1,1'-Carbonyldiimidazole
[CAS# 530-62-1]

Identification

• Classification: Biochemical >> Condensing agent
• Name: 1,1'-Carbonyldiimidazole
• Synonyms: 1,1'-Carbonylbis-1H-imidazole; N,N'-Carbonyldiimidazole; CDI
• Molecular Formula: C₇H₆N₄O
• Molecular Weight: 162.15
• CAS Registry Number: 530-62-1
• EC Number: 208-488-9
• SMILES: C1=CN(C=N1)C(=O)N2C=CN=C2

Properties

• Solubility: Soluble 0.6 mmole (2 ml DMF)
• Density: 1.303 g/mL
• Melting point: 118-120 °C

Safety Data

• Hazard Symbols: GHS05;GHS07;GHS08 Danger
• Risk Statements: H302-H314-H315-H318-H319-H360
• Safety Statements: P203-P260-P264-P264+P265-P270-P280-P301+P317-P301+P330+P331-P302+P352-P302+P361+P354-P304+P340-P305+P351+P338-P305+P354+P338-P316-P317-P318-P321-P330-P332+P317-P337+P317-P362+P364-P363-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Skin corrosion	Skin Corr.	1B	H314
Serious eye damage	Eye Dam.	1	H318
Reproductive toxicity	Repr.	1B	H360
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Skin corrosion	Skin Corr.	1C	H314
Skin corrosion	Skin Corr.	1A	H314
Acute toxicity	Acute Tox.	4	H332
Skin corrosion	Skin Corr.	1	H314
Acute toxicity	Acute Tox.	4	H312

Discovery and Applications

1,1'-Carbonyldiimidazole (CDI) is a widely used reagent in organic synthesis, primarily valued for its role as a carbonylating and coupling agent. Its discovery can be traced back to efforts in the mid-20th century aimed at developing reagents capable of facilitating peptide bond formation and other key reactions in organic chemistry. As a versatile compound, CDI has found significant applications in pharmaceutical, polymer, and peptide synthesis due to its efficiency in mediating various transformations.

CDI is synthesized by reacting phosgene with imidazole, resulting in a reagent that contains two imidazole groups bonded to a central carbonyl group. This molecular structure gives CDI its unique reactivity, particularly its ability to activate carboxylic acids for amide or ester formation. This makes CDI an excellent reagent for peptide coupling, where it promotes the formation of peptide bonds by converting carboxylic acids to reactive intermediates, which can then react with amines to form amides.

In peptide synthesis, CDI offers several advantages over other coupling agents. It is relatively mild, does not produce toxic by-products, and is highly selective, minimizing side reactions. These characteristics make it particularly useful in solid-phase peptide synthesis, where CDI can be used to efficiently build peptide chains in a stepwise manner. Additionally, CDI is effective in ester formation, serving as a coupling agent in the synthesis of esters from alcohols and carboxylic acids.

Beyond peptide synthesis, CDI has been employed in a range of carbonylation reactions, including the formation of carbamates and ureas. Its ability to introduce carbonyl groups into organic molecules has made it an important tool in the development of pharmaceuticals and biologically active compounds. For example, CDI-mediated reactions are commonly used to synthesize urea derivatives, which are important pharmacophores in various drugs.

CDI also plays a critical role in the synthesis of polymers, particularly in the modification of polymer backbones and the introduction of functional groups. Its use in the preparation of biodegradable polymers and other advanced materials is an area of ongoing research, highlighting the compound's versatility beyond small-molecule chemistry.

One of the key benefits of CDI is its stability and ease of handling. Unlike other carbonylating reagents, such as phosgene or carbonyldiimidazolium salts, CDI is relatively safe to use and can be stored under standard laboratory conditions. This has contributed to its widespread adoption in both academic and industrial laboratories.

CDI has also been explored in green chemistry applications due to its potential to minimize hazardous by-products. In certain contexts, it can replace more toxic reagents, providing a cleaner and more environmentally friendly alternative for coupling reactions and other transformations. Its utility in solvent-free reactions and as a solid-phase reagent further enhances its appeal for sustainable chemistry practices.

Overall, 1,1'-Carbonyldiimidazole remains a cornerstone reagent in organic synthesis, with a wide array of applications spanning from pharmaceuticals to materials science. Its discovery and subsequent development have paved the way for more efficient and versatile methods in modern synthetic chemistry, contributing to advancements in drug discovery, polymer synthesis, and sustainable chemistry.

References

2021. Recent Progress in the Selective Functionalization of P(O)-OH Bonds. Topics in current chemistry (Cham), 379(1).
DOI: 10.1007/s41061-020-00319-1

2016. Corn starch ferulates with antioxidant properties prepared by N,N′-carbonyldiimidazole-mediated grafting procedure. Food Chemistry, 206.
DOI: 10.1016/j.foodchem.2016.03.094

2005. Conventional and Microwave-Assisted Conversion of Substituted 3-Amino-oxazolidin-2,4-diones into N‘,N‘-Disubstituted α-Hydroxyhydrazides. The Journal of Organic Chemistry, 70(6).
DOI: 10.1021/jo047879b