Synthesis and characterization of novel quinoline selenium compounds: X-ray structure of 6-methoxy-3H-[1,2]diselenolo[3,4-b]quinoline

Article abstract of DOI:10.1016/j.jorganchem.2010.01.012

A series of novel and synthetically important quinoline selenium compounds have been successfully synthesized using an efficient and simple strategy. The method employed leads to the synthesis of both cyclic as well as open chain quinoline selenium compounds. The prepared selenium compounds have been characterized with the help of various spectroscopic techniques viz., NMR (¹H, ¹³C), FT-IR, mass spectrometry. The structure of 6-methoxy-3H-[1,2]diselenolo[3,4-b]quinoline has been determined by X-ray crystallography.

Full text of DOI:10.1016/j.jorganchem.2010.01.012

Journal of Organometallic Chemistry 695 (2010) 1065–1068
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis and characterization of novel quinoline selenium compounds: X-ray
structure of 6-methoxy-3H-[1,2]diselenolo[3,4-b]quinoline
a
b
a
K.K. Bhasin a, , Ekta Arora , Chee-Hun Kwak , S.K. Mehta
*
a Department of Chemistry and Centre of Advanced Studies in Chemistry, Panjab University, Chandigarh 160 014, India
b Department of Chemistry, Suncheon National University, Suncheon 540-742, South Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of novel and synthetically important quinoline selenium compounds have been successfully syn-
thesized using an efficient and simple strategy. The method employed leads to the synthesis of both cyc-
lic as well as open chain quinoline selenium compounds. The prepared selenium compounds have been
characterized with the help of various spectroscopic techniques viz., NMR (1H, 13C), FT-IR, mass spectrom-
etry. The structure of 6-methoxy-3H-[1,2]diselenolo[3,4-b]quinoline has been determined by X-ray
crystallography.
Received 14 October 2009
Received in revised form 6 January 2010
Accepted 7 January 2010
Available online 14 January 2010
Keywords:
Quinoline
Ó 2010 Elsevier B.V. All rights reserved.
Selenium
Vilsmeier cyclisation
Diselenolo quinoline
1. Introduction
hydrogen selenide in the presence of strong hydrochloric
acid. The synthesis of various diselenides by an amine catalysed
Organic compounds containing selenium are of considerable
interest since they exhibit diverse biological activities with numer-
ous therapeutic applications [1,2]. In addition, the presence of a
heterocyclic ring as the organic moiety in these compounds alters
their properties to a great extent. A pharmacologically active het-
erocycle is the quinoline ring that occurs in several natural prod-
reaction of carbonyl compounds with hydrogen selenide has also
been reported [10]. In all these methods, long reaction times
are required and the products are found to be invariably contami-
nated with elemental selenium and oligoselenides. The latter are
difficult to remove from the desired diselenides and show decom-
position with liberation of elemental selenium upon storage and
handling.
ucts and displays
a broad range of biological activity [3,4]
including antitumour, hypoglycemic, antihistamine and anticarci-
nogenic properties [5], etc. Due to their importance as substruc-
An alternative method avoiding the use of hydrogen selenide
gas involves the reductive selenation of aromatic and heteroaro-
matic aldehydes (ArCHO) employing Se/CO/H2O system in DMF
[11]. However, this method is less effective in case of aliphatic
aldehydes. Consequently, there is a great interest in the synthesis
of diselenide derivatives of quinoline by a simple method using
reactants containing both carbonyl and halide species.
In continuation of our work on the synthesis of organic sele-
nium compounds [12] and the convenient synthesis of 2-chloro-
3-formylquinolines, the present paper deals with the synthesis of
quinoline selenium compounds.
tures in
a broad range of natural and designed products,
significant efforts have been directed into the development of
new quinoline based structures [6]. Amongst methodologies re-
ported for the preparation of quinolines, Vilsmeier [7] cyclisation
is the most straightforward protocol (Scheme 1). Therefore, for
the synthesis of 2-chloro-3-formylquinolines in the present re-
ported work, Vilsmeier reagent was prepared and reacted with
the corresponding acetanilides.
Among potentially attractive new starting materials for the
preparation of organic selenium compounds are carbonyl com-
pounds, and their reaction with hydrogen selenide and its salts
have been explored under a variety of alkaline and acidic condi-
tions to give low yield of diselenides and selenoaldehyde oligo-
mers, respectively [8].
2. Result and discussion
The Vilsmeier cyclisation was performed to prepare the
precursors for the synthesis of quinoline selenium compounds
(Scheme 1).
Margolis and Pittman [9] obtained low yields of aliphatic disel-
enides when the corresponding ketones were treated with excess
A survey of literature has revealed that compounds containing
Se–Se bond, acyclic and cyclic, are potential labilizing agents for
lysosomes and mitochondria in vitro [13]. In this paper we wish
* Corresponding author. Tel.: +91 172 2534407; fax: +91 172 254 5074.
E-mail address: kkbhasin1950@yahoo.co.in (K.K. Bhasin).
0022-328X/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2010.01.012

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K.K. Bhasin et al. / Journal of Organometallic Chemistry 695 (2010) 1065–1068
Acetic
CHO
Cl
DMF-POCl3
80-900C
anhydride
N
R
R
NH2
R
NH COCH3
R=CH3, OCH3
Scheme 1. Vilsmeier cyclisation.
H2
C
R
CHO
Cl
R
Piperidine hydrochloride,
C2H5OH
Se
+
NaHSe
N
N
Se
R= CH3,OCH3
3H-[1,2]diselenolo[3,4-b]quinoline
II a-b
I a-b
+
H2
C
H2
C
R
Se Se
R
N
Cl
Cl
N
1,2-bis((2-chloroquinolin-3-yl)methyl)diselenide
III a-b
Scheme 2. Reaction scheme for synthesis of quinoline selenium compounds.
H
N
N
N
H
R
C
R
CHO
+
Cl
R
C H
OH
Cl
N
+
H2O
N
H.HCl
N
Cl
N
N
2
1
R= CH3, OCH3
H+
I a-c
H+
+
R
C
H
Cl
N
N
_
R
C
H
Cl
Se
+
HSe
N
H
R
C Se
H
H
+
N
N
N
H
N
Cl
3
Selenoaldehyde
_
HSe
_
R
C Se Se H
_
H2
H2
C
R
C
Se Se
R
H
Se
N
Cl
4
N
N
II
Se
Cl
diselenol anion
H+
H2
_
Se C
Cl
R
R
C
Se Se
H2
H2
C
R
C
Se Se
R
N
N
Cl
+
Se
N
Cl
Cl
N
III
Scheme 3. Mechanistic pathway for diselenolo[3.4-b]quinoline (II a–b) and quinolinyl methyl diselenide (III a–b).
to report the synthesis and characterization of a few hitherto
unknown derivatives of the titled heterocycles and a viable mech-
anism for the unusual ring closure involved in the reaction.
The present article reveals the synthesis of 3H-[1,2]diselenol-
o[3,4-b]quinoline (II a–b) and 1,2-bis((2-chloroquinolin-3-yl)-
methyl)diselenide (III a–b) systems (Scheme 2) wherein sodium

K.K. Bhasin et al. / Journal of Organometallic Chemistry 695 (2010) 1065–1068
1067
Fig. 1. (a) ORTEP representation and (b) crystal packing of 6-methoxy-3H-[1,2]diselenolo[3,4-b]quinoline (II b).
hydrogen selenide (NaHSe) has been used as an nucleophilic re-
agent for 2-chloro-3-formylquinolines (I a–b) in the presence of
piperidine hydrochloride.
Table 1
Crystallographic data and measurements of II b.
Formula
C11H9NOSe2
Assymetric unit
Formula weight
C11H9NOSe2
329.11
2.1. Spectroscopic studies
T/K
100(1)
Monoclinic
P 21/n
6.112(4)
7.474(5)
22.779(6)
94.345(5)
1037.6(10)
4
7.095
2.107
632.0
57.56
It was observed that the 1H NMR spectra for the diselenolo [3,4-
b]quinoline (II a–b) display four different sets of protons in aro-
matic region and one peak in aliphatic region corresponding to
the methylene moiety .
Crystal system
Space group
a/Å
b/Å
c/Å
b/°
Compounds (III a–b) whose identity has been tentatively pre-
dicted on the basis of NMR studies give rise to four distinct set of
signals, three of which correspond to quinolinyl ring protons,
whereas the remaining one signal in aliphatic region resonate
much upfield (d 3.60 for III a and d 3.75 for III b) as compared to
the methylene signal in corresponding cyclised selenium com-
pounds (d 4.51 for II a and d 4.49 for II b). This indicates that the
methylene protons are presumably located on a side chain rather
than being in a cyclic structure. The two different environments
experienced by the selenium atoms in the compounds II a–b is also
3
V/Å
Z
Absorption coefficient/mmÀ1
Dcalc/g cm3
F(0 0 0)
2h/°
Index ranges
Reflections collected [Rint
Reflections unique
Parameters
À8 < h < 6; À9 < k<9; À30 < l < 23
]
6378 [0.0745]
2552
137
1.144
0.0716/0.1933
0.0933/0.2683
0.915
GOF
R1/wR2 [I > 2
77
confirmed by the appearance of two signals in Se NMR.
r(I)]
R1/wR2 (all data)
In the mass spectrum of 6-methyl-3H-[1,2]diselenolo[3,4-
b]quinoline (II a), ([M]++1) ion peak appears at m/z value of 316.
1,2-Bis((2-chloro-6-methoxyquinolin-3-yl)methyl)diselenide (III
b) display the molecular ion peak at m/z value of 573. Mass frag-
ments of II b and III a have also been characterized by mass
spectroscopy.
Largest res. peak/e ÅÀ3
shows that the two molecules facing each other have the selenium
atoms in the opposite directions.
A plausible mechanism for the reaction has been demonstrated
in Scheme 3. In this sequence, the initial reaction involves the for-
mation of an amine–aldehyde adduct such as hemiaminal or ami-
nal 1 or 2. Nucleophilic displacement by the hydrogen selenide
anion on 1 or 2 followed by an intramolecular elimination leads
to a short lived selenoaldehyde intermediate 3. In this reaction se-
quence, two displacement steps, i.e. oxygen by nitrogen, and nitro-
gen, in turn, by selenium are taking place. Furthermore, it is
proposed that the reduction of this selenoaldehyde 3 involves ini-
tial selenophilic attack by the hydrogen selenide anion, forming
the diselenol anion 4. This diselenol anion then can undergo intra-
molecular nucleophilic displacement of chloride ion at second po-
sition, giving the cyclic diselenide II a–b or it can react with
selenoaldehyde to give the diselenide III a–b.
3. Experimental
3.1. General
All the experimental manipulations were carried out in dry and
deoxygenated nitrogen atmosphere. Absolute ethanol (Fluka, pur-
ity > 99%) was used as the solvent for the reactions. Sodium boro-
hydride (Loba, purity > 99.5%), elemental selenium (Hi-media,
purity > 99%) and piperidine hydrochloride (Hi-media, pur-
ity > 99%) were newly purchased and stored in dessicator prior to
use. 2-Chloro-3-formyl quinolines were prepared by reported
methods [14]. All the compounds prepared were fully character-
ized using elemental analysis on a Perkin–Elmer 2400 CHN ana-
lyzer. 1H, 13C NMR spectra were recorded on a Jeol AL 300 MHz
spectrometer in CDCl3/CCl4. Tetramethylsilane (TMS) was used as
an internal standard for 1H NMR and 13C NMR. Infrared spectra
were obtained between KBr plates using CCl4 as mulling agent on
a Perkin–Elmer model 1430 spectrophotometer. Mass spectrome-
try was carried out on ES-MS Q-TOF.
2.2. X-ray crystallographic studies
Perspective view of the compound II b is shown in Fig. 1 and all
other relevant details about crystal structure determination and
refinement parameters are given in Table 1.
The Se–Se bond length is 2.354 Å. The most predominant short
contact is observed between Se (1)Á Á ÁH (10) as depicted by the
interatomic distance of 3.010 Å which is less than the sum of the
Vander wall radii (3.100 Å). Nonbonding interactions present in
the crystal structure are shown in Fig. 1. The crystal packing also
3.2. General procedure for the synthesis of quinoline chalcogen
compounds (II a–b, III a–b)
Grey powdered selenium (60 mmol) and sodium borohydride
(70.6 mmol) were placed into a 500 mL, three necked flask fitted

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K.K. Bhasin et al. / Journal of Organometallic Chemistry 695 (2010) 1065–1068
with a nitrogen inlet, addition funnel, and reflux condenser. The
flask was flushed with nitrogen, immersed in an ice bath, and abso-
lute ethanol (100 mL) was added slowly with stirring. Stirring was
continued until all selenium has dissolved and a colorless solution
resulted. To this solution was added piperidine hydrochloride
(50 mmol) followed by aldehyde (47 mmol). The reaction mixture
was heated under reflux for 1 h and cooled to room temperature to
give red solution. Addition of sodium borohydride (12 mmol) in
small doses resulted in a vigorous reaction. The reaction was mon-
itored by TLC. After completion of reaction, it is diluted with about
250 mL of distilled water and extracted in dichloromethane
(3 Â 50 mL). The organic layer was decanted and solvent was evap-
orated to get the crude product in solid form. The product was sub-
jected to purification on a silica column using hexane and ethyl
acetate as eluant (5:1).
CCl4/CDCl3, d ppm) 162.1, 142.2, 132.8, 132.4, 127.2, 126.8, 115.2,
102.5, 52.2, 28.1; IR (KBr,
cmÀ1): 2925.2, 1732.1, 1552.7,
1252.1, 1108.1, 1058.2, 1002.3, 620.2, 478.6. ES-MS: m/z
(Assignment, R.I.%): 573 ([C22H18N2Se2Cl2O2]+Å, 17), 493
([C22H18N2SeCl2O2]+Å, 8), 207 ([C11H9NClO]+Å + 1, 100).
m
3.2.5. Single crystal X-ray analysis
Diffraction quality red hexagonal crystals of 6-methoxy-3H-
[1,2]diselenolo[3,4-b]quinoline (II b) were grown in dichlorometh-
ane–hexane (3:1) solution of the compound. A selected specimen
was diffracted using a Bruker Smart Apex diffractometer using
graphite monochromated Mo
Ka radiation (0.71069 Å) at
100(1) K. The data integration and reduction were processed with
SAINT software. All the non-hydrogen atoms were refined aniso-
tropically. The hydrogen atoms were included in the ideal position
with fixed isotropic U values and were riding. The empirical
absorption corrections for these compounds were performed using
SADBAS program. The structure was solved by direct methods and
refined on F2 by full-matrix least-squares using SHELX-97 program
package. The compound crystallizes into monoclinic form with P
21/n space group.
3.2.1. 6-Methyl-3H-[1,2]diselenolo[3,4-b]quinoline (II a)
Red crystalline solid, M.Pt. 122–124 °C, Yield. 57%, Anal. Calcd
(%) for C11H9NSe2, C, 42.19; H, 2.89; N, 4.47. Found: C, 40.31; H,
2.28; N, 4.06%; 1H NMR (300 MHz, CCl4/CDCl3, d ppm) 7.71 (d,
1H, J 6.0 Hz), 7.64 (s, 1H), 7.37 (d, 1H, J 6.0 Hz), 7.34 (s, 1H), 4.51
(s, 2H), 2.47 (s, 3H); 13C NMR (75 MHz, CCl4/CDCl3, d ppm) 162.0,
143.7, 134.2, 133.1, 129.9, 128.8, 125.8, 124.3, 122.9, 60.3, 29.2;
4. Conclusion
77Se NMR (57 MHz, CCl4/CDCl3, d ppm) 413.0, 366.9; IR (KBr,
cmÀ1): 2925.7, 1723.5, 1559.3, 1259.9, 1107.8, 1009.5, 624.8,
554.8, 483.5; ES-MS: m/z (Assignment, R.I.%): 316
([C11H9NSe2]+Å + 1, 20).
m
In this paper the authors have used a convenient methodology
for the synthesis of hitherto unknown quinoline selenium com-
pounds. The diselenolo[3,4-b]quinoline and quinoline methyl
diselenide systems can act as suitable candidates for coordination
chemistry.
3.2.2. 6-Methoxy-3H-[1,2]diselenolo[3,4-b]quinoline (II b)
Red crystalline solid, M.Pt. 118–120 °C, Yield. 59%, Anal. Calcd
(%) for C11H9NOSe2, C, 40.14; H, 2.76; N, 4.25. Found: C, 39.82; H,
2.90; N, 4.30%. 1H NMR (300 MHz, CCl4/CDCl3, d ppm) 7.71 (d,
1H, J 9.0 Hz), 7.63 (s, 1H), 7.17 (d, 1H, J 9.0 Hz), 6.84 (s, 1H), 4.49
(s, 2H), 3.83 (s, 3H); 13C NMR (75 MHz, CCl4/CDCl3, d ppm) 133.4,
128.5, 127.4, 119.9, 103.3, 53.3, 29.2; 77Se NMR (57 MHz, CCl4/
Acknowledgement
The authors are thankful to CSIR for their financial assistance.
Appendix A. Supplementary data
CDCl3, d ppm) 409.8, 369.9; IR (KBr,
m
cmÀ1): 2925.7, 1727.2,
1559.7, 1255.5, 1107.8, 1067.28, 624.8, 529.0, 478.6; ES-MS: m/z
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jorganchem.2010.01.012.
(Assignment, R.I.%): 301 ([C10H6NSe2]+Å + 1, 5).
3.2.3. 1,2-Bis((2-chloro-6-methylquinolin-3-yl)methyl)diselenide (III
a)
References
Yellow crystalline solid, M.Pt. 135–137 °C, Yield. 26%, Anal.
Calcd (%) for C22H18Cl2N2Se2, C, 49.00; H, 3.64; N, 5.19. Found: C,
48.56; H, 3.12; N, 4.93%; 1H NMR (300 MHz, CCl4/CDCl3, d ppm)
8.07 (s, 1H), 7.80 (d, 1H, J 8.4 Hz), 7.50 (s, 1H), 7.41 (d, 1H, J
8.4 Hz), 3.60 (s, 2H), 2.46 (s, 3H); 13C NMR (75 MHz, CCl4/CDCl3,
d ppm) 145.4, 137.2, 136.6, 132.0, 130.7, 128.0, 127.5, 126.3,
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m
cmÀ1): 2925.0, 1718.3, 1550.3, 1248.9,
1102.8, 1002.5, 620.8, 552.2, 478.3. ES-MS: m/z (Assignment,
R.I.%): 190 ([C11H9NCl]+Å, 10).
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3.2.4. 1,2-Bis((2-chloro-6-methoxyquinolin-3-yl)methyl)diselenide
(III b)
Yellow crystalline solid, M.Pt. 127–129 °C, Yield. 23%, Anal.
Calcd (%) for C22H18Cl2N2O2Se2, C, 46.25; H, 3.17; N, 4.90. Found:
C, 45.80; H, 3.02; N, 4.65%; 1H NMR (300 MHz, CCl4/CDCl3, d
ppm) 7.78 (d, 1H, J 9.0 Hz), 7.72 (s, 1H), 7.23 (d, 1H, J 9.0 Hz),
6.91 (s, 1H), 3.75 (s, 2H), 3.89 (s, 3H); 13C NMR (75 MHz,
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