Name: how alkenes form epoxides
Uploaded: 2023-04-30T18:28:41.000Z
Duration: 3 min
Channel: JoVE

Epoxides are prepared by the oxidation of alkenes using various oxidizing agents, and the reaction is known as epoxidation. 
Some of the most common oxidizing agents are peroxy acids, such as meta-chloroperoxybenzoic acid or mCPBA.
Peroxy acids are unique in having an electrophilic oxygen atom in the carboxylic group, which acts as the center for nucleophilic attacks.
Consider the oxidation of cis-2-butene using mCPBA to give cis-2,3-dimethyloxirane, with the mCPBA itself getting reduced to 3-chlorobenzoic acid.
The reaction proceeds via a cyclic transition state, wherein the alkene&#39;s &#960; bond acts as a nucleophile and attacks the electrophilic oxygen of the peroxy acid to form the first carbon&#8211;oxygen bond of the epoxide.
Simultaneously, the oxygen&#8211;oxygen bond of the peroxy acid breaks, forming a new carbonyl bond.
Further, the &#960;-electrons of the peroxy acid&#39;s original carbonyl bond abstract a proton from the OH bond to form a new OH bond. The oxygen then attacks the other carbon of the alkene, forming the second carbon&#8211;oxygen bond.
Overall, the electrophilic oxygen from the peroxy acid gets transferred to the double bond of the alkene, thus forming the epoxide ring. Since all the bond-breaking and bond-making occurs in a single step, the reaction is said to be concerted.
Stereospecifically, the epoxide ring installation on the alkene follows syn addition. Hence, a cis-alkene gives a cis-epoxide, and a trans-alkene gives a trans-epoxide.
Moreover, alkene&#39;s planar structure facilitates the nucleophilic attack and the formation of the epoxide ring from either face, yielding a meso compound for the cis- and a racemic mixture for the trans-epoxide. 
Halohydrins of alkenes, when treated with a base, can also form epoxides. The reaction is an intramolecular variation of the Williamson ether synthesis.
Consider the cyclization of 3-chloro-2-butanol, a halohydrin derived from cis-2-butene, to give cis-2,3-dimethyloxirane.
The reaction proceeds via the deprotonation of halohydrin&#39;s hydroxyl group by the base to form the alkoxide ion, a nucleophile.
Typical of an SN2 reaction, the nucleophile attacks from the backside and displaces the chloride ion on the adjacent carbon forming the oxirane ring. Consequently, the epoxide formed retains the alkene stereospecificity.

preparation of epoxides

Preparation of Epoxides

<h4>Overview</h4>
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
<h4>Epoxidation with Peroxy Acids</h4>
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon&#8211;carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O&#8211;O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to alkenes occurs with ease, thereby following syn addition. Hence, the epoxides are produced with the retention of the alkene configuration.
<h4>Epoxidation via Air Oxidation</h4>
Although peroxy-mediated epoxidation is the most common method for alkene oxidation, ethylene oxide is synthesized at the industrial scale via air oxidation by treating a mixture of ethylene and air in the presence of a silver catalyst.
<h4>Cyclization of Halohydrins</h4>
Cyclization of halohydrins of alkenes in the presence of a base also yields epoxides, and the reaction follows the SN2 substitution mechanism. Hence, the nucleophile&#8212;the oxygen anion&#8212;and the leaving group&#8212;the chloride ion&#8212;must orient anti to each other in the transition state to make the halohydrins cyclization feasible.
<img alt="Molecular internal rotation diagram showing ethane-chair conversion via stereochemistry." src="/files/ftp_upload/12094/12094Figure%201.svg" style="text-align: center; height: 260x;" data-altupdatedat="1761830439000" data-alt="Figure1" />
In noncyclic halohydrins, this anti-relationship is achieved by an internal rotation. For instance, in 1-chloro-2-methyl-2-propanol, shown in Figure 1, the hydroxyl and the chloro group are not oriented anti to each other. To achieve the anti-relationship, the carbon-bearing chloro group undergoes an internal rotation, thereby making the nucleophile attack&#8212;from the backside of the C&#8211;X bond&#8212;and the ejection of the leaving group feasible. Thus, the epoxides formed via halohydrin cyclization also retain the alkene configuration.
Similarly, the cyclic halohydrins must undergo conformational changes to achieve the anti-relationship. For example, the halohydrin of cyclohexane, shown in Figure 2, undergoes a conformational change from diequatorial to diaxial to successfully form an epoxide.
<img alt="Cyclohexane ring flip; diaxial to diequatorial conformation; chemical reaction mechanism diagram." src="/files/ftp_upload/12094/12094Figure%202.svg" style="text-align: center; height: 120px;" data-altupdatedat="1761830439000" data-alt="Figure2" />

Overview
Epoxides result from&#160;alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin ...

Education

JoVE Core

Organic Chemistry

Unit 1

Ethers, Epoxides, Sulfides

KEY TERMS AND CONCEPTS

how alkenes form epoxides

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 easily and follows syn addition. As a result, the epoxide keeps the same alkene configuration.

Another route to epoxides is air oxidation. This method is used on an industrial scale to make ethylene oxide. Ethylene is treated with air in the presence of a silver catalyst. Halohydrin cyclization also gives epoxides when a base is added, and this reaction follows an SN2 mechanism.

For halohydrin cyclization to work, the oxygen anion and the chloride leaving group must be anti to each other in the transition state. In noncyclic halohydrins, internal rotation can create this arrangement. For example, in 1-chloro-2-methyl-2-propanol, the hydroxyl and chloro groups are not initially anti, so rotation makes backside attack possible and allows the leaving group to leave. Cyclic halohydrins also need a conformational change, such as the diequatorial to diaxial shift in cyclohexane halohydrin, before the epoxide can form.

How Alkenes Form Epoxides

structure and nomenclature of ethers

Ethers: Bonding, Types, and Naming

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...

physical properties of ethers

Ether Solubility and Boiling Points

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 from alcohols: alcohol dehydration and williamson ether synthesis

ethers-from-alcohols-alcohol-dehydration-williamson-ether

Making Ethers by Dehydration and Synthesis

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 from alkenes: alcohol addition and alkoxymercuration-demercuration

ethers-from-alkenes-alcohol-addition-alkoxymercuration

Making Ethers with Alkene Reactions

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 to alkyl halides: acidic cleavage

Cleaving Ethers with HBr and HI

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...

autoxidation of ethers to peroxides and hydroperoxides

autoxidation-of-ethers-to-peroxides-and-hydroperoxides

Why Stored Ethers Can Form Explosive Peroxides

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

Crown Ether Binding and Ion Solubility

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...

structure and nomenclature of epoxides

Epoxide Ring Strain and Naming Rules

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

Chiral Control in Sharpless Epoxidation

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...

acid-catalyzed ring-opening of epoxides

Epoxide Ring Strain and Acidic Opening

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...

base-catalyzed ring-opening of epoxides

Epoxide Ring Opening by Strong Nucleophiles

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...

structure and nomenclature of thiols and sulfides

structure-and-nomenclature-of-thiols-and-sulfides

Sulfur in Thiols and Sulfides

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...

preparation and reactions of thiols

Thiols: Making and Oxidizing Sulfur Compounds

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.

preparation and reactions of sulfides

Sulfide Synthesis and Oxidation

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...

key terms and concepts

See how alkenes form epoxides through peroxy acids, air oxidation, and halohydrin cyclization, including MCPBA, ethylene oxide, and SN2 ring closure.

How Alkenes Form Epoxides | JoVE K12

organic chemistry

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How Alkenes Form Epoxides

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