Aldehydes & Ketones

The Carbonyl Group  Compounds containing the carbonyl group, C=O aldehydes and ketones carboxylic acids, Carboxylic acid derivatives : Acid halides, acid anhydrides, esters, amides.

Structure The functional group of an aldehyde is a carbonyl group bonded to a H atom and a carbon atom The functional group of a ketone is a carbonyl group bonded to two carbon atoms

Nomenclature  IUPAC names: the parent chain is the longest chain that contains the functional group -e–alfor an aldehyde, change the suffix from -e to –al

Position of substituents or side chains for aliphatic aldehydes is indicated by numbers.

When –CHO (aldehydic group) is a substituent: –CHO group (as a terminal group) in IUPAC and Common names is given the name formyl. N.B: Priority of functional groups: COOH, SO 3 H, acid derivatives (esters, acid halides, amides, nitriles), CHO, C=O, OH, SH, NH 2, OR, X.

Nomenclature: Ketones  IUPAC names: select as the parent alkane the longest chain that contains the carbonyl group -e- oneindicate its presence by changing the suffix -e to - one number the chain to give C=O the smaller number

when the carbonyl group is a substituent: The =O is given the name oxo; its position is indicated by a number.

Common Names 1) Aldehydes for an aldehyde, the common name is derived from the common name of the corresponding carboxylic acid. The ending ic or oic of the acid is dropped, and the suffix aldehyde is added.

Position of substituents or side chains for aliphatic aldehydes is indicated by Greek letters ( ∝,β,γ,δ ……ω), α- carbon is the carbon attached to CHO group.

for a ketone, name the two alkyl or aryl groups bonded to the carbonyl carbon and add the word ketone 2) Ketones

Position of substituents on side chains for aliphatic ketones is indicated by Greek letters, the α-carbon being the one adjacent to the carbon of the carbonyl group.

Position of substituents for aromatic Ketones is indicated by o,m and p. Aromatic ketones are named phenone and the second group is named as the corresponding acid Ex ; CH 3 COph is named acetophenone. phCOph is named benzophenone.

Synthesis of Aldehydes and Ketones I. From alcohols: A-Oxidation of alcohols: 1) Oxidation of primary alcohols

The oxidation of aldehydes to carboxylic acids usually takes place with milder oxidizing agents than those required to oxidize alcohols to aldehydes, so it is difficult to stop the oxidation at the aldehyde stage. To avoid this problem, the aldehyde as soon as it is formed is removed by distillation, but poor yields are obtained with aldehydes b.p >100 C 0. Higher yields (93%) are obtained by using pyridiniumchlorochromate (PCC) at room temperature

2) Oxidation of secondary alcohols :

B. Dehydrogenation of alcohols:

II. From Acid Derivatives: 1) From Acid Chlorides: Aldehydes from acid chlorides: Rosenmund Reduction: The catalyst is poisoned with quinoline and sulfur to stop the reaction at the aldehyde stage.

Ketones from acid chlorides: Reaction with organocadmium compounds  We don’t use Grignard reagent, as it reacts with the formed ketone and gives 3 ◦ alcohol.  Dialkylcadmium R 2 Cd act as Grignard reagent but it is less reactive

2) From Esters: Aldehyde From Esters: i) Reduction of Carboxylic acid esters using DIBAL-H ( Diisobutyl Aluminium Hydride ) ii) Reaction of orthoformic esters with Grignard reagent:

Ketones From Esters (RCOOR):  Can’t be prepared by reaction with RMgX which can react with ketone produced to give 3 ry alcohol  So we use orthoesters but orthoacetate to give the ketone

3) From Nitriles: Stephen’s reaction: Aldehyde from Alkyl or aryl cyanides “nitriles”:

Ketones from Alkyl or Aryl Nitriles: Ketones from Alkyl or Aryl Nitriles: Reaction with Grignard reagent

III. From alkenes a ) Ozonolysis of alkenes:

b) Hydration of alkynes All alkynes give ketones except acetylene gives aldehyde

C ) From geminal dihalides: 1) Aldehydes from terminal geminal dihalides: 2) Ketones from non terminal geminal dihalides:

Special Methods for Synthesis of Aromatic Aldehydes Special Methods for Synthesis of Aromatic Aldehydes  A. Oxidation of methyl group:  CrO 3/ Ac 2 O is specific reagent to stop reaction at the formation of aldehyde & not acid.

Special Methods for Synthesis of Aromatic Ketones Friedel Crafts Acylation:

Physical Properties  Oxygen is more electronegative than carbon (3.5 vs 2.5) and, therefore, a C=O group is polar aldehydes and ketones are polar compounds and interact in the pure state by dipole-dipol interaction they have higher boiling points and are more soluble in water than nonpolar compounds of comparable molecular weight

 they are not capable to form intermolecular hydrogen bonding, since, they contain hydrogen bonded only to carbon (no NH or OH group) they have lower b.p. than the corresponding alcohols and carboxylic acids.

 low molecular weight aldehydes and ketones (C 1 -C 4 ) are soluble in water due to H.b formation with water e.g. acetone and acetaldehyde are miscible with water in all proportions.

Chemical Reactions of Aldehydes and Ketones  Structure of carbonyl group: The carbonyl carbon atom is sp 2 hybridized, thus it and the three groups attached to it lie in the same plane. The bond angles between the three attached atoms are approximately 120 o

 The carbon-oxygen double bond consists of a σ bond and a π bond. The more electronegative oxygen atom strongly attracts the electrons of both σ bond and π bond causing the carbonyl group to be highly polarized. The carbon atom bears a partial positive charge and the oxygen atom bears a partial negative charge.

 Aldehydes and ketones undergo nucleophilic reactions due to polarization of carbonyl group (# C=C).  Nucleophiles Neutral Weak nucleophiles (need acid catalyst) Negatively charged Strong nucleophiles H—OH water R—OH alcohol H 3 N: ammonia RNH2 amine - OH hydroxide H - hydride R3C - carbanion R—O - alkoxide ion - C≡N cyanide ion

Relative reactivity of aldehydes and ketones in nucleophilic addition reactions:  Aldehydes are generally more reactive than ketones in nucleophilic addition reactions for two reasons: 1. Electronic factor (I and R) positive charge of the carbonyl carbon is diminished by electron donating groups. So aldehydes are more reactive than ketones in nucleophilic addition reactions because ketones have two alkyl groups at carbonyl carbon (+ I effect of 2 R groups).

 II- Steric factor The intermediate in case of aldehydes is less sterically hindered than in ketones i.e. more stable

I) Addition reactions a) Addition of alcohols  This reaction is acid catalyzed as alcohols is weak Nu & reversible.  Used to protect CO group in alkaline medium, then hydrolyzed with acid to alc & ald or ketone

Mechanism

b) Addition of HCN (formation of cyanohydrins)  Aldehydes & ketones react with aqueous CN and drops of acid  The products are useful to prepare α-hydroxy acids by hydrolysis with acidified H 2 O

c) Addition of Grignard reagent  RMgX is a strong nucleophile and do not need catalyst, it adds to aldehyde & ketones and the products are hydrolyzed to produce the proper alcohols.

c) Reaction with ammonia derivatives “NH 2 -y”:  This reaction is addition followed by elimination  The reaction needs weak acid medium

 These derivatives are used for purification and identification of carbonyl compounds.  N.B. Reaction with secondary amines:  Aldehydes and ketones containing at least one α- hydrogen react with 2 0 amines to give enamines. The reaction is catalyzed by acid.

Mechanism

II) Cannizzaro reaction ( Reaction of Aldehydes containing no α-hydrogen)  For aldehydesonly lacking α- hydrogen  For aromatic aldehydes and aliphatic aldehydes containing no α- hydrogen.  The products of Cannizzaro reaction are an alcohol and the salt of a carboxylic acid "self oxidation reduction ". The concentration of NaOH not less than 30%.

 Mechanism:  Carboxylate anion is more stable than alkoxide anion

Crossed Cannizaro reaction:  If two different aldehydes having no α-H, it is called crossed Cannizzaro.  Mechanism

 N. B:  The molecule which is attacked by hydroxide anion is the one which is oxidized, and the one which is attacked by hydride ion is the one which is reduced.  Hydroxide anion attacks the more reactive aldehyde (i.e.contains the more elecrophilic carbonyl carbon).

Intramolecular Cannizaro reaction: ( i.e. occur inside the same molecule)  Mechanism

III) Aldol reaction “Aldol condensation”  Reaction of Aldehydes or ketones having α-hydrogen  (e.g.acetaldehyde and acetone)when heated with dil NaOH the product is aldol

Mechanism

 By heating aldol or warming with dil. Acids, it loses H 2 O to give α,β-unsat. Carbonyl compound.

 Reaction of ketones: acetone also undergo aldol reaction, but they are less reactive than aldehydes.

Crossed aldol  Reaction between acetaldehyde (α-H) and formaldehyde (no α-H) in the presence of dil. or conc. NaOH will proceed aldol and not Cannizzaro.

Claisen reaction “Claisen Schmidt reaction”:  Reaction between an aromatic aldehyde (no α-H) and an aliphatic aldehyde or ketone containing α- hydrogen in the presence of dil. alkali leads to formation of α-β-unsaturated carbonyl compound immidiately because of extended conjugation with the ring.

Mechanism

 These condensation products are used for different synthesis.

Halogenation  It takes place at the α – carbon of ald. Or ketone and is accelerated by acids or bases.  A ) Base induced halogenation :  Haloform Reaction

Mechanism: 1. Substitution of 3H by 3X Multiple halogenations occur, because introduction of the 1 st halogen makes the remaining α- hydrogens more acidic (due to –I effect of the introduced halogen).

2. Nucleophilic attack of - OH on carbonyl carbon:

B) Acid-catalyzed halogenation Mechanism:

Acid-catalyzed halogenations lead only to mono halogenations, because the halogen introduced has "-I effect", which makes lone pair of electrons on oxygen less available for protonation

Oxidation of Aldehydes and ketones  Aldehydes are oxidized to carboxylic acids by a variety of mild oxidizing agents, including Tollen’s reagent and fehling solution.  Ketones are oxidized with H 2 O 2 or Peracids to esters and this is called Baeyer-Villiger oxidation.

Mechanism Mechanism

Reduction aldehydes can be reduced to 1° alcohols using H 2 / catalyst or Metal Hydride. ketones can be reduced to 2° alcohols using H 2 / catalyst or Metal Hydride. the C=O group of an aldehyde or ketone can be reduced to a -CH 2 - group via two methods ;Clemmensen Reduction and Wolff-Kishner Reduction

Clemmensen Reduction refluxing an aldehyde or ketone with amalgamated zinc in concentrated HCl converts the carbonyl group to a methylene group Wolff-Kishner Reduction