Infrared Spectroscopy

Aldehydes and ketones show a strong C═O bond absorption in the IR region from 1660 to 1770 cm^–1, as the spectra of benzaldehyde and cyclohexanone demonstrate (Figure 19.15). In addition, aldehydes show two characteristic C–H absorptions between 2700–2760 and 2800–2860 cm^–1. These absorbances are important for distinguishing between aldehydes and ketones. The higher-frequency absorbance is sometimes obscured in cases where the compound has numerous saturated C–H groups, but the lower-frequency peak is almost always visible.

Figure 19.15 Infrared spectra of (a) benzaldehyde and (b) cyclohexanone.

The exact position of the C═O absorption is diagnostic of the nature of the carbonyl group. As the data in Table 19.2 indicate, saturated aldehydes usually show carbonyl absorptions near 1730 cm–1 in the IR spectrum, but conjugation of the aldehyde to an aromatic ring or a double bond lowers the absorption by 25 cm^–1 to near 1705 cm^–1. Saturated aliphatic ketones and cyclohexanones both absorb near 1715 cm^–1, and conjugation with a double bond or an aromatic ring again lowers the absorption by 30 cm^–1 to 1685–1690 cm^–1. Angle strain in the carbonyl group, caused by reducing the ring size of cyclic ketones to four or five, raises the absorption position. Cyclohexanone has its C═O stretch absorbance at 1715 cm^–1 while cyclopentanone’s carbonyl stretch is at 1750 cm^–1 and cyclobutanone’s is at 1785 cm^–1.

Table 19.2 Infrared Absorptions of Some Aldehydes and Ketones

Nuclear Magnetic Resonance Spectroscopy

Aldehyde protons (RCHO) absorb near 10 δ in the ¹H NMR spectrum and are very distinctive because no other absorptions occur in this region. The aldehyde proton shows spin–spin coupling with protons on the neighboring carbon, with coupling constant J ≈ 3 Hz. Acetaldehyde, for example, shows a quartet at 9.79 δ for the aldehyde proton, indicating that there are three protons neighboring the –CHO group (Figure 19.16).

Figure 19.16 ¹H NMR spectrum of acetaldehyde. The absorption of the aldehyde proton appears at 9.79 δ and is split into a quartet.

Hydrogens on the carbon next to a carbonyl group are slightly deshielded and usually absorb near 2.0 to 2.3 δ. The acetaldehyde methyl group in Figure 19.16, for instance, absorbs at 2.20 δ. Methyl ketones are particularly distinctive because they always show a sharp three-proton singlet near 2.1 δ.

The carbonyl-group carbon atoms of aldehydes and ketones have characteristic ¹³C NMR resonances in the range 190 to 215 δ. Since no other kinds of carbons absorb in this range, the presence of an NMR absorption near 200 δ is clear evidence for a carbonyl group.

Saturated aldehyde or ketone carbons usually absorb in the region from 200 to 215 δ, while aromatic and α,β-unsaturated carbonyl carbons absorb in the 190 to 200 δ region.

Mass Spectrometry

As discussed in Section 12.3, aliphatic aldehydes and ketones that have hydrogens on their gamma (γ) carbon atoms undergo a characteristic mass spectral cleavage called the McLafferty rearrangement. A hydrogen atom is transferred from the γ carbon to the carbonyl oxygen, the bond between the α and β carbons is broken, and a neutral alkene fragment is produced. The charge remains with the oxygen-containing fragment.

In addition to fragmentation by the McLafferty rearrangement, aldehydes and ketones also undergo cleavage of the bond between the carbonyl group and the α carbon, called an α cleavage. Alpha cleavage yields a neutral radical and a resonance-stabilized acyl cation.

Fragment ions from both McLafferty rearrangement and α cleavage are visible in the mass spectrum of 5-methyl-2-hexanone shown in Figure 19.17. McLafferty rearrangement with loss of 2-methylpropene yields a fragment with m/z = 58. Alpha cleavage occurs primarily at the more substituted side of the carbonyl group, leading to a [CH₃CO]⁺ fragment with m/z = 43.

Figure 19.17 Mass spectrum and the related reactions of 5-methyl-2-hexanone. The peak at m/z = 58 is due to McLafferty rearrangement. The abundant peak at m/z = 43 is due to α cleavage at the more highly substituted side of the carbonyl group. Note that the peak due to the molecular ion is very small.

Problem 19-25

How might you use mass spectrometry to distinguish between the following pairs of isomers?

(a) Methyl-2-hexanone and 4-methyl-2-hexanone

(b) 3-Heptanone and 4-heptanone

(c) 2-Methylpentanal and 3-methylpentanal

Problem 19-26

Describe the prominent IR absorptions and mass spectral peaks you would expect for the following compound:

Problem 19-27

Each of the following substances can be prepared by a nucleophilic addition reaction between an aldehyde or ketone and a nucleophile. Identify the reactants from which each was prepared. If the substance is an acetal, identify the carbonyl compound and the alcohol; if it is an imine, identify the carbonyl compound and the amine; and so forth.

(a)

(b)

(c)

(d)

Problem 19-28

The following molecular model represents a tetrahedral intermediate resulting from addition of a nucleophile to an aldehyde or ketone. Identify the reactants, and write the structure of the final product when the nucleophilic addition reaction is complete.

Problem 19-29

The enamine prepared from acetone and dimethylamine is shown in its lowest-energy form.

(a) What is the geometry and hybridization of the nitrogen atom?

(b) What orbital on nitrogen holds the lone pair of electrons?

(c) What is the geometric relationship between the p orbitals of the double bond and the nitrogen orbital that holds the lone pair? Why do you think this geometry represents the minimum energy?

Mechanism Problems

Problem 19-30

Predict the product(s) and propose a mechanism for each of the following reactions:

(a)

(b)

Problem 19-31

Predict the product(s) and propose a mechanism for each of the following reactions:

(a)

(b)

Problem 19-32

Predict the product(s) and propose a mechanism for each of the following reactions:

(a)

(b)

Problem 19-33

Predict the product(s) and propose a mechanism for each of the following reactions:

(a)

(b)

Problem 19-34

Predict the product(s) and propose mechanisms for the following reactions:

(a)

(b)

Problem 19-35

The following reaction begins with an acetal and converts it into a different acetal. Predict the product(s) and propose a mechanism.

(a)

(b)

Problem 19-36

When α-glucose is treated with an acid catalyst in the presence of an alcohol, an acetal is formed. Propose a mechanism for this process and give the structure of the stereoisomeric acetal that you would also expect as a product.

Problem 19-37

Predict the products of the following Wolff–Kishner reactions. Write the mechanism for each, beginning from the hydrazone intermediate.

(a)

(b)

Problem 19-38

Aldehydes can be prepared by the Wittig reaction using (methoxymethylene)triphenylphosphorane as the Wittig reagent and then hydrolyzing the product with acid. For example,

(a) How would you prepare the necessary phosphorane?

(b) Propose a mechanism for the hydrolysis step.

Problem 19-39

One of the steps in the metabolism of fats is the reaction of an unsaturated acyl CoA with water to give a β-hydroxyacyl CoA. Propose a mechanism.

Problem 19-40

Aldehydes and ketones react with thiols to yield thioacetals just as they react with alcohols to yield acetals. Predict the product of the following reaction, and propose a mechanism:

Problem 19-41

Ketones react with dimethylsulfonium methylide to yield epoxides. Suggest a mechanism for the reaction.

Problem 19-42

Propose a mechanism for the following reaction.

Problem 19-43

Paraldehyde, a sedative and hypnotic agent, is prepared by treatment of acetaldehyde with an acidic catalyst. Propose a mechanism for the reaction.

Problem 19-44

The Meerwein–Ponndorf–Verley reaction involves reduction of a ketone by treatment with an excess of aluminum triisopropoxide, [(CH3)2CHO]3Al. The mechanism of the process is closely related to the Cannizzaro reaction in that a hydride ion acts as a leaving group.

Propose a mechanism.

Problem 19-45

Propose a mechanism to account for the formation of 3,5-dimethylpyrazole from hydrazine and 2,4-pentanedione. What has happened to each carbonyl carbon in going from starting material to product.

Problem 19-46

In light of your answer to Problem 19-45, propose a mechanism for the formation of 3,5- dimethylisoxazole from hydroxylamine and 2,4-pentanedione.

Problem 19-47

Trans alkenes are converted into their cis isomers and vice versa on epoxidation followed by treatment of the epoxide with triphenylphosphine. Propose a mechanism for the reaction.

Problem 19-48

Treatment of an α,β-unsaturated ketone with basic aqueous hydrogen peroxide yields an epoxy ketone. The reaction is specific to unsaturated ketones; isolated alkene double bonds do not react. Propose a mechanism.

Problem 19-49

One of the biological pathways by which an amine is converted to a ketone involves two steps: (1) oxidation of the amine by NAD+ to give an imine and (2) hydrolysis of the imine to give a ketone plus ammonia. Glutamate, for instance, is converted by this process into α– ketoglutarate. Show the structure of the imine intermediate, and propose mechanisms for both steps.

Problem 19-50

Primary amines react with esters to yield amides: RCO2R′ + R″NH2 → RCONHR″ + R′OH. Propose a mechanism for the following reaction of an α,β-unsaturated ester.

Problem 19-51

When crystals of pure α-glucose are dissolved in water, isomerization occurs slowly to produce β-glucose. Propose a mechanism for the isomerization.

Problem 19-52

The Wharton reaction converts an epoxy ketone to an allylic alcohol by reaction with hydrazine. Review the Wolff–Kishner reaction in Section 19.9 and then propose a mechanism.

Naming Aldehydes and Ketones

Problem 19-53

Draw structures corresponding to the following names:

(a) Bromoacetone

(b) (S)-2-Hydroxypropanal

(c) 2-Methyl-3-heptanone

(d) (2S,3R)-2,3,4-Trihydroxybutanal

(e) 2,2,4,4-Tetramethyl-3-pentanone

(f) 4-Methyl-3-penten-2-one

(g) Butanedial

(h) 3-Phenyl-2-propenal

(i) 6,6-Dimethyl-2,4-cyclohexadienone

(j) p-Nitroacetophenone

Problem 19-54

Draw and name the seven aldehydes and ketones with the formula C₅H₁₀O. Which are chiral?

Problem 19-55

Give IUPAC names for the following compounds:

(a)

(b)

   

(c)

(d)

(e)

(f)

Problem 19-56

Draw structures of compounds that fit the following descriptions:

(a) An α,β-unsaturated ketone, C₆H₈O

(b) An α-diketone

(c) An aromatic ketone, C₉H₁₀O

(d) A diene aldehyde, C₇H₈O

Reactions of Aldehydes and Ketones

Problem 19-57

Predict the products of the reaction of (1) phenylacetaldehyde and (2) acetophenone with the following reagents:

(a) NaBH₄, then H₃O⁺

(b) Dess–Martin reagent

(c) NH₂OH, HCl catalyst

(d) CH₃MgBr, then H₃O⁺

(e) 2 CH₃OH, HCl catalyst

(f) H₂NNH₂, KOH

(g) (C₆H₅)₃P=CH₂

(h) HCN, KCN

Problem 19-58

Show how you might use a Wittig reaction to prepare the following alkenes. Identify the alkyl halide and the carbonyl components.

(a)

(b)

Problem 19-59

How would you use a Grignard reaction on an aldehyde or ketone to synthesize the following compounds?

(a) 2-Pentanol

(b) 1-Butanol

(c) 1-Phenylcyclohexanol

(d) Diphenylmethanol

Problem 19-60

How might you carry out the following selective transformations? One of the two schemes requires a protection step. (Recall from Section 19.4 that aldehydes are more reactive than ketones toward nucleophilic addition.)

(a)

 

(b)

Problem 19-61

How would you prepare the following substances from 2-cyclohexenone? More than one step may be needed.

(a)

(b)

(c)

(d)

Problem 19-62

How would you synthesize the following substances from benzaldehyde and any other reagents needed?

(a)

(b)

(c)

Problem 19-63

Carvone is the major constituent of spearmint oil. What products would you expect from reaction of carvone with the following reagents?

(a) (CH₃)₂Cu^– Li⁺, then H₃O⁺

(b) LiAlH₄, then H₃O⁺

(c) CH₃NH₂

(d) C₆H₅MgBr, then H₃O⁺

(e) H₂/Pd

(f) HOCH₂CH₂OH, HCl

(g) (C₆H₅)₃PCHCH₃

Problem 19-64

How would you synthesize the following compounds from cyclohexanone?

(a) Methylcyclohexene

(b) Phenylcyclohexanone

(c) cis-1,2-Cyclohexanediol

(d) 1-Cyclohexylcyclohexanol

Spectroscopy

Problem 19-65

At what position would you expect to observe IR absorptions for the following molecules?

(a)

(b)

(c)

(d)

Problem 19-66

Acid-catalyzed dehydration of 3-hydroxy-3-phenylcyclohexanone leads to an unsaturated ketone. What possible structures are there for the product? At what position in the IR spectrum would you expect each to absorb? If the actual product has an absorption at 1670 cm^–1, what is its structure?

Problem 19-67

Choose the structure that best fits the IR spectrum shown.

Problem 19-68

Propose structures for molecules that meet the following descriptions. Assume that the kinds of carbons (1°, 2°, 3°, or 4°) have been assigned by DEPT–NMR.

(a) C₆H₁₂O; IR: 1715 cm^–1; ¹³C NMR: 8.0 δ (1°), 18.5 δ (1°), 33.5 δ (2°), 40.6 δ (3°), 214.0 δ (4°)

(b) C₅H₁₀O; IR: 1730 cm^–1; ¹³C NMR: 22.6 δ (1°), 23.6 δ (3°), 52.8 δ (2°), 202.4 δ (3°)

(c) C₆H₈O; IR: 1680 cm^–1; ¹³C NMR: 22.9 δ (2°), 25.8 δ (2°), 38.2 δ (2°), 129.8 δ (3°), 150.6 δ (3°), 198.7 δ (4°)

Problem 19-69

Compound A, C₈H₁₀O₂, has an intense IR absorption at 1750 cm^–1 and gives the ¹³C NMR spectrum shown. Propose a structure for A.

Problem 19-70

Propose structures for ketones or aldehydes that have the following ¹H NMR spectra:

(a) C₄H₇ClO

      IR: 1715 cm^–1

(b) C₇H₁₄O

      IR: 1710 cm^–1

General Problems

Problem 19-71

When 4-hydroxybutanal is treated with methanol in the presence of an acid catalyst, 2- methoxytetrahydrofuran is formed. Explain.

Problem 19-72

The S_N2 reaction of (dibromomethyl)benzene, C₆H₅CHBr₂, with NaOH yields benzaldehyde rather than (dihydroxymethyl)benzene, C₆H₅CH(OH)₂. Explain.

Problem 19-73

Reaction of 2-butanone with HCN yields a chiral product. What stereochemistry does the product have? Is it optically active?

Problem 19-74

The amino acid methionine is biosynthesized by a multistep route that includes reaction of an imine of pyridoxal phosphate (PLP) to give an unsaturated imine, which then reacts with cysteine. What kinds of reactions are occurring in the two steps?

Problem 19-75

Each of the following reaction schemes has one or more flaws. What is wrong in each case? How would you correct each scheme?

(a)

(b)

(c)

Problem 19-76

6-Methyl-5-hepten-2-one is a constituent of lemongrass oil. How could you synthesize this substance from methyl 4-oxopentanoate?

Problem 19-77

Tamoxifen is a drug used in the treatment of breast cancer. How would you prepare tamoxifen from benzene, the following ketone, and any other reagents needed?

Problem 19-78

Compound A, MW = 86, shows an IR absorption at 1730 cm^–1 and a very simple ¹H NMR spectrum with peaks at 9.7 δ (1 H, singlet) and 1.2 δ (9 H, singlet). Propose a structure for A.

Problem 19-79

Compound B is isomeric with A (Problem 19-78) and shows an IR peak at 1715 cm^–1. The ¹H NMR spectrum of B has peaks at 2.4 δ (1 H, septet, J = 7 Hz), 2.1 δ (3 H, singlet), and 1.2 δ (6 H, doublet, J = 7 Hz). What is the structure of B?

Problem 19-80

The ¹H NMR spectrum shown is that of a compound with the formula C₉H₁₀O. How many double bonds and/or rings does this compound contain? If the unknown compound has an IR absorption at 1690 cm^–1, what is a likely structure?

Problem 19-81

The ¹H NMR spectrum shown is that of a compound isomeric with the one in Problem 19- 80. This isomer has an IR absorption at 1730 cm^–1. Propose a structure. [Note: Aldehyde protons (CHO) often show low coupling constants to adjacent hydrogens, so the splitting of aldehyde signals is not always apparent.]

Problem 19-82

Propose structures for ketones or aldehydes that have the following ¹H NMR spectra:

(a) C₉H₁₀O₂

      IR: 1695 cm–1

(b) C₄H₆O

      IR: 1690 cm^–1

Problem 19-83

Propose structures for ketones or aldehydes that have the following ¹H NMR spectra.

(a) C₁₀H₁₂O

      IR: 1710 cm^–1

(b) C₆H₁₂O₃

       IR: 1715 cm^–1

Problem 19-84

When glucose (Problem 19-51) is treated with NaBH₄, reaction occurs to yield sorbitol, a polyalcohol commonly used as a food additive. Show how this reduction occurs.

Problem 19-85

The proton and carbon NMR spectra for each of three isomeric ketones with the formula C₇H₁₄O are shown. Assign a structure to each pair of spectra.

Problem 19-86

The proton NMR spectrum for a compound with formula C₁₀H₁₂O₂ is shown below. The infrared spectrum has a strong band at 1711 cm^–1. The broadband-decoupled ¹³C NMR spectral results are tabulated along with the DEPT-135 and DEPT-90 information. Draw the structure of this compound.