Imidazole 4-carbinols

N-propinylazoles of the BAY d 9603 type have a close structural relationship to the tritylazoles. They have a wide range of activity, particularly effective against mould fungi. Starting material here is the readily available diphenyl-propinol obtained by ethinyla-tion of benzophenone. The method for the conversion of this carbinol into the corresponding N-substituted imidazole is the reaction with carbonyl or thionyl-bis-imidazole, or preferably with the tris-imidazolide of phosphoric acid in a polar solvent. All other alkylation methods in which carbocations occur as intermediates completely fail. 

Acyloins have also been employed extensively as starting materials for the synthesis of imidazoles, usually in the presence of added aldehyde (or acid) and using ammoniacal cupric acetate to oxidize the acyloin to the corresponding a-dicarbonyl compound.24 Alicyclic and aromatic ketols and ketol acetates in an alcoholic solution of cupric acetate and ammonia undergo ring closure to the corresponding 2-imidazoyl ketones. Hence, benzoyl carbinol refluxed for 1 hour in... 

A number of additional cyclizations involving alkynes have been reported. For instance, it has been shown that indoles may also be accessed from 2-bromo- or 2-chloroanilines, as illustrated by the regioselective preparation of the carbinol 373 in the presence of the ferrocene 374 (Equation 104) <20040L4129>, whereas a one-pot sequence featuring titanium catalyzed hydroamination of 2-chloroanilines with acetylenes, followed by intramolecular Heck cyclization in the presence of an imidazol-2-ylidene palladium complex, has also been reported <2004CC2824>. A set of aryl-2-indolyl carbinols have been prepared in high enantiomeric purity by palladium-catalyzed annulation of... 

It is generally much more difficult to exchange at the 4-position, but an alternative approach to the generation of imidazol-4-yl anions in 2-unsubslituted imidazoles adds elhylmagnesium bromide to an 7V-protected 4-iodoimidazole. Quenching with a variety of aldehydes and ketones gives good yields of imidazolyl-4-carbinols uncontaminated by 2-substituted products [24],... 

The most common reactions with aldehydes and ketones reported have been those of lithio-imidazoles. The products are usually alcohols, but sometimes ketones are formed on aerial oxidation of the primary products. Access to 2-, 4-, and 5-carbinols is now readily available <94H(38)2487>. 

Prodncts of 2- and 4-snbstitntion of hydrogen are obtained by reaction of the sodium salt of imidazole with the phenyl pyrimidin-5-yl carbinol mesylate, with none of the product of direct substitution. Similar resnlts are obtained with the sodium salts of pyrrole and indole, but other nucleophiles, such as amines, give complex product mixtures. " ... 

X-Ray studies of carbonic anhydrase show that the active center is composed of three imidazole ligands which have distorted tetrahedral coordination to the Zn(II) ion. Molecular models suggested that a similar geometry could be attained with a tris(imidazolyl) methane derivation. For this reason, R. Breslow s team (218) in 1978 synthesized tris[4(5)imidazolyl] carbinol (4-TIC) and tris(2-imidazolyl) carbinol (2-TIC) as models for the zinc binding site of carbonic anhydrase and alkaline phosphatase. Similarly, bis[4(5)-... 

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