2‐Methoxyethyl Nitrite as a Reagent for Chemoselective On‐Water Nitration

Abstract

An on-water approach has been developed that allows a nitration of tyrosines and phenols under mild conditions. We envisioned that the assembly of tyrosine/ tyrosyl radical couples with interfacial water molecules would realize a biomimetic stacking hydrogen atom transfer (HAT) transition state to facilitate the electron-transfer process. The optimal organic nitrite, 2-methoxyethyl nitrite, resulted in rapid coupling of the tyrosyl radicals with * NO 2 at the oilwater interface to afford the nitrated phenols. Many characteristics found in our on-water strategy are distinct from other complementary systems that include radical nitration. These enticing roles of water in the reaction process introduce new avenues to explore in the design of synthetic organic chemistry systems.

Water vs. Organic Solvents: Water‐Controlled Divergent Reactivity of 2‐Substituted Indoles

“…Encouraged by the successful prevention of an overreaction in tyrosine nitration under mild conditions, [2] we explored the capability of 2‐methoxyethyl nitrite to furnish indolenine oximes that were heretofore less accessible (Scheme 1c). For instance, indole‐2‐carboxylate derivatives are deemed attractive molecules because they possess unique bioactivity [6] and because carboxylates are easily converted into a variety of functional groups.…”

“…In a recent study, our group reported 2-methoxyethyl nitrite as a nitrating agent that works efficiently under on-water conditions. [2] In contrast to commonly used organic nitrites bearing small nonpolar hydrocarbon chains, such as tert-butyl nitrite, [3] 2-methoxyethyl nitrite could prevent undesirable Nnitrosation and bisnitration in the reaction with tyrosines. The advantage of this protocol over precedents using organic solvents was highlighted in several examples of selective mononitration.…”