Aldehide Keton

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19.1 Naming Aldehydes and Ketones
Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions
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 McMurrys Organic Chemistry, 6th edition
Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003
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
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
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Ketones with Common Names

IUPAC retains well-used but unsystematic names for a few ketones
19.2 Preparation of Aldehydes and Ketones
Preparing Aldehydes Oxidize primary alcohols using pyridinium chlorochromate Reduce an ester with diisobutylaluminum hydride (DIBAH)
Ketones and Aldehydes as Substituents

The RC=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
Preparing Ketones
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
Oxidize a 2 alcohol (see Section 17.8) Many reagents possible: choose for the specific situation (scale, cost, and acid/base sensitivity)
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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)
Methyl Ketones by Hydrating Alkynes
Hydration of terminal alkynes in the presence of Hg2+ (catalyst: Section 8.5)
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Aryl Ketones by Acylation

FriedelCrafts acylation of an aromatic ring with an acid chloride in the presence of AlCl3 catalyst (see Section 16.4)
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)
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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
19.4 Nucleophilic Addition Reactions of Aldehydes and Ketones
Nu- approaches 45 to the plane of C=O and adds to C A tetrahedral alkoxide ion intermediate is produced
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Ketones Oxidize with Difficulty

Undergo slow cleavage with hot, alkaline KMnO4 CC bond next to C=O is broken to give carboxylic acids Reaction is practical for cleaving symmetrical ketones
Nucleophiles
Nucleophiles can be negatively charged ( : Nu) or neutral ( : Nu) at the reaction site The overall charge on the nucleophilic species is not considered
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19.5 Relative Reactivity of Aldehydes and Ketones

Aldehydes are generally more reactive than ketones in nucleophilic addition reactions The transition state for addition is less crowded and lower in energy for an aldehyde (a) than for a ketone (b) Aldehydes have one large substituent bonded to the C=O: ketones have two
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
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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
19.6 Nucleophilic Addition of H2O: Hydration
Aldehydes and ketones react with water to yield 1,1diols (geminal (gem) diols) Hydration is reversible: a gem diol can eliminate water
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Relative Energies
Equilibrium generally favors the carbonyl compound over hydrate for steric reasons
Acetone in water is 99.9% ketone form
Acid-Catalyzed Addition of Water
Protonation of C=O makes it more electrophilic
Exception: simple aldehydes

In water, formaldehyde consists is 99.9% hydrate
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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
Addition of H-Y to C=O
Reaction of C=O with H-Y, where Y is electronegative, gives an addition product (adduct) Formation is readily reversible
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19.7 Nucleophilic Addition of HCN: Cyanohydrin Formation

Aldehydes and unhindered ketones react with HCN to yield cyanohydrins, RCH(OH)CN
Uses of Cyanohydrins
The nitrile group (CN) can be reduced with LiAlH4 to yield a primary amine (RCH2NH2) Can be hydrolyzed by hot acid to yield a carboxylic acid
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Mechanism of Formation of Cyanohydrins

Addition of HCN is reversible and base-catalyzed, generating nucleophilic cyanide ion, CN Addition of CN to C=O yields a tetrahedral intermediate, which is then protonated Equilibrium favors adduct
19.8 Nucleophilic Addition of Grignard Reagents and Hydride Reagents: Alcohol Formation
Treatment of aldehydes or ketones with Grignard reagents yields an alcohol
Nucleophilic addition of the equivalent of a carbon anion, or carbanion. A carbonmagnesium bond is strongly polarized, so a Grignard reagent reacts for all practical purposes as R : MgX +.
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Mechanism of Addition of Grignard Reagents

Complexation of C=O by Mg2+, Nucleophilic addition of R : , protonation by dilute acid yields the neutral alcohol Grignard additions are irreversible because a carbanion is not a leaving group
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)
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Hydride Addition
Convert C=O to CH-OH LiAlH4 and NaBH4 react as donors of hydride ion Protonation after addition yields the alcohol
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 30
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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 2,4dinitrophenylhydrazine readily forms 2,4dinitrophenylhydrazones
These are usually solids and help in characterizing liquid ketones or aldehydes by melting points
19.10 Nucleophilic Addition of Hydrazine: The WolffKishner Reaction
Treatment of an aldehyde or ketone with hydrazine, H2NNH2 and KOH converts the compound to an alkane Originally carried out at high temperatures but with dimethyl sulfoxide as solvent takes place near room temperature
See Figure 19.11 for a mechanism

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Enamine Formation
After addition of R2NH, proton is lost from adjacent carbon
19.11 Nucleophilic Addition of Alcohols: Acetal Formation
Two equivalents of ROH in the presence of an acid catalyst add to C=O to yield acetals, R2C(OR)2 These can be called ketals if derived from a ketone
R R R R R R
R R O C C H + R2NH H O C C H C H H C NH HO
H+
H2O C H H
N N C C H C H + H3O+
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Formation of Acetals
Alcohols are weak nucleophiles but acid promotes addition forming the conjugate acid of C=O Addition yields a hydroxy ether, called a hemiacetal (reversible); further reaction can occur Protonation of the OH and loss of water leads to an oxonium ion, R2C=OR+ to which a second alcohol adds to form the acetal
19.12 Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction
The sequence converts C=O is to C=C A phosphorus ylide adds to an aldehyde or ketone to yield a dipolar intermediate called a betaine The intermediate spontaneously decomposes through a four-membered ring to yield alkene and triphenylphosphine oxide, (Ph)3P=O Formation of the ylide is shown below
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Uses of Acetals
Acetals can serve as protecting groups for aldehydes and ketones It is convenient to use a diol, to form a cyclic acetal (the reaction goes even more readily)
Uses of the Wittig Reaction
Can be used for monosubstituted, disubstituted, and trisubstituted alkenes but not tetrasubstituted alkenes The reaction yields a pure alkene of known structure For comparison, addition of CH3MgBr to cyclohexanone and dehydration with, yields a mixture of two alkenes
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Mechanism of the Wittig Reaction
The Biological Analogue of the Canizzaro Reaction
Enzymes catalyze the reduction of aldehydes and ketones using NADH as the source of the equivalent of HThe transfer resembles that in the Cannizzaro reaction but the carbonyl of the acceptor is polarized by an acid from the enzyme, lowering the barrier
Enzymes are chiral and the reactions are stereospecific. The stereochemistry depends on the particular enzyme involved.
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19.13 The Cannizzaro Reaction: Biological Reductions

The adduct of an aldehyde and OH can transfer hydride ion to another aldehyde C=O resulting in a simultaneous oxidation and reduction (disproportionation)
19.14 Conjugate Nucleophilic Addition to ,Unsaturated Aldehydes and Ketones
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A nucleophile can add to the C=C double bond of an ,unsaturated aldehyde or ketone (conjugate addition, or 1,4 addition) The initial product is a resonancestabilized enolate ion, which is then protonated Based on McMurry, Organic Chemistry, Chapter
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19, 6th edition, (c) 2003
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Conjugate Addition of Amines

Primary and secondary amines add to , unsaturated aldehydes and ketones to yield -amino aldehydes and ketones
Mechanism of Alkyl Conjugate Addition
Conjugate nucleophilic addition of a diorganocopper anion, R2Cu, an enone Transfer of an R group and elimination of a neutral organocopper species, RCu
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Conjugate Addition of Alkyl Groups: Organocopper Reactions

Reaction of an , -unsaturated ketone with a lithium diorganocopper reagent Diorganocopper (Gilman) reagents from by reaction of 1 equivalent of cuprous iodide and 2 equivalents of organolithium 1, 2, 3 alkyl, aryl and alkenyl groups react but not alkynyl groups
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)
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Aldehide Keton

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3/1/2012

19.1 Naming Aldehydes and Ketones

Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions

The CHO carbon is numbered as C1

Aldehydes and Ketones

Numbering begins at the end nearer the carbonyl carbon

Ketones with Common Names

19.2 Preparation of Aldehydes and Ketones

Ketones and Aldehydes as Substituents

Ketones from Ozonolysis

Methyl Ketones by Hydrating Alkynes

Hydration of terminal alkynes in the presence of Hg2+ (catalyst: Section 8.5)

Aryl Ketones by Acylation

19.3 Oxidation of Aldehydes and Ketones

19.4 Nucleophilic Addition Reactions of Aldehydes and Ketones

Ketones Oxidize with Difficulty

19.5 Relative Reactivity of Aldehydes and Ketones

Reactivity of Aromatic Aldehydes

Electrophilicity of Aldehydes and Ketones

19.6 Nucleophilic Addition of H2O: Hydration

Acid-Catalyzed Addition of Water

Protonation of C=O makes it more electrophilic

Exception: simple aldehydes

Base-Catalyzed Addition of Water

Addition of H-Y to C=O

19.7 Nucleophilic Addition of HCN: Cyanohydrin Formation

Mechanism of Formation of Cyanohydrins

Treatment of aldehydes or ketones with Grignard reagents yields an alcohol

Mechanism of Addition of Grignard Reagents

19.9 Nucleophilic Addition of Amines: Imine and Enamine Formation

Mechanism of Formation of Imines

Note that overall reaction is substitution of RN for O

19.10 Nucleophilic Addition of Hydrazine: The WolffKishner Reaction

See Figure 19.11 for a mechanism

19.11 Nucleophilic Addition of Alcohols: Acetal Formation

19.12 Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction

Uses of the Wittig Reaction

Mechanism of the Wittig Reaction

The Biological Analogue of the Canizzaro Reaction

19.13 The Cannizzaro Reaction: Biological Reductions

19.14 Conjugate Nucleophilic Addition to ,Unsaturated Aldehydes and Ketones

19, 6th edition, (c) 2003

Conjugate Addition of Amines

Mechanism of Alkyl Conjugate Addition

Conjugate Addition of Alkyl Groups: Organocopper Reactions

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