Chapter 19 Aldehydes and Ketones Nucleophilic Addition Reactions

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Chapter 19 Aldehydes and Ketones Nucleophilic Addition Reactions Powered By Docstoc
					Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions

Based on McMurry’s Organic Chemistry, 7th edition

Aldehydes and Ketones
 Aldehydes (RCHO) and ketones (R2CO) are

characterized by the the carbonyl functional group (C=O)  The compounds occur widely in nature as intermediates in metabolism and biosynthesis

2

Why this Chapter?
 Much of organic chemistry involves the

chemistry of carbonyl compounds
 Aldehydes/ketones are intermediates in

synthesis of pharmaceutical agents, biological pathways, numerous industrial processes
 An understanding of their properties is essential

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19.1 Naming Aldehydes:
 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

Ethanal acetaldehyde

Propanal Propionaldehyde

2-Ethyl-4-methylpentanal

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19.1 Naming Aldehydes and Ketones

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Naming Aldehydes
 If the CHO group is attached to a ring, use the

suffix carbaldehyde.

Cyclohexanecarbaldehyde

2-Naphthalenecarbaldehyde

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Naming Aldehydes:
 Common Names end in aldehyde

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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 grp  Numbering begins at the end nearer the carbonyl carbon

3-Hexanone (New: Hexan-3-one)

4-Hexen-2-one 2,4-Hexanedione (New: Hex-4-en-2-one) (New: Hexane-2,4-dione)

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Ketones with Common Names
 IUPAC retains well-used but unsystematic names for a few

ketones

Acetone

Acetophenone

Benzophenone

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Ketones and Aldehydes as Substituents
 The R–C=O as a substituent is an acyl group, used with the

suffix -yl from the root of the carboxylic acid

 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

10

Learning Check:
 Name the following:

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Solution:
 Name the following:
2-methyl-3-pentanone (ethyl isopropyl ketone) 2,6-octanedione

3-phenylpropanal (3-phenylpropionaldehyde)

4-hexenal Trans-2-methylcyclohexanecarbaldehyde Cis-2,5-dimethylcyclohexanone
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19.2 Preparation of Aldehydes
Aldehydes  Oxidation of 1o alcohols with pyridinium chlorochromate PCC

 Oxidative cleavage of Alkenes with a vinylic hydrogen with

ozone

13

Preparation of Aldehydes
Aldehydes  Reduction of an ester with diisobutylaluminum hydride (DIBAH)

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Preparing Ketones
Ketones  Oxidation of a 2° alcohol


Many reagents possible: Na2Cr2O7, KMnO4, CrO3


choose for the specific situation (scale, cost, and acid/base sensitivity)

15

Ketones from Ozonolysis
Ketones  Oxidative cleavage of substituted Alkenes with ozone

16

Aryl Ketones by Acylation
Ketones  Friedel–Crafts acylation of an aromatic ring with an acid chloride in the presence of AlCl3 catalyst

17

Methyl Ketones by Hydrating Alkynes
Ketones  Hydration of terminal alkynes in the presence of Hg2+ cat

18

Preparation of Ketones
Ketones  Gilman reaction of an acid chloride

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Learning Check:
 Carry out the following transformations:

3-Hexyne  3-Hexanone

Benzene  m-Bromoacetophenone

Bromobenzene  Acetophenone 1-methylcyclohexene  2-methylcyclohexanone

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Solution:
 Carry out the following transformations:

3-Hexyne  3-Hexanone
O CH3 CH2 C C CH2 CH3

Hg(OAc)2,C H 3 H 3 O+

CH2

C

CH2

CH2

CH3

Benzene  m-Bromoacetophenone
O
O 1) C H 3 C C l , A lC l 3

Br

2) B r 2 , F eB r 3

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Solution:
 Carry out the following transformations:

Bromobenzene  Acetophenone
1 ) M g in eth er

O

Br
2) C H 3 3 ) H 3O 4) PC C
+

O C H

1-methylcyclohexene  2-methylcyclohexanone
CH3
1) B H 3 2 ) H 2 O 2 , N aO H 3) PC C

CH3 O

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19.3 Oxidation of Aldehydes & Ketones
 CrO3 in aqueous acid oxidizes aldehydes to carboxylic

acids (acidic conditions)

 Tollens’ reagent Silver oxide, Ag2O, in aqueous ammonia

oxidizes aldehydes (basic conditions)

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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

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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

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19.4 Nucleophilic Addition Reactions of Aldehydes and Ketones
 Nu-

approaches 75° to the plane of C=O and adds to C
 A tetrahedral

alkoxide ion intermediate is produced

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Nucleophiles

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Reactions variations

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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

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Relative Reactivity of Aldehydes and Ketones
 Aldehydes are generally more reactive than ketones in

nucleophilic addition reactions
 

Aldehyde C=O is more polarized than ketone C=O Ketone has more electron donation alkyl groups, stabilizing the C=O carbon inductively

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Reactivity of Aromatic Aldehydes
 Aromatic Aldehydes Less reactive in nucleophilic addition

reactions than aliphatic aldehydes


Electron-donating resonance effect of aromatic ring makes C=O less reactive electrophile than the carbonyl group of an aliphatic aldehyde

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19.5 Nucleophilic Addition of H2O: Hydration
 Aldehydes and ketones react with water to yield 1,1-diols

(geminal (gem) diols)  Hydration is reversible: a gem diol can eliminate water

32

Base-Catalyzed Addition of Water
 Addition of water

is catalyzed by both acid and base  The basecatalyzed hydration nucleophile is the hydroxide ion, which is a much stronger nucleophile than water
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Acid-Catalyzed Addition of Water
 Protonation

of C=O makes it more electrophilic

34

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

35

19.6 Nucleophilic Addition of HCN: Cyanohydrin Formation
 Aldehydes and unhindered ketones react with HCN to yield

cyanohydrins, RCH(OH)CN

 Addition of HCN is reversible and base-catalyzed,

generating nucleophilic cyanide ion, CN-

A cyanohydrin

36

Uses of Cyanohydrins
 The nitrile group (CN) 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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19.7 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 carbon–magnesium bond is strongly polarized, so a Grignard reagent reacts for all practical purposes as R :  MgX +.

38

Mechanism of Addition of Grignard Reagents
 Complexation of

C=O by Mg2+, Nucleophilic addition of R : , protonation by dilute acid yields the neutral alcohol are irreversible because a carbanion is not a leaving group

 Grignard additions

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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

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19.8 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, R2NCR=CR2 (after loss of HOH) (ene + amine = unsaturated amine)

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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
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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.
These are usually solids and help in characterizing liquid ketones or aldehydes by melting points
 For example,


hydroxylamine forms oximes

2,4-dinitrophenylhydrazine readily forms 2,4dinitrophenylhydrazones


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Enamine Formation
 After

addition of R2NH, proton is lost from adjacent carbon

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Imine / Enamine Examples

45

19.9 Nucleophilic Addition of Hydrazine: The Wolff–Kishner 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
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The Wolff–Kishner Reaction: Examples

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19.10 Nucleophilic Addition of Alcohols: Acetal Formation
 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

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Acetal Formation

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Uses of Acetals
 Acetals can be protecting groups for aldehydes & ketones  Use a diol, to form a cyclic acetal (reaction goes faster)

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19.11 Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction
 The sequence converts C=O  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

An ylide

51

Mechanism of the Wittig Reaction

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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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19.12 The Cannizaro Reaction
 The adduct of an aldehyde and OH can transfer hydride

ion to another aldehyde C=O resulting in a simultaneous oxidation and reduction (disproportionation)

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19.13 Conjugate Nucleophilic Addition to Unsaturated Aldehydes and Ketones
 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
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Conjugate Addition of Amines
 Primary and secondary amines add to , -unsaturated

aldehydes and ketones to yield -amino aldehydes and ketones

Reversible so more stable product predominates
56

Conjugate Addition of Alkyl Groups: Organocopper Reactions
 Reaction of an , -unsaturated ketone with a lithium

diorganocopper reagent
 Diorganocopper

(Gilman) reagents form 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

57

Mechanism of Alkyl Conjugate Addition
 Conjugate nucleophilic addition of a diorganocopper

anion, R2Cu, to an enone  Transfer of an R group and elimination of a neutral organocopper species, RCu

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19.14 Spectroscopy of Aldehydes and Ketones
 Infrared

Spectroscopy  Aldehydes and ketones show a strong C=O peak 1660 to 1770 cm1  aldehydes show two characteristic C–H absorptions in the 2720 to 2820 cm1 range.

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C=O Peak Position in the IR Spectrum
 The precise position of the peak reveals the

exact nature of the carbonyl group

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NMR Spectra of Aldehydes
 Aldehyde proton signals are at  10 in 1H NMR -

distinctive spin–spin coupling with protons on the neighboring carbon, J  3 Hz

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13C

NMR of C=O

 C=O signal is at  190 to  215  No other kinds of carbons absorb in this range

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Mass Spectrometry – McLafferty Rearrangement
 Aliphatic aldehydes and ketones that have hydrogens

on their gamma () carbon atoms rearrange as shown

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Mass Spectroscopy: -Cleavage
 Cleavage of the bond between the carbonyl group

and the  carbon  Yields a neutral radical and an oxygen-containing cation

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