Chemistry 351 Laboratory - Spring Semester 2011

Expt #6. Microwave Accelerated Alkyne Hydration

Relevant textbook reading - Smith, Chapter 11.9.

Overview - In this lab, you will use a Microwave Accelerated Reaction System (MARS)^1,2 for the hydration of an assigned alkyne, either, 4-ethynylanisole or 4-ethynyltoluene. The product, a subsituted acetophenone, will be analyzed by ¹H NMR,¹³C NMR and IR spectroscopy.

Background - Terminal alkynes can be hydrated to form methyl ketones. The inititally formed enol intermediate rapidly rearranges to the more stable ketone product, a process called keto-enol tautomerism. Alkyne hydration is a valuable method for organic synthesis, in part, because a great variety of terminal alkynes can be prepared from alkyl halides simply by S_N2 reactions that use acetylide ion as the nucleophile.

The reaction requires a catalyst, however, and traditionally mercury (II) salts such as HgO have been used. Mercury salts are highly toxic and special care is required to work with them safely. In addition, there is the problem of how to safely dispose of the wastes in a reaction that uses a mercury catalyst. Therefore, there has been significant research interest in developing alternative methods to mercury-catalysis for alkyne hydration.

In 2004, scientists at Abbott Laboratories³ reported that phenyl alkynes, such as 4-ethynylanisole, can be hydrated to form ketones by reacting them in water solvent by superheating the water to 200 °C using microwave irradiation. In this lab, you will use this method for the hydration of an assigned alkyne either 4-ethynylanisole or 4-ethynyltoluene.

Procedure

1. Add 1.0 mmol of the assigned alkyne to a pressure tube. Add 3.0 mL distilled water and seal the tube use the supplied torque tool as demonstrated by the instructor. Label the tube near the top using a Sharpie.

2. Place the tube on the turntable in the MARS unit. Make sure to note its position on the turntable.

3. The instructor will demonstrate the use of the MARS instrument. An internal fiberoptic temperature probe will be used to bring the reaction solutions to 200 °C and held at that temperature for 20 min.

4. After a 15 minute cooling period retrieve your tube and carefully open the tube (wearing gloves and pointing the top away from you in the fume hood.)

5. Transfer the contents to a test tube. Add 2.0 mL of CH₂Cl₂. Shake gently to extract the organic products. Allow the layers to separate and transfer the lower organic layer to another test tube.

6. Extract the aqueous layer once more with 2.0 mL CH₂Cl₂. Combine the CH₂Cl₂ layer with the previous organic extract.

7. Wash the combined organic layers with 2.0 mL saturated NaCl(aq). Transfer the organic layer to a small dry Erlenmeyer flask and dry over sodium sulfate.

8. Decant the liquid into a dry 10-mL round bottom flask and remove the solvent using the rotary evaporator.

9. Determine the yield and obtain ¹H and ¹³C NMR spectra using CDCl₃ as solvent. Also obtain an IR spectrum.

Data Analysis

Make sure to integrate the ¹H NMR spectrum before printing. Identify and label all peaks in both spectra. Be aware that there is a possibility that some unreacted alkyne may still be present and visible in the ¹H NMR. A spectrum of the starting material (4-ethynylanisole or 4-ethynyltoluene), which you can use to identify peaks due to it, will be available in the class storage folder. is available on the Sigma-Aldrich website. If reactant peaks are visible, then use the integrations of the methyl protons’ peaks of the product and the reactant to calculate the percent conversion of alkyne to ketone product in your experiment. (Divide the product peak integration by the sum of the integrations and multiply by 100.)

References

(1) For the basic theory of how microwaves can accelerate reactions see the video at http://www.cem.com/page9.html

(2) The MARS unit that we will be using is described here: http://www.cem.com/content643.html

(3) Vasudevan, A.; Verzal, M. K. Synlett 2004, 631-634.