Dicyclohexylcarbodiimide
[CAS# 538-75-0]

Identification

• Classification: Biochemical >> Amino acids and their derivatives >> Other protected amino acids
• Name: Dicyclohexylcarbodiimide
• Synonyms: DCC; N,N'-dicyclohexylcarbodiimide; Bis(cyclohexyl)carbodiimide; 1,3-dicyclohexylcarbodiimide
• Molecular Formula: C₁₃H₂₂N₂
• Molecular Weight: 206.33
• CAS Registry Number: 538-75-0
• EC Number: 208-704-1
• SMILES: C1CCC(CC1)N=C=NC2CCCCC2

Properties

• Density: 1.325
• Melting point: 33-35 ºC
• Boiling point: 122-124 ºC (6 torr)
• Flash point: 87 ºC
• Water solubility: Reaction

Safety Data

• Hazard Symbols: GHS05;GHS06;GHS07 Danger
• Hazard Statements: H302-H311-H315-H317-H318-H413
• Precautionary Statements: P261-P262-P264-P264+P265-P270-P272-P273-P280-P301+P317-P302+P352-P305+P354+P338-P316-P317-P321-P330-P332+P317-P333+P317-P361+P364-P362+P364-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	3	H311
Serious eye damage	Eye Dam.	1	H318
Skin sensitization	Skin Sens.	1	H317
Skin irritation	Skin Irrit.	2	H315
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Skin corrosion	Skin Corr.	1A	H314
Acute toxicity	Acute Tox.	2	H330
Skin corrosion	Skin Corr.	1B	H314

Discovory and Applicatios

Dicyclohexylcarbodiimide (DCC) is a highly valuable reagent in organic chemistry, primarily used for coupling reactions, especially in peptide synthesis. The discovery of DCC dates back to the mid-20th century when chemists were actively developing reagents that could efficiently mediate the formation of amide bonds. Its structure, consisting of two cyclohexyl groups attached to a central carbodiimide (-N=C=N-) functional group, imparts unique reactivity that makes it a versatile tool in synthetic organic chemistry.

DCC’s primary application is in the activation of carboxylic acids to facilitate their reaction with amines, leading to the formation of amides. This makes DCC a crucial reagent in the synthesis of peptides, where it is used to couple amino acids by promoting the formation of peptide bonds. When DCC is added to a mixture of a carboxylic acid and an amine, it reacts with the carboxyl group to form an active O-acylisourea intermediate. This intermediate is highly reactive and can be attacked by the nucleophilic amine, forming the desired amide bond. In this process, DCC is converted into dicyclohexylurea (DCU), which is insoluble in most organic solvents and can be easily removed by filtration.

The use of DCC in peptide synthesis is well-documented, and it has played a critical role in both solution-phase and solid-phase peptide synthesis techniques. DCC is often used in combination with other reagents, such as 1-hydroxybenzotriazole (HOBt), to improve yields and reduce side reactions, such as racemization of the amino acids.

In addition to peptide coupling, DCC has found use in the esterification of carboxylic acids with alcohols, where it facilitates the formation of esters. This reaction proceeds through the same O-acylisourea intermediate, which can then be attacked by an alcohol instead of an amine, leading to ester formation. This versatility makes DCC a popular reagent in both small-scale academic research and industrial chemical synthesis.

DCC’s applications extend beyond simple coupling reactions. It has been employed in the preparation of anhydrides, in the synthesis of nucleotides, and in the formation of ureas from primary amines and carbon dioxide. DCC is also a common reagent for activating hydroxyl groups in alcohols and phenols for further functionalization, making it a powerful tool for modifying complex organic molecules.

Despite its wide applicability, DCC does have limitations and potential hazards. One of the challenges associated with its use is the formation of DCU, which can sometimes interfere with reactions if not properly removed. Furthermore, DCC can be a skin and respiratory irritant, and proper safety measures must be observed when handling the reagent. Alternatives to DCC, such as EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide), have been developed to mitigate some of these issues, particularly in aqueous reactions.

Nevertheless, DCC remains an essential reagent in the field of organic synthesis due to its efficiency and versatility. It continues to play a pivotal role in peptide chemistry and other areas of synthetic organic chemistry, where coupling reactions are fundamental to building complex molecules.

References

Sheehan, J. C., & Hess, G. P. (1955). "A new method of forming peptide bonds." Journal of the American Chemical Society, 77(4), 1067-1068.

Bodanszky, M. (1993). "Principles of Peptide Synthesis." Springer-Verlag, Berlin.

Harris, P. A., & Verbicky, C. A. (2000). "Dicyclohexylcarbodiimide and peptide synthesis: Mechanism and applications." Journal of Organic Chemistry, 65(10), 3146-3153.