Nitrosation of Phenolic Substrates under Mildly Basic Conditions: Selective Preparation of p-Quinone Monooximes and Their Antiviral Activities

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Abstract
Nitrosation of 3-methoxyphenol and 1-naphthol were examined under both acidic (NaNO2−EtCO2H−H2O) and basic (i-AmNO2−K2CO3−DMF) conditions. Acidic nitrosations afforded ortho-directed products, whereas para-directed nitrosations were observed under basic conditions to yield p-quinone monooximes. The basic para-directed nitrosation was further examined using 15 phenols, two naphthols, and four phenolic heterocyclics. A one-pot operation of the basic nitrosation followed by methylation with dimethyl sulfate gave the corresponding methyl ethers in high yield. Two p-quinone monooximes derived from 3-methoxyphenol and 8-hydroxyquinoline showed a moderate activity against HSV-1, and the latter oxime was also effective against HSV-2. On the other hand, p-quinone monooximes derived from methyl salicylate, 1-naphthol, 7-hydroxy-2-methylbenzo[b]furan, and 8-hydroxycoumarin showed the comparable activity to that of DDI against HIV-1.