Lithiation 1 Mannich reaction / Alkylation 1 Grignard reaction 1 Condensation Phenols and naphthols are benzotriazolylmethylated by 1-(hy-droxymethy1)-lH-benzotriazole (13) (a formaldehyde derivative) in the 0-or (if both o-positions are occupied) in the p-position. The reaction can be extended to other aldehydes in the case of the naphthols. The methylene group in the o-(benzotri-azolylmethy1)phenols can be lithiated (but only after trimeth-ylsilyl protection of the hydroxy group) and then substituted by various electrophiles. The benzotriazole residues in both the primary products and in their substituted derivatives can be displaced by the alkyl anions of Grignard reagents or by hydride ions allowing the elaboration of many new types of substituted phenols.
Classical Mannich reactions condense active CHcompounds, including phenols, with formaldehyde and an amine'). Important cxtensions of the Mannich reaction in which amides, imides, ureas, thioureas, etc. replace the amine component are well documented 'I. Phenols have been cmployed as the active CH-compounds in these Mannich condensations with aldehydes and amides or imides under various conditions'). The ortho-substituted derivatives are obtained unless both ortho-positions are occupied, when the Mannich reaction occurs at the para-position'). Zaugg4) attributed the high ortho-to para-preference to the assistance of the phenolic Scheme 1 H H / x p o + HN. y 1 H), 6.90 (d, J = 7.0 Hz, 1 H), 7.05 (d, J = 7.0 Hz, 1 H), 7.38 (t, J = 7.0 Hz, IH), 7.51 (t, J = 7.0 Hz, IH), 7.79 (d, J = 8.0 Hz,