Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Introduction to Organic Chemistry 2 ed William H. Brown

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Aldehydes & Ketones Chapter 15 Chapter 11

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. The Carbonyl Group In this and three following chapters we study the physical and chemical properties of classes of compounds containing the carbonyl group, C=O aldehydes and ketones (Chapter 11) carboxylic acids (Chapter 12) carboxyl derivatives (Chapter 13) enolate anions (Chapter 14)

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. The Carbonyl Group Consists of one sigma bond formed by overlap of sp 2 hybrid orbitals one pi bond formed by overlap of parallel 2p orbitals

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Structure of Aldehydes The functional group of an aldehyde is a carbonyl group bonded to a H atom in methanal, it is bonded to two H atoms in all other aldehydes, it is bonded to one H and one carbon atom

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Structure of Ketones The functional group of a ketone is a carbonyl groups bonded to two carbon atoms

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature - Aldehydes IUPAC namesIUPAC names: select as the parent alkane the longest chain of carbon atoms that contains the carbonyl group because the carbonyl group of the aldehyde must be on carbon 1, there is no need to give it a number anenFor unsaturated aldehydes, show the presence of the C=C by changing the infix -an- to -en- the location of the suffix determines the numbering pattern

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature - Aldehydes

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature - Aldehydes carbaldehydeFor cyclic molecules in which the -CHO group is attached to the ring, the name is derived by adding the suffix -carbaldehyde to the name of the ring

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature - Ketones IUPAC names: select as the parent alkane the longest chain that contains the carbonyl group, eonechanging the suffix -e to -one number to give C=O the smaller number

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature - Ketones The IUPAC system retains these names

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Order of Precedence For compounds that contain more than one functional group indicated by a suffix

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Physical Properties Oxygen is more electronegative than carbon (3.5 vs 2.5) and, therefore, a C=O group is polar aldehydes and ketones have higher boiling points and are more soluble in water than nonpolar compounds of comparable molecular weight

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Reaction Theme One of the most common reaction themes of the carbonyl group is addition of a nucleophile to form a tetrahedral carbonyl addition compound

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Add’n of C 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 We study addition of carbon nucleophiles called Grignard reagents Victor Grignard was awarded the Nobel Prize for Chemistry in 1912 for their discovery and application to organic synthesis

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Grignard Reagents Magnesium metal reacts with alkyl and aryl halides to give organomagnesium halides

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Grignard Reagents Given the difference in electronegativity between carbon and magnesium ( ), the C-Mg bond is polar covalent, with C  and Mg  a Grignard reagent behaves as a carbanion and as a nucleophile CarbanionCarbanion: an anion in which carbon has an unshared pair of electrons and bears a negative charge

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Grignard Reagents Grignard reagents are very strong bases and react with a variety of acids to give alkanes

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Grignard Reagents they also react with these acids ( proton donors) to give alkanes

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Grignard Reagents Grignard reagents provide a way to form new carbon-carbon bonds a carbanion is a good nucleophile and adds to the carbonyl group of an aldehyde or ketone to form a tetrahedral carbonyl addition compound the driving force for this reaction is the attraction of the partial negative charge on the carbon of the Grignard reagent for the partial positive carbon of the carbonyl group

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Grignard Reagents addition of a Grignard reagent to formaldehyde followed by H 3 O + gives a 1° alcohol

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Grignard Reagents addition to any other RCHO gives a 2° alcohol

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Grignard Reagents addition to a ketone gives a 3° alcohol

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Grignard Reagents addition to CO 2 gives a carboxylic acid

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Grignard Reagents addition to ethylene oxide gives a 1° alcohol

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Grignard Reagents ProblemProblem: 2-phenyl-2-butanol can be synthesized by three different combinations of a Grignard reagent and a ketone. Show each combination

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Addition of Alcohols Addition of one molecule of alcohol to the C=O group of an aldehyde or ketone gives a hemiacetal HemiacetalHemiacetal: a molecule containing an -OH and an -OR or -OAr bonded to the same carbon

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Addition of Alcohols Hemiacetals are only minor components of an equilibrium mixture, except where a five- or six- membered ring can form (the trans isomer is shown here)

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Addition of Alcohols Hemiacetals react with alcohols to form acetals AcetalAcetal: a molecule containing two -OR or -OAr groups bonded to the same carbon

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Addition of Alcohols Steps 1 and 2: proton transfer from the acid catalyst, HA, to the carbonyl oxygen followed by loss of H 2 O

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Addition of Alcohols Steps 3 and 4: reaction of the oxonium ion with ROH followed by proton transfer to A -

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Addition of Alcohols with a glycol, such as ethylene glycol, the product is a five-membered cyclic acetal

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Add’n of N Nucleophiles Ammonia, 1° aliphatic amines, and 1° aromatic amines react with the C=O group of aldehydes and ketones to give imines (Schiff bases)

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Add'n of N Nucleophiles Formation of an imine occurs in two steps Step 1: formation of a TCAI Step 2: loss of water

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Add'n of N Nucleophiles Rhodopsin (visual purple) is the imine formed between 11-cis-retinal (vitamin A aldehyde) and the protein opsin

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Rhodopsin

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Keto-Enol Tautomerism  -carbon  -hydrogenA carbon adjacent to a carbonyl group is called an  -carbon, and a hydrogen atom bonded to it is called an  -hydrogen.

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Keto-Enol Tautomerism A carbonyl compound with an a-hydrogen is in equilibrium with a constitutional isomer called an enol (an alkene + an alcohol)

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Keto-Enol Tautomerism keto-enol equilibria for simple aldehydes and ketones lie far toward the keto form

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Keto-Enol Tautomerism Keto-enol tautomerism is acid catalyzed Step 1: proton transfer from H-A Step 2: proton transfer to A -

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Racemization Racemization at an  -carbon is catalyzed by acid

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Oxidation of Aldehydes Aldehydes are oxidized to carboxylic acids by a variety of oxidizing agents, including chromic acid

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Oxidation of Aldehydes Aldehydes are also oxidized by Ag(I) in one method, a solution of the aldehyde in aqueous ethanol or THF is shaken with a slurry of silver oxide

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Oxidation of Aldehydes Tollens’ reagent, another form of Ag(I), is prepared by dissolving silver nitrate in water, adding NaOH to precipitate Ag(I) as Ag 2 O, and then adding aqueous ammonia to redissolve Ag(I) as a silver-ammonia complex ion

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Oxidation of Aldehydes Tollens’ reagent oxidizes an aldehyde to a carboxylic anion and silver(1) is reduced to metallic silver this reaction is used to silver mirrors

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Oxidation of Aldehydes aldehydes are oxidized by molecular oxygen and by hydrogen peroxide liquid aldehydes are so sensitive to air that they must stored under N 2

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Reduction An aldehyde can be reduced to a 1° alcohol and a ketone to a 2° alcohol

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Catalytic Reduction Catalytic reductions are generally carried out from 25° to 100°C under 1 to 5 atm H 2

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Catalytic Reduction A carbon-carbon double bond may also be reduced under these conditions by careful choice of experimental conditions, it is often possible to selectively reduce a carbon-carbon double in the presence of an aldehyde or ketone

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Metal Hydride Reduction The most common laboratory reagents for the reduction of aldehydes and ketones are NaBH 4 and LiAlH 4 both reagents are sources of hydride ion, H: -, a very powerful nucleophile

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. NaBH 4 Reduction Reductions with NaBH 4 are most commonly carried out in aqueous methanol, in pure methanol, or in ethanol one mol of NaBH 4 reduces four mol of aldehyde or ketone

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. NaBH 4 Reduction the key step in metal hydride reduction is transfer of a hydride ion to the C=O group to form a tetrahedral carbonyl addition compound

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. LiAlH 4 Reduction Unlike NaBH 4, LiAlH 4 reacts violently with water, methanol, and other protic solvents reductions using this reagent are carried out in diethyl ether or tetrahydrofuran (THF)

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Metal Hydride Reduction Metal hydride reducing agents do not normally reduce carbon-carbon double bonds, and selective reduction of C=O or C=C is often possible

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Reductive Amination A value of imines is that the carbon-nitrogen double bond can be reduced to a carbon-nitrogen single bond

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Aldehydes & Ketones End Chapter 11