Chapter 1--Title

Aldehydes and Ketones II. NUCLEOPHILIC ADDITIONS TO THE CARBONYL GROUP

OBJECTIVES1. Describe the reactivity of carbonyl group towards the nucleophilic addition (PAGE : 741)2. Predict the products of cyanohydrin from synthesis of -hydroxy acids and hydrolysis of nitriles (PAGE : 755)3. Predict the products from the addition of Organometallic Reagents Grignard and alkyl lithium reagents) to aldehydes and ketones. (PAGE : 566-568, 776)4. Predict the products from the addition of water (hydration) to aldehydes and ketones (PAGE : 746)5.. Predict the products of acetals and hemiacetal from the addition of Alcohols and describe the formation of cyclic acetals (PAGE : 748) and its uses as protecting group. (PAGE : 749)6. Predict the products from the addition of amines to aldehydes and ketones which produce Imines from 1o Amines (PAGE : 751), Enamines from 2o Amines (PAGE : 754), Enamines for Alkylation of Ketones (PAGE : 755)7. Predict the products from Wittig Reaction (PAGE : 757-760)1. Describe the reactivity of carbonyl group towards the nucleophilic addition (PAGE : 741)Chapter 163Chapter 164Nucleophilic Addition to the Carbonyl GroupsAddition of a nucleophile to a carbonyl carbon occurs because of the d+ charge at the carbon

Addition of strong nucleophiles such as hydride or Grignard reagents result in formation of a tetrahedral alkoxide intermediateThe carbonyl p electrons shift to oxygen to give the alkoxideThe carbonyl carbon changes from trigonal planar to tetrahedral

Chapter 165

Chapter 166acid catalyst is used to facilitate reaction of weak nucleophiles with carbonyl groups Protonating the carbonyl oxygen enhances the electrophilicity of the carbon

REACTIVITY OF ALDEHYDE AND KETONEChapter 167Chapter 168Relative Reactivity: Aldehydes versus KetonesAldehydes are generally more reactive than ketonesThe tetrahedral carbon resulting from addition to an aldehyde is less sterically hindered than the tetrahedral carbon resulting from addition to a ketoneAldehyde carbonyl groups are more electron deficient because they have only one electron-donating group attached to the carbonyl carbon

2. Predict the products of cyanohydrin from synthesis of -hydroxy acids and hydrolysis of nitriles (PAGE : 755)Chapter 169Chapter 1610The Addition of Hydrogen Cyanide (PAGE : 755)

Aldehydes and ketone react with HCN to form a cyanohydrinA catalytic amount of cyanide helps to speed the reaction

The cyano group can be hydrolyzed or reducedHydrolysis of a cyanohydrin produces an a-hydroxycarboxylic acid (Sec. 18.8H)

Chapter 1611

Reduction of a cyanohydrin produces b-aminoalcohol

Chapter 1612

3. Predict the products from the addition of Organometallic Reagents Grignard and alkyl lithium reagents) to aldehydes and ketones. (PAGE : 566-568, 776)Chapter 1613Chapter 1214Reaction of Grignard Reagents with Carbonyl CompoundsNucleophilic attack of Grignard reagents at carbonyl carbons is the most important reaction of Grignard reagents

Reaction of Grignard reagents with aldehydes and ketones yields a new carbon-carbon bond and an alcohol

14Chapter 1615

Chapter 1216Alcohols from Grignard Reagents

16Chapter 1217Alkyl Lithium ReagentsOrganolithium reagents react similarly to Grignard reagents

174. . Predict the products from the addition of water (hydration) to aldehydes and ketones (PAGE : 746)Chapter 1618Nucleophilic Addition of H2O: HydrationAldehydes and ketones react with water to yield 1,1-diols (geminal (gem) diols)Hyrdation is reversible: a gem diol can eliminate water

Base-Catalyzed Addition of WaterAddition of water is catalyzed by both acid and baseThe base-catalyzed hydration nucleophile is the hydroxide ion, which is a much stronger nucleophile than water

Acid-Catalyzed Addition of WaterProtonation of C=O makes it more electrophilic

5. Predict the products of acetals and hemiacetal from the addition of Alcohols and describe the formation of cyclic acetals (PAGE : 748) and its uses as protecting group. (PAGE : 749)Chapter 1622Chapter 1623The Addition of Alcohols: Hemiacetals and AcetalsHemiacetalsAn aldehyde or ketone dissolved in an alcohol will form an equilibrium mixture containing the corresponding hemiacetalA hemiacetal has a hydroxyl and alkoxyl group on the same carbonAcylic hemiacetals are generally not stable, however, cyclic five- and six-membered ring hemiacetals are

Chapter 1624Hemiacetal formation is catalyzed by either acid or base

Chapter 1625Dissolving aldehydes (or ketones) in water causes formation of an equilibrium between the carbonyl compound and its hydrateThe hydrate is also called a gem-diol (gem i.e. geminal, indicates the presence of two identical substituents on the same carbon)The equilibrum favors a ketone over its hydrate because the tetrahedral ketone hydrate is sterically crowded

Chapter 1626AcetalsAn aldehyde (or ketone) in the presence of excess alcohol and an acid catalyst will form an acetalFormation of the acetal proceeds via the corresponding hemiacetal An acetal has two alkoxyl groups bonded to the same carbon

Chapter 1627Acetals are stable when isolated and purifiedAcetal formation is reversibleAn excess of water in the presence of an acid catalyst will hydrolyze an acetal to the corresponding aldehyde (or ketone)

Chapter 1628Acetal formation from ketones and simple alcohols is less favorable than formation from aldehydes Formation of cyclic 5- and 6- membered ring acetals from ketones is, however, favorableSuch cyclic acetals are often used as protecting groups for aldehydes and ketonesThese protecting groups can be removed using dilute aqueous acid

Chapter 1629Acetals as Protecting GroupsAcetal protecting groups are stable to most reagents except aqueous acidExample: An ester can be reduced in the presence of a ketone protected as an acetal

6. Predict the products from the addition of amines to aldehydes and ketones which produce Imines from 1o Amines (PAGE : 751), Enamines from 2o Amines (PAGE : 754), Enamines for Alkylation of Ketones (PAGE : 755)Chapter 1630Chapter 1631The Addition of Primary and Secondary AminesAldehydes and ketones react with primary amines (and ammonia) to yield iminesThey react with secondary amines to yield enamines

Chapter 1632Imines

These reactions occur fastest at pH 4-5

Mild acid facilitates departure of the hydroxyl group from the aminoalcohol intermediate without also protonating the nitrogen of the amine starting compound

Chapter 1633

Chapter 1634Enamines

Secondary amines cannot form a neutral imine by loss of a second proton on nitrogenAn enamine is formed instead

Chapter 1635

7. Predict the products from Wittig Reaction (PAGE : 757-760)

Chapter 1636Chapter 1637The Addition of Ylides: The Wittig ReactionAldehydes and ketones react with phosphorous ylides to produce alkenesAn ylide is a neutral molecule with adjacent positive and negative charges

Chapter 1638Reaction of triphenylphosphine with a primary or secondary alkyl halide produces a phosphonium salt The phosphonium salt is deprotonated by a strong base to form the ylide

Chapter 1639Addition of the ylide to the carbonyl leads to formation of a four-membered ring oxaphosphetaneThe oxaphophetane rearranges to the alkene and triphenylphosphine oxideThe driving force for the last reaction is formation of the very strong phosphorus-oxygen double bond in triphenylphosphine oxide

Chapter 1640Solved Problem: Make 2-Methyl-1-phenylprop-1-ene by a Wittig reaction