1,1'-Carbonyldiimidazole

Description

1,1'-Carbonyldiimidazole (CDI) is a highly efficient coupling reagent commonly used in peptide synthesis and organic chemistry. CDI can be used to activate carboxylic acids. These activated carboxylic acids react with nucleophiles to form products such as amides, esters, ureas, and carbamates. CDI reactions do not usually require a base because the released imidazole anion acts as the base. CDI is humidity sensitive and readily reacts with H2O to form CO2.

Chemical properties

The substance appears as a white to slightly pale-yellow crystalline powder with a melting point range of 115.5-116°C. It exhibits poor solubility in water, while displaying solubility in alcohol and ether.

The Uses of 1,1'-Carbonyldiimidazole

Peptide coupling reagent1,1'-Carbonyldiimidazole acts as a coupling reagent and utilized for coupling of amino acids in order to prepare peptide in organic synthesis. It is also used in the preparation of beta-keto sulfones, sulfoxides and beta-enamino acid derivatives. It is used to convert alcohols and amines into carbamates, esters, and ureas. It is involved in the preparation of formylized imidazole by reaction with formic acid. Further, it is used in the synthesis of dipolar polyamides compounds. In addition to this, it is considered as an equivalent of phosgene and used to prepare asymmetric bis alkyl carbonate.

The Uses of 1,1'-Carbonyldiimidazole

The acid (152 mg, 0.801 mmol) was added to a solution of CDI (130 mg, 0.801 mmol) in dry THF (1 mL) at RT under N2. The mixture was stirred for 90 min at RT, after which time it was added over 25 min to a solution of the amine (200 mg, 0.400 mmol) in THF (1.5 mL) at RT under N2. The reaction mixture was stirred at RT for 16 h. Additional acid (152 mg, 0.801 mmol) and CDI (130 mg, 0.801 mmol) in dry THF (1 mL) was added slowly at RT. The reaction mixture was stirred at RT for 2 h. TFA (1 mL, 26.1 mmol) was added at RT, and the mixture was stirred 22 h. Additional TFA (1 mL, 26.1 mmol) was added, and the mixture was stirred 18 h. The reaction mixture was then stirred at 80 C for 160 min. The mixture was diluted with H2O and extracted with EtOAc. The org phase was washed with brine, dried (MgSO4), and concentrated to give an oil. The oil was purified by Prep LC (12 g silica, 100% DCM to 90:9:1 DCM/MeOH/NH3) to provide the product as a white solid. [158 mg, 80%]

The Uses of 1,1'-Carbonyldiimidazole

CDI, also known as 1,1'-carbonyldiimidazole, is a commonly used peptide coupling reagent in the synthesis of peptides and nucleoside triphosphates. It usually contains approximately 10% imidazole and reacts rapidly with carboxylic acids to produce acyl imidazoles. Later, it readily reacts with amines to create amides. In addition, CDI is useful in converting alcohols and amines into a range of chemical compounds, including carbamates, esters, and ureas.

What are the applications of Application

N,N′-Carbonyldiimidazole is a versatile coupling agent used in the synthesis of dipolar polyamides

Preparation

1,1'-Carbonyldiimidazole has been prepared by the reaction of imidazole and phosgene in anhydrous benzene and anhydrous tetrahydrofuran. It has also been obtained by the reaction of 1-(trimethylsilyl)imidazole and phosgene in anhydrous benzene, but that method offers no advantages that justify the more extensive preparative effort required.
DOI: 10.15227/orgsyn.048.0044

General Description

1,1′-Carbonyldiimidazole (N,N′-carbonyldiimidazole) is a versatile peptide-forming reagent.

Purification Methods

Crystallise it from *benzene or tetrahydrofuran in a dry-box and store it dry. [Hearn Methods Enzymol 135 102 1987, Beilstein 23/4 V 245.]

Precautions

1,1'-Carbonyldiimidazole is incompatible with oxidizing agents and strong acids and should not be stored or handled near them. Store in a refrigerator, under inert gas and protected from moisture. This substance is heat sensitive and moisture sensitive.