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Organic Chemistry 6 th Edition Paula Yurkanis Bruice

Organic Chemistry 6 th Edition Paula Yurkanis Bruice. Chapter 19 Carbonyl Compounds III Reactions at the a -Carbon. The a -Hydrogen Is Acidic. The anion is stabilized by resonance. A carbon acid is a compound with a relatively acidic hydrogen bonded to an sp 3 -hybridized carbon.

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Organic Chemistry 6 th Edition Paula Yurkanis Bruice

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  1. Organic Chemistry 6th Edition Paula Yurkanis Bruice Chapter 19 Carbonyl Compounds III Reactions at the a-Carbon

  2. The a-Hydrogen Is Acidic The anion is stabilized by resonance A carbon acid is a compound with a relatively acidic hydrogen bonded to an sp3-hybridized carbon

  3. Esters Are Less Acidic Than Aldehydes and Ketones The electrons are not as readily delocalized because of resonance electron release by -OR (green arrows)

  4. In the following compounds, the anion resulting from deprotonation can be delocalized into electronegative atoms (oxygen and nitrogen):

  5. The acidity of the a-hydrogens is attributed to anion stabilization by resonance:

  6. Keto–Enol Tautomerism

  7. The enol tautomer can be stabilized by intramolecular hydrogen bonding: In phenol, the enol tautomer predominates because it is aromatic:

  8. Mechanism for base-catalyzed keto–enol interconversion:

  9. Mechanism for acid-catalyzed keto–enol interconversion:

  10. An Enol Is a Better Nucleophile Than an Alkene Carbonyl compounds that form enol undergo substitution reactions at the a-carbon: an a-substitution reaction

  11. Mechanism for base-catalyzed a-substitution:

  12. Mechanism for acid-catalyzed a-substitution:

  13. An Enolate Is an Ambident Nucleophile Reaction at the C or O site depends on the electrophile and on the reaction condition Protonation occurs preferentially on the O site Otherwise, the C site is likely the nucleophile

  14. Acid-Catalyzed Halogenation Under acidic conditions, one a-hydrogen is substituted for a halogen

  15. Mechanism for acid-catalyzed halogenation:

  16. Base-Promoted Halogenation Under basic conditions, all the a-hydrogens are substituted for halogens

  17. Mechanism for base-promoted halogenation:

  18. Conversion of a Methyl Ketone to a Carboxylic Acid

  19. Halogenation of the a-Carbon of Carboxylic Acids Mechanism for the Hell–Volhard–Zelinski reaction:

  20. a-Halogenated Carbonyl Compounds Are Useful in Synthesis Removing a proton from an a-carbon makes the a- carbon a nucleophile:

  21. When the a-carbon is halogenated, it becomes electrophilic: An E2 elimination will occur if a bulky base is used:

  22. LDA is a strong base but a poor nucleophile Why? Because the steric bulk of the isopropyl groups prevents an SN2 reaction

  23. Using LDA to Form an Enolate

  24. Keto–Enol Tautomerization

  25. Alkylation of the a-Carbon of Carbonyl Compounds This method can be used to alkylate ketones, esters, and nitriles at the a-carbon; however, aldehydes give a poor yield

  26. Enol and Enolate Reactions: Halogenation and Alkylation

  27. Two different products can be formed if the ketone is not symmetrical:

  28. The less substituted a-carbon can be alkylated if the hydrazone is used:

  29. Alkylation and Acylation of the a-Carbon Using an Enamine Intermediate

  30. The alkylation step is an SN2 reaction:

  31. Direct alkylation of a carbonyl compound yields several products: In contrast, alkylation of an aldehyde or a ketone using an enamine intermediate yields the monoalkylated product

  32. Aldehydes and ketones can be acylated via an enamine intermediate:

  33. The a-carbon of an aldehyde or a ketone can be made to react with an electrophile: The a-carbon of an aldehyde or a ketone can also be made to react with a nucleophile:

  34. The Michael Addition

  35. Michael reactions form 1,5-dicarbonyl compounds:

  36. Mechanism for the Michael Addition Reaction

  37. The Stork Enamine Reaction Enamines are used in place of enolates in these Michael addition reactions:

  38. Aldol Addition Reaction

  39. One molecule of a carbonyl compound acts as a nucleophile, and the other carbonyl compound acts as an electrophile:

  40. Ketones are less susceptible than aldehydes to attack by nucleophiles for steric reasons:

  41. An aldol addition product loses water to form an aldol condensation product:

  42. Conjugation stabilizes the dehydrated product:

  43. The Mixed Aldol Addition

  44. One product will be formed if one of the carbonyl compounds does not have any a-hydrogen:

  45. Primarily one product can be formed by using LDA to deprotonate one of the carbonyl compounds:

  46. Condensation of Two Ester Molecules: The Claisen Condensation

  47. Anion formation results in an irreversible reaction The reaction can be driven to completion by removing a proton from the b-keto ester: The Claisen condensation requires an ester with two a-hydrogens and an equivalent amount of base

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