Asam Karboksilat Dan Turunannya

Asam Karboksilat dan Turunannya

Ayik Rosita P., M.Farm., Apt

Bagian Kimia Farmasi

Universitas Jember

Asam KarboksilatSenyawa yang memiliki satu gugus karbonil

yang berikatan dengan 1 gugus hidroksil

R C

O

O H

Karbonil

Hidroksil

Karbonil + Hidroksil gugus “Karboksil”

O

OH

O

O

aspirin

3

• The C—O single bond of a carboxylic acid is shorter than the C—O bond of an alcohol.

• This can be explained by looking at the hybridization of the respective carbon atoms.

Structure and Bonding

• Because oxygen is more electronegative than either carbon or hydrogen, the C—O and O—H bonds are polar.

Tata Nama IUPACMengganti akhiran –a dari alkana induk

dengan imbuhan asam –oatKarbon karboksil diberi no. 1Jika memiliki 2 gugus karboksilat, penamaan

diberi akhiran -dioat

C

O

OH

H C

O

OH

H3C

C

O

OH

HC

H2C C

O

OH

H2CC

Br

O

HO

Asam metanoat Asam etanoat

Asam 2-bromobutanoat

H3C

Asam propanadioat

5

• Compounds containing two carboxy groups are called diacids. Diacids are named using the suffix –dioic acid.

• Metal salts of carboxylate anions are formed from carboxylic acids in many reactions. To name the metal salt of a carboxylate anion, put three parts together:

H3C CO2H

CO2H

CO2H

CO2HH2C CHCO2H

asam p-toluat asam o-ftalat

asam sikloheksanakarboksilat

asam akrilat

Penamaan IUPAC, Struktur cincin mgd gugus karboksil‘Asam (struktur cincin)karboksilat’

IUPAC

Tata Nama TrivialTanpa sistematika4 asam karboksilat pertama, sering dinamai

dengan nama trivial

Banyaknya atom C Struktur Nama Trivial Penurunan nama

1 HCOOH Asam format semut

2 CH3CO2H Asam asetat cuka

3 CH3CH2CO2H Asam propionat susu, keju

4 CH3(CH2)2CO2H Asam butirat mentega

5 CH3(CH2)3CO2H Asam valerat akar valeria

6 CH3(CH2)4CO2H Asam kaproat kambing

7 CH3(CH2)5CO2H Asam enantat anggur

8 CH3(CH2)6CO2H Asam kaprilat kambing

Chapter 20 8

Common Names

Many aliphatic acids have historical names.Positions of substituents on the chain are

labeled with Greek letters.

CH3CH2CHC

Cl

OH

O

-chlorobutyric acid

CH3CH2CH2CHCH2COOH

Ph

-phenylcaproic acid

=>

Chapter 20 9

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(salicylic acid)

=>

10

Give the IUPAC and common names:

A. CH3—COOH

CH3

|B. CH3—CH—COOH

C.

Learning Check

COOH

Br

11

A. CH3—COOH ethanoic acid (acetic acid) CH3

|B. CH3—CH—COOH 2-methylpropanoic acid

(-methylpropionic acid)

C. 2-bromobenzoic acid(o-bromobenzoic acid)

Solution

COOH

Br

Sifat Fisika KimiaAsam karboksilat memiliki 3 ikatan kovalen

polar senyawa polar

H3C

C

O

O

H

Asam karboksilat mampu membentuk ikatan H dg Sesamanya atau dengan air dijumpai dlm bentuk dimer (bahkan dalam fase uap)

H3C C

O

O H

H O

C CH3

O

H3C C

O

O H

H

O H

Sifat Fisika KimiaKarena ikatan H asam karboksilat > alkohol

m.p & b.p lebih tinggi dari alkohol dg mw ekivalen

Karena As. Karboksilat mampu membentuk ikatan H dengan air mudah larut air

H3CH2C C

OH

O

H3CH2C

H2C OH

m.p -220Cb.p 1410C

m.p -1260Cb.p 97,20C

H3CH2C C

OH

OGugus polar

Rantai C non polar

Physical Properties

Highest bp of compounds studied so far!

Alcohols

Alkyl halidesAlkanes

Incr

easi

ng B

P

Ethers/Aldehydes/Ketones

Carboxylic acids

Solubility of Organics

One electronegative group per four carbons will make a compound dissolve in water

Fatty AcidsLong un-branched carboxylic acidsMost have between 12 and 20 carbonsDerived from the hydrolysis of fatsMost have an even number of C’s If unsaturated, the cis isomer predominatesUnsaturated have lower melt points than saturated

Melting PointsSaturated have higher melting points than

unsaturated fatty acids

Soap

Soap is made by adding NaOH to a fatThis reaction is called soponificationThis cleaves each of the fatty acids

producing the solid fatty acid salt (soap)The other product is glycerol

C

C

C

O C

O

O C

O

O C

O

H

H

H

H

H

+ NaOH3

C

O

ONa+

3

+H

H OH

OHH

OHH

Hfat or oil

glycerol

soap

Soap

C

O

ONa+

soap

polar non polar

Soap Micelles

O

O

OO O

O O O

OO

O

O

O

O

O

O

Modern Detergents

Dodecylbenzene Sodium

4dodecylbenzenesulfonate

CH2(CH2)10CH2

H2SO4

NaOHCH2(CH2)10CH2 SO3-Na+

Keasaman Asam Karboksilat

Mrpk sifat kimia yang paling menonjolAsam karboksilat terionisasi dalam air mbtk larutan

yang bersifat sedikit asamKeasaman < dari asam anorganik……. Karena bersifat

asam lemahDibanding alkohol, pKa as. Karboksilat lebih kecil

karena asam karboksilat dapat beresonansi terstabilkan & meningkatkan Ka

H3C C

O

O- H3C C

O-

O

Acidic Properties

It is the release of the hydrogen ion (proton) to the water molecule

This forms the acid particles H+ or H3O+

Reactions due to the acidic nature of carboxylic acidsThis release of protons when in water

gives the solution a pH of less than 7. The usual reactions of acids are present. The conditions for all these reactions is

room temperature.

Acids as Proton Doners

The carboxylate anion helps in the understanding of the carboxyl group to release a proton.

The extra negative charge can be on either oxygen. It is partially delocalised and adds to the stability of the anion

This extra stability increased the chances of it being formed.

CH3 CO

O-CH3 C

O-

O

26

Carboxylic Acids—Strong Organic BrØnsted-Lowry Acids

• Carboxylic acids are strong organic acids, and as such, readily react with BrØnsted-Lowry bases to form carboxylate anions.

27

• An acid can be deprotonated by a base that has a conjugate acid with a higher pKa.

• Because the pKa values of many carboxylic acids are ~5, bases that have conjugate acids with pKa values higher than 5 are strong enough to deprotonate them.

28

29

• Carboxylic acids are relatively strong acids because deprotonation forms a resonance-stabilized conjugate base—a carboxylate anion.

• The acetate anion has two C—O bonds of equal length (1.27 Å) and intermediate between the length of a C—O single bond (1.36 Å) and C=O (1.21 Å).

30

• Resonance stabilization accounts for why carboxylic acids are more acidic than other compounds with O—H bonds—namely alcohols and phenols.

• To understand the relative acidity of ethanol, phenol and acetic acid, we must compare the stability of their conjugate bases and use the following rule:

- Anything that stabilizes a conjugate base A:¯ makes the starting acid H—A more acidic.

31

• Ethoxide, the conjugate base of ethanol, bears a negative charge on the O atom, but there are no additional factors to further stabilize the anion. Because ethoxide is less stable than acetate, ethanol is a weaker acid than acetic acid.

• Phenoxide, the conjugate base of phenol, is more stable than ethoxide, but less stable than acetate because acetate has two electronegative O atoms upon which to delocalize the negative charge, whereas phenoxide has only one.

32

• Note that although resonance stabilization of the conjugate base is important in determining acidity, the absolute number of resonance structures alone is not what is important!

Figure 19.7Summary: The relationship

between acidity and conjugatebase stability for acetic acid,

phenol, and ethanol

33

The Inductive Effect in Aliphatic Carboxylic Acids

34

35

Substituted Benzoic Acids

Recall that substituents on a benzene ring either donate or withdraw electron density, depending on the balance of their inductive and resonance effects. These same effects also determine the acidity of substituted benzoic acids.

[1] Electron-donor groups destabilize a conjugate base, making an acid less acidic—The conjugate base is destabilized because electron density is being donated to a negatively charged carboxylate anion.

36

[2] Electron-withdrawing groups stabilize a conjugate base, making an acid more acidic. The conjugate base is stabilized because electron density is removed from the negatively charged carboxylate anion.

37

Figure 19.8How common substituents

affect the reactivity of abenzene ring towards

electrophiles and the acidity ofsubstituted benzoic acids

38

Sulfonic Acids

• Sulfonic acids have the general structure RSO3H.

• The most widely used sulfonic acid is p-toluenesulfonic acid.

• Sulfonic acids are very strong acids because their conjugate bases (sulfonate anions) are resonance stabilized, and all the resonance structures delocalize negative charge on oxygen.

Pembuatan Asam Karboksilat

1. Hidrolisis derivat asam karboksilatDerivat diserang air / OH- pada C karbonilex derivat : ester, amida, anhidrida, dll

RC OR' + H2O

O

RCO2H + R'OH

RC X + H2O

O

RCO2H + X-

2. Reaksi Grignard Reagen Grignard (1o, 2o, 3o,vinil, aril) dan gas CO2

kering

- Terjadi pemanjangan rantai (1 C lebih banyak)

RX RMgX RCO2HMg

Eter kering

1. CO2

2. H2O, H+

RX RCN RCO2HCN- H2O, H+

SN2

MgBr CO2H

fenilmagnesium bromida asam benzoat (85%)

Ex:

3. Reaksi Oksidasi

Oksidasi alkohol primer dan aldehida

H2C OH + K2Cr2O7

H+H2CH3C C

H2CH3C

O

OHH2C OH + KMnO4

H2C

H2CH3C

H+

CH2C

H2C

O

OH

H3C

Oksidator kuat

C + Ag(NH3)2+

H2CH3C

O

H

NH4OHC

H2CH3C

O

OHOksidator lemah

3. Reaksi OksidasiOksidasi alkena

H3C

C

H3C

CH

H2C CH3

OKsidator

Kuat

H3C

C

H3C

O CH2C CH3

O

H

+

OKsidator

KuatCO2H

CO2H

sikloheksena asam adipat

Derivat Asam Karboksilat

Senyawa yang menghasilkan asam karboksilat bila direx dg air

C

R X

O

Halida asam(asil halida)

C

R O

O

Anhidrida asam

C

O

R'

C

R O

O

R'

Ester

C

R N

O

Amida

R C N

Nitril

Halida Asam

Acyl halides are compounds that have a halogen atom in place of the OH group of a carboxylic acid. The most common acyl halides are acyl chlorides and acyl bromides.

C

R X

O

Halida asam(asil halida)

F, Cl, Br, I

Tata Nama Klorida/Bromida Asam Nama As. Karboksilat induk, dengan

mengubah imbuhan asam –at menjadi –il klorida/bromida

C

H3C Cl

O

Etanoil kloridaasetil klorida

CCH2

Br

O

CH

CH3

H2CH3C

3-metilpentanoil bromida-metilvaleril bromida

C

O

Cl

siklopentanakarbonil kloridaIUPACTrivial

46

Nomenclature of Acid Halides

IUPAC: alkanoic acid alkanoyl halide Common: alkanic acid alkanyl halide

C

O

Cl

CH2

NH2

CH2 C

O

Cl

I: 3-aminopropanoyl chloride

c: -aminopropionyl chloride

I: benzenecarbonyl bromide

c: benzoyl bromide

Rings: (IUPAC only): ringcarbonyl halide

I: 3-cylcopentenecarbonyl chloride

CH2 C

O

ClC

O

Cl 4

I: hexanedioyl chloride

c: adipoyl chloride

C

O

Br

CH

NO2

CH2 CH2H3C C

O

Cl

I: 4-nitropentanoyl chloride

c: -nitrovaleryl chloride

R C

O

Cl

: :

:....

Chapter 21 47

ReactivityReactivity decreases as leaving group

becomes more basic.

=>

Chapter 21 48

Interconversion of Derivatives

More reactive derivatives can be converted to less reactive derivatives.

=>

Chapter 21 49

Hydrolysis of Acid Chlorides and Anhydrides

Hydrolysis occurs quickly, even in moist air with no acid or base catalyst.

Reagents must be protected from moisture.

+CH3 C

O

Cl HOH CH3 C

O

OH + HCl

=>

Pembuatan Klorida AsamKlorida asam didapat dari asam karboksilat

induk melalui reaksi dengan tionil klorida (SOCl2) / zat penghalogen aktif lain (ex PCl3)

R

C

O

OH

+ SOCl2

R

C

O

Cl

+ SO2 + HCl

R

C

O

OH

+ PCl3

R

C

O

Cl

+ H3PO3

H3C

C

O

OH H3C

C

O

Cl

+ H3PO3+ PCl3

contoh

Asam asetatAsetil klorida

Anhidrida Asam

Loss of water from two molecules of a carboxylic acid results in an acid anhydride.

“Anhydride” means “without water.”

Tatanama Anhidrida asam

If the two carboxylic acid molecules forming the acid anhydride are the same, the anhydride is a symmetrical anhydride.

If the two carboxylic acid molecules are different, the anhydride is a mixed anhydride.

Symmetrical anhydrides are named by using the acid name and replacing “acid” with “anhydride.”

Mixed anhydrides are named by stating the names of both acids in alphabetical order, followed by “anhydride.”

tatanama indonesia Anhidrida ditempatkan di awal

The word acid is replaced with anhydride.For a mixed anhydride, name both acids.Diacids may form anhydrides if a 5- or 6-membered ring

is the product.

O

O

O

1,2-benzenedicarboxylic anhydridephthalic anhydride

54

Nomenclature of Acid Anhydrides

Acid anhydrides are prepared by dehydrating carboxylic acids

CH3 C

O

OH H O C

O

CH3+

CH3 C

O

O C

O

CH3- H2O

acetic acid acetic anhydrideethanoic anhydrideethanoic acid

R RC

O

O C

O: : : :....

CH3 C

O

O C

O

HC

O

O C

O

H

C

O

O C

O

C CO OO

I: benzenecarboxylic anhydride

c: benzoic andhydride

I: butanedioic acid

c: succinic acid

I: benzoic methanoic anhydride

c: benzoic formic anhydride

C C

O

OH

O

HOC C

O OO

- H2O

I: butanedioic anhydride

c: succinic anhydride

I: cis-butenedioic anhydride

c: maleic anhydride

Some unsymmetrical anhydrides

I: ethanoic methanoic anhydride

c: acetic formic anhydride

Pembuatan Anhidrida

Umumnya, anhidrida asam tidak dapat dibentuk langsung dari as. Karboksilat induk harus dibuat bentuk derivat yang reaktif (klorida asam)

R

C

O

Cl

+

R

C

O

O

OC

O

R'

klorida asam ion karboksilat

C

O

R'

anhidrida

56

Conversion of Carboxylic Acids to Acid Anhydrides

• High temperature dehydration of carboxylic acids results in two molecules of the acid combining and eliminating one molecule of water.

CH3 C

O

OH H O C

O

CH3+

CH3 C

O

O C

O

CH3- H2O

acetic acid acetic anhydrideethanoic anhydrideethanoic acid

• Cyclic anhydrides with 5 or 6-membered rings are prepared by dehydration of diacids.

2HC

2HCC

OH

OHC

O

O

2HC

2HCC

O

C

O

O

H2O-

I: butanedioic acid

c: succinic acid

I: butanedioic anhydride

c: succinic anhydride

• Draw a reaction showing the preparation of cyclohexanecarboxylic anhydride.

C

O

OC

O

H2O-C

O

O H2

Ester

An ester is a compound that has an OR’ group in place of the OH group of a carboxylic acid

Siklik ester lakton

C

R O

O

R'

Ester

Tatanama Ester

Nama suatu ester tdd 2 kataKata pertama gugus Alkil yang terikat

pada O karboksilKata kedua dari nama asam karboksilat

dengan membuatng kata asam

(inggris –ic acid -ate)

Naming of Esters

Esters are named from the acid and alcohol stem.

CH3 CO

O C2H5

Alcohol Stem

Acid Stem

Naming of Esters

the alcohol stem comes at the start of the ester name

the acid stem provides the second part of the name

the name of the ester usually ends with –anoate.

The previous ester is ethyl ethanoate.

61

Nomenclature of Esters

CH3 O C

O

CH3

alkyl

I: alkanoatec: alkanate

R C

O

OH

: :

..

..R RC

O

O....

: :

+H2O-

carboxylicacid

alcohol esterH+

H O R....

O C

O

H

• Esters occur when carboxylic acids react with alcohols

I: methyl ethanoate

c: methyl acetate

C

O

O CH(CH3)2 O C CH(CH3)2

O

C O C(CH3)3

O

CH3 O C

O

C

O

O CH3

I: phenyl methanoate

c: phenyl formateI: t-butyl benzenecarboxylate

c: t-butyl benzoate

I: isobutyl cyclobutanecarboxylate

c: noneI: cyclobutyl 2-methylpropanoate

c: cyclobutyl -methylpropionate

I: dimethyl ethanedioate

c: dimethyl oxalate

Uses of Esters

Esters can be used as AdhesivesPerfumesFlavouringspainkillers.

63

Ester Products

Aspirin Is used to relieve pain and

reduce inflammation. Is an ester of salicylic acid

and acetic acid.

Oil of wintergreen Is used to soothe sore

muscles. Is an ester of salicylic acid

and methanol.

CH3

O

CO

OH

O

C

OH

CH3O

O

C

64

Esters in Plants

Esters give flowers andfruits theirpleasant fragrances and flavors.

TABLE 16.4

Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Some Esters and usesEthyl 2-methylbutanoate CH3CH2CH(CH3)COOCH2CH3 Apple flavour 3-Methylbutyl ethanoate CH3COOCH2CH2CH(CH3)2 Pear flavour 1-Methylpropyl ethanoate CH3COOCH(CH3)CH2CH3 Banana flavour Ethyl methanoate HCOOCH2CH3 Raspberry flavour Butyl butanoate CH3CH2CH2COOCH2CH2CH2CH3 Pineapple flavour Phenylmethyl ethanoate CH3COOCH2C6H5 Oil of Jasmine 2-Ethanoyloxybenzoic acid (acetylsalicylic acid)

OCOCH3

COOH

Aspirin

Methyl 2-hydroxybenzoate (methyl salicylate)

OH

COOCH3

Muscle rub

Ethyl ethanoate CH3COOCH2CH3 Glue solvent Methyl 2-cyanopropenoate CH2=C(CN)COOCH3 Superglue Ethenyl ethanoate CH3COOCH=CH2 PVA glue

Pembuatan Ester Dari asam karboksilat dan alkohol

CH2CH2CH2COH

O

asam 4-fenilbutanoat

+ CH3CH2OH CH2CH2CH2COCH2CH3

O

etanol etil 4-fenilbutanoat (85%)

Dari suatu karboksilat dan alkil halida yang reaktif

CH2Cl

benzil klorida

CH2OCCH3

O

Benzil asetat (93 %)

+ OC

O

R'

ion karboksilat

Cyclic esters are called lactones. In systematic nomenclature, they are named as “2-oxacycloalkanones.”

four-membered ring lactones are β-lactones (the carboxyl oxygen is on the β-carbon),

five-membered ring lactones are γ-lactones and six-membered ring lactones are δ-lactones

68

CH2

CH2 CH2

OH

C

O

OHH+

H2O-

CH2

CH2 CH2

O

C

O

OC

O

OO

I: 4-hydroxybutanoic acid

c: -hydroxybutyric acid

I: 4-hydroxybutanoic acid lactone

c: -butyrolactone

O

O

O

H3C

O

O

CH3

O

Nomenclature of Cyclic Esters, “Lactones”

Cyclic esters, “lactones”, form when an open chain hydroxyacid reacts intramolecularly. 5 to 7-membered rings are most stable.

‘lactone’ is added to the end of the IUPAC acid name. ‘olactone’ replaces the ‘ic acid’ of the common name and ‘hydroxy’ is dropped but its

locant must be included.

I: 4-hydroxypentanoic acid lactone

c: -valerolactone

I: 6-hydroxy-3-methylhexanoic acid lactone

c: -methyl--caprolactone

I: 5-hydroxypentanoic acid lactone

c: -valerolactone

I: 3-hydroxypentanoic acid lactone

c: -valerolactone

Chapter 21 69

Lactones

Formation favored for five- and six-membered rings.

O

OCOOH

OH H+

H2O+

• For larger rings, remove water to shift equilibrium toward products

H+

H2O+O

O

OH

COOH

=>

70

• Esters react like acid halides and anhydrides but are less reactive toward nucleophiles because the carbonyl C is less electrophilic. Both acyclic esters and cyclic esters (lactones) react similarly. Esters are hydrolyzed by HOH to carboxylic acids, react with amines to amides, are reduced by hydrides to aldehydes, then to 1alcohols, and react with Grignards to 3 alcohols.

Reactions of Esters

R C

O

OH

: :..

H2O

R C

O

NH2

: :..

NH3

R C

O

H

: :

[H]

RCH2OH[H]

R':- MgBr+

R C

O

R'

R C

OH

R'

R'

R':- MgBr+

3º alcohol

1º alcohols

amide

acid

ketone

aldehyde

R C

O

O

: :..

R'..

+R'OH

H+

71

• Esters are hydrolyzed (broken down by water) to carboxylic acids or carboxylates by heating in acidic or basic media, respectively.

• Base-promoted ester hydrolysis is called saponification (Latin ‘soap-making’). Boiling animal fat (which contains ester groups) in an aqueous solution of a strong base (NaOH, KOH, etc.) makes soap. A soap is long hydrocarbon chain with an ionic end group.

Base Hydrolysis of Esters

• The mechanism of base hydrolysis is nucleophilic acyl substitution in which OH - adds to the ester carbonyl group producing a tetrahedral intermediate. The carbonyl group reforms as the alkoxide ion leaves, yielding a carboxylate.

CH3(CH2)10C

O

O CH3

K+OH-

CH3(CH2)10C

O

O H

OCH3-

-

c: potassium laurate

CH3(CH2)10C

O

O - K+ + CH3OH

liquid soap

• The leaving group, methoxide (OCH3-), like all alkoxides, is a strong base (pKb = -2).

It will deprotonate the carboxylic acid intermediate converting it to a carboxylate. The alkoxide, when neutralized, becomes an alcohol.

c: sodium laurate

I: sodium dodecanoateC

O

O- Na+

bar soap

Hydrolysis of Esters

Hydrolysis means the break-up of a molecule using water.

Esters can be hydrolysed by both acids and alkalis.

CH3 CO

O C2H5

+ H2Oreflux CH3 C

O

O H+ C2H5OH

Hydrolysis of Esters

Alkali hydrolysis gives the carboxylate salt.Acid hydrolysis leads to equilibrium, the yield

of products is never 100%Alkaline hydrolysis breaks up the ester

completely.

CH3 CO

O C2H5

+ H2O CH3 CO

O-+ C2H5OH

alkali

74

Base hydrolysis (also called saponification) Is the reaction of an ester with a strong base. Produces the salt of the carboxylic acid and an alcohol. O ||

CH3—C—O—CH2—CH3 + NaOH O

CH3—C—O– Na+ + HO—CH2—CH3

salt of carboxylic acid alcohol

Base Hydrolysis (Saponification)

R OCH3

O

RO

CH3

O

HO

addition elimination

R O

O

Ester

O-HNa+

Na+

O-CH3H

Na+

R O

OO-CH3

Na+

Hsodium saltof carboxylicacid

75

Cleaning Action of Soap

A soap Contains a nonpolar end

that dissolves in nonpolar fats and oils, and a polar end that dissolves in water.

Forms groups of soap molecules called micelles that dissolve in water and are washed away.

Copyright © 2007 by Pearson Education, Inc.Publishing as Benjamin Cummings

76

C

O

OCH3

H

OHH

+

• Acidic hydrolysis of an ester yields a carboxylic acid (and an alcohol). The mechanism of acidic ester hydrolysis is the reverse of Fischer esterification. The ester is protonated by acid then attacked by the nucleophile HOH. Transfer of a proton and elimination of ROH yields the carboxylic acid. The reaction is not favorable. It requires at least 30 minutes of refluxing.

• Draw the complete mechanism of acid hydrolysis of methyl cyclopentanecarboxylate.

Acid Hydrolysis of Esters

C

O

OCH3

H+

H2O

H2O

C

O

OCH3

H

+

..

C

O

OCH3

H

OH

H+

..

C

O

OH + +H3O+ CH3OH

• Acid hydrolysis of an ester can be reversed by adding excess alcohol. The reverse reaction is called Fischer Esterification. Explain why base hydrolysis of an ester is not reversible.

77

In acid hydrolysis An ester reacts with water to produce a carboxylic acid and an alcohol. An acid catalyst is required.

O O H+ H—C—O—CH2—CH3 + H2O H—C—OH + H—O—CH2—CH3

Acid Hydrolysis of Esters

78

+H+

R RC

O

O....

: :

ester alcohol

H O R'....

R R'C

O

O....

: :

ester

+

alcohol

H O R....

• Nucleophilic acyl substitution of an ester with an alcohol produces a different ester. The mechanism is the same as acid hydrolysis of esters except that that the nucleophile is an alcohol rather than water. A dry acid catalyst must be used, e.g., HCl(g) or H2SO4. If water is present, it will compete with the alcohol as the nucleophile producing some carboxylic acid in place of the ester product.

• The process is also called Ester Exchange or Transesterification

Alcoholysis of Esters

CH3CH2OH2H2SO4

C

O

OC

O

O

C

O

OCH2CH3C

O

CH3CH2O + OH2

dicyclobutyl terephthalate

dicyclobutyl 1,4-benzenedicarboxylate

diethyl terephthalate

diethyl 1,4-benzenedicarboxylate

cyclobutanol

79

CH C

O

OCH3

H3C

H3CNH3

• Amines can react with esters via nucleophilic acyl substitution yielding amides but the reaction is difficult, requiring a long reflux period. Aminolysis of acid chlorides is preferred.

• Draw the mechanism aminolysis of methyl isobutyroxide with ammonia.

Aminolysis of Esters

CH C

O

NH3C

H3CH

H

H- OCH3-

+

CH C

O

NH3C

H3CH

H+ CH3OH

c: -methylpropionamide

I: 2-methylpropanamide

• Write an equation showing how the following amide can be prepared from an ester.

C

O

N(CH3)2C

O

(CH3)2N C

O

OCH3C

O

CH3O + 2 NH(CH3)2

• Note that the amide intermediate must deprotonate to form a stable, neutral amide. Thus the amine must have at least one H. NH3, 1° and 2° amines will work but not 3°.

80

• Esters are easily reduced with LiAlH4 to yield 1 alcohols. The mechanism is similar to that of acid chloride reduction. A hydride ion first adds to the carbonyl carbon temporarily forming a tetrahedral alkoxide intermediate. Loss of the –OR group reforms the carbonyl creating an aldehyde and an OR - ion. Further addition of H: - to aldehyde gives the 1 alcohol. Draw the mechanism and show all products.

Hydride Reduction of Esters

• The hydride intermediate can be isolated if DIBAH is used as a reducing agent instead of LiAlH4. 1 equivalent of DIBAH is used at very low temp. (-78 C).

1.

2. H3O+

excessLiAlH4

O

O• Draw and name the products.

1 equiv.1.

2. H3O+

78°C-

DIBAHO

O

CH3

O

CH3

H

OH

CH2OHOH

c: -butyrolactone

I: 4-hydroxybutanoic acid lactonec: none

I: 1,4-butanediol

c: -valerolactone

I: 4-hydroxypentanoic acid lactoneI: 4-hydroxypentanal

c: -hydroxyvaleraldehyde

R C

O

O R'LiAlH4

R C

O

H- OR'-

LiAlH4R C

O

H

H

-

R C

O

H

H

H

+ R'OHH3O+

81

• Esters and lactones react with 2 equivalents of Grignard reagent to yield 3 alcohols in which the 2 substituents are identical. The reaction occurs by the usual nucleophilic substitution mechanism to give an intermediate ketone, which reacts further with the Grignard to yield a 3 alcohol.

Grignard Reduction of Esters

C

O

OCH3

MgBr

C

O

- OCH3-

MgBr

C

O-

C

O

H

+ CH3OH

H3O+

O -

O

CH3

CH3 MgBr

O -CH3

CH3O -

H3O+

OH

CH3

CH3OH

I: 4-hydroxybutanoic acid lactone

methyl benzoate benzophenone

triphenylmethanol

triphenylmethoxide

c: -butyrolactone

4-methyl-1,4-pentanediol

CH3 MgBr

O

O

Amida

Senyawa yang mempunyai satu Nitrogen trivalen yang terikat pada suatu gugus karbonil

An amide has an NH2,NHR, NR2 or group in place of the OH group of a carboxylic acid.

C

R N

O

Amida

Tatanama AmidaAmides are named by using the acid

name, replacing “oic acid” or “ic acid” with“amide.”

For acids ending with “carboxylic acid,” “ylic acid” is replaced with “amide.”

84

R C

O

NH

H

R C

O

NH

R R C

O

NR

R

CH3CH2CH2 C

O

NH

HC

O

NH

H

Cl

CH3CH

CH3

C

O

NCH3

HC

O

NH

H3CC

O

NCH3

CH2CH3

Nomenclature of Amides

1° amide2° amideN-substituted amide

3° amideN,N-disubstituted amide

1° amides: ‘alkanoic acid’ + amide ‘’alkanamide’ a ring is named ‘ringcarboxamide’

I: butanamide

c: butyramideI: 3-chlorocyclopentanecarboxamide

c: none

I: p-nitrobenzenecarboxamide

c: p-nitrobenzamide

C

O

NH

HNO2

2° and 3° amides are N-substituted amides

I: N,2-dimethylpropanamide

c: N,-dimethylpropionamide

I: N-phenylethanamide

c: N-phenylacetamide

I: N-ethyl-N-methylcyclobutanecarboxamide

c: none

c: acetanilide

NO

H2N

nicotinamideO

N

N

NN

O

caffeine

• Cyclic amides are called lactams. •Their nomenclature is similar to that of lactones.•They are named as “2-azacycloalkanones” in systematic nomenclature

(“aza” is used to designate the nitrogen atom).

86

Nomenclature of Cyclic Amides, “Lactams”

CH2

CH2 CH2

NH

C

O

OH

H H2O-

CH2

CH2 CH2

NH

C

O

NH

O

NH

OBr

Cyclic amides, “lactams”, form when an open chain aminoacid reacts intramolecularly. 5 to 7-membered rings are most stable.

I: 4-aminobutanoic acid

c: -aminobutyric acid

I: 4-aminobutanoic acid lactam

c: -butyrolactam

‘lactam’ is added to the end of the IUPAC acid name. ‘olactam’ replaces the ‘ic acid’ of the common name and ‘amino’ is dropped but its

locant must be included.

I: 5-aminohexanoic acid lactam

c: -caprolactam

I: 3-amino-2-bromopropanoic acid lactam

c: -bromo--propionolactam

I: 4-amino-3-methylbutanoic acid lactam

c: -methyl--butyrolactam

NH

O

H3C

NH

O

CH3

Pembuatan AmidaDisintesis dari derivat asam karboksilat dan

amonia atau amina yang sesuai

C

R

O

Cl

C

R

O

O

C

R

O

O

C

R'

O

R'

R'2NH

R'2NH

R'2NH

C

R

O

NR'2

89

CH3 C N CN CH2CH2CH2 I

CH3O CN

CNHS

R C

O

NH

H H2O-

POCl3R C N

Nomenclature of Nitriles

Nitriles are produced when 1° amides are dehydrated with reagents like POCl3

• IUPAC: alkane + nitrile ‘alkanenitrile’• IUPAC rings: ‘ringcarbonitrile’• Common: alkanic acid + ‘onitrile’ ‘alkanonitrile’

I: ethanenitrilec: acetonitrile

I: 4-iodobutanenitrile

c: -iodobutyronitrile

I: 3-methoxycyclohexanecarbonitrile

c: none

I: p-thiobenzenecarbonitrile

c: p-mercaptobenzonitrile

COOH

CN

I: 2-cyanocyclopentanecarboxylic acid

c: none

Chapter 21 90

Thioesters

More reactive than esters because:-S-R is a better leaving group than -O-RResonance overlap is not as effective.

=>

Chapter 21 91

Carbonic Acid Esters

CO2 in water contains some H2CO3.

Diesters are stable.Synthesized from phosgene.

+C

O

ClCl CH3CH2OCOCH2CH3

O

2 CH3CH2OH

diethyl carbonate

=>

Chapter 21 92

Urea and Urethanes

Urea is the diamide of carbonic acid.Urethanes are esters of a monoamide

of carbonic acid.

+C

O

ClCl C

O

NH2H2N2 NH3urea

N C O

H2ONH C OH

O

a carbamic acid

ROHNH C OR

O

a urethane =>

Chapter 21 93

Polymers

Polycarbonates are long-chain esters of carbonic acid.

Polyurethanes are formed when a diol reacts with a diisocyanate.

N C ONCO

CH3

HOCH2CH2OH

NH CHN

CH3

C

O

OCH2CH2O

O

n

=>