ORGANIC - CLUTCH CH ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION

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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: 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 5

6 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 6

7 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 7

8 CONCEPT: WEAK OXIDATIVE CLEAVAGE Ozonolysis: Ketones + Aldehydes + Formaldehyde PRACTICE: Predict the products of the following reaction Page 8

9 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 9

10 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 10

11 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 11

12 CONCEPT: CYANOHYDRINS Cyanide Addition: Cyanohydrins Cyanohydrin Hydrolysis: Cyanohydrin Reduction: Page 12

13 PRACTICE: Provide the major product for the following reaction. Page 13

14 CONCEPT: ORGANOMETALLICS 1. Nucleophilic Addition on Ketones and Aldehydes EXAMPLE: Show the mechanism and predict the product for the following reaction. Page 14

15 PRACTICE: Provide the major product for the following reaction. Page 15

16 PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent. O Mg H 3 O + Br Ether (ROR) Page 16

17 PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent. Page 17

18 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 18

19 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 19

20 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 20

21 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 21

22 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 22

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

24 PRACTICE: Provide the chemical steps necessary for the following synthesis. Page 24

25 PRACTICE: Determine the starting materials based on the acetal group present. O O Page 25

26 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 26

27 PRACTICE: Provide the chemical steps necessary for the following synthesis. Page 27

28 PRACTICE: Provide the chemical steps necessary for the following synthesis. O N? O O H H CH 3 Page 28

29 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 29

30 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 30

31 CONCEPT: ADDITION OF AMMONIA DERIVATIVES EXAMPLE: Predict the products of the following reaction. Page 31

32 CONCEPT: WOLFF-KISCHNER REDUCTION This reaction sequence is used to completely remove carbonyls from alkane chains, much like: a. b. Mechanism: Page 32

33 CONCEPT: KETONES FROM ACID CHLORIDES When a good leaving group is present on a carbonyl, organometallics tend to react twice, yielding disubstituted alcohols. Nucleophilic Acyl Substitution on Esters and Acid Chlorides From Acid Chlorides: We can reduce the power of the organometal by using a Gilman to yield from RCOCl This reagent stops after the first nucleophilic addition Page 33

34 PRACTICE: Provide the major product for the following reaction. O Cl (CH 3 CH 2 ) 2 CuLi Ether Page 34

35 CONCEPT: KETONES FROM NITRILES Nitriles can act very much like carbonyl compounds when exposed to a strong Nu - like a Grignard Mechanism: Page 35

36 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 36

37 PRACTICE: Determine the carbonyl and ylide that formed the following product. Page 37

38 PRACTICE: Provide the major product for the following reaction. Page 38

39 PRACTICE: Provide the major product for the following reaction. Page 39

40 PRACTICE: Provide the chemical steps necessary for the following synthesis. Page 40

41 PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent. Page 41