Ionic liquids reagents

Bortolini, O., Bottai, M., Chiappe, C., Conte, V and Pieraccini, D., Trihalide-based ionic liquids. Reagent-solvents for stereoselective iodination of alkenes and alkynes. Green Chem. 4, 621-627 (2002). 

Viewed in conjunction with the solid-like, nonvolatile nature of ionic liquids, it is apparent that TSILs can be thought of as liquid versions of solid-supported reagents. Unlike solid-supported reagents, however, TSILs possess the added advantages of kinetic mobility of the grafted functionality and an enormous operational surface area (Figure 2.3-1). It is this combination of features that makes TSILs an aspect of ionic liquids chemistry that is poised for explosive growth. 

It should be emphasized that ionic liquids are simply organic salts that happen to have the characteristic of a low melting point. Many ionic liquids have been widely investigated with regard to applications other than as liquid materials as electrolytes, phase-transfer reagents [12], surfactants [13], and fungicides and biocides [14, 15], for example. 

In pyridinium chloride ionic liquids and in l,2-dimethyl-3-hexylimida2olium chloride ([HMMIMjCl), where the C(2) position is protected by a methyl group, only [PdClJ was observed, whereas in [HMIMjCl, the EXAFS showed the formation of a bis-carbene complex. In the presence of triphenylphosphine, Pd-P coordination was observed in all ionic liquids except where the carbene complex was formed. During the Heck reaction, the formation of palladium was found to be quicker than in the absence of reagents. Overall, the EXAFS showed the presence of small palladium clusters of approximately 1 nm diameter formed in solution. 

A similar study performed by Welton and co-workers studied the rate and selec-tivities of the Diels-Alder reaction between cyclopentadiene and methyl acrylate in a number of neutral ionic liquids [44]. It was found that endo. exo ratios decreased slightly as the reaction proceeded, and were dependent on reagent concentration and ionic liquid type. Subsequently, they went on to demonstrate that the ionic liquids controlled the endo. exo ratios through a hydrogen bond (Lewis acid) interaction with the electron-withdrawing group of the dienophile. 

Fig. 34 Preparation of a 4-thiazolidinone library using an ionic liquid support. Reagents and conditions a MW 100 °C, l-2h, open vessel b R"NH2, t-BuOK, MW 100-150°C, 10-20 min. R = H, Me, CH2COOH R = Pr, i-Pr, i-Bu, Bn, piperonyl, CH2CH(OMe)2, CH2CH CH2 R" = Pr, Bu, Bn, or cyclic derivatives as piperonyl, piperidine, pyrrolidine,...

Fig. 36 Synthesis of a polysubstituted pyran on ionic liquid support. Reagents and conditions a ethyl acetoacetate, MW 200 W, reflux, 10 min b arylidenemalononitriles, pyridine, MeCN, MW 200 W, reflux, 15-20 min c NaOMe, MeOH, rt, 6h...

Apart from being employed solely as solvents, ILs can also be used as reagent carriers (TSlLs, task-specific ionic liquids). An efficient system that uses ILs as solvents and anchoring/acylating reagents for the CAL B-catalyzed separation of racemic alcohols is shown in Scheme 5.17 [69]. 

From reviewing much of the literature it is easy to conclude that ionic liquids are excellent solvents for catalysts and reagents but not for products, which is obviously not the case. Whilst some products can be decanted from the liquid and others can be recovered by distillation, there are many useful reactions in which removal of the product (or residual reactants) from the ionic liquid is challenging. Extraction with an organic solvent, or even water, would reduce the overall eco-efficiency. Initial... 

In order to overcome these problems, attention was focused on the use of heterogeneous catalysis. We have found that functionalized solid materials, e.g., ionic liquids or tin triflates immobilized into mesoporous materials, can be used in N-acylation reactions as environmentally friendly replacements for traditional homogeneous acids which are useful but environmentally unacceptable catalysts [17, 18]. They had comparable activity to homogeneous reagents but can offer greater stability, safer and easier handling and can be... 

One of the important new directions in the study of addition reactions of organozinc compounds to aldehydes is the use of ionic liquids. Usually, application of these compounds in reactions with common organometallic reagents has a serious problem ionic solvents are usually reactive toward them, particularly Grignard and organolithium derivatives. It has been recently reported that carbonyl compounds react with allylzinc bromide formed in situ from allyl bromide and zinc in the ionic liquid 3-butyl-l-methylimidazolium tetrafluoroborate, [bmim][BF4].285 Another important finding is that the more reactive ZnEt2 alkylates aldehydes in a number of ionic liquids at room temperature.286 The best yields (up to 96%) were obtained in A-butylpyridinium tetrafluoroborate, [bpy][BF4] (Scheme 107). 

Additions of the Reformatsky-type reagents to aldehydes can also proceed in ionic solvents (Scheme 108).287 Three ionic liquids have been tested 8-ethyl-l,8-diazbicyclo[5,4,0]-7-undecenium trifluoromethanesulfonate ([EtDBU][OTf]), [bmim][BF4], and [bmim][PF6]. The reactions in the first solvent provided higher yields of alcohols 194 (up to 93%), although results obtained for two other ionic liquids were also comparable with those reported for conventional solvents. 

The microwave-assisted thionation of amides has been studied by Ley and coworkers using a polymer-supported thionating reagent [115]. This polymer-supported amino thiophosphate serves as a convenient substitute for its homogeneous analogue in the microwave-induced rapid conversion of amides to thioamides. Under microwave conditions, the reaction is complete within 15 min, as opposed to 30 h by conventional reflux in toluene (Scheme 7.95). The reaction has been studied for a range of secondary and tertiary amides and GC-MS monitoring showed that it proceeded almost quantitatively. More importantly, this work was the first incidence of the use of the ionic liquid l-ethyl-3-methylimidazolium hexafluorophosphate... 

Using day supported ammonium nitrate (dayan), selective deprotection of methoxyphenyl methyl (MPM) ether has been achieved recently using microwave irradiation in solvent-free conditions (Scheme 6.15) [56]. The same reagent has been used for the cleavage of tetrahydropyranyl (THP) ethers. A similar selective preparation and deavage of THP ethers has been achieved under microwave irradiation catalyzed by iodine [57] or neat reaction in an ionic liquid [28],... 

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

The development of phase transfer catalysis, of supercritical fluids, of ionic liquids and of course, new reagents, should also have considerable potential in the labeling area. Furthermore there is the possibility of combining these approaches with energy-enhanced conditions - in this way marked improvements can be expected. 

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