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Chemistry 2600 Lecture Notes
Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
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Addition Reactions of aldehydes and ketones; introduction to sugar chemistry
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Next six chapters in the text deal with the carbonyl group (three to be covered in Chem2600)
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This chapter deals with nucleophilic addition to aldehydes and ketones (only)
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We start by reviewing what we have already learned in this course about carbonyl chemistry
1.
Synthesis of carbonyl compounds was covered in Chapter 8:
Type of alcohol
Oxidation reaction
Result
H
Primary
R
OH
O
[O]
R
Aldehydes under mild oxidation conditions
H
H
H
Primary
R
OH
O
[O]
R
Carboxylic acids under aggresive oxidation conditions
O
H
H
R'
Secondary
R
OH
O
[O]
R
R'
Ketones under all oxidation conditions,
mild conditions generally prefered
H
R'
Tertiary
R
OH
[O]
No reaction because no H to eliminate
R''
Name of reagent
Reagent/condition
Result
Swern
Enzymes (alcohol dehydrogenase)
• DMSO, ClCOCOCl
‚NEt3
NAD+ or NADP + “coenzyme”
Collin’s reagent
CrO 3 .py2 in CH2 Cl2 at R.T.
Corey’s reagent
PCC = (pyH+)(CrO 3 Cl)–
Jones’ reagent
(high valence Cr in acid condit.)
MnO4 –
(high valence Mn in base condit.)
MnO2 (freshly prepared)
CrO 3 in H2 SO4 = “H2 Cr2 O7 ”
or CrO 3 in CH3 COOH
• MnO4 – in H2 O, OH–
‚ H3 O+ (workup to release acid)
MnO2 in acetone, R.T.
or MnO2 in benzene, R.T.
°1 ROH to aldehyde
°2 ROH to ketone
°1 ROH to aldehyde
°2 ROH to ketone
°1 ROH to aldehyde
°2 ROH to ketone
°1 ROH to aldehyde
°2 ROH to ketone
°1 ROH to carboxylic acids
(°2 ROH to ketone – not best!)\
°1 ROH to carboxylic acids
(°2 ROH to ketone – not best!)\
Allylic and benzylic alcohols only
°1 ROH to aldehyde
°2 ROH to ketone
Chemistry 2600 Lecture Notes
2.
Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
Addition of organomagnesium, organolithium, organocopper and acetylides (Chapter 13)
Grignard Reagents
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Chemistry 2600 Lecture Notes
3.
Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
Reduction of addition products: Hydride Reduction
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Chemistry 2600 Lecture Notes
4.
Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
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Hydrogen reduction of aldehydes and ketones
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Metal-catalyzed addition of hydrogen to a double bond (p. 416)
O
•
H
H2, Pt
OH
Hydrogenolysis occurs for benzylic alcohols
O
H
H
H2, Pt
5.
Zinc amalgam reduction of aldehydes and ketones
6.
The Baeyer-Villager Oxidation
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The conversion of a ketone to an ester using a peroxo-carboxylic acid, usually PTFA
H
O
R
R'
H
O3CCF 3
H
+
O
R
-:O
O
3CCF3
R
R'
+
O
R
H
H
O
-:O CCF
2
3
O
R
R'
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This differs from oxidations learned in Ch. 8. Why?
O
R'
O
O
R'
O
CF3
Chemistry 2600 Lecture Notes
•
Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
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Cyclic ketones lead to an important class of cyclic esters called LACTONES
O
O
CF3CO3H
Remember, CF3CO3H is of course:
O
O
CF3
O
O
H
“Migratory aptitude of R’ group”
Aryl > 4° > 3° > 2° > 1° > Methyl
•
So for asymmetric ketones the following happens:
O
O
CF3CO3H
O
AND
O
R
•
O
CF3CO 3H
CH3
R
O
CH3
R > one carbon
Hydrolysis of the products leads to alcohols (e.g. ROH and acetic acid for above right)
(see Chapter 19)
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The conversion of an aldehyde to a carboxylic acid is another consequence of the
Baeyer-Villager reaction.
O
CF3CO3H
H
O
OH
(this is not a new concept; just another way to oxidize aldehydes, p.355 to p.358)
Chemistry 2600 Lecture Notes
Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
Nucleophilic addition reactions to aldehydes and ketones: Mechanism
1.
•
Order of reactivity of aldehydes and ketones:
•
Reason:
Nucleophilic HCN addition under basic conditions gives a cyanohydrin
There are two workup reactions indicatated:
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Chemistry 2600 Lecture Notes
Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
2.
Nucleophilic addition of HX form geminal halohydrins
3.
Nucleophilic addition of Water: formation of “hydrates” or “Gem-diols”
•
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For most aldehydes and ketones, the hydrate is not stable, but there are important exceptions:
Chemistry 2600 Lecture Notes
4.
Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
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Nucleophilic addition of alcohols: formation of Acetals (sometimes called Ketals)
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Addition to aldehydes is always potentially a two-stage reaction:
1.)
2.)
•
Mechanism involves acid catalysis (a crucial mechanism, learn it well):
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The same mechanism applies for the addition of thiols and dithiols
Chemistry 2600 Lecture Notes
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Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
Addition to ketones is also two-stage but requires more forcing conditions
A hemiacetal (older: hemiketal)
An acetal (older: ketal)
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The mechanism is the same as for addition to aldehydes
•
We met acetals in Chapter 13 as protecting groups for with alcohols and ketones
Alcohol + vinylic ether
Alcohol + a-chloroether
Ketone + vicinal diol
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Chemistry 2600 Lecture Notes
5.
Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
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Hemiacetals are the key to understanding the carbohydrates (“sugars”)
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Ring-chain tautomerism of hemiacetals result in stable rings under special conditions
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Stable rings are commonly seen among sugars
Chain-glucose
a-glucopyranose
ß-glucopyranose
Chemistry 2600 Lecture Notes
Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
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Sugars are classified by the number of carbon atoms in the chain
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There are three-carbon, four-carbon, five-carbon and six-carbon sugars
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Sugars may be aldoses (contain an aldehyde) or ketoses (contain a ketone)
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Chemistry 2600 Lecture Notes
Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
Molecular Modeling of Sugars – relation to Fischer and Haworth projections
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Chemistry 2600 Lecture Notes
Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
β-D-Glucopyranose
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α-D-Glucopyranose
Take β-D-Glucopyranose, and place on its side, with CH2 OH group at bottom, then break bond
to anomeric carbon, and open up the chain:
Chemistry 2600 Lecture Notes
Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
Sugar Chemistry
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Acetal derivatives are made by addition of alcohol to aldose carbonyl groups
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The alcohol can be from another sugar, producing di- and polysaccharides
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Sucrose and Lactose are common disaccharides
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Carbohydrates are polysaccharides:
Amylose (starch)
Cellulose
•
Polysacharides are hydrolysed to sugars under acid conditions because they are acetals
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Chemistry 2600 Lecture Notes
Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones
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Reduction of the carbonyl groups of sugars produces alditols which are polyols
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Oxidation of sugars leads to: carboxylic acids using aqueous Br2
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Such long-chain carboxylic acids can also cyclise to give cyclic esters (lactones)
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With concentrated nitric acid, dicarboxylic acids also called aldaric acids are produced
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