19-1Dr. Wolf's CHM 201 & 202

19.16-Halogenation of Carboxylic

Acids:The Hell-Volhard-Zelinsky

Reaction

19-2Dr. Wolf's CHM 201 & 202

analogous to analogous to -halogenation of aldehydes and -halogenation of aldehydes and ketonesketones

key question: Is enol content of carboxylic key question: Is enol content of carboxylic acids high enough to permit reaction to occur acids high enough to permit reaction to occur at reasonable rate?at reasonable rate? (Answer is NO) (Answer is NO)

-Halogenation of Carboxylic Acids

-Halogenation of Carboxylic Acids

++ XX22 ++ HHXXRR22CCOHCCOH

OO

HH

RR22CCOHCCOH

OO

XX

19-3Dr. Wolf's CHM 201 & 202

reaction works well if a small amount ofreaction works well if a small amount ofphosphorus or a phosphorus trihalide is added tophosphorus or a phosphorus trihalide is added tothe reaction mixturethe reaction mixture

this combination is called the Hell-Volhard-this combination is called the Hell-Volhard-Zelinsky reactionZelinsky reaction

But...But...

++ XX22 ++ HHXXRR22CCOHCCOH

OO

HH

RR22CCOHCCOH

OO

XX

P or PXP or PX33

19-4Dr. Wolf's CHM 201 & 202

ExampleExample CHCH22COHCOH

OO

PClPCl33 benzenebenzene80°C80°C

CHCOHCHCOH

OO

BrBr

(60-62%)(60-62%)

++ BrBr22

19-5Dr. Wolf's CHM 201 & 202

ValueValue

CHCH33CHCH22CHCH22COHCOH

OOBrBr22

PPCHCH33CHCH22CHCOHCHCOH

OO

BrBr

(77%)(77%)

-Halogen can be replaced by nucleophilic -Halogen can be replaced by nucleophilic substitutionsubstitution

19-6Dr. Wolf's CHM 201 & 202

ValueValue

CHCH33CHCH22CHCH22COHCOH

OOBrBr22

PPCHCH33CHCH22CHCOHCHCOH

OO

BrBr

CHCH33CHCH22CHCOHCHCOH

OO

OHOH

(77%)(77%)

(69%)(69%)

KK22COCO33

HH22OO

heatheat

19-7Dr. Wolf's CHM 201 & 202

Synthesis of -Amino AcidsSynthesis of -Amino Acids

(CH(CH33))22CHCHCHCH22COHCOH

OOBrBr22

PClPCl33(CH(CH33))22CHCHCOHCHCHCOH

OO

BrBr

(CH(CH33))22CHCHCOHCHCHCOH

OO

NHNH22

(88%)(88%)

(48%)(48%)

NHNH33

HH22OO

19-8Dr. Wolf's CHM 201 & 202

19.17Decarboxylation of Malonic

Acidand Related Compounds

19-9Dr. Wolf's CHM 201 & 202

Decarboxylation of Carboxylic Acids

Decarboxylation of Carboxylic Acids

Simple carboxylic acids do not decarboxylateSimple carboxylic acids do not decarboxylatereadily.readily.

RHRH ++ COCO22RCOHRCOH

OO

19-10Dr. Wolf's CHM 201 & 202

Decarboxylation of Carboxylic Acids

Decarboxylation of Carboxylic Acids

Simple carboxylic acids do not decarboxylateSimple carboxylic acids do not decarboxylatereadily.readily.

But malonic acid does.But malonic acid does.

RHRH ++ COCO22RCOHRCOH

OO

150°C150°CCHCH33COHCOH

OO

++ COCO22HOCCHHOCCH22COHCOH

OO OO

19-11Dr. Wolf's CHM 201 & 202

Mechanism of DecarboxylationMechanism of Decarboxylation

One carboxyl group assists the loss of the other.One carboxyl group assists the loss of the other. OO OO

OHOHHOHO

HH HH

OO

HOHO OO

OO

HH HH

HH

19-12Dr. Wolf's CHM 201 & 202

Mechanism of DecarboxylationMechanism of Decarboxylation

This compound is This compound is the enol form of the enol form of acetic acid.acetic acid.

OO OO

OHOHHOHO

HH HH HH

HH

OHOH

HOHO

OO

HOHO OO

OO

HH HH

HH ++ CC

OO

OO

One carboxyl group assists the loss of the other.One carboxyl group assists the loss of the other.

19-13Dr. Wolf's CHM 201 & 202

Mechanism of DecarboxylationMechanism of Decarboxylation OO OO

OHOHHOHO

HH HH HH

HH

OHOH

HOHO

OO

HOHO OO

OO

HH HH

HH ++ CC

OO

OO

One carboxyl group assists the loss of the other.One carboxyl group assists the loss of the other.

HOCCHHOCCH33

OO

19-14Dr. Wolf's CHM 201 & 202

Mechanism of DecarboxylationMechanism of Decarboxylation OO OO

OHOHHOHO

HH HH HH

HH

OHOH

HOHO

OO

HOHO OO

OO

HH HH

HH ++ CC

OO

OO

One carboxyl group assists the loss of the other.One carboxyl group assists the loss of the other.

HOCCHHOCCH33

OO

These hydrogens play no role.These hydrogens play no role.

19-15Dr. Wolf's CHM 201 & 202

Mechanism of DecarboxylationMechanism of Decarboxylation OO OO

OHOHHOHO

RR R'R' RR

R'R'

OHOH

HOHO

OO

HOHO OO

OO

RR R'R'

HH ++ CC

OO

OO

One carboxyl group assists the loss of the other.One carboxyl group assists the loss of the other.

HOCCHHOCCHR'R'

OO

Groups other than H may be present.Groups other than H may be present.

RR

19-16Dr. Wolf's CHM 201 & 202

185°C185°C

Decarboxylation is a general reaction for 1,3-dicarboxylic acids

Decarboxylation is a general reaction for 1,3-dicarboxylic acids

160°C160°C

COCO22HH

COCO22HH

COCO22HH

HH

(74%)(74%)

(96-99%)(96-99%)

CH(COCH(CO22H)H)22

CHCH22COCO22HH

19-17Dr. Wolf's CHM 201 & 202

Mechanism of DecarboxylationMechanism of Decarboxylation OO OO

OHOHHOHO

RR R'R' RR

R'R'

OHOH

HOHO

OO

HOHO OO

OO

RR R'R'

HH ++ CC

OO

OO

One carboxyl group assists the loss of the other.One carboxyl group assists the loss of the other.

This OH group plays no role.This OH group plays no role.

HOCCHHOCCHR'R'

OO

RR

19-18Dr. Wolf's CHM 201 & 202

Mechanism of DecarboxylationMechanism of Decarboxylation OO OO

OHOHR"R"

RR R'R'

RR

CC

OO

OO

One carboxyl group assists the loss of the other.One carboxyl group assists the loss of the other.

Groups other than OH may be present.Groups other than OH may be present.

R"R"CCHCCHR'R'

OO

RR

OO

OO

OO

RR R'R'

HH R"R"

R'R'

OHOH

++R"R"

19-19Dr. Wolf's CHM 201 & 202

Mechanism of DecarboxylationMechanism of Decarboxylation OO OO

OHOHR"R"

RR R'R'

This kind of compoundThis kind of compoundis called a is called a -keto acid.-keto acid.

R"R"CCHCCHR'R'

OO

RR

Decarboxylation of a Decarboxylation of a -keto acid gives a -keto acid gives a ketone.ketone.

19-20Dr. Wolf's CHM 201 & 202

Decarboxylation of a -Keto AcidDecarboxylation of a -Keto Acid

CCCHCH33CC

OO

CHCH33

CHCH33

COCO22HH25°C25°C

COCO22

CCCHCH33CC

OO

CHCH33

CHCH33

HH

++

19-21Dr. Wolf's CHM 201 & 202

Section 19.18Section 19.18Spectroscopic Analysis ofSpectroscopic Analysis of

Carboxylic AcidsCarboxylic Acids

19-22Dr. Wolf's CHM 201 & 202

A carboxylic acid is characterized by peaks due toA carboxylic acid is characterized by peaks due toOH and C=O groups in its infrared spectrum.OH and C=O groups in its infrared spectrum.

C=O stretching gives an intense absorptionC=O stretching gives an intense absorptionnear 1700 cmnear 1700 cm-1-1..

OH peak is broad and overlaps with C—H OH peak is broad and overlaps with C—H absorptions.absorptions.

Infrared SpectroscopyInfrared SpectroscopyInfrared SpectroscopyInfrared Spectroscopy

Dr. Wolf's CHM 201 & 202 19-23

2000200035003500 30003000 25002500 1000100015001500 500500

Wave number, cmWave number, cm-1-1

Figure 19.8 Infrared Spectrum of 4-Phenylbutanoic acidFigure 19.8 Infrared Spectrum of 4-Phenylbutanoic acidFigure 19.8 Infrared Spectrum of 4-Phenylbutanoic acidFigure 19.8 Infrared Spectrum of 4-Phenylbutanoic acid

C=OC=O

O—H and C—H stretchO—H and C—H stretch

monosubstitutedmonosubstitutedbenzenebenzene

CC66HH55CHCH22CHCH22CHCH22COCO22HH

19-24Dr. Wolf's CHM 201 & 202

proton of OH group of a carboxylic acid is normallyproton of OH group of a carboxylic acid is normallythe least shielded of all of the protons in a the least shielded of all of the protons in a 11HHNMR spectrum: (NMR spectrum: ( 10-12 ppm; broad). 10-12 ppm; broad).

11H NMRH NMR11H NMRH NMR

19-25Dr. Wolf's CHM 201 & 202

Chemical shift (Chemical shift (, ppm), ppm)

Figure 19.9Figure 19.9

CCHH22CCHH22CCHH22COCOHH

OO

01.02.03.04.05.06.07.08.09.010.011.012.0

19-26Dr. Wolf's CHM 201 & 202

1313C NMRC NMR1313C NMRC NMR

Carbonyl carbon is at low field (Carbonyl carbon is at low field ( 160-185 ppm), 160-185 ppm), but not as deshielded as the carbonyl carbon of but not as deshielded as the carbonyl carbon of an aldehyde or ketone (an aldehyde or ketone ( 190-215 ppm). 190-215 ppm).

19-27Dr. Wolf's CHM 201 & 202

UV-VISUV-VISUV-VISUV-VIS

Carboxylic acids absorb near 210 nm, butCarboxylic acids absorb near 210 nm, butUV-VIS spectroscopy has not proven to UV-VIS spectroscopy has not proven to be very useful for structure determination of be very useful for structure determination of carboxylic acids.carboxylic acids.

19-28Dr. Wolf's CHM 201 & 202

Aliphatic carboxylic acids undergo a varietyAliphatic carboxylic acids undergo a varietyof fragmentations.of fragmentations.Aromatic carboxylic acids first form acylium ions,Aromatic carboxylic acids first form acylium ions,which then lose CO.which then lose CO.

Mass SpectrometryMass SpectrometryMass SpectrometryMass Spectrometry

ArCArCOHOH

••••OO ••

••

ArCArCOHOH

••++OO ••

••

ArCArC OO ••••

++ArAr+

+

19-29Dr. Wolf's CHM 201 & 202

End of Chapter 19