Lecture 21- Carb A Derivatives

General

Organic Chemistry Two credits Second Semester 2009

King Saud bin Abdulaziz University for Health Science

Reference Book: Organic Chemistry: A Brief Course, by Robert C. Atkins and Francis A. Carey Third Edition

Instructor: Rabih O. Al-Kaysi, PhD.

Lecture 21

Chapter 13

Carboxylic Acid Derivatives

Nomenclature of Carboxylic Acid Derivatives

Acyl Halides O RC

X

name the acyl group and add the word chloride, fluoride, bromide, or iodide as appropriate acyl chlorides are, by far, the most frequently encountered of the acyl halides

Acyl Acyl Halides Halides O CH3CCl

acetyl chloride O

H2C

CHCH2CCl

3-butenoyl chloride

O F

CBr

p-fluorobenzoyl bromide

Acid Acid Anhydrides Anhydrides O O RCOCR' when both acyl groups are the same, name the acid and add the word anhydride when the groups are different, list the names of the corresponding acids in alphabetical order and add the word anhydride

Acid Acid Anhydrides Anhydrides O O CH3COCCH3

acetic anhydride

O O C6H5COCC6H5

benzoic anhydride

O O C6H5COC(CH2)5CH3

benzoic heptanoic anhydride

Esters Esters O RCOR' name as alkyl alkanoates cite the alkyl group attached to oxygen first (R') name the acyl group second; substitute the suffix -ate for the -ic ending of the corresponding acid

Esters Esters O CH3COCH2CH3

ethyl acetate

O CH3CH2COCH3

methyl propanoate

O COCH2CH2Cl

2-chloroethyl benzoate

Amides Amides having having an an NH NH22 group group O RCNH2 identify the corresponding carboxylic acid replace the -ic acid or -oic acid ending by -amide.

Amides Amides having having an an NH NH22 group group O CH3CNH2

acetamide

O (CH3)2CHCH2CNH2

3-methylbutanamide

O CNH2

benzamide

Amides Amides having having substituents substituents on on N N O RCNHR'

O and

RCNR'2

name the amide as before precede the name of the amide with the name of the appropriate group or groups precede the names of the groups by the letter N(standing for nitrogen and used as a locant)

Amides Amides having having substituents substituents on on N N O

CH3CNHCH3

N-methylacetamide

O CN(CH2CH3)2

N,N-diethylbenzamide

O CH3CH2CH2CNCH(CH3)2 CH3

N-isopropyl-N-methylbutanamide

Structure of Carboxylic Acid Derivatives

O Most reactive

CH3C O CH3C

Cl O

Least stabilized

OCCH3

O CH3C

SCH2CH3 SCH

O CH3C Least reactive

OCH2CH3

O CH3C

NH2

Most stabilized

Electron Delocalization and the Carbonyl Group The main structural feature that distinguishes acyl chlorides, anhydrides, thioesters, esters, and amides is the interaction of the substituent with the carbonyl group. It can be represented in resonance terms as: •• •– •• O •

•• • O•

RC

••

X

RC +

•• •– •• O • ••

X

RC

+ X

Electron Delocalization and the Carbonyl Group The extent to which the lone pair on X can be delocalized into C=O depends on: 1) the electronegativity of X 2) how well the lone pair orbital of X interacts with the π orbital of C=O •• •– •• O •

•• • O•

RC

••

X

RC +

•• •– •• O • ••

X

RC

+ X

Acyl Chlorides – •• • •• O •

•• • O•

R

C •• Cl •• ••

R

C •• Cl + ••

acyl chlorides have the least stabilized carbonyl group delocalization of lone pair of Cl into C=O group is not effective because C—Cl bond is too long

least stabilized C=O O RCCl

most stabilized C=O

Acid Anhydrides •• • O•

R

C

–• •• • •O •

•• • O• ••

O ••

C

R

R

C

•• • O•

+ O

C

••

lone pair donation from oxygen stabilizes the carbonyl group of an acid anhydride the other carbonyl group is stabilized in an analogous manner by the lone pair

R

least stabilized C=O O RCCl

O O RCOCR'

most stabilized C=O

Esters –• •• • •O •

•• • O•

R

C

••

OR' ••

R

C

+ OR' ••

lone pair donation from oxygen stabilizes the carbonyl group of an ester stabilization greater than comparable stabilization of an anhydride or thioester

least stabilized C=O O RCCl

O O RCOCR' O RCOR'

most stabilized C=O

Amides –• •• • •O •

•• • O•

R

C

••

NR'2

R

C

+ NR'2

lone pair donation from nitrogen stabilizes the carbonyl group of an amide N is less electronegative than O; therefore, amides are stabilized more than esters and anhydrides

Amides –• •• • •O •

•• • O•

R

C

••

NR'2

R

C

+ NR'2

amide resonance imparts significant double-bond character to C—N bond activation energy for rotation about C—N bond is 75-85 kJ/mol C—N bond distance is 135 pm in amides versus normal single-bond distance of 147 pm in amines

least stabilized C=O O RCCl

O O RCOCR' O RCOR'

O RCNR'2

most stabilized C=O

Carboxylate ions –• •• • •O •

•• • O•

R

C

•• • – O• ••

R

C

O •• ••

very efficient electron delocalization and dispersal of negative charge maximum stabilization

least stabilized C=O O RCCl

O O RCOCR' O RCOR'

O RCNR'2

O RCO–

most stabilized C=O

Reactivity is related to structure Stabilization

Relative rate of hydrolysis

RCCl O O

very small

1011

RCOCR' O

small

107

RCOR' O

moderate

1.0

RCNR'2

large

< 10-2

O

The more stabilized the carbonyl group, the less reactive it is.

Nucleophilic Acyl Substitution In general: •• • O•

R

C

•• • O•

+ X

HY R

C

+ Y

Reaction is feasible when a less stabilized carbonyl is converted to a more stabilized one (more reactive to less reactive).

HX

most reactive O RCCl

O O RCOCR'

a carboxylic acid derivative can be converted by nucleophilic acyl substitution to any other type that lies below it in this table

O RCOR'

O RCNR'2

O RCO–

least reactive

Nucleophilic Substitution in Acyl Chlorides

Preparation of Acyl Chlorides from carboxylic acids and thionyl chloride

O (CH3)2CHCOH

SOCl2 heat

O (CH3)2CHCCl + SO2 + HCl (90%)

Reactions of Acyl Chlorides O RCCl

O O RCOCR'

O RCOR'

O RCNR'2

O RCO–

Reactions of Acyl Chlorides Acyl chlorides react with carboxylic acids to give acid anhydrides: O

O O

O

RCCl + R'COH

RCOCR' H

via:

R

O

O

C

OCR'

Cl

+

HCl

Example O

O

CH3(CH2)5CCl +

CH3(CH2)5COH pyridine

O O CH3(CH2)5COC(CH2)5CH3 (78-83%)

Reactions of Acyl Chlorides Acyl chlorides react with alcohols to give esters:

O

O RCCl + R'OH

RCOR' H

via:

R

O C Cl

OR'

+

HCl

Example O

O C6H5CCl + (CH3)3COH

pyridine

C6H5COC(CH3)3 (80%)

Reactions of Acyl Chlorides Acyl chlorides react with ammonia and amines to give amides: O

O RCCl + R'2NH + HO– H via:

R

RCNR'2 + H2O + Cl–

O C Cl

NR'2

Example O

O C6H5CCl + HN

NaOH H2O

C6H5CN (87-91%)

Reactions of Acyl Chlorides Acyl chlorides react with water to give carboxylic acids (carboxylate ion in base): O RCCl + H2O O RCCl + 2HO–

O RCOH

+

HCl

O RCO–

+

Cl– + H2O

Reactions of Acyl Chlorides Acyl chlorides react with water to give carboxylic acids (carboxylate ion in base): O

O RCCl + H2O

RCOH H

via:

R

O C Cl

OH

+

HCl

Example O C6H5CH2CCl + H2O

O C6H5CH2COH + HCl

Preparation of Carboxylic Acid Anhydrides Anhydrides can be prepared from acyl chlorides

Some anhydrides are industrial chemicals

O O CH3COCCH3

O O O

Acetic anhydride

Phthalic anhydride

O O O Maleic anhydride

From dicarboxylic acids Cyclic anhydrides with 5- and 6-membered rings can be prepared by dehydration of dicarboxylic acids O H

H

C C

COH tetrachloroethane

H

O

130°C

COH O

O

H

O (89%)

+ H2O

Reactions of Carboxylic Acid Anhydrides

Reactions of Anhydrides O O RCOCR'

O RCOR'

O RCNR'2

O RCO–

Reactions of Acid Anhydrides Carboxylic acid anhydrides react with alcohols to give esters: O O RCOCR + R'OH

O RCOR'

O + RCOH

normally, symmetrical anhydrides are used (both R groups the same) reaction can be carried out in presence of pyridine (a base) or it can be catalyzed by acids

Reactions of Acid Anhydrides Carboxylic acid anhydrides react with alcohols to give esters: O

O O RCOCR + R'OH

RCOR' H

via:

R

O C

OR'

OCR O

O + RCOH

Example O O CH3COCCH3

+ CH3CHCH2CH3 OH H2SO4 O

CH3COCHCH2CH3 CH3

(60%)

Reactions of Acid Anhydrides

Acid anhydrides react with ammonia and amines to give amides: O

O O RCOCR

+ 2R'2NH

RCNR'2 + RCO– H

via:

O

R

+ R'2NH2

O NR'2

C

OCR O

Example O O CH3COCCH3

+ H2N

CH(CH3)2

O CH3CNH

CH(CH3)2 (98%)

Reactions of Acid Anhydrides

Acid anhydrides react with water to give carboxylic acids (carboxylate ion in base): O O RCOCR + H2O O O RCOCR + 2HO–

O 2RCOH O 2RCO–

+

H2O

Reactions of Acid Anhydrides Acid anhydrides react with water to give carboxylic acids (carboxylate ion in base): O O RCOCR + H2O

O H R

2RCOH O C

OH

OCR O

Example O O + H2O O

O COH COH O

Sources of Esters

Esters are very common natural products O CH3COCH2CH2CH(CH3)2 3-methylbutyl acetate also called "isopentyl acetate" and "isoamyl acetate" contributes to characteristic odor of bananas

Esters of Glycerol O O CH2OCR' RCOCH CH2OCR" O R, R', and R" can be the same or different called "triacylglycerols," "glyceryl triesters," or "triglycerides" fats and oils are mixtures of glyceryl triesters

Esters of Glycerol O O CH2OC(CH2)16 CH3 CH3(CH2)16 COCH CH2OC(CH2)16 CH3 O Tristearin: found in many animal and vegetable fats

Cyclic Esters (Lactones) O

O

CH2(CH2)6CH3 H H

(Z)-5-Tetradecen-4-olide (sex pheromone of female Japanese beetle)

Preparation of Esters Fischer esterification from acyl chlorides from carboxylic acid anhydrides Baeyer-Villiger oxidation of ketones

Physical Properties of Esters

Boiling Points CH3

boiling point

CH3CHCH2CH3 O

28°C

CH3COCH3

57°C

OH CH3CHCH2CH3

99°C

Esters have higher boiling points than alkanes because they are more polar. Esters cannot form hydrogen bonds to other ester molecules, so have lower boiling points than alcohols.

Solubility in Water CH3

Solubility (g/100 g)

CH3CHCH2CH3 O

~0

CH3COCH3

33

OH CH3CHCH2CH3

12.5

Esters can form hydrogen bonds to water, so low molecular weight esters have significant solubility in water. Solubility decreases with increasing number of carbons.

Reactions of Esters: A Review and a Preview

Reactions of Esters with Grignard reagents reduction with LiAlH4 with ammonia and amines hydrolysis

Acid-Catalyzed Ester Hydrolysis

Acid-Catalyzed Ester Hydrolysis is the reverse of Fischer esterification O RCOR'

+

H2O

H+

O RCOH + R'OH

maximize conversion to ester by removing water maximize ester hydrolysis by having large excess of water equilibrium is closely balanced because carbonyl group of ester and of carboxylic acid are comparably stabilized

Example O CHCOCH2CH3 + H2O Cl HCl, heat O CHCOH Cl (80-82%)

+ CH3CH2OH