An efficient aqueous phase synthesis of benzimidazoles/benzothiazoles in the presence of β-cyclodextrin

Article abstract of DOI:10.1039/c4ra16222f

Benzimidazoles/benzothiazoles were synthesized in water under neutral conditions by the reaction of aromatic aldehydes, o-phenylenediamine/2-amino thiophenol mediated by β-cyclodextrin in high yields. β-Cyclodextrin can be recovered and reused without sig

Full text of DOI:10.1039/c4ra16222f

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PAPER
An efficient aqueous phase synthesis of benzimidazoles/benzothiazoles in
the presence of βꢀcyclodextrin.
Ramesh Katla,a Rakhi Chowrasia,b Padma Sunitha Manjari,b Nelson Luís C. Domingues.a*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
Benzimidazoles/benzothiazoles were synthesized in water under neutral conditions by the reaction of aromatic aldehydes, oꢀ
phenylenediamine/2ꢀamino thiophenol mediated by βꢀcyclodextrin in high yields. βꢀCyclodextrin can be recovered and reused
without significant loss of activity.
50
Introduction
benzimidazoles, benzoxazoles and benzothiazoles by using
phenylene diamines/2ꢀamino thiophenol/2ꢀamino thiol and acid
10
Benzimidazole/benzothiazole moieties are important scaffolds
in pharmaceutical applications, associated with a wide variety of
medicinal, biological activities such as antifungal, antiviral,
oneꢀpot
synthesis
of
benzimidazoles
using
1,2ꢀ
phenylenediamines, and aldehydes in wet DMF at rt.12 Srinivasan
55 and coꢀworkers developed the synthesis of 2ꢀaryl chlorides under
ambient conditions using ionic liquids, 1ꢀbutylimidazolium
tetraflouroborate [Hbim]BF4) and 1,3ꢀdiꢀnꢀbutylimidazolium
tetrafluoroborate ([bbim]BF4).13
antibacterial,
antihypertensive,
anticancer,
antiꢀinflammatory,
antiulcer,
and
antihistaminic,
anticonvulsant,
15 antiparkinsonian activities.[1ꢀ3]In addition, their analogues exhibit
significant activity against several viruses, such as HIV, herpes
(HSVꢀ1), RNA influenza and human cytomegalovirus (HCMV).4
They are also widely used in organic synthesis as intermediates.
Especially benzimidazoles are useful in controlling the diseases
20 such as hypertension,5 ischemiaꢀreperfusion injury,6 as well as
obesity.7
There
are
numerous
drugs
containing
benzimidazole/benzothiazole skeletons as shown in Figure 1.
Several methodologies have been developed for the synthesis of
benzimidazole/benzothiazoles. Mirkhani et al. has reported the
25 synthesis of 2ꢀimidazolines and bisꢀimidazolines by the reaction
of ethylenediamine, and nitriles in the presence of sulfur under
ultrasonic irradiation.8 Das et al. described benzimidazoles from
60
Figure 1. Some marketed drugs with benzimidazole/benzothiazole
skeleton.
Ranu et al. described the synthesis of 2ꢀsubstituted
benzimidazoles by using oꢀphenylenediamine with aromatic
1,2ꢀphenylenediamine,
with
aldehydes
by
using
(bromodimethyl)sulfonium bromide at room temperature.9 65 aldehydes in the presence of an ionic liquid, 1ꢀmethylꢀ3ꢀ
pentylimidazolium tetrafluoroborate, [pmim]BF4 at room
30 Hornberger has developed oneꢀpot synthesis of disubstituted
benzimidazoles from 2ꢀnitro anilines with palladium charcoal as a
catalyst in the presence of trimethyl orthoformate and catalytic
pyridinium pꢀtoluenesulfonate (PPTS) at rt.10 Lin and coꢀworkers
synthesized some benzimidazoles from phenylenediamines, and
35 aldehydes, in the presence of molecular iodine.11 Pierre L.
Beaulieu et al demonstrated the oxone mediated
temperature.14
aOrganic Catalysis and Biocatalysis Laboratory OCBL/ FACET, Federal
University of Grande Dourados—UFGD, Dourados/Itahúm rod. km 12
40 s/n, Zip Code 79804ꢀ970, Dourados, MS, Brazil.
bDepartment of Chemistry, Osmania University, Hyderabad, Indiaꢀ
500004.
70 Scheme 1. Synthesis of benzothiazoles/benzimidazoles.
However, the above mentioned methods have been associated
with different draw backs such as the use of hazardous organic
solvents, strongly acidic conditions, expensive moistureꢀsensitive
catalysts, or tedious workup conditions as well as low yields. In
75 continuation of our efforts towards the development of novel
environmentally benign methodologies,15 herein we report an
Eꢀmail: nelsondomingues@ufgd.edu.br
45 † Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/b000000x/
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45 After the reaction, the reaction mass was cooled and βꢀCD was
filtered and washed with iceꢀcold water and dried. The recovered
βꢀCD was further used with the same substrates as a catalyst and
checked for the yields as well as the catalytic activity of the
recovered βꢀCD, as shown in Figure 2. As we observed that the
50 yields of benzimidazoles/benzothiazoles slightly decreased after
three to fourth cycle as indicated in Figure 2.
efficient
oneꢀpot
protocol
for
the
synthesis
of
benzimidazole/benzothiazole derivatives by a twoꢀcomponent
reaction, involving 1,2ꢀdiamino benzene/2ꢀamino thiophenol for
the first time promoted by recyclable βꢀCD in aqueous medium
(Scheme 1). Presently organic reactions in aqueous phase have
attracted the attention of researchers because of the added
advantages of water, as an ecoꢀfriendly and economically
affordable solvent. However, the fundamental problem in
performing the reactions in water is that many organic substrates
5
Table 1. Synthesis of benzimidazoles/benzothiazoles.a
10 are hydrophobic and are insoluble in aqueous medium.
Results and Discussion
Cyclodextrins (CDs) are cyclic oligosaccharides
possessing hydrophobic cavities, which bind substrates
selectively and catalyze the chemical reactions with high
15 selectivity. They promote the reactions by supramolecular
catalysis involving reversible formation of hostꢀguest
complexation by nonꢀcovalent bonding. We describe, herein, the
synthesis of 2ꢀsubstituted benzimidazoles/benzothiazoles
demonstrating the remarkable catalytic activity of βꢀcyclodextrin
20 (Scheme 1). In general, the reaction was carried out by the in situ
formation of the βꢀCD complex of the aldehyde in water followed
o
by the addition of 2ꢀaminothiophenol and stirring at 60ꢀ65 C to
gave the corresponding 2ꢀphenylbenzo[d] thiazole in high yield
(81%) (Table 1, entry 1). These reactions proceeded efficiently
25 without the need of any metal or acid catalyst. The reaction goes
to completion in a short time (4–10 h). The reactions also take
place with αꢀCD and γꢀCD, with lesser yields, however, βꢀCD has
been chosen as the mediator as it is inexpensive and easily
accessible. Several examples illustrating this simple and practical
30 methodology are summarized in Table 1. All the compounds
were characterized by 1H NMR, IR, and mass spectrometry. The
catalytic activity of cyclodextrins for these reactions is
established by the fact that no reaction was observed in the
absence of cyclodextrin. Evidence for the complexation between
35 the pꢀhydroxy benzaldehyde and cyclodextrin is supported by 1H
NMR spectroscopy. A comparison of the 1H NMR spectra
(DMSOꢀd6) of βꢀCD, βꢀCD pꢀhydroxy benzaldehyde complex
was studied and as indicated in Figure 3. All the reactions βꢀCD
was recovered and reused.
40
Figure 2. Recyclability of βꢀCD.
55
2
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this clear solution, aldehyde was added, stirred for 15 min,
followed by the addition of 1,2ꢀdiamino benzene/2ꢀamino
thiophenol (1.0 mmol). The reaction mixture was heated at 60ꢀ65
oC until completion of the reaction as indicated by TLC. The
30 reaction mixture was cooled to 5 oC and βꢀcyclodextrin was
filtered. The aqueous layer was extracted with ethyl acetate (3 x
10 ml). The combined organic layers were washed with water,
saturated brine solution, and dried over anhydrous Na2SO4. The
combined organic layers were evaporated under reduced pressure
35 and the resulting crude product was purified by column
chromatography using ethyl acetate and hexane (1:9) as an eluent.
The identity and purity of the products were confirmed by 1H, 13
NMR, and mass spectra.
C
2ꢀPhenylbenzo[d]thiazole (Table 1, Entry 1); 1H NMR (300 MHz,
40 CDCl3) δ = 8.11ꢀ8.07 (m, 3H), 7.90 (d, 1H, J = 7.9 Hz), 7.52ꢀ7.47 (m,
3H), 7.42ꢀ7.36 (m, 2H); 13C NMR (50 MHz, CDCl3) δ = 130.93, 128.98,
127.50, 126.27, 125.14, 123.18, 121.57; MS (ESI): m/z = 212 [M+H]+.
2ꢀ(4ꢀbromophenyl)benzo[d]thiazole (Table 1, Entry 2); 1H NMR (300
MHz, CDCl3) δ = 8.08 (d, 1H, , J = 8.1 Hz), 7.99ꢀ7.94 (m, 2H), 7.91 (d,
45 1H, J = 7.9 Hz), 7.65ꢀ7.61 (m, 2H), 7.53ꢀ7.48 (m, 1H), 7.43ꢀ7.38 (m, 1H);
13C NMR (50 MHz, CDCl3) δ = 166.62, 154.04, 135.00, 132.18, 128.86,
126.46, 125.40, 123.28, 121.62, 132.18, 128.86, 126.46, 125.40, 123.28,
121.62; MS (ESI): m/z = 290 [M+2]+.
2ꢀ(4ꢀfluorophenyl)benzo[d]thiazole (Table 1, Entry 3); 1H NMR (300
50 MHz, CDCl3) δ = 8.09ꢀ8.05 (m, 4H), 7.89 (d, 1H, J = 7.6 Hz), 7.49 (t, 1H,
J = 7.1 Hz), 7.18 (t, 2H, , J = 7.0 Hz); 13C NMR (50 MHz, CDCl3) δ =
166.61, 153.91, 134.90, 129.44, 129.37, 126.31, 125.15, 123.06, 121.50,
116.12, 115.94; MS (ESI): m/z = 230 [M+H]+.
2ꢀ(2ꢀmethoxyphenyl)benzo[d]thiazole (Table 1, Entry 4); 1H NMR
55 (300 MHz, CDCl3) δ = 8.53 (d, 1H, J = 1.8 Hz), 8.52 (d, 1H, J = 1.6 Hz),
8.09 (d, 1H, J = 8.2 Hz), 7.50 (d, 1H, J = 1.2 Hz), 7.49ꢀ7.44 (m, 2H),
7.38ꢀ7.35 (m, 2H), 4.06 (s, 3H); 13C NMR (50 MHz, CDCl3) δ = 157.15,
152.09, 131.72, 129.45, 125.82, 124.51, 122.71, 121.13, 111.59; MS
(ESI): m/z = 242 [M+H]+.
aReaction conditions: Aldehyde (1.0 mmol), 2ꢀAmino thiophenol/1,2ꢀ
b
Diamino benzene (1.0 mmol), βꢀCyclodextrin (10 mol%), 60ꢀ65 oC.
Isolated yield.
60 2ꢀ(2ꢀbromophenyl)benzo[d]thiazole (Table 1, Entry 5); 1H NMR (300
MHz, CDCl3) δ = 8.15 (d, 1H, J = 7.9 Hz), 8.01ꢀ7.94 (m, 2H), 7.73 (d,
1H, J = 7.9 Hz), 7.56ꢀ7.30 (m, 4H); 13C NMR (50 MHz, CDCl3) δ =
165.61, 152.50, 133.96, 132.07, 131.17, 127.48, 126.23, 125.41, 123.43,
121.34; MS (ESI): m/z = 290 [M+2]+.
5
65 4ꢀ(benzo[d]thiazolꢀ2ꢀyl)phenol (Table 1, Entry 6); 1H NMR (300
MHz, CDCl3) δ = 8.37 (s, 1H), 8.03ꢀ7.95 (m, 2H), 7.89ꢀ7.77 (m, 2H),
7.47 (t, 1H, J = 7.1 Hz), 7.36 (t, 1H, J = 6.9 Hz), 6.96ꢀ6.92 (m, 2H); 13C
NMR (50 MHz, CDCl3) δ = 167.16, 159.71, 153.28, 133.79, 128.31,
125.34, 123.97, 123.87, 121.66, 120.75, 115.32; MS (ESI): m/z = 228
70 [M+H]+.
4ꢀ(benzo[d]thiazolꢀ2ꢀyl)benzeneꢀ1,2ꢀdiol (Table 1, Entry 7); 1H NMR
(300 MHz, CDCl3) δ = 7.22ꢀ7.15 (m, 2H), 7.10ꢀ7.04 (m, 2H), 7.00ꢀ6.93
(m, 2H), 6.85ꢀ6.79 (m, 1H), 5.27 (s, 2H); 13C NMR (50 MHz, CDCl3) δ
= 143.64, 128.20, 128.08, 127.81, 127.69, 127.62, 127.24, 126.94,
75 125.67, 36.94, 36.66, 31.91, 31.80, 30.16, 30.04, 29.71, 29.34, 29.24,
27.72, 27.64, 22.82, 22.68, 22.58, 14.11; MS (ESI): m/z = 244 [M+H]+.
2ꢀ(3,4,5ꢀtrimethoxyphenyl)benzo[d]thiazole (Table 1, Entry 8); 1H
NMR (300 MHz, CDCl3) δ = 8.06 (d, 1H, J = 8.2 Hz), 7.89 (d, 1H, J =
7.6 Hz), 7.51ꢀ7.48 (m, 2H), 7.33 (s, 1H), 7.13 (s, 1H), 3.99 (s, 9H); 13C
80 NMR (50 MHz, CDCl3) δ = 153.89, 153.48, 134.83, 126.31, 125.09,
122.97, 121.48, 104.64, 60.94, 56.29; MS (ESI): m/z = 302 [M+H]+.
2ꢀ(1Hꢀindolꢀ3ꢀyl)benzo[d]thiazole (Table 1, Entry 9); 1H NMR (300
MHz, CDCl3) δ = 8.94 (s, 1H), 8.44 (d, 1H, J = 7.1 Hz), 8.02 (d, 1H, J =
8.1 Hz), 7.93 (d, 1H, J = 2.8 Hz), 7.87 (d, 1H, J = 7.9 Hz), 7.48ꢀ7.27 (m,
85 5H); 13C NMR (50 MHz, CDCl3) δ = 163.24, 153.61, 136.44, 133.78,
126.42, 126.05, 124.85, 124.19, 123.35, 121.98, 121.75, 121.29, 120.91,
112.24, 111.72; MS (ESI): m/z = 251 [M+H]+.
Figure 3. 1H NMR (300 MHz, DMSOꢀd6) spectrum of (a) βꢀCD (b) pꢀ
hydroxy benzaldehyde (c) βꢀCD–pꢀhydroxy benzaldehyde inclusion
10 complex.
Conclusion
In summary, we have developed an ecoꢀfriendly, oneꢀpot protocol
for the synthesis of 2ꢀsubstituted benzothiazoles/benzimidazoles
15 in good to excellent yields under neutral conditions promoted by
βꢀcyclodextrin in aqueous medium. This simple and novel
methodology will be useful to green chemistry with some
advantage that the reaction excludes nonꢀtoxic, moisture sensitive
or hazardous catalysts and elevated reaction temperatures, longer
20 reaction times, and the catalyst βꢀCD is economically viable,
readily available, easily handling.
2ꢀ(3,5ꢀdimethylphenyl)benzo[d]thiazole (Table 1, Entry 10); 1H NMR
(300 MHz, CDCl3) δ = 7.52ꢀ7.45 (m, 2H), 7.41ꢀ7.33 (m, 2H), 7.29 ꢀ7.25
90 (m, 1H), 7.19ꢀ7.05 (m, 2H), 2.58 (s, 3H) 2.38 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ = 139.9, 129.4, 128.8, 128.2, 123.6, 119.2, 117.9, 22.6, 21.2;
ESIꢀMS: m/z = 240 [M + H]+.
Experimental Section
2ꢀphenylꢀ1Hꢀbenzo[d]imidazole (Table 1, Entry 11); 1H NMR (300
MHz, CDCl3) δ = 8.07 (d, 1H, J = 6.2 Hz), 7.68ꢀ7.64 (m, 3H), 7.49ꢀ7.44
95 (m, 2H), 7.29ꢀ7.27 (m, 2H), 7.10 (d, 1H, J = 6.8 Hz), 5.47 (s, 1H); 13C
NMR (50 MHz, CDCl3) δ = 151.52, 129.95, 129.25, 128.26, 126.35,
121.78; MS (ESI): m/z = 195 [M+H]+.
General experimental procedure for the synthesis of 2ꢀ
substituted/benzothiazoles
using
βꢀcyclodextrin:
βꢀ
25 Cyclodextrin (10 mol %) was dissolved in water (10 ml), and to
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2ꢀ(2ꢀmethoxyphenyl)ꢀ1Hꢀbenzo[d]imidazole (Table 1, Entry 12); 1H
NMR (300 MHz, CDCl3) δ = 8.01ꢀ7.98 (m, 5H), 6.93ꢀ6.90 (m, 4H), 3.86
(s, 3H); 13C NMR (50 MHz, CDCl3) δ = 157.47, 156.38, 152.33, 143.03,
135.37, 132.26, 131.40, 128.33, 127.63, 122.44, 121.94, 120.70, 120.29,
119.60, 110.73, 109.83, 55.12, 55.03, 43.48; MS (ESI): m/z = 225
[M+H]+.
Boryska, D. D. Wise, L. L. Wotring, L. B. Townsend, J. Med. Chem.
1993, 36, 3843e3848.
4. M. J. Tebbe, W. A. Spitzer, F. Victor, S. C. Miller, C. C. Lee, T. R.
Sattelberg, E. Mckinney, C. J. Tang, J. Med. Chem. 1997, 40, 3937.
70 5. (a) D. I. Shah, M. Sharma, Y. Bansal, G. Bansal, M. Singh, Eur. J.
Med. Chem. 2008, 43, 1808; (b) R. N. Sharma, F. P. Xavier, K. K.
Vasu, S. C. Chaturvedi, S. S. Pancholi, J. Enzym. Inhib. Med. Chem.
2009, 24, 890e897.
5
2ꢀ(4ꢀethoxyphenyl)ꢀ1Hꢀbenzo[d]imidazole (Table 1, Entry 13); 1H
NMR (300MHz, DMSOꢀd6) d = 7.59ꢀ7.55 (m, 2H), 7.25ꢀ7.14 (m, 3H),
6.77 (d, 1H, J = 8.3 Hz), 6.92ꢀ6.88 (m, 2H), 4.08ꢀ3.94 (q, 2H), 1.43 (t,
6. Y. Ogino, N. Ohtake, Y. Nagae, K. Matsuda, M. Moriya, M. Suga,
10 3H, J = 7.5 Hz); 13C NMR (300 MHz, DMSOꢀd6): δ = 160.28, 158.50,
153.97, 143.09, 136.03, 130.66, 128.14, 127.11, 122.66, 119.71, 114.62,
110.32, 63.34, 14.80; MS (ESI): m/z = 239 [M+H]+.
2ꢀ(4ꢀchlorophenyl)ꢀ1Hꢀbenzo[d]imidazole (Table 1, Entry 14); 1H
NMR (300 MHz, CDCl3) δ = 7.57 (d, 1H, J = 7.6 Hz), 7.41 (d, 2H, J =
15 7.6 Hz), 7.32ꢀ7.20 (m, 3H), 7.12 (d, 1H, J = 7.6 Hz), 7.01 (d, 1H, J = 7.6
Hz); 13C NMR (50 MHz, CDCl3) δ = 130.93, 128.98, 127.50, 126.27,
125.14, 123.18, 121.57; MS (ESI): m/z = 229 [M+H]+.
2ꢀ(2ꢀchlorophenyl)ꢀ1Hꢀbenzo[d]imidazole (Table 1, Entry 15); 1H
NMR (300 MHz, CDCl3) δ = 8.62 (s, 1H), 7.93 (d, 3H, J = 5.8 Hz), 7.47
20 (s, 2H), 7.25 (s, 1H), 6.70 (d, 1H, J = 8.3 Hz), 4.92 (s, 1H); 13C NMR
(50 MHz, CDCl3) δ = 158.20, 130.92, 128.96, 127.52, 126.25, 125.13,
123.17, 121.56; MS (ESI): m/z = 229 [M+H]+.
2ꢀ(4ꢀnitrophenyl)ꢀ1Hꢀbenzo[d]imidazole (Table 1, Entry 16); 1H
NMR (300 MHz, CDCl3) δ = 7.66ꢀ7.64 (m, 2H), 7.44ꢀ7.40 (m, 3H), 7.32ꢀ
25 7.25 (m, 3H); 13C NMR (50 MHz, CDCl3) δ = 160.27, 158.51, 153.96,
143.08, 136.00, 130.64, 128.12, 127.10, 122.62, 119.70, 114.63, 110.32;
MS (ESI): m/z = 240 [M+H]+.
2ꢀ(pꢀtolyl)ꢀ1Hꢀbenzo[d]imidazole (Table 1, Entry 17); 1H NMR (300
MHz, CDCl3) δ = 8.12 (d, 4H, J = 8.3 Hz), 7.32 (d, 4H, J = 8.1 Hz), 3.13
30 (s, 1H), 2.44 (s, 3H); 13C NMR (50 MHz, CDCl3) δ = 140.31, 137.77,
132.74, 129.77, 129.45, 128.81, 125.70, 123.20, 120.52, 110.45, 21.03;
MS (ESI): m/z = 209 [M+H]+.
2ꢀ(4ꢀmethoxyphenyl)ꢀ1Hꢀbenzo[d]imidazole (Table 1, Entry 18); 1H
NMR (300 MHz, CDCl3) δ = 8.11 (d, 1H, J = 8.6 Hz), 7.65ꢀ7.46 (m, 3H),
35 6.98ꢀ6.93 (m, 3H), 6.79 (d, 1H, J = 8.6 Hz), 3.73 (s, 3H); 13C NMR (50
MHz, CDCl3) δ = 166.63, 164.10, 154.82, 132.97, 58.43; MS (ESI): m/z =
225 [M+H]+.
75
M. Ishikawa, Y. Kanesaka, J. Ito Mitobe, T. Kanno, T. A. Ishiara, H.
Iwaasa, T. Ohe, A. Kanatani, T. Fukami, Bioorg. Med. Chem. Lett.
2008, 18, 5010.
7. P. Ghosh, A. Mandal. Catalysis Communications. 2011, 12, 744.
8. V. Mirkhani, M. Moghadam, S. Tangestaninejad, H. Kargar,
Tetrahedron Lett. 2006, 47, 2129.
9. B. Das, H. Holla, Y. Srinivas, Tetrahedron Lett. 2007, 48, 61.
10. K. R. Hornberger, G. M. Adjabeng, H. D. Dickson, R. G. Davisꢀ
Ward, Tetrahedron Lett. 2006, 47, 5359.
80
11. S. Lin, L. Yang, Tetrahedron Lett. 2005, 46, 4315.
85 12. P. L. Beaulieu, B. Haché, E. V. Moos, Synthesis 2003, 11, 1683.
13. R. N. Nadaf, S. A. Siddiqui, T. Daniel, R. J. Lahoti, K. V. Srinivasan,
J. Mol. Cat. A: Chem. 2004, 214, 155.
14. D. Saha, A. Saha, B. C. Ranu, Green Chem. 2009, 11, 733.
15. (a) S. N. Murthy, B. Madhav, A. V. Kumar, K. R. Rao, Y. V. D.
90
Nageswar, Helv Chim. Acta. 2009, 92, 2118; (b) S. N. Murthy, B.
Madhav, A. V. Kumar, K. R. Rao, Y. V. D. Nageswar, Tetrahedron
2009, 65, 5251; (c) B. Madhav, S. N. Murthy, V. P. Reddy, K. R.
Rao, Y. V. D. Nageswar, Tetrahedron Lett. 2009, 50, 6025; (d) S. N.
Murthy, B. Madhav, V. P. Reddy, Y. V. D. Nageswar, Tetrahedron
Lett. 2010, 51, 3649; (e) J. Shankar, K. Karnakar, B. Srinivas, Y. V.
D. Nageswar, Tetrahedron Lett. 2010, 51, 3938; (f) S. N. Murthy, B.
Madhav, Y. V. D. Nageswar, Tetrahedron Lett. 2010, 51, 5252; (g)
K. Ramesh, S. N. Murthy, K. Karnakar, Y. V. D. Nageswar,
Tetrahedron Lett. 2011, 52, 3937; (h) K. Ramesh, S. N. Murthy, K.
Karnakar, Y. V. D. Nageswar, Tetrahedron Lett. 2011, 52, 4734; (i)
B. S. P. Anil Kumar, B. Madhav, K. Harsha Vardhan Reddy, Y. V.
D. Nageswar. Tetrahedron Lett. 2011, 52, 2862; (j) K. Ramesh, S. N.
Murthy, K. Karnakar, Y. V. D. Nageswar, K. Vijayalakhshmi, B. L.
A. Prabhavathi Devi, R. B. N. Prasad, Tetrahedron Lett. 2012, 53,
1126; (k) K. Ramesh, B. Madhav, S. N. Murthy, Y. V. D. Nageswar,
Synth. Commun. 2012, 42, 258; (l) K. Ramesh, S. N. Murthy, Y. V.
D. Nageswar, Synth. Commun. 2012, 42, 2471; (m) K. Ramesh, S.
N. Murthy, Y. V. D. Nageswar, Tetrahedron Lett. 2011, 52, 2362; (n)
S. S. Panda, S. C. Jain, Synth.Comm, 2011, 41, 729.
95
100
105
110
Acknowledgements
40
Brazilian authors (R. K. and N. L. C. D) thanks to Conselho
Nacional de Desenvolvimento Científico e Tecnológico for BJT
fellowship and the financial support Processos: 314140/2014ꢀ0
and 400706/2014ꢀ8 CNPq ꢀ Brazil). The authors thanks to Dr. Y.
45 V. D. Nageswar, Chief Scientist in Indian Institute of Chemical
Technology (IICT) Hyderabad, India for the spectroscopic
analysis.
References
1
(a) O. I. ElꢀSabbagh, M. M. Baraka, S. M. Ibrahim, C. Pannecouque,
G. Andrei, R. Snoeck, J. Balzarini, A. A. Rashad, Eur. J. Med. Chem.
2009, 44, 3746e3753; (b) V. Zaharia, A. Ignat, N. Palibroda, B.
Ngameni, V. Kuete, C. N. Fokunang, M. L. Moungang, B. T.
Ngadjui, Eur. J. Med. Chem. 2010, 45, 5080e5085; (c) I. Hutchinson,
S. A. Jennings, B. R. Vishnuvajjala, A. D. Westwell, M. F. G.
Stevens, J. Med. Chem. 2002, 45, 744e747.
50
55
60
65
2. (a) J. S. Kim, B. Gatto, C. Yu, A. Liu, L. F. Liu, E. J. LaVoie, J.
Med. Chem. 1996, 39, 992; (b) A. Kamal, M. N. A. Khan, K. S.
Reddy, K. Rohini, Bioorg. Med. Chem. 2007, 15, 1004e1013; (c) R.
B. Pathak, B. Jahan, S. C. Bahel, Bokin Bobai 1981, 9, 477e480; (d)
D. D. Erol, U. Calis¸ R. Demirdamar, N. Yulug, M. Ertan, J. Pharm.
Sci. 1995, 84, 462e465.
3. (a) T. Roth, M. L. Morningstar, P. L. Boyer, S. H. Hughes, R. W. Jr.
Buckheit, C. J. Michejda, J. Med. Chem. 1997, 40, 4199; (b) F.
Azam, B. A. ElꢀGnidi, I. A. Alkskas, M. A. Ahmed, J. Enzym. Inhib.
Med. Chem. 2010, 25, 818e826; (c) Y. Kumar, R. Green, K. Z.
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