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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
Recommended