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Chapter 1: Study of Hydrotropes
1
CHAPTER 1
Study of Hydrotropes
1.1 Introduction
Organic studies involve various synthetic strategies such as use of
different catalysts, reaction media, reagents etc. They play an important role in
the formation of various medicinally as well as commercially important
products. This traditional organic synthesis usually focuses on optimizing
yields, with very little regard to a chemical impact on the environment. Organic
solvents are conventionally used in organic synthesis and in industrial
processes on large scale. These solvents are often problematic owing to their
toxicity and flammability. There is now a realization that more benign chemical
synthesis is required, as an integral part of developing sustainable technologies
[1]. Eliminating the use of organic solvents can reduce the generation of waste
and this is a requirement of one of the principles of green chemistry. Most
effective alternative available to make process greener is the use of alternative
reaction media including ionic liquids [2], supercritical fluids [3], polyethylene
and polypropylene glycol [4], fluorous media [5] water [6] etc.
Water is the matrix of life [7], unique extraordinary and safer reaction
medium for organic studies comes under the heading of green chemistry [8]. In
the solvent life water meets the valuable demand to enhance the reversible
aggregation processes. In comparison with other solvents, the aqueous
solutions principally support with hydrophobic interactions, albeit with
different strength [9]. Water acts as important mediator in interactions of
proteins [10]. Recently it has been used in supramolecular chemistry [11].
Some of the practical advantages of water such as it is abundant in nature,
inexpensive, nontoxic, nonflammable, nonexplosive etc. are well known. The
aqueous medium is more convenient than organic solvents because it can avoid
protection of functional groups, such as -OH and -COOH, water-soluble
compounds can be used directly without derivatization and the high heat
capacity of water allows the reaction temperature to be easily controlled. The
mineral salts, surfactants, and cyclodextrins can be used as additives. The
Chapter 1: Study of Hydrotropes
2
possibility of controlling pH of reaction medium and isolating solid
hydrophobic products by decanting or by filtering thereby avoiding the use of
any organic solvent. The water itself acts as catalyst in many reactions, for
example, the hydrogen-bond stabilized activated complex [12]. The numerous
synthetic transformations proceed in aqueous solution and sometimes these are
more stereo selective in water-rich environment [13]. In essence, water is an
interesting and beneficial solvent in organic synthesis, but the poor solubility of
apolar substances is the main obstacle to the use of water as solvent. However,
a variety of strategies have been investigated to solubalize apolar as well as
other organic compounds in water in order to expand the scope of water based
organic synthesis. Some of such important techniques are:
1. Organic co-solvents
One of the efficient and versatile methods of enhancing solubility of
organic compounds in water is to use organic co-solvent. The co-solvent
reduces the hydrogen bond density of aqueous systems, so that it is less
effective in squeezing out non-polar solutes from solutions. Some of the most
commonly used co-solvents are DMF, acetone and acetonitrile.
2. Ionic derivatisation (pH control)
Adding a positive or negative charge to an ionizable solute usually
brings about a remarkable increase in solubility in water. Adjustment of pH of
solution is therefore an efficient method of solubilizing weak electrolytes in
aqueous medium. This approach, however changes the chemical nature of the
reactant and may limit it’s use as method of solubilzation for synthetic
purposes.
3. Surfactants
An intriguing means of achieving aqueous solubility is by using
surfactants. Surfactant is amphiphilic substances which contain one distinctly
polar and other distinctly non-polar region. In water, surfactants tend to orient
themselves so that they minimize contact between non-polar region and polar
water molecule and when the concentration of surfactant monomer exceeds a
certain critical value then micellization occurs. Micelles are spherical
Chapter 1: Study of Hydrotropes
3
arrangement of surfactant monomer with highly hydrophobic interior and a
polar, water- exposed surface. Organic solutes interact with micelles according
to their polarity; non-polar solutes are buried in the interior of the micelles.
Moderately polar molecules locate themselves closer to the polar surface, while
distinctly polar solute will be found at surface of the micelle. This
compartmentalization of solutes is believed to be responsible for observed
catalytic or inhibitory influence on organic reactions in micellar media.
4. Hydrophilic Auxiliaries
The other method to increase the solubility of practically insoluble
compound is by grafting hydrophilic groups on to insoluble reactants. This
strategy has been seldom used for synthetic purposes but has a pivotal role in
pharmaceutical chemistry and modern drug design because of the limited water
solubility of many drugs, which causes limited bioavailability and thus reduced
therapeutic efficacy. One strategy of improving solubility of drugs is by
converting them into water soluble pro-drugs through covalent attachment of a
hydrophilic auxiliary. It is essential that the attachment should be transient and
reversible nature, allowing for release of original drug from the auxiliary upon
distribution, either by enzymatic or chemical means.
5. Phase Transfer Catalysts
A Phase Transfer Catalyst (PTC) is a catalyst that facilitates the
migration of reactants in a heterogeneous system from one phase to another so
that the reaction can take place. This methodology is applicable to a great
variety of reactions in which inorganic and organic anions react with organic
substrates. It consists the use of heterogeneous two-phase systems: one phase
being a reservoir of reacting anions or base for generation of organic anions,
whereas organic reactants and catalyst (source of lipophilic cations) are located
in second, organic phase. The reacting anions are continuously introduced into
the organic phase in the form of lipophilic ion pairs with lipophilic cations
supplied by the catalyst. Most often tetraalkylammonium cations serve this
purpose. The corresponding catalysts for cations are often crown ethers. By
using a PTC process, one can achieve faster reactions, obtain higher conversion
Chapter 1: Study of Hydrotropes
4
and yield, make fewer by-products, eliminate the need for expensive or
dangerous solvents which can dissolves all reactants in one phase, eliminate the
need for expensive raw materials and/or minimize waste problems. Phase
transfer catalysts are especially useful in green chemistry since they allow the
use of water thereby reducing the amount of organic solvents.
All the above mentioned methods involving greener approaches for the
organic synthesis and these are environmentally benign.
Green Chemistry
The term Green Chemistry was coined in 1991 by Anastas [14]. “Green
Chemistry is the design, manufacture and use of environmentally benign
chemical products and process that prevent pollution and reduce environmental
and human health risks.”
Green chemistry protects the environment, not by cleaning up, but by
inventing new chemical processes that do not pollute the environment.
Chemists from all over the world are using their creativity and innovation to
develop new synthetic methods, reaction conditions, analytical tools, catalysts
and processes under the new paradigm of Green Chemistry due to their
valuable contribution in research Fig 1.1. Green chemistry approach has
received extensive attention [15-22] and involves many names including Green
Chemistry, Environmentally Benign Chemistry, Clean Chemistry, Atom
Economy and Benign by Design Chemistry.
Chapter 1: Study of Hydrotropes
5
Fig 1.1
To enrich the Green methodology the twelve principles play an
important role Fig.1.2. It is widely acknowledged that there is a growing need
for more environmentally acceptable processes in the chemical industry. This
trend towards what has become known as ‘Green Chemistry’ or ‘Sustainable
Technology’ necessitates a paradigm shift from traditional concepts of process
efficiency, that focus largely on chemical yield, to one that assigns economic
value to eliminating waste at source and avoiding the use of toxic and
hazardous substances [23, 24].
Organic transformation in aqueous medium has become a crucial and
demanding research area in modern synthetic chemistry. In the year 1980,
Breslow discovered that huge rate (i.e. 700 times faster reaction rate)
accelerations occurred when the Diels-Alder reaction was performed in water
[25]. This observation increased the interest of synthetic organic chemists to
analyze organic reactions in aqueous medium.
Chapter 1: Study of Hydrotropes
6
Fig 1.2
Soon it was discovered that other organic reactions, like the Claisen
rearrangement [26], the Aldol condensation [27], the Benzoin condensation
[28] and the Barbier-Grignard reaction [29] exhibit rate enhancement in water.
To date, many more organic transformations have been carried out in water.
The use of environmentally benign solvents like water [30] and solvent
free reactions represent very powerful green chemical technology from the
economical and synthetic point of view. They not only reduce the burden of
organic solvent disposal, but also enhance the rate of many organic reactions
[31]. Choice of solvent is one of the problems to face to perform eco-efficient
processes.
Water used as solvent in organic synthesis is beneficial but the
insolubility of organic compounds is major disadvantage. This problem is
overcome by the addition of amiphiphiles for example, Hydrotropes and
Surfactants. We initially focused on the use of hydrotropes in aqueous
solution for the solubilisation of apolar compounds. It performs as a greener
reaction media alternative to organic solvent in organic synthesis Fig 1.3. This
is one of the most important synthetic methodologies for organic
transformations in aqueous medium which comes under the heading of green
chemistry.
Chapter 1: Study of Hydrotropes
7
Greener Reaction Media
WaterFluorousMedia
Ionic Liquids
SC-fluids
Hydrotrope
Fig 1.3
1.2 Hydrotropes
Hydrotropes are highly water soluble surface active organic salts that at
higher concentration enhance the solubility of sparingly soluble as well as
practically insoluble organic compounds in aqueous medium. This
phenomenon was first reported by Neuberg in 1916 [32]. Hydro means water
and tropes mean something other is called Hydrotrope. The phenomenon of
increasing solubility of normally insoluble or sparingly soluble compounds in
water by a third component or additive is termed as Hydrotropy or
Hydrotropism. The substance that causes the solubility enhancement is called
Hydrotrope or Hydrotropic agents and are characterized by an amphiphilic
association structure [33]. Importance of hydrotropes and their many
synergistic properties appeared when it combined with other amphiphilic
molecules [34, 35].
The molecular characteristic of a hydrotropic molecule is that it is a
saturated hydrotropic ring and ionic compound [36]. Hydrotropes normally
comprise hydrophilic and hydrophobic moieties, the hydrophobic moiety being
typically too small to induce micelle formation [37]. The volume of
hydrophobic parts studied additives roughly evaluated by simple calculations
which show efficiency of hydrotrope. Generally, larger is the parts of additives
better is the hydrotropic efficiency and in contrast the hydrophilic part carrying
a charge or not is of minor importance. Therefore the hydrophobic part of the
molecule is the key matter in hydrotrope [38]. The mechanism of self
Chapter 1: Study of Hydrotropes
8
association of hydrotropes being suggested by non-cooperative [39] as well as
cooperative self aggregation [40-42]. Hydrotropes form aggregation in aqueous
solution that are reminiscent of surfactant micelles and the formation of
associated structures important to show hydrotropic effect and they assumed to
aggregate by a stacking mechanism of the planner aromatic ring present in their
chemical structure. For aliphatic hydrotropes the staking mechanism does not
make sense. The characteristic aggregation of hydrotrope induces the origin of
the solubilization process of sparingly soluble hydrophobic compound in water
is analogy to a micillization process [43]. Saleh and co-workers proposed the
necessity of a planer structure is important for association and for the
hydrotropic effect [44].
The ability of hydrotrope to increase the solubility of organic compounds
in water is strongest when the hydrotrope concentration is sufficient to induce
the formation of associated structure and after which solubility remain
unchanged [45]. After certain threshold concentration the sudden increase in
solubilisation by hydrotropes, called as minimum hydrotrope concentration
(MHC). Minimum hydrotropic concentration changes when solution properties
changes such as viscosity, conductivity, surface tension and solubility. The
relatively high concentration required to reach MHC. Kumar et.al reported a
novel approach for reducing the MHC [46]. Aggregation and MHC are the
exact mechanism of solubilisation by hydrotropes [47]. The most important is
the presence of minimum hydrotrope concentration (MHC) analogues to
critical micellar concentration (CMC).
The solubilisation of organics in hydrotropes differ from the other
typical salting-in compounds and co-solvents, in this the solubility increases
sigmoidally depending on the concentration of hydrotrope. The salting-in co-
solutes and co-solvents at higher concentration usually cause a monotonic
increasing solubility without leveling off [43]. Hydrotropes are more effective
in solubilising organic solutes and more selective than the micelle-forming
surfactant [45, 48]. The self aggregation of hydrotropes are differs from that for
micelles [49]. The potential use of hydrotropes in industry was stressed in 1946
Chapter 1: Study of Hydrotropes
9
by McKee [50]. Friberg and Blute reported a detailed description of hydrotrope
for their historical development and industrial applications [51]. However,
hydrotropes have received much less attention in chemical literature than
micelle forming surfactants. Despite the lack of attention, hydrotropes are
widely used in drug solubilization, detergent formulation, health care, and
household applications as well as being an extraction agent for fragrances [52,
53]. Hydrotrope have been applied in household liquid detergents, shampoos,
degreasing compounds and printing paste, used to extract pentosans and lignins
in the paper industry and additives for glues used in leather industry [54]. The
various areas have been benefited by the use of hydrotropes.
Aqueous solution of hydrotropes represents the unique properties of an
alternative reaction media for organic synthesis. Besides being a cheap, non-
toxic and environment friendly, aqueous hydrotropic solutions possess the
other physico-chemical characteristics required to be an alternative greener
solvents for organic transformations. The various organic transformations
carried out in hydrotropic aqueous medium are beneficial, for example,
Claisen-Schmidt reaction in hydrotropic aqueous solution [55], in the
microwave-enhanced Hantzsch dihydropyridine ester synthesis [56], in
synthesis of quinolines by Friedlander′s Heteroannulation method [57]. In
addition, hydrotrope enhance the rate of multiphase reaction [58] which can
lead to autocatalysis in the biphasic alkaline hydrolysis of aromatic esters [59].
The hydrotropes are also used in variety of applications other than organic
synthesis such as, in formulation of pharmaceuticals [60-64], extraction and
separation processes [48, 65-66] and the most recent research of hydrotropic
action has been performed on these above two processes. They show influence
on oil-in-water (OW) for micro-emulsions [52, 67] and related cleaning and
washing processes. Their biological action has also received more attention
[50].
As discussed earlier, an intriguing means of achieving aqueous solubility is
by using hydrotropes. Aqueous solutions of certain salts, such as those of
benzoic, salicyclic, benzene-sulfonic, naphthoic and various hydro-aromatic
Chapter 1: Study of Hydrotropes
10
acids have ability of dissolving certain substances that are not soluble in water.
These salts act as hydrotropes. They structurally resemble to surfactants in the
sense that they have hydrophilic and hydrophobic moieties in the same
molecule, but the alkyl chain is shorter. Some representative examples of
hydrotropes are shown in Fig 1.4.
Fig 1.4
Hydrotropes and Surfactants
SURFace ACTive AgenNTS means Surfactants (Fig 1.5), the most
outstanding property of surfactants is their tendency to form the micelles, at
sharply defined critical micelle concentration (CMC) [68]. The most important
difference between Hydrotropes and Surfactants:
� In case of hydrotrope the dissolved solute is precipitated on dilution ,
whereas with surfactant dilution leads to emulsification with
consequent problem of separation.
� The hydrotropic solubilzation occurs in the molar concentration
while surfactant show solubility enhancements at milimolar range.
Chapter 1: Study of Hydrotropes
11
� Hydrotropes have strong ionic group and a relatively smaller
hydrocarbon/non-polar group as compared to surfactant.
� Hydrotrope induce maximum solubility of solute at MHC while in
surfactant it occurs at CMC.
� The lamellar liquid crystal region absent in the aqueous solution of
hydrotropes while it is prominent in the micelle-forming surfactant.
� Phase diagram of aqueous solution of hydrotropes display a single
continuous isotropic liquid phase [69-71].
Fig 1.5
Hydrotropic Action
A huge amount of theoretical work has been reported on the behavior of
non-electrolytes in aqueous solutions, but very little information is available on
hydrotropy, probably due to lack of clear distinction between hydrotropes and
salts, and the resulting tendency to group hydrotropes with salting-in
substances. A salting-in substance enhances the solubility of a non electrolyte
in a solvent, that is, the solute is greater in the salt solution than in the
corresponding pure solvent. A more common occurrence, however is, one
where the converse is true that is the solubility of a non electrolyte in a salt
Chapter 1: Study of Hydrotropes
12
solution is lower that in the corresponding solvent, a situation refereed to a
generally as the salting-out effect. Assuming that hydrotropes behave in a
similar fashion, the following equation can be used to predict the solubility of
an organic compound in a hydrotropic solution.
log SSH = Ks [H] ………….......Eqn 1.1
Where Ks is the Setsschenow constant, H is the hydrotrope, and SH and
H are the solubilities of an organic solute in water with and without the
hydrotrope, respectively. For a positive hydrotropic effect corresponding to a
salting-in process, Ks is positive, and for a negative hydrotropic effect
corresponding to a salting-out process, Ks is negative. This empirical equation
is applicable to hydrotrope only in a limited concentration range.
Hydrotrope reduce the surface tension of water and at certain
concentration the surface tension become constant. This shows that the
association of the hydrotrope molecules in solution [72]. The balancing of
favorable hydrophobic interaction and unfavorable charge repulsion results in
the hydrotropes being soluble over a large concentration range. Hydrotrope
contains a hydrophobic moiety albeit small, that is able to participate in
relatively strong hydrophobic interaction with an uncharged apolar molecules.
If a hydrophobic moieties are large enough for the hydrophobic interaction to
overcome the charge repulsion, cooperative self-association take place
presumably producing highly dynamic and loose micellar type aggregates.
Hydrotrope designate the increase in solubility in water due to presence of
large amount of additives.
Applications of Hydrotropes in Organic Synthesis
Any technique that enhances the solubility of a sparingly soluble solute
in water finds immediate applications in organic synthesis. One of the
important strategies for organic chemistry is to develop simple, safe,
environmental friendly and inexpensive procedures for the synthesis of
valuable organic compounds. The synthesis of heterocyclic as well as
biologically active compound represent a broad class of compounds, which
have received considerable attention due to their wide range of biological
Chapter 1: Study of Hydrotropes
13
activities. Synthesis of these compound through greener and safer methods to
be required and that achieved by use of hydrotrope in aqueous medium. For
synthetic chemistry in aqueous solutions, the use of hydrotropes can be
beneficial and this can be realized from the reported literature.
Khadilkar and Madyar [56] reported a scaling up of dihydropyridine
ester synthesis in aqueous hydrotropic solution under a continuous microwave
reactor. They showed use of aqueous hydrotropic solution as a cheap, safe and
green alternative to organic solvent to carry out homogeneous reaction under
microwave heating (Scheme 1.1).
O
R
COOR1
COOCH3
NH3
N
COOR1COOR1
CH3
CH3
H
R
% NaPTSA
+ +Aqueous hydrotrope
Microwave
50
Scheme 1.1
Chandratre and Filmwala [57] synthesized quinolines by Friedlander′s
Heteroannulation method in aqueous hydrotropic medium. Here, they report
the effect of different concentration of hydrotropes on the yield of product
(Scheme 1.2).
O
R
NH2
+O R1
R2
Aqueous hydrotropeN
R
R2
R1
SXS
Scheme 1.2
Laxman and Sharma [73] showed the ability of hydrotrope to change the
regioselectivity in the reduction of isophorone with sodium borohydride. In this
reaction 1,4-reduction of isophrone by NaBH4 in presence of polyalkylene
glycol as hydrotrope. An anomalous effect of temperature was also observed
using sodium salicylate as hydrotrope (Scheme 1.3).
Chapter 1: Study of Hydrotropes
14
CH3
O
CH3
CH3
HO-(CH2-CH
2-O)-H
NaBH4
NaOH
OH
O
O
CH3
CH3 CH
3
O
O
O
O
OO
O
H
H
CH3
O
CH3
CH3
+ n
+
Selective 1,4-attack
Scheme 1.3
In our research laboratory the first application of hydrotropic solution in
facile synthesis of ferrocenylamines [74] using microwaves has been reported
by Salunkhe and co-workers. Microwave-assisted synthesis of secondary and
tertiary ferrocenylamines is achieved by using an amine exchange reaction
between ferrocenylmethyltrimethyl ammonium iodide and aryl amines in
aqueous hydrotropic solution. The synthesis proceeds in excellent yields within
short reaction times (Scheme 1.4).
N
Fe
Me
Me
Me
+I
Ar-NH2
50 % NaPTSA
MW
50 % NaPTSA
MW
Ar-NH-R
Fe
NH Ar
Fe
NAr
R
NH
50 % NaPTSA
MW
Secondary ferrocenylamines
Tertiary ferrocenylamines
Fe
N
Ferrocenyl azoles
Ferrocenylmethyltrimethylammonium iodide
Scheme 1.4
Chapter 1: Study of Hydrotropes
15
As hydrotopes are usually salts, their aqueous solutions are likely to
enhance dielectric heating rates in view of above discussion. This factor
coupled with their ability to solubilize organic compounds should make them
highly efficient solvents. Although the use of hydrotopes is barely exploited
field, it won’t be wonder if their aqueous solutions will occupy a unique
position in organic synthesis.
Selection of Hydrotropes
Our investigations began with the selection of appropriate hydrotropes
for the organic synthesis. The different hydrotropes such as Sodium Benzene
Sulphonate (NaBS), Sodium p-Xylene Sulphonate (NaXS) and Sodium p-
Toluene Sulphonate (NaPTS) were selected for this purpose. Our investigation
began with the optimization of aqueous concentration of the selected
hydrotropes. After considerable experimentation, we optimized 50 % aqueous
solution of hydrotropes as solvent since this concentration was suitable for the
solubilization of organic compounds in sufficient quantities. These
hydrotropes are most attractive since they are air and moisture stable salts and
easily accessible by a high yielding method [75]. We decided to use 50 %
aqueous solution of NaPTS as solvent since this concentration was fairly
enough for solubilizing organic compounds in appreciably minimum quantities.
The glycerin used as hydrotrope and it shows excellent hydrotropic
properties [76, 77]. Glycerin is non-toxic, colorless and odorless liquid which is
highly stable and compatible with other solvents. Many compounds are soluble
in glycerin easier than water and alcohol, therefore it acts as excellent solvent.
The dilution of glycerin with water is important because it prevents the liquid
from attaining any staying power, and so the liquid can no longer coat or attach
itself to another surface. After series of experiment we observed that, the 50%
solution of glycerin was suitable for the organic synthesis to solubilise organic
compounds.
Chapter 1: Study of Hydrotropes
16
General Method for Preparation of Hydrotropes
Synthesis of Sodium p-Toluene Sulphonate
A mixture of 0.65 mol (60 g) toluene and 33 mL of concentrated
sulphuric acid was taken in a 500 mL three-necked flask, provided with a
sealed mechanical stirrer and a reflux condenser. The mixture was heated with
stirring in an oil bath maintained at 110-120°C. When the toluene layer was
disappeared, the reaction mixture was cooled to room temperature and poured
with stirring into 250 mL cold water. The acid in solution was partly
neutralized by adding cautiously in small portions 30 g of sodium hydrogen
carbonate. The resulting solution was heated to boiling and saturated with 100
g sodium chloride. The hot solution was filtered through a Buchner funnel
previously warmed to about 100°C. The filtrate was cooled in ice with stirring
to form precipitate of sodium p- toluene sulphonate was filtered. The resulting
crude product was recrystalized by dissolving in 200-250 mL of water and
heated to boil and then saturated with sodium chloride. The solution was
allowed to cool somewhat, and then stirred with 2-3g of decolorizing charcoal
and filtered while hot with suction through a previously warmed Buchner
funnel. The warm filtrate was transferred to a beaker and cooled in ice to get
the precipitate of sodium p-toluene sulphonate. The precipitate was pressed
well and finally washed with a little alcohol and was dried in air and finally in
an oven at 100-110°C [78].
Synthesis of Sodium Benzene Sulphonate
The Sodium Benzene Sulphonate was prepared according to reported
method [78].
Sodium Xylenesulphonate
The Sodium salt of Xylenesulphonic acid (ZEONOL) used in the
present study was gifted from the Pharma products, Panvel, Maharashtra.
Characterization of Hydrotropes
Sodium p-Toluene Sulphonate
IR spectrum (Fig 1.10) showed the streching vibrations of aromatic
proton at 3065 cm-1. The characteristic S=O streching vibrations observed at
Chapter 1: Study of Hydrotropes
17
1134 cm-1 and 1050 cm-1 respectively. In methyl group the C-H gives strong
starching vibrations at 2919 cm-1. In 1H NMR (Fig 1.11) strong singlet at 2.24
is of methyl proton which is desheilded due to aromatic ring. There are two
peaks of protons Ha and Hb appeared at aromatic region. The doublet at 7.21
having coupling constant J= 7.8Hz is of two Ha protons ortho coupled with Hb
is slightly shielded due to –CH3 group. The doublet at 7.55 having coupling
constant J=8.1 Hz is due to two Hb protons ortho coupled with Ha and is
highly deshielded due to sulphonate group. 13 C NMR (Fig 1.12) showed peak
at 20.4 is of methyl carbon while the four aromatic carbons appeared at 125.3,
129.4, 139.3 and 142.4.
The spectroscopic data of Sodium p- Toluene Sulphonate is follows:
IR (KBr): υ = 3065, 3036, 2919, 187, 1134, 1050, 816, 693 cm-1. 1H NMR(300MHz, D2O, δ ppm): 2.24 (s, 3H), 7.21(d, J= 7.8Hz, 2H), 7.55 (d,
J=8.1Hz, 2H) 13
C NMR (75 MHz, D2O, δ ppm): 20.4, 125.3, 129.4, 139.3, 142.4
Sodium Benzene Sulphonate
The IR spectrum (Fig 1.13) of Sodium Benzene Sulphonate showed the
C-H starching vibarations of aromatic ring at 3059 cm-1. The characteristic
S=O starching vibrations observed at 1136 cm-1 and 1043 cm-1 respectively. 1H
NMR spectra (Fig 1.14) showed two sets of aromatic protons. The multiplate at
δ 7.38 to 7.46 are of three protons Hb, Hb′ and Hc while signal at 7.66 is
doublet of doublet for protons Ha and Ha′ having J value 1.2 Hz and 3.9Hz
respectively and is deshielded due to sulphonate group. In 13 C NMR (Fig 1.15)
there are four sets of carbon, peak at 142.1 is of aromatic carbon attached to
substituted sulphonate group, peaks at 131.5, 128.9 and 125.2 are of ortho,
meta and para carbon respectively.
The spectroscopic data of Sodium Benzene Sulphonate is follows:
IR (KBr): υ = 3059, 1211, 1136, 1043 cm-1. 1H NMR (300MHz, D2O, δ ppm): 7.38 to 7.46 (m, 3H), 7.66 (dd, J=1.2 Hz
and 3.9Hz, 2H) 13
C NMR (75 MHz, D2O, δ ppm): 125.2, 128.9, 131.5, 142.1
Chapter 1: Study of Hydrotropes
18
X-ray Diffraction (XRD)
Powder X-ray diffraction pattern of Sodium salt of p-Toluene
Sulphonate was obtained on the Philips diffractometer (PW-3071), using Ni
filtered Cu Kα radiation (λ=1.5406 Å) and scintillation counter as detector. The
pattern was recorded in the 2ө range of 20-60º with step of 0.1º. The phase
purity of the sample was checked by comparing the X-ray diffraction data
simulated from the crystal structure data available in the literature. The
comparison of the simulated and experimental powder XRD pattern of
synthesized compound is displayed in the (Fig 1.6). The exact matching of the
peak positions or reflections originating from the sample under study to the
peak positions in the simulated powder XRD pattern confirms the monoclinic
crystal structure for the Sodium p-Toluene Sulphonate. The absence of extra
reflections other than the monoclinic phase indicates that the sample is free
from any crystalline impurities originating from other phases. The three-
dimensional crystal structure of the salt based on the crystallographic
information reported by Reinke et al is displayed in the (Fig 1.7) viewed along
the ‘b’ axis. Thus from the XRD data we have confirmed the phase purity and
crystal structure of Sodium p-Toluene Sulphonate [79].
25 30 35 40
0
400
800
Inte
nsi
ty (
A.U
.)
2θθθθo
Experimental Simulated
Fig 1.6
Chapter 1: Study of Hydrotropes
19
Fig 1.7
Scanning Electron Microscopy (SEM)
Scanning Electron Microscopy pictures were taken on JEOL JSM to
study the morphology of the synthesized Sodium p-Toluene Sulphonate. The
SEM image (Fig 1.8) shows agglomerates of particals with diameters in the
range of several hundred of nanometer up to micrometers. This observation
suggests the probable layered stacking during crystal growth and is expected,
based on its three dimensional structure derived from XRD data.
Fig 1.8
Chapter 1: Study of Hydrotropes
20
Thermo Gravimetric Analysis (TGA) and Differential Thermal Analysis
(DTA)
TGA-DTA analysis was carried out to study the thermal stability of Sodium p-
Toluene Sulphonate. TGA-DTA profile as shown in (Fig 1.9). Weight loss is
mainly divided into three temperature regions. The first weight loss of probably
corresponds physically bound water species and is around 18.76%. The second
and third weight loss of approximately ~ 8.5% and 34.5 % could be due to the
evaporation of decomposition of organic groups present in the compound. The
residual weight percent was expected to be 16% but might be due to the
incomplete decomposition, we have the residual percentage of ~34%.
Fig 1.9: TGA graph of Sodium salt of p-Toluene Sulphonic Acid
Chapter 1: Study of Hydrotropes
27
1.3 References
[1] P. Anastas, J. C. Warner, Green Chemistry: Theory and Practice 1998 ,
Oxford University Press.
[2] (a) J. D. Holbrey, K. R. Seddon, J. Chem. Soc. Dalton Trans., 1999,
2133; (b) T. Welton, Chem. Rev. 1999, 99, 2071-2084; (c) M. J. Earle,
P. B. McCormac, K. R. Seddon, Green Chem., 1999, 1, 23. (d) M. T.
Reetz, W. Wiesenhöfer, G. Franciò , W. Leitner, Chem. Commun.,
2002, 992; (e)Y. Gu, C. Ogawa, S. Kobayashi, Org. Lett., 2007, 9, 175;
(f) H. Olivier-Bourbigou, L. Magna, J. Mol. Catal. A: Chem. 2002, 182.
[3] Noyori, R. Super critical fluids. Chem. Rev., 1999, 99, 353.
[4] J. Chen, K. Spear, J. G. Huddleston, R. D. Rogers, Green Chem., 2005,
7, 64.
[5] I. T. Horv´ath, Acc. Chem. Res., 1998, 31, 641.
[6] H. C. Hailes, Org. Process Res. Dev., 2007, 11, 114.
[7] P. Ball, “H2O A Biography of Water” Phoenix, London, 2000.
[8] (a) C. J. Li, T. H. Chang, Organic Reactions in Aqueous Media,Wiley:
New York, 1997; (b) P. A. Grieco, Organic Synthesisin Water; Blackie
Academic and Professional: London,1998.
[9] S. E. Thompson, D. B. Smithrud, Am. Che. Soc., 2002, 124, 442.
[10] S. L. Johnson, Adv. Phys. Org. Chem., 1967, 5, 237.
[11] T. C. Bruice, A. Donzel, R. W. Huffman, A. R. Butler, J. Chem. Soc.,
1967, 89, 2106.
[12] G. K. van der Wel, J. W. Wijnen, J. B. Engberts, J. Org.Chem, 1996, 61,
9001.
[13] (a) P. A. Grieco, ed. “Organic Synthesis in Water” Blackie, London,
1998; (b) U. M. Lindstrom, Chem. Rev., 2002, 102, 2751; (c) A.
Lubineau, J. Auge, Y. Queneau, Synthesis, 1994, 741; (d) C. Li, Chem.
Rev., 1993, 93, 2023.
[14] P. T. Anastas, J. C. Warner, Green Chemistry: Theory and Practice;
Oxford University Press: New York, 1998, 30.
[15] N. Hall, Science, 1994, 266, 32.
Chapter 1: Study of Hydrotropes
28
[16] A. Newman, Environ. Sci. Technol., 1994, 28(11), 463.
[17] R. Wedin, Today's Chemist at Work, 1994 (June), 114.
[18] R. A. Sheldon, Chemtech., 1994 (March), 38.
[19] I. Amato, Science, 1993, 259, 1538.
[20] D. L. Illman, Chem. Eng. News, 1993 (Sept. 6), 26.
[21] R. Wedin, Today's Chemist at Work, 1993 (July/Aug.), 16.
[22] L. Ember, Chemtech, 1993 (June), 3.
[23] P. T. Anastas and T. C. Williamson, Frontiers in green chemistry, Green
Chem. 1998, 1.
[24] P. T. Anastas, M. M. Kirchhoff, Origins, current status, and future
challenges of green chemistry, Acc. Chem. Res., 2002, 35, 686.
[25] D. C. Rideout, R. Breslow, J. Am. Chem. Soc., 1980, 102, 7816.
[26] P. A. Grieco, E. B. Brandes, S. McCann, J. D. Clark, J. Org. Chem.,
1993, 93, 2023.
[27] A. Lubineau, E. Mayer, Tetrahedron, 1988, 44, 6065.
[28] R. Breslow, Acc. Chem. Res., 1991, 24, 159.
[29] C. J. Li, J. Chem. Rev., 1993, 93, 2023.
[30] U. M. Lindatrom, Chem. Rev., 2002, 102, 2751.
[31] T. S. Jin, J. S. Zang, A. Q. Wang, T. S. Li, Synth. Commun., 2004, 34,
2611.
[32] C. Neuberg, Hydrotropy, Biochem. Z., 1916, 76, 107.
[33] (a) P. Ekwall, G. H. Brown (Ed.), Advances in Liquid Crystals,
Academic Press, New York, 1975, 1, 1; (b)Y. P. Koparkar, V. G.
Gaikar, J. Chem. Eng. Data, 2004, 49, 800.
[34] S. E. Friberg, R. V. Lochhead, I. Blute, T. Warnheim, J. Dispers Sci.
Technol., 2004, 25, 243.
[35] B. K. Roy, S. P. Moulik, Curr. Sci., 2003, 85, 1148.
[36] T. K. Hodgdon, E. W. Kaler, Current Option in Colloid & Interface
Science, 2007, 12, 121.
[37] A. Matero, In Handbook of Applied Surface and Colloide Chemistry,
Vol.1, K. Holmberg, Ed., Wiley-VCH, New York, 2002, 407.
Chapter 1: Study of Hydrotropes
29
[38] P. Bauuin, A. Renoncourt, A. Kopf, D. Touraud, W. Kunz, Langmuir,
2005, 21, 6769.
[39] S. E. Friberg, Curr. Opin. Colloid Interface Sci., 1997, 2, 490.
[40] B. Schobert, Naturwissenschaften, 1997, 64, 386.
[41] B. Schobert, H. Tschesche, Biochim. Biophys. Acta, 1978, 541, 270.
[42] P. Mukerjee, J. Pharm.Sci., 1974, 63, 972.
[43] D. Balasubramanian, V. Shrinivas, V. G. Gaikar, M. M. Sharma, J.
Phys. Chem. , 1989, 93, 3865.
[44] (a) A. M. Saleh, L. K. El-khordagui, Int. J. Pharm., 1985, 24, 132; (b) A.
A. Badwan, L. K. El-khordagui, A. M. Saleh, S. A. Khalil, J. Pharm.
Pharmacol, 1980, 32, 74.
[45] (a) V. Srinivas, D. Balasubramanian, Langmuir, 1998, 14, 6658; (b) V.
Srinivas, G. A. Rodley, K. Ravikumar, W. T. Robinson, M. M.
Turnbull, D. Balasubramanian, Langmuir, 1997, 13, 3235; (c) O. R. Pal,
V. G. Gaikar, J. V. Joshi, P. S. Goyal, V. k. Aswal, Pramana-J. Phys.,
2004, 63, 357.
[46] S. Kumar, N. Praveen, Kabir-ud-Din, J. Surfactants Deterg., 2005, 8,
109.
[47] G. Horvath-Szabo, Q. Yin, S. E. Friberg, Colloid Interface Sci., 2001,
236, 52.
[48] G. K. Poochiikian, J. C. Cradock, Pharm. Sci., 1979, 68, 728.
[49] J. C. Eriksson, G. Gillberg, Acta Chem. Scand., 1966, 20, 2019.
[50] R. H. McKee, Use of hydrotropic solutions in industy, Ind. Eng. Chem.,
1946, 38, 382.
[51] S. E. Friberg, I. Blute, In: Lai K-Y, editor. Hydrotropy. In Surfactant
Science Series 129 ( Liquid Detergents , 2 nd Edition), CRC Press LLC,
2006, 19.
[52] S. E. Friberg, C. Brancewicz, D. S. Morrison, Langmuir, 1994, 10,
2945.
[53] S. E Friberg, J. Yang, T. A. Huang, Ind. Eng. Chem. Res., 1996, 35,
2856.
Chapter 1: Study of Hydrotropes
30
[54] Usage of sodium dimethylbenzenesulfonate (mixture of isomers)
according to the National Toxicology Program (US).
[55] V. G. Sadvilkar, S. D. Samant, V. G. Gaikar, J. Chem. Technol.
Biotechnol., 1995, 62, 405.
[56] B. M. Khadilkar, V. R. Madyar, Org. Process Research and
Devlopment., 2001, 5, 452.
[57] S. J. Chandratre, Z. A. Filmwala, J. of Dispersion Science and
Technology, 2007, 28, 279.
[58] B. Janakiraman, M. M. Sharma, Chem. Eng. Sci., 1985, 40, 2156.
[59] X. N. Chen, J. C. Micheau, Colloid Interface Sci., 2002, 249, 172.
[60] G. D. Gupta, S. Jain, N. K. Jain, Pharmazie, 1997, 52, 709.
[61] R. M. Khalil, Pharmazie, 1997, 52, 866.
[62] G. D. Gupta, S. Jain, N. K. Jain, Pharmazie, 1997, 52, 621.
[63] S. A. ElNahhas, Pharmazie, Pharmazie, 1997, 52, 624.
[64] N. K. Jain, S, Jain, A. K. Singhai, Pharmazie, 1997, 52, 942.
[65] N. S. Tavare, E. J. Colonia, J. Eng. Data, 1997, 42, 631.
[66] J. E. Colonia, A. B. Dixit, N. S. Tavare, Ind. Eng. Chem. Res., 1998, 37,
1956.
[67] G. Horvath-Szabo, J. H. Masliyah, J. J. Czarnecki, J. Colloid Interface
Sci., 2001, 242, 274.
[68] M. J. Lawrence, Chem. Soc. Rev., 1994, 23, 417.
[69] D. Balasubramanian, S. E. Friberg, Suface and Colloid Science, (E.
Matejevic, ed.), Plenum, New York, 1993, 15, 197.
[70] T. Flaim, S. E. Friberg, J. Colloid Interface Sci., 1984, 97, 26.
[71] S. E. Friberg, S. B. Rananavare, W. D. Osborne, J. Colloid Interface
Sci., 1986, 109, 487.
[72] I. A. Darwish, F. A. Ismail, L. K. EI-Koradagui, Alex. J. Pharm. Sci.,
1992, 6, 101.
[73] M. Laxman, M. M. Sharma, Synth. Commun., 1990, 20 (1), 111.
[74] G. Rashinkar, S. Kamble, A. Kumbhar, R. Salunkhe, Transition Met.
Chem., 2010, 35, 185.
Chapter 1: Study of Hydrotropes
31
[75] H. -X. Wang, Y. -J. Li, R. Jin, J. R. Niu, H. -F. Wu, H. -C. Zhou, J. Xu,
R. -Q. Gao, F. -Y. Geng, J. Organomet. Chem., 2006, 691, 987.
[76] Q. Se´bastien, P. Bauduin, D. Touraud,b W. Kunzb and J-M. Aubry,
Green Chem., 2006, 8, 822.
[77] http://www.ehow.com/about_6644358_glycerine-hydrotrope.html
[78] B. S. Furnis, A. J.Hannaford, P. W. G. Smith, A. R. Tatchell, (1996)
Vogel’s textbook of practical organic chemistry. Prentice Hall.
[79] H. Reinke, S. Rudershausen, (1999). Private communication (refcode
HORSUC). CCDC, Cambridge, England.
Chapter 1: Study of Hydrotropes
32
21
Fig 1.10: Sodium salt of p-Toulene Sulphonic Acid
22
Fig 1.11: Sodium salt of p-Toulene Sulphonic Acid
23
Fig 1.12: Sodium salt of p-Toulene Sulphonic Acid
24
Fig 1.13 Sodium salt of Benzene Sulphonic Acid
25
Fig 1.14: Sodium salt of Benzene Sulphonic Acid
26
Fig 1.15: Sodium salt of Benzene Sulphonic Acid
Chapter 1: Study of Hydrotropes
27
1.3 References
[1] P. Anastas, J. C. Warner, Green Chemistry: Theory and Practice 1998 ,
Oxford University Press.
[2] (a) J. D. Holbrey, K. R. Seddon, J. Chem. Soc. Dalton Trans., 1999,
2133; (b) T. Welton, Chem. Rev. 1999, 99, 2071-2084; (c) M. J. Earle,
P. B. McCormac, K. R. Seddon, Green Chem., 1999, 1, 23. (d) M. T.
Reetz, W. Wiesenhöfer, G. Franciò , W. Leitner, Chem. Commun.,
2002, 992; (e)Y. Gu, C. Ogawa, S. Kobayashi, Org. Lett., 2007, 9, 175;
(f) H. Olivier-Bourbigou, L. Magna, J. Mol. Catal. A: Chem. 2002, 182.
[3] Noyori, R. Super critical fluids. Chem. Rev., 1999, 99, 353.
[4] J. Chen, K. Spear, J. G. Huddleston, R. D. Rogers, Green Chem., 2005,
7, 64.
[5] I. T. Horv´ath, Acc. Chem. Res., 1998, 31, 641.
[6] H. C. Hailes, Org. Process Res. Dev., 2007, 11, 114.
[7] P. Ball, “H2O A Biography of Water” Phoenix, London, 2000.
[8] (a) C. J. Li, T. H. Chang, Organic Reactions in Aqueous Media,Wiley:
New York, 1997; (b) P. A. Grieco, Organic Synthesisin Water; Blackie
Academic and Professional: London,1998.
[9] S. E. Thompson, D. B. Smithrud, Am. Che. Soc., 2002, 124, 442.
[10] S. L. Johnson, Adv. Phys. Org. Chem., 1967, 5, 237.
[11] T. C. Bruice, A. Donzel, R. W. Huffman, A. R. Butler, J. Chem. Soc.,
1967, 89, 2106.
[12] G. K. van der Wel, J. W. Wijnen, J. B. Engberts, J. Org.Chem, 1996, 61,
9001.
[13] (a) P. A. Grieco, ed. “Organic Synthesis in Water” Blackie, London,
1998; (b) U. M. Lindstrom, Chem. Rev., 2002, 102, 2751; (c) A.
Lubineau, J. Auge, Y. Queneau, Synthesis, 1994, 741; (d) C. Li, Chem.
Rev., 1993, 93, 2023.
[14] P. T. Anastas, J. C. Warner, Green Chemistry: Theory and Practice;
Oxford University Press: New York, 1998, 30.
[15] N. Hall, Science, 1994, 266, 32.
Chapter 1: Study of Hydrotropes
28
[16] A. Newman, Environ. Sci. Technol., 1994, 28(11), 463.
[17] R. Wedin, Today's Chemist at Work, 1994 (June), 114.
[18] R. A. Sheldon, Chemtech., 1994 (March), 38.
[19] I. Amato, Science, 1993, 259, 1538.
[20] D. L. Illman, Chem. Eng. News, 1993 (Sept. 6), 26.
[21] R. Wedin, Today's Chemist at Work, 1993 (July/Aug.), 16.
[22] L. Ember, Chemtech, 1993 (June), 3.
[23] P. T. Anastas and T. C. Williamson, Frontiers in green chemistry, Green
Chem. 1998, 1.
[24] P. T. Anastas, M. M. Kirchhoff, Origins, current status, and future
challenges of green chemistry, Acc. Chem. Res., 2002, 35, 686.
[25] D. C. Rideout, R. Breslow, J. Am. Chem. Soc., 1980, 102, 7816.
[26] P. A. Grieco, E. B. Brandes, S. McCann, J. D. Clark, J. Org. Chem.,
1993, 93, 2023.
[27] A. Lubineau, E. Mayer, Tetrahedron, 1988, 44, 6065.
[28] R. Breslow, Acc. Chem. Res., 1991, 24, 159.
[29] C. J. Li, J. Chem. Rev., 1993, 93, 2023.
[30] U. M. Lindatrom, Chem. Rev., 2002, 102, 2751.
[31] T. S. Jin, J. S. Zang, A. Q. Wang, T. S. Li, Synth. Commun., 2004, 34,
2611.
[32] C. Neuberg, Hydrotropy, Biochem. Z., 1916, 76, 107.
[33] (a) P. Ekwall, G. H. Brown (Ed.), Advances in Liquid Crystals,
Academic Press, New York, 1975, 1, 1; (b)Y. P. Koparkar, V. G.
Gaikar, J. Chem. Eng. Data, 2004, 49, 800.
[34] S. E. Friberg, R. V. Lochhead, I. Blute, T. Warnheim, J. Dispers Sci.
Technol., 2004, 25, 243.
[35] B. K. Roy, S. P. Moulik, Curr. Sci., 2003, 85, 1148.
[36] T. K. Hodgdon, E. W. Kaler, Current Option in Colloid & Interface
Science, 2007, 12, 121.
[37] A. Matero, In Handbook of Applied Surface and Colloide Chemistry,
Vol.1, K. Holmberg, Ed., Wiley-VCH, New York, 2002, 407.
Chapter 1: Study of Hydrotropes
29
[38] P. Bauuin, A. Renoncourt, A. Kopf, D. Touraud, W. Kunz, Langmuir,
2005, 21, 6769.
[39] S. E. Friberg, Curr. Opin. Colloid Interface Sci., 1997, 2, 490.
[40] B. Schobert, Naturwissenschaften, 1997, 64, 386.
[41] B. Schobert, H. Tschesche, Biochim. Biophys. Acta, 1978, 541, 270.
[42] P. Mukerjee, J. Pharm.Sci., 1974, 63, 972.
[43] D. Balasubramanian, V. Shrinivas, V. G. Gaikar, M. M. Sharma, J.
Phys. Chem. , 1989, 93, 3865.
[44] (a) A. M. Saleh, L. K. El-khordagui, Int. J. Pharm., 1985, 24, 132; (b) A.
A. Badwan, L. K. El-khordagui, A. M. Saleh, S. A. Khalil, J. Pharm.
Pharmacol, 1980, 32, 74.
[45] (a) V. Srinivas, D. Balasubramanian, Langmuir, 1998, 14, 6658; (b) V.
Srinivas, G. A. Rodley, K. Ravikumar, W. T. Robinson, M. M.
Turnbull, D. Balasubramanian, Langmuir, 1997, 13, 3235; (c) O. R. Pal,
V. G. Gaikar, J. V. Joshi, P. S. Goyal, V. k. Aswal, Pramana-J. Phys.,
2004, 63, 357.
[46] S. Kumar, N. Praveen, Kabir-ud-Din, J. Surfactants Deterg., 2005, 8,
109.
[47] G. Horvath-Szabo, Q. Yin, S. E. Friberg, Colloid Interface Sci., 2001,
236, 52.
[48] G. K. Poochiikian, J. C. Cradock, Pharm. Sci., 1979, 68, 728.
[49] J. C. Eriksson, G. Gillberg, Acta Chem. Scand., 1966, 20, 2019.
[50] R. H. McKee, Use of hydrotropic solutions in industy, Ind. Eng. Chem.,
1946, 38, 382.
[51] S. E. Friberg, I. Blute, In: Lai K-Y, editor. Hydrotropy. In Surfactant
Science Series 129 ( Liquid Detergents , 2 nd Edition), CRC Press LLC,
2006, 19.
[52] S. E. Friberg, C. Brancewicz, D. S. Morrison, Langmuir, 1994, 10,
2945.
[53] S. E Friberg, J. Yang, T. A. Huang, Ind. Eng. Chem. Res., 1996, 35,
2856.
Chapter 1: Study of Hydrotropes
30
[54] Usage of sodium dimethylbenzenesulfonate (mixture of isomers)
according to the National Toxicology Program (US).
[55] V. G. Sadvilkar, S. D. Samant, V. G. Gaikar, J. Chem. Technol.
Biotechnol., 1995, 62, 405.
[56] B. M. Khadilkar, V. R. Madyar, Org. Process Research and
Devlopment., 2001, 5, 452.
[57] S. J. Chandratre, Z. A. Filmwala, J. of Dispersion Science and
Technology, 2007, 28, 279.
[58] B. Janakiraman, M. M. Sharma, Chem. Eng. Sci., 1985, 40, 2156.
[59] X. N. Chen, J. C. Micheau, Colloid Interface Sci., 2002, 249, 172.
[60] G. D. Gupta, S. Jain, N. K. Jain, Pharmazie, 1997, 52, 709.
[61] R. M. Khalil, Pharmazie, 1997, 52, 866.
[62] G. D. Gupta, S. Jain, N. K. Jain, Pharmazie, 1997, 52, 621.
[63] S. A. ElNahhas, Pharmazie, Pharmazie, 1997, 52, 624.
[64] N. K. Jain, S, Jain, A. K. Singhai, Pharmazie, 1997, 52, 942.
[65] N. S. Tavare, E. J. Colonia, J. Eng. Data, 1997, 42, 631.
[66] J. E. Colonia, A. B. Dixit, N. S. Tavare, Ind. Eng. Chem. Res., 1998, 37,
1956.
[67] G. Horvath-Szabo, J. H. Masliyah, J. J. Czarnecki, J. Colloid Interface
Sci., 2001, 242, 274.
[68] M. J. Lawrence, Chem. Soc. Rev., 1994, 23, 417.
[69] D. Balasubramanian, S. E. Friberg, Suface and Colloid Science, (E.
Matejevic, ed.), Plenum, New York, 1993, 15, 197.
[70] T. Flaim, S. E. Friberg, J. Colloid Interface Sci., 1984, 97, 26.
[71] S. E. Friberg, S. B. Rananavare, W. D. Osborne, J. Colloid Interface
Sci., 1986, 109, 487.
[72] I. A. Darwish, F. A. Ismail, L. K. EI-Koradagui, Alex. J. Pharm. Sci.,
1992, 6, 101.
[73] M. Laxman, M. M. Sharma, Synth. Commun., 1990, 20 (1), 111.
[74] G. Rashinkar, S. Kamble, A. Kumbhar, R. Salunkhe, Transition Met.
Chem., 2010, 35, 185.
Chapter 1: Study of Hydrotropes
31
[75] H. -X. Wang, Y. -J. Li, R. Jin, J. R. Niu, H. -F. Wu, H. -C. Zhou, J. Xu,
R. -Q. Gao, F. -Y. Geng, J. Organomet. Chem., 2006, 691, 987.
[76] Q. Se´bastien, P. Bauduin, D. Touraud,b W. Kunzb and J-M. Aubry,
Green Chem., 2006, 8, 822.
[77] http://www.ehow.com/about_6644358_glycerine-hydrotrope.html
[78] B. S. Furnis, A. J.Hannaford, P. W. G. Smith, A. R. Tatchell, (1996)
Vogel’s textbook of practical organic chemistry. Prentice Hall.
[79] H. Reinke, S. Rudershausen, (1999). Private communication (refcode
HORSUC). CCDC, Cambridge, England.
Chapter 1: Study of Hydrotropes
32