Chapter 12: Carbonyl Compounds II Learning bjectives: 1. Recognize and assign names to aldehydes and ketones. 2. Write the mechanism for nucleophilic addition and nucleophilic addition-elimination reactions of aldehydes and ketones, and be able to predict the products of such reactions. 3. Be able to explain the relative reactivity of carbonyl compounds toward nucleophilic addition. 4. Be able to describe the concept of employing protecting groups. 5. Predict the products of the reactions of carbonyl compounds with Grignard reagents and hydride ion donors. 6. Be able to write the reactions and electron-pushing mechanisms for the formation of geminal diol, hemiacetal (hemiketal), acetal (ketal), and imine. Sections: 12.1 Nomenclature of Aldehydes and Ketones 12.2 ow Aldehydes and Ketones React (Carbon-based Nucleophiles) 12.3 ow Aldehydes and Ketones React (ydrogen-based Nucleophiles) 12.4 ow Aldehydes and Ketones React (Nitrogen-based Nucleophiles) 12.5 ow Aldehydes and Ketones React (xygen-based Nucleophiles) 12.1 Nomenclature of Aldehydes and Ketones 1
A. Examples Cl C 2 C 3 C 2 C 3 C 2
C 3 3
B. Self-assessment Questions Can you recognize the general structures of oxo group, carbonyl group, acyl group, aldehyde and ketone? Can you provide both IUPAC and common names (when applicable) for aldehydes and ketones? 12.2 ow Aldehydes and Ketones React (Carbon-based Nucleophiles) Know the difference of nucleophilic addition in basic and acidic conditions. A. Structural Analysis 4
B. Relative Reactivity of Class I and Class II Carbonyl Compounds C. Nucleophilic Addition (Class II) (i) In basic condition (two separated steps) Nu Nu R (R) R (R) R (R) Nu ( Z) tetrahedral intermediate 5
(ii) In acidic condition (usually in one step) B B + B R (R) R (R) R (R) D. Types of Nucleophile for Class II Carbonyl Groups (i) Carbon as the nucleophilic atom (ii) ydrogen as the nucleophilic atom 6
(iii) Nitrogen as the nucleophilic atom (iv) xygen as the nucleophilic atom E. Carbon as the Nucleophilic Atom: Grignard Reagents (i) Carboanions are highly reactive. (ii) Formation of Grignard reagents 7
(iii) Reaction of Grignard reagents Reaction of aldehydes and ketones with Grignard reagent 8
Reaction of other functional groups with Grignard reagent 9
Reaction of esters with Grignard reagent 10
(iv) Reactions of carbonyl groups with acetylide ions F. Self-assessment Questions Can you describe the difference of nucleophilic addition in basic and acidic conditions? Can you explain the relative reactivity of classes I and I carbonyl compounds? Can you recognize the carbon-based nucleophiles (Grignard reagents and acetylide ions), and describe the chemical properties and provide the syntheses of these reagents? Can you provide the products for the reactions between various carbonyl groups and epoxide, and carbon-based nucleophiles (Grignard reagents and acetylide ions)? Can you write the electron-pushing mechanisms for the reactions between various carbonyl groups and epoxide, and carbon-based nucleophiles (Grignard reagents and acetylide ions)? 12.3 ow Aldehydes and Ketones React (ydrogen-based Nucleophiles) A. ydride-based reagents LiAl4 NaB4 11
B. General reactions: C. Examples (i) General mechanism 12
(ii) Comparison of LiAl4 and NaB4 Relative Reactivity Amide Ester Carboxylic acid Ketone Aldehydde LiAl4 NaB4 (iii) Examples of reduction Reduction of Ester with LiAl4 13
Reduction of Carboxylic Acids with LiAl4 Reduction of Amides with LiAl4 14
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(iv) Selective reduction D. Self-assessment Questions Can you recognize the hydrogen-based nucleophiles (lithium aluminum hydride and sodium borohydride), and describe the chemical properties of these reagents? Can you provide the products for the reactions between various carbonyl groups and hydrogen-based nucleophiles (lithium aluminum hydride and sodium borohydride)? Can you write the electron-pushing mechanisms for the reactions between various carbonyl groups and hydrogen-based nucleophiles (lithium aluminum hydride and sodium borohydride)? 17
12.4 ow Aldehydes and Ketones React (Nitrogen-based Nucleophiles) A. General mechanism in acidic condition B. Roles and Reactivity of Amines 1 and 2 Amines function as weak bases or nucleophiles. 3 Amines function as weak bases. C. Formation of Imines from Primary Amines NR' R + + + R 2 NR' 2 18
D. Mechanism for the Formation of Imines 19
E. Self-assessment Questions Can you describe the differences among primary, secondary and tertiary amines when function as nucleophile or base? Can you provide the products for the reactions between various carbonyl groups and primary amines? Can you write the electron-pushing mechanisms for the reactions between various carbonyl groups and primary amines? 12.5 ow Aldehydes and Ketones React (xygen-based Nucleophiles) A. General mechanism in acidic condition B. Roles and Reactivity of Alcohols 1 and 2 Alcohols function as weak bases or nucleophiles. 3 Alcohols function as weak bases. 20
C. Reactions of Aldehydes and Ketones with Alcohols (i) Example and mechanism for the formation of hydrate, gem-diol, geminal diol 21
Mechanism (ii) Examples and mechanism for the formation of acetal and/or ketal 22
Mechanism 23
(iii) Formation of cyclic hemiacetals or hemiketals Intramolecular reaction: formation of 5 or 6-membered rings 24
(iv) Cyclic hemiacetals in carbohydrates D. Self-assessment Questions Can you describe the differences among primary, secondary and tertiary alcohols when function as acid, nucleophile or base? Can you provide the products for the reactions between various carbonyl groups and primary alcohols? Can you write the electron-pushing mechanisms for the reactions between various carbonyl groups and primary alcohols? 25