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CARBONYL COMPOUNDSALDEHYDES AND KETONES
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Aldehydes and Ketones
CH
RO C
R
RO
Aldehyde Ketone
C OH3C
H118o
121oC C
H
H
H
H118o
121o
C OH3C
HC O
H3C
H
δ−δ+
Resonance Structures
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Some naturally occurring aldehydes and ketones
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Formalin, 35-40% formadehyde in waterPreservative that reacts with proteins causing them to resist decay Coelacanth, “prehistoric fish”
OH
Acrolein (2-propenal)
- lachrymator and pleasant "odor" from barbacuing meat
HCO
H
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Preparation of Carbonyls
1. Oxidation of Alcohols
Primary alcohols can be oxidized with pyridinium chlorochromate(PCC) to aldehydes. Ketones can be obtained from secondary alcohols by oxidation with sodium dichromate/sulfuric acid or KMnO4.
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Preparation of Carbonyls
2. Friedel Crafts AcylationAromatic ketones (acyl benzenes) can be produced from the reaction of benzenoid compounds with acyl chlorides, which are derived from carboxylic acids.
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Preparation of Carbonyls
3. Ozonolysis of AlkenesThe cleavage of an alkene with ozone produces carbonyl compounds. Recall that disubstituted double-bonded carbons become ketones and monosubstituted double-bonded carbons become aldehydes through ozonolysis.
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Preparation of Carbonyls 4. Aldehydes from Acid ChloridesAldehydes are easily oxidized to carboxylic acids but carboxylic acids are difficult to reduce to aldehydes. This difficulty is circumvented by converting a carboxylic acid into the more reactive acid chloride, which can be readily reduced to an aldehyde. Lithium tri-t-butoxyaluminum hydride is a mild reducing agent that displaces chloride with hydride to produce an aldehyde.
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Preparation of Carbonyls 4. Ketones from Acid Chlorides
Alkyl groups can replace the chlorine to produce ketones.
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A Grignard (or organolithium) reagent would react with an acid chloride to produce a ketone, but then the ketone would react immediately with additional Grignard reagent in the solution to form a tertiary alcohol. This problem is circumvented by using the weakest of the organometallicreagents, an organocuprate, which is too weak a nucleophile to add to a ketone.
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Reactions of Aldehydes and Ketones
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Addition to Carbonyls: Simple Nucleophile
Carbonyls readily undergo Nucleophilic Attack
OC
δ−
δ+OCNuc
OCNuc
H
Nuc
H+
Alkoxide Alcohol
Aldehyde is more reactive than ketone
OC
R H
δ−
δ+OC
R R
δ−
δ+
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1. Reduction of CarbonylsThe most useful reagents for reducing aldehydes and ketones are the metal hydride reagents.The two most common metal hydride reagents are sodium borohydride (NaBH4) and lithium aluminum hydride (LiAlH4). These reagents contain a polar metal-hydrogen bond that serves as a source of the nucleophile hydride, H:-. LiAlH4 is a stronger reducing agent than NaBH4, because the Al-H bond is more polar than the B-H bond.
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MECHANISM LiAlH4 Reduction of RCHO and R2C=O
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2. Reaction of Carbonyls with Cyanide Ion• The reaction is conducted using sodium cyanide at pH 10 to yield
cyanohydrin.
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Addition to Carbonyls: Primary Amines and Alcohols1. Addition of primary amimes
Condensation Reaction – Elimination of water
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Reaction between an amine and a carbonyl compound
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General reactionGeneral reaction
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DNP test for aldehydes & ketones gives crystalline hydrazones
C OCH3
CH3
N NH H
H
O2N
O2NC N
CH3
CH3
NH
NO2
NO2
+
2,4-diphenylhydrazine
acetonehydrazone of acetone
- H2O
2,4-dinitrophenylhydrazine orange crystals
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Nucleophilic Addition of Hydrazine:The Wolff-Kishner Reduction
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Mechanism: The Wolff-Kishner Reduction
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Addition to Carbonyls: Primary Amines and Alcohols2. Addition of alcohols
Weak nucleophiles “Acid catalyzed”
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Mechanism ofhemiacetal formation
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Mechanism of acetal formation
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Addition to Carbonyls: Carbanions
Carbanion : strong Nucleophile- Grignard reagent : an organomagnesium bromide (RMgBr or ArMgBr). - Organolithium compounds (RLi and ArLi)
1. Addition of Grignard reagents
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Professor Victor Grignard (1912 Nobel Prize)Developed this chemistry with Professor P. A. Barbier
CR X
H
H
X = I or Br
δ+ δ−CH
HMgXR δ− δ+
Grignard Reagent
Ether
RCH2
MgXMg
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MgBr
C OH
H
EtherCH
HO MgBr C
H
HO H
Benzylalcohol
H3O+
C O MgBr1.
Ether
C OH
Triphenylmethanol
2. H3O+
Grignard reagent add to carbonyls to give alcohols
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OC
H H
OC
R HOC
R R
MgIPh MgIPh MgIPh
OCH H
H
Ph
OCR H
H
Ph
OCR R
H
Ph
+ + +
Primary alcohols Secondary alcohols tertiary alcohols
KetoneAldehydesFormaldehyde
Nucleophilic Addition Reactions
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CR X
H
H
X = I or Br
δ+ δ−CH
HLiR δ− δ+ RCH2
Li
Organolithium Reagent
Li
Ether
2. Addition of Organolithium compounds (RLi and ArLi)
C O
R Liδ+
δ−
δ−
δ+
CR OADDITION
Li
CR O
Protonation
H
Alcohol
H+
H2O
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Problems
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Problems
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Oxidation of AldehydesThe most common oxidation reaction of carbonyl compounds is the oxidation of aldehydes to carboxylic acids. A variety of oxidizing agents can be used, including CrO3, Na2Cr2O7, K2Cr2O7 and KMnO4. Aldehydes are also oxidized selectively in the presence of other functional groups using silver(I) oxide in aqueous ammonium hydroxide. This is called Tollens reagent. Because ketones have no H on the carbonyl carbon, they do not undergo this oxidation reaction.
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Problems
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Reactivity of Enolate Ions
CO
CH
α Base
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Reactivity of Enolate Ions
Reaction on carbon is more common.
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1. Haloform reactionIf excess base and halogen are used, a methyl ketone is triply halogenated and then cleaved by base in the haloform reaction. The product are carboxylic and haloform.
+ -CX3
+CHX3
haloform
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2. Alkylation of Enolate Ionsเกิดขึ้นไดกับ ketone ที่มี α-hydrogen โดยทําปฏิกิริยากับเบสจะให enolate ion ซึ่งสามารถทําปฏิกิริยาไดอยางรวดเร็วกับ alkyl halide เกิดสารผลิตภัณฑคือ α- alkylketone
LDA = lithium diisopropylamide
C CH
O 1) LDA, THF2) R-X
ketone
C CR
O
α-alkylketone
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3. Aldol Condensationเกิดเมื่อ aldehyde หรือ ketone ที่มี α-hydrogen เปลี่ยนเปน enolate ion และทําหนาที่เปน nucleophile เพิ่มเขาไปที่ aldehyde หรือ ketone อีกโมเลกุลหนึ่ง เกิดสารผลิตภัณฑคือ β-hydroxy carbonyl หรือที่เรียกกันวา aldol (aldehyde + alcohol)
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Mechanism: Aldol Condensation
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สาร β-hydroxy aldehyde หรือ ketone ที่เกิดขึ้น ถายังมี α-hydrogen เหลืออยูจะสูญเสียโมเลกุลของน้ําไดงายโดยเกิดเปนสารที่ไมอิ่มตัวโดยมีพันธะที่ตําแหนง α,β เรียกวา α,β-unsaturated aldehyde หรือ ketone ซึง่สารที่เกิดขึ้นนี้เปนสารที่เสถียรมีการเคลื่อนที่ของ electron ไปไดทั่วทั้ง 4 atom
+ H2O
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Crossed Aldol Condensationเกิดระหวาง aldehyde หรือ ketone ตางชนิดกัน สวนใหญมักเลือกใหสารหนึ่งมี α-hydrogen และอีกสารหนึ่งไมมี α-hydrogen เพือ่ปองกันการเกิดผลิตภัณฑหลายชนิดผสมกัน
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Problem : จงเลือกสารตั้งตนที่ใชสําหรับสังเคราะหสารในแตละขอตอไปนี้
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CARBOXYLIC ACIDS
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Carboxylic Acids
OC
O H H2O+
OC
O H3O+
pKa = 4 - 5 , water = 16
OC
O H NaOH+
OC
OH2O
Na
Benzoic acid Sodium Benzoate
ClCClCl
COH
O HCClCl
COH
OHCClH
COH
O HCHH
COH
O
pKa = 0.7 1.48 2.86 4.76
Carboxylic acids are strong organic acids
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Highly PolarLow molecular weight acids show Appreciable Solubility in Water
High B.p.– Extensive H-bonds to themselves and water
Carboxylic Acids
Methanoic acid
Ethanoic acid
4-Bromo-2-ethylpentanoic acidrhubarbRed ants
O
H OH
Vinegar
O
H3C OH
Acetic acid
O
OH
OCH3
OAspirin
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Reactions of Carboxylic Acids
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Conversion of RCOOH to RCOClCarboxylic acids can't be converted to acid chlorides by using Cl- as a nucleophile, because the attacking nucleophile Cl- is a weaker base than the departing leaving group, -OH. But carboxylic acids can be converted to acid chlorides using thionyl chloride, SOCl2.
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Mechanism
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Conversion of RCOOH to (RCO)2OCarboxylic acids cannot be readily converted to anhydrides, but dicarboxylic acid can be converted to cyclic anhydrides by heating to high temperatures. This is a dehydration reaction because a water molecule is lost from the diacid.
OHOH
O
O
O
O
O
+ H2O
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Conversion of RCOOH to RCOORTreatment of a carboxylic acid with an alcohol in the presence of an acid catalyst forms an ester. This reaction is called a Fischer esterification.
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Mechanism
R OH
O
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Esterification of a carboxylic acid occurs in the presence of acid but not in the presence of base. Base removes a proton from the carboxylic acid, forming a carboxylate anion, which does not react with an electron-rich nucleophile.
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Intramolecular esterification of γ- and δ-hydroxy carboxylic acids forms five- and six-lactones.
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Draw the products of each reaction
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Conversion of RCOOH to RCONR’2The direct conversion of a carboxylic acid to an amide with NH3 or an amine is very difficult. The problem is that carboxylic acids are strong organic acids and NH3 and amines are bases, so they undergo an acid-base reaction to form an ammonium salt before any nucleophilic substitution occurs.
The overall conversion of RCOOH to RCONH2 requires two steps:[1] Acid-base reaction of RCOOH with NH3 to form an ammonium salt [2] Dehydration at high temperature (>100 oC)
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A carboxylic acid and an amine readily react to form an amide in the presence of an additional reagent, dicyclohexylcarbodiimide (DCC), which is converted to the by-product dicyclohexylurea in the course of the reaction.
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Mechanism
R OH
O
R'NH2
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Cleaning Action of Soaps