Organic Chemistry II  | Lecture | Laboratory 

Organic Chemistry Laboratory II
The Diels Alder Reaction:  Reaction of 2,4-Hexadien-1-ol with Maleic Anhydride

Experiment Description and Background

In this two-week experiment, students will work individually to prepare a Diels-Alder adduct, which subsequently undergoes further reaction to form a bicyclic lactone.   The substituted diene used in the reaction (2,4-hexadiene-1-ol) reacts with the dienophile (maleic anhydride) by briefly heating in toluene.  The Diels-Alder adduct continues to react in an intramolecular nucleophilic acyl substitution to form a lactone (cyclic ester) and a carboxylic acid.   The crude product is initially characterized by TLC and compared with the starting materials.  After purification,  the product structure is elucidated by IR spectroscopy, which allows for distinction of the anhydride of the starting material and the ester/carboxylic acid in the product.  A melting point of the prepared product is determined and compared to the literature melting point value .  An NMR spectrum is provided for interpretation and a yield is also determined.  A reaction scheme of the Diels-Alder reaction of 2,4-hexadien-1-ol with maleic anhydride is shown below.


The Diels-Alder reaction, discovered by German chemists Otto Paul Hermann Diels and Kurt Alder in 1928  (Nobel Prize in Chemistry, 1950) is among the most important synthetic reactions in organic chemistry.  Its importance lies in the simplicity and ease with which the reaction occurs to form multiple bonds in a single reaction,  and in that the reaction results in the formation of six-membered rings in a regio- and stereoselective manner.  The Diels-Alder reaction is a concerted cycloaddition reaction between a conjugated diene and an alkene, also referred to as a "dienophile".  In its simpliest example, the Diels-Alder reaction occurs between 1,3-butadiene and ethylene to form cyclohexene.  The diene serves as the electron-rich species in the reaction and the dieneophile is the electron-deficient reagent.  The product of the Diels-Alder reaction is often referred to as an "adduct" or "cycloadduct".

The Diene
The diene in the Diels-Alder reaction is the electron-rich species and its electron-rich character may be enhanced by the presence of substituents on the carbon atoms of the diene.  Electron-donating substituents (EDG) increase the electron density ("negative character") of the diene rendering it more reactive in the Diels-Alder reaction.  Through resonance effects, specific atoms of the diene adopt an enhanced negative character that influeneces the regiochemistry of the reaction if an unsyummetrical substituted dienophile is used in the reaction.  Alkoxy (eg. methoxy) and amino groups, and alkyl groups are all electron- donating and enhance the reactivity of dienes.  By contrast, electron-withdrawing groups such as cyano, nitro and carbonyl-containing substituents diminish the Diels-Alder reactivity of dienes. 2,4-Hexadien-1-ol has a methyl substituent on one of the alkenes of the diene and a hydroxymethyl substituent on the other alkene.  Both of these groups are electron-donating, although there is no obvious resonance effect to illustrate this.

The alkene functional groups of the diene may have cis or trans stereochemistry.  In the case of 2,4-hexadien-1-ol, both alkenes  have trans stereochemistry.  In addition, the conjugated diene has both an s-cis conformation and an s-trans conformation that refers to the conformational isomers that result due to rotation around the sigma bond between the two conjugated pi bonds of the diene. 

The diene must adopt an s-cis conformation in order for the Diels-Alder reaction to proceed.  2,4-Hexadien-1-ol can adopt the required s-cis conformation and still retain the trans stereochemistry of the two alkenes of the diene.

The Dienophile
The dienophile in the Diels-Alder reaction is the electron-deficient species and its electron-deficient character is enhanced by substitution of carbon atoms of the alkene with electron-withdrawing groups (EWG).  Electron-withdrawing substituents (EWG) decrease the electron density, rendering the alkene more positive and more reactive with the electron-rich diene in the Diels-Alder reaction.  Through resonance effects, specific atoms of the alkene adopt an enhanced positive character that influeneces the regiochemistry of the reaction.  Cyano, nitro and carbonyl-containing substituents enhance the reactivity of dienophiles in the Diels-Alder reaction. Conversely, dienonphiles containing electron-donating groups (alkoxy, amino, alkyl) tend to be less reactive in the Diels-Alder reaction.  

Maleic anhydride contains a symmetrical alkene with two electron-withdrawing carbonyl substituents.  This alkene is also part of a five membered ring system.  The five membered ring does not have a significant influence on the reaction and the ring is usually retained in the Diels-Alder adduct.  However, in this reaction with 2,4-hexadien-1-ol,  the anhydride ring in the Diels-Alder adduct reacts with a nucleophile resulting in opening of the ring. 

Spectroscopic Characterization of Reaction Products
Infrared (IR) and proton nuclear magnetic resonance (NMR) spectroscopy are complementary and powerful analytical methods for elucidating the structure of reaction products.  IR spectroscopy provides information about specific functional group transformations that occur in the reaction, while NMR spectroscopy allows for the verification of the carbon skeleton in the product.  To learn more about IR and proton NMR spectroscopy click on the link here.

IR Spectroscopy
For the reaction of 2,4-hexadien-1-ol with maleic anhydride, IR spectroscopy helps to demnostrate that the functional groups in the starting materials have been converted to different functional groups in the product.  2,4-Hexadien-1-ol contains a conjugated diene, thus it is anticipated that the IR spectrum will contain peaks corresponding to this conjugated functional group.  Likewise, maleic anhydride contains anhydride carbonyl groups that have characteristic absorptions in the IR spectrum, one near 1830-1800 cm-1 and one near 1775-1740 cm-1 and no absorbance in the -OH region between 3200-3400 cm-1.  In the predicted product, there is an ester which has a carbonyl absorbance in the 1720-1735cm-1 range, a carboxylic acid, which has a carbonyl absorbance in the 1700-1730cm-1 range and a broad stretch in the OH region between 3200-3600cm-1.   The differences between the product IR spectrum and the starting materials, should indicate the reaction occurred.  However, additional verification by NMR spectroscopy, melting point determination and TLC analysis are needed for further verification of the reaction product.

Proton NMR Spectroscopy
Only protons (i.e., hydrogen atoms) in a compound give rise to peaks in the NMR spectrum.  Depending on what other atoms that proton is bonded to, it will have a specific chemical shift (i.e., ppm value) that is characteristic of that proton type.  FOr example, a hydrogen atom directly bonded to a carbon of an alkene or diene is referred to as vinylic and will have a chemical shift between 4.5 and 6.5 ppm.  Examination of the structure of the starting materials and the reaction product, specifically focussing on the hydrogen atoms in these structures reveals that each structure has a unique set of proton types that will give rise to very different NMR spectra.  Each proton in the structure must correspond to a peak in the NMR spectrum.  Maleic anhydride has a very simple NMR spectrum since there is only one type of proton (vinylic).  2,4-Hexadien-1-ol has a more complex spectrum, with allylic, vinylic and OH protons.  The reaction product has many different proton types and is predicted to have quite a complex spectrum.  Use the guidelines outlined at this link to interpret the NMR spectrum of your reaction product, matching each peak in the spectrum to a specific proton in the structure.