Ketones and Aldehydes The carbonyl group is of central importance in organic chemistry because of its ubiquity Without studying the carbonyl group in depth we have already encountered numerous examples of this functional group (ketones,aldehydes,carboxylic acids,acid chlorides.etc). The simplest carbonyl compounds are aldehydes and ketone. A ketone has two alkyl (or aryl)groups bonded to the carbonyl carbon. 0 R-C-H R-C-R aldehyde ketone An aldehyde has one alkyl (or aryl)group and one hydrogen bonded to the carbonyl carbon. Structure of the carbonyl group The carbonyl carbon is sp'hybridized,and has a partially filled unhybridized p orbital perpendicular to the o framework. length energy ketone C=0 bond 1.23A 178 kcal/mol (745 kJ/mol) alkene C=C bond 1.34 146 kcal/mol (611 kJ/mol) Chl8 Ketones and Aldehydes (landscape) Page I
Ch18 Ketones and Aldehydes (landscape) Page 1 Ketones and Aldehydes The carbonyl group is of central importance in organic chemistry because of its ubiquity. Without studying the carbonyl group in depth we have already encountered numerous examples of this functional group (ketones, aldehydes, carboxylic acids, acid chlorides, etc). The simplest carbonyl compounds are aldehydes and ketone. A ketone has two alkyl (or aryl) groups bonded to the carbonyl carbon. An aldehyde has one alkyl (or aryl) group and one hydrogen bonded to the carbonyl carbon. Structure of the carbonyl group The carbonyl carbon is sp2 hybridized, and has a partially filled unhybridized p orbital perpendicular to the framework. R C H O R C R O aldehyde ketone
The oxygen is also sp hybridized,with the 2 lone pairs occupying sp'orbitals.This leaves one electron in a p orbital. These p orbitals form the carbon oxygen bond. The C=O double bond is like a C=C double bond except the carbonyl double bond is shorter and stronger. The carbonyl group has a large dipole moment due to the polarity of the double bond. Oxygen is more electronegative than carbon,and so the bond is polarized toward the oxygen. The attraction of the weakly held nt electrons toward oxygen can be represented by the two following resonance structures. R major minor The first resonance structure is the major contributor,but the other contributes in a small amount,which helps explain the dipole moment. It is this polarization that creates the reactivity of the carbonyl groups(carbon is electrophilic/LA,and the oxygen is nucleophilic/LB). Chl8 Ketones and Aldehydes (landscape) Page 2
Ch18 Ketones and Aldehydes (landscape) Page 2 The oxygen is also sp2 hybridized, with the 2 lone pairs occupying sp2 orbitals. This leaves one electron in a p orbital. These p orbitals form the carbon oxygen bond. The C=O double bond is like a C=C double bond except the carbonyl double bond is shorter and stronger. The carbonyl group has a large dipole moment due to the polarity of the double bond. Oxygen is more electronegative than carbon, and so the bond is polarized toward the oxygen. The attraction of the weakly held electrons toward oxygen can be represented by the two following resonance structures. The first resonance structure is the major contributor, but the other contributes in a small amount, which helps explain the dipole moment. It is this polarization that creates the reactivity of the carbonyl groups (carbon is electrophilic/LA, and the oxygen is nucleophilic/LB)
Nomenclature IUPAC nomenclature requires ketones to be named by replacing the -e ending of the alkyl name with -one Alkane-→alkanone Eg CH;O CH CH- -CH2一CH CH-CH-C-CH-CH CH2一CH 1 old IUPAC names in blue: 2-butanone 2.4-dimethyl-3-pentanone 1-phenyl-1-propanone new IUPAC names in green: butan-2-one 2.4-dimethylpentan-3-one 1-phenylpropan-1-one 0 OH CH3一C-CH2一C一CH CH CH 3-methylcyclopentanone 2-cyclohexenone 4-hydroxy-4-methyl-2-pentanone cyclohex-2-en-1-one 4-hydroxy-4-methylpentan-2-one Chl8 Ketones and Aldehydes (landscape) Page3
Ch18 Ketones and Aldehydes (landscape) Page 3 Nomenclature IUPAC nomenclature requires ketones to be named by replacing the -e ending of the alkyl name with -one. Alkane alkanone E.g
Systematic names for aldehydes are obtained by replacing -e with-al. An aldehyde has to be at the end of a chain,and therefore it is carbon number 1. 0 CHg-C-H H3C-CH2-CH=CH-CHO ethanal pent-2-enal If the aldehyde is attached to a large unit,the suffix-carbaldehyde is used. CHO cyclohexanecarbaldehyde Chl8 Ketones and Aldehydes(landscape) Page 4
Ch18 Ketones and Aldehydes (landscape) Page 4 Systematic names for aldehydes are obtained by replacing -e with -al. An aldehyde has to be at the end of a chain, and therefore it is carbon number 1. If the aldehyde is attached to a large unit, the suffix -carbaldehyde is used. CH3 C H O H3C CH2 CH CH CHO ethanal pent-2-enal CHO cyclohexanecarbaldehyde
A ketone or aldehyde group can also be named as a substituent on a molecule with another functional group as its root. The ketone carbonyl is given the prefix oxo-,and the aldehyde group is named as a formyl-group.(Especially common for carboxylic acids). 0 CH CH2-C-CH2-CHO HgC-C-CH2-CO2H CO,H 3-oxopentanal 2-formylbenzoic acid 3-oxobutanoic acid Common Names The wide spread use of carbonyl compounds means many common names are entrenched in their everyday use. E.g. 0 HgC-C-CH acetone acetophenone benzophenone Chl8 Ketones and Aldehydes (landscape) Page 5
Ch18 Ketones and Aldehydes (landscape) Page 5 A ketone or aldehyde group can also be named as a substituent on a molecule with another functional group as its root. The ketone carbonyl is given the prefix oxo-, and the aldehyde group is named as a formyl- group. (Especially common for carboxylic acids). Common Names The wide spread use of carbonyl compounds means many common names are entrenched in their everyday use. E.g. CH3CH2 C CH2 -CHO O 3-oxopentanal C CO2H O H H3C C O CH2 -CO2H 2-formylbenzoic acid 3-oxobutanoic acid H3C C CH3 O acetone C O CH3 acetophenone C O benzophenone
Syntheses of the Aldehydes and Ketones(Recap?) From Alcohols (Ch 11) Secondary alcohols are readily oxidized to ketones by Chromic acid (or KmnO4). Na2Cr2O7 H2S04 borneol camphor Complicated ketones can be made by the oxidation of alcohols,which in turn can be made from reaction of a Grignard and an aldehyde OH Na2Cr207 0 R-MgBr R-C-H- R'-C-H 分 H2S04 R'-C-R Aldehydes are made from the oxidation of primary alcohols.This oxidation needs to be done carefully to avoid overoxidation to carboxylic acids. PCC CH2-OH CHO This is achieved by the use of PCC Chl8 Ketones and Aldehydes (landscape) Page 6
Ch18 Ketones and Aldehydes (landscape) Page 6 Syntheses of the Aldehydes and Ketones (Recap?) From Alcohols (Ch 11) Secondary alcohols are readily oxidized to ketones by Chromic acid (or KmnO4). Complicated ketones can be made by the oxidation of alcohols, which in turn can be made from reaction of a Grignard and an aldehyde. Aldehydes are made from the oxidation of primary alcohols. This oxidation needs to be done carefully to avoid overoxidation to carboxylic acids. This is achieved by the use of PCC. H OH O borneol camphor Na2Cr2O7 H2SO4 R MgBr + R' C H O R' C OH R H R' C R O H2SO4 Na2Cr2O7 CH2 -OH CHO PCC
Ozonolysis(Ch 8) Alkenes can be cleaved by ozone(followed by a mild reduction)to generate aldehydes and/or ketones. CH3 (1)03 (2)CH3SCH3 Phenyl Ketones and Aldehydes(Ch 17) Friedal Crafts acylation is an excellent method for the preparation of alkyl aryl ketones. 02N para-nitrobenzophenone The Gatterman-Koch reaction produces benzaldehyde systems. CO,HCI CH CuCl,AICl Chl8 Ketones and Aldehydes(landscape) Page 7
Ch18 Ketones and Aldehydes (landscape) Page 7 Ozonolysis (Ch 8) Alkenes can be cleaved by ozone (followed by a mild reduction) to generate aldehydes and/or ketones. Phenyl Ketones and Aldehydes (Ch 17) Friedal Crafts acylation is an excellent method for the preparation of alkyl aryl ketones. The Gatterman-Koch reaction produces benzaldehyde systems. CH3 (1) O3 (2) CH3SCH3 O O CH3 H C O Cl O2N + C O O2N para-nitrobenzophenone AlCl3 CH O CO, HCl CuCl, AlCl3
Hydration of Alkynes(Ch 9) Hydration of alkynes can either be achieved with Markovnikov (acid and mercury(II)catalyzed reaction)or anti- Markovnikov (hydroboration-oxidation)regiochemistry. Hg2+,H2S04 HO H C≡C-H C=C-H C-CHg H20 enol In both cases the enols produced rearrange to their more stable keto forms(in the hydroboration case the keto form is an aldehyde). C=C-H (1)Sia2BH H OH C=C-H -cn-8-m (2②H202 Na●H enol Chl8 Ketones and Aldehydes (landscape) Page 8
Ch18 Ketones and Aldehydes (landscape) Page 8 Hydration of Alkynes (Ch 9) Hydration of alkynes can either be achieved with Markovnikov (acid and mercury (II) catalyzed reaction) or antiMarkovnikov (hydroboration-oxidation) regiochemistry. In both cases the enols produced rearrange to their more stable keto forms (in the hydroboration case the keto form is an aldehyde). C C H Hg 2+ , H2SO4 H2O C C H enol HO H C O CH3 C C H C C H enol H OH CH2 (1) Sia2BH (2) H2O2 NaOH C O H
Other Syntheses of Aldehydes and Ketones Use of 1,3-Dithiane Dithiane has relatively acidic hydrogens located between the two sulfur atoms,and these can be removed by a strong base. The anion is stabilized by the electron withdrawing effect of the highly polarizable sulfur atoms. CaHg-Li +C4H10 H The dithiane anion can react as a nucleophile with primary alkyl halides,and this alkylation generates a thioacetal H",HgCl 0 R一X H20 R H The hydrolysis of a thioacetal generates an aldehyde. Alternatively,the thioacetal can be further deprotonated and reacted with another(different)alkyl halide to generate a new thioacetal with two alkyl substituents.On hydrolysis,this thioacetal produces a ketone. (1)BuLi H",HgCl2 (2)R-X H2O R R Chl8 Ketones and Aldehydes (landscape) Page 9
Ch18 Ketones and Aldehydes (landscape) Page 9 Other Syntheses of Aldehydes and Ketones Use of 1,3-Dithiane Dithiane has relatively acidic hydrogens located between the two sulfur atoms, and these can be removed by a strong base. The anion is stabilized by the electron withdrawing effect of the highly polarizable sulfur atoms. The dithiane anion can react as a nucleophile with primary alkyl halides, and this alkylation generates a thioacetal. The hydrolysis of a thioacetal generates an aldehyde. Alternatively, the thioacetal can be further deprotonated and reacted with another (different) alkyl halide to generate a new thioacetal with two alkyl substituents. On hydrolysis, this thioacetal produces a ketone. H + , HgCl2 H2O R R' (1) BuLi O (2) R'-X S S R H S S R R
This is a good route for the construction of unsymmetrical ketones. Eg (1)BuLi (1)BuLi H*,HgCl2 (2)PhCH,Br (2)CHaBr H2O HaC CH2Ph H CH2Ph CH2Ph The dithiane can be thought of as a"masked"carbonyl group. Ketones from Carboxylic Acids Organolithium reagents are very reactive towards carbonyl compounds. So much so,that they even attack the lithium salts of carboxylate anions. These dianions can then be protonated,which generates hydrates,which then lose water and produce ketones E.g OH R-C-OH LiOH R-C-0-+Li R'-Li HO+ H20 -O-Li+ OH R-C-R carboxylic acid lithium carboxylate dianion hydrate ketone 92的rn6中enn Chl8 Ketones and Aldehydes (landscape) Page 10
Ch18 Ketones and Aldehydes (landscape) Page 10 This is a good route for the construction of unsymmetrical ketones. E.g. The dithiane can be thought of as a "masked" carbonyl group. Ketones from Carboxylic Acids Organolithium reagents are very reactive towards carbonyl compounds. So much so, that they even attack the lithium salts of carboxylate anions. These dianions can then be protonated, which generates hydrates, which then lose water and produce ketones. E.g. H + , HgCl2 H2O H3C CH2Ph (1) BuLi O S S (2) PhCH2Br S S H CH2Ph (1) BuLi (2) CH3Br S S H3C CH2Ph