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KOT 323 ORGANIC CHEMISTRY III

CHAPTER 21

ALDEHYDES and KETONES

NUCLEOPHILIC ADDITION

Carbonyl Compounds

Compounds containing carbonyl group, C=O

Carbonyl Compounds Compounds containing carbonyl group, C=O

Two structural features determine the chemistry and properties of aldehydes and ketones.

the chemistry and properties of aldehydes and ketones. The carbonyl group is sp 2 hybridized and
the chemistry and properties of aldehydes and ketones. The carbonyl group is sp 2 hybridized and

The carbonyl group is sp 2 hybridized and trigonal planar, making it relatively uncrowded. The electronegative oxygen atom polarizes the carbonyl group, making the carbonyl carbon electrophilic.

Reactions of Aldehydes and Ketones

Aldehydes and ketones react with nucleophiles. As the number of R groups around the carbonyl carbon increases, the reactivity of the carbonyl compound decreases, resulting in the following order of reactivity:

carbon increases, the reactivity of the carbonyl compound decreases, resulting in the fo llowing order of

Naming Aldehydes

IUPAC: Replace - e with - al . The aldehyde carbon is number 1. If -CHO is attached to a ring, use the suffix - carbaldehyde .

CH 3

O CH 2 CH 3 CH CH 2 C H
O
CH 2
CH 3
CH CH 2
C H

3-methylpentanal

. CH 3 O CH 2 CH 3 CH CH 2 C H 3-methylpentanal CHO 2-cyclopentenecarbaldehyde
. CH 3 O CH 2 CH 3 CH CH 2 C H 3-methylpentanal CHO 2-cyclopentenecarbaldehyde

CHO

2-cyclopentenecarbaldehyde

cyclopent-2-en-1-carbaldehyde

. CH 3 O CH 2 CH 3 CH CH 2 C H 3-methylpentanal CHO 2-cyclopentenecarbaldehyde

Common Names of Aldehydes

Like carboxylic acids, many simple aldehydes have common names that are widely used.

A common name for an aldehyde is formed by taking the common parent name and adding the suffix –aldehyde.

the common parent name and adding the suffix –aldehyde . • Greek letters are used to

Greek letters are used to designate the location of substituents in common names.

adding the suffix –aldehyde . • Greek letters are used to designate the location of substituents

Aldehyde Common Names

Use the common name of the acid. Drop - ic acid and add - aldehyde . 1 C: formic acid, formaldehyde 2 C’s: acetic acid, acetaldehyde 3 C’s: propionic acid, propionaldehyde 4 C’s: butyric acid, butyraldehyde

CH 3

Br CH CH 2 O C H β
Br
CH CH 2
O
C H
β

-bromobutyraldehyde

3-bromobutanal

IUPAC Names for Ketones

Replace -e with -one . Indicate the position of the carbonyl with a number. Number the chain so that carbonyl carbon has the lowest number. For cyclic ketones the carbonyl carbon is assigned the number 1.

CH 3

O C CH CH 2 OH CH 3
O
C
CH CH 2 OH
CH 3

4-hydroxy-3-methyl-2-butanone

4-hydroxy-3-methylbutan-2-one

O Br
O
Br

3-bromocyclohexanone

Common Names of Ketones

Most common names for ketones are formed by naming both alkyl groups on the carbonyl carbon, arranging them alphabetically, and adding the word “ketone”.

them alphabetically, and adding the word “ketone”. • Three widely used common names for some simple

Three widely used common names for some simple ketones do not follow this convention:

adding the word “ketone”. • Three widely used common names for some simple ketones do not

Naming Acyl Groups

Sometimes, acyl groups must be named as substituents. The three most common acyl groups are shown below:

Acyl Groups Sometimes, acyl groups must be named as substituents. The three most common acyl groups
Acyl Groups Sometimes, acyl groups must be named as substituents. The three most common acyl groups

Boiling Points

More polar (dipole-dipole interactions), so higher boiling point than comparable alkane or ether. Cannot form H-bond with each other, so lower boiling point than comparable alcohol.

comp arable alkane or ether. Cannot form H-bond with each other, so lower boiling point than
comp arable alkane or ether. Cannot form H-bond with each other, so lower boiling point than
comp arable alkane or ether. Cannot form H-bond with each other, so lower boiling point than

Solubility

Solubility Lone pair of electrons on oxygen of carbonyl can accept a hydrogen bond from O-H

Lone pair of electrons on oxygen of carbonyl can accept a hydrogen bond from O-H or N-H.

Solubility Lone pair of electrons on oxygen of carbonyl can accept a hydrogen bond from O-H

Spectroscopic Properties—IR Spectra

Aldehydes and ketones exhibit a strong peak at ~1700 cm 1 due to the C=O.

The sp 2 hybridized C–H bond of an aldehyde shows one or two peaks at ~2700 –2830 cm 1 .

the C=O. • The sp 2 hybridized C–H bond of an aldehyde shows one or two

Ring size effects

Most aldehydes have a carbonyl peak around 1730 cm 1 , whereas for ketones, it is typically around 1715 cm 1 .

Ring size affects the carbonyl absorption in a predictable manner.

it is typically around 1715 cm − 1 . • Ring size affects the carbonyl absorption

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Conjugation Effects

Conjugation

leads

to

a

somewhat

weaker

C=O

bond,

thus

shifting the carbonyl absorption to longer wavelengths.

• Conjugation leads to a somewhat weaker C=O bond, thus shifting the carbonyl absorption to longer
• Conjugation leads to a somewhat weaker C=O bond, thus shifting the carbonyl absorption to longer

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1 H NMR Spectra of Ketones and Aldehydes

1 H NMR Spectra of Ketones and Aldehydes
1 H NMR Spectra of Ketones and Aldehydes
1 H NMR Spectra of Ketones and Aldehydes
1 H NMR Spectra of Ketones and Aldehydes

13 C NMR absorptions

1 3 C NMR absorptions • There are three signals due to the three different kinds

There are three signals due to the three different kinds of carbons, labeled C a , C b , and C c .

The deshielded carbonyl carbon absorbs downfield at 203 ppm (190 – 215 ppm).

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MS of Ketones and Aldehydes

Loss of an alkyl group to give the acylium ion.

MS of Ketones and Aldehydes Loss of an alkyl group to give the acylium ion.
MS of Ketones and Aldehydes Loss of an alkyl group to give the acylium ion.

MS for Butyraldehyde

McLafferty rearrangement
McLafferty
rearrangement
MS for Butyraldehyde McLafferty rearrangement

McLafferty Rearrangement

Cyclic intramolecular transfer of a γ hydrogen to the carbonyl oxygen. Equivalent to α, β cleavage + transfer of one mass unit for the hydrogen. Loss of alkene (even mass number).

Equivalent to α , β cleavage + transfer of one mass unit for the hydrogen. Loss
Equivalent to α , β cleavage + transfer of one mass unit for the hydrogen. Loss
Industrial Importance Acetone and methyl ethyl ketone are important solvents. Formaldehyde used in polymers like

Industrial Importance

Acetone and methyl ethyl ketone are important solvents. Formaldehyde used in polymers like Bakelite ®

(1907) .

Flavorings and additives like vanilla, cinnamon, artificial butter.

like Bakelite ® (1907) . Flavorings and additives like vanilla, cinnamon, artificial butter. 1949 Bakelite TV

1949 Bakelite TV set

like Bakelite ® (1907) . Flavorings and additives like vanilla, cinnamon, artificial butter. 1949 Bakelite TV
like Bakelite ® (1907) . Flavorings and additives like vanilla, cinnamon, artificial butter. 1949 Bakelite TV

Natural Aldehydes and Ketones with Strong Odors

Natural Aldehydes and Ketones with Strong Odors

Preparation of Aldehydes

Preparation of Aldehydes

Preparation of Ketones

Preparation of Ketones

Oxidative Cleavage of Alkenes

Aldehydes and ketones are also both obtained as products of the oxidative cleavage of alkenes.

Aldehydes and ketones are also both obtained as products of the oxidative cleavage of alkenes. Unlike

Unlike strong oxidation:

Aldehydes and ketones are also both obtained as products of the oxidative cleavage of alkenes. Unlike

General Reactions of Aldehydes and Ketones

[1] Reaction at the carbonyl carbon—the elements of H and Nu are added to the carbonyl group.

elements of H and Nu are added to the carbonyl group. Addition of a nucleophile and

Addition of a nucleophile and a proton across the C=O double bond. Examples are like attack of Grignard reagent and hydride reduction to give alcohols Can take place under acid-catalyzed or base- catalyzed condition.

[2] Reaction at the α carbon.

[2] Reaction at the α carbon. Formation of resonance- stabilized enolate anion made the C-H bond

Formation of resonance-stabilized enolate anion made the C-H bond on the α carbon more acidic.

Enolates are nucleophiles that react with electrophiles to form new bonds on the α carbon.

Nucleophilic Addition

Nucleophilic Addition • In this process, nucleophilic attack precedes protonation. • This mechanism occurs with

In this process, nucleophilic attack precedes protonation.

This mechanism occurs with negatively charged or strong neutral nucleophiles under:

Base-catalyzed addition

Acid-catalyzed nucleophilic addition

Acid-catalyzed nucleophilic addition • In this mechanism, protonation precedes nucleophilic attack as shown above. •
Acid-catalyzed nucleophilic addition • In this mechanism, protonation precedes nucleophilic attack as shown above. •

In this mechanism, protonation precedes nucleophilic attack as shown above.

With some neutral nucleophiles, nucleophilic addition only occurs if an acid is present to activate the carbonyl by protonation.

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Nucleophiles in Nucleophilic Adition

Nucleophilic trends in carbonyl attack are not the same as in straightforward substitution reactions at sp 3 carbon atoms.

Cl¯, Br¯, and I¯ are good nucleophiles in substitution reactions at sp 3 hybridized carbons, but they are ineffective nucleophiles in addition.

When these nucleophiles add to the sp 2 carbonyl carbon, they cleave the C–O π bond, forming an alkoxide.

Since X¯ is a much weaker base than the alkoxide formed, equilibrium favors the starting materials, not the addition product.

is a much weaker base than the alkoxide formed, equilibrium favors the starting materials, not the

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Other nucleophiles add to carbonyl groups to form unstable intermediates which rapidly undergo elimination.

This addition–elimination process, particularly with amine- related nitrogen nucleophiles, replaces a C=O with a C=N.

For example, amines (RNH 2 ) add to carbonyl groups in the presence of mild acid to form unstable carbinolamines, which readily lose water to form imines.

carbonyl groups in the presence of mild acid to form unstable carbinolamines, which readily lose water

Nucleophilic Addition Reactions

Nucleophilic Addition Reactions 33

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Nucleophilic Addition of Hydride

Treatment of an aldehyde or ketone with either NaBH 4 or LiAlH 4 followed by protonation forms a 1° or 2° alcohol.

or LiAlH 4 followed by protonation forms a 1° or 2° alcohol. Hydride reduction occurs via

Hydride reduction occurs via a two-step mechanism.

or LiAlH 4 followed by protonation forms a 1° or 2° alcohol. Hydride reduction occurs via

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Nucleophilic Addition of R¯

Treatment of an aldehyde or ketone with either an organolithium (RLi) or Grignard reagent (RMgX) followed by water forms a 1°, 2°, or 3° alcohol containing a new C–C bond.

a 1°, 2°, or 3° alcohol containing a new C–C bond. • Nucleophilic addition of the

Nucleophilic addition of the carbanion-like species occurs via a two-step mechanism.

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Formation of Cyanohydrins

Addition of HCN across C=O. Treatment of an aldehyde or ketone with NaCN and a strong acid such as HCl.

Cyanohydrins Addition of HCN across C=O. Treatment of an aldehyde or ketone with NaCN and a

Hydrolysis of Cyanohydrins

Cyanohydrins can be reconverted to carbonyl compounds by treatment with base.

The reverse of the addition of HCN: deprotonation followed by elimination of ¯CN.

of HCN: deprotonation followed by elimination of ¯CN. • The cyano group of a cyanohydrin is

The cyano group of a cyanohydrin is readily hydrolyzed to a carboxy group by heating with aqueous acid or base.

• The cyano group of a cyanohydrin is readily hydrolyzed to a carboxy group by heating

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Cyanohydrins in Nature

Linamarin and Amygdalin are two naturally occurring cyanohydrin derivatives.

are two naturally occurring cyanohydrin derivatives. • Both compounds are toxic because they are metabolized

Both compounds are toxic because they are metabolized to cyanohydrins, which are hydrolyzed to carbonyl compounds and HCN gas.

compounds are toxic because they are metabolized to cyanohydrins, which are hydrolyzed to carbonyl compounds and

Wittig Reaction

converts the carbonyl group of a ketone or an aldehyde into a new C=C double bond. Wittig reagent, phosphorus ylide is used as the carbonnucleophile.

a ketone or an aldehyde into a new C=C double bond. Wittig reagent, phosphorus ylide is
a ketone or an aldehyde into a new C=C double bond. Wittig reagent, phosphorus ylide is

Wittig Reagents

The Wittig reagent is an organophosphorus reagent. A typical Wittig reagent has a phosphorus atom bonded to three phenyl groups, plus another alkyl group that bears a negative charge.

plus another alkyl group that bears a negative charge. • A Wittig reagent is an ylide

A Wittig reagent is an ylide, a species that contains two oppositely charged atoms bonded to each other, with both atoms having octets.

Phosphorus ylides are also called phosphoranes.

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Preparation of Phosphorus Ylides

From nucleophilic attack of triphenylphosphine on an unhindered alkyl halide.

Preparation of Phosphorus Ylides From nucleophilic attack of triphenylphosphine on an unhindered alkyl halide.
Preparation of Phosphorus Ylides From nucleophilic attack of triphenylphosphine on an unhindered alkyl halide.
Preparation of Phosphorus Ylides From nucleophilic attack of triphenylphosphine on an unhindered alkyl halide.

Mechanism of Wittig Reaction – two steps

Mechanism of Wittig Reaction – two steps
Mechanism of Wittig Reaction – two steps
Mechanism of Wittig Reaction – two steps
Mechanism of Wittig Reaction – two steps

Use of the Wittig Reaction

One limitation of the Wittig reaction is that a mixture of stereoisomers sometimes forms.

is that a mixture of stereoisomers sometimes forms. • The Wittig reaction has been used to

The Wittig reaction has been used to synthesize many natural products.

a mixture of stereoisomers sometimes forms. • The Wittig reaction has been used to synthesize many

Retrosynthesis of Wittig Reaction

Retrosynthesis of Wittig Reaction
Retrosynthesis of Wittig Reaction
Retrosynthesis of Wittig Reaction
The Wittig Reaction Leads to Precise Placement of the Double Bond • An advantage of
The Wittig Reaction Leads to Precise Placement of the Double Bond • An advantage of

The Wittig Reaction Leads to Precise Placement of the Double Bond

An advantage of the Wittig reaction over elimination methods used to synthesize alkenes is that the Wittig reaction always gives a single constitutional isomer.

Consider the two methods that can be used to convert cyclohexanone into cycloalkene B.

constitutional isomer. • Consider the two methods that can be used to convert cyclohexanone into cycloalkene

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Comparison of Alkene Formation Methods

Addition of a Grignard reagent followed by dehydration gives a mixture of products with the desired compound being the minor product.

products with the desired compound being the minor product. • Using the Wittig reaction to achieve

Using the Wittig reaction to achieve the same synthesis gives only the desired compound.

being the minor product. • Using the Wittig reaction to achieve the same synthesis gives only

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Formation of Imines

Acid-catalyzed nucleophilic addition of ammonia or 1 o amine, followed by elimination of water molecule. C=O becomes C=N-H / C=N-R (Schiff base).

Treatment of an aldehyde or a ketone with a 1° amine affords an imine (also called a Schiff base).

(Schiff base). Treatment of an aldehyde or a ketone with a 1° amine affords an imine

Imine Properties

Imine formation is fastest when the reaction medium is weakly acidic (pH 4–5).

Imine Properties • Imine formation is fastest when the reaction medium is weakly acidic (pH 4–5).

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Mechanism

Mechanism
Mechanism

Role of Acidity in Imine Formation

In imine formation, mild acid is needed for protonation of the hydroxy group in step 3 to form a good leaving group. Under strongly acidic conditions, the reaction rate decreases because the amine nucleophile is protonated. With no free electron pair, it is no longer a nucleophile, and so nucleophilic addition cannot occur.

protonated. With no free electron pair, it is no longer a nucleophile, and so nucleophilic addition

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Imines in Nature

Many imines play vital roles in biological systems.

A key molecule in the chemistry of vision is the highly conjugated imine rhodopsin, which is synthesized by the rod cells of the eye from 11-cis-retinal and a 1° amine in the protein opsin.

which is synthesized by the rod cells of the eye from 11- cis -retinal and a

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The Key Reaction in the Chemistry of Vision

The Key Reaction in the Chemistry of Vision

RecapRecap

Recap Recap … … Wittig Reactions: • Formation of phosphorus ylide From nucleophilic attack of triphenylphosphine

Wittig Reactions:

Formation of phosphorus ylide From nucleophilic attack of triphenylphosphine on an unhindered alkyl halide.

• Formation of more specific alkenes (stereoisomers).

• Retrosynthesis of Wittig reaction.

Formation of imines (Schiff bases):

• Reaction of carbonyl compounds with NH 3 or NH 2 R.

• An acid-catalyzed reaction.

Formation of Enamines

A 2° amine reacts with an aldehyde or ketone to give an enamine. Enamines have a nitrogen atom bonded to a C–C double bond.

reacts with an aldehyde or ketone to give an enamine . Enamines have a nitrogen atom
reacts with an aldehyde or ketone to give an enamine . Enamines have a nitrogen atom
reacts with an aldehyde or ketone to give an enamine . Enamines have a nitrogen atom

Mechanism

Mechanism
Mechanism
Mechanism

Formation of Imines vs. Enamines

Formation of Imines vs. Enamines With a 1 o amine, the intermediate iminium ion still has

With a 1 o amine, the intermediate iminium ion still has a proton on the N atom that may be removed to form a C=N. With a 2 o amine, the intermediate iminium ion has no proton on the N atom. A proton must be removed from an adjacent C–H bond, and this forms a C=C.

Hydrolysis of Imines and Enamines

Imines and enamines can be converted back to carbonyl compounds by hydrolysis with mild acid.

The mechanism of hydrolysis is the exact reverse of the mechanism written for formation of imines and enamines.

acid. • The mechanism of hydrolysis is the exact reverse of the mechanism written for formation
acid. • The mechanism of hydrolysis is the exact reverse of the mechanism written for formation

Give the mechanism of Hydrolysis of Imines

Give the mechanism of Hydrolysis of Imines
Give the mechanism of Hydrolysis of Imines 30
Give the mechanism of Hydrolysis of Imines 30
Give the mechanism of Hydrolysis of Imines 30
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Hydration of Aldehydes and Ketones

Treatment of a carbonyl compound with H 2 O in the presence of an acid or base catalyst adds the elements of H and OH across the C–O π bond, forming a gem-diol or hydrate.

the C–O π bond, forming a gem-diol or hydrate . Gem -diol product yields are good

Gem-diol product yields are good only when unhindered aldehydes or aldehydes with nearby electron withdrawing groups are used.

product yields are good only when unhindered aldehydes or aldehydes with nearby electron withdrawing groups are
Hydration Level vs. Stability Increasing the number of alkyl groups on the carbonyl carbon decreases
Hydration Level vs. Stability
Increasing
the
number
of
alkyl
groups
on
the
carbonyl
carbon decreases the amount of hydrate at equilibrium.
This can be illustrated by comparing the amount of hydrate
formed from formaldehyde, acetaldehyde and acetone.

Electronic Factors Affecting Hydrate Stability

Electron-donating groups near the carbonyl carbon stabilize the carbonyl group, decreasing the amount of the hydrate at equilibrium.

Electron-withdrawing

carbon

destabilize the carbonyl group, increasing the amount of hydrate at equilibrium.

groups

near

the

carbonyl

amount of hydrate at equilibrium. groups near the carbonyl Three electron-withdrawing Cl atoms result in a
amount of hydrate at equilibrium. groups near the carbonyl Three electron-withdrawing Cl atoms result in a

Three electron-withdrawing Cl atoms result in a partial positive charge on the α carbon of the carbonyl, destabilizing the carbonyl group, and therefore increasing the amount of hydrate at equilibrium.

The Kinetics of Hydrate Formation

Both acid and base catalyze carbonyl group.

the

Base Catalyzed Hydration

addition of H 2 O

to the

With base, the nucleophile is ¯OH, and the mechanism follows the usual two steps: nucleophilic attack followed by protonation. The reaction rate increases under basic conditions because of the higher concentration of ¯OH, a stronger nucleophile.

The reaction rate increases under basic conditions because of the higher concentration of ¯OH, a stronger

Acid Catalyzed Hydration

The acid protonates the carbonyl group, making it more electrophilic and thus more susceptible to nucleophilic attack.

The acid protonates the carbonyl group, making it more electrophilic and thus more susceptible to nucleophilic
The acid protonates the carbonyl group, making it more electrophilic and thus more susceptible to nucleophilic

Formation of Acetals

Formation of Acetals Involves addition of two alcohol molecules and elimination of one water molecule. Must

Involves addition of two alcohol molecules and elimination of one water molecule. Must be acid-catalyzed, commonly with p - toluenesulfonic acid (TsOH).

• When a diol such as ethylene glycol is used in place of two equivalents

When a diol such as ethylene glycol is used in place of two equivalents of ROH, a cyclic acetal is formed.

• When a diol such as ethylene glycol is used in place of two equivalents of

Mechanism

Part 1: Acid-catalyzed addition of alcohol.

Mechanism Part 1: Acid-catalyzed addition of alcohol. Hemiacetal is too unstable to be isolated and purified.

Hemiacetal is too unstable to be isolated and purified.

Part 2: Acid-catalyzed dehydration

S N 1
S
N 1
HO H+
HO
H+

OCH 3

Part 2: Acid-catalyzed dehydration S N 1 HO H+ OCH 3 H + OCH 3 HO
H + OCH 3 HO OCH 3 + + HOH
H
+
OCH 3
HO
OCH 3
+
+ HOH
HOCH 3 Attack of second alcohol H + OCH 3 CH 3 O OCH 3
HOCH 3
Attack of second alcohol
H
+
OCH 3
CH 3 O
OCH 3
CH 3 O
OCH 3
+
HOCH 3

acetal

When a diol such as ethylene glycol is used in place of two equivalents of ROH, a cyclic acetal is formed.

of two equivalents of ROH, a cyclic acetal is formed. Like gem -diol formation, the synthesis

Like gem-diol formation, the synthesis of acetals is reversible, and often, the equilibrium favors the reactants. In acetal synthesis, since water is formed as a by-product, the equilibrium can be driven to the right by removing H 2 O as it is formed using distillation or other techniques.

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Dean-Stark Trap for Removing Water

Figure 21.11

Dean-Stark Trap for Removing Water Figure 21.11 73
Dean-Stark Trap for Removing Water Figure 21.11 73

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Hydrolysis of Acetals

Because conversion of an aldehyde or ketone to an acetal is a reversible reaction, an acetal can be hydrolyzed to an aldehyde or ketone by treatment with aqueous acid.

Since the reaction is also an equilibrium process, it is driven to the right by using a large excess of water for hydrolysis.

reaction is also an equilibrium process, it is driven to the right by using a large

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Mechanism

Mechanism
Mechanism
Mechanism
Require a strong acid to make a good leaving group (ROH, a weak base and

Require a strong acid to make a good leaving group (ROH, a weak base and neutral leaving group).

Acetal hydrolysis does not occur in base.

RecapRecap

Recap Recap … … Formation of enamines • How it different from the formation of imines.

Formation of enamines How it different from the formation of imines. Acidic hydrolysis of imines & enamines

Hydration of aldehydes / ketones

of imines. • Acidic hydrolysis of imines & enamines Hydration of aldehydes / ketones Formation of

Formation of acetals

of imines. • Acidic hydrolysis of imines & enamines Hydration of aldehydes / ketones Formation of

Acetals as Protecting Groups

Acetals hydrolyzed easily in acid, but stable to strong bases and nucleophiles. Prevent ketones or aldehydes from reacting with strong bases, oxidizing/reducing agents or nucleophiles.

strong bases, oxidizing/reducing agents or nucleophiles. LiAlH 4 will reduce the ester to yield an alcohol,

LiAlH 4 will reduce the ester to yield an alcohol, but the keto group will also be reduced

The keto group is protected as a ketal in this synthesis

The keto group is protected as a ketal in this synthesis The more reactive aldehyde is

The more reactive aldehyde is protected with the diol before reaction with the Grignard reagent

a ketal in this synthesis The more reactive aldehyde is protected with the diol before reaction

Cyclic Hemiacetals

Cyclic hemiacetals (lactols) containing five- and six- membered rings are stable compounds that are readily isolated.

Cyclic hemiacetals (lactols) containing five- and six- membered rings are stable compounds that are readily isolated.

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Formation of Cyclic Hemiacetals

Cyclic hemiacetals are formed by intramolecular cyclization of hydroxy aldehydes.

formed by intramolecular cyclization of hydroxy aldehydes. Such intramolecular reactions to form five- and six-membered

Such intramolecular reactions to form five- and six-membered rings are faster than the corresponding intermolecular reactions. The two reacting functional groups (OH and C=O), are held in close proximity, increasing the probability of reaction.

Mechanism

Hemiacetal formation is catalyzed by both acid and base.

Mechanism • Hemiacetal formation is catalyzed by both acid and base. equal amount
Mechanism • Hemiacetal formation is catalyzed by both acid and base. equal amount
Mechanism • Hemiacetal formation is catalyzed by both acid and base. equal amount
Mechanism • Hemiacetal formation is catalyzed by both acid and base. equal amount

equal amount

Conversion of Hemiacetals to Acetals

Cyclic hemiacetals can be converted to acetals by treatment with an alcohol and acid.

to acetals by treatment with an alcohol and acid. Overall result: Replacement of hemiacetal OH group
to acetals by treatment with an alcohol and acid. Overall result: Replacement of hemiacetal OH group
to acetals by treatment with an alcohol and acid. Overall result: Replacement of hemiacetal OH group

Overall result:

Replacement of hemiacetal OH group by an OCH 3 group.

This reaction occurs readily because the carbocation formed in step 2 is stabilized by resonance, making the hemiacetal OH group different from the hydroxy group in other alcohols. Thus, when a compound with both an alcohol OH and a hemiacetal OH is treated with an alcohol and acid, only the hemiacetal OH reacts to form the acetal.

an alcohol OH and a hemiacetal OH is treated with an alcohol and acid, only the

Introduction to Carbohydrates

Carbohydrates, commonly referred to as sugars and starches, are polyhydroxy aldehydes and ketones, or compounds that can be hydrolyzed to them.

Many carbohydrates contain cyclic acetals or hemiacetals.

Examples include glucose and lactose.

to them. • Many carbohydrates contain cyclic acetals or hemiacetals. • Examples include glucose and lactose.
to them. • Many carbohydrates contain cyclic acetals or hemiacetals. • Examples include glucose and lactose.
to them. • Many carbohydrates contain cyclic acetals or hemiacetals. • Examples include glucose and lactose.

Hemiacetals in sugars are formed by cyclization of hydroxy aldehydes. The hemiacetal in glucose is formed by cyclization of an acyclic polyhydroxy aldehyde (A), as shown.

of an acyclic polyhydroxy aldehyde (A), as shown. When the OH group on C5 is the

When the OH group on C5 is the nucleophile, cyclization yields a six-membered ring, and this ring size is preferred. Cyclization forms a new stereogenic center—the new OH group of the hemiacetal can occupy the equatorial or axial position.

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