An Easily Introduced and Removed Protecting Group for Imidazole Nitrogen: A Convenient Route to 2-Substituted Imidazoles

Article abstract of DOI:10.1021/jo01308a019

Orthoamides (3-5) prepared from imidazoles and triethyl or trimethyl orthoformate are rapidly metalated at -40 deg C in THF or ether to give the corresponding 2-lithio anion which reacts with a variety of electrophiles.The dialkoxymethyl protecting group is readily hydrolyzed under neutral or acidic conditions at room temperature, giving the 2-substituted 1H-imidazole 1 (R = H, X = COOH, n-C4H9, COCH3, CHOHC6H5, C(CH3)OH-2-pyridyl,9-hydroxyfluorenyl, 1-hydroxycyclohex-2-enyl, C(OH)(C6H5)2; R = CH3, R' = H, X = CHO) and the tris(2-imidazolyl)phosphines (R = H, CH3, CH(CH3)2).A mechanism for the deprotection of 3 is proposed.