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1 CHAPTER 17 Aldehydes and Ketones: The Carbonyl Group 17-1 Naming the Aldehydes and Ketones The aldehyde function takes precedence over the ketone group in nomenclature. Simpler aldehydes often retain their common names. These are constructed by dropping the –ic or –oic acid ending and replacing it with –aldehyde: Many ketones also have common names consisting of the substituent names followed by the word ketone. Dimethyl ketone is best known as acetone. Phenyl ketones have common names ending in –phenone. IUPAC nomenclature treats aldehydes as derivatives of alkanes. The ending –e is replaced by –al. An alkane becomes an alkanal. Chem Abstracts retains the common names of the first two aldehydes: The names parallel those of the 1-alkanols except that the aldehyde carbon is assumed to be C1 and does not have to be specified. When an aldehyde is attached to a ring it is called a carbaldehyde. The carbon atom bearing the aldehyde is C1. The simplest aromatic aldehyde, benzenecarbaldehyde, is referred to using its common name, benzaldehyde, by Chem Abstracts. Ketones are called alkanones, the ending –e of the alkane is replaced with –one. IUPAC provides an exception for the simplest ketone, propanone, the common name of which is acetone. The carbonyl carbon of a ketone is assigned the smallest possible number, regardless of the presence of other substituents or the – OH, C=C or C≡C functional groups. Aromatic ketones are named as aryl-substituted alkanones. Ketones are called cycloalkanones when part of a ring. The carbonyl carbon is assigned C1 in this case. The systematic name of the fragment is “alkanoy.” The older term “acyl” is widely used. Both IUPAC and Chemical Abstracts retain the older names “formyl” and “acetyl” for the groups and . The term “oxo” denotes the location of a ketone carbonyl group when present with an aldehyde function
17-2 Structure of the Carbonyl Group toteeupcontaihnsasho rt,strong and y0aaiom9 ow up入又， 9≥9c8 he&edmsarterratgenot他enaeannopobitalon o 影 One of the simplest aldehyde is acetaldehyde .The oxygen contains two lone pairs in two sp?orbitals o6 H.e Deseriptiens of a Carbenyl Group 1-rieoyde ad IeorR,aesheaed.heeamgat6nomanaaenvoes his is caused by two fact lypoitvecarbonyncaus ibie with wster.As the 2
2 Several conventions can be used to denote the structure of an aldehyde or ketone: The condensed formula of an aldehyde must be written as RCHO and not RCOH, which might be confused with the hydroxy group of an alcohol. 17-2 Structure of the Carbonyl Group The carbonyl group contains a short, strong and very polar bond. The hybridization of the C and O atoms of the carbonyl group are sp2 hybridized. The C and O atoms of the carbonyl group and the two atoms attached to the carbon all lie in the same plane. The bond angles about the carbonyl are about 120o. The π bond of the carbonyl is made of the remaining p orbital on the carbon and a similar p orbital on the oxygen. One of the simplest aldehyde is acetaldehyde: The primary electronic differences between a carbonyl group and an ordinary double bond are: •The oxygen contains two lone pairs in two sp2 orbitals; •The oxygen is more electronegative than carbon. The C=O bond is polarized; the carbon possesses a slight positive charge and the oxygen a slight negative charge. Polarization alters the physical constants of aldehydes and ketones. Due to the polarization of their carbonyl groups, the boiling points of aldehydes and ketones are higher than hydrocarbons of similar molecular weights. Acetaldehyde and acetone are completely miscible with water. As the hydrocarbon length increases, solubility decreases. Carbonyl compounds have more than six carbons and are relatively insoluble in water. Spectroscopic Properties of Aldehydes and Ketones 17-3 The 1H NMR spectrum of the formyl hydrogen of an aldehyde is very strongly deshielded, appearing at 9-10 ppm. This is caused by two factors: •Similar to alkenes, the movement of the π electrons in the magnetic field strengthens the external field; •The partially positive carbonyl carbon causes additional deshielding
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3 The formyl hydrogens are seen at δ = 9.79 ppm, split into a triplet (J = 2 Hz) by the neighboring C2 hydrogens. The C2 hydrogens are also slightly deshielded by the partially positive carbonyl carbon. The α hydrogens of ketones also appear in the region δ = 2.0 – 2.8 ppm. The carbonyl carbon of both aldehydes and ketones show a characteristic chemical shift in 13C NMR. The carbonyl carbons are shifted to about 200 ppm, lower than those of the sp2 carbons of alkenes. Carbons next to the carbonyl carbon deshielded compared to those farther away. The presence of a carbonyl group is directly indicated in an infrared spectrum. C=O stretching: intense band at 1690-1750 cm-1 •Aldehydes: about 1735 cm-1 •Acyclic alkanones and cyclohexanone: about 1715 cm-1 Conjugation with alkene or benzene systems reduces these frequencies by about 30-40 cm-1. (1-phenylethanone 1680 cm-1.) Carbonyls in rings having fewer than 6 atoms show an increase in frequency (cyclopentanone 1745 cm-1; cyclobutanone 1780 cm-1). Carbonyl groups exhibit absorptions in the UV (electronic) as the non-bonding lone electron pairs on the oxygen atom undergo low energy nÆπ* transitions. The nÆπ* transition in acetone occurs at 280 nm (ε=15) in hexane. The corresponding πÆπ* transition occurs at 190 nm (ε=1100)
ggonoa2egiahdaonsshstne keoneepoeleemeaiatanaealnetodesand Elctrnic Tranitions fAcetone and 3-Buten--one 网gm6g3G CH.CCH CH-CHecH, 调 M-CHy The symmetric ketone generates a single acylium peak 4
4 Conjugation of carbonyl groups with double bonds shifts the absorption to longer wavelengths: Mass spectral fragmentation of aldehydes and ketones provides structural information. 2-Pentanone, 3-pentanone and 3-methyl-2-butanone all fragment by α cleavage yielding the corresponding acylium cation and an alkyl radical. Note that the two acylium fragments identify the composition of the ketone. The peak at mass 58 results from a McLafferty rearrangement. This occurs in compounds having a hydrogen atom γ to the carbonyl oxygen and enough flexibility to allow them to get close together. This extra peak allows 2-pentanone to be distinguished from 3-methyl-2- butanone, which give otherwise identical fragments. The symmetric ketone generates a single acylium peak. Note the absence of a peak at 58, which is present in the mass spectrum of 2-pentanone
17-Preparation of Aldehydes and Ketones Oxidation of alcohols: bboronmheiaofaldahydesandketonesus As-e5络时e 四。 Ozonol小sis rleuaone 85 17-Reactivity of the Carbonyl Group:Mechanisms of Friedel-Crufts Alkanoylation (Acylation) Regons f Reactiity Aldchydesand Ketemes 5
5 17-4 Preparation of Aldehydes and Ketones Laboratory syntheses of aldehydes and ketones use four common methods. Oxidation of alcohols: Ozonolysis: Hydration of the carbon-carbon triple bond yields enols that tautomerize to carbonyl compounds. In the presence of mercuric ion, addition of water follows Markovnikov’s rule to furnish ketones. Actual electronic control. Friedel-Crafts alkanoylation (acylation): Reactivity of the Carbonyl Group: Mechanisms of Addition 17-5 There are three regions of reactivity in aldehydes and ketones
The carbonyl group undergoes lonic additions. ab6ianab6n6StS8oastoaMgroupsbutnet 17-6 Addition of Water to Form Hydrates Water hydrates the carbonyl group. aaopeakniceophgaeionmcsteahoforthe atasc-Catalyend Hydration is reversible. + - 5 可 For ordinary aldehydes,the equilit 一酬 ←→》- 6
6 The carbonyl group undergoes ionic additions. Polar reagents add to the dipolar carbonyl group according to Coulomb’s law and the fundamentals of Lewis acid-Lewis base interactions. Nucleophiles bond to the carbonyl carbon and electrophiles bond to the carbonyl oxygen. NaBH4 and LiAlH4 reduce carbonyl groups but not carbon-carbon double bonds: The following reagents are strong bases and their reactions are irreversible. Less basic nucleophiles, such as water, alcohols, thiols and amines are not strongly exothermic and establish equilibria that can be pushed in either direction depending upon reaction conditions. Relatively weak nucleophiles are more suitable for the electrophilic protonation-addition mechanism. Addition of strongly basic nucleophiles typically follow the nucleophilic addition-protonation pathway. 17-6 Addition of Water to Form Hydrates Water hydrates the carbonyl group. The addition of water to an aldehyde or ketone is catalyzed by either acid or base. The equilibrium reaction forms geminal diols, also called carbonyl hydrates: Hydration is reversible. The equilibrium for the hydration of ketones lies to the left, while that for formaldehyde and aldehydes bearing electronwithdrawing substituents lies to the right. For ordinary aldehydes, the equilibrium lies close to unity. These results can be explained by examining the resonance structures of the carbonyl group: The carbocation-like carbon atom is stabilized by alkyl groups and destabilized by electron-withdrawing groups, such as CCl3 and CF3. The stabilities of the product diols are affected to a lesser extent
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7 Relative to formaldehyde, hydrations of aldehydes and ketones are progressively more endothermic, while hydrations of carbonyl compounds containing electron-withdrawing groups are more exothermic. The thermodynamic effects are paralleled by kinetic reactivity: Although hydration is favorable in certain cases, it is usually impossible to isolate carbonyl hydrates as pure substances. Carbonyl hydrates play a role as intermediates in subsequent chemistry, such as the oxidation of aldehydes to ketones under aqueous conditions. Addition of Alcohols to Form Hemiacetals and Acetals 17-7 Aldehydes and ketones form hemiacetals reversibly. The reaction of alcohols with aldehydes and ketones parallels the reaction with water: These equilibria usually favor the starting carbonyl compound. Stable hemiacetals are formed from reactive carbonyl compounds (formaldehyde or 2,2,2-trichloroacetaldehyde) or when relatively strain-free, five- and six-membered rings are formed: Acids catalyze acetal formation. In the presence of excess alcohol, two molecules of alcohol are added to an aldehyde or ketone in the acid-catalyzed reaction. The resulting compounds are called acetals (an older term for an acetal derived from a ketone is a ketal)
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8 Each step is reversible in the presence of acid. The equilibrium can be shifted towards acetal by using excess alcohol or removing water or towards aldehyde or ketone by adding excess water (acetal hydrolysis). Acetals, unlike hydrates and hemiacetals, may be isolated as pure substances by neutralizing the acid used as the catalyst. 17-8 Acetals as Protecting Groups Cyclic acetal formation protects carbonyl groups from attack by nucleophiles. 1,2-Ethanediol is a particularly effective reagent for forming acetals compared to ordinary alcohols because it forms a more stable cyclic intermediate. The stability of the cyclic acetal is due to a more favorable entropy change upon formation (2 reactant molecules become 2 product molecules) compared to a noncyclic acetal (3 reactant molecules become 2 product molecules). Cyclic acetals can be hydrolized by aqueous acid, but are stable to many basic, organometallic and hydride reagents. These properties allow cyclic acetals to be used as protecting groups for the carbonyl function in aldehydes and ketones. The alkynyl anion attacks the carbonyl group in the unprotected 3-iodopropanal. Thiols react with the carbonyl group to form thioacetals. Thiols react with aldehydes and ketones in the presence of a Lewis acid, such as BF3 or ZnCl2, to form thioacetals. The cyclic thioacetal is stable in aqueous acid. Thioacetals are hydrolyzed by using mercuric chloride in aqueous acetonitrile (formation of insoluble mercuric sulfides drives the reaction). Thioacetals can be desulfurized to the corresponding hydrocarbon using Raney nickel:
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9 Nucleophilic Addition of Ammonia and Its Derivatives 17-9 Ammonia and primary and secondary amines add to aldehydes and ketones in a manner analogous to water and alcohols. However, the products of these reactions then lose water, forming imines and enamines. Ammonia and primary amines form imines. Amines and aldehydes or ketones react to form hemiaminals, the nitrogen analogs of hemiacetals. The hemiaminals of primary amines then lose water to form an imine (previously, Schiff base). This is the nitrogen analog of the carbonyl group. Reactions between a primary amine and an aldehyde or ketone, in which two molecules are joined with the elimination of water, are called “condensations.” When an imine is used as reaction intermediate, the carbonyl compound and amine are usually mixed with the subsequent reagent and the imine is consumed immediately upon formation. Imines can be isolated, often in high yield, if water formed is removed from the condensation process (continuous distillation). Special imines aid in the identification of aldehydes and ketones. Several amine derivatives condense with aldehydes and ketones to form imines that are highly crystalline and have sharp melting points. These derivatives are more stable than simple imines due to resonance stabilization. For instance, in an oxime: Comparison of the melting point of an unknown imine derivative to a catalog of known values was used as a method of identification of aldehydes and ketones prior to the development of spectroscopic methods
ond th secondary mneglve 17-10 Deoxygenation of the Carbony Group 觉 app Kishner reduction aids 17-11Ad Cyanide to ve eaddstthtform g=a8eaapawwman 9 6学8 , 10
10 Condensations with secondary amines give enamines. Aldehydes and ketones react with secondary amines to produce enamines. In this reaction, water is eliminated between the hydroxyl group and the neighboring carbon atom, rather than the nitrogen atom. Enamine formation is reversible and hydrolysis occurs readily in the presence of aqueous acid. 17-10 Deoxygenation of the Carbonyl Group Strong base converts simple hydrazones into hydrocarbons. Hydrazones are formed from the condensation of an aldehyde or ketone with hydrazine. When treated with a base at elevated temperatures, hydrazones decompose, liberating the corresponding hydrocarbon and nitrogen gas. This reaction is known as the Wolff-Kishner reduction.(Wolff-Kishner-Minglong Huang reduction) In practice, the intermediate hydrazone is not isolated. Instead, it is generated in the presence of strong base and is used up as it is formed. Wolff-Kishner reduction aids in alkylbenzene synthesis. The Wolff-Kishner-Minglong Huang deoxygenation is frequently used in lieu of Friedel-Crafts alkanoylation, particularly for acidsensitive, base-stable substrates. Addition of Hydrogen Cyanide to Give Cyanohydrins 17-11 Hydrogen cyanide adds to the carbonyl group to form cyanohydrins. Slow addition of HCl to an excess of NaCN is typically used to generate HCN in a moderately alkaline mixture. This reaction requires the presence of both a free cyanide ion and undissociated HCN (satisfied by maintaining a moderately basic pH)