Formation Of Racemic Mixture With Sodium Borohydride

Abstract

When 4-tert-butylcyclohexanone is microwaved in sodium borohydride and silica gel, a racemic mixture is formed. The racemic mixture is cis/trans-4-t-cyclohexanol. The reaction scheme can be seen in Figure 1.

Figure 1: Mechanism for the reduction of 4-t-butylcyclohexanone shown using chair conformations. The major product is the trans product.

To determine the major product, an NMR spectroscopy is done. When examining the 1H NMR, the peaks must be measured and compared to determine which has the highest diastereometric ratio. The major product for this reaction is the trans form.

Experimental:

Instruments Used:

To evaporate all the extra solvent, a Buchi Rotovapor R-300 was used. To determine the to figure out the Infrared Spectroscopy, the FT-IR spectrophotometer Nicolet Ik100FT-IR was used. To determine the melting point, a Thomas Hoover Uni-Melt was used.

Procedure:1

The glassware was dried before any reagents were added. Sodium borohydride (0.220g), 4-tert-butylcyclohexanone (0.481g), and silica gel (0.420g) were all combined into a mortar and grinded to form a fine powder. The contents were poured into a reaction vial with a magnetic stir bar. A cap was placed onto the vial and the vial was placed into a microwave chamber. The vial sat in the microwave chamber for five minutes at 60°C and then left to cool for five minutes. Once cooled, ethyl acetate (2mL) was added to extract the alcohol. The mixture was filtered through a Pasteur pipet that was plugged with cotton. The filtered mixture was pipetted into a pre-weighed 25 mL round-bottom flask. The flask was attached to a rotary evaporator and the solvent was removed. The round bottom flask was hit with some pressurized air to solidify the product. The round-bottom flask was put into the drawer until the next week.

The next week the sample was weighed and it was determined that the product weighed 0.301 grams. A few drops of product were placed in a test tube and deuterated chloroform was added to melt it. This was transferred into a Nuclear Magnetic Resonance tube. The product and deuterated chloroform was placed into the NMR to find the 1H NMR. This was done to determine the diastereoselectivity. A KBr pallet was formed using some of the product and an Infrared Spectroscopy was performed. The melting point was determined to be 52°C.

Results and Discussion

The reduction of a ketone to form an alcohol is a very common reaction done in labs. Reduction refers to the addition of a hydrogen, and in the case of the experiment, a hydrogen to the ketone molecule to form an alcohol1. The NaBH4 was used as the reducing agent while the silica gel was used to support the formation of the 4-t-butylcyclohexanol. The ethyl acetate is used to extract the alcohol off the silica gel support. This process can be seen in Figure 1 of the abstract. The percent yield of the reaction was 61.806%. Some sources of error that occurred were loss of some reactants while transferring them to different glassware. Also, more ethyl acetate was added than was needed to maximize the yield.

Diastereoselectivity was calculated using the area of the signal at the 3.5ppm which is where the trans- isomer would show up, divided by the area of the 4.0ppm (cis-isomer) signal plus the area of the 3.5ppm signal all multiplied by 100% to get the amount of the trans- isomer. The product came out to be 85.372% of the trans-isomer. The melting point of the product that was produced was 52℃. The literature value for melting point is 60-69℃; the melting point of the product produced was lower most likely due to some impurities.

Compared to the traditional procedure, the procedure using the microwave instrument was much faster and did not involve an extraction step using HCl. The microwave-assisted procedure used principles from the idea of green chemistry too. The use of the solid support, silica gel, helped to decrease the number of chemicals that were used which reduces waste, as well as the use of the microwave as a heat source to reduce reaction times making it more energy efficient. As compared to the old procedure, the loss of the extraction step made the procedure much “greener” by the philosophy of green chemistry2.

Conclusion

During the microwave-assisted reduction of the 4-t-butylcyclohexanone the product, 4-t-butylcyclohexanol, was formed. The product has both cis and trans forms, while over 85% of the product is in the trans configuration as seen in the H NMR spectra. IR data is also shown in the appendix.