Chemistry 351 Laboratory - Fall Semester 2012

Experiment #7. Microwave Accelerated Alkyne Hydration

Relevant textbook reading - Klein, Chapter 10.

Overview - In this lab, you will use a Microwave Accelerated Reaction System (MARS)1,2 for the hydration of a para-substituted ethynylbenzene. The product will be analyzed by 1H NMR and 13C NMR 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 SN2 reactions that use acetylide ion as the nucleophile.

The reaction requires a catalyst to proceed at a reasonable rate and mercury (II) compounds, such as HgO and HgCl2, have traditionally been used. Mercury compounds 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 can be hydrated to form ketones by reacting them in water solvent by superheating the water to 200 °C using microwave irradiation. They also reported that the reaction works well at slightly lower temperatures when p-toluenesulfonic acid (TsOH) is included as a catalyst. In this lab, you will attempt to use this relatively green method for the hydration of one of the following compounds: 4-tert-butyl-1-ethynylbenzene (groups 2-4), 1-ethynyl-4-pentylbenzene (groups 5-8), or 4-ethynylanisole (groups 10-ace).

Procedure

1. Add 1.0 mmol of the alkyne, 3.0 mL distilled water, and 15 mg of TsOH to a GlassChem™ pressure tube. Add a micro stirbar and then seal the tube using the torque tool as demonstrated by the instructor.

2. Label the tube near the top using a Sharpie and place the tube on the turntable for 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 175 °C and held at that temperature for 30 min. After a 10 minute cooling period retrieve your tube and carefully open the tube (wearing gloves and pointing the top away from you in the fume hood.)

4. Transfer the contents to a test tube. Add 2.0 mL of diethyl ether. Shake gently to extract the organic products. Allow the layers to separate in the test tube and then use a Pasteur pipet to separate the organic and aqueous layers.

5. Extract the aqueous layer once more with 2.0 mL ether. Combine the ether layer with the previous organic extract.

6. 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.

7. Decant the liquid into a dry 10-mL round bottom flask and remove the solvent using a rotary evaporator. The instructor or TA will assist you with the operation of the "rotovap".

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

10. Submit the product in a fully-labeled vial.

Report and Data Analysis

For this lab a very abbreviated report consisting only of fully labeled printouts of the spectra is required. Do not include Results and Discussion, Results Tables, or References. Identify and label all peaks in both NMR spectra.

Make sure to integrate the 1H NMR spectrum before printing. Use the integrations of the product and reactant peaks (if present) to calculate the percent conversion of reactant to product in your reaction. Show the calculation of % conversion somewhere on the proton NMR.

Also label the proton NMR spectrum with the yield information for the experiment (mass yielded, theoretical and % yield).

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.