Monosaccharides - Kiliani-Fischer: Videos & Practice Problems

The Kiliani-Fischer Synthesis is a method used to extend monosaccharide chains, transforming simpler sugars into more complex forms. This process leverages the versatility of saccharides, which contain functional groups such as alcohols and carbonyls. A key aspect of this synthesis is the nucleophilic addition reaction involving aldehydes, where hydrogen cyanide (HCN) reacts with an aldehyde to form a cyanohydrin. This reaction is reminiscent of the mechanisms studied in carbonyl chemistry, where the cyanide ion (CN^-) attacks the carbonyl carbon, resulting in a new functional group.

To extend the carbon chain, the cyano group can be hydrolyzed and reduced to form a new aldehyde. The reduction of the cyano group typically involves a selective reducing agent that converts the cyano group (C≡N) to an imine (C=N) without fully reducing it to an amine (C-NH₂). This imine can then undergo hydrolysis, converting the nitrogen to an oxygen and yielding a new aldehyde. The overall reaction can be summarized as follows:

1. Formation of cyanohydrin:
RCHO + HCN → RCH(OH)C≡N

2. Reduction of cyano group:
RCH(OH)C≡N → RCH(OH)C=N (using a selective reducing agent)

3. Hydrolysis of imine:
RCH(OH)C=N + H₂O → RCH(OH)C=O + NH₃

This cycle can be repeated multiple times, allowing for the transformation of a pentose sugar into a hexose or even longer chains. However, a notable limitation of the Kiliani-Fischer Synthesis is the generation of a mixture of stereoisomers at each chiral center introduced during the process. As the synthesis progresses, the chirality at certain carbons becomes ambiguous, leading to a mixture of configurations. This results in a blend of diastereomers, which may exhibit different physical properties, complicating the purification and characterization of the final product.

In summary, the Kiliani-Fischer Synthesis is a powerful technique for elongating monosaccharide chains, utilizing established reactions from carbonyl chemistry while introducing challenges related to stereochemistry and product purity.

The modern Kiliani-Fischer synthesis is an important reaction in organic chemistry that builds upon the foundational work of chemists Kiliani and Fischer. Initially, the synthesis involved the formation of a cyanohydrin through the addition of a cyanide (CN) group, which remains a key step in the modern version. However, advancements in reagents have significantly improved the efficiency and yield of the reaction.

In the modern approach, a new reducing agent is employed, specifically hydrogen (H₂) in combination with palladium on barium sulfate (Pd/BaSO₄). This catalyst is referred to as a "poison" reducing agent, indicating that it is less reactive than standard catalysts. The term "poison" in this context means that the catalyst is designed to selectively reduce the cyanide group to an imine (C=NH) rather than fully reducing it to an amine (NH₂), which would occur with a typical catalytic hydrogenation.

Once the imine is formed, it undergoes hydrolysis, a process that converts the imine back into a carbonyl compound, specifically an aldehyde. This reaction is facilitated by the presence of water in an aqueous solution. The resulting product is an alcohol, and due to the nature of the reaction, a mixture of diastereomers is produced, as the exact position of the hydroxyl (OH) group attachment can vary.

In summary, the modern Kiliani-Fischer synthesis utilizes palladium on barium sulfate as a selective reducing agent to convert cyanohydrins into imines, which are then hydrolyzed to yield aldehydes. Understanding each step of this process, including the formation of intermediates and the final products, is crucial for mastering this synthesis in organic chemistry.