21- Carboxylic Acid Derivatives

Chapter 21: Carboxylic Acid Derivatives Start with:

Use:

Hydrolysis

carboxylic derivative

H or OH

Transesterification

ester acid/acid chloride/ester

Reduction

Grignard Addition

Reactions of Acid Chlorides

acid chloride

+

-

R''-OH (excess)/ +

-

H or OR'' LiAlH4 Li(t -BuO) -BuO)3AlH  /ether

amide

1) LiAlH4 2) H2O

ester/acid chloride

1) 2 R''-MgX +

2) H3O

Product:

Notes

carboxylic acid

amides and nitriles require stronger conditions (heat)

different ester o

1 alcohol aldehyde amine o

3 alcohol

H2O

carboxylic acid

R-'OH

ester

R'-NH2

amide

R'-COOH

anhydride

1) LiAlH4 2) H2O

1 alcohol

1) 2 R'MgX 2) H2O

3 alcohol

R2CuLi

ketone

acid chloride

aldehyde intermediate

o

o

alkoxide salt intermediate

Chapter 21: Carboxylic Acid Derivatives Li(t -BuO) -BuO)3AlH  /ether

Synthesis of  Anhydrides

Reactions of  Anhydrides

carboxylic ac acid

anhydride

carboxylic acid/acid chloride/anhydrid Synthesis of Esters e/ester carboxylic acid

Reactions of Esters

ester

aldehyde

acti activ vate ated be benzen nzene e

acy acylbe lbenzen nzene e

acid ch chloride

acid an anhydride

H2O

carboxylic acid

R'OH/H

ester

R'NH 2

amide

+

+

R'OH/H

ester

CH2N2

methyl ester

H2O/H or OH

+

-

carboxylic acid + alcohol

R''OH/H or OR''

+

-

different ester + alcohol

R''NH2

amide + alcohol

1) LiAlH4 2) H2O

1 alcohol + alcohol

o

transesterification

Chapter 21: Carboxylic Acid Derivatives 1) 2 R''MgX 2) H2O Lac Lacton tone Forma ormati tion on

o

3 alcohol + alcohol

hydro droxy acid acid

H

lactone

carboxylic acid

R'NH2 (300 C)

amide

acid chloride

2 R'2NH

amide

anhydride

R'2NH

amide + carboxylic acid

ester

R'NH2

amide + alcohol

nitrile

H2O/H or OH

+

o

Synthesis of Amides

amide

+

-

+

-

distilling out the water formed drives the reaction past equilibrium

o

1 amide

H2O/H or OH

carboxylic acid

1) LiAlH4 2) H2O

amine

Reactions of Amides -

o

1 amide Formation of  Lactams

amino acid o

1 amide

o

Br2, OH

1 amine

POCl3

nitrile

heat

lactam

POCl3

nitrile

Hoffmann Rearangement Rearangement

Chapter 21: Carboxylic Acid Derivatives Synthesis of Nitriles

alkyl halide

NaCN

nitrile

diazonium salt (Ar-NN)

CuCN

aryl nitrile

ketone/aldehyde

HCN/KCN

cyanohydrin

H2O/H or OH

amide, then carboxylic acid (with heat)

1) LiAlH4 2) H2O

amine

+

Reactions of of Ni Nitriles

nitrile

-

+

Thioester Formation

carboxylic acid

1) R'MgX 2) H3O

ketone

R'SH

thioester

imine salt intermediate