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CHAPTER-3 CHARACTERIZATION OF 3-[(8-HYDROXY QUINOLIN-5-
YL) AMINO METHYL]-5-ARYLOXY ACETYL-1,3,4-OXADIAZOLE-2(3H)-THIONE [RCC-1 TO RCC-6].
Chapter-3
49
Chapter-3
Characterization of 3-[(8-hydroxy quinolin-5-yl)
amino methyl]-5-aryloxy acetyl-1,3,4-oxadiazole-
2(3H)-thione [RCC-1 to RCC-6].
The present chapter deals with the characterization of 3-[(8-hydroxy quinolin-
5-yl) amino methyl]-5-aryloxy acetyl-1,3,4-oxadiazole-2(3H)-thione (i.e.RCC-1 to
RCC-6) derivatives described in Chapter 2 by,
(I) Elemental analysis
(II) IR, NMR and Mass spectral studies
(III) Hydroxyl group determination and
(IV) Oxidation
3.1 ELEMENTAL ANALYSIS.
The general properties of ligands RCC-1 to RCC-6 are:
Melting points (oC) of all the compounds were measured by capillary method.
All the mp’s are uncorrected.
The yields of all compounds reported are of crystallized. All solvents used
were distilled and dried. The purity of the compounds was checked by TLC.
Column chromatography was performed on silica gel (60-120 mesh).
All the ligands synthesized and described in an earlier chapter were analyzed
by their elemental contents. The C, H and N elements of all the samples were
measured by Elemental analyzer Thermofinigan flash1101 EA (Italy). The halogen
and sulfur contents as case may be determined by Carius method [1]. The method
was adopted as follow:
Chapter-3
50
100 mg of the sample was placed in a dried Carius tube (80 cm long, 1 cm
diameter). Then about 25 mg of silver nitrate (for halogen) or Barium Chloride (for
sulfur) was added. Finally 5 to 7 drops of fuming nitric acid were added and sealed
the tube and placed in a furnace for 6 hrs with maintaining the temperature 300 0C.
After cooling the tube was opened and the obtained precipitates of silver halide or
barium sulfur transferred into pre-weighted G-4 funnel and the precipitates weighed.
Finally the halogen or sulfur percentages were calculated. The C, H, and N
contents of all RCC-1 to RCC-6 derivatives are shown in Table 3.1. The data are
consistent with the predicted structures of ligands.
Chapter-3
51
Table 3.1 Characterization of Ligands RCC-1 to RCC-6.
Ligand No. Molecular
formula
Mol. Wt.
Gm/Mole
% Yield
RCC-1 C19H16N4O3S 380 70
RCC-2 C19H15N4O3SCl 414.5 78
RCC-3 C19H15N4O3SBr 459 70
RCC-4 C19H15N5O5S 425 74
RCC-5 C19H14N4O3SCl2 449 73
RCC-6 C23H18N4O3S 430 75
For, RCC-2 = %Cl = 8.56 (Cal.), 8.50 (Found)
RCC-3 = %Br = 17.42 (Cal.), 17.50 (Found)
RCC-5 = %Cl = 15.81 (Cal.), 15.80 (Found)
Ligand
No.
%C %H %N %S
Cal. Found Cal. Found Cal. Found Cal. Found
RCC-1 60.00 60.00 4.21 4.20 14.73 14.70 8.42 8.50
RCC-2 55.00 55.00 3.61 3.60 13.51 13.50 7.72 7.70
RCC-3 49.67 50.00 3.26 3.20 12.20 12.20 6.97 7.00
RCC-4 53.64 54.00 3.52 3.50 16.47 16.50 7.52 7.50
RCC-5 50.77 50.50 3.11 3.10 12.47 12.50 7.12 7.10
RCC-6 64.18 64.10 4.18 4.20 13.02 13.00 7.44 7.40
Chapter-3
52
3.2 INFRARED SPECTROSCOPY.
The atoms of a molecular behave as if they were connected by flexible
spizing, rather than by rigid bound resembling the connectors of a ball and stick
model. Their component parts can oscillate in different vibrational modes, designed
by such terms as rocking, scissoring, twisting, wagging and symmetrical and
asymmetrical stretching. When infra red radiation is passed through a sample of a
given compound, its molecules can absorb radiation of the energy (and frequency)
needed to bring about transitions between vibration of ground states and vibration of
excited states.
For example, a C-H bond, that vibrates 90 trillion times a second, must absorb
infrared radiation of just that frequency to jump to its first vibration excited state.
This absorption of energy at various frequencies can be detected by an infrared
spectrometer, which plots and amount of infrared radiation transmitted through the
sample as a function of the frequency (or wavelength) of the radiation. An infrared
spectrum consists of comparatively broad absorption bands rather than sharp peaks
such as those seen in NMR spectra. The bands are also usually “Inverted”-a deep
valley rather than a peak represents strong absorption.
Infrared spectroscopy is extremely useful [2-6] in qualitative analysis. It can
be used both to detect the presence of specific functional groups and other structural
features from band positions and intensities and to establish the identity of an
unknown compound with a known standard. The fingerprint region of the infrared
spectrum, (1250-670 cm-1, 8-15 lym) is best for showing that two substance are
identical, since the distinctive patterns found in this region are usually characterizes of
the whole molecule and not of isolated groups. Infrared spectra can also be used in
establishing the purity of compounds, monitoring reaction rates, measuring the
constructions of solubility, determining the structures of Chelate molecules, and
carrying out theoretical studies of hydrogen bonding in other phenomena.
Chapter-3
53
3.2.1 Experimental
Infrared scanning for the produced ligands was made in the range 4000-
600cm-1 in KBr. AR grade KBr was used for this purpose. It was first fused,
powdered and dried in vacuum. The absence of moisture in this dried KBr pellet was
checked by scanning and IR spectra of purified KBr. Then the pellet of KBr with
polymer was prepared as under.
A mixture of 4mg of pure dried sample and 1gm KBr powder was ground in a
mini ball mill for about 10 minutes. The resulting mixture was placed on the disc and
compressed at high pressure about 20,000 psi giving the transparent pellet. The IR
spectrum of this transparent pellet was scanned on Nicollet FTIR 760
spectrophotometer.
3.2.2 Results and discussion
The anticipated IR spectral frequencies of all the 3-[(8-hydroxy quinolin-5-yl)
amino methyl]-5-aryloxy acetyl-1,3,4-oxadiazole-2(3H)-thione ligands are given in
Table 3.2. The infrared spectra of selected ligands are shown in Figures 3.1 to 3.4.
The inspection of the infrared spectra of all the ligands reveals following.
Chapter-3
54
Table – 3.2 Anticipated IR spectral features for Ligands RCC-1 to RCC-6.
Sr.
No. Group IR frequencies (Cm-1)
1. -CH2- 2920, 2850, 1450
2. -NH- 3400
3. -OH of 8-hydroxy quinoline 3800-2700 broad
4. Aromatic 1600, 1500, 3030
5. 8-Hydroxy quinoline moiety 1575, 1560, 1470
6. C=S of Oxadiazole 1630
Chapter-3
55
Figure: 3.1 IR Spectrum of Ligand RCC-1
Chapter-3
56
Figure: 3.2 IR Spectrum of Ligand RCC-2
Chapter-3
57
Figure: 3.3 IR Spectrum of Ligand RCC-3
Chapter-3
58
Figure: 3.4 IR Spectrum of Ligand RCC-4
Chapter-3
59
(a) All the IR spectra comprise the broad band from 3800 to 2700 cm-1
with the inflections. The broad band is appeared due to phenolic
OH group of 8-hydroxy quinoline moiety.
(b) The inflections around 2920 cm-1 and 2850 cm-1 are attributed to
asymmetric and symmetric stretching vibration of -CH2 of
The supporting band at 1450 cm-1 is also appeared due to CH2 bending
vibrations.
(c) The bands around 1500 and 1600 cm-1 in the region of double bond are
appeared. Then might be raised from aromatic segment of 8-hydroxy
quinoline.
(d) The weak band around 3030 cm-1 might be due to aromatic C-H stretching
vibrations.
(e) The strong band around 3400 cm attributed to –NH- stretching vibrations.
(f) The other bands in the fingerprint region are appeared at their respective
position. The bands around 1220 and 1020 cm-1 are mainly due to C-N
bending vibrations while the C=N stretching vibration features is appeared
around 1690 and 1660 cm-1. The weak bands due to out of plane deformation
of 1, 2, 3 or 1,3 or 1,4-disubstituted benzene ring systems are appeared at 760,
860 and 810 cm-1 respectively.
Chapter-3
60
Table 3.3 IR Spectrum data of Ligands RCC-1 to RCC-6
Ligands Frequencies cm-1
-OH Aromatic 8-HQ Moiety -NH- -CH2-
RCC-1 2700-3800
1500
1600
3033
1470
1578
1630
3400
1448
2850
2920
RCC-2 2700-3800
1500
1600
3033
1470
1578
1630
3400
1448
2850
2920
RCC-3 2700-3800
1500
1600
3033
1470
1578
1630
3400
1448
2850
2920
RCC-4 2700-3800
1500
1600
3033
1470
1578
1630
3400
1448
2850
2920
RCC-5 2700-3800
1500
1600
3033
1470
1578
1630
3400
1448
2850
2920
RCC-6 2700-3800
1500
1600
3033
1470
1578
1630
3400
1448
2850
2920
Chapter-3
61
3.3 PROTON NUCLEAR MAGNETIC RESONANCE
SPECTROSCOPY:
Nuclear magnetic resonance (NMR) spectroscopy is supplementary technique
to IR spectroscopy to get details information about structure of organic compounds.
Most widely studied nucleus is proton and then the technique is called NMR
spectroscopy.
IR spectra give information about the functional group while NMR spectra
provide information about the exact nature of proton and its environment [7-9]. Thus
this technique is more useful in the elucidation of an organic compound. IR spectra of
isomers may appear same but their NMR spectra will markedly differ.
The phenomenon of nuclear magnetic resonance was first reported
independently in 1946 by two groups of physicists: Block, Hansen and Packard at
Stanford University detected a signal from the protons of water, and Purcell, Torrey
and Pound at Harvard University observed a signal from the protons in paraffin wax.
Block and Purcell were jointly awarded the Nobel Prize for physics in 1952 for this
discovery. Since that time, the advances in NMR techniques leading to wide spread
applications in various branches of science resulted in the Nobel Prize in chemistry in
1991. The applications of NMR in clinical, solid state and biophysical sciences are
really marvelous.
The proton magnetic resonance (NMR) spectroscopy is the most important
technique used for the characterization of organic compounds. It gives information
about the different kinds of protons in the molecule. In other words it tells one about
different kinds of environments of the hydrogen atoms in the molecule. PMR also
gives information about the number of protons of each type and the ratio of different
types of protons in the molecule.
It is well known that all nuclei carry a positive charge. In some nuclei this
charge ‘spins’ on the nuclear axis, and this circulation of nuclear charge generates a
Chapter-3
62
magnetic dipole along the axis. Thus, the nucleus behaves like a tiny bar magnet. The
angular momentum of the spinning charge is described in terms of spin number (I).
The magnitude of generated dipole is expressed in terms of nuclear magnetic moment
().
The spinning nucleus of a hydrogen atom (1H or proton) is the simplest and is
commonly encountered in organic compounds. The hydrogen nucleus has a magnetic
moment, = 2.79268 and its spin number (I) is + ½. Hence, in an applied external
magnetic field, its magnetic moment may have two possible orientations.
The orientations in which the magnetic moment is aligned with the applied
magnetic field is more stable (lower energy) than in which the magnetic moment is
aligned against the field (high energy). The energy required for flipping the proton
from its lower energy alignment to the higher energy alignment depends upon the
difference in energy (∆E) between the two states and is equal to h(∆E = h
In principle, the substance could be placed in a magnetic field of constant
strength, and then the spectrum can be obtained in the same way as an infrared or an
ultraviolet spectrum by passing radiation of steadily changing frequency through the
substance and observing the frequency at which radiations is absorbed. In practice,
however, it has been found to be more convenient to keep the radiation frequency
constant and vary the strength of the magnetic field. At some value of the field
strength the energy required to flip the proton matches the energy of the radiation,
absorption occurs and a signal is obtained. Such a spectrum is called a nuclear
magnetic resonance (NMR) spectrum.
Two types of NMR spectrometers are commonly encountered. They are:
a) Continuous wave (CW) NMR spectrometer
b) Fourier transform (FT) NMR spectrometer.
The CW-NMR spectrometer detects the resonance frequencies of nuclei in a
sample placed in a magnetic field by sweeping the frequency of RF radiation through
Chapter-3
63
a given range and directly recording the intensity of absorption as a function of
frequency. The spectrum is usually recorded and plotted simultaneously with a
recorder synchronized to the frequency of the RF source.
In FT-NMR spectroscopy, the sample is subjected to a high power short
duration pulse of RF radiation. This pulse of radiation contains a broad band of
frequencies and causes all the spin-active nuclei to resonate all at once at their Larmor
frequencies. Immediately following the pulse, the sample radiates a signal called free
induction decay (FID), which is modulated by all the frequencies of the nuclei excited
by the pulse. The signal detected as the nuclei return to equilibrium (intensity as a
function of time) is recorded, digitized and stored as an array of numbers in a
computer. Fourier transformation of the data affords a conventional (intensity as a
function of frequency) representation of the spectrum.
The first step in running NMR spectrum is the complete dissociation of a
requisite amount of the sample in the appropriate volume of a suitable NMR solvent.
Commonly used solvents are: CCl4, deuteron chloroform, deuteron DMSO, deuteron
methanol, deuteron water, deuteron benzene, trifluroacetic acid.
TMS is generally employed as internal standard for measuring the position of 1H, 13C, and 29Si in the NMR spectrum because it gives a single sharp peak, is
chemically inert and miscible with a large range of solvents, being a highly volatile,
can easily be removed if the sample has to be recovered, does not involve in
intramolecular association with the sample.
3.3.1 INTERPRETATION OF THE NMR SPECTRA:
It is not possible to prescribe a set of rules which is applicable on all
occasions. The amount of additional information available will most probably
determine the amount of information it is necessary to obtain from the NMR
spectrum. However, the following general procedure will form a useful initial
approach to the interpretation of most spectra.
Chapter-3
64
By making table of the chemical shifts of all the groups of absorptions in the
spectrum. In some cases it will not be possible to decide whether a particular group of
absorptions arises from separate sets of nuclei, or from a part of one complex
multiplet. In such cases it is probably best initially to include them under one group
and to note the spread of chemical shift values.
By measuring and recording the heights of the integration steps corresponding
to each group of absorptions. With overlapping groups of protons it may not be
possible to measure these exactly, in which case a range should be noted. Work out
possible proton ratios for the range of heights measured, by dividing by the lowest
height and multiplying as appropriate to give integral values.
By noting any obvious splitting of the absorptions in the table (e.g., doublet,
triplet, etc.). For spectra which appear to show first-order splitting, the coupling
constants of each multiplet should be determined by measuring the separation
between adjacent peaks in the multiplet. Any other recognizable patterns which are
not first order should be noted.
By noting any additional information such as the effect of shaking with D2O,
use of shift reagent, etc.
By considering both the relative intensities and the multiplicities of the
absorptions attempt to determine which groups of protons are coupled together. The
magnitude of the coupling constant may give indication of the nature of the proton
involved.
By relating the information to obtain other information available on the
compound under considerations.
Chapter-3
65
3.3.2 EXPERIMENTAL:
NMR spectra were recorded on Bruker NMR spectro-photometer. NMR
chemical shifts are recorded in value using TMS as an internal standard in
CDCl3/D6-DMSO. Typical NMR spectra are shown in figures 3.5 to 3.7. The NMR
data of all the ligands are covered in results and discussion.
3.3.3 RESULTS AND DISCUSSION:
The NMR spectra of all the ligands show the following common features,
while individual having additional signals are given below:
Chapter-3
66
Table 3.4 NMR Spectral data of Ligands RCC-1 to RCC-6
On the basis of structure of known reactants and their reactive sites, the
structures of all ligands shown are in chapter-2. The structures are confirmed by NMR
spectral data shown above and typical spectra shown in Figures: 3.5 to 3.7.
RCC-1 to
RCC-6
δ ppm 7.00 to 8.13 Multiplet, Quinoline and or
benzene rings
δ ppm 6.00-6.35 Singlet of phenolic OH
δ ppm 3.35-3.7 CH2 bridge of -CH2NH-
δ ppm 11.1-11.35 -NH-
δ ppm 3.7 – 3.8 -O-CH2- bridge
RCC-6 δ ppm 7.45 – 7.70
-Naphthyl
Chapter-3
67
Figure: 3.5 NMR Spectrum of Ligand RCC-1
Chapter-3
68
Figure: 3.6 NMR Spectrum of Ligand RCC-2
Chapter-3
69
Figure: 3.7 NMR Spectrum of Ligand RCC-3
Chapter-3
70
3.4 ESTIMATION OF NUMBER OF HYDROXYL (-OH) GROUPS IN LIGANDS RCC-1 TO RCC-6.
The structures of ligands were examined by estimation of number of
carboxylic–OH groups per mole of ligand. The non aqueous conductometric titration
was employed for -OH group estimation following the method reported in the
literature [10-13]. The titrant used for this non-aqueous titration was sodium
methanolate (NaOMe) in pyridine. The details procedure followed in titrations
described here for one of the selected ligand.
3.4.1 NON-AQUEOUS CONDUCTOMETRIC TITRATION. EXPERIMENTAL:
The ligand sample dried at 900C was finely powdered and used for non-
aqueous Conductometric titration. A weighed amount of ligand sample (50 mg) was
dissolved in 40 ml of anhydrous pyridine.
The solution was allowed to stand overnight for complete dissolution. This
ligand solution was transferred into conductance cell and it was then stirred
magnetically. The base sodium methoxide (0.1 N) in pyridine was added to the
conductance cell at regular interval of 0.01 ml of titrant beyond the stage of
equivalence. The conductance measurement after addition of each volume of titrant
base was carried out by following 2-3 minutes to lapse. During the titration the
temperature of solution was maintained constant about 250C when the point of
equivalence was exceeded; there it was a continuous increase in conductance on
addition of every additional aliquot of sodium methoxide indicating the stage of
complete neutralization of all the OH groups in the given amount of ligand sample.
The volume of base added is converted into millimoles of sodium methoxide required
for 100 gm of ligand. A plot of conductance against millimoles of sodium methoxide
per 100 gm of ligand sample was made as shown in figure 3.8. Inspection of such plot
revealed that was observed one break from the plot, the millimoles per 100 gm of
ligand sample corresponding to the break was noted and the numbers of OH groups
Chapter-3
71
were estimated. Each titration was reported twice as an independent experiments
using different amount of the ligand samples.
Figure – 3.8
Non Aqueous Conductometric Titration Curve for Ligand RCC-1
Estimations are agreed each other with 5% variation.
The No. of hydroxyl group per mole of ligand (X) was calculated as follow:
(X) = Millimoles of NaOMe per 100g of sample at the neutralization point (Y) X Mol. Wt of ligand (M) 100 X 103
Similarly, for all other ligands the values estimated for number of hydroxyl (-OH)
groups are reported in Table 3.5.
Chapter-3
72
3.4.2 RESULTS AND DISCUSSION:
The non-aqueous conductometric titration curves of each of the six ligands
have shown the presence of one break and the estimation of number of one –OH
group from the break has shown the values in the range of 0.98 to 1.10 indicating the
presence of one –OH groups. This is quite consistent with the proposed structure
shown in scheme-1.
Chapter-3
73
Table 3.5 Non-aqueous Conductometric titration of Ligands
Estimation of OH groups for RCC-1 to RCC-6
Solvent: - Anhydrous pyridine
Reagent :- 0.1 N sodium methanolate
Ligand
Molecular
weight
gm
Millimoles of NaOMe at
neutralization break per 100
gm of sample.
Estimated
No. of
–OH group
[RCC-1] 380 258 0.98
[RCC-2] 414.5 241 1.00
[RCC-3] 459 216 0.99
[RCC-4] 425 259 1.10
[RCC-5] 449 220 0.99
[RCC-6] 430 230 0.99
Chapter-3
74
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[1] S. Bance, Hand book of practical organic microanalysis, John willy and
sons N.Y. (1988).
[2] R.M. Silvestein, Spectrometric Identification of organic Compounds, 5th Edn.,
John Wiley, 123 (1991).
[3] Lyulin, O. M, Kurlovets, E. V, J. of quantitative spectroscopy & radiative
transfer, 113(17), 2167 (2012).
[4] A.I. Vogel, A Textbook of Quantitativ e Chemical Analysis Revised by J.
Bessett, R.C. Denny, J.H. Feffery and J. Mondhaus, EIBS, 5th Edn., London
(1996).
[5] G. Socrates;Infrared and Raman characteristics group’s frequencies: Table and
charts (2004).
[6] G. Peter, D. H. James; Fourier Transform Infrared Spectroscopy, 2nd Edition,
Wiley-Interscience (2007).
[7] D. N. Sathyanarayana, Introduction to Magnetic resonance spectroecopy
(Second edition) (2013).
[8] James Keeler, Understanding NMR Spectroscopy, Second edition (2010).
[9] Ray Freeman, A handbook of Nuclear magnetic resonance (1997)
[10] Petrenko, D.; Bulletin of the Moscow state regional university (Article), Issue
no. 1, 157 (2012).
[11] P. Patnaik, Dean’s Analytical Chemistry Handbook, 2nd edition, McGraw-Hill
(2004).
[12] S.K. Chatterjee and P.R. mitra, J. Polymer Sci., Part. A-1, 1299 (1970).
[13] S.K. Chatterjee and N.D. Gupta., J. Polymer Sci. Part A-1, 11, 1261 (1973).