Synthesis solvent-free

Although the initial reason of the development of solvent-free conditions for micro-wave irradiation was safety, it soon became apparent that use of these conditions had many other benefits - simplicity, efficiency, easy work-up, very often higher yields, and enhanced reaction rates. The absence of solvent is, furthermore, time and moneysaving and often enables elimination of waste treatment. This class of synthesis is now clearly seen as a basis of green chemistry . 

Solvent-free synthesis can be realized under a variety of conditions we will give selected results and, when available, comparisons with the same solvent-free conditions but with classical heating. 

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Solvent-free synthesis of heterocyclic compounds using microwaves 99JHC1565. 

Scheme 34 Solvent-free synthesis of hexahydrochromeno[4,3-fc]pyrroles 78 and 79...

Thiazolines (2,3-dihydrothiazoles) were also prepared under microwave irradiation. Hamelin and coworkers have described the alumina-supported solvent-free synthesis of various 4-iminothiazolines by condensation of disymmetric thioureas and a-chloro ketone (Scheme 10). The experiments... 

Scheme 11 Solvent-free synthesis of polysubstituted thiophenes...

Scheme 18 Solvent-free synthesis of oxazoles mediated by hypervalent iodine(III) sulfonates...

Scheme 72 Solvent-free synthesis of pyrazolo-pyridines...

Scheme 76 Solvent-free synthesis of polycyclic heterocycles...

A solvent-free synthesis of flavones was recently reported by microwave-assisted reaction of phloroglucinol 231 and differently substituted /1-ketoesters 232 [148]. The reaction was simply carried out by mixing the phenol and the ester in an open test tube followed by irradiation for 2-3 min. The internal temperature reached 240 °C and yields were in the range from 68 to 96%. Scheme 85 describes the application of this procedure to the synthesis of the natural product chrysin 233. 

The potential for solvent-free synthesis is relatively large, with examples of many well-known reaction types proceeding quite well under this type of regime these include transesterification, condensation and rearrangement reactions. Many workers have moved away from conventional thermal sources for providing the energy needed for these reactions -... 

A solvent-free synthesis of benzo[b]furan derivatives 10-79, a class of compounds which is often found in physiologically active natural products, was described by Shanthan Rao and coworkers. These authors heated phosphorane 10-71 for 8 min in a microwave oven and obtained the benzo[b]furan 10-74 in 73% yield (Scheme 10.18) [25]. The sequence is initiated by an intramolecular Wittig reaction, providing alkyne 10-72 this underwent a subsequent Claisen rearrangement to give the intermediate 10-73. Also in this case, normal oil-bath heating gave much lower yields (5%) of the desired product the authors hypothesize that the micro-... 

Scheme 10.17. Microwave-assisted solvent-free synthesis of 1,3-thiazines.

Toma and coworkers have described the solvent-free synthesis of salicylanilides from phenyl salicylate or phenyl 4-methoxysalicylate and substituted anilines (Scheme 6.155) [302]. By exposing an equimolar mixture of the ester and the amine to microwave irradiation at 150-220 °C for 4—8 min under open-vessel conditions, good yields of the corresponding salicylanilides were obtained. This synthesis was carried out on a multigram scale (0.1 mol). 

A solvent-free synthesis of substituted spiroindolinonaphth[2,l-fo][l,4]oxazines through condensation of 2-methylene-l,3,3-trimethylindoline derivatives with 1-nitroso-2-naphthol under microwave irradiation has been described by Fedorova and colleagues (Scheme 6.263) [453], In a typical reaction, an equimolar mixture of the two starting materials was irradiated at 65-110 °C for 15 min to produce the desired spiroindolinonaphth[2,l-fo][l,4]oxazines, which are useful as photochromic compounds. In a related procedure, addition of morpholine to the reaction mixture led to the formation of the corresponding 6 -amino-functionalized spiroindolino-naphth[2,l-fo][l,4]oxazines, which exhibit a strong hypsochromic color shift (not shown) [453]. 

A large specific microwave effect was observed in the solvent-free synthesis of N-sulfonylimines, a similar type of reaction [64] (Eq. 12). 

Finally, the magnitude of a specific microwave effect could be indicative of a polar mechanism or to access the rate-determining step in a procedure involving several steps. For instance, during the study of microwave effect in the solvent-free synthesis... 

A solvent-free synthesis of flavones has been achieved that simply involves the MW irradiation of o-hydroxydibenzoylmethanes adsorbed on montmorillonite K 10 clay for 1-1.5 min. A rapid and exclusive formation of cyclized flavones occurs in good yields (Scheme 6.41) [140], The intramolecular Michael addition of o-hydroxy-... 

Organic Synthesis Using Microwaves and Supported Reagents 6.2.7.6 Solvent-free Synthesis of Ionic Liquids... 

Solvent-free Synthesis under Acidic Conditions... 

Quite recently [71] an expeditious solvent-free synthesis of imidazoline derivatives, using basic or neutral alumina under microwave irradiation, was reported. The reaction time was reduced from hours to minutes with improved yield compared with conventional heating. 

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