Separation of Aldehydes and Reactive Ketones from Mixtures Using a Bisulfite Extraction Protocol

Here, we present a protocol to remove aldehydes and reactive ketones from mixtures by a liquid-liquid extraction protocol directly with saturated sodium bisulfite in a miscible solvent. This combined protocol is rapid and facile to perform. The aldehyde or ketone can be re-isolated by the basification of the aqueous layer.

The purification of organic compounds is an essential component of routine synthetic operations. The ability to remove contaminants into an aqueous layer by generating a charged structure provides an opportunity to use extraction as a simple purification technique. By combining the use of a miscible organic solvent with saturated sodium bisulfite, aldehydes and reactive ketones can be successfully transformed into charged bisulfite adducts that can then be separated from other organic components of a mixture by the introduction of an immiscible organic layer. Here, we describe a simple protocol for the removal of aldehydes, including sterically-hindered neopentyl aldehydes and some ketones, from chemical mixtures. Ketones can be separated if they are sterically unhindered cyclic or methyl ketones. For aliphatic aldehydes and ketones, dimethylformamide is used as the miscible solvent to improve removal rates. The bisulfite addition reaction can be reversed by basification of the aqueous layer, allowing for the re-isolation of the reactive carbonyl component of a mixture.

The separation of components of mixtures from one another is essential to the preparation of pure materials. The method described herein allows for the facile separation of aldehydes and sterically unhindered cyclic and methyl ketones from other organic molecules¹. The technique relies on the reactivity of bisulfite with the carbonyl group to create a charged adduct that can be separated into an aqueous layer, while other components separate into an immiscible organic layer. The key to achieving reactivity between bisulfite and the carbonyl is the use of a miscible solvent, which allows the reaction to take place prior to the separation into se....

1. Standard Protocol for The Separation of Aromatic Aldehydes from a Mixture. Example: Separation of Benzyl Butyrate from a 1:1 Mixture with Anisaldehyde.

1. Dissolve 175 μL of anisaldehyde and 250 μL of benzyl butyrate in 5 mL of methanol and transfer the solution to a separatory funnel.
   Caution: Sodium bisulfite can generate sulfur dioxide gas, thus this protocol should be carried out with proper ventilation, such as in a fume hood.
2. Add 1 mL of saturated aqueous sodium bisulfite and shake vigorously for approximately 30 s.
3. Add 25 mL of deionized water and 25 mL of 10% ethyl acetate/hexanes and shake vigorously.

Procedure 1 for aldehyde removal is used for aromatic aldehydes. Procedure 2, in which dimethylformamide is used as the miscible solvent, should be used for aliphatic aldehydes and ketones. Procedure 2 should also be used for mixtures that are not fully soluble in methanol. The material obtained from each of the protocols is analyzed for purity using ¹H NMR integration analysis and for recovery rate by mass. Typical purities an.......

Initial attempts to use the bisulfite reaction as a method to remove aldehydes using a typical two-phase extraction led to very low levels of removal. We hypothesized that the reaction was not fast enough to occur during the very limited time that the two layers were in contact. To increase the contact between the reactants, we developed a two-stage extraction protocol in which a water-miscible solvent is used initially to allow sufficient mixing of the reactants prior to the introduction of an immiscible solvent. The in.......

The authors have nothing to disclose.

Acknowledgment is made to the Donors of the American Chemical Society Petroleum Research Fund for partial support of this research. We are grateful to the National Science Foundation (CHE-0619275 and CHE-0963165) for renovation and instrumentation grants that supported this research.