Jones M., Fleming S.A. Organic Chemistry

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16.3 Nomenclature of Carbonyl Compounds 769

CIVETONE

This simple, but unusual cycloalkenone is called civetone,

as it is isolated from a gland present in both male and

female civet cats, Viverra civetta and Viverra zibetha. The

cats use it as a sexual attractant and marking agent. It has a

strong musky odor, overwhelming when concentrated (to

humans, that is, probably not to civet cats). In high dilution

the odor becomes quite pleasant, and civetone and the

related cyclic 15-membered ring ketone, muskone, are

important starting materials in the perfumery industry.

In the old days, you had to catch yourself a mess o’ civet

cats, described as “savage and unreliable,” to make your

perfumes. Nowadays, this compound can be made quite

easily in the laboratory, a fact presumably reassuring to the

civet cat population.

Civet

Civetone

Acetophenone

(methyl phenyl ketone)

2-Methyl-1-phenyl-1-propanone

(isopropyl phenyl ketone)

Benzophenone

(diphenyl ketone)

WEB 3D

FIGURE 16.12 Ketones containing

benzene rings are phenyl ketones.

This figure also shows the “ophenone”

method of naming these molecules.

Aromatic ketones are often named by treating the benzene ring as a phenyl group,

as in isopropyl phenyl ketone (Fig. 16.12). A few can be named through the IUPAC

system in which the framework Ph—C O is indicated by the term “ophenone” and

the remainder of the molecule designated by one of the alternative names in Figure 16.12.

Thus, diphenyl ketone is benzophenone, methyl phenyl ketone is acetophenone, ethyl

phenyl ketone is propiophenone,and phenyl propyl ketone is butyrophenone (Fig.16.12).

Carboxylic acid Acid anhydrideAcid chlorideEster Amide

R Cl

WEB 3D WEB 3D

FIGURE 16.13 Some names for

other carbonyl compounds in

which one R group is neither

hydrogen nor a hydrocarbon

group.

Figure 16.13 gives the names of some compounds containing carbon–oxygen dou-

ble bonds in which one of the R groups is neither hydrogen nor a hydrocarbon group.

We met these compounds in earlier chapters and we will see them again in later

chapters and deal with their nomenclature more extensively there.

770 CHAPTER 16 Carbonyl Chemistry 1: Addition Reactions

16.4 Physical Properties of Carbonyl

Compounds

Carbonyl compounds are all somewhat polar, and the smaller, less hydrocarbon-like

molecules are all at least somewhat water soluble. Acetone and acetaldehyde are

miscible with water, for example. Their polarity means that they can profit

energetically by associating in solution, and therefore their boiling points are

considerably higher than those of hydrocarbons containing the same number of

carbons and oxygens. For example, propane and propene are gases with boiling

points of 42.1 °C and 47.4 °C, respectively. By contrast, acetaldehyde boils at

20.8 °C, about 63 degrees higher. Acetone boils more than 60 degrees higher

than 2-methylpropene (isobutene).

Table 16.1 gives some physical properties of a number of common carbonyl-

containing compounds (and some related hydrocarbons in parentheses).

TABLE 16.1 Some Physical Properties of Carbonyl Compounds

Compound bp (°C) mp (°C) Density (g/mL) Dipole Moment (D)

Formaldehyde 21 92 0.815 2.33

Acetaldehyde 20.8 121 0.783 2.69

Propionaldehyde 48.8 81 0.806 2.52

(Propane)

42.1

(Propene)

47.4

Benzaldehyde 178.6 26 1.04

Acetone 56.2 95.4 0.789 2.88

(Isobutene)

6.9

Ethyl methyl ketone 79.6 86.3 0.805

Cyclohexanone 155.6 16.4 0.948

Methyl phenyl ketone 202.6 20.5 1.03

Diphenyl ketone 305.9 48.1 1.15 2.98

Hydrocarbons for comparison purposes.

16.5 Spectroscopy of Carbonyl Compounds

16.5a Infrared Spectroscopy Carbonyl compounds are ubiquitous in

nature. The C O bond is one of the most widely found of the “functional

groups.” Spectroscopy, especially IR spectroscopy, played an important role in

identifying many medicinally and otherwise important compounds.The carbon–

oxygen double bond has a diagnostically useful and quite strong stretching fre-

quency in the IR, generally near 1700 cm

1

(p. 711). This absorption is at

substantially higher frequency than that of carbon–carbon double bonds.

This shift should be no surprise, because we already know that carbon–oxygen

double bonds are stronger than carbon–carbon double bonds, and therefore

require more energy for stretching. A useful diagnostic for aldehydes is the

pair of bands observed in the C—H stretching region at about 2850 cm

1

and

2750 cm

1

. Table 16.2 gives some IR, NMR, and UV data for a few aldehydes

and ketones.

16.5 Spectroscopy of Carbonyl Compounds 771

TABLE 16.2 Some Spectral Properties of Carbonyl Compounds

Compound IR

C NMR UV

(CCl

1

)(δ C O) [nm (ε)]

Formaldehyde 1744 (gas phase) 270

Acetaldehyde 1733 199.6 293.4 (11.8)

Propanal 1738 201.8 289.5 (18.2)

Acetone 1719 205.1 279 (14.8)

Cyclohexanone 1718 207.9 285 (14)

Cyclopentanone 1751 213.9 299 (20)

Cyclobutanone 1788 208.2 280 (18)

Butanone 1723 206.3 277 (19.4)

3-Butenone 1684 197.2 219 (3.6)

2-Cyclohexenone 1691 197.1 224.5 (10,300) (ππ*)

Benzaldehyde 1710 191.0 244 (15,000) (ππ*)

328 (20) (n π*)

Benzophenone 1666 195.2 252 (20,000) (ππ*)

325 (180) (n π*)

Acetophenone 1692 196.8 240 (13,000) (ππ*)

319 (50) (n π*)

Note that conjugated carbonyl compounds are always found at lower frequency

than their unconjugated relatives.For example,cyclohexanone appears at 1718 cm

1

and 2-cyclohexenone at 1691 cm

1

(Fig. 16.14).Thus there is reduced double-bond

character in the C O group in conjugated molecules.The resonance formulation

of 2-cyclohexenone clearly shows the partial single-bond character of the carbon–

oxygen bond in these compounds.

stretching

frequency

Cyclohexanone 2-Cyclohexenone

1718 cm

–1

1691 cm

–1

IR C

–

WEB 3D

–

FIGURE 16.14 Conjugation reduces the double-bond character of a carbonyl

group. The result is a shift of the IR stretching band to lower frequency.

δ 2.1 δ 2.4

δ 1.6

δ 0.9

FIGURE 16.15 Hydrogens on the

α carbons are affected most by the

electron-withdrawing carbonyl

group. Hydrogens on the β carbon

are only slightly shifted. Hydrogens

that are further away are not

significantly affected (δ in ppm).

16.5b Nuclear Magnetic Resonance Spectroscopy The carbonyl group

inductively withdraws electrons from the nearby positions, and this inductive effect

results in a deshielding of adjacent hydrogens.The further away from the carbonyl

group, the less effective the deshielding.This effect is well illustrated by 2-pentanone

(Fig. 16.15).

In aldehydes, hydrogens directly attached to the carbonyl group resonate far

downfield,δ 8.5–10 ppm. Not only does the carbon bear a partial positive charge

that deshields the attached hydrogen, but the applied magnetic field B

creates an

induced field B

in the carbonyl group that augments the applied field in the region

772 CHAPTER 16 Carbonyl Chemistry 1: Addition Reactions

At this point

and B

reinforce

each other

FIGURE 16.16 Aldehyde hydrogens

are in a strongly deshielded region in

which the induced magnetic field B

augments the applied field B

of aldehydic hydrogens (Fig. 16.16). Accordingly, a relatively weak applied magnetic

field is required to reach the resonance frequency, and they appear unusually far

downfield (p. 720).

The carbon atoms of carbonyl groups carry partial positive charges and are

greatly deshielded by their relative lack of surrounding electrons. They, too, res-

onate especially far downfield in the

C NMR. Table 16.2 shows typical reso-

nance positions.

16.5c Ultraviolet Spectroscopy Simple aldehydes and ketones, like

simple alkenes, do not have a ππ* absorption in the region of the UV spec-

trum accessible to most spectrometers. However, unlike alkenes, carbonyl com-

pounds have another possible absorption which, though weak, is detectable.

This absorption involves promotion of a nonbonding, or

n, electron to the antibonding π* orbital, the n π*

absorption. Table 16.2 gives wavelengths for UV absorp-

tions of a few compounds.

As for alkenes (p. 528), conjugation of the carbonyl group

greatly reduces the energy necessary to promote an electron

from the highest occupied π molecular orbital to the

LUMO. So, the strong ππ* transition in unsaturated

carbonyl compounds can be detected because of the conju-

gation-induced shift to the longer wavelengths (lower ener-

gy) observable by normal UV/vis spectrometers (Table 16.2;

Fig. 16.17).

16.5d Mass Spectrometry There is a diagnostic cleav-

age reaction that occurs for many simple carbonyl-containing

compounds. It involves breaking the bond attached directly to

the carbonyl carbon, with the charge remaining on the car-

bonyl group. Cleavage of this bond generates a resonance-

stabilized acylium ion. It is this resonance stabilization that

accounts for the prominence of this particular fragmentation.

Figure 16.18 shows the mass spectrum for acetone, the arche-

typal methyl ketone.

π*

LUMO

ν (π π*)

LUMO

This lower energy

absorption can be

observed

Energy

hν (π π*)

FIGURE 16.17 Conjugation leads to lower energy (longer

wavelength) π→π* absorptions that are observable by UV/vis

spectrometers.

m/z

100

Relative Abundance

100 110 120 130 140 1502010 30 40 50 60 70 90

m/z = 43

The acylium ion

M = 68

WEB 3D

FIGURE 16.18 In the mass

spectrum of acetone, the

base peak results from

formation of the

resonance-stabilized

acylium ion.

16.6 Reactions of Carbonyl Compounds: Simple Reversible Additions 773

16.6 Reactions of Carbonyl Compounds: Simple

Reversible Additions

In simple addition reactions, carbonyl compounds can behave as either Lewis acids

or Lewis bases depending on the other reagents present. As we might expect, there

is some correspondence between addition reactions of carbon–oxygen double bonds

and those of the carbon–carbon double bonds we saw in Chapters 9 and 10. As we

might also expect, additional complexity is introduced by the presence of two

different atoms in the carbon–oxygen double bond. Figure 16.19 compares the

reaction between water and a generic carbonyl compound (the formation of a

hydrate) with the hydration of an alkene.

Three factors must be considered in predicting which way the addition will go.

First of all, addition to the carbon of the carbon–oxygen double bond places the neg-

ative charge on the highly electronegative oxygen atom, whereas addition at oxygen

generates a much less stable carbanion (Fig. 16.21).Second,addition to oxygen forms

a weak oxygen–oxygen bond, whereas addition to the carbon makes a stronger

oxygen–carbon bond.

Alkene Alcohol

Carbonyl Hydrate

OHH H

OHH

FIGURE 16.19 Addition of water to

an alkene to give an alcohol is

analogous to addition to a ketone or

aldehyde to give a hydrate.

If water acts as a nucleophile and adds to the Lewis acid carbonyl group, there

is a choice to be made. In principle, water could add to either the carbon or the

oxygen of the carbonyl group (Fig. 16.20).

–

C C

Oor

C C

FIGURE 16.20 In principle, addition of water to a carbonyl group could occur in two ways.

–

.. ..

Weak O O bond

Strong O C bond

Negative

charge

on oxygen

Negative

charge

on carbon

FIGURE 16.21 Addition to the

carbon end, which puts the negative

charge on the relatively

electronegative oxygen atom, will be

greatly preferred.

WORKED PROBLEM 16.7 Explain how the thermodynamic preference for placing

a negative charge on oxygen, rather than carbon, can influence the rates of addi-

tion to the two ends of the carbon–oxygen double bond.

ANSWER The rates of reaction depend, of course, on the heights of the tran-

sition states, not on the energies of the products in which a full nega-

tive charge resides on either oxygen or carbon. In the transition states for

addition, there will be a partial negative charge on either oxygen or carbon.

The factors that favor a full negative charge on oxygen rather than carbon

(electronegativity) will also favor a partial negative charge (δ



) on oxygen.

(continued)

774 CHAPTER 16 Carbonyl Chemistry 1: Addition Reactions

Therefore, in the transition state, a partial negative charge will be more stable

on oxygen than on carbon.

Transition state

–

The third factor to consider involves the orbitals making up the carbonyl π

bond. If we look at the molecular orbitals involved, we can see how they influence

the direction in which the reaction occurs. As in all organic reactions, we look for

the combination of a nucleophile (here, water) and an electrophile.The electrophile

in this case must be the empty π* orbital of the carbonyl group. Figure 16.22 shows

the orbital interactions graphically, and gives pictures of the orbital lobes involved.

–

Empty π* orbital

A filled orbital n

π*

σ*

bond

Energy

New O

FIGURE 16.22 In the addition of water to a carbonyl group, a filled n orbital of water overlaps with the

empty π* orbital of the carbonyl group. This interaction between a filled and an empty orbital is stabilizing.

As we saw in our earlier section on structure (p. 764), neither the π nor the π*

of the carbonyl group is symmetric with respect to the midpoint of the carbon–

oxygen bond. In particular, the π* is much larger in the region of the carbon atom

than it is near the oxygen. Because the magnitude of stabilization depends on the

amount of orbital overlap, it is no surprise to see that addition at the carbon, where

the π* is largest, dominates the reaction. So, not only is the direction of the addi-

tion affected by the electronegativities and the bond strengths, but it’s affected by

the shapes of the orbitals involved as well.

–

Transition state

–

16.6 Reactions of Carbonyl Compounds: Simple Reversible Additions 775

After the addition of water to form the alkoxide, a proton must be removed and

a proton added to give the hydrate, not necessarily in that order (Fig. 16.23). It is

not necessary that the proton lost from one molecule be re-added to the same mol-

ecule.The protonation–deprotonation process is very likely to be intermolecular, as

shown in Figure 16.23.

Now consider how we might make the carbonyl addition reaction easier.Two ways

seem possible—we could make either the electrophile or the nucleophile stronger. Let’s

start with the acid-catalyzed reaction in which the carbonyl group is converted into a

stronger electrophile. If we take as our model for the mechanism the acid-catalyzed

additions to alkenes, a reasonable first step for hydration of a carbonyl would be pro-

tonation. But which end is protonated? Again, there are two possiblities (Fig. 16.24).

protonation

+–

deprotonation

....

HO C

.. ..

deprotonation

OCO

+–

protonation

+–

HO HC

HO C

.... ..

FIGURE 16.23 The carbonyl hydration reaction is completed by two proton transfers. The order of the

two steps is not certain.

C CCHC

Resonance stabilized

Protonation of an alkene (more stable intermediate formed)

Protonation of a carbonyl (two possibilities, more stable intermediate formed)

FIGURE 16.24 Protonation of the

carbonyl group can occur in two

ways. The placement of a proton on

oxygen to give a resonance-stabilized

cation will be greatly preferred.

The choice is easy this time. First, the carbonyl oxygen atom is a good Brønsted

base because it has two lone pairs of nonbonding electrons. Moreover, it is surely bet-

ter to protonate on oxygen, and thus place the positive charge on the relatively elec-

tropositive carbon rather than to protonate on carbon, which would place the positive

charge on the highly electronegative oxygen atom.Finally, protonation at oxygen gives

a resonance-stabilized cation, whereas protonation at carbon does not, as shown in

Carbonyl hydration

776 CHAPTER 16 Carbonyl Chemistry 1: Addition Reactions

Figure 16.24. So there is not really much choice in the direction of the protonation

step, and the result is a very electrophilic species, the protonated carbonyl compound.

In the second step of the reaction, water acts as a nucleophile and adds to the

Lewis acid (the protonated carbonyl) to generate a protonated diol (Fig. 16.25). In

the final step of this acid-catalyzed reaction, the protonated diol is deprotonated by

a water molecule to generate the neutral diol and regenerate the acid catalyst, H



A diol with both OH groups on the same carbon is called a gem-diol (gem stands

for geminal) or a hydrate. Note how closely related are the acid-catalyzed additions

of water to an alkene and to a carbonyl group. Each reaction is a sequence of three

steps: protonation, addition of water, and deprotonation.

protonation deprotonationaddition

The case for an alkene…

…and for a carbonyl

Alcohol

Hydrate

protonation deprotonationaddition

H H

(a)

(b)

FIGURE 16.25 A comparison of the

acid-catalyzed hydration reactions of

(a) an alkene and (b) a carbonyl

compound.

What about making the nucleophile more reactive? There is another mechanism

for hydration and it operates under basic conditions. Here the active agent is the

hydroxide ion,



OH. The first step in the base-catalyzed hydration reaction is

the addition of the strong nucleophile hydroxide to the carbonyl group (Fig. 16.26).

COH

The case for an alkene…

…and for a carbonyl

–

Hydrate

Hydroxide ion regenerated

FIGURE 16.26 Although strong bases

such as hydroxide ion do not add to

alkenes, they do attack carbonyl

groups.The final step in the base-

catalyzed hydration reaction is

protonation of the newly formed

alkoxide ion by water. Hydroxide is

regenerated.

16.7 Equilibrium in Addition Reactions 777

Unlike protonation, the first step in the acid-catalyzed reaction,this reaction has no

counterpart in the chemistry of simple alkenes. After addition,a proton is transferred

from water to the newly formed alkoxide, generating the hydrate and regenerating

the hydroxide ion.

Summary

The carbonyl group is hydrated under acidic (Fig. 16.25), basic (Fig. 16.26), and

neutral conditions (Figs. 16.20 and 16.23). In acid, the mechanism is accelerated

by protonation of the carbon–oxygen double bond to generate a strong electrophile

(Lewis acid).The relatively weak nucleophile,water, then adds.In base, the strong

nucleophile hydroxide adds to the relatively weak Lewis acid, the carbonyl group.

PROBLEM 16.8 Explain why bases such as the hydroxide ion do not add to the

oxygen of the carbon–oxygen double bond, nor to alkenes.

2.3  10

OHH

1.06

Ethanal

(acetaldehyde)

Methanal

(formaldehyde)

2  10

–3

Acetone

WEB 3D

FIGURE 16.27 The equilibrium

constant for hydration of a

carbonyl-containing molecule can

favor either the hydrate or the

carbonyl compound.The

equilibrium constants shown

here are for pH  7 conditions.

Why should there be such great differences among these rather similar com-

pounds? First of all, remember that a little difference in energy goes a long way at

equilibrium (p.336). Recall also that alkyl groups stabilize double bonds (Table 3.1).

The more highly substituted an alkene, the more stable it is. The same phenom-

enon holds for carbon–oxygen double bonds. So, the stability of the carbonyl

16.7 Equilibrium in Addition Reactions

Carbonyl hydration reactions consist of several consecutive equilibria.In basic, acidic,

or even neutral water, simple carbonyl compounds are in equilibrium with their

hydrates,as Figure 16.27 shows.Even for molecules as similar as acetone and ethanal

(acetaldehyde), these equilibria settle out at widely different points. If we include

formaldehyde, the difference is even more striking.For these three molecules, which

differ only in the number of methyl groups attached to the carbonyl, there is a

difference in K of about a factor of 10

778 CHAPTER 16 Carbonyl Chemistry 1: Addition Reactions

compound increases along the series: formaldehyde, acetaldehyde, acetone as the

substitution of the carbon–oxygen double bond increases (Fig. 16.28, left side).

If we now look at the molecule at the other side of the equilibrium, the hydrate,

we can see that increased methyl substitution introduces steric destabilization.

The more substituted the hydrate, the less stable it is (Fig. 16.28, right side). We

can immediately see the sources of the difference in K of 10

(Fig. 16.29). They

are the increased stabilization of the starting carbonyl compounds and destabi-

lization of the hydrates, both of which are induced by increased substitution by

methyl groups.

Increasing stability

Note increased

substitution by

methyls

Note steric

destabilization

by methyls

FIGURE 16.28 Like alkenes, more

substituted carbonyl groups are more

stable than their less substituted

counterparts. In the hydrates,

increasing substitution results in

increasing destabilization through

steric interactions.

Energy

Acetone is more stable and

its hydrate is less stable

K ~ 1K < 1 K > 1

The aldehyde and hydrate

are of comparable energy

Formaldehyde is less stable

and its hydrate is more stable

Energy

FIGURE 16.29 The magnitude of the equilibrium constant (K) depends on the relative energies of the carbonyl compounds

and their hydrates.We know that for acetaldehyde the energies of hydrate and aldehyde are comparable, because K 1.

Acetone is more stable than acetaldehyde and formaldehyde is less stable. Steric factors make the acetone hydrate less stable

than the acetaldehyde hydrate. By contrast, the formaldehyde hydrate is more stable than the acetaldehyde hydrate. The

equilibrium constants reflect these changes.

We can see other striking effects on this equilibrium process in Table 16.3. For

example, benzene rings, which can interact with the carbon–oxygen double bond by

resonance,decrease the amount of hydrate present at equilibrium. However,electron-

withdrawing groups on the α position adjacent to the strongly favor theC