Chem 239 Exam 1

Aldehydes and ketones are

Electrophiles, most can be catalyzed by an acid or base

A reversible reaction is dependent on

Nucleophility and LG ability in both directions

Why does an aldehyde have a higher K value than a ketone

Because ketones are more stable due to hyperconjugation, while an aldehyde only has one donating group

Reduction of aldehydes and ketones

NaBH4 and LiAlH4 act as H-

Why are NaBH4 and LiAlH4 vs H2 sometimes selective

A polar source of H vs a nonpolar source of H

You cannot do an ____ or ____ with a Grignard reagent

Alcohol or carboxylic acid

Grignard, organolithium, and barbier reagents all create

A nucleophilic carbon

Hemiacetal

Half alcohol half ester

Acetal

2 esters

Acetal formation is a

Sn1 reaction

Hemiacetal always

proceeds to the acetal

Acetals can act as

Protecting groups

Protecting acetal groups

Treat with double pronged alcohol, add acid to turn it back

Amine to imine formation (pH5)

Requires both acidic and basic conditions, pH 5 works

Aldehyde/Ketone + secondary amine =

Enamine

Carbonic acid is in equilibrium with

CO2 and water

Large carboxylic acids have

Polar and nonpolar regions

Grignard + CO2

Makes a carboxylate, then workup to give carboxylic acid

Fischer Ester Synthesis

Reaction reversible, eq favors both sides evenly, can manipulate with Le Chatlier’s

Carboxylic acids require a ___ to act as a base

Very strong acid

Esterification under basic conditions mechanism

Sn2 reaction

Acid chlorides can be made from

SOCl2

The best way to make anhydrides is from

Acid chlorides

LiAlH4 is a

Strong reducing agent

NaBH4 is a

Weak reducing agent

Decarboxylation reactions

Lose a CO2 exactly 2 carbons away, like a diels alder

Decarboxylation mechanism

Is concerted, both C=O groups participate

Carboxylic acid derivatives (why are they called derivatives)

If you add water to any of the derivatives, you get carboxylic acid

Intermolecular reactions can occur

If carbonyl and appropriate nucleophile is available (H+ catalyzed)

Reactivity trends of carboxylic acid derivatives

Nitriles < amides < esters < thioesters, acids « anhydrides < acid chlorides

Relative reactivity of carboxylic acid derivatives - Trend 1

Stability of reactant —> consider resonance for each derivative

Induction becomes more important than

Bad resonance

Relative reactivity of carboxylic acid derivatives - Trend 2

The derivative with the best leaving group reacts best → can only compare with certain groups

Ester hydrolysis - acidic conditions

Reverse of Fischer mechanism

Ester hydrolysis - basic conditions

Hydroxide attacks right away

Saponification (ester basic hydrolysis) occurs via

Nucleophilic acyl substitution

Acidic hydrolysis is

Reversible

Basic hydrolysis is

Irreversible; in favor of the carboxylate (most stable ion)

Amide hydrolysis is

Irreversible

Reactions that are irreversible

Grignard reagents and reductions

Why can amides react uphill?

Because either ammonium or carboxylate is the most stable ion → drives reaction forward

Nitrile hydrolysis

Occurs in both conditions; nitrile → amide → carboxylic acid

Acyl chloride and anhydride hydrolysis

Don’t require an acid or base catalyst, very reactive

All mechanisms involve a

Tetrahedral intermediate (except CO2)

A reaction that releases gas is

Irreversible

Ester/amide/thioester under acidic conditions

Derivative is protonated first

Acyl chlorides can

Become any other carboxylic derivative

Anhydrides react downhill to

Esters and amides

Drawbacks of anhydride reactions

1) Waste

2) Unsymmetric anhydrides have selectivity and multiple products

Reactions involving esters/thioesters

React downhill to amides, react sideways to other esters

Thioesters are

The most reactive that are not sensitive to water (acetyl coA)

Amides are very stable but they can react during

1) Hydrolysis under harsh conditions

2) Strained amide rings

DCC is

A reagent to creates amides by reacting with a large built in leaving group

Ways to synthesize amides

1) Carboxylic acid → acyl chloride/ester → amide

2) DCC

3) Heat reaction a lot for a long time

Amide reduction

Amide → imine → reduced like a ketone. Involves an aluminum complex and deletes an oxygen

Nitrile reductions

Can get double reduced

Ester reduction

Gets double reduced, forms primary alcohols

Thioester reductions

React with LiAlH4 to form alcohols