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17.2 How Aldehydes and Ketones React (Part I)

Main Menu. 17.2 How Aldehydes and Ketones React (Part I). Electron rich (Lewis base, Nu). d -. d +. Electron deficient (Lewis acid, E + ). R = alkyl or aryl (C). Y = alkyl, aryl or H (class II) ( No leaving group ). Class I. Class II. Class I vs. Class II Carbonyl Compounds.

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17.2 How Aldehydes and Ketones React (Part I)

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  1. Main Menu 17.2 How Aldehydes and Ketones React (Part I) Electron rich (Lewis base, Nu) d- d+ Electron deficient (Lewis acid, E+) R = alkyl or aryl (C) Y = alkyl, aryl or H (class II) (No leaving group)

  2. Class I Class II Class I vs. Class II Carbonyl Compounds Y = H (aldehyde) = R’’ (ketone) Y = NR’2 (amide) = OR’ (ester, carboxylic acid) = OCOR’ (acid anhydride) = X (acyl halide) H-H (pKa = 35) R-H (pKa = 50) Hydride (H-) and carboanion are not leaving groups

  3. Relative Reactivity of Class I and Class II Carbonyl Compounds > > >> > > H R’ ester amide ketone aldehyde acyl halide acid anhydride Esters and amides are more stable than ketones and aldehydes due to their resonance stabilization.

  4. 1. General mechanism in basic condition: Nucleophilic Addition (Class II) 2. General mechanism in acidic condition:

  5. Important pKa to Remember

  6. 1. Carbon as the nucleophilic atom Basic condition Types of Nucleophile for Class II Carbonyl Groups pKa = 25 Acetylide ion pKa = 50 carboanion 2. Hydrogen as the nucleophilic atom Mostly basic condition hydride 3. Nitrogen as the nucleophilic atom Mostly acidic condition 1° and 2° amines 4. Oxygen as the nucleophilic atom Acidic condition 1° alcohols

  7. Carboanions are highly reactive. Carbon as the Nucleophilic Atom: Grignard Reagents Hard to find a base to do the deprotonation. pKa = 50 carboanion Formation of Grignard reagent THF or Et2O X = Cl, Br or I The carbonanions can be stabilized. THF: tetrahydrofuran Et2O: diethyl ether

  8. Reactions of Grignard Reagents

  9. Reactions of Grignard Reagents 3° alcohols 2° alcohols

  10. 1° alcohols (one extra carbon) Reactions of Grignard Reagents 1° alcohols (two extra carbons) Carboxylic acid

  11. 1 mol. Reactions of Grignard Reagents with Esters 0.5 mol. 0.5 mol. 1 mol. 1 mol. 2 mol. 1 mol.

  12. Why two equivalents of Grignard reagent are needed? Reactions of Grignard Reagents with Esters A ketone (more reactive than ester)

  13. pKa = 25 Acetylide ion pKa = 50 carboanion Carbon as the Nucleophilic Atom: Acetylide Ions Why the pKa of acetylide is much lower? 2Pz The radius of 2S orbital is smaller than the radius of 2Porbitals. 2S 2Py 2Px Order for the radius of hybridized orbitals: SP3 > SP2 > SP Order for the electronegativity of hybridized orbitals: SP3 < SP2 < SP Order for the acidity of H’s of hybridized orbitals: SP3 < SP2 < SP pKa = 40

  14. Reactions of Carbonyl Groups with Acetylide Ions pKa = 38 Acetylide ion pKa = 25

  15. Hydrogen cyanide is weakly acidic. Carbon as the Nucleophilic Atom: Cyanide Cyanide is highly poisonous. cyanide pKa = 9.1 Addition of cyanide to aldehydes or ketones: HCl Stable in acidic condition but unstable in basic condition. H+, H2O heat H2, Pt/C a-hydroxy carboxylic acid

  16. Reagents that can provide hydrides as nucleophiles: Hydrogen as the Nucleophilic Atom: Hydride Reagents NaBH4 LiAlH4 Sodium boroydride Lithium aluminum hydride Theoretically, one molecule of LiAlH4 or NaBH4 can provide four hydrides. Diisobutylaluminum hydride (DIBAL) Reagents that can provide hydrides as bases: NaH CaH2

  17. General Reactions: Reactions of Aldehydes and Ketones with Hydride Reagents LiAlH4 or NaBH4 H2O Examples:

  18. General Mechanism for the Reduction of Aldehydes and Ketones Using Hydride Reagents d- Repeat 3 times d- The three H’s can still act as hydrides. H2O

  19. Relative Reactivity > > > LiAlH4 DIBAL NaBH4 NaBH3CN Comparison of LiAlH4, DIBAL and NaBH4 Unstable in weak acid Stable in weak acid

  20. General reaction LiAlH4 H2O Reduction of Ester with LiAlH4 Mechanism Reduction cannot stop at the stage of aldehyde H2O

  21. General reaction LiAlH4 H2O Reduction of Carboxylic Acids with LiAlH4 Reduction cannot stop at the stage of aldehyde Mechanism H2O

  22. General reaction LiAlH4 H2O Reduction of Amides with LiAlH4 Mechanism H2O

  23. General reaction DIBAL, -78°C H2O, -78°C Reduction can stop at the stage of aldehyde Reduction of Ester with DIBAL DIBAL, -78° - 0°C H2O, 0°C Control of temperature is important for the reduction to stop at the stage of aldehyde.

  24. Examples

  25. Examples

  26. Examples No reaction No reaction

  27. In most of the cases, hydride reducing reagents cannot reduce C=C. Selective Reduction

  28. 1. What could be the reagent needed for this transformation? Learning Check 2. What could be reagent needed for this transformation?

  29. 3. What could be the product for the following reaction? Learning Check 4. What could be the product for the following reaction?

  30. 5. What could be the reagent needed for the following reaction? Learning Check 6. What could be the product for the following reaction?

  31. 7. What could be the product for the following reaction? Learning Check

  32. Main Menu 8. What could be the product for the following reaction? Learning Check

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