Presentation on theme: "17.2 How Aldehydes and Ketones React (Part I) 1 ++ R = alkyl or aryl (C) Y = alkyl, aryl or H (class II) (No leaving group) -- Electron rich (Lewis."— Presentation transcript:
17.2 How Aldehydes and Ketones React (Part I) 1 ++ R = alkyl or aryl (C) Y = alkyl, aryl or H (class II) (No leaving group) -- Electron rich (Lewis base, Nu) Electron deficient (Lewis acid, E + ) Main Menu
Class I vs. Class II Carbonyl Compounds 2 Class II Y = NR’ 2 (amide) = OR’ (ester, carboxylic acid) = OCOR’ (acid anhydride) = X (acyl halide) Class I Y = H (aldehyde) = R’’ (ketone) H-H (pKa = 35) R-H (pKa = 50) Hydride (H - ) and carboanion are not leaving groups
Relative Reactivity of Class I and Class II Carbonyl Compounds 3 acyl halide >> >> >> acid anhydride ketone aldehyde esteramide Esters and amides are more stable than ketones and aldehydes due to their resonance stabilization. H R’
Nucleophilic Addition (Class II) 4 1. General mechanism in basic condition: 2. General mechanism in acidic condition:
Important pKa to Remember 5 Names Acids H-Z Approx. pKa Conjugate Base, :Z General Roles of :Z Alkane (2°)51 Base as Li + salt Nucleophile as Grignard reagent Amine38Base and Nucleophile Hydrogen35 Base in NaH, CaH 2 Nucleophile in LiAlH 4, NaBH 4 Alcohol water 15-16 Often as a base but can be a nucleophile Ammonium10-11 Weak base, but can be a nucleophile Thiol10-11Nucleophile Carboxylic Acid 4-5Weak base, poor leaving group Hydrochloric Acid -7Leaving group, poor nucleophile
Types of Nucleophile for Class II Carbonyl Groups 6 1. Carbon as the nucleophilic atom pKa = 50 Basic condition 2. Hydrogen as the nucleophilic atom carboanion hydride Mostly basic condition 3. Nitrogen as the nucleophilic atom 1° and 2° amines Mostly acidic condition 4. Oxygen as the nucleophilic atom Acidic condition 1° alcohols pKa = 25 Acetylide ion
Carbon as the Nucleophilic Atom: Grignard Reagents 7 Carboanions are highly reactive. pKa = 50 Hard to find a base to do the deprotonation. carboanion Formation of Grignard reagent X = Cl, Br or I THF or Et 2 O THF: tetrahydrofuran Et 2 O: diethyl ether The carbonanions can be stabilized.
Reactions of Grignard Reagents 10 1° alcohols (one extra carbon) Carboxylic acid 1° alcohols (two extra carbons)
Reactions of Grignard Reagents with Esters 11 1 mol. 0.5 mol. 2 mol. 1 mol.
Reactions of Grignard Reagents with Esters 12 Why two equivalents of Grignard reagent are needed? A ketone (more reactive than ester)
Carbon as the Nucleophilic Atom: Acetylide Ions 13 pKa = 50 carboanion pKa = 25 Acetylide ion Why the pKa of acetylide is much lower? 2P x 2P z 2P y 2S The radius of 2S orbital is smaller than the radius of 2P orbitals. Order for the radius of hybridized orbitals: SP 3 > SP 2 > SP Order for the electronegativity of hybridized orbitals: SP 3 < SP 2 < SP Order for the acidity of H’s of hybridized orbitals: SP 3 < SP 2 < SP pKa = 40
Reactions of Carbonyl Groups with Acetylide Ions 14 pKa = 25 Acetylide ion pKa = 38
Carbon as the Nucleophilic Atom: Cyanide 15 Hydrogen cyanide is weakly acidic. pKa = 9.1 Cyanide is highly poisonous. cyanide Addition of cyanide to aldehydes or ketones: HCl Stable in acidic condition but unstable in basic condition. H +, H 2 O heat H 2, Pt/C -hydroxy carboxylic acid
Hydrogen as the Nucleophilic Atom: Hydride Reagents 16 Reagents that can provide hydrides as nucleophiles: Theoretically, one molecule of LiAlH 4 or NaBH 4 can provide four hydrides. Lithium aluminum hydride LiAlH 4 NaBH 4 NaHCaH 2 Sodium boroydride Reagents that can provide hydrides as bases: Diisobutylaluminum hydride (DIBAL)
Reactions of Aldehydes and Ketones with Hydride Reagents 17 General Reactions: Examples: 1)LiAlH 4 or NaBH 4 2)H 2 O
General Mechanism for the Reduction of Aldehydes and Ketones Using Hydride Reagents 18 -- -- The three H’s can still act as hydrides. Repeat 3 times H2OH2O
Comparison of LiAlH 4, DIBAL and NaBH 4 19 Relative Reactivity > LiAlH 4 DIBALNaBH 4 > AmideEster Carboxylic acid KetoneAldehyde LiAlH 4 yes DIBALnoyes? NaBH 4 no yes NaBH 3 CN > Stable in weak acid Unstable in weak acid
Reduction of Ester with LiAlH 4 20 General reaction 1)LiAlH 4 2)H 2 O Mechanism H2OH2O Reduction cannot stop at the stage of aldehyde
Reduction of Carboxylic Acids with LiAlH 4 21 General reaction 1)LiAlH 4 2)H 2 O Mechanism H2OH2O Reduction cannot stop at the stage of aldehyde
Reduction of Amides with LiAlH 4 22 General reaction 1)LiAlH 4 2)H 2 O Mechanism H2OH2O
Reduction of Ester with DIBAL 23 General reaction 1)DIBAL, -78°C 2)H 2 O, -78°C 1)DIBAL, -78° - 0°C 2)H 2 O, 0°C Reduction can stop at the stage of aldehyde Control of temperature is important for the reduction to stop at the stage of aldehyde.