CHEM 286L – Organic Chemistry Laboratory II Synthesis of Sulcatol (PDF)

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					                                 D E PA RT M E N T O F C H E M I S T RY

                            CHEM 286L – Organic Chemistry Laboratory II

                                                Synthesis of Sulcatol (Part 1)

Introduction Sodium borohydride reduction is a convenient way to synthesize alcohols from aldehydes or ketones.
                If the ketone starting material is unsymmetrically substituted, the resulting alcohol will be chiral.
                However, as the carbonyl group is planar, the reducing agent can transfer the hydride ion as easily
                from the top of the molecule as from the bottom and a racemic mixture is produced. TLC can easily
                check the progress of the reduction, as the alcohol product generally has smaller Rf values that the
                ketone starting material.

 Chemical       The 6-methyl-5-hepten-2-one will be reduced to the corresponding alcohol (sulcatol) and the product

  reaction      will be purified by distillation in the second part of the experiment.

                                              O                                 OH
                                                                1. NaBH4

                                                                2. H+, H2O

 Textbook       Sodium borohydride reductions involve nucleophilic addition of hydride ions (H-) to the carbonyl

 reference      carbon, but apparently no free hydride ions are generated. Kinetic evidence suggests that the solvent
                plays a role, but it is probably easier to think of the process in terms of steric hindrance on the boron.
                After the first hydride is transferred, the boron will coordinate with either the newly formed alcohol or
                a solvent molecule. If it binds the newly reduced alcohol, it will depend on the size of it whether
                another hydride transfer is possible.
Chapter 17.6

Chapter 19.1
                              D E PA RT M E N T O F C H E M I S T RY

                                           O                     BH3                R    O   O
                                                             O         Na                  B
                             NaBH4 +                                                                     Na
                                       R                                                  H H R

                                                      OMe H
                        OH        OH   H2O, HCl          B
                                                       O   OMe          Na              OMe     OMe      Na
                             +    B                                                           B
                    R          HO   OH                                                       H H

 Safety      Sodium borohydride is toxic and corrosive, and it can react violently with concentrated acids,

Concerns     oxidizing agents, and other substances. Avoid contact with it, do not breath its dust, and work in your

Procedure    At the start of the lab period, you will be given a 10-dram vial containing you ketone (2 g) and a
             1-dram vial containing you NaBH4 (0.25 g).

             Into the 10-dram vial, add 15 mL of aqueous methanol (70%, already prepared), and a stir bar. Place
  Step 1
             the vial into an ice-bath and begin stirring the mixture, allow it to cool down to about 5 oC. When the
             solution is cooled, using a spatula, start adding the NaBH4 in small portions over a 5 minutes period.
             After the complete addition of NaBH4, remove the ice-bath and allow the reaction to stir for 30

             In this step you will check the completion of your reaction by TLC. You will use TLC on silica gel,
  Step 2
             with petroleum ether/ethyl acetate : 6/1 as eluent. You will need to develop your TLC using an iodine
             chamber to be able to visualize your compounds. So pay attention to your Instructor “Demo”.
             Run a TLC after 5 minutes and after 20 minutes to follow the progress of your reduction reaction.

             When the TLC confirms that the reaction is complete (i.e. complete disappearance of your starting
             material), add water (8 mL), carefully followed by HCl (6 M) until the pH reaches approximately 2.
  Step 3
             This step will be performed using your separatory funnel in your hood. Transfer your reaction mixture
             to your separatory funnel and extract the aqueous solution with diethyl ether (3 x 10 mL). Combine
Extraction   the ether extracts in an Erlenmeyer, discard the aqueous, layer and clean your separatory funnel.
  Step 4
                              D E PA RT M E N T O F C H E M I S T RY

            Transfer your ether layer in your funnel and wash it with brine (15 mL).

            Dry the ether layer over magnesium sulfate and filter it into your 100 mL round-bottom flask.
            Remove the ether using either a stream of pressured air, or a warm water bath in your hood. Stopper
 Step 5
            your flask and store it until the next lab period.

Questions      1. What is the purpose of adding the 6 M HCl solution at the end of your reaction?

  and          2. What is the purpose of doing thin-layer chromatography in this synthesis?
Exercises      3. What reducing reagents (reaction conditions) would you use for the following transformations?

                  O                          HO                                O                         OH
                                     ?                                                   ?

                  O                               O                                                       O
                                     ?                                          O        ?
                          O                                OH
                                                                           O                        OH
                  O                                   OH
                                         ?                                               ?
                              OCH3                                  OCH3
                                                                                    O                     O
                          O                                     O