1. Aldehydes and Ketones Dr. Talat R. Al-Ramadhany

2. Introduction Aldehydes are compounds of the general formula RCHO; Ketones are compounds of the general formula RR´CO. The groups R and R´ may be aliphatic or aromatic. Both aldehydes and ketones contain the carbonyl group, C=O, and are often called carbonyl compounds.

3.  An aldehyde is often written as RCHO. Remember that the H atom is bonded to the carbon atom, not the oxygen.  Likewise, a ketone is written as RCOR, or if both alkyl groups are the same, R 2 CO. Each structure must contain a C––O for every atom to have an octet.  The three bonds (carbon, oxygen, and the two other atoms attached to carbonyl carbon) lie in a plane; the three bond angels of carbon are very close to 120º.

4. Nomenclature Both IUPAC and common names are used for aldehydes and ketones.  Naming Aldehydes in the IUPAC System To name an aldehyde using the IUPAC system: [1] If the CHO is bonded to a chain of carbons, find the longest chain containing the CHO group, and change the -e ending of the parent alkane to the suffix -al. If the CHO group is bonded to a ring, name the ring and add the suffix -carbaldehyde. [2] Number the chain or ring to put the CHO group at C 1

5. Example: Give the IUPAC name for the compound:

9. Common Names for Aldehydes The common names of aldehydes are derived from the names of the corresponding carboxylic acids by replacing –ic acid by –aldehyde. Greek letters are used to designate the location of substituents in common names. The carbon adjacent to the CHO group is the ` carbon, and so forth down the chain.

11. Naming Ketones in the IUPAC System  To name an acyclic ketone using IUPAC rules: [1] Find the longest chain containing the carbonyl group, and change the -e ending of the parent alkane to the suffix -one. [2] Number the carbon chain to give the carbonyl carbon the lower number. Apply all of the other usual rules of nomenclature.

15. Common Names for Ketones Most common names for ketones are formed by naming both alkyl groups on the carbonyl carbon, arranging them alphabetically, and adding the word ketone. Using this method, the common name for 2-butanone becomes ethyl methyl ketone.

17. Physical properties: Boiling point:  Aldehydes and ketones are polar compounds due to the polarity of carbonyl group and hence they have higher boiling points than non polar compounds of comparable molecular weight.  But they have lower boiling points than comparable alcohols or carboxylic acids due to the intermolecular hydrogen bonding.

18. Solubility: The lower aldehydes and ketones soluble in water, because of hydrogen bonding between carbonyl group and water, also they soluble in organic solvents.

19. Preparation of aldehydes & Ketones.

20. Preparation of aldehydes. 1.Oxidation of primary alcohols:  Primary alcohols can be oxidized to give aldehydes by using of K 2 Cr 2 O 7.

21. 2.Oxidation of Methylbenzenes: In the case of methylbenzenes, oxidation of the side chain can be interrupted by trapping with acetic anhydride to form gem-diacetate, which on hydrolysis its return to aldehydes.

23. 3.Partial reduction of acid chlorides Strong reducing agents (like LiAlH 4 ) reduce acid chlorides all the way to primary alcohols. Lithium aluminum tri(t-butoxy)hydride is a milder reducing agent that reacts faster with acid chlorides than with aldehydes. Reduction of acid chlorides with lithium aluminum tri(t-butoxy)hydride gives good yields of aldehydes. (-78ºC)

24. 4.Partial reduction of esters Sterically bulky reducing agents, e.g. Diisobutylaluminium hydride (DIBAH), can selectively reduce esters to aldehydes. The reaction is carried out at low temperature (-78ºC) in toluene. Ester Aldehyde Diisobutylaluminium hydride (mild reducing agent)

25. 5.Reduction of Nitriles Reduction of nitrile with a less powerful reducing reagent, e.g. DIBAH, produces aldehyde. The reaction is carried out at low temperatures (-78ºC) in toluene.

27. Preparation of Ketones 1.Oxidation of Secondary alcohols: Secondary alcohols are oxidized to ketones by chromic acid (H 2 CrO 4 ) in a form selected for the job at hand: aqueous K 2 Cr 2 O 7, CrO 3 in glacial acetic acid, CrO 3 in pyridine, etc. Hot permanganate also oxidizes alcohols; it is seldom used for the synthesis of ketones.

28. 2.Cleavage of Carbon–Carbon double bond by Ozone: Oxidative cleavage of an alkene breaks both the σ and π bonds of the double bond to form two carbonyl groups. Depending on the number of R groups bonded to the double bond, oxidative cleavage yields either ketones or aldehydes.

29. 3.Friedel-Crafts acylation. The Friedel-Crafts reaction involves the use of acid chlorides rather than alkyl halides. An acyl group (RCO–) becomes attached to the aromatic ring. Thus forming a ketone; the process is called acylation.

30. 4.Synthesis of Ketones from Nitriles. A Grignard or organolithium reagent attacks a nitrile to give the magnesium salt of an imine. Acidic hydrolysis of the imine leads to the ketone.

31. 5.Hydration of alkynes. Alkynes undergo acid-catalyzed addition of water across the triple bond in the presence of mercuric ion as a catalyst. A mixture of mercuric sulfate in aqueous sulfuric acid is commonly used as the reagent.

33. Reactions of aldehydes and Ketones Aldehydes and Ketones undergo many reactions to give a wide variety of useful derivatives. There are two general kinds of reactions that aldehydes and ketones undergo: [1] Reaction at the carbonyl carbon (Nucleophilic addition reactions).

34. [2] Reaction at the α carbon. A second general reaction of aldehydes and ketones involves reaction at the α carbon. A C–H bond on the α carbon to a carbonyl group is more acidic than many other C–H bonds, because reaction with base forms a resonance-stabilized enolate anion.

35. [1] Nucleophilic addition reaction. Two general mechanisms are usually drawn for nucleophilic addition, depending on the nucleophile (negatively charged versus neutral) and the presence or absence of an acid catalyst. With negatively charged nucleophiles, nucleophilic addition follows the two-step process first (nucleophilic attack) followed by protonation.

36. Step [1]: The nucleophile attacks the carbonyl group, cleaving the π bond and moving an electron pair onto oxygen. This forms a sp 3 hybridized intermediate with a new C–Nu bond. Step [2]: protonation of the negatively charged O atom by H 2 O forms the addition product.  Absence of an acid catalyzed nucleophilic addition

37.  Acid-catalyzed nucleophilic addition Step [1] Protonation of the carbonyl group The general mechanism for this reaction consists of three steps (not two), but the same product results because H and Nu - add across the carbonyl π bond. In this mechanism protonation precedes nucleophilic attack.

38. Steps [2]–[3] Nucleophilic attack and deprotonation In Step [2], the nucleophile attacks, and then deprotonation forms the neutral addition product in Step [3].

39. a) Addition of Alcohols (Acetal Formation): Aldehydes and ketones react with two equivalents of alcohol to form acetals. In an acetal, the carbonyl carbon from the aldehyde or ketone is now singly bonded to two OR" (alkoxy) groups.

40. b) Nucleophilic Addition of H - (Reduction reaction) Treatment of an aldehyde or ketone with either Sodium borohydride (NaBH 4 ) or Lithium hydride (LiAlH 4 ) followed by protonation forms a 1° or 2° alcohol.

41. Hydride reduction of aldehydes and ketones occurs via the two-step mechanism of nucleophilic addition, that is, nucleophilic attack of H: – followed by protonation.

42. Examples:

43. c) Reduction to alkane (Deoxygenation of Ketones and Aldehydes): i) Clemmensen reduction. ii) Wolff–Kishner reduction.

44. Clemmensen reduction: The Clemmensen reduction is most commonly used to convert acylbenzenes (from Friedel-Crafts acylation) to alkylbenzenes, but it also works with other ketones or aldehydes that are not sensitive to acid. The carbonyl compound is heated with an excess of amalgamated zinc (zinc treated with mercury; Zn (Hg), and concentrated hydrochloric acid (HCl). The actual reduction occurs by a complex mechanism on the surface of the zinc. The Clemmensen reduction uses zinc and mercury in the presence of strong acid.

46. Compounds that cannot survive treatment with hot acid can be deoxygenated using the Wolff–Kishner reduction. The ketone or aldehyde is converted to its hydrazone, which is heated with Hydrazine (NH 2 NH 2 ), and strong base such as KOH. Ethylene glycol, diethylene glycol, or another high-boiling solvent is used to facilitate the high temperature (140-200°C) needed in the second step. Wolff–Kishner reduction:

48. Summary:

49. d) Nucleophilic Addition of CN – : Treatment of an aldehyde or ketone with NaCN and a strong acid such as HCl adds the elements of HCN across the carbon–oxygen π bond, forming a cyanohydrin.

52. e) Addition of Bisulfate. Sodium bisulfate adds to most aldehydes and to many ketones (especially methyl ketones and cycloketones) to form bisulfate addition products:

53. Examples:

54. Ketones containing bulky groups usually fail to react with bisulfate, because of steric effect.

55. f) Addition of organometallic reagents (R – ) The addition of Grignard reagents to aldehydes and ketones yields alcohols. The organic group, transferred with a pair of electrons from magnesium to carbonyl carbon, is a powerful nucleophile.

57. g) Addition of derivatives of Ammonia (Formation of imine).  Treatment of an aldehyde or ketone with a 1° amine affords an imine (also called a Schiff base).  Nucleophilic attack of the 1° amine on the carbonyl group forms an unstable carbinolamine, which loses water to form an imine. The overall reaction results in replacement of C=O by C=NR.

61. Oxidation reaction  Aldehydes are readily oxidized to yield carboxylic acids; but ketones are generally inert toward oxidation.  The difference is a consequence of structure: aldehydes have a –CHO proton that can be abstracted during oxidation, but ketones do not.

62.  Many oxidizing agents, including KMnO 4 and hot HNO 3, convert aldehydes into carboxylic acid.  But CrO 3 in aqueous acid is a more common choice in the laboratory. The oxidation occurs rapidly at room temperature and results in good yields.

63. Tollen's reagent In the laboratory, oxidation of an aldehyde can be carried out using a solution of silver oxide (Ag 2 O) in aqueous ammonia, the so-called Tollen's reagent. Oxidation of aldehyde is accompanied by reduction of silver ion to free silver (in the form of a mirror under the proper conditions).

65. Methyl ketones: Oxidation of ketones required breaking of C–C bond next to the carbonyl group and takes place only under vigorous conditions, except for methyl ketones which oxidized smoothly by mean of hypohalite (NaOX) to form Haloform (Haloform reaction).

66. Reactions of aldehydes and Ketones Aldehydes and Ketones undergo many reactions to give a wide variety of useful derivatives. There are two general kinds of reactions that aldehydes and ketones undergo: [1] Reaction at the carbonyl carbon (Nucleophilic addition reactions).

67. [2] Reaction at the α carbon. A second general reaction of aldehydes and ketones involves reaction at the α carbon. A C–H bond on the α carbon to a carbonyl group is more acidic than many other C–H bonds, because reaction with base forms a resonance-stabilized enolate anion.

68. [2] Reaction involving acidic α-hydrogen  The carbonyl strengthens the acidity of the hydrogen atoms attached to the α-carbon and, by doing this, gives rise to a whole set of chemical reactions.  Ionization of an α-hydrogen, yields a carbanion (I) that is a resonance hybrid of two structures: Keto form and Enol form.

69. a) Halogenation of ketones:  When a ketone is treated with a halogen and base, an α-halogenation reaction occurs.

71. b) Aldol condensation  Under the influence of or, two molecules of an aldehyde or a ketone, which, may combine to form a β-Hydroxy aldehyde or β-Hydroxy ketone. This reaction is called the. dilute basedilute acid contained α-hydrogen Aldol condensation

72. Mechanism:

73.  If aldehyde or ketone does not contain an α-hydrogen, a simple Aldol condensation cannot take place.  For example:

74. Cannizzaro reaction. In the presence of concentrated alkali, aldehydes containing no α-hydrogen undergo self-oxidation and reduction to yield a mixture of an alcohol and a salt of a carboxylic acid. This reaction is known as the Cannizzaro reaction.

75. Examples:

76.  If two different aldehydes with no α-hydrogen undergo Cannizzaro reaction yield a mixture of products. This reaction is called crossed Cannizzaro reaction. Crossed Cannizzaro reaction