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Chapter 18: Ketones and Aldehydes I. Introduction
We have already encountered numerous examples of this functional group (ketones, aldehydes, carboxylic acids, acid chlorides, etc).
The three-dimensional structure and hybridization of aldehydes and ketones is shown below:
All C=O compounds have a minor contributing resonance structure that heavily influences their chemistry:
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II. Nomenclature of Aldehydes and Ketones
A. IUPAC Nomenclature of Aldehydes
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B. IUPAC Nomenclature of Ketones Functional Group Priorities:
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Common Nomenclature of Ketones (Systematic)
1) Name each carbon group attached to the carbonyl (C=O) carbon as an alkyl group.
2) List the alkyl groups, separated by spaces, in front of the word “ketone.”
III. Spectroscopy:
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IV. Review of the synthesis of Ketones and Aldehydes
A) Oxidation of Alcohols (to aldehydes and ketones)
Observed Reaction: 1o Alcohols to Aldehydes
Observed Reaction: 2o Alcohols to Ketones
B) Ozonolysis of Alkenes
Observed Reaction
C) Friedel-Crafts Acylation
Observed Reaction
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D) Hydration of Alkynes Two Cases here…
1. Markovnikov
2. Anti-Markovnikov
E). Hydride Addition (to form alcohols)
Mechanism:
Sodium borohydride (NaBH4) and lithium aluminum hydride (LiAlH4) are sources of “H:–”(hydride).
Hydride is a hydrogen nucleophile. It reacts with the C=O carbon:
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F. Organometallic Additions Mechanism:
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V. Reactions of Aldehydes and Ketones CASE 1:
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CASE 2:
A. Grignards and ketones: B. Hydride sources and ketones:
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VI. Relative Reactivity of Aldehydes and Ketones 1. Electronic Effects
Ketones have two alkyl substituents whereas aldehydes only have one.
2. Sterics
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VII. Nucleophilic Addition of Water (Hydration) and Alcohols (Acetals) 1. Hydration In aqueous solution, ketones (and aldehydes) are in equilibrium with their
hydrates (geminal diols).
Hydration proceeds through the two classic nucleophilic addition mechanisms with water (in acid) or hydroxide (in base) acting as the nucleophile.
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B. Mechanism of Acetal Formation
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Note that cyclic hemiacetals are reasonably stable (found in sugar chemistry,
for example glucose)
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if alpha-1,4 = carbohydrates C. Acetal Hydrolysis
The mechanism of hydrolysis is exactly the same as the mechanism of formation, just in reverse.
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D. Formation of Cyclic Acetals and the use of Acetals as Protecting Groups More commonly, instead of two molecules of alcohols being used, a diol is
used (entropically more favorable). This produces cyclic acetals. Example:
Acetals
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E. Selective Acetal Formation
We have previously seen that aldehydes are more reactive than ketones (two reasons), and therefore aldehydes will react to form acetals preferentially over ketones.
Example:.
This is a useful way to perform reactions on ketone functionalities in molecules that contain both aldehyde and ketone groups.
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VIII. Nitrogen Addition (formation of imines, hydrazones, oximes)
General Mechanism: (can react with ketones or aldehydes)
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Different Z groups lead to similar products with different names
Z Group (All 1o Amines) H2N–Z Name
Product Name
Product Structure
C=N can be converted back to C=O by acid-catalyzed hydrolysis.
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IX. Aldehydes and Ketones from Acid Chlorides
1. Aldehydes
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Generation of Acid Chlorides The reaction of carboxylic acids with thionyl chloride (SOCl2) generates acid
chlorides. Observed Reaction
Mechanism
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2. Ketones Acid chlorides react with Grignard (and organolithium) reagents.
Question: How can we stop the reaction at the ketone? Answer: Use a weaker organometallic reagent: ___________________
Observed Reaction
The lithium dialkyl cuprate is produced by the reaction of two equivalents of
the organolithium reagent with copper (I) iodide.
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X. CARBANIONIC NUCLEOPHILES 1. Nucleophilic Addition of Hydrogen Cyanide (Cyanohydrins)
Hydrogen cyanide is toxic volatile liquid (b.p.26°C).
Cyanide is a strong base (HCN weak acid) and a good nucleophile. Cyanide reacts rapidly with carbonyl compounds producing cyanohydrins, via
the base catalyzed nucleophilic addition mechanism.
Like hydrate formation, cyanohydrin formation is an equilibrium governed reaction (i.e. reversible reaction), and accordingly aldehydes are more reactive than ketones.
Cyanohydrin formation is readily reversed by treating the cyanohydrin with
base:
2. Addition of acetylide ions and organometallic reagents
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3. Addition of Phosphorus Ylides (Wittig Reaction)
In 1954 Wittig (Nobel Prize in 1979) discovered that the addition of a
phosphorus stabilized anion to a carbonyl compound did not generate an alcohol, but an alkene!
Observed Reaction
Mechanism:
Part One
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Part Two
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XI. Oxidation of Alcohols Unlike ketones, aldehydes can be oxidized easily to carboxylic acids
(Chromic acid, permanganate etc).
Even weak oxidants like silver (I) oxide can perform this reaction, and this is a good, mild selective way to prepare carboxylic acids in the presence of other (oxidizable) functionalities.
Silver Mirror Test (Tollen's Test)
Tollen's reagent is added to an unknown compound, and if an aldehyde is present, it is oxidized.
This process reduces the Ag+ to Ag, and the Ag precipitates - it sticks to the flask wall, and forms a silver mirror (pretty!).
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Catalytic Hydrogentation:
Just as C=C double bonds can be reduced by the addition of hydrogen across the double bond, so can C=O double bonds.
Example
XIII. Deoxygenation of Ketones and Aldehydes
Deoxygenation involves the removal of oxygen, and its replacement with two hydrogen atoms.
This reduction takes the carbonyl (past the alcohol) to a methylene group.
Compare the following reduction processes:
