Synthesis of Naphthoxazinones in a One-Pot Two-Step Manner by the Application of Propylphosphonic Anhydride (T3P®)

Valentina Varga,Péter Ábrányi-Balogh,Mátyás Milen

doi:10.3390/chemistry2020037

Valentina Varga, Péter Ábrányi-Balogh + Show 1 more

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https://doi.org/10.3390/chemistry2020037

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Abstract

A sequential one-pot two-step protocol has been elaborated for the synthesis of naphthoxazinones from 2-naphthol, methyl carbamate, and aromatic aldehydes. First, a three-component reaction was optimized with the dehydrating additive propylphosphonic anhydride (T3P®), resulting in 1-carbamatoalkyl 2-naphthols in good to excellent yields. Following the successful multicomponent approach, intramolecular acylation was performed at high temperature, again with the contribution of T3P®, resulting in naphthoxazinone derivatives in moderate yields. These two steps were optimized together in one-pot as well, and the sequential rise in the requisite temperature eventuated the optimal procedure for the multistep cascade.

Highlights

Multicomponent reactions play a significant role in organic synthesis [1], medicinal chemistry [2], and materials science [3]
1-Carbamatoalkyl 2-naphthols, important intermediates of biologically active compounds, can be prepared in a three-component reaction of 2-naphthol, methyl carbamate, and aromatic aldehydes (Scheme 1). This condensation reaction has been investigated in the presence of various catalysts, such as cerium ammonium nitrate [4], ionic liquids [5,6,7,8,9,10,11,12], magnesium
We have investigated six reaction pathways (A–F) to the one-pot ring-closing synthesis of naphtha[1,2-e]oxazinone derivatives

Summary

Introduction

Multicomponent reactions play a significant role in organic synthesis [1], medicinal chemistry [2], and materials science [3]. In this highly atom-efficient process, three or more starting materials react in a single operational step to form the product. This condensation reaction has been investigated in the presence of various catalysts, such as cerium ammonium nitrate [4], ionic liquids [5,6,7,8,9,10,11,12], magnesium. The hydrolyzed products 1-aminoalkyl2-naphthols exhibit cardiovascular activity [24], while naphthalene-condensed 1,3-oxazin-3-ones possess an antibacterial effect [25]

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