Acylation

A4

DERIVATIVES OF CARBOXYLIC ACIDS

ACYL (ACID) CHLORIDES - RCOCl named from corresponding acid remove -ic add -yl chloride CH3COCl C6H5COCl ethanoyl chloride benzene carbonyl chloride
+

ACID ANHYDRIDES - (RCO)2O named from corresponding acid remove acid add anhydride (CH3CO)2O ethanoic anhydride
+ +

CH3 C CH3 C

O O

CH3 C

Cl

bonding in acyl chlorides

bonding in acid anhydrides

Chemical Properties

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 Aspirin (acetyl salicylic acid) Ethanoic anhydride is more useful - making fibres - analgaesic

cheaper less corrosive less vulnerable to hydrolysis less dangerous reaction

Laboratory

Used to make

carboxylic acid, esters, amines, N-substituted amines is more reactive gives a cleaner reaction

Ethanoyl chloride is used as it

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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A4

Acylation

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

Cl C R H O H O

Cl R C O H O H
+

H + H O C R Cl O R C

O HCl OH

RCOCl

H2O

>

RCOOH

HCl

ACID ANHYDRIDES
O O R C O R C O H O H R C O R C H O H
+

H + H O O R RCOO C O R C

O RCOOH OH

(RCO)2O

H2O

>

2RCOOH

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

SYNTHETIC POSSIBILITIES
PRODUCT WITH
WATER ACYL CHLORIDE ACID ANHYDRIDE CARBOXYLIC ACID CARBOXYLIC ACID ALCOHOLS ESTER ESTER AMMONIA AMIDE AMIDE AMINES N-SUBSTITUTED AMIDE N-SUBSTITUTED AMIDE

By-product
HCl CARBOXYLIC ACID

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Acylation

A4

ADDITION ELIMINATION - the reactions

ACYL (ACID) CHLORIDES - RCOCl Water Product(s) Conditions Equation Mechanism carboxylic acid + HCl (fume in moist air / strong acidic solution formed) cold water CH3COCl(l) + H2O(l) > CH3COOH(aq) + HCl(aq) addition-elimination
H + H O C CH3 Cl O CH3 C
+

Cl C CH3 H O H O

Cl CH3 C O H O H

O HCl OH

Alcohols

Product(s) Conditions Equation Mechanism

ester + hydrogen chloride reflux in dry (anhydrous) conditions CH3COCl(l) + CH3OH(l) > CH3COOCH3(l) + HCl(g) addition-elimination
CH3 H O
+ +

Cl C CH3 H O CH3 O

Cl CH3 C O H O

O C O Cl CH3 C HCl O 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 C6H5COOCH3 butyl methanoate CH3COOC(CH3)2

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Ammonia Product(s) Conditions Equation or Mechanism Amide + hydrogen chloride

A4

Acylation

Low temperature and excess ammonia. Vigorous reaction. CH3COCl(l) CH3COCl(l) + NH3(aq) + 2NH3(aq) > > CH3CONH2(s) + HCl(g) CH3CONH2(s) + NH4Cl(s)

addition-elimination
H + H N H C CH3

Cl C CH3 H H N H O

Cl CH3 C O H N H H
+

O O Cl CH3 C HCl NH2

Amines

Product(s) Conditions Equation or Mechanism

N-substituted amide + hydrogen chloride anhydrous CH3COCl(l) + C2H5NH2(aq) CH3COCl(l) + 2C2H5NH2(aq) > > CH3CONHC2H5(s) + HCl(g) CH3CONHC2H5(s) + C2H5NH3Cl(s)

addition-elimination - similar to that with ammonia

H + R N H C CH3

Cl C CH3 H R N H O

Cl CH3 C O H N H R
+

O O Cl CH3 C HCl 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 CH3CON(CH3)2 C2H5CONH2 N-phenylethanamide

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Acylation

A4

ACID ANHYDRIDES - (RCO)2O Water Product(s) Conditions Equation Mechanism

O O CH3 C CH3 C H O H O O CH3 C O H + H O C CH3 CH3COO O CH3 C O OH CH3COOH

carboxylic acid (weak acidic solution formed) cold water - but can be slow (CH3CO)2O(l) + H2O(l) > 2CH3COOH(aq)

CH3 C O + H O H

Alcohols

Product(s) Conditions Equation Mechanism

ester + carboxylic acid reflux in dry (anhydrous) conditions (CH3CO)2O(l) + CH3OH(l) > CH3COOCH3(l) + CH3COOH(aq)

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) Conditions Equation or Amide + carboxylic acid

A4

Acylation

Low temperature and excess ammonia. (CH3CO)2O(l) + NH3(aq) > CH3CONH2(s) + CH3CONH2(s) + CH3COOH(aq) CH3COONH4+(s)

(CH3CO)2O(l) + 2NH3(aq) >

Mechanism

Amines

Product(s) Equation or

N-substituted amide + carboxylic acid (CH3CO)2O(l) + C2H5NH2(aq) > CH3CONHC2H5(s) + CH3COOH(aq) (CH3CO)2O(l) + 2C2H5NH2(aq) > CH3CONHC2H5(s) + CH3COONH4+(s)

Mechanism

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

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