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Ionic Liquids in Green Chemistry

Dr. Nie Wanli

Chemistry Department of NWU, Xi’an

• What are Ionic liquids (ILs)?• Why consider of ILs?• The characteristic properties of ionic

liquids• The synthetic methods• Research with ILs• Outlook

Ionic Liquids in Green Chemistry

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.

------ Ionic liquids are salts that are liquid at low temperature (<100 oC) which represent a new class of solvents with nonmolecular, ionic character..

What are ionic liquids?

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

The driving forcesThe 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

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.

What is “green chemistry” ?

• 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.

Why consider Ionic liquids ?

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

Great promise• Designability. By combining different anions with cati

ons, 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.

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.

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

• Room temperature ionic liquids consist of bulky and asymmetric organic cations such as :

Imidazolium ion Pyridium ion Ammonium ion Phosphonium ion

Scheme 1. Important types of cation Scheme 1. Important types of cation

Typical RTIL Cations

•A wide range of anions is employed, from simple halides which inflect high melting points, to inorganic anions such as:

Anions:

Anions for RTIL

• [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]

CF3SO2- CF3(CF2)3SO2

-

Bis(triflyl)amide [Tf2N] Trifluoroacetate [TA]

(CF3SO2)2N- CF3CO2-

Heptafluorobutanoate [HB]

CF3(CF2)3CO2-

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.

Ionic liquid synthesis

Direct quaternization to form cation

------Alkylation reagents

Indirect quaternization to form cation

Direct quaternization to form cation

------Alkylation reagents

Indirect quaternization to form cation

Ionic liquid synthesis

NR3

[R'R3N]+X-

[R'R3N]+[MXy+1]- [R'R3N]+[A]-

+ R'XStep I

Step IIa Step IIb

+ Lewis acid MXy

1. + Metal salt M+[A]-

- MX (precipition)

2. + Bronsted acid H+[A]-

- HX (evaporation)

3. Ion exchange resin

Scheme 2. synthesis paths for the preparation of ionic liquids examplified for an ammonium salt.

General procedures:General procedures:

• organoaluminates

• air- and water-stable ionic liquids

• organoaluminates

• air- and water-stable ionic liquids

The types of RTILS

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:

Al2Cl7- + Cl- = 2 AlCl4

-

Acidic basic neutral

• Basic haloaluminates preclude solvation and solvolysis of metal ion species

NNCl-

Me Et

AlCl3NN

Me Et

NN

Me Et

AlCl3AlCl4- Al2Cl7

-

basic neutral acidic

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

Table 1.Table 1. Table 1.

x (p) Mp (oC) PH

0.36 1.59 - 60 basic

0.50 0.20 2 neutral

0.66 0.16 - 80 acidic

Table 1. Melting Point (Mp) and Viscosity () of 1-Ethyl-3-methylimidazolium Chloride/Aluminum Chloride Ionic liquid at

different Molar Fractions (x) of the Aluminum Compound

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.

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

•Because of their properties, ionic liquids attract great attention in many fields, including organic chemistry, electrochemistry, physical chemistry, and engineering.

Applications

1. as reaction media for synthesis and catalysts2. in electrochemistry 3. in separation processes4. as electrolytes in solar cells5. as lubricants6. as propellants in small satellites7. matrixes in MALDI mass spectrometry8. Applications in other areas

1. as reaction media for synthesis and catalysts2. in electrochemistry 3. in separation processes4. as electrolytes in solar cells5. as lubricants6. as propellants in small satellites7. matrixes in MALDI mass spectrometry8. Applications in other areas

• 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.

Catalysis in ionic liquids ------general considerations

potentially attractive media for homogeneous catalysis:

• 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’.

• 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.

•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.

Applications

• Solvent Properties• Transition Metal Catalysed Reaction • Carbocation Chemistry• Separations • Electrochemistry • Photochemistry

Solvent Properties

Diels-Alder reaction Aldol condensation Others

Diels-Alder reaction

OMe

O

ionic liquid

H

CO2Me

CO2Me

H

endo-from exo-form

+ +r.t

cyclopentadiene methyl acrylate ester

Ionic liquids Composition

(% AlCl3)

Time (h) Endo/exo Y. (%)

ratio

emimCl/(AlCl3)x 48 (basic) 22 4.88 32.3

emimCl/(AlCl3)x 48 (basic) 72 5.25 95

emimCl/(AlCl3)x 51 (acidic) 22 19 53

emimCl/(AlCl3)x 51 (acidic) 72 19 79.4

bmimBF4 - 72 4.3 91

Endo selectivity ----highly polar solvents Increases in the reaction rate Allows water sensitive reagents to be used Simple workup Ionic liquid can be reused

Aldol Condensation

H

O

H

O

H

O

H

O

H

O

+

Aldol I

Aldol II

2 NaOH aq.

solvent,reflux, 3h

hydrogenation

1

3

NaOH aq.

solvent,reflux, 3h

entry solventreaction

typeconv.(%)

selectivity (%)

1 2* 3 4**

1 bmimBF4 Aldol I 99 64 2 - 33

2 H2O Aldol I 100 82 0 - 18

3 emimBF4 Aldol II 100 4 6 69 21

4 bmimBF4 Aldol II 100 3 3 80 14

5 H2O Aldol II 100 36 0 59 5 Solubility

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

• Hydrogenation • Heck reaction• Stille reaction• Other reactions

Transition Metal Catalyzed Reaction

Hydrogenation reaction

H2, [RuCl2-(S)-BINAP]2.NEt3 (cat.)

iPrOH-bmimBF4, r.t., 20 hO

OH OH

O

*

P (atm) conv.(%) % e.e

1st use 50 100 78 (S)

2nd use 75 100 84 (S)

3rd use 25 90 79 (S)

4th use 100 95 67 (S)

Two phase system Simple workup -------decantation Ionic liquid/catalyst phase can be reused

Dupont et al.

IL in Two-Phase Catalytic Reactions

Heck Reaction (1)

R

X

R

+Pd(OAc)2

bmimBrNaOAc, 100 ~ 110 oC, 24h

entry X R conv.(%)

1 I H 100

2 Br CHO 100

3 Br MeCO 79

Polar solvent Expensive Phosphine ligand

Less expensive High yields Without phosphine

styrene stilbenes

Heck reaction (2)

OBu

Br

OBu OBu

+ +

Pd(OAc)2 (2.5 mol%), DPPP(2.75 mol%)

solvent, Et3N, 100 oC, 18h

Dppp = 1,3-bis(diphenylphosphino)propane -form -form

entry solvent conv.(%) / E/Z Y.(%)

1 toluene 23 46/54 68/32

2 DMSO 100 75/25 79/21

3 bmimBF4 50 >99/1

4* bmimBF4 100 >99/1 95

High regioselectivity Simple workup -------distillation

enol ethers

Stille reaction

I

O O

SnBu3

PdCl2(PhCN)2 (cat.)

bmimBF4

Ph3As, CuI, 80 oC, 2h

+

Y. (%)

1st use 82

2nd use 78

3rd use 72*

Simple workup -------extraction Ionic liquid/catalyst phase can be reused Air and moisture stable

vinyltributyltin

iodocyclohexenone

Stabilize catalystsSimple workupAtom economy

Other reactions

• Suzuki-Miyaura coupling reaction• Trost-Tsuji coupling • Hydroformylation (biphase)

• Friedel-Crafts alkylations and acylations

• Arene exchange reactions

•The ionic liquids acts as both a solvent and catalyst for a acid catalysed processes involve cationic intermediates, e,g. carbenium and acylium ions

Carbocation Chemistry

• IL containing chloroaluminate anions are strong Lewis acids and if protons are present they are superacidic.

Friedel-Crafts reaction---acylation

OMe O

Cl

O

OMe+Cu(OTf)2

bmimBF4

Y. quant. ( p-/o-ratio = 94/4 )anisole

• quantitatively• regioselective

methoxybenzophenone

• Y 64% in acetonitrile•p-/o- = ratio of 93/7

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.

• 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 [Al2

Cl7]- 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

Fe

Arene exchange reactions

Separations

• Witting reaction• Others

Witting reactionO

C MeCH

PPh3

O

C MeCH

HCPhPhCHO Ph3PO bmimBF4

60 oC, 2.5 h+ +

Y. (%) E/Z (%)

1st use 82 97/3

2nd use 83

6th use 91

• The separation of the product and triphenylphosphine oxide

• Extractions • Reuse IL

Reduction

CHO CH2OH

Bu3B (1 eq.)

ionic liquid

ionic liquid temp. (oC) time (h) Y. (%)

bmimBF4 100 16 93

emimBF4 100 16 90

emimPF6 100 16 96

emimPF6 r.t. 48 94

• Lower temperature

Fluorination

NH

Me

NH

Me

O

F

1

NH

Me

O

H

2

+

N

N

F

CH2Cl

. 2 BF4-

+

+

bmimBF4 / MeOH (1 / 1), 20 oC, 3 h

entry solvent cosolvent Temp.(oC) Time (h) 1 (%) 2 (%)

1 MeCN H2O r.t.over

night71

small

amount

2 bmimBF4 MeOH 20 3 99 -

• Short reaction time• High yield

N-fluoro-N’-(chloromethyl)triethylenediamine bis(tetrafluoroborate) 3-fluorinated 2-oxoindoles

Ring opening reaction

O

R1 R2

OH

R2

NHR3

R1NHR3

R2

OH

R1R3-NH2 bmimBF4, r.t.+ +

entry R1 R2 R3 product Time (h) Y. (%)

1 Ph H Ph 5.0 85

2 -(CH2)4- Ph 6.0 83

3 PhOCH2 H Ph 6.0 89

4 Bu H p-tol 6.0 85OH

BuNH-p-tol

NHPh

PhOH

OH

NHPh

PhO NHPh

OH

• room temperature, economic

epoxide

•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.

Enzymatic reaction

Ph

OH

O Ph

OoAc

lipase

bmimBF4, r. t., 3.5 h+

Y. 44% (>99 % e.e.)

• similar yields to those of organic solvent systems

Others

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

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:

Other types of ionic liquids

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

Further information regarding physical properties, chemistry, and uses of ionic liquids:[1] Welton T. Chem . Rev., 1999, 99: 2071.[2] Wasserscheid P, Keim W. Angew Chem. .Int. Ed. Engl., 2000, 39: 3722.[3] Freemantle M. (a) Chem . Eng . News, 2000, 78 (May)15: 37-39; (b) Chem . Eng . News, 2001, 79 (Jan)1: 21-25.[4] Earle M J, Seddon K R. Pure Appl, Chem., 2000, 72 (7): 1391-1398.[5] Chum H L, Koch V N et al. J. Am. Chem, Soc., 1975, 97: 3264 . [6] Wilkes JS et al . Inorg . Chem., 1982, 21: 1236.[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, Mumann L, Olivier H. Angew. Chem. Int. Engl., 1995, 34: 2698.[9] Monteiro A L et al. Tetrahedron Asymmetry, 1997, 2: 177-179.[10] Song C E, Roh E J. Chem. Commun., 2000: 837-838.[11] Dullins J E L et al. Organometallics, 1998, 17: 815.[12] Kakfman D E et al. Synlett., 1996: 1091.

REFERENCES

[13] Mathews C J, Smith P J, Welton T. Chem. Commun., 2000: 1249-1250.[14] Bellefon C de et al . J. Mol . Catal., 1999, 145: 121.[15] Adam C J et al. Chem. Commun., 1998: 2097-2098.[16] Boon J A et al. J. Org. Chem., 1986, 51: 48.[17] Kun Qian, Yonquan Deng. J. Mol. Catal. A: Chem., 2001, 171: 81-84.[18] Surretle J K D, Green L, Singer R D. Chem. Commun., 1996: 2753-2754.[19] Wheeler C et al . Chem. Commun., 2001: 887.[20] Earle M J, McCormac P B, Seddon K R. Chem. Commun, 1998: 2245.[21] Hagiwara R, Ito Y J. Fluorine Chem., 2000, 105: 221.[22] Boularre V L, Gree R. Chem. Commun., 2000: 2195-2196.[23] Gordone L M, McClusky A. Chem. Commun., 1999: 1431-1432.[24] Kanalka G W, Maladi R R. Chem. Commun., 2000: 2191.[25] Fischer F, Sethi A , Welton T et al. Tetranedron letters, 1999, 40: 793-796.[26] Earle M J, McCormac P B, Seddon K R. Gree. Chem., 1999, 1:23-25.[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.

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