carboxylic acids the functional group of carboxylic acids...

The functional group of carboxylic acids consists of a C=O with

to the same carbon.

Structure of Carboxyl Carbon is

120°. O-H eclipsed with C=O, to get overlap of

pair on oxygen.

Carboxyl group is usually written

bonded to -COOH. Aromatic acids have an aryl group.

chain aliphatic acids. Almost all naturally occurring

acids (-CO2H).

Carboxylic acid groups are always terminal groups with a carbonyl carbon

also bound to a hydroxyl group.

For example:

Formic acid is the principal ingredient and stinging agent of most ant bites.

Benzoic acid is found in many plants: for example, the Voodoo lily uses it to

attract insects needed for

(fat) and (after reaction with NaOH) is one of the

lye soap as well as modern soaps (sodium tallowa

ingredient labels of soaps, it is a mixture of several similar sodium salts of

carboxylic acids, one of which is sodium stearate).

112

Carboxylic Acids

The functional group of carboxylic acids consists of a C=O with -OH bonded

Carbon is sp2 hybridized. Bond angles are close to

H eclipsed with C=O, to get overlap of π orbital with orbital of lone

Carboxyl group is usually written -COOH. Aliphatic acids have an alkyl group

omatic acids have an aryl group. Fatty acids are long

Almost all naturally occurring acids are carboxylic


hydroxyl group.


n many plants: for example, the Voodoo lily uses it to

attract insects needed for pollination. Stearic acid is found in beef tallow

(fat) and (after reaction with NaOH) is one of the active components in old

lye soap as well as modern soaps (sodium tallowate appears on the


of which is sodium stearate).

OH bonded

Bond angles are close to

orbital with orbital of lone

Aliphatic acids have an alkyl group

Fatty acids are long-

acids are carboxylic



n many plants: for example, the Voodoo lily uses it to

pollination. Stearic acid is found in beef tallow

active components in old

te appears on the


113

Dicarboxylic acids have 2 -CO2H groups and tricarboxylic acids have 3 -CO2H

groups (citric acid has 3 -CO2H groups).

Nomenclature

1. Common Names

Many aliphatic acids have historical names.

Some common names

HCO2H formic acid L. formica ant

CH3CO2H acetic acid L. acetum vinegar

CH3CH2CO2H propionic acid G. “first salt”

CH3CH2CH2CO2H butyric acid L. butyrum butter

CH3CH2CH2CH2CO2H valeric acid L. valerans

Positions of substituents on the chain are labeled with Greek letters

α-chlorobutyric acid

CH3CH2CHC

Cl

OH

O

114

IUPAC Names

1-Remove -e from alkane (or alkene) name, add -oic acid.The carbon of the

carboxyl group is #1.

HCOOH methanoic acid

CH3CO2H ethanoic acid

CH3CH2CO2H propanoic acid

CH3

CH3CHCOOH 2-methylpropanoic acid

Br

CH3CH2CHCO2H 2-bromobutanoic acid

2-chlorobutanoic acid

2-Cycloalkanes bonded to -COOH are named as cycloalkanecarboxylic acids.

3-Aromatic acids are named as benzoic acids.

2-isopropylcyclopentanecarboxylic acid o-hydroxybenzoic acid

(Salicylic acid)

CH3CH2CHC

Cl

OH

O

C O O H

C H (C H 3 ) 2

COOH

OH

115

Some Important Acids

• Acetic acid is in vinegar and other foods, used industrially as solvent,

catalyst, and reagent for synthesis.

• Fatty acids from fats and oils.

• Benzoic acid in drugs, preservatives.

• Adipic acid used to make nylon 66.

• Phthalic acid used to make polyesters

Physical properties

Carboxylic acids hydrogen bond to themselves to form a dimer:

• Carboxylic acids also form hydrogen bonds to water molecules:

Since carboxylic acids can form more than one set of hydrogen bonds, their

boiling points are usually higher than those of other molecules of the same

molecular weight (MW). Low-MW carboxylic acids are generally liquids at

room temp. (often, they are somewhat oily); higher- MW carboxylic acids

are generally waxy solids. Carboxylic acids with 12 to 20 carbon atoms are

often referred to as fatty acids, since they are found in the triglycerides in

fats and oils (more later). Short-chain carboxylic acids are also generally

more soluble in water than compounds of similar MW, since they can

hydrogen bond to more than one water molecule. As the number of

carbons in a carboxylic acid series becomes greater, the boiling point

increases and the solubility in water decrease. Many carboxylic acids that

are liquids at room temperature have characteristically sharp or unpleasant

odors.

116

– Ethanoic acid/acetic acid is the main ingredient in vinegar.

– Butanoic acid is partially responsible for the odor of locker rooms and

unwashed socks.

– Hexanoic acid is responsible for the odor of Limburger cheese.

Like most acids, carboxylic acids tend to have a sour taste (e.g., vinegar,

citric acid, etc.)

Acidity of Carboxylic Acids Since all carboxylic acids are weak acids, all exist

in equilibrium in water. The generic equilibrium equation is:

Where [H3O+] ≡ [H

+]. (Recall that the water does not change concentration

and therefore is incorporated into the Ka constant.) Most simple carboxylic

acids have acid dissociation constants equal to about 10-5

. Such a small Ka

means that very little of the acid is ionized in water. Nonetheless, carboxylic

acids are much stronger acids than phenols (typical Ka = 10-10

).

Carboxylic acids react with bases, but only strong bases completely remove

the proton (hydrogen ion) from the acid group. The resulting carboxylate

ion is then a weak base. When a strong acid is added to a solution

containing carboxylate ions, the acid protonates it, regenerating the parent

carboxylic acid.

As we saw earlier, small carboxylic acids are quite water soluble. However,

these acids don’t normally reside in our bodies (except sometimes as food,

e.g. acetic acid (vinegar)). The carboxylic acids that are found in human

tissue are typically fatty acids. These are acids with long carbon chains that

cause them to have very low solubility. When a proton is removed from a

fatty acid, the resulting carboxylate ion will always have a significantly

higher solubility (even if in absolute terms the solubility is still low).

117

Preparation of acids

1- From the oxidation of alkylbenzenes

2- from the oxidation of the alkenes and alkynes

118

3- from the oxidation of aldehydes

4- From the oxidation of the primary alcohols

5- from hydrolysis of nitriles

119

6- From the carboxylation of the Grignards

Carboxylic acids, reactions:

1. as acids

2. conversion into functional derivatives

a) � acid chlorides

b) � esters

c) � amides

d) � anhydrides

3. reduction

4. alpha-halogenation

5. EAS

1. as acids:

a) with active metals

RCO2H + Na � RCO2-Na

+ + H2(g)

b) with bases

RCO2H + NaOH � RCO2-Na

+ + H2O

c) Relative acid strength?

CH4 < NH3 < HC≡CH < ROH < HOH < H

d) quantitative

HA + H2O � H

Ka = [H3O+] [A

-] / [HA]

2. Conversion into functional derivatives:

The group bonded to the acyl carbon

a -OH, carboxylic acid

b -Cl, acid chloride

c -OR’, ester

d -NH2, amide

e- OCOR acid

These interconvert via nucleophilic acyl substitution.

Esterification

• Acid + alcohol yields ester + water.

• Acid catalyzed for weak nucleophile.

• All steps are reversible.

• Reaction reaches equilibrium.

120

CH < ROH < HOH < H2CO3 < RCO2H < HF

H3O+ + A

- ionization in water

] / [HA]

Conversion into functional derivatives:

The group bonded to the acyl carbon determines the class of compound:

OH, carboxylic acid

Cl, acid chloride

OR’, ester

, amide

acid anhydride


yields ester + water.

Acid catalyzed for weak nucleophile.

All steps are reversible.

Reaction reaches equilibrium.

determines the class of compound:


Amides

are synthesized by first reacting a carboxylic acid

The product, an ammonium carboxylate salt, when heated

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 phosphorous pentachloride

Anhydrides

Removing water from a carboxylic acid can

121

are synthesized by first reacting a carboxylic acid with ammonia, NH

The product, an ammonium carboxylate salt, when heated releases water:

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 phosphorous pentachloride with the acid.

Removing water from a carboxylic acid can make an anhydride.

with ammonia, NH3.

releases water:

Chloride is a good leaving group, so undergoes acyl

chloride, oxalyl

3- Reduc!on to 1°°°° Alcohols

• Use strong reducing agent, LiAlH

• Borane, BH3 in THF, reduces carboxylic acid to alcohol, but does not

reduce ketone

4. Alpha-halogenations

RCH2COOH + X

X2 = Cl2, Br2

5. EAS: (-COOH is deactivating and

122

Alcohols

Use strong reducing agent, LiAlH4.

in THF, reduces carboxylic acid to alcohol, but does not

halogenations: (Hell-Volhard-Zelinsky reaction)

COOH + X2, P � RCHCOOH + HX

X

α-haloacid

COOH is deactivating and meta- directing)

in THF, reduces carboxylic acid to alcohol, but does not

123

Phenols Ar-OH

Phenols are compounds with an –OH group attached to an aromatic

carbon. Although they share the same functional group with

alcohols, where the –OH group is attached to an aliphatic carbon, the

chemistry of phenols is very different from that of alcohols.

Nomenclature.

Phenols are usually named as substituted phenols. The

methylphenols are given the special name, cresols. Some other

phenols are named as hydroxy compounds.

Physical properties

Phenols are polar and can hydrogen bond. Phenols are water

insoluble. Phenols are stronger acids than water and will

dissolve in 5% NaOH. Phenols are weaker acids than carbonic acid

and do not dissolve in 5% NaHCO3.

Intramolecular hydrogen bonding is possible in some ortho-

substituted phenols. This intramolecular hydrogen bonding reduces

water solubility and increases volatility. Thus, o-nitrophenol is steam

distillable while the isomeric p-nitrophenol is not.

124

Reactions:

alcohols phenols

1. HX NR

2. PX3 NR

3. dehydration NR

4. as acids phenols are more acidic

5. ester formation similar

6. oxidation NR

125

Phenols, reactions:

1. as acids

2. ester formation

3. ether formation

4. EAS

a) nitration f) nitrosation

b) sulfonation g) coupling with diaz. salts

c) halogenation h) Kolbe

d) Friedel-Crafts alkylation i) Reimer-Tiemann

e) Friedel-Crafts acylation

126

We use the ionization of acids in water to measure acid strength (Ka):

HBase + H2O H3O+ + Base

-

Ka = [H3O+ ][ Base ] / [ HBase]

ROH Ka ~ 10-16

- 10-18

ArOH Ka ~ 10-10

Why are phenols more acidic than alcohols?

127

Resonance stabilization of the phenoxide ion, lowers the PE of the products

of the ionization, decreases the ΔH, shifts the equal farther to the right,

makes phenol more acidic than an alcohol

Effect of substituent groups on acid strength?

Electron withdrawing groups will decrease the negative charge in the

phenoxide, lowering the PE, decreasing the ΔH, shifting the equal farther to

the right, stronger acid.

Electron donating groups will increase the negative charge in the

phenoxide, increasing the PE, increasing the ΔH, shifting the equilibrium to

the left, weaker acid.

Number the following acids in decreasing order of acid strength (let # 1 =

most acidic, etc.)

130

At low temperature the reaction is non-reversible and the lower Eact ortho-

product is formed (rate control).

At high temperature the reaction is reversible and the more stable para-

product is formed (kinetic control).

131

f) nitrosation

g) coupling with diazonium salts

(EAS with the weak electrophile diazonium)

132

h) Kolbe reaction (carbonation)

i) Reimer-Tiemann reaction

133

Amines

Structure, Naming, and Physical Properties

Amines are one of the six nitrogen-containing functional groups we use

(amide, nitrile, imine, azide, and nitro are the others.)

Structure

An amine has an sp3-hybridized nitrogen with three bonds and a lone pair

of electrons. As a result of the sp3-hybridization, bond angles around the

nitrogen are approximately 109.5º (typically a liSle smaller, such as 107º).

Amines exhibit an unusual inversion at room temperature, so we will not

observe chirality at the nitrogen of a neutral amine.

Besides ammonia, which is the simplest amine, substituted amines are

categorized as:

Primary if they have one bond from nitrogen to carbon (H2NR)

Secondary if they have two bonds from nitrogen to carbon (HNR2), and

Tertiary if they have three bonds from nitrogen to carbon (NR3).

Naming

• Official IUPAC name is based on analogous alcohol. The “-ol” ending gets

replaced by “-amine.”

134

Two “common” naming systems:

1) “alkyl” precedes the word “amine”

2) “amino” (-NH2) substituent on a parent alkane.

• For secondary and tertiary amines, the longest continuous carbon chain

acts as the parent, and an “N” locant is used to describe the position of the

extra alkyl groups, which are listed in alphabetical order at the beginning of

the name. (In the common system, simply list the alkyl groups before the

word “amine.”)

• “Aniline” is the IUPAC and common name for the aromatic amine

C6H5NH2, which is used a parent compound for other aromatic amines.

• Ammonium salts are tetrasubstituted, cationic versions of amines:

135

Physical Properties

Amines are slightly basic. This because they have a lone pair of electrons to

donate to a proton. This same feature makes them nucleophiles.

Typical amines have Kb values = 10-3

to 10-4

Water solubility: Amines are mostly insoluble in water; however, those with

fewer than ~5 carbon atoms are water soluble. (With fewer than ~5 carbon

atoms, the polarity of the N-part of the molecule dominates over the non-

polar hydrocarbon part of the molecule.) Boiling point/melting point.

Hydrogen bonding is possible in amines that contain NH or NH2 groups. An

NH2 exhibits stronger hydrogen bonding than an NH. However, when

comparing amines to alcohols, an OH group exhibits stronger hydrogen

bonding than an NH2, since oxygen is more electronegative than nitrogen.

Preparation of amines

1-Reduction of Nitriles

Nitriles may be reduced with lithium aluminum hydride to generate primary

amines.

RNH2 + H OH RNH3 + OH

Kb = [RNH3 ] [OH ]

[RNH2]

136

2- Reduction of Amides

Amides may be reduced with LiAlH4 to generate subsVtuted amines.

3-Reduction of Nitro Compounds

Nitro groups may be reduced by H2 and palladium on carbon to generate

amines. This reaction is particularly useful for aromatic systems because of

the ease of installing a nitro group selectively.

4-The Hofmann Rearrangement

The Hofmann rearrangement allows us to shorten a chain by one carbon by

the conversion of an amide to a primary amine. The overall conversion and

the mechanism are given below.

5-The Gabriel Amine Synthesis

137

This phthalimide derivative may then be hydrolyzed with aqueous base to

generate phthalic acid and the desired primary amine. Alternatively, the

phthalimide may be heated with hydrazine to generate the free amine.

carboxylic acids the functional group of carboxylic acids...

Documents