Solvent-free procedure

Although the 0-silylation reaction of the tertiary alcohol 1,1-dimethyl-2-phenylethanol (37) with 27 required a reaction temperature of 120 °C and two equivalents of 27, the 0-silyl ether 38 was still obtained in 86% yield by the simple solvent-free procedure. By contrast, the sterically hindered hydroxyl group of 37 was not silylated at all by heating with 27 in DMF at 120 °C for 5 h [8]. 

Oxazolines can be readily synthesized by means of a noncatalyzed solvent-free procedure by two successive nucleophilic additions on a carbonyl group with the formation of an amide as an intermediate [68] (Eq. 16). 

Significant improvements in yields or reaction conditions can be achieved, together with considerable simplification of operating procedures. The powerful synergistic combination of PTC and microwave techniques has certainly enabled an ever increasing number of reactions to be conducted under clean and mild conditions. The inherent simplicity of the method can, furthermore, be allied with all the advantages of solvent-free procedures in terms of reactivity, selectivity, economy, safety, and ease in manipulation. 

There are distinct advantages of these solvent-free procedures in instances where catalytic amounts of reagents or supported agents are used since they provide reduction or elimination of solvents, thus preventing pollution at source . Although not delineated completely, the reaction rate enhancements achieved in these methods may be ascribable to nonthermal effects. The rationalization of microwave effects and mechanistic considerations are discussed in detail elsewhere in this book [25, 193]. A dramatic increase in the number of publications [23c], patents [194—203], a growing interest from pharmaceutical industry, with special emphasis on combinatorial chemistry, and development of newer microwave systems bodes well for micro-wave-enhanced chemical syntheses. 

Ketene acetals and dithioacetals have been prepared in a solvent-free procedure by base catalyzed / -elimination under PTC conditions. The yields obtained by use of irradiation are much higher than those obtained by use of ultrasound or conventional heating under the same conditions [82] (Scheme 8.58). 

Large-Scale, Organic Solvent-Free Procedure for the Synthesis of Tetrazoles. To... 

The compound 3 can be easily prepared, in one pot, through a solvent-free procedure by nitroaldol reaction of nitroalkane 1 (2.2 mmol) and aldehyde 2 (2.2 mmol, freshly distilled), on activated neutral alumina (0.6 g, the alumina was added to a mechanically stirred solution of 1 and 2, at 0°C, then at room temperature for 20 h). Then, in situ addition (0°C) of wet-alumina supported chro-mium(VI) oxide (0.88 g (8.8 mmol) of C1O3 and 2.64 g of wet alumina). After standing for additional 20 h, the product was extracted with diethyl ether and passed through a bed of alumina. Evaporation of the organic solvent and flash chromatographic purification afforded the pure a-nitro ketone 3 in good yields (68-86%). 

Microwave heating has also been applied in the solvent-free phosphorylation of microcrystalline cellulose (Gospodinova et al., 2002). In the isolation step of this procedure, only water and ethanol were used as additional solvents. Wax esters have been produced from vegetable oils using a solvent-free enzymatic process (Petersson et al, 2005) this is particularly noteworthy as enzymes are often intolerant to high concentrations of substrates. The examples of solvent-free procedures described here show that solvents are not always required in the transformation of naturally sourced biopolymers and also in the chemistry of small molecules that can be obtained from a biorefinery. 

Today, in the field of organic chemistry, increasing attention is being given to Green Chemistry [19], using environmentally safe reagents and, in particular, solvent-free procedures. Reactions performed without the use of a solvent can indeed... 

The three types of solvent free procedures that can be coupled with microwave activation can be listed as ... 

Loupy, A., Pigeon, P., Ramdani, M., Jacquault, P. A new solvent-free procedure using microwave technology as an alternative to the Krapcho reaction. J. Chem. Res., Synop. 1993, 36-37. 

Dieckmann condensation reactions of diesters normally should be carried out in dried solvent under reflux under an inert atmosphere [21, 22]. Furthermore, Dieckmann reactions are often carried out under high dilution conditions in order to avoid intermolecular reaction [21, 22], However, it was found that the reaction of diethyl adipate (58a) or pimelate (58b) proceeds efficiently in the absence of solvent under air [23]. It is also possible to isolate the reaction products from the reaction mixture directly by distillation [23], These results establish a completely solvent-free procedure throughout the reaction and work-up of the reaction mixture. This is a very clean, green, simple and economical procedure. 

The solvent-free procedure allows the use of less reactive chloro electrophiles (here 1,1-dichloroethane) when compared to the technique using solvent. The reaction can then be performed in a one-step procedure leading to a better yield and an interesting simplified process as the tedious separation of mono- and dimethylated products necessary in the previous procedure is now avoided. [Eq. (37)]... 

The solvent-free procedure allows operation at a lower temperature (50 °C) at which the salt remains stable. The yield can be elevated up to 75% under simplified and mild conditions [Eq. (39)] [70]. 

The choice and use of solvents is both an intuition and a tradition for most organic chemists. The development of solvent-free procedures is a current topic which can harmoniously connect research and the environment. On an industrial scale these methods essentially become unavoidable when one considers the inconvenience involved in solvent use due to handling, cost, toxicity and the safety and pollution problems they generate. 

Microwave irradiation is confirmed as a new, more efficient mode of activation when compared to classical heating resulting in rapid reactions with better yields and purer compounds. Coupling microwave and solvent-free procedures is shown to be of great interest and offers attractive potential. More and more, classical conditions should be revisited in this direction thus taking advantage of clean, efficient, safe and economical technology. 

Starting from n-butyl (n-butyl a-o-mannopyranosiduronate) 4, uronamides 10 bearing a short butyl chain at the anomeric position and a longer alkyl (dodecyl, octadecyl, and oleyl) chain amide-linked to the sugar head were prepared following a one-step solvent-free procedure (Scheme 8). The aminolysis reaction was performed at 65°C to make the fatty amine liquid and under reduced pressure (3 mbar) to eliminate the butanol formed all through the reaction. To avoid significant... 

Reusability is a characteristic of the sensitizers prepared by stirring Ceo-fullerene with aminomethylated poly(styrene/vinylbenzene). They have been used to promote the standard O2 oxidation processes such as ene and Diels-Alder reactions (Scheme 7), and catalysts suitable for photoxidations in water have been prepared from them by reaction with poly(allylamine). The same reactions have been carried out using a novel solvent-free procedure which involves loading a porphyrin into solvent-swollen polystyrene beads and carrying out the photo-oxidation in neat liquid substrate. The formation of the allylic hydroperoxide (89) from p-pinene, with complete conversion and in 84% yield, is particularly noteworthy, as the standard liquid-phase reaction can be problematic. It is suggested that the possibility of using this approach under solar conditions is further evidence of the sustainable, green chemistry potential of synthetic photochemistry. 

Also a solvent-free procedure was applied, at 140 °C (m.p. biphenyl is 70 °C). Selectivity was distinctly lower, however, than when applying dichloromethane solvent. 

Another efficient way of using microwaves safely in organic synthesis is the use of solvent-free procedures (Ref [81] and Chapter 8 in this book). 

Carbonyl compounds are also rapidly regenerated from the corresponding semi-carbazone and phenylhydrazone derivatives by use of montmorillonite KIO clay impregnated with ammonium persulfate (Scheme 8.16) [59]. Interestingly, the microwave or ultrasound irradiation techniques can be used in these solvent-free procedures. Microwave exposure achieves deprotection in minutes whereas ultrasound-promoted reactions require 1-3 h for regeneration of carbonyl compounds [59]. 

Practical access to l,6-anhydro-/i-D-hexopyranoses by a solid-supported solvent-free procedure has been demonstrated by Bailliez et al. [106]. Microwave irradiation of 6-O-tosyl or 2,6-di-O-tosyl peracetylated hexopyranoses absorbed on basic alumina furnished the corresponding 1,6-anhydro-yS-D-hexopyranoses. Direct access to l,6 3,4-dianhydro-yS-D-altro-pyranose from D-glucose is also described (Scheme 8.38). 

---