Synthesis and characterization of pyrimidyl- and pyrazinylselenium compounds: X-ray structure of 2,5-bis(methylselenenyl)pyrazine

Article abstract of DOI:10.1016/j.ica.2014.06.025

A methodology for the lithiation of pyrimidine (1a) was developed and used for the synthesis of pyrimidylselenium compounds. The procedure involved prior complexation of 1a with 2.2 equiv. of BF₃·Et₂O followed by a reaction with LDA or LTMP. The pyrazinylselenium derivatives were synthesized from the direct lithiation of pyrazine (1b) as the BF ₃-directed lithiation failed to give the desired products. All the synthesized compounds were characterized by elemental analysis, NMR ( ¹H and ¹³C) and Mass spectroscopy. In addition, 2,5-bis(methylselenenyl)pyrazine (9b) was characterized by single crystal X-ray crystallography.

Full text of DOI:10.1016/j.ica.2014.06.025

Inorganica Chimica Acta 421 (2014) 359–363
Contents lists available at ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Synthesis and characterization of pyrimidyl- and pyrazinylselenium
compounds: X-ray structure of 2,5-bis(methylselenenyl)pyrazine
a
a
a
b
c
Jaspreet S. Dhau a, , Avtar Singh , Amritpal Singh , Rupy Dhir , Paula Brandão , Vítor Félix
⇑
a Department of Chemistry, Punjabi University, Patiala 147002, India
b Departamento de Química, CICECO, Universidade de Aveiro, Aveiro 3810-193, Portugal
c Departamento de Química, CICECO, and Secção Autónoma de Ciências da Saúde, Universidade de Aveiro, Aveiro 3810-193, Portugal
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 May 2014
Received in revised form 25 June 2014
Accepted 26 June 2014
Available online 4 July 2014
A methodology for the lithiation of pyrimidine (1a) was developed and used for the synthesis of pyrimid-
ylselenium compounds. The procedure involved prior complexation of 1a with 2.2 equiv. of BF3ÁEt2O fol-
lowed by a reaction with LDA or LTMP. The pyrazinylselenium derivatives were synthesized from the
direct lithiation of pyrazine (1b) as the BF3-directed lithiation failed to give the desired products. All
the synthesized compounds were characterized by elemental analysis, NMR (1H and 13C) and Mass
spectroscopy. In addition, 2,5-bis(methylselenenyl)pyrazine (9b) was characterized by single crystal
X-ray crystallography.
Keywords:
Selenium
Pyrimidine
Pyrazine
Ó 2014 Elsevier B.V. All rights reserved.
Lithiation
1. Introduction
tetramethylpiperdide (LTMP). The present paper provides detailed
investigation on the lithiation of 1a and 1b in the presence and
Organoseleniums with electron-deficient heterocycles have
shown tremendous potential as biologically active agents [1–5], pre-
cursors to semi-conducting materials [6–8] and synthons in organic
synthesis [9,10]. The chemistry of pyridylseleniums has grown
substantially in the last couple of decades [11–15], and that of
pyrimidylseleniums has recently shown some activity [11,16–21].
Surprisingly, there is no report on the chemistry of pyrazinylseleni-
um compounds. We are reporting here the synthesis and character-
ization of pyrimidyl- and pyrazinylselenium compounds by a
methodology that involves the lithiation of pyrimidine (1a) and
pyrazine (1b), respectively. The direct lithiation of unsubstituted
pyrimidine has always been a challenge due to the instability of
the lithiated pyrimidine species [22], whereas that of 1b has been
achieved with moderate success [22,23]. Recently, the BF3-directed
metallation of substituted pyrimidines (2,4-dimethoxy-, 2-butoxy-
pyrimidine, etc.) and pyrazines (2-chloro-, 2-bromopyrazine, etc.)
has been reported with highly expensive bimetallic tetramethylpip-
erdine (TMP) bases, TMPZnClÁLiCl and (TMP)2MgÁ2LiCl [24].
However, there is no report on the BF3-directed lithiation of
1a and 1b with lithium diisopropylamide (LDA) or lithium
absence of BF3ÁEt2O with LDA and LTMP as the lithiating reagents,
and selenium as the electrophile.
2. Experimental
2.1. General
All the reagents and solvents were purified by standard proce-
dures, and were freshly distilled prior to use [25]. LTMP and LDA
were prepared by the reaction of n-BuLi with 2,2,6,6-tetramethyl-
piperidine and diisopropylamine, respectively [26]. All the experi-
ments were carried out in flame-dried round bottom flasks and
under moisture-free nitrogen atmosphere. 1H and 13C NMR spectra
were obtained on a Bruker 400 MHz spectrophotometer in CDCl3.
1H NMR and 13C NMR chemical shifts were cited with respect to
tetramethylsilane as the internal standard. The EI mass spectra
were measured using a Shimadzu GC-Mass Spectrometer equipped
with an Rtx-1MS (30 m  0.25 mm ID  0.25
lm) capillary col-
umn. Elemental analysis for C, H and N was carried out on a Vario
MICRO Elementar analyzer.
2.2. 2-(Methylselenenyl)pyrimidine (4a)
⇑
Corresponding author. Present address: Electrical Engineering Department,
University of South Florida, Tampa, FL 33647, USA. Tel.: +91 813 974 4787; fax: +91
813 974 2050.
1a (0.72 g, 0.70 mL, 9.0 mmol) was treated with a solution of
BF3.Et2O in diethyl ether (2.81 g, 2.48 mL, 19.8 mmol) at 0 °C. The
E-mail address: jassiv02@yahoo.co.in (J.S. Dhau).
http://dx.doi.org/10.1016/j.ica.2014.06.025
0020-1693/Ó 2014 Elsevier B.V. All rights reserved.

360
J.S. Dhau et al. / Inorganica Chimica Acta 421 (2014) 359–363
temperature of the resulting suspension was lowered to À78 °C
and LDA/LTMP (18.0 mmol) was added via cannulation. The orange
solution thus formed was stirred for 15 min at À78 °C and elemen-
tal selenium (1.41 g, 18.0 mmol) was added to it. The temperature
of the reaction mixture was slowly raised to the room temperature
and stirring was continued till most of the selenium was dissolved.
The resulting solution was re-cooled to À78 °C and reacted with
iodomethane (2.56 g, 1.11 mL, 18.0 mmol). The reaction mixture
was slowly brought back to the room temperature and hydrolyzed
with distilled water (30 mL). The organic layer was extracted with
diethyl ether and dried over anhydrous sodium sulfate. The solvent
was removed using a rota-evaporator and the crude product was
purified with column chromatography (silica gel 60–120 mesh,
hexane/EtOAc, 50:1) to give 4a (1.09 g, 70%, LDA and 1.12 g, 71%,
LTMP) as a brownish red viscous liquid. 1H NMR: (400 MHz,
CDCl3): d (ppm): 8.60–8.61 (d, J = 4.8 Hz, 2H), 7.23–7.25 (t, 1H),
2.40 (s, 3H). 13C NMR (100 MHz, CDCl3): d (ppm): 169.0, 157.6,
2.3.1. 2-(Methylselenenyl)pyrazine (4b)
Iodomethane (1.95 g, 0.85 mL, 13.75 mmol) was used as the
electrophile in the above reaction to give 4b (1.3 g, 64%) as a pale
yellow liquid. 1H NMR (400 MHz, CDCl3): d (ppm): 8.55–8.56 (d,
J = 1.5 Hz, 1H), 8.38–8.40 (dd, J = 1.7 and 2.4 Hz, 1H), 8.22–8.23
(d, J = 2.6 Hz, 1H), 2.47 (s, 3H). 13C NMR (100 MHz, CDCl3): d
(ppm): 154.1, 145.7, 144.8, 140.1, 5.3. MS (EI, 70 eV) m/z (relative
intensity): 174 (25, [M]ꢀ+, 80Se), 132 (7), 94 (100), 79 (17), 52
(49). Anal. Calc. for C5H6N2Se: C, 34.69, H, 3.49, N, 16.18. Found:
C, 34.77, H, 3.55, N, 16.07%.
2.3.2. 2-(Propylselenenyl)pyrazine (5b)
Iodopropane (2.3 g, 1.34 mL, 13.75 mmol) was used instead of
iodomethane to give 5b (1.30 g, 53%) as a pale yellow liquid. 1H
NMR: (400 MHz, CDCl3): d (ppm): 8.53–8.54 (d, J = 1.5 Hz, 1H),
8.37–8.38 (dd, J = 1.6 and 2.5 Hz, 1H), 8.21–8.22 (d, J = 2.6 Hz,
1H), 3.17–3.20 (t, 2H), 1.77–1.86 (m, 2H), 1.02–1.06 (t, 3H). 13C
NMR (100 MHz, CDCl3): d (ppm): 154.1, 146.4, 144.9, 140.2, 23.9,
23.5, 14.4. MS (EI, 70 eV) m/z (relative intensity): 204 (6, [M]ꢀ+,
80Se), 202 (32), 160 (90), 121 (100), 107 (24), 94 (12), 79 (63), 68
(26), 52 (83). Anal. Calc. for C7H10N2Se: C, 41.80, H, 5.01, N,
13.92. Found: C, 42.03, H, 5.18, N, 13.81%.
+
117.7, 6.4. MS (EI, 70 eV) m/z (relative intensity): 174 (18, [M]_ ,
80Se) 94 (100), 80 (25), 67 (6), 53 (41). Anal. Calc. for C5H6N2Se:
C, 34.69, H, 3.49, N, 16.18. Found: C, 34.82, H, 3.39, N, 16.27%.
2.2.1. 2-(Ethylselenenyl)pyrimidine (5a)
1a (0.72 g, 0.70 mL, 9.0 mmol), LDA (18.0 mmol), selenium
(1.41 g, 18.0 mmol) and iodoethane (2.81 g, 1.45 mL, 18.0 mmol)
were used to obtain 5a (1.08 g, 64%) as a red viscous liquid. 1H
NMR: (400 MHz, CDCl3): d (ppm): 8.58–8.59 (d, J = 4.8 Hz, 2H),
7.20–7.22 (t, 1H), 2.91–2.96 (q, 2H), 1.41–1.44 (t, 3H). 13C NMR
(100 MHz, CDCl3): d (ppm): 168.8, 157.5, 117.4, 23.1, 15.0. MS
(EI, 70 eV) m/z (relative intensity): 188 (22, [M]ꢀ+, 80Se), 173 (4),
159 (4), 107 (100), 79 (31), 68 (4), 53 (22). Anal. Calc. for C6H8N2Se:
C, 38.29, H, 4.25, N, 14.89. Found: C, 38.01, H, 4.16, N, 14.96%.
2.3.3. 2-(Butylselenenyl)pyrazine (6b)
Iodobutane (2.53 g, 1.56 mL, 13.75 mmol) was used as the elec-
trophile to give 6b (1.37 g, 51%) as a pale yellow liquid. 1H NMR:
(400 MHz, CDCl3): d (ppm): 8.53–8.54 (d, J = 1.5 Hz, 1H), 8.37–
8.38 (dd, J = 1.6 and 2.5 Hz, 1H), 8.21–8.22 (d, J = 2.6 Hz, 1H),
3.18–3.22 (t, 2H), 1.73–1.80 (m, 2H), 1.41–1.50 (m, 2H), 0.92–
0.95 (t, 3H). 13C NMR (400 MHz, CDCl3): d (ppm): 154.2, 146.3,
144.9, 140.2, 32.1, 25.5, 23.0, 13.0. MS (EI, 70 eV) m/z (relative
intensity): 218 (5, [M]ꢀ+, 80Se), 216 (26), 187 (8), 160 (100), 135
(44), 107 (29), 94 (21), 79 (44), 52 (51). Anal. Calc. for C8H12N2Se:
C, 44.65, H, 5.62, N, 13.02. Found: C, 44.89, H, 5.79, N, 12.89%.
2.2.2. 2,4-Bis(methylselenenyl)pyrimidine (6a)
1a (0.72 g, 0.70 mL, 9.0 mmol), LDA (19.8 mmol), selenium
(1.56 g, 19.8 mmol) and iodomethane (2.80 g, 1.22 mL, 19.8 mmol)
were used to get 6a (0.50 g, 21%) as a red viscous liquid. 1H NMR:
(400 MHz, CDCl3): d (ppm): 7.94–7.96 (d, J = 5.2 Hz, 1H), 6.91–6.92
(d, J = 5.4 Hz, 1H), 2.39 (s, 6H). 13C NMR (100 MHz, CDCl3): d (ppm):
168.2, 154.0, 117.8, 6.7, 5.2. MS (EI, 70 eV) m/z (relative intensity):
268 (77, [M]ꢀ+, 80Se), 252 (2), 185 (18), 174 (29), 108 (27), 93 (100),
79 (31), 65 (2), 52 (30). Anal. Calc. for C6H8N2Se2: C, 27.08, H, 3.03,
N, 10.52. Found: C, 27.19, H, 3.16, N, 10.41%.
2.3.4. 2-(Benzylselenenyl)pyrazine (7b)
(Chloromethyl)benzene (1.74 g, 1.58 mL, 13.75 mmol) was used
as the electrophile to obtain 7b (1.30 g, 44%) as a dark reddish liquid.
1H NMR: (400 MHz, CDCl3): d (ppm): 8.50–8.51 (d, J = 1.6 Hz, 1H),
8.42–8.43 (dd, J = 1.7 and 2.5 Hz, 1H), 8.24–8.25 (d, J = 2.6 Hz, 1H),
7.34–7.37 (dd, J = 1.5 and 5.1 Hz, 2H), 7.25–7.29 (td, J = 1.5 and
5.1 Hz, 1H), 7.18–7.22 (dd, J = 1.4 and 4.5 Hz, 2H), 4.44 (s, 2H). 13C
NMR (400 MHz, CDCl3): d (ppm): 153.9, 146.2, 144.9, 140.7, 138.3,
129.0, 128.6, 128.5, 128.4, 127.2, 29.1. MS (EI, 70 eV) m/z (relative
intensity): 250 (4, [M]ꢀ+, 80Se), 169 (35), 132 (9), 91 (100), 65 (20),
52 (9). Anal. Calc. for C11H10N2Se: C, 52.80, H, 4.00, N, 11.20. Found:
C, 52.92, H, 4.06, N, 11.27%.
2.2.3. 2,4,6-Tris(methylselenenyl)pyrimidine (7a)
1a (0.72 g, 0.70 mL, 9.0 mmol), LDA (29.7 mmol), selenium
(2.34 g, 29.7 mmol) and iodomethane (4.21 g, 1.50 mL, 29.7 mmol)
were used to obtain 7a (0.16 g, 5%) as an orange viscous liquid. 1
H
NMR: (400 MHz, CDCl3): d (ppm): 6.98 (s, 1H), 2.45 (s, 3H), 2.42 (s,
6H). 13C NMR (100 MHz, CDCl3): d (ppm): 168.1, 154.1, 117.2, 6.7,
5.4. MS (EI, 70 eV) m/z (relative intensity): 360 (70, [M]ꢀ+, 80Se), 343
(59), 327 (11), 281 (41), 267 (18), 251 (17), 207 (83), 193 (19), 173
(28), 147 (29), 118 (18), 95 (82), 85 (100), 73 (88), 57 (39). Anal.
Calc. for C7H10N2Se3: C, 23.41, H, 2.80, N, 7.80. Found: C, 23.48,
H, 2.89, N, 7.88%.
2.3.5. Bis(2-pyrazinylselenium)methane (8b)
Diiodomethane (1.80 g, 0.55 mL, 6.87 mmol) was used as the
electrophile to generate 8b (1.13 g, 27%) as a light red solid. M.P.
94–97 °C. 1H NMR: (400 MHz, CDCl3): d (ppm): 8.66–8.68 (dd,
J = 2.5 and 3.8 Hz, 2H), 8.45–8.46 (dd, J = 1.6 and 4.2 Hz, 2H),
8.28–8.30 (dd, J = 2.6 and 5.6 Hz, 2H), 4.85 (s, 2H). 13C NMR
(100 MHz, CDCl3): d (ppm): 154.1, 146.4, 144.9, 140.2, 14.4. MS
(EI, 70 eV) m/z (relative intensity): 332 (2, [M]ꢀ+, 80Se), 253 (4),
173 (74), 161 (13), 132 (10), 119 (3), 106 (5), 93 (37), 79 (65), 66
(4), 52 (100). Anal. Calc. for C9H8N4Se2: C, 32.53, H, 2.40, N,
16.86. Found: C, 32.77, H, 2.51, N, 16.91%.
2.3. General method for the preparation of selenolate anion of pyrazine
(1b)
A solution of 1b (1 g, 12.5 mmol) in dry THF (30 mL) was cooled
to –78 °C and LDA (13.75 mmol) was added slowly via cannulation.
After 15 min of stirring, elemental selenium (1.08 g, 13.75 mmol)
was added to it. The temperature was slowly raised till all of the
selenium was dissolved. Different electrophiles (13.75 mmol) were
added to the selenolate anion at –78 °C to give the desired
products.
2.4. 2,5-Bis(methylselenenyl)pyrazine (9b)
1b (1 g, 12.5 mmol), LDA (27.5 mmol), selenium (2.18 g,
27.5 mmol) and iodomethane (3.90 g, 1.71 mL, 27.5 mmol) were
used to obtain 9b (0.38 g, 12%) as a colorless crystalline solid.
M.P. 108–110 °C. 1H NMR: (400 MHz, CDCl3): d (ppm): 8.40

J.S. Dhau et al. / Inorganica Chimica Acta 421 (2014) 359–363
361
(s, 2H), 2.45 (s, 6H). 13C NMR (400 MHz, CDCl3): d (ppm): 148.6,
Table 1
145.6, 5.5. MS (EI, 70 eV) m/z (relative intensity): 268 (13, [M]ꢀ+,
80Se), 187 (59), 174 (2), 145 (2), 120 (26), 107 (100), 94 (12), 66
(19), 52 (23). Anal. Calc. for C6H8N2Se2: C, 27.08, H, 3.03, N,
10.52. Found: C, 27.19, H, 3.01, N, 10.59%.
Crystal data and structure refinement details for 9b.
Empirical formula
Formula weight
Crystal system
Space group
a (Å)
C6H8N2Se2
266.06
triclinic
ꢀ
P1
4.09270(10)
5.4402(2)
2.5. Crystallography
b (Å)
c (Å)
9.7101(3)
The single crystal X-ray data of compound 9b was collected on a
Bruker SMART Apex II CCD-based diffractometer at 180(2) K using
a
b (°)
(°)
84.885(2)
83.101(2)
72.689(2)
204.583(11)
1
2.160
8.961
126.0
0.32 Â 0.26 Â 0.1
4.23 to 58.19°
À5 6 h 6 5, À7 6 k 6 7,
À13 6 l 6 13
2390
1090 (0.0169, 0.0214)
1090/0/47
1.139
R1 = 0.0186, wR2 = 0.0438
R1 = 0.0202, wR2 = 0.0442
0.47/À0.50
c
(°)
graphite monochromatized Mo K
a radiation (k = 0.71073 Å). The
V (Å3)
data reduction was carried out using the SAINT-NT software pack-
age from Bruker AXS [27]. The raw intensities were corrected for
absorption effects using the multi-scan method with the SADABS
[28]. The structure was solved by a combination of direct methods
and subsequent difference Fourier syntheses and refined by full
matrix least squares on F2 using the SHELX-2013 suite [29]. The
hydrogen atoms were inserted at geometrical positions and refined
with isotropic parameters equivalent 1.2 times those of the atom
to which they are attached. Anisotropic thermal parameters were
used for all non-hydrogen atoms. The ORTEP view was drawn with
the OLEX2 [30]. The crystal data and refinement details of 9b are
summarised in Table 1.
Z
qcalc (mg/mm3)
l
(mmÀ1
)
F(000)
Crystal size (mm3)
2h range for data collection
Index ranges
Reflections collected
Independent reflections (Rint, Rsigma
Data/restraints/parameters
Goodness-of-fit (GOF) on F2
Final R indexes [I P 2
Final R indexes (all data)
Largest difference in peak/hole (e ÅÀ3
)
r(I)]
)
3. Results and discussion
improved further when we used 3.3 equiv. of LDA (Table 2, entry
5). The later reaction also afforded a triselenated product, 7a, in a
very low yield (Scheme 1). All the synthesized pyrimidylselenium
compounds are stable in air and soluble in conventional organic
solvents, like THF, diethyl ether, DMF, etc.
3.1. Synthesis of pyrimidylselenium compounds
Complexation of 1a with 1.1 equiv. of BF3.Et2O failed to promote
the lithiation of 1a with LDA or LTMP (1.1–2.0 equivs). The use of
different solvents (diethyl ether and THF), reaction conditions, and
electrophiles (selenium, dimethyl disulfide, benzaldehyde and ace-
tone) did not give the desired products. It appears that the com-
plexation of 1a with a single BF3 molecule is not able to generate
a stable lithiated species that can participate in the subsequent
electrophile quenching reaction.
Next, we investigated the lithiation of 1a in the presence of 2.2
equiv. of BF3ÁEt2O. Treatment of 1a with BF3ÁEt2O (2.2 equiv.) and
LDA/LTMP (2.0 equiv.) followed by reaction with elemental sele-
nium and iodomethane/iodoethane afforded 2-(methyl/ethylse-
lenenyl)pyrimidine (4a/5a) in excellent yields (Scheme 1, Table 2,
entries 1–3). The isolation of 4a/5a establishes the efficient lithia-
tion of 2a at the C-2 position leading to a stable lithiated species,
3a (Scheme 1). Based on the inductive and electrostatic effect this
position is most likely to get lithiated. We then monitored the
effect of the amount of LDA on the lithiation of 2a. 2,4-Bis
(methylselenenyl)pyrimidine (6a) and 4a were obtained when
2.2 equiv. of LDA was used (Table 2, entry 4). The yield of 6a
3.2. Synthesis of pyrazinylselenium compounds
Contrary to 1a, BF3 complexation failed to promote the lithiation
of 1b. Different reaction conditions, like the use of 1.1 or 2.2 equiv.
of BF3.Et2O, LDA or LTMP (1.1/2.2 equiv.) as the lithiating reagents,
THF or diethyl ether as the solvents, and different reaction temper-
atures, had no effect on the outcome of the reaction. A number of
electrophiles (selenium, dimethyl disulfide, hexachloroethane,
and benzaldehyde) were used but none gave products correspond-
ing to the lithiation of 1b. It appears that the BF3 complexation
prevents the lithiation of 1b with LDA or LTMP. As mentioned ear-
lier, the metallation of substituted pyrazinyl derivatives has been
achieved through its prior complexation with 1.1 equiv. of BF3.Et2O
[24]. This indicates that the bimetallic bases and substituents on the
pyrazine ring promote the metallation in these moieties.
Next, we investigated the direct lithiation of 1b with LDA as the
lithiating reagent. Treatment of 1b with LDA (1.1 equiv.) at À78 °C
BF3
BF3
N
N
N
BF .Et O (2.2 eq.)
3
2
LDA/LTMP
o
o
0
C, Dry Et O
2
(2.0 eq.), -78 C
N
N
Li
N
1a
BF3
BF3
3a
2a
o
i) LDA (3.3 eq.)
ii) Se (3.3 eq.)
iii) CH I (3.3 eq.)
i) Se (2.0 eq.) -78 C to rt
o
ii) RI (2.0 eq.) -78
C
ii) H O
2
3
iv) H O
2
SeCH3
N
N
N
N
SeR
H3CSe
H3CSe
N
SeCH3
N
SeCH3
4a (R= CH ; 70%,LDA; 71%, LTMP)
3
5
7a
(5%)
5a (R= C H ; 64%,LDA)
6a (37%)
2
Scheme 1. Synthesis of pyrimidylselenium compounds.

362
J.S. Dhau et al. / Inorganica Chimica Acta 421 (2014) 359–363
Table 2
Synthesis of selenium derivatives of 1a and 1b.
Entry
Substrate
Solvent
BF3ÁEt2O (equiv)
Lithiating reagent (equiv)
Electrophile (1.3 equiv)
Product
1.
2.
3.
4.
5.
6.
7.
8.
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
Et2O
Et2O
Et2O
Et2O
Et2O
THF
THF
THF
THF
THF
THF
2.2
2.2
2.2
2.2
2.2
–
–
–
–
–
LDA (2.0)
LTMP (2.0)
LDA (2.0)
LDA (2.3)
LDA (3.3)
LDA (1.1)
LDA (1.1)
LDA (1.1)
LDA (1.1)
LDA (1.1)
LDA (2.2)
Se + CH3I
Se + CH3I
Se + C2H5I
Se + CH3I
Se + CH3I
Se + CH3I
Se + C3H7I
Se + CH3I
Se + C4H9I
Se + CH2I2
Se + CH3I
4a (70%)
4a (72%)
5a (64%)
4a (51%), 6a (21%)
6a (37%), 7a (5%)
4b (64%)
5b (53%)
6b (51%)
9.
10.
11.
7b (44%)
8b (27%)
9b (12%), 4b (19%)
–
N
N
N
LDA (1.1 eq.)
Se (1.1 eq.)
-78 oC, Dry Et2O
-78 oC to rt
N
Li
N
N
SeLi
1b
3b
2b
-78 o
C
i) LDA (2.2 eq.), -78 o
ii) Se (2.2 eq.)
iii) CH3I (2.2 eq.)
iv) H2O
C
i) RX (1.1 eq.)
ii) H2O
i) CH2I2 (0.55 eq.)
ii) H2O
N
N
H3CSe
N
N
N
SeR
N
SeCH2
(27%)
SeCH3
4b (R = CH3, 64%)
2
5b
(R = C3H7, 53%)
9b (12%)
8b
6b (R = C4H9, 51%)
7b (R = CH2Ph, 44%)
Scheme 2. Synthesis of pyrazinylselenium compounds.
afforded the carbanion 2b (Scheme 2). The reaction of 2b with sele-
nium gave the selenolate anion, 3b, which on quenching with iodo-
methane (1.1 equiv.) afforded 2-(methylselenenyl)pyrazine (4b) in
a 64% yield. Similarly, a variety of 2-pyrazinylselenium compounds
were synthesized by reacting 3b with different electrophiles
(Table 2, entries 6–10). The dilithiation of 1b was attempted with
2.2 equiv. of LDA at À78 °C. Subsequent reaction with elemental
selenium and iodomethane (2.2 equiv.) afforded 2,5-bis(methylse-
lenenyl)pyrazine (9b) and 4b in 12% and 19% yields, respectively
(Scheme 2). All the synthesized pyrazinylselenium compounds
are stable under normal environmental conditions and do not
require special handling procedures.
non-equivalent –SeCH3 units, which is evident from the
signals at d 6.7 (–SeCH3 at C-2) and d 5.2 (ÀSeCH3 at C-4) ppm.
Conversely, the compound 9b has two equivalent –SeCH3 carbons
that resonate at d 5.5 ppm The mass spectrum of 4a shows the
molecular ion [C5H6N2 80Se]+ꢀ peak at m/z 174 due to the loss of
an electron from the molecule that contains the most abundant
80Se isotope. The base ion peak is observed at m/z 94 due to
_
the fragment [C5H6N2]+ formed by the loss of 80Se radical from
the molecular ion. Similar to 4a, the mass spectrum of 4b displays
the base ion peak at m/z 94. The mass spectrum of 6a shows the
_
molecular ion peak at m/z 268. The loss of Se and [SeCH3]+ frag-
ments from the molecular ion gives the base ion peak at m/z 93.
3.4. Solid state structural features of 9b
3.3. Spectroscopic studies
The 1H NMR spectrum of 4a contains a doublet at d 8.61–8.60
(J = 4.8 Hz) ppm due to H-6 and H-4 ring protons. The H-5 signal
appears as a triplet at d 7.23–7.25 (J = 4.8 Hz) ppm. The spectrum
of 6a contains two doublets in the range d 7.94–7.96 (J = 5.2 Hz)
and 6.91–6.92 (J = 5.4 Hz) ppm that suggests the dilithiation of
1a at the C-2 and C-4 position. The spectra of the pyrazinylseleni-
ums (4b-8b) have lower coupling constant values than the
pyrimidyl derivatives. The H-5 signals in these compounds appear
downfield (ꢀd 8.40 ppm) due to its proximity to the nitrogen atom.
The signal corresponding to the –SeCH3 protons in the pyrimidyl
(4a and 6a) and pyrazinyl (4b and 9b) derivatives appears as sin-
glet in the d 2.39–2.47 ppm range. In the 13C NMR spectra of the
pyrimidylseleniums, the C-2 signal appears downfield than the
corresponding pyrazinyl derivatives. For example, in 4a the
C-2 signal is observed at d 169.0 ppm, whereas it appears at d
154.1 ppm in 4b. The –SeCH3 signals in 4a and 4b appear at d
6.4 and 5.3 ppm, respectively. The compound 6a has two
The position of the second –SeCH3 unit in 9b was determined by
single crystal X-ray crystallography as the NMR spectral data was
inconclusive. The crystals of 9b were grown in a solution of hexane
and ethyl acetate. In the solid state, the individual molecules of 9b
display a centrosymmetric structure with the inversion center
located in the middle of the aromatic ring leading to two indepen-
dent C–N and Se–C distances and one single C–C distance. Their
lengths are given in Table 3 together with selected angles involving
the selenium center. An ORTEP view of 9b with the crystallo-
Table 3
Selected bond distances (Å) and angles (°) for compound 9b.
Se(21)–C(2)
N(1)–C(2)
C(2)–C(3a)
C(2)–Se(21)–C(22)
C(2)–Se(21)–C(22)
1.907(2)
1.332(2)
1.388(3)
98.08(8)
119.08(14)
Se(21)–C(22)
N(1)–C(2)
1.935(2)
1.338(2)
N(1)–C(2)–Se(21)
119.14(13)

J.S. Dhau et al. / Inorganica Chimica Acta 421 (2014) 359–363
363
Fig. 1. ORTEP view of 9b with thermal ellipsoids drawn at the 50% probability level and showing the atom numbering scheme adopted, in which à denotes the symmetry
operator 1 À x, Ày, Àz.
[2] K. Kloc, I. Maliszewska, J. Młochowski, Synth. Commun. 33 (2003) 3805.
graphic notation scheme used is shown in Fig. 1. The compound 9b
´
[3] A. Molter, G.N. KaluCerovic, H. Kommera, R. Paschke, T. Langer, R. Pöttgen, F.
has the shortest Se–C(sp2) bond lengths (1.907(2) Å) among all the
reported bis(methylselenenyl) derivatives [26,31,32]. However, the
two Se–C(sp3) bond lengths are similar to that of bis(methylselene-
nyl) derivatives [26,31,32]. In the crystal structure each nitrogen
atom of the pyrazine ring is involved in C–HÁ Á ÁN hydrogen bonds
with CÁ Á ÁN distances of 3.392 Å and C–HÁ Á ÁN angles of 142°. No
significant intermolecular SeÁ Á ÁSe secondary interactions were
observed in the crystal structure.
Mohr, J. Organomet. Chem. 701 (2012) 80.
[4] R.F. Schinazi, J. Arbiser, J.J.S. Lee, T.I. Kalman, W.H. Prusoffi, J. Med. Chem. 29
(1986) 1293.
[5] G. Zhao, H. Lin, S. Zhu, H. Sun, Y. Chen, Anticancer Drug Des. 13 (1998)
769.
[6] R.K. Sharma, G. Kedarnath, V.K. Jain, A. Wadawale, C.G.S. Pillai, M. Nalliath, B.
Vishwanadh, Dalton Trans. 40 (2011) 9194.
[7] Y. Cheng, T.J. Emge, J.G. Brennan, Inorg. Chem. 35 (1996) 7339.
[8] S. Dey, V.K. Jain, J. Singh, V. Trehan, K.K. Bhasin, B. Varghese, Eur. J. Inorg. Chem.
(2003) 744.
[9] D.M. Browne, O. Niyomura, T. Wirth, Org. Lett. 9 (2007) 3169.
[10] J. Burés, M. Martín, F. Urpí, J. Vilarrasa, J. Org. Chem. 74 (2009) 2203.
[11] G. Kedarnath, V.K. Jain, Coord. Chem. Rev. 257 (2013) 1409.
[12] J.S. Dhau, A. Singh, A. Singh, B.S. Sooch, Phosporus Sulfur Relat. Elem. 189
(2014) 687.
[13] C.P. Prabhu, P.P. Prasad, A.P. Wadawale, K.I. Priyadarsini, V.K. Jain, J.
Organomet. Chem. 713 (2012) 42.
[14] J.S. Dhau, R. Dhir, A. Singh, J. Organomet. Chem. 696 (2011) 2406.
[15] K.K. Bhasin, V. Arora, Appl. Organomet. Chem. 18 (2004) 359.
[16] K.K. Bhasin, E. Arora, K. Kaur, S.K. Kang, M. Gobel, T.M. Klapoetke, S.K. Mehta,
Tetrahedron 65 (2009) 247.
[17] K.K. Bhasin, E. Arora, S.K. Mehta, T.M. Klapoetk, J. Organomet. Chem. 696
(2011) 835.
[18] A.S. Hodage, P.C. Parashiva, Prasad.P. Phadnis, A. Wadawale, K.I. Priyadarsini,
V.K. Jain, J. Organomet. Chem. 720 (2012) 19.
[19] R.K. Sharma, A. Wadawale, G. Kedarnath, B. Vishwanath, V.K. Jain, Inorg. Chim.
Acta 411 (2014) 90.
4. Conclusion
In conclusion, we have reported an effective lithiation of the
pyrimidine ring through its complexation with 2.2 equiv. of BF3-
ÁEt2O. The developed methodology provides a convenient pathway
to synthesize a variety of pyrimidylselenium compounds. The syn-
thesis of pyrazinylselenium compounds was achieved by the direct
lithiation route as the BF3-complexation could not facilitate the
lithiation of the pyrazine ring.
Acknowledgements
[20] R.S. Chauhan, R.K. Sharma, G. Kedarnath, D.B. Cordes, A.M.Z. Slawin, V.K. Jain, J.
Organomet. Chem. 717 (2012) 180.
We are grateful to the CSIR, New Delhi, India, for the financial
support (Scheme No.: 01(2345)/09/EMR-II). We are also thankful
to Mr. Avtar Singh for the NMR spectra.
[21] R.K. Sharma, A. Wadawale, G. Kedarnath, D. Manna, T.K. Ghanty, B.
Vishwanadh, V.K. Jain, Dalton Trans. 43 (2014) 6525.
[22] N. Plé, A. Turck, K. Couture, G. Quéguiner, J. Org. Chem. 60 (1995) 3781.
[23] A. Turck, N. Plé, F. Mongin, G. Quéguiner, Tetrahedron 57 (2001) 4489.
[24] K. Groll, S.M. Manolikakes, X.M. Jourdin, M. Jaric, A. Bredihhin, K. Karaghiosoff,
T. Carell, P. Knochel, Angew. Chem., Int. Ed. 52 (2013) 6776.
[25] D.D. Perrin, W.L.F. Armarego, Purification of Laboratory Chemicals, third ed.,
Pergamon Press, Oxford, 1988.
[26] J.S. Dhau, A. Singh, R. Dhir, J. Organomet. Chem. 696 (2011) 2008.
[27] Bruker SAINT-plus Bruker AXS Inc., Madison, Wisconsin, USA. 2007.
[28] G.M. Sheldrick, SADABS, University of Göttingen, Germany, 1996.
[29] G.M. Sheldrick, Acta Crystallogr., Sect. A 64 (2008) 112.
[30] O.V. Dolomanov, L.J. Bourhis, R.J. Gildea, J.A.K. Howard, H. Puschmann, J. Appl.
Crystallogr. 42 (2009) 339.
Appendix A. Supplementary material
CCDC 1001267 contains the supplementary crystallographic
data for 9b. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif. Supplementary data associated with this article
can be found, in the online version, at http://dx.doi.org/10.1016/
j.ica.2014.06.025.
[31] J.S. Dhau, A. Singh, A. Singh, B.S. Sooch, P. Brandão, V. Félix, Inorg. Chim. Acta
392 (2012) 335.
[32] J.S. Dhau, R. Dhir, A. Singh, P. Brandão, V. Félix, Inorg. Chim. Acta 404 (2013)
108.
References
[1] C.A. Collins, F.H. Fry, A.L. Holme, A. Yiakouvaki, A. Al-Qenaei, C. Pourzand, C.
Jacob, Org. Biomol. Chem. 3 (2005) 1541.