Aldehydes and Ketones. Dr. Munther A. M. Ali

Transcription

1 Aldehydes and Ketones Dr. Munther A. M. Ali

2 ALDYHYDES AND KETONES Aldehydes are compounds of the general formula RCHO Ketones are compounds of the general formula RR'CO Aldehydes A ketone Both aldehydes and ketones contain the carbonyl group, C=O This difference in structure affects their properties in two ways: (a) Aldehydes are quite easily oxidized, whereas ketones are oxidized only with difficulty. (b) Aldehydes are usually more reactive than ketones toward nucleophilic addition, the characteristic reaction of carbonyl compounds.

3 The structure of the carbonyl group Carbonyl carbon is joined to three other atoms by a bonds; since these bonds utilize sp2 orbitals, they lie in a plane, and are 120 apart. The remaining p orbital of the carbon overlaps a p orbital of oxygen to form a p bond; carbon and oxygen are thus joined by a double bond.

4 The electrons of the carbonyl double bond hold together atoms of quite different electronegativity, and hence the electrons are not equally shared; in particular, the mobile p cloud is pulled strongly toward the more electronegative atom, oxygen.

5 Aldehydes Nomenclature The common names of aldehydes are derived from the names of the corresponding carboxylic acids by replacing -ic add by -aldehyde. Common name of carboxylic acid Formula Common name of aldehydes Formula Formic acid HCOOH Formaldehyde HCHO Acetic acid CH 3 COOH Acetaldehyde CH 3 CHO Propionic acid CH 3 CH 2 COOH Propioaldehyde CH 3 CH 2 CHO The IUPAC names of aldehydes: The longest chain carrying the CHO group is considered the parent structure and is named by replacing the -e of the corresponding alkane by -al. The position of a substituent is indicated by a number, the carbonyl carbon always being considered as C-l. Here we notice that C-2 of the IUPAC name corresponds to alpha a of the common name.

6 Aldehyde Formaldehyde Acetaldehyde Propionaldehyde Butyraldehyde Veleraldehyde Caproaldehyde Enanthaldehyde Caprylaldehyde Pelargonaldehyde Capraldehyde

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8 Aromatic aldehyde: derived from simplest benzaldehyde

9 Ketones The simplest aliphatic ketone has the common name of acetone, CH 3 COCH 3. For most other aliphatic ketones we name the two groups that are attached to carbonyl carbon, and follow these names by the word ketone. According to the IUPAC system, the longest chain carrying the carbonyl group is considered the parent structure, and is named by replacing the -e of the corresponding alkane with -one.

10 A ketone in which the carbonyl group is attached to a benzene ring is named as a phenone.

11 Physical properties The polar carbonyl group makes aldehydes and ketones polar compounds, and hence they have higher boiling points than non-polar compounds of comparable molecular weight. For example; compare n-butyraldehyde (b.p, 76) and methyl ethyl ketone (b.p. 80) with n-pentane (b.p. 36). They are not capable of intermolecular hydrogen bonding; as a result they have lower boiling points than comparable alcohols or carboxylic acids. For example; compare n-butyraldehyde (b.p, 76) and methyl ethyl ketone (b.p. 80) with n-butyl alcohol (b.p. 118) and propionic acid (b.p. 141). The lower aldehydes and ketones are appreciably soluble in water, borderline solubility is reached at about five carbons. Aldehydes and ketones are soluble in the usual organic solvents. Formaldehyde is a gas (b.p. -21), and is handled either as an aqueous solution (Formalin 37%), or as one of its solid polymers: paraformaldehyde (CH 2 O)n, or trioxane, (CH 2 O) 3.

12 Preparation of aldehydes 1. Oxidation of primary alcohols. Preparation Aldehydes may prepare by oxidation of primary alcohol by acidic dichromate, but the aldehydes are easily oxidized to carboxylic acids by the same reagent, therefore, the aldehyde must remove as fast as it is formed. Specific reagent may be used to yield aldehyde without further oxidation reaction, as pyridinium chlorochromate. Pyridinium chlorochromate CH 3 CH 2 CH 2 CHO n-butyl alcohol 1-Butanol CH 3 CH 2 CH 2 CH 2 OH n-butyraldehyde Butanal

13 2. Oxidation of methylbenzenes. Oxidation of the side chain can be interrupted by trapping the aldehyde in the form of a non-oxidizable derivative, the gemdiacetate, which is isolated and then hydrolyzed. gem-diacetate 1-Bromo-4-dichloromethylbenzene

14 3. Reduction of acid chlorides. LiAlH(Bu-t) 3 = Lithium tri-t-butoxy aluminum hydride, reducing agent

15 4. Reimer-Tiemann reaction. Phenolic aldehydes. Treatment of a phenol with chloroform and aqueous hydroxide introduces an aldehyde group, -CHO, into the aromatic ring, generally ortho to the -OH. For example: substituted benzal chloride The Reimer-Tiemann reaction involves electrophilic substitution on the highly reactive phenoxide ring. The electrophilic reagent is dichlorocarbene, :CCl 2, generated from chloroform by the action of base.

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17 Preparation of ketones 1. Oxidation of secondary alcohols. Aliphatic ketones are readily prepared from the corresponding secondary alcohols. More complicated aliphatic ketones can be prepared by the reaction of acid chlorides with organocopper compounds. R H C R' CrO 3 OH R C R' SOCl 2 R COOH R COCl R' 2 CuLi O

18 2. Friedel-Crafts acylation. An acyl group, RCO-, becomes attached to the aromatic ring, thus forming a ketone; the process is called acylation. As usual for the Friedel-Crafts reaction catalysis by aluminum chloride or another Lewis acid is required. The most likely mechanism for Friedel-Crafts acylation and involves the following steps:

19 In the preparation of m-nitrobenzophenone, for example, the nitro group can be present in the acid chloride but not in the ring undergoing substitution, since as a strongly deactivating group it prevents the Friedel-Crafts reaction.

20 3. Reaction of acid chlorides with organocopper compounds. Treatment of alkyl or aryl halides with lithium metal gives organolithium compounds which on treatment with a cuprous halides form lithium organocuprates, R 2 CuLi or Ar 2 CuLi. Lithium organocuprates react readily with acid chlorides to yield ketones:

21 4. Acetoacetic ester synthesis. using of ethyl acetoacetate (acetoacetic ester), CH 3 COCH 2 COOC 2 H 5.

22 In the acetoacetic ester synthesis, give the mechanism of the following: 1- Hydrolysis of ester in the alkaline condition. 2- Thermal decarboxylation

23 Reactions. Nucleophilic addition The carbonyl group, C=O, governs the chemistry of aldehydes and ketones. It does this in two ways: (a) by providing a site for nucleophilic addition, and (b) by increasing the acidity of the hydrogen atoms attached to the alpha carbon. The carbonyl group contains a carbon-oxygen double bond; since the mobile p electrons are pulled strongly toward oxygen, carbonyl carbon is electrondeficient and carbonyl oxygen is electron-rich. Because it is flat, this part of the molecule is open to relatively unhindered attack from above or below, in a direction perpendicular to the plane of the group.

24 What is the effect of acid? If acid is present, hydrogen ion becomes attached to carbonyl oxygen. This prior protonation lowers the Eact for nucleophilic attack, since it permits oxygen to acquire the p electrons without having to accept a negative charge. Thus nucleophilic addition to aldehydes and ketones can be catalyzed by acids (sometimes, by Lewis acids).

25 Reactions of aldehydes and ketones 1. Oxidation (a) Oxidation of aldehydes Aldehydes are easily oxidized to carboxylic acids; ketones are not. This process is due to their difference in structure, an aldehyde has a hydrogen atom attached to the carbonyl carbon, and a ketone has not. Tollens' reagent contains the silver ammonia ion, Ag(NH3) Oxidation of the aldehyde is accompanied by reduction of silver ion to free silver (in the form of a mirror under the proper conditions). Colorless solution Silver mirror

26 (b) Oxidation of methyl ketones (iodoform test) The ketone is treated with iodine and sodium hydroxide (sodium hypoiodite, NaOI). A ketone of the structure yields a yellow precipitate of iodoform (CHI 3 ). The reaction involve halogenation and cleavage:

27 Hypohalites can not only halogenate but also oxidize: As a result, an alcohol of the structure oxidize to a methyl ketone, and hence gives a positive test.

28 2. Reduction (a) Reduction to alcohols. Aldehydes can be reduced to primary alcohols, and ketones to secondary alcohols, either by catalytic hydrogenation (H 2, Ni) or by use of chemical reducing agents like lithium aluminum hydride, LiAlH 4. Sodium borohydride, NaBH 4, does not reduce carbon-carbon double bonds, not even those conjugated with carbonyl groups, and is thus useful for the reduction of such unsaturated carbonyl compounds to unsaturated alcohols.

29 Mechanism of alcohol formation: nucleophilic addition, this time the nucleophile is hydrogen transferred with a pair of electrons as a hydride ion, H:- from the metal to carbonyl carbon (b) Reduction to hydrocarbons. Aldehydes and ketones can be reduced to hydrocarbons by the action (a) of amalgamated zinc and concentrated hydrochloric acid, the Clemmensen reduction; or (b) of hydrazine, NH 2 NH 2, and a strong base like KOH or potassium tert-butoxide, the Wolff-Kishner reduction.

30 (c) Reductive amination. Reduction of aldehydes and ketones in the presence of ammonia or amine to the corresponding amines.

31 3. Addition of cyanide The elements of HCN add to the carbonyl group of aldehydes and ketones to yield compounds known as cyanohydrins: Addition appears to involve nucleophilic attack on carbonyl carbon by the strongly basic cyanide ion; subsequently (or possibly simultaneously) oxygen accepts a hydrogen ion to form the cyanohydrin product :

32 Cyanohydrins are nitriles, they undergo hydrolysis; in this case the products are a-hydroxyacids or unsaturated acids. For example:

33 Give the chemical structure instead of A, B, C, D and E and the name of reaction instead of 1, 2, 3, 4 an d 5: (A) HCN (1) H 3 C H 2 C CH 3 C CN H 2 SO 4 / heat (2) (B) OH (4) -CO 2 (3) -H 2 O (E) dry HCl / HCHO (5) (D) (C)

34 4. Addition of derivatives of ammonia Ammonia derivatives add to the carbonyl group to form derivatives containing C=N

35 The solution must be acidic enough for an appreciable fraction of the carbonyl compound to be protonated 5- Addition of alcohols. Acetal formation. Alcohols add to the carbonyl group of aldehydes in the presence of anhydrous acids to yield acetals:

36 The mechanism including formation of hemiacetal (alcohol) by the addition of the nucleophilic alcohol molecule to the carbonyl group. What is the mechanism of hemiacetal formation. In the presence of acid the hemiacetal, acting as an alcohol, reacts with more of the solvent alcohol to form the acetal. an ether:

37 The mechanism of reaction involves the formation (step 1) of the ion I, which then combines (step 2) with a molecule of alcohol to yield the protonated acetal.

38 6- Cannizzaro reaction In the presence of concentrated alkali, aldehydes containing no a-hydrogen undergo self-oxidation-and-reduction to yield a mixture of an alcohol and a salt of a carboxylic acid.

39 The mechanism includes two successive additions, * addition of hydroxide ion (step 1) to give intermediate I * addition of a hydride ion from I (step 2) to a second molecule of aldehyde. The presence of the negative charge on I aids in the loss of hydride ion.

40 Crossed Cannizzaro Reaction In the case of Crossed Cannizzaro with formaldehyde, the formaldehyde carbonyl is extremely reactive and the equilibrium will lie strongly on the side of the formaldehyde tetrahedral intermediate, and consequently most of the other aldehyde will remain present as the aldehyde.

41 Furfural and benzaldehyde O H + O H OH - O OH O O O OH OH OH O Furfuryl alcohol + benzyl alcohol + Furoic acid + benzoic acid

42 7- Aldol condensation Under the influence of dilute base or dilute acid, two molecules of an aldehyde or a ketone containing a-hydrogen may combine to form a b-hydroxyaldehyde or b-hydroxyketone.

43 Hydroxide ion abstracts (step 1) a hydrogen ion from the a-carbon of the aldehyde to form carbanion I, which attacks (step 2) carbonyl carbon to form ion II. An alkoxide (II) abstracts (step 3) a hydrogen ion from water to form the b-hydroxyaldehyde III, regenerating hydroxide ion

44 Crossed aldol condensation An aldol condensation between two different carbonyl compounds,

45 Crossed aldol condensation An aldol condensation between two different carbonyl compounds,

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48 Q/ Give the product for the following reactions: Q/ Give the mechanism of reactions (1) and (2). Q/ Give the mechanism of aldol condensation under the influence of dilute acid.

49 Q/ Are these compounds subject to Cannizzaro reaction or aldol condensation in the presence of alkaline medium, give the products:

50 8- Addition of Grignard reagents. The Grignard reagent has the formula RMgX, and is prepared by the reaction of metallic magnesium with the appropriate organic halide. This halide can be alkyl (1, 2, 3), allylic, aralkyl (e.g., benzyl), or aryl (phenyl or substituted phenyl). Grignard reagent reacts with aldehydes and ketones to yield alcohols.

51 Mechanism The carbon-magnesium bond of the Grignard reagent is a highly polar bond, carbon being negative relative to electropositive magnesium. It is not surprising, then, that in the addition to carbonyl compounds, the organic group becomes attached to carbon and magnesium to oxygen. The product is the magnesium salt of the weakly acidic alcohol and is easily converted into the alcohol itself by the addition of the stronger acid, water.

52 Organolithium compounds are used instead of Grignard because, give less unwanted side reactions and lithium is more electropositive than magnesium, C O R Li C O - Li + H 2 O C OH R R Products of the Grignard synthesis The class of alcohol that is obtained from a Grignard synthesis depends upon the type of carbonyl compound used: formaldehyde, HCHO, yields primary alcohols; other aldehydes, RCHO, yield secondary alcohols; and ketones, R 2 CO, yield tertiary alcohols.

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