Chapter 21: The Chemistry of Carboxylic Acid Derivatives

carboxylic acid derivative

compounds that can be converted to carboxylic acids by hydrolysis

How do you name a carboxylic ester?

alkyl / phenyl alkan-oate

How do you name an acid halide?

replace the -ic ending with -yl followed by the name of the halide

How do you name a nitrile?

drop the -ic or -oic ending and add onitrile;

nitrile carbon counts as part of the chain length

How do you name an amide?

drop the -ic or -oic and add -amide

Amides are classified according to the number of __ on the amide nitrogen (1º, 2º, 3º, etc.).

hydrogens

A nitrogen with two hydrogens is a ____ amide.

primary (1º)

A nitrogen with one hydrogen is a ____ amide.

secondary (2º)

A nitrogen with no hydrogens is a ____ amide.

tertiary (3º)

lactam

cyclic amide

imide

nitrogen analog of anhydride

Which has higher priority in nomenclature, acid or nitrile?

acid

What is the IR spectroscopy for an acid chloride?

1800 cm^-1

What is the IR spectroscopy for an amide?

1650 - 1655 cm^-1

^{and at}

3100 - 3400 cm^-1

What is the IR spectroscopy for a nitrile?

2200 - 2250 cm^-1

What is the IR spectroscopy for a ketone, aldehyde, and carboxylic acid?

~ 1700 cm^-1

What is the IR spectroscopy for an ester?

1735 - 1745 cm^-1

distinguished from COOH, aldehydes, and ketones bc there is not broad peak

What is the ¹H NMR for amides?

7.5 - 8.5 ppm

What is the ¹H NMR for alpha hydrogens next to carbonyl?

1.9 - 3.0 ppm

What is the ¹³C NMR for carbonyls and esters?

165 - 180 ppm

What is the ¹³C NMR for C≡N?

115 - 120 ppm

What is the ¹³C NMR for aromatic compounds?

100 - 160 ppm

Which is more basic, amides or nitriles?

amides

Nitriles typically undergo ____ rxns.

addition

What is the order of carboxylic acid derivatives in increasing reactivity?

nitriles < amides < esters/thioesters, acids < anhydrides < acid chlorides

What are the two most important factors that influence reactivity?

1. stability of the starting carboxylic acid

2. characteristics of the leaving group

Acid chlorides and anhydrides react (rapidly/slowly) with water.

rapidly

saponification

ester hydrolysis in aqueous hydroxide

What does acid-catalyzed hydrolysis of esters require?

an excess of water

draw the mechanism for acid catalyzed hydrolysis of esters

What is the difference between acid- and base-catalyzed hydrolysis of esters?

Acid:

1. Carbonyl carbon can react with water bc carbonyl O is protonated

2. Acid catalyzes ester hydrolysis

3. Reversible

Base:

1. Carbonyl O is not protonated so a stronger base is needed

2. Base is not a catalyst, but a reactant

3. Saponification is irreversible

What reagent is used to hydrolyze amides to carboxylic acids?

heat in acidic or basic solution

What reagent is needed to hydrolyze nitriles to carboxylic acids and ammonia?

heat in strongly acidic or basic solution

draw the mechanism of hydrolysis of nitriles in acidic conditions

draw the mechanism of hydrolysis of nitriles in basic conditions

draw the mechanism for reaction of an acid chloride with an amine

Schotten-Baumann technique

rxn is run w acid chloride in a separate layer over an aqueous solution of NaOH

How is an amide formed from an anhydride?

carbon from anhydride forms a bond with the nitrogen and the O from the anhydride leaves and is protonated

How is an ester formed from an anhydride?

carbon from anhydride forms a bond with the alc oxygen and the O from the anhydride leaves and is protonated

What is the product of this rxn?

What reagent is used to reduce amides to primary amines?

LiAlH₄, THF

What reagent is used to reduce nitriles to primary amines?

LiAlH₄, THF
or
Raney Ni

Rosenmund reduction

selective catalytic hydrogenation rxn that converts acyl chlorides into aldehydes

What readily reacts with organocuprates (R₂CuLi) to form ketones?

acid chlorides

What reagent is used to convert acid chlorides to ketones?

organocuprates (R₂CuLi), THF