Reactions under Solvent-free Conditions

To avoid pollution and high cost, solvent-free methods are of great interest to improve on conventional procedures and render them cleaner, safer, and easier to perform. Several advantages of this approach in cycloaddition reactions are described in reviews by de la Hoz [3j] and Bougrin [13c]. This interest in solvent-free pro- 

Although many interesting transformations with dry-media reactions, including cycloadditions, have been published in the literature [13c, 31], technical difficulties relating to nonuniform heating, mixing, and the precise determination of the reaction temperature remain unsolved, in particular when scale-up issues need to be addressed. In addition, phase-transfer catalysis (PTC) solvent-free conditions have rarely been applied to cycloaddition reactions [4c]. 

Nonetheless, microwave-assisted solvent-free conditions have wide applications in industrial processes and enable classification of microwave chemistry as an environmentally benign method, or green chemistry [3e-g, 28, 32). 

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Scheme 6.89 Diels-Alder cycloaddition reactions under solvent-free conditions.

Jacobs-Gould Reactions under Solvent-free Conditions... 

Asymmetric catalytic reactions under solvent-free conditions have also been reported. Contrary to the previous result, a neutral rhodium(I) complex provided comparable enantioselectivity with high chemical yield [24c], Eor certain cases, benzaldehyde gave improved enantioselectivity over cirmamaldehyde (Tab. 11.6), although the rationale behind choosing this particular CO source is not entirely clear. Additionally it should be noted that when the reaction was carried out using a stoichiometric amount of an aldehyde as the CO source in xylene, the reaction takes much longer and the enantioselectivity decreases substantially. 

Nagarapu L, Kumari MD, Kumari NV, Kantevari S (2007) MCM-41 catalyzed rapid and efficient one-pot synthesis of polyhydroquinolines via the Hantzsch reaction under solvent-free conditions. Catal Commun 8 1871-1875... 

Han XY, Xu F, Luo YQ, Shen Q (2005) An efficient one-pot synthesis of dihydropyrimidi-nones by a samarium diiodide catalyzed Biginelli reaction under solvent-free conditions. Eur J Org Chem 1500-1503... 

It was found that basic alumina worked well as the basic catalyst for the in situ dipole generation from the AT-acyl pyridinium salt. A three-component mixture of phenacyl bromide (1 mmol), pyridine (1.2 equiv.) and the acetylene (1.2 equiv.) was thoroughly mixed in basic alumina (1 g) and then irradiated for 8 min at 80% power in a domestic microwave. The products were formed in 87-94% yields when running the reaction under solvent-free conditions and in 60-71% yields when using anhydrous toluene as the solvent. 

For microwave-heated reactions under solvent-free conditions, the following major benefits have been claimed, particularly with regard to green chemistry [36] ... 

Yadav and Kapoor [13] synthesized the acyclic C-nucleosides (xii) incorporating the thiazole-s-triazine structure as a nucleobase following a three-component, one-pot reaction under solvent free condition and microwave irradiation. 

Figure 2.9 Base catalysed Baylis-Hillman reaction under solvent free conditions and using an HSBM.

Peng, J., Deng, Y. Ionic liquids catalyzed Biginelli reaction under solvent-free conditions. Tetrahedron Lett. 2001, 42, 5917-5919. 

Cross Cannizzaro reactions. Under solvent-free conditions the microwave irradiation of a mixture of aldehydes with formaldehyde and barium hydroxide gives alcohols. 

MANNICH REACTIONS UNDER SOLVENT-FREE CONDITIONS... 

Like alumina, SiO2 also shows catalytic efficiency for organic reactions under solvent-free conditions. A good example is catalysis of the Diels-Alder reaction (Scheme 5.34) by silica gel with high regio- and stereoselectivity. 

Solvendess organic reactions, neat reagents (solid-solid or solid-liquid) react together in the absence of a solvent and have been well reviewed as a fast developing technology [14a, 15] the postulated model by Scott et al. for such solventless reactions was proposed for better understanding the mechanism [16], Some selected representative reactions under solvent-free conditions are discussed below with emphasis on product separation. 

A facile ring-expansion reaction under solvent-free conditions accelerated by microwaves on an alumina surface has also been described (Scheme 2.2-35) which is preferable to the one conducted in methanol [101]... 

A solvent-free approach has been used to scale up a Heck reaction to the 1 mol level. Again, this study was preceded by optimization and investigation of substituent effects. However, on 0.5-1.0 molar scale under solvent-free conditions, the reaction was markedly exothermic, self-heating to 150 °C from the 100 °C set point. It is important to stress the importance of taking every precaution when performing reaction under solvent-free conditions on larger scales. In this case, the reaction mixture was heated slowly, and an over-sized flask was used. 

Asymmetric carbon-carbon bond formation reaction under solvent-free conditions was carried out by Bolm et al. in ball mill [58]. Here, nickel(II) complex 206 was used as a chiral auxiliary in alkylation with various bromides (Schane 2.67). Optimized reaction conditions were set to increase the stereoselectivity however, the desired monoalkylated product 207 was often accompanied by small amount of doubly alkylated side product 208. Two different bases were used (NaOMe/MgS04 or CS2CO3) and grinding of nickel complex 206 with bromides for 30-75 min afforded alkylation products in moderate to high yields and with complete stereoselectivity (selected examples. Table 2.54). 

Nielsen SF, Peters D, Axelsson O. The Suzuki reaction under solvent-free conditions. Synth Commun 2000 30 3501-9. 

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