1

Chapter 2

Synthesis of Ionic Liquids

16

2.1. Introduction and literature survey

Menschutkin [63] recognized the importance of solvents to chemical reactivity

before the turn of the 19th

century, and the reaction which bears his name has provided

much information on how the solvents can affect the rates of reaction [36, 64].

Menschutkin reaction is a process of central importance in biochemistry and a widely

used strategy in organic synthesis; it is the reaction generally used to prepare ILs [65].

Despite the ever-growing number of articles describing the applications of ILs, their

preparation and purification in recent years have taken on an air of ―need to know‖.

As is well known, the whole field of ILs developed since 1914, by the synthesis of

first IL ethyl-ammonium nitrate. Although most researchers employ similar basic

types of chemistry, it appears that everyone has their own tricks to enhance yields and

product purity. Since the applications of ILs in present day science were becoming

extremely important in the last decade or so, it was not surprising that several research

articles should appear dealing with this material. Rogers and co-workers [66-71],

papers dealt with various novel methods of the synthesis of ILs. Seddon and co-

workers [72-76], described excellent strategies in order to popularise the field in

industry as well as academia. Wasserscheid and co-workers [77-80], synthesized new

chiral ILs very effectively. Leveque et al [81, 82] suggest improvements in IL

synthesis using ultrasound as a source, in particular the metathesis step, which should

lead to a cleaner route to the production of these solvents. Baker et al [83-85]

described a convenient and efficient one-pot route to a new family of cost-effective,

highly proton conductive RTILs. A solvent free sonochemical, and microwave

assisted synthesis of IL was reported by Varma et al [86, 87]. In addition to that

Merrigan et al [88] developed less-polluting, ‗neoteric‘ solvents which are assisted by

emulsification of fluro-alkanes with IL phases. Dzyuba et al [89] introduced an

17

efficient protocol for the synthesis of symmetrical 1-3-dialkylimidazolium cation,

while Abbott et al [90] pioneered the synthesis of moisture stable ILs, which consist

of an eutectic mixture of Zn or Sn to the quaternary ammonium salts. Pyrrolidinone

based ILs grabs the attention because they requires longer refluxing time, might be

due to the fact that the basicity of pyrrolidinone is changed because the nitrogen atom

conjugates its unshared electron pair with the carbonyl π electron. In this context

tuning of organic cation was initiated by Demberelnyamba et al [91] in their work

they introduce pyrrolidinone cation. Matsumoto et al [92] and MacFarlane et al [93]

reported a systematic route for the preparation of ILs having low viscosity and

melting point by tuning of anion. Ishida et al [94] reported a systematic illustration of

effect of structure on the physical properties of imidazolium salts, and reported

synthesis of cyclophane type imidazolium salts. Direct alkylation of azoles and

azabenzene is widely accepted conventional route for the synthesis of ILs. Zhang et al

[95] documented an effective strategy for direct methylation of imidazole and

pyridine. The first catalytically active Organometallic ILs was synthesized and

generalized by Schottenberger et al [96], Matsumoto et al [97] reported details of

syntheses, structures and properties of 1-ethyl-3-methylimidazolium salts of

fluorocomplex anions. ILs based on marpholine and their applications as an

electrolyte was documented by Kim et al [98], Clavier et al [99] synthesized

imidazolium salts which are derived from L-Valine. An enzyme catalysed synthesis of

ILs was reported by Park et al [100]. Matsumi et al [101] and Zhao et al [102]

provided new dimensions to the chemistry of organo-boranes by synthesizing organo-

borane molten salts having imidazolium cation, a series of ‗dual-functionalised‘ ILs,

comprising imidazolium cations with various functionalities and the nitrile

functionalised anion. A novel one pot synthesis of crystalline quaternary ammonium

18

salts was proposed by Ropponen et al [103]. An Immobilized metal ion-containing IL

catalyst were prepared and generalized by Sasaki et al [104]. By making use of

supercritical fluid CO2 in the synthesis of ILs a greener approach was reported by Wu

et al [105]. Weng et al [106] reported a classical route for the synthesis of ILs.

Organic synthesis particularly synthesis of innovative materials (includes ILs)

requires adaptation of an applicative alternative reaction condition from the

perspectives of green synthesis is a demand of time. Fringuelli et al [103] claimed

more efficient process and new catalyst system for the synthesis of ILs. A synthetic

strategy for halide free triflate imidazolium ILs with exceptionally high purity was

reported by Leclercq et al [108], Harjani et al [109] reported a synthesis of

biodegradable pyridinium based ILs from the perspectives of green chemistry.

Phosphonium based ILs having unique set of applications from this perspective

Tindale et al [110] and Bradaric et al [111] have described a simple and efficient

method for the synthesis of phosphonium ILs. A new version of low water content

protic ILs, succinimidyl activated ester a versatile reagent facilitates a number of

organic transformations [112-114]. Walkiewicz et al [115] prepared an azolate anion

based ILs, while a systematic study of Schleicher et al [116] provides a database

which gives information about the kinetics and the solvent effect on the synthesis of

ILs. Solvent free one pot microwave assisted syntheses of ILs were also reported in

the literature [117, 118]. New version of ILs based on amino acids was successfully

synthesized and implemented by many researchers [119-122]. After synthesis

purification of IL is another challenging task before the practical implementation of

the IL methodology, Nockemann et al [123] described an excellent account of the

methods involved in purification of ILs. A similar work on purification of ILs is

discussed by Stark et al [124]. Their survey accounts to information on the methods

19

required this purpose. An excellent method for the separation of both hydrophobic

and hydrophilic room-temperature ILs using carbon dioxide has been reported by

Scruito et al [125], which describes the enhancement of the purity of ILs.

A great many ILs are prepared by a metathesis reaction [6, 126] from a halide

or similar salt of the desired cation. The

general metathesis reaction can be

divided into two categories (inset)

depending on the water solubility of the

target IL, metathesis via [1] Free acids or group 1 metals/ammonium salts, or [2] Ag

salt metathesis.

Imidazoles and more specifically tri-aryl-imidazoles represent a common

scaffold innumerous bio-active [123] compounds which have proven to be key

compounds for the synthesis of therapeutic agents (anti-inflamatory, analgesic,

glucagon receptor antagonists). In addition, the exclusive survey of the applications of

2-4-5-triarylimidazoles was reported by Chauveau et al [124] and covering their

optical properties (fluorescence and chemiluminescence). In this context, they have

given great attention for the development of fluorescence labelling agents, materials

for biological imaging application, blue light emitting materials, luminophores for

optoelectronic applications or chromophores for nonlinear optic systems. Recently,

some distriarylimidazoles have been investigated for their piezochromism,

photochromism and thermochromism properties, and the results reported suggest

potential applications in molecular photonics and sensing.

The synthesis of 2-4-5-triphenylimidazole (Lophine) has been known for a

long time. Such a compound and its derivatives are principally obtained by a multi-

component reaction involving benzoin (benzil or a substituted benzil), an aryl

R+X- Metathesis

M+A-R+A- + M+X-

Ag Gp 1 NH4+

Water Miscible ILs Water Immiscible ILs [Li, K, Na]

20

aldehyde and ammonium acetate as an ammonia source. In the last decade, increasing

interest has been devoted to optimize the reaction conditions in order to reach very

high yields and highly pure products. For this purpose, many catalysts [128-130] have

been investigated for example silica/sulfuric acid, oxalic acid, iodine,

sodium bisulphite, sulfanilic acid, tetra-butyl-ammonium bromide,

CAN, have been used. Similarly different activation modes, thermal

activation, microwave irradiation or ultrasounds [131-133] were also found to be

adopted. These reactions are performed either in solution, or in solvent less condition.

In 1971, Starks [134] introduced the term ―phase-transfer catalysis‖ to explain

the critical role of tetra-alkyl-ammonium or phosphonium salts (QpX) in the reactions

between two substances located in different immiscible phases. More precisely, in

1981 the principle of phase transfer catalysis (PTC) is brought forth well by Reuben

and Sjoberg [135] who wrote that all boundaries are difficult to cross: political, legal

and geographic boundaries, and also phase boundaries in chemical systems. Many

desirable reactions cannot be brought about because the reactants are inaccessible to

each other. Nowadays, phase-transfer catalysis appears to be a prime synthetic tool,

being appreciated not only in various fields of organic chemistry but also among

widespread industrial applications. In addition to that MacFarlane and co-workers

[136] cited the pioneering work by Gordon and Subba Rao, which stresses that the

total number of carbons as well as the symmetry of the quaternary ammonium cation

effectively elucidates the melting point of a molten salt of the quaternary ammonium

cation. In their comprehensive book G. Charlot and B. Tremillon [137], reported that

some of the quaternary ammonium salts which in the melt state behaves like an

ionized solvent. Successful utilization of these ionized solvent (molten tetra-butyl-

ammonium bromide) in the synthesis of palladium nanoparticles reported by

21

J. L. Bras and co-workers [138]. The significant role of molten tetra-butyl-ammonium

bromide in thio-acetalization of acetals is pointed out by B. C. Ranu et al [139].

Here, we report an efficient, one pot synthetic methodology which has been

designed and adopted for Menschutkin quaternization reaction. In other words a

strategy for the synthesis of 1-ethyl-3-methylimidazolium bromide [emim][br], 1-

methyl-3-propylimidazolium bromide [prmim][br], 1-butyl-3-methylimidazolium

bromide [bmim][br], N-butyl-pyridinium bromide [bpy][br], N-octyl-pyridinium

bromide, 4-vinyl-N-butyl-pyridinium bromide employing molten salt as a medium is

described. As a preliminary our search was aimed to find if molten quaternary

ammonium salt (ionized solvent) acts as an effective solvent for Menschutkin

quaternization reaction (Scheme 1) of 1-methylimidazole and pyridine with alkyl

halides in the synthesis of [emim][Br], [prmim][Br], [bmim][Br], [bpy][Br],

[opy][Br], [b-(4-vinyl)py][Br] and [bHbenzim][Br]. Further utilization of the

technique, in the synthesis of 2-4-5-tri-arylimidazole and bis-(indolyl)-methanes

derivatives was also accomplished.

During the course of the reaction, temperature required to melt tetra-butyl-

ammonium bromide (i.e. 110-115oC) is higher than the boiling temperature of the

reactants (particularly alkyl halides). Thus, to avoid the loss in reaction mass gradual

addition of the volatile reactants through the water condenser has been adopted.

2.2. Experimental

All commercially available reagents were used with prior purification.

Chemical shifts of 1H (300 MHz) spectra were recorded in ppm (δ), using a Varian

Mercury YH300 instrument. Mass spectra were recorded using ESI-MS/MS set ups

having triple quadruple detection system. The representative 1H-NMR spectrums for

the compounds 1-butyl-3-methyl imidazolium bromide and 2, 4, 5-triaryl imidazole

22

are exhibited for the purpose of confirmation at the end of this chapter as figure 2.4

and 2.5 respectively.

2.2.1. General procedure for Menschutkin quaternization of 1-methylimidazole

A stirred solution of 1-methylimidazole (30 mmol) and alkyl halide (30 mmol)

was gradually added to molten tetra-butyl-ammonium bromide. After addition, the

reaction mixture was cooled to room temperature, and ethyl-methyl-ketone was

added. The resulting mixture separated in two layers, was separated, after washing

with excess ethyl-methyl-ketone, the products were collected, and transferred to

vacuum oven for drying. The ethyl-methyl-ketone plays a significant role to separate

the IL from the reaction mixture because all the reactants including catalyst were

soluble in ethyl-methyl-ketone except the product which was immiscible. Solvents

like acetonitrile, chloroform, ethanol, methanol, tetrahydrofuran gave a homogeneous

solution (no separation was achieved). The products obtained were identified from

FT-IR and 1H-NMR spectra by comparison with the data reported in literature or with

those of authentic samples [140]. ESI-MS/MS studies were done to confirm molecular

weights of the products. The interpretations of ESI-MS/MS results for the synthesized

compounds are discussed in chapter 4A of the thesis.

1a] 1-ethyl-3-methylimidazolium bromide:

Water Content (KF): 1.27 %

UV-Visible: Absorption maximum λ max below 400 nm.

FTIR (NaCl plate):

1H-NMR (δ) (D2O): 1.54 [t, 3H, CH3-CH2], 3.91 [s, 3H, N-CH3], 4.26 [q, 2H, -N-

CH2-CH3], 7.44-7.50 [d, 2H, -N-CH-CH-N-], 8.73 [s, 1H, -N-

CH-N-].

ESI-MS/MS: 303.11 Da. - 111.21 Da.

23

1b] 1-propyl-3-methylimidazolium bromide:

Water Content (KF): .

UV-Visible: Absorption maximum λ max below 400 nm.

FTIR (NaCl plate): .

1H-NMR (δ) (D2O): 0.93 [t, 3H, CH3-CH2-], 1.90 [m, 2H, -CH2-CH2-CH3], 3.92 [s,

3H, -N-CH3], 4.19 [t, 2H, N-CH2-CH2-CH3], 7.46-7.51 [d, 2H, -

N-CH-CH-N-], 8.75 [s, 1H, -N-CH-N-]

ESI-MS/MS: 329.12 Da - 125.22 Da.

1c] 1-butyl-3-methylimidazolium bromide:

Water Content (KF): .

UV-Visible: Absorption maximum λ max below 400 nm.

FT-IR (NaCl plate):

1H-NMR(δ)(D2O): 0.98 [t, 3H, CH3-CH2-], 1.38 [m, 2H, -CH2-CH2-CH3], 1.89 [m,

2H,CH2-CH2-CH2-CH3], 3.93 [s, 3H, N-CH3], 4.24 [t, 2H, N-

CH2-CH2-CH2-CH3], 7.48-7.53 [d, 2H, - N-CH-CH-N-], 8.77 [s,

1H, -N-CH-N-]

ESI-MS/MS: 139.2 Da - 42.5 Da.

2.2.2. Procedure for the synthesis of N-butyl-pyridinium bromide

A stirred solution of pyridine (10 mmol) and butyl bromide (10 mmol) was

slowly added to molten tetra-butyl-ammonium bromide. After this addition, the

reaction mixture was cooled to room temperature and had the appearance of a white

solid. It was washed with an excess of tetrahydrofuran, and the oily white solid of N-

butyl-pyridinium bromide was collected, and transferred to vacuum oven for drying.

In this case the removal of catalyst was successfully performed by using

tetrahydrofuran or benzene. The similar problem mentioned earlier was arises by

using the solvents acetonitrile, chloroform, ethanol, and methanol.

The product was identified and confirmed by comparing FT-IR and1H-NMR spectra

of the synthesized compound with those reported in literature [141]. A discussion on

the results of ESI-MS/MS study is summarized in chapter 4A.

24

2a] N-butyl-pyridinium bromide:

Water Content (KF): .

UV-Visible: Absorption maximum λ max below 400 nm.

FTIR (KBr pellet):

1H-NMR (δ) (D2O):

.

ESI-MS/MS: 351.3 Da - 136.1 Da.

2.2.3. Procedure for the synthesis of N-octyl-pyridinium bromide

A stirred solution of pyridine (10 mmol) and octyl bromide (10 mmol) was

slowly added to molten tetra-butyl-ammonium bromide. After this addition, the

reaction mixture was cooled to room temperature. Then, all the reaction mass was

dissolved in chloroform giving a homogeneous solution, which was washed with

water. After removal of water, the chloroform layer is dried with anhydrous sodium

sulfate. Finally chloroform was removed on rotary evaporator, giving N-octyl-

pyridinium bromide as a viscous liquid.

2b] N-octyl-pyridinium bromide:

1H-NMR (δ)(D2O): 8.15 [t, 2H], 8.62 [t, 1H], 9.8[d, 2H], a complicated pattern of 7-

CH2 and 1-CH3 is found between 0.8 ppm -3.4 ppm.

2.2.4. Procedure for synthesis of 4-vinyl-N-butyl-pyridinium bromide

A stirred solution of 4-vinylpyridine (10 mmol) and butyl bromide (10 mmol)

was slowly added to molten tetra-butyl-ammonium bromide. After addition, the

reaction mixture was cooled to room temperature, and ethyl-methyl-ketone was

added. The resulting mixture found to be separated in two layers. Then after cooling

the scratching a colorless solid of 4-vinyl-N-butyl-pyridinium bromide was obtained.

The salt was found to be tremendously hygroscopic which needed to be shifted

25

directly shifted in desiccators. Thermal Gravimetric Analysis of the compound clears

that the compound is stable up to 280 0C.

3a] 4-vinyl-N-butyl-pyridinium bromide:

Water Content (KF): ESI-MS: 404 Da.

2.2.5. Procedure for the synthesis of N-butyl-benzimidazolium bromide

In a melt of tetra-butyl-ammonium bromide benzimidazole pyridine (10

mmol) and butyl bromide (10 mmol) was slowly added. After this addition, the

reaction mixture was cooled to room temperature. Then, all the reaction mass was

dissolved in chloroform yielding a homogeneous solution, and rinsed with water.

After removal of water, the chloroform layer was dried with anhydrous sodium

sulfate. Finally chloroform was removed on rotary evaporator, and N-butyl-

benzimidazolium bromide was obtained as a viscous liquid.

4a] N-butyl-benzimidazolium bromide:

FTIR (NaCl plate):

2.2.6. Procedure for the synthesis of 2-4-5-tri-arylimidazole

Using two-necked flasks benzoin (5 mmol), benzaldehyde (10 mmol) and

ammonium acetate (20 mmol) were gradually added to the molten tetra-butyl-

ammonium iodide (7.5 mmol). The progress of the reaction was monitored by TLC.

After completion of the reaction the reaction froth was dissolved into ethanol, which

yielded a white solid of 2-4-5-tri-arylimidazole. The similar condensation reaction

was carried out by using molten tetra-butyl-ammonium bromide. However, it was

noted that the process is slow and also fails to give satisfactory yield.

The product was identified by 1H-NMR spectra by comparison with the data reported

in literature [129]. ESI-MS/MS studies were done to confirm molecular weight of the

product.

26

2-4-5-triarylimidazole:

M.p: .

FTIR (KBr pellet): .

1H-NMR (δ) (DMSO): 7.22–7.56 [complicated spectra is observed for three benzene

rings], 8.07 [s, 1H].

ESI-MS/MS: 296.20 Da.

2.2.7. General procedure for the synthesis of bis-(indolyl)-methanes

The reaction involves the addition of indole (10 mmol) and aldehyde (5 mmol)

to molten tetra-butyl-ammonium bromide (5 mmol). Further processing the reaction

product with acidified methanol and keeping ice-cold conditions causes the solid bis-

(indolyl)-methanes separating out. Purification of the derivatives of bis-(indolyl)-

methane: in a 100ml, beaker the solids of bis-(indolyl)-methane was dissolved in

dichloromethane, which gives a homogeneous solution, washing with water

(approx.10 times), and further removing the water layer with the help of separating

funnel. Anhydrous sodium sulfate was used to dry the layer of dichloromethane.

Finally dichloromethane was removed off with the help of rotary evaporator, and the

crystals of bis-(indolyl)-methane were obtained.

The products were identified on the basis of physical constant and FT-IR values.

2,2'-(Phenylmethylene)bis(indole):

M.p.

FT-IR (KBr, cm-1

): 3414 [N-H], 1618-1417 [C=C], 1091-1030 [C-N], 798.

2,2'-((4-Chlorophenyl)methylene)bis(indole):

M.p.

FT-IR (KBr, cm-1

): 3416 [N-H], 1413 [C=C], 1093-1018 [C-N], 696-802 [C-Cl].

27

2,2'-((4-Nitrophenyl)methylene)bis(indole):

M.p.

FT-IR (KBr, cm-1

): 3414 [N-H], 1599-1415 [C=C], 1344 [-NO2], 1095-1024 [C-N],

694-802.

2.3. Instrumentation

2.3.1. Karl-Fischer titrimetry

The SYSTRONICS 349 AUTO KARL- FISCHER TITRATOR instrument

was used for the analysis. The calibration of Karl-Fisher Titrator was done by using

Sodium tartarate dehydrate, Oxalic acid dihydrate. The water content in molten salts

and ILs [emim][Br], [prmim][Br], [bmim][Br], [bpy][Br], and [b-(4-vinyl)-py][Br]

was determined. The data are collected in characterization tables. The Karl Fischer

reagent was supplied by Qualigens Fine Chemicals and it was of high purity.

2.3.2. UV-Visible spectrophotometry

Shimadzu UV-Visible spectrophotometer with UV-Probe 3.5 software was

used for the analysis. As we know UV-Visible spectrophotometry is widely used

method for the analysis of colored as well as colorless complexes.

Figure 2.1: UV-Visible spectrum of 0.01m KNO3

28

The calibration of UV- Visible spectrophotometer was done by analyzing

0.01M KNO3. The salt exhibits absorption maximum (λ-max) at 302 nm, and having

extinction coefficient of .

Figure.2.2: UV-Visible spectrum of [emim][br], [prmim][br] and [bmim][br]

Absorption measurements for ILs were made. The spectrum of pure ILs is

interesting. In visible region, there is no absorption while in UV region between 200

to 400 nm, there is an appreciable absorption (Figure 2.2). This can be attributed to

electrons of the imidazolium ring moieties. The transitions are due to

molecular orbitals. It seems that substitution of ethyl, propyl and

butyl substituent‘s affect the magnitude of absorption appreciably.

2.4. Results and Discussion

The toxic and volatile natures of many organic solvents, particularly

chlorinated hydrocarbons that are widely used in organic synthesis have posed a

serious threat to the environment. Though ILs have been successfully employed as

solvents with catalytic activities for a variety of important reactions (mentioned in the

chapter 1 of the thesis), their use as a real catalyst under solvent free conditions has

not been explored to any great extent. The high cost of most of the conventional ILs

0

0.5

1

1.5

0 100 200 300 400 500 600 700 800

A

b

s

o

r

b

a

n

c

e

Wavelength (nm)

[bmim][Br]

[emim][Br]

[prmim][Br]

29

prompted us to initiate an investigation to explore the catalytic (minimum) use of less

expensive and readily available ILs or molten ionic salts for useful organic

transformations. We used tetra-butyl-ammonium bromide as a template for

Menschutkin quaternization of 1-methylimidazole, pyridine, 4-vinyl-pyridine and

benzimidazole, in the synthesis of 2-4-5-triarylimidazole, and derivatives of bis-

(indolyl)-methanes.

Figure.2.3:TGA-DTA analysis of TBAB under nitrogen atmosphere by maintaining heating

rate 40c/min.

Tetra-butyl-ammonium bromide is the quaternary ammonium salt with 16

carbon atom and higher symmetry in the cation has a melting point of .

Thermal gravimetric analysis of TBAB manifests that the salt is stable up to .

2.4.1. Mechanism of the action of molten salt [3c]

Molten salts can be good media to carry out chemical reactions. The rate of all

reactions increases exponentially with temperature. A liquid medium causes a higher

rate of reaction to occur in a solute compared with that in a gas at the same

temperature because of the proximity required for collisions. Why is this? The

situation needs thought. In the gaseous state, reactants experience only a fleeting

30

contact when they collide, which is often too brief a contact to reach thermal

activation and a successful product formation. Thus, gas molecules fly around at

about at room temperature. When they collide, the actual time of contact

is less than

A different situation is observed in liquids. Here, the time one reactant spends

next to another is much longer than that in the gas phase. For this reason, the two

particles can enlarge the possibilities from those of fleeting acquaintance to the more

productive ones of prolonged contact, leading much more often to permanent

association. One can determine the order of magnitude of the time of contact

(equation 1) as

Where, D is the diffusion coefficient, k is the rate constant for diffusion, and l is the

distance a particle covers in one jump of its movement in diffusion. From the above

equation,

Here in equation 2, is the residence time, the time between ―hops,‖ the time

the two reactant particles have to decide whether to react. Near the melting point of a

molten salt, the diffusion coefficient in solutes is on the order of With l

chosen as (a typical value of the distance between sites within the

molten salt structure), one obtains for the residence time, which is about 100

times longer than that in the gas phase at the same temperature and hence there is a

hundredfold greater chance to react.

However, there is another reason why the molten salt is often a more effective

medium for carrying out a reaction quickly. Reaction rates are proportional to

⁄ where, Ea is the energy of activation of the reaction. Assuming Ea = 105 J

31

mol–1

. If one compares the rates at 300 and 600 K, the reaction rate is 108 higher at the

higher temperature if the rate-determining step in the reaction remains the same.

Consider, for example, a dissolved organic molecule, RH, reacting with

dissolved O2 to give CO2 and H2O. If the reaction is at 300 K and occurs at a rate ν1,

that at 600 K should occur at a greatly increased rate. Could this be achieved by

heating the dissolved materials in an aqueous solution? Of course not! For unless one

uses a pressure vessel (with the added expense of having one made), the aqueous

solution cannot be heated much above 373 K before the solution boils. On the other

hand, molten salts are available over the whole temperature range—from room

temperatures with the AlCl3 complexes in organics such as imidazoline—to molten

silicates at 2000 K. It is the feeling of the author, that if attempts are made, one can

find effective molten-salt media which because of electrostatic interaction abilities

can be used for transformations in organic synthesis.

Hereafter, this section is further divided into two sections [2.4.2] and [2.4.3]

respectively.

2.4.2. Menschutkin quaternization of 1-methyl-imidazole, pyridine, 4-

vinyl-pyridine and benzimidazole in molten TBAB

In order to generalize a strategy; fused salt mediated organic transformations,

we now report the results obtained for the preparation of ILs with molten tetra-butyl-

ammonium bromide as a catalyst. This salt is eco-friendly and easily available under

neutral and solvent-free conditions. The use of this method not only affords the

products in excellent yields but also avoids the problems associated with catalyst cost,

handling, safety and pollution. This catalyst can act as eco-friendly for a variety of

organic transformations and as well as non-volatile, recyclable, non-explosive, easy to

handle, and thermally robust species.

32

Our initial studies were focused on the optimization of the reaction conditions

for the synthesis of imidazolium and pyridinium based ILs (Scheme 2.1 a-e), 1-

methylimidazole or pyridine and alkyl halide(s) were chosen as model substrates. The

reaction in the presence of variable catalyst concentration at melting temperature of

tetra-butyl-ammonium bromide (approx. ), in the absence of solvent,

afforded the corresponding product in higher yield. We found that lower catalyst

loading can be used with only a marginal drop in a reaction rate. With the optimized

reaction conditions, we next studied the reaction of a series of alkyl halides with 1-

methylimidazole, pyridine, 4-vinyl pyridine and benzimidazole.

The experimental procedure is thus very simple, convenient, and has the

ability to tolerate a variety of functional groups. Thus, alkyl halides with different

carbon chain were converted to the corresponding products within some minutes.

Furthermore, benzo-fused-azole, presence of substituent on pyridine was also reacting

with butyl-bromide, and reaction of pyridine with octyl-bromide to produce the

corresponding product in fixed reaction format. In this case the yield was relatively

low. The removal of the catalyst was achieved by extracting a reaction froth (the froth

may also be worked as IL) with ethyl-methyl-ketone ( . After removal of

the solvent, on rotary evaporator the catalyst was recovered.

The UV-Visible spectrophotometric studies of synthesized ionic liquid

confirms the purity of the synthesized compounds, other characterizations like FT-IR,

NMR values are in good agreement with the reported pattern. An ESI-MS/MS study

of the salts enlightened the gas phase association of ILs (please refer chapter 4A of

the thesis).

33

a]

N

N

R-Br Molten TBAB

CH3

Where,

R: -CH2-CH3,

-CH2-CH2-CH3,

-CH2-CH2-CH2-CH3N

N

CH3

R

Br-

b]

NN

Br-Molten TBABBr

c]

NN

C8H17

Br-Molten TBABC8H17-Br

d]

NN

Br-Molten TBABBr

e]

N

N

Molten TBAB

HN

N

H

C4H9

Br-C4H9-Br

Scheme.2.1: Menschutkin quaternization of a) 1-methyl imidazole, b and c) pyridine, d) 4-

vinyl pyridine and e) benzimidazole

In order to show the general applicability of the method, various alkyl halides

were efficiently reacted with 1-methylimidazole in the same conditions. As shown in

Table 2.1 yields are almost quantitative in most cases. We have thus established that

molten tetra-butyl-ammonium bromide as a medium or working catalyst, and activate

34

the interaction between alkyl halide and azoles or aza-benzene moieties to promote

the product formation.

Table.2.1: Scope and limitations of molten ammonium salts as a solvent for menschutkin

quaternization reaction

Entry Reactant(s) Product(s) Catalyst

(mmol)

Time (min) Yield

(%)

1 N

N CH3

C2H5-Br 1a

20

30 55 10 30 69 7.5 30 80 5 30 70

C3H7-Br 1b

15 30 59 10 30 89 7.5 30 93 5 30 86

C4H9-Br 1c

15 30 22 10 30 37 7.5 30 52 5 30 88

2 N

C4H9-Br 2a 20 30 90 15 30 65 10 30 38

C8H17-Br 2b*

10 30 > 40

3 N

C4H9-Br 3a$

10 30 > 40

4

N

N

H

C4H9-Br 4a*

10 30 > 40

1a - [emim][Br], 1b - [prmim][Br], 1c - [bmim][Br],

2a - [bpy][Br], 2b – [opy][Br],

3a – [b-(4-vinyl)-py][Br], and 4a – [bbenzim][Br] *-very low yield $-highly hygroscopic product

It is well known that tetra-butyl-ammonium bromide salts form complexes

with urea [142], thus such interaction can cause as interference if the concentration is

high. The examination of Table 2.1 indicates that when the concentration of the

catalyst (i.e. the salt) is far less than the stoichiometric concentration, the product

yield is high (in case of 1-3-dialkylimidazolium bromide product entry 1), which also

points out that the catalyst at high concentrations probably interact with the reactants.

The situation is similar however, it seems that some critical concentration of the salt

35

in terms of stoichiometry is needed, although less than that of 1:1 stoichiometric

concentration to achieve maximum yield of the product for (entry 2).

Some advantages of this developed procedure are: the experimental simplicity

and the easy work-up procedure use of a green, easy to handle and recyclable catalyst,

high yields, and absence of volatile and hazardous solvents. Moreover, there is no

need for dry solvents or protecting gas atmospheres.

2.4.3. Synthesis of 2-4-5-tri-arylimidazole and bis-(indolyl)-methanes in molten

tetra-butyl-ammonium halide medium

In this work, a three-component reaction between benzoin, benzaldehyde and

ammonium acetate was chosen as a benchmark reaction for the formation of a 2-4-5-

tri-arylimidazole compound (please refer to Scheme 2.2).

Ph Ph

O OH

O

NH+4 -OAc Molten TBAI

NH

N

Ph

Ph

Ph

Scheme.2.2: Synthesis of 2-4-5-tri-arylimidazole

In order to find out the optimum reaction conditions for the eco-friendly

synthesis of 2-4-5-triarylimidazole, we have selected condensation of benzoin,

benzaldehyde (Table 2.2, entry 2.1) and ammonium acetate as a model reaction in

molten tetra-butyl ammonium bromide and molten tetra-butyl ammonium iodide

medium. The reaction was carried out using 1:1:2.5 molar ratios of reactants in fused

salt medium and the results of this synthetic route are found to be encouraging.

36

Table.2.2: Scope and limitations of molten ammonium salts as a solvent for the synthesis of

2-4-5-tri-arylimidazole and bis-(indolyl)-methanes

Entry Reactant(s) Product Catalyst

(mmol)

Time

(min)

Yield

(%) TBAB TBAI

2.1 Ph Ph

OHO

OHC

NH4+OAC

-

N

NH

Ph

Ph

Ph

7.5 -- 60 >40

10 -- 60 >40

-- 7.5 50 58

2.2 N

H

OHC

NH

R

NH

30 -- 30 74

OHC Cl

30 -- 30 78

OHC NO2 30 -- 30 83

In similar fashion an electrophilic substitution reaction (Scheme 2.3) between

indole and aromatic aldehydes was studied in molten tetra-butyl ammonium bromide.

Varieties of substituted BIMs were synthesized using different aldehydes and in each

case it is observed that, the time period for condensation was reduced considerably

with excellent yields for products (Table 2.2, entry 2.2).

NH

O

R

Molten TBAB

NH

R

NH

R: -H, -Cl, -NO2

Scheme.2.3: Synthesis of bis-(indolyl)-methanes

The notable merits of this method are short reaction times, simple work-up

procedure, excellent yield of products (including few exceptions), non-toxic, cost

efficiency and reusability of the catalyst. All these positive aspects make this method

a valid contribution to the existing methodologies.

37

Figure.2.4: 1H-NMR spectrum of [bmim][Br]

NN+

H9C4

CH3

Br-

38

Figure.2.5: 1H-NMR spectrum of 2-4-5-triarylimidazole

N

NH