The borohydride reduction of a ketone hydrobenzoin from benzil

Formal Report For Organic Chemistry

Multistep Synthesis

Step 1: The Benzoin Condensation: Cyanide Ion Catalyzed

The reaction of two moles of benzaldehyde to form a new carbon-carbon bond is known as the benzoin condensation. It has been catalyzed by two rather different catalysts, cyanide ion and the vitamin, thiamine. Both of which on close examination appear to function in exactly the same way.

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Benzaldehyde MW 106.12

bp 178°C

Benzoin

MW 212.24

mp 135°C

Caution: Do not handle the potassium cyanide if you have open cuts on your hands. Wash your hands immediately after handling the crystals. Never acidify a cyanide solution, HCN gas (the killer) would be given off !

Procedure:

In a round bottom flask place 20 mg of potassium cyanide (POISON!), dissolve the solid in 0.25 mL of water, add 0.50 mL of 95% ethanol and from a micropipette 0.400 mL of pure benzaldehyde. Introduce a stirring bar, and while stirring, reflux the solution gently with the heating block for 30 minutes. Remove the round bottom flask and cool it in an ice bath, and if no crystals appear within a few minutes scratch the inside of the reaction flask to induce crystallization. When the crystallization is complete, remove the solvent by filtration using a Hirsch funnel. Wash the crystals twice with separate 0.4 mL portions of a cold, one to one mixture of 95% ethanol to water. The product is usually colorless crystals with a melting point of 134-135°C. Weigh the dry product and save some solid to take a melting point. 150 mg of dry product is needed for the next step. If your synthesis does not yield over 100 mg, your instructor will provide additional benzoin to make up the difference (a few points will be deducted).

Clean up: This is the most important step in the whole experiment. Discard all filtrate into a waste bottle labeled CYANIDE WASTE in the fume hood. The waste bottle contains 1 % sodium hydroxide and bleach solution (5.25% sodium hypochlorite) that oxidize the cyanide ion.

Step 2: Oxidation of Benzoin to Benzil

Benzoin can be oxidized to the a -diketone, benzil, by a variety of mild oxidizing agents. Too vigorous oxidation by sodium dichromate or potassium permanganate yields chiefly benzaldehyde by cleavage of the bond between the two oxidized carbon atoms, activated by both of the attached phenyl groups. In this procedure, benzoin is oxidized with two equivalents of copper (II) acetate in an acetic acid­-water mixture. Purportedly, this procedure offers the advantage that the benzil obtained is well crystallized and of high purity.

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Procedure:

Weigh out ~150 mg of the benzoin product and calculate the stoichiometric amount of cupric acetate monohydrate necessary, and weigh this out. Add the two solid reactants into a 10 mL round bottom flask. Add 4 mL glacial acetic acid and 1.3 mL distilled water and attach a reflux condenser. After refluxing has started, continue refluxing for fifteen minutes. The reaction mixture must then be filtered hot by normal gravity filtration to remove cuprous oxide. Preheat the funnel on a hot plate and filter into an 50 mL beaker which remains on the hot plate, using a stemless funnel. Rinse the round bottom flask with 0.5 mL of hot acetic acid and transfer this to the filter paper. To the filtrate in the beaker add 10 mL of water and crystallize the product by cooling. The solid product is then filtered with the Hirsch funnel using vacuum and washed with cold water. Dry the crystals under vacuum for around 5 minutes and then dry it by pressing in between a sheet of filter paper. Save this product in a small vial. You will need to save a small portion of the product for a melting point determination. A weight of 50 mg of benzil will be used in the next step. Less benzil may be used by calculating the appropriate reduction of the reactants in the next step or your instructor can provide additional benzil with a deduction from your product grade.

Clean up: After your solid product has been recovered all filtrates may be washed down the sink with water.

Step 3: Borohydride Reduction of a Ketone: Synthesis of Hydrobenzoin

Sodium borohydride, NaBH­­4 is a mild and selective reducing agent. In ethanol solution it reduces aldehydes and ketones rapidly at 25°C. Esters are reduced very slowly, and sodium borohydride is inert toward functional groups that are readily reduced by lithium aluminum hydride, such as, carboxylic acids, epoxides, lactones, nitro groups, nitriles, azides, amides and acid chlorides. The present experiment is a typical sodium borohydride reduction. These same conditions and isolation procedures could be applied to hundreds of other ketones and aldehydes.

Addition of two atoms of hydrogen to benzoin or four atoms of hydrogen to benzil would give a mixture of. stereoisomeric diols as products. The predominant isomer is the nonresolvable (1R, 2S)-hydrobenzoin, which is a meso isomer, accompanied by two enantiomers, the (1R, 2R) and (1S, 2S)- hydrobenzoins. The reaction proceeds rapidly at room temperature. The use of benzil as the starting material allows you to follow the progress of the reduction as the yellow color of benzil disappears and a white product is formed.

Procedure:

In a 10 mL round bottom flask from the microkit, dissolve 50 mg of benzil in 0.5 mL of 95% ethanol and cool the solution in ice to form a fine suspension by stirring it. Add to this suspension 10 mg of sodium borohydride. (This is a large excess.) As the mixture warms up to room temperature, the benzil dissolves and the yellow color of the benzil should disappear in 2-5 minutes. After a total of 10 minutes stirring at room temperature, add 0.5 mL of water into the reaction mixture and heat the solution to boiling in a boiling water bath. If the solution is not clear at this point filter the hot solution and rinse with 0.5 mL of hot ethanol. This is usually not necessary, however, you must check. Then add to the clear hot solution, hot water from a pasteur pipette until cloudiness appears. This may require up to 1.5 mL of hot water. The product will crystallize when the clear solution of reaction mixture is cooled in an ice bath, but by selective crystallization, one isolates only one isomer, the 1R,2S-hydrobenzoin. Collect the product by vacuum filtration using Hirsch funnel. Wash the product with 1 mL of ice cold water and dry the product as before. Save the crystals which can form thin, lustrous plates, m.p. 136-137°C.

Calculate the percent yield and melting points on each product from each step of the synthesis and the total three step procedure. Turn in the final product on an index card with necessary information.

Cleaning Up: The aqueous filtrate should be diluted with water and neutralized with acetic acid to destroy borohvdride before flushing the mixture down the drain.