Aliphatic Nitro Compounds as Key Precursors for the Eco-Friendly Synthesis of Fine Chemicals under Solvent-Free Conditions

In the last decades, there has been a phenomenal growth of the global economy and a continuous improvement of the living standards in industrialized countries. Sustainable development has consequently become an ideal goal. In the early 1990s, the concept of “green chemistry” was initiated in the United States as new paradigm, and since 1993 it has been promoted by the National Science Foundation (NSF) and the Environmental Protection Agency (EPA). Sustainability has become an important issue in the wider context dealing with population, health, the environment, energy, technology, and renewable resources, and in the sciences, an integral part of the rapidly emerging field called green chemistry. This is a multidisciplinary field, requiring integrated study in the chemical, biological, and physical sciences. The 12 principles of green chemistry, as defined by Anastas and Warner, generally internationally accepted, cover complex issues, including minimization of waste, reduction in energy usage, and the use of renewable resources. In the chemical sciences, there is a need to develop benign synthetic pathways that, in addition to being high yielding (historically the most important measure of the success of a reaction), are simple, exhibit high atom efficiency, hence a reduced number of steps and no waste, are safe, and are environmentally acceptable. Further green metrics that are commonly used to quantify the “greenness” of a reaction are as follows: (1) the E-factor (environmental factor), which is the ratio of the mass of waste per mass of product (kilograms of waste/kilograms of product), and (2) the process mass intensity (PMI), that is the ratio of the total mass of materials used in the process to the mass of the isolated product, which, for pharmaceuticals, is typically >100. Removing organic solvents in chemical synthesis is important in the drive toward benign chemical technologies. Organic solvents are high on the list of toxic or otherwise damaging compounds because of the large volumes used in industry and difficulties in containing volatile compounds. Replacement reaction media include water, supercritical CO2, ionic liquid, and polyethylene or polypropylene glycol. Another alternative are the so-called solvent-free reactions (SFRs), which drastically minimize the environmental pollution, the exposure issues, and the E-factor. In fact, as reported by Tanaka and Toda, observing the natural phenomena, it could be obvious to say that conversion of one material into another occurs in the liquid state but not in the solid state (i.e., crushed grapes give wine by fermentation, but dried grapes do not result in wine, or shaking of milk gives cheese while dried milk can be kept unaltered) and, in this context, Aristotle summarized that no corpora nisi Fluida, which means “no reaction occurs in the absence of solvent.” Such philosophies had a big influence on the evolution of the modern sciences, and this provides one historical reason to explain way most organic reactions have been studied in solution. On the contrary, often chemists still carry out their reaction in solution, even when the use of solvent is unnecessary. In this regard, aliphatic nitro compounds have demonstrated a great reactivity under neat conditions, mainly in the formation of new C–C bonds. Thus, the main focus of this report is to show the most important examples in which aliphatic nitro derivatives favor the reactivity under neat conditions and their application for preparing a variety of fine chemicals.