Aldehydes and Ketones - Lecture Notes | CH 332, Study notes of Organic Chemistry

Download Aldehydes and Ketones - Lecture Notes | CH 332 and more Study notes Organic Chemistry in PDF only on Docsity! Aldehydes & Ketones - Page 1 Chapter 16 Aldehydes and Ketones Contain the CARBONYL GROUP O C R H Aldehyde O C R R' Ketone Structure of FORMALDEHYDE: O C H H 121.8o 116.4o 1.203 A 1.101 A o o Planar sp2 hybridized Aldehydes & Ketones - Page 2 Aldehydes - Common Nomenclature Derived from the names of the carboxylic acids. Examples: O C H OH Formic acid O C H H Formaldehyde O C CH3CH2 OH Propionic acid O C CH3CH2 H Propionaldehyde O C CH OH CH3 CH3 Isobutyric acid O C CH H CH3 CH3 Isobutyraldehyde O C OH Benzoic acid O C H Benzaldehyde Aldehydes & Ketones - Page 5 Ketones - IUPAC Nomenclature The longest chain carrying the carbonyl group is considered the parent structure. The final “-e” of the parent alkane is dropped and “-one” is added. Positions are designated with numbers. Examples: O C CH3 CH2CH3 Butanone CH3 CH2 CH CH2 CH3 CH2 C O CH2 CH3 5-Ethyl-3-heptanone OCH3 3-Methylcyclohexanone Aldehydes & Ketones - Page 6 Physical Properties The carbonyl group is POLAR: O Cδ+ δ− They can participate in intermolecular dipole-dipole attractions: O C C Oδ+ δ− δ− δ+ Thus, aldehydes and ketones have higher boiling points and melting points than hydrocarbons of similar molecular weights. The dipolar nature of the C=O group makes is a good polar organic solvent for polar molecules and (in some cases) ions. Examples: H2O is soluble in acetone NaI is soluble in acetone Aldehydes & Ketones - Page 7 Oxygen lone pairs can participate in hydrogen- bonding: O C O H H But, they can't hydrogen-bond with each other. Thus, boiling points and melting points tend to be lower than alcohols of similar molecular weights. As the alkyl or aryl substituents become large, solubility in H2O decreases. Example: CH3 C O Slightly soluble in H2O C O Insoluble in H2O Aldehydes & Ketones - Page 10 Example: O3 O OO H HH Zn aq HOAc CHO + H2CO 6-methyl-1-heptene 5-methylhexanal (62% yield) • Oxidative Cleavage of Glycols R CH C OH OH C O R H O C [O] + Use NaIO4 / H2O or Pb(OAc)4 / HOAc Example: KMnO4 (cold) OR aq. peracid OH OH CHOPb(OAc)4 HOAc + H2CO Aldehydes & Ketones - Page 11 • Oxidation of Methylbenzenes [O] Ar CH3 O C Ar H Use CrO3 / Ac2O Example: NO2 CH3 NO2 CH OCOCH3 OCOCH3 NO2 CH OH OH NO2 C HO CH3 C O C CH3 O O CrO3 H3O (−2 HOAc) −H2O Aldehydes & Ketones - Page 12 • Reduction of Carboxylic Acid Derivatives Acid chlorides: O C R Cl O C R H [H] Use H2 / cat or LiAlH(OBu-t)3 Examples: CH2 C Cl O CH2 C H O H2 / toluene Pd-BaSO4-S LiAlH(OBu-t)3 Et2O / -78 oC C H O C Cl O Aldehydes & Ketones - Page 15 Preparation of Ketones • Oxidation of Secondary Alcohols R CH R' OH O C R R' [O] Use K2Cr2O7 / H2SO4 CrO3 KMnO4 / OH - • Oxidation of Alkenes C C R R' O3 Zn H2O / HOAc C R R' O CO+ Example: 1) O3 2) Zn / aq HOAc O + H2CO Aldehydes & Ketones - Page 16 • Oxidative Cleavage of Glycols R C R' OH C OH O C R R' O C NaIO4 + Example: NaIO4 C O HO CH2 C O HO O C O HO OH CH2OHKMnO4 cold + H2CO Aldehydes & Ketones - Page 17 • Friedel-Crafts Acylation of Aromatic Compounds O C R Cl O C R Ar + ArH AlCl3 Mechanism: O C R Cl O C R Cl AlCl3 O C R Cl AlCl3 R C O R C O H C R O C R O + AlCl3 δ+ δ− δ+ δ− AlCl4 AlCl4 Example: O C CH3 Cl C CH3 O + AlCl3+ Aldehydes & Ketones - Page 20 N M C R R' O C R R' R' M+R C N H3O Use R'-MgX or R'-Li Examples: CH3 O CH2 C N MgBr C O CH2 O CH3 + Et2O H3O (78% yield) H3O CH2 CH3 CN CH2 CH3 C CH3 O CH3Li (91% yield) Aldehydes & Ketones - Page 21 Reactions of Aldehydes and Ketones The chemistry of carbonyl compounds may be divided into two mechanistic categories: 1. Nucleophilic attack at the carbonyl carbon 1. Reactions involving the acidic α-protons (enolization) O C C H δ+ δ− α Nucleophilic Addition δ+ δ−O C R R' Nu: O C R R' Nu trigonal sp2 tetrahedral sp3 Aldehydes & Ketones - Page 22 May be acid catalyzed - to make the carbonyl carbon more electrophilic (in case the nucleophile is weakly nucleophilic): O C R R' O C R R' H O C R R' H O CR R' Nu H H Nu: • Hydration (Nucleophilic addition of H2O) acetone hydrate (a gem diol) CH3 C OH OH CH3 O CCH3 CH3 O H H O C CH3 CH3 O H H If the carbonyl is very electrophilic: O C CCl3 H CCl3 C OH OH H chloral hydrate chloral + H2O Aldehydes & Ketones - Page 25 • Sodium Bisulfite Addition O C R R' OH CR R' SO3 Na + Na SO3H O CR R' SO3H bisulfite addition product (crystalline solid) But, the carbonyl compound must NOT be sterically hindered. Example: Useful for purification of aldehydes or methyl ketones O C R H O C R CH3 The carbonyl compound can be regenerated by reaction with mild acid or base. Aldehydes & Ketones - Page 26 • Reduction (Nucleophilic addition of hydride) O C R R' H Al H H H O CR R' H OH C R' H R Li H3O + Lithium aluminum hydride, LiAlH4 (LAH) is a very poweful reducing agent. It reduces: • Aldehydes • Ketones • Carboxylic acids • Esters • Amides • Nitriles Reactions with LiAlH4 are normally done with diethyl ether CH3CH2OCH2CH3 Et2O tetrahydrofuran O THF as solvent. Aldehydes & Ketones - Page 27 Sodium borohydride, NaBH4 is a milder reducing agent. It reduces only • Aldehydes • Ketones Normally use alcohols (MeOH or EtOH) as solvents in NaBH4 reductions. In general, neither LiAlH4 nor NaBH4 will reduce C=C double bonds. Example: CH3 CH CH CH2 C H O CH3 CH CH CH2 CH2 OH 1) NaBH4 2) H3O 3-pentenal 3-penten1-ol • Addition of Organometallic Compounds O C R R' R" M+ CR R" R' O M Grignard reagent R-MgX Alkyllithium reagent R-Li Aldehydes & Ketones - Page 30 Mechanism: Acetal/Ketal Formation ONLY acid-catalyzed (SN1) OH CR R' OR" OHR" + H O CR R' OR" H H −H2O CR R' OR" O CR R' OR" R" H OR" CR R' OR" −H Important Points: • Acetal/Ketal formation and hemiacetal/hemiketal formation equilibrium generally lies on the left - in favor of starting materials. Exceptions: formation of 5- or 6-membered rings: Example: C O OH H C O H O H H intramolecular hemiacetal (6-mem. ring) Aldehydes & Ketones - Page 31 Very important in sugars. Example: O OH OH OH CH2OH HO H H H H H Glucose a cyclic hemiacetal • Acetal/Ketal formation can be pushed to the right by elimination of the H2O that is formed (usually by distilling it away). Example: O O O OHHO + H2O H / ∆ + (80% yield) Generally use p-toluenesulfonic acid (TsOH) in refluxing benzene. CH3 SO3H TsOH Aldehydes & Ketones - Page 32 • Acetals/Ketals are good protecting groups for 1,2- diols as well as aldehydes and ketones. VERY IMPORTANT in Organic Synthesis! Examples: O CO2Et O CH2OH HO OH / TsOH C6H6 / ∆ (−H2O) CO2Et O O 1) LiAlH4 / Et2O 2) H2O CH2OH O O H3O Aldehydes & Ketones - Page 35 O C R R' + R" NH2 1o amine −H2O N C R R' R" imine (generally unstable) O C R R' + HO NH2 hydroxylamine −H2O N C R R' OH oxime O C R R' + H2N NHR" hydrazine −H2O N C R R' NHR" hydrazone O C R R' + H2N NH C NH2 O semicarbazide −H2O N C R R' NHCNH2 O semicarbazone Aldehydes & Ketones - Page 36 Examples: O C CH3 CH3 N C CH3 CH3 OH + NH2OH H acetone oxime acetone O N NH2 O N N + H2N-NH2 cyclopentanone hydrazone cyclopentanone azine Aldehydes & Ketones - Page 37 O C CH3 H N C CH3 H NHC6H5 + H2N-NHC6H5 O C H O C H2N-NH NH2 + N C H NHCNH2 O Aldehydes & Ketones - Page 40 • The Clemmenson Reduction O C R R' R CH2 R' Zn / Hg HCl Example: CH2 CH3 O C CH3 Zn / Hg HCl Aldehydes & Ketones - Page 41 • The Cannizzaro Reaction R-CHO + RCHO RCH2OH + RCO2 OH Aldehyde with NO α-hydrogens Mechanism: + R-CH2-OH O C R O + O CR H H O C R OH OH O C R H O CR H OH O C R H Aldehydes & Ketones - Page 42 • Oxidation of Aldehydes O C R H O C R OH [O] Not generally synthetically useful, but a good test for aldehydes: • K2Cr2O7 / H2SO4 / H2O • KMnO4 / KOH / H2O • AgNO3 / NH3 / H2O (Tollen's reagent - very mild) Mechanism: involves nucleophilic attack of oxidizing agent at carbonyl carbon: Example: O C R H O CR H O CrO3H H OH C R H O C R OH H HCrO4 + H + HCrO3