Reactions in neutral ionic liquids

As already stated, chloroaluminate (III) ionic liquids are excellent solvents in many reactions. The main problem arises due to their moisture sensitivity and difficulty in separation of products (containing heteroatoms) from the ionic liquid. In view of this, water-stable ionic liquids have been developed. One example of this is the ionic liquid [bmin][PF ] [(bmin) = l-butyl-3-methylimidazolium)]. The ionic liquid [bmin][PFJ forms triphasic mixture with water and alkanes, which makes it useful for clean synthesis. Such ionic liquids can be used without any special conditions needed to exclude moisture and the isolation of the reaction products is convenient. 

Some applications in the use of neutral ionic liquids are discussed here. 

Solvent Diene Dienophile Product Time Yield a b ratio 

7 Stoichiometric Organic Reactions and Acid-Catalyzed Reactions in Ionic Liquids 

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. 

These reactions occur with similar rates to those carried out in dipolar aprotic solvents such as DMF or DMSO. An advantage of using the room-temperature ionic liquid for this reaction is that the lower reaction temperatures result in higher selec-tivities for substitution on the oxygen or nitrogen atoms. The by-product (sodium or potassium halide) of the reaction can be extracted with water and the ionic liquid recycled. 

A quantitative study of the nucleophihc displacement reaction of benzoyl chloride with cyanide ion in [BMIM][PF6] was investigated by Eckert and co-workers [52]. 

McCluskey et al. have also used [BMlM][Bp4] as a solvent for the allylation of aldehydes and Weinreb amides [56]. Similar diastereoselectivities and similar or slightly lower yields were obtained in this ionic liquid, compared with reachons carried 

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Miscellaneous reactions in neutral ionic liquids Kitazume et al. have also investigated the use of [EDBU][OTf as a medium in the formation of heterocyclic compounds [58]. Compounds such as 2-hydroxymethylaniline readily condense with... 

Earle and coworkers [54] have performed Diels-Alder reactions in neutral ionic liquids. The results of reactions of cyclopentadiene with dimethyl maleate, ethyl acrylate and acrylonitrile are reported in Table 6.10. The cycloadditions proceeded at room temperature in all of the ionic liquids tested, except [BMIMJPF4, and gave almost quantitative yields after 18-24h. The endo/exo selectivity depends on dienophile. No enantioselectivity was observed in the [BMIM] lactate reaction. 

The field of reaction chemistry in ionic liquids was initially confined to the use of chloroaluminate(III) ionic liquids. With the development of neutral ionic liquids in the mid-1990s, the range of reactions that can be performed has expanded rapidly. In this chapter, reactions in both chloroaluminate(III) ionic liquids and in similar Lewis acidic media are described. In addition, stoichiometric reactions, mostly in neutral ionic liquids, are discussed. Review articles by several authors are available, including Welton [1] (reaction chemistry in ionic liquids), Holbrey [2] (properties and phase behavior), Earle [3] (reaction chemistry in ionic liquids), Pagni [4] (reaction chemistry in molten salts), Rooney [5] (physical properties of ionic liquids), Seddon [6, 7] (chloroaluminate(III) ionic liquids and industrial applications), Wasserscheid [8] (catalysis in ionic liquids), Dupont [9] (catalysis in ionic liquids) and Sheldon [10] (catalysis in ionic liquids). 

Diels-Alder reactions Neutral ionic liquids have been found to be excellent solvents for the Diels-Alder reaction. The first example of a Diels-Alder reaction in an ionic liquid was the reaction of methyl acrylate with cyclopentadiene in [EtNH3][N03] [40], in which significant rate enhancement was observed. Howarth et al. investigated the role of chiral imidazolium chloride and trifluoroacetate salts (dissolved in dichloromethane) in the Diels-Alder reactions between cyclopentadiene and either crotonaldehyde or methacroline [41]. It should be noted that this paper describes one of the first examples of a chiral cationic ionic liquid being used in synthesis (Scheme 5.1-17). The enantioselectivity was found to be < 5 % in this reaction for both the endo (10 %) and the exo (90 %) isomers. 

Table 6.10 Diels-Alder reactions of cyclopentadiene with dimethyl maleate, ethylacrylate and acrylonitrile in neutral ionic liquids...

The Diels-Alder reaction is an important and widely used reaction in organic synthesis (Sauer and Sustmann, 1980), and in the chemical industry (Griffiths and Previdoli, 1993). Rate enhancement of this reaction has been achieved by the use of solvents such as water, surfactants, very high pressure, lithium amides, alkylammonium nitrate salts, and macrocyclic hosts (Sherman et ak, 1998). Diels-Alder reactions can be ran in neutral ionic liquids (such as 1-butyl-3-methylimidazolium trifluoromethanesulfo-nate, l-butyl-3-methylimidazolium hexafluorophophate, l-butyl-3-methylimidazolium tetrafluoroborate, and l-butyl-3-methylimidazolium lactate). Rate enhancements and selectivities are similar to those of reactions performed in lithium perchlorate-diethyl ether mixtures. 

Neutral ionic liquids have been found to be excellent solvents for the Diels-Alder reaction. The first example of a Diels-Alder reaction in an ionic liquid was in the... 

Fig. 7-2 Acyclic diene metathesis polymerization (ADMET) reaction carried out in neutral ionic liquid [EMIMJCl-AICb (- (AlCb) = 0.5) [52].

As well as viscosity, other factors to be aware of include the purity of the ionic liquids. The presence of residual halide ions in neutral ionic liquids can poison transition metal catalysts and different levels of proton impurities in chloroalumi-nate(iii) ionic liquids can alter the product distribution of the reaction. The reduced temperatures required for many polymerization reactions in ionic liquids, together with the reduced solubility of oxygen in ionic liquids compared to conventional solvents, means that two of the most common quenching methods are reduced in effectiveness. When detailed studies are being carried out, in particular kinetic studies, it is necessary to completely stop further reaction so that accurate data are obtained. 

Ionic liquids are excellent solvents for the Diels-Alder reaction providing significant increases in rate and selectivity. Diels-Alder reactions conducted in chloroa-luminate ionic liquids show considerable promise. For example, the endo.exo ratio for the reaction between cyclopentadiene and methyl acrylate (Scheme 7.5) could be varied by changing the composition of the ionic liquid (see Chapter 4) [11]. Although a high yield was obtained, in order to extract the products it was necessary to quench the ionic liquid in water. This is a considerable disadvantage and for this reason neutral ionic liquids have been the focus of subsequent attention. 

Neutral ionic liquids such as [AMIM]BF4 and [AMIMJPF function as catalysts for a limited number of reported reactions. The purities of such ionic liquids have been a concern. Because unknown impurities could give misleading results, care needs to be taken in the preparations 153). 

The pH-neutral ionic liquids are highly polar and noncoordinating. These liquids have potential applications as solvents for metallic and organometallic reagents in two-phase reactions, and as replacements for polar, aprotic solvents like dimethyl-foimamide. The Lewis-acidic and superacidic ionic liquids are being investigated for use as catalytic solvents. 

This simple example may illustrate that in general the reaction of an organic halide salt [cation]X with an excess of a Lewis-acid MXy can result in new catalytic materials even if other Lewis-acids are applied than AICI3. In contrast, the use of other Lewis-acids to form the ionic liquid of type [cation][MXy+i] + excess MXy (the excess of MXy may be dissolved in the neutral ionic liquid or may form acidic anionic species such as e.g. [M2X2y+i]-) gives access to new combinations of properties (e.g. a liquid, less oxophilic, Lewis-acidic catalyst with defined solubility and acidity properties). In Table 2 other examples of ionic liquids are presented which are formed by the reaction of an organic halide salt with different Lewis-acids. All these systems should be in principle useful acidic catalysts for synthetic organic chemistry even if not all displayed examples have been already discribed in the literature for this application. 

In some ionic liquids, acid (proton) impurities are significant. This is common in the phosphonium cation family of ionic liquids and can also be the case with nitrogen-based cations if the synthetic method involves a neutralization reaction. It is relatively easy to deal with this situation. Acidity should be determined by a standard titration method and then the acidity neutralized by addition of an appropriate base. Carbonates are particularly useful in this regard since they produce CO2 as the product. 

Comparable results were further observed when neutral cyclopentadienyl-molybdenum(II) compounds like MoCpCl(CO)3 were used as catalysts in that immobilisation of the catalyst in an ionic liquid afforded lower turnover frequencies relative to the reaction in neat substrate.[33]... 

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