CH 2280 Procedure for Sodium Borohydride Reduction

Materials From the Chemicals Hood: From the Stockroom (Blue Bin): Week one: Week two: 1” stirbar Ethanol 3-(1-hydroxyethyl)aniline Stirbar retriever Sodium borohydride 3-(1-hydroxyethyl) 3 M hydrochloric acid nitrobenzene Diethyl ether 3-aminoacetophenone Brine Dichloromethane Sodium bicarbonate aqueous 97% dichloromethane/ Separatory funnel solution 3% methanol solution Glass stopper Sodium sulfate

Introduction Sodium borohydride (NaBH4) is a fairly stable white crystalline substance that will decompose on contact with water. Each unit of NaBH4 contains four active hydrogens that can take part in a reduction.

Safety Sodium borohydride is harmful if swallowed, inhaled or absorbed through the skin. It decomposes into flammable hydrogen gas and should be handled in the hood. Diethyl ether is volatile and flammable, use only in the hoods.

Procedure Dissolve 1.5 g of your product from the Sn/HCl reduction in about 40 mL of ethanol in a 125 mL Erlenmeyer flask containing a one-inch magnetic stir bar. If you do not have 1.5 g of product from the Sn/HCl reaction you must get some 3-aminoacetophenone (also called m-aminoacetophenone) from the balance room to make your starting material weigh 1.5 g. Add about 1.5 g of NaBH4. Stir the mixture at ambient temperature for 20 minutes.

After 20 minutes of stirring, cool the reaction mixture in an ice bath for 10 min while swirling occasionally. Destroy the remaining borohydride and any complexes it may have formed by carefully adding FIRST about 30 mL of water (add one “squirt” of the plastic disposable pipet at a time) and SECOND 4-8 mL of 3M HCl SLOWLY. (It will bubble and foam!). Make sure the solution is neutral. (Use pH paper on side shelf.) To check the pH of a solution, tear off a strip of paper ~1 inch long, dip your clean glass stirring rod into the solution and touch it to the pH paper. Rinse the glass rod off with water between uses.

The resulting mixture is warmed IN a steam bath for 10 minutes to complete the decomposition of the intermediate complex and then cooled in an ice-water bath. The cooled solution is extracted with ether (diethyl ether) (3 x 20 mL) (SEPARATORY FUNNEL). The first addition of 20 mL of ether may not result in formation of two layers after you shake the mixture. This is because there is ethanol along with the water and ether. Ethanol is soluble in water and ether is soluble in ethanol. If you do not see two layers, add another 20 mL of ether, shake the mixture as before and the ether layer should separate on the top. If you still do not see two layers, add 20 mL of brine (saturated aqueous NaCl) and shake the separatory funnel again. Continue ether extractions with 20 mL portions. The ether extracts are combined and washed successively with H2O (25 mL) and aqueous NaHCO3 (25 mL).

After the aqueous washes are removed the ether layer is removed to an Erlenmeyer flask, dried (Na2SO4), gravity filtered (using fluted filter paper and stemless plastic funnel) or decanted into another clean, dry Erlenmeyer flask, and the filtrate evaporated on a steam bath with a wooden stick in the ether to aid boiling. The residue will probably form an oil. Label the flask and let it stand until next period.

Next lab period characterize your purified product by TLC, IR, NMR and mp (if you have a recrystallized solid). Weigh it and record the percent yield in your notebook. Dissolve your compound in dichloromethane (DCM) in a test tube to prepare a sample for TLC. Commercial samples of the three possible compounds are available in the balance room for TLC comparison. The TLC solvent is 97% dichloromethane/3% methanol. It has been prepared and is in the hood.

What is the structure of your final product? Compare your spectra with those on the website. Write your results in your notebook. This should include correlations of functional groups with peaks in the IR spectrum and which protons correspond to the signals and splitting patterns in your NMR spectrum.

Disposal The aqueous extracts from the reaction can be poured into the Acidic Waste bottle. The sodium sulfate drying agent should be placed in the solid organic waste bucket. Ethanol filtrate goes into the Flammable Organic Waste bottle in the hood. The TLC developing solvent and your DCM solution of your purified compound should be disposed of in the Halogenated Waste bottle.