Organic Chemistry II  | Lecture | Laboratory 

Reduction of Ketones with Sodium Borohydride
Experimental Procedure

Procedure
Synthesis of 2-Methylcyclohexanol
Add 10 ml of methanol (CH3OH) and 1.2g of 2-methylcyclohexanone to a 50ml Erlenmeyer flask.  Add a magnetic stir bar to the flask.  Set up a stirrer/hot plate in the hood, with two ring stands positioned on either side.  Set an ice bath, filled ~½ - ¾ full of ice on the stirrer/hot plate.  Clamp your flask (along with your benchmate's) to each of the two ring stands, inserting the flasks into the ice bath as you clamp (see Figure 2 for set-up).  Turn the stirrer (not the heat!) to the "on" position.

Figure 2:  Reaction Set-Up
(Note:  The actual experiment will not have a blue color) 
 Add 200mg of sodium borohydride (NaBH4) in 2, 100mg portions to the flask as the contents continues to stir.  (Caution: The reaction is very exothermic!)  After all of the NaBH4 has been added, allow the reaction to subside (~5-10 minutes), then remove the ice bath.  Stir the reaction mixture at room temperature for an additional 15 minutes. Add 5 ml of 10% NaOH solution, 5 ml of de-ionized water, and 15 ml of hexane to the reaction flask.  Stir the reaction flask vigorously for 3-5 minutes.  Set up a 125 ml separatory funnel on a ring stand as shown in Figure 3.  Stop the stirring, remove the magnetic stir bar and transfer the reaction mixture to the125ml separatory funnel (Be sure the stopcock is in the closed position).  Two layers should appear. 
Label two 50ml beakers or Erlenmeyer flasks as “water layer” and “organic layer”. Separate the layers from the separatory funnel into the appropriate beaker or flask.  Add 10ml of hexane to the separatory funnel along with the water layer.  Stopper the funnel and shake vigorously for 1-2 minutes.  Set the separatory funnel back onto the ring stand and allow the two layers to separate.  Once again, separate the layers from the separatory funnel into the appropriate beaker or flask.  Add 10ml of fresh hexane to the separatory funnel with the water layer and repeat the process one last time, combining all of the hexane layers into the flask or beaker labeled “organic layer”.   Add ~100mg of magnesium sulfate drying agent to the beaker or flask labeled “organic layer”.   Swirl the flask, then allow the drying agent to settle to the bottom.  Carefully decant the solution into a pre-weighed, clean, very dry 25ml Erlenmeyer flask, leaving the drying agent behind.

Figure 3:  Set-up for Separatory Funnel
Set a water bath, filled ~½ - ¾ full of tap water on the stirrer/hot plate. Clamp your flask to a ring stand, inserting it into the water bath as you clamp. Turn the heat to the "on" position and gently warm the solution until the CH2Cl2 evaporates, leaving a clear or slightly yellow oil as product.  Remove the flask from the water bath and wipe off the outside to remove any residual water.  Weigh the flask again to determine the weight of the product.  Calculate the percent yield.
back to top
Product Analysis by IR Spectroscopy
Run an infrared (IR) spectrum of both the starting material and the product.  One IR spectrum of the starting material can be run per lab bench, however, each student pair must run their own IR spectrum of the product.  Run the  IR spectrum according to the procedures described in the experimental procedure section of the IR Spectroscopy experiment.
 
Running the IR Spectrum
Intepreting the IR Spectrum

Product Analysis by Chemical Tests
Jones Oxidation Test for Alcohols   Caution: reaction is very exothermic!  Test tube will become very hot!
Set up a test tube rack containing four, small (75mm X 12mm) test tubes. Be sure that the test tubes are clean and dry.   Label the test tubes #1-4.  In test tube 1, place 2 drops of cyclohexanol (+control), in test tube 2 place two drops of cyclohexanone (- control), in test tube #3 place ~10mg the starting material, 2-methylcyclohexanone, and in test tube 4, place ~10mg of your product.   Add ~1ml of acetone to each tube and vortex to dissolve the compounds.  Add one drop of the Jones reagent into each test tube.  If a primary or secondary alcohol is present, a blue-green color will appear in about a minute.  (Tertiary alcohols do not react). If an alcohol is not present, the solution will remain orange-yellow.  To be able to see the colors better, try and  fill the test tube approximately half-full with distilled water.  Record the results in tabular form in your notebook.

Brady's Test for Ketones
Set up 4 small (75mm X 12mm) test tubes in a test tube rack in the hood.  Be sure that the test tubes are clean and dry.  Label the test tubes #1-4.  In test tube 1, place 2 drops of cyclohexanone (+ control), in test tube 2,  place two drops of cyclohexanol (- control), in test tube 3 place ~10mg of the starting material, 2-methylcyclohexanone, and in test tube 4, place ~10mg of your product. Add ~2 ml of ethanol to each tube and vortex to dissolve the compounds.  Add ~2 ml of the Brady’s reagent to each test tube.  Vortex each mixture and observe each  for the formation of a orange-yellow precipitate or color change.  If no preciptate forms, allow the tubes to sit for ~15 minutes and observe again. Record the results in tabular form in your notebook.
Product Analysis by Gas Chromatography
A gas chromatogram (GC) of an experimental product mixture of 2-methylcyclohexanol is provided in Figure 4.  The chromotogram must be interpreted.
 

Peak @ rt=26.2 min  A = 125.33
Peak @ rt = 27.2 min  A = 496.33
Response Factor = 0.963

Figure 4:  Gas Chromatogram of Product Mixture from Reaction of 2-Methylcyclohexanone with Sodium Borohydride
(Printable Version of Chromatogram)

1.  Label each peak in the chromatogram and list its retention time and area in a table.
2.  Calculate the concentration of each compound that corresponds to each peak in the chromatogram using the information provided in
     the background information about interpretation of the gas chromatogram.  Add this information to the table.
     The relative concentrations of the products is related to the relative stability of the products (­ concentration; ­ stability)
3.  Identify and draw the structure of each product that corresponds to each peak based on:
     a)  your interpretation of the GC and
     b)  your knowledge of the relative stabilities of cis and trans-2-methylcyclohexanol (conformational analysis).

References
Feiser, L.F.; Williamson, K.L. Organic Experiments, 8th Edition, Houghton Mifflin Co.: New York, 1998.
McMurry, John  Organic Chemistry, 4th edition, Brooks/Cole Publishing: Pacific Grove, 1996.
Fox, M.A.; Whitesell, J.K. Organic Chemistry, Jones & Bartlett: Boston, 1994.