Aldehydes, Ketones & Carboxylic Acids - Cross Cannizzaro Reaction

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Introduction

  • The Cross Cannizzaro Reaction is a type of organic redox reaction.
  • It involves the oxidation of an aldehyde and the reduction of a ketone simultaneously.
  • This reaction takes place in the presence of a strong base and alcohol.
  • It is named after the Italian chemist Stanislao Cannizzaro.

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Reaction Mechanism

  1. A strong base, such as hydroxide ion (OH-), abstracts a proton from the aldehyde to form a carbanion intermediate.
  1. The carbanion attacks the carbonyl carbon of the ketone, leading to the formation of an alkoxide ion and an alcohol.
  1. The alkoxide ion is then protonated by water to give the corresponding alcohol.
  1. The carbonyl carbon of the aldehyde is oxidized to a carboxylate ion during the reaction.

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Example

  • Let’s consider the reaction between formaldehyde (CH2O) and acetone (CH3COCH3). HCHO + CH3COCH3 -> CH3CH2OH + CH3COO-
  • Formaldehyde is oxidized to form methanol (CH3OH), while acetone is reduced to form ethanol (CH3CH2OH).

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Importance

  • The Cross Cannizzaro Reaction is important for synthesizing primary alcohols from aldehydes and ketones.
  • It provides a useful tool for the conversion of aldehydes and ketones into alcohols.
  • The reaction is commonly used in organic synthesis for the preparation of various chemical compounds.

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Application

  • The Cross Cannizzaro Reaction can be used for the conversion of aldehydes and ketones into their corresponding alcohols.
  • It is utilized in the pharmaceutical industry for the production of drugs and intermediates.
  • This reaction also finds application in the synthesis of various flavoring agents and fragrances.

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Limitations

  • The Cross Cannizzaro Reaction is not suitable for all aldehydes and ketones.
  • Aldehydes and ketones with strong electron-donating groups or bulky substituents may not undergo this reaction.
  • Some aldehydes and ketones may undergo side reactions, such as aldol condensation, instead of the Cross Cannizzaro Reaction.

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Industrial Use

  • The Cross Cannizzaro Reaction is employed in the industrial production of certain alcohols.
  • It is used for manufacturing large-scale quantities of primary alcohols from aldehydes and ketones.
  • The reaction conditions can be optimized to achieve high yields and efficiency in large-scale production.

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Importance in Pharmaceutical Industry

  • The Cross Cannizzaro Reaction is extensively used in the synthesis of pharmaceuticals.
  • It allows for the efficient conversion of aldehydes and ketones into alcohol intermediates.
  • These alcohol intermediates serve as building blocks for the synthesis of complex drug molecules.

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Safety Considerations

  • The Cross Cannizzaro Reaction involves the use of strong bases, such as hydroxide ions.
  • Caution should be taken while handling strong bases as they can cause skin and eye irritation.
  • Proper safety measures, such as wearing gloves and safety goggles, should be followed during the reaction.

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Summary

  • The Cross Cannizzaro Reaction is a valuable tool for the conversion of aldehydes and ketones into alcohols.
  • The reaction involves the simultaneous oxidation of an aldehyde and reduction of a ketone.
  • It is commonly used in organic synthesis and finds application in the pharmaceutical and fragrance industries.
  • Safety precautions should be followed while handling strong bases during this reaction. “slide 11”

Factors Affecting the Cross Cannizzaro Reaction

  • Reactant concentration: Higher concentrations of aldehyde and ketone increase the rate of the reaction.
  • Temperature: Higher temperatures generally lead to faster reaction rates.
  • Solvent: The choice of solvent can influence the reaction rate and selectivity.
  • Nature of the base: Strong bases like hydroxide ion (OH-) are commonly used for the reaction.
  • Steric hindrance: Bulky substituents can hinder the reaction and affect the yield.

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Solvent Effects

  • The choice of solvent can impact the selectivity and rate of the Cross Cannizzaro Reaction.
  • Generally, polar solvents such as water, ethanol, or methanol are used.
  • These solvents provide a suitable medium for the reaction to occur.
  • The polarity of the solvent affects the stability of the reaction intermediates and the rate of the reaction.

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Role of Hydroxide Ion

  • Hydroxide ion (OH-) acts as a strong base and abstracts a proton from the aldehyde.
  • This deprotonation leads to the formation of the carbanion intermediate.
  • The carbanion then attacks the carbonyl carbon of the ketone, resulting in the formation of the alkoxide ion.

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Example Equation

  • Let’s consider the reaction between formaldehyde and acetone in the presence of hydroxide ion: HCHO + CH3COCH3 + OH- -> CH3CH2OH + CH3COO-
  • Formaldehyde is oxidized to methanol, while acetone is reduced to ethanol.

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Mechanism of Oxidation

  • The carbonyl carbon of the aldehyde is oxidized to a carboxylate ion during the Cross Cannizzaro Reaction.
  • This oxidation involves the transfer of a hydride ion from the aldehyde to the solvent or base.

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Mechanism of Reduction

  • The carbonyl carbon of the ketone is reduced to an alcohol during the Cross Cannizzaro Reaction.
  • This reduction involves the transfer of a hydride ion from the aldehyde to the carbonyl carbon of the ketone.

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Scope of Substrates

  • The Cross Cannizzaro Reaction can be applied to a variety of aldehydes and ketones.
  • Aliphatic (straight-chain or branched-chain) as well as aromatic aldehydes and ketones can participate in the reaction.
  • However, the reaction may not proceed efficiently when sterically hindered aldehydes or ketones are used.

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Influence of Substituents

  • The presence of electron-withdrawing groups on the aldehyde or ketone can enhance the reactivity of the reaction.
  • The reaction rate may also be influenced by the nature of other functional groups present in the substrate.

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Synthetic Applications

  • The Cross Cannizzaro Reaction is a versatile tool in organic synthesis.
  • It is often used for the conversion of aldehydes and ketones into their corresponding alcohols.
  • The reaction can be employed for the synthesis of various intermediates and complex organic molecules.

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Summary

  • The Cross Cannizzaro Reaction is influenced by factors such as reactant concentration, temperature, solvent, base, and steric hindrance.
  • Solvents play a role in the reaction selectivity and rate.
  • Hydroxide ion acts as a strong base and plays a crucial role in the reaction.
  • The reaction involves the oxidation of aldehydes and the reduction of ketones.
  • Various aldehydes and ketones can undergo the reaction, but steric hindrance and electron-donating/withdrawing groups may impact efficiency. “slide 21”

Applications in Organic Synthesis

  • The Cross Cannizzaro Reaction can be used in the synthesis of various organic compounds.
  • It provides a method for the conversion of aldehydes and ketones into alcohols, which are valuable intermediates in organic synthesis.
  • The reaction can also be utilized for the preparation of complex molecules by utilizing the alcohol products as starting materials. “slide 22”

Example Reaction

  • Let’s consider the reaction between benzaldehyde (C6H5CHO) and acetophenone (C6H5COC6H5) in the presence of hydroxide ion: C6H5CHO + C6H5COC6H5 + OH- -> C6H5CH2OH + C6H5COCOO-
  • Benzaldehyde is oxidized to benzyl alcohol, while acetophenone is reduced to benzophenone. “slide 23”

Importance in Fragrance Industry

  • The Cross Cannizzaro Reaction has significant applications in the fragrance industry.
  • It allows for the synthesis of various aroma compounds, such as esters and alcohols, which contribute to the fragrance of perfumes and colognes.
  • The reaction is commonly employed in the production of fragrance ingredients for a wide range of products. “slide 24”

Reaction Conditions

  • The Cross Cannizzaro Reaction typically requires the presence of a strong base, such as hydroxide ion (OH-).
  • The reaction is typically carried out under basic conditions in a suitable solvent like water, ethanol, or methanol.
  • The reaction mixture is heated and stirred to facilitate the reaction. “slide 25”

Selectivity of the Cross Cannizzaro Reaction

  • The selectivity of the Cross Cannizzaro Reaction can be influenced by several factors.
  • The nature of the base, type of solvent, reaction temperature, and steric hindrance can all impact the selectivity of the reaction.
  • In some cases, side reactions such as aldol condensation or intramolecular reactions can occur instead of the Cross Cannizzaro Reaction. “slide 26”

Scope in Pharmaceutical Industry

  • The Cross Cannizzaro Reaction plays a crucial role in the synthesis of pharmaceuticals.
  • It allows for the efficient transformation of aldehydes and ketones into alcohol intermediates, which serve as key building blocks in drug synthesis.
  • The use of the reaction enables the synthesis of complex drug molecules and intermediates with high yield and efficiency. “slide 27”

Variation of the Cannizzaro Reaction

  • Variations of the Cannizzaro Reaction have been developed to expand its synthetic applications.
  • For example, the nucleophilic version of the Cannizzaro Reaction involves the use of nucleophiles instead of aldehyde or ketone substrates.
  • This variation enables the synthesis of various functionalized compounds, such as α-hydroxy acids and esters. “slide 28”

Comparison with Other Reactions

  • The Cross Cannizzaro Reaction differs from other organic redox reactions, such as the Beckmann rearrangement or the Cannizzaro disproportionation reaction.
  • While the Beckmann rearrangement involves the rearrangement of an oxime to form an amide, the Cannizzaro disproportionation reaction involves the self-disproportionation of an aldehyde.
  • It is important to differentiate between these reactions and understand their specific mechanisms and applications. “slide 29”

Summary

  • The Cross Cannizzaro Reaction is commonly used for the conversion of aldehydes and ketones into alcohols.
  • It finds applications in various industries such as pharmaceuticals and fragrances.
  • Factors such as reactant concentration, temperature, solvent, base, and steric hindrance can influence the reaction.
  • Care should be taken to optimize reaction conditions to achieve desired selectivity and yield.
  • Variations of the Cannizzaro Reaction offer further synthetic opportunities. “slide 30”

Questions

  1. What is the Cross Cannizzaro Reaction?
  1. Explain the mechanism of the Cross Cannizzaro Reaction.
  1. Give an example equation for the Cross Cannizzaro Reaction.
  1. What are the applications of the Cross Cannizzaro Reaction?
  1. How does the reaction selectivity of the Cross Cannizzaro Reaction vary?
  1. What are the safety considerations while performing the Cross Cannizzaro Reaction?
  1. What are the variations of the Cannizzaro Reaction?
  1. Compare the Cross Cannizzaro Reaction with other organic redox reactions.
  1. How is the Cross Cannizzaro Reaction utilized in the fragrance industry?
  1. Discuss the importance of the Cross Cannizzaro Reaction in the pharmaceutical industry.