1,1-Carbonyldiimidazole Staab

FIGURE 6.10 The side chain of histidine is readily acylated (A) by activated residues. The imidazolide produced is an activated species similar to the intermediate generated by reaction (B) of a carboxylic acid with coupling reagent carbonyldiimidazole. (Staab, 1956). Imida-zolides acylate amino and hydroxyl groups. Isomerization of histidyl during activation results from abstraction (C) of the a-proton by the 7t-nitrogen. 

The success achieved with dicyclohexylcarbodiimide stimulated an unrelenting search for even better coupling reagents. Some really effective compounds could be found, for instance carbonyldiimidazole (Staab 1957) which mediates coupling in a novel manner, through reactive N-acyl intermediates ... 

Dehydrative cyclization of A-(4-methoxyphcnyl) protected 7-aminoalcohols 157 by the Staab reagent (1,1 -carbonyldiimidazole, CDI) led to the formation of iV-(4-methoxyphenyl)azetidines 158 (Equation 37) <2004SL2751>. The reactions were carried out in a Kugelrohr apparatus. The imidazole formed in the reaction was separated by filtration through silica gel. 

This method was introduced by Staab and is suitable for the acylation of primary, secondary and tertiary alcohols. First the carboxylic acid is converted into the imidf lide (42) with carbonyldiimidazole (41), and then the alcohol is added together with a catalytic amount of strong base (alkoxide). The ester is formed at room temperature within a few hours (equation 17). If functional groups in the acid or alcohol prevent the use of base, the imidazolide and the alcohol have to be heated to 70 °C for 1-2 h. 

A novel and efficient coupling reagent, carbonyldiimidazole (CDI) was discovered [45] by H.A. Staab in Heidelberg, in 1957. The reactive intermediates, acylimidazoles were known before as potent acylating agents [5,35]. In spite of... 

Dicarboxylic acid anhydrides. An ethereal soln. of N-trifluoroacetylimidazole added dropwise with stirring to a suspension of phthalic acid in abs. ether, and stirring continued 6 hrs. at room temp. -> phthalic acid anhydride. Y 89%. F. e., also with N-trichloroacetylimidazole and N,N -carbonyldiimidazole, s. H. A. Staab, G. Walther, and W. Rohr, B. 95, 2073 (1962). 

Gyclohexylamine added dropwise to a soln. of N,N -carbonyldiimidazole in tetra-hydrofuran, the solvent removed, and the residue distilled in vacuo cyclohexyl isocyanate. Y 80%.—N,N-carbonyldibenzimidazole may be used for higher boiling isocyanates. H. A. Staab and W. Benz, Ang. Ch. 73, 66 (1961). 

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