Preparation of 2-Arylethynylselanylacetonitriles from 4-Aryl-1,2,3-selenadiazoles

Article abstract of DOI:10.1002/jhet.2216

Base decomposition of 4-(substituted phenyl)-1,2,3-selenadiazoles at room temperature resulted in 2-(substituted phenyl)-ethynylselenolate anions, which were immediately reacted with bromoacetonitrile to give a series of 2-(substituted phenyl)ethynylselan

Full text of DOI:10.1002/jhet.2216

Month 2014
Preparation of 2-Arylethynylselanylacetonitriles from 4-Aryl-1,2,3-
selenadiazoles
a
b
a
*
N. A. O’Connor, N. D. Sachinvala, and I. Ganjian
aDepartment of Chemistry, Lehman College, Bronx, NY 10468
bSouthern Regional Research Center, USDA-ARS, New Orleans, LA
*
E-mail: iraj.ganjian@lehman.cuny.edu
Received December 6, 2013
DOI 10.1002/jhet.2216
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
Base decomposition of 4-(substituted phenyl)-1,2,3-selenadiazoles at room temperature resulted in
2-(substituted phenyl)-ethynylselenolate anions, which were immediately reacted with bromoacetonitrile to
give a series of 2-(substituted phenyl)ethynylselanylacetonitriles.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
Addition of potassium tert-butoxide to solutions of
1,2,3-selenadiazoles in tetrahydrofuran resulted in the in
situ formation of selenolate anions 4 and nitrogen gas.
Immediately after the evolution of nitrogen gas, within
10–15 s, bromoacetonitrile was added. It is important to
observe the time limitation because delay in adding the
bromoacetonitrile results in dimerization of selenolate
anions to corresponding 1,4-diselenafulvenes [20,21].
Good yields were observed for the para-substituted
methoxy, chloro, and nitro analogs. The unsubstituted
and the meta-substituted analogs were recovered in lower
yields of 48% and 32%, respectively. The position of the
substitution also seems to have a significant effect on
the physical properties of selenoacetonitriles. All para-
substituted analogs were solids with melting points above
76°C, whereas unsubstituted and the meta-substituted
analogs both were oils.
In a previous investigation, we prepared α-selenketones
from 4-aryl-1,2,3-selenodiazoles and examined the action
of phenylmagnesium bromide on the α-selenoketones
[18]. We concluded that selenium, instead of the competi-
tive carbonyl group, was the site of nucleophilic attack by
the organic group of the Grignard reagent. This
selenophilic reaction introduced a route to the preparation
of selenoethers. In another investigation, we examined
the Grignard reaction on α-thioketones [22]. Unlike
the selenophilic reaction of the Grignard reagents with
α-selenoketones, the carbonyl group was the site of
nucleophilic attack and we did not detect any sign of
thiophilic attack by the phenylmagnesium bromide.
Likewise, it is worth to study the reaction between
α-selenonitriles with Grignard reagents and determine the
competitive site for nucleophilic attack. Preparation of
(2-arylethynyl)selenoacetonitriles also provides a route to
α-selenoaminoacids and heterocycles with a promise of
interesting biological activities.
Organoselenium compounds are of great interest for
their biological properties and are well studied as
antibacterial and antifungal agents [1]. Selanyl acetonitriles
have been reported as synthetic intermediates for preparing
heterocycles and biologically active organoselenium
compounds. For example, selanyl acetonitriles were
utilized to prepare selenium-containing tetrazoles with
antifungal activity, by cycloaddition of the nitrile group
with sodium azide [2]. They have also been used to prepare
selenium heterocycles with anti-inflammatory, analgesic,
and antimicrobial activities [3,4]. Generally, selanyl
acetonitriles have been prepared by substitution reactions
using haloacetonitriles with selenolate ions, which were
commonly accessed by the cleavage of diselenides [5,6].
Since the first development of 1,2,3-selenadiazoles by I.
Lalazari et al. in 1969 [7], they have been widely used as
intermediates for developing organoselenium compounds
[8] and used as a route for the synthesis of compounds with
anti-tumor [9–13], anti-HIV [14], and antimicrobial activity
[15–17]. We have previously reported the synthesis of
ethynylselenoketones [18] and selenium analogs of glycerol
[19] by the nucleophilic attack of 2-arylethynylselenolates
on α-bromoketones and epichlorohydrin, respectively.
Herein, we describe the synthesis of selenoacetonitriles 5
by the base-catalyzed decomposition of 4-(substituted
aryl)-1,2,3-selenadiazoles 3 to generate selonolate anions 4
that subsequently react with bromoacetonitrile by a nucleo-
philic substitution reaction to give the products.
RESULTS AND DISCUSSION
The selenoacetonitriles 5 were synthesized according to
the route shown in Scheme 1. The 1,2,3-selenadiazoles 3
were prepared from the selenium dioxide oxidation of
arylketone semicarbazones as reported in the literature [7].
© 2014 HeteroCorporation

N. A. O'Connor, N. D. Sachinvala, and I. Ganjian
Vol 000
Scheme 1
115.7 (C), 123.0 (2CH), 128.9 (C), 132.0 (2CH), 147.1 (C).
Anal. Calcd. for C10H6N2O2Se: C, 45.30; H, 2.28. Found: C,
45.25; H, 2.30.
EXPERIMENTAL
Melting points were taken on Fisher–Johns hot stage apparatus.
The H and 13C NMR were recorded on a Varian Unity 400 WB
1
2-(((3-Nitrophenyl)ethynyl)selanyl)acetonitrile (5d).
Yield
32%, oil; IR 2174 (C≡C), 2244 (C≡N); 1H NMR (400 MHz,
C6D12) δ 3.51 (s, 2H), 7.50 (t, 1H), 7.73 (d, 1H), 8.16 (d, 1H),
8.26 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 8.7 (CH2), 70.4
(C), 101.7 (C), 115.8 (C), 123.5 (CH), 124.0 (CH), 126.0 (CH),
128 (CH), 137.0 (CH), 147.1 (C). Anal. Calcd. for
C10H6N2O2Se: C, 45.30; H, 2.28. Found: C, 45.34; H, 2.28.
instrument (Palo Alto, CA). Infrared spectra were obtained on a
Perkin Elmer Infracord spectrophotometer (Waltham, MA). The
compounds were used as a thin film or Nujol mull. Silica gel for
flash column chromatography was obtained from J.T. Baker
Chemical Co. with an average particle size of about 40μm. The
4-substituted-1,2,3-selenadiazoles, as starting material, were pre-
pared following the previously described methods [6].
General procedure for reaction of potassium 4-substituted-2-
arylethynylselenolate 4 with bromoacetonitrile. To a stirred ice-
cold solution of 4-aryl-1,2,3-selenadiazole (3, 0.012mol) in
anhydrous tetrahydrofuran (100 mL). Potassium tert-butoxide
(0.012 mol) was added in one portion. Immediately after the
evolution of nitrogen gas ceased (10–15 s), bromoacetonitrile (0.012
mol) was added in one portion and the solution was further stirred for
1 h. The solvent was removed under reduced pressure, by a
Rotavapor. Water (50 mL) was added to the residue and the mixture
was extracted with dichloromethane (3 × 30 mL). After the organic
portion was dried over anhydrous magnesium sulfate, the solvent was
removed completely and the dark residue was purified by flash
column chromatography and on a column (20 cm × 7.5 cm) packed
with silica gel as the stationary phase for flash chromatography, using
ethyl acetate–hexane (1:9) as mobile phase.
2-((p-Tolylethynyl)selanyl)acetonitrile (5e).
Yield 33.8%,
mp 76°C; IR 2156 (C≡C), 2235 (C≡N); 1H NMR (400 MHz,
C6D12) δ 2.34 (s, 3H), 3.41 (s, 2H), 7.11 (d, 2H), 7.36 (d, 2H);
13C NMR (100 MHz, CDCl3) δ 8.7 (CH2), 21.5 (CH3) 65.7 (C),
104.3 (C), 116.72 (C), 119.2 (C), 129.0 (2CH), 131.9 (2CH),
139.4 (C). Anal. Calcd. for C11H9NSe: C, 56.42; H, 3.87.
Found: C, 56.42; H, 3.91.
2-(((4-bromophenyl)ethynyl)selanyl)acetonitrile (5f). Yield
77%, mp 126°C; IR 2156 (C≡C), 2235 (C≡N); 1H NMR
(400 MHz, C6D12) δ 3.44 (s, 2H), 7.30 (d, 2H), 7.44 (d, 2H);
13C NMR (100 MHz, CDCl3) δ 8.6 (CH2), 68.0 (C), 103.1 (C),
115.9 (C), 121.1 (C), 123.1 (C), 131.6 (2CH), 133.2 (2CH).
Anal. Calcd. for C10H6BrNSe: C, 40.17; H, 2.02. Found: C,
40.43; H, 1.99.
2-(((4-Methoxyphenyl)ethynyl)selanyl)acetonitrile (5g).Yield
95%, mp 74–75°C; IR 2146 (C≡C), 2243 (C≡N); 1H NMR
(400 MHz, C6D12) δ 3.41 (s, 2H), 3.79 (s, 3H), 6.82 (d, 2H),
7.40 (d, 2H); 13C NMR (100 MHz, CDCl3) δ 8.6 (CH2), 55.3
(CH3), 64.7 (C), 104.2 (C), 113.9 (2CH), 114.3 (C), 116.2 (C),
133.8 (2CH), 160.2 (C). Anal. Calcd. for C11H9NOSe: C, 52.82;
H, 4.43. Found: C, 52.73; H, 4.33.
The choice of the mobile phase for flash chromatography was based
on the results obtained from TLC. The use of ethyl acetate–hexane
(3:7) for TLC showed spots with retardation factors (Rf) in the range
of 0.32–0.43, depending on the nature of the products. Because of
close proximity of the impurity spots to the products on TLC, the
choice of using 10% ethyl acetate in hexane proved to be an optimal
eluent for the purification of the products by flash chromatography.
REFERENCES AND NOTES
2-((Phenylethynyl)selanyl)acetonitrile (5a). Yield 48%, oil;
IR 2156 (C≡C), 2243 (C≡N); 1H NMR (400 MHz, C6D12) δ 3.44
(s, 2H), 7.32 (m, 3H), 7.46 (m, 2H); 13C NMR (100 MHz, CDCl3)
δ 8.6 (CH2), 66.7 (C), 104.2 (C), 116.1 (C), 122.3 (C), 128.3
(2CH), 129.1 (CH), 131.8 (2CH). Anal. Calcd. for C10H7NSe:
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C, 54.56; H, 3.21. Found: C, 54.51; H, 3.19.
2-(((4-Chlorophenyl)ethynyl)selanyl)acetonitrile (5b). Yield
85%, mp 125°C; IR 2165 (C≡C), 2235 (C≡N); 1H NMR
(400 MHz, CDCl3) δ 3.44 (s, 2H), 7.30 (m, 4H). 13C NMR
(100 MHz, CD2Cl2) 11.6 (CH2), 73.4 (C), 103.2 (C), 103.3 (C),
123.5 (C), 130.9 (2CH), 135.1 (2CH), 136.0 (C). Anal. Calcd.
for C10H6ClNSe: C, 47.18; H, 2.38. Found: C, 47.22; H, 2.36.
2-(((4-Nitrophenyl)ethynyl)selanyl)acetonitrile (5c).
Yield
86%, mp 131–2°C; IR 2156 (C≡C), 2244 (C≡N); 1H NMR
(400 MHz, C6D12) δ 3.52 (s, 2H), 7.56 (d, 2H), 8.16 (d, 2H);
13C NMR (100 MHz, CDCl3) δ 9.6 (CH2), 73.6 (C), 102.5 (C),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Preparation of 2-Arylethynylselanylacetonitriles from 4-Aryl-1,2,3-selenadiazoles
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet