Carbonyl Chemistry. aldehydes ketones. carboxylic acid and derivatives. Wednesday, April 29, 2009

Transcription

1 Carbonyl Chemistry X aldehydes ketones carboxylic acid and derivatives

2 Electrophiles (eg. + ) Nucleophiles (eg. C 3 MgBr) an enolate Base

3 β β β α α α Nuc- 1 2 Nuc 3 4 1,2-addition Nuc Nuc 4 tautomerize Nuc 4 1,4-addition (conjugate addition)

4 C 3 N 2 1,4-addition 1) Ph 2 CuLi 2) 3 + NC 3 Ph 1,4-addition 1) PhMgBr 2) 3 + Ph 1,2-addition 1) PhLi 2) 3 + Ph 1,2-addition 1) NaB 4 2) 3 + 1,2-addition 1) LiAl 4 2) 3 + 1,2-addition

5 + + 2 (+ ) (+ ) a hemiacetal (- 2 ) an acetal NEED T KNW MECANISM Mechanism for Acetal Formation A A A resonance structures emiacetal - 2 A resonance structures

6 Wittig eaction Both aldehydes and ketones participate. The Wittig reagent is made from the alkyl halide by S N 2 reactions. + Ph 3 P C 2 phosphonium ylide + Ph 3 P easier method + Ph 3 P Br + Ph 3 P: easier to prepare Wittig reagent - substitution on a primary bromide. arder method + PPh 3 Br + Ph 3 P:

7 Y Nuc Nuc Y Nuc + Y Cl C 3 N 2 Acid alides (acetyl chloride) Acid anhydrides (acetic anhydride) Esters (methyl acetate) Amides (acetamide) More eactive Less eactive

8 Y + Nuc- + Y General NAS eaction Nuc Y Y ydrolysis Y + '- + Y Alcoholysis ' Y + N 3 + Y Aminolysis N 2

9 - Y + Y - - eduction Y 'MgB r ' + Y 'MgB r ' Grignard ' ' 2 CuLi DIBAL Cl ' C 3

10 xidation Methods C 3 KMn 4 ther Methods C N 3 + KMn 4 2 KMn 4 2 MgBr C MgBr Cr Ag 2 N 4 Tollen's xidation

11 Carboxylic Acids SCl 2 Cl Na then C 3 I S N 2 C 3 limited to primary alkyl halides A, C 3 Fischer Esterification C 3 limited to inexpensive alcohol solvents - methanol and ethanol most practical LiAl 4 then 3 + B 3 selective for carboxylic acid reduction - then 3 + will not react with esters!

12 Acid Chlorides 2 + Cl Cl Cl 'C 2 Na ' + NaCl Cl ', pyridine ' + pyridine Cl Cl 'N 2, pyridine N' + pyridine Cl LiAl 4 Cl then 3 + Adds Twice Cl 'MgBr then 3 + ' ' Adds Twice Cl ' 2 CuLi ' Adds nce!

13 Acid Anhydrides 2 + ', pyridine ' + pyridine 2 CC 3 'N 2, pyridine N' + pyridine 2 CC 3 LiAl 4 then 3 + Adds Twice 'MgBr then 3 + ' ' Adds Twice

14 Esters C 3 2, Na + C 3 then 3 + C 3 LiAl 4 then 3 + Adds Twice C 3 'MgBr then 3 + ' ' Adds Twice DIBAL C 3 then 3 + Adds nce Amides 2, 3 + N 2 heat N 2 LiAl 4 then 3 + N 2 Adds Twice - Nitrogen is retained.

15 Acid Catalyzed Enol Equilibrium A A Base Catalyzed Enol Equilibrium A

16 + Br Br Br + Br Br 2 Br pyridine C 3 C 2 PBr 3 Br 2 then 2 Br

17 + N Li + N LDA lithium diisopropyl amide 100% 1) LDA 2) C 3 I C 3

18 pk a = 20 pk a = 9 Et Et pk a =13 NaEt, Et Et Et Br Et Et

19 pk a = 20 pk a = 9 Et Et pk a =13 3 +, eat Et Et + C tautomerize eat -C 2

20 Et NaEt Et C 2 Et + Br 3 +, eat + C 2

21 NEED T KNW MECANISM Mechanism for Acetal Formation A A A resonance structures emiacetal - 2 A resonance structures

22 NEED T KNW MECANISM Fischer Esterification A ' ' A ' A A ' ' ' '

23 NEED T KNW MECANISMS Acid Catalyzed ydrolysis A 2 A C 3 C 3 C 3 C 3 C 3 A A - C 3 C 3 BEST METD Base Catalyzed ydrolysis (Saponification) C 3 C 3 + C 3 + C 3 apid acidbase reaction takes place Carboxylate is a thermodynamic sink and makes the reaction essentiall non-reversible. To get the carboxylic acid, add acid to protonate.

24 N 2 A (cat) 2 Amide ydrolysis NEED T KNW MECANISMS Acid Catalyzed ydrolysis A 2 A N 2 N 2 N 2 N 2 N 2 A A - N 3 N 2

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