Selenium-containing heterocycles: Synthetic investigation of 3-amino-2-ethylselenopyridine carboxylate using sodium borohydride

Article abstract of DOI:10.1080/10426500600616795

3-amino-4,6-dimethyl-2-ethylseleno[2,3-b]pyridine carboxylate (5) was prepared by a reaction of dipyridyl diselenide derivative (3) with sodium borohydride as a reducing agent followed by α-haloester. The reaction of 5 with hydrazine hydrate afforded the

Full text of DOI:10.1080/10426500600616795

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Selenium-Containing
Heterocycles: Synthetic
Investigation of 3-Amino-2-
Ethylselenopyridine
Carboxylate Using Sodium
Borohydride
Sh. H. Abdel-Hafez a , Sh. A. Abdel-Mohsen a & Y. A.
El-Ossaily a
a Chemistry Department, Assiut University, Assiut,
Egypt
Version of record first published: 22 Sep 2006.
To cite this article: Sh. H. Abdel-Hafez , Sh. A. Abdel-Mohsen & Y. A. El-Ossaily
(2006): Selenium-Containing Heterocycles: Synthetic Investigation of 3-Amino-2-
Ethylselenopyridine Carboxylate Using Sodium Borohydride, Phosphorus, Sulfur, and
Silicon and the Related Elements, 181:10, 2297-2305
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Phosphorus, Sulfur, and Silicon, 181:2297–2305, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600616795
Selenium-Containing Heterocycles: Synthetic
Investigation of 3-Amino-2-Ethylselenopyridine
Carboxylate Using Sodium Borohydride
Sh. H. Abdel-Hafez
Sh. A. Abdel-Mohsen
Y. A. El-Ossaily
Chemistry Department, Assiut University, Assiut, Egypt
3-amino-4,6-dimethyl-2-ethylseleno[2,3-b]pyridine carboxylate (5) was prepared by
a reaction of dipyridyl diselenide derivative (3) with sodium borohydride as a re-
ducing agent followed by α-haloester. The reaction of 5 with hydrazine hydrate
afforded the corresponding carbohydrazide 8. The benzylidene derivative 9 pro-
vided novel heterocycles of pyrimidoseleno pyridine and thiazinoseleno pyridine
derivatives (10–12), upon treatment with triethylorthoformate, acetic anhydride,
and carbon disulfide, respectively.
Keywords Dipyridyl diselenide; pyrimidoseleno pyridine; seleno[2,3-b]pyridine; thiazi-
noseleno pyridine
INTRODUCTION
In recent years, many exciting research results have indicated that
selenium is a very important element that has attracted the at-
tention of scientists working in a variety of fields. The interest in
selenium-containing compounds has increased not only because of their
reactivates and chemical properties1−5 but also because of their phar-
maceutical applications.6−9 Organ selenium compounds have proven to
be an important class of biological active products as antioxidants,10
antibacterial agents,11 and catalysts.12 On the other hand, many
pyridines are reported to be useful as herbicides,13 bactericides,14 and
fungicides,15 as well as pharmaceuticals.16 With the goal of using less-
toxic selenium compounds for the synthesis of selenium-containing het-
erocyclic compounds and in continuation of our studies on the prepara-
tion of a novel heterocyclic systems containing sulfur and/or selenium
Received December 4, 2005; accepted January 30, 2006.
Address correspondence to Sh. H. Abdel-Hafez, Assiut University, Chemistry Depart-
ment, Faculty of Science, Assiut 71516, Egypt. E-mail: shams@acc.aun.edu.eg
2297

2298
Sh. H. Abdel-Hafez et al.
TABLE I Reaction Condition of NaBH4/Se in Ethanol
Products/yield %
Reaction condition
NaBH4/Se in ethanol
Time
(h)
Compound 2
Compound 3
(A) Ice bath
(B) Rt
(C) Reflux
24
7
2
70
52
—
—
17
63
atoms,17−20 the present article describes the synthesis of new heterocy-
cles on the basis of the seleno[2,3-b]pyridine derivative (5).
RESULTS AND DISCUSSION
It was reported that 4,6-dimethyl-3-cyanopyridine-2(1H) selenone (2)
was obtained in a (67%) yield by the reaction of 4,6-dimethyl-2-chloro-
3-cyanopyridine (1) with sodium hydrogen selenide21 under reflux. In
order to improve the yields and to investigate the synthesis of the
title compound 5, we decided to modify the procedure as follows: first,
when the reaction was carried out in an ice bath, we got 4,6-dimethyl-
3-cyanopyridine-2(1H) selenone 2 in a good yield (70%); second, at
r.t. we obtained compound 2 and new compound 2ꢀ,2-bis(3-cyano-4,6-
dimethyl)dipyridyl diselenide (3) in low yield. The two compounds 2
and 3 were isolated by fractional crystallization from ethanol. Upon
recrystallization, compound 2 crystallized from ethanol as yellow crys-
tals, while compound 3 crystallized from dioxan as red crystals. Un-
der reflux, only the dipyridyl diselenide derivative, 3, was obtained
(Table I, Scheme 1).
SCHEME 1

Selenium-Containing Heterocycles
2299
The two prepared compounds 2 and 3 were characterized by chemical
and spectral data.
From Scheme 1, it was clear that the natural oxidation of a selenol
into diselenide can be accelerated by air and heating.22 The structure
elucidation of 2ꢀ,2-bis(3-cyano-4,6-dimethyl)dipyridyl diselenide 3 was
confirmed by elemental analysis, IR, 1H NMR, and mass spectra. Mass
spectra indicate that the presence of molecular ion m/e 420 (14.5%)
and 421 (15.9%) with a low relative abundance reflects the instability
of this molecular ion under electron impact. The molecular ion under-
went extensive skeletal rearrangement to give several fragment ions
(Scheme 2).
SCHEME 2
On the other hand, attempts to synthesize the title compound 5 in a
one-pot reaction using the starting compound 1 and sodium borohydride
followed by α-haloester leads only to the compound 5 in a low yield
(15 %) (Scheme 3).
Another new synthetic pathway to improve the overall reaction yield
of the target compound 5 is the treatment of the dipyridyl diselenid 3
with sodium borohydride followed by the addition of α-haloester under
a reflux condition. The expected ethylseleno ester derivative (4) was not
detected (Scheme 4), and this is may be attributed the double function of

2300
Sh. H. Abdel-Hafez et al.
SCHEME 3
NaBH4 as a reducing agent and a basic catalyst to furnish the cyclized
product 5.
By the same way, compounds 6 and 7 were prepared. Synthesized
compounds 5–7 had nearly identical spectral data as the reported
compounds.21
SCHEME 4

Selenium-Containing Heterocycles
2301
SCHEME 5
Further reactions of 3-amino-2-ethylseleno[2,3-b]pyridine carboxy-
late 5 with hydrazine hydrate, aromatic aldehyde, and carbon disul-
fide provides novel selenium containing heterocycles as follows: When
5 was allowed to react with hydrazine hydrate by fusion, it gave the
corresponding carbohydrazide (8), while reflux in ethanol failed. Re-
fluxing compound 8 with benzaldehyde in an equimolar ratio gave
benzylidene carbohydrazone (9). A new series of pyrimidoseleno pyri-
dine derivatives 10 and 11 were synthesized via the reaction of com-
pound 9 with triethylorthoformate and acetic anhydride, respectively.
Refluxing 9 with carbon disulfide in pyridine for a long time gave
2,4-dimethyl-8-oxo[1.3]thiazino[2ꢀ,3ꢀ:4,5]seleno[2,3-b] Pyridine-6(5H)-
thion (12) (Scheme 5).
CONCLUSION
New series of seleno pyridine, pyrimidoseleno pyridine, thiazinose-
leno pyridine derivatives were synthesized from 3-cyanopyridine-
2(1H)selenone (2). Modification of a literature procedure to prepare
selenopyridino derivatives was done with improving the yield.
EXPERIMENTAL
Melting points were determined using a Kofler melting point appara-
tus and are uncorrected. IR spectra were recorded on a Pye-Unicam

2302
Sh. H. Abdel-Hafez et al.
SP3-100 instrument in KBr. 1H NMR spectra were obtained on a
JNM-LA spectrometer (400 MHz) using tetramethylsilane as an inter-
nal reference. The instrument for measuring mass spectra was JEOL
JMS600. Elemental analyses were obtained on a Perkin-Elmer 240 C
analyzer; the results coincided with the calculated values within 0.4%.
The progress of reactions and purity of products were monitored by
TLC.
4,6-Dimethyl-3-cyanopyridine-2(1H)selenones (2; C8H8N2Se)
and 2’,2-Bis(3-cyano-4,6-dimethyl)dipyridyldiselenide
(3; C16H14N4Se2)
The modified procedures are as follows:
Procedure A
4,6-dimethyl-2-chloro-3-cyanopyridine 1(1 mmoles) was added step-
wise in a mixture of selenium metal (1 g, 12 mmoles) and sodium boro-
hydride (1.2 g, 32 mmoles) in ethanol. The reaction mixture was stirred
in ice bath for 24 h; then the reaction mixture was poured onto an ice
water and acidified by conc. hydrochloric acid. The precipitate was iso-
lated by filtration, washed with water, and recrystallized from ethanol
to give compound 2 as yellow crystals, yield 0.9 g (70%) (reported 67%).
The melting point and all spectral data were in agreement with the
reported compound.21
Procedure B
Using the same procedure was used as in A, but with stirring for 7 h
at r.t. we got compound 2 in a yield of 0.66 g (52%) and 2ꢀ,2-bis(3-cyano-
4,6-dimethyl) dipyridyl diselenide 3 as red crystals with a yield 0.44 g
(17%) (Table I).
Procedure C
The same procedure was used as in A and B, but the reaction mixture
was refluxed for 2 h. This gave compound 3, which was recrystallized
from dioxan as red crystals, a yield of 1.57 g (63%). Anal. calcd. for
C16H14N4Se2: C, 45.71; H, 3.33; N, 13.33. Found: C, 45.31; H, 3.00; N,
1
13.03. IR: ν = 2200, 1575 cm−1; H NMR (DMSO-d6), δ : 2.41(s, 6H);
2.49 (s, 6H); 7.26 (s, 2H-CH-pyridine) ppm. MS: m/z (%) = 421 [M + 1]
(15.9%), 420 [M+] (14.5%), 340 (100), 315 (33.6), 313 (18.1), 290 (4.6),
260 (61.8), 211 (12.6), 131 (12.9), 130 (42.3), 210 (5.8), 105 (1.8), 104
(38.4), 103 (38.4).

Selenium-Containing Heterocycles
2303
3-Aminoseleno[2,3-b]pyridine derivatives (5;C12H14N2O2e), (6;
C10H9N3Se) and (7; C16H14N2OSe) from compound 3
General Procedure
To a solution of 3 (1 g, 2.3 mmoles) in 15 mL of ethanol, sodium
borohydride to an ethanolic solution of 3 (1 g, 2.3 mmoles) was added in
small portions (0.2 g, 7.0 mmoles). The reaction mixture was stirred at
r.t. for 1 h; then 2.3 mmoles of chloro ethylacetate or chloro acetonitrile
or benzoyl chloride should be added instead of halo ester or alkyl halide.
The resulting mixture was refluxed for 3 h and then poured onto an
icewater. The precipitated compounds were collected as follows:
Compound 5: yield 0.65 g (93%) (reported 88%);
Compound 6: yield 0.5 g (85%) (reported 76%); and
Compound 7: yield 0.70 g (89%) (reported 81%).
m.p.s. and all spectral data were in agreement with those of the reported
compounds.21
3-Amino-4,6-dimethyl-2-ethylseleno[2,3-b]pyridine
Carboxylate (5;C12H14N2O2Se) from Compound 1
To a suspension of selenium metal (1 g, 12 mmoles) in 15 mL of ethanol
(1.2 g, 32 mmoles) of sodium borohydride was added in small portions,
and then the corresponding 2-chloro-3-cyanopyridine derivative 1 (1.66
g, 10 mmoles) was added in small portions. The reaction mixture was
stirred in an ice bath for 7 h, and then α-haloester (1.22 g, 10 mmoles)
was added. After that the reaction mixture was refluxed for 3 h, cooled,
and poured onto cold water, followed by acidification with conc. hy-
drochloric acid. The product was collected in a low yield, 0.45 g (15%).
Spectra of 5 were in agreement with earlier measurements.21
3-Amino-4,6-dimethylseleno[2,3-b]pyridine-2-carbohydrazide
(8; C10H12N4OSe)
A mixture of the selenopyridine derivative 5 (2 g, 4.7 mmoles) and hy-
drazine hydrate (5 mL, 85%) was fused together for 5 h. The hot solid
product was separated by filtration, washed well with ethanol, and re-
crystallized from dioxan as yellow crystals, m.p. > 300◦C, yield 1.6 g
(84%). calcd. for C10H12N4OSe: C, 42.40; H, 4.24; N, 19.78. Found: C,
42.01; H, 3.93; N, 19.47. IR: ν = 3100, 3195, 3290 cm−1 (NHNH2); 1620
cm−1. 1H NMR (CDCl3), δ: 2.41 (s, 3H); 2.52 (s, 3H); 4.5 (s,2H,NH2-
hydrazide); 6.01 (s, 2H, NH2-attached to selenophene ring); 7.09 (s, 1H);
7.4 (1H, NH) ppm.

2304
Sh. H. Abdel-Hafez et al.
3-Amino-2-benzyledine Carbohydrazone-4,6-dimethylseleno-
[2,3-b]pyridine(9); C17H16N4 OSe)
A mixture of selenopyridine carbohydrazide 8 (2.83 g, 10 mmoles), ben-
zaldehyde (1.06 g, 10 mmoles) in 30 mL of ethanol, and 2 drops of piperi-
dine was refluxed for 3 h. It was then allowed to cool. The solid product
was collected and recrystallized from dioxan, m.p. > 300◦C, yield 3 g
(81%). calcd. for C17H16N4OSe: C, 54.98; H, 4.31; N, 15.09. Found: C,
54.59; H, 4.13; N, 14.88. IR: ν = 3450, 3300, 3170 (NH2) ; 1625 (C O)
cm−1.1H NMR (DMSO-d6), δ : 2.40 (s, 3H); 2.62 (s, 3H); 6.82 (s,2H, NH2);
7.17 (s, 1H), 8.5 (s, 1H, N CH); 9.20 (s, 1H, NH) ppm.
2,4-Dimethyl-7-benzyledineamino-8-oxopyrimido[4’,5’:4,5]-
seleno[2,3-b]pyridine (10; C18H14N4OSe)
To a mixture of 9 (1 g, 2.7 mmoles) and triethylorthoformate (5 mL),
drops of acetic acid (5 drops) were added. The reaction mixture was
heated under reflux for 1 h. The solid product was collected and recrys-
tallized from acetic acid, m.p. > 300◦C, yield 0.52 g (51%). calcd. for
C18H14N4OSe: C, 56.69; H, 3.67; N, 14.69. Found: C, 56.37; H, 3.38;
N, 14.29. IR: ν = 1670 (C O); 1610 (C N) cm−1
.
1H NMR (DMSO-
d6), δ : 2.39 (s, 3H); 2.65 (s, 3H); 7.06 (s, 1H); 7.30–7.70 (m, 5H, Ar-H);
8.5 (s,1H, N CH); 9.30 (s, 1H, CH-pyrimidine) ppm.
2,4,6-Trimethyl-7-benzyledineamino-8-oxopyrimido[4’,5’:4,5]-
seleno[2,3-b]pyridine (11; C19H16N4OSe)
Compound 9 (0.5 g, 1.3 mmoles) was heated in 10 mL of acetic anhydride
under reflux for 6 h and then allowed to cool. The solid product was
filtered and recrystallized from acetic acid, m.p. > 300◦C, yield 0.3 g
(56%). Calcd. for C19H16N4OSe : C, 57.72; H, 4.05; N, 14.17. Found: C,
57.44; H, 3.89; N, 13.95. IR: ν = 1680 (C O); 1600 (C N) cm−1
.
2,4-Dimethyl-8-oxo-[1.3]thiazino[2’,3’:4,5]seleno[2,3-b]-
pyridine-6(5H)-thion (12; C11H8N2OS2Se)
A mixture of 9 (2 g, 5.4 mmoles) and carbon disulfide (2 mL) in pyridine
(20 mL) was heated on a water bath for 3 days and then allowed to cool,
the solid product was collected and recrystallized from dioxan, m.p. =
265–267◦C, yield 1.2 g (68 %). calcd. for C11H8N2OS2Se: C, 40.36; H,
4.89; N, 8.56; S, 19.57. Found: C, 40.01; H, 4.58; N, 8.34; S, 19.29. IR:
ν = 33100 (NH);1685 (C O) cm−1. 1H NMR (DMSO-d6), δ : 2.43 (s, 3H);
2.52 (s, 3H); 7.09 (s, 1H); 9.2 (s, 1H) ppm.

Selenium-Containing Heterocycles
2305
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