Synthesis of new dyes from imidazo[1,2-a]pyridine: Tautomerism, spectroscopic characterisation, DFT/TD-DFT calculations, atoms in molecules analyses and antibacterial activities

Article abstract of DOI:10.3184/174751917X14873588907684

The synthesis, optical properties, theoretical calculations and antibacterial activity of a series of new heterocyclic dyes from imidazo[1,2-a] pyridine are described. The key intermediate 2-[3-(hydroxyimino)imidazo[1,2-a]pyridin-2(3H)-ylidene]malononitrile was obtained via the nucleophilic substitution of hydrogen in 3-nitroimidazo[1,2-a]pyridine with malononitrile in basic methanol solution. Tautomerism, oxidation and alkylation studies on the dye led to the synthesis of new heterocyclic indigo-coloured, purple, and orange dyes in good yields. The structures of all newly synthesised compounds were confirmed by spectral and analytical data. The optical properties of the dyes were spectrally characterised and shown to exhibit interesting photophysical properties including high extinction coefficients. Density functional theory calculations of the dyes were performed to provide the optimised geometries and relevant frontier orbitals. Calculated electronic absorption spectra were also obtained by the time-dependent density functional theory method. In addition, electrostatic potential maps and electron density maps of the dyes were evaluated by AIM (atoms in molecules) analysis. Moreover, the new dyes exhibited potent antibacterial activity and their antibacterial activities (MIC) against Gram-positive and Gram-negative bacterial species were determined.

Full text of DOI:10.3184/174751917X14873588907684

JOURNAL OF CHEMICAL RESEARCH 2017
VOL. 41 MARCH, 143–148
RESEARCH PAPER 143
Synthesis of new dyes from imidazo[1,2-a]pyridine: tautomerism,
spectroscopic characterisation, DFT/TD-DFT calculations, atoms in
molecules analyses and antibacterial activities
Samaneh Mohammadi, Mehdi Pordel*, Sadegh Allameh and Hamed Chegini
Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran
The synthesis, optical properties, theoretical calculations and antibacterial activity of a series of new heterocyclic dyes from imidazo[1,2-a]
pyridine are described. The key intermediate 2-[3-(hydroxyimino)imidazo[1,2-a]pyridin-2(3H)-ylidene]malononitrile was obtained via
the nucleophilic substitution of hydrogen in 3-nitroimidazo[1,2-a]pyridine with malononitrile in basic methanol solution. Tautomerism,
oxidation and alkylation studies on the dye led to the synthesis of new heterocyclic indigo-coloured, purple, and orange dyes in good
yields. The structures of all newly synthesised compounds were confirmed by spectral and analytical data. The optical properties of
the dyes were spectrally characterised and shown to exhibit interesting photophysical properties including high extinction coefficients.
Density functional theory calculations of the dyes were performed to provide the optimised geometries and relevant frontier orbitals.
Calculated electronic absorption spectra were also obtained by the time-dependent density functional theory method. In addition,
electrostatic potential maps and electron density maps of the dyes were evaluated by AIM (atoms in molecules) analysis. Moreover, the
new dyes exhibited potent antibacterial activity and their antibacterial activities (MIC) against Gram-positive and Gram-negative bacterial
species were determined.
Keywords: imidazo[1,2-a]pyridine, optical properties, density function theory calculations, 3D-electrostatic potential maps, antibacterial activity
Heterocyclic dyes are one of the most important and versatile
class of synthetic organic compounds, with an enormous
variety of applications. In recent years, heterocyclic dyes
have found great success because of their higher tinctorial
strength, brighter dyeing and excellent light, washing and
sublimation fastness, and chromophoric strength in relation to
synthetic organic dyes based uniquely on benzene derivatives.1
Heterocyclic dyes have wide applications as high-level dying
agents in the dyestuff industries.2,3 The increasing usage of
these dyes in the electronics industry, such as colorimetric
sensors, nonlinear optical (NLO) devices and liquid crystalline
displays (LCDs) have been investigated as has their potential as
sensitisers for photodynamic therapy (PDT) that has attracted
much attention.4 Also, they have been evaluated and employed
in the new areas of optoelectronic devices,5 photoconductors,6
solar-energy utilisation,7 sensitisers,8 biomedical probes,9
photo-catalysts,10 and so on. Furthermore, heterocyclic dyes
have been used extensively in the preparation of disperse dyes
with outstanding dischargeability on cellulose acetate.11
On the other hand, imidazo[1,2-a]pyridines are bicyclic
ring systems with multiple applications. They are potent
biological agents and possess potent activities such as
antiviral,12 anticancer,13 anxiolytic,14 antimalarial,15 hypnotic,16
antiprotozoal,17 and anti-inflammatory18 agents, which has
rendered this ring system an attractive target. Recently,
imidazo[1,2-a]pyridine moieties became of interest as dyes
and fluorescent compounds.19–21 Furthermore, the analytical
properties of some imidazo[1,2-a]pyridine dyes show they can
be used as an acid-base indicator.22
tautomerism, oxidation, alkylation, optical properties, DFT/
TD-DFT calculations, AIM (atoms in molecules) analyses and
antibacterial activity of the dyes have also been examined.
Results and discussion
As depicted in Scheme 1, the reaction of 2-aminopyridine
with 2-bromo-1,1-dimethoxyethane and then nitration of
imidazo[1,2-a] pyridine in H2SO4 and HNO3 led to the
formation of 3-nitroimidazo[1,2-a]pyridine (1).26 When
3-nitroimidazo[1,2-a]pyridine 1 and malononitrile 2 were
reacted in basic MeOH solution, the new 2-[3-(hydroxyimino)
imidazo[1,2-a]pyridin-2(3H)-ylidene]malononitrile
3
was
obtained via nucleophilic substitution of hydrogen25 in
excellent yield (Scheme 1). A plausible mechanism to explain
the formation of dye 3 is shown in Scheme 1. The initial steps
follow those proposed for the condensation of 1 and 2 in basic
MeOH solution.24
The structure of the new dye 3 was deduced from its
spectral and microanalytical data. The presence of one broad
1
exchangeable peak at δ 11.87 (OH) in the H NMR spectrum
of 3, weak 2218 cm–1 and 2215 cm–1 (diastereotopic CN groups)
and broad 3455 cm–1 (OH) absorption bands in the FTIR
spectrum and a molecular ion peak at m/z 211 (M+) confirmed
the structure of dye 3.
The new purple dye 4 was obtained in excellent yield when
compound 3 was heated under reflux in EtOAc (Scheme 2). The
IR spectrum of 4 showed a stretching vibration band at 1561
1
cm–1 indicative of an N=O group. The H NMR spectrum of
4 showed a singlet at δ 5.55 for the methine proton while the
13C NMR spectrum displayed a signal at δ 23.4 confirming the
presence of the dicyanomethyl group. The mass spectrum of 4
showed the molecular ion peak at m/z 211 (M+) corresponding
to the molecular formula C10H5N5O.
The new orange dye 5 was obtained from the oxidation of
purple dye 4 with 30% H2O2 in MeOH in high yield (Scheme 2).
The structural assignments of compound 5 were based on the
analytical and spectral data. For example, in the IR spectrum
of 5, two strong absorption bands at 1337 and 1543 cm–1 are
Taking these facts into consideration and in continuation
of our previous studies on the synthesis of new heterocyclic
dyes,19–24 in the present study, we have synthesised some new
heterocyclic indigo-coloured, purple and orange dyes derived
from 3-nitroimidazo[1,2-a]pyridine. The key intermediate
2-[3-(hydroxyimino)imidazo[1,2-a]pyridin-2(3H)-ylidene]
malononitrile was obtained via the nucleophilic substitution
of
hydrogen25 in
3-nitroimidazo[1,2-a]pyridine
with
malononitrile in KOH/MeOH, in high yield. In addition,
* Correspondent. E-mail: mehdipordel58@mshdiau.ac.ir

144 JOURNAL OF CHEMICAL RESEARCH 2017
Br
N
1. HCl, reflux
2. NaHCO3, 22 h reflux
N
HNO3, H2SO4
+
O
N
N
NH2
N
O
1,4-Dioxane, H2O
N
O2
1
pyridin-2-amine 2-bromo-1,1-
dimethoxyethane
imidazo[1,2-a]pyridine
CH(CN)2
H
N
C
H
C
C
N
N
N
N
N
C
N
N
KOH, MeOH
+
N
N
N
H
N
C
( )
2
C
N
N
H
2
N
C
N
C
C
−
, 4h, 85%
∆
N
N
N
N
H
O
N
O2
l
C
O
O
O
O
N
1
2
O
B
O
A
3
Scheme 1 Synthesis route and reaction mechanism for formation of new indigo-coloured dye 3.
CN
CN
N
EtOAC
CN
CN
CN
CN
N
N
H2O2, MeOH
reflux, 6 h, 75%
KOH, MeOH
N
N
reflux, 2 h, 80%
N
NO2
N
N
H
O
O
3
4
5
Scheme 2 Synthesis of new purple dye 4 and orange dye 5.
CN
CN
N
N
CN
CN
CN
CN
N
N
CN
CH3
CN
N
DMS, K2CO3
MeCN, rt, 12 h, 75%
MeI, t-BuOK
t-BuOH, rt, 4 h, 60%
N
N
N
N
N
N
N
H3C
H
O
O
O
O
7
4
3
6
Scheme 3 Methylation of dyes 3 and 4 to new dyes 6 and 7.
assignable to the nitro group. Furthermore, the mass spectrum of
5 showed the molecular ion peak at m/z 227 (M+) corresponding
to the molecular formula C10H5N5O2.
The purple solution of dye 4 in KOH/MeOH was smoothly
turned to an indigo colour and dye 3 was precipitated after
neutralisation of the solution with dilute HCl. It can be
concluded that dyes 3 and 4 are not particularly stable and
they can be converted into each other under appropriate
conditions. However, alkylation of active protons in dyes 3
and 4 prevents tautomerisation of these dyes. Compound 3 was
methylated by dimethyl sulfate (DMS) in K2CO3 and MeCN to
give a new indigo-coloured compound, 2-[3-(methoxyimino)
imidazo[1,2-a]pyridin-2(3H)-ylidene]malononitrile 6 at room
temperature (Scheme 3). New purple dye, 2-methyl-2-(3-
nitrosoimidazo[1,2-a]pyridin-2-yl)malononitrile 7 was also
synthesised from the reaction of dye 4 with methyl iodide in
tert-butanol in the presence of potassium tert-butoxide, in high
yield (Scheme 3). All the newly synthesised dyes have been
characterised by elemental analysis and spectroscopic data.
The spectral details of all these are given in the experimental
section.
The new dyes 3–7 were characterised by their UV-Vis
spectra in the region 200–800 nm. Figure 1 shows the visible
absorption spectrum of compounds 3–7 in dilute (1 × 10–5 M)
methanol solution. Characteristics of the absorption spectra
for 3–7 in methanol are presented in Table 1. Values of the
extinction coefficient (ε) were calculated as the slope of the plot
of absorbance vs concentration. The absorbance intensity and
extinction coefficient (ε) in the indigo-coloured dye 3 were the
biggest values.
Fig. 1 Visible absorption spectra of compounds 3–7 in methanol solution
(1 × 10–5 mol L–1).
Table 1 Spectroscopic properties of dyes 3–7 in MeOH solvent
Dye
3
4
5
6
7
λ
max (nm)a
ε × 10–3 (M–1 cm–1)b
605
525
480
595
520
41.0
40.7
16.8
24.1
25.5
aWavelengths of maximum absorbance (λmax).
bExtinction coefficient.
The absorption spectra of dyes 3–7 were measured in different
solvents. As shown in Table 2, the absorption spectra of 3–7
in polar solvents undergo a red shift. Increasing the solvent
polarity stabilises the excited state molecule comparative to
the ground-state molecule with the observed red shift of the
absorption maximum as the experimentally observed result

JOURNAL OF CHEMICAL RESEARCH 2017 145
π-system overlap in its HOMO and LUMO frontier orbitals
which led to the lower separation energy between the HOMO
and LUMO compared to dyes 4 and 5. In the ESI (Scheme S1),
neutral and some charge-separated mesomeric structures of
dyes 3–5 are presented.
Calculated electronic absorption spectra were also obtained
by time-dependent density functional theory (TD-DFT)
method. The TD-DFT electronic spectra calculations on 3
show two electronic transition bands. There is a relatively
sharp peak at 316 nm (oscillator strength: 0.0003), which can
be attributed to π–π* transitions (donor endocyclic N-4 to the
acceptor CN group), and a relatively broad band in the range
of 400 to 700 nm with an oscillator strength of 0.2899, which
can be linked to n–π* transitions from the donor OH group to
the acceptor CN group, compared with the experimental values
of 500–700 nm. The TD-DFT electronic spectra calculations
of 4 reveal a relatively sharp peak in the range of 450 to 650
nm which corresponds to the experimental data (400–600 nm)
with oscillator strength of 0.2414. These bands can be linked to
π–π* transitions from the donor endocyclic N-4 to the acceptor
N=O group. Also, the TD-DFT electronic spectra calculations
on dye 5 show that there is a relatively sharp peak at 447 nm
(oscillator strength: 0.2836), which can be attributed to π–π*
transitions from donor endocyclic N-4 to the acceptor NO2
group. This electronic transition band can be compared with the
experimental values of 480 nm.
Fig. 2 Visible absorption spectra of compound 3 in different solvents
(1 × 10–5 mol L–1).
Table 2 Spectroscopic data for 3–7 at 298 K in dependence of the
solvent
Solvent
λ
abs/nm (3) λabs/nm (4) λabs/nm (5) λabs/nm (6) λabs/nm (7)
n-Hexane 505
Chloroform 520
500
505
455
465
505
525
495
505
Acetone
MeCN
DMF
595
595
625
515
520
530
480
480
485
595
595
620
515
520
525
(Tables 2). For example, in the absorption spectra of indigo-
coloured 3, λabs shifts from 505 to 625 nm, as the solvent
changes from n-hexane to DMF (Fig. 2 and Table 2).
The calculated electronic absorption spectra of compounds
3–5 are shown in the ESI (Fig. S1–S3).
The colour intensity of dyes 3–7 indicates efficient
intramolecular charge transfer (ICT) states23 from the donor site
(endocyclic N-4 in dyes 3–7 or OH group in dyes 3 and 6) to
the acceptor moiety (CN in dyes 3 and 6 or N=O group in dyes
4, 5 and 7). To gain a deeper insight into the optical properties
and the UV-Vis absorption spectra of the dyes, we performed
DFT and TD-DFT (time-dependent density functional theory)
calculations at the B3LYP/6-311++G(d,p) level and obtained
the optimised geometries, HOMO and LUMO frontier orbitals
and electronic spectra of dyes 3–5.
The optimised geometries of the compounds 3–5 are shown
in Fig. 3. In the optimised geometry of the dye 3, imidazo[1,2-a]
pyridine ring and cyano groups are essentially planar and the
C=C bond lengths (1.38–1.44 Å) of the aromatic rings are in the
expected range27 (Tables S1–S3; see ESI).
AIM analysis
The electrostatic potential map, VS(r),28 of three dye’s structures
are shown in Fig. 5. As is clear from the 3D-electrostatic
potential maps, dye 3 due to a strong resonance has a greater
charge distribution throughout the structure, but as can be seen
from the electrostatic potential maps of structures 4 and 5, there
is noticeable charge separation.
In Fig. 5, the negative potential region VS(r) is located at the
outermost part of CN and shown in red.
On the other hand, according to the 3D-electron density map
(Fig. 6) is well defined that the structure 3 due to its planar
structure has a good chance to resonance than other structures
having nonplanar structure, which is principally associated
with the π-electronic structure; this advantage has led to much
denser electron density on CN groups.
The antibacterial activity of compounds 3–7 was tested
against standard strains of two Gram-negative bacteria
(Salmonella typhimurium ATCC 14028 and Escherichia
coli ATCC 10538) and two Gram-positive (Staphylococcus
aureus ATCC 29213 and Bacillus subtilis ATCC 6633) species
(Table 3), using the broth microdilution method as previously
described.29 Amoxicillin and ciprofloxacin were used as
reference compounds in the study on the antibacterial activity.
The energy difference between the HOMO and LUMO
frontier orbitals is one of the important characteristics of
molecules, which has a determining role in such cases as
electrical properties, electronic spectra and photochemical
reactions. The HOMO and LUMO maps of 3–5 are shown in
Fig. 4. Separation energies between the HOMO and LUMO
(Δε = ε
– εHOMO) in dyes 3–5 are 2.78, 3.35 and 3.97 eV,
respectiLvUeMlyO. It can be seen from Fig. 4 that dye 3 has more
Fig. 3 Optimised geometries of the new dyes 3–5.

146 JOURNAL OF CHEMICAL RESEARCH 2017
Fig. 4 The HOMO (lower) and LUMO (upper) frontier orbitals of the dyes 3–5.
Fig. 5 The 3D-electrostatic potential maps of dyes 3–5.
Fig. 6 The 3D-electron density maps of dyes 3–5.
The lowest concentration of the antibacterial agent that prevents
compound 7 shows higher antibacterial activity against the
Salmonella typhimurium ATCC 14028, Staphylococcus aureus
ATCC 29213 and Escherichia coli ATCC 10538 species
compared to the well-known antibacterial agents ciprofloxacin
and amoxicillin (Table 3).
growth of the test organism, as detected by lack of visual
turbidity (matching the negative growth control), is assigned
the minimum inhibitory concentration (MIC). Experimental
details of the tests can be found in our earlier studies.20,30,31
As demonstrated in Table 3, compounds 3–7 are effective
against both Gram-positive and Gram-negative bacteria.
The test results revealed that compounds 4 and 7 (nitroso
compounds) show the greater inhibitory effects against
Escherichia coli ATCC 10538, Salmonella typhimurium
ATCC 14028, Staphylococcus aureus ATCC 29213, and
Bacillus subtilis ATCC 6633 species than the other compounds.
Moreover, as the data in Table 3 reveals, the antibacterial
activity of the alkylated compounds 6 and 7 is higher compared
to that of compounds 3 and 4 respectively. Gratifyingly,
Conclusion
In conclusion, we have synthesised some new donor-acceptor
indigo-coloured, purple and orange heterocyclic dyes from
imidazo[1,2-a]pyridine. The interesting optical properties of
the dyes were examined and the solvent effects on the absorption
spectra of the dyes were studied. DFT and TD-DFT calculations
of the dyes 3–5 were performed to gain a deeper insight into
the charge transfer properties, optimised geometries, HOMO
and LUMO frontier orbitals and electronic spectra by using the

JOURNAL OF CHEMICAL RESEARCH 2017 147
Table 3 Inhibitory activity (MIC, μg mL–1) of references and compounds 3–7 against bacteria
Compound
Staphylococcus aureus (ATCC 29213) Bacillus subtilis (ATCC 6633) Escherichia coli (ATCC10538) Salmonella typhimurium (ATCC14028)
3
4
5
6
75
25
50
75
5
25
1
5
15
0.5
50
1
15
15
150
75
150
50
7
0.5
50
Ciprofloxacin
Amoxicillin
16
25
0.05
0.06
1
150
>128
>128
investigation of the solvent effects. The PCM calculations have been
performed in the MeOH solution and the zero-point corrections were
considered to obtain energies. Based on the optimised geometries and
TD-DFT36–38 methods, the electronic spectra of the compounds 3–5 were
predicted.
B3LYP hybrid functional and the 6-311++G(d,p) basis set. The
results showed that the imidazo[1,2-a]pyridine ring and cyano
groups in dye 3 are essentially planar and the separation energies
between the HOMO and LUMO in dyes 3–5 were 2.78, 3.35 and
3.97 eV, respectively. Also, electronic spectra of dyes 3–5 were
in relatively good agreement with visible absorption spectra.
In addition, AIM analysis was conducted to investigate the
3D-electrostatic potential maps and 3D-electron density maps
in these dyes. The results show that concentration of electron
density through the C–N bond in the cyano fragment of three
dyes is different, and dye 3 has a greater charge distribution
throughout the structure due to a strong resonance. Comparing
the quantum-chemical investigations with the experimental
results reveals that they are in good agreement and DFT and
TD-DFT calculations and AIM analysis can prove the higher
maximum absorption wavelength in dye 3 compared to 4 and
5. Moreover, results from the antimicrobial screening tests
show the synthesised compounds are effective against standard
strains of Gram-positive and Gram-negative growth inhibitors.
This property, together with optical properties, can offer an
excellent opportunity for the study of physiological functions of
bacteria such as at single-cell level.32
Synthesis of 3 from 1 and 2
3-Nitroimidazo[1,2-a]pyridine (1) (3.26 g, 20 mmol) and malononitrile
(2) (1.98 g, 30 mmol) were added with stirring to a solution of KOH
(20 g, 357 mmol) in methanol (70 mL). The mixture was refluxed with
stirring for 4 h, and then poured into water. After neutralisation with
dilute HCl solution, the precipitate was collected by filtration, washed
with water and then air dried to give crude 3. More purification was
achieved by crystallisation from acetone-H2O (1:1).
2-[3- (Hydroxyimino)imidazo[1,2-a]pyridin-2(3H)-ylidene]
malononitrile (3) was obtained as a dark indigo-coloured powder
(acetone-H2O; 1:1), yield 85%, m.p. >300 °C; IR (KBr disk): νmax
/
cm–1 3455 (OH), 2218 and 2215 (diastereotopic CN groups); H NMR
(DMSO-d6): δ 7.69 (1H, d, J = 5.5 Hz, ArH), 7.75 (1H, d, J = 7.1 Hz,
ArH), 7.91–8.05 (2H, m, ArH), 11.87 (1H, br s, OH); 13C NMR (CDCl3):
δ 85.7, 112.5, 112.7, 114.6, 126.0, 135.6, 137.5, 151.3, 151.7, 168.5; MS
(m/z) 211 (M+). Anal. calcd for C10H5N5O (211.2): C, 56.87; H, 2.39; N,
33.16; found: C, 56.71; H, 2.36; N, 32.97%.
1
Further investigation into the scope and application of these
new dyes is in progress and will be reported soon.
Synthesis of 4 from 3
The indigo-coloured solution of dye 3 (1.05 g, 5 mmol) in EtOAc (50
mL) was heated for 6 h under reflux. After concentration of the purple
solution at reduced pressure, the precipitate was recrystallised from
MeOH to give pure dye 4.
Experimental
Methanol, acetone, acetonitrile, chloroform, n-hexane, N,N-
dimethylformamide (DMF), methyl iodide, dimethyl sulfate (DMS),
potassium tert-butoxide, tert-butanol, 2-aminopyridine, 2-bromo-
1,1-dimethoxyethane and malononitrile were purchased from Merck.
Amoxicillin, ciprofloxacin and potassium hydroxide was purchased
from Sigma-Aldrich. The microorganisms Escherichia coli ATCC
10538, Salmonella typhimurium ATCC 14028, Staphylococcus aureus
ATCC 29213 and Bacillus subtilis ATCC 6633 were purchased from
Pasteur Institute of Iran. All solvents were dried according to standard
procedures. Compound 1 was synthesised as described in the literature.26
Absorption spectra were recorded on a Varian Cary 50-bio UV-Vis
spectrophotometer. UV-Vis scans were recorded from 200 to 800
nm. Melting points were measured on an Electrothermal type-9100
melting-point apparatus. The IR (as KBr discs) spectra were obtained
on a Tensor 27 spectrometer and only noteworthy absorptions are listed.
2-(3-Nitrosoimidazo[1,2-a]pyridin-2-yl)malononitrile
(4)
was
obtained as dark purple powder (MeOH), yield 75%, m.p. >300 °C; IR
(KBr disk): νmax/cm–1 2204 (CN), 1561 (N=O); 1H NMR (DMSO-d6): δ
5.55 (1H, s, benzylic H), 6.67 (1H, td, J1 = 7.1 Hz, J2 = 1.2 Hz, ArH), 6.78
(1H, td, J1 = 5.5 Hz, J2 = 1.5 Hz, ArH), 7.53 (1H, d, J = 5.5 Hz, ArH),
7.67 (1H, d, J = 7.1 Hz, ArH); 13C NMR (CDCl3): δ 23.4, 110.7, 114.1,
114.8, 126.8, 127.4, 127.8, 142.6, 147.6; MS (m/z) 211 (M+). Anal. calcd
for C10H5N5O (211.2): C, 56.87; H, 2.39; N, 33.16; found: C, 56.67; H,
2.34; N, 32.89%.
Synthesis of 5 from 4
H2O2 (0.55 mL, 30%, 2 mmol) was added to a stirred solution of dye 4
(0.2 g, 1 mmol) in MeOH (5.0 mL) at 60 °C. After the 2 h, the orange
solution was diluted with H2O (50 mL), chilled and filtered, and then
the solid was washed with H2O and air dried to give crude 5. Dye 5 was
recrystallised from MeOH.
1
The 13C NMR (100 MHz) and the H NMR (400 MHz) spectra were
recorded on a Bruker Avance DRX-400 Fourier-transform spectrometer
for DMSO-d6 and CDCl3 solutions. Chemical shifts are reported in parts
per million downfield from TMS as the internal standard; coupling
constants J are given in hertz. The mass spectra were recorded on a
Varian Mat, CH-7 at 70 eV. Elemental analysis was performed on a
Thermo Finnigan Flash EA microanalyser. All measurements were
carried out at room temperature.
DFT calculations have been performed with the Gaussian 98 software
package33 by using the B3LYP hybrid functional34 and the 6-311++G
(d,p) basis set. Firstly, geometry of the compounds 3–5 was fully
optimised in the MeOH solution.
2-(3-Nitroimidazo[1,2-a]pyridin-2-yl)malononitrile (5) was obtained
as orange needles (MeOH), yield 80%, m.p. 253–255 °C; IR (KBr disk):
1
ν
max/cm–1 2245 (CN), 1337, 1543 (NO2). H NMR (DMSO-d6): δ 5.63
(1H, s, benzylic H), 6.71 (1H, td, J1 = 7.1 Hz, J2 = 1.2 Hz, ArH), 6.75 (1H,
td, J1 = 5.5 Hz, J2 = 1.5 Hz, ArH), 7.69 (1H, d, J = 5.5 Hz, ArH), 7.81 (1H,
d, J = 7.1 Hz, ArH); 13C NMR (CDCl3): δ 24.1, 111.1, 114.4, 114.6, 126.8,
127.2, 140.1, 142.9, 158.1; MS (m/z) 227 (M+). Anal. calcd for C10H5N5O2
(227.2): C, 52.87; H, 2.22; N, 30.83; found: C, 52.69; H, 2.19; N, 30.75%.
Synthesis of 6 from 3
Here, one of the self-consistent reaction field methods, the
sophisticated Polarised Continuum Model (PCM)35 has been used for
Dimethyl sulfate (DMS) (0.9 g, 7 mmol) and K2CO3 (5.5 g, 40 mmol)
were added to an indigo-coloured solution of compound 3 (1.02 g,

148 JOURNAL OF CHEMICAL RESEARCH 2017
5 mmol) in acetonitrile (40 mL). The mixture was stirred for 12 h
at room temperature and then poured into water. The product was
extracted with CH2Cl2 (2 × 50 mL). The extract was dried (MgSO4),
treated with charcoal and evaporated to give crude 6. Further
purification was achieved by recrystallisation from acetone.
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1
H. Yousefi, A.Yahyazadeh, M.R. Yazdanbakhsh, M. Rassa and E.O. Moradi-
e-Rufchahi, J. Mol. Struct., 2012, 1015, 27.
2
3
H.S. Bhatti and S. Seshadri, Color. Technol., 2004, 120, 151.
A.H. Shridhar, J. Keshavayya and J. Hoskeri, Int. J. Pharm. Pharm. Sci.,
2002, 4, 386.
2-[3- (Methoxyimino)imidazo[1,2-a]pyridin-2(3H)-ylidene]
malononitrile (6) was obtained as indigo-coloured needles (acetone),
yield 72%, m.p. 195–197 °C; IR (KBr disk): νmax/cm–1 2223 and 2219
4
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5
6
7
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1
(diastereotopic CN groups); H NMR (CDCl3): δ 4.21 (s, 3H, OCH3),
7.71 (1H, d, J = 5.5 Hz, ArH), 7.74 (1H, d, J = 7.1 Hz, ArH), 7.95–8.07
(2H, m, ArH); 13C NMR (CDCl3): δ 63.6, 84.6, 112.7, 113.4, 114.6,
125.3, 136.1, 137.3, 151.2, 151.8, 168.9; MS (m/z) 225 (M+). Anal. calcd
for C11H7N5O (225.2): C, 58.67; H, 3.13; N, 31.10; found: C, 58.49; H,
3.12; N, 30.88%.
8
9
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Synthesis of 7 from 4
Methyl iodide (1.4 g, 10 mmol) and potassium tert-butoxide (1.12 g,
10 mmol) were added to a solution of compound 4 (2.76 g, 10 mmol)
in tert-butanol (50 mL). After the mixture was stirred for 4 h at room
temperature, it was concentrated at reduced pressure and then water
(50 mL) was added to the mixture. The product was extracted with
CH2Cl2 (2 × 40 mL). The extract was dried (MgSO4), treated with
charcoal and evaporated to give crude 7. Further purification was
performed by recrystallisation from n-hexane-EtOAc (1:1).
2-Methyl-2-(3-nitrosoimidazo[1,2-a]pyridin-2-yl)malononitrile
(7) was obtained as a purple powder (acetone), yield 65%, m.p.
169–172 °C; IR (KBr disk): νmax/cm–1 2204 (CN), 1535 (N=O);
1H NMR (DMSO-d6): δ 2.33 (3H, s, CH3), 6.72 (1H, td, J1 = 7.2 Hz,
J2 = 1.2 Hz, ArH), 6.76 (1H, td, J1 = 5.6 Hz, J2 = 1.5 Hz, ArH), 7.61 (1H,
d, J = 5.6 Hz, ArH), 7.64 (1H, d, J = 7.2 Hz, ArH); 13C NMR (CDCl3):
δ 19.5, 22.9, 110.5, 112.5, 115.3, 126.7, 127.5, 128.3, 142.5, 147.1; MS
(m/z) 225 (M+). Anal. calcd for C11H7N5O (225.2): C, 58.67; H, 3.13; N,
31.10; found: C, 58.41; H, 3.10; N, 30.95%.
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Acknowledgments
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We would like to express our sincere gratitude to Research
Office, Mashhad Branch, Islamic Azad University, Mashhad-
Iran, for financial support of this work. We also acknowledge
Maryam Jajarmi (Khorasan Razavi Rural Water and Wastewater
Co.) for her assistance with antibacterial studies.
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Electronic supplementary information
The ESI (bond lengths and angles, mesomeric structures and
calculated UV-Vis spectra of compounds 3–5) is available
through stl.publisher.ingentaconnect.com/content/stl/jcr/supp-
data.
Received 30 August 2016; accepted 20 January 2017
Paper 1604295 DOI: 10.3184/174751917X14873588907684
Published online: 3 March 2017