ABSTRACT
Synthesis of many specialty chemicals involves use of organic solvents. The objective of this chapter is to describe the feasibility of carrying out organic reactions in supercritical fluids. Supercritical fluids have properties that could make them nearly the ideal media for conducting synthetic reactions. This chapter, after a revision of chemical reactions in scCO2, addresses the synthesis of organic complex molecules using this fluid as a solvent. The first section revises the formation of macrocycles in scCO2, where Schiff-based (C=N) and polycyclic ring compounds are prepared through a cyclocondensation reaction between amines and aromatic aldehydes
in the absence of any template and catalyst or cosolvent. The second section explores the preparation of hybrid materials through a ship-in-a-bottle approach in scCO2. These hybrid materials are composed of medium-sized organic cationic molecules synthetized into zeolite cages. 10.1 Introduction to Chemical Reactions in
scCO2The blooming of the study of the chemical reactions carried out us-ing supercritical carbon dioxide (scCO2) as a solvent started in the early 1980s, when the potential of this solvent started to inspire sci-entist into the research of different methods of chemical synthesis. Later in the 1990s, the concern of carrying out chemical reactions in a greener way increased the interest in developing new approaches where all, the chemical reagents, solvents, and by-products, are en-vironmentally friendly or, at least, less harmful [1]. This interest was reflected by McHungh and Krukonis [2] who described the advantages of carrying out the reactions in supercritical fluids, relating the increased reactions rates and selectivities resulting from the rapid diffusion and the low solvation of the reacting species. scCO2 has unique properties that makes it an excellent medium in which conduct chemical reactions. Despite the potential of scCO2 as a sol-vent medium to carry out organic synthesis, there are still some disadvantages that slow down the development of new synthetic strategies. Among these disadvantages are found the low solubility of high-molecular-weight molecules in scCO2 and the difficulty of working with polar compounds in the absence of cosolvents. Supercritical fluids are becoming increasingly important in industry, partly in response to the adverse environmental impact of solvent use and disposal. As a reaction medium, the attractive physical and toxicological inertness properties of scCO2 have made it superior to conventional organic solvents in a large number of synthetic transformations [3]. Research is focused on reactions in which the outcome either cannot be obtained using traditional organic solvents or is influenced to a great extent by the unique properties of scCO2. Two main categories of organic reactions in scCO2 have been developed-(i) those in which scCO2 is used as a
solvent/reaction medium [4] and (ii) those in which scCO2 takes part in the reaction as a reactant or simultaneously as a reagent and a solvent [5]. 10.1.1 Organic Reactions in an scCO2 MediumIn 1999, a special issue of Chemical Reviews was dedicated to organic reactions in supercritical media [6]. From them, the various aspects of reactions performed in scCO2, used as a solvent, have been extensively reviewed [7-13]. scCO2 is used as a medium in the following chemical reactions: enzyme-catalyzed [14], polymerization [15-17], radical [18], cycloaddition [19], and transition metal-catalyzed reactions [20, 21]. 10.1.1.1 Transition metal-catalyzed reactionsResearchers in organometallic catalysis started to contemplate a broad use of CO2 as a solvent in the mid-1990s, especially after sufficiently “CO2-philic” organometallic catalysts became generally available [22, 23]. Organic reactions catalyzed by transition metals in scCO2 include oxidation, reduction, carbonylation, radical addition, C-C coupling, and cycloaddition reactions [24]. All these reactions can be performed in scCO2 with equal or even better results than in conventional organic solvents, owing to the high diffusion and low viscosity of scCO2. Selective examples using Pd, Rh, Ru, Ir, Pt, Ni, Co, Cu, Ag, and Au are reviewed in [25]. Particularly, palladium-catalyzed C-C coupling reactions are finding increasing importance for industrial synthesis of fine chemicals, including biologically active compounds. The most studied chemical transformations in scCO2 involving the C-C bond formation include the Diels-Alder reaction, the thermal cracking of hydrocarbons, the hydroformylation reactions, and Suzuki coupling [26]. Another well-described type of reaction is the hydrogenation of fats [27]. In scCO2, such coupling processes occur at high rates and with excellent selectivity [28-30]. In oxidation reactions, the advantage of the process is related with the fact that oxygen and CO2 are completely miscible under supercritical conditions. Also, CO2 cannot be oxidized further during catalytic oxidation. Hence, oxidation reactions in scCO2 eliminate side products formation due to oxidation of organic solvents. The addition of suitable amounts of cosolvents in scCO2 is necessary
in most reactions, because it not only improves the solubility of transition metal salts in scCO2 but also regulates the ratio of products and raises the selectivity as well. 10.1.1.2 Polymerization reactionsThe first homogeneous free-radical polymerization in scCO2 was reported in 1992 [31]. scCO2 is an ideal solvent for the polymerization of fluoropolymers and silicon-based polymers, which display limited solubility in organic solvents [32]. Moreover, although most commercial polymers are not soluble in scCO2, they can be synthesized in biphasic dispersion and emulsion polymerization modes [33, 34]. The molecular weights and polymer properties prepared in scCO2are similar to those obtained by analogous polymerization methods in organic solvents. Therefore, the incentives of using scCO2 as a solvent lie not in the polymerization reaction but in the decreased cost of polymer processing [35]. Polymers synthesized in scCO2can be isolated simply by depressurization of the reaction vessel. Moreover, due to the increased plasticity of polymers in scCO2, the residual monomer and catalysts are easily removed from the polymer matrix. 10.1.1.3 Enzyme-catalyzed reactionsThe stability and activity of enzymes exposed to CO2 under high pressure depend on enzyme species, water content in the solution, and the pressure and temperature in the reaction system, as well as the depressurization step [36, 37]. The three-dimensional structure of enzymes may be significantly altered under extreme conditions, causing their denaturation and consequent loss of their activity. If the conditions are less adverse, the protein structure may largely be retained [38]. The initial applications of scCO2 treatments involv-ing enzymes were designed as an alternative to thermal microbial inactivation, which can be safely used in foods and bioactive mate-rials at relatively low temperatures [39]. This method has received increasing attention since scCO2 was shown to be effective for the treatment of Escherichia coli [40]. It was stated that enzyme inac-tivation with scCO2 could be predominantly attributed to the pH-lowering effect during treatment [41]. Further, the finding that some enzymes, such as lipases, several phosphatases, dehydrogenases, ox-idases, amylases, and others, are well suited for enzymatic reactions
in scCO2 has broadened immensely the scope of their applications as highly enantioselective catalysts in synthesis carried out in scCO2. Interestingly, the activity and selectivity of enzymes can be modulated by changes in the working pressure or temperature, increasing the range of products that a single enzyme can form [42]. The appli-cation of scCO2 as a solvent in enzyme-catalyzed reactions has been a matter of considerable research because of its favorable transport properties, which accelerate mass-transfer-limited reactions [43]. There are several reports in the literature on enzymatic hydrolysis of vegetable oil or triacylglycerol in scCO2 solvent, most of them in enzymes immobilized into porous silica supports. The major advan-tage of immobilized enzymes consisted in an easier separation from the product [44, 45]. 10.1.2 Reactions Involving CO2 as a ReactantIn addition to acting as a solvent with unique physical properties, scCO2 proves to have synthetic utility in a variety of organic and inorganic reactions. CO2 is an inert molecule in most organic environments; however, it is a Lewis acid and reacts with strong bases, such as amines or phosphines. The use of scCO2 as a labile-protecting group for secondary amines has been reported [46]. Moreover, scCO2 has been used as a C1 building block, that is, as a carbon source, in the formation of formic acid, methyl formate, and dimethyl formamide [47, 48]. The application of scCO2 is now reasonably established for hydrogenation and hydroformilation. The high degree of solubility of H2 gas in scCO2 is one factor contributing to the improved results of these reactions in this medium. In addition to carbamate formation in the reaction of CO2 and amines, the fluid can also form carbonates. An important class of these materials is inorganic carbonates formed by the reaction of CO2 and alkaline earth metals [49]. 10.2 Schiff Base Synthesis in Supercritical CO2The richness of amine and organonitrogen functional groups and the potential that they have in natural and synthetic process make them an important class of family in reactive chemistry.
