Fluconazole-Associated Birth Defects: A Comprehensive Review

Abstract

Conflicts of interest: None to disclose

Nucleophilic Nitration of Arynes by Sodium Nitrite and its Multicomponent Reaction Leading to Double-Functionalized Arenes

“…Nitroaromatics constitute an important class of compounds that are commonly found in pigments, dyes, advanced materials, polymers, agrochemicals, rubber, specialty chemicals, intermediates, colorants, explosives, and pharmaceuticals. − They are important building blocks in organic synthesis for accessing complex molecules of pharmaceutical interest . Nitration is at least one of the steps in the whole synthetic process of almost 65% of active pharmaceutical ingredients .…”

“…In view of the above-mentioned applications, nitration of aromatics is one of the most utilized transformations of industrial interest . Generally it is achieved by strong-acid-catalyzed electrophilic substitution using HNO 3 or by dinitrogen pentoxide, but examples of nucleophilic aromatic nitrations are also known, although not very common initially. , Poor regioselectivity, poor functional group tolerance under harsh reaction conditions, and overnitration are some of the major issues in nitration processes. Over the past century, several important advances in the area of aromatic nitration have been reported (Figure ).…”

“…Over the past century, several important advances in the area of aromatic nitration have been reported (Figure ). − In continuation of our research interest in the development of novel and original methodologies using arynes as reactive intermediates, we were curious to see whether an alternative protocol using simple reagents and mild reaction conditions could be developed for the synthesis of nitroaromatics by hitherto unknown nucleophilic nitration of arynes. Herein we present our results on the outcome of our envisioned transformation and its application in a multicomponent reaction.…”

Nitration Using Fuming HNO3 in Sulfolane: Synthesis of 6-Nitrovanillin in Flow Mode

“…For instance, the use of fuming nitric acid with organic solvents mandated a thorough interrogation of their mutual compatibility. Furthermore, the reaction mass containing excess nitrating agent and a potentially energetic product can pose a thermal risk, which can be exacerbated by the presence of polynitrated byproducts, which are likely to form due to the electron-rich nature of the substrate under these conditions …”

A Method for Heteroaromatic Nitration Demonstrating Remarkable Thermal Stability

“…In addition to the preparative challenges associated with pyrrole nitration, there are some significant safety concerns . The inherent hazards of handling concentrated nitric acid and other related strong oxidants, compatibility issues, thermal hazards, and the risk of overnitration leading to the production of highly energetic polynitrated species must all be managed safely . In recent years, these risks have been mitigated through the use of flow reactors .…”