ALDEHYDES & KETONES (ALKANALS & ALKANONES) 1 ALDEHYDES & KETONES (ALKANALS & ALKANONES) : O: R :O: C H R C R' ketone aldehyde : O: Aldehydes & ketones both contain the carbonyl group. C carbonyl group The simplest aldehyde is formaldehyde (CH2O). It is the only aldehyde without an alkyl group attached to the carbonyl C. : O: H C All other aldehydes, such as acetaldehyde (CH3CHO), have one alkyl group and one H attached to the carbonyl C. H formaldehyde : O: CH3 C H acetaldehyde All ketones have two alkyl groups attached to the carbonyl C. H3C : O: : O: C C CH3 dimethyl ketone (acetone) H3C : O: CH2CH3 methyl ethyl ketone (MEK) C CH3 methyl phenyl ketone (acetophenone) 2 Aldehydes and Ketones are Electrophiles Nu:- The carbonyl group has a strong dipole. : O: d DEN(O-C) = (3.5-2.5) = 1.0 (a polar bond) d+ C The d+ carbon is an electron acceptor, E+ (an electrophile). Good nucleophiles (CH3MgBr) and even fair nucleophiles (NH3) will readily add to the carbonyl group of aldehydes and ketones. tetrahedral .. alkoxide : O : : O: R sp2 C C R H Nu: - 3 sp Nu R The weak p bond breaks as the Nu:- adds, so that C remains tetravalent ( 5 bonds). The alkyl group and the H atom bonded to the carbonyl are not leaving groups. They are not displaced because hydride (H:-) and alkanides (R:-) are extremely strong bases. pKb H:- = -21 and pKb :CH3- = -40! (:CH3- = methide). 3 Aldehydes and Ketones are Electrophiles Aldehydes and ketones are moderately reactive as electrophiles (electron acceptors) among the carboxylic acid derivatives. :O: R C .. O .. acid chloride : O: R C C : O: R C .. OH .. C N: most reactive : O: R R C .. Cl .. : acid anhydride C H ketone ester :O: R carboxylic acid amide R R aldehyde : O: R : O: :O: R C :O: nitrile carboxylate C R C .. O .. .. R H N H .. _ O ..: least reactive 4 Basicity of Aldehydes and Ketones Nu:- The d- oxygen is a weak base (pKb ca. 21) Its non bonded e’s are protonated by strong acids. R C H HSO4- R R C E+ : O: : O+ + + d C H H : O: : O: d R R C + R The + charge is shared with the carbonyl C by resonance forming a carbocation – a very good E+. Even weak Nu:-’s (like H2O and ROH) will donate electrons to an aldehyde or ketone in the presence of a strong acid catalyst, e.g., H2SO4 or HCl. : O: R C H H H R : O: : O: + HSO4R C + R .. CH3CH2OH .. R C R + CH3CH2OH .. 5 Acidity of Aldehydes and Ketones The a-carbon is the carbon bonded to the carbonyl, not the carbonyl carbon itself. Hydrogens bonded to the carbonyl carbon, the a-carbon, the b-carbon, etc. are not polar and thus are not acidic hydrogens. pKa = ca. 55 for b-hydrogens in aldehydes and ketones H H :O : H b C C H a-hydrogens pKa = ca. 17 in aldehydes pKa = ca. 19 in ketones a C H H The carbonyl H of an aldehyde is not acidic. It's pKa is ca. 50. The a-hydrogens can be removed by strong bases because the carbanion that forms is stabilized by resonance with the adjacent carbonyl oxygen forming an enolate. H H H b C :O : H C H a C H H OH- C H H H :O : C .. C .. H H C H H H :O : C C enolate H 6 Boiling Points and Solubility of Aldehydes and Ketones The carbonyl group is strongly polar but does not produce hydrogen bonding (It has no polar hydrogens). As a result, the boiling points of aldehydes and ketones are higher than the nonpolar hydrocarbons and the alkyl halides but lower than those of alcohols. Formaldehyde is a gas at room temperature (b.p. = -21 C) but heavier aldehydes are liquids. Acetone, the simplest ketone, is a liquid at room temperature (b.p. = 56 C). Lower molecular weight aldehydes and ketones are water soluble. Acetone, formaldehyde and acetaldehyde are miscible in water. 7 IUPAC Nomenclature of Aldehydes Aldehydes: in open chains: alkane+al “alkanal” OH O CH3CHBrCH2C H 4 3 2 1 3-bromobutanal O O CH2C H CH3CHCH2CH2C H 5 4 3 2 2 1 4-hydroxypentanal 1 2-phenylethanal The parent chain must contain the CHO- group, and this group is numbered as carbon 1 (because it is always at a chain end). Aldehydes: attached to rings: ring+carbaldehyde “ringcarbaldehyde” O O C H C H benzenecarbaldehyde HO CHO 3-hydroxycyclopentanecarbaldehyde cyclohexanecarbaldehyde 8 Functional Group Precedence in Nomenclature Functional Group Name as Suffix Name as Prefix Carboxylic Acids -oic acid –carboxylic acid carboxy Acid Anhydrides -oic anhydride -carboxylic anhydride Esters -oate -carboxylate alkoxycarbonyl Acid Halides -oyl halide -carbonyl halide halocarbonyl Amides -amide -carboxamide amido Nitriles -nitrile -carbonitrile cyano Aldehydes -al -carbaldehyde oxo Ketones -one oxo Alcohols -ol hydroxy Phenols -ol hydroxy Thiols -thiol mercapto Amines -amine amino Imines -imine imino Alkenes -ene alkenyl Alkynes -yne alkynyl Alkanes -ane alkyl Principal Groups 9 Common Names of Aldehydes In the common system, aldehydes are named from the common names of the corresponding carboxylic acid. The ‘ic acid’ ending is replaced with ‘aldehyde’. Structure IUPAC name HCO2H methanoic acid CH3CO2H ethanoic acid CH3CH2CO2H propanoic acid CH3(CH2)2CO2H butanoic acid CH3(CH2)3CO2H pentanoic acid CH3(CH2)4CO2H hexanoic acid Common name Structure IUPAC Common name formic acid acetic acid propionic acid butyric acid valeric acid caproic acid HCHO methanal CH3CHO ethanal CH3CH2CHO propanal CH3(CH2)2CHO butanal CH3(CH2)3CHO pentanal CH3(CH2)4CHO hexanal formaldehyde acetaldehyde propionaldehyde butyraldehyde valeraldehyde caproaldehyde Substituents locations are given using Greek letters (a, b, , d, , .) beginning with the carbon next to the carbonyl carbon, the a-carbon. O CH3CHBrCH2C H b a b-bromobutyraldehyde OH O O CH3CHCH2CH2C H d b a -hydroxyvaleraldehyde CH2C H a a-phenylacetaldehyde 10 IUPAC Nomenclature of Ketones Ketones: in both open chains and rings: alkane+one “alkanone” The parent chain must contain the C=O group , and this chain is numbered to give the carbonyl group as low a number as possible. In cyclic ketones, the carbonyl group is assigned the number ‘1’. O4 5 CH3 CHCCHCH3 1 O CH3 CCH2 CH3 1 4 2 3 2-butanone 2 O Cl C CH2 CH2 CH3 1 2 3 4 CH3 2-chloro-4-methyl-3-pentanone 1-phenyl-1-butanone Ketones are just below aldehydes in nomenclature priority. A ketone group is named as an ‘oxo’ substituent in an aldehyde. O CH3CH2CCH2CHO 5 4 3 2 1 3-oxopentanal H3C 4 1 O An olefinic ketone is named 2 3 as an ‘enone’, literally: 4-methyl-2-cyclohexen-1-one “#-alken-#-one”. 11 Common Names of Ketones :O: The two alkyl groups attached to the carbonyl are named and the word ‘ketone’ is added as a R C R' separate word. It is literally ‘alkyl alkyl ketone’. The alkyl groups are listed alphabetically or in alkyl alkyl ketone order of increasing size. As with aldehydes, substituents locations are given in common names using Greek letters (a, b, , d, , .) beginning with the a-carbon. O CH3 CH3CCH2CHCH3 b a O CH3CHCCHCH3 Cl CH3 methyl isobutyl ketone a-chloroethyl isopropyl ketone (MIBK) Some historic names persist: O OCH3 C CH2CH2CH2 a b -methoxypropyl phenyl ketone O O O C CH3 C C H acetophenone benzophenone benzaldehyde 12 Nomenclature Practice Name these in IUPAC and, where possible, common nomenclature. O CH2 C O F CH3 C (I) 1-phenyl-2-propanone O C H H (I) 4-fluorocyclohexane-1-carbaldehyde (I) 3-cylcopentene-1-carbaldehyde (c) methyl benzyl ketone Draw the structures of the following compounds. butanedial bromomethyl b-bromoethyl ketone 2,4-pentanedione O O O HCCH2CH2CH BrCH2 C O CH2CH2Br H3C C O And these: CH3CH CH C (I) 2-butenal O CH2 C CH3 O H CH2 CH C CH3 (I) 3-buten-2-one (c) methyl vinyl ketone 13 Preparation of Aldehydes (2 Methods) 1. Mild oxidation of 1° Alcohols: (with anhydrous oxidants, PCC in CHCl2 or Collins reagent (CrO3 in pyridine). 1,3-cyclobutanedicarbaldehyde HOCH2 2. CH2OH PCC in CH2Cl2 O O HC CH Dry ice (solid CO2) sublimes at –78°C. Reduction of acid chlorides,esters, and nitriles. : O: acid chloride R C .. Cl : .. -78°C 1equiv. R : O: ester nitrile R R C C : O: .. .. OR N: 1 DIBAH + 2 H3O C aldehyde H Only 1 equivalent of very cold DIBAH is used to avoid further reduction of the aldehyde to an alcohol. 14 Preparation of Aldehydes (2 Methods) Recall that 1° alcohols are readily oxidized to carboxylic acids by most oxidants in aqueous media. moderate to strong oxidation (Cr+6, HNO3, KMnO4, etc.) R OH 1° alcohol mild oxidation CrO3 in N or PCC in CH2Cl2 R C : O: moderate to strong oxidation : O: R H aldehyde Jones reagent CrO3 in H2SO4 C .. .. OH carboxylic acid 1 LiAlH4 + 2 H3O In non aqueous media, moderate to strong oxidants become mild, oxidizing 1° alcohols only as far as the aldehyde. Carboxylic acids can be reduced to 1° alcohols with LiAlH4, but no reagent has been found that will stop the reduction at the aldehyde. 15 Preparation of Aldehydes (2 Methods) Carboxylic acids are difficult to reduce and any reducing agent strong enough to reduce them, e.g., LiAlH4, will not stop at the aldehyde but always produces the 1° alcohol. Several ‘derivatives’ of carboxylic acids can be reduced to aldehydes under carefully controlled conditions. Acid chlorides, esters, and nitriles are reduced to aldehydes using very cold conditions (-78°C) and only 1 equivalent of a mild reducing agent, ‘diisobutylaluminum hydride’ = DIBAH (usually in toluene). CH3 H CH3CHCH2 Al CH3 CH3 CH2CHCH3 CH3CHCH2 + Al diisobutyl aluminum hydride (DIBAH) CH3 CH2CHCH3 + H: _ H Al H H aluminum hydride DIBAH is weaker than LiAlH4. DIBAH is neutral; LiAlH4 is ionic. DIBAH is similar to AlH3 but is hindered by its bulky isobutyl groups. Only one mole of H:- is released per mole of DIBAH. 16 Preparation of Aldehydes (2 Methods) Study the following examples and note which groups are displaced by the hydride (H:-) from DIBAH. O CH3CH2 C O CH3 methyl propanoate toluene 1. DIBAH -78ºC propanal CH3CH2 + O C H + CH3OH 2. H3O O _ _ HCl NH3 CH3CH2C propanenitrile CH3CH2 C Cl propanoyl chloride a) Write equations showing the preparation of: pentanal from 1-pentanol CH3CH2CH2CH2CH2OH b) butanal from an ester c) benzaldehyde from a nitrile C CH3CH2CH2CH2CH CrO3 in N -78°C 1equiv. CH3CH2CH2COCH3 -78°C 1equiv. 1 DIBAH + 2 H3O O C O PCC in CH2Cl2 or O N N 1 DIBAH + 2 H3O O CH3CH2CH2CH H 17 Preparation of Ketones (4 Methods) 1. Oxidation of 2° Alcohols: with mild (anhydrous) oxidants, moderate, or strong oxidants, e.g., H2CrO4, HNO3, KMnO4, NaOCl, etc. (CH3 )3 C PCC (CH3 )3 C OH or Jones reagent 2. O 4-t-butylcyclohexanone Friedel Crafts Acylation of Aromatics: yields ketones when an acid chloride is used as the electrophile. O O + HO CH3CH2 C AlCl3 propanoyl chloride 3. HO Cl EAS C CH2CH3 1-(4-hydroxyphenyl)propanone Hydration of Alkynes: with Hg+2 and H3O+ yields an enol, that ‘tautomerizes’ to a ketone. Hg(OAc)2 CH3 (CH2)3 C 1-hexyne CH + H3O O CH3 (CH2)3 C an enol H CH H O CH3 (CH2)3 C 2-octanone H CH H 18 Preparation of Ketones (4 Methods) 4. Acid Chlorides + Lithium Dialkyl Copper (Gilman Reagent): produces ketones. The reaction is unique to these two reagents and the mechanism is uncertain. As with DIBAH for aldehyde reductions, a low temperature (78 C) solvent (ether) is used to prevent further alkyl addition to the ketone to form an alcohol. (Acid chlorides are very good electrophiles). Carboxylic acids, esters, anhydrides and amides are not reduced by diorganocopper reagents. They are not as reactive as acid chlorides. O CH3 (CH2)4 C Cl dimethyl copper lithium Gilman reagent hexanoyl chloride O ether CH3 (CH2)4 C CH3 2-heptanone Recall that a stronger reducing reagent, such as a Grignard (RMgBr) will also reduce an acid chloride to a ketone, but reduction cannot be stopped here. The ketone is further reduced to an alcohol. .. : O: R (CH3)2 Cu- Li+ + - 78ºC C .. Cl : .. acid chloride .. CH3MgBr R C :O :O: : O: CH3MgBr CH3 ketone R C alkoxide CH3 + 2 H3O CH3 R C 3° alcohol CH3 H CH3 19 Preparation of Ketones Problems Write equations to show how the following transformations can be carried out. Show all reagents and intermediate products. a) 3-hexyne 3-hexanone CH3CH2C CCH2CH3 CH3CH2C +2 + H : O: 3-hexanone H3C .. Cl : .. C O C AlCl3 MgBr H C Br CH CH3 1 BH3, THF 2 NaOH, H2O2, pH8 CH3 OH CCH2CH3 H O C CH3 + HBr m-bromoacetophenone .. :OH H3O+ CH CH3 CH3 Cr+6, H+ +6 + O C CH3 acetophenone 1-methylcyclohexene 2-methylcyclohexanone CH3 H CH3 acetophenone bromobenzene acetophenone .. :O: : O: Br Mg in ether FeBr3 Br2 acetyl chloride d) CH3CH2C benzene m-bromoacetophenone + c) CCH2CH3 Hg , H3O 3-hexyne b) O OH CH3 Cr , H O 20 Preparation of Ketones Problems Recall the effects of substituents on aromatic rings. They affect both the reactivity of aromatics and the position at which Electrophilic Aromatic Substitution (EAS) will occur. o- and pdirecting NH2 OCH3 o- and pdirecting F CH3 m-directing Br O O CH C OH O NH C CH3 activators NO2 Reactivity Reactivity OH SO3H H Cl deactivators I O O COCH3 C CH3 C N + N R3 deactivators 21