Scribd
Upload
86 views

Organic Chemistry Ii CHM 301: (Chapter 4)

This document discusses carboxylic acid derivatives, including their general formula, common types (acyl chlorides, anhydrides, esters, amides), and reactivity toward nucleophilic acyl substitution reactions. It explains that carboxylic acid derivatives are formed by replacing the -OH group of carboxylic acids with other nucleophiles like Cl-, RO-, or NH2-. The reactivity of these derivatives toward nucleophilic substitution decreases in the order of acyl chlorides, anhydrides, esters, and amides, due to the basicity and bond strength of the leaving groups. The mechanisms of the substitution reactions are also outlined, involving addition-elimination steps through a tetrahedral intermediate.

Uploaded by

WAN NUR AISYAH WAN AZIZAN
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
86 views

Organic Chemistry Ii CHM 301: (Chapter 4)

This document discusses carboxylic acid derivatives, including their general formula, common types (acyl chlorides, anhydrides, esters, amides), and reactivity toward nucleophilic acyl substitution reactions. It explains that carboxylic acid derivatives are formed by replacing the -OH group of carboxylic acids with other nucleophiles like Cl-, RO-, or NH2-. The reactivity of these derivatives toward nucleophilic substitution decreases in the order of acyl chlorides, anhydrides, esters, and amides, due to the basicity and bond strength of the leaving groups. The mechanisms of the substitution reactions are also outlined, involving addition-elimination steps through a tetrahedral intermediate.

Uploaded by

WAN NUR AISYAH WAN AZIZAN
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
You are on page 1/ 14

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 

You might also like