Exam # 3 Study Guide Lectures March 2 to April 6 Chapter 16: Ketones and Aldehydes I. Nomenclature • the parent chain is the longest chain that contains the functional group a. Aldehydes – als - for an aldehyde, change the suffix from -e to -al - for an unsaturated aldehyde, change the infix from -an- to -en-; the location of the suffix determines the numbering pattern - for a cyclic molecule in which -CHO is bonded to the ring, add the suffix –carbaldehyde - the IUPAC retains the common names benzaldehyde and cinnamaldehyde, as well formaldehyde and acetaldehyde b. Ketones – ones • the parent alkane is the longest chain that contains the carbonyl group • indicate the ketone by changing the suffix -e to -one • number the chain to give C=O the smaller number CHM 262 1st EditionEdited with the trial version of Foxit Advanced PDF EditorTo remove this notice, visit:www.foxitsoftware.com/shopping• the IUPAC retains the common names acetone, acetophenone, and benzophenone c. Order of precedence - For compounds that contain more than one functional group indicated by a suffix II. Physical properties of the carbonyl a. Polarization • aldehydes and ketones are polar compounds and interact in the pure state by dipole-dipole interaction • they have higher boiling points and are more soluble in water than nonpolar compounds of comparable molecular weight i. Dipole-dipole interactions ii. Nucleophiles react at carbon iii. Electrophiles react at oxygen HCOOHOCOOHOCOOHHOOHHSCOOHNH2Functional GroupCarboxyl -oic acidAldehyde -al oxo-Ketone -one oxo-Alcohol -ol hydroxy-Amino -amine amino-3-Oxopropanoic acid3-Oxobutanoic acid4-Hydroxybutanoic acid3-Aminobutanoic acidExample when the functional group has a lower prioritySulfhydryl -thiol mercapto 2-MercaptoethanolSuffix if higherpriorityPrefix iflowerpriorityIncreasing precedenceiv. Addition reactions normally lead to racemic mixtures III. Addition of carbon nucleophiles - Addition of carbon nucleophiles is one of the most important types of nucleophilic additions to a C=O group • a new carbon-carbon bond is formed in the process a. Grignard reagents i. Electronic structure of Grignard reagents Given the difference in electronegativity between carbon and magnesium (2.5 - 1.3), the C-Mg bond is polar covalent, with Cd- and Mgd+ • in its reactions, a Grignard reagent behaves as a carbanion • Carbanion: an anion in which carbon has an unshared pair of electrons and bears a negative charge • a carbanion is a good nucleophile and adds to the carbonyl group of aldehydes and ketones ii. Addition to aldehydes and ketones • addition of a Grignard reagent to formaldehyde followed by H3O+ gives a 1° alcohol RMgXRLi- C RC C -NA GrignardreagentAn organolithiumreagentAn alkyneanionCyanide ion• addition to any other RCHO gives a 2° alcohol • addition to a ketone gives a 3° alcohol iii. Organolithium Organolithium compounds are generally more reactive in C=O addition reactions than RMgX, and typically give higher yields CH3CH2-MgBrOH-C-HO -[MgBr]+CH3CH2-CH2 HClH2OOHCH3CH2-CH2Mg2+ether1-Propanol(a 1° alcohol)Formaldehyde++A magnesiumalkoxideMgBrHOO -[MgBr]+HClH2OOHMg2++etherAcetaldehyde(an aldehyde)+A magnesiumalkoxide 1-Cyclohexylethanol(a 2° alcohol;(racemic)Ph-MgBrOPhO -[MgBr]+HClH2OPhOHMg2++Acetone(a ketone)ether+ A magnesiumalkoxide2-Phenyl-2-propanol(a 3° alcohol)Phenyl-magnesium bromideb. Salts of terminal alkynes Addition of an alkyne anion followed by H3O+ gives an a-acetylenic alcohol i. pKas of alkynes c. Addition of Cyanide (HCN) • HCN adds to the C=O group of an aldehyde or ketone to give a cyanohydrin i. Cyanohydrins o a molecule containing an -OH group and a -CN group bonded to the same carbon LiOO- Li+HClH2OOH3,3-Dimethyl-2- butanone3,3-Dimethyl-2-phenyl-2-butanol(racemic)+Phenyl-lithiumA lithium alkoxide(racemic)C:- Na+HCOC O -Na+HCHClH2OCOHHC1-Ethynyl-cyclohexanolA sodiumalkoxide+CyclohexanoneSodiumacetylideH2OHOCCHH2SO4, HgSO41. (sia)2BH2. H2O2, NaOHOHOCCH3HOCH2CHOAn -hydroxyketoneA -hydroxyaldehydeii. Mechanism of cyanohydrin formation iii. dehydration • acid-catalyzed dehydration of alcohol gives an alkene iv. hydrogenation (hydroxy amines) • catalytic reduction of the cyano group gives a 1° amine d. Wittig reaction • The Wittig reaction is a very versatile synthetic method for the synthesis of alkenes from aldehydes and ketones Propenenitrile(Acrylonitrile)+ acidcatalyst 2-Hydroxypropanenitrile(Acetaldehyde cyanohydrin)CH3CHC N NCH2=CHC H2OOHCHCOHN 2H2NiOHCHCH2NH22-Amino-1-phenylethanol(racemic)+Benzaldehydecyanohydrin(racemic)Triphenyl-phosphine oxideMethylene-cyclohexaneA phosphoniumylide++-+CH2Ph3P=OPh3P-CH2CyclohexanoneOi. Phosphonium ylides Phosphonium ylides are formed in two steps: 1. Nucleophilic substitution by triphenylphosphine 2. Deprotonation with butyllithium (BuLi) or another very strong base, most commonly NaH, or NaNH2 ii. Addition to carbonyls o Phosphonium ylides react with the C=O group of an aldehyde or ketone to give an alkene Step 1: nucleophilic addition of the ylide to the electrophilic carbonyl carbon Step 2: decomposition of the oxaphosphatane iii. Z or E isomers can be formed • some Wittig reactions are Z selective, others are E selective Ph3P CH3-IPh3P-CH3ITriphenylphosphine++SN2Methyltriphenylphosphonium iodide(an alkyltriphenylphosphine salt)CH3CH2CH2CH2 - Li +H-CH2-PPh3 I-- CH2-PPh3CH3CH2CH2CH3LiIA phosphoniumylideButaneButyllithium+++++CR2OCH2Ph3PCH2-:O CR2Ph3PO CR2Ph3P CH2-+An oxaphosphetane+ A betaineCH2O CR2Ph3PPh3P=OR2C=CH2An alkene+Triphenylphosphineoxide1. Wittig reagents with an anion-stabilizing group, such as a carbonyl group, adjacent to the negative charge are generally E selective • 2. Wittig reagents without an anion-stabilizing group are generally Z selective iv. Horner-Emmons-Wadsworth uses (MeO)3P 1. Phosphonoesters  phosphonoesters are prepared by successive SN2 reactions  treatment of a phosphonoester with a strong base followed by an aldehyde or ketone gives an alkene 2. E selective  a particular value of using a phosphonoester-stabilized anion is that they are almost exclusively E selective Br-CH2-C-OEtO(MeO)3PBr-CH2-C-RO(MeO)2P-CH2-C-ROO(MeO)2P-CH2-C-OEtOOMeBrMeBran -bromoesteran -bromoketone++An -phosphonoesterAn -phosphonoketoneTrimethyl-phosphite(MeO)3P