Synthesis of novel 2-seleno-1,8-naphthyridines derivatives

Article abstract of DOI:10.1080/10426500701839601

Synthesis of series of new 2-phenyl-3-(2-seleno-1,8-naphthyridin-3-yl)-2,3, 3a,6-tetrahydro-5H-pyrazolo[3,4-d][1,3]thiazol-5-ones (4a-e) has been reported. The replacement of halogen with NaHSe in the substituted 2-chloro-3-formyl-1,8- naphthyridi afforded 2-seleno-3-formyl-1,8-naphthyridins (2a - e). The reaction between (2a-e) and 1,3-thiazolidine-2,4-dione produced corresponding derivatives of substituted compounds (3a-e), which on reflux with phenyl hydrazine in DMF to generate (4a-e), with good to excellent yields. Structure of newly synthesized compounds were established based on elemental analysis, IR, 1H NMR, and mass spectral data. Copyright Taylor & Francis Group, LLC.

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Synthesis of Novel 2-
Seleno-1,8-naphthyridines
Derivatives
Tangali R. Ravikumar Naik a , Halehatty S.
Bhojya Naik a , Halehatty R. Prakash Naik a , M.
Raghavendra a & S. Ramesha a
a Department of P. G. Studies and Research in
Industrial Chemistry, School of Chemical Sciences ,
Kuvempu University , Shankaraghatta, India
Published online: 28 Jul 2008.
To cite this article: Tangali R. Ravikumar Naik , Halehatty S. Bhojya Naik , Halehatty
R. Prakash Naik , M. Raghavendra & S. Ramesha (2008) Synthesis of Novel 2-
Seleno-1,8-naphthyridines Derivatives, Phosphorus, Sulfur, and Silicon and the Related
Elements, 183:8, 1968-1974, DOI: 10.1080/10426500701839601
To link to this article: http://dx.doi.org/10.1080/10426500701839601
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Phosphorus, Sulfur, and Silicon, 183:1968–1974, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701839601
Synthesis of Novel 2-Seleno-1,8-naphthyridines
Derivatives
Tangali R. Ravikumar Naik, Halehatty S. Bhojya Naik,
Halehatty R. Prakash Naik, M. Raghavendra, and
S. Ramesha
Department of P. G. Studies and Research in Industrial Chemistry,
School of Chemical Sciences, Kuvempu University, Shankaraghatta,
India
Synthesis of series of new 2-phenyl-3-(2-seleno-1,8-naphthyridin-3-yl)-2,3,3a,6-
tetrahydro-5H-pyrazolo[3,4-d][1,3]thiazol-5-ones (4a–e) has been reported. The
replacement of halogen with NaHSe in the substituted 2-chloro-3-formyl-1,8-
naphthyridi afforded 2-seleno-3-formyl-1,8-naphthyridins (2a–e). The reaction be-
tween (2a–e)and 1,3-thiazolidine-2,4-dione produced corresponding derivatives of
substituted compounds (3a–e), which on reflux with phenyl hydrazine in DMF to
generate (4a–e), with good to excellent yields. Structure of newly synthesized com-
pounds were established based on elemental analysis, IR, 1H NMR, and mass spec-
tral data.
Keywords 2-selenonaphthyridines; naphthyridies; phenyl hydrazine; thiazolidine
INTRODUCTION
The functionalized naphthyridine derivatives have found a widespread
application in the field of antibiotic, diagnostic, chemotherapy, and
infectious diseases of humans including AIDS. Some of new 1,8-
naphthyridne derivatives has also been patented as growth regulators
fungicides, bactericides, herbicides, insecticides, and nemathocides of
new generation.1–4
On the other hand, organoselenium compounds had substantially
greater bioavailability and less toxicity than that of inorganic selenium.
Received 9 July 2007; accepted 9 October 2007.
One of the author (T.R.R) thankful to UGC, NEW DELHI for awarding Rajiv Gandhi
research fellowship and Indian Institute of Science for providing spectral facilities.
Address correspondence to Halehatty S. Bhojya Naik, Department of P. G. Studies
and Research in Industrial Chemistry, School of Chemical Sciences, Kuvempu University,
Shankaraghatta 577 451, India. E-mail: hsb naik@rediffmail.com
1968

Seleno-1,8-naphthyridines derivatives
1969
Recent report5 shows that, the micronutrient, selenium has potential
anticarcinogenic activity of fused compounds such as selenocyanate,6
triphenylselenonium, and diphenylselenide7 have also been shown to
be inhibitory in different tumor models. The condensed fused quino-
line derivatives containing selenium atom and studies for their DNA
binding, cytotoxic, anticancer activities.8–10 Therefore, the develop-
ment of organoselenium compounds with higher anticarcinogenic ef-
ficacy but better tolerance continues to be a priority in chemotherapy
research.
Further, a large number of thiazolidinones are reported in liter-
ature for their biological activities such as anticonvulsant,11 anti-
inflammatory,12 hypnotic,13 amoebicidal,14 analgesic,15 anti AIDS,16etc.
4-Thiazolidinone derivatives substituted at 2, 3, 4 or 5 positions are
antidiabetic drugs.17 Similarly Pyrazole derivatives are also reported
to possess antifungal,18 antidiabetic,19 herbicidal,20 antifertility,21
sedative,22 and antimicrobial activities,23 and so on.
Hence, in view of the biological importance of these moieties and
in continuation of our interest in the synthesis of novel heterocyclic
framework,24 we synthesized substituted 2-phenyl-3-(2-seleno-1,8-
naphthyridin-3-yl)-2,3,3a,6-tetrahydro-5H-pyrazolo[3,4-d][1,3]thiazol-
5-ones (4a-e) in good to excellent yield.
RESULTS AND DISCUSSION
The synthesized naphthyridine derivatives (4a–e) has include bioac-
tive compounds like sulfur and selenium, which render them valuable
pharmacological activities as mentioned earlier and they are a use-
ful material in drug research and also naphthyridines might afford in
better yields opening a chance for their DNA binding and antitumour
activities.
2-chloro-3-formyl-1,8-naphthyridin was submitted to react with
NaHSe in ethanol to obtained 85–90% yields of 2-seleno-3-formyl-1,8-
naphthyridin 2a. The IR spectra displayed bands at 1634 cm−1 (-C=
Se), 3280 cm−1 (-NH) and 1690 cm−1 (-C=O). Its 1H NMR spectra
showed singlet at δ 13.4 for (-NH), δ10.56 for (-CHO), multiplet at
7.10–7.80. The obtained 2-seleno-3-formyl-1,8-naphthyridin 2a treated
with 1,3-thiazolidine-2,4-dione in the presence of glacial acetic acid
and fused sodium acetate to offered 3a. However, in contrast, 5-[(2-
seleno-1,8-naphthyridin-3-yl)methylidene]-1,3-thiazolidine-2,4-dione
3a up on reaction with excess of phenyl hydrazine in DMF solvent
in a short reaction time afforded the products in a quantitative yield
which were characterized as 2-phenyl-3-(2-seleno-1,8-naphthyridin-3-

1970
T. R. Ravikumar Naik et al.
yl)-2,3,3a,6-tetrahydro-5H-pyrazolo[3,4-d][1,3]thiazol-5-ones 4a from
their spectral data. Thus, IR spectrum of 4a showed characteristic
absorption at 1728 cm−1 (-C=O) for thiazolidinone ring, 1170 cm−1
(-N-N). Its 1H NMR spectrum showed singlet at δ13.2 for (-NH)
(toutomeric form) and absence of aldehydic proton at δ 10.56 ppm and
its mass spectra with the m/z value at 428 (M+2).
H
N
O
H
N
S
O
O
O
O
R
R
S
CH COONa/CH COOH
N
N
H
Se
N
N
H
Se
3
3
2a-e
3a-e
Ar-NH-NH2
DMF/5% KOH
NaHSe
Ethanol
O
R
O
S
R
NH
N
N
H
N
N
N
N
Cl
Se
Ar
1a-e
O
S
R
NH
R= H, CH3, OCH3, Br, Cl
N
N
H
N
N
Se
4a-e
Ar
SCHEME 1 2-phenyl-3-(2-seleno-1,8-naphthyridin-3-yl)-2,3,3a,6-tetrahydro-
5H-pyrazolo[3,4-d][1,3]thiazol-5-ones.
EXPERIMENTAL SECTION
Melting points were determined in an open capillary tube with a Buchi
melting point apparatus and are uncorrected. Elemental analyses were
carried out using Perkin-Elmer 240C CHNS-analyzer. IR spectra were
recorded on a FT-IR spectrophotometer.1H NMR spectra was run in
(DMSO-d6) solvent at 300 MHz and 75 MHz on a NMR spectropho-
tometers (chemical shifts in δ ppm). Mass spectra were recorded on a
LC MS Mass spectrometer. The absorption spectral studies were carried
out by Ultraviolet-visible spectrophotometer.

Seleno-1,8-naphthyridines derivatives
1971
General Procedure for the Synthesis of
2-Seleno-3-formyl-1,8-naphthyridines (2a)
A mixture 2-chloro-3-formyl-1,8-naphthyridine (1.91 g, 1 mmol) and
freshly prepared solution of sodium hydrogen selenide were taken in
a round bottom flask in ethanol (20 ml). The reaction mixture was re-
fluxed for 2–3 hrs at 80–90◦C, the completion of reaction was monitored
by TLC eluting the phase ethyl acetate: carbon tetrachloride (70:30),
cooled, the reaction mixture was poured in to crushed ice and made
acidified with dil (4N HCl). The product was filtered and washed with
water, dried, and was pure enough for further use, recrystallized from
excess alcohol. The same procedure was used for the synthesis of other
compounds (2b–e).
General Procedure for the Synthesis of
1,3-Thiazolidine-2,4-dion+
An ethanolic solution of thiourea (7.6 g, 0.5 mmol) and chloroacetic
acid (3.8 g 0.6 mmol) was refluxed for 4–5 h. Then it was allowed to
cool. The separated solid was filtered and washed with cold ethanol.
The obtained hydrochloride was dissolved in boiling water (60 ml) after
24 h the separated crystals was filtered and refluxed for 1–2 h in aque-
ous KOH (20%, 15 ml). The reaction mixture was cooled and poured
into dilute acetic acid (1:1, 50 ml). The precipitated solid was filtered
and recrystallized from ethanol.
General Procedure for the Synthesis of 5-[(2-Seleno-1,8-
naphthyridin-3-yl)methylidene]-1,3-thiazolidine-2,4-dione (3a)
Compound 2a (1.185 g, 0.05 mmol), glacial acetic acid 30 ml, fused
sodium acetate (0.589g, 0.05 mmol) and 1,3-thiazolidine-2,4-dione
(0.05 mmol) were refluxed for 5–6 hrs at 80–90◦C, the completion of
reaction was monitored by TLC eluting the phase ethyl acetate: carbon
tetrachloride (80:20), After cooling, reaction mixture was slowly poured
into crushed ice and yellow solid obtained was filtered and washed
with ethanol. The crude solid mass was recrystallized from glacial
acetic acid. The same procedure was used for the synthesis of other
compounds (3b–e).
General Procedure for the Synthesis of
2-Seleno-3-formyl-1,8-naphthyridines (4a)
An equimolar amount of compound 3a (1.68 g, 0.05 mmol) and phenyl
hydrazine (5.4 ml, 0.05 mmol) were dissolved in DMF with constant

1972
T. R. Ravikumar Naik et al.
stirring. To this stirred solution, 5% KOH (4 ml) was added dropwise
during 20–30 min, and the reaction mixture was refluxed for 6–7 h
at 80–90◦C, the completion of reaction was monitored by TLC eluting
the phase ethyl acetate: carbon tetrachloride (80:20), After cooling, the
reaction mixture was poured in to crushed ice. The solid product so
obtained was filtered, washed, dried, and crystallized from glacial acetic
acid. The same procedure was used for the synthesis of other compounds
(4b–e).
3-(2-Selenoquinolin-3-yl)-2-phenyl-2,6-dihydro-5H-
pyrazolo[3,4-d][1,3]thiazol-5-one (4a)
Yellow solid. Yield 75%; m.p. 233◦C; FT-IR (KBr): 1725 (C=O) cm−1
,
1
1170 (-N-N) cm−1. H NMR (DMSO-d6, 300 MHz): δ (ppm) = 13.02 (s,
1H, NH), 7.10–8.22 (m, 10H, Ar-H), Mass, m/z; 428 (M.+2). Elemen-
tal analysis (%): calcd., for C18H13N5OSSe: C; 50.71, H; 3.07, N; 10.43
Found: C; 50.69, H; 3.06, N; 10.40.
6-Methyl 3-(2-selenoquinolin-3-yl)-2-phenyl-2,6-dihydro-5H-
pyrazolo[3,4-d][1,3]thiazol-5-one (4b)
Yellow solid. Yield 70%; m.p. 208◦C; FT-IR (KBr): 1728 (C=O) cm−1
,
1
1175 (-N-N) cm−1. H NMR (DMSO-d6, 300 MHz): δ (ppm) = 13.10 (s,
1H, NH), 7.00–8.05 (m, 9H, Ar-H), 2.85 (s, 3H, -CH3), Mass, m/z; 442
(M.+2). Elemental analysis (%): calcd. for C19H15N5OSSe: C; 51.82, H;
3.43, N; 15.90 Found: C; 51.80, H; 3.41, N; 15.88.
6-Methoxy 3-(2-selenoquinolin-3-yl)-2-phenyl-2,6-dihydro-5H-
pyrazolo[3,4-d][1,3]thiazol-5-one (4c)
Yellow solid. Yield 70%; m.p. 216◦C; FT-IR (KBr): 1720 (C=O) cm−1
,
1
1168 (-N-N) cm−1. H NMR (DMSO-d6, 300 MHz): δ (ppm) = 12.90 (s,
1H, NH), 7.05–8.10 (m, 9H, Ar-H), 3.90 (s, 3H, -O-CH3), Mass, m/z; 458
(M.+2). Elemental analysis (%): calcd. for C19H15N5O2SSe: C; 50.00, H;
3.31, N; 15.35 Found: C; 49.98, H; 3.30, N; 15.33.
6-Bromo 3-(2-selenoquinolin-3-yl)-2-phenyl-2,6-dihydro-5H-
pyrazolo[3,4-d][1,3]thiazol-5-one (4d)
Yellow solid. Yield 65%; m.p. 210◦C; FT-IR (KBr): 1718 (C=O) cm−1
,
1
1185 (-N-N) cm−1. H NMR (DMSO-d6, 300 MHz): δ (ppm) = 13.20 (s,
1H, NH), 7.00–8.02 (m, 8H, Ar-H), Mass, m/z; 507 (M.+2). Elemental
analysis (%): calcd., for C18H12BrN5OSSe: C; 42.79, H; 2.39, N; 13.86
Found: C; 42.77, H; 2.38, N; 13.87.

Seleno-1,8-naphthyridines derivatives
1973
6-Chloro 3-(2-selenoquinolin-3-yl)-2-phenyl-2,6-dihydro-5H-
pyrazolo[3,4-d][1,3]thiazol-5-one (4e)
Yellow solid. Yield 65%; m.p.215◦C; FT-IR (KBr): 1690 (C=O) cm−1
,
1
1173 (-N-N) cm−1. H NMR (DMSO-d6, 300 MHz): δ (ppm) = 13.05 (s,
1H, NH), 7.05–8.10 (m, 8H, Ar-H), Mass, m/z; 462 (M.+2). Elemental
analysis (%): calcd., for C18H12ClN5OSSe: C; 46.92, H; 2.62, N; 15.20
Found: C; 46.90, H; 2.61, N; 15.17.
CONCLUSIONS
In conclusion, we have successfully developed a facile convenient
method, a new access to different class of biological importance of
2-seleno-3-formyl-1,8-naphthyridines by a simple methodology. These
moieties have the potential to provide the basis for some biological
importance.
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