Organic Chemistry Ii CHM 301: (Chapter 4)

ORGANIC CHEMISTRY II

CHM 301

( CHAPTER 4)

CARBOXYLIC ACIDS
DERIVATIVES
1
SUBTOPICS
• General formula
• Nucleophilic acyl substitution
- mechanism
• Reactivity of carboxylic acid derivatives
toward nucleophilic acyl substitution reaction
GENERAL FORMULA
• Carboxylic acid derivatives:
- groups of compounds which the acyl group (RCO-)
attached to electronegative atom or substituent.
• The –OH group in carboxylic acid is replaced by
nucleophiles (Cl-, RCOO2-, RO- or NH2-).
O O
R C OH R C Y
Carboxylic acid Carboxylic acid derivatives
• Four common derivatives:

- acyl chlorides/acid chlorides, acid anhydrides, esters and
amides.
CARBOXYLIC ACID DERIVATIVES
Group replacing Classes of General Example
the –OH group compound formula
of RCOOH
-Cl Acyl O O
chloride/acid R C Cl H3C C CI
chlorides ethanoyl chloride
-OR’ Ester O
O
H3C C OC2H5
R C OR'
ethyl ethanoate
-NH2 Amide O
O
H3C C NH2
R C NH2
ethanamide
O Acid anhydride O O O O
H3C C O C CH3
O C R' R C O C R'
ethanoic anhydride
NUCLEOPHILIC ACYL SUBSTITUTION
REACTION
O O
R C Y Nu-H R C Nu H-Y
• Carboxylic acids (and their derivatives) more

commonly react by nucleophilic acyl substitution.
- one nucleophile replaces another on the acyl
(C=O) carbon atom.
• The nucleophile forms a new bond with
nucleophilic site and the leaving group (Y = Cl-, Br-,
RO- or RNH-) detaches from the molecule.
MECHANISM OF NUCLEOPHILIC ACYL SUBSTITUTION
• Occurs through an addition-elimination process in which a nucleophile
forms a bond with the electrophilic carbonyl carbon atom forming a
tetrahedral intermediate.
• The tetrahedral intermediate undergoes an elimination to yield the
products.
• STEP 1: Nucleophile attacks on carbonyl carbon results in the π – bond
cleaved.
O O
R C Y Nuc-H R C Y
Nuc-H
• Step 2: The regeneration of the double bond and the leaving group Y
detaches from the molecule.
O O
R C Y R C Nuc H Y
Nuc-H
• Step 3: H+ ion is removed from the molecule by the leaving group Y.
O O
R C Nuc H Y R C Nuc HY
Nuc = OH, OR, OCOR, NH2, NHR

Y = Cl, Br, OCOR, OR, NHR
ACID CATALYZED VARIATION MECHANISM
• STEP 1: Protonation of carbonyl oxygen to increase the reactivity
which carbonyl carbon becomes more positive for the
nucleophilic attack.
O OH
R C Y HA R C Y A
• STEP 2: The π-bond breaks as nucleophile attached to the

molecule.
OH OH
R C Y Nuc H R C Y A
Nuc H
• STEP 3: As H+ ion bonded to nucleophile detaches, double
bonds regenerates and the leaving group is pushed out from
the molecule.
OH OH
R C Y R C Nuc Y
Nuc
• STEP 4: The leaving group, Y- removes the H+ ion, reestablishes

carbonyl carbon in the product.
O H O
R C Nuc Y R C Nuc HY
RELATIVE REACTIVITIES OF CARBOXYLIC ACID
DERIVATIVES TOWARD NUCLEOPHILIC ACYL
SUBSTITUTION REACTION
• Example: Hydrolisis of carboxylic acid derivatives.
- Carboxylic acid derivatives, RCOY undergoes hydrolysis with
water.
- During hydrolysis, the C-Y bond is broken.
- The rate of hydrolysis depends on the bond strength of C-Y.
• The bond length decreases in the order:
C-Cl (in acyl chlorides) > C-O (in anhydride) > C-O (in ester) > C-N (in amide)
(longest bond) (shortest bond)
• Bond strength is inversely proportional to bond length. The longest
bond is the weakest bond. Bond strength increases in the order:
C-Cl (in acyl chlorides) > C-O (in anhydride) > C-O (in ester) > C-N (in amide)
(weakest bond) (strongest bond)
• Reactivity carboxylic acid derivatives decreases in the
order:
RCOCl > (RCO)2O > RCOOR’ > RCONH2

(most reactive) (least reactive)
• Carboxylic acids and esters are very similar in reactivity.

• The less reactive acid derivatives can be prepared from
the more reactive ones.
- Example, anhydrides, esters and amides can be prepared
from acid chlorides.
- Esters, anhydrides and acid chlorides cannot be prepared
from amides.
• The order of reactivity can be explained by
considering the basicity of the leaving group.
- strong bases are not good leaving groups.
- the reactivity of derivatives decreases as the
leaving group become more basic.
- example: Cl- is a weakest base and a good
leaving group. Acyl chlorides is the most reactive
compared to other carboxylic acid derivatives.
• The reactivity of the carboxylic acid derivatives
are influences by the substituents:
i) if the substituent is electron donating, the

carbonyl carbon becomes less reactive.
ii) if the substituents is electron withdrawing, the

carbonyl carbon become more reactive.
The End….TQ 
Love Organic Chemistry …in shaa Allah 

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ORGANIC CHEMISTRY II

• Four common derivatives:

• Carboxylic acids (and their derivatives) more

Nuc = OH, OR, OCOR, NH2, NHR

• STEP 2: The π-bond breaks as nucleophile attached to the

• STEP 4: The leaving group, Y- removes the H+ ion, reestablishes

RCOCl > (RCO)2O > RCOOR’ > RCONH2

• Carboxylic acids and esters are very similar in reactivity.

i) if the substituent is electron donating, the

ii) if the substituents is electron withdrawing, the

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