2. Ionic Liquids in Green Chemistry
Dr. Nie Wanli
Chemistry Department of NWU, Xi’an

3. Ionic Liquids in Green Chemistry
What are Ionic liquids (ILs)?
Why consider of ILs?
The characteristic properties of ionic liquids
The synthetic methods
Research with ILs
Outlook

4. What are ionic liquids? Definition:
Quite simply, they are liquids that are composed entirely of ions.
In the broad sense, this term includes all the molten salts, for instance, sodium chloride at temperatures higher than 800 oC.
Most of the liquids with which you are familiar (e.g. water, ethanol, benzene etc) are molecular. That is, regardless of whether they are polar or non-polar, they are basically constituted of molecules. Unlike the molecular liquids, they are basically constituted of ions.

5. What are ionic liquids?
Ionic liquids are salts that are liquid at low temperature (<100 oC) which represent a new class of solvents with nonmolecular, ionic character.
Today, however, the term "ionic liquid" is used for the salts whose melting point is relatively low (below 100°C). In particular, the salts that melt at room temperature are called "room-temperature ionic liquids" (RTILs).

6. Room temperature Ionic liquids
Room temperature ionic liquids (RTIL) are salts that are liquid over a wide temperature range, including room temperature.
Variations in cations and anions can produce literally millions of ionic liquids, including chiral, fluorinated, and antibacterial IL.
Large number of possibilities allows for fine-tuning the ionic liquid properties for specific applications

7. The driving forces
The problems in the chemical industry with the volatile organic compounds (VOCs) :
toxic and/or hazardous
serious environmental issues, such as atmospheric emissions and contamination of aqueous effluents
The driving force in the quest for novel reaction media:
greener processes
recycling homogeneous catalysts
The chemical industry is under considerable pressure to replace many of the volatile organic compounds (VOCs) that are currently used as solvents in organic synthesis. The toxic and/or hazardous properties of many solvents, notably chlorinated hydrocarbons, combined with serious environmental issues, such as atmospheric emissions and contamination of aqueous effluents is making their use prohibitive. This is an important driving force in the quest for novel reaction media. The current emphasis on novel reaction media is also motivated by the need for efficient methods for recycling homogeneous catalysts.

8. The key to waste minimization
The key to waste minimization in chemicals manufacture is the substitution of classical ‘stoichiometric’ syntheses by atom efficient, catalytic alternatives.

9. What is “green chemistry” ?
Recently ionic liquids have often been discussed as promising solvents for “clean processes” and “green chemistry”.
These two catchwords means to reduce drastically
the amounts of side and coupling products and
the solvent and catalyst consumption in chemical processes.
the use of ionic liquids as novel reaction media may offer a convenient solution to both the solvent emission and the catalyst recycling problem.

10. Why consider Ionic liquids ?
ILs are environmentally-friendly alternatives to organic solvents for liquid/liquid extractions. Catalysis, separations, and electrochemistry.
ILs will reduce or eliminate the related costs, disposal requirements, and hazards associated with volatile organic compounds (VOCs).
The ability to fine-tune the properties of the IL medium will allow selection of IL to replace specific solvents in a variety of different processes.
the use of ionic liquids as novel reaction media may offer a convenient solution to both the solvent emission and the catalyst recycling problem.

11. Important IL Properties
High ionic conductivity
Non-flammable
Non-volatile
High thermal stability
Wide temperature range for liquid phase (- 40 to + 200°C)
Highly solvating, yet non-coordinating
Good solvents for many organic and inorganic materials

12. Great promise
Designability. By combining different anions with cations, it is possible to generate a huge number of different ionic liquids, each with their own specific solvent properties. Some ionic liquids are water soluble, others are not. Some dissolve typical organic solvents, other are not.
They can be functionalized to act as acids, bases or ligands and have the potential to catalyze certain reactions in certain systems.
Ionic liquids are non-volatile, hence they may be used in high vacuum systems and high temperature reactions without the requirement of a pressure vessel to contain the vapors.
A number of simple physical properties of ILs suggested that they have great promise.

13. They are good solvents for a wide range of both inorganic, organic and polymeric materials and unusual combinations of reagents can be brought into same phase. However they do not dissolve glass, polyethylene, or Teflon. High solubility usually implies small reactor volumes in the final process.
They are immiscible with a number of organic solvents and provide a non-aqueous, polar alternative for two phase systems, this has been used to effect total catalyst recovery in a number of transition metal catalyzed reactions. Hydrophobic ionic liquids can also be used as immiscible polar phase with water.
They are often composed of poorly coordinating ions, so they have the potential to be highly polar non-coordinating solvents, this is particularly important when using transition-metal based catalysts.

14. Characteristics of RTIL
Choice of cation and anion determine physical properties (e.g. melting point, viscosity, density, water solubility, etc.)
Cations are typically big, bulky, and asymmetric accounting for the low melting points
The anion contributes more to the overall characteristics of the IL and determines the air and water stability
Melting point can be easily changed by structural variation of one of the ions or combining different ions

15. Typical RTIL Cations
Room temperature ionic liquids consist of bulky and asymmetric organic cations such as :
Among the various known ionic liquids, those based in quaternary ammonium or phosphonium salts show a wide range of applications including in the fields of organic syntheses and biphasic catalysis and in other areas, e. g. surfactants, electrochemistry, separations, and photochemistry.
Ionic liquids are generally salts of organic cations, such as imidazolium, pyridinium, quaternary ammonium and quaternary phosphonium, and anions such as halogen, triflate, tetrafluoroborate and hexafluorophosphate, which exist in the liquid state at relatively low temperatures.
1-alkyl-3-methylimidazolium, 1-alkylpyridinium, N-methyl-N-alkylpyrrolidinium or ammonium ions
Imidazolium ion Pyridium ion Ammonium ion Phosphonium ion
Scheme 1. Important types of cation

16. Anions for RTIL
A wide range of anions is employed, from simple halides which inflect high melting points, to inorganic anions such as:
Anions:
A wide range of anions is employed, from simple halides which inflect high melting points, to inorganic anions such as tetrafluoroborate and hexafluorophosphate and to large organic anions like bis-trifluorsulfonimide, triflate or tosylate.

17. [PF6]- for moisture stable, water immiscible IL
[BF4]- for moisture stable, but water miscible IL depending on the ratio of ionic liquid: water, system temperature, and alkyl chain length in the cation.
Less common anions include:
Triflate [TfO] Nonaflate [NfO]
CF3SO CF3(CF2)3SO2-
Bis(triflyl)amide [Tf2N] Trifluoroacetate [TA]
(CF3SO2)2N CF3CO2-
Heptafluorobutanoate [HB]
CF3(CF2)3CO2-

19. Historical Development
Ethylammonium nitrate, which is liquids at RT was first described in 1914.
In the later 1940s, n-alkylpyridinium chloroaluminates were studied as electrolytes for electroplating aluminum.
The first examples of ionic liquids based on dialkylimidazolium cations were reported in the early 1980s. They contain chloroaluminate anions and proved to be useful catalysts/solvents for Friedel-Crafts acylations.
The first example of the new ionic liquids, that currently are receiving so much attention as novel media for homogeneous catalysis, ethylmethylimidazolium tetrafluoroborate was reported in 1992.
Room temperature ionic liquids are not new !
Even though the first representative has been known since 1914, ionic liquids have only been investigated as solvents for transition metal catalysis in the past ten years.

21. Ionic liquid synthesis
Direct quaternization to form cation
------Alkylation reagents
Indirect quaternization to form cation
General procedures:

22. Ionic liquid synthesis
General procedures:
The initial step in the synthesis of ionic liquids is the quaterization, of an amine or phosphane for example to from cation.
In case where it is not possible to from the desired anion directly by the quternization reaction, a further step follows( synthesis steps Iia or Iib in Scheme 2).
for example, starting from an ammonium halide, two different paths to vary the anion are possible:
first, the halide can be treated with a lewis acid. This lead to an ionic liquid of type……
alternatively it is possible to exchange the halide ion for the desired anion, this can be done by
the addition of a metal salt with precipitation of another salt
or over an ion exchange
or by displacement of the halide ion by a stronge acid with the release of HX.

23. The types of RTILS organoaluminates
air- and water-stable ionic liquids

24. Organoaluminates
Since the organoaluminate ionic liquids have donor and acceptor patterns, The Lewise acidity can be modulated by the relative amount of the aluminum compound. Acidic or basic IL attainable through varying the concentration of the following species:
Al2Cl Cl- = AlCl4-
Acidic basic neutral
Basic haloaluminates preclude solvation and solvolysis of metal ion species

25. Large electrochemical windows for both chloro and bromo ionic liquids.
The advantage of this controlled Lewis acid ionic liquids is their use in Ziegler-Natta Type catalytic reactions
BUT: moisture sensitive

26. Table 1.
Table 1. Table 1.
Table 1. Melting Point (Mp) and Viscosity (n ) of 1-Ethyl-3-methylimidazolium Chloride/Aluminum Chloride Ionic liquid at different Molar Fractions (x) of the Aluminum Compound x
n (p)
Mp (oC) PH
0.36
1.59
- 60
basic
0.50
0.20 2
neutral
0.66
0.16
- 80
acidic
Organoaluminate melts are the most investigated class of molten salts.
These compounds are easily prepared by mixing quaternary ammonium salts with AlCl3.
The physical-chemical properties depend maily upon the molar fraction of the alumium compounds.
Thus, ionic liquids with the liquid phase ranging down to –80 C can be prepared with relatively small viscosity.
Since the organoaluminate ionic liquids have donor and acceptor patterns, The Lewise acidity can be modulated by the relative amount of the aluminum compound. This Lewis acidity can be expressed by the molar fraction (x) of the aluminum compound.-----
The advantage of this controlled Lewis acid ionic liquids is their use in Ziegler-Natta Type catalytic reactions.
F-C and D-A reactions, and for the polymerization of olefins and in Z-N type reactions
Since these melts are extremely air and water unstable and several organic substances and organometallic compounds are not chemically inert in these media, their applications as immobilizing agents for biphase catalysis is limited.

27. Ambient-Temperature, Air- and Water- stable Ionic liquids
Can be obtained by the substitution of the halide anion of the 1,3- dialkylimidazolium cation by other weekly coordinating anions.
In order to be liquid at room temperature, the cation should preferably be unsymmetrical. The melting point is also influenced by the nature of anion.
Can be used for the immobilization of transition-metal catalyst precursors in biphase catalysis.
Due to their inherent ionic nature, ionic liquids can effectively stabilize cationic transition-metal special that are known to be more attractive than their neutral analogues.

28. “The melting point is influenced by” the nature of cation and anion

29. Applications 1. as reaction media for synthesis and catalysts
Because of their properties, ionic liquids attract great attention in many fields, including organic chemistry, electrochemistry, physical chemistry, and engineering.
1. as reaction media for synthesis and catalysts
2. in electrochemistry
3. in separation processes
4. as electrolytes in solar cells
5. as lubricants
6. as propellants in small satellites
7. matrixes in MALDI mass spectrometry
8. Applications in other areas

31. ------general considerations
Catalysis in ionic liquids: general considerations
Room temperature ionic liquids exhibit many properties which make them potentially attractive media for homogeneous catalysis:
4 They have essentially no vapour pressure, i.e. they do not evaporate and are easy to contain.
4 They generally have reasonable thermal stability. While tetraalkylammonium salts have limited thermal stability, owing to decomposition via the Hoffmann elimination, emimBF4 is reportedly stable up to 300 °C and emim-
(CF3SO2)2N up to 400 °C.16a In other words many ionic
liquids have liquid ranges of more than 300 °C, compared to the 100 °C liquid range of water.
4 They are able to dissolve a wide range of organic, inorganic and organometallic compounds.
4 The solubility of gases, e.g. H2, CO and O2, is generally good
which makes them attractive solvents for catalytic hydrogenations, carbonylations, hydroformylations, and aerobic oxidations.
4 They are immiscible with some organic solvents, e.g. alkanes, and, hence, can be used in two-phase systems. Similarly, lipophilic ionic liquids can be used in aqueous biphasic systems.
4 Polarity and hydrophilicity/lipophilicity can be readily adjusted by a suitable choice of cation/anion (see earlier) and ionic liquids have been referred to as ‘designer solvents’.7
4 They are often composed of weakly coordinating anions, e.g. BF42 and PF62 and, hence, have the potential to be highly
Catalysis in ionic liquids
------general considerations
potentially attractive media for homogeneous catalysis:
They have essentially no vapour pressure which facilitates product separation by distillation.
They are able to dissolve a wide range of organic, inorganic and organometallic compounds.
The solubility of gases, e.g. H2, CO and O2, is generally good which makes them attractive solvents for catalytic hydrogenations, carbonylations, hydroformylations, and aerobic oxidations.
Room temperature ionic liquids exhibit many properties which make them potentially attractive media for homogeneous catalysis:

32. They are immiscible with some organic solvents, e. g
They are immiscible with some organic solvents, e.g. alkanes, and, hence, can be used in two-phase systems. This gives rise to the possibility of a multiphase reaction procedure with easy isolation and recovery of homogeneous catalysts.
Polarity and hydrophilicity / lipophilicity can be readily adjusted by a suitable choice of cation/anion and ionic liquids have been referred to as ‘designer solvents’.

33. They are often composed of weakly coordinating anions, e. g
They are often composed of weakly coordinating anions, e.g. BF4- and PF6- and, hence, have the potential to be highly polar yet non-coordinating solvents. They can be expected, therefore, to have a strong rate-enhancing effect on reactions involving cationic intermediates.
Ionic liquids containing chloroaluminate ions are strong Lewis, Franklin and Brønsted acids. Protons present in emimAlCl4 have been shown to be superacidic. Such highly acidic ionic liquids are, nonetheless, easily handled and offer potential as non-volatile replacements for hazardous acids such as HF in several acid-catalysed reactions.

34. Publications to date show that replacing an organic solvent by an ionic liquid can lead to remarkable improvements in well-known processes.
There are also indications that switching from a normal organic solvent to an ionic liquid can lead to novel and unusual chemical reactivity.
This opens up a wide field for future investigations into this new class of solvents in catalytic application.
Publications

35. Applications Solvent Properties Transition Metal Catalysed Reaction
Carbocation Chemistry
Separations
Electrochemistry
Photochemistry

36. Solvent Properties
Diels-Alder reaction
Aldol condensation
Others

37. Diels-Alder reaction Ionic liquids Composition (% AlCl3) Time (h)
cyclopentadiene
methyl acrylate ester
Ionic liquids
Composition
(% AlCl3)
Time (h)
Endo/exo Y. (%)
ratio
emimCl/(AlCl3)x
48 (basic) 22 72
51 (acidic)
bmimBF4 -
Diels-Alder reaction
the D-A reaction between cyclopentadiene and methyl acrylate ester has been reported. In the D-A reaction using 1-ethy-3-methylimidazolium chloride/chloroaliuminate[emimCl/(AlCl3)x], the endo/exo ration of the products varies largely, depending on the ratio of emimCl/(AlCl3)x. when the same reaction is carried out with 1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF4), it showed similar reactivity to Lewis base emimCl/(AlCl3)x.

38. Endo selectivity ----highly polar solvents
Increases in the reaction rate
Allows water sensitive reagents to be used
Simple workup
Ionic liquid can be reused
The IL have a dramatic effect on this reaction. They generate endo selectivities that show they are highly polar solvents only be rivalled by water. The increased endo selectivity is accompanied by dramatic increases in the rate of the reaction. Use of the ionic liquids allow water sensitive reagents to be used, so increasing the range of materials that may be generated. In addition to this it is simple to remove traces of organic material left in the ionic liquids after the reaction and reuse the solvent, something that is notoriously difficult in water.

39. Aldol Condensation Solubility entry solvent reaction type conv.(%)
selectivity (%) 1 2* 3
4**
bmimBF4
Aldol I 99 64 2 - 33
H2O
100 82 18
emimBF4
Aldol II 4 6 69 21 80 14 5 36 59
Aldol condensation
the aldol condensation reaction using ionic liquids has been reported. In the reaction for obtaining 2,4-dimethyl-hept-a-enal 3 from propanal via two aldol condensations, the conversion values of the ionic liquid phase is comparable to water medium in the aldol I reaction. However, the product selectivity is reduced, as can be seen in the figure below. This is due to a side reaction proceeding from the high solubility of product 1 toward the ionic liquid. In contrast, in the aldol II reaction, as compared with the reaction in water. The product selectivity in ionic liquids are increased. This is because the hydrogenated product of 1 is difficult to dissolve in water but easy in ionic liquids.
Solubility

40. Recent activity with RTIL as solvent
sc-CO2 Stripping after Extraction (J. Brennecke)
Conductive RTIL (P. Bonhote)
Ionic liquid-polymer gel electrolytes (R. Carlin)
Catalytic hydrogenation reaction (J. Dupont)
Electrochemistry in RTIL (C. Hussey)
Butene dimerization (H. Olivier)
Benzene polymerization (B. Osteryong)
Two-phase separations (R. D. Rogers)
Friedel-Crafts; regioselectivie alkyl. (K. seddon)
Organometallic synthesis (T. welton)
… This list is not exhaustive

41. Transition Metal Catalyzed Reaction
Hydrogenation
Heck reaction
Stille reaction
Other reactions
The ionic liquids are good solvents for many transition metal catalysts, particularly those that are salts.

42. Hydrogenation reaction
Dupont et al.
P (atm)
conv.(%)
% e.e
1st use 50
100
78 (S)
2nd use 75
84 (S)
3rd use 25 90
79 (S)
4th use 95
67 (S)
Hydrogenation reaction
In the asymmetrix hydrogenation of C-C double bond using homogenous chiral transition metal complexes, the recovery of the catalyst and the seperation of the products are often troublesome. Dupont et al. have reported an example in which the reagents are allowed to react in a two phase system of an ionic liquid and an alcohol. After the reaction is complete, the product exists in the alcoholic phase, while the catalyst in the ionic liquid phase. Thus, the product and the catalyst can be easily seperated by decantation. In addition, the catalyst which exists in the ionic liquid phase can be reused with loss in activity.
Two phase system
Simple workup decantation
Ionic liquid/catalyst phase can be reused

43. IL in Two-Phase Catalytic Reactions
investigating the use of ionic liquids in two-phase catalysis. Here the catalyst is immobilised in the ionic liquid layers and the organic starting materials and products are introduced and removed in a separate organic layer. The catalyst stays in the ionic liquids and is reused later.

44. Heck Reaction (1) Polar solvent Expensive Phosphine ligand
styrene
stilbenes
entry X R
conv.(%) 1 I H
100 2 Br
CHO 3
MeCO 79
2. Heck reaction
in the heck reaction using palladium catalysts, polar solvents such as DMF and acetonitrile are employed, and aryl iodides are normally used as substrates. In cases where the less expensive but less reactive aryl bromides or chlorides are employed, it is necessary to use more active catalysts or add phosphine ligands in order to retain the catalytic activity. By utilizing 1-butyl-3-methylimidazolium bromide (bmimBr) as solvent, aryl bromides react with styrene to afford stilbenes in high yields without adding a phosphine ligand.
Polar solvent
Expensive
Phosphine ligand
Less expensive
High yields
Without phosphine

45. Heck reaction (2) High regioselectivity
enol ethers
entry
solvent
conv.(%)
a/b
E/Z
Y.(%) 1
toluene 23
46/54
68/32 2
DMSO
100
75/25
79/21 3
bmimBF4 50
>99/1 4* 95
under the normal heck reaction conditions The reaction of enol ethers bearing an electron donating group with aryl halides generates a mixture of –substituents and –substituents. However the reaction of vinyl ethers with aryl halides using bmimBF4 as solvent gives only –subsituents specifically.
High regioselectivity
Simple workup distillation

46. Stille reaction Simple workup -------extraction
vinyltributyltin
iodocyclohexenone
Y. (%)
1st use 82
2nd use 78
3rd use
72*
Stille reaction
The stille reaction is a useful reaction, to form a c-c bond under mild conditions in the presence of palladium catalyst where an organotin compound and an electrophilic reagent are reacted. In the reaction of vinyltributyltin and iodocyclohexenone in an ionic liquid, the product can be extracted with ether, and the catalyst is retained in the ionic liquid. The ionic liquid and the catalyst can be reused as they are. This ionic liquid/catalyst phase is air and moisture stable. And thus can be used after a long strorage without loss in activity.
Simple workup extraction
Ionic liquid/catalyst phase can be reused
Air and moisture stable

47. Suzuki-Miyaura coupling reaction Trost-Tsuji coupling
Other reactions
Suzuki-Miyaura coupling reaction
Trost-Tsuji coupling
Hydroformylation (biphase)
Stabilize catalysts
Simple workup
Atom economy

48. Carbocation Chemistry
IL containing chloroaluminate anions are strong Lewis acids and if protons are present they are superacidic.
The ionic liquids acts as both a solvent and catalyst for a acid catalysed processes involve cationic intermediates, e,g. carbenium and acylium ions
The ionic liquids acts as both a solvent and catalyst for a acid catalysed processes
Since Lewis and Bronsted acid-mediated processes generally involve cationic intermediates, e,g. carbenium and acylium ions, one would also expect to see substantial rate enhancement in ionic liquid. Indeed, some of the first reactions to be studied in ionic liquids were F-C akylations and acylations.
Friedel-Crafts alkylations and acylations
Arene exchange reactions

49. Friedel-Crafts reaction---acylation
methoxybenzophenone
anisole
quantitatively
regioselective
Y 64% in acetonitrile
p-/o- = ratio of 93/7
Friedel-Crafts reaction
here is an example of the Friedel-Crafts reaction. In the benzoylation of anisoles catalyzed by copper triflate in bmimBF4, methoxybenzophenone is quantitatively obtained within 1h, with a p-/o-product ratio of 96/4. The same reaction performed using acetonitrile gave a lower conversion of 64% at 1 h, with the reduced p-/o-product ratio of 93/7.
The Friedel-Crafts alkylation of benzene with long chain –olefin catalyzed by chloroaluminate ionic liquids modified by HCl were shown to give higher rated and more favourable product distributions, which was attributed to the superacidities of these media.

50. Friedel-Crafts reaction---akylations
The Friedel-Crafts alkylation of benzene with long chain –olefin catalyzed by chloroaluminate ionic liquids modified by HCl which was attributed to the superacidities of these media, were shown to give higher rates and more favorable product distributions.

52. Arene exchange reactions
IL can function as both catalyst and solvent
In a series of arene exchange reactions on ferrocene, an acidic [bmim]+ chloroaluminate IL was used where [Al2Cl7]- is the active Lewis acid.
Conventional problems with these reactions (e.g., lower yields with solid arenes) are eliminated.
Reactant
Arene
Product
Yield (%)
Benzene
Fe(C5H5)(C6H6)+ 53
toluene
Fe(C5H5)(C6H5Me)+ 64
napthalene
Fe(C5H5)(C10H8)+

53. Separations
Witting reaction
Others

54. Witting reaction
Y. (%)
E/Z (%)
1st use 82
97/3
2nd use 83
6th use 91
Witting reaction
The reaction is a useful method for C-C double bond formation. However, the separation of the product and the by-product, triphenylphosphine oxide, is a classic problem. The separation and purification and usually carried out by crytallization or chromatography. When an ionic liquid is used as solvent, the product and phosphine oxide can be easily separated by combining an ether extraction and a toluene extraction after the reaction is complete. In addition, it is possible to efficiently reuse the ionic liquid.
The separation of the product and triphenylphosphine oxide
Extractions
Reuse IL

57. Reduction Lower temperature ionic liquid temp. (oC) time (h) Y. (%)
bmimBF4
100 16 93
emimBF4 90
emimPF6 96
r.t. 48 94
Reduction
The reduction of aldehydes using trialkyboranes is an important organic transformation reaction. However, reductions using simple trialkyboranes generally require reaction temperatures in excess of 150 C. Kabalka et al. have reported this reduction using trialkyboranes in which bmimBF4 , emimBF4, and 1-ethyl-3-methylimidazolium hexafluorophosphate(emimPF6) are used as solvents. For example, when benzaldehyde was reduced by tributylborane in emimPF6, the reaction proceeded rapidly at 100 C to give the product in high yield. Although long reaction time is needed comparatively, the product can be obtained even at room temperature. In addition, a photoreduction has also been reported using ionic liquids.
Lower temperature

58. Fluorination Short reaction time High yield entry solvent cosolvent
N-fluoro-N’-(chloromethyl)triethylenediamine bis(tetrafluoroborate)
3-fluorinated 2-oxoindoles
entry
solvent
cosolvent
Temp.(oC)
Time (h)
1 (%)
2 (%) 1
MeCN
H2O
r.t.
over
night 71
small
amount 2
bmimBF4
MeOH 20 3 99 -
Fluorination
The fluorinaiton of fluorines into heterocyclic compounds is important in the synthesis of bioactive compounds. In the electrophilic fluorination of indoles using N-fluoro-N’-(chloromethyl)triethylenediamine bis(tetrafluoroborate) as fluorinating agent and bmimBF4 as a solvent, 3-fluorinated 2-oxoindoles can be obtained in high yield in a short period of time compared to the conventional method.
Short reaction time
High yield

59. room temperature, economic
Ring opening reaction
epoxide
entry R1 R2 R3
product
Time (h)
Y. (%) 1 Ph H
5.0 85 2
-(CH2)4-
6.0 83 3
PhOCH2 89 4 Bu
p-tol
Ring opening reaction
ß-aminoalcohols are as useful building blocks for the synthesis of bioactive compounds. One of the synthetic methods to obtain –aminoalcohols involves the ring opening using amines. However, this reactions require a large excess of the amines at elevated temperatures. The high temperature of epoxides reaction conditions are not only detrimental to certain functional groups but also to the control of regioselectivity. Subsequently, a variety of activators or promotyers such as metal amides, metal triflates and transition metal halides have been developed. However, many of these are often expensive or are needed in stoichiometric amounts, thus limiting their practicality. In the system using ionic liquids, the reaction proceeds at room temperature to give -aminoalcohols in high yield.
in the cases of glycidyl ether or alkyoxiranes in entries 3 and 4, amines attack on the less sterically hindered site on the epoxides. After the reaction, the product was extracted with ether, followed by drying at 80 C under reduced pressure. The ionic liquid was reused in five runs without any loss of activity.
room temperature, economic

60. This reactions require a large excess of the amines at elevated temperatures. The high temperature reaction conditions are not only detrimental to certain functional groups but also to the control of regioselectivity.
Subsequently, a variety of activators or promoters such as metal amides, metal triflates and transition metal halides have been developed. However, many of these are often expensive or are needed in stoichiometric amounts, thus limiting their practicality.
In the system using ionic liquids, the reaction proceeds at room temperature to give -aminoalcohols in high yield. After the reaction, the product was extracted with ether.The ionic liquid was reused in five runs without any loss of activity.

61. similar yields to those of organic solvent systems
Enzymatic reaction
similar yields to those of organic solvent systems
Enzymatic reaction
enzymatic reactions using ionic liquids have also been reported. It is known that lipase tolerates non-natural reaction conditions, and reactions in organic solvents have intensively been carried out. For example, transesterificationa in organic solvents are well known as a useful synthetic methods for the preparation of optically-active compounds. In the asymmetric transesterification of allylic alcohols using ionic liquids, the desired products are afforded in similar yields to those of organic solvent systems.

62. Others
As described above , a variety of reactions utilizing ionic liquids have been conducted, and the improvement of yields and the recovery and reuse of solvents have been reported. Furthermore, they are also applied to alkylations, allylations, epoxidations, cycloadditions, hydroesterifications and reactions using supercritical CO2, in which they are reported to be effective. Ionic liquids are used not only as reaction solvents but also reported in electrochemical applications as the electrolyte of a secondary battery. Dure to their high ionic conductivity.
Ionic liquid are attracting attention as environmentally-friendly excellent solvents, because they are safe , easy to separate and purify from the products, recyclable as solvents, and often can be reused with the catalyst. polymerizations

64. Electrochemistry
Unique features of chloroaluminate ionic liquids include a large electrochemical window, although these anions are moisture sensitive
Possible applications include low cost and recyclable electrolytes for batteries, photoelectrochemical cells, and electroplating
BF4- and PF6- ionic liquids have been developed as moisture stable electrolytes
Ionic liquids are used not only as reaction solvents but also reported in electrochemical applications as the electrolyte of a secondary battery. Dure to their high ionic conductivity.

65. Other types of ionic liquids
As the range of application for ionic liquids increase, the need for ionic liquids with special chemical and physical properties also increases. With this in mind, the term “tast-specific ionic liquid” has been introduced to described ‘designer’ligands prepared for special applications. Other types of ionic liquids:
The new types of ionic liquids:
As the range of application for ionic liquids increase, the need for ionic liquids with special chemical and physical properties also increases. With this in mind, the term “tast-specific ionic liquid” has been introduced to described ‘designer’ligands prepared for special applictions.

71. New types of cations and anions

73. Concluding remarks Future IL research Needs:
Comprehensive toxicity data
Combinatorial approach to IL development
Database of physical properties, chemistries, etc.
Comparators for direct comparison of IL and traditional solvents
Industrial input into a research Agenda
Economic synthetic pathways
Wider availability
Concluding remarks
However, it remains to be seen how 'environmentally-friendly' ILs will be once widely used by industry. Research into IL aquatic toxicity has shown them to be as toxic or more so than many current solvents already in use. Available research also shows that mortality isn't necessarily the most important metric for measuring their impacts in aquatic environments, as sub-lethal concentrations have been shown to change organisms' life histories in meaningful ways. Balancing between zero VOC emissions, and avoiding spills into waterways (via waste ponds/streams, etc.) should become a top priority. That said, with the enormous diversity of substituents available to make useful ILs, they ought to be designed with the foresight of having useful physical properties and less toxic chemical properties.

74. REFERENCES
Further information regarding physical properties, chemistry, and uses of ionic liquids:
[1] Welton T. Chem . Rev., 1999, 99: [2] Wasserscheid P, Keim W. Angew Chem. .Int. Ed. Engl., 2000, 39: [3] Freemantle M. (a) Chem . Eng . News, 2000, 78 (May)15: 37-39; (b) Chem . Eng . News, 2001, 79 (Jan)1: [4] Earle M J, Seddon K R. Pure Appl, Chem., 2000, 72 (7): [5] Chum H L, Koch V N et al. J. Am. Chem, Soc., 1975, 97: [6] Wilkes JS et al . Inorg . Chem., 1982, 21: [7] a) Blanchard L A et al. Nature, 1999, 399: 28; b) Blanchard L A et al. Ind. Egn. Chem. Res., 2001, 40: 287. [8] Chauvin Y, Mubmann L, Olivier H. Angew. Chem. Int. Engl., 1995, 34: [9] Monteiro A L et al. Tetrahedron Asymmetry, 1997, 2: [10] Song C E, Roh E J. Chem. Commun., 2000: [11] Dullins J E L et al. Organometallics, 1998, 17: 815. [12] Kakfman D E et al. Synlett., 1996: 1091.

75. [13] Mathews C J, Smith P J, Welton T. Chem. Commun. , 2000: 1249-1250
[13] Mathews C J, Smith P J, Welton T. Chem. Commun., 2000: [14] Bellefon C de et al . J. Mol . Catal., 1999, 145: 121. [15] Adam C J et al. Chem. Commun., 1998: [16] Boon J A et al. J. Org. Chem., 1986, 51: 48. [17] Kun Qian, Yonquan Deng. J. Mol. Catal. A: Chem., 2001, 171: [18] Surretle J K D, Green L, Singer R D. Chem. Commun., 1996: [19] Wheeler C et al . Chem. Commun., 2001: 887. [20] Earle M J, McCormac P B, Seddon K R. Chem. Commun, 1998: [21] Hagiwara R, Ito Y J. Fluorine Chem., 2000, 105: 221. [22] Boularre V L, Gree R. Chem. Commun., 2000: [23] Gordone L M, McClusky A. Chem. Commun., 1999: [24] Kanalka G W, Maladi R R. Chem. Commun., 2000: [25] Fischer F, Sethi A , Welton T et al. Tetranedron letters, 1999, 40: [26] Earle M J, McCormac P B, Seddon K R. Gree. Chem., 1999, 1: [27] Visser A E, Swatloski R P, Reichert W M et al. Chem. Commun., 2001: 135. [28] Lall S I, Mancheno D, Castro S. Chem. Commun., 2000: 2413.

76. Thanks