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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
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
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
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
CONCEPT: ORGANOMETALLICS 1. Nucleophilic Addition on Ketones and Aldehydes EXAMPLE: Show the mechanism and predict the product for the following reaction. Page 6
PRACTICE: Provide the major product for the following reaction. Page 7
PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent. O Mg H 3 O + Br Ether (ROR) Page 8
PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent. Page 9
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
CONCEPT: CYANOHYDRINS Cyanide Addition: Cyanohydrins Cyanohydrin Hydrolysis: Cyanohydrin Reduction: Page 11
PRACTICE: Provide the major product for the following reaction. Page 12
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
PRACTICE: Determine the carbonyl and ylide that formed the following product. Page 14
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
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
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
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
PRACTICE: Provide the chemical steps necessary for the following synthesis. O? O O Page 19
PRACTICE: Provide the chemical steps necessary for the following synthesis. Page 20
PRACTICE: Determine the starting materials based on the acetal group present. O O Page 21
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
PRACTICE: Provide the chemical steps necessary for the following synthesis. Page 23
PRACTICE: Provide the chemical steps necessary for the following synthesis. O N? O O H H CH 3 Page 24
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
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
CONCEPT: ADDITION OF AMMONIA DERIVATIVES EXAMPLE: Predict the products of the following reaction. Page 27
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
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
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
CONCEPT: WEAK OXIDATIVE CLEAVAGE Ozonolysis: Ketones + Aldehydes + Formaldehyde PRACTICE: Predict the products of the following reaction Page 31
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
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
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
CONCEPT: WOLFF-KISCHNER REDUCTION This reaction sequence is used to completely remove carbonyls from alkane chains, much like: a. b. Mechanism: Page 35
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
PRACTICE: Draw the enol tautomer for the following compound. Cyclopentanone Page 37
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
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
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
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
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
PRACTICE: Provide the major product for the following reaction. Page 43
PRACTICE: Provide the major product for the following reaction. Page 44
PRACTICE: Provide the chemical steps necessary for the following synthesis. Page 45
PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent. Page 46