Reactions solventless

Opt for solventless reactions, recycle solvents, or use benign solvents (e.g., water, ionic liquids, supercritical media). 

Solventless reaction of 6-bromo-8-cyclopentyl-2-methylsulfinyl-8//-pyrido[2,3-r7 pyrimidin-7-one 195 with tert-butyl 4-(6-aminopyridin-3-yl)piperazine-l-carboxylate 196 at 120 °C for 1 h followed by deprotection in the presence of gaseous HCl afforded the amine derivative 197 (Equation 14) <2003W02003062236>. 

The field is rapidly developing, and the most important issues also relevant to hydrocarbon chemistry include the development of solventless reactions, use of alternative solvents, and, most important of all, replacement of old technologies with clean catalytic processes. Combinatorial chemistry, a method to produce a large number of chemical compounds rapidly on a small scale, can be regarded as a particularly useful tool from the point of view of environmental protection. 

Continuing the trend for solventless reactions, a microwave variant of the classical Paal-Knoor thiophene synthesis has been reported11. Thionation-cyclisation of a range... 

The work of Jones and Lu has embraced a wide range of reactions including hydrogenations, borohydride reductions, aromatic dehalogenations, decarboxylations and hydrogen isotope exchange processes, (Scheme 9.3, Eqs. 1-3). In addition to the accelerated rates of reaction, new environmentally friendly routes have been developed, particularly solventless reactions that minimise waste production and facilitate containment107-110. 

Minkwitz et al.250 have obtained tris(methylthio)sulfonium hexafluoroantimonate in a solventless reaction at low temperature [Eq. (4.69)] and characterized the salt by Raman, IR, H and 13C NMR to spectroscopy. The salt is stable below 10°C but decomposes in S02 solution at —45°C with rapid elimination of sulfur. It possesses C3 symmetry with a pyramidal trithiosulfonium unit and the methyl groups point to the central sulfur atom (ab initio calculations). 

The reaction of iV,iV-bis(phenacyl)anilines 133-141 with hydrazine hydrochloride in EtOH or ethylene glycol under reflux led to the formation of novel 1,2,5-triazepines (1, 142-149) (Scheme 32). The precursors 133-141 were, in turn, prepared from the solventless reaction of various phenacyl bromides 131 and anilines 132 in the presence of potassium carbonate <2007JHC133>. 

Throughout the chemical industry, many products, such as poly(propylene) are made without the use of a solvent or are performed in the gas phase. In many cases, one of the reactants also acts as the solvent. As the field of green chemistry has grown, so has the number of so-called solventless reactions, including... 

The same differential behavior can be observed with amine nucleophiles. For example, calcium triflate promotes the aminolysis of propene oxide 84 with benzylamine to give 1-(A -benzyl)amino-2-propanol 85, the result of attack at the less substituted site <03T2435>, and which is also seen in the solventless reaction of epoxides with heterocyclic amines under the catalysis of ytterbium(III) triflate <03SC2989>. Conversely, zinc chloride directs the attack of aniline on styrene oxide 34 at the more substituted carbon center <03TL6026>. A ruthenium catalyst in the presence of tin chloride also results in an SNl-type substitution behavior with aniline derivatives (e.g., 88), but further provides for subsequent cyclization of the intermediate amino alcohol, thus representing an interesting synthesis of 2-substituted indoles (e.g., 89) <03TL2975>. 

Solventless reactions of 5(4//)-oxazolones 139 with hydroxycoumarins 140 exhibited excellent control of chemoselectivity leading to O- and C-acylation products 141 and 142 <03SL1710>. 

Supramolecular self-assembly has been found to be dramatically accelerated in some cases, and this is perhaps the reason why solventless reactions have been rapidly adopted by coordination chemists. For example, the formation of a platinum-containing square is dramatically accelerated compared with the same reaction in water (Figure 2.3). In water, the reaction needed to be heated at 100 °C for 4 weeks. In a solvent free approach, approximately the same yield was achieved in 10 min at room temperature. Water and ethanol were the only solvents used in the work up of the reaction. This approach was then extended to bowl-shaped and helical supramolecular structures. 

The presence of gaseous (subcritical) CO2 above a solid compound can cause the compound to melt at a temperature 20 or more degrees below its normal melting point. This phenomenon can make it possible to perform solventless reactions at temperatures at which the substrate would normally be solid (132). The method, which requires much less CO2 pressure than supercritical techniques, has been used for nonasymmetric hydrogenations and hydro-formylations (132) and for an asymmetric hydroformylation (101). 

The elimination of solvents in chemical processes, or the replacement of hazardous solvents with environmentally benign ones, is one of the Twelve Principles of Green Chemistry [13]. The main advantage of solventless chemistry is that it is conceptually the simplest solution for the problems with solvents. However, not many reactions can be carried out under such conditions, as exothermic reactions can be dangerous, heating and stirring can be inefficient, especially if solid reactants or products are present, and usually solvents are needed for working up the product from solventless reaction media. 

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 solvent-free self-assembly offullerene Cjq using high-speed vibration milling has been described [19]. This simple, efficient, and green pathway to the synthesis of a supramolecular complex in the solid state opened a new avenue for the application of solventless reactions. 

Microwave-assisted Solventless Reactions on Solid Supports... 

---