The overall goal of this procedure, is to remove aldehydes and reactive ketones from mixtures, by liquid-liquid extraction directly with saturated sodium bisulfite in a miscible solvent. This method can help purify mixtures, into their individual components. Specifically, this method can be used to separate compounds that contain aldehyde or ketone functional groups, from other compounds.

The main advantage of this technique is that it is extremely easy to perform and gives very high separation and recovery rates. Following unsuccessful attempts to remove leftover aldehyde reactant from the reaction product using column chromatography, we specifically reacted the contaminate with bisulfite to form a charged adduct, which is removable by liquid-liquid extraction. Demonstrating the procedure will be Maria Boucher and Max Furigay, who are undergraduate research students in my laboratory.

The separation of aromatic aldehydes from a mixture is demonstrated here, for the separation of benzyl butyrate from a one to one mixture with anisaldehyde. Throughout this procedure sodium bisulfite can generate sulfur dioxide gas, thus this protocol should be carried out with proper ventilation, such as in a fume hood. To begin, dissolve 175 microliters of anisaldehyde and 250 microliters of benzyl butyrate in five milliliters of methanol.

Transfer the solution to a separatory funnel add one milliliter of saturated aqueous sodium bisulfite and shake vigorously for approximately 30 seconds. Then, add 25 milliliters of deionized water and 25 milliliters of 10%ethyl acetate hexanes and shake vigorously. Separate the layers.

Dry the organic layer with anhydrous magnesium sulfate. Filter the solution to remove magnesium sulfate. Then, concentrate the solution in vacuo using a rotary evaporator.

The separation of aliphatic aldehydes and ketones from a mixture is demonstrated here through the separation of benzyl butyrate from one to one mixture with benzyl acetone. Dissolve 213 microliters of benzyl acetone and 250 microliters of benzyl butyrate and 10 milliliters of dimethylformamide. After transferring the solution to a separatory funnel add 25 milliliters of saturated aqueous sodium bisulfite, shake the solution vigorously for approximately 30 seconds.

Then, add 25 milliliters of deionized water and 25 milliliters of 10%ethyl acetate hexanes and shake vigorously. If the bi-aqueous layer appears cloudy add more water and shake the separatory funnel again. If you still see a solid after separation filter all of the material through Celite to remove the solid before proceeding to the next step.

Next separate the layers. Return the aqueous layer to the separatory funnel add another 25 milliliters of 10%ethyl acetate hexanes and shake vigorously. Drain the aqueous layer, leaving the organic layer in the separatory funnel.

Then, add the previous organic layer back to the separatory funnel. Wash the combined organic layers three times with deionized water. Dry the organic layer with anhydrous magnesium sulfate.

After filtering the solution to remove magnesium sulfate concentrate in vacuo using a rotary evaporator. The separation of aldehydes from a mixture containing an alkyne is demonstrated here through the separation of benzyl butyrate from a one to one mixture with citronellal Dissolve 255 microliters of citronellal and 250 microliters of benzyl butyrate in ten milliliters of dimethylformamide and transfer the solution to a separatory funnel. Then, add 25 milliliters of saturated aqueous sodium bisulfite and shake vigorously for approximately 30 seconds.

Add 25 milliliters of deionized water and 25 milliliters of hexanes and shake vigorously. Dry the organic layer with anhydrous magnesium sulfate. Filter the solution to remove magnesium sulfate before concentrating in vacuo using a rotary evaporator.

The re-isolation of aldehydes from a mixture is demonstrated here through the separation of piperonyl from a one to one mixture with benzyl butyrate. Dissolve 217 milligrams of piperonyl and 250 microliters of benzyl butyrate in five milliliters of methanol and transfer the solution to a separatory funnel. Add one milliliter of saturated aqueous sodium bisulfite and shake vigorously for approximately 30 seconds.

Then, add 25 milliliters of deionized water and 25 milliliters of 10%ethyl acetate hexanes. After shaking vigorously separate the layers. Return the aqueous layer back to the separatory funnel.

Wash the aqueous layer once with 25 milliliters of 10%ethyl acetate hexanes to remove the small amount of remaining benzyl butyrate. Then, add 25 milliliters of ethyl acetate followed by 50%sodium hydroxide until a pH strip indicates that the pH is 12. Then, shake the solution vigorously.

Gas evolution has been observed during this step and can cause pressure build up. Make sure to properly vent the separatory funnel. Piperonyl, our example aldehyde, is not sensitive to base but aldehydes with enolizable alpha-hydrogens may be unstable to sodium hydroxide.

Substituting saturated sodium phosphate tribasic for sodium hydroxide may mitigate unwanted side reactions caused by a strong base. After separating the layers return the aqueous layer to the separatory funnel. Add 25 milliliters of ethyl acetate and shake vigorously.

After separating the layers combine the organic layer with the organic layer from the previous step before drying. Filter and concentrate the solution as before. The success of this protocol can be judged by proton NMR.

If the protocol is unsuccessful the aldehyde or ketone will remain in the mixture and can be detected by its characteristic signals in the NMR spectrum. Aldehydes have characteristic signals between nine and 10 PPM so the presence of a peak in this region indicates a failed separation. A successful separation will not have a peak in this region and will only contain the peaks associated with the non-aldehyde component of the original mixture.

When using an alkyne containing mixture side reactions with the alkyne are sometimes observed. These can be detected by the appearance of peaks unassociated with either original component. This problem can be mitigated by using hexanes, a solvent with low sulfur dioxide solubility, which is responsible for the unwanted side reactions.

A successful separation will not contain peaks in the NMR unassociated with the original components. When re-isolating the aldehyde a small amount of the other component can be detected by proton NMR. This component can be nearly entirely removed by performing the optional wash of the aqueous layer prior to reversing the bisulfite reaction.

Once mastered this technique can be done in 15 minutes if performed properly. This protocol is effective for aromatic and aliphatic aldehydes including sterically hindered neopentyl aldehydes. Methyl and cyclic ketones can be removed while sterically more hindered or conjugated ketones are unreactive.

Nearly all functional groups are tolerated in the protocol including electrophilic functional groups such as epoxides or benzyl chlorides. One exception is aliphatic amines, which undergo an acid base reaction with bisulfite and are therefore partially ionized during the protocol.