Synthesis, structure and toxicity evaluation of ethanolamine nitro/chloronitrobenzoates: a combined experimental and theoretical study

Manuela Crisan,Liliana Halip,Paulina Bourosh,Sergiu Adrian Chicu,Yurii Chumakov

doi:10.1186/s13065-017-0346-5

Abstract

BackgroundNitroaromatic and chloronitroaromatic compounds have been a subject of great interest in industry and recently in medical-pharmaceutic field. 2-Chloro-4-nitro/2-chloro-5-nitrobenzoic acids and 4-nitrobenzoic acid are promising new agents for the treatment of main infectious killing diseases in the world: immunodeficiency diseases and tuberculosis.ResultsNew ethanolamine nitro/chloronitrobenzoates were synthesized and characterized by X-ray crystallography, UV–vis, FT-IR and elementary analysis techniques. The toxicity of the compounds prepared and correspondent components was evaluated using Hydractinia echinata as test system. A significant lower toxicity was observed for nitro-derivative compared with chloronitro-derivatives and individual components. Crystallographic studies, together with the chemical reactivity and stability profiles resulted from density functional theory and ab initio molecular orbital calculations, explain the particular behavior of ethanolamine 4-nitrobenzoate in biological test.ConclusionsThe experimental and theoretical data reveal the potential of these compounds to contribute to the design of new active pharmaceutical ingredients with lower toxicity.

Highlights

Nitroaromatic and chloronitroaromatic compounds are versatile precursors, the vast majority synthetic and frequently employed as important intermediates for the synthesis of industrial chemicals, dyes, pigments and pharmaceutical drugs [1,2,3]
Taking into account the prospects of nitro- and chloronitrobenzoic acids and the fact that about a half of all active pharmaceutical ingredients are used today as salts due to their improved drug’s physicochemical properties, Crisan et al Chemistry Central Journal (2017) 11:129 we have focused to prepare new nitro/chloronitroderivatives with lower toxicity
The position of nitro-substituent leads to change in the system of hydrogen bonds between anion and cation in compound 2 which crystallizes as hydrate

Summary

Introduction

Nitroaromatic and chloronitroaromatic compounds are versatile precursors, the vast majority synthetic and frequently employed as important intermediates for the synthesis of industrial chemicals, dyes, pigments and pharmaceutical drugs [1,2,3]. The functional groups nitro and chloride provide chemical and structural diversity and a significant impact on properties and reactivities of chemicals, making these compounds attractive in different research fields over the past decades. Many pharmaceuticals have their chemical origins in nitro- and chloronitroaromatic compounds. Taking into account the prospects of nitro- and chloronitrobenzoic acids and the fact that about a half of all active pharmaceutical ingredients are used today as salts due to their improved drug’s physicochemical properties, Crisan et al Chemistry Central Journal (2017) 11:129 we have focused to prepare new nitro/chloronitroderivatives with lower toxicity. Nitroaromatic and chloronitroaromatic compounds have been a subject of great interest in industry and recently in medical-pharmaceutic field. 2-Chloro-4-nitro/2-chloro-5-nitrobenzoic acids and 4-nitrobenzoic acid are promising new agents for the treatment of main infectious killing diseases in the world: immunodeficiency diseases and tuberculosis

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