Imidazole reaction with, phosgene

Imidazole, purification of, 48, 45 reaction with phosgene, 48, 44 Imldazole, 1,1 -carbonyldi-, 48, 44 Imidazolium chloride, 48, 46 3-Imino-l-( -tolylsulfonyl)pyrazolidine, from 3-amino-3-pyrazoline sulfate and / -toluenesulfonyl chloride, 48, 9... 

Double amidation of phosgene, to give symmetrical ureas, is considerably easier to perform. Considerable interest is attached to the recent reaction of imidazole with phosgene, which led to l,T-carbonyldiimidazole, an extremely reactive compound on account of the lability of its amide bonds 597 The ease with which the imidazole group can be replaced by other groups offers the widest possibilities for synthesis of other carbonic acid derivatives, carboxylic esters, amides, and hydrazides, peptides, phosphoric esters, etc., all under the mildest conditions.598 Since l,T-carbonyldiimidazole is hydrolysed even by atmospheric moisture, it must be prepared under the most strictly anhydrous conditions. 

Ureas and Carbonates. Reagent (1) may be used as a direct replacement for the highly toxic Phosgene in reactions with alcohols and amines. Reaction of (1) with two equivalents of a primary aliphatic or aromatic amine at room temperature rapidly yields a symmetrical urea (eq 9). If only one equivalent of a primary amine is added to (1), then the imidazole-Al-carboxamide (4) is formed (eq 10). These compounds can dissociate into isocyanates and imidazole, even at room temperature, and distillation from the reaction mixture provides a useful synthesis of isocyanates (eq 10).7 Secondary amines react only at one side of (1) at room temperature, again giving the imidazole-Al-carboxamide of type... 

Carbonyldiimidazoles (e.g. GDI) are prepared in high yield with little by-product formation by the reaction of imidazoles [(un)substituted in the 4- and/or 5-positions] (e.g. imidazole) with phosgene in the presence of a tertiary amine (e.g. tributylamine), which acts as an HCl scavenger. This amine has a lower pKb value than the imidazole. The reaction is performed in an aromatic hydrocarbon solvent (e.g. xylene), from which the product is crystallized. The tertiary amine hydrochloride salt is extracted into water, neutralized with an aqueous solution of an inorganic base (e.g. NaOH), and the free amine is re-extracted into an organic solvent (EtOAc). 

A V -Carbonyldiimidazole (CDI) is prepared in a convenient and safe procedure from phosgene and imidazole as a non-toxic crystalline compound (m.p. 116-118 °C).[5],[6] It reacts almost quantitatively at room temperature or by short and moderate heating with an equimolar quantity of a carboxylic acid in tetrahydrofuran, chloroform, or similar inert solvents within a few minutes to give the corresponding carboxylic acid imidazolide, which is formed under release of carbon dioxide, together with one equivalent of readily separable and recyclable imidazole.Thus, this reaction leads under very mild conditions to the activation of a carboxylic acid appropriate for transacylation onto a nucleophile with an alcohol to an ester, with an amino compound to an amide or peptide, etc. 

The same idea leads to the use of Carbonyl Dilmidazole (CDI) as a double electrophile when we want to link two nucleophiles together by a carbonyl group. Phosgene (COCl2) has been used for this but it is appallingly toxic (it was used in the First World War as a poison gas with dreadful effects). CDI is safer and more controlled. In these reactions imidazole acts (twice) as a leaving group, carbonyl diimidazole... 

The reactions of IV-SiMe 3-substituted derivatives of imidazole, 3(5)-methylpyrazole, 3,5-dimethylpyrazole, benzotriazole and benzimidazole (see below, X = SiMej) with an excess of phosgene have been examined recently [1855], and are found to give high yields of the Af-chloroformyl derivatives illustrated below ... 

Reactions and Properties of l,A-Diazepines. 2-Amino-5-phenyl-3//-l,4-benzodiazepines were converted into their 1-oxides, e.g. (Ill), by m-chloroper-oxybenzoic acid when these oxides reacted with phosgene in the presence of imidazoles they underwent an interesting rearrangement to give the 3-imidazolyl derivatives, e.g. (113), apparently via primary formation of the unstable compound (112). Treatment of (111) with acetic anhydride gave the 2-acetamido-3-oxo-derivative. ... 

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