Rod cells in the human eye.Inset: a model of ll-cis-retinal,an oxidized form of vitamin A.For the reaction of ll-cis-retinalwith opsin to form visual purple,see Section 16.8A.

OUTLINE16.1 Structure and Bonding16.2 Nomenclature16.3 Physical Properties16.4 Reactions16.5 Addition of Carbon

Nucleophiles16.6 The Wittig Reaction16.7 Addition of Oxygen

Nucleophiles16.8 Addition of Nitrogen

Nucleophiles16.9 Keto-Enol Tautomerism16.10 Oxidation16.11 Reduction16.12 Reactions at an a-Carbon

Online homework for thischapter may be assignedin Organic OWL.

560

I n this and several of the following chapters, we study the physical and chemi-cal properties of compounds containing the carbonyl group, C=O. Becausethe carbonyl group is the functional group of aldehydes, ketones, carboxylicacids, and carboxyl derivatives, it is one of the most important functional groups inorganic chemistry. The chemical properties of this functional group are straight-forward, and an understanding of its few characteristic reaction themes leads veryquickly to an understanding of a wide variety of organic reactions.

16.1 Structure and BondingThe functional group of an aldehyde is a carbonyl group bonded to a hydrogen atomand a carbon atom (Section 1.3C). In methanal (always called formaldehyde), the sim-plest aldehyde, the carbonyl group is bonded to two hydrogen atoms. In other alde-hydes, it is bonded to one hydrogen atom and one carbon atom. Following are Lewisstructures for formaldehyde and ethanal (which is always called acetaldehyde).

:0: :0: :0:II II II

HCH CH3CH CH3CCH3Methanal Ethanal Propanone

(Formaldehyde) (Acetaldehyde) (Acetone)

The functional group of a ketone is a carbonyl group bonded to two carbon atoms(Section 1.3C). The simplest ketone is propanone, which is always called acetone.

According to valence bond theory, the carbon-oxygen double bond consists ofone (J bond formed by the overlap of sjJ hybrid orbitals of carbon and oxygen andone 1T bond formed by the overlap of parallel 2p orbitals. The two nonbonding pairsof electrons on oxygen lie in the remaining sjJ hybrid orbitals (Figure 1.25).

16.2 NomenclatureA. IUPAC NomenclatureIUPAC names for aldehydes and ketones follow the familiar pattern of select-ing as the parent alkane the longest chain of carbon atoms that contains thefunctional group. We show the aldehyde group by changing the suffix -e of theparent alkane to -al (Section 2.3). Because the carbonyl group of an aldehydecan only appear at the end of a parent chain and because numbering muststart with it as carbon-I, its position is unambiguous; there is no need to use anumber to locate it.

For unsaturated aldehydes, the presence of a carbon-earbon double or triplebond is indicated by the infix -enr or -yn-. As with other molecules with both aninfix and a suffix, the location of the group corresponding to the suffix determinesthe numbering pattern.

3-Methylbutanal

o

~H2-Propenal(Acrolein)

~H8 642

(2E)-3,7-Dimethyl-2,6-octadienal(Geranial)

For cyclic molecules in which -CHO is bonded directly to the ring, the mol-ecule is named by adding the suffix -carbaldehyde to the name of the ring. The atomof the ring to which the aldehyde group is bonded is numbered 1.

o-CHO

Cyclopentane-carbaldehyde

~1HO~"''''CHOtrans-4-Hydroxycyclo-hexanecarbaldehyde

Among the aldehydes for which the IUPAC system retains common names arebenzaldehyde and cinnamaldehyde, as well as formaldehyde and acetaldehyde.Note here the alternative ways the phenyl group can be written. In benzaldehyde,it is written as a line-angle formula; in cinnamaldehyde, it is written C6H 5-.

0 0 00 if d\)~A

Propanone Acetophenone Benzophenone I-Pheny~l-pentanone(Acetone)

In the IUPAC system, ketones are named by selecting as the parent alkanethe longest chain that contains the carbonyl group and then indicating itspresence by changing the suffix from -e to -one (Section 2.3). The parent chainis numbered from the direction that gives the carbonyl carbon the smaller num-ber. The IUPAC system retains the common names acetone, acetophenone, andbenzophenone.

can illustrate how they are derived, however, by reference to a few common nameswith which you are familiar. The name formaldehyde is derived from formic acid;the name acetaldehyde is derived from acetic acid.

IIHCH

Fonnaldehyde

IIHCOH

Fonnicacid

IICHgCH

Acetaldehyde Acetic acid

Common names for ketones are derived by naming the two alkyl or aryl groupsbonded to the carbonyl group as separate words, followed by the word ketone.

Ethyl isopropyl ketone

o

~Diethyl ketone Dicyclohexyl ketone

16.3 Physical PropertiesOxygen is more electronegative than carbon (3.5 compared with 2.5); therefore, acarbon-oxygen double bond is polar, with oxygen bearing a partial negative chargeand carbon bearing a partial positive charge. In addition, the resonance structureshown on the right emphasizes the reactivity of the carbonyl oxygen as a Lewis baseand the carbonyl carbon as a Lewis acid. The bond dipole moment of a carbonylgroup is 2.3 D (Table 1.7).

An electrostatu potential mapfor acetone. Note the large nega-tive charge oxygen (red) and thepositive charges (blue) on the threecarbons.

"-8+ 8-c=o/

Polarity of acarbonyl group

"- f"j.c=o/ ..

More importantcontributing

structure

"-+ .. -c-o:/ V

Because of the polarity of the carbonyl group, aldehydes and ketones are polarcompounds and interact in the pure liquid by dipole-dipole interactions; they havehigher boiling points than nonpolar compounds of comparable molecular weight(Table 16.2).

Table 16.2 Boiling Points of Six Compounds of ComparableMolecular Weight

Molecular BoilingWeight Point

Name Structural Fonnula (g/mol) ("C)Diethyl ether CHgCH2OCH2CHg 74 34Pentane CHgCH2CH2CH2CHg 72 36Butanal CHgCH2CH2CHO 72 762-Butanone CHgCH2COCHg 72 80I-Butanol CHgCH2CH2CH2OH 74 117Propanoic acid CHgCH2COOH 74 141

564 Chapter 16 Aldehydes and Ketones

nucleophiles. This cation then reacts with nucleophiles, followed by removal of aproton, to give a tetrahedral carbonyl addition compound.

R H\ ..~ r-../+c=o + H-LO:/ \

R H

H R H R H

~ / \ 0,1+ \ /~ :0: + c=o +----------+ + c-o:

\ / /H R R

slow------+

:O-H+ /

H-Nu-C"~'IIIR

R

:0: +/

H

H :O-H\ ~ + /

H,!'Ju - C."\.7' ~'IIIR

R

:O-H/

:Nu-C,~'IIIRR

Tetrahedral carbonyladdition compound

+

H/+H-O:\H

Both of these reactivities can be predicted based on the large bond dipole of thecarbonyl group. Using acetaldehyde as an example, Lewis acids such as protonsare attracted to the partial negative charge (red color of the electrostatic poten-tial map) of the carbonyl oxygen, while electron-rich nucleophiles are attractedto the partial positive charge (blue color of the electrostatic potential map) of thecarbonyl carbon.

Site of interaction withLewis acids and e1ectrophiles

Often, the tetrahedral product of nucleophile addition to a carbonyl is a newchiral center. If none of the starting materials is chiral, then the two enantio-mers will be created in equal amounts because the nucleophile will approach thecarbonyl from either side with equal probability. As a result, the carbonyl additionproduct will consist of a racemic mixture.

Approach fromthe top face

Approach fromthe bottom face

-

NUr \W', 0:-R .R'

+RR'~6'-NU/ ..

NU~ ..R"'1 QH

R'

+RR'~6HNtf ..

566 Chapter 16 Aldehydes and Ketones

A new chiral centeris created

A racemic mixture

Table 16.4 Derivatives of Ammonia and Hydrazine Used for Forming Imines

Reagent, HzN-R Name of Reagent Name of Derivative Formed

H 2N-OH Hydroxylamine Oxime

H 2N-NH--\ > Phenylhydrazine PhenylhydrazoneH,N-NH-) t-NO' 2,4-Dinitrophenylhydrazine 2,4-Dinitrophenylhydrazone

2N

II Semicarbazide SemicarbazoneH 2N-NHCNH2

a-CarbonA carbon atom adjacent to acarbonyl group.a-HydrogenA hydrogen on a carbon adjacentto a carbonyl group.Enolate anionAn anion derived by loss of ahydrogen from a carbon alphato a carbonyl group; the anion ofan enol.

16.9 Keto-Enol TautomerismA. Acidity of a-HydrogensA carbon atom adjacent to a carbonyl group is called an a-carbon, and hydrogenatoms bonded to it are called a-hydrogens.

a-hydrogensTI\CH3-C-CH2-CH3

a-carbonsL-/'Table 16.5

Type of Bond pK"

CH3CH2O-H 16

IICH3CCH2-H 20CH3C=C-H 25CH2=CH-H 44CH3CH2-H 51

Because carbon and hydrogen have comparable electronegativities, a C-H bondnormally has little polarity. In addition, carbon does not have a high electro-negativity (compare it, for example, with oxygen, which has an electronegativityof 3.5), so that an anion based on carbon is relatively unstable. As a result, a hydrogenbonded to carbon usually shows very low acidity. The situation is different, how-ever, for hydrogens alpha to a carbonyl group. a-Hydrogens are more acidic thanacetylenic, vinylic, and alkane hydrogens but less acidic than -OH hydrogens ofalcohols (Table 16.5)

The greater acidity of a-hydrogens arises because the negative charge on theresulting enolate anion is delocalized by resonance, thus stabilizing it relative to analkane, alkene, or alkyne anion.

Resonance-stabilized enolate anion

H-A+--

An electrostatic potential map ofan enolate anion.

An enolate anion is also stabilized by the electron-withdrawing inductiveeffect of the electronegative oxygen. Recall that we used these same factors inSection 4.6C to explain the greater acidity of carboxylic acids compared withalcohols.

586 Chapter 16 Aldehydes and Ketones

Tollens' reagentA solution prepared by dissolvingAg20 in aqueous ammonia; usedfor selective oxidation of an alde-hyde to a carboxylic acid.

Tollens' reagent, another form of Ag(I), is prepared by dissolving silver nitrate inwater, adding sodium hydroxide to precipitate Ag(I) as Ag20, and then addingaqueous ammonia to redissolve silver(I) as the silver-ammonia complex ion.

Reaction with oxygen is a radical chain reaction (Section 8.7). Molecular oxygen isthe least expensive and most readily available of all oxidizing agents. On an indus-trial scale, air oxidation of organic compounds, including aldehydes, is very com-mon. Air oxidation of aldehydes can also be a problem. Aldehydes that are liquidat room temperature are so sensitive to oxidation by molecular oxygen that theymust be protected from contact with air during storage. Often this is done by seal-ing the aldehyde in a container under an atmosphere of nitrogen.

When Tollens' reagent is added to an aldehyde, the aldehyde is oxidized to a car-boxylic anion, and Ag(I) is reduced to metallic silver. If this reaction is carried outproperly, silver precipitates as a smooth, mirror-like deposit, hence the name silver-mirror test. Ag(I) is rarely used at the present time for the oxidation of aldehydesbecause of the cost of silver and because other, more convenient methods exist forthis oxidation. This reaction, however, is still used for silvering glassware, includingmirrors. In this process, formaldehyde or glucose (Section 25.1) is generally usedas the aldehyde to reduce Ag(I).

Aldehydes are also oxidized to carboxylic acids by molecular oxygen and byhydrogen peroxide.

Benzoic acidBenzaldehyde

A silvered mirror has been depos-ited in the inside ofthis flask bythe reaction ofan aldehyde withTollens'reagent.

I!~jciIIii'j!!It=L- ...... @

Example 16.11Draw a structural formula for the product formed by treating each compound withTollens' reagent followed by acidification with aqueous HCI.(a) Pentanal (b) CyclopentanecarbaldehydeSolutionThe aldehyde group in each compound is oxidized to a carboxyl group.

o

(a)~OH (b)Pentanoic acid Cyclopentane

carboxylic acid

Problem 16.11Complete the equations for these oxidations.(a) Hexanal + H 20 2~ (b) 3-Phenylpropanal + Tollens' reagent~

B. Oxidation of KetonesIn contrast to aldehydes, ketones are oxidized only under rather special conditions.For example, they are not normally oxidized by chromic acid or potassium perman-ganate. In fact, chromic acid is used routinely to oxidize secondary alcohols to ketonesin good yield (Section 10.8A).

590 Chapter 16 Aldehydes and Ketones

Connections to~~- Biological Chemistry NADH: The Biological Equivalent of a HydrideReducing AgentI

For the reduction of aldehydes and ketones to alcohols,biological systems use NADH, a reagent whose resultsare equivalent to our laboratory hydride-reducingagents. As an example, the final step in alcoholicfermentation-the process by which yeast convertscarbohydrates such as glucose to ethanol and carbondioxide-is the enzyme-catalyzed reduction of acetalde-hyde to ethanol.

ship to each other. Then follows a redistribution ofvalenceelectrons, one part of which is the transfer of a hydrogenatom with its pair of electrons (in effect a hydride ion)from NADH to the carbonyl compound.

Arrows 1 and 2: Electrons within the ring flow fromnitrogen.

Arrow 3: Transfer of a hydride ion from the - CH2-of the six-membered ring to the carbonyl carbon creates

Acetaldehyde

Alcoholic fermentation is the basis for the brewing ofbeersand the fermentation of grape sugar in wine making.

As another example, the end product of glycolysisis pyruvate and the reduced coenzyme NADH. In theabsence of an adequate supply of oxygen (anaerobicmetabolism) to reoxidize NADH to NAD+ and therebyallow glycolysis to continue, cells use the reduction ofpyruvate to lactate as a way to regenerate NAD+:

o OHII lactate_

/"'COO- + NADH dehydrogenase) /"'COO- + NAD+

Ethanol

the new C-H bond to the carbonyl carbon.Arrow 4: The C=O 7i bond breaks as the new C-H

bond forms.Arrow 5: An acidic group, -BH, on the surface of

the enzyme transfers a proton to the newly formed alk-oxide ion to complete formation of the hydroxyl groupof the product.

The enzyme-catalyzed reduction of pyruvate iscompletely stereoselective; in muscle tissue, only theS enantiomer of lactate is produced. This stereoselec-tivity arises because the reduction takes place in a chi-

Anyone who exercises to the point of consumingall available oxygen knows the cramps and fatigue as-sociated with the buildup of lactate in muscles. Withrest and a renewed supply of oxygen, the concentra-tion of lactate decreases rapidly and muscle cramps arerelieved. Lactate production by anaerobic organismsduring fermentation is responsible for the taste of sourmilk and the characteristic taste and fragrance of sauer-kraut (fermented cabbage).

In still other aldehyde and ketone reductions, bio-logical systems use NADPH as a reducing agent. This mol-ecule, which is a phosphate ester of NADH, functions inthe same manner as NADH as a biological reducing agent.

The mechanism for NADH reduction of the carbonylgroup of an aldehyde or ketone follows. First the carbonyl-containing compound and NADH are positioned on thesurface of the enzyme catalyst in a highly specific relation-

ral environment created by the enzyme. At the actualreduction step, both pyruvate and NADH are posi-tioned precisely on the chiral surface of the enzymewith the result that the hydride ion from NADH canbe delivered only to one face of pyruvate, in this caseproducing only the S enantiomer.

Pyruvate (S)-Lactate @~B----CH

'-.9:II-c-

~H:O: ~ II .. C-NH2CB) ~ I.r.-.NI

AdNADH

:B----H

/:0:I

-C-IHH :0:

all ..C-NHreduction) ~ I 2N+IAd

NAD+

16.11 Reduction 593

PROBLEMS

Assignable in OWL

(b) 3-Hydroxybutanal(d) 3-Methyl-3-phenylbutanal(f) 3-Methyl-3-buten-2-one(h) 2,2-Dimethykyclohexanecarbaldehyde

(a) l-Chloro-2-propanone(e) 4-Hydroxy-4-methyl-2-pentanone(e) 1,3-Cyclohexanedione(g) 5-0xohexanal(i) 3-0xobutanoic acid

0 0 CHO

(a)~ ~)& (e)~0 OH

CHO (e)OZI(d) H\\\"i ......... (f)CH20HCHg

0 0(.)~ (h) OHC~CHO (i) vyBr

0

16.15 Draw a structural formula for each compound.

KOH VI+ HNNH l +N +HO2 2 diethylene glycol ~ 2 2

H dr (reflux)y azme

~~"L'''" Online homework for this chapter may be assigned in Organic OWL. indicate problems assignable in Organic OWL.A Red number indicate an applied problems.

Structure and Nomenclature16.14 Name each compound, showing stereochemistry where relevant.

o 0II DC! II

CHgCCHg + 6D20~ CDgCCDg + 6HOD

Chapter 16 Aldehydes and Ketones

20. Deuterium Exchange at an a-Carbon (Section 16.1281 Acid- or base-catalyzeddeuterium exchange at an a-carbon involves formation of an enol or enolate anionintermediate:

21. Halogenation at an a-Carbon (Section 16.12CI The rate-determining step in acid-cat-alyzed a-halogenation is the formation of an enol. In base-promoted a-halogenation, itis formation of an enolate anion. Acid catalyzed a-halogenation involves reaction of thehalogen with the enol form at the carbonyl compound. Base promoted a-halogenationinvolves reaction of the enolate anion intermediate with the halogen.

606