23: Alpha Substitutions and Condensations of Carbonyl Compounds
- Page ID
- 424420
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After reading this chapter and completing ALL the exercises, a student can be able to
- predict the relative acidity of the a-hydrogens on various carbonyl compounds (section 23.1)
- explain or predict the equilibrium of enol-keto tautomers (section 23.2)
- predict the products and specify the reagents for the following reactions
- Halogenation of the a-carbon of aldehydes and ketones (section 23.3 and 23.4)
- Halogenation of the a-carbon of carboxylic acids (Hell-Vollhard-Zelinski) (section 23.3 and 23.5)
- Alkylation of the a-carbon of carbonyl compounds via the LDA pathway (section 23.3 and 23.6)
- Alkylation of the a-carbon of aldehydes and ketones via the enamine intermediate (section 23.3 and 3.7)
- Aldol addition and condensation reactions – 2 aldehydes, 2 ketones, 1 aldehyde with 1 ketone (section 23.3 and 23.8)
- Claisen condensation reactions – 2 esters or 1 ester with 1 ketone (section 23.3 and 23.9)
- Diekmann condensation reactions (intramolecular Claisen) - (section 23.9)
- Conjugate Addition a.k.a. Michael reaction (section 23.3 and 23.10)
- Robinson annulation (section 23.10)
- Decarboxylation of 3-oxocarboxylic acids (section 23.3 and 23.12)
- Malonic ester synthesis of carboxylic acids
- Acetoacetic ester synthesis of methyl ketones
Designing synthesis using all of the reactions through this chapter with an emphasis on increasing the size of the carbon backbone by forming new carbon-carbon bonds
- 23.1: Relative Acidity of alpha-Hydrogens
- The alpha hydrogen of aldehydes, ketones, and esters can be ionized because the resulting conjugate bases are resonance stabilized.
- 23.2: Enols, Enolate Ions and Tautomerization
- Because of the acidity of the alpha-hydrogens, carbonyls undergo keto-enol tautomerism.
- 23.3: Reaction Overview
- The reactivity of the the alpha carbon and alpha,beta-unsaturated carbonyls is introduced with an emphasis on the functional group conversions without the specific details of each reaction pathway. These details are discussed in the subsequent sections of this chapter.
- 23.4: Alpha Halogenation of Carbonyls
- Ketones containing alpha hydrogens can undergo a substitution reaction with halogens under acidic or basic conditions. Aldehydes are oxidized by the halogen before the substitution reaction can occur.
- 23.5: Bromination of Acids- The HVZ Reaction
- Carboxylic acids can be brominated in the alpha position in a reaction called the Hell-Volhard-Zelinskii reaction.
- 23.6: Alkylation of the alpha-Carbon via the LDA pathway
- Aldehydes and ketones can be alkylated at the alpha carbon if the enolate is formed with a strong base like lithium diisopropyl amide or equivalent.
- 23.7: Alkylation of the Alpha-Carbon via the Enamine Pathway
- The Stork enamine alkylation reaction is a gentler alternative to direct alkylation method using LDA or equivalent.
- 23.8: The Aldol Reaction and Condensation of Ketones and Aldehydes
- The aldol reaction is the dimerization of two aldehydes or ketones to a beta-hydroxy carbonyl. This product can undergo dehydration (condensation) to form an alpha,beta-unsaturated carbonyl. The reactants of an aldol reaction can be two different carbonyls if they are selected strategically.
- 23.9: The Claisen Condensation Reactions of Esters
- Esters can also undergo condensation reactions called Claisen Condensations. When the reaction occurs within a diester, it forms a ring and is called a Dieckmann Condensation.
- 23.10: Conjugate Additions- The Michael Reaction
- In the 1,4 Michael addition, the nucleophile is added to the carbon β to the carbonyl while the hydrogen is added to the carbon alpha to the carbonyl. Many times the product of a Michael addition produces a dicarbonyl which can then undergo an intramolecular aldol reaction called Robinson Annulation.
- 23.11: Decarboxylation Reactions
- The malonic ester synthesis and acetoacetic ester synthesis are decarboxylation reactions that use the reactivity of the alpha carbon to increase the carbon skeleton while converting an alkyl halide into a carboxylic acid or methyl ketone, respectively.
- 23.12: Additional Exercises
- This section has additional exercises for the key learning objectives of the chapter.
- 23.13: Solutions to Additional Exercises
- This section has the solutions to the additional exercises from the previous section.