Chapter 19.

Aldehydes and Ketones: Nucleophilic Addition Reactions

Based on McMurrys Organic Chemistry, 6th edition
2003 Ronald Kluger Department of Chemistry University of Toronto

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

Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003

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

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

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

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

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

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

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

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

Aryl Ketones by Acylation

FriedelCrafts 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

CC 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 22

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

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

R R O C H + R2NH H C O C C H C H H C NH HO

R R N H+ H2O C H

R R N C C H

R N

+ H3O+

C 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)

Based on McMurry, Organic Chemistry, Chapter 19, 6th edition, (c) 2003

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