Diels-Alder Reaction

Introduction:

One of the most versatile synthetic routes for creating cyclic compounds is the Diels-Alder reaction.  This particular class of [4+2] cycloaddition reaction was discovered by Otto Paul Hermann Diels and his student Kurt Alder in Germany during the 1930s.  They won the Chemistry Noble Prize in 1950 for their pioneering work.

Up to this point we have been studying reactions that involve either polar (electrophilic, and nucleophilic addition and substitution) or radical mechanisms that procedure through several steps.  Pericyclic reactions on the other hand are characterized by a single concerted step that proceeds through a cyclic intermediate.  The Diels-Alder cycloaddition is a pericyclic reaction between a diene (containing 4 pi electrons) and a dienophile (containing 2 pi electrons).  Because this reaction is concerted and proceeds through a cyclic intermediate, there are several interesting consequences.  First, since the reaction involves the precise overlap of the 'p'  orbitals in the HOMO and the LUMO of the reactants, the product always shows 'syn' addition.  If a bicyclic product is formed, the 'endo' isomer is formed in preference to the 'exo' isomer (you may want to use your molecular models to convince yourself of this).  In addition, the diene must adopt an 's-cis' conformation for the reaction to proceed.  In the 's-trans', the terminal 'p' orbitals of the diene are spread too far apart to allow sufficient overlap with the diene.  The dienophile must have an electron withdrawing group attached to the double bond.  This essentially makes it an electrophile with the diene providing the sought after electrons.  Finally, since the reaction is concerted, the steriochemistry of both the diene and the dienophile are maintained. 


Purpose:

The purpose of this experiment is synthesize all cis-1,3,3a,4,5,7a-Hexahydro-5-methyl-3-oxo-4-isobenzofuran-carboxylic acid (m.p. 161 °C, J.Chem. Soc., Perkin Trans. 1 1977, 2385) from 2,4-hexadien-1-ol and maleic anhydride.  This is a very interesting synthesis because two separate reactions will be carried out sequentially in the same vessel.  The first step in the synthesis is the Diels-Alder reaction of the 2,4-hexadien-1-ol with the maleic anhydride:



Note that the product contains a cyclic anhydride and a pendent hydroxyl group that are both cis to each other.  If you build a model of this compound, you will notice that the carbonyl group of the anhydride is perfectly aligned to undergo nucleophilic attach by the pendent hydroxyl group (see Chapter 21 for reactions of carboxylic acid anhydrides):



Attack by the hydroxyl opens the cyclic anhydride to form a carboxylic acid and a cyclic ester (lactone).  This reaction is so favored, that the intermediate Diels-Alder product can not be isolated.  Again, you should build a model of this compound to convince yourself of the steriochemistry of the product.

You will also be following the progress of these reactions using thin layer chromatography (see CHEM1120 TLC lab for background).


Procedure:

Before you come into lab, make sure you have filled in your table of reagents and products.  You will need these values (particularly the molecular formula and molecular weight) to determine the identify of your products and to calculate your final yield.  You will also need to come to lab with IRs of your starting materials and expected product(s) already in your notebooks (this link may be helpful:   http://webbook.nist.gov/chemistry/).  Finally, it is important that you know exactly what you are going to be doing so you can work more efficiently:

IF YOUR DO NOT UNDERSTAND AN ASPECT OF THE LAB, USE THE INTERNET TO LOOK IT UP OR ASK YOUR INSTRUCTOR.  DO NOT COME INTO LAB UNPREPARED!!

Synthesis of all cis-1,3,3a,4,5,7a-Hexahydro-5-methyl-3-oxo-4-isobenzofuran-carboxylic acid:
  1. Weigh approximately 0.5 g of maleic anhydride and 0.5 g of E,E-2,4-hexadien-1-ol into a large Pyrex test tube.
  2. Add approximately 7 mL of toluene and a boiling stick to the test tube.
  3. Place an aluminum bead heating bath on a hot plate.
  4. Clamp the test tube upright so the bottom 3/4" is buried in the aluminum beads.
  5. Heat the mixture until it refluxs and continue for an additional 15 minutes.  Follow the progress of the reaction by taking samples of the mixture during this time and spotting them on your TLC plate (see below).
  6. Pour the hot solution (CAUTION) into a 100 mL beaker and allow it to cool to room temperature.
  7. Then cool it in an ice bath for 10 minutes to ensure complete crystallization.  You may have to scratch the bottom of the beaker with your glass stirring rod to initiate crystallization.
  8. Use vacuum filtration to collect the product.
  9. Rinse the beaker with several portions of COLD toluene.  Use these rinses to wash your product.
  10. Allow the product to air dry for several minutes.
  11. Determine the melting point of your product.  If it does not have a fairly sharp melting point, recrystallize it from toluene.
  12. Determine your yield, purity (FTIR), and turn in the product in a properly labeled vial:
Your Name:
 Class/Section:
 Date:
Compound:
 M.P./ B.P.:
 R.I.:
Actual Yield (g):
 Theoretical Yield (g):
 Percent Yield:
Purity (GC):
 Purity (RI):
 Purity (IR):

Thin Layer Chromatography (TLC):
  1. Create a TLC chamber by pouring about 5 mL of ethylacetate into a 150 mL beaker and placing plastic wrap over it.  Be sure to do this early enough in the period so the air in the beaker is saturated with the ethylacetate.
  2. Prepare your silica TLC plate by lightly placing a pencil mark approximately 1 cm from the bottom (origin).
  3. At 0, 1, 5, 10, and 15 minutes spot the reaction mixture on the origin of your TLC plate.
  4. After you have spotted your samples, develop the plate.
  5. Use the UV lamp to mark the position of all reaction components.
  6. Be sure to measure your Rfs and record a drawing of your TLC plate in your notebook.

Conclusions:

 (Updated 2/7/04 by C.R. Snelling)