Cannizzaro Reaction
TLDRThe Cannizzaro reaction, a classic in organic chemistry, involves the disproportionation of a non-enolizable aldehyde into an alcohol and a carboxylic acid. Discovered by Stanislao Cannizzaro in 1853, it highlights the early empirical nature of organic chemistry. Although its synthetic utility is limited due to better alternatives, it's crucial for understanding aldehyde reactivity under basic conditions. The complex mechanism involves hydride transfer, and recent studies have shown its potential for intramolecular reactions and enantioselective synthesis, keeping Cannizzaro's legacy vibrant in modern chemistry.
Takeaways
- 🔍 The Cannizzaro reaction is a chemical process involving the disproportionation of two equivalents of a non-enolizable aldehyde, resulting in the formation of an alcohol and a carboxylic acid.
- 👨🔬 Discovered by Stanislao Cannizzaro in 1853, the reaction is named after him and was first observed with benzaldehyde and aqueous sodium hydroxide, yielding benzoic acid and benzyl alcohol.
- 🧪 The reaction occurs under strongly basic conditions, and the products are often water-soluble salts, such as sodium benzoate, which can be separated by extraction.
- 😄 A humorous anecdote about Cannizzaro's supposed limited resources in the lab, which led to the discovery of the reaction, highlights the empirical nature of early organic chemistry.
- 🚫 The Cannizzaro reaction is not suitable for enolizable aldehydes, as they tend to form enolates and undergo aldol reactions instead.
- 🔑 Synthetic utility of the Cannizzaro reaction is limited due to more efficient methods available for converting aldehydes to carboxylic acids or alcohols.
- ⚠️ Chemists must be aware of the potential for Cannizzaro reactions when planning reactions of aldehydes under basic conditions, to avoid unwanted side reactions.
- 🌐 The mechanism of the Cannizzaro reaction involves a complex series of steps, including the formation of a dianion and the transfer of a hydride to another aldehyde molecule.
- 🔄 The rate equation for the reaction is second order in aldehyde and between one and two orders in hydroxide ion, indicating a complex role for the base.
- 🔬 Applications of the Cannizzaro reaction include crossed-aldol reactions and intramolecular hydride transfer in molecules with adjacent carbonyl groups.
- 🌟 Recent studies, such as one by Xiaoming Feng in 2015, have demonstrated the potential for enantioselective Cannizzaro reactions using chiral catalysts and strong nucleophilic bases.
Q & A
What is the Cannizzaro reaction?
-The Cannizzaro reaction is a chemical reaction that involves the disproportionation of two equivalents of a non-enolizable aldehyde, resulting in the formation of one equivalent of an alcohol and one equivalent of a carboxylic acid.
Who discovered the Cannizzaro reaction?
-The Cannizzaro reaction was discovered by Italian chemist Stanislao Cannizzaro at the University of Palermo in Sicily, and he published his results in 1853.
What are the products of the Cannizzaro reaction involving benzaldehyde?
-In the case of benzaldehyde, the reaction yields one molecule of benzoic acid and one of benzyl alcohol, with the actual product being sodium benzoate due to the strongly basic conditions of the reaction.
How can benzyl alcohol be separated from sodium benzoate after the Cannizzaro reaction?
-Benzyl alcohol can be separated from sodium benzoate by extraction into ether, followed by the addition of dilute hydrochloric acid to protonate the benzoate and yield benzoic acid.
Why is the synthetic utility of the Cannizzaro reaction limited?
-The synthetic utility of the Cannizzaro reaction is limited because there are better methods available for oxidizing an aldehyde to a carboxylic acid or reducing it to an alcohol.
What is the significance of the Cannizzaro reaction in planning reactions of aldehydes under basic conditions?
-It is important to be aware of the Cannizzaro reaction's reactivity when planning reactions of aldehydes under basic conditions to avoid unwanted side reactions, such as the formation of methanol and formic acid when using formaldehyde.
What is the role of hydroxide ion in the rate equation of the Cannizzaro reaction?
-The rate equation of the Cannizzaro reaction is second order in aldehyde and partially second-order in hydroxide ion, indicating a complex role for the base in the reaction mechanism.
What is the key step in the mechanism of the Cannizzaro reaction?
-The key step in the Cannizzaro reaction mechanism is the irreversible expulsion of a hydride from a dianion, which is then passed to a second molecule of neutral aldehyde, forming a carboxylate and an alkoxide.
How can the Cannizzaro reaction be applied in crossed-aldol reactions?
-The Cannizzaro reaction may be observed in crossed-aldol reactions when an enolizable, substituted aldehyde is reacted with a non-enolizable, reactive aldehyde, preventing homo aldol reactions and allowing for the formation of the desired crossed-aldol product.
What is an example of a clever synthetic application of the Cannizzaro reaction?
-A clever synthetic application of the Cannizzaro reaction involves the intramolecular hydride transfer in a molecule containing two carbonyl groups that are not enolizable, such as the transformation to yield mandelic acid.
How can the Cannizzaro reaction be made enantioselective?
-The Cannizzaro reaction can be made enantioselective by using a chiral catalyst to guide the reaction, which must be very effective to overshadow the uncatalyzed, racemic-producing reaction.
What is the significance of the study by Xiaoming Feng from Sichuan University in the context of the Cannizzaro reaction?
-Xiaoming Feng's study highlights the intramolecular nature of the Cannizzaro reaction, the catalytic potential of metal salts like iron(III), and the possibility of using other strong nucleophilic bases besides hydroxide ion, contributing to the advancement of the reaction's synthetic applications.
Outlines
🧪 Cannizzaro Reaction Overview
The Cannizzaro reaction is a classic organic chemistry reaction that involves the disproportionation of a non-enolizable aldehyde into an alcohol and a carboxylic acid. Discovered by Stanislao Cannizzaro in 1853, the reaction typically occurs in an aqueous sodium hydroxide solution, resulting in the formation of a carboxylate and an alcohol. The reaction is characterized by its second-order dependence on the aldehyde and a complex order with respect to hydroxide ions, indicating a more intricate role for the base. The mechanism involves the formation of a dianion intermediate, which then undergoes an irreversible hydride transfer to a second aldehyde molecule. While the synthetic utility of the reaction is limited due to more efficient methods for aldehyde oxidation and reduction, it is crucial to be aware of its potential side reactions, particularly with aldehydes under basic conditions.
🔍 Applications and Mechanistic Insights of the Cannizzaro Reaction
Beyond its historical significance, the Cannizzaro reaction has found creative applications in synthetic chemistry. It can be observed in crossed-aldol reactions, where a non-enolizable aldehyde reacts with an enolizable one, preventing homo aldol reactions and yielding the desired product in high yield. Furthermore, the reaction can be harnessed for intramolecular hydride transfer, as demonstrated by the conversion of a molecule with two carbonyl groups into mandelic acid. Recent advancements, such as the work by Xiaoming Feng in 2015, have shown that the reaction can be made enantioselective with the use of a chiral catalyst, overcoming the racemic outcome and allowing for the synthesis of optically pure compounds. The study also highlighted that the reaction can proceed without hydroxide ions, utilizing other strong nucleophilic bases, and that the reaction can be catalyzed by metal salts, expanding the synthetic potential of the Cannizzaro reaction.
Mindmap
Keywords
💡Cannizzaro Reaction
💡Disproportionation
💡Non-enolizable Aldehyde
💡Aldol Reaction
💡Synthetic Utility
💡Enolate
💡Catalyst
💡Enantioselectivity
💡Intramolecular Reaction
💡Chiral Template
💡Mandelic Acid
Highlights
The Cannizzaro reaction involves the disproportionation of two equivalents of a non-enolizable aldehyde, producing an alcohol and a carboxylic acid.
The reaction was discovered by Italian chemist Stanislao Cannizzaro in 1853.
In the original formulation, benzaldehyde reacts with aqueous sodium hydroxide to yield benzoic acid and benzyl alcohol.
The product is actually sodium benzoate, which is water-soluble, allowing for extraction and separation of benzyl alcohol.
The enduring joke about Cannizzaro's limited lab resources leading to his name reaction is highlighted.
The reaction is general for non-enolizable aldehydes but has limited synthetic utility due to better methods for oxidation and reduction.
Aldol reactions are a competing pathway for enolizable aldehydes under basic conditions.
The Cannizzaro reaction mechanism involves a complex rate equation with second-order dependence on aldehyde and a fractional order on hydroxide ion.
The key step in the mechanism is the irreversible expulsion of a hydride from a dianion, leading to the formation of a carboxylate and alkoxide.
Crossed-aldol reactions can lead to Cannizzaro reactions if not carefully controlled, as demonstrated with cyclohexyl carboxaldehyde and formaldehyde.
Intramolecular hydride transfer is possible with adjacent carbonyls on the same molecule, as shown in the synthesis of mandelic acid.
The Cannizzaro reaction can be made enantioselective using a chiral catalyst to guide the reaction.
Xiaoming Feng's 2015 study from Sichuan University demonstrates intra- and intermolecular Cannizzaro reactions and the use of metal catalysts.
The hydroxide ion is not strictly required for the reaction; any strong nucleophilic base can initiate the hydrogen transfer.
The Cannizzaro reaction has been creatively applied in synthetic chemistry, with numerous innovative uses beyond its initial discovery.
The old chemistry of the Cannizzaro reaction is still relevant and utilized in modern organic synthesis.
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