Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions
Based on McMurry’s Organic Chemistry, 6th edition©2003 Ronald KlugerDepartment of ChemistryUniversity of Toronto
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Aldehydes and Ketones
Aldehydes and ketones are characterized by the the carbonyl functional group (C=O)
The compounds occur widely in nature as intermediates in metabolism and biosynthesis
They are also common as chemicals, as solvents, monomers, adhesives, agrichemicals and pharmaceuticals
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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19.1 Naming Aldehydes and Ketones
Aldehydes are named by replacing the terminal -e of the corresponding alkane name with –al
The parent chain must contain the CHO group The CHO carbon is numbered as C1
If the CHO group is attached to a ring, use the suffix See Table 19.1 for common names
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Naming Ketones
Replace the terminal -e of the alkane name with –one Parent chain is the longest one that contains the
ketone group Numbering begins at the end nearer the carbonyl
carbon
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Ketones with Common Names
IUPAC retains well-used but unsystematic names for a few ketones
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Ketones and Aldehydes as Substituents The R–C=O as a substituent is an acyl group is used
with the suffix -yl from the root of the carboxylic acid CH3CO: acetyl; CHO: formyl; C6H5CO: benzoyl
The prefix oxo- is used if other functional groups are present and the doubly bonded oxygen is labeled as a substituent on a parent chain
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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19.2 Preparation of Aldehydes and Ketones
Preparing Aldehydes Oxidize primary alcohols using pyridinium
chlorochromate Reduce an ester with diisobutylaluminum
hydride (DIBAH)
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Preparing Ketones
Oxidize a 2° alcohol (see Section 17.8) Many reagents possible: choose for the specific
situation (scale, cost, and acid/base sensitivity)
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Ketones from Ozonolysis
Ozonolysis of alkenes yields ketones if one of the unsaturated carbon atoms is disubstituted (see Section 7.8)
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Aryl Ketones by Acylation
Friedel–Crafts acylation of an aromatic ring with an acid chloride in the presence of AlCl3 catalyst (see Section 16.4)
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Methyl Ketones by Hydrating Alkynes
Hydration of terminal alkynes in the presence of Hg2+ (catalyst: Section 8.5)
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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19.3 Oxidation of Aldehydes and Ketones CrO3 in aqueous acid oxidizes aldehydes to
carboxylic acids efficiently Silver oxide, Ag2O, in aqueous ammonia (Tollens’
reagent) oxidizes aldehydes (no acid)
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Hydration of Aldehydes
Aldehyde oxidations occur through 1,1-diols (“hydrates”)
Reversible addition of water to the carbonyl group Aldehyde hydrate is oxidized to a carboxylic acid by
usual reagents for alcohols
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Ketones Oxidize with Difficulty
Undergo slow cleavage with hot, alkaline KMnO4
C–C bond next to C=O is broken to give carboxylic acids
Reaction is practical for cleaving symmetrical ketones
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Nucleophiles
Nucleophiles can be negatively charged ( : Nu) or neutral ( : Nu) at the reaction site
The overall charge on the nucleophilic species is not considered
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Electrophilicity of Aldehydes and Ketones Aldehyde C=O is more polarized than ketone C=O As in carbocations, more alkyl groups stabilize +
character Ketone has more alkyl groups, stabilizing the C=O
carbon inductively
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Reactivity of Aromatic Aldehydes
Less reactive in nucleophilic addition reactions than aliphatic aldehydes
Electron-donating resonance effect of aromatic ring makes C=O less reactive electrophilic than the carbonyl group of an aliphatic aldehyde
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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19.6 Nucleophilic Addition of H2O: Hydration Aldehydes and ketones react with water to yield 1,1-
diols (geminal (gem) diols) Hyrdation is reversible: a gem diol can eliminate
water
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Base-Catalyzed Addition of Water
Addition of water is catalyzed by both acid and base
The base-catalyzed hydration nucleophile is the hydroxide ion, which is a much stronger nucleophile than water
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Acid-Catalyzed Addition of Water
Protonation of C=O makes it more electrophilic
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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19.9 Nucleophilic Addition of Amines: Imine and Enamine Formation
RNH2 adds to C=O to form imines, R2C=NR (after loss of HOH)
R2NH yields enamines, R2NCR=CR2 (after loss of HOH)
(ene + amine = unsaturated amine)
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Mechanism of Formation of Imines
Primary amine adds to C=O Proton is lost from N and adds to O to yield a neutral
amino alcohol (carbinolamine) Protonation of OH converts into water as the leaving
group Result is iminium ion, which loses proton Acid is required for loss of OH – too much acid blocks
RNH2
Note that overall reaction is substitution of RN for O
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Imine Derivatives
Addition of amines with an atom containing a lone pair of electrons on the adjacent atom occurs very readily, giving useful, stable imines
For example, hydroxylamine forms oximes and 2,4-dinitrophenylhydrazine readily forms 2,4-dinitrophenylhydrazones These are usually solids and help in characterizing
liquid ketones or aldehydes by melting points
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Enamine Formation
After addition of R2NH, proton is lost from adjacent carbon
CC
O
C
C
O
H++ R2NH
NH
R
C
C
HON
R
C
C
H2ON
R
C
CN
R
+ H3O+
R
H
H HH
H H
R R R
H H H
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Protons on Carbons Adjacent to C=O
Slightly deshielded and normally absorb near 2.0 to 2.3
Methyl ketones always show a sharp three-proton singlet near 2.1
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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Summary Aldehydes are from oxidative cleavage of alkenes, oxidation of 1°
alcohols, or partial reduction of esters Ketones are from oxidative cleavage of alkenes, oxidation of 2°
alcohols, or by addition of diorganocopper reagents to acid chlorides. Aldehydes and ketones are reduced to yield 1° and 2° alcohols ,
respectively Grignard reagents also gives alcohols Addition of HCN yields cyanohydrins 1° amines add to form imines, and 2° amines yield enamines Reaction of an aldehyde or ketone with hydrazine and base yields an
alkane Alcohols add to yield acetals Phosphoranes add to aldehydes and ketones to give alkenes (the
Wittig reaction) -Unsaturated aldehydes and ketones are subject to conjugate
addition (1,4 addition)
Recommended