Synthetic reagent & its applications:Dicyclohexyl carbodiimide

1. Dicyclohexyl
carbodiimide
(DCC)
Presented by
Sapna Sivanthie Suresh Kumar
S1, M.Pharm. Pharmaceutical Chemistry
Amrita School of Pharmacy, Kochi
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2. Topics to be discussed
Introduction
Properties
Synthesis
Reactions involving DCC
Application
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3. Introduction
 N,N dicyclohexylcarbodimide
 Organic compound
 Also known as DCC, DCCD or DCCI
 Potent allergen
 Sensitizer
 Can cause skin rashes
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N C N
N,N'-dicyclohexylmethanediimine

4. Properties
 Under standard conditions, it exists in the form of white crystals
with a heavy, sweet odour.
 Melting point: 30-35°C
 Boiling point: 122-124°C
 Soluble in tetrahydrofuran, acetonitrile, and dimethylformamide
dichloromethane
 Insoluble in water.
 Moisture sensitive.
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5. Synthesis
Method 1:
 It can also be prepared by oxidation of dicyclohexylurea with p-
toluene sulfonyl chloride in hot pyridine
S
O
O
Cl
C
H3
N
N C
+ O
H2
N,N'-dicyclohexylurea
N,N'-dicyclohexylmethanediimine
O
NH
NH
N,N'-dicyclohexylurea
4-methylbenzene-1-sulfonyl chloride
Hot pyridine
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6. Method 2:
 By heating dicyclohexylthiourea with yellow mercuric oxide
N
N C
+ O
H2
N,N'-dicyclohexylmethanediimine
S
NH
NH
+ S
H2
Hg2O
N,N'-dicyclohexylthiourea
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7. Reactions involving DCC
1. Synthesis of Esters
2. Synthesis of Amides
3. Synthesis of Ethers
4. Synthesis of Acid anhydride
5. Synthesis of Diacyl Peroxide
6. Synthesis of lactones
7. Synthesis of Lactams
8. Synthesis of Peptides
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8. Reactions involving DCC
1. Synthesis of Esters:
Acid + alcohol +DCC  ester + N,N dicyclohexylyrea +
water
RCOOH + R’OH + C6H5 –N=C=N- C6H5
RCOOR’ + C6H5 –N-CO-N- C6H5+ H2O
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9. Mechanism:
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10. Reactions involving DCC
2. Synthesis of Amides:
2Acid + Amine +DCC  Amide + N,N dicyclohexyl urea
+ Acid
2RCOOH + R’NH2 + C6H5 –N=C=N- C6H5
RCONHR’ + C6H5 –N-CO-N- C6H5+ RCOOH
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11. Mechanism:
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12. Reactions involving DCC
3. Synthesis of Ethers:
A mixture of phenol, alcohol and DCC on prolonged heating under pressure produces
aryl alkyl ether.
C6H5 OH + C2H5 OH + C6H5 –N=C=N- C6H5
C6H5 O C2H5 + C6H5 –N-CO-N- C6H5
phenol ethanol DCC
Ethyl phenyl
ether
N,N dicyclohexylurea
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13. Reactions involving DCC
4. Synthesis of Acid Anhydride:
A mixture of phenol, alcohol and DCC on prolonged heating under pressure produces
aryl alkyl ether.
2COOH + C6H5 –N=C=N- C6H5
(RCO)2O + C6H5 –N-CO-N- C6H5
Acid DCC
Acid
anhydride
N,N dicyclohexylurea
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14. Reactions involving DCC
5. Synthesis of Diacyl peroxide:
Diacyl peroxide can be synthesized by the treatment of carboxylic acids with
hydrogen peroxide under the mild condition with DCC
2RCOOH + C6H5 –N=C=N- C6H5
R-CO-O-O-CO-R + C6H5 –N-CO-N- C6H5
Acid DCC
Diacylperoxide N,N dicyclohexylurea
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15. Reactions involving DCC
6. Synthesis of Lactams:
 Lactams are cyclic amides.
 B- Lactams are highly strained ring, sensitive to acids while most reagents
for amide linkage involves strongly acid reagents.
 This caused a serious problem in penicillin synthesis. However, the difficulty
was overcome by using DCC for the amide linkage.
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16. Reactions involving DCC
7. Synthesis of Peptides:
The amino acids in the amino function have been protected by Pthalyl
[C6H4(CO)2] or Carbobenzoxy [C6H5CH2-O-C=O] that condense with amino
acid esters in the presence of DCC at room temperature to give Peptides.
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17. Application
 Couple amino acids during peptide synthesis
 Dehydrating agent for the synthesis of amides, ketones, nitriles and in
the inversion and esterification of secondary alcohols.
 Synthesis of Lactam ring (B- lactum in penicillin)
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20. REFERENCES
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 March’s Advanced Organic Chemistry: Reactions, Mechanisms and
Structures, 7th edition, Pg. No. 1205-1217

21. THANK YOU
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