Reaction solvent-free

Microwave effects are mostly likely to be observed in solvent-free reactions [4]. In addition to the preparative interest of these methods in terms of use, separation, and economical, safe, and clean procedures (green chemistry), absorption of micro-wave radiation should now be limited to the reactive species only. The possible specific effects will therefore be optimum, because they are not moderated or impeded by solvents. They can be accomplished by to following three methods [4, 58]  

reactions between the neat reagents, in quasi-equivalent amounts, requiring at least one liquid phase in heterogeneous media and leading to interfacial reactions [58-61]  

solid-liquid phase-transfer catalysis (PTC) conditions, in amonic reactions using the liquid electrophile as both reactant and organic phase and a catalytic amount of tetraalkylammonium salts as the transfer agent [62] and 

reactions using impregnated reagents on solid mineral supports (aluminas, silicas, clays) in dry media [4, 12, 63]. 

Finally, because the interpretation proposed for specific MW nonthermal effects is rather similar to that for solvent effects (Hughes-Ingold theory), one can expect that aprotic polar solvents can be removed and replaced by MW activation requiring operation with a nonpolar solvent or, much better, under solvent-free conditions. In this situation we add also advantages of green chemistry conditions. In 

In modern microwave synthesis, a variety of different processing techniques can be utilized, aided by the availability of diverse types of dedicated microwave reactors. While in the past much interest was focused on, for example, solvent-free reactions under open-vessel conditions [1], it appears that nowadays most of the published examples in the area of controlled microwave-assisted organic synthesis (MAOS) involve the use of organic solvents under sealed-vessel conditions [2] (see Chapters 6 and 7). Despite this fact, a brief summary of alternative processing techniques is presented in the following sections. 

Microwaves in Organic and Medicinal Chemistry. C. Oliver Kappe, Alexander Stadler Copyright 2005 WILEY-VCH Veriag GmbH Co. KGaA, Weinheim ISBN 3-527-31210-2 

Apart from examples where the inorganic support merely acts as a catalyst, there are many instances where a solid-supported reagent can be used very effectively in 

Since graphite is a very strong absorber of microwave heating, the temperature must be carefully controlled to avoid melting of the reactor. The use of a quartz reactor is highly preferable. 

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In the solvent-free reactions, however, a strong base such as Bu OK can be used for any kind of ester substrate, since such exchange does not occur. This is also a considerable advantage. 

The cross-condensation reaction of benzyl benzoate (46) and 44 was carried out under solvent-free conditions. Treatment of a 1 1 mixture of 46 and 44a with Bu OK at 120 °C for 1 h gave the cross-condensed product 47a in 42% yield (Scheme 7). Similar reaction of 46 with 44b gave 47b in 45% yield. Because heating of46,44, and Bu OK in toluene under reflux for 16 h did not give any product, it is clear that the solvent-free reaction is again effective for the cross-condensation. In these cases, self-condensation of 44 itself did not occur probably because of the high reactivity of 46 [9]. 

The solvent-free Cannizzaro reaction has some advantages. In addition to simplicity and cleanness of the procedure, the solvent-free reaction proceeds much faster than a solution reaction. For example, reaction of 51 in 60% aqueous NaOH takes 24 h to complete [10], although the solvent-free reaction is completed within 5 min [9]. 

Fig. 2 IR monitoring of the K2C03-assisted solvent-free reaction of 89a with 90a by spectroscopic measurements in Nujol mulls. I-IV measured every 15 min...

There are different ways in which the nanoparticles prepared by ME-technique can be used in catalysis. The use of ME per se [16,17] implies the addition of extra components to the catalytic reaction mixture (hydrocarbon, water, surfactant, excess of a metal reducing agent). This leads to a considerable increase of the reaction volume, and a catal5fiic reaction may be affected by the presence of ME via the medium and solubilization effects. The complex composition of ME does not allow performing solvent-free reactions. 

Oxidation of these model sulfur compounds was studied without solvent to investigate the chemical structure of the products using S K-edge XANES. A solvent free tri-phase (organic/ H202aq./catalyst) was used under the described conditions. Figure 1 shows the XANES spectra from the organic and aqueous phases as well as reference materials. The thiophene oxidized to thiophene-sesquioxide [3a,4,7,7a-tetrahydro-4,7-epithiobenzo[b]-thiophene 1,1.8-trioxide ] first.. The sesquioxide solid precipitated from the solvent free reaction mixture and was identified by NMR, IR and C,H,S elemental analytical. The sesquioxide oxidized to sulfate. 2-MT and 2,5 DMT also oxidized to... 

Most of these publications describe important accelerations of a wide range of organic reactions especially when performed under solvent-free conditions. The combination of solvent-free reaction conditions and microwave irradiation leads to large reductions in reaction times, enhancement of yield, and, sometimes [3, 4] in selectivity with several advantages of an eco-friendly approach, termed green chemistry . 

Microwave effects are most likely to be observed under solvent-free reactions [3]. In addition to the preparative interest of these methods in terms of use, separation, and economical, safe and clean procedures, absorption of microwave radiation... 

This study was prompted by a report that phthalimidoacetic acid (R = CH2C02H, see also Scheme 4.11, vide supra) could be synthesized by the reaction of phthalic anhydride with glycine in the absence of solvent, which involves the reaction between two solids [56], However, in this study [45], it was established that the synthesis of phthalimides under solvent-free reactions requires at least one liquid reactant in order to occur. This was possible when reacting a liquid amine (e.g. R = CH2Ph) or a solid with a sufficiently low melting point to melt rapidly under MW (e.g. R = (CH2)6OH, m.p. 56-58). In these cases, the reaction temperature was typically over 135 °C after 2 or 3 min of MW heating resulting in dissolution of phthalic anhydride in the molten... 

Because observed rate enhancements are usually small, or zero, nonthermal effects do not seem to be important in MW heated reactions in homogeneous media, except possibly in some reactions of polymers and reactions in nonpolar solvents. Relatively few studies have been conducted on MW-assisted reactions of polar reactants in nonpolar solvents. Also, since there is some disagreement as to whether or not these reactions are accelerated significantly by MW, in comparison with conventionally heated reactions at the same temperature, more research on the effect of MW irradiation on the rates of these reactions is required. Nonthermal effects may, however, explain the more substantial MW rate enhancements in solvent-free reactions on solid supports [44] (see Chapt. 5) and solid state reactions [68, 69]. 

For these reasons, and because avoidance of solvents makes the technique more environmentally friendly, the majority of recent papers on MW-assisted organic synthesis have reported the use of solvent-free reactions. 

Knoevenagel condensation reaction of creatinine with aldehydes occurs rapidly under solvent-free reaction conditions at 160-170 °C using focused microwave irradiation (Scheme 6.18) [66],... 

Solvent-free Reactions without Support or Catalyst... 

Quite recently this reaction was revisited by Kappe [91] et al. who reinvestigated the Biginelli synthesis under the action of microwave irradiation under a variety of different conditions. At atmospheric pressure in ethanol solution there is no difference from conventional heating. Under pressure the yield is reduced and byproducts are formed. In an open system rate and yield enhancements are significant and this is rationalized by the rapid evaporation of the solvent which means that this is in fact a solvent-free reaction. This was confirmed by running the reaction without solvent under the action of microwaves and with thermal heating. (Scheme 8.65)... 

J. L. Luche, A. Petit, Tetrahedron 1999, 55, 10851-10870 c) A. Loupy, Solvent-free Reactions in Modem Solvents in Organic Chemistry. Topics in Current Chemistry Vol. 206, pp 155-207,1999. 

Furthermore, many SCFs possess economical, technical, environmental, and health advantages. The high volatility of C02, for example, allows it to be completely and easily removed from the product, resulting in an overall solvent-free reaction. scC02 is a promising alternative to hazardous organic solvents. 

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