* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Chapter 19. Aldehydes and Ketones
Aromaticity wikipedia , lookup
Physical organic chemistry wikipedia , lookup
George S. Hammond wikipedia , lookup
Kinetic resolution wikipedia , lookup
Elias James Corey wikipedia , lookup
Discodermolide wikipedia , lookup
Aromatization wikipedia , lookup
Ring-closing metathesis wikipedia , lookup
Hofmann–Löffler reaction wikipedia , lookup
1,3-Dipolar cycloaddition wikipedia , lookup
Ene reaction wikipedia , lookup
Stille reaction wikipedia , lookup
Tiffeneau–Demjanov rearrangement wikipedia , lookup
Petasis reaction wikipedia , lookup
Aldol reaction wikipedia , lookup
Wolff rearrangement wikipedia , lookup
Strychnine total synthesis wikipedia , lookup
Baylis–Hillman reaction wikipedia , lookup
Hydroformylation wikipedia , lookup
Wolff–Kishner reduction wikipedia , lookup
Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Aldehydes and Ketones Aldehydes (RCHO) and ketones (R2CO) are characterized by the the carbonyl functional group (C=O) The compounds occur widely in nature as intermediates in metabolism and biosynthesis 2 Why this Chapter? Much of organic chemistry involves the chemistry of carbonyl compounds Aldehydes/ketones are intermediates in synthesis of pharmaceutical agents, biological pathways, numerous industrial processes An understanding of their properties is essential 3 19.1 Naming Aldehydes: Aldehydes are named by replacing the terminal -e of the corresponding alkane name with –al The parent chain must contain the CHO group The CHO carbon is numbered as C1 Ethanal acetaldehyde Propanal Propionaldehyde 2-Ethyl-4-methylpentanal 4 19.1 Naming Aldehydes and Ketones Methanal (Common) (IUPAC) (Common) Propanone (IUPAC) 5 Naming Aldehydes If the CHO group is attached to a ring, use the suffix carbaldehyde. Cyclohexanecarbaldehyde 2-Naphthalenecarbaldehyde 6 Naming Aldehydes: Common Names end in aldehyde 7 Naming Ketones Replace the terminal -e of the alkane name with –one Parent chain is the longest one that contains the ketone grp Numbering begins at the end nearer the carbonyl carbon 3-Hexanone (New: Hexan-3-one) 4-Hexen-2-one 2,4-Hexanedione (New: Hex-4-en-2-one) (New: Hexane-2,4-dione) 8 Ketones with Common Names IUPAC retains well-used but unsystematic names for a few ketones Acetone Acetophenone Benzophenone 9 Ketones and Aldehydes as Substituents The R–C=O as a substituent is an acyl group, used with the suffix -yl from the root of the carboxylic acid The prefix oxo- is used if other functional groups are present and the doubly bonded oxygen is labeled as a substituent on a parent chain 10 Learning Check: Name the following: 11 Solution: Name the following: 2-methyl-3-pentanone (ethyl isopropyl ketone) 2,6-octanedione 3-phenylpropanal (3-phenylpropionaldehyde) 4-hexenal Trans-2-methylcyclohexanecarbaldehyde Cis-2,5-dimethylcyclohexanone 12 19.2 Preparation of Aldehydes Aldehydes Oxidation of 1o alcohols with pyridinium chlorochromate PCC Oxidative cleavage of Alkenes with a vinylic hydrogen with ozone 13 Preparation of Aldehydes Aldehydes Reduction of an ester with diisobutylaluminum hydride (DIBAH) 14 Preparing Ketones Ketones Oxidation of a 2° alcohol Many reagents possible: Na2Cr2O7, KMnO4, CrO3 choose for the specific situation (scale, cost, and acid/base sensitivity) 15 Ketones from Ozonolysis Ketones Oxidative cleavage of substituted Alkenes with ozone 16 Aryl Ketones by Acylation Ketones Friedel–Crafts acylation of an aromatic ring with an acid chloride in the presence of AlCl3 catalyst 17 Methyl Ketones by Hydrating Alkynes Ketones Hydration of terminal alkynes in the presence of Hg2+ cat 18 Preparation of Ketones Ketones Gilman reaction of an acid chloride 19 Learning Check: Carry out the following transformations: 3-Hexyne 3-Hexanone Benzene m-Bromoacetophenone Bromobenzene Acetophenone 1-methylcyclohexene 2-methylcyclohexanone 20 Solution: Carry out the following transformations: 3-Hexyne 3-Hexanone O CH3 CH2 C C CH2 CH3 Hg(OAc)2, CH3 CH2 C CH2 CH2 CH3 + H 3O Benzene m-Bromoacetophenone O O 1) CH3 C Cl , AlCl3 Br 2) Br2, FeBr3 21 Solution: Carry out the following transformations: Bromobenzene Acetophenone Br O 1) Mg in ether O 2) CH3 C H 3) H3O+ 4) PCC 1-methylcyclohexene 2-methylcyclohexanone CH3 1) BH3 2) H2O2, NaOH CH3 O 3) PCC 22 19.3 Oxidation of Aldehydes & Ketones CrO3 in aqueous acid oxidizes aldehydes to carboxylic acids (acidic conditions) Tollens’ reagent Silver oxide, Ag2O, in aqueous ammonia oxidizes aldehydes (basic conditions) 23 Hydration of Aldehydes Aldehyde oxidations occur through 1,1-diols (“hydrates”) Reversible addition of water to the carbonyl group Aldehyde hydrate is oxidized to a carboxylic acid by usual reagents for alcohols 24 Ketones Oxidize with Difficulty Undergo slow cleavage with hot, alkaline KMnO4 C–C bond next to C=O is broken to give carboxylic acids Reaction is practical for cleaving symmetrical ketones 25 19.4 Nucleophilic Addition Reactions of Aldehydes and Ketones Nu- approaches 75° to the plane of C=O and adds to C A tetrahedral alkoxide ion intermediate is produced 26 Nucleophiles 27 Reactions variations 28 Relative Reactivity of Aldehydes and Ketones Aldehydes are generally more reactive than ketones in nucleophilic addition reactions The transition state for addition is less crowded and lower in energy for an aldehyde (a) than for a ketone (b) Aldehydes have one large substituent bonded to the C=O: ketones have two 29 Relative Reactivity of Aldehydes and Ketones Aldehydes are generally more reactive than ketones in nucleophilic addition reactions Aldehyde C=O is more polarized than ketone C=O Ketone has more electron donation alkyl groups, stabilizing the C=O carbon inductively 30 Reactivity of Aromatic Aldehydes Aromatic Aldehydes Less reactive in nucleophilic addition reactions than aliphatic aldehydes Electron-donating resonance effect of aromatic ring makes C=O less reactive electrophile than the carbonyl group of an aliphatic aldehyde 31 19.5 Nucleophilic Addition of H2O: Hydration Aldehydes and ketones react with water to yield 1,1-diols (geminal (gem) diols) Hydration is reversible: a gem diol can eliminate water 32 Base-Catalyzed Addition of Water Addition of water is catalyzed by both acid and base The basecatalyzed hydration nucleophile is the hydroxide ion, which is a much stronger nucleophile than water 33 Acid-Catalyzed Addition of Water Protonation of C=O makes it more electrophilic 34 Addition of H-Y to C=O Reaction of C=O with H-Y, where Y is electronegative, gives an addition product (“adduct”) Formation is readily reversible 35 19.6 Nucleophilic Addition of HCN: Cyanohydrin Formation Aldehydes and unhindered ketones react with HCN to yield cyanohydrins, RCH(OH)CN Addition of HCN is reversible and base-catalyzed, generating nucleophilic cyanide ion, CN- A cyanohydrin 36 Uses of Cyanohydrins The nitrile group (CN) can be reduced with LiAlH4 to yield a primary amine (RCH2NH2) Can be hydrolyzed by hot acid to yield a carboxylic acid 37 19.7 Nucleophilic Addition of Grignard Reagents and Hydride Reagents: Alcohol Formation Treatment of aldehydes or ketones with Grignard reagents yields an alcohol Nucleophilic addition of the equivalent of a carbon anion, or carbanion. A carbon–magnesium bond is strongly polarized, so a Grignard reagent reacts for all practical purposes as R : MgX +. 38 Mechanism of Addition of Grignard Reagents Complexation of C=O by Mg2+, Nucleophilic addition of R : , protonation by dilute acid yields the neutral alcohol Grignard additions are irreversible because a carbanion is not a leaving group 39 Hydride Addition Convert C=O to CH-OH LiAlH4 and NaBH4 react as donors of hydride ion Protonation after addition yields the alcohol 40 19.8 Nucleophilic Addition of Amines: Imine and Enamine Formation RNH2 adds to C=O to form imines, R2C=NR (after loss of HOH) R2NH yields enamines, R2NCR=CR2 (after loss of HOH) (ene + amine = unsaturated amine) 41 Mechanism of Formation of Imines Primary amine adds to C=O Proton is lost from N and adds to O to yield a neutral amino alcohol (carbinolamine) Protonation of OH converts into water as the leaving group Result is iminium ion, which loses proton Acid is required for loss of OH – too much acid blocks RNH2 42 Imine Derivatives: Addition of amines with an atom containing a lone pair of electrons on the adjacent atom occurs very readily, giving useful, stable imines. These are usually solids and help in characterizing liquid ketones or aldehydes by melting points For example, hydroxylamine forms oximes 2,4-dinitrophenylhydrazine readily forms 2,4dinitrophenylhydrazones 43 Enamine Formation After addition of R2NH, proton is lost from adjacent carbon 44 Imine / Enamine Examples 45 19.9 Nucleophilic Addition of Hydrazine: The Wolff–Kishner Reaction Treatment of an aldehyde or ketone with hydrazine, H2NNH2 and KOH converts the compound to an alkane Originally carried out at high temperatures but with dimethyl sulfoxide as solvent takes place near room temperature 46 The Wolff–Kishner Reaction: Examples 47 19.10 Nucleophilic Addition of Alcohols: Acetal Formation Alcohols are weak nucleophiles but acid promotes addition forming the conjugate acid of C=O Addition yields a hydroxy ether, called a hemiacetal (reversible); further reaction can occur Protonation of the OH and loss of water leads to an oxonium ion, R2C=OR+ to which a second alcohol adds to form the acetal 48 Acetal Formation 49 Uses of Acetals Acetals can be protecting groups for aldehydes & ketones Use a diol, to form a cyclic acetal (reaction goes faster) 50 19.11 Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction The sequence converts C=O C=C A phosphorus ylide adds to an aldehyde or ketone to yield a dipolar intermediate called a betaine The intermediate spontaneously decomposes through a four-membered ring to yield alkene and triphenylphosphine oxide, (Ph)3P=O An ylide 51 Mechanism of the Wittig Reaction 52 Uses of the Wittig Reaction Can be used for monosubstituted, disubstituted, and trisubstituted alkenes but not tetrasubstituted alkenes The reaction yields a pure alkene of known structure For comparison, addition of CH3MgBr to cyclohexanone and dehydration with, yields a mixture of two alkenes 53 19.12 The Cannizaro Reaction The adduct of an aldehyde and OH can transfer hydride ion to another aldehyde C=O resulting in a simultaneous oxidation and reduction (disproportionation) 54 19.13 Conjugate Nucleophilic Addition to Unsaturated Aldehydes and Ketones A nucleophile can add to the C=C double bond of an ,unsaturated aldehyde or ketone (conjugate addition, or 1,4 addition) The initial product is a resonancestabilized enolate ion, which is then protonated 55 Conjugate Addition of Amines Primary and secondary amines add to , -unsaturated aldehydes and ketones to yield -amino aldehydes and ketones Reversible so more stable product predominates 56 Conjugate Addition of Alkyl Groups: Organocopper Reactions Reaction of an , -unsaturated ketone with a lithium diorganocopper reagent Diorganocopper (Gilman) reagents form by reaction of 1 equivalent of cuprous iodide and 2 equivalents of organolithium 1, 2, 3 alkyl, aryl and alkenyl groups react but not alkynyl groups 57 Mechanism of Alkyl Conjugate Addition Conjugate nucleophilic addition of a diorganocopper anion, R2Cu, to an enone Transfer of an R group and elimination of a neutral organocopper species, RCu 58 19.14 Spectroscopy of Aldehydes and Ketones Infrared Spectroscopy Aldehydes and ketones show a strong C=O peak 1660 to 1770 cm1 aldehydes show two characteristic C–H absorptions in the 2720 to 2820 cm1 range. 59 C=O Peak Position in the IR Spectrum The precise position of the peak reveals the exact nature of the carbonyl group 60 NMR Spectra of Aldehydes Aldehyde proton signals are at 10 in 1H NMR - distinctive spin–spin coupling with protons on the neighboring carbon, J 3 Hz 61 13C NMR of C=O C=O signal is at 190 to 215 No other kinds of carbons absorb in this range 62 Mass Spectrometry – McLafferty Rearrangement Aliphatic aldehydes and ketones that have hydrogens on their gamma () carbon atoms rearrange as shown 63 Mass Spectroscopy: -Cleavage Cleavage of the bond between the carbonyl group and the carbon Yields a neutral radical and an oxygen-containing cation 64