Sodium borohydride reduction of a ketone
Preparation of meso-hydrobenzoin

Purpose
In this laboratory we will use sodium borohydride as a reducing agent to convert a ketone to a 2° alcohol. In this reaction the starting material (benzil) is difunctional, giving rise to a product (hydrobenzoin) with two alcohol groups.


Interestingly, this reaction is diastereoselective, yielding almost exclusively the (R,S)- or meso-hydrobenzoin. Below is a mechanism consistent with this observation.

It is interesting to note the many ways that hydrogen is used in organic synthesis. We often think of hydrogen in its role as an acid, written as H+ and described simply as a proton. We have described the extremely reactive hydrogen atom, H., in our discussion of radical reactions. In lecture we have also learned of the reaction that hydrogen molecules, H2, can affect via catalytic hydrogenation.

This laboratory demonstrates yet another mode of hydrogen reactivity, as the strongly nucleophilic hydride anion, H:, is used. This anion is attracted to the partial positive charge of the carbon in the carbonyl group. Since the carbonyl has a π bond which can break, no leaving group is involved. Thus, this mechanism is referred to as nucleophilic addition, rather than the familiar nucleophilic substitution.

Procedure
 Into the flat-bottomed culture tube, add 2.5 mmol benzil and 4 mL 95% ethanol. Cap the tube and swirl for a minute or so (note that the benzil will not completely dissolve). Add 2.5 mmol sodium borohydride. Use about 1 mL 95% ethanol to wash any of the powder down the walls of the tube and into the liquid. Loosely cap the tube and observe as the reaction takes place, swirling occasionally. The reaction should be complete about 10 minutes after adding the borohydride reagent.

To hydrolyze the borate ester which has formed, add 5 mL water, replace the cap loosely and gently heat just to a boil. If the resultant solution is not clear, filter through a cotton plug (usually not necessary). Add more water until the solution begins to appear cloudy, or to a maximum of 10 mL. Set the solution aside to crystallize. The product should form as "lustrous thin plates."1 Cool for 20-30 minutes in an ice water bath and filter on a small Büchner funnel. Move the filter paper and crystals to a labelled watch glass and set aside in your locker. Determine mass, yield and melting point next week.

Prelab Questions

  1. Using online resources, find safety information about the reagents/product
  2. Based on your data, which material must be handled most cautiously?
  3. In this reaction, the diketone is reduced to a diol. The borohydride, BH4- is oxidized to BH2O3-. Based on this information, write the balanced chemical reaction.
  4. What is the mass (in grams) of 2.5 mmol of benzil?
  5. What is the mass (in grams) of 2.5 mmol of sodium borohydride?
  6. What is the limiting reagent?
  7. What is the theoretical yield, assuming you begin with exactly 2.5 mmol of each reagents?
  8. What is the melting point of the product?

Endnotes

1. Adapted from Macroscale and Microscale Organic Experiments, by Kenneth L. Williamson, DC Heath and Company, Lexington, MA, 1989.
Resources

Background material

Todd, D. J. Chem. Educ. 1979, 56, 540; Rowland, A. T. J. Chem. Educ. 1983, 60, 1084.
Cram, D. J.; Kopecky, K. R. J. Am. Chem. Soc. 1959, 81, 2748.
Chemical Safety Data:

Online sources for melting point, formula weight, etc.

Chemical calculations needed to complete lab: