Chem 242, Lab Section Reviewed 1-20-14

EXPERIMENT #3: DIELS -ALDER REACTION

Please see the last page for pre and post lab questions.

The Diels-Alder reaction is a cycloaddition reaction, in which two molecules add together in a concerted reaction to form a cyclic compound. It is one of the most important chemical reactions used to synthesize six-membered ring organic compounds. In Part 1 of this experiment, we will react butadiene sulfone with maleic anhydride to form cyclohex-4-ene-cis-1,2-dicarboxylic anhydride. Butadiene sulfone forms butadiene in situ with heating, and is easier to work with than 1,3-butadiene.

In Part 2 of this experiment, we will hydrolyze the product of part 2 with acid to produce cyclohex-4-ene-cis-1,2-dicarboxylic acid:

READING ASSIGNMENT:  Background and Experiment, see attached.  Supplementary information in Bruice, pp 314-322.

CAUTION Butadiene sulfone (3-sulfolene) is an irritant. Wear gloves, avoid all contact with skin, eyes, and clothing, and do all work in an efficient fume hood. This compound emits toxic corrosive sulfur dioxide when it is heated. Be sure that the gas trap is positioned before you begin heating the reaction mixture. Maleic anhydride is toxic and corrosive. Avoid breathing dust and avoid contact with skin,eyes, and clothing. Xylene is flammable.

1 1. The laboratory background and experimental protocol was adapted from the VCU Chemistry department and was written by Albert T. Sneden and L.M. Moses

Chem 242, Lab Section Reviewed 1-20-14

NOTES FOR WRITING YOUR DISCUSSION:

Your Results section should include:  Appearance and melting point of the product.  Yield of the product and calculation of % yield.

Your Theory subsection should include:  A brief overview of the Diels-Alder reaction: mechanism, regioselectivity, stereospecificity/selectivity and electronic requirements for the two partners.  A arrow pushing mechanism of the Diels-Alder reaction that you will perform.

Your analysis of results subsection should include:  Discuss the identity and purity of the compound you isolated at the end.  Discuss the % yield of the product.  Discuss purity of the sample using melting point as a guide.

Your Sources of Error subsection should include:  Evaluate how reliable your results are: how certain are you of the identity and purity of the product you isolated? Propose different experiments or techniques that would help you address these issues.

2 1. The laboratory background and experimental protocol was adapted from the VCU Chemistry department and was written by Albert T. Sneden and L.M. Moses

Chem 242, Lab Section Reviewed 1-20-14 Background1

The Diels-Alder reaction is one of the most well-known of organic "name" reactions, reactions which are known by the names of the chemists who discovered the reaction or demonstrated the utility of the reaction in a general sense. The reaction of a conjugated or 1,3-diene (a 4 π electron system) with a substituted alkene or alkyne, the dienophile (a 2 π electron system), was discovered by Otto Diels and Kurt Alder and patented in 1927.1 A year later the work was published in the chemical literature,2 and due to the widespread utility of the reaction in organic synthesis, particularly for the construction of six-membered rings, Diels and Alder were awarded the Nobel Prize in Chemistry in 1950. Today, one can look through almost any issue of an organic chemistry journal such as the Journal of Organic Chemistry and find at least one article which describes the use of the Diels-Alder reaction.

Although there are many variations of the reaction used in organic syntheses, the basic principles remain the same. In the Diels-Alder reaction, a diene such as 1,3-butadiene is allowed to react with a dienophile such as maleic anhydride in an inert solvent such as toluene, often at low temperature and without additional reagents. The reaction is often exothermic (giving off heat) and proceeds in high yield to create the desired six-membered ring which contains one double bond, in this case, 4-cyclohexene-cis-1,2-dicarboxylic anhydride.

The two new sigma bonds and one new π bond appear to form simultaneously with the breaking of the original π bonds, leading to a cyclic transition state such as A (below). This process is known as a concerted process, and those reactions which result in the formation of a new ring through a cyclic transition state (depicted in A) are known as cycloaddition reactions. In the case of the Diels-Alder reaction, this is called a 4+2 cycloaddition reaction, indicating the number of π electrons from each starting material which are involved in the reaction.

O

O

O A

Almost any conjugated (1,3-) diene can be used in the Diels-Alder reaction, providing certain criteria are met. The diene must be relatively stable and the double bonds must be able to assume the s-cis conformation. For this reason, cyclic dienes such as cyclopentadiene, 1,3- cyclohexadiene, or furan are often used in the Diels-Alder reactions. When a cyclic diene, e.g., cyclopentadiene, is used, the product obtained is a bicyclic compound. A diene which cannot assume the s-cis conformation, e.g., methylenecyclohexene, will not undergo the Diels-Alder 3 1. The laboratory background and experimental protocol was adapted from the VCU Chemistry department and was written by Albert T. Sneden and L.M. Moses

Chem 242, Lab Section Reviewed 1-20-14 reaction. The dienophile must also meet certain criteria. For the basic Diels-Alder reaction, the dienophile must bear electron withdrawing groups such as a carbonyl or nitrile to activate the double bond for the Diels-Alder reaction. Some representative dienophiles are shown below.

Common Dieneophiles (Though there are many more!)

O O CO2CH3 H CO2R RO2C H O

H CO2R H CO2R O CO2CH3

If the above criteria for the diene and dienophile are met, the Diels-Alder reaction usually proceeds without catalysis or extreme conditions. Because the reaction is concerted, the reaction proceeds in a stereospecific fashion. Substituents on the dienophile which are cis to one another, will be cis to one another in the product (see below). In a similar fashion, substituents on the dienophile which are trans to one another, will be trans to one another in the product.

CO R H CO2R 2 + Diels-Alder CO R H CO2R 2 Cis Cis

RO2C H CO R Diels-Alder 2 + H CO R 2 CO2R Trans Trans

Preparation Of 4-Cyclohexene-Cis-1,2-Dicarboxylic Anhydride Using The Diels-Alder Reaction.

You will be performing a Diels-Alder reaction of 1,3-butadiene with maleic anhydride to form 4- cyclohexene-cis-1,2-dicarboxylic anhydride. However, 1,3-butadiene is a gas at room temperature and would require special apparatus to conduct the reaction. To surmount this problem, the 1,3-butadiene will be generated in situ (in the reaction medium) from the thermal

4 1. The laboratory background and experimental protocol was adapted from the VCU Chemistry department and was written by Albert T. Sneden and L.M. Moses

Chem 242, Lab Section Reviewed 1-20-14 decomposition of 3-sulfolene (butadiene sulfone). While 3-sulfolene is a relatively stable solid at room temperature, when heated it decomposes to give 1,3-butadiene and sulfur dioxide (See chemical reaction below). If the decomposition is carried out in the presence of a good dienophile, in this case maleic anhydride, the 1,3-butadiene will react in a Diels-Alder reaction while the sulfur dioxide is eliminated from the reaction mixture as a gas.

O

O H O o 137-140 C O SO2 SO2 + O (gas) H O

Procedure:

Since sulfur dioxide (SO2) is an irritating and toxic gas, it is necessary to trap the gas before it enters the atmosphere. In this case, it is not sufficient enough to carry out the reaction in the hood, since the gas would just enter the atmosphere outside of the building, adding to air pollution. Instead, the SO2 will be trapped by allowing it to dissolve in water. This will create a dilute solution of sulfurous acid which may be disposed of safely down the drain.

Mix 2.29 g of butadiene sulfone, 1.22 g of finely powdered maleic anhydride, a boiling stone and 3.0 ml of xylene in a 50 ml round-bottom flask which will serve as the solvent. Attach a reflux condenser to the flask. Connect a rubber septum containing a needle and tubing to the top of the condenser. The end of the tubing will go into a 500 mL beaker half full of tap water. Clamp the tubing in so the end in the beaker of water cannot easily be removed (you do not want the tubing falling out of the water during the reaction). Place some wet (water) paper towels around the top

of the beaker. This will serve as the gas trap for SO2 vapors.

5 1. The laboratory background and experimental protocol was adapted from the VCU Chemistry department and was written by Albert T. Sneden and L.M. Moses

Chem 242, Lab Section Reviewed 1-20-14

Rubber Septum

Tubing H2O out

H2O in Beaker with water

Heating mantle will go here

Heat the solution at a gentle reflux for 30 minutes using a heating mantle, then allow it to cool to room temperature (about 5 minutes of cooling).

Remove the rubber septa and tubing from the top of the septa and pour 5 mL of distilled water down the condenser. Add an additional boiling stone then heat to reflux for 30 minutes. Cool to room temperature and over the course of 5 minutes crystals should develop. If crystals do not form add 3-4 drops of concentrated sulfuric acid. Collect the crystals by vacuum filtration and wash them with 2 x 2 mL portions of ice-cold water. Dry the crystals between two pieces of filter paper and weigh the product and take a melting point.

References:

1. O. Diels and K. Alder, Brit. Pat. 300130 (1927). 2. O. Diels and K. Alder, Justus Liebigs Annalen der Chemie, 98, 460 (1928).

6 1. The laboratory background and experimental protocol was adapted from the VCU Chemistry department and was written by Albert T. Sneden and L.M. Moses

Chem 242, Lab Section Reviewed 1-20-14 Prelab Questions:

1. In this reaction we will be heating butadiene sulfone to perform a Diels-Alder reaction. What side product is generated apon heating butadiene sulfone and how will we trap this side product? 2. In most chemical reactions it is a bad idea to create a closed system, that is a system which cannot attenuate to pressure changes. In this reaction what measures are taken to avoid a closed system and why would it be a particularly bad idea to create a closed system for this Diels-Alder reaction?

Postlab Questions:

1. Suppose you did not feel confident that actually formed cyclohex-4-ene-cis-1,2- dicarboxlic acid (1) and felt that you formed only cyclohex-4-ene-cis-1,2-dicarboxlic anhydride (2). How could you proved the presence or absence of cyclohex-4-ene-cis-1,2- dicarboxlic acid using IR spectrometry?

O H H O OH O OH H O H O 1 2

2. Predict the relative rates for the reaction of butadiene and (a) ethane (b) methyl propenoate (c) maleic anhydride

O

O O H CO 3 O Ethene Methyl propionate a e c an r e M l i hyd id

3. What product is expected from the reaction of fumaric acid (trans-2-butenedioic acid) with 1,3-butadiene?

7 1. The laboratory background and experimental protocol was adapted from the VCU Chemistry department and was written by Albert T. Sneden and L.M. Moses