Ionic liquids nucleophilic substitution with

The alkylation process possesses the advantages that (a) a wide range of cheap haloalkanes are available, and (b) the substitution reactions generally occur smoothly at reasonable temperatures. Furthermore, the halide salts formed can easily be converted into salts with other anions. Although this section will concentrate on the reactions between simple haloalkanes and the amine, more complex side chains may be added, as discussed later in this chapter. The quaternization of amines and phosphines with haloalkanes has been loiown for many years, but the development of ionic liquids has resulted in several recent developments in the experimental techniques used for the reaction. In general, the reaction may be carried out with chloroalkanes, bromoalkanes, and iodoalkanes, with the reaction conditions required becoming steadily more gentle in the order Cl Br I, as expected for nucleophilic substitution reactions. Fluoride salts cannot be formed in this manner. 

Ionic liquids also showed a catalytic activity for the cyclocondensation of a-tosyloxyketones with 2-aminopyridine [210], the nucleophilic substitution... 

A similar distinction between a system with pre-electrolysis with only one electrode (in this case anodic) process, and a system with simultaneous anodic and cathodic processes (in which anode and cathode are on opposite walls of a microchannel so that each liquid is only in contact with the desired electrode potential, analogous to the fuel cell configurations discussed above) was made by Horii et al. (2008) in their work on the in situ generation of carbocations for nucleophilic reactions. The carbocation is formed at the anode, and the reaction with the nucleophile is either downstream (in the pre-electrolysis case) or after diffusion across the liquid-liquid interface (in the case with both electrodes present at opposite walls). The concept was used for the anodic substitution of cyclic carbamates with allyltrimethylsilane, with moderate to good conversion yields without the need for low-temperature conditions. The advantages of the approach as claimed by the authors are efficient nucleophilic reactions in a single-pass operation, selective oxidation of substrates without oxidation of nucleophile, stabilization of cationic intermediates at ambient temperatures, by the use of ionic liquids as reaction media, and effective trapping of unstable cationic intermediates with a nucleophile. 

For example, acetylation reactions of alcohols and carbohydrates have been performed in [Bmim]-derived ionic liquids.If the dicyanamide anion [N(CN)2] is incorporated into the liquid, mild acetylations of carbohydrates can be performed at room temperature, in good yields, without any added catalyst.In this example, it was shown that the RTIL was not only an effective solvent but also an active base catalyst. In a recent study, Welton and co-workers performed calculations on the gas phase basicity of the conjugate acids of possible anions from which to construct their liquid.Using these data, they were able to choose the optimum RTIL in which to conduct a nucleophilic aromatic substitution reaction of an activated aniline with an activated arylhalide. Given the enormous number of possible anions and cations from which to build up an ionic liquid, the role of computation in experimental design such as this will become increasingly important. 

The Tsuji-Trost ally lie substitution catalyzed by Pd complexes using CH-acidic nucleophiles can be performed in an ionic liquid of type 1 alone [30] as well as in a biphasic system [31]. In the latter case the use of trisulfonated triphenylphosphine (TPPTS) prevents the catalyst from leaching into the organic phase. In comparison with water as the catalyst-supporting phase, the ionic liquid system exhibits higher activity and selectivity. The enantio-selective version of the allylic substitution with dimethyl malonate can also be performed in ionic liquids with a homochiral ferrocenylphosphine as the ligand [32]. 

Especially, the eco-friendly ionic liquids have obtained extensive attention in organic synthesis with the merits provided as above. The ionic liquids as the unusual green solvents are applied extensively in various organic synthesis reactions, such as Friedel-Crafts reactions, oxidation reactions, reduction reactions, addition reactions, C-C formation reactions, nucleophilic substitution reactions, esterifications, rearrangements, hydroformylations, and nitration reactions [7-14]. Besides, the ionic liquids also have applications in the extraction separation, the electrochemistry, and preparation of nanostructured materials, the production of clean fuel, environmental science, and biocatalysis. This chapter would present in detail the application of the ionic liquids as the unusual green solvents (also as dual green solvent and catalyst) for the alkylation and acylation. 

Abstract This chapter presents the design and analysis of the microscopic features of binary solvent systems formed by ionic liquids, particularly room temperature ionic liqnids with molecular solvents. Protic ionic liquids, ethylammonium nitrate and l-n-butyl-3-methylmidazohum (bmim)-based ILs, were selected considering the differences in their hydrogen-bond donor acidity. The molecular solvents chosen were aprotic polar (acetonitrile, dimethylsulphoxide and MA(-dimethylformide) and protic (different alcohols). The empirical solvatochromic parameters n, a and P were employed in order to analyse the behaviour of each binary solvent system. The study focuses on the identification of solvent mixtures of relevant solvating properties to propose them as new solvents . Kinetic study of aromatic nucleophilic substitution reactions carried out in this type of solvent systems is also presented. On the other hand, this is considered as a new approach on protic ionic liquids. Ethylammonium nitrate can act as both Bronsted acid and/or nucleophile. Two reactions (aromatic nucleophilic substitution and nncleophilic addition to aromatic aldehydes) were considered as model reactions. 

Ionic liquids are proposed as designer solvents for nucleophilic aromatic substitution. Coating with a layer of ionic liquid onto silica-supported sulfonic acid improves its utility (such as acetalization) boasting selectivity in aqueous media. ... 

The first attempt at a nucleophilic substitution reaction in an ionic liquid was carried out by Ford and coworkers [124-126]. Here, the rates of reaction of halide ion (in the form of its triethylammonium salt) with methyl tosylate in the molten salt triethylhexylammonium triethylhexylborate were studied (Scheme 5.2-56). This was compared with similar reactions in dimethyl formamide (DMF) and methanol. The reaction rates in the molten salt appeared to be intermediate in rate between methanol and DMF (a dipolar aprotic solvent known to accelerate Sn2 substitution reactions). 

Shreeve et al. have synthesized a range of new ionic liquids based on oxazoli-dine, morpholine and 1,2,4-triazole. These have been found to be good solvents for the Cu(I)-mediated nucleophilic trifluoromethylation of benzyl bromide [155]. Nucleophilic substitution has also been carried out on alkenes in the form of 2-tosyltropone, where the tosyl group was substituted for a chloride in [BMIM][BF4] [156]. Aminopyridines [157] and aminopyrimidines [158] react with a-halo ketones to form imidazopyridines and imidazopyrimidines. These reactions have been investigated in [Bp4] and [PFs]" ionic liquids and found to give fester reaction rates than in organic solvents [159]. 

Even though most of the supported ionic liquid catalysts prepared thus far have been based on silica or other oxide supports, a few catalysts have been reported where other support materials have been employed. One example involves a polymer-supported ionic liquid catalyst system prepared by covalent anchoring of an imidazolium compound via a linker chain to a polystyrene support [79]. Using a multi-step synthetic strategy the polymeric support (e.g. Merrifield resin among others) was modified with l-hexyl-3-methylimidazolium cations (Scheme 5.6-4) and investigated for nucleophilic substitution reactions including fluorina-tions with alkali-metal fluorides of haloalkanes and sulfonylalkanes (e.g. mesylates, tosylates and triflates). 

Welton et al. [127] have used the linear solvation energy relationships (LSERs) approach to study the effects of ionic liquids on the kinetics of various Sfj2 nucleophilic substitution reactions. These take several forms, with different forms of charge distribution behavior (Table 2.1) [90]. 

With this in mind, the Welton group reasoned that the same approach could be taken to the study of the effects of ionic liquids on the rates of reactions. They used the Kamlet-Taft polarity scales to develop Linear Solvation Energy Relationships (LSERs) to describe the effects of solvents on the reaction kinetics of various 8 2 nucleophilic substitution reactions f Schemes 10.1-10.4). 8 2 reactions occur in a concerted step in which the nucleophile replaces the nucleofuge or leaving group as it dissociates from the subsmate. Their reaction profiles have the form of that in Figure 10.1. 

As expected by the application of the Hughes-lngold rules, the reactions of Cr with dimethyl-4-nitrophenylsulfonium salts [4-N02CeH4S(CH3)2]X, Scheme 10.4) in ionic liquids were considerably slower than the same reactions in most molecular solvents. However, these reactions also followed a different reaction mechanism in the ionic liquids to those seen in molecular solvents [15]. In molecular solvents, the reactions follow a mechanism that is initiated by a fast ion metathesis to form the reactive ion pairs, which go on to give the products via a nucleophilic substitution reaction fScheme 10.51. 

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