Chapter 18
Ketones and Aldehydes
18-00-01T01

Labeled
Title
 Some Common Classes of Carbonyl Compounds
Caption
 Table 18-1 Some common classes of carbonyl compounds.
Notes
Keywords
 ketones, aldehydes, carboxylic acids, esters, acid chlorides, amides
18-00-03UN

Labeled
Title
 Orbital Overlap of Carbonyl Groups
Caption
 The unhybridized p orbital of the carbon overlaps with a p orbital of the oxygen to form a pi bond. The double bond between carbon and oxygen is similar to an alkene C=C double bond, except that the carbonyl is shorter, stronger, and polarized.
Notes
 The C=O bond is shorter because it is polarized. This polarization is also responsible for the reactivity of the carbonyl group.
Keywords
 carbonyl group, polarization, pi orbital
18-00-04UN

Labeled
Title
 Polarization of the Carbonyl Group
Caption
 The double bond of the carbonyl group has a large dipole moment because oxygen is more electronegative than carbon, and the bonding electrons are not shared equally.
Notes
 Nucleophiles will attack the carbonyl carbon because it is electrophilic, as suggested by the minor resonance structure.
Keywords
 nucleophile, dipole moment, electrophile
18-00-17UN1-5

Labeled
Title
 Boiling Points of Ketones and Aldehydes
Caption
 The ketones and the aldehyde are more polar and higher boiling than the ether and the alkane, but lower boiling than the hydrogen-bonded alcohol.
Notes
 The dipole moment of the carbonyl group is responsible for the higher boiling points for aldehydes and ketones. Hydrogen bonding is a stronger interaction so alcohols will boil at higher temperatures.
Keywords
 dipole moment, hydrogen bonding
18-00-22UN

Labeled
Title
 IR Spectra of Ketones and Aldehydes
Caption
 The carbonyl (C=O) stretching vibrations of ketones and aldehydes occur around 1710 cm-1. Conjugation lowers the carbonyl stretching frequencies to about 1685 cm-1.
Notes
 Rings that have ring strain have higher C=O frequencies.
Keywords
 stretching vibration, frequency, conjugation
18-00-23UN1-3

Labeled
Title
 Proton NMR Spectra of Ketones and Aldehydes
Caption
 Aldehyde protons normally absorb at chemical shifts between d9 and d10. Protons of the a-carbon atom of a ketone or aldehyde usually absorb at a chemical shift between d2.1 and d2.4 if there are no other electron-withdrawing groups nearby.
Notes
 Methyl ketones have a 1H-NMR singlet at 2.1 ppm.
Keywords
 chemical shift, NMR, a-carbon, methyl ketone
18-01

Labeled
Title
 Proton NMR Spectrum of Butanal
Caption
 Figure 18-1 The proton NMR spectrum of butanal (butyraldehyde) shows the aldehyde proton at d9.8, split into a triplet (J = 1 Hz) by the two a protons. The a, b, and g protons appear at values of d that decrease with increasing distance from the carbonyl group.
Notes
 Protons closer to the carbonyl group are more deshielded.
Keywords
 a protons
18-02

Labeled
Title
 Carbon NMR Spectra of 2-Heptanone
Caption
 Figure 18-2 The spin-decoupled carbon NMR spectrum of 2-heptanone shows the carbonyl carbon at 208 ppm and the a carbon at 30 ppm (methyl) and 44 ppm (methylene).
Notes
 The signal for the carbonyl is usually small.
Keywords
 spin-decoupled, carbonyl carbon
18-03

Labeled
Title
 Mass Spectrum of 2-butanone
Caption
 Figure 18-3 The mass spectrum of 2-butanone shows a prominent molecular ion and a base peak from loss of an ethyl radical to give an acylium ion.
Notes
 The acylium ion is formed when the ketone or aldehyde lose an alkyl group.
Keywords
 mass spectrum, molecular ion, base peak, acylium ion
18-04

Labeled
Title
 Mass Spectrum of Butyraldehyde
Caption
 Figure 18-4 The mass spectrum of butyraldehyde shows the expected ion of masses 72, 57, and 29. The base peak at m/z 44 results from the loss of ethylene via McLafferty rearrangement.
Notes
 The main peaks of the spectrum arise from loss of a propyl radical, a b,g cleavage, and the McLafferty rearrangement.
Keywords
 b,g cleavage, McLafferty rearrangement, mass spectrum
18-05

Labeled
Title
 Mechanism of the McLafferty Rearrangement
Caption
 Figure 18-5 Mechanism of the McLafferty rearrangement. This rearrangement may be concerted, as shown here, of the g hydrogen may be transferred first, followed by fragmentation.
Notes
 The net result of this rearrangement is the breaking of the a,b bond, and the transfer of a proton from the g carbon to the oxygen. An alkene is formed as a product of this rearrangement.
Keywords
 McLafferty rearrangement, concerted, fragmentation
18-06

Labeled
Title
 Electronic Transitions of the Carbonyl Group
Caption
 Figure 18-6 Comparison of the p - p* and the n - p* transitions. The n - p* transition requires less energy because the nonbonding (n) electrons are higher in energy than the bonding p electrons.
Notes
 The p - p* occurs more frequently than the n - p* transition.
Keywords
 electronic transitions, nonbonding electrons
18-07-08UN

Labeled
Title
 Oxidation of Secondary Alcohols to Ketones
Caption
 Secondary alcohols are readily oxidized to ketones with sodium dichromate (Na2Cr2O7) in sulfuric acid or by potassium permanganate (KMnO4).
Notes
 Primary alcohols cannot be oxidized to the aldehyde by using sodium dichromate (Na2Cr2O7) potassium permanganate (KMnO4).
Keywords
 secondary alcohol, sodium dichromate, potassium permanganate
18-07-09UN

Labeled
Title
 Oxidation of Primary Alcohols to Aldehydes
Caption
 Oxidation of a primary alcohol to an aldehyde requires careful selection of an oxidizing agent. Because aldehydes are easily overoxidized to carboxylic acids, strong oxidants like chromic acid often give overoxidation. Pyridinium chlorochromate (PCC), a complex of chromium trioxide with pyridine and HCl, provides good yields of aldehydes without overoxidation.
Notes
 PCC can oxidize secondary alcohols to the corresponding ketone but it is most often used to selectively oxidize primary alcohols to aldehydes.
Keywords
 chromic acid, pyridinium chlorochromate (PCC), overoxidation
18-07-10UN

Labeled
Title
 Ketones and Aldehydes from Ozonolysis of Alkenes
Caption
 Ozonolysis, followed by mild reduction, cleaves alkenes to give aldehydes and ketones.
Notes
 Zn/HCl could be used as a reducing agent instead of dimethyl sulfide.
Keywords
 ozone, ozonolysis, reducing agent, bond cleavage
18-07-12UN

Labeled
Title
 Friedel-Craft Acylation
Caption
 Friedel-Craft acylation is an excellent method for making alkyl aryl ketones or diaryl ketones. It cannot be used on strongly deactivated systems, however.
Notes
 A catalyst must be used for the reaction to occur.
Keywords
 Friedel-Craft acylation, alkyl aryl ketones, diaryl ketones, deactivated ring, catalyst
18-07-14UN

Labeled
Title
 Mercuric Catalyzed Hydration of Alkynes
Caption
 The initial product of Markovnikov hydration is an enol, which quickly tautomerizes to its keto form. Internal alkynes can be hydrated, but mixtures of ketones often result.
Notes
 Terminal alkynes will produce methyl ketones after tautomerization.
Keywords
 hydration, tautomerization, keto form, internal alkynes
18-07-15UN

Labeled
Title
 Hydroboration Oxidation of Alkynes
Caption
 Hydroboration-oxidation of an alkyne gives anti-Markovnikov addition of water across the triple bond.
Notes
 Terminal alkynes give aldehydes after tautomerization.
Keywords
 Hydroboration-oxidation, tautomerization
18-07-25P18.6UN

Labeled
Title
 Synthesis of Ketones and Aldehydes Using 1,3-Dithianes
Caption
 1,3-Dithiane can be deprotonated by strong bases such as n-butyllithium. The resulting carbanion is stabilized by the electron withdrawing effects of two polarizable sulfur atoms. Alkylation of the dithiane anion by a primary alkyl halide or tosylate gives a thioacetal that can be hydrolyzed using an acidic solution of mercuric chloride.
Notes
 The dithiane anion is a good nucleophile and can react with alkyl halides. Monoalkylation and removal of the thioacetal gives an aldehyde.
Keywords
 1,3-dithiane, carbanion, dithiane anion
18-07-28UN

Labeled
Title
 Double Alkylation of 1,3-Dithiane
Caption
 The thioacetal can be alkylated once more to give a thioketal. Hydrolysis of the thioketal gives a ketone.
Notes
 Monoalkylation of 1,3-dithiane produces aldehydes and double alkylation produces ketones after hydrolysis.
Keywords
 thioacetal, thioketal
18-07-29UN

Labeled
Title
 Synthesis of Ketones from Carboxylic Acids
Caption
 Organolithium reagents can be used to synthesize ketones from carboxylic acids. Organolithiums are so reactive toward carbonyls that they attack the lithium salts of carboxylate anions to give dianions. Protonation of the dianion forms the hydrate of a ketone, which quickly loses water to give the ketone.
Notes
 Hydrates are not stable species so they lose water to form the more stable ketone product.
Keywords
 organolithium reagents, dianion, hydrate
18-07-30UN

Labeled
Title
 Synthesis of Ketones from Carboxylic Acids
Caption
 If the organolithium reagent is inexpensive, we can simply add 2 equivalents to the carboxylic acid. The first equivalent generates the carboxylate salt, and the second attacks the carbonyl group. Subsequent protonation gives the ketone.
Notes
 Hydrates are not stable species so they lose water to form the more stable ketone product.
Keywords
 organolithium reagents, dianion, hydrate
18-07-34UN

Labeled
Title
 Synthesis of Ketones from Nitriles
Caption
 A Grignard or organolithium reagent attacks a nitrile to give the magnesium salt of an imine. Acidic hydrolysis of the imine leads to a ketone.
Notes
 The ketone is only produced after hydrolysis of the imine intermediate.
Keywords
 imine, hydrolysis
18-07-38UN

Labeled
Title
 Reduction of Acid Chlorides with Lithium Aluminum tri(t-Butoxy)hydrate
Caption
 Strong reducing agents reduce acid chlorides all the way to primary alcohols. Lithium aluminum tri(t-butoxy)hydrate is a milder reducing agent that reacts faster with acid chlorides than with aldehydes.
Notes
 Lithium aluminum tri(t-butoxy)hydrate is a modified lithium aluminum hydrate that is less reactive and more selective.
Keywords
 Lithium aluminum tri(t-butoxy)hydrate, reducing agent
18-07-41UN

Labeled
Title
 Synthesis of Ketones Using Lithium Dialkyl Cuprate Reagents
Caption
 To stop at the ketone stage, a weaker organometallic reagent is needed: one that reacts faster with acid chlorides than with ketones. A lithium dialkylcuprate (Gilman reagent) is such a reagent.
Notes
 The organocuprate tranfer one of its alkyl groups to the acid chloride.
Keywords
 organometallic reagent, lithium dialkylcuprate, Gilman reagent
18-07-56UN

Labeled
Title
 Nucleophilic Additions to Carbonyl Groups
Caption
 As a nucleophile attacks the carbonyl group, the carbon atom changes hybridization from sp2 to sp3. The electrons of the pi bond are forced out of the oxygen atom to form an alkoxide anion, which protonates to give the product of nucleophilic addition.
Notes
 The carbon is electrophilic due to the polarization of the C=O double bond.
Keywords
 alkoxide anion
18-07-60UN

Labeled
Title
 Activation of the Carbonyl Group Toward Nucleophilic Attack
Caption
 A carbonyl group that is protonated (or bonded to some other electrophile) is strongly electrophilic, inviting attack by a weak nucleophile.
Notes
 Once the carbonyl has been protonated a water molecule can attack the carbonyl forming the hydrate. The hydrate is not stable and easily loses water to form the ketone.
Keywords
 electrophilic, protonation, hydrate
18-07-67Summ

Labeled
Title
 Mechanism of Nucleophilic Addition to Carbonyl Groups
Caption
 Nucleophiles can add under acidic or basic conditions to carbonyl groups.
Notes
 Strong nucleophiles can add to the carbonyl carbon easily. Weak nucleophiles cannot add to the carbonyl unless it is activated by protonation or interaction with other electrophile.
Keywords
 activated carbonyl, protonation
18-07-68UN

Labeled
Title
 The Wittig Reaction
Caption
 In effect, the Wittig reaction converts the carbonyl group of a ketone or an aldehyde into a new C=C double bond where no bond existed before.
Notes
 A phosphorus ylide is used as the nucleophile in the reaction. Triphenylphosphine oxide is a by product of the reaction.
Keywords
 Wittig reaction, phosphorus ylide, triphenylphosphine oxide
18-07-69UN

Labeled
Title
 Preparation of Phosphorus Ylides
Caption
 The phosphorus stabilized carbanion is an ylide - a molecule that bears no overall charge but has a negatively charged carbon atom bonded to a positively charged heteroatom.
Notes
 Triphenyl phosphine is alkylated with an alkyl halide forming a phosphonium salt. Butyl lithium deprotonates the phosphonium salt producing the ylide.
Keywords
 Wittig reaction, phosphorus ylide, triphenylphosphine
18-07-70UN

Labeled
Title
 Mechanism of the Witting Reaction
Caption
 The ylide attacks a carbonyl carbon to give a charge separated intermediate called a betaine. Phosphorus and oxygen form strong bonds, and the attraction of opposite charges promotes the fast formation of a four-membered oxaphosphetane ring. The ring quickly collapses to give the alkene and triphenylphosphine oxide.
Notes
 Mixtures of cis and trans isomers often result when geometric isomerism is possible.
Keywords
 ylide, betaine, oxaphosphetane
18-07-78UN

Labeled
Title
 Hydration of Ketones and Aldehydes
Caption
 In an aqueous solution, a ketone or an aldehyde is in equilibrium with its hydrate, a geminal diol. With most ketones, the equilibrium favors the unhydrated keto form of the carbonyl.
Notes
 The hydration can occur in acidic or basic media.
Keywords
 hydrate, geminal diol, keto form
18-07-79UN

Labeled
Title
 Mechanism of Hydration of Ketones and Aldehydes
Caption
 Hydration occurs through the nucleophilic addition mechanims, with water (in acid) or hydroxide (in base) serving as the nucleophile.
Notes
 In acid media the carbonyl is protonated first to activate it toward nucleophilic attack by water.
Keywords
 hydration
18-07-84UN

Labeled
Title
 Mechanism of Cyanohydrin Formation
Caption
 The mechanism is a base catalyzed nucleophilic addition: attack by cyanide ion on the carbonyl group, followed by protonation of the intermediate.
Notes
 Cyanohydrin formation is reversible. Aldehydes are favored more than ketones toward cyanohydrin formation.
Keywords
 cyanohydrin, cyanide ion
18-07-89UN

Labeled
Title
 Formation of Imines
Caption
 Under the proper conditions, either ammonia or a primary amine react with a ketone or an aldehyde to form an imine. Imines are nitrogen analogues of ketones and aldehydes with a carbon-nitrogen bond in place of the carbonyl group.
Notes
 The amine adds to the carbonyl forming and intermediate carbinolamine which loses water to give an imine.
Keywords
 imine, carbinolamine
18-07-90UN

Labeled
Title
 Mechanism of Imine Formation
Caption
 The mechanism of imine formation begins with a basic nucleophilic addition of the amine to the carbonyl group. Attack by the amine, followed by protonation of the oxygen atom gives an unstable intermediate called carbinolamine.
Notes
 The reaction must be carried out under weakly acidic conditions.
Keywords
 imine, carbinolamine
18-07-91UN

Labeled
Title
 Mechanism of Imine Formation
Caption
 A carbinolamine converts to an imine by losing water and forming a double bond: a dehydration. Protonation of the hydroxyl group converts it to a good leaving group, and it leaves as water. Loss of a proton gives the imine.
Notes
 The rate of imine formation is fastest around pH = 4.5
Keywords
 carbinolamine, dehydration
18-08-009Summ

Labeled
Title
 Condensations of Amines with Ketones and Aldehydes
Caption
 Summary of condensations of amines with ketones and aldehydes
Notes
 Depending on the substituent on the primary amine, different types of imines can be formed.
Keywords
 imines, oxime, hydrazone, phenylhydrazone, semicarbazone
18-08-018UN

Labeled
Title
 Formation of Acetals
Caption
 Just as ketones and aldehydes react with water to form hydrates they also react with alcohols to form acetals. In the formation of an acetal, two molecules of alcohol add to the carbonyl group, and one molecule of water is eliminated.
Notes
 Acetals are only formed under acidic conditions.
Keywords
 acetals, hydrates
18-08-020UN

Labeled
Title
 Mechanism of Acetal Formation
Caption
 The first half of the mechanism is an acid catalyzed addition to the carbonyl. The acid protonates the carbonyl group and the alcohol (a weak nucleophile) attacks the protonated, activated carbonyl. Loss of a proton from the positively charged intermediate gives a hemiacetal.
Notes
 Most hemiacetals are too unstable to be isolated.
Keywords
 acetal, hemiacetal
18-08-021UN

Labeled
Title
 Mechanism of Acetal Formation
Caption
 The second half of the mechanism converts the hemiacetal to the more stable acetal. Protonation of the hydroxyl group, followed by loss of water, gives a resonance-stabilized carbocation. Attack on the carbocation by methanol, followed by loss of a proton, gives the acetal.
Notes
 The acid protonates the hydroxyl group making it a good leaving group. This is why the reaction is acid-catalyzed.
Keywords
 hemiacetal, acetal, dehydration
18-08-024UN

Labeled
Title
 Cyclic Acetals
Caption
 Ethylene glycol is often used to make cyclic acetals; its acetals are called ethylene acetals. Dithiane and its alkylated derivativesare examples of cyclic thioacetals (sulfur acetals).
Notes
 Formation of cyclic acetals is more favored than the formation of acetals. Cycic acetals are used to protect carbonyl groups from nucleophilic attack and other reactions.
Keywords
 cyclic acetals, thioacetals, ethylene glycol, dithiane
18-08-051UN

Labeled
Title
 Oxidation of Aldehydes
Caption
 Unlike ketones, aldehydes are easily oxidized to carboxylic acids by common oxidants such as chromic acid, chromium trioxide, permanganate, and peroxy acids. Because aldehydes oxidize so easily, mild reagents such as Ag2O, can oxidize them selectively in the presence of other oxidizable functional groups.
Notes
 Reaction of an aldehyde with the Tollen's reagent (silver-ammonia complex) under basic conditions will oxidize the aldehyde to the carboxylate ion and will reduce the silver (I) to silver(0). This reaction is used as a qualitative test for aldehyde.
Keywords
 oxidants, chromic acid, chromium trioxide, permanganate, peroxy acids
18-08-059UN

Labeled
Title
 Deoxygenation of Ketones and Aldehydes
Caption
 A deoxygenation replaces the carbonyl oxygen atom of a ketone or aldehyde with two hydrogen atoms, reducing the carbonyl group past the alcohol stage all the way to a methylene group.
Notes
 The Clemmensen reduction or the Wolff-Kishner redution can be used to deoxygenate ketones and aldehydes.
Keywords
 deoxygenation, Clemmensen, Wolff-Kishner
18-08-063UN

Labeled
Title
 Mechanism of the Wolff-Kishner Reduction
Caption
 The mechanism for the formation of the hydrazone is the same as the mechanism for imine formation. The actual reduction step involves two tautomeric proton transfers from nitrogen to carbon.
Notes
 A molecule of nitrogen is lost in the last steps of the reaction.
Keywords
 hydrazone, imine, Wolff-Kishner reduction
18-08-145SP18.76b

Labeled
Title
Caption
Notes
Keywords
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