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Carboxylic Acid & Carboxylic Acid & Carboxylic Acid & Carboxylic Acid & Their Derivatives Their Derivatives Their Derivatives Their Derivatives

Jully TanSchool of Engineering

EP101 / EG101 �

Learning OutcomeLearning OutcomeLearning OutcomeLearning 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

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EP101 / EG101 �

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 σσσσ-bond and a ππππ-bond. The carbon atom is sp2 hybridized, which explains the trigonal planar geometry at this center.

C ORHO σσσσ

ππππ

R may be alkyl, aryl or simply H

EP101 / EG101 �

Naming RulesNaming RulesNaming RulesNaming 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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EP101 / EG101 �

IUPAC NamesIUPAC NamesIUPAC NamesIUPAC 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

EP101 / EG101 �

Naming Cyclic AcidsNaming Cyclic AcidsNaming Cyclic AcidsNaming 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

COOH

NO2

Cl

2-Chloro-4-nitrobenzoic acid

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EP101 / EG101 �

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.

EP101 / EG101 �

Boiling PointsBoiling PointsBoiling PointsBoiling 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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EP101 / EG101

SolubilitySolubilitySolubilitySolubility

� 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.

EP101 / EG101 �

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.

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EP101 / EG101 ��

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.

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EP101 / EG101 ��

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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EP101 / EG101 ��

Substituent Effects Substituent Effects Substituent Effects Substituent Effects on Acidityon Acidityon Acidityon Acidity

EP101 / EG101 ��

Synthesis of Carboxylic AcidsSynthesis of Carboxylic AcidsSynthesis of Carboxylic AcidsSynthesis of Carboxylic Acids

� Oxidation of 1° ROH & aldehydes� Side chain oxidation of alkylbenzenes� Conversion of Grignards.

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EP101 / EG101 ��

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

i) Oxidation of 1°ROH / Aldehydes

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

EP101 / EG101 ��

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

ii) Side chain oxidation of alkylbenzenes

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EP101 / EG101 ��

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-MgXδδδδ- δδδδ++++

+ C:O:=

:O:

= R-C-O:O:

= :

::

-MgX+

Nucleophilicaddition

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

EP101 / EG101 ��

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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EP101 / EG101 �

InterconversionInterconversionInterconversionInterconversion of Derivativesof Derivativesof Derivativesof Derivatives

More reactive derivatives can be converted to less reactive derivatives.

EP101 / EG101 �

Typical RCOOH Reactions Typical RCOOH Reactions Typical RCOOH Reactions Typical RCOOH Reactions –––– Formation of Acid DerivativesFormation of Acid DerivativesFormation of Acid DerivativesFormation 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:

R-C-NH2

OAmidesR-C-X

O

R-C-OO

O

Acyl (acid) halides

-C-R'O

Acid anhydrides R-C-OR'O

Esters

Another class of carboxylic acid

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EP101 / EG101 ��

Nomenclature of Acid DerivativesNomenclature of Acid DerivativesNomenclature of Acid DerivativesNomenclature of Acid Derivatives

Acid 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 fromcarboxylic acid to -carbonyl.

CCl

OCH3CH2CH2C

O

Cl

butanoyl chloridebutyryl chloride

benzoyl chloride

Br

O

Benzoyl Bromide

Cyclohexanacarbonyl chloride

EP101 / EG101 ��

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

CO CH2CH3

O

ethyl benzoate

CH3CH2CH2CO

O CH3

methyl butanoatemethyl butyrate

Ethy 4-pentenoate Ethyl cyclohexanecarboxylate

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EP101 / EG101 ��

Acid Anhydrides

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

OCH3

O O

Benzoic ethanoic anhydride

EP101 / EG101 ��

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

CNH2

OCH3CH2CH2C

O

NH2

butanamidebutyramide

benzamide

N-metylbutanamide

Cyclohexanecarboxamide

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EP101 / EG101 ��

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)i)i)i) Formation of Ester Formation of Ester Formation of Ester Formation of Ester

EP101 / EG101 ��

Reactions of EstersReactions of EstersReactions of EstersReactions 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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EP101 / EG101 ��

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)ii)ii)ii) Formation of Acid HalidesFormation of Acid HalidesFormation of Acid HalidesFormation of Acid Halides

or PCl3

EP101 / EG101 ��

Acid Chloride Reactions Acid Chloride Reactions Acid Chloride Reactions 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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EP101 / EG101 �

Carboxylic 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)iii)iii)iii) Formation of AmidesFormation of AmidesFormation of AmidesFormation of Amides

EP101 / EG101 �

Reactions of AmidesReactions of AmidesReactions of AmidesReactions 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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EP101 / EG101 ��

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)iv)iv)iv) Formation of Acid AnhydridesFormation of Acid AnhydridesFormation of Acid AnhydridesFormation of Acid Anhydrides

EP101 / EG101 ��

Anhydride ReactionsAnhydride ReactionsAnhydride ReactionsAnhydride Reactions

R C

O

O C

O

R

R C

O

OH + RCOOH

R C

O

OR'

R C

O

NHR' + RCOOH

+ RCOOH

H2O

R'OH, H+

R'NH2

acid

ester

amide

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EP101 / EG101 ��

Conclusion Conclusion Conclusion 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.