Chapter 18: Ketones and Aldehydes. I. Introduction

Transcription

1 1 Chapter 18: Ketones and Aldehydes I. Introduction We have already encountered numerous examples of this functional group (ketones, aldehydes, carboxylic acids, acid chlorides, etc). The three-dimensional structure and hybridization of aldehydes and ketones is shown below: All C=O compounds have a minor contributing resonance structure that heavily influences their chemistry:

2 2

3 3 II. Nomenclature of Aldehydes and Ketones A. IUPAC Nomenclature of Aldehydes

4 4 B. IUPAC Nomenclature of Ketones Functional Group Priorities:

5 5 Common Nomenclature of Ketones (Systematic) 1) Name each carbon group attached to the carbonyl (C=O) carbon as an alkyl group. 2) List the alkyl groups, separated by spaces, in front of the word ketone. III. Spectroscopy:

6 6 IV. Review of the synthesis of Ketones and Aldehydes A) Oxidation of Alcohols (to aldehydes and ketones) Observed Reaction: 1 o Alcohols to Aldehydes Observed Reaction: 2 o Alcohols to Ketones B) Ozonolysis of Alkenes Observed Reaction C) Friedel-Crafts Acylation Observed Reaction

7 7 D) Hydration of Alkynes Two Cases here 1. Markovnikov 2. Anti-Markovnikov E). Hydride Addition (to form alcohols) Mechanism: Sodium borohydride (NaBH 4 ) and lithium aluminum hydride (LiAlH 4 ) are sources of H: (hydride). Hydride is a hydrogen nucleophile. It reacts with the C=O carbon:

8 8 F. Organometallic Additions Mechanism:

9 9 V. Reactions of Aldehydes and Ketones CASE 1:

10 10 CASE 2: A. Grignards and ketones: B. Hydride sources and ketones:

11 11 VI. Relative Reactivity of Aldehydes and Ketones 1. Electronic Effects Ketones have two alkyl substituents whereas aldehydes only have one. 2. Sterics

12 12 VII. Nucleophilic Addition of Water (Hydration) and Alcohols (Acetals) 1. Hydration In aqueous solution, ketones (and aldehydes) are in equilibrium with their hydrates (geminal diols). Hydration proceeds through the two classic nucleophilic addition mechanisms with water (in acid) or hydroxide (in base) acting as the nucleophile.

13 13 Aldehydes are more likely to form hydrates since they have the largerr partial positive charge on the carbonyl carbon (larger charge = lesss stable = more reactive) 2. Formation of Hemiacetals and Acetals In an similar fashion to the formation of hydrates with water, aldehydes and ketones form acetals and hemiacetals through reaction with alcohols. Sugars commonly exist as acetals or hemiacetals (Chapter 23, carbs ). A. Observed Reaction

14 14 B. Mechanism of Acetal Formation

15 15 Note that cyclic hemiacetals are reasonably stable (found in sugar chemistry, for example glucose) HO HO HOH H H Hemiacetal H O H OH OH Two glucose subunits can link via acetal formation HOH H O HO HO H H OH H O H OH H H O HO H OH OH H Cellulose (beta-1,4 links) if alpha-1,4 = carbohydrates C. Acetal Hydrolysis The mechanism of hydrolysis is exactly the same as the mechanism of formation, just in reverse.

16 16 D. Formation of Cyclic Acetals and the use of Acetals as Protecting Groups More commonly, instead of two molecules of alcohols being used, a diol is used (entropically more favorable). This produces cyclic acetals. Example: Acetals

17 17 E. Selective Acetal Formation We have previously seen that aldehydes are more reactive than ketones (two reasons), and therefore aldehydes will react to form acetals preferentially over ketones. Example:. This is a useful way to perform reactions on ketone functionalities in molecules that contain both aldehyde and ketone groups.

18 18 VIII. Nitrogen Addition (formation of imines, hydrazones, oximes) General Mechanism: (can react with ketones or aldehydes)

19 19 Different Z groups lead to similar products with different names Z Group (All 1 o Amines) H 2 N Z Name Product Name Product Structure C=N can be converted back to C=O by acid-catalyzed hydrolysis.

20 20 IX. Aldehydes and Ketones from Acid Chlorides 1. Aldehydes

21 21 Generation of Acid Chlorides The reaction of carboxylic acids with thionyl chloride (SOCl 2 ) generates acid chlorides. Observed Reaction Mechanism

22 22 2. Ketones Acid chlorides react with Grignard (and organolithium) reagents. Question: How can we stop the reaction at the ketone? Answer: Use a weaker organometallic reagent: Observed Reaction The lithium dialkyl cuprate is produced by the reaction of two equivalents of the organolithium reagent with copper (I) iodide.

23 23 X. CARBANIONIC NUCLEOPHILES 1. Nucleophilic Addition of Hydrogen Cyanide (Cyanohydrins) Hydrogen cyanide is toxic volatile liquid (b.p.26 C). Cyanide is a strong base (HCN weak acid) and a good nucleophile. Cyanide reacts rapidly with carbonyl compounds producing cyanohydrins, via the base catalyzed nucleophilic addition mechanism. Like hydrate formation, cyanohydrin formation is an equilibrium governed reaction (i.e. reversible reaction), and accordingly aldehydes are more reactive than ketones. Cyanohydrin formation is readily reversed by treating the cyanohydrin with base: 2. Addition of acetylide ions and organometallic reagents

24 24 3. Addition of Phosphorus Ylides (Wittig Reaction) In 1954 Wittig (Nobel Prize in 1979) discovered that the addition of a phosphorus stabilized anion to a carbonyl compound did not generate an alcohol, but an alkene! Observed Reaction Mechanism: Part One

25 25 Part Two

26 26 XI. Oxidation of Alcohols Unlike ketones, aldehydes can be oxidized easily to carboxylic acids (Chromic acid, permanganate etc). Even weak oxidants like silver (I) oxide can perform this reaction, and this is a good, mild selective way to prepare carboxylic acids in the presence of other (oxidizable) functionalities. Silver Mirror Test (Tollen's Test) Tollen's reagent is added to an unknown compound, and if an aldehyde is present, it is oxidized. This process reduces the Ag + to Ag, and the Ag precipitates - it sticks to the flask wall, and forms a silver mirror (pretty!).

27 27 Catalytic Hydrogentation: Just as C=C double bonds can be reduced by the addition of hydrogen across the double bond, so can C=O double bonds. Example XIII. Deoxygenation of Ketones and Aldehydes Deoxygenation involves the removal of oxygen, and its replacement with two hydrogen atoms. This reduction takes the carbonyl (past the alcohol) to a methylene group. Compare the following reduction processes: