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

Tsutomu Ishikawa; Toshiko Watanabe; Hisashi Tanigawa; Tatsuru Saito; Ken-Ichiro Kotake; Yoshiaki Ohashi; Hisashi Ishii

doi:10.1021/jo951873s

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

J Org Chem. 1996 Apr 19;61(8):2774-2779. doi: 10.1021/jo951873s.

Authors

Tsutomu Ishikawa¹, Toshiko Watanabe, Hisashi Tanigawa, Tatsuru Saito, Ken-Ichiro Kotake, Yoshiaki Ohashi, Hisashi Ishii

Affiliation

¹ Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi, Inage, Chiba 263, Japan.

PMID: 11667112
DOI: 10.1021/jo951873s

Abstract

Nitrosation of 3-methoxyphenol and 1-naphthol were examined under both acidic (NaNO(2)-EtCO(2)H-H(2)O) and basic (i-AmNO(2)-K(2)CO(3)-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.