1H and 13C assignments of three series bioactive imidazo[2,1-b]thiazole derivatives

Full text of DOI:10.1002/mrc.4115

Letter - spectral assignment
Received: 10 June 2014
Revised: 27 June 2014
Accepted: 2 July 2014
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/mrc.4115
1
13
H and C assignments of three series
bioactive imidazo[2,1-b]thiazole derivatives
Alexander S. Bunev,a* Elena V. Sukhonosova,b Gennady I. Ostapenko,a
Andzhela P. Pavlovac and Alexander S. Peregudovd
the 13C with a spectral width of 39.06 KHz, data points of 64 K,
relaxation delay of 2.0 s and 30° pulse width of 5.6 μs. The HMQC
Introduction
Imidazo[2,1-b]thiazoles make an interesting group of heterocyclic
molecules. The compounds containing imidazo[2,1-b]thiazole
moiety show interesting pharmacological activities as well as
properties useful from the technological and agricultural point
of view.[1–3] Their antitumor,[4–6] antiallergic,[7] anesthetic,[8]
anticancer,[9–12] antiviral,[13] antimicrobial[14] and antioxidant[15]
activities have been widely investigated. In spite of the informa-
tion on the wide range of imidazo[2,1-b]thiazoles applications
and extensive studies on their chemistry, no systematic studies
on their NMR properties have been published. Therefore, 13
compounds with typical substitute group from these three series
were selected to carry out a detailed NMR investigation using 1D
and 2D NMR experiments including 1H NMR, 13C NMR, HMQC and
HMBC. Here, we present the detailed 1H and 13C NMR assign-
ments of these compounds and further analyze and compare
the NMR data of these compounds.
spectra were collected as a 128 × 1024 matrix with one transient
per t1 increment and processed as a 1024 × 1024 matrix, and the
one bond heteronuclear coupling value was set to 145 Hz. The
HMBC spectra were collected as a 128 × 4096 matrix with one
transient per t1 increment and processed as a 2048 × 1024 matrix,
and the long-range coupling value was set to 10 Hz.
Result and Discussion
The structures and numbering of representative compounds of
each series are presented in Fig. 1. 1D and 2D NMR experiments
were used for the complete 1H and 13C chemical shift
assignments of these compounds. Protonated carbons were
assigned unequivocally from HMQC spectra. The remaining
quaternary carbons were assigned mainly based on HMBC spec-
tra. The 1H and 13C NMR data of compounds 1–3 are summarized
in Tables 2–4.
The 1H NMR spectra of all the described compounds were well
resolved, and unambiguous proton chemical shift assignments
were based on the multiplicity pattern of proton resonances
and confirmed by two-dimensional experiments. Some typical
proton and carbon resonances can be found in the NMR spectra
imidazo[2,1-b]thiazoles 1, namely the singlet at δ 2.41–2.45 ppm
as a result of the 3-CH3 proton resonance (Fig. 1 and Table 2),
its carbon resonance at δ 13.3 ppm and in the NMR spectra
imidazo[2,1-b]thiazoles 3, namely the multiplets at δ 1.93–1.79 ppm
and δ 2.73–2.69 ppm as a result of the 6,7 and 5,8 proton resonance
(Fig. 1 and Table 4), its carbon resonance at δ 21.6–22.6 ppm
and δ 23.1–24.2 ppm.
Experimental
Synthesis
Typical procedure for synthesis of imidazo[2,1-b]thiazole.[16–18]
A mixture of corresponding 2-aminothiazole (20 mmol) and 2-
bromo-1-arylethanone (20 mmol) was dissolved in acetone
(20 ml). The reaction mixture was stirred for 24 h. The resulting
precipitate was collected, suspended in water (100 ml) and
heated under reflux for 6 h. The warm solution basified with
20% NH4OH yielded the expected imidazo[2,1-b]thiazole after
cooling up to room temperature. The residue crystallized from
N,N-dimethylformamide.
Physical and elemental analysis data for the imidazo[2,1-b]
thiazoles (1a–g, 2a–b, 3a–d) are presented in Table 1.
*
Correspondence to: Alexander S. Bunev, Department of Chemistry, Chemical
Process and Technology, Togliatti State University, 14 Belorusskaya St.,
Togliatti 445667, Russia. E-mail: a.s.bunev@gmail.com
NMR measurements
All experiments were performed on a Bruker AvanceTM 600
spectrometer operating at 600.22 and 150.93 MHz for 1H and
13C respectively at room temperature in dimethyl sulfoxide
(DMSO) – d6. 1H and 13C chemical shifts are reported in parts
per million downfield from TMS; for 1H NMR spectra, residual
signal of DMSO-d6 was used as reference (2.50 ppm). In 13C NMR
measurements, the signal of DMSO-d6 was used as reference
(35.9 ppm). The H NMR spectra were recorded with a spectral
width of 7.1 KHz, data point of 64 K, digital resolution of 0.22 Hz,
relaxation delay of 1.0 s and 30° pulse width of 2.8 μs, whereas
a Department of Chemistry, Chemical Process and Technology, Togliatti State
University, 14 Belorusskaya St., Togliatti 445667, Russian Federation
b Department of Organic, Bioorganic and Medicinal Chemistry, Samara State
University, 1 Akademica Pavlova St., Samara 443011, Russian Federation
c
Department of General and Theoretical Physics, Togliatti State University, 14
Belorusskaya St., Togliatti 445667, Russian Federation
1
d NMR laboratory, A. N. Nesmeyanov Institute of Organoelement Compounds,
Russian Academy of Sciences, 28 Vavilov St., Moscow B-334 119991, Russian
Federation
Magn. Reson. Chem. (2014)
Copyright © 2014 John Wiley & Sons, Ltd.

A. S. Bunev et al.
Table 1. Physical and elemental analysis data for imidazo[2,1-b]thiazole derivatives
Analysis (%)
Compound
Melting point (°C/mmHg)
Molecular formula
Formula weight
214.3
C
H
N
1a
112–113
C
C
12H10N2S
13H12N2S
Calc.
Found
Calc.
Found
Calc.
Found
Calc.
Found
Calc.
Found
Calc.
Found
Calc.
Found
Calc.
Found
Calc.
Found
Calc.
Found
Calc.
Found
Calc.
Found
Calc.
67.26
67.31
68.39
68.45
59.97
60.06
57.95
58.02
49.16
49.24
55.59
55.67
54.52
54.61
72.70
72.77
61.01
61.11
70.83
70.92
71.61
71.72
62.38
62.45
54.06
54.13
4.70
4.76
5.30
5.35
4.65
4.71
3.65
4.73
3.09
3.14
3.50
3.56
3.66
3.72
4.58
4.64
3.07
3.14
5.55
5.61
6.01
6.09
4.54
4.60
3.93
4.02
13.07
13.12
12.27
12.33
10.76
10.81
11.26
11.31
9.55
1b
1c
1d
1e
1f
121–122
132–135
122–123
131–132
221–222
235–237
161–162
>260
228.3
260.4
248.7
293.2
259.3
220.3
264.3
295.3
254.4
268.4
288.8
333.3
C13H12N2S2
12H9ClN2S
12H9BrN2S
C12H9N3O2S
10H8N2S
C16H12N2S
C
C
9.60
16.21
16.27
12.72
12.79
10.60
10.66
14.23
14.29
11.01
11.11
10.44
10.49
9.70
1g
2a
2b
3a
3b
3c
3d
C
C
15H9N3O2S
167–168
191–192
162–163
163–164
C15H14N2S
C
16H16N2S
15H13ClN2S
C15H13BrN2S
C
9.77
8.41
8.47
Found
Figure 1. Sctructures and numbering of compounds 1–3 series.
The aromatic region of the 1H NMR spectra is slightly different
among the described compounds because of the substitution
pattern. In the case of compounds 1a–g and taking 6-(4-
bromophenyl)-3-methylimidazo[2,1-b]thiazole 1e as an example,
one can identify two singlets at δ 6.89 and 8.29 ppm corres-
ponding to H-2 and H-5. The aromatic substitution pattern in
phenyl ring of the reported compounds causes some characteris-
tic signals in the 1H NMR spectra. The most common is the pres-
ence of a pair of doublets at δ 7.75–7.86 and δ 7.20–7.58 ppm
(Table 2) corresponding, respectively, to the resonances of
H-2′,6′ and H-3′,5′. The coupling constants are characteristic
of an ortho-coupling in a para-substituted aromatic ring. In
the case of compound series 2–3, one can identify one singlet
at δ 8.11–8.91 ppm (Tables 3 and 4) corresponding to H-3
annulation imidazole ring.
The 1H NMR spectra of compounds 2a–2b show two doublets
and one singlet corresponding to the proton resonances of the
annelated benzene ring. In addition, the pair of doublets
corresponding to the resonances of H-5 and H-6 protons at,
respectively, δ 7.84–8.47 and δ 7.84–8.47 ppm, with a typical
ortho-coupling constants 3J 8.2 Hz (an example of the case of 2a).
The analysis of the 13C spectra of imidazo[2,1-b]thiazole
derivatives 1–3 with the aid of the 2D heteronuclear correlation
experiments (HMQC, 1H, 13C) allowed the assignments of all
protonated carbon resonances. For instance, the carbon
resonance of the 3-methyl group can be easily assigned at δ
2.41–2.45 ppm, as well as the aromatic carbon resonances of
the protonated carbons (Tables 2–4).
To confirm the assignments made from HMQC and assigned,
the signals corresponding to quaternary carbons HMBC spectra
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Copyright © 2014 John Wiley & Sons, Ltd.
Magn. Reson. Chem. (2014)

Three series bioactive imidazo[2,1-b]thiazole derivatives
Magn. Reson. Chem. (2014)
Copyright © 2014 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/mrc

A. S. Bunev et al.
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Copyright © 2014 John Wiley & Sons, Ltd.
Magn. Reson. Chem. (2014)

Three series bioactive imidazo[2,1-b]thiazole derivatives
were recorded. The correlation of H-5 with C-6 (2JCH), C-7a (3JCH
)
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