1

Carboxylic Acid & Their

Derivatives Jully TanSchool of Engineering

EP101 / EG101 2

Learning Outcome At the end of this chapter, students are able to:

Provide nomenclature of the carboxylic acid & its derivatives Physical properties of carboxylic acid Synthesis and reaction of carboxylic acid & its derivatives

EP101 / EG101 3

Chapter 18

Carboxylic Acids and Their Derivatives:Nucleophilic Addition-Elimination at the Acyl Carbon

Carboxylic acids are a family of organic compounds with the functional group

-C-OHO= which is also written as -CO2H or COOH.

The carbon-oxygen double bond is made up of a -bond and a -bond. The carbon atom is sp2 hybridized, which explains the trigonal planar geometry at this center.

C ORHO

R may be alkyl, aryl or simply H

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Naming Rules Uses the name of alkane that corresponds to the longest continuous chain of the

carbon atom. The final –e in the alkane name is replaced by suffix –oic acid The chain is numbered, starting with carboxyl carbon (COO-) atom as C1. Position of the substituent is indicated by a number. Acid which has C=O attached to ring are named by adding the name carboxylic

acid to the name of the cyclic compound. When the acid has C=C in their structure, stereochemical term of cis and trans or E

and Z are used as they are with other alkenes.

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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

PhC

HC

H

COOH

trans-3-phenyl-2-propenoic acid

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Naming Cyclic Acids Cycloalkanes bonded to -COOH are named as cycloalkanecarboxylic acids. Aromatic acids are named as benzoic acids.

COOH

CH(CH3)2

2-isopropylcyclopentanecarboxylic acid

COOH

OH

o-hydroxybenzoic acid

Aromatic Acids: Benzoic AcidsThe carboxylic acids derived from benzene are named as derivatives of benzoic acid, using the standard notations to indicate positions of substituent groups.

COOH

Benzoic acid

COOH COOH

NO2

m-Nitrobenzoic acidNO2

Cl

2-Chloro-4-nitrobenzoic acid

Salts of Carboxylic AcidsTo name a salt, use the name of the cation (sodium, ammonium, etc.) followed by the name of the acid with "ic acid" changed to "ate."

CO2- Na+

(CH3CH2CO2-)2 Mg2+

Sodium benzoate

Magnesium propanoate or

Magnesium propionate

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Physical Properties of Carboxylic acids

Carboxylic acids are polar protic molecules. They form strong hydrogen bonds. One example of this is that they exist as dimers in the liquid state.

CO

O-HR

OC

H-OR

The boiling points are about 20 oC higher than alcohols of comparable size.

Carboxylic acids, in neutral solvents, have solubility properties similar to those of alcohols. The first members of the aliphatic series (formic acid through butanoic acid) are miscible with water. Water solubility decreases with increasing chain length, with hexanoic acidbeing marginally soluble. On neutralization, because of ionic salt formation, most carboxylic acids become water soluble.

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Boiling PointsHigher boiling points than similar alcohols, due to dimer formation, resulting from the association of two molecules of the acid, facilitated by hydrogen bonding.

Carbonyl compound have the following relative BP:

Amide>COOH>nitrile>ester=acyl chloride>aldehyde>ketone

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Solubility 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.

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The Acid Strength of Carboxylic AcidsCarboxylic acids are weaker acids than mineral acids like HCl, HNO3, or H2SO4, but they are more acidic than organic weak acids such as aliphatic alcohols. Carboxylic acids are converted into their carboxylate salts by aqueous solutions of hydroxide.

RCOOH HO-/H2O

H3O+RCO2

-

Carboxylate anionof resulting salt

Aqueous solutions of mineral acids convert the salts back into the carboxylic acids.

Large carboxylic acids with limited or no solubility in water (those with 6 or more C's per carboxyl group) may be solubilized through their carboxylate salts:

R-COOH + Na+ -OH H2O R-CO2- Na+ + H2O

Waterinsoluble

Watersoluble

These solubility properties are the basis for separating carboxylic acids from neutral organic compounds.

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A Comparison of the Acid Strength of Carboxylic Acids and Alcohols

Carboxylic acids are considerably more acidic than alcohols in the absence of special electronic influences.

RCOOH + H2O RCO2- + H3O+ pKa ~ 5

ROH + H2O RO- + H3O+ pKa ~ 16

The enhanced acidity of carboxylic acids is attributed to the greater stability of the carboxylate anion compared with the alkoxide anion, which shifts the equilibrium more to the product side.

Resonance theory explains this stability through two equivalent resonance structures that contribute to the hybrid.

R-CO

R-C-

R-C

1/2 -

1/2 -

O.. ..

.... - O..

O.... .. O..

O

..

....

....

X-ray analysis of sodium formate shows equivalent C-O bond lengths of 1.27 A, consistent with this picture of a resonance hybrid.

o

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Effect of Substituents on AcidityAny factor that stabilizes the anion more than it stabilizes the acid should increase acidity (decrease the magnitude of pKa). Any factor that destabilizes the anion relative to the acid should decrease acidity.

RCOOH + H2O RCO2- + H3O+

Electronic Influences

The electronic effect of a substituent G operates more strongly on the anion (charged species) than on the carboxylic acid (neutral species).

G CO

O-

Electron withdrawalStabilizes the anion and

increases acidity

G CO

O-

Electron releaseDestabilizes the anion and decreases acidity

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Substituent Effects on Acidity

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Synthesis of Carboxylic Acids Oxidation of 1° ROH & aldehydes Side chain oxidation of alkylbenzenes Conversion of Grignards.

EP101 / EG101 15

Preparation of Carboxylic Acids

Oxidation of Aldehydes and 1o Alcohols

Oxidation of Alkenes

Aldehydes are easily oxidized to carboxylic acids, even by mild oxidants such as Ag(NH3)2

+OH-, which is used in the Tollens' test for distinguishing aldehydes from ketones. Stronger reagents such as chromic acid (H2CrO4) or KMnO4 can oxidize either aldehydes or 1o alcohols to carboxylic acids.

R H

O

R OH

O

R OH

Ag(NH3)2+OH-

H2CrO4 or KMnO4

Alkenes can be oxidatively cleaved to carboxylic acids by use of either KMnO4 or ozone.

RR'

RR'

(1) KMnO4, OH- (hot)

(2) H3O+

(1) O3

(2) H2O2

R OH

O

R' OH

O+

i) Oxidation of 1° ROH / Aldehydes

The alcohol is first oxidized to an aldehyde and then to carboxylic acid

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Oxidation of AlkylbenzenesVigorous oxidation by KMnO4 of primary and secondary (but not tertiary) alkyl groups directly attached to a benzene ring produces aromatic acids.

CHRR'(1) KMnO4, HO-, H2O

(2) H3O+

COOH

Oxidation of Alkylbenzenes

R

The benzene ring of an alkylbenzene can be converted to a carboxyl group by ozonolysis.

(1) O3, CH3COOH

(2) H2O2 R OH

O

ii) Side chain oxidation of alkylbenzenes

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Carbonation of Grignard ReagentsA more general way to prepare carboxylic acids from alkyl or aryl halides is by carbonation (reaction with CO2) of the corresponding Grignard reagents. The strongly nucleophilic organomagnesium reagents add to CO2 to produce magnesium carboxylates. Acidification of these salts yields the carboxylic acids.

R-MgX-

+ C:O:=

:O:

= R-C-O:O:

= ::

:-

MgX+Nucleophilic

addition

All alkyl (1o, 2o, 3o) and aryl Grignard reagents undergo the carboxylation reaction. This reaction is accomplished by either bubbling dry gaseous CO2 through an ether solution of the Grignard reagent or by pouring the Grignard reagent onto crushed dry ice (solid CO2).

H3O+

R-C-OH:O:

=:

:

iii) Conversion of Grignards Reagent

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Syntheses Using the Grignard Carbonation Reaction

Mgether CH3C-MgCl

CH3

CH3

tert-Butylmagnesiumchloride

CH3C-ClCH3

CH3

tert-Butylchloride

CH3C-COOHCH3

CH3

2,2-Dimethyl-propanoic acid

(1) CO2

(2) H3O+

H3C CH3

CH3

Br

Mgether

CH3

CH3

MgBr

2,4,6-Trimethylphenyl-magnesium bromide

CH3

CH3

COOH

2,4,6-Trimethylbenzoicacid

(1) CO2

(2) H3O+

H3C H3C

2,4,6-Trimethyl-bromobenzene

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Interconversion of Derivatives

More reactive derivatives can be converted to less reactive derivatives.

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Typical RCOOH Reactions – Formation of Acid Derivatives

When the –OH of a carboxylic acid is replaced by nucleophile, :Nu, a carboxylic acid derivatives is produced.

The carboxylic acid derivatives are:

Carboxylic Acid DerivativesThe carboxyl group consists of two parts, the acyl group and the attached hydroxyl group:

R-C-OHO

The acid derivatives are compounds in which the hydroxyl group is replaced with another group or a halogen atom. The principal examples are:

R-C-XO

R-C-OO

R-C-OR'O

R-C-NH2

O

R-C-NHR'O

R-C-NR'R''O

R-C N

Acyl (acid) halides

-C-R'O

Acid anhydrides

Esters

Amides

N-MonosubstitutedAmides

N,N-DisubstitutedAmides

Another class of carboxylic acid derivatives are the nitriles, which qualify because on hydrolysis, like all of the other derivatives above, they yield carboxylic acids. Nitriles

Carboxylic Acid DerivativesThe carboxyl group consists of two parts, the acyl group and the attached hydroxyl group:

R-C-OHO

The acid derivatives are compounds in which the hydroxyl group is replaced with another group or a halogen atom. The principal examples are:

R-C-XO

R-C-OO

R-C-OR'O

R-C-NH2

O

R-C-NHR'O

R-C-NR'R''O

R-C N

Acyl (acid) halides

-C-R'O

Acid anhydrides

Esters

Amides

N-MonosubstitutedAmides

N,N-DisubstitutedAmides

Another class of carboxylic acid derivatives are the nitriles, which qualify because on hydrolysis, like all of the other derivatives above, they yield carboxylic acids. Nitriles

Carboxylic Acid DerivativesThe carboxyl group consists of two parts, the acyl group and the attached hydroxyl group:

R-C-OHO

The acid derivatives are compounds in which the hydroxyl group is replaced with another group or a halogen atom. The principal examples are:

R-C-XO

R-C-OO

R-C-OR'O

R-C-NH2

O

R-C-NHR'O

R-C-NR'R''O

R-C N

Acyl (acid) halides

-C-R'O

Acid anhydrides

Esters

Amides

N-MonosubstitutedAmides

N,N-DisubstitutedAmides

Another class of carboxylic acid derivatives are the nitriles, which qualify because on hydrolysis, like all of the other derivatives above, they yield carboxylic acids. Nitriles

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Nomenclature of Acid DerivativesAcid Halides

Replace the –ic acid suffix of carboxylic acids with –yl chloride. If the acyl group is a branch of a cyclic compound, replace the ending from

carboxylic acid to -carbonyl.

Br

O

Benzoyl Bromide

Cyclohexanacarbonyl chloride

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Esters

The alkyl group (which replace of the hydrogen of the carboxylic acid) is named first followed by the name of the parent acid, with the ending –ate in place of –ic acid

Ethy 4-pentenoate Ethyl cyclohexanecarboxylate

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Acid Anhydrides

Anhydrides acids are named by replacing the word acid with anhydride.

OCH3

O O

Benzoic ethanoic anhydride

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AmidesAmides An substituted –NH2 group is named by replacing the –oic acid of the carboxylic acid with –

amide and –carboxylic acid with –carboxamide. A substituted compound is named by identification of the substituent followed by the

parent amide.

CH3

O

NH2

ethylamide

N-metylbutanamide

Cyclohexanecarboxamide

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R C

O

OR'R C

O

OH + R'OHH+

+ HOH

acid

R C

O

OR'R C

O

Cl + R'OH + HClacid chloride

R C

O

OR'R C

O

O C

O

R + R'OHH+

+ RCOOH

acid anhydride

i) Formation of Ester

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Reactions of Esters

R C

O

OR'

R C

O

OH + R'OH

R C

O

OR''

R C

O

NHR'' + R'OH

+ R'OH

R CH2OH

R C

OH

R''

R''H2O(2)

(1) 2 R''MgX

(1)(2) H2O

LiAlH4

H2O

R''OH,

R''NH2

H+ or -OR''

acid

ester

amide

1° alcohol

3° alcohol

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Synthesis of Acyl ChloridesBecause of their reactivity, acyl chlorides must be prepared under conditions that exclude exposure to good nucleophiles like water. Common reagents that convert carboxylic acids into acyl chlorides are phosphorus trichloride (PCl3) phosphorus pentachloride (PCl5), and thionyl chloride (SOCl2).

Typical Synthetic Procedures

The carboxylic acid is heated with the reagent, with or without the presence of an inert solvent.

COHO=

Benzoic acid

+ SOCl2Thionyl chloride

(bp 75-76 oC)

heat

CClO=

Benzoyl chloride

+ SO2 + HCl

Thionyl chloride is an especially convenient reagent because the byproducts are gases and easily removed. Excess thionyl chloride is easy to remove by distillation.

ii) Formation of Acid Halides

or PCl3

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Acid Chloride Reactions

H2O

R'OH

R'NH2

R'COOH

R C

O

Cl

R C

O

OH + HCl

R C

O

OR'

R C

O

NHR'

R C

O

O C

O

R' + HCl

+ HCl

+ HCl

acid

ester

amide

acid anhydride

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Amides from EstersEsters undergo nucleophilic addition-elimination at the acyl carbon with nitrogen nucleophiles such as ammonia (ammonolysis) or amines (amination).

CH3COC2H5

O=

Ethyl acetate+ :NH3 H2O

ammonolysisCH3CNH2 + C2H5OH

O=

Acetamide

Amides from Carboxylic AcidsCarboxylic acids react with aqueous ammonia to produce ammonium carboxylates in an acid-base reaction:

RCOHO=

+ :NH3Acid Base

RCO-O=

NH4+

Ammonium carboxylateSalt

Recovery of the ammonium carboxylate and heating of the dry salt leads to dehydration and formation of the amide.

RCO-O=

NH4+

As the dry saltRCNH2 + H2O

O=heat

AmideThis method is generally not used in organic synthesis because the vigorous heating required will often decompose the sample.

iii) Formation of Amides

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Reactions of Amides

R C

O

OH + R'NH2

R C

O

NHR'

R CH2NHR'(1)(2) H2O

LiAlH4

H2OH+ or -OH

Br-, OH-R NH2 + CO2

POCl3(or P2O5)

R C N

acid and amine

amine

1° amine

nitrile

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The most general method for the preparing an acid anhydride is by nucleophilic acyl substitution reaction of an acid chloride with a carboxylate anion.

iv) Formation of Acid Anhydrides

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Anhydride Reactions

R C

O

O C

O

R

R C

O

OH + RCOOH

R C

O

OR'

R C

O

NHR' + RCOOH

+ RCOOH

AlCl3

H2O

R'OH, H+

R'NH2

ZC

O

RZ

acid

ester

amide

EP101 / EG101 33

Conclusion At the end of the chapter…. You suppose able to:

Understand the nomenclature of carboxylic acid and its derivatives The physical properties of carboxylic acid The 3 main methods of synthesis carboxylic acid The reaction of carboxylic acid to form its derivatives.

EP101 / EG101School of Engineering

Functional Group InterconversionsR C N

R C OH

O

R C O

O

R' R C O

O

R C Cl

O

R C NH2

O

RC

O

R C O

O

R C NR'2

O

H2O

SOCl2

NH3

NR’2H

OH-

R’OH

RCOOH

H2O

NH3

NR’2HRCOOH

R’OH OH-

H2O

H2O

NH3

NR’2H

NH3

NR’2H