Synthesis of 2,4(5)-Bis(hydroxymethyl)imidazoles and 2,4(5)-Bis[(2-hydroxyethoxy)methyl]imidazoles: Precursors of 2,4(5)-Connected Imidazole Crown Ethers

Two syntheses of l-[(dimethylamino)sulfonyl]-2,4-bis[(2-hydroxyethoxy)methyl]imidazole, 3, a precursor to imidazole-containing crown ethers, are described. The first involved hydroxymethylation of 1-benzylimidazole with formaldehyde to afford l-benzyl-2,5-bis(hydroxymethyl)imidazole (5) (20% yield), which was elaborated into 3 in four steps. An alternative and more efficient route involved coupling of diamine 17b with the imino ether obtained from nitrile l1b to afford imidazoline 18b. The imidazoline was found to oxidize under Swern conditions, providing a mild new method of imidazole synthesis. Sulfamylation and debenzylation produced 3. This approach was also applied to the synthesis of l-[(dimethylamino)sulfonyl]-2,4-bis(hydroxymethyl)imidazole (2). Diol 3 was converted into 2,4-connected imidazole crown ethers, one of which (4) formed a crystalline complex with water. The complex structure was determined by X-ray crystallography.