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Confirming Pages O R G A N I C C H E M I S T RY Aldehydes and Ketones LEARNING GOALS 1 ▶ Draw the structures and discuss the physical 2 ▶ 3 ▶ 4 ▶ 5 ▶ 6 ▶ 7 ▶ 8 ▶ 9 ▶ properties of aldehydes and ketones. From the structures, write the common and I.U.P.A.C. names of aldehydes and ketones. List several aldehydes and ketones that are of natural, commercial, health, and environmental interest and describe their significance. Write equations for the preparation of aldehydes and ketones by the oxidation of alcohols. Write equations representing the oxidation of carbonyl compounds. Write equations representing the reduction of carbonyl compounds. Write equations for the preparation of hemiacetals, hemiketals, acetals, and ketals. Draw the keto and enol forms of aldehydes and ketones. Write equations showing the aldol condensation. OUTLINE Introduction 422 13.1 Structure and Physical Properties 423 13.2 I.U.P.A.C. Nomenclature and Common Names 425 Naming Aldehydes 425 Naming Ketones 427 13.3 Important Aldehydes and Ketones 430 13.4 Reactions Involving Aldehydes and Ketones 432 Preparation of Aldehydes and Ketones 432 Oxidation Reactions 432 A Medical Perspective: Formaldehyde and Methanol Poisoning 433 A Human Perspective: Alcohol Abuse and Antabuse 436 Reduction Reactions 436 A Medical Perspective: That Golden Tan Without the Fear of Skin Cancer 438 Addition Reactions 439 Keto-Enol Tautomers 442 Aldol Condensation 443 421 den02621_ch13_421-450.indd 421 11/24/09 6:24:12 PM Confirming Pages INTRODUCTION Cinnamon tree blossoms. For centuries we have used bloodhounds to locate missing persons or criminals. This works because of the amazing ability of bloodhounds to detect scent molecules, and because individuals have characteristic odor prints that are as unique as their fingerprints or DNA. Forensic scientists are now making the next step in developing this technology for more accurate detection of people associated with a crime scene. The first step is to identify the components of the odor print and an appropriate source of the sample. Some scientists suggest that odor molecules should be collected from the hands, since this is the part of the body that would handle a gun, bomb, or other materials at a crime scene. When samples are collected from hands, complex mixtures of compounds are collected. Among the molecules identified as prominent in these mixtures are some large and complex members of the two groups of compounds we will study in this chapter, the aldehydes and ketones. Among these are the aldehydes nonanal, decanal, and undecanal and the ketones 6-methyl-5-hepten-2-one and 6,10-dimethyl-5,9-undecadien-2-one. The next step in using this information to identify individuals will be the development of an instrument to detect, identify, and quantify these and other components of the human odor print samples found at the scene of a crime so that that pattern can be compared with suspects in the case. O C Nonanal H O C H Decanal O C Undecanal H O C 6-Methyl-5-hepten-2-one O C 6,10-Dimethyl-5,9-undecadien-2-one The aldehydes and ketones are characterized by the presence of the carbonyl group, a functional group made up of a carbon atom bonded to an oxygen atom by a double bond. a O + C d Carbonyl group 13-2 den02621_ch13_421-450.indd Sec1:422 11/24/09 6:24:49 PM Confirming Pages 13.1 423 Structure and Physical Properties Compounds containing a carbonyl group are called carbonyl compounds. These include the aldehydes and ketones covered in this chapter, as well as the carboxylic acids and amides discussed in Chapters 14 and 15. 0 - 0 - Aldehyde - R R R Ketone 0 H O + C - R O + C OH R Carboxylic Acid O + C 0 O + C NR2 Amide 13.1 Structure and Physical Properties Aldehydes and ketones are carbonyl group containing compounds distinguished by the location of the carbonyl group within the carbon chain. In aldehydes the carbonyl group is always located at the end of the carbon chain (carbon-1). In ketones the carbonyl group is located within the carbon chain of the molecule. Thus, in ketones the carbonyl carbon is attached to two other carbon atoms. However, in aldehydes the carbonyl carbon is attached to at least one hydrogen atom; the second atom attached to the carbonyl carbon of an aldehyde may be another hydrogen or a carbon atom (Figure 13.1). Aldehydes and ketones are polar compounds because of the polar carbonyl group. LEARNING GOAL 1▶ Draw the structures and discuss the physical properties of aldehydes and ketones. 2 Od 1 Cd # ! Because of the dipole-dipole attractions between molecules, they boil at higher temperatures than hydrocarbons or ethers that have the same number of carbon atoms or are of equivalent molecular mass. Because they cannot form intermolecular hydrogen bonds, their boiling points are lower than those of alcohols of comparable molecular mass. These trends are clearly demonstrated in the following examples: d2O d1C [ Y1 Cd 2 Od Y[ Dipole-dipole attraction CH3CH2CH2CH3 CH3—O—CH2CH3 CH3CH2CH2 —OH O CH3CH2 —C—H Butane (butane) M.M. 58 b.p. 0.5 C Methoxyethane (ethyl methyl ether) M.M. 60 b.p. 7.0 C 1-Propanol (propyl alcohol) M.M. 60 b.p. 97.2 C Propanal (propionaldehyde) M.M. 58 b.p. 49 C O CH3—C—CH3 Propanone (acetone) M.M. 58 b.p. 56 C Aldehydes and ketones can form intermolecular hydrogen bonds with water (Figure 13.2). As a result, the smaller members of the two families (five or fewer carbon atoms) are reasonably soluble in water. However, as the carbon chain R O O C C R H Aldehyde R H, R, or Ar An aldehyde Propanal (a) R Figure 13.1 The structures of alde- Ketone R R or Ar A ketone Propanone (b) hydes and ketones. (a) The general structure of an aldehyde and a balland-stick model of the aldehyde propanal. (b) The general structure of a ketone and a ball-and-stick model of the ketone propanone. 13-3 den02621_ch13_421-450.indd Sec2:423 11/24/09 6:24:59 PM Confirming Pages 424 Chapter 13 Aldehydes and Ketones O R H H O O C H R R between the carbonyl group of an aldehyde or ketone and water. (b) Polar interactions between carbonyl groups of aldehydes or ketones. C R (a) O H C O R O C O Figure 13.2 (a) Hydrogen bonding R R R R C R (b) length increases, the compounds become less polar and more hydrocarbonlike. These larger compounds are soluble in nonpolar organic solvents. Question 13.1 Which member in each of the following pairs will be more water-soluble? O a. CH3(CH2)2CH3 or CH3CCH3 b. CH3CCH 2CH2CH3 or CH3CHCH 2CH2CH3 | O OH Question 13.2 Which member in each of the following pairs will be more water-soluble? CH3 or H*C+O a. b. HOCH 2 CH2 OH or C H HCC OO Question 13.3 Which member in each of the following pairs would have a higher boiling point? a. CH3CH2COH or CH3CH2CH O O O b. CH3COH or CH3CCH3 O Question 13.4 Which member in each of the following pairs would have a higher boiling point? O a. CH3CH2OH or CH3CH b. CH3(CH2)6CH3 or CH3(CH2)5CH O 13-4 den02621_ch13_421-450.indd Sec3:424 11/24/09 6:25:00 PM Confirming Pages 425 13.2 I.U.P.A.C. Nomenclature and Common Names 13.2 I.U.P.A.C. Nomenclature and Common Names Naming Aldehydes In the I.U.P.A.C. system, aldehydes are named according to the following set of rules: • Determine the parent compound, that is, the longest continuous carbon chain containing the carbonyl group. • Replace the final -e of the parent alkane with -al. • Number the chain beginning with the carbonyl carbon (or aldehyde group) as carbon-1. • Number and name all substituents as usual. No number is used for the position of the carbonyl group because it is always at the end of the parent chain. Therefore, it must be carbon-1. LEARNING GOAL 2▶ From the structures, write the common and I.U.P.A.C. names of aldehydes and ketones. Several examples are provided here with common names given in parentheses: O 1+ H8C8H O 2 1+ CH38C8H O 3 2 1+ CH3CH28C8H Methanal (formaldehyde) Ethanal (acetaldehyde) Propanal (propionaldehyde) O 5 4 3 2 1+ CH3CH2CH2CH8C8H * CH3 2-Methylpentanal EXAMPLE 13.1 Using the I.U.P.A.C. Nomenclature System to Name Aldehydes For many years, scientists were puzzled about what compounds give the nutty flavor to expensive, aged cheddar cheeses. In 2004, Dr. Mary Anne Drake of North Carolina State University solved this puzzle. She identified a group of aldehydes that impart this desirable flavor. Use the I.U.P.A.C. Nomenclature System to name two of these aldehydes shown below. LEARNING GOAL 2▶ From the structures, write the common and I.U.P.A.C. names of aldehydes and ketones. Solution O + CH3CHC8H 3 2* 1 CH3 O + CH3CHCH2C8H 4 *3 2 1 CH3 Parent compound: propane (becomes propanal) butane (becomes butanal) Position of carbonyl group: carbon-1 (must be!) carbon-1 (must be!) Substituents: 2-methyl 3-methyl Name: 2-Methylpropanal 3-Methylbutanal Notice that the position of the carbonyl group is not indicated by a number. By definition, the carbonyl group is located at the end of the carbon chain of an Continued— 13-5 den02621_ch13_421-450.indd Sec4:425 11/24/09 6:25:01 PM Confirming Pages 426 Chapter 13 Aldehydes and Ketones aldehyde. The carbonyl carbon is defined to be carbon-1; thus, it is not necessary to include the position of the carbonyl group in the name of the compound. Practice Problem 13.1 Many molecules contribute to the complex flavors of olive oils. Among these are hexanal and trans-2-hexenal, which have flavors described as “green, grassy” and “green, bitter,” respectively. Draw the structures of these two compounds. Another aldehyde associated with the nutty flavor of cheddar cheese is 2-methylbutanal. Draw the condensed formula of this molecule. Carboxylic acid nomenclature is described in Section 14.1. ▶ For Further Practice: Questions 13.5, 13.29, and 13.36a, b, and c. The common names of the aldehydes are derived from the same Latin roots as the corresponding carboxylic acids. The common names of the first five aldehydes are presented in Table 13.1. In the common system of nomenclature, substituted aldehydes are named as derivatives of the straight-chain parent compound (see Table 13.1). Greek letters are used to indicate the position of the substituents. The carbon atom bonded to the carbonyl group is the ␣-carbon, the next is the -carbon, and so on. d g b a O *C*C*C*C*C*H Consider the following examples: O CH3CH2CH2CH*C*H CH3 O CH3CH2CHCH2*C*H CH3 2-Methylpentanal (a-methylvaleraldehyde) 3-Methylpentanal (b-methylvaleraldehyde) d g b a d g b a Table 13.1 I.U.P.A.C. and Common Names and Formulas for Several Aldehydes I.U.P.A.C. Name Methanal Ethanal Propanal Butanal Pentanal Common Name Formula Formaldehyde O + H—C—H Acetaldehyde O + CH3C—H Propionaldehyde O + CH3CH2C—H Butyraldehyde O + CH3CH2CH2C—H Valeraldehyde O + CH3CH2CH2CH2C—H 13-6 den02621_ch13_421-450.indd Sec5:426 11/24/09 6:25:02 PM Confirming Pages 427 13.2 I.U.P.A.C. Nomenclature and Common Names EXAMPLE 13.2 Using the Common Nomenclature System to Name Aldehydes Name the aldehydes represented by the following condensed formulas. LEARNING GOAL 2▶ Solution O d g b a CH3CHCH2CH2C*H Br O g b a CH3CHCH2C*H CH3 From the structures, write the common and I.U.P.A.C. names of aldehydes and ketones. Parent compound: pentane butane (becomes valeraldehyde) (becomes butyraldehyde) Position of carbonyl group: carbon-1 (must be!) carbon-1 (must be!) Substituents: ␥-bromo -methyl Name: ␥-Bromovaleraldehyde -Methylbutyraldehyde Notice that the substituents are designated by Greek letters, rather than by Arabic numbers. In the common system of nomenclature for aldehydes, the carbon atom bonded to the carbonyl group is called the ␣-carbon, the next is the -carbon, etc. Remember to use these Greek letters to indicate the position of the substituents when naming aldehydes using the common system of nomenclature. Also remember that by definition, the carbonyl group is located at the beginning of the carbon chain of an aldehyde. Thus, it is not necessary to include the position of the carbonyl group in the name of the compound. Practice Problem 13.2 Use the common nomenclature system to name each of the following compounds. O O CH3 | b. CH3CH2CH2CHCH a. CH3CHCHCH2CH | | CH3 CH2CH3 O c. CH 3CHCH | Cl O d. CH3CHCH2CH | OH ▶ For Further Practice: Questions 13.6, 13.41c and d, 13.42b and d. Naming Ketones The rules for naming ketones in the I.U.P.A.C. Nomenclature System are directly analogous to those for naming aldehydes. In ketones, however, the -e ending of the parent alkane is replaced with the -one suffix of the ketone family, and the location of the carbonyl carbon is indicated with a number. The longest carbon chain is numbered to give the carbonyl carbon the lowest possible number. For example, O + CH38C8CH3 1 2 3 O + CH3CH28C8CH3 4 3 2 1 Propanone Butanone (no number necessary) (no number necessary) (acetone) (methyl ethyl ketone) LEARNING GOAL 2▶ From the structures, write the common and I.U.P.A.C. names of aldehydes and ketones. O + CH3CH2CH2CH28C8CH2CH2CH3 8 7 6 5 4 3 2 1 4-Octanone (not 5-octanone) (butyl propyl ketone) 13-7 den02621_ch13_421-450.indd Sec6:427 11/24/09 6:25:05 PM Confirming Pages 428 Chapter 13 Aldehydes and Ketones EXAMPLE 13.3 LEARNING GOAL 2▶ From the structures, write the common and I.U.P.A.C. names of aldehydes and ketones. Using the I.U.P.A.C. Nomenclature System to Name Ketones Two molecules associated with the aroma of blue cheese are the ketones shown below. Name these ketones using the I.U.P.A.C. Nomenclature System. Solution O O + + CH3CH2CH2CH2CH2CCH3 CH3CCH2CH2CH2CH2CH2CH2CH3 7 6 5 4 3 2 1 1 2 3 4 5 6 7 8 9 Parent compound: heptane nonane (becomes heptanone) (becomes nonanone) Position of carbonyl group: carbon-2 (not carbon-6) carbon-2 (not carbon-8) Name: 2-Heptanone 2-Nonanone Practice Problem 13.3 Provide the I.U.P.A.C. name for each of the following ketones. Two other molecules that contribute to the aroma of blue cheese are hexanoic acid and butanoic acid, two carboxylic acids we will study in Chapter 14. Refer to Table 10.2 for the structure of carboxylic acids and draw the condensed structural formula for each of these molecules. O + a. CH3CH2CHCH2CH2CH2CCH3 | CH2CH3 O + b. CH3CH2CH2CCHCH3 | CH3 O + c. CH3CHCCHCH3 | | CH3 CH3 ▶ For Further Practice: Questions 13.7, 13.41a, b, and e, and 13.42a and c. The common names of ketones are derived by naming the alkyl groups that are bonded to the carbonyl carbon. These are used as prefixes followed by the word ketone. The alkyl groups may be arranged alphabetically or by size (smaller to larger). EXAMPLE 13.4 LEARNING GOAL 2▶ From the structures, write the common and I.U.P.A.C. names of aldehydes and ketones. Using the Common Nomenclature System to Name Ketones Name the ketones represented by the following condensed formulas. Solution Identify the alkyl groups that are bonded to the carbonyl carbon. O CH3CH2CH2*C*CH3 Alkyl groups: Name: O CH3CH2*C*CH2CH2CH2CH2CH3 propyl and methyl Methyl propyl ketone ethyl and pentyl Ethyl pentyl ketone 13-8 den02621_ch13_421-450.indd Sec7:428 11/24/09 6:25:05 PM Confirming Pages 13.2 I.U.P.A.C. Nomenclature and Common Names 429 Practice Problem 13.4 Provide the common names for each of the following ketones: O O a. CH3CH2CCH2CH3 b. CH3CH2CH2CH2CCH2CH3 O d. CH3CHCCHCH3 O c. CH3CH2CH2CH2CH2CH2CCH3 | | CH3 CH3 ▶ For Further Practice: Questions 13.41a, b, and e and 13.44. Because the two groups bonded to the carbonyl carbon are named, a ketone is actually one carbon longer than an aldehyde with a similar common name. For example, methyl butyl ketone has six carbons, but -methylbutyraldehyde has only five. O CH3*C*CH2CH2CH2CH3 1 2 3 4 5 6 Methyl butyl ketone O 4 3 2 CH3CHCH2*C*H | 1 CH3 5 b-Methylbutyraldehyde This is because the aldehyde carbonyl carbon is included in the name of the parent chain, butyraldehyde. The carbonyl carbon of the ketone is not included in the common name. It is treated only as the carbon to which the two alkyl or aryl groups are attached. Question 13.5 From the I.U.P.A.C. names, draw the structural formula for each of the following aldehydes. a. b. c. d. e. 2,3-Dichloropentanal 2-Bromobutanal 4-Methylhexanal Butanal 2,4-Dimethylpentanal Question 13.6 Write the condensed formula for each of the following compounds. a. b. c. d. 3-Methylnonanal -Bromovaleraldehyde 4-Fluorohexanal ␣,-Dimethylbutyraldehyde Question 13.7 Use the I.U.P.A.C. Nomenclature System to name each of the following compounds. O + a. CH3CHCCH3 * I O + b. CH3CHCH2CCH3 * CH2CH2CH2CH3 13-9 den02621_ch13_421-450.indd Sec8:429 11/24/09 6:25:09 PM Confirming Pages 430 Chapter 13 Aldehydes and Ketones O + c . CH3CHCCH3 * CH3 e. O + d. CH3CHCCH2CH3 * CH3 O + CH3CHCCH2CH3 * F Question 13.8 Write the condensed formula for each of the following compounds. a. Methyl isopropyl ketone (What is the I.U.P.A.C. name for this compound?) b. 4-Heptanone c. 2-Fluorocyclohexanone d. Hexachloroacetone (What is the I.U.P.A.C. name of this compound?) 13.3 Important Aldehydes and Ketones LEARNING GOAL List several aldehydes and ketones that are of natural, commercial, health, and environmental interest and describe their significance. O + C H Methanal O + C 0 - CH3 CH3 H Ethanal O + C CH3 Propanone 0 - 0 - H O + C 0 - 3▶ CH3 CH2CH3 Butanone Methanal (formaldehyde) is a gas (b.p. ⫺21⬚C). It is available commercially as an aqueous solution called formalin. Formalin has been used as a preservative for tissues and as an embalming fluid. See A Medical Perspective: Formaldehyde and Methanol Poisoning for more information on methanal. Ethanal (acetaldehyde) is produced from ethanol in the liver. Ethanol is oxidized in this reaction, which is catalyzed by the liver enzyme alcohol dehydrogenase. The ethanal that is produced in this reaction is responsible for the symptoms of a hangover. Propanone (acetone), the simplest ketone, is an important and versatile solvent for organic compounds. It has the ability to dissolve organic compounds and is also soluble in water. As a result, it has a number of industrial applications and is used as a solvent in adhesives, paints, cleaning solvents, nail polish, and nail polish remover. Propanone is flammable and should therefore be treated with appropriate care. Butanone, a four-carbon ketone, is also an important industrial solvent. Many aldehydes and ketones are produced industrially as food and fragrance chemicals, medicinals, and agricultural chemicals. They are particularly important to the food industry, in which they are used as artificial and/or natural additives to food. Vanillin, a principal component of natural vanilla, is shown in Figure 13.3. Artificial vanilla flavoring is a dilute solution of synthetic vanillin dissolved in ethanol. Figure 13.3 also shows other examples of important aldehydes and ketones. Question 13.9 Draw the structure of the aldehyde synthesized from ethanol in the liver. Question 13.10 Draw the structure of a ketone that is an important, versatile solvent for organic compounds. 13-10 den02621_ch13_421-450.indd Sec9:430 11/24/09 6:25:09 PM Confirming Pages 431 13.3 Important Aldehydes and Ketones CH3O O C O H Benzaldehyde—almonds HO O CH CH C C H Vanillin—vanilla beans CH3 H Cinnamaldehyde—cinnamon CH3 C CH3 CH CH2 CH2 C O CH C H Citral—lemongrass O ␣-Demascone—berry flavoring O CH3CH2CH2CH2CH2CH2 C CH3 2-Octanone—mushroom flavoring Figure 13.3 Important aldehydes and ketones. 13-11 den02621_ch13_421-450.indd Sec10:431 11/24/09 6:25:10 PM Confirming Pages 432 Chapter 13 Aldehydes and Ketones 13.4 Reactions Involving Aldehydes and Ketones Preparation of Aldehydes and Ketones LEARNING GOAL 4▶ Write equations for the preparation of aldehydes and ketones by the oxidation of alcohols. Aldehydes and ketones are prepared primarily by the oxidation of the corresponding alcohol. As we saw in Chapter 12, the oxidation of methyl alcohol gives methanal (formaldehyde). The oxidation of a primary alcohol produces an aldehyde, and the oxidation of a secondary alcohol yields a ketone. Tertiary alcohols do not undergo oxidation under the conditions normally used. EXAMPLE 13.5 LEARNING GOAL 4▶ Write equations for the preparation of aldehydes and ketones by the oxidation of alcohols. Differentiating the Oxidation of Primary, Secondary, and Tertiary Alcohols Use specific examples to show the oxidation of a primary, a secondary, and a tertiary alcohol. Solution The oxidation of a primary alcohol to an aldehyde: H * CH3CH2CH28C8OH * H Pyridinium dichromate 1-Butanol (butyl alcohol) O + CH3CH2CH28C8H Butanal (butyraldehyde) A mild oxidizing agent must be used in the oxidation of a primary alcohol to an aldehyde. Otherwise, the aldehyde will be further oxidized to a carboxylic acid. The oxidation of a secondary alcohol to a ketone: CH3 * CH3CH2CH2CH28C8OH * H KMnO4, OH , H2O 2-Hexanol O + CH3CH2CH2CH28C8CH3 2-Hexanone Tertiary alcohols cannot undergo oxidation: CH3 * CH3CH2CH28C8OH * CH3 H2CrO4 No reaction 2-Methyl-2-pentanol Practice Problem 13.5 Write equations showing the oxidation of (a) 1-propanol and (b) 2-butanol. ▶ For Further Practice: Questions 13.61 and 13.62. LEARNING GOAL 5▶ Write equations representing the oxidation of carbonyl compounds. Oxidation Reactions Aldehydes are easily oxidized further to carboxylic acids, whereas ketones do not generally undergo further oxidation. The reason is that a carbon-hydrogen bond, present in the aldehyde but not in the ketone, is needed for the reaction 13-12 den02621_ch13_421-450.indd Sec11:432 11/24/09 6:25:24 PM Confirming Pages 13.4 433 Reactions Involving Aldehydes and Ketones A Medical Perspective Formaldehyde and Methanol Poisoning Most aldehydes have irritating, unpleasant odors, and formaldehyde is no exception. Formaldehyde is also an extremely toxic substance. As an aqueous solution, called formalin, it has been used to preserve biological tissues and for embalming. It has also been used to disinfect environmental surfaces, body fluids, and feces. Under no circumstances is it used as an antiseptic on human tissue because of its toxic fumes and the skin irritations that it causes. Formaldehyde is used in the production of some killedvirus vaccines. When a potentially deadly virus, such as polio virus, is treated with heat and formaldehyde, the genetic information (RNA) is damaged beyond repair. The proteins of the virus also react with formaldehyde. However, the shape of the proteins, which is critical for a protective immune response against the virus, is not changed. Thus, when a child is injected with the Salk killed-virus polio vaccine, the immune system recognizes viral proteins and produces antibodies that protect against polio virus infection. Formaldehyde can also be produced in the body! As we saw in Chapter 12, methanol can be oxidized to produce formaldehyde. In the body, the liver enzyme alcohol dehydrogenase, whose function it is to detoxify alcohols by oxidizing them, catalyzes the conversion of methanol to formaldehyde (methanal). The formaldehyde then reacts with cellular macromolecules, including proteins, causing severe damage (remember, it is used as an embalming agent!). As a result, methanol poisoning can cause blindness, respiratory failure, convulsions, and death. Clever physicians have devised a treatment for methanol poisoning that is effective if administered soon enough after ingestion. Since the same enzyme that oxidizes methanol to formaldehyde (methanal) also oxidizes ethanol to acetaldehyde (ethanal), doctors reasoned that administering an intravenous solution of ethanol to the patient could protect against the methanol poisoning. If the ethanol concentration in the body is higher than the methanol concentration, most of the alcohol dehydrogenase enzymes of the liver will be carrying out the oxidation of the ethanol. This is called competitive inhibition because the methanol and ethanol molecules are competing for binding to the enzymes. The molecule that is in the higher concentration will more frequently bind to the enzyme and undergo reaction. In this case, the result is that the alcohol dehydrogenase enzymes are kept busy oxidizing ethanol and producing the less-toxic (not nontoxic) product, acetaldehyde. This gives the body time to excrete the methanol before it is oxidized to the potentially deadly formaldehyde. For Further Understanding ▶ Acetaldehyde is described as less toxic than formaldehyde. Do some background research on the effects of these two aldehydes on biological systems. ▶ You have studied enzymes in previous biology courses. Using what you learned in those classes with information from Sections 19.4 and 19.10 in this text, put together an explanation of the way in which competitive inhibition works. Can you think of other types of poisoning for which competitive inhibition might be used to develop an effective treatment? to occur. In fact, aldehydes are so easily oxidized that it is often very difficult to prepare them because they continue to react to give the carboxylic acid rather than the desired aldehyde. Aldehydes are susceptible to air oxidation, even at room temperature, and cannot be stored for long periods. The following example shows a general equation for the oxidation of an aldehyde to a carboxylic acid: O + R8C8H [O] Aldehyde O + R8C8OH Carboxylic acid Many oxidizing agents can be used. Both basic potassium permanganate and chromic acid are good oxidizing agents, as the following specific example shows: O CH3*C*H Ethanal (acetaldehyde) KMnO4, H2O, OH O CH3*C*O Ethanoate anion (acetate anion) In basic solution, the product is the carboxylic acid anion: O + CH3—C—O The rules for naming carboxylic acid anions are described in Section 14.1. 13-13 den02621_ch13_421-450.indd Sec12:433 11/24/09 6:25:25 PM Confirming Pages 434 Chapter 13 Aldehydes and Ketones The oxidation of benzaldehyde to benzoic acid is an example of the conversion of an aromatic aldehyde to the corresponding aromatic carboxylic acid: O + 8C8H H2CrO4 Benzaldehyde Silver ions are very mild oxidizing agents. They will oxidize aldehydes but not alcohols. O + 8C8OH Benzoic acid Aldehydes and ketones can be distinguished on the basis of differences in their reactivity. The most common laboratory test for aldehydes is the Tollens’ test. When exposed to the Tollens’ reagent, a basic solution of Ag(NH3)2⫹, an aldehyde undergoes oxidation. The silver ion (Ag⫹) is reduced to silver metal (Ag0) as the aldehyde is oxidized to a carboxylic acid anion. O R*C*H 1 Aldehyde Ag(NH3)2 Silver ammonia complex— Tollens’ reagent O R*C*O 1 Ag0 Carboxylate anion Silver metal mirror Silver metal precipitates from solution and coats the flask, producing a smooth silver mirror, as seen in Figure 13.4. The test is therefore often called the Tollens’ silver mirror test. The commercial manufacture of silver mirrors uses a similar process. Ketones cannot be oxidized to carboxylic acids and do not react with the Tollens’ reagent. EXAMPLE 13.6 LEARNING GOAL 5▶ Write equations representing the oxidation of carbonyl compounds. Writing Equations for the Reaction of an Aldehyde and of a Ketone with Tollens’ Reagent Write equations for the reaction of propanal and 2-pentanone with Tollens’ reagent. Solution O + CH3CH2C8H Ag(NH3)2 Propanal O + CH3CH2C8O Ag0 Propanoate anion O + CH3CH2CH2CCH3 Ag(NH3)2 No reaction 2-Pentanone Practice Problem 13.6 Write equations for the reaction of (a) ethanal and (b) propanone with Tollens’ reagent. ▶ For Further Practice: Questions 13.66 and 13.71. Cu(II) is an even milder oxidizing agent than silver ion. Another test that is used to distinguish between aldehydes and ketones is Benedict’s test. Here, a buffered aqueous solution of copper(II) hydroxide and sodium citrate reacts to oxidize aldehydes but does not generally react with 13-14 den02621_ch13_421-450.indd Sec13:434 11/24/09 6:25:26 PM Confirming Pages 13.4 Reactions Involving Aldehydes and Ketones 435 Figure 13.4 The silver precipitate produced by the Tollens’ reaction is deposited on glass. The progress of the reaction is visualized in panels (a) through (d). Silver mirrors are made in a similar process. (a) (b) (c) (d) ketones. Cu2⫹ is reduced to Cu⫹ in the process. Cu2⫹ is soluble and gives a blue solution, whereas the Cu⫹ precipitates as the red solid copper(I) oxide, Cu2O. All simple sugars (monosaccharides) are either aldehydes or ketones. Glucose is an aldehyde sugar that is commonly called blood sugar because it is the sugar found transported in the blood and used for energy by many cells. In uncontrolled diabetes, glucose may be found in the urine. One early method used to determine the amount of glucose in the urine was to observe the color change of the Benedict’s test. The amount of precipitate formed is directly proportional to the amount of glucose in the urine (Figure 13.5). The reaction of glucose with the Benedict’s reagent is represented in the following equation: O H 6 C * H8C8OH * HO8C8H * H8C8OH * H8C8OH * CH2OH 2Cu2 OH O O 6 C * H8C8OH * HO8C8H * H8C8OH * H8C8OH * CH2OH Cu2O Glucose We should also note that when the carbonyl group of a ketone is bonded to a OCH2OH group, the molecule will give a positive Benedict’s test. This occurs because such ketones are converted to aldehydes under basic conditions. In Chapter 16 we will see that this applies to the ketone sugars, as well. They are converted to aldehyde sugars and react with Benedict’s reagent. Figure 13.5 The amount of precipitate formed and thus the color change observed in the Benedict’s test are directly proportional to the amount of reducing sugar in the sample. 13-15 den02621_ch13_421-450.indd Sec14:435 11/24/09 6:25:26 PM Confirming Pages 436 Chapter 13 Aldehydes and Ketones A Human Perspective Alcohol Abuse and Antabuse According to a recent study carried out by the Centers for Disease Control and Prevention,1 more than 75,000 Americans die each year as a result of alcohol abuse. Of these, nearly 35,000 people died of cirrhosis of the liver, cancer, or other drinkingrelated diseases. The remaining nearly 41,000 died in alcoholrelated automobile accidents. Of those who died, 72% were men and 6% were under the age of twenty-one. In fact, a separate study has estimated that 1400 college-age students die each year of alcohol-related causes. These numbers are striking. Alcohol abuse is now the third leading cause of preventable death in the United States, outranked only by tobacco use and poor diet and exercise habits. As the study concluded, “These results emphasize the importance of adopting effective strategies to reduce excessive drinking, including increasing alcohol excise taxes and screening for alcohol misuse in clinical settings.” H3C CH2 H2C H3C N C H 3C CH2 N S S CH3 S Tetraethylthiuram disulfide (disulfiram) Antabuse C C H2 S One approach to treatment of alcohol abuse, the drug tetraethylthiuram disulfide or disulfiram, has been used since 1951. The activity of this drug, generally known by the trade name Antabuse, was discovered accidentally by a group of Danish researchers who were testing it for antiparasitic properties. They made the observation that those who had taken disulfiram became violently ill after consuming any alcoholic beverage. Further research revealed that this compound inhibits one of the liver enzymes in the pathway for the oxidation of alcohols. In Chapter 12 we saw that ethanol is oxidized to ethanal (acetaldehyde) in the liver. This reaction is catalyzed by the enzyme alcohol dehydrogenase. Acetaldehyde, which is more toxic than ethanol, is responsible for many of the symptoms of a hangover. The enzyme acetaldehyde dehydrogenase oxidizes acetaldehyde into ethanoic acid (acetic acid), which then is used in biochemical pathways that harvest energy for cellular work or that synthesize fats. Antabuse inhibits acetaldehyde dehydrogenase. This inhibition occurs within 1 to 2 hours (h) of taking the drug and continues up to 14 days. When a person who has taken Antabuse drinks an alcoholic beverage, the level of acetaldehyde quickly reaches levels that are five to ten times higher than would normally occur after a drink. Within just a few minutes, the symptoms of a severe hangover are experienced and may continue for several hours. Experts in drug and alcohol abuse have learned that drugs such as Antabuse are generally not effective on their own. However, when used in combination with support groups and/or psychotherapy to solve underlying behavioral or psychological problems, Antabuse is an effective deterrent to alcohol abuse. 1. Alcohol-Attributable Deaths and Years of Potential Life Lost—United States, 2001, Morbidity and Mortality Weekly Report, 53 (37): 866–870, September 24, 2004, also available at http://www.cdc.gov/mmwr/preview/mmwrhtml/ mm5337a2.htm. For Further Understanding ▶ Antabuse alone is not a cure for alcoholism. Consider some of the reasons why this is so. ▶ Write equations showing the oxidation of ethanal to ethanoic acid as a pathway with the product of the first reaction serving as the reactant for the second. Explain the physiological effects of Antabuse in terms of these chemical reactions. Reduction Reactions LEARNING GOAL 6 ▶ Write equations representing the reduction of carbonyl compounds. One way to recognize reduction, particularly in organic chemistry, is the gain of hydrogen. Oxidation and reduction are discussed in Section 12.6. Hydrogenation was first discussed in Section 11.5 for the hydrogenation of alkenes. Aldehydes and ketones are both readily reduced to the corresponding alcohol by a variety of reducing agents. Throughout the text the symbol [H] over the reaction arrow represents a reducing agent. The classical method of aldehyde or ketone reduction is hydrogenation. The carbonyl compound is reacted with hydrogen gas and a catalyst (nickel, platinum, or palladium metal) in a pressurized reaction vessel. Heating may also be necessary. The carbon-oxygen double bond (the carbonyl group) is reduced to a carbon-oxygen single bond. This is similar to the reduction of an alkene to an alkane (the reduction of a carbon-carbon double bond to a carbon-carbon single bond). The addition of hydrogen to a carbon-oxygen double bond is shown in the following general equation: O H + C * - 0 2 H R1 R Aldehyde or ketone Hydrogen Pt OH * R 8C8H * R2 1 Alcohol 13-16 den02621_ch13_421-450.indd Sec15:436 11/24/09 6:25:31 PM Confirming Pages 13.4 437 Reactions Involving Aldehydes and Ketones The hydrogenation (reduction) of a ketone produces a secondary alcohol, as seen in the following equation showing the reduction of the ketone, 3-octanone: O CH3CH2CCH2CH2CH2CH2CH3 Hydrogen 3-Octanone (A ketone) EXAMPLE 13.7 H2 Ni OH CH3CH2CCH2CH2CH2CH2CH3 H 3-Octanol (A secondary alcohol) Writing an Equation Representing the Hydrogenation of a Ketone Write an equation showing the hydrogenation of 3-pentanone. LEARNING GOAL 6▶ Solution The product of the reduction of a ketone is a secondary alcohol, in this case, 3-pentanol. O CH3CH2 CCH2CH3 H2 Pt 3-Pentanone Write equations representing the reduction of carbonyl compounds. OH CH3CH2 CCH2CH3 H 3-Pentanol Practice Problem 13.7 Write an equation for the hydrogenation of (a) propanone and (b) butanone. ▶ For Further Practice: Question 13.68. The hydrogenation of an aldehyde results in the production of a primary alcohol, as seen in the following equation showing the reduction of the aldehyde, butanal: O CH3CH2CH2CH Butanal (An aldehyde) EXAMPLE 13.8 H2 Pt Hydrogen OH CH3CH2CH2 C H H 1-Butanol (A primary alcohol) Writing an Equation Representing the Hydrogenation of an Aldehyde Write an equation showing the hydrogenation of 3-methylbutanal. LEARNING GOAL 6▶ Solution Recall that the reduction of an aldehyde results in the production of a primary alcohol, in this case, 3-methyl-1-butanol. O OH Pt CH3CHCH2 C H CH3CHCH2 C H H2 H CH3 CH3 3-Methylbutanal Write equations representing the reduction of carbonyl compounds. 3-Methyl-1-butanol Continued— 13-17 den02621_ch13_421-450.indd Sec16:437 11/24/09 6:25:32 PM Confirming Pages 438 Chapter 13 Aldehydes and Ketones A Medical Perspective That Golden Tan Without the Fear of Skin Cancer Self-tanning lotions have become very popular in recent years. This seems to be the result of our growing understanding of the link between exposure to the sun and skin cancer and to improvements in the quality of the tan produced by these selftanners. The active ingredient in most self-tanners is dihydroxyacetone (DHA). CH2OH | C+O | CH2OH Dihydroxyacetone DHA is a ketone, but because it also has hydroxyl groups, DHA is a sugar, more precisely, a keto sugar. A researcher by the name of Eva Wittgenstein discovered the tanning reaction while she was studying a human genetic disorder in children. These children were unable to store glycogen, a polysaccharide, or sugar polymer, which is our major energy storage molecule in the liver. She was trying to treat the disease by feeding large doses of DHA to the children. Sometimes, however, the children spit up some of the sickeningly sweet solution, which ended up on their clothes and skin. Dr. Wittgenstein noticed that the skin darkened at the site of these spills and decided to investigate the observation. DHA works because of a reaction between its carbonyl group and a free amino group (ONH3⫹) of several amino acids in the skin protein keratin. Amino acids are the building blocks of the biological polymers called proteins (Chapter 18); keratin is just one such protein. The DHA produces brown compounds called melanoids when it bonds to the keratins. These polymeric melanoids are chemically linked to cells of the stratum corneum, the dead, outermost layer of the skin. DHA does not penetrate this outer layer, so the chemical reaction that causes tanning only affects the stratum corneum. As this dead skin sloughs off, so does your tan! Over the years research has improved the quality of the tan that is produced. Early self-tanning lotions produced an orange tan; the tans from today’s lotions are much more natural. The DHA used today is in a much purer form and the other components of the lotion have been redesigned to promote greater penetration. Research has also taught us that the tanning reaction works best at acid pH; so newer formulations are buffered to pH 5. All of these changes have resulted in self-tanners that produce a longer lasting tan with a more natural, golden color. We have also learned that it is important to exfoliate before using a self-tanner. Anywhere that the dead skin layer is thicker, there will be more keratin. From our study of chemistry, we have learned that when we begin with more reactant, we often get more product. The greater the amount of product in this case, the darker the color! The resulting tan often looked splotchy or streaky. By gently removing some of the stratum corneum by a gentle exfoliation process, the surface of the skin, and hence the tanning reaction, becomes more uniform. People often ask whether the tan from a bottle can protect against burn, much as a natural tan does. The melanoids do absorb light of the same wavelengths absorbed by melanin (the substance formed by suntanning), so you might expect some protection against sunburn. However, the protection is minimal, rated at a sun protection factor (SPF) of only 2 or 3. Self-tanners offer an excellent substitute for a suntan, producing the same golden tan without the danger of overexposure to the sun’s harmful ultraviolet rays. For Further Understanding ▶ Explain in terms of a chemical reaction why using a selftanner daily results in an increasingly darker tan. ▶ The incidence of skin cancer in men and women has risen dramatically in recent years. Using the Internet and Chapter 20 in this book, develop a hypothesis to explain this observation. Practice Problem 13.8 Write equations for the hydrogenation of 3,4-dimethylhexanal and 2-chloropentanal. ▶ For Further Practice: Questions 13.69 and 13.70. 13-18 den02621_ch13_421-450.indd Sec17:438 11/24/09 6:25:33 PM Confirming Pages 13.4 A biological example of the reduction of a ketone occurs in the body, particularly during strenuous exercise when the lungs and circulatory system may not be able to provide enough oxygen to the muscles. Under these circumstances, the lactate fermentation begins. In this reaction, the enzyme lactate dehydrogenase reduces pyruvate, the product of glycolysis (a pathway for the breakdown of glucose) into lactate. The source of hydrogen ions for this reaction is nicotinamide adenine dinucleotide (NADH), which is oxidized in the course of the reaction. O O Lactate dehydrogenase CH3*C*C*O2 NADH NAD+ a. b. c. d. e. The role of the lactate fermentation in exercise is discussed in greater detail in Section 21.4. OH O CH3* C*C*O2 H Pyruvate Question reaction. 439 Reactions Involving Aldehydes and Ketones Lactate 13.11 Label each of the following as an oxidation or a reduction Ethanal to ethanol Benzoic acid to benzaldehyde Cyclohexanone to cyclohexanol 2-Propanol to propanone 2,3-Butanedione (found in butter) to 2,3-butanediol Question 13.12 Write an equation for each of the reactions in Question 13.11. Addition Reactions The principal reaction of the carbonyl group is the addition reaction across the polar carbon-oxygen double bond. This reaction is very similar to some that we have already studied, addition across the carbon-carbon double bond of alkenes. Such reactions require that a catalytic amount of acid be present in solution, as shown by the H⫹ over the arrow, for the reactions shown in the following examples. An example of an addition reaction is the reaction of aldehydes with alcohols in the presence of catalytic amounts of acid. In this reaction, the hydrogen of the alcohol adds to the carbonyl oxygen. The alkoxyl group of the alcohol (OOR) adds to the carbonyl carbon. The predicted product is a hemiacetal. LEARNING GOAL 7▶ Write equations for the preparation of hemiacetals, hemiketals, acetals, and ketals. Addition reactions of alkenes are described in detail in Section 11.5. OH * R8C8OR * H General structure of a hemiacetal However, this is not the product typically isolated from this reaction. Hemiacetals are quite reactive. In the presence of acid and excess alcohol, they undergo a substitution reaction in which the OOH group of the hemiacetal is exchanged for another OOR group from the alcohol. The product of this reaction is an acetal. Acetal formation is a reversible reaction, as the general equation shows: O + C - 0 R1 H H * OR2 Aldehyde Alcohol H OH * 1 R 8C8OR2 * H Hemiacetal H * OR2 H OR2 * R18C8OR2 * H H2O Acetal 13-19 den02621_ch13_421-450.indd Sec18:439 11/24/09 6:25:38 PM Confirming Pages 440 Chapter 13 Aldehydes and Ketones Consider the acid-catalyzed reaction between propanal and methanol: O + CH3CH28C8H CH3OH Propanal Methanol OH * CH3CH28C8OCH3 * H H OCH3 * CH3CH28C8OCH3 * H H CH3OH Hemiacetal H2O Propanal dimethyl acetal Addition reactions will also occur between a ketone and an alcohol. In this case the more reactive intermediate is called a hemiketal and the product is called a ketal. The general equation for ketal formation is shown here: O + C - 0 2 R1 R H * OR3 Ketone Alcohol H OH * R18C8OR3 * R2 H * OR3 H OR3 * R18C8OR3 * R2 Hemiketal H2O Ketal A simple scheme is helpful in recognizing these four types of compounds. Begin by drawing a carbon atom with four bonds and follow the flowchart as additional groups are added that will identify the molecules. * 8C8 * Add an alkyl group and an H atom. Add two alkyl groups. R * H8C8 * R * R8C8 * Add a hydroxyl group and an alkoxyl group. Add a hydroxyl group and an alkoxyl group. Add two alkoxyl groups. R * H8C8 OH * OR R * H8C8 OR * OR R * R8C8 OR * OR R * R8C8 OH * OR Hemiacetal Acetal Ketal Hemiketal A ketal is the final product in the reaction between propanone and ethanol, seen in the following equation: O CH3*C*CH3 CH3CH2OH Propanone Ethanol H OH CH3*C*OCH2CH3 CH3 Hemiketal CH3CH2OH H OCH2CH3 CH3*C*OCH2CH3 CH3 H2O Ketal 13-20 den02621_ch13_421-450.indd Sec19:440 11/24/09 6:25:39 PM Confirming Pages 13.4 Reactions Involving Aldehydes and Ketones 441 Question 13.13 Identify each of the following structures as a hemiacetal, acetal, hemiketal, or ketal. CH3 | a. H—C—OH | OCH3 CH3 | b. H3C—C—OCH3 | OCH3 CH3 | c. H—C—OCH3 | OCH3 CH3 | d. H3C—C—OH | OCH3 Question 13.14 Identify each of the following structures as a hemiacetal, acetal, hemiketal, or ketal. CH2CH3 | a. H—C—OH | OCH3 CH3 | b. CH3CH2 —C—OH | OCH3 CH3 | c. H—C—OCH2CH3 | OCH3 CH3 | d. H3C—C—OCH3 | OCH2CH3 Hemiacetals and hemiketals are readily formed in carbohydrates. Monosaccharides contain several hydroxyl groups and one carbonyl group. The linear form of a monosaccharide quickly undergoes an intramolecular reaction in solution to give a cyclic hemiacetal or hemiketal. Earlier we noted that hemiacetals and hemiketals formed in intermolecular reactions were unstable and continued to react, forming acetals and ketals. This is not the case with the intramolecular reactions involving five- or six-carbon sugars. In these reactions the cyclic or ring form of the molecule is more stable than the linear form. This reaction is shown for the sugar glucose (blood sugar) in Figure 13.6, and is discussed in detail in Section 16.2. When the hemiacetal or hemiketal of one monosaccharide reacts with a hydroxyl group of another monosaccharide, the product is an acetal or a ketal. A sugar molecule made up of two monosaccharides is called a disaccharide. The Figure 13.6 Hemiacetal formation in CH2OH 6 5 H H O C OH 6 2 HO C H H C OH C C OH HO 3 H 4 H 1 HO 1 H 4 5 CH2OH 6 D-Glucose (open-chain form) H H 4 C OH CH2OH H H OH H C C 3 H H OH 2 3 H OH 5C sugars, shown for the intramolecular reaction of D-glucose. O OH ␣-D-Glucose C 1 O CH2OH 2 6 5 OH H O OH H 4 HO 1 OH 3 H H H 2 OH -D-Glucose 13-21 den02621_ch13_421-450.indd Sec20:441 11/24/09 6:25:40 PM Confirming Pages 442 Chapter 13 Aldehydes and Ketones Glycosidic bond 6 CH2OH 5 H 4 1 H ⫹ OH 2 3 5 O H HO H CH2OH CH2OH O H OH 6 1 OH ␣-Glucose 2 H H HO H 5 4 CH2OH 6 HO 3 4 H OH CH2OH O H 1 H 3 H 2 O HO H OH H -Fructose 1 O 2 H HO 3 OH 5 ⫹ H2O CH2OH 6 4 OH H Sucrose Figure 13.7 Acetal formation, demonstrated in the formation of the disaccharide sucrose, common table sugar. The reaction between the hydroxyl groups of the monosaccharides glucose and fructose produces the acetal sucrose. The bond between the two sugars is a glycosidic bond. COOOC bond between the two monosaccharides is called a glycosidic bond (Figure 13.7). LEARNING GOAL 8▶ Draw the keto and enol forms of aldehydes and ketones. Keto-Enol Tautomers Many aldehydes and ketones may exist in an equilibrium mixture of two constitutional or structural isomers called tautomers. Tautomers differ from one another in the placement of a hydrogen atom and a double bond. One tautomer is the keto form (on the left in the following equation). The keto form has the structure typical of an aldehyde or ketone. The other form is called the enol form (on the right in the following equation). The enol form has a structure containing a carbon-carbon double bond (en) and a hydroxyl group, the functional group characteristic of alcohols (ol). H O OH R1 * + 0 1 3 (R1, R2, and R3 R 8C8C8R C9C 0 * H or alkyl group) R2 R3 R2 Keto form Enol form Because the keto form of most simple aldehydes and ketones is more stable, they exist mainly in that form. EXAMPLE 13.9 LEARNING GOAL 8▶ Draw the keto and enol forms of aldehydes and ketones. Writing an Equation Representing the Equilibrium Between the Keto and Enol Forms of a Simple Aldehyde Draw the keto form of ethanal and write an equation representing the equilibrium between the keto and enol forms of this molecule. Solution H O H*C*C*H H Ethanal Keto form More stable O*H H*C+C*H H Enol form Less stable Practice Problem 13.9 Draw the keto and enol forms of (a) propanal and (b) 3-pentanone. ▶ For Further Practice: Questions 13.89 and 13.90. 13-22 den02621_ch13_421-450.indd Sec21:442 11/24/09 6:25:41 PM Confirming Pages 13.4 443 Reactions Involving Aldehydes and Ketones Phosphoenolpyruvate is a biologically important enol. In fact, it is the highest energy phosphorylated compound in living systems. O * O C9O + * O8P8O C + * CH2 O Phosphoenolpyruvate Phosphoenolpyruvate is produced in the next-to-last step in the metabolic pathway called glycolysis, which is the first stage of carbohydrate breakdown. In the final reaction of glycolysis, the phosphoryl group from phosphoenolpyruvate is transferred to adenosine diphosphate (ADP). The reaction produces ATP, the major energy currency of the cell. The glycolysis pathway is discussed in detail in Chapter 21. Aldol Condensation The aldol condensation is a reaction in which aldehydes or ketones react to form larger molecules. A new carbon-carbon bond is formed in the process: O R1*CH2*C*R R O R2*CH2*C*R OH2or enzyme H, alkyl, or aryl group Aldehyde or Ketone Aldehyde or Ketone LEARNING GOAL 9▶ Write equations showing the aldol condensation. OH O R1*CH2*C*CH*C*R R R2 Aldol This is actually a very complex reaction that occurs in multiple steps. Here we focus on the end results of the reaction, using the example of the reaction between two molecules of ethanal. As shown in the equation below, the ␣-carbon (carbon-2) of one aldehyde forms a bond with the carbonyl carbon of a second aldehyde (shown in blue). A bond also forms between a hydrogen atom on that same ␣-carbon and the carbonyl oxygen (shown in red). H O H* C*C*H H Ethanal H O H*C*C*H H OH H OH O H*C— C— CH2*C*H H H 3-Hydroxybutanal (b-hydroxybutyraldehyde) Ethanal The result is similar when two ketones react: O CH3*C*CH3 H O H*C*C*CH3 H Propanone Propanone OH OH O CH3*C*CH2*C*CH3 CH3 4-Hydroxy-4-methyl-2-pentanone In the laboratory, the aldol condensation is catalyzed by dilute base. But the same reaction occurs in our cells, where it is catalyzed by an enzyme. This reaction is one of many in a pathway that makes the sugar glucose from smaller molecules. This pathway is called gluconeogenesis (gluco- [sugar], neo- [new], genesis [beginnings]), 13-23 den02621_ch13_421-450.indd Sec22:443 11/24/09 6:25:41 PM Confirming Pages 444 Chapter 13 Aldehydes and Ketones Gluconeogenesis is described in Chapter 21. which simply means origin of new sugar. This pathway is critical during starvation or following strenuous exercise. Under those conditions, blood glucose concentrations may fall dangerously low. Because the brain can use only glucose as an energy source, it is essential that the body be able to produce it quickly. One of the steps in the pathway is an aldol condensation between the ketone dihydroxyacetone phosphate and the aldehyde glyceraldehyde-3-phosphate. O 0 3 C * H8C8OH * CH2OPO32 CH2OPO32 * C9O * HO8C8H * H8C8OH * H8C8OH * CH2OPO32 H CH2OPO32 * C9O * H—COH * H Dihydroxyacetone phosphate is a phosphorylated form of dihydroxyacetone (DHA), the active ingredient in self-tanning lotions. See A Medical Perspective: That Golden Tan Without the Fear of Skin Cancer on page 438. Dihydroxyacetone phosphate Aldolase Glyceraldehyde3-phosphate Fructose1,6-bisphosphate The speed and specificity of this reaction are ensured by the enzyme aldolase. The product is the sugar fructose-1,6-bisphosphate, which is converted by another enzyme into glucose-1,6-bisphosphate. Removal of the two phosphoryl groups results in a new molecule of glucose for use by the body as an energy source. Gluconeogenesis occurs under starvation conditions to provide a supply of blood glucose to nourish the brain. However, when glucose is plentiful, it is broken down to provide ATP energy for the cell. The pathway for glucose degradation is called glycolysis. In glycolysis, the reaction just shown is reversed. In general, aldol condensation reactions are reversible. These reactions are called reverse aldols. ATP, the universal energy currency, is discussed in Section 21.1. Question 13.15 Write an equation for the aldol condensation of two molecules of propanal. Question 13.16 Write an equation for the aldol condensation of two molecules of butanal. SUMMARY OF REACTIONS Aldehydes and Ketones Reduction of Aldehydes and Ketones Oxidation of an Aldehyde O + R8C8H [O] Aldehyde O H + C * - 0 2 H R1 R O + R8C8OH Carboxylic acid Aldehyde or Ketone Pt Hydrogen OH * R 8C8H * R2 1 Alcohol Addition Reactions Addition of an alcohol to a ketone—ketal formation: O + C - 0 2 R1 R H * OR3 Ketone Alcohol H OH * 1 R 8C8OR3 * R2 Hemiketal H * OR3 H OR3 * R18C8OR3 * R2 H2O Ketal 13-24 den02621_ch13_421-450.indd Sec23:444 11/24/09 6:25:42 PM Confirming Pages 445 Summary Addition of an alcohol to an aldehyde—acetal formation: O + C - 0 R1 H H * OR2 Aldehyde Alcohol H OH * R18C8OR2 * H H * OR2 Hemiacetal Aldol Condensation H O R1*C*C*R3 R2 O R1*CH2*C*R Keto form Enol form O R2*CH2*C*R Aldehyde or ketone R H, alkyl, or aryl group SUMMARY 13.1 Structure and Physical Properties The carbonyl group (1 . C9O) is characteristic of the aldehydes and ketones. The carbonyl group and the two groups attached to it are coplanar. In ketones the carbonyl carbon is attached to two carbon-containing groups, whereas in aldehydes the carbonyl carbon is attached to at least one hydrogen; the second group attached to the carbonyl carbon in aldehydes may be another hydrogen or a carbon atom. Owing to the polar carbonyl group, aldehydes and ketones are polar compounds. Their boiling points are higher than those of comparable hydrocarbons but lower than those of comparable alcohols. Small aldehydes and ketones are reasonably soluble in water because of the hydrogen bonding between the carbonyl group and water molecules. Larger carbonyl-containing compounds are less polar and thus are more soluble in nonpolar organic solvents. 13.2 I.U.P.A.C. Nomenclature and Common Names In the I.U.P.A.C. Nomenclature System, aldehydes are named by determining the parent compound and replacing the final -e of the parent alkane with -al. The chain is numbered beginning with the carbonyl carbon as carbon-1. Ketones are named by determining the parent compound and replacing the -e ending of the parent alkane with the -one suffix of the ketone family. The longest carbon chain is numbered to give the carbonyl carbon the lowest possible number. In the common system of nomenclature, substituted aldehydes are named as derivatives of the parent compound. Greek letters indicate the position of substituents. Common names of ketones are derived by naming the alkyl groups bonded to the carbonyl carbon. These names are followed by the word ketone. H2O Acetal Keto-enol Tautomerization OH R1 # ! C+C ! # 3 R2 R H OR2 * R18C8OR2 * H Aldehyde or ketone OH2or enzyme OH O R1*CH2*C*CH*C*R R R2 Aldol 13.3 Important Aldehydes and Ketones Many members of the aldehyde and ketone families are important as food and fragrance chemicals, medicinals, and agricultural chemicals. Methanal (formaldehyde) is used to preserve tissue. Ethanal causes the symptoms of a hangover and is oxidized to produce acetic acid commercially. Propanone is a useful and versatile solvent for organic compounds. 13.4 Reactions Involving Aldehydes and Ketones In the laboratory, aldehydes and ketones are prepared by the oxidation of alcohols. Oxidation of a primary alcohol produces an aldehyde; oxidation of a secondary alcohol yields a ketone. Tertiary alcohols do not react under these conditions. Aldehydes and ketones can be distinguished from one another on the basis of their ability to undergo oxidation reactions. The Tollens’ test and Benedict’s test are the most common such tests. Aldehydes are easily oxidized to carboxylic acids. Ketones do not undergo further oxidation reactions. Aldehydes and ketones are readily reduced to alcohols by hydrogenation. The most common reaction of the carbonyl group is addition across the highly polar carbon-oxygen double bond. The addition of an alcohol to an aldehyde produces a hemiacetal. The hemiacetal reacts with a second alcohol molecule to form an acetal. The reaction of a ketone with an alcohol produces a hemiketal. A hemiketal reacts with a second alcohol molecule to form a ketal. Hemiacetals and hemiketals are readily formed in carbohydrates. Aldol condensation is a reaction in which aldehydes and ketones form larger molecules. Aldehydes and ketones may exist as an equilibrium mixture of keto and enol tautomers. 13-25 den02621_ch13_421-450.indd Sec24:445 11/24/09 6:25:43 PM Confirming Pages 446 Chapter 13 Aldehydes and Ketones 13.31 acetal (13.4) addition reaction (13.4) aldehyde (13.1) aldol condensation (13.4) Benedict’s test (13.4) carbonyl group (Intro) hemiacetal (13.4) hemiketal (13.4) hydrogenation (13.4) ketal (13.4) ketone (13.1) oxidation (13.4) Tollens’ test (13.4) 13.32 13.33 QUESTIONS AND PROBLEMS * Structure and Physical Properties Foundations Explain the relationship between carbon chain length and water solubility of aldehydes or ketones. Explain the dipole-dipole interactions that occur between molecules containing carbonyl groups. Applications 13.21 13.22 13.23 13.24 13.35 13.36 Foundations 13.26 13.27 13.28 Briefly describe the rules of the I.U.P.A.C. Nomenclature System for naming aldehydes. Briefly describe the rules of the I.U.P.A.C. Nomenclature System for naming ketones. Briefly describe how to determine the common name of an aldehyde. Briefly describe how to determine the common name of a ketone. 13.37 13.30 Draw each of the following using complete formulas and line formulas: a. Ethanal b. 3,4-Dimethylpentanal c. 2-Ethylheptanal d. 5,7-Dichloroheptanal Draw each of the following using condensed formulas and line formulas: a. 2-Nonanone b. 4-Methyl-2-heptanone c. 4,6-Diethyl-3-octanone d. 5-Bromo-4-octanone CH3 O + c. CH3CHCH2CH * Br CH3 O + * d. CH3CCH2CCH2CH2CH3 * Cl The molecule shown below has a lovely aroma of lily-of-thevalley. Discovered in 1908, it has been used in hundreds of perfumes. What is the I.U.P.A.C. name of this molecule? O OH + * CH3CCH2CH2CH2CHCH2CAH * * CH3 CH3 Applications 13.29 HO OH Name each of the following using the I.U.P.A.C. Nomenclature System: O Br O | a. CH3CH2CH2CH b. CH3CCH2CH2CH | Nomenclature 13.25 Cl Name each of the following using the I.U.P.A.C. Nomenclature System: O NO2 a. b. + O + H8C8 - 13.20 Simple ketones (for example, acetone) are often used as industrial solvents for many organically based products such as adhesives and paints. They are often considered “universal solvents,” because they dissolve so many diverse materials. Why are these chemicals such good solvents? Explain briefly why simple (containing fewer than five carbon atoms) aldehydes and ketones exhibit appreciable solubility in water. Draw intermolecular hydrogen bonding between ethanal and water. Draw the polar interactions that occur between acetone molecules. Why do alcohols have higher boiling points than aldehydes or ketones of comparable molecular mass? Why do hydrocarbons have lower boiling points than aldehydes or ketones of comparable molecular mass? - 13.19 CH2CH2CH2CH3 Name each of the following using the I.U.P.A.C. Nomenclature System: b. O Cl O * + a. ClACACACH3 * Cl - 13.18 13.34 + 13.17 Draw each of the following using condensed formulas and line formulas: a. Ethyl isopropyl ketone b. Ethyl propyl ketone c. Dibutyl ketone d. Heptyl hexyl ketone Draw each of the following using condensed formulas and line formulas: a. -Methylbutyraldehyde b. ␣-Hydroxypropionaldehyde c. ␣,-Dimethylvaleraldehyde d. ␥-Chlorovaleraldehyde Use the I.U.P.A.C. Nomenclature System to name each of the following compounds: O O + + b. HCCHCH2CH3 a. CH3CCH2CH3 0 KEY TERMS 13.38 Give the I.U.P.A.C. name for each of the following compounds: O CH2CH3 * + a. CH3CCH2CCH2CH3 * CH2CH3 O + b. CH3CCH2CHCH2CH3 * Cl 13-26 den02621_ch13_421-450.indd Sec25:446 11/24/09 6:25:43 PM Confirming Pages 447 Questions and Problems 13.39 Give the I.U.P.A.C. name for each of the following compounds: O + a. CH3CHCH2CHCCH2CH3 * * CH3 CH3 b. CH3 13.49 13.50 O 3 0 CH3 - 13.51 Give the I.U.P.A.C. name for each of the following compounds: O CH3 + * a. CH3CH2CHCH2CH b. O Cl 8Cl - 13.40 Reactions Involving Aldehydes and Ketones Foundations 13.52 13.53 13.54 13.55 + 13.56 13.41 13.42 13.43 13.44 Give the common name for each of the following compounds: O O + + b. CH3CH2CCH3 a. CH3CCH3 O O + + c. CH3CH d. CH3CH2CH O + e. CH3CHCCH3 * CH3 Give the common name for each of the following compounds: O + a. CH3CH2CCH2CH3 O + b. CH3CH2CH2CHCH * CH3 O + c. CH3CCH2CH2CH3 O + d. CH3CH2CH2CH2CH2CH Draw the structure of each of the following compounds: a. 3-Hydroxybutanal b. 2-Methylpentanal c. 4-Bromohexanal d. 3-Iodopentanal e. 2-Hydroxy-3-methylheptanal Draw the structure of each of the following compounds: a. Dimethyl ketone b. Methyl propyl ketone c. Ethyl butyl ketone d. Diisopropyl ketone Important Aldehydes and Ketones 13.45 13.46 13.47 13.48 Why is acetone a good solvent for many organic compounds? List several uses for formaldehyde. Ethanal is produced by the oxidation of ethanol. Where does this reaction occur in the body? List several aldehydes and ketones that are used as food or fragrance chemicals. 13.57 13.58 13.59 13.60 Explain what is meant by oxidation in organic molecules and provide an example of an oxidation reaction involving an aldehyde. Explain what is meant by reduction in organic reactions and provide an example of a reduction reaction involving an aldehyde or ketone. Define the term addition reaction. Provide an example of an addition reaction involving an aldehyde or ketone. Define the term aldol condensation. Provide an example of an aldol condensation using an aldehyde or ketone. Write a general equation representing the oxidation of an aldehyde. What is the product of this reaction? Write a general equation representing the reduction of an aldehyde. What is the product of this reaction? Write a general equation representing the oxidation of a ketone. What is the product of this reaction? Write a general equation representing the addition of one alcohol molecule to an aldehyde. Write a general equation representing the addition of two alcohol molecules to an aldehyde. Write a general equation representing the addition of one alcohol molecule to a ketone. Write a general equation representing the addition of two alcohol molecules to a ketone. Write a general equation for an aldol condensation. Applications 13.61 13.62 13.63 13.64 13.65 13.66 Draw the structure of each of the following alcohols. Then draw and name the product that you would expect to produce by the oxidation of each. a. 4-Methyl-2-heptanol b. 3,4-Dimethyl-1-pentanol c. 4-Ethyl-2-heptanol d. 5,7-Dichloro-3-heptanol Draw the structure of each of the following alcohols. Then draw and name the product that you would expect to produce by the oxidation of each. a. 1-Nonanol b. 4-Methyl-1-heptanol c. 4,6-Diethyl-3-methyl-3-octanol d. 5-Bromo-4-octanol Draw the generalized equation for the oxidation of a primary alcohol. Draw the generalized equation for the oxidation of a secondary alcohol. Draw the structures of the reactants and products for each of the following reactions. Label each as an oxidation or a reduction reaction: a. Ethanal to ethanol c. 2-Propanol to propanone b. Cyclohexanone to cyclohexanol An unknown has been determined to be one of the following three compounds: O O + + CH3CH2CH2CH2CH CH3CH2CCH2CH3 3-Pentanone Pentanal CH3CH2CH2CH2CH3 Pentane The unknown is fairly soluble in water and produces a silver mirror when treated with the silver ammonia complex. A red precipitate appears when it is treated with the Benedict’s reagent. Which of the compounds is the correct structure for the unknown? Explain your reasoning. 13-27 den02621_ch13_421-450.indd Sec26:447 11/24/09 6:25:45 PM Confirming Pages 448 13.68 13.69 13.70 13.71 13.72 13.73 13.74 13.75 13.76 13.77 13.78 Write a balanced equation for the hydrogenation of each of the following aldehydes: a. -Methylvaleraldehyde b. ␣-Hydroxypropionaldehyde c. ␣,-Dimethylvaleraldehyde d. ␥-Chlorovaleraldehyde Write a balanced equation for the hydrogenation of each of the following ketones: a. Ethyl isopropyl ketone c. Dibutyl ketone b. Ethyl propyl ketone d. Heptyl hexyl ketone Write a balanced equation for the hydrogenation of each of the following aldehydes: a. Butanal b. 3-Methylpentanal c. 2-Methylpropanal Write a balanced equation for the hydrogenation of each of the following aldehydes: a. -Methylbutyraldehyde b. ␥-Bromovaleraldehyde c. Propionaldehyde Which of the following compounds would be expected to give a positive Tollens’ test? a. 3-Pentanone d. Cyclopentanol b. Cyclohexanone e. 2,2-Dimethyl-1-pentanol c. 3-Methylbutanal f. Acetaldehyde Write an equation representing the reaction of glucose with the Benedict’s reagent. How was this test used in medicine? What is the general name for the product that is formed when an aldehyde reacts with one molecule of alcohol? Write an equation for the addition of one ethanol molecule to each of the following aldehydes: O O + + b. CH3CH a. CH3 CH2CH What is the general name of the product that is formed when a ketone reacts with one molecule of alcohol? Write an equation for the addition of one ethanol molecule to each of the following ketones: O O + + b. CH3CCH2CH2CH3 a. CH3 CCH3 What is the general name for the product that is formed when an aldehyde reacts with two molecules of alcohol? Write an equation for the addition of two methanol molecules to each of the following aldehydes: O O + + b. CH3CH a. CH3 CH2CH What is the general name of the product that is formed when a ketone reacts with two molecules of alcohol? Write an equation for the addition of two methanol molecules to each of the following ketones: O O + + b. CH3CCH2CH2CH3 a. CH3 CCH3 An aldehyde can be oxidized to produce a carboxylic acid. Draw the carboxylic acid that would be produced by the oxidation of each of the following aldehydes: a. Pentanal c. Heptanal b. Hexanal d. Octanal An aldehyde can be oxidized to produce a carboxylic acid. Draw the carboxylic acid that would be produced by the oxidation of each of the following aldehydes: a. 3-Methylpentanal b. 2,3-Dichlorobutanal c. 2,4-Diethylhexanal d. 2-Methylpropanal 13.79 13.80 13.81 13.82 13.83 13.84 13.85 13.86 13.87 13.88 13.89 An alcohol can be oxidized to produce an aldehyde or a ketone. What aldehyde or ketone is produced by the oxidation of each of the following alcohols? a. Methanol b. 1-Propanol An alcohol can be oxidized to produce an aldehyde or a ketone. What aldehyde or ketone is produced by the oxidation of each of the following alcohols? a. 3-Pentanol b. 2-Methyl-2-butanol Indicate whether each of the following statements is true or false. a. Aldehydes and ketones can be oxidized to produce carboxylic acids. b. Oxidation of a primary alcohol produces an aldehyde. c. Oxidation of a tertiary alcohol produces a ketone. d. Alcohols can be produced by the oxidation of an aldehyde or ketone. Indicate whether each of the following statements is true or false. a. Ketones, but not aldehydes, react in the Tollens’ silver mirror test. b. Addition of one alcohol molecule to an aldehyde results in formation of a hemiacetal. c. The cyclic forms of monosaccharides are intramolecular hemiacetals or intramolecular hemiketals. d. Disaccharides (sugars composed of two covalently joined monosaccharides) are acetals, ketals, or both. Write an equation for the aldol condensation of two molecules of ethanal. Write an equation for the aldol condensation of two molecules of hexanal. Write an equation for the aldol condensation of two molecules of acetone. Write an equation for the aldol condensation of two molecules of 2-pentanone. Draw the keto and enol forms of propanone. Draw the keto and enol forms of 2-butanone. Draw the hemiacetal or hemiketal that results from the reaction of each of the following aldehydes or ketones with ethanol: O + a. CH3CH2CH2CCH3 O + 13.67 Chapter 13 Aldehydes and Ketones b. CH3C8 c. 9O 13.90 Identify each of the following compounds as a hemiacetal, hemiketal, acetal, or ketal: a. d. OH O O ! *OCH3 CH3 b. OH ! # OCH2CH3 OH c. CH3CCH3 OCH2CH3 # CH3 OCH3 e. CH3CCH3 OCH2CH3 OCH3 f. CH3CH+CHCCH3 OH 13-28 den02621_ch13_421-450.indd Sec27:448 11/24/09 6:25:46 PM Confirming Pages 449 Critical Thinking Problems 13.91 Complete the following synthesis by supplying the missing reactant(s), reagent(s), or product(s) indicated by the question marks: O + CH3CCH3 ?(1) ?(2) 13.92 CH2OH OCH2CH3 * CH3CCH3 * OCH2CH3 O O CH3 O a. CH3CHCH2CCH3 O O b. HCCH2CH2CH O O d. HCCH2CCH3 O *CH2CH CH3 O e. CH3CCH2CH2CH CH3 f. O+ +O O HO H H OH H H OH H H CH2OH H2SO4 CH3CHCH3 ?(3) Heat * OH Which alcohol would you oxidize to produce each of the following compounds? c. 5. Lactose is the major sugar found in mammalian milk. It is a dissacharide composed of the monosaccharides glucose and galactose: H OH H H H OH OH Is lactose a hemiacetal, hemiketal, acetal, or ketal? Explain your choice or choices. 6. The following are the keto and enol tautomers of phenol: OAH * O + -H 0H Enol form Keto form of phenol of phenol We have seen that most simple aldehydes and ketones exist mainly in the keto form because it is more stable. Phenol is an exception, existing primarily in the enol form. Propose a hypothesis to explain this. CRITICAL THINKING PROBLEMS 1. Review the material on the chemistry of vision found on the Web at www.mhhe.com/denniston and, with respect to the isomers of retinal, discuss the changes in structure that occur as the nerve impulses (that result in vision) are produced. Provide complete structural formulas of the retinal isomers that you discuss. 2. Classify the structure of -d-fructose as a hemiacetal, hemiketal, acetal, or ketal. Explain your choice. CH2OH O H H HO OH CH2OH OH H 3. Design a synthesis for each of the following compounds, using any inorganic reagent of your choice and any hydrocarbon or alkyl halide of your choice: a. Octanal b. Cyclohexanone c. 2-Phenylethanoic acid 4. When alkenes react with ozone, O3, the double bond is cleaved, and an aldehyde and/or a ketone is produced. The reaction, called ozonolysis, is shown in general as: ! ! # # C+O 1 O+C C+C 1 O3 ! ! # # Predict the ozonolysis products that are formed when each of the following alkenes is reacted with ozone: a. 1-Butene b. 2-Hexene c. cis-3,6-Dimethyl-3-heptene 13-29 den02621_ch13_421-450.indd Sec28:449 11/24/09 6:25:47 PM den02621_ch13_421-450.indd Sec28:450 11/24/09 6:25:48 PM