Bài giảng hoá học hữu cơ caboxylic

Acid Chlorides• The functional group of an acid halide is an acyl group bonded to a halogen.. Acid Anhydrides• The functional group of an acid anhydride is two acyl groups bonded to an

Carboxylic Acids

• The functional group of carboxylic acids

COOH consists of a C=O with -OH

bonded to the same carbon

• Aliphatic acids have an alkyl group

Some Important Acids

• CH3COOH is in vinegar and other foods, used industrially as solvent, catalyst,

and reagent for synthesis

• Fatty acids from fats and oils

• C6H5COOH-Benzoic acid in drugs,

preservatives

• Adipic acid used to make nylon 66

• Phthalic acid used to make polyesters =>

Nobel Prize 1982

BiochemistSune K.Bergstrom, Bengt I.Samuelsson và John R.Vane

lessens pain, anti inflammation

Biosynthesis of Shikimic acid

Tamiflu

L-Ascorbic acid (Vitamin C)

Antioxidant

Common Names

• Aliphatic acids have historical names

• Positions of substituents on the chain are

labeled with Greek letters

CH3CH2CHC

Cl

OH O

IUPAC Names

• Remove -e from alkane (or alkene)

name, add -oic acid.

• The carbon of the carboxyl group is #1

CH3CH2CHC

Cl

OH O

2-chlorobutanoic acid

Ph

C H

C

H COOH

trans-3-phenyl-2-propenoic

acid (cinnamic acid)

=>

Naming Cyclic Acids

• Cycloalkanes bonded to -COOH are named

Dicarboxylic Acids

• Aliphatic diacids are usually called by

their common names

• IUPAC name, number the chain from the end closest to a substituent

• Two carboxyl groups on a benzene ring indicate a phthalic acid

HOOCCH2CHCH2CH2COOH

Br

3-bromohexanedioic acid

β -bromoadipic acid =>

Butenedioic acid

C

COOH

H C

H

maleic acid fumaric acid

Butenedioic acid

C

H C

H

C

O H O

C

H

C H

C O C

O

O H O

But on releasing the second proton, such extra stability may be lost and therefore Ka2 is smaller for cis-isomer.

Butenedioic acid

C

H C

H

C

O H OH

C

H C

H

C

O heated to 100 Co

Structure of Carboxyl

• Carbon is sp2 hybridized

• Bond angles are close to 120°

• O-H eclipsed with C=O, to get overlap of π

orbital with orbital of lone pair on oxygen

=>

Boiling Points

Higher boiling points than similar

alcohols, due to dimer formation

Acetic acid, b.p 118 ° C Ethanol, b.p 78 ° C =>

Melting Points

• Aliphatic acids with more than 8

carbons are solids at room temperature

• Double bonds (especially cis) lower the melting point Note these 18-C acids:

Stearic acid (saturated): 72 ° C

Oleic acid (one cis double bond): 16 ° C

Linoleic acid (two cis double bonds): -5 ° C =>

• Water solubility decreases with the length

of the carbon chain

• Up to 4 carbons, acid is miscible in water

• More soluble in alcohol

• Also soluble in relatively nonpolar

solvents like chloroform because it

dissolves as a dimer

=>

Acidity

Resonance Stabilization

=>

Substituent Effects on Acidity

Salts of Carboxylic Acids

• Sodium hydroxide removes a proton to

form the salt

• Adding a strong acid, like HCl,

regenerates the carboxylic acid

=>

Naming Acid Salts

• Name the cation

• Then name the anion by replacing the -ic acid with -ate

CH3CH2CHCH2COO- K+

Cl

potassium β -chlorovalerate potassium 3-chloropentanoate =>

Properties of Acid Salts

• Usually solids with no odor

• Carboxylate salts of Na+, K+, Li+, and NH4+

are soluble in water

• Soap is the soluble sodium salt of a

long chain fatty acid

• Salts can be formed by the reaction of

an acid with NaHCO3, releasing CO2

=>

Purifying an Acid

Synthesis Review

• Oxidation of primary alcohols and

aldehydes with chromic acid

• Cleavage of an alkene with hot KMnO4produces a carboxylic acid if there is a hydrogen on the double-bonded carbon

• Alkyl benzene oxidized to benzoic acid

by hot KMnO4 or hot chromic acid

=>

Oxidation of primanry alcohol

OH

Preparation aromatic acid

Hydrolysis of Nitriles

Basic or acidic hydrolysis of a nitrile

produces a carboxylic acid

Ethanedioic acid (Oxalic acid)

O O

H

Ethanedioic acid (Oxalic acid)

Ozonolysis of ethyne

C

O

OH C

O O

H C

O3 / CCl4

Zn dust / H+

Characteristic Reactions

• Nucleophilic acyl substitution: An

addition-elimination sequence resulting in

substitution of one nucleophile for another

Tetrahedral carbonyl addition intermediate

Acid Chlorides

• The functional group of an acid halide is an acyl

group bonded to a halogen.

The most common are the acid chlorides.

To name, change the suffix -ic acid -ic acid to -yl halide -yl halide

O Cl

O

Benzoyl chloride

Ethanoyl chloride (Acetyl chloride)

An acyl

Acid Anhydrides

• The functional group of an acid anhydride is two acyl groups bonded to an oxygen atom

The anhydride may be symmetrical (two

identical acyl groups) or mixed (two different

Acid Anhydrides

• Cyclic anhydrides are named from the dicarboxylic acids from which they are derived

Maleic anhydride

O O

O

Phthalic anhydride

Succinic anhydride

O O

O

O O

O

Acid Chlorides

• An activated form of the carboxylic acid

• Chloride is a good leaving group, so

undergoes acyl substitution easily

• To synthesize acid chlorides use thionyl chloride or oxalyl chloride with the acid

C

O OH

C

O C

O

Cl Cl +

C

O

Cl + HCl + CO + CO 2

=>

Ethyl ethanoate

(Ethyl acetate) D iethyl butanedioate (Diethyl s uccinate)

Is opropyl benzoate

• Lactone: A cyclic ester.

name the parent carboxylic acid, drop the suffix -ic acid -ic acid and add -olactone -olactone

α β

3 4

5 6

Esters of Phosphoric Acid

• Phosphoric acid forms mono-, di-, and triesters.

• Name by giving the name of the alkyl or aryl

group(s) bonded to oxygen followed by the word

phosphate

• In more complex phosphoric esters, it is common

to name the organic molecule and then indicate the presence of the phosphoric ester by the word

phosphate or the prefix phospho- phospho-

-CH 2

O P O

-O

-O O

Dimethyl

phosphate Glyceraldehyd e 3-phosph ate Pyridoxal phosp hate Phosphoenol- pyruvate

Fischer Esterification

• Acid + alcohol yields ester + water

• Acid catalyzed for weak nucleophile

• All steps are reversible

• Reaction reaches equilibrium

Fischer Mechanism (1)

Protonation of carbonyl and attack of

alcohol, a weak nucleophile

COH

+ COH

OH

COH OH

+

CH 3 CH 2 OH

COH OH

O H

CH 2 CH 3

O H R

COH OH

O

CH 2 CH 3

=>

CH 2 CH 3

O

CH 2 CH 3 O

=>

Esters from Acid Chlorides

• Acid chlorides react with alcohols to

give esters in good yield

• Mechanism is nucleophilic addition of

the alcohol to the carbonyl as chloride

ion leaves, then deprotonation

CCl O + CH 3 OH

COCH 3 O

+ HCl

=>

• IUPAC: drop -oic acid from the name of the parent acid and add -amide -amide For the common name, drop

-ic of the parent name and add -amide -amide

• if the amide nitrogen is bonded to an alkyl or aryl group, name the group and show its location on

(a 3° amide)

• Lactams : A cyclic amides are called lactams.

Name the parent carboxylic acid, drop the suffix -ic acid -ic acid and add -lactam -lactam

α β

H 3 C

O NH

5 6 3

3-Butanolactam

NH 2

H H

The cephalosporins d iffer in the group bonded to the acyl carbon and the s ide chain of the thiazin e rin g

Cephalexin (Keflex)

β-lactam

Amides from Acid Chlorides

• Acid chlorides react with ammonia and

amines to give amides

• A base (NaOH or pyridine) is added to

remove HCl by-product

CCl O + CH 3 NH 2

Amides from Acids

• Amine (base) removes a proton from

the carboxylic acid to form a salt

• Heating the salt above 100°C drives off

steam and forms the amide

H 2 O

=>

• The functional group of a nitrile is a cyano

group

IUPAC names: name as an alkanenitrile alkanenitrile

common names: drop the -ic acid -ic acid and add -onitrile

Ethanenitrile

(A cetonitrile) Benzon itrile Phenylethanenitrile (Phenylacetonitrile)

O O

Reaction with Grignard Reagents

1 Addition of 1 mole of RMgX to the carbonyl

carbon of an ester gives a TCAI.

2 Collapse of the TCAI gives a ketone (an

aldehyde from a formic ester).

O

CH 3 -C-OCH 3 R MgX

O R

A ketone

2

2

Reaction with Grignard Reagents

Treating a formic ester with two moles of Grignard reagent followed by hydrolysis in aqueous acid gives a 2° alcohol

A 2° alcohol

An ester of

formic acid

+

Reaction with Grignard Reagents

Treating an ester other than formic with a Grignard reagent followed by hydrolysis in aqueous acid gives a 3° alcohol.

A 3° alcohol

An ester of any acid

other than formic acid

+

Reaction with Grignard

Reagents

3 Reaction of the ketone with a second mole

of RMgX gives a second TCAI.

4 Treatment with aqueous acid gives the alcohol.

(4)

Reactions with RLi

• Organolithium compounds are even more

powerful nucleophiles than Grignard

Reduction Ester to 1 ° Alcohols

• Most reductions of carbonyl compounds now use hydride reducing agents

Esters are reduced by LiAlH4 to two alcohols.

The alcohol derived from the carbonyl group is primary.

Methanol

propanol (racemic)

OCH 3

OH

Reduction Ester to 1 ° Alcohols

• Use strong reducing agent, LiAlH4

• Borane, BH3 in THF, reduces carboxylic

acid to alcohol, but does not reduce ketone

=>

Reduction Ester to 1 ° Alcohols

• Reduction occurs in three steps plus workup:

 Steps 1 and 2 reduce the ester to an aldehyde.

 Step 3: Reduction of the aldehyde followed by work-up gives a 1° alcohol derived from the carbonyl group.

A 1° alcohol

R C H

O

O H

(4)

R C H

OH H

A tetrahedral carbonyl addition intermediate

O

(2)

OR'

+

Reduction - Esters by NaBH4

• NaBH4 does not normally reduce esters, but

it does reduce aldehydes and ketones

• Selective reduction is often possible by the proper choice of reducing agents and

Reduction - Esters by DIBALH

• Diisobutylaluminum hydride at -78°C

selectively reduces an ester to an aldehyde

At -78°C, the TCAI does not collapse and it is not until hydrolysis in aqueous acid that the

carbonyl group of the aldehyde is liberated.

Reduction - Amides by LiAlH4

• LiAlH4 reduction of an amide gives a 1°, 2°,

or 3° amine, depending on the degree of

substitution of the amide

Reduction - Amides by LiAlH4

• The mechanism is divided into 4 steps:

Step 1: Transfer of a hydride ion to the carbonyl carbon.

Step 2: A Lewis acid-base reaction and formation of an oxygen-aluminum bond.

AlH 3

(1)

O H

(2)

AlH 3

+

Reduction - Amides by LiAlH4

Step 3: Redistribution of electrons and ejection

of H3AlO - gives an iminium ion.

Step 4: Transfer of a second hydride ion to the iminium ion completes the reduction to the

H

R C N

H

H H

R-CH 2 -NH 2

An iminium ion

A 1° amine

Reduction - Nitriles by LiAlH4

The cyano group of a nitrile is reduced by LiAlH4 to

Reduction to Aldehyde

• Difficult to stop reduction at aldehyde

• Use a more reactive form of the acid (an

acid chloride) and a weaker reducing agent,

lithium aluminum tri(t-butoxy)hydride.

=>

Problem: Show reagents and experimental

conditions to bring about each reaction.

Ph

OH

Ph

Cl O