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DERIVATIVES OF CARBOXYLIC ACIDS

ChemicalProperties colourless liquids which fume in moist air

acyl chlorides are more reactive than anhydrides

attacked at the positive carbon centre by nucleophiles

nucleophiles include water, alcohols, ammonia and amines

undergo addition-elimination reactions

Uses of Acylation

Industrially Manufacture of Cellulose acetate - making fibres

Aspirin (acetyl salicylic acid) - analgaesic

Ethanoic anhydride is more useful cheaper

less corrosive

less vulnerable to hydrolysis

less dangerous reaction

Laboratory Used to make carboxylic acid, esters, amines, N-substituted amines

Ethanoyl chloride is used as it is more reactive

gives a cleaner reaction

Acylation 1A4

ACYL (ACID) CHLORIDES - RCOCl

named from corresponding acid

remove -ic add -yl chloride

CH3COCl ethanoyl chloride

C6H5COCl benzene carbonyl chloride

bonding in acyl chlorides

O

CCl

CH3

+

ACID ANHYDRIDES - (RCO)2O

named from corresponding acidremove acid add anhydride

(CH3CO)2O ethanoic anhydride

bonding in acid anhydrides

O

CCH3+

O

CCH3+

O

Q.1 Investigate how aspirin is made industrially and in the laboratory.Why are the reagents and chemicals different?

What properties of Aspirin make it such a useful drug?

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ADDITION ELIMINATION REACTIONS - OVERVIEW

Mechanism species attacked by nucleophiles at the positive carbon end of the C=O bond

the nucleophile adds to the molecule

either Cl or RCOO is eliminated

a proton is removed

General example - with water

ACID CHLORIDES

RCOCl + H2O > RCOOH + HCl

ACID ANHYDRIDES

(RCO)2O + H2O > 2RCOOH

Use these mechanisms to help construct others in the spaces which follow

SYNTHETIC POSSIBILITIES

2 AcylationA4

C

Cl

O C OR R

Cl

C O+

R

Cl +

H O

H

H O

H

H O

H

C

O

R HClOH

OO

C O

RCR

O

C O

+

R

C

O

R

O

O

O

CR

O

H O

H

H O

H

+H O

H

RCOOHC

O

R

OH

RCOO

PRODUCT WITHBy-product

WATER ALCOHOLS AMMONIA AMINES

ACYL CHLORIDE CARBOXYLICACID

ESTER AMIDE N-SUBSTITUTEDAMIDE

HCl

ACID ANHYDRIDECARBOXYLIC

ACIDESTER AMIDE

N-SUBSTITUTED

AMIDE

CARBOXYLIC

ACID

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ADDITION ELIMINATION - the reactions

ACYL (ACID) CHLORIDES - RCOCl

Water Product(s) carboxylic acid + HCl (fume in moist air / strong acidic solution formed)

Conditions cold waterEquation CH3COCl(l) + H2O(l) > CH3COOH(aq) + HCl(aq)

Mechanism addition-elimination

Alcohols Product(s) ester + hydrogen chloride

Conditions reflux in dry (anhydrous) conditions

Equation CH3COCl(l) + CH3OH(l) > CH3COOCH3(l) + HCl(g)

Mechanism addition-elimination

Acylation 3A4

C

Cl

O C O

Cl

C O

+

Cl +

H O

H

H O

H

H O

H

C

O

HCl

OHCH3

CH3

CH3

CH3

C

Cl

O C O

Cl

C O

+

Cl +

H O

H O

H O

C

O

HCl

OCH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

Q.2 What organic product is formed when the following pairs react? C3H7COCl and H2O C2H5COCl and C2H5OH

Q.3 How would you synthesis the following? methyl butanoate butyl methanoate

C6H5COOCH3 CH3COOC(CH3)2

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Ammonia Product(s) Amide + hydrogen chloride

Conditions Low temperature and excess ammonia. Vigorous reaction.

Equation CH3COCl(l) + NH3(aq) > CH3CONH2(s) + HCl(g)

or CH3COCl(l) + 2NH3(aq) > CH3CONH2(s) + NH4Cl(s)

Mechanism addition-elimination

Amines Product(s) N-substituted amide + hydrogen chloride

Conditions anhydrous

Equation CH3COCl(l) + C2H5NH2(aq) > CH3CONHC2H5(s) + HCl(g)

or CH3COCl(l) + 2C2H5NH2(aq) > CH3CONHC2H5(s) + C2H5NH3Cl(s)

Mechanism addition-elimination - similar to that with ammonia

4 AcylationA4

C

Cl

O C O

Cl

C O

+

Cl +

C

O

HCl

CH3

CH3

CH3

CH3

H N

H

H

H N H

H

H N H

H

NH2

C

Cl

O C O

Cl

C O

+

Cl +

C

O

HCl

CH3

CH3

CH3

CH3

R N

H

H

H N H

R

R N H

H

NH

R

Q.4 Why are two moles of ammonia (or amine) required in each equation?

Q.5 What pairs of chemicals would you use to synthesis the following? butanamide C 2H5CONH2

CH3CON(CH3)2 N-phenylethanamide

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ACID ANHYDRIDES - (RCO)2O

Water Product(s) carboxylic acid (weak acidic solution formed)

Conditions cold water - but can be slow

Equation (CH3CO)2O(l) + H2O(l) > 2CH3COOH(aq)

Mechanism

Alcohols Product(s) ester + carboxylic acid

Conditions reflux in dry (anhydrous) conditions

Equation (CH3CO)2O(l) + CH3OH(l) > CH3COOCH3(l) + CH3COOH(aq)

Mechanism

Acylation 5A4

CH3

OO

C O

C

O

C O

+

C

O

O

O

O

C

O

H O

H

H O

H

+H O

H

C

O

OH

COO

CH3

CH3

CH3

CH3

CH3

CH3

COOHCH3

Q.6 What organic product(s) is/are formed when the following pairs react?

(C3H7CO)2O and H2O

(CH3CO)2O and C2H5OH

(CH3CO)2O and (CH3)2CHOH

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Ammonia Product(s) Amide + carboxylic acid

Conditions Low temperature and excess ammonia.

Equation (CH3CO)2O(l) + NH3(aq) > CH3CONH2(s) + CH3COOH(aq)

or (CH3CO)2O(l) + 2NH3(aq) > CH3CONH2(s) + CH3COONH4+

(s)

Mechanism

Amines Product(s) N-substituted amide + carboxylic acid

Equation (CH3CO)2O(l) + C2H5NH2(aq) > CH3CONHC2H5(s) + CH3COOH(aq)

or (CH3CO)2O(l) + 2C2H5NH2(aq) > CH3CONHC2H5(s) + CH3COONH4+

(s)

Mechanism

6 AcylationA4

Q.7 What organic product(s) is/are formed when the following pairs react?

(C3H7CO)2O and NH3

(CH3CO)2O and C2H5NH2

(CH3CO)2O and (CH3)2NH