Reactions of imidoyl isoselenocyanates with aromatic 2-amino N-heterocycles and 1-methyl-1H-imidazole

Article abstract of DOI:10.1002/hlca.201100230

The reaction of N-phenylimidoyl isoselenocyanates 1 with 2-amino-1,3-thiazoles 10 in acetone proceeded smoothly at room temperature to give 4H-1,3-thiazolo[3,2-a] [1,3,5]triazine-4-selones 13 in fair yields (Scheme 2). Under the same conditions, 1 and 2-a

Full text of DOI:10.1002/hlca.201100230

Helvetica Chimica Acta – Vol. 94 (2011)
1575
Reactions of Imidoyl Isoselenocyanates with Aromatic 2-Amino
N-Heterocycles and 1-Methyl-1H-imidazole
by Yuehui Zhou1), Anthony Linden, and Heinz Heimgartner*
Organisch-Chemisches Institut der Universitꢀt Zꢁrich, Winterthurerstrasse 190, CH-8057 Zꢁrich
(phone: þ 41-44-6354282; fax: þ 41-44-6356812; e-mail: heimgart@oci.uzh.ch)
The reaction of N-phenylimidoyl isoselenocyanates 1 with 2-amino-1,3-thiazoles 10 in acetone
proceeded smoothly at room temperature to give 4H-1,3-thiazolo[3,2-a][1,3,5]triazine-4-selones 13 in
fair yields (Scheme 2). Under the same conditions, 1 and 2-amino-3-methylpyridine (11) underwent an
addition reaction, followed by a spontaneous oxidation, to yield the 3H-4l4-[1,2,4]selenadiazo-
lo[1’,5’:1,5][1,2,4]selenadiazolo[2,3-a]pyridine 14 (Scheme 3). The structure of 14 was established by
X-ray crystallography (Fig. 1). Finally, the reaction of 1-methyl-1H-imidazole (12) and 1 led to 3-methyl-
1-(N-phenylbenzimidoyl)-1H-imidazolium selenocyanates 15 (Scheme 4). In all three cases, an initially
formed selenourea derivative is proposed as an intermediate.
Introduction. – The interest in Se-containing organic compounds is continuing,
mainly because of their biological activities [1][2]. For this reason, convenient
syntheses of selenaheterocycles and heterocyclic selones are much sought after. In
recent years, the use of isoselenocyanates as easily accessible and safe building blocks
has been demonstrated successfully [3]. Among them, the imidoyl derivatives of type 1,
which can be prepared conveniently from N-phenylimidoyl chlorides and potassium
selenocyanate [4][5] are of special interest because of their bifunctional nature.
We have shown that the reaction of 1 with primary or secondary amines leads to
selenourea derivatives, which, by subsequent reaction with activated bromomethylene
compounds and treatment with a strong base, yield 2-amino-1,3-selenazoles 2 [5]
(Scheme 1). Imidoyl isoselenocyanates 1, R1 ¼ 2-(chloromethyl)phenyl, react with
amines to give 6H-5,1,3-benzoselenadiazocines 3 [6]. In both cases, the initial reaction
is a nucleophilic attack of the amine onto the isoselenocyanate, followed by an addition
of the intermediate thiourea derivative with an electrophile in an inter- or intra-
molecular fashion. With amidines 4 and 6, 1,3,5-triazineselones 5 and 7, respectively, are
formed smoothly at room temperature [7] (Scheme 1). Similarly, 2-amino-4,5-dihydro-
1,3-thiazole (8) reacts with 1 to give the fused triazine-selones 9. The formation of the
triazine-selones 5, 7, and 9 has been rationalized by the initial formation of a selenourea
derivative, followed by cyclization and elimination of aniline (Ar2 ¼ Ph).
The aim of the present study was the extension of the reaction of 1 with amidines to
produce aromatic 2-amino azaheterocycles, such as 2-amino-1,3-thiazoles 10 and 2-
1
)
Postdoctoral stay at the University of Zꢁrich, August 1998 – December 1999; present address:
Jiangsu Pioneer Biotechnology Research Center, 403 Chenghuang Rd., Huangqiao, Taixing, P. R.
China.
ꢂ 2011 Verlag Helvetica Chimica Acta AG, Zꢁrich

1576
Helvetica Chimica Acta – Vol. 94 (2011)
Scheme 1
aminopyridines 11, i.e., aromatic heterocycles with a formal amidine group, as well as to
1-methyl-1H-imidazole (12).
Results and Discussion. – The starting materials, i.e., N-phenylbenzimidoyl
isoselenocyanates 1a – 1c were prepared as described in [5]. In acetone at room
temperature, they underwent a smooth reaction with equimolar amounts of 2-amino-
1,3-thiazoles 10a and 10b, respectively, to give 4H-1,3-triazolo[3,2-a][1,3,5]triazine-4-
selones 13 in 53 – 63% yield (Scheme 2 and Table 1). The products precipitated from
the reaction mixture as orange-yellow solids. Their structures were deduced from the
spectroscopic data, the elemental analyses, and by analogy to the earlier described 6,7-
dihydro derivative 9 (Ar1 ¼ 4-ClꢀC6H4), the structure of which has been established by
X-ray crystallography [7]2). The formation of 13 can be rationalized as shown in
Scheme 2: nucleophilic addition of the ring N-atom of 10 to the isoselenocyanate 1
leads to the intermediate selenourea derivative B, which spontaneously undergoes
cyclization to give the fused ring system C. Elimination of aniline from the latter affords
the product 13.
2
)
The analogous reaction of phenylbenzimidoyl isothiocyanate with 10a has been described by
Barnikov and Ebeling [8]. Furthermore, 2-aryl-4H-1,3-thiazolo[3,2-a][1,3,5]triazine-4-thiones have
been obtained from the reaction of 10a with aroyl isothiocyanates, which were prepared in situ from
aroyl chlorides and NH4SCN [9]. On the other hand, 10a and alkoxycarbonyl isothiocyanates
reacted in a non-selective manner via nucleophilic addition of either the NH2 group or the ring N-
atom [10].

Helvetica Chimica Acta – Vol. 94 (2011)
1577
Scheme 2
Table 1. Prepared 2-Aryl-4H-1,3-thiazolo[3,2-a][1,3,5]triazole-4-selones 13
1
Ar
10
R
13
Yield [%]
1a
1b
1c
1a
1b
1c
Ph
10a
10a
10a
10b
10b
10b
H
H
H
Me
Me
Me
13a
13b
13c
13d
13e
13f
53
60
60
57
63
63
4-MeꢀC6H4
4-ClꢀC6H4
Ph
4-MeꢀC6H4
4-ClꢀC6H4
The next experiment was carried out with 2-amino-3-methylpyridine (11) and 1c. It
is worth mentioning that the reaction in acetone also occurred at room temperature.
After stirring for 3 h, the mixture was poured into H2O, leading to a yellowish,
crystalline product in ca. 65% yield. The NMR spectra indicated clearly that no aniline
was eliminated, and also the elemental analyses were in accordance with a 1:1 adduct.
Therefore, the structure of the selenourea derivative D was proposed (Scheme 3).
Surprisingly, the 1H-NMR spectrum as well as the CI-MS (NH3) data indicated that two
H-atoms were missing. For this reason, a crystal-structure determination of the product
was conducted to confirm that 2-(4-chlorophenyl)-9-methyl-3-phenyl-3H-4l4-[1,2,4]se-
lenadiazolo[1’,5’:1,5][1,2,4]selenadiazolo[2,3-a]pyridine (14) was formed (Fig. 1).
The Se-atom appears to be three-coordinated in that it receives two dative bonds,
one from the N-atom of the pyridine ring and the other from the N-atom adjacent to the
unsubstituted Ph group. These NꢀSe bonds are asymmetric, differing by ca. 0.12 ꢃ, and
they are 0.08 – 0.20 ꢃ longer than the CꢀSe bond. A normal NꢀSe bond is ca. 1.85 ꢃ,
which is in the range of 0.15 – 0.27 ꢃ shorter than the NꢀSe bonds observed here. The
CꢀSe bond (1.918(2) ꢃ) is ca. 0.10 ꢃ longer than the C¼Se bond found in an analog of
13c [7], which is consistent with the effect induced by the NꢀSe interactions and is

1578
Helvetica Chimica Acta – Vol. 94 (2011)
Scheme 3
Fig. 1. ORTEP Plot [11] of the molecular structure of 14 (50% probability ellipsoids, arbitrary
numbering of the atoms)
indicative of partial delocalization of the electron density in this bond. Similar CꢀSe
bond lengths of ca. 1.90 ꢃ have been observed in some related structures [12], where a
formal CꢀSe bond is adjacent to a p-system. The dative bonds complete two fused five-
membered rings. The bond lengths around these rings show considerable delocalization
of all CꢀN bonds and the CꢀSe bond, which probably implies the existence of canonical
forms of a resonance structure. None of the N-atoms in the structure are protonated,
which is consistent with the NMR spectra.

Helvetica Chimica Acta – Vol. 94 (2011)
1579
The two five-membered rings are quite planar with the maximum deviation from
the mean plane being 0.053(2) ꢃ for C(7). This plane is nearly coplanar with that of the
fused six-membered ring, the angle between the planes being only 5.09(9)8. If the three
fused rings are considered together, the maximum deviation from the mean plane is
0.095(2) ꢃ for N(2). The planes of the chlorophenyl ring and the remaining Ph ring
make angles of 18.8(1)8 and 75.39(9)8, respectively, with the mean plane of the two
fused five-membered rings.
The unexpected formation of 14 may be explained by the initial addition of the
amino N-atom of 11 onto the isoselenocyanate to yield the intermediate selenourea D.
A spontaneous oxidation leads then to the isolated product. In contrast to the reactions
with 10, in which the ring N-atom was the most nucleophilic center, the NH2 group of 11
acted as nucleophile. This observation may be rationalized by the higher aromaticity of
the pyridine ring compared with that of the 1,3-thiazole ring.
Finally, 1-methyl-1H-imidazole (12), with a formal amidine structure integrated in
the five-membered ring, was reacted with 1b and 1c, respectively, in acetone
(Scheme 4). The reaction also proceeded at room temperature. After stirring the
mixture overnight, it was poured into H2O, and the formed precipitate was recrystal-
lized from AcOEt. The elemental analyses showed that the molecular formulae of the
products 15b and 15c correspond to the sum of the respective starting materials, i.e., no
elimination of aniline occurred. The NMR spectra also indicated clearly the presence of
all expected H- and C-atoms, e.g., in the case of 15b, two signals for Me groups
appeared at 4.19 and 37.7, and 2.36 and 21.5 ppm. Most remarkable was the appearance
of a singlet at 9.30 ppm for the H-atom attached to C(2) of the imidazole ring
(136.9 ppm). Furthermore, the most dominant absorption band in the IR spectrum
(KBr) appeared at 2061 cmꢀ1. On the basis of extended NMR investigations (HSQC,
1
1H/13C and H/15N HMBC, TOCSY, and NOESY), the structures of 3-methyl-1-(N-
phenylbenzimidoyl)-1H-imidazolium selenocyanates 15b and 15c were proposed
(Scheme 4).
The resonances of the three N-atoms of the 1-(benzimidoyl)-1H-imidazolium
moiety of 15c were unambiguously localized at ꢀ 202.4 (N(1)), ꢀ 177.1 (N(3)), and
ꢀ 72.9 ppm (C¼N) (Fig. 2). They showed the expected HMBC correlations with the H-
atoms of the imidazolium ring as well as the ortho-H-atoms of the Ph ring; e.g., N(1)
exhibits correlations with HꢀC(2) at 9.35 ppm, HꢀC(4) at 7.81 ppm, HꢀC(5) at
7.67 ppm, and MeꢀN(1) at 4.18 ppm, whereas N(3) correlates with HꢀC(2), HꢀC(4),
and HꢀC(5). The correlations of the imidoyl N-atom with the ortho-H-atoms of Ph and
the imidoyl C-atom with the ortho-H-atoms of the 4-ClꢀC6H4 moiety are indicative of
the molecular structure. The HꢀC group absorbing at remarkably low field (9.35/
137.1 ppm) is attributed to HꢀC(2) of the imidazolium ring. The characteristic chemical
shifts for the selenocyanate ion are 117.8 (13C) and ꢀ 129.2 ppm (15N). These as well as
the IR absorption for the NCSeꢀ ion are in very good agreement with the data of the
recently studied ionic liquid 1-butyl-3-methyl-1H-imidazol-3-ium selenocyanate (16;
Fig. 2) [13].
A reaction mechanism for the unexpected formation of 15 is proposed in Scheme 4.
The first step, in analogy to the reaction of 2-amino-1,3-thiazoles 10 (Scheme 2), may
be the nucleophilic addition of imidazole 12 to the isoselenocyanate 1 to give a
zwitterionic intermediate I. The latter undergoes a cyclization to give the fused triazine-

1580
Helvetica Chimica Acta – Vol. 94 (2011)
Scheme 4
Fig. 2. Selected 1H-, 13C-, and 15N-NMR chemical shifts of 15c in CDCl3 (d in ppm)
selone derivative K, which then forms a new zwitterion L via ring opening. Subsequent
ring closure may form the fused 1,3-diazetidine M, which, via elimination of NCSeꢀ,
leads to the isolated imidazolium salt.
Conclusions. – The presented results extend the knowledge on reactions of
amidines with imidoyl isoselenocyanates 1 to heterocycles containing an ꢄamidine-likeꢅ
moiety. The reaction of 2-amino-1,3-thiazoles 10 parallels those with amidines and,
most likely, can be extended further to similar five-membered 2-amino heterocycles
such as 2-amino-1,3-oxazoles, 2-aminoimidazoles, etc. We assume that all the reactions
proceed via initial nucleophilic attack of the ring N-atom of the 2-amino heterocycle at
the most electrophilic heterocumulene C-atom, in contrast to the mechanism
formulated for the analogous reaction with aroyl isothiocyanates [9]. On the other
hand, the NH2 group of 2-aminopyridine (11) is the most nucleophilic center in the

Helvetica Chimica Acta – Vol. 94 (2011)
1581
reaction with 1, leading to a selenourea derivative, which undergoes a spontaneous
oxidation. Again a different type of product is formed in the reaction with 1-methyl-
1H-imidazole (12), in which the initially formed adduct cannot stabilize and, therefore,
undergoes a sequence of further reactions to give the imidazolium salts.
In conclusion, isoselenocyanates 1 are prone to react with various ꢄamidine-likeꢅ
molecules leading to new Se-containing heterocycles, a reaction type, which deserves to
be studied further.
We thank the analytical units of our institute for spectra and analyses, in particular, Dr. G. Hopp-
Rentsch, for detailed NMR studies. Financial support of the work by the Dr. Helmut Legerlotz-
Foundation and F. Hoffmann-La Roche AG, Basel, is gratefully acknowledged.
Experimental Part
1. General. TLC: Silica gel 60 F254 plates (0.25 mm, Merck); hexane/AcOEt 1:1 or 2 :1 as eluents.
Column chromatography (CC): silica gel 60 (0.040 – 0.063 mm; Merck). M.p.: Bꢀchi B-540 apparatus; in
capillary; uncorrected. IR Spectra: Perkin-Elmer-Spektrum 1600 FT-IR spectrophotometer; in KBr, in
cmꢀ1. 1H- (300 or 600 MHz), 13C- (75 or 150 MHz), and 15N-NMR (60.6 MHz) spectra: Bruker ARX-300
or AMX-600 instrument, in CDCl3; chemical shifts in ppm (rel. to TMS (1H and 13C) or MeNO2 (15N)),
coupling constants J in Hz; multiplicities of the 13C signals were determined with DEPT spectra. EI-
(70 eV) and CI-MS (NH3 as carrier gas): Finnigan MAT-95 or Finnigan SSQ-700 instrument; ESI-MS:
Finnigan TSQ-700. Elemental analyses: Gerber Elementar Analysator EL instrument.
2. Starting Materials. The preparation of N-phenylimidoyl isoselenocyanates 1a – 1c has been
described in [5]. All other starting materials, 10a, 10b, 11, and 12, were commercially available (Fluka,
Sigma-Aldrich) and were used without purification.
3. Reactions of 1 with 2-Amino-1,3-thiazoles 10. To a stirred soln. of 1 (3 – 4.5 mmol) in acetone
(20 ml) at r.t. was added the equivalent amount of 10. Immediately, a yellow-to-orange precipitate
formed. The mixture was stirred at r.t. for 1 h, the formed precipitate was filtered under vacuum, washed
with some acetone, and dried in vacuum. The products were recrystallized from acetone or DMF.
2-Phenyl-4H-[1,3]thiazolo[3,2-a][1,3,5]triazine-4-selone (13a). From 878 mg (3.4 mmol) of 1a and
340 mg (3.4 mmol) of 10a. Yield: 0.53 g (53%). Orange crystals. M.p. 281.4 – 282.48 (acetone/DMF). IR
(KBr): 3095m, 1548m, 1538m, 1513s, 1492m, 1456s, 1391vs, 1346m, 1325vs, 1296vs, 1279m, 1255s, 1164w,
1130m, 1093m, 1072w, 1022w, 999w, 978w, 942w, 892m, 848s, 800w, 756w, 716s, 693s. 1H-NMR (300 MHz,
CDCl3): 8.93 (d, J ¼ 4.9, 1 H); 8.61 – 8.57 (m, 2 arom. H); 7.64 – 7.57 (m, 1 arom. H); 7.53 – 7.48 (m, 2 arom.
H); 7.32 (d, J ¼ 4.9, 1 H). 13C-NMR (75 MHz, CDCl3): 179.4 (s, C¼Se); 167.5, 160.3 (2s, C(2), C(8a));
133.1 (s, 1 arom. C); 133.6, 130.5, 128.8 (3d, 5 arom. CH); 128.6, 112.9 (2d, C(5), C(6)). EI-MS: 295 (5),
294 (3), 293 (22, Mþ), 291 (10), 290 (4), 289 (4), 188 (13), 187 (100), 104 (8), 103 (15), 84 (14), 77 (70).
Anal. calc. for C11H7N3SSe (292.22): C 45.21, H 2.41, N 14.38, S 10.97; found: C 45.26, H 2.40, N 14.38, S
10.96.
2-(4-Methylphenyl)-4H-[1,3]thiazolo[3,2-a][1,3,5]triazine-4-selone (13b). From 987 mg (3.3 mmol)
of 1b and 330 mg (3.3 mmol) of 10a. Yield: 0.60 g (59%). Yellow crystals. M.p. 295 – 2968 (acetone). IR
(KBr): 3131w, 3039m, 1604w, 1572w, 1536s, 1521vs, 1506s, 1422s, 1392vs, 1328s, 1300s, 1292s, 1254s, 1176w,
1166m, 1122m, 1016w, 892m, 845s, 790w, 772m, 740s, 711w. CI-MS: 310 (20), 309 (13), 308 (100, [M þ
1]þ), 307 (8), 306 (48), 305 (16), 304 (16). Anal. calc. for C12H9N3SSe (306.25): C 47.06, H 2.96, N
13.72, S 10.47; found: C 47.04, H 3.07, N 13.63, S 10.46.
2-(4-Chlorophenyl)-4H-[1,3]thiazolo[3,2-a][1,3,5]triazine-4-selone (13c). From 991 mg (3.1 mmol)
of 1c and 310 mg (3.1 mmol) of 10a. Yield: 0.59 g (58%). Yellow crystals. M.p. 2808 (dec.; acetone).
1H-NMR (300 MHz, CDCl3): 8.92 (d, J ¼ 4.9, 1 H); 8.53, 7.47 (AA’BB’, JAB ¼ 8.9, 4 arom. H); 7.31 (d, J ¼
4.9, 1 H). 13C-NMR (75 MHz, CDCl3): 179.4 (s, C¼Se); 167.6, 159.3 (2s, C(2), C(8a)); 140.2, 130.5 (2s, 2
arom. C); 131.7, 129.1 (2d, 4 arom. CH); 128.6, 113.0 (2d, C(5), C(6)). Anal. calc. for C11H6ClN3SSe
(326.67): C 40.45, H 1.85, N 12.86, S 9.82; found: C 40.26, H 2.04, N 12.83, S 9.96.

1582
Helvetica Chimica Acta – Vol. 94 (2011)
7-Methyl-2-phenyl-4H-[1,3]thiazolo[3,2-a][1,3,5]triazine-4-selone (13d). From 878 mg (3.4 mmol)
of 1a and 388 mg (3.4 mmol) of 10b. Yield: 0.60 g (58%). Orange crystals. M.p. 280 – 2818 (acetone/
DMF). IR (KBr): 3101w, 3053w, 3031w, 2967w, 1587m, 1518vs, 1492m, 1456s, 1401vs, 1384vs, 1341s, 1326s,
1298m, 1273m, 1256s, 1182m, 1137m, 1100m, 1080m, 1021w, 996w, 941w, 879m, 838s, 807m, 743s, 693m.
1H-NMR (300 MHz, CDCl3): 8.66 (q-like, J ¼ 1.4, 1 H); 8.56 – 8.54 (m, 2 arom. H); 7.62 – 7.51 (m, 1 arom.
H); 7.49 – 7.46 (m, 2 arom. H); 2.53 (d, J ¼ 1.4, Me). 13C-NMR (75 MHz, CDCl3): 178.7 (s, C¼Se); 167.1,
160.0 (2s, C(2), C(8a)); 133.9, 127.1 (2s, 1 arom. C, C(7)); 133.4, 130.4, 128.7 (3d, 5 arom. CH); 126.8 (d,
C(6)); 13.5 (q, Me). EI-MS: 309 (12), 308 (8), 307 (55, Mþ), 305 (27), 304 (10), 303 (9), 202 (13), 201
(100), 198 (15), 197 (14). Anal. calc. for C12H9N3SSe (306.25): C 47.06, H 2.96, N 13.72, S 10.47; found: C
46.99, H 2.83, N 13.85, S 10.63.
7-Methyl-2-(4-methylphenyl)-4H-[1,3]thiazolo[3,2-a][1,3,5]triazine-4-selone (13e). From 1.376 g
(4.6 mmol) of 1b and 524 mg (4.6 mmol) of 10b. Yield: 0.93 g (63%). Orange-yellow crystals. M.p.
2918 (dec.; DMF). IR (KBr): 3074m, 2933w, 1606w, 1589m, 1573w, 1530vs, 1508s, 1456m, 1420s, 1393vs,
1359s, 1333s, 1298s, 1275s, 1257s, 1179m, 1140s, 1111m, 1100m, 1018w, 992w, 877m, 848s, 852w, 836s, 764s.
CI-MS: 324 (21), 323 (15), 322 (100, [M þ 1]þ), 321 (8), 320 (49), 319 (17), 318 (17), 258 (7). Anal. calc.
for C13H11N3SSe (320.28): C 48.75, H 3.46, N 13.12, S 10.01; found: C 48.58, H 3.37, N 13.07, S 10.11.
2-(4-Chlorophenyl)-7-methyl-4H-[1,3]thiazolo[3,2-a][1,3,5]triazine-4-selone (13f). From 991 mg
(3.1 mmol) of 1c and 353 mg (3.1 mmol) of 10b. Yield: 0.65 g (62%). Orange crystals. M.p. 282.0 –
1
282.58 (DMF). H-NMR (300 MHz, CDCl3): 8.65 (q-like, J ¼ 1.4, 1 H); 8.50, 7.46 (AA’BB’, JAB ¼ 8.7, 4
arom. H); 2.54 (d, J ¼ 1.4, Me). 13C-NMR (75 MHz, CDCl3): 179.0 (s, C¼Se); 168.0, 158.0 (2s, C(2),
C(8a)); 140.2, 132.2, 127.5 (3s, 2 arom. C, C(7)); 131.5, 129.0 (2d, 4 arom. CH); 126.7 (d, C(6)); 13.4 (q,
Me). EI-MS: 343 (17), 342 (6), 341 (38, Mþ), 340 (5), 339 (17), 338 (6), 337 (6), 268 (23), 253 (45), 237
(37), 236 (12), 235 (100). Anal. calc. for C12H8ClN3SSe (340.69): C 42.31, H 2.37, N 12.33, S 9.41; found: C
42.10, H 2.29, N 12.26, S 9.27.
4. Reaction of 1c with 2-Amino-3-methylpyridine (11). To a stirred soln. of 1c (992 mg, 3.1 mmol) in
acetone (20 ml) at r.t., 1 equiv. of 11 (335 mg, 3.1 mmol) was added, and the mixture was stirred for 3 h,
until the starting materials were completely consumed (TLC). Then, the mixture was poured into H2O
and stirred for another 1 h. The yellowish precipitate was filtered under vacuum and recrystallized from
Et2O to give 0.85 g (64%) of 2-(4-chlorophenyl)-9-methyl-3-phenyl-3H-4l4-[1,2,4]selenadiazolo-
[1’,5’:1,5][1,2,4]selenadiazolo[2,3-a]pyridine (14). M.p. 189.5 – 190.5. IR: 3041w, 2955w, 2948w, 1605w,
1592w, 1567w, 1511s, 1463s, 1445m, 1401s, 1367vs, 1319m, 1300m, 1286s, 1274s, 1223m, 1196s, 1125m,
1
1104m, 1089m, 1071w, 1015m, 992w, 951m, 892w, 838m, 778m, 765w, 748m, 734m. H-NMR (300 MHz,
CDCl3): 8.24 (dd-like, J ¼ 8.7, 0.8, 1 H); 7.63 – 7.54 (m, 3 H); 7.35 – 7.20 (m, 5 H); 7.08 – 7.04 (m, 2 H); 6.84
(dd-like, J ¼ 7.0, 5.8, 1 H); 2.64 (s, Me). 13C-NMR (75 MHz, CDCl3): 174.4 (s, C¼Se); 162.2, 156.4, 141.2,
136.2, 131.0, 130.5 (6s, 3 arom. C, 3 C); 137.0, 135.0, 126.2, 115.4 (4d, 1 arom. CH, 3 CH); 131.5, 129.3,
128.1, 125.5 (4d, 8 arom. CH); 17.5 (q, Me). CI-MS: 430 (5), 429 (38), 428 (19), 427 (100, [M þ 1]þ), 426
(13), 425 (46), 424 (15), 423 (15), 349 (14), 347 (25), 233 (13), 231 (41), 136 (7), 134 (12). Anal. calc. for
C20H15ClN4Se (425.78): C 56.42, H 3.55, N 13.16, Cl 8.33; found: C 56.00, H 3.66, N 12.97, Cl 8.50.
Suitable crystals for the X-ray crystal-structure determination were obtained from Et2O/AcOEt.
5. Reactions of 1 with 1-Methyl-1H-imidazole (12). To a soln. of 1b (987 mg, 3.3 mmol) or 1c
(895 mg, 2.8 mmol) in acetone (30 ml), 1 equiv. of 12 (271 and 230 mg, resp.) was added, and the mixture
was stirred at r.t. overnight. TLC indicated that the starting materials were completely consumed. Then,
the mixture was poured into ice/H2O and stirred for another 2 h. The yellowish precipitate was filtered
under vacuum and recrystallized from AcOEt.
3-Methyl-1-[(Z)-(4-methylphenyl)(phenylimino)methyl]-1H-imidazol-3-ium Selenocyanate (15b).
Yield: 0.66 g (52%). Pale yellow crystals. M.p. 116.5 – 117.58 (AcOEt). IR: 3181w, 3083m, 2061vs, 1654s,
1608m, 1583s, 1537s, 1509w, 1484m, 1449w, 1417m, 1333s, 1272m, 1233s, 1211m, 1189m, 1143s, 1088m,
1
1023w, 927s, 907w, 831m, 794w, 766m, 727m, 695s. H-NMR (600 MHz, CDCl3): 9.30 (br. s, HꢀC(2));
7.78 – 7.76, 7.74 – 7.72 (2m, 2 H); 7.33 – 7.27 (m, 2 arom. H); 7.27 – 7.15 (m, 4 arom. H); 7.12 – 7.02 (m, 1
arom. H); 6.84 – 6.78 (m, 2 arom. H); 4.19 (s, MeN); 2.36 (s, Me). 13C-NMR (150 MHz, CDCl3): 148.7 (s,
C¼N); 145.2, 142.8, 123.8 (3s, 3 arom. C); 136.9 (d, C(2)); 130.2, 129.6, 129.0, 121.2 (4d, 2 arom. CH
each); 125.5 (d, 1 arom. CH); 124.5, 119.8 (2d, C(4), C(5)); 117.6 (s, NCSe); 37.7 (q MeN); 21.5 (q, Me).

Helvetica Chimica Acta – Vol. 94 (2011)
1583
Table 2. Crystallographic Data for Compound 14
Crystallized from
Empirical formula
Formula weight
Crystal color, habit
Crystal dimensions [mm]
Temp. [K]
Et2O/AcOEt
C20H15ClN4Se
425.72
yellow, prism
0.30 ꢁ 0.35 ꢁ 0.45
173(1)
Crystal system
Space group
triclinic
P1
ꢀ
Z
2
Reflections for cell determination
25
2q Range for cell determination [8]
39 – 40
Unit cell parameters:
a [ꢃ]
b [ꢃ]
c [ꢃ]
a [8]
9.021(1)
9.503(1)
10.849(2)
86.66(1)
76.76(1)
89.33(1)
903.7(3)
1.564
b [8]
g [8]
V [ꢃ3]
Dx [g cmꢀ3
]
m(MoKa) [mmꢀ1
Scan type
]
2.235
w/2q
2q(max) [8]
60
Transmission factors (min; max)
Total reflections measured
Symmetry independent reflections
Reflections with I > 2s(I)
Parameters refined
0.867; 1.000
5584
5290
4284
236
Final R(F) (I > 2s(I) reflections)
0.0362
0.0973
0.053, 0.1553
1.056
wR(F2) (all data)
Weighting parameters: a, ba)
Goodness-of-fit
Final Dmax/s
D1 (max; min) [e ꢃꢀ3
0.003
0.84; ꢀ 0.79
]
a) wꢀ1 ¼ [s2(F2o ) þ (aP)2 þ bP], where P ¼ (Fo2 þ 2F2c )/3.
15N-NMR (60.6 MHz, CDCl3): ꢀ 205.3 (N(1)); ꢀ 178.3 (N(3)); ꢀ 78.6 (C¼N)3). Anal. calc. for
C19H18N4Se (381.34): C 59.84, H 4.76, N 14.69; found: C 59.71, H 4.76, N 14.61.
1-[(4-Chlorophenyl)(phenylimino)methyl]-3-methyl-1H-imidazol-3-ium Selenocyanate (15c).
Yield: 0.62 g (55%). Pale yellow crystals. M.p. 1448 (dec.; AcOEt). IR: 3140m, 3071s, 2060vs, 1672vs,
1594s, 1532s, 1489s, 1449w, 1415m, 1402m, 1359m, 1332m, 1274m, 1256s, 1214w, 1180w, 1142s, 1110m,
1089s, 1015m, 927s, 904w, 838m, 778w, 765m, 741s, 699s. 1H-NMR (600 MHz, CDCl3): 9.34 (br. s,
HꢀC(2)); 7.82 – 7.80, 7.68 – 7.60 (2m, 2 H); 7.48 – 7.39 (m, 4 arom. H); 7.28 – 7.20 (m, 2 arom. H); 7.11 – 7.06
(m, 1 arom. H); 6.83 – 6.79 (m, 2 arom. H); 4.17 (s, MeN). 13C-NMR (150 MHz, CDCl3): 147.6 (s, C¼N);
144.8, 138.4, 125.2 (3s, 3 arom. C); 137.1 (d, C(2)); 131.3, 129.8, 129.1, 121.1 (4d, 2 arom. CH each); 125.7
(d, 1 arom. CH); 124.5, 119.7 (2d, C(4), C(5)); 117.6 (s, NCSe); 37.7 (q MeN). 15N-NMR (60.6 MHz,
The signal for SeCNꢀ could not be detected.
3
)

1584
Helvetica Chimica Acta – Vol. 94 (2011)
CDCl3): ꢀ 202.4 (N(1)); ꢀ 177.1 (N(3)); ꢀ 129.2 (NCSe); ꢀ 72.9 (C¼N). Anal. calc. for C18H15ClN4Se
(401.76): C 53.81, H 3.76, Cl 8.82, N 13.95; found: C 53.71, H 3.79, Cl 8.94, N 13.82.
X-Ray Crystal-Structure Determination of 14 (Table 2 and Fig. 1)4). All measurements were
performed on a Rigaku AFC5R diffractometer using graphite-monochromated MoKa radiation (l
0.71073 ꢃ) and a 12-kW rotating anode generator. The data collection and refinement parameters are
given in Table 2, and a view of the molecule is shown in Fig. 1. The intensities were corrected for Lorentz
and polarization effects. An empirical absorption correction based on azimuthal scans of several
reflections [14] was applied. The structure was solved by direct methods using SIR92 [15], which revealed
the positions of all non-H-atoms. The non-H-atoms were refined anisotropically. 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 1.2 Ueq of its parent atom (1.5 Ueq
for the Me group). Refinement of the structure was carried out on F2 using full-matrix least-squares
procedures, which minimized the function Sw(F2o ꢀ Fc2 )2. A correction for secondary extinction was not
applied. Neutral atom scattering factors for non-H-atoms were taken from [16a], and the scattering
factors for H-atoms were taken from [17]. Anomalous dispersion effects were included in Fc [18]; the
values for f ’ and f ’’ were those of [16b]. The values of the mass attenuation coefficients are those of [16c].
All calculations were performed using the SHELXL97 program [19].
REFERENCES
[1] J. Mlochowski, K. Kloc, R. Lisiak, P. Potaczek, H. Wojtowicz, ARKIVOC 2007, (vi), 14; M. Soriano-
Garcia, Curr. Med. Chem. 2004, 11, 1657; C. W. Nogueira, G. Zeni, J. B. T. Rocha, Chem. Rev. 2004,
104, 6255; M. Koketsu, H. Ishihara, Curr. Org. Chem. 2003, 7, 175; G. Mugesh, W.-W. du Mont, H.
Sies, Chem. Rev. 2001, 101, 2125.
[2] D. R. Garud, M. Makimura, M. Koketsu, New J. Chem. 2011, 35, 581; H. Tao, Y. Weng, R. Zhuo, G.
´
˜
Chang, I. L. Urbatsch, Q. Zhang, ChemBioChem 2011, 12, 868; E. Ibanez, D. Plano, M. Font, A.
Calvo, C. Prior, J. A. Palop, C. Sanmartꢆn, Eur. J. Med. Chem. 2011, 46, 265; M. Kaname, M.
Minoura, H. Sashida, Tetrahedron Lett. 2011, 52, 505; Y. Xie, J. Liu, J. Li, Tetrahedron Lett. 2011, 52,
´
´
˜
932; D. Plano, Y. Baquedano, E. Ibanez, I. Jimenez, J. A. Palop, J. E. Spallholz, C. Sanmartꢆn,
Molecules 2010, 15, 7292; E. H. Lee, Y.-J. Lim, S. K. Ha, T. H. Kang, M. Koketsu, C. Kang, S. Y. Kim,
´
´
J.-H. Park, J. Pharm. Pharmacol. 2010, 62, 352; P. Suchocki, I. Misiewicz-Krzeminska, K. Skupinska,
´
K. Niedzwiecka, K. Lubelska, Z. Fijałek, T. Kasprzycka-Guttman, Pharmacol. Reports 2010, 62, 352;
C. Ling, Z. Zheng, X. C. Jiang, W. Zhong, S. Li, Bioorg. Med. Chem. Lett. 2010, 20, 5123; H. Sashida,
C. Pan, M. Kaname, M. Minoura, Synthesis 2010, 3091.
[3] M. Ninomiya, D. R. Garud, M. Koketsu, Heterocycles 2010, 81, 2027; H. Heimgartner, Y. Zhou, P. K.
Atanassov, G. L. Sommen, Phosphorus, Sulfur Silicon Relat. Elem. 2008, 183, 840; D. R. Garud, M.
Koketsu, H. Ishihara, Molecules 2007, 12, 504; M. L. Petrov, N. I. Zmitrovich, Russ. J. Gen. Chem.
(Transl. of Zh. Obshch. Khim.) 1999, 69, 245.
[4] N. A. Kirsanova, G. I. Derkach, Ukr. Khim. Zh. 1970, 36, 372; Chem. Abstr. 1970, 73, 45417q.
[5] Y. Zhou, A. Linden, H. Heimgartner, Helv. Chim. Acta 2000, 83, 1576.
[6] P. K. Atanassov, A. Linden, H. Heimgartner, Helv. Chim. Acta 2004, 87, 1452.
[7] Y. Zhou, A. Linden, H. Heimgartner, Heterocycles 2011, 84, accepted (DOI: 10.3987/COM-11-
S(P)9).
[8] G. Barnikov, H. Ebeling, Z. Chem. 1973, 13, 468.
[9] S. Saeed, N. Rasid, P. G. Jones, U. Yunas, J. Heterocycl. Chem. 2010, 47, 908; U. Yunus, M. K. Tahir,
M. H. Bhatti, S. Ali, M. Helliwell, Acta Crystallogr., Sect. E 2007, 63, o3690.
[10] M. Nagano, J. Tobitsuka, T. Matsui, K. Oyamada, Chem. Pharm. Bull. 1972, 20, 2618.
[11] C. K. Johnson, ꢄORTEP IIꢅ, Report ORNL-5138, Oak Ridge National Laboratory, Oak Ridge, 1976.
4
)
CCDC-827538 contains the supplementary crystallographic data for this article. These data can be
obtained free of charge from the Cambridge Crystallographic Data Centre via http://www.ccdc.ca-
m.ac.uk/data_request/cif.

Helvetica Chimica Acta – Vol. 94 (2011)
1585
[12] Y. Zhou, H. Heimgartner, Helv. Chim. Acta 2000, 83, 539; cf. also P. K. Atanassov, A. Linden, H.
Heimgartner, J. Sulfur Chem. 2006, 27, 181.
[13] A. Solangi, A. M. Bond, I. Burgar, A. F. Hollenkamp, M. D. Horne, T. Rꢁther, C. Zhao, J. Phys.
Chem. B 2011, 115, 6843.
[14] A. C. T. North, D. C. Phillips, F. S. Mathews, Acta Crystallogr., Sect. A 1968, 24, 351.
[15] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M. C. Burla, G. Polidori, M. Camalli, J.
Appl. Crystallogr. 1994, 27, 435.
[16] a) E. N. Maslen, A. G. Fox, M. A. OꢅKeefe, in ꢄInternational Tables for Crystallographyꢅ, Ed. A. J. C.
Wilson, Kluwer Academic Publishers, Dordrecht, 1992, Vol. C, Table 6.1.1.1, p. 477; b) D. C. Creagh,
W. J. McAuley, in ꢄInternational Tables for Crystallographyꢅ, Ed. A. J. C. Wilson, Kluwer Academic
Publishers, Dordrecht, 1992, Vol. C, Table 4.2.6.8, p. 219; c) D. C. Creagh, J. H. Hubbell, in
ꢄInternational Tables for Crystallographyꢅ, Ed. A. J. C. Wilson, Kluwer Academic Publishers,
Dordrecht, 1992, Vol. C, Table 4.2.4.3, p. 200.
[17] R. F. Stewart, E. R. Davidson, W. T. Simpson, J. Chem. Phys. 1965, 42, 3175.
[18] J. A. Ibers, W. C. Hamilton, Acta Crystallogr. 1964, 17, 781.
[19] G. M. Sheldrick, Acta Crystallogr., Sect. A 2008, 64, 112.
Received June 3, 2011