《有机化学》课程教学资源（教材文献，英文版）CHAPTER 17 ALDEHYDES AND KETONES：

CHAPTER 17 ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP A ldehydes and ketones contain an acyl group RC- bonded either to hydrogen or to another carbon HCH RCH RCR′ Although the present chapter includes the usual collection of topics designed to acquaint us with a particular class of compounds, its central theme is a fundamental reaction typ cleophilic addition to carbonyl groups. The principles of nucleophilic addition to alde des and ketones developed here will be seen to have broad applicability in later chap- ters when transformations of various derivatives of carboxylic acids are discussed 17.1 NOMENCLATURE The longest continuous chain that contains the -CH group provides the base name for aldehydes. The -e ending of the corresponding alkane name is replaced by -al, and sub- stituents are specified in the usual way. It is not necessary to specify the location of the -CH group in the name, since the chain must be numbered by starting with this group as C-1. The suffix -dial is added to the appropriate alkane name when the com pound contains two aldehyde functions. The -e ending of an alkane name is dropped before a suffix beginning with a vowel (-aln) and retained be- fore one beginning with a consonant (-dial Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

654 CHAPTER 17 ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP Aldehydes and ketones contain an acyl group bonded either to hydrogen or to another carbon. Although the present chapter includes the usual collection of topics designed to acquaint us with a particular class of compounds, its central theme is a fundamental reaction type, nucleophilic addition to carbonyl groups. The principles of nucleophilic addition to alde￾hydes and ketones developed here will be seen to have broad applicability in later chap￾ters when transformations of various derivatives of carboxylic acids are discussed. 17.1 NOMENCLATURE The longest continuous chain that contains the group provides the base name for aldehydes. The -e ending of the corresponding alkane name is replaced by -al, and sub￾stituents are specified in the usual way. It is not necessary to specify the location of the group in the name, since the chain must be numbered by starting with this group as C-1. The suffix -dial is added to the appropriate alkane name when the com￾pound contains two aldehyde functions.* ±CH O X ±CH O X RCH O X Aldehyde HCH O X Formaldehyde RCR O X Ketone RC± O X * The -e ending of an alkane name is dropped before a suffix beginning with a vowel (-al) and retained be￾fore one beginning with a consonant (-dial). Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

CHaCCHCHCH CH=CHCHCHoCHCH HCCHCH 4, 4-Dimethylpentanal 5-Hexenal 2-Phenylpropanedial When a formyl group(-CH-O)is attached to a ring, the ring name is followe by the suffix -carbaldehyde CH CH yclopentanecarbaldehyde nthalenecarbaldehyde Certain common names of familiar aldehydes are acceptable as IUPAC few examples include O HCH Benzaldehyde (ethanal) (benzenecarbaldehyde) PROBLEM 17.1 The common names and structural formulas of a few aldehydes follow Provide an iuPac name (a)(CH3)2CHCH (C)C6HsCH=CHCH (isobutyraldehyde) (cinnamaldehyde) (b)HCCH2 CH, CH2 CH d)Ho一 (glutaraldehyde) CHO SAMPLE SoLUTION (a) Don ' t be fooled by the fact that the common name is isobutyraldehyde the longest continuous chain has three carbons, and so the base name is propanal. there is a methyl group at C-2; thus the compound is 2-methyl- CH3 CHCH (isobutyraldehy Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

When a formyl group (±CHœO) is attached to a ring, the ring name is followed by the suffix -carbaldehyde. Certain common names of familiar aldehydes are acceptable as IUPAC names. A few examples include PROBLEM 17.1 The common names and structural formulas of a few aldehydes follow. Provide an IUPAC name. (a) (c) (b) (d) SAMPLE SOLUTION (a) Don’t be fooled by the fact that the common name is isobutyraldehyde. The longest continuous chain has three carbons, and so the base name is propanal. There is a methyl group at C-2; thus the compound is 2-methyl￾propanal. 2-Methylpropanal (isobutyraldehyde) CH3CHCH O CH3 3 2 1 HO CH CH3O O (vanillin) HCCH2CH2CH2CH O O (glutaraldehyde) C6H5CH CHCH O (cinnamaldehyde) (CH3)2CHCH O (isobutyraldehyde) HCH O Formaldehyde (methanal) CH3CH O Acetaldehyde (ethanal) CH O Benzaldehyde (benzenecarbaldehyde) CH O Cyclopentanecarbaldehyde CH O 2-Naphthalenecarbaldehyde CH3CCH2CH2CH CH3 O CH3 4,4-Dimethylpentanal CHCH2CH2CH2CH O CH2 5-Hexenal HCCHCH O O 2-Phenylpropanedial 17.1 Nomenclature 655 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group with ketones, the -e ending of an alkane is replaced by -one in the longest con- tinuous chain containing the carbonyl group The chain is numbered in the direction that provides the lower number for this group CH3CH,CCH-CH,CH3 CH3CHCH_ CCH3 CH3 3-Hexanone 4-Methyl-2-pentanone 4-Methylcyclohexanone Although substitutive names of the type just described are preferred, the IUPAC rules also permit ketones to be named by functional class nomenclature. The groups attached to the carbonyl group are named as separate words followed by the word ketone. The groups are listed alphabetically O CHa,CCH,CH,CH3 CH,CCH, CH3 CH=CHCCH=CH2 Ethyl propy Benzyl ethyl ketone Divinyl ketone PROBLEM 17.2 Convert each of the following functional class IUPAC names to a substitutive name (b)Ethyl isopropyl ketone (cMethyl 2, 2-dimethylpropyl ketone d) Allyl methyl ketone SAMPLE SOLUTION (a)First write the structure corresponding to the name Dibenzyl ketone has two benzyl groups attached to a carbonyl CH2CCH benzyl ketone The longest continuous chain contains three carbons, and C-2 is the carbon of the carbonyl group. The substitutive IUPAC name for this ketone is 1, 3-diphenyl-2- A few of the common names acceptable for ketones in the IUPAC system are CH3CCH3 CCH Acetophenone Benzophenone (The suffix -phenone indicates that the acyl group is attached to a benzene ring. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

With ketones, the -e ending of an alkane is replaced by -one in the longest con￾tinuous chain containing the carbonyl group. The chain is numbered in the direction that provides the lower number for this group. Although substitutive names of the type just described are preferred, the IUPAC rules also permit ketones to be named by functional class nomenclature. The groups attached to the carbonyl group are named as separate words followed by the word “ketone.” The groups are listed alphabetically. PROBLEM 17.2 Convert each of the following functional class IUPAC names to a substitutive name. (a) Dibenzyl ketone (b) Ethyl isopropyl ketone (c) Methyl 2,2-dimethylpropyl ketone (d) Allyl methyl ketone SAMPLE SOLUTION (a) First write the structure corresponding to the name. Dibenzyl ketone has two benzyl groups attached to a carbonyl. The longest continuous chain contains three carbons, and C-2 is the carbon of the carbonyl group. The substitutive IUPAC name for this ketone is 1,3-diphenyl-2- propanone. A few of the common names acceptable for ketones in the IUPAC system are (The suffix -phenone indicates that the acyl group is attached to a benzene ring.) CH3CCH3 O Acetone CCH3 O Acetophenone C O Benzophenone CH2CCH2 O 1 23 Dibenzyl ketone CH3CH2CCH2CH2CH3 O Ethyl propyl ketone CH2CCH2CH3 O Benzyl ethyl ketone CH2 O CHCCH CH2 Divinyl ketone CH3CH2CCH2CH2CH3 O 3-Hexanone CH3CHCH2CCH3 O CH3 4-Methyl-2-pentanone CH3 O 4-Methylcyclohexanone 656 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

17.2 Structure and Bonding: The Carbonyl Group 17.2 STRUCTURE AND BONDING: THE CARBONYL GROUP Two notable aspects of the carbonyl group are its geometry and its polarity. The car bonyl group and the atoms directly attached to it lie in the same plane. Formaldehyde, for example, is planar. The bond angles involving the carbonyl group of aldehydes and ketones are close to 120 121.7°121.7° 1239°1186° 121.4° making erify their gemalds by tone. Make sure you execute the H H HC H 116.5° 1175° Formaldehyde Acetaldehyde Aceton At 122 pm, the carbon-oxygen double bond distance in aldehydes and ketones is sig- nificantly shorter than the typical carbon-oxygen single bond distance of 141 pm in alco- ols and ethers The carbonyl group makes aldehydes and ketones rather polar, with molecular dipole moments that are substantially larger than those of comparable compounds that contain carbon-carbon double bonds CH,CH=CH CH3CH,CH=O 1-Butene Propanal Dipole moment: 0.3D Dipole moment: 2.5D Bonding in formaldehyde can be described according to an sp 2 hybridization model on Learning By Mo analogous to that of ethylene, as shown in Figure 17.1 Figure 17. 2 compares the electrostatic potential surfaces of ethylene and formalde hyde and vividly demonstrates how oxygen affects the electron distribution in formalde- hyde. The electron density in both the o and T components of the carbon-oxygen dou ble bond is displaced toward oxygen. The carbonyl group is polarized so that carbon is partially positive and oxygen is partially negative FIGURE 17.1 Similari- ties between the orbital idization bonding in (a)ethylene and In resonance terms, electron delocalization in the carbonyl group is represented by (b) formaldehyde. Both mol contributions from two principal resonance structures z-hybridized in both I carbons is replaced by an sp hybridized xvaen in red). Oxygen has two hybridized orbital. Like the carbon-carbon double bond formaldehyde is composed of a two-electron nent and a two-electron TT (b) Formaldehyde Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

17.2 STRUCTURE AND BONDING: THE CARBONYL GROUP Two notable aspects of the carbonyl group are its geometry and its polarity. The car￾bonyl group and the atoms directly attached to it lie in the same plane. Formaldehyde, for example, is planar. The bond angles involving the carbonyl group of aldehydes and ketones are close to 120°. At 122 pm, the carbon–oxygen double bond distance in aldehydes and ketones is sig￾nificantly shorter than the typical carbon–oxygen single bond distance of 141 pm in alco￾hols and ethers. The carbonyl group makes aldehydes and ketones rather polar, with molecular dipole moments that are substantially larger than those of comparable compounds that contain carbon–carbon double bonds. Bonding in formaldehyde can be described according to an sp2 hybridization model analogous to that of ethylene, as shown in Figure 17.1. Figure 17.2 compares the electrostatic potential surfaces of ethylene and formalde￾hyde and vividly demonstrates how oxygen affects the electron distribution in formalde￾hyde. The electron density in both the and components of the carbon–oxygen dou￾ble bond is displaced toward oxygen. The carbonyl group is polarized so that carbon is partially positive and oxygen is partially negative. In resonance terms, electron delocalization in the carbonyl group is represented by contributions from two principal resonance structures: C O   or C O CH3CH2CH CH2 1-Butene Dipole moment: 0.3 D CH3CH2CH O Propanal Dipole moment: 2.5 D C O H H 116.5° 121.7° 121.7° Formaldehyde C O H3C H 117.5° 123.9° 118.6° Acetaldehyde C O H3C CH3 117.2° 121.4° 121.4° Acetone 17.2 Structure and Bonding: The Carbonyl Group 657 (a) Ethylene (b) Formaldehyde FIGURE 17.1 Similari￾ties between the orbital hy￾bridization models of bonding in (a) ethylene and (b) formaldehyde. Both mol￾ecules have the same num￾ber of electrons, and carbon is sp2 -hybridized in both. In formaldehyde, one of the carbons is replaced by an sp2 - hybridized oxygen (shown in red). Oxygen has two unshared electron pairs; each pair occupies an sp2 - hybridized orbital. Like the carbon–carbon double bond of ethylene, the carbon–oxy￾gen double bond of formaldehyde is composed of a two-electron compo￾nent and a two-electron component. Verify their geometries by making models of formalde￾hyde, acetaldehyde, and ace￾tone. Make sure you execute the minimization routine. Compare the dipole mo￾ments and electrostatic potential maps of 1-butene and propanal on Learning By Modeling. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group FIGURE 17.2 Differ- ences in the electron distribu tion of (a) ethylene and (b)formaldehyde. The region of highest electrostatic tential (red )in ethylene lies above and below the plane of the atoms and is associated with the electrons. the re- gion close to oxygen is the site of highest electrostatic potential in formaldehyde (a) Ethylene (b) Formaldehyde stry of the hat carbon is partially posi- A tive(has carbocation charac- ter)and oxygen is partially Of these two, A, having one more covalent bond and avoiding the separation of positive and negative charges that characterizes B, better approximates the bonding in a carbonyl group. Alkyl substituents stabilize a carbonyl group in much the same way that they sta bilize carbon-carbon double bonds and carbocations-by releasing electrons to sp hybridized carbon. Thus, as their heats of combustion reveal, the ketone 2-butanone more stable than its aldehyde isomer butanal CH3 CH,CH,CH CH3 CH, CCH3 Butanal 2-Butanone Heat of combustion: 2475 kJ/mol(592 kcal/mol) 2442 k/mol (584 kcal/mol) The carbonyl carbon of a ketone bears two electron-releasing alkyl groups; an aldehyde carbonyl group has only one. Just as a disubstituted double bond in an alkene is more stable than a monosubstituted double bond, a ketone carbonyl is more stable than an aldehyde carbonyl. We'll see later in this chapter that structural effects on the relative stability of carbonyl groups in aldehydes and ketones are an important factor in their rel ative reactivity. 17.3 PHYSICAL PROPERTIES In general, aldehydes and ketones have higher boiling points than alkenes because they int, boiling point, are more polar and the dipole-dipole attractive forces between molecules are stronger. ty in water are ected for a variety of But they have lower boiling points than alcohols because, unlike alcohols, two carbonyl aldehydes and ketones in groups can't form hydrogen bonds to each other. Appendix 1 CH3CH, CH=CH, CH3 CH,CH=O CH3 CH,CH,OH 1-Butene bp(I atm) Solubility in Negligible Miscible in alll water(g/100 mL) Aldehydes and ketones can form hydrogen bonds with the protons of oH groups. This makes them more soluble in water than alkenes. but less soluble than alcohols Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

Of these two, A, having one more covalent bond and avoiding the separation of positive and negative charges that characterizes B, better approximates the bonding in a carbonyl group. Alkyl substituents stabilize a carbonyl group in much the same way that they sta￾bilize carbon–carbon double bonds and carbocations—by releasing electrons to sp2 - hybridized carbon. Thus, as their heats of combustion reveal, the ketone 2-butanone is more stable than its aldehyde isomer butanal. The carbonyl carbon of a ketone bears two electron-releasing alkyl groups; an aldehyde carbonyl group has only one. Just as a disubstituted double bond in an alkene is more stable than a monosubstituted double bond, a ketone carbonyl is more stable than an aldehyde carbonyl. We’ll see later in this chapter that structural effects on the relative stability of carbonyl groups in aldehydes and ketones are an important factor in their rel￾ative reactivity. 17.3 PHYSICAL PROPERTIES In general, aldehydes and ketones have higher boiling points than alkenes because they are more polar and the dipole–dipole attractive forces between molecules are stronger. But they have lower boiling points than alcohols because, unlike alcohols, two carbonyl groups can’t form hydrogen bonds to each other. Aldehydes and ketones can form hydrogen bonds with the protons of OH groups. This makes them more soluble in water than alkenes, but less soluble than alcohols. CH3CH2CH CH2 1-Butene 6°C Negligible bp (1 atm) Solubility in water (g/100 mL) CH3CH2CH O Propanal 49°C 20 CH3CH2CH2OH 1-Propanol 97°C Miscible in all proportions CH3CH2CH2CH O Butanal 2475 kJ/mol (592 kcal/mol) CH3CH2CCH3 O 2-Butanone Heat of combustion: 2442 kJ/mol (584 kcal/mol)  C  O B C O A 658 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group The chemistry of the car￾bonyl group is considerably simplified if you remember that carbon is partially posi￾tive (has carbocation charac￾ter) and oxygen is partially negative (weakly basic). Physical constants such as melting point, boiling point, and solubility in water are collected for a variety of aldehydes and ketones in Appendix 1. (a) Ethylene (b) Formaldehyde FIGURE 17.2 Differ￾ences in the electron distribu￾tion of (a) ethylene and (b) formaldehyde. The region of highest electrostatic po￾tential (red) in ethylene lies above and below the plane of the atoms and is associated with the electrons. The re￾gion close to oxygen is the site of highest electrostatic potential in formaldehyde. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

17. 4 Sources of Aldehydes and Ketones 17. 4 SOURCES OF ALDEHYDES AND KETONES As we'll see later in this chapter and the next, aldehydes and ketones are involved in many of the most used reactions in synthetic organic chemistry. Where do aldehydes and ketones come from? Many occur naturally. In terms of both variety and quantity, aldehydes and ketones rank among the most common and familiar natural products. Several are shown in Igure Many are made in the laboratory from alkenes, alkynes, arenes, and alcohols by reactions that you already know about and are summarized in Table 17.1 To the synthetic chemist, the most important of the reactions in Table 17.1 are th last two: the oxidation of primary alcohols to aldehydes and secondary alcohols to ketones. Indeed, when combined with reactions that yield alcohols, the oxidation meth ods are so versatile that it will not be necessary to introduce any new methods for prepar- ing aldehydes and ketones in this chapter A few examples will illustrate this point Let's first consider how to prepare an aldehyde from a carboxylic acid. There are no good methods for going from RCO2H to RCHO directly. Instead, we do it indirectly by first reducing the carboxylic acid to the corresponding primary alcohol, then oxidiz ing the primary alcohol to the aldehyde CHOH →>RCH Carboxylic acid Primary alcohol Aldehyde O L LIAIH PDC COH CHOH CH Benzoic acid Benzyl alcohol (81%) Benzaldehyde (83%) (sex pheromone of greater wax moth) (component of alarm pheromone of bees) (alarm pheromone of myrmicine ant) (present in lemon grass oil) (found in oil of jasmine) FIGURE 17.3 African civet cat) naturally occurring Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

17.4 SOURCES OF ALDEHYDES AND KETONES As we’ll see later in this chapter and the next, aldehydes and ketones are involved in many of the most used reactions in synthetic organic chemistry. Where do aldehydes and ketones come from? Many occur naturally. In terms of both variety and quantity, aldehydes and ketones rank among the most common and familiar natural products. Several are shown in Figure 17.3. Many are made in the laboratory from alkenes, alkynes, arenes, and alcohols by reactions that you already know about and are summarized in Table 17.1. To the synthetic chemist, the most important of the reactions in Table 17.1 are the last two: the oxidation of primary alcohols to aldehydes and secondary alcohols to ketones. Indeed, when combined with reactions that yield alcohols, the oxidation meth￾ods are so versatile that it will not be necessary to introduce any new methods for prepar￾ing aldehydes and ketones in this chapter. A few examples will illustrate this point. Let’s first consider how to prepare an aldehyde from a carboxylic acid. There are no good methods for going from RCO2H to RCHO directly. Instead, we do it indirectly by first reducing the carboxylic acid to the corresponding primary alcohol, then oxidiz￾ing the primary alcohol to the aldehyde. COH O Benzoic acid CH2OH Benzyl alcohol (81%) CH O Benzaldehyde (83%) 1. LiAlH4 2. H2O PDC CH2Cl2 RCO2H Carboxylic acid RCH2OH Primary alcohol RCH O Aldehyde reduce oxidize 17.4 Sources of Aldehydes and Ketones 659 O O O Undecanal (sex pheromone of greater wax moth) 2-Heptanone (component of alarm pheromone of bees) O trans-2-Hexenal (alarm pheromone of myrmicine ant) O Citral (present in lemon grass oil) O Civetone (obtained from scent glands of African civet cat) Jasmone (found in oil of jasmine) H H H FIGURE 17.3 Some naturally occurring alde￾hydes and ketones. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

TABLE 17.1 Summary of Reactions Discussed in Earlier Chapters That Yield Aldehydes and Ketones Reaction(section) and comments General equation and specific example Ozonolysis of alkenes(Section 6. 19)This H cleavage reaction is more often seen in structural analysis than in synthesis. The RCR+RCH 2. H-O. Zn substitution pattern around a double R bond is revealed by identifying the carbonyl-containing compounds that Alkene Two carbonyl compounds make up the product Hydrolysis of the ozonide intermediate in the presence of CH3 zinc(reductive workup) permits alde- CH3 CCH3 HCCH2 CH2 CHCH2CH3 hyde products to be isolated without further oxidation 2, 6-Dimethyl-2-octene Acetone 4-Methylhexanal (91%) Hydration of alkynes(Section 9.12)Reac- ate formed by Markovnikov addition of RC=CR+H,o HS0a, RCCH2R tion occurs by way of an enol intermedi ater to the triple bond Alkyne Ketone HC=C(CH2)5 CH3+h. aC(CH2)sCH 1-Octyne 2-Octanone(91%) Friedel-Crafts acylation of aromatic compounds(Section 12.7) Acyl chloride and carboxylic acid anhydrides acylate ArH+RCCl Ch ArCR +Hcl o aromatic rings in the presence of alum num chloride. The reaction is electrophile ic aromatic substitution in which acylium ArH+ RCOCR RCO2H ions are generated and attack the ring (90-94% Oxidation of primary alcohols to alde- hydes(Section 15.10)Pyridinium dichro- mate( PDo) or pyridinium chlorochro- RCH2OH DC or PCC mate(PCC)in anhydrous media such as Primary alcohol Aldehyde dichloromethane oxidizes primary alco- hols to aldehydes while avoiding overox CH3(CH2)CH2OH CH2)&CH 1-Decanol Oxidation of secondary alcohols to tones (Section 15.10)Many oxidizing agents are available for converting sec- RCHR ondary alcohols to ketones. PDC or PCC may be used as well as other cr(vi)- based agents such as chromic acid or Secondary alcohol Ketone potassium dichromate and sulfuric acid C6HsCHCH2 CH2 H2 CH3 -i CsHs CH2CH2 CH OH 1-Phenyl-1-pentanol 1-Phenyl-1-pentanone(93%) Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

TABLE 17.1 Summary of Reactions Discussed in Earlier Chapters That Yield Aldehydes and Ketones Reaction (section) and comments Ozonolysis of alkenes (Section 6.19) This cleavage reaction is more often seen in structural analysis than in synthesis. The substitution pattern around a double bond is revealed by identifying the carbonyl-containing compounds that make up the product. Hydrolysis of the ozonide intermediate in the presence of zinc (reductive workup) permits alde￾hyde products to be isolated without further oxidation. Friedel-Crafts acylation of aromatic compounds (Section 12.7) Acyl chlorides and carboxylic acid anhydrides acylate aromatic rings in the presence of alumi￾num chloride. The reaction is electrophil￾ic aromatic substitution in which acylium ions are generated and attack the ring. Oxidation of primary alcohols to alde￾hydes (Section 15.10) Pyridinium dichro￾mate (PDC) or pyridinium chlorochro￾mate (PCC) in anhydrous media such as dichloromethane oxidizes primary alco￾hols to aldehydes while avoiding overox￾idation to carboxylic acids. Oxidation of secondary alcohols to ketones (Section 15.10) Many oxidizing agents are available for converting sec￾ondary alcohols to ketones. PDC or PCC may be used, as well as other Cr(VI)- based agents such as chromic acid or potassium dichromate and sulfuric acid. Hydration of alkynes (Section 9.12) Reac￾tion occurs by way of an enol intermedi￾ate formed by Markovnikov addition of water to the triple bond. General equation and specific example Two carbonyl compounds RCR O X RCH O X  1. O3 2. H2O, Zn Alkene CœC ± ± ± ± R H R R Acetone CH3CCH3 O X HCCH2CH2CHCH2CH3 O X W CH3 4-Methylhexanal (91%)  1. O3 2. H2O, Zn 2,6-Dimethyl-2-octene Alkyne RCPCR  H2O H2SO4 HgSO4 RCCH2R O X Ketone ArH HCl or   AlCl3 ArCR O X RCCl O X RCH2OH Primary alcohol PDC or PCC CH2Cl2 Aldehyde RCH O X RCHR W OH Secondary alcohol Cr(VI) Ketone RCR O X C6H5CHCH2CH2CH2CH3 W OH 1-Phenyl-1-pentanol CrO3 acetic acid/ water 1-Phenyl-1-pentanone (93%) C6H5CCH2CH2CH2CH3 O X CH3(CH2)8CH2OH 1-Decanol PDC CH2Cl2 Decanal (98%) CH3(CH2)8CH O X ArH RCO   2H AlCl3 ArCR O X RCOCR O X O X 1-Octyne HCPC(CH2)5CH3  H2O H2SO4 HgSO4 CH3C(CH2)5CH3 O X 2-Octanone (91%)  AlCl3 CCH3 O X CH3O p-Methoxyacetophenone (90–94%) CH3COCCH3 O X O X Acetic anhydride CH3O Anisole Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

17.5 Reactions of Aldehydes and Ketones: A Review and a Preview PROBLEM 17.3 Can catalytic hydrogenation be used to reduce a carboxylic acid to a primary alcohol in the first step of this sequence? It is often necessary to prepare ketones by processes g carbon-carbon bond formation In such cases the standard method combines of a Grignard reagent to an aldehyde with oxidation of the resulting secondary OH 1. RMgX, diethyl eth Aldehyde Secondary alcohol OH I CH3(CH,)3MgBr →CH2CH2CHCH2)CH2C CH3CH,C(CH2)3CH 3-Heptanol 3-Heptanone PROBLEM 17.4 Show how 2-butanone could be prepared by a procedure in hich all of the carbons originate in acetic acid (CHa,H) Many low-molecular-weight aldehydes and ketones are important industrial chemi- The name aldehyde was in. cals. Formaldehyde, a starting material for a number of plastics, is prepared by oxidation of vented to stand for alcohol methanol over a silver or iron oxide/molybdenum oxide catalyst at elevated temperature. that aldehydes are related to CH3OH+ Jo, cataly HCH H,O Methanol Oxygen Formaldehyde Water Similar processes are used to convert ethanol to acetaldehyde and isopropyl alcohol to acetone The "linear a-olefins described in Section 14 15 are starting materials for the preparation of a variety of aldehydes by reaction with carbon monoxide. The process is called hydroformylation RCH=CH,+ CO H RCH,,CH Alkene Carbon Excess hydrogen brings about the hydrogenation of the aldehyde and allows the process to be adapted to the preparation of primary alcohols. Over 2 X 10 lb/year of a variety of aldehydes and alcohols is prepared in the United States by hydroformylation. A number of aldehydes and ketones are prepared both in industry and in the lab- oratory by a reaction known as the aldol condensation, which will be discussed in detail in Chapter 18. 17.5 REACTIONS OF ALDEHY DES AND KETONES: A REVIEW AND A PREVIEW Table 17.2 summarizes the reactions of aldehydes and ketones that you ve seen in ear- lier chapters. All are valuable tools to the synthetic chemist. Carbonyl groups provide access to hydrocarbons by Clemmensen of Wolff-Kishner reduction(Section 12. 8),to Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

PROBLEM 17.3 Can catalytic hydrogenation be used to reduce a carboxylic acid to a primary alcohol in the first step of this sequence? It is often necessary to prepare ketones by processes involving carbon–carbon bond formation. In such cases the standard method combines addition of a Grignard reagent to an aldehyde with oxidation of the resulting secondary alcohol: PROBLEM 17.4 Show how 2-butanone could be prepared by a procedure in which all of the carbons originate in acetic acid (CH3CO2H). Many low-molecular-weight aldehydes and ketones are important industrial chemi￾cals. Formaldehyde, a starting material for a number of plastics, is prepared by oxidation of methanol over a silver or iron oxide/molybdenum oxide catalyst at elevated temperature. Similar processes are used to convert ethanol to acetaldehyde and isopropyl alcohol to acetone. The “linear -olefins” described in Section 14.15 are starting materials for the preparation of a variety of aldehydes by reaction with carbon monoxide. The process is called hydroformylation. Excess hydrogen brings about the hydrogenation of the aldehyde and allows the process to be adapted to the preparation of primary alcohols. Over 2  109 lb/year of a variety of aldehydes and alcohols is prepared in the United States by hydroformylation. A number of aldehydes and ketones are prepared both in industry and in the lab￾oratory by a reaction known as the aldol condensation, which will be discussed in detail in Chapter 18. 17.5 REACTIONS OF ALDEHYDES AND KETONES: A REVIEW AND A PREVIEW Table 17.2 summarizes the reactions of aldehydes and ketones that you’ve seen in ear￾lier chapters. All are valuable tools to the synthetic chemist. Carbonyl groups provide access to hydrocarbons by Clemmensen of Wolff–Kishner reduction (Section 12.8), to   RCH2CH2CH O Aldehyde Co2(CO)8 Hydrogen H2 Carbon monoxide CO Alkene RCH CH2 CH3OH Methanol   HCH O Formaldehyde H2O Water catalyst 500°C Oxygen O2 1 2 RCH O Aldehyde RCHR OH Secondary alcohol RCR O Ketone 1. RMgX, diethyl ether 2. H3O oxidize CH3CH2CH O Propanal CH3CH2CH(CH2)3CH3 OH 3-Heptanol CH3CH2C(CH2)3CH3 O 3-Heptanone (57% from propanal) 1. CH3(CH2)3MgBr diethyl ether 2. H3O H2CrO4 17.5 Reactions of Aldehydes and Ketones: A Review and a Preview 661 The name aldehyde was in￾vented to stand for alcohol dehydrogenatum, indicating that aldehydes are related to alcohols by loss of hydrogen. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group TABLE 17.2 Summary of Reactions of Aldehydes and Ketones Discussed in Earlier Chapters Reaction(section) and comments General equation and specific example Reduction to hydrocarbons(Section 12.8) Two methods for converting carbonyl groups to methylene units are the Clem- ensen reduction(zinc amalgam and con- Aldehyde centrated hydrochloric acid) and the or ketone Wolff-Kishner reduction(heat with hydra- zine and potassium hydroxide in a high ing alcohol). glycol, heat Citronellal 2, 6-Dimethyl-2-octene Reduction to alcohols (Section 15.2)Alde- hydes are reduced to primary alcohols, and ketones are reduced to secondary alcohols RCR RCHR by a variety of reducing agents. Catalytic hydrogenation over a metal catalyst and eduction with sodium borohydride or Aldehyde Alcohol lithium aluminum hydride are genera CHO ->CH laO p-Methoxybenzaldehyde p-Methoxybenzyl alcohol (96%) Addition of Grignard reagents and organolithium compounds(Sections 14.6-14.7)Aldehydes are converted to RCR′+R"M )RCR H RCR' secondary alcohols and ketones to tertiary HO CH2CH CHICH,MgBr 1 die toether Cyclohexanone Ethylmagnesiun 1-Ethylcyclohexanol alcohols by reduction(Section 15. 2)or by reaction with Grignard or organolithium The most important chemical property of the carbonyl group is its tendency to undergo nucleophilic addition reactions of the type represented in the general equation Aldehyde Product of Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

alcohols by reduction (Section 15.2) or by reaction with Grignard or organolithium reagents (Sections 14.6 and 14.7). The most important chemical property of the carbonyl group is its tendency to undergo nucleophilic addition reactions of the type represented in the general equation: C O   Aldehyde or ketone  X Y   C Y O X Product of nucleophilic addition 662 CHAPTER SEVENTEEN Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group TABLE 17.2 Summary of Reactions of Aldehydes and Ketones Discussed in Earlier Chapters Reaction (section) and comments Reduction to hydrocarbons (Section 12.8) Two methods for converting carbonyl groups to methylene units are the Clem￾mensen reduction (zinc amalgam and con￾centrated hydrochloric acid) and the Wolff–Kishner reduction (heat with hydra￾zine and potassium hydroxide in a high￾boiling alcohol). Addition of Grignard reagents and organolithium compounds (Sections 14.6-14.7) Aldehydes are converted to secondary alcohols and ketones to tertiary alcohols. Reduction to alcohols (Section 15.2) Alde￾hydes are reduced to primary alcohols, and ketones are reduced to secondary alcohols by a variety of reducing agents. Catalytic hydrogenation over a metal catalyst and reduction with sodium borohydride or lithium aluminum hydride are general methods. General equation and specific example NaBH4 CH3OH CH O X CH3O p-Methoxybenzaldehyde CH3O CH2OH p-Methoxybenzyl alcohol (96%) Hydrocarbon RCR RCH2R O X Aldehyde or ketone H2NNH2, KOH diethylene glycol, heat Citronellal 2,6-Dimethyl-2-octene (80%) CH O X RCHR OH W Alcohol RCR O X Aldehyde or ketone RCR R OM W W RCR R OH W W RCR O X  RM H3O CH3CH2MgBr Ethylmagnesium bromide Cyclohexanone O  1. diethyl ether 2. H3O 1-Ethylcyclohexanol (74%) HO CH2CH3 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

17.6 Principles of Nucleophilic Addition: Hydration of Aldehydes and Ketones A negatively polarized atom or group attacks the positively polarized carbon of the car- bonyl group in the rate-determining step of these reactions. Grignard reagents, organo- lithium reagents, lithium aluminum hydride, and sodium borohydride, for example, all react with carbonyl compounds by nucleophilic addition. The next section explores the mechanism of nucleophilic addition to aldehydes and ketones. There we'll discuss their hydration a reaction in which water adds to the c=o group. After we use this reaction to develop some general principles, we'll then survey a number of related reactions of synthetic, mechanistic, or biological interest. 17.6 PRINCIPLES OF NUCLEOPHILIC ADDITION: HYDRATION OF ALDEHYDES AND KETONES Effects of structure on Equilibrium: Aldehydes and ketones react with water in a d equilibrium: RCR′+H2O [carbonyl compound][water] Aldehyde Water Geminal diol Overall. the reaction is classified as an addition. The elements of water add to the car- bonyl group. Hydrogen becomes bonded to the negatively polarized carbonyl oxyger hydroxyl to the positively polarized carbon. Table 17.3 compares the equilibrium constants Khydr for hydration of some simple aldehydes and ketones. The position of equilibrium depends on what groups are attached to C=O and how they affect its steric and electronic environment. Both effects con- tribute, but the electronic effect controls Khvdr more than the steric effect. TABLE 17.3 Equilibrium Constants(Khyd )for Hydration of Some Aldehydes and Ketones Percent conversion Hydrate K HCH CH2(OH)2 CHCH CHa CH(OH)2 1.8×10-2 CH3)3CCH (CH3)aCCH(OH)2 4.1×10-3 CHaCCH (CH3)2C(OH)2 25×10-5 0.14 Total concentration(hydrate plus carbonyl compound) assumed to be 1 M. Water concentration is 55.5 M. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

A negatively polarized atom or group attacks the positively polarized carbon of the car￾bonyl group in the rate-determining step of these reactions. Grignard reagents, organo￾lithium reagents, lithium aluminum hydride, and sodium borohydride, for example, all react with carbonyl compounds by nucleophilic addition. The next section explores the mechanism of nucleophilic addition to aldehydes and ketones. There we’ll discuss their hydration, a reaction in which water adds to the CœO group. After we use this reaction to develop some general principles, we’ll then survey a number of related reactions of synthetic, mechanistic, or biological interest. 17.6 PRINCIPLES OF NUCLEOPHILIC ADDITION: HYDRATION OF ALDEHYDES AND KETONES Effects of Structure on Equilibrium: Aldehydes and ketones react with water in a rapid equilibrium: Overall, the reaction is classified as an addition. The elements of water add to the car￾bonyl group. Hydrogen becomes bonded to the negatively polarized carbonyl oxygen, hydroxyl to the positively polarized carbon. Table 17.3 compares the equilibrium constants Khydr for hydration of some simple aldehydes and ketones. The position of equilibrium depends on what groups are attached to CœO and how they affect its steric and electronic environment. Both effects con￾tribute, but the electronic effect controls Khydr more than the steric effect. RCR O Aldehyde or ketone  H2O Water RCR OH OH Geminal diol (hydrate) fast Khydr  [hydrate] [carbonyl compound][water] 17.6 Principles of Nucleophilic Addition: Hydration of Aldehydes and Ketones 663 TABLE 17.3 Equilibrium Constants (Khydr) for Hydration of Some Aldehydes and Ketones Hydrate CH2(OH)2 CH3CH(OH)2 (CH3)3CCH(OH)2 (CH3)2C(OH)2 Khydr* 41 1.8  102 4.1  103 2.5  105 Percent conversion to hydrate† 99.96 50 19 0.14 Carbonyl compound HCH O X CH3CH O X (CH3)3CCH O X CH3CCH3 O X † Total concentration (hydrate plus carbonyl compound) assumed to be 1 M. Water concentration is 55.5 M. *Khydr  . Units of Khydr are M1 . [hydrate] [carbonyl compound][water] Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website