ORGANIC - BROWN 8E CH ALDEHYDES AND KETONES.

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2 CONCEPT: ALDEHYDE NOMENCLATURE Replace the suffix of the alkane -e with the suffix On the parent chain, the carbonyl is always terminal, and receive a location As substituents, they receive the name and receive a location EXAMPLE: Correctly name the following aldehyde. EXAMPLE: Correctly name the following aldehyde. Page 2

3 CONCEPT: KETONE NOMENCLATURE Replace the suffix of the alkane -e with the suffix Ketones have higher priority than most groups in Orgo 1, including alcohols When assigning common names to ketones, name both R-groups alphabetically, ending with EXAMPLE: Correctly name the following ketone. 1. EXAMPLE: Correctly name the following ketone. 2. Page 3

4 CONCEPT: INTRO TO REDOX Oxidation reactions involve an increase in the content of a molecule Reduction reactions involve an increase in the content of a molecule EXAMPLE: Label the following transformations as oxidation or reduction. a. b. c. Page 4

5 CONCEPT: NUCLEOPHILIC ADDITION One of the most important ways that carbonyl compounds react is through nucleophilic addition. The carbonyl carbon is Nucleophilic Addition General Mechanism: Nucleophilic Addition General Reactions: Page 5

6 CONCEPT: ORGANOMETALLICS 1. Nucleophilic Addition on Ketones and Aldehydes EXAMPLE: Show the mechanism and predict the product for the following reaction. Page 6

7 PRACTICE: Provide the major product for the following reaction. Page 7

8 PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent. O Mg H 3 O + Br Ether (ROR) Page 8

9 PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent. Page 9

10 PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent. Br O TMS-Cl Mg OH N(Et) 3 A Ether (ROR) B H 3 O + C Page 10

11 CONCEPT: CYANOHYDRINS Cyanide Addition: Cyanohydrins Cyanohydrin Hydrolysis: Cyanohydrin Reduction: Page 11

12 PRACTICE: Provide the major product for the following reaction. Page 12

13 CONCEPT: THE WITTIG REACTION The Wittig forms new carbon-carbon bonds between carbonyl and reactive intermediate called an ylide to yield regiospecific Formation of the Ylide: STEP 1 Alkyl Halide + Triphenylphosphine STEP 2 Deprotonation with a Strong Base STEP 3 Form Oxaphosphetane (mechanism) or Box-Out Method (product). Page 13

14 PRACTICE: Determine the carbonyl and ylide that formed the following product. Page 14

15 CONCEPT: NUCLEOPHILIC ADDITION OF SOLVENTS These are reactions that are induced primarily by the extraordinary reactivity at the carbonyl carbon The carbonyl carbon is so reactive that it even reacts with some Most of these mechanisms are acid-catalyzed all are fully reversible in mild acid (H3O + ). Protonation is always the first step, deprotonation is always the last (restores the catalyst) Page 15

16 CONCEPT: HYDRATES Carbonyl + Water In carbonyls with large R groups, the equilibrium is greatly shifted to the EXAMPLE: Show the mechanism and predict the equilibrium for the following reaction. Page 16

17 CONCEPT: HEMIACETALS Technically, an is the product of alcohol and aldehyde, while is alcohol and ketone. We will simply use the word acetal to represent these gem-diether structures in general Hemiacetals are only stable when they are. Carbonyl + 1 Eq. Alcohol Acid-Catalyzed Hemiacetal Formation Base-Catalyzed Hemiacetal Formation Page 17

18 CONCEPT: ACETALS Acetals are stable in and are easily hydrolyzed back to carbonyls using Cyclic acetals are formed by reacting carbonyls with a Carbonyl + 2 Eq. Alcohol Acid-Catalyzed Hemiacetal Formation Acid-Catalyzed Acetal Formation Page 18

19 PRACTICE: Provide the chemical steps necessary for the following synthesis. O? O O Page 19

20 PRACTICE: Provide the chemical steps necessary for the following synthesis. Page 20

21 PRACTICE: Determine the starting materials based on the acetal group present. O O Page 21

22 CONCEPT: ACETALS AS PROTECTING GROUPS There is a huge difference in reactivity between a carbonyl and an acetal. Which do you think is more reactive? Acetals are used to protect sensitive aldehydes and ketones from reaction with other reagents, since they are reversible. EXAMPLE: Propose a reagent to perform the following transformation. More than one reagent may be required. Page 22

23 PRACTICE: Provide the chemical steps necessary for the following synthesis. Page 23

24 PRACTICE: Provide the chemical steps necessary for the following synthesis. O N? O O H H CH 3 Page 24

25 CONCEPT: THIOACETALS AND RANEY NICKEL REDUCTION Via an almost identical mechanism, thiols can react with aldehydes and ketones to produce thioacetals The Raney nickel catalyst is a convenient way to carbonyls altogether EXAMPLE: Predict the products of the following reaction Page 25

26 CONCEPT: IMINES AND ENAMINES Primary Amine Addition: Imines Secondary Amine Addition: Enamines All products produce iminium cation, where the deprotonation step will depend on type of amine used. Imine Mechanism: Enamine Mechanism: Page 26

27 CONCEPT: ADDITION OF AMMONIA DERIVATIVES EXAMPLE: Predict the products of the following reaction. Page 27

28 CONCEPT: OXIDATION Oxidizing agents are used to oxidize molecules Most oxidizing agents add as much oxygen as possible while not breaking ANY C-C bonds. EXAMPLE: Which of the following compounds could be oxidized? These are called strong oxidizing agents. They include KMnO4 and the Cr 6+ reagents (H2Cr2O4, CrO3, K2Cr2O7, etc.) EXAMPLE: Draw the products of the previous molecules with a strong oxidizing agent PCC is a weak oxidizing agent. It reacts similar but can only add equivalent of oxygen to 1º alcohols. Page 28

29 PRACTICE: Provide the major product for the following oxidation reaction. CH 3 OH CH 3 PCC H 3 C OH OH CH 2 Cl 2 PRACTICE: Provide the major product for the following oxidation reaction. H 2 C CH 3 1. O 3 2. Zn, CH 3 CO 2 H PRACTICE: Provide the major product for the following oxidation reaction. OH HO OH KMnO 4 H + PRACTICE: Provide the major product for the following oxidation reaction. Page 29

30 PRACTICE: Determine the major product for the following reaction. PRACTICE: Determine the major product for the following reaction. PRACTICE: Provide the necessary reagents for the following transformation. Page 30

31 CONCEPT: WEAK OXIDATIVE CLEAVAGE Ozonolysis: Ketones + Aldehydes + Formaldehyde PRACTICE: Predict the products of the following reaction Page 31

32 CONCEPT: ALDEHYDES VIA REDUCING AGENTS All of the reducing agents we have learned so far are so powerful that they yield alcohols. We need to use milder reducing agents to yield aldehydes. 1. Typical strong reduction of carbonyls is accomplished via the use of 2. We can reduce the power of the reducing agent by making it sterically hindered: 3. There is another reagent we can use to only induce one equivalent of hydrogen to a carbonyl: Page 32

33 CONCEPT: REDUCTIVE AMINATION Recall that ketones and aldehydes can react with primary amines in acidic conditions to form imines. This mechanism passed through an important intermediate called an iminium cation. Ketones and aldehydes can be made to form amines instead by using the reducing agent, NaBH3CN on the imine. This mechanism starts the same, except for the fact that we reduce the imine instead of deprotonating it EXAMPLE: Provide the major product for the following reaction. Page 33

34 CONCEPT: ALKYNE HYDRATION Vinyl alcohols are uniquely reactive due to a phenomenon called tautomerization. They reversibly swap the positions of a and a bond. Oxymercuration of Alkynes Product: Hydroboration of Alkynes Product: Page 34

35 CONCEPT: WOLFF-KISCHNER REDUCTION This reaction sequence is used to completely remove carbonyls from alkane chains, much like: a. b. Mechanism: Page 35

36 CONCEPT: ALPHA CARBONS AND TAUTOMERIZATION We have discussed the high reactivity of the carbonyl carbon. However, carbonyls contain another highly reactive component. What is the acidity of the β-carbon? What is the acidity of the α-carbon? Which phenomenon is responsible for this difference? Tautomerization General Reaction: Acid-Catalyzed Mechanism: Base-Catalyzed Mechanism: Page 36

37 PRACTICE: Draw the enol tautomer for the following compound. Cyclopentanone Page 37

38 CONCEPT: TAUTOMERS OF DICARBONYL COMPOUNDS Most carbonyl compounds favor the tautomer β-dicarbonyl compounds favor the tautomer due to and β-dicarbonyl compounds are exceptionally acidic due to the high stability of the conjugate base If the α-carbon exists as a chiral center, that carbon will ALWAYS BE EXAMPLE: Which of the following ketones is the most acidic? Page 38

39 CONCEPT: ENOLATES Upon deprotonation, the α-carbon forms a resonance-stabilized intermediate structure called an Both notations can be used to represent an enolate Note that the negative charge now rests on the This makes the α-carbon of the enolate a good General Reactions of Enolates: Page 39

40 CONCEPT: ELECTROPHILIC α-halogenations Acid-Catalyzed α-halogenation: Always yields -halogenation PRACTICE: Provide the major product for the following reaction. O Br 2 CH 3 H + Page 40

41 CONCEPT: ELECTROPHILIC α-halogenations Base-Catalyzed α-halogenation: May yield -halogenation PRACTICE: Provide the major product for the following reaction. O Br 2 excess NaOH Page 41

42 CONCEPT: ELECTROPHILIC α-halogenations The Haloform Reaction: Base-Catalyzed α-halogenation of The α-carbon is transformed into a good through successive halogenations. PRACTICE: Provide the major product for the following reaction. O Br 2 excess NaOH Page 42

43 PRACTICE: Provide the major product for the following reaction. Page 43

44 PRACTICE: Provide the major product for the following reaction. Page 44

45 PRACTICE: Provide the chemical steps necessary for the following synthesis. Page 45

46 PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent. Page 46