1. acid chlorides

2. acid anhydrides

3. esters

4. amides

5. nitriles

-amides=comparable to alcohols in acidity

*H2O insoluble amides don't react w/ NaOH/other alkali metal hydroxides to form H2O soluble salts

-sulfonamides and imides=more acidic than amides

*imides=more acidic bcuz:

1. e- w/drawing inductive effect of 2 adjacent C=O groups weakens NH bond

2. imid anion is stabilized by resonance delocalization of neg. charge

-nucleophilic acyl substitution: an addition-elimination sequence resulting in substitution of one nucleophile for another

-weaker the base, the better the LG

-halide ion=weakest base and best LG

*most reactive toward Nu acyl substitution

-amide ion=strongest B and poorest LG

*least reactive toward Nu acyl substitution

-low MW acid chlorides react rapidly w/ H2O

*higher MW acid chlorides=less soluble in H2O and react less readily

-low MW anhydrides react readily w/ H2O to give 2 molecules of of COOH

*higher MW anhydrides also react w/ H2O but less readily

-2 steps:

1. addition of H2O to give TCAI

2. protonation followed by collapse of TCAI

-esters hydrolyzed slowly, even in boiling H2O

*hydrolysis becomes more rapid if heated w/ aqueous A or B

-hydrolysis in aqueous A=reverse of Fischer esterification

*Acid catalyst protonates C=O O and increases its electrophilic character toward attack by H2O (weak Nu) to form TCAI

*collapse of intermediate gives COOH and alcohol

-saponification: hydrolysis of an ester in aqueous B

*each mole of ester hydrolyzed requires 1 mole B

*involves formation of TCAI followed by its collapse and proton transfer

3 steps:

1. attack of hydroxide ion (Nu) on C=O C (electrophile)

2. collapse of TCAI

3. proton transfer to alkoxide ion; this step=irreversible and drives saponification to completion

-hydrolysis of amide in aqueous acid requires 1 mole A per mole of amide

*rxn driven to completion by A-B rxn btwn amine or ammonia and A

-hydrolysis in aqueous B requires 1 mole B per mole amide

*rxn driven to completion by irreversible formation of carboxylate salt

2 steps in aqueous A:

1. protonation of C=O O gives resonance-stabilized cation intermediate

2. addition of H2O (Nu) to C=O C (electrophile) followed by proton transfer gives TCAI

-cyano group is hydrolyzed in aqueous A to a carboxyl group and ammonium ion

*protonation of cyano N gives cation that reacts w/ H2O to give imidic acid

*keto-enol tautomerism gives the amide

-hydrolysis in aqueous B gives carboxylic anion and ammonia; acidification then converts anion to carb. acid

-hydrolysis of nitriles=valuable route to carb acids

-acid halides react w/ alcohols to give esters

*acid halides=so reactive to even weak Nus like alcohols that no catalyst needed

-where alcohol/resulting ester=sensitie to HCl, rxn carried out in presence of 3' amine to neutralize acid

-sulfonic acid esters prepared by rxn of alkane/arenesulfonyl chloride w/ alcohol or phenol

*key pt is that OH- (poor LG) transformed into sulfonic ester (good LG) w/ retention of configuration at chiral center

-acid anhydrides react w/ alcohols to give 1 mole ester and 1 mole carb. acid

*cyclic anhydrides react w/ alcohols to give 1 ester group and 1 carboxyl group

-acid halides react w/ ammonia, 1' amines, and 2' amines to form amides

*2 moles amine required per mole of acid chloride

-acid anhydrides react w/ ammonia, and 1' and 2' amines to form amides

*2 moles ammonia/amine required

-esters react w/ ammonia and w/ 1' and 2' amines to form amides

*esters=less reactive than acid halides and anhydrides

-amides don't react w/ ammonia or w/ 1' or 2' amines

-acid chlorides react w/ salts of carb. acids to give anhydrides

*most commonly used are Na or K salts

-treating formic ester w/ 2 moles Grignard followed by hydrolysis in aqueous A gives 2' alcohol

-treating ester other than formic acid w/ Grignard followed by hydrolysis in aqueous A gives 3' alcohol

-4 steps:

1. addition of 1 mole RMgX to C=O C of ester gives TCAI

2. collapse of TCAI gives ketone (aldehyde from formic ester)

3. rxn of ketone w/ 2nd mole of RMgX give 2nd TCAI

4. treatment w/ aqueous A give alcohol

-even more powerful Nus than Grignard

-react w/ esters to give same 2' and 3' alcohols as Grignard but higher yields

-acid chlorides at -78degrees C react w/ Gilman to give ketones

*in these conditions TCAI=stable and it's not til acid hydrolysis that the ketone is liberated

-react only w/ acid chlorides

*don't react w/ acid anhydrides, esters, amides, or nitriles under these conditions

-most reductions of C=O compounds now use hydride reducing agents

*esters reduced by LiAlH4 to 2 alcohols

*alcohol derived from C=O group is primary

-3 steps plus workup:

1 and 2. reduce ester to an aldehyde

3. reduction of aldehyde followed by workup gives 1' alcohol derived from C=O group

-NaBH4 doesn't normally reduce esters but it does reduce aldehydes/ketones

-selective reduction often possible by proper choice of reducing agents and experimental conditions

-Diisobutylaluminum hydride (DIBAlH) at -78 selectively reduces ester to aldehyde

*at -78 TCAI doesn't collapse and it's not til hydrolysis in aqueous A that C=O group of aldehyde is liberated

-LiAlH4 reduction of amide gives 1', 2' or 3' amine, depending on degree of substitution of amide

4 steps:

1. transfer of hydride ion to C=O C

2. lewis A-B rxn and formation of O-Al bond

3. redistribution of e-s and ejection of H3AlO- gives iminium ion

4. transfer of 2nd hydride ion to iminium ion completes reduction to amine