Selenium-containing heterocycles from isoselenocyanates: Synthesis of 2-methylidene-1,3-selenazolidine derivatives

Article abstract of DOI:10.1016/j.tet.2006.01.077

A convenient and unequivocal synthesis of the title compounds from isoselenocyanates, malononitrile or 2-cyanoacetate, and 1,2-dibromoethane or α-halogenated carboxylic acid derivatives is reported. The proposed reaction mechanism involves in situ cyclization of different halogenated compounds with an intermediate keten-N,Se-acetal, generated by the base promoted nucleophilic addition of the acidic cyanomethylenes to aliphatic and aromatic isoselenocyanates. Chemical and spectroscopic evidence for the structures of the new compounds is presented.

Full text of DOI:10.1016/j.tet.2006.01.077

Tetrahedron 62 (2006) 3344–3354
Selenium-containing heterocycles from isoselenocyanates:
synthesis of 2-methylidene-1,3-selenazolidine derivatives
*
Geoffroy L. Sommen, Anthony Linden and Heinz Heimgartner
*
¨ ¨ ¨
Organisch-Chemisches Institut der Universitat Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
Received 16 November 2005; revised 16 January 2006; accepted 17 January 2006
Abstract—A convenient and unequivocal synthesis of the title compounds from isoselenocyanates, malononitrile or 2-cyanoacetate, and
1,2-dibromoethane or a-halogenated carboxylic acid derivatives is reported. The proposed reaction mechanism involves in situ cyclization of
different halogenated compounds with an intermediate keten-N,Se-acetal, generated by the base promoted nucleophilic addition of the acidic
cyanomethylenes to aliphatic and aromatic isoselenocyanates. Chemical and spectroscopic evidence for the structures of the new compounds
is presented.
q 2006 Elsevier Ltd. All rights reserved.
1. Introduction
For the reaction of isoselenocyanates with nucleophiles it is
known that nitrogen, oxygen, sulfur, and selenium nucleo-
philes add to the central carbon atom,16 whereas phosphorus
nucleophiles attack either the central carbon atom or the
selenium atom.17 Although only a few examples of the
reaction of isoselenocyanates with carbon nucleophiles have
been described, it was recently reported that suitable
carbanions and isoselenocyanates can produce selenium-
containing compounds.18 To the best of our knowledge, only
one paper describes such a reaction being used for the
synthesis of 1,3-selenazoles.19 On the other hand, 1,3-
selenazolidinones have been prepared from different starting
materials, such as isothiocyanates,20 selenazadienes,21 and
widely from selenoureas,22 but never with isoselenocyanates.
For this reason, we have investigated the use of isoselenocya-
nates 1, which are conveniently prepared by Barton’s
procedure,5 as building blocks in the synthesis of selenahe-
terocycles and heterocyclic selones.23–34 For example, it has
been shown that the reactions of bifunctional nucleophiles 2
with 1 yield five to seven-membered heterocycles of type 4
and 5 (Scheme 1). A likely intermediate is the adduct 3, which
undergoes the ring closure by nucleophilic substitution of
the leaving group X either by the Se or the N-atom. As a
continuation of previous work, we decided to investigate
the addition of carbon nucleophiles with 1 and to trap the
intermediate by a suitably substituted electrophilic reagent.
The explosive growth of the interest in organoselenium
chemistry over the past 25 years can be attributed to the
specific properties of organic selenium compounds,
which fit into the requirements of modern organic
synthesis. Most of them are well adapted to chemo-,
regio-, and stereoselective reactions.1 In particular, sele-
nium-containing heterocyclic compounds have been well
recognized not only because of their remarkable reactivities
and chemical properties,2 but also because of their diverse
pharmaceutical applications.3 For this reason we are
interested in the use of isoselenocyanates 1 in heterocyclic
synthesis.4 They are useful starting materials, since they are
easy to prepare5 and are safe to handle and store. In addition,
they typically react under mild conditions, which are
compatible with the low stability of substrates and products
in the preparation of complex molecules.
Several reviews6 have described the preparation and
pharmaceutical potential of 1,3-selenazoles.7 They have
been studied in diverse areas of interest, for example as
antitumor8 and antiradiation agents,9 enzyme inhibitors,10
antifilarial11 and antiviral compounds,12 delivery agents,13
and prodrugs of selenocysteine,14 and are also well
recognized in the chemistry of dyes.15
2. Results and discussion
Keywords: Isoselenocyanates; Selenaheterocycles; 1,3-Selenazolidines.
*
Corresponding author. Tel.: C41 44 6354282; fax: C41 44 6356812;
e-mail: heimgart@oci.unizh.ch
After several unsuccessful attempts at reactions of
isoselenocyanates with b-diketons like acetylacetone and
* Postdoctoral stay at the University of Zu¨rich (8.2004-8.2005).
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.01.077

G. L. Sommen et al. / Tetrahedron 62 (2006) 3344–3354
3345
Nu
Nu
CH2
CH2
R1N
Se
X
n
n
Base
Nu
Se
CH2
X
n
N
R1
C
Se
+
X
HNu
CH2
4
n
R1N
Se
1
2
3
N
R1
5
Scheme 1.
dibenzoylmethane, we were successful by using cyano-
methylene derivatives. Malononitrile and ethyl cyanoace-
tate react at rt with aryl and alkyl isoselenocyanates in the
presence of a base to afford an intermediate keten-N,Se-
acetal 7, which subsequently can react with different
halogenated compounds (Scheme 2).
groups are coplanar with the atoms Se(1), C(2), N(3), and
C(6), but the bond angles at the dicyanomethylidene C-atom
are significantly different: whereas the angles C(2)–C(6)–
C(7) and C(7)–C(6)–C(8) are small (118.2(1) and 115.7(1)8,
respectively), the angle C(2)–C(6)–C(8) is widened
(126.1(2)8), that is, the CN group is tilted away from the
phenyl residue. In turn, the latter is twisted out of the above
mentioned plane by ca. 868. Furthermore, the CN group
pointing toward the phenyl residue is slightly bent away
from the phenyl ring (N(8)–C(8)–C(6)Z175.2(2)8) whereas
the other one is linear (N(7)–C(7)–C(6)Z179.3(2)8). In the
case of 10c, the five-membered ring has a half-chair
conformation twisted on C(4)–C(5). The other structure
parameters of 10c are very similar to those of 10a. In both
compounds, the C(2), C(6) bond longer (1.392(2) and
For example, the carbanion obtained from malononitrile
(6a) and triethylamine in DMF added to isoselenocyanates 1
to give an intermediate of type 7. The latter reacted with 1,2-
dibromoethane (8) to give another intermediate 9, which
cyclized to yield 1,3-selenazolidine derivatives of type 10.
After stirring for 4 h, the reaction mixture was evaporated to
dryness and the residue was purified by column chromato-
graphy on silica gel and recrystallization from ethyl acetate
(Table 1). Similar reactions were performed starting with
ethyl cyanoacetate (6b). It is worth mentioning that only one
isomer was obtained in the case of the cyanoacetates 10e–g
(Table 1).
˚
1.399(3) A, respectively) than a normal C]C bond. On the
other hand, the formal single bonds C(6), C(7) and C(6),
˚
C(8) are short (1.421(2), 1.428(2) and 1.424(2), 1.418(3) A,
respectively) as well as the N(3), C(2) and the Se(1), C(2)
˚
bonds (1.332(2), 1.900(2) and 1.328(2), 1.898(2) A,
The structures of the products were established on the basis of
their spectroscopic data and, in the cases of 10a and 10c, by
X-ray crystallography (Fig. 1). The 2-(1,3-selenazolidin-2-
ylidene)malononitriles 10a–d show two different CN absorp-
tions in the IR spectra (KBr; ca. 2203 and 2190 cmK1) and
13C NMR spectra (DMSO; ca. 112 and 118 ppm). For the
2-cyano-2-(1,3-selenazolidin-2-yliden)acetates 10e–g, the
CN absorption appears at ca. 2195 cmK1 and 114 ppm.
respectively). Together with the remarkable chemical shifts
of C(2) and C(6) (ca. 172 and 51 ppm, respectively), dipolar
structures containing the unit –CH2(Ar)NC–CK(CN)2 are
most likely.
The analogous reaction of 1, 6a, and methyl 2-chloroacetate
(11a) gave the 2-(4-oxo-1,3-selenazolidin-2-ylidene)malo-
nonitriles of type 13 (Scheme 2, Table 2). We propose that
12 is the intermediate, which is the product of the reaction of
the initially formed 7 with the halogenated compound. A
subsequent condensation by elimination of methanol then
yields 13. In the case of 13a and 13d, the same products
were obtained in increased yield by using ethyl
In the crystal structure of 10a, the two CH2 groups in the
five-membered ring are disordered over two approximately
equally occupied positions, which result from alternate half-
chair puckering of the ring conformation. The two cyano
Br
NC
Y
NC
Y
Br
Et3N / DMF
R1 NCSe
Y
CN
8
+
Br
HN
R1
Se
rt / 1 h
H
HN
Se
1
6
Br
R1
7
9
Y = CN, CO2Et; R1= Ph, 4-F-C6H4, 4-Cl-C6H4, 4-Br-
C6H4, 4-MeO-C6H4,4-Me-C6H4, 2,6-DiMe-C6H3,
Cyclohexyl ; X = Cl, Br; R2 = H, Me; R3 = Me, Et
R2
Et3N
HBr
X
X
CO2R3
11
NC
R1
Y
NC
R1
Y
NC
Y
R2
Et3N
ROH
N
Se
N
Se
HN
R1
Se
CO2R3
O
R2
12
10
13
Scheme 2.

3346
G. L. Sommen et al. / Tetrahedron 62 (2006) 3344–3354
Table 1. Preparation of 1,3-selenazolidines 10 from isoselenocyanates 1
Entry
R1
Y
1,3-Selenazolidines 10
Yield (%)
62
NC
CN
a
Phenyl
CN
N
Se
NC
CN
F
b
c
d
e
f
4-F–C6H4
4-MeO–C6H4
Cyclohexyl
Phenyl
CN
54
61
42
31
36
31
N
Se
CN
NC
MeO
CN
N
Se
NC
N
CN
Se
CN
NC
CO2Et
Se
CO2Et
CO2Et
CO2Et
N
NC
CO2Et
F
4-F–C6H4
4-Me–C6H4
N
Se
CO2Et
NC
Me
g
N
Se
bromoacetate (11b). Furthermore, the reaction with methyl
2-chloropropionate 11c led to the 5-methyl derivatives 13h
and 13i (Table 2).
was established by X-ray crystallography (Fig. 2). Although
the compound is achiral, it has crystallized in a polar space
group and the absolute structure has been determined by the
diffraction experiment. The five-membered ring is almost
planar, but is puckered slightly towards an envelope
As in the case of the malononitriles 10a–d, the 4-oxo
derivatives of type 13 show two CN absorptions in the IR
(ca. 2220 and 2210 cmK1) and in the 13C NMR spectrum
(ca. 110 and 115 ppm). In addition, the CO group appears at
1733–1743 cmK1 and 160–173 ppm. The structure of 13a
˚
conformation where atom C(5) lies 0.149(2) A from the
mean plane defined by the other four ring atoms. The
adjacent atoms O(4) and C(9), as well as the dicyano-
methylidene group, are also lying in this ring plane.
Figure 1. ORTEP plot35 of the molecular structure of (a) the major conformation of 10a and (b) of 10c (arbitrary numbering of atoms; 50% probability
ellipsoids).

G. L. Sommen et al. / Tetrahedron 62 (2006) 3344–3354
Table 2. Preparation of 1,3-selenazolidin-4-ones 13 from isoselenocyanates 1
3347
Entry
R1
Acetate
1,3-Selenazolidin-4-ones 13
Yield (%)
NC
CN
Se
Cl
Br
MeO2C
74
81
11a
11b
EtO2C
BrOC
Phenyl
a
N
Br
85
14a
14a
O
NC
CN
F
b
4-F–C6H4
Br
83
BrOC
N
Se
O
NC
CN
Se
Cl
c
4-Cl–C6H4
MeO2C
Cl
N
68
11a
O
NC
CN
Se
Cl
Br
MeO2C
EtO2C
87
95
11a
Br
d
4-Br–C6H4
4-MeO–C6H4
2,6-DiMe–C6H3
Cyclohexyl
Phenyl
N
11b
O
NC
CN
Se
MeO
e
f
Br
Br
N
74
83
BrOC
BrOC
14a
14a
O
NC
CN
N
Se
O
NC
CN
Se
Cl
Br
MeO2C
BrOC
34
33
11a
g
h
N
14a
O
NC
CN
Me
N
O
Se
63
Cl
Cl
MeO2C
MeO2C
11c
Me
Me
NC
CN
89
63
Me
11c
Me
4-Me–C6H4
i
N
O
Se
Me
CO2Et
Br
BrOC
14b
NC
Cl
Cl
Cl
k
Phenyl
MeO2C
N
O
Se
64
86
78
11a
NC
CO2Et
Se
Br
l
4-Br–C6H4
4-Me–C6H4
MeO2C
N
11a
11a
O
NC
CO2Et
Se
Me
m
MeO2C
N
O

3348
G. L. Sommen et al. / Tetrahedron 62 (2006) 3344–3354
small rotation in the orientation of the terminal ethyl group.
The five-membered heterocyclic rings deviate only slightly
from perfect planarity with the maximum deviation from the
˚
mean plane of the ring in molecule B being 0.032(2) A for
atom C(22). The ring in molecule A has a flattened envelope
conformation puckered on atom Se(1), where Se(1) lies
˚
0.204(1) A from the mean plane defined by the other four
ring atoms. As in the cases of 10a, 10c, and 13a, the bond
lengths and the 13C NMR data indicate a significant dipolar
character of the molecule.
Treatment of the intermediates 7 with bromoacetyl bromide
(14a) led to a surprising result. As the reaction between
thioureas and acyl halides is known to give S-acylated
isothioureas,36 we expected that 7 and 14a would give 15 by
the reaction of the more nucleophilic Se-atom with the more
electrophilic acyl C-atom (Scheme 3). Under the basic
reaction conditions, the subsequent cyclization via nucleo-
philic substitution of bromide by the N-atom could lead to
the 5-oxo-1,3-selenazolidine derivatives 16, which are
isomers of 13. Mohareb,37 Bukowski,38 and more recently
Metwally and coworkers,39 described analogous reactions
with isothiocyanates, which led to 1,3-thiazolidin-5-ones.
On the other hand, Koketsu et al.40 reported the synthesis of
1,3-selenazolidine-4-ones from selenourea and a-haloacyl
halides. Although NMR analysis should differentiate clearly
between the two isomeric structures, some doubts about the
structures remain.
Figure 2. ORTEP plot35 of the molecular structure of 13a (arbitrary
numbering of atoms; 50% probability ellipsoids).
The phenyl group is oriented almost orthogonal to the above
defined heterocyclic ring plane (dihedral angle ca. 868). The
other structure parameters are very similar to those of 10a
and 10c, and the chemical shifts of C(2) and C(6) in the 13
C
NMR spectra (173.3 and 56.7 ppm, respectively) show that
again a dipolar structure has to be considered.
The corresponding ethyl 2-cyano-2-(4-oxo-1,3-selena-
zolidin-2-yliden)acetates 13k–m were prepared in a similar
manner from 1, 6b, and 11a (Scheme 2, Table 2). Again,
only one isomer was obtained (TLC, NMR). In the case of
13k, the molecular structure was established by X-ray
crystallography (Fig. 3). The exocyclic C, C-double bond is
(Z)-configured, that is, the sterically more demanding ester
group is pointing away from the N-phenyl group. There are
two symmetry-independent molecules in the asymmetric
unit. One of these molecules (A) has disorder in the terminal
ethyl group of the ester substituent, with the major
conformation being present in ca. 58% of the molecules.
Molecules A and B have almost identical conformations
with the only significant conformational difference being a
The reaction of 1a with 6a and 14a under the usual
conditions led to a single product in 85% yield, which was
identified as 13a by direct comparison with the product
obtained from the reaction with 11a. Analogously, only one
product was formed in all the other reactions of 1 with 6a,b
1
and 14a. By comparison of their H and 13C NMR spectra
with those of 13a, we attributed the structures 13b, 13e, 13f,
and 13g to these products (Table 2). Furthermore, the
product 13g obtained from cyclohexyl isoselenocyanate,
malononitrile (6a), and 2-bromoacetyl bromide (14a) was in
all respects identical with 13g formed in the reaction with
methyl 2-chloroacetate. With 4-methylphenyl isoseleno-
cyanate, 6a, and 2-bromopropanoyl bromide (14b), 13i was
obtained in 63% yield (Table 2).
The unexpected formation of the 4-oxo-1,3-selenazolidine
derivatives 13 in the reactions with 2-bromoacetyl bromide
14a can be explained by the reaction mechanism shown in
Scheme 3. The intermediate 15, which is formed by the
nucleophilic substitution of the acyl bromide of 14a by the
Se-atom of 7 undergoes a base catalyzed 1,3-acyl shift to give
the rearranged intermediate 17. Similar S/N migrations of
the acetyl group are known and have been studied in depth
kinetically41 and described recently by Pihlaja and
coworkers.42 Finally, the Se-atom attacks the a-carbon
atom of the amide group and forms the 1,3-selenazolidinone
ring by displacing the bromide ion to give 13.
Another goal of the present study was the synthesis of
analogous 1,3-selenazolidin-4,5-diones. In the first instance,
we tried to trap 7 with oxalyl chloride, but we did not
succeed in obtaining the dioxo derivatives. Furthermore, all
attempts to use diethyl oxalate or the recently described
ethyl 2-chloro-oxoacetate43 were also unsuccessful. In
Figure 3. ORTEP plot35 of the molecular structure of the major
conformation of molecule A of 13k (arbitrary numbering of atoms; 50%
probability ellipsoids).

G. L. Sommen et al. / Tetrahedron 62 (2006) 3344–3354
3349
NC
R1
Y
NC
HN
Y
NC
R1
Y
Br
Br
N
Se
Se
N
Se
O
+
O
R1
O
13
7
14a
16
Br
Br
NC
R1
Y
NC
R1HN
Y
O
Et3N
H
Br
N
Se
Se
O
Br
17
15
Scheme 3.
addition, the oxidation of 13a by selenium dioxide44 failed
to give the corresponding 1,3-selenazolidine-4,5-dione.
extracted with ether, the combined organic extracts were
dried over MgSO4, and evaporated under reduced pressure.
The crude products were purified by recrystallization
in water.
3. Conclusion
General procedure for the preparation of 1,3-selenazolidine
derivatives. A 25 mL round-bottom flask equipped with a
magnetic stirrer and condenser was charged with a solution
of malononitrile (6a; 73 mg, 1.1 mmol) in DMF (10 mL).
Triethylamine (0.15 mL, 1.1 mmol) was added and the
mixture was stirred for 30 min at rt. Isoselenocyanate (1;
1.1 mmol) was added and the mixture was stirred for 1 h at
rt. Then, the a-halogenated compound (1.1 mmol) was
added dropwise and the mixture was stirred for 4 h before
being evaporated to dryness under reduced pressure. The
crude product was purified by column chromatography on
silica gel with hexane–ethyl acetate (100/0–50/50) as eluant
and recrystallized from ethyl acetate.
In conclusion, we have shown that malononitrile (6a) and
alkyl 2-cyanoacetates (6b,c) react with isoselenocyanates 1
in DMF in the presence of excess triethylamine to
give intermediates 7, which react with 1,2-dibromoethane
or a-halogenated acyl derivatives to give 1,3-selenazoli-
dines 10 and 1,3-selenazolidin-4-ones 13, respectively, in
moderate to good yields. This one-pot reaction offers a
convenient access to these selenium-containing five-
membered heterocycles by starting with isoselenocyanates
1 as building blocks.
4. Experimental
4.1. General
4.2. Preparation of 2-methylene-1,3-selenazolidines 10
4.2.1. 2-(3-Phenyl-1,3-selenazolidin-2-ylidene)malononi-
trile (10a). Yield: 187 mg (62%). Yellowish crystals. Mp
295–297 8C. IR: 2935w, 2205s, 2191s, 1594w, 1527s,
1492m, 1453w, 1432w, 1388m, 1310m, 1238w, 1220w,
Thin-layer chromatography (TLC): silica gel 60 F254 plates
(0.25 mm; Merck). Column chromatography (CC): silica
gel 60 (0.040–0.063 mm; Merck). Mp: Bu¨chi B-540
apparatus in capillary tubes; uncorrected. IR Spectra:
Perkin-Elmer-1600 FT-IR spectrophotometer; in KBr;
1
1064w, 1057w, 759w, 691m. H NMR: 3.49 (t, JZ7.1 Hz,
CH2), 4.46 (t, JZ7.1 Hz, CH2), 7.31 (d-like, JZ8.2 Hz, 2
arom. H), 7.46–7.51 (m, 3 arom. H). 13C NMR: 22.2 (CH2),
51.8 (C(CN)2), 64.6 (CH2), 112.0 (CN), 117.7 (CN), 126.4
(2CH), 129.8 (CH), 129.9 (2CH), 138.9 (Car), 171.9
(CNSe). ESI-MS: 298 (100, [M(80Se)CNa]C), 276 (22,
[M(80Se)C1]C). Anal. Calcd for C12H9N3Se (274.19): C
52.57, H 3.31, N 15.33; found: C 52.54, H 3.49, N 15.41.
1
absorptions in cmK1. H NMR (300 MHz) and 13C NMR
(75.5 MHz) Spectra: Bruker ARX-300 instrument; in
(D6)DMSO unless otherwise stated; chemical shifts (d) in
ppm; couplig constants J in Hz. CI-MS: Finnigan SSQ-700
or MAT-90 instrument; NH3 as carrier gas.
Starting materials. Malononitrile (6a) and all halogenated
compounds are commercially available (Fluka). Isoseleno-
cyanates (1) were prepared according to Barton’s pro-
cedure5 by starting from formamides. Formanilide and
N-cyclohexylformamide were purchased (Fluka and
Aldrich), N-(4-chlorophenyl)-, N-(4-bromophenyl)-, N-(4-
fluorophenyl)-, and N-(4-methoxyphenyl)formamide were
prepared from the respective anilines and 95% formic acid
(Ref. 45). The solution was heated to reflux for 30 min and
then evaporated to dryness in vacuo. The residue was
dissolved in ether and washed with diluted acetic acid (5%),
water, and aqueous NaHCO3 (5%). The aqueous layer was
Suitable crystals for the X-ray crystal structure determination
were grown from CH2Cl2 by slow evaporation of the solvent.
4.2.2. 2-[3-(4-Fluorophenyl)-1,3-selenazolidin-2-ylide-
ne]malononitrile (10b). Yield: 174 mg (54%). White
crystals. Mp 193–195 8C. IR: 2985w, 2202s, 2191s, 1535s,
1505s, 1453w, 1394w, 1319w, 1236w, 1214m, 1054w,
1
846w. H NMR: 3.54 (t, JZ7.1 Hz, CH2), 4.42 (t, JZ
7.1 Hz, CH2), 7.27 (t-like, JZ8.9 Hz, 2 arom. H), 7.50 (dd-
like, JZ9.0, 4.9 Hz, 2 arom. H). 13C NMR: 23.6 (CH2), 51.1
2
(C(CN)2), 65.5 (CH2), 113.1 (CN), 117.4 (d, JCFZ22 Hz,

3350
G. L. Sommen et al. / Tetrahedron 62 (2006) 3344–3354
1
2CH), 118.7 (CN), 129.7 (d, 3JCFZ9 Hz, 2CH), 141.9 (Car),
137.2 (Car), 163.4 (d, JCFZ256 Hz, CF), 167.5 (CO2),
1
167.4 (d, JCFZ248 Hz, CF), 173.7 (CNSe). CI-MS: 311
171.9 (CNSe). CI-MS: 358 (100, [M(80Se)CNH4]C), 341
(33, [M(80Se)C1]C).
(100, [M(80Se)CNH4]C), 294 (7, [M(80Se)C1]C).
4.2.3. 2-[3-(4-Methoxyphenyl)-1,3-selenazolidin-2-ylide-
ne]malononitrile (10c). Yield: 205 mg (61%). Yellowish
crystals. Mp 187–189 8C. IR: 2939w, 2839w, 2203s, 2190s,
1607w, 1587w, 1539s, 1509w, 1474m, 1443w, 1391s,
1319m, 1299m, 1246s, 1171w, 1109w, 1056w, 1026m,
4.2.7. Ethyl 2-cyano-2-[3-(4-methylphenyl)-1,3-selenazo-
lidin-2-ylidene)acetate (10g). Yield: 115 mg (31%).
Yellowish crystals. Mp 144–146 8C. IR: 2982w, 2918w,
2198s, 1669s, 1511s, 1392m, 1370w, 1287s, 1192w, 1170m,
1
1129s, 1058w, 1029w, 921w, 766m. H NMR: 1.27 (t, JZ
1
985w, 864w, 831m, 803w. H NMR: 3.47 (t, JZ7.1 Hz,
7.1 Hz, CH3), 2.39 (s, CH3), 3.09 (t, JZ7.2 Hz, CH2), 4.18–
4.28 (m, 2CH2), 7.15, 7.25 (AA0BB0, JABZ8.1 Hz, 4 arom.
H). 13C NMR: 14.3 (CH3), 19.9 (CH2), 21.2 (CH3), 61.1
(CH2), 62.6 (CH2), 73.1 (C(CN)), 114.6 (CN), 126.2 (2CH),
130.2 (2CH), 138.8 (Car), 139.0 (Car), 167.7 (CO2), 171.6
(CNSe). CI-MS: 354 (100, [M(80Se)CNH4]C), 337 (43,
[M(80Se)C1]C). Anal. Calcd for C15H16N2O2Se (335.26):
C 53.74, H 4.81, N 8.36; found: C 53.60, H 5.01, N 8.43.
CH2), 3.83 (s, CH3), 4.40 (t, JZ7.1 Hz, CH2), 6.96, 7.21
(AA0BB0, JABZ8.2 Hz, 4 arom. H). 13C NMR: 22.0 (CH2),
51.2 (C(CN)2), 55.5 (CH3O), 64.8 (CH2), 112.2 (CN), 115.0
(2CH), 118.0 (CN), 127.8 (2CH), 131.4 (Car), 160.5 (Car),
172.2 (CNSe). CI-MS: 323 (100, [M(80Se)CNH4]C), 306
(8, [M(80Se)C1]C). Anal. Calcd for C13H11N3OSe
(304.21): C 51.33, H 3.64, N 13.81; found: C 51.22, H
3.62, N 13.77.
4.3. Preparation of 2-methylene-1,3-selenazolidin-4-ones
13
Suitable crystals for the X-ray crystal structure determi-
nation were grown from CH2Cl2 by slow evaporation of the
solvent.
4.3.1. 2-(4-Oxo-3-phenyl-1,3-selenazolidin-2-ylidene)-
malononitrile (13a). Yield: 235–270 mg (74–85%). Color-
less crystals. Mp 265–267 8C. IR: 2985w, 2216s, 1733s,
1596w, 1522s, 1493m, 1368m, 1223s, 851w, 758w, 698m.
1H NMR: 4.39 (s, CH2), 7.43 (d-like, JZ7.9 Hz, 2 arom. H),
7.50–7.60 (m, 3 arom. H). 13C NMR: 29.1 (CH2), 56.7
(C(CN)2), 110.1 (CN), 115.1 (CN), 128.9 (2CH), 129.4
(2CH), 130.8 (CH), 134.8 (Car), 173.3, 173.9 (CO, CNSe).
CI-MS: 307 (100, [M(80Se)CNH4]C); CI-MS (i-butane):
290 (100, [M(80Se)C1]C). Anal. Calcd for C12H7N3OSe
(288.16): C 50.02, H 2.45, N 14.58; found: C 49.98, H 2.60,
N 14.34.
4.2.4. 2-(3-Cyclohexyl-1,3-selenazolidin-2-ylidene)malo-
nonitrile (10d). Yield: 130 mg (42%). Yellowish crystals.
Mp 187–189 8C. IR: 2937s, 2850m, 2202s, 2188s, 1527s,
1457m, 1396w, 1372m, 1350w, 1308w, 1241w, 1192w,
1124w, 1010w, 982w, 893w, 879w, 823w. 1H NMR: 1.40–
1.52 (m, 4H), 1.60–1.70 (m, 2H), 1.75–1.98 (m, 4H), 3.26 (t,
JZ7.1 Hz, CH2), 4.13 (t, JZ7.1 Hz, CH2) 4.35–4.45 (m,
CH). 13C NMR: 21.7 (CH2), 24.8 (2CH2), 24.9 (CH2), 31.4
(2CH2), 48.0 (C(CN)2), 55.6 (CH), 59.4 (CH2), 115.1 (CN),
118.3 (CN), 171.4 (CNSe). CI-MS: 299 (100, [M(80Se)C
NH4]C), 282 (7, [M(80Se)C1]C). Anal. Calcd for
C12H15N3Se (280.23): C 51.43, H 5.40, N 15.00; found: C
51.33, H 5.45, N 14.88.
Suitable crystals for the X-ray crystal structure determi-
nation were grown from CH2Cl2 by slow evaporation of the
solvent.
4.2.5. Ethyl 2-cyano-2-(3-phenyl-1,3-selenazolidin-2-yli-
dene)acetate (10e). Yield: 110 mg (31%). Yellowish
crystals. Mp 151–153 8C. IR: 2969w, 2195s, 1668s,
1595w, 1512s, 1458m, 1431w, 1392m, 1367w, 1283s,
4.3.2. 2-[3-(4-Fluorophenyl)-4-oxo-1,3-selenazolidin-2-
ylidene]malononitrile (13b). Yield: 280 mg (83%). Color-
less crystals. Mp 244–246 8C. IR: 2995w, 2982w, 2219s,
2210s, 1737s, 1600w, 1528s, 1516s, 1507s, 1373m, 1222s,
1208s, 1161w, 858w, 826w, 791w. 1H NMR: 4.65 (s, CH2),
7.67 (t-like, JZ9 Hz, 2 arom. H), 7.49–7.59 (m, 2 arom. H).
13C NMR: 29.0 (CH2), 56.7 (C(CN)2), 110.2 (CN), 114.9
1
1254w, 1187w, 1172m, 1023w, 921w, 763m, 695m. H
NMR: 1.27 (t, JZ7.1 Hz, CH3), 3.10 (t, JZ7.2 Hz, CH2),
4.21 (q, JZ7.2 Hz, CH2), 4.28 (t, JZ7.1 Hz, CH2), 7.26 (d-
like, JZ8.2 Hz, 2 arom. H), 7.40–7.49 (m, 3 arom. H). 13C
NMR: 14.3 (CH3), 20.0 (CH2), 61.1 (CH2), 62.5 (CH2), 73.3
(C(CN)), 114.6 (CN), 126.5 (2CH), 128.9 (CH), 129.6
(2CH), 141.3 (Car), 167.6 (CO2), 171.6 (CNSe). CI-MS: 340
(100, [M(80Se)CNH4]C), 323 (53, [M(80Se)C1]C). Anal.
Calcd for C14H14N2O2Se (321.24): C 52.35, H 4.39, N 8.72;
found: C 51.98, H 4.46, N 8.70.
2
(CN), 116.4 (d, JCFZ23 Hz, 2CH), 131.1 (Car), 131.5 (d,
1
3JCFZ9 Hz, 2CH), 163.2 (d, JCFZ248 Hz, CF), 173.7,
173.9 (CO, CNSe). CI-MS: 325 (100, [M(80Se)CNH4]C).
Anal. Calcd for C12H6N3OSeF (306.16): C 47.08, H 1.98, N
13.73; found: C 47.01, H 2.21, N 14.02.
4.2.6. Ethyl 2-cyano-2-[3-(4-fluorophenyl)-1,3-selenazo-
lidin-2-ylidene]acetate (10f). Yield: 135 mg (36%). Yel-
lowish crystals. Mp 162–164 8C. IR: 3048w, 2976m,
2878w, 2190s, 1671s, 1603m, 1510s, 1454s, 1432m,
1387s, 1365m, 1288s, 1234m, 1221m, 1191w, 1171w,
1117s, 1057w, 1029w, 995m, 918m, 845s, 767s, 735w,
4.3.3. 2-[3-(4-Chlorophenyl)-4-oxo-1,3-selenazolidin-2-
ylidene]malononitrile (13c). Yield: 242 mg (68%). Color-
less crystals. Mp 245–247 8C. IR: 2947w, 2223m, 2213m,
1733s, 1529s, 1485m, 1404w, 1370m, 1219s, 1172w,
1084w, 1015w, 845w, 813w, 722w. 1H NMR: 4.33 (s,
CH2), 7.45, 7.58 (AA0BB0, JABZ8.7 Hz, 4 arom. H). 13C
NMR: 29.1 (CH2), 56.7 (C(CN)2), 110.3 (CN), 114.9 (CN),
129.5 (2CH), 131.0 (2CH), 133.7 (Car), 135.5 (Car), 173.4,
173.8 (CO, CNSe). CI-MS: 341 (100, [M(80Se, 35Cl)C
NH4]C). Anal. Calcd for C12H6N3OSeCl (322.61): C 44.68,
H 1.87, N 13.03; found: C 44.75, H 2.10, N 12.92.
1
717w. H NMR: 1.28 (t, JZ7.1 Hz, CH3), 3.11 (t, JZ
7.2 Hz, CH2), 4.19–4.27 (m, 2CH2), 7.11–7.17 (m, 2 arom.
H), 7.23–7.29 (m, 2 arom. H). 13C NMR: 14.3 (CH3), 19.9
(CH2), 61.2 (CH2), 62.5 (CH2), 73.1 (C(CN)), 114.5 (CN),
3
116.7 (d, 2JCFZ23 Hz, 2CH), 128.4 (d, JCFZ9 Hz, 2CH),

G. L. Sommen et al. / Tetrahedron 62 (2006) 3344–3354
3351
4.3.4. 2-[3-(4-Bromophenyl)-4-oxo-1,3-selenazolidin-2-
ylidene]malononitrile (13d). Yield: 351–383 mg (87–
95%). Colorless crystals. Mp 247–249 8C. IR: 2947w,
2222s, 2211s, 1736s, 1585w, 1526s, 1481s, 1399w,
1371m, 1218s, 1171m, 1066w, 1012m, 842m, 809m,
NH4]C). Anal. Calcd for C13H9N3OSe (302.19): C 51.67, H
3.00, N 13.91; found: C 51.50, H 4.10, N 14.15.
4.3.9. 2-[5-Methyl-3-(4-methylphenyl)-4-oxo-1,3-selena-
zolidin-2-ylidene)malononitrile (13i). Yield: 220–310 mg
(63–89%). White crystals. Mp 223–225 8C. IR: 2933w,
2216m, 2208m, 1741s, 1521s, 1216s, 1160w, 1071w, 996w,
1
711w. H NMR: 4.67 (s, CH2), 7.71, 8.05 (AA0BB0,
JABZ8.7 Hz, 4 arom. H). 13C NMR: 29.1 (CH2), 56.8
(C(CN)2), 110.3 (CN), 114.9 (CN), 129.5 (2CH), 131.0
(2CH), 133.7 (Car), 135.6 (Car), 173.4, 173.8 (CO, CNSe).
CI-MS: 387 (79, [M(80Se, 81Br)CNH4]C), 385 (100,
[M(80Se, 79Br)CNH4]C). Anal. Calcd for C12H6N3OSeBr
(367.07): C 39.27, H 1.65, N 11.45; found: C 39.44, H 1.86,
N 11.49.
1
814w, 771w, 734w. H NMR: 1.92 (d, JZ7.3 Hz, CH3),
2.44 (s, CH3), 4.53 (q, JZ7.2 Hz, CH), 7.10, 7.35 (AA0BB0,
JABZ8.1 Hz, 4 arom. H). 13C NMR: 19.4 (CH3), 21.4
(CH3), 38.6 (CH), 61.6 (C(CN)2), 109.3 (CN), 113.9 (CN),
128.2 (2CH), 130.7 (2CH), 131.6 (Car), 142.2 (Car), 167.5
(CO), 176.4 (CNSe). CI-MS: 335 (100, [M(80Se)CNH4]C).
Anal. Calcd for C14H11N3OSe (316.22): C 53.18, H 3.51, N
13.29; found: C 53.31, H 43.59, N 13.30.
4.3.5. 2-[3-(4-Methoxyphenyl)-4-oxo-1,3-selenazolidin-2-
ylidene]malononitrile (13e). Yield: 259 mg (74%). Orange
crystals. Mp 193–195 8C. IR: 2945w, 2216m, 2210m,
1752m, 1606w, 1523s, 1508s, 1369m, 1303w, 1255m,
4.3.10. Ethyl2-cyano-2-(4-oxo-3-phenyl-1,3-selenazolidin-
2-ylidene)acetate (13k). Yield: 236 mg (64%). Brownish
crystals. Mp 189–191 8C. IR: 2982w, 2936w, 2206s, 1739s,
1679s, 1595w, 1511s, 1496s, 1367w, 1355m, 1290s, 1210s,
1176s, 1167s, 1119s, 1016w, 846w, 768w, 696m. 1H NMR:
1.31 (t, JZ7.2 Hz, CH3), 3.83 (s, CH2), 4.29 (q, JZ7.1 Hz,
CH2O), 7.26 (d, JZ8.2 Hz, 2 arom. H), 7.52–7.62 (m, 3 arom.
H). 13C NMR: 14.1 (CH3), 24.2 (CH2), 62.2 (CH2), 81.4
(C(CN)), 111.7 (CN), 128.7 (2CH), 129.8 (2CH), 131.0 (CH),
135.8 (Car), 166.4, 168.1 (CO, CO2), 174.6 (CNSe). CI-MS:
354 (100, [M(80Se)CNH4]C). Anal. Calcd for C14H12N2O3Se
(335.22): C 50.16, H 3.61, N 8.36; found: C 50.01, H 3.93, N
8.04.
1
1212m, 1015w, 822w. H NMR: 3.83 (s, CH3O), 4.38 (s,
CH2), 7.07, 7.35 (AA0BB0, JABZ8.0 Hz, 4 arom. H). 13C
NMR: 28.9 (CH2), 55.4 (CH3), 56.6 (C(CN)2), 110.2 (CN),
114.6 (2CH), 115.1 (CN), 127.3 (Car), 130.2 (2CH), 132.4
(Car), 160.8 (CO), 173.9 (CNSe). CI-MS: 337 (100,
[M(80Se)CNH4]C). Anal. Calcd for C13H9N3O2Se
(318.20): C 49.07, H 2.85, N 13.21; found: C 48.84, H
3.01, N 13.57.
4.3.6. 2-[3-(2,6-Dimethylphenyl)-4-oxo-1,3-selenazoli-
din-2-ylidene]malononitrile (13f). Yield: 289 mg (83%).
Colorless crystals. Mp 296–298 8C. IR: 3000w, 2944w,
2217s, 2206s, 1742s, 1517s, 1474m, 1392w, 1352s, 1217m,
1205s, 1183m, 1151m, 1035w, 837w, 785m, 736w. 1H
NMR: 2.16 (s, 2CH3), 4.72 (s, CH2), 7.28 (d, JZ7.8 Hz, 2
arom. H), 7.44 (t, JZ7.9 Hz, 1 arom. H). 13C NMR: 16.7
(2CH3), 28.7 (CH2), 57.1 (C(CN)2), 109.3 (CN), 114.7
(CN), 128.3 (2CH), 130.9 (CH), 132.4 (Car), 136.5 (2Car),
171.5, 173.3 (CO, CNSe). CI-MS: 335 (100, [M(80Se)C
NH4]C). Anal. Calcd for C14H11N3OSe (316.22): C 53.18,
H 3.51, N 13.29; found: C 53.18, H 3.58, N 13.03.
Suitable crystals for the X-ray crystal structure determi-
nation were grown from CH2Cl2 by slow evaporation of the
solvent.
4.3.11. Ethyl 2-[3-(4-bromophenyl)-4-oxo-1,3-selenazoli-
din-2-ylidene]-2-cyanoacetate (13l). Yield: 392 mg (86%).
Pale yellow crystals. Mp 191–193 8C. IR: 2984w, 2206s,
1743s, 1678s, 1509s, 1498s, 1486s, 1360m, 1292s, 1210m,
1176s, 1165s, 1129m, 1066w, 1013m, 845w, 834w, 821w,
1
770w, 714w. H NMR: 1.31 (t, JZ7.2 Hz, CH3), 3.81 (s,
4.3.7. 2-(3-Cyclohexyl-4-oxo-1,3-selenazolidin-2-ylidene)-
malononitrile (13g). Yield: 107–110 mg (33–34%). Brown-
ish crystals. Mp 123–125 8C. IR: 2996w, 2942s, 2855m,
2217m, 2206m, 1738s, 1701w, 1573m,1507s, 1448m, 1400w,
1335m, 1254w, 1202m, 1193m, 1179m, 1141m, 1052w,
980w, 895w, 696m. 1H NMR: 1.23–1.54 (m, 4H), 1.71–1.90
(m, 4H), 2.27–2.40 (m, 2H), 3.98 (s, CH2), 4.51–4.61 (m, CH).
13C NMR: 24.4 (CH2), 24.8 (2CH2), 28.7 (2CH2), 32.2 (CH),
59.4 (C(CN)2), 61.7 (CH), 112.0 (CN), 114.3 (CN), 170.1
(CO), 173.5 (CNSe). CI-MS: 313 (100, [M(80Se)CNH4]C).
Anal. Calcd for C12H13N3OSe (294.21): C 48.99, H 4.45, N
14.28; found: C 50.23, H 4.54, N 14.40.
CH2), 4.29 (q, JZ7.1 Hz, CH2O), 7.12, 7.67 (AA0BB0,
JABZ8.3 Hz, 4 arom. H). 13C NMR: 14.0 (CH3), 24.1
(CH2), 62.3 (CH2), 81.6 (C(CN)), 111.9 (CN), 125.3 (Car),
130.3 (2CH), 133.1 (2CH), 134.7 (Car), 166.2, 167.4 (CO,
CO2), 174.3 (CNSe). CI-MS: 434 (80, [M(80Se, 81Br)C
NH4]C), 432 (100, [M(80Se, 79Br)CNH4]C). Anal. Calcd
for C14H11N2O3SeBr (414.12): C 40.60, H 2.68, N 6.76;
found: C 40.71, H 2.91, N 6.68.
4.3.12. Ethyl 2-cyano-2-[4-oxo-3-(4-methylphenyl)-1,3-
selenazolidin-2-ylidene)acetate (13m). Yield: 300 mg
(78%). Pale yellow crystals. Mp 187–189 8C. IR: 2982w,
2930w, 2204s, 1740s, 1679s, 1505s, 1359m, 1291m, 1211s,
1180s, 1169s, 1117m, 1016w, 846w, 770w, 716w. 1H NMR:
1.30 (t, JZ7.2 Hz, CH3), 2.44 (s, CH3), 3.81 (s, CH2), 4.28
(q, JZ7.1 Hz, CH2O), 7.12, 7.33 (AA0BB0, JABZ8.3 Hz, 4
arom. H). 13C NMR: 14.0 (CH3), 21.4 (CH3), 24.2 (CH2),
62.2 (CH2), 81.3 (C(CN)), 111.8 (CN), 128.4 (2CH), 130.5
(2CH), 133.1 (Car), 141.3 (Car), 166.5, 168.4 (CO, CO2),
174.7 (CNSe). CI-MS: 368 (100, [M(80Se)CNH4]C). Anal.
Calcd for C15H14N2O3Se (349.25): C 51.59, H 4.04, N 8.02;
found: C 52.06, H 4.38, N 7.94.
4.3.8. 2-(5-Methyl-4-oxo-3-phenyl-1,3-selenazolidin-2-
ylidene)malononitrile (13h). Yield: 210 mg (63%). White
crystals. Mp 173–175 8C. IR: 2961w, 2217m, 2202m,
1735s, 1593w, 1518s, 1493m, 1363m, 1266w, 1222s,
1
1069w, 996w, 940w, 763w, 728w, 697w. H NMR: 1.94
(d, JZ7.3 Hz, CH3), 4.55 (q, JZ7.3 Hz, CH), 7.26 (d, JZ
8.1 Hz, 2 arom. H), 7.54–7.63 (m, 3 arom. H). 13C NMR:
19.4 (CH3), 38.7 (CH), 61.6 (C(CN)2), 109.3 (CN), 113.8
(CN), 128.6 (2CH), 130.1 (CH), 131.6 (2CH), 134.3 (Car),
167.4 (CO), 176.3 (CNSe). CI-MS: 321 (100, [M(80Se)C

3352
G. L. Sommen et al. / Tetrahedron 62 (2006) 3344–3354
4.4. X-ray crystal-structure determination of 10a, 10c,
13a, and 13k
monoclinic, space group P21/c, ZZ4, reflections for cell
determination 22243, 2q range for cell determination 4–608,
˚
˚
˚
aZ7.5986(1) A, bZ16.6005(3) A, cZ8.8620(1) A, bZ
3
˚
All measurements were performed on
a Nonius
94.199(1)8, VZ1114.86(3) A , TZ160 K, DXZ
KappaCCD area-diffractometer46 using graphite-mono-
1.633 g cmK3, m(Mo Ka)Z3.339 mmK1, scan type f and
u, 2q(max)Z608, transmission factors (min; max) 0.542;
0.792, total reflections measured 33680, symmetry inde-
pendent reflections 3253, reflections with IO2s(I) 2814,
reflections used in refinement 3252, parameters refined 164;
restraints 3, R(F) [IO2s(I) reflections]Z0.0267, wR(F2)
˚
chromated Mo Ka radiation (l 0.71073 A) and an Oxford
Cryosystems Cryostream 700 cooler. The data collection
and refinement parameters are given below47 and views
of the molecules are shown in Figures 1–3. Data
reduction was performed with HKL Denzo and Scale-
pack.48 The intensities were corrected for Lorentz and
polarization effects, and absorption corrections based on
the multi-scan method49 were applied. Equivalent
reflections, other than the Friedel pairs in 13a, were
merged. The structures were solved by direct methods
using SIR92,50 which revealed the positions of all non-H-
atoms. In the case of 10a, the two CH2 groups in the
five-membered ring are disordered over two confor-
mations. Two sets of positions were defined for the
atoms of these groups and the site occupation factor of
the major conformation refined to 0.51(1). Similarity
restraints were applied to the chemically equivalent bond
lengths and angles involving all disordered C-atoms. In
the case of 13k, there are two symmetry-independent
molecules in the asymmetric unit. The atomic coordi-
nates of the two molecules were tested carefully for a
relationship from a higher symmetry space group using
the program PLATON,51 but none could be found. The
terminal ethyl group in one molecule is disordered over
two conformations. Two sets of overlapping positions
were defined for the atoms of this group and the site
occupation factor of the major conformation of this
group refined to 0.58(2). Similarity restraints were
applied to the chemically equivalent bond lengths and
angles involving all disordered C-atoms, while neigh-
boring atoms within and between each conformation of
the disordered ethyl group were restrained to have
similar atomic displacement parameters. The non-H-
atoms were refined anisotropically. All of the H-atoms
were placed in geometrically calculated positions and
refined using a riding model where each H-atom was
assigned a fixed isotropic displacement parameter with a
value equal to 1.2Ueq of its parent C-atom (1.5Ueq for
the methyl groups). The refinement of each structures was
carried out on F2 using full-matrix least-squares procedures,
which minimized the function Sw(F2oKFc2)2. Corrections
for secondary extinction were applied in the cases of 10c,
13a, and 13k. In 10a and in 10c, one reflection, whose
intensity was considered to be an extreme outlier, was
omitted from the final refinement. Refinement of the
absolute structure parameter52 of 13a yielded a value of
K0.021(7), which confidently confirms that the refined
coordinates represent the true absolute structure. Neutral
atom scattering factors for non-H-atoms were taken from,53
and the scattering factors for H-atoms were taken from Ref.
54. Anomalous dispersion effects were included in Fc;55 the
values for f0 and f00 were those of Ref. 56. The values of the
mass attenuation coefficients are those of Ref. 57. All
calculations were performed using the SHELXL9758
program.
[all data]Z0.0647 (wZ[s2(Fo2)C(0.0275P)2C0.5667P]K1
,
where PZ(F2oC2Fc2)/3), goodness of fit 1.058, final Dmax/s
K3
˚
0.001, Dr (max; min) Z0.41; K0.73 e A
.
Crystal data for 10c. C13H11N3OSe, MZ304.15, pale
yellow, prism, crystal dimensions 0.10!0.23!0.28 mm,
ꢀ
triclinic, space group P1, ZZ2, reflections for cell
determination 13000, 2q range for cell determination
˚
˚
˚
4–608, aZ8.4715(2) A, bZ8.6795(2) A, cZ8.8012(2) A,
aZ98.756(2), bZ91.399(2)8, gZ100.280(1), VZ
3
628.44(3) A , TZ160 K, DXZ1.607 g cmK3, m(Mo Ka)Z
˚
2.976 mmK1, scan type f and u, 2q(max)Z608, transmission
factors (min; max) 0.489; 0.751, total reflections measured
18210, symmetry independent reflections 3671, reflections
with IO2s(I) 3252, reflections used in refinement 3670,
parameters refined 165; R(F) [IO2s(I) reflections]Z
0.0326, wR(F2) [all data]Z0.0838 (wZ[s2(F2o)C
(0.0458P)2C0.1693P]K1, where PZ(Fo2C2Fc2)/3), good-
ness of fit 1.058, secondary extinction coefficient 0.012(2),
K3
˚
final Dmax/s 0.001, Dr (max; min)Z0.74; K0.95 e A
.
Crystal data for 13a. C12H7N3OSe, MZ288.11, colorless,
needle, crystal dimensions 0.10!0.10!0.28 mm, mono-
clinic, space group Cc, ZZ4, reflections for cell determi-
nation 9429, 2q range for cell determination 4–608, aZ
˚
˚
˚
17.0737(4) A, bZ9.5587(2) A, cZ7.0931(2) A, bZ
3
˚
104.623(1)8, VZ1120.11(5) A , TZ160 K, DXZ
1.708 g cmK3, m(Mo Ka)Z3.335 mmK1, scan type f and
u, 2q(max)Z608, transmission factors (min; max) 0.508;
0.723, total reflections measured 14521, symmetry inde-
pendent reflections 3197, reflections with IO2s(I) 3084,
reflections used in refinement 3197, parameters refined 155;
restraints 2, R(F) [IO2s(I) reflections]Z0.0236, wR(F2)
[all data]Z0.0544 (wZ[s2(Fo2)C(0.0253P)2C0.7032P]K1
,
where PZ(F2oC2F2c)/3), goodness of fit 1.046, secondary
extinction coefficient 0.0064(5), final Dmax/s 0.001, Dr
K3
˚
(max; min)Z0.30; K0.46 e A
.
Crystal data for 13k. C14H12N2O3Se, MZ335.16, yellow,
prism, crystal dimensions 0.10!0.22!0.25 mm, mono-
clinic, space group P21/c, ZZ8, reflections for cell
determination 89915, 2q range for cell determination 4–
˚
˚
˚
558, aZ9.6396(1) A, bZ12.9321(2) A, cZ21.8547(3) A,
3
˚
bZ94.4025(8)8, VZ2716.37(6) A , TZ160 K, DXZ
1.639 g cmK3, m(Mo Ka)Z2.771 mmK1, scan type f and
u, 2q(max)Z558, transmission factors (min; max) 0.590;
0.761, total reflections measured 55029, symmetry inde-
pendent reflections 6222, reflections with IO2s(I) 5276,
reflections used in refinement 6222, parameters refined 384;
restraints 39, R(F) [IO2s(I) reflections]Z0.0305, wR(F2)
[all data]Z0.0712 (wZ[s2(Fo2)C(0.0288P)2C2.26P]K1
,
Crystal data for 10a. C12H9N3Se, MZ274.12, pale
yellow, prism, crystal dimensions 0.07!0.12!0.20 mm,
where PZ(F2oC2F2c)/3), goodness of fit 1.046, secondary

G. L. Sommen et al. / Tetrahedron 62 (2006) 3344–3354
3353
Streeter, D. G.; Robins, R. K. Biochem. Biophys. Res.
Commun. 1983, 115, 544–550. (c) Srivastava, P. C.; Robins,
R. K. J. Med. Chem. 1983, 26, 445–448.
extinction coefficient 0.0012(2), final Dmax/s 0.001, Dr
˚
K3
(max; min)Z0.60; K0.49 e A
.
9. Chu, S.-H.; Mautner, H. G. J. Org. Chem. 1962, 27,
2899–2901.
Acknowledgements
10. (a) Park, Y.-J.; Koketsu, M.; Kim, J. M.; Yeo, J.-H.; Ishihara,
H.; Lee, K.-G.; Kim, S. Y.; Kim, C.-K. Biol. Pharm. Bull.
2003, 26, 1657–1660. (b) Koketsu, M.; Choi, S. Y.; Ishihara,
H.; Lim, B. O.; Kim, H.; Kim, S. Y. Chem. Pharm. Bull. 2002,
50, 1594–1596.
We thank the analytical units of our institute for spectra and
analyses and Mr. B. Bu¨rgi for his assistance with the
determination of the crystal structures. Financial support of
this work by the Dr. Helmut Legerlotz-Foundation and F.
Hoffmann-La Roche AG, Basel, is gratefully
acknowledged.
11. Kumar, Y.; Green, R.; Borysko, K. Z.; Wise, D. S.;
Wotring, L. L.; Townsend, L. B. J. Med. Chem. 1993, 36,
3843–3848.
12. Kirsi, J. J.; North, J. A.; McKernan, P. A.; Murray,
B. K.; Canonico, P. G.; Huggins, J. W.; Srivastava,
P. C.; Robins, R. K. Antimicrob. Agents Chemother.
1983, 24, 353–361.
References and notes
13. Xie, Y.; Short, M. D.; Cassidy, P. B.; Roberts, J. C. Bioorg.
Med. Chem. Lett. 2001, 11, 2911–2915.
1. (a) Liotta, D. Acc. Chem. Res. 1984, 17, 28–34. (b) Wirth, T.
Liebigs Ann. Recl. 1997, 2189. (c) Wirth, T. Tetrahedron 1999,
55, 1–28. (d) Reich, H. J. In Wirth, T., Ed.; Topics in Current
Chemistry: Organoselenium Chemistry, Modern Development
in Organic Synthesis; Springer: Berlin, 2000; Vol. 208.
2. (a) Sonoda, N. Pure Appl. Chem. 1993, 65, 699–706. (b)
Litvinov, V. P.; Dyachenko, V. D. Russ. Chem. Rev. 1997, 66,
923–951. (c) Klayman, D. L.; Gu¨nther, W. H. H. Organic
Selenium Compounds: Their Chemistry and Biology; Wiley:
New York, 1973. (d) Reich, H. J. Acc. Chem. Res. 1979, 12,
22–30. (e) Paulmier, C. Selenium Reagents and Intermediates
in Organic Synthesis; Pergamon: Oxford, 1986. (f) Renson, M.
In Patai, S., Rappoport, Z., Eds.; The Chemistry of Organic
Selenium and Tellurium Compounds; Wiley: New York,
1986; Vol. 1. (g) Back, T. G. Organoselenium Chemistry, A
Practical Approach; Oxford University: Oxford, 1999.
3. (a) Selenium in Biology and Medicine; Wengel, E., Ed.;
Springer: Berlin, 1989. (b) Selenium in Biology and Human
Health; Burk, R. F., Ed.; Springer: New York, 1994. (c)
Hatfield, D. L. Selenium. Its Molecular Biology and Role in
Human Health; Kluwer Academic: Boston, 2001. (d) May,
S. W. Exp. Opin. Invest. Drugs 2002, 11, 1261–1269.
4. Petrov, M. L.; Zmitrovich, N. I. Russ. J. Gen. Chem. 1999, 69,
245–256.
14. (a) Li, L.; Xie, Y.; El-Sayed, W. M.; Szakacs, J. G.; Roberts,
J. C. Life Sci. 2004, 75, 447–459. (b) Southan, G. J.; Salzman,
´
A. L.; Szabo, C. Life Sci. 1996, 58, 1139–1148.
15. (a) Synthetic Dyes; Singh, R., Ed.; Mittal: New Delhi, 2002.
(b) Bulka, E.; Patzwaldt, H.-G.; Peper, F.-K.; Beyer, H. Chem.
¨
Ber. 1961, 94, 2759–2763. (c) Bulka, E.; Morner, M.; Beyer,
H. Chem. Ber. 1961, 94, 2763–2768.
16. Witczak, Z. J. Tetrahedron 1985, 41, 4781–4785.
17. (a) Stec, W. J.; Lesiak, K.; Sudol, M. Synthesis 1975, 785–787.
(b) Stangeland, L. J.; Austad, T.; Songstad, J. Acta Chem.
Scand. 1973, 27, 3919–3928.
18. (a) Becher, J.; Frandsen, E. G.; Dreier, C.; Henriksen, L. Acta
Chem. Scand. 1977, B31, 843–847. (b) Henriksen, L.; Dreier,
C. Chem. Scr. 1975, 8, 112–114. (c) Henriksen, L. Int. J. Sulfur
Chem. 1973, 8, 389–396.
19. Maeda, H.; Kambe, N.; Sonoda, N.; Fuyjiwara, S.; Shin-Ike, T.
Tetrahedron 1997, 53, 13667–13680.
20. Raja, T. K.; Ananthapadmanabhan, S.; Gopalakrishnan, R.;
Vimala, K. M. Curr. Sci. 1988, 57, 795–796.
21. Koketsu, M.; Nada, F.; Mio, T.; Ishihara, H. Heterocycles
2003, 60, 1211–1218.
22. (a) Zhao, H.-R.; Zhang, Y.-H.; Yu, Q.-S. Youji Huaxue 2002,
22, 599–601. (b) Koketsu, M.; Nada, F.; Ishihara, H. Synthesis
2002, 195–198. (c) Giudicelli, J.-F.; Menin, J.; Najer, H. Bull.
Soc. Chim. Fr. 1968, 3, 1099–1106. (d) Giudicelli, J.-F.;
Menin, J.; Najer, H. C.R. Acad. Sci. Paris, Ser. C 1966, 262,
285–288. (e) Zingaro, R. A.; Bennett, F. C.; Hammar, G. W.
J. Org. Chem. 1953, 18, 292–296.
5. (a) Barton, D. H. R.; Parekh, S. I.; Tajbakhsh, M.;
Theodorakis, E. A.; Tse, C.-L. Tetrahedron 1994, 50,
639–654. (b) Bakhsh, M. T.; Behshtiha, Y. S.; Heravi,
M. M. J. Chem. Soc. Pakistan 1996, 18, 159–162.
6. (a) Koketsu, M.; Ishihara, H. Curr. Org. Chem. 2003, 7,
175–185. (b) Bulka, E. Chem. Scr. 1975, 8A, 39–44. (c) Bulka,
E. Adv. Heterocycl. Chem. 1963, 2, 343–364. (d) Handbook of
Heterocyclic Chemistry; Katritzky, A. R., Ed.; Pergamon:
Oxford, 2000.
23. Zhou, Y.; Heimgartner, H. Helv. Chim. Acta 2000, 83,
539–553.
24. Zhou, Y.; Linden, A.; Heimgartner, H. Helv. Chim. Acta 2000,
83, 1576–1598.
25. Atanassov, P. K.; Zhou, Y.; Linden, A.; Heimgartner, H. Helv.
Chim. Acta 2002, 85, 1102–1117.
7. (a) Huang, X.; Chen, W.-L.; Zhou, H.-W. Synlett 2004, 2,
329–331. (b) De Marco, C.; Coccia, R.; Rinaldi, A.; Cavallini,
D. Ital. J. Biochem. 1977, 26, 51–58. (c) Siaglo, H.;
Andrzejewski, S.; Kleczek, E.; Prelicz, D. Pol.
J. Pharmacol. Pharm. 1975, 27, 57–60. (d) Draguet, C.;
Renson, M. Bull. Soc. Chim. Belg. 1972, 81, 279–287. (e)
Draguet, C.; Renson, M. Bull. Soc. Chim. Belg. 1972, 81,
289–294. (f) Draguet, C.; Renson, M. Bull. Soc. Chim. Belg.
1972, 81, 295–302. (g) Draguet, C.; Renson, M. Bull. Soc.
Chim. Belg. 1972, 81, 303–306.
26. Atanassov, P. K.; Linden, A.; Heimgartner, H. Heterocycles
2003, 61, 569–579.
27. Atanassov, P. K.; Linden, A.; Heimgartner, H. Helv. Chim.
Acta 2003, 86, 3235–3243.
28. Atanassov, P. K.; Linden, A.; Heimgartner, H. Heterocycles
2004, 62, 521–533.
29. Atanassov, P. K.; Linden, A.; Heimgartner, H. Helv. Chim.
Acta 2004, 87, 1452–1466.
8. (a) Kumar, Y.; Green, R.; Wise, D. S.; Wotring, L. L.;
Townsend, L. B. J. Med. Chem. 1993, 36, 3849–3852. (b)
30. Atanassov, P. K.; Linden, A.; Heimgartner, H. Helv. Chim.
Acta 2004, 87, 1873–1887.

3354
G. L. Sommen et al. / Tetrahedron 62 (2006) 3344–3354
31. Sommen, G. L.; Linden, A.; Heimgartner, H. Helv. Chim. Acta
2005, 88, 766–773.
45. Katritzky, A. R.; Parris, R. L.; Ignatchenko, E. S.; Allin, S. M.;
Siskin, M. J. Prakt. Chem. 1997, 339, 59–65.
32. Sommen, G. L.; Linden, A.; Heimgartner, H. Eur. J. Org.
Chem. 2005, 3128–3137.
46. Hooft, R. KappaCCD Collect Software, Nonius BV: Delft, The
Netherlands, 1999.
33. Sommen, G. L.; Linden, A.; Heimgartner, H. Heterocycles
2005, 65, 1903–1915.
47. CCDC-283202-283205 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from the Cambridge Crystallographic Data Centre, via
www.ccdc.cam.ac.uk/data_request/cif.
34. Sommen, G. L.; Linden, A.; Heimgartner, H. Tetrahedron Lett.
2005, 46, 6723–6725.
35. Johnson, C. K. ORTEP II, Report ORNL-5138; Oak
Ridge National Laboratory: Oak Ridge, Tennessee,
1976.
48. Otwinowski, Z.; Minor, W. In Methods in Enzymology; Carter,
C. W., Jr., Sweet, R. M., Eds.; Macromolecular Crystallo-
graphy Part A; Academic: New York, 1997; Vol. 276,
pp 307–326.
36. (a) Murai, T. Top. Curr. Chem. 2005, 251, 247–272. (b)
Baskakov, Yu. A.; Volovnik, L. L.; Vasil’ev, A. F.; Aryutkina,
N. L.; Tibanov, P. V.; Negrebetskii, V. V. Khim. Geterotsikl.
Soedin. 1971, 3, 104–107. (c) Velkov, Z. Bulg. Chem.
Commun. 2003, 35, 227–230. (d) Jagodzinski, T. S. Chem.
Rev. 2003, 103, 197–227. (e) Mitchell, S. C.; Steventon, G. B.
Sulfur Rep. 1994, 16, 117–137. (f) Bobbitt, J. M.; Bourque,
A. J. Heterocycles 1987, 25, 601–616.
49. Blessing, R. H. Acta Crystallogr., Sect. A 1995, 51, 33–38.
50. Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A.;
Burla, M. C.; Polidori, G.; Camalli, M. J. Appl. Crystallogr.
1994, 27, 435.
51. Spek, A. L. PLATON, Program for the Analysis of
Molecular Geometry; University of Utrecht: The Nether-
lands, 2004.
37. Mohareb, R. M.; Sherif, S. M. Arch. Pharm. (Weinheim) 1991,
324, 469–471.
52. Flack, H. D.; Bernardinelli, G. Acta Crystallogr., Sect. A 1999,
55, 908–915. Flack, H. D.; Bernardinelli, G. J. Appl. Crystal-
logr. 2000, 33, 1143–1148.
38. Bukowski, L.; Janowiec, M.; Zwolska-Kwiek, Z.;
Andrzejczyk, Z. Pharmazie 1998, 53, 373–376.
39. (a) El-Desoky, S. I.; Bondock, S. B.; Etman, H. A.; Fadda,
A. A.; Metwally, M. A. Sulfur Lett. 2003, 26, 127–135. (b)
Metwally, M. A.; Abdel-Latif, E.; Amer, F. A. J. Textile Assoc.
2001, 11–12, 155–159.
53. Maslen, E. N.; Fox, A. G.; O’Keefe, M. A. In Wilson,
A. J. C., Ed.; International Tables for Crystallography;
Kluwer: Dordrecht, 1992; Vol. C, pp 477–486;
Table 6.1.1.1.
54. Stewart, R. F.; Davidson, E. R.; Simpson, W. T. J. Chem. Phys.
1965, 42, 3175–3187.
40. Koketsu, M.; Nada, F.; Ishihara, H. Synlett 2002, 2, 195–198.
ˇ
41. (a) Kavalek, J.; Jirman, J.; Sterba, J. V. Collect. Czech. Chem.
´
´
Commun. 1985, 50, 766–778. (b) Kavalek, J.; Jirman, J.;
˘
55. Ibers,J.A.;Hamilton,W.C.ActaCrystallogr.1964,17,781–782.
56. Creagh, D. C.; McAuley, W. J. In Wilson, A. J. C., Ed.;
International Tables for Crystallography; Kluwer: Dordrecht,
1992; Vol. C, pp 219–222; Table 4.2.6.8.
ˇ
˘
Sterba, V. Collect. Czech. Chem. Commun. 1982, 47,
2702–2704. (c) Pratt, R. F.; Bruice, T. C. J. Am. Chem. Soc.
1972, 94, 2823–2837. (d) Pratt, R. T.; Bruice, T. C.
Biochemistry 1971, 10, 3178–3185.
57. Creagh, D. C.; Hubbell, J. H. In Wilson, A. J. C., Ed.;
International Tables for Crystallography; Kluwer: Dordrecht,
1992; Vol. C, pp 200–206; Table 4.2.4.3.
´
42. Klika, K. D.; Janovec, L.; Imrich, J.; Suchar, G.; Kristian, P.;
¨¨
Sillanpaa, R.; Pihlaja, K. Eur. J. Org. Chem. 2002, 1248–1255.
58. Sheldrick, G. M. SHELXL97, Program for the Refinement of
¨ ¨
Crystal Structures; University of Gottingen: Gottingen,
43. Albrecht, U.; Langer, P. Synlett 2004, 11, 1963–1964.
44. (a) Rabjohn, N. Org. React. 1949, 5, 331–386. (b) Rabjohn, N.
Org. React. 1976, 24, 261–415.
Germany, 1997.