Exam 2 Reactions

Cyclic Acetal

acyclic acetal

a carbon chain with OH on either end and an acid catalyst

a two sets of carbon chains with OH at the end and an acid catalyst

[carbon chain] [magnesium] [halogen] R-Mg-X

Turns a carbonyl (ketone or aldehyde) into an alcohol. The Grignard Reagent acts like nucleophile and attacks the carbonyl, shifting the double bond to a lone pair on the oxygen. The alkoxide ion is protonated (H added) from water creating an alcohol. A new C-C bond is formed.

LiAlH4 and THF or NaBH4 and an alcohol

• Oxidation of Primary alcohols (PCC, CH2Cl2 or DMP, CH2Cl2, or 1. DMSO, (COCl)2, 2. Et3N • ozonolysis of alkenes (1. O3, 2. DMS) • Hydroboration-Oxidation (1. R2B-H, 2. H2)2, NaOH

• Oxidation of Secondary Alcohols (Na2Cr2O7, H2SO4, H2O) • Ozonoloysis of Alkenes (1. O3, 2. DMS) • Acid-Catalyzed Hydration of Terminal Alkynes (H2SO4, H2O, HgSO4 • Friedel-Crafts Acylation (Cl-(C=O)-R, AlCl3)

Nucleophilic Attack followed by Proton Transfer • nucleophile attacks the Carbon of the carbonyl. • electrons in double bond migrate to Oxygen becoming a lone pair • Proton transfer: lone pair on Oxygen attacks the hydrogen on water • OH created and nucleophile stays attached to Carbon

nucleophilic addition under basic conditions • nucleophile attacks the Carbon of the carbonyl. • electrons in double bond migrate to Oxygen becoming a lone pair • Proton transfer: lone pair on Oxygen attacks the hydrogen on water • OH created and nucleophile stays attached to Carbon

nucleophilic addition under acidic conditions • Proton Transfer: lone pairs on carbonyl oxygen attacks hydrogen on an acid. • Nucleophilic Attack: a nucleophile attacks the Carbon of the carbonyl. • electrons in double bond migrate to Oxygen becoming a lone pair • OH created and nucleophile stays attached to Carbon

Proton Transfer followed by Nucleophilic Attack • Proton Transfer: lone pairs on carbonyl oxygen attacks hydrogen on an acid. • Nucleophilic Attack: a nucleophile attacks the Carbon of the carbonyl. • electrons in double bond migrate to Oxygen becoming a lone pair • OH created and nucleophile stays attached to Carbon

Base-Catalyzed Hydration • Carbon of Carbonyl group attacked by lone pairs on the oxygen of a hydroxide (-OH) • electrons in double bond migrate to Oxygen becoming a lone pair • OH attaches and an anionic intermediate forms • lone pair of negatively charged oxygen (previously carbonyl oxygen) attacks hydrogen in H2O and protonates • two OH groups are now attached to carbonyl carbon

Nucleophilic Attack followed by Proton Transfer • Carbon of Carbonyl group attacked by lone pairs on the oxygen of a hydroxide (-OH) • electrons in double bond migrate to Oxygen becoming a lone pair • OH attaches and an anionic intermediate forms • lone pair of negatively charged oxygen (previously carbonyl oxygen) attacks hydrogen in H2O and protonates • two OH groups are now attached to carbonyl carbon

Acid-Catalyzed Hydration • Protonation of carbonyl making it more electrophilic • Protonated carbonyl attacked by water forming oxonium intermediate (positively charge H2O) 2b. oxygen of water molecule attaches to carbon making it positively charged • Oxonium intermediate deprotonated by water, forming the hydrate 3b. Lone pairs of another H2O attacks hydrogen on oxonium, removing the hydrogen • Creates two OH groups on carbon

Proton Transfer followed by Nucleophilic Attack followed by Proton Transfer • Protonation of carbonyl making it more electrophilic • Protonated carbonyl attacked by water forming oxonium intermediate (positively charge H2O) 2b. oxygen of water molecule attaches to carbon making it positively charged • Oxonium intermediate deprotonated by water, forming the hydrate 3b. Lone pairs of another H2O attacks hydrogen on oxonium, removing the hydrogen • Creates two OH groups on carbon

Acetal Formation Proton Transfer»_space; Nucleophilic Attack»_space; Proton Transfer»_space; Proton Transfer»_space; Loss of Leaving Group»_space; Nucleophilic Attack»_space; Proton Transfer • carbonyl protonates making it more electrophilic • First alcohol (from reagent) attacks protonated carbonyl and attaches to the carbon, creating oxonium intermediate (+H2O) • Oxonium deprotonated to form hemiacetal • OH protonated transforming into Good Leaving Group • Leaving Group leaves creating a R–C=O–R double bond • Second alcohol (from reagent) attacks C=O and attaches to carbon creating oxonium intermediate • Oxonium ion deprotonated creating acetal

Proton Transfer»_space; Nucleophilic Attack»_space; Proton Transfer»_space; Proton Transfer»_space; Loss of Leaving Group»_space; Nucleophilic Attack»_space; Proton Transfer • carbonyl protonates making it more electrophilic • First alcohol (from reagent) attacks protonated carbonyl and attaches to the carbon, creating oxonium intermediate (+H2O) • Oxonium deprotonated to form hemiacetal • OH protonated transforming into Good Leaving Group • Leaving Group leaves creating a R–C=O–R double bond • Second alcohol (from reagent) attacks C=O and attaches to carbon creating oxonium intermediate • Oxonium ion deprotonated creating acetal

Hydrolysis of Acetals Proton Transfer»_space; Loss of leaving group»_space; nucleaophilic attack»_space; Proton transfer»_space; proton transfer»_space; loss of leaving group»_space; proton transfer

• protonation of one carbonyl from H3O • 1 R–OH is ejected, creating C=O with remaining oxygen • Nucleophilic attack of C=O by water, oxonium attaches • Water deprotonates oxonium creating OH • protonation of hemiacetal H3O creating good leaving group • lone pair from OH migrates creating C=O, R–OH is ejected • H-C=O is deprotonated by water creating a ketone

• The ring must contain a powerful electron-withdrawing group (typically a nitro group). • The ring must contain a leaving group (usually a halide). • The leaving group must be either ortho or para to the electron-withdrawing group. If the leaving group is meta to the nitro group, the reaction is not observed.