Ionic liquids (IL) Introduction

Most of the organic solvents are volatile that are used in organic synthesis. The toxic

and hazardous properties of many solvents, notably chlorinated hydrocarbons, combines with

serious environmental issues, such as atmospheric emission and contamination of aqueous

effluents is making their use prohibitive.

Recently ionic liquids (IL) are emerging as novel replacement for volatile organic

compounds traditionally used as solvents and reduce the volatility, environmental and human

health and safety concerns that accompany exposure to organic solvents.

The ionic bond is usually stronger than the Van der Waals forces between the molecules

of ordinary liquids. For that reason, common salts tend to melt at higher temperatures than

other solid molecules. Some salts are liquid at or below room temperature.

Ex: - Pyridinium chloride (C5H6N+Cl−) that melts at 144.5 °C (292.1 °F), 1-ethyl-3-

methylimidazolium dicyanamide ((C2H5)(CH3)C3H3N+2N(CN)−2) that melts at −21 °C (−6 °F)

and 1-butyl-3,5-dimethylpyridinium bromide which becomes a glass below −24 °C (−11 °F).

Low-temperature ionic liquid can be compared to ionic solutions, liquids that contain

both ions and neutral molecules, and in particular to the so-called deep eutectic solvents,

mixtures of ionic and non-ionic solid substances which have much lower melting points than

the pure compounds. Certain mixtures of nitrate salts can have melting points below 100 °C.

Ionic liquid (IL) is a salt in the liquid state. In some contexts, the term has been

restricted to salts whose melting point is below some arbitrary temperature, such as 100 °C

(212 °F). While ordinary liquids such as water and gasoline are predominantly made of

electrically neutral molecules, ionic liquids are largely made of ions and short-lived ion pairs.

“Any salt that melts without decomposing or vaporizing usually yields an ionic liquid”.

Eg: - Sodium chloride (NaCl) melts at 801 °C (1,474 °F) into a liquid that consists largely of

sodium cations (Na+) and chloride anions (Cl−).

These substances are also called as –

liquid electrolytes

ionic melts

ionic fluids

fused salts

liquid salts or

ionic glasses.

Definition:

“The ionic liquid (IL) implies an ionic material that is liquid at ambient temperature or

salt that are liquid at near-ambient temperature, is colorless, has a low viscosity and is easily

handled”, i.e., a material with attractive properties for a solvent.

Ex: -

Ionic liquids have many applications, such as powerful solvents and electrically

conducting fluids (electrolytes). Salts that are liquid at near-ambient temperature are important

for electric battery applications, and have been used as sealants due to their very low vapor

pressure.

Ionic liquids are made up of at least two components which can be varied (the cation

and the anion). Properties such as melting point, viscosity, density and hydrophobicity can be

varied by simple changes to the structure of ions.

Another important property that changes with structure is the miscibility of water in

these ionic liquids. By choosing the correct ionic liquid, higher product yield can be obtained

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INCLUDEPICTURE "http://upload.wikimedia.org/wikipedia/commons/thumb/b/bf/Bmim.svg/128px-Bmim.svg.png" \* MERGEFORMATINET

1-Butyl-3-methylimidazolium (bmim) salt

Commonly used cations for ionic liquids

and a reduced amount of waste can be produced in a given reaction. Often the ionic liquids can

be recycled and this leads to a reduction of the costs of the process. The reactions are often

quicker and easier to carry out than in conventional organic solvents.

Ionic liquids are good solvents for a wide range of both inorganic and organic materials.

They are often composed of poorly coordinating ions, so they have the potential to be highly

polar non-coordinating solvents. They are also immiscible with a number of organic solvents

and provide a non-aqueous, polar alternative for two phase system. Hydrophobic ionic liquids

can also be used as immiscible polar phases with water. The use of ionic liquids can enhance

activity, selectivity and stability of transition metal catalysts.

Types of Ionic Liquids

An ionic liquid consists of a salt where one or both the ions are large and the cation has

a low degree of symmetry. These factors tend to reduce the lattice energy of the crystalline

form of the salt and hence lower the melting point.

Ionic liquids come in two main categories, namely:

i) Simple salts and ii) Binary ionic liquids

i) Simple salts: The salts which are containing only one salt comes under this category.

e.g., [EtNH3][NO3]

The most common salts in use are those with cations such as tetraalkyl ammonium,

tetraalkyl phosphonium and tetraalkyl sulphonium salts.

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The common anions are

ii) Binary ionic liquids (salts where equilibrium is involved)

The salts which are containing two salts in combining state are come under this category.

e.g.: - Mixture of aluminium chloride and 1,3-dialkylimidazolium chloride contain several

different ionic species and their melting point and properties depend upon the mole fractions

of the aluminium chloride and 1,3-dialkylimidiazolium chloride present.

In order to be liquid at room temperature, the cation should preferably be

unsymmetrical e.g. R1 and R2 should be different alkyl groups in the dialkylimidazolium cation.

The melting point is also influenced by the nature of the anion.

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The hydrophilicity/ lipophilicity of an ionic liquid can be modified by a suitable choice

of anion, [bmin]BF4 (bmin:- 1-butyl-3-methylimidiazolium) is completely miscible with water

while the PF salt is largely immiscible with water. The lipophilicity of dialkylimidazolium salts

or other ionic liquids can also be increased by increasing the chain length of the alkyl groups.

Properties

Room temperature ionic liquids exhibit many properties which make them potentially

attractive media for many organic reactions.

i. They have essentially no vapour pressure or negligible vapour pressures and therefore do

not evaporate under normal conditions.

ii. They possess generally non-flammability and good thermal stability and do not

decompose over a large temperature range, thereby making it feasible to carry out

reactions requiring high temperature conveniently.

iii. Ionic liquids have a wide range of solubilities and miscibilities and therefore, they are able to

dissolve a wide range of organic, inorganic and organometallic compounds.

iv. They serve as good medium to solubilise gases such as H2, CO, O2 and CO2 and many

reactions are now being performed using ionic liquids and supercritical CO2.

v. The solubility of ionic liquids depends upon the nature of the cations and counteranions.

vi. They generally do not co-ordinate to metal complexes, enzymes and different organic

substrates.

vii. Most of the ionic liquids can be stored without decomposition for a long period of time.

viii. They show a high degree of potential for enantioselective reactions as a significant

impact on the reactivities and selectivities due to their polar and non-coordinating

properties. In addition, chiral ionic liquids have been used to control the

stereoselectivity.

ix. The viscosity of l-alkyl-3-methyl imidazolium salts can be decreased by using hightly

branched and compact alkyl chain, as well as by changing the nature of anion. The

viscosity decreases in the order of

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x. Ionic liquids have wide clectrochemical windows.

xi. Ionic liquids can be used as reaction media and, or catalysts for a wide variety of chemical

reactions.

xii. Ionic liquids can also be used for separations and extractions of chemicals from aqueous

and molecular organic solvents.

xiii. The physical, chemical and biological properties of ionic liquids can be “tuned” or

“tailored” by:

a. switching anions or cations,

b. by designing specific functionalities into the cations and/or anions,

c. by mixing two or more simple ionic liquids.

xiv. Because ionic liquids consist of cations and anions, they have dual functionality. They

therefore impart a unique architectural platform compared with molecular liquids.

Consequently, ionic liquids can potentially be exploited as solvents and new materials

for wide- ranging applications spanning, for example, electrochemistry, organic

chemistry, inorganic chemistry, biochemistry, materials science and pharmaceuticals.

xv. Ionic liquids could contribute significantly to the development of green chemistry and

green technology by, for example:

a. replacing toxic, flammable volatile organic solvents,

b. reducing or preventing chemical wastage and pollution,

c. improving the safety of chemical processes and products.

Preparation of Ionic Liquids

Room temperature ionic liquids are prepared by direct quaterisation of the appropriate

amines or phosphines.

1). Alkylation reaction:

The 1-alkylimididazoles that are used as starting material for the synthesis of many [Cnmim]Cl

type of ionic liquids by alkylation reaction.

a). [C2mim]Cl is prepared by the reaction of 1-methylimididazoles and compressed gaseous chlorobutane.

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b). [C4mim]Cl is commonly used as a precursor for preparing other ionic liquids. It is obtained by the reaction of 1-methylimididazoles and 1-chlorobutane.

c). Halogenalkanes are also used to alkylate pyridine in the preparation of alkylpyridinium salts. [C2py]Br is prepared by the reaction of pyridine and bromoethane.

d). Trihexyl(tetradecyl)phosphonium choride [P6 6 6 14]Cl is prepared from trihexylphosphine (P(C6H13)3) and 1-chlorotetradecane (C14H29Cl).

The aliphatic quaternary ammonium cations are prepared from alkylammonium halides

which are commercially available or they can be prepared simply by the reaction of the

appropriate halogenoalkane and amine.

2). Anion exchange preparation

Ionic liquids with the [NTf2] anion, are prepared by exchange reaction between an

organic halide salt and lithium bis[tri(fluoromethyl)sulfonyl]amide (Li[NTf2]).

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3). Ionic liquids with functionalized alkyl chains

The introduction of hydroxyl or ether functional groups in the alkyl chain considerably

modifies the solubility behavior, while modification of anion ( ) does not seem to

have any significant influence.

The synthesis of functionalised ionic liquids required multistep procedures. These

include the synthesis of a functionalised alkylating agent, followed by alkylation of amine.

The desired functional group is obtained by modification of obtained salt followed by

an anion exchange reaction if required e.g. the Michael-type addition of a protonated tert.amine

or phosphine to α,β-unsaturated compounds.

In the first step, the tert.amine, N-methylimidazole or pyridine, was protonated with an

acid, giving the ammonium salt, and the anion of the final ionic liquid was introduced in this

step. In the second step, the protonated amine was reacted with a,-unsaturated compound in the

presence of weak and volatile bases such as pyridine at 70°C for about 16 h to yield the ionic

liquid.

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4). Chiral ionic liquids synthesis

Numerous ionic liquids have been synthesized with either chiral cations or chiral anions. Chiral ionic liquids are potentially useful as solvents or chiral catalysts for asymmetric organic synthesis. Other

potential applications include resolution of racemates by co-crystallization or extraction and their use as

mobile or stationary phases in chromatography.

Much of the research activity on chiral ionic liquids has focused on ionic liquids with chiral

cations. One example is the chiral ionic liquid, di(1-phcnylethyl)imidazolium nitrate, [dpeirn][NO3], the

cation of which can exist as the (R) optical isomer or the (S)-isomer. The cation was prepared using the

chiral amine 1-phenylethylamine.

Chiral ionic liquid, [dmeim][NO3]

Synthetic Applications

Friedal-Craft Reaction

Friedal-Craft alkylation and acylation are of great commercial importance. The

conventional catalyst in Friedal-Craft reaction is AlCl3 which gives rise to disposal and by-

product problems. The use of ionic liquid [bmim]Cl-AlCl3 in place of solid AlCl3 enhances the

reaction rates and selectivity and also it act as solvent for the reaction. Friedal-Craft alkylation

of aromatic compounds with alkenes using Sc(OTf)3-ionic liquid system giving the benefits of

simple procedures, easy recovery and reuse of catalysts, contributing to development of

environmentally benign and waste free processes.

Friedel–Crafts ReactionFriedel−Crafts acylations are of industrial importance and are associated with a massive consumption of aluminum(III) chloride. It has been demonstrated that acylation reactions can be carried out in acidic chloroaluminate (III) ionic liquids. The regioselectivities and rates observed in these reactions are comparable to the best values known for the traditional acylations. The Friedel−Crafts acylation of benzene has been conducted in acidic chloroaluminate(III) ionic liquid.75 The monoacylated products were obtained as a result of the deactivation of the aromatic ring by the acyl substituent. In addition to benzene and other simple aromatic rings, a range of organic and organometallic substrates (e.g., ferrocene) have been acylated in acidic chloroaluminate(III) ionic liquids.76,77 An in situ IR spectroscopic

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study was performed on the Friedal−Crafts acetylation of benzene in ionic liquids using AlCl3 and FeCl3.78 The results revealed that the mechanism of the Friedel−Crafts acetylation of benzene in ionic liquids was exactly the same as that in 1,2-dichloroethane.Another interesting development is the use of [BMIM][chloroaluminate] as Lewis acid catalyst for the Friedel−Crafts sulfonylation of benzene and substituted benzenes with TsCl (eq 22).79 The substrates exhibited enhanced reactivity, and furnished the corresponding unsymmetrical diaryl sulfones in 83–91% yields under ambient conditions.

Hydroformylation

Hydroformylation of olefins is industrially important reaction. The reaction is carried

out in aqueous-organic biphasic system catalyzed by water soluble Rh catalyst. But, the use of

water as polar phase limits this process to C1-C5 olefins due to low water solubility of higher

olefins.

This solubility problem is overcome by using ionic liquids containing PF, SbF and BF

in an ionic liquid organic biphasic system. The products are separated as an organic phase and

the catalyst can also be used. A small amount of catalyst leaching into organic phase causes

some loss in activity after each run. These problems have been improved by varying the ligand

and the ions of ionic liquids. The platinum catalyzed hydroformylation of 1-octene in

chlorostannate melts in [bmim][Cl] give high n/iso selectivities. The biphasic nature of the

reaction enabled very simple product isolation and leaching of the platinum catalyst into the

product phase was not observed.

3.7. Trost–Tsuji CouplingThe Trost-Tsuji coupling is an important method for synthesizing carbon-carbon bonds

through nucleophilic, allylic substitution. An interesting example is the monophasic reaction of

3-acetoxy-1,3-diphenylpropene with dimethyl malonate in [bmim][BF4]. The product is

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obtained in 91% yield after 5 h at room temperature using Pd(OAc)2/PPh3 as the catalyst system

and K2CO3 as the base.

Biphasic Trost−Tsuji couplings have been conducted by de Bellefon et al., in [bmim]

[Cl]/methylcyclohexane. These workers observed a tenfold improvement in the catalytic

activity due to the higher solubility of the substrates in the ionic liquid (eq 17). Enhanced

selectivity was also achieved, since the formation of cinnamyl alcohol and phosphonium salts

was suppressed.

4.6. Stereoselective HalogenationThe analysis of alkenes in a complex hydrocarbon mixture, such as gasoline, is a difficult process. The analysis of alkenes in the presence of alkanes, however, can be achieved after their transformation into the corresponding dihalo derivatives.88 Several ionic liquids—[BMIM][PF6], [BMIM][BF4], [BMIM][Br], and [BMIM][Cl]—have been studied as alternatives to toxic chlorinated solvents for the stereoselective halogenation of alkenes and alkynes (eq 26).89

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Background

There is growing interest in Ionic Liquids (IL's) as a green solvent

 Features that make IL’s attractive for use in organic synthesis in general and catalytic processes in particular are

their insignificant vapour pressure (even at high temperatures), non-flammability, high thermal, chemical and electrochemical stability, high solvating properties ease of recycling.

 Another important feature is the possibility of tuning their physical and chemical properties by varying the nature of the anion and side chain.

 The drawback is that they are expensive.  However, their high cost stems not from the cost of ingredients but from the challenges faced in the synthesis (which is usually carried out in batch). 

The synthesis is highly exothermic, and in batch must be carefully controlled in case hotspots form in the reactor which will lessen the overall purity of the product.  Reaction times may be up to 24 hrs, with temperatures kept low, and dilution solvents are used which must be removed later.

 In continuous flow, however, these challenges are straightforward to address.  Large surface area to volume ratios and consistent, steady conditions throughout the reactor enable ILs to be synthesized using neat reagents, at far higher reaction temperatures (resulting in radically shorter reaction tiomes, of the order of minutes).

 Application Note 16 - Bromination of Alkenes with NBS under continuous flow

 

Bromination of unsaturated C-C bonds with NBS is a well known and widely used procedure, although when carried out in batch, slow and careful addition of the NBS is often required in order to prevent over-bromination & avoid thermal runaway. This study demonstrates how with flow chemistry these factors are no longer an issue.

 Application Note 15 - Bromination of Ketones

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Bromination with molecular bromine in batch mode usually requires slow and careful addition of the bromine reagent to control thermal kinetics, and often results in poor selectivity. This study demonstrates safe bromination in flow, giving rapid complete conversion and high selectivity.

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Fischer Indole Synthesis

The conversion of aryl hydrazones to indoles; requires elevated temperatures and the addition of Brønsted or Lewis acids. Some interesting enhancements have been published recently; for example a milder conversion when N-trifluoroacetyl enehydrazines are used as substrates. .

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The 1,4-dicarbonyl compounds were converted to pyrrole rings via acid-mediated

dehydrative cyclization in presence of primary amines. The mine limitation of the standard

protocol is the hars reaction conditions (reflux in acetic acid for extended times). The use of

microwaves slashes the reaction times to few minutes, giving good isolated yields of the

desired products.

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Functionalized organozinc reagents readily react regioselectively with various

aryldiazonium salts to yield polyfunctional indoles after heating with microwave irradiation.

This new organometallic variation of the Fischer indole synthesis tolerates a wide range of

functional groups and can be readily scaled up.

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Regioselective Friedal-Crafts acylation of aromatics with acetyl chloride was performed in chloroaluminate ILs. High selectivity for the formation of para-products was obtained, in excellent yields. It should be noted, however, that separation of the product is difficult due to AlCl3-ketone complex.

The total synthesis of the pharmaceutical Pravadoline was carried out in ILs as shown below. In this two-step reaction, a base promoted nucleophilic displacement reaction and a Friedal-Crafts acylation readily occur in [bmim]PF6] IL giving 94% yield of the pharmaceutical.

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Ionic Liquids

Ionic Liquids are a peculiar and fascinating class of new chemicals with the potential to improve development in organic chemistry and chemical technology, stimulating progress in a lot of different research fields. The designing of chemical processes and products that reduce or eliminate the use and generation of hazardous substances has become a new focus in many aspects of pure and applied chemistry. In this context, Ionic Liquids are regarded as environmentally friendly substitutes for volatile organic compounds (VOCs) essentially because of their low vapour pressures and their specific advantage to act as solvent or catalyst.

WHAT'S SO SPECIAL ABOUT IONIC LIQUIDS?

Ionic Liquids are compounds consisting entirely of ionic species with an organic cation and an inorganic or organic anion. They have intrinsically useful properties such as high ionic conductivity, thermal stability (over 300 ºC), negligible vapour pressure and a large electrochemical window. Depending on the anion and substitute groups of the cation, these compounds can solubilize alcohols, alkyl halides, carbonyl compounds, supercritical CO2 (scC02) and also transition metal complexes. Simultaneously, they present a low miscibility in alkanes, dialkyl ethers and water.

APLICATIONS OF IONIC LIQUIDS

ORGANIC CHEMISTRYThe use of ionic liquids as a recyclable and environmentally benign medium has been attracting considerable attention for chemical transformations including non-catalytic reactions, biocatalytic and catalytic reactions in monophasic systems (both substract and catalyst dissolved in the ionic liquid, and sometimes the ionic liquid works like a catalyst itself), biphasic systems (with the catalyst dissolved in the ionic liquid and the substract/product in a second phase or vice versa) and triphasic systems( with an ionic liquid phase, an organic phase and an aqueous phase).Reactions like oxidations, hydrogenations, hydroformylations, Heck reaction, olefin oligomerisation, Trost-Tsuji coupling, dihydroxylations and epoxidations among several others have been tried successfully using such systems.• Organic synthesis• Catalysis

ELECTROCHEMISTRY• Electrolytes

ANALYTICAL CHEMISTRY

. Stationary phase for chromatography

• Matrices for MS

PHYSICAL CHEMISTRY

• Material with relatively unusual thermodynamic and stability properties.

CHEMICAL ENGINEERING

Solute extraction and recovery using supported liquid membranes is recognized as one of the most promising membrane-based processes. The use of ionic liquids (RTILs) as an immobilized phase in a supporting membrane is particularly interesting due to the nonvolatile character of the RTILs and their solubility properties in the surrounding phases, which makes it possible to obtain very stable supported liquid membranes without any observable loss of the RTIL to the atmosphere or the contacting phases.

• Separation processes

• Extraction processes

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BIOTECHNOLOGY• Enzymes

ENERGY• Fuel and solar cells

• Lubricants

• Batteries

MATERIALS• Nanomaterials

• Liquid Crystals

Volatile organic solvents (VOC’s) are used in a variety of industrial applications such as in the production of pharmaceuticals, the manufacture of electronic components, processing of polymers, refrigeration systems, electrodeposition, batteries electrochemical sensors, capacitors and the synthesis of chemicals. As a result of their volatile nature, such solvents easily evaporate into the environment.

The use of VOC’s poses a risk to people working with them or living in close proximities to facilities using them. In addition VOC’s have been heavily implicated in causing changes to the global climate, the formulation of smog as well as being identified as a source of ozone depletion. Protocol has forced many industries and organizations to re-evaluate their chemical operations, due to the adverse environmental impact caused by the use of VOC’s by investing in clean technology that reduces waste and by-products from industrial processes to a minimum. It is from this background that the pioneering work on IL was commenced.

Specific IL have the potential to be classified as ideal green solvents as they have negligible vapour pressure and do not evaporate into the atmosphere.

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