium sulfide. Asymmetrical sulfides are prepared from thiols, an alkyl halide, and a base. This...