Diels–Alder reaction

The Diels-Alder reaction is a chemical reaction between a conjugated diene, which is an unsaturated hydrocarbon that has two double bonds between carbon atoms, and an alkene known as a dienophile. This interaction results in a single-step reaction that produces a bicyclic compound and unsaturated six-membered rings. Unsaturated means that the molecule in question contains double or triple carbon bonds. The reaction was first identified in the late nineteenth century and was eventually recognized as having such an important function that the men who first published an article detailing its versatility were awarded the Nobel Prize in Chemistry. The Diels-Alder reaction is an important factor in many organic chemistry applications, including the development of new ways to produce pharmaceutical compounds and the design of organic materials.

Background

Organic chemical reactions are those that include carbon atoms bonded to other carbon atoms or other elements such as hydrogen, nitrogen, or oxygen. They are important to the function of living cells. They are also a key factor for the development of new products and services in the pharmaceutical, cosmetic, agricultural, and biotechnology industries.

During a thirty- to forty-year period spanning the end of the nineteenth century and the early twentieth century, scientists identified examples of what became known as the Diels-Alder reaction. German chemist Ernst Carl Theodor Zincke experimented with diene synthesis in the 1890s, and others continued this work throughout the early part of the twentieth century, revealing additional information about the diene synthesis process.

In the 1920s, German chemist Otto Diels and his student Kurt Alder were conducting experiments at the University of Kiel. As their work progressed, they increasingly recognized the role played by reactions that involved adding dienes to other compounds to synthesize new compounds. In 1928, they published their findings in the European Journal of Organic Chemistry. Their work emphasized the versatility and potential of these reactions. This was considered to be a very significant advancement even though they had not discovered the reaction itself.

For this accomplishment, the men received two honors. First, the diene synthesis reaction was named after them; this was the first time a chemical process was named after people instead of the chemistry that was involved in the process. Second, the pair was awarded the Nobel Prize in Chemistry in 1950.

Overview

The Diels-Alder reaction is a frequent and important reaction in the field of organic chemistry. It plays a key role in naturally occurring chemical reactions and can help scientists to replicate, or create synthetic versions of, a number of natural substances. Unlike some reactions that require multiple factors to be correct, the Diels-Alder reaction can occur with relative ease with few requirements.

One of the requirements for the diene is that it must be configured in the correct orientation to allow the reaction to occur. This orientation is known as the s-cis conformation.This means the molecule’s double bonds are properly aligned on the same side of its single bond to allow the reaction to occur. The dienophiles, on the other hand, can be in either s-cis conformation or its opposite, trans conformation, meaning they are not aligned on the same side. One characteristic of the Diels-Alder reaction is that it results in consistency in the final reaction. Regardless of whether the dienophiles start as c-sis or trans, they are the same in the end product. This consistency and predictability is part of what makes the Diels-Alder reaction so valuable to organic chemists.

While the reaction can occur between any dienes and dienophiles, some combinations work better than others. The reaction happens very quickly when the dienes are formed into rings because this keeps them in the s-cis conformation that facilitates the reaction. Also, in most cases, the dienes that work best in a Diels-Alder reaction are electron rich and part of a group of molecules known as electron-donating groups, while the dienophiles that work best are electron poor and part of the electron-withdrawing groups. This results in faster reactions.

The Diels-Alder reaction can result in either an endo or exo product. An endo product is formed when both of the substituents in the dienophile are cis, while an exo product results when one or more is trans. Substituents are atoms that replace one or more hydrogen atoms in a hydrocarbon. The Diels-Alder reaction is more likely to produce endo products.

The Diels-Alder reaction is important and very useful to organic chemists and students of the science. However, the reaction can appear very confusing to those who are diagramming it. Experts recommend several steps to make this easier. These include making sure that the dienes and dienophiles are correctly aligned with the dienes in the s-cis conformation and the double bonds on the diene are lined up with the dienophile. Once aligned, the carbons can be numbered one through four to facilitate keeping track of them while working the reaction. After the bonds between the first and fourth carbons and their corresponding sides of the dienophile have been drawn, the double bonds between them can be completed. The final product can be double-checked by making sure that substituents that started s-cis or trans have remained that way.

The versatility and potential that Diels and Alder uncovered in the reaction have led to many chemists considering the process named after them to be among the most powerful synthetic reactions known. It has had a significant impact on a number of biochemical fields, including pharmaceuticals. It was instrumental in the first synthesizing of cortisone and cholesterol in the 1950s by Robert Burns Woodward and the early efforts to synthesize prostaglandins in the 1960s by Elias James Corey. It continued to be important in the development of new pharmaceutical products and delivery methods. In addition, it has proven invaluable in making synthetic versions of organic products, including dyes, terpenes, hormones, and vitamins.

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