New selenosemicarbazides derived from imidazole-based carbohydrazides

Article abstract of DOI:10.1002/hlca.201200620

Imidazole-based carbohydrazides, i.e., 3-oxidoimidazole-4-carbohydrazides 1 and 2-[(imidazol-2-yl)sulfanyl]acetohydrazides 6, react with aryl isoselenocyanates 4 in MeOH at room temperature to give the corresponding selenosemicarbazides 5 and 7, respectiv

Full text of DOI:10.1002/hlca.201200620

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New Selenosemicarbazides Derived from Imidazole-Based Carbohydrazides
by Adam M. Pieczonka1), Krzysztof Ciepielowski2), Zofia Cebulska3), and Grzegorz Mloston´*
´
´
´
´
University of Łodz, Department of Organic and Applied Chemistry, Tamka 12, PL-91-403 Łodz
(phone: þ 48-42-6355761; fax: þ 48-42-6655162; e-mail: gmloston@uni.lodz.pl)
and Anthony Linden and Heinz Heimgartner*
Organisch-chemisches Institut, Universitꢀt Zꢁrich, Winterthurerstrasse 190, CH-8057 Zꢁrich
(phone: þ 41-44-6354282; fax: þ 41-44-6356812; e-mail: heimgart@oci.uzh.ch)
Imidazole-based carbohydrazides, i.e., 3-oxidoimidazole-4-carbohydrazides 1 and 2-[(imidazol-2-
yl)sulfanyl]acetohydrazides 6, react with aryl isoselenocyanates 4 in MeOH at room temperature to give
the corresponding selenosemicarbazides 5 and 7, respectively, in good yields. On heating 7b in DMF in
the presence of air to 1008, 1,3,4-oxadiazole 8a was formed via cyclization and formal elimination of
H2Se. Product 8a was also obtained after heating of a mixture of 4a and 6b under the same conditions. On
the other hand, on heating of a solution of 7c in MeOH at reflux, a cyclization occurred to give the
corresponding 1,2,4-triazole-3-selone 9b. Again, the same product was formed when a mixture of 4b and
6b was heated in MeOH. Surprisingly, analogous cyclizations of selenosemicarbazides of type 5 under the
same conditions failed, and only decomposition was observed. The structures of 7a, 7d, and 9b have been
established by X-ray crystallography.
1. Introduction. – Isoselenocyanates are well-known as versatile building blocks for
the preparation of linear and cyclic selenoorganic compounds [1]. It is also well-
documented that many Se-containing products display diverse biological activities, and
some are of significant importance in the pharmaceutical and agrochemical fields [2].
In analogy to isocyanates and isothiocyanates, isoselenocyanates easily react with N-
nucleophiles, such as primary and secondary amines, furnishing the corresponding
selenoureas [1][3]. Hydrazines display a similar reactivity leading to selenosemicar-
bazides [4]. In the case of carbohydrazides, only a few reactions with isoselenocyanates
have been reported to date [4a][4b][5]. Whereas, to the best of our knowledge,
carbohydrazides derived from heterocyclic carboxylic acids have not yet been used in
such reactions [6], reactions of benzohydrazide with aliphatic and aromatic isosele-
nocyanates are known [4a][4c], and, in a recent study, selenosemicarbazides obtained
thereby were shown to form 1,3,4-oxadiazole derivatives upon heating in DMF solution
to 1008 in the presence of air O2 [5]. This reaction was accompanied by the formation of
elemental Se. Other reactions aimed at the synthesis of Se-containing heterocycles
starting with selenosemicarbazides have not been described so far.
In a series of recent publications, we reported on the preparation and some
reactions of imidazole-based carbohydrazides. For example, carbohydrazides of 3-
1
´
´
In part from the Ph.D. thesis of A. M. P., University of Łodz, 2012.
)
)
)
2
3
´
´
In part from the Diploma thesis of K. C., University of Łodz, 2007.
Dr. Z. Cebulska passed away on August 8, 2007.
ꢂ 2013 Verlag Helvetica Chimica Acta AG, Zꢁrich

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oxido-1H-imidazole-4-carboxyhydrazide 1 reacted with isocyanates and isothiocya-
nates leading to semicarbazides 2 and thiosemicarbazides 3, respectively, in good yields
[7] (Scheme 1). Both types of products were subsequently used as starting materials for
the preparation of bis-heterocyclic systems.
Scheme 1
The aim of the present study was the synthesis of new selenosemicarbazides derived
from imidazole-carbohydrazides and their potential application for the preparation of
Se-containing bis-heterocyclic products.
2. Results and Discussion. – The starting carbohydrazides of type 1 are conveniently
accessible via cyclocondensation of a-hydroxyimino b-keto esters with formaldimines
and subsequent treatment of the 3-oxidoimidazole-4-carboxylates with NH2NH2 · H2O
[7b]. Under standard conditions, the carbohydrazides 1 are stable, crystalline materials.
The reactions of 1 with aryl isoselenocyanates 4 were performed at room temperature
in MeOH under light protection. In all cases, selenosemicarbazides 5 were isolated
after ca. 2 d as crystalline materials in good yields (Scheme 2).
Scheme 2
The spectroscopic data confirmed the expected structures. For example, in the case
1
of 5a, the characteristic H-NMR absorption of HꢀC(2) was observed at 8.48 ppm,
indicating a 2-unsubstituted imidazole N-oxide. The CONH group absorbed at
1671 cmꢀ1 in the IR spectrum, and the corresponding signal in the 13C-NMR spectrum
appeared at 179.4 ppm. In addition, the C¼Se signal was found at 159.9 ppm. The HR-
ESI-MS showed the typical pattern for Se-containing substances with m/z 372.0367
([M þ H]þ). These data evidence that the reactions occurred via nucleophilic attack of
the hydrazide NH2 group on the isoselenocyanate, and the N-oxide function is
preserved under the reaction conditions.
In an extension of the study, hydrazides of type 6 were used for the reactions with 4.
These hydrazides were prepared via alkylation of enolizable imidazole-2-thiones with

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2-bromoethanoates [8]. The esters obtained thereby were converted to the hydrazides
by standard treatment with excess NH2NH2 · H2O [7b]. The reactions of 6 with 4 were
also carried out in MeOH at room temperature to yield crystalline products in all cases.
The structures of the formed selenosemicarbazides 7 were established by the
1
spectroscopic data (Scheme 3). The H-NMR spectra revealed the presence of the
SCH2CO fragment by an absorption at 3.95 – 3.45 ppm. In analogy to compounds 5, the
C¼Se and C¼O resonances in the 13C-NMR spectra appeared at ca. 180 and 160 ppm,
respectively. In the cases of 7a and 7d, single crystals suitable for X-ray crystallography
were obtained, and the molecular structures of these compounds were unambiguously
confirmed (cf. the Table in the Exper. Part).
Scheme 3
The molecular structure of 7d is shown in Fig. 1. The asymmetric unit contains a
single molecule. All three NH groups are involved in H-bonds. HꢀN(20) forms a weak
Fig. 1. ORTEP Plot [9] of the molecular structure of 7d (50% probability ellipsoids; arbitrary numbering
of the atoms; the MeOH molecule is not shown)

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intramolecular H-bond with the unsubstituted N(1)-atom in the five-membered ring.
This interaction creates a loop which can be described by a graph set motif [10] of
S(10). HꢀN(17) forms an intermolecular H-bond with the same acceptor atom (N(1))
in an adjacent molecule related to the donor molecule by a center of inversion.
Therefore, this interaction links pairs of molecules into dimers and can be described by
a graph set motif of R22(14). HꢀN(18) forms an intermolecular H-bond with the Se-
atom in a different adjacent molecule which is also related to the donor molecule by a
center of inversion. This interaction also links pairs of molecules and can be described
by a graph set motif of R22(8). The combination of the intermolecular interactions links
the molecules into extended chains, which run parallel to the [110] direction.
The molecular structure of 7a is quite similar to that of 7d, but there are two
symmetry-independent molecules, A and B, of 7a and one disordered molecule of
CHCl3 in the asymmetric unit. The space group of 7a is centrosymmetric. For
convenience, the asymmetric unit was chosen such that molecule B is related to
molecule A by a non-crystallographic center of inversion at (0.24, 0.0, 0.25). The two
independent molecules have very similar conformations with an r.m.s. fit of 0.084 ꢃ
between the non-H-atoms of molecule A and the inverted atoms of molecule B. The H-
bonding pattern and motifs in 7a are the same as those observed in 7d, except that,
where the intermolecular interactions in 7d link molecules across crystallographic
centers of inversion to form the extended chains, the interactions in 7a link molecules A
and B in an alternating fashion across non-crystallographic centers of inversion to give
extended chains which run parallel to the [100] direction.
Both types of selenosemicarbazides, 5 and 7, are stable at room temperature in the
crystalline state as well as in solution. Prompted by recently published results [5], we
selected 7b for the attempted thermal formation of the corresponding 1,3,4-oxadiazole
derivatve 8a (Scheme 4). Thus, a solution of 7b in dry DMF was heated to 1008 under
an air atmosphere. After 6 h, the 1H-NMR spectra evidenced the disappearance of the
starting material and the presence of a new product. The same product was obtained
when a mixture 4a/6b was heated in DMF under air for 6 h4).
Scheme 4
To check whether the formation of Se-containing products from 5 and 7 is possible,
solutions of 5b and 7c in MeOH were heated at reflux. Under these conditions, after
4 h, 7c was completely converted to a new compound, which was isolated as a
crystalline material in 57% yield. The ESI-MS exhibited the [M þ H]þ peak at m/z 534,
which corresponds to the molecular formula C16H19N5OSSe, differing from that of 7c
4
)
The analogous experiments with 5a and 1a þ 4a, respectively, failed, and only decomposition and
formation of Se was observed.

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by elimination of H2O. The IR spectrum indicated that the new product does not
contain a C¼O group. The 13C-NMR signal at 160.3 ppm suggested the preservation of
the selenourea moiety. Based on these data, the structure of 1,2,4-triazole-3-selone 9b is
proposed (Scheme 5)5). The same product was obtained from 6b and 4b in boiling
MeOH. Finally, crystals of 9b suitable for a crystal-structure determination were
obtained from MeOH, and the structure of 9b was established (Fig. 2).
Scheme 5
The asymmetric unit contains one molecule of 9b plus one molecule of MeOH. The
crystal was of poor quality and produced very broad reflection profiles. Consequently,
the R-factor remains high and the precision of the geometric parameters is low.
Nonetheless, the overall structure of the molecule is unambiguous. The space group is
non-centrosymmetric, but the presence of mirror or glide planes dictates that the
compound in the crystal is racemic. The absolute structure has been determined by the
diffraction experiment. The intermolecular H-bonds N(3)ꢀH ··· O(2’) and O(2)ꢀH ···
N(5) link the molecules 9b and the MeOH molecule in an alternating fashion into
extended chains, which run parallel to the [001] direction and have a graph set motif of
C22(10).
3. Conclusions. – In the present study, we showed that imidazole-based carbohy-
drazides 1 and 6 react smoothly with aromatic isoselenocyanates 4 to yield the
5
)
The analogous reactions with 5b failed.

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Fig. 2. ORTEP Plot [9] of the molecular structure of 9b (50% probability ellipsoids; arbitrary numbering
of the atoms; solvent molecules omitted)
corresponding selenosemicarbazides 5 and 7, respectively. It is worth mentioning that,
in the case of 1, the N-oxide function is preserved. Upon heating in DMF at 1008 in the
presence of air O2, 7b undergoes a cyclization to give 1,3,4-oxadiazole 8a, whereas
compounds 5 decompose under these conditions. The same product 8a is formed from
6b and 4a in DMF under air atmosphere at 1008. In contrast to thiosemicarbazides [7a],
the Se analogs 7 undergo cyclization to give 1,2,4-triazole-3-selones 9 under mild
thermal conditions, and no catalyst is required. To the best of our knowledge, this is the
first type of cyclization of selenosemicarbazides, which occurs without loss of Se.
The authors thank PD Dr. L. Bigler, University of Zurich, for recording of the HR-ESI mass spectra.
A. M. P. is grateful for financial support within the project co-funded by the European Union under the
European Social Fund ꢀ HUMAN – BEST INVESTMENT!ꢁ
Experimental Part
1. General. M.p.: Melt-Temp. II (Aldrich) or STUART SMP30; uncorrected. IR Spectra: NEXUS FT-
.
IR spectrophotometer; in KBr; ˜n in cmꢀ1 1H- and 13C-NMR spectra: Bruker Avance III (600 and
150 MHz, resp.), using solvent signal as reference; d in ppm; J in Hz; assignments of signals in 13C-NMR
spectra accomplished by HMQC experiments. HR-ESI-MS: Bruker maXis spectrometer; in m/z.
2. Starting Materials. All solvents are commercially available and were used as received.
Carbohydrazides 1a and 1b were prepared from the corresponding esters by treatment with NH2NH2 ·
H2O as described in [7b].
3. Synthesis of Selenosemicarbazides 5a – 5d and 7a – 7g. General Procedure. A mixture of 1 or 6
(1 mmol), and the corresponding isoselenocyanate 4 (1.1 mmol) in MeOH (5 ml) was stirred for 48 h.
Then, the product formed was filtered off, washed with MeOH, and crystallized from an acetone/MeOH
mixture (1:1).
2-[(1,5-Dimethyl-3-oxido-1H-imidazol-4-yl)carbonyl]-N-(4-fluorophenyl)hydrazinecarboseleno-
amide (5a). Yield: 0.326 g (88%). Colorless crystals. M.p. 198 – 2008 (MeOH). IR (KBr): 3154s (NH),
3054m, 2934m, 1671vs (C¼O), 1636vs, 1597s, 1510s, 1463s, 1227m. 1H-NMR ((D6)DMSO): 10.13 (br. s,
NH); 8.48 (s, HꢀC(2)); 7.41 – 7.13 (m, 4 arom. H); 3.59 (s, MeN); 2.49 (s, Me). 13C-NMR ((D6)DMSO):
179.4 (C¼O); 159.9 (C¼Se); 149.5, 137.8, 132.0, 120.5 (2 arom. C, C(4,5)); 129.2, 115.0 (4 arom. CH);
126.9 (C(2)); 32.4 (MeN); 9.5 (MeꢀC(5)). HR-ESI-MS: 372.0367 ([M þ H]þ, C13H15FN5O2Seþ; calc.
372.0370).

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2-[(1,5-Dimethyl-3-oxido-1H-imidazol-4-yl)carbonyl]-N-(4-methoxyphenyl)hydrazinecarboseleno-
amide (5b). Yield: 0.272 g (71%). Colorless crystals. M.p. 175 – 1768 (MeOH). IR (KBr): 3157s (NH),
1
2933m, 1671vs (C¼O), 1637vs, 1601s, 1512s, 1459s, 1255m. H-NMR ((D6)DMSO): 10.02 (br. s, NH);
8.48 (s, HꢀC(2)); 7.27, 6.88 (AA’BB’, JAB ¼ 7.6, 4 arom. H); 3.75 (s, MeO); 3.59 (s, MeN); 2.49 (s, Me).
13C-NMR ((D6)DMSO): 179.7 (C¼O); 159.9 (C¼Se); 155.0, 137.4, 131.8, 119.1 (2 arom. C, C(4,5)); 128.4,
114.8 (4 arom. CH); 126.8 (C(2)); 55.7 (MeO); 32.4 (MeN); 9.5 (MeꢀC(5)). HR-ESI-MS: 384.0567
([M þ H]þ, C14H18N5O3Seþ; calc. 384.0570).
2-[(1-Benzyl-5-methyl-3-oxido-1H-imidazol-4-yl)carbonyl]-N-(4-fluorophenyl)hydrazinecarbosele-
noamide (5c). Yield: 0.381 g (85%). Colorless crystals. M.p. 180 – 1818 (MeOH). IR (KBr): 3127s (NH),
3061m, 1667vs (C¼O), 1598s, 1508s, 1481s, 1215m. 1H-NMR ((D6)DMSO): 10.17, 10.10 (2br. s, NH); 8.74
(s, HꢀC(2)); 7.43 – 7.13 (m, 9 arom. H); 5.26 (s, CH2); 2.45 (s, Me). 13C-NMR ((D6)DMSO): 180.0
(C¼O); 164.7 (C¼Se); 143.5, 139.9, 135.8, 131.4, 119.3 (3 arom. C, C(4,5)); 126.8 (C(2)); 129.5, 128.7,
127.8, 127.1, 116.2 (9 arom. CH); 48.8 (CH2); 9.8 (Me). HR-ESI-MS: 448.0681 ([M þ H]þ,
C19H19FN5O2Seþ; calc. 448.0683).
2-[(1-Benzyl-5-methyl-3-oxido-1H-imidazol-4-yl)carbonyl]-N-phenylhydrazinecarboselenoamide
(5d). Yield: 0.270 g (63%). Colorless crystals. M.p. 192 – 1938 (MeOH). IR (KBr): 3216m, 3127s (NH),
3044m, 1667vs (C¼O), 1597s, 1479s, 1328m. 1H-NMR ((D6)DMSO): 10.13 (br. s, NH); 8.72 (s, HꢀC(2));
7.41 – 7.17 (m, 10 arom. H); 5.26 (s, CH2); 2.45 (s, Me). 13C-NMR ((D6)DMSO): 179.6 (C¼O); 159.8
(C¼Se); 139.9, 135.8, 131.4, 121.9 (2 arom. C, C(4,5)); 126.8 (C(2)); 129.5, 128.7, 128.6, 127.7, 127.6, 126.3
(10 arom. CH); 48.8 (CH2); 9.8 (Me). HR-ESI-MS: 430.0774 ([M þ H]þ, C19H20N5O2Seþ; calc.
430.0777).
N-(4-Methoxyphenyl)-2-{[(1,4,5-trimethyl-1H-imidazol-2-yl)sulfanyl]acetyl}hydrazinecarboseleno-
amide (7a). Yield: 0.246 g (58%). Colorless crystals. M.p. 132 – 1348 (MeOH). IR (KBr): 3273m, 3124m
(NH), 2943m, 1692s (C¼O), 1540s, 1512vs, 1246m. 1H-NMR ((D6)DMSO): 10.31 (br. s, NH); 9.98 (br. s,
NH); 7.21, 6.88 (AA’BB’, JAB ¼ 7.6, 4 arom. H); 3.75 (s, MeO); 3.52 (s, CH2); 3.48 (s, MeN); 2.04, 1.67 (2s,
2 Me). 13C-NMR ((D6)DMSO): 179.8 (C¼O); 164.8 (C¼Se); 157.8, 136.3, 133.7, 126.3, 119.1 (2 arom. C,
C(2,4,5)); 128.8, 114.8 (4 arom. CH); 55.7 (MeO); 36.8 (CH2); 31.5 (MeN); 12.4, 9.2 (2 Me). HR-ESI-
MS: 428.0654 ([M þ H]þ, C16H22N5O2SSeþ; calc. 428.0654).
N-(4-Fluorophenyl)-2-{[(1-methyl-4,5-diphenyl-1H-imidazol-2-yl)sulfanyl]acetyl}hydrazinecarbose-
lenoamide (7b). Yield: 0.323 g (60%). Colorless crystals. M.p. 143 – 1448 (MeOH). IR (KBr): 3289s,
1
3214s (NH), 2976m, 1686s (C¼O), 1530vs, 1506vs, 1208m. H-NMR ((D6)DMSO): 10.48 (br. s, NH);
10.19 (br. s, NH); 9.95 (br. s, NH); 7.34 – 7.07 (m, 14 arom. H); 3.95 (s, CH2); 3.40 (s, MeN). 13C-NMR
((D6)DMSO): 167.8 (C¼O); 160.7 (C¼Se); 157.6, 141.1, 137.8, 131.4, 126.5, 119.1 (4 arom. C, C(2,4,5));
131.0, 130.7, 129.6, 129.4, 129.2, 128.5, 126.5, 115.1 (14 arom. CH); 36.0 (CH2); 32.2 (MeN). HR-ESI-MS:
540.0763 ([M þ H]þ, C25H23FN5OSSeþ; calc. 540.0768).
N-(4-Methoxyphenyl)-2-{[(1-methyl-4,5-diphenyl-1H-imidazol-2-yl)sulfanyl]acetyl}hydrazinecarbo-
selenoamide (7c). Yield: 0.336 g (61%). Colorless crystals. M.p. 175 – 1768 (MeOH). IR (KBr): 3370s,
1
3208s (NH), 2953m, 1690s (C¼O), 1541vs, 1510s, 1244m. H-NMR ((D6)DMSO): 10.47 (br. s, NH);
10.07 (br. s, NH); 9.87 (br. s, NH); 7.52 – 6.82 (m, 14 arom. H); 3.94 (s, CH2); 3.74 (s, MeO); 3.40 (s,
MeN). 13C-NMR ((D6)DMSO): 165.3 (C¼O); 162.6 (C¼Se); 157.7, 141.7, 137.7, 131.4, 126.5, 113.6 (4
arom. C, C(2,4,5)); 134.5, 131.0, 130.6, 129.6, 129.4, 128.5, 128.4, 126.8 (14 arom. CH); 55.7 (MeO); 36.1
(CH2); 32.2 (MeN). HR-ESI-MS: 552.0965 ([M þ H]þ, C26H26N5O2SSeþ; calc. 552.0968).
2-{[(1,5-Dimethyl-4-phenyl-1H-imidazol-2-yl)sulfanyl]acetyl}-N-(4-methoxyphenyl)hydrazinecar-
boselenoamide (7d). Yield: 0.312 g (64%). Colorless crystals. M.p. 169 – 1718 (MeOH). IR (KBr): 3301s,
1
3154s (NH), 2947m, 1697vs (C¼O), 1530s, 1512s, 1245m. H-NMR ((D6)DMSO): 10.36 (br. s, NH);
10.01 (br. s, NH); 9.90 (br. s, NH); 7.35 – 6.81 (m, 9 arom. H); 3.77 (s, CH2); 3.73 (s, MeO); 3.57 (s, MeN);
2.33 (s, Me). 13C-NMR ((D6)DMSO): 179.7 (C¼O); 167.9 (C¼Se); 157.7, 138.9, 137.5, 135.2, 132.9, 126.5
(3 arom. C, C(2,4,5)); 128.7, 128.5, 127.2, 127.0, 113.6 (9 arom. CH); 55.7 (MeO); 36.6 (CH2); 31.5
(MeN); 10.7 (Me). HR-ESI-MS: 490.0810 ([M þ H]þ, C21H24N5O2SSeþ; calc. 490.0811).
2-{[(1,5-Dimethyl-4-phenyl-1H-imidazol-2-yl)sulfanyl]acetyl}-N-(4-fluorophenyl)hydrazinecarbose-
lenoamide (7e). Yield: 0.400 g (83%). Colorless crystals. M.p. 172 – 1738 (MeOH). IR (KBr): 3256s
(NH), 3055m, 1686vs (C¼O), 1541s, 1508s, 1212m. 1H-NMR ((D6)DMSO): 10.00 (br. s, NH); 7.50 – 6.65
(m, 9 arom. H); 3.70 (s, CH2); 3.60 (s, MeN); 2.30 (s, Me).

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2-{[(1-Benzyl-4,5-dimethyl-1H-imidazol-2-yl)sulfanyl]acetyl}-N-(4-fluorophenyl)hydrazinecarbose-
lenoamide (7f). Yield: 0.370 g (75%). Colorless crystals. M.p. 158 – 1608 (MeOH). IR (KBr): 3330m,
1
3126m (NH), 3030m, 1698vs (C¼O), 1552s, 1508s, 1215m. H-NMR ((D6)DMSO): 10.65 (br. s, NH);
7.60 – 6.80 (m, 9 arom. H); 5.20 (s, PhCH2); 3.45 (s, SCH2); 2.00, 1.75 (2s, 2 Me).
2-{[(1-Benzyl-4,5-dimethyl-1H-imidazol-2-yl)sulfanyl]acetyl}-N-(4-methoxyphenyl)hydrazinecarbo-
selenoamide (7g). Yield: 0.430 g (86%). Colorless crystals. M.p. 142 – 1448 (MeOH). IR (KBr): 3165m,
1
3127m (NH), 2955m, 1696vs (C¼O), 1510s, 1455m, 1243m. H-NMR ((D6)DMSO): 9.80 (br. s, NH);
8.30 (br. s, NH); 7.50 – 6.75 (m, 9 arom. H); 5.05 (s, PhCH2); 3.75 (s, MeO); 3.50 (s, SCH2); 1.95, 1.90 (2s,
2 Me).
4. General Procedure for the Synthesis of Hydrazides 6 [8]. To a soln. of a 1H-imidazole-2-thione
(1 mmol) in CH2Cl2 (5 ml) was added methyl 2-bromoacetate (1 mmol). The mixture was stirred for 48 h
at r.t., then, the solvent was evaporated i.v., and the residue was used immediately without further
purification. The oily residue was dissolved in EtOH (5 ml), and NH2NH2 · H2O (2 mmol) was added.
The mixture was heated at reflux for 4 h, the solvent was evaporated i.v., and the residue was crystallized
from MeOH.
2-[(1,4,5-Trimethyl-1H-imidazol-2-yl)sulfanyl]acetohydrazide (6a). Yield: 0.208 g (97%). Colorless
crystals. M.p. 135 – 1368 (MeOH). IR (KBr): 3336m, 3285m (NH), 2941m, 1683s (C¼O), 1551s, 1436vs,
1
1229m. H-NMR ((D6)DMSO): 9.88 (br. s, NH); 3.59 (s, CH2); 3.43 (s, MeN); 2.14, 2.11 (2s, 2 Me).
13C-NMR ((D6)DMSO): 170.3 (C¼O); 138.1, 134.0, 125.3 (C(2,4,5)); 35.0 (CH2); 30.8 (MeN); 12.7, 9.0 (2
Me). HR-ESI-MS: 215.0961 ([M þ H]þ, C8H15N4OSþ; calc. 215.0961).
2-[(1-Methyl-4,5-diphenyl-1H-imidazol-2-yl)sulfanyl]acetohydrazide (6b). Yield: 0.311 g (92%).
Colorless oil. IR (KBr): 3316m (NH), 2944m, 1672vs (C¼O), 1602s, 1503s, 1320m. 1H-NMR
((D6)DMSO): 9.99 (br. s, NH); 7.48 – 7.15 (m, 10 arom. H); 3.83 (s, CH2); 3.37 (s, MeN). 13C-NMR
((D6)DMSO): 170.2 (C¼O); 142.1, 137.9, 133.6, 131.0, 126.4 (2 arom. C, C(2,4,5)); 130.7, 130.1, 129.2,
129.0, 128.3, 126.8 (10 arom. CH); 34.3 (CH2); 31.6 (MeN). HR-ESI-MS: 339.1272 ([M þ H]þ,
C18H19N4OSþ; calc. 339.1274).
2-[(1,5-Dimethyl-4-phenyl-1H-imidazol-2-yl)sulfanyl]acetohydrazide (6c). Yield: 0.207 g (75%).
Colorless crystals. M.p. 112 – 1138 (MeOH). IR (KBr): 3301m, 3218m (NH), 2980m, 1697vs (C¼O),
1661s. 1H-NMR ((D6)DMSO): 9.33 (br. s, NH); 7.58 – 7.22 (m, 5 arom. H); 3.63 (s, CH2); 3.54 (s, MeN);
2.36 (s, Me). 13C-NMR ((D6)DMSO): 167.6 (C¼O); 138.8, 137.4, 135.5, 126.5 (1 arom. C, C(2,4,5)); 128.8,
127.2, 126.9 (5 arom. CH); 36.4 (CH2); 31.4 (MeN); 10.9 (Me). HR-ESI-MS: 277.1118 ([M þ H]þ,
C13H17N4OSþ; calc. 277.1118).
2-[(1-Benzyl-4,5-dimethyl-1H-imidazol-2-yl)sulfanyl]acetohydrazide (6d). Yield: 0.258 g (89%).
Colorless crystals. M.p. 131 – 1328 (MeOH). IR (KBr): 3321m, 3223m (NH), 2969m, 1671vs (C¼O),
1542s, 1496s, 1421m. 1H-NMR (CDCl3): 9.90 (br. s, NH); 7.45 – 6.85 (m, 5 arom. H); 5.05 (s, PhCH2); 3.80
(br. s, NH2); 3.50 (s, SCH2); 2.15, 2.00 (2s, 2 Me).
5. Synthesis of 8a. Procedure A. A mixture of 6b (1 mmol) and 4a (1.1 mmol) in DMF (10 ml) was
heated to 1008 for 6 h under air atmosphere. The black Se powder was filtered off and washed with
CH2Cl2 (10 ml). The combined filtrate was concentrated i.v., and the residue was crystallized from
acetone/MeOH 1:1.
Procedure B. Selenosemicarbazide 7b (1 mmol) in DMF (10 ml) was heated to 1008 for 6 h under air
atmosphere, and the mixture was worked up as described in Procedure A.
N-(4-Fluorophenyl)-5-{[(1-methyl-4,5-diphenyl-1H-imidazol-2-yl)sulfanyl]methyl}-1,3,4-oxadiazol-
2-amine (8a). Yield: 0.330 g (72%; Procedure A); 0.321 g (70%; Procedure B). Colorless crystals. M.p.
123 – 1248 (MeOH). IR (KBr): 3224s (NH), 2996m, 1504vs, 1238m. 1H-NMR ((D6)DMSO): 10.44 (br. s,
NH); 7.57 – 7.10 (m, 14 arom. H); 4.51 (s, CH2); 3.31 (s, MeN). 13C-NMR ((D6)DMSO): 181.9, 160.7,
157.6, 138.5, 131.2, 126.5, 119.1 (oxadiazol C(2,5), 4 arom. C, imidazole C(2’,4’,5’)); 130.9, 129.7, 129.6,
129.4, 129.0, 128.5, 126.9, 116.0 (14 arom. CH); 36.3 (CH2); 32.2 (MeN). HR-ESI-MS: 458.1448 ([M þ
H]þ, C25H21FN5OSþ; calc. 458.1445).
6. Synthesis of 1H-1,2,4-Triazole-5-selones 9a – 9d. Procedure A. A mixture of 6 (1 mmol) and the
corresponding isoselenocyanate 4 (1.1 mmol) in MeOH (10 ml) was heated at reflux for 4 h under N2.
Then, the product formed was filtered off, washed with MeOH, and crystallized from acetone/MeOH
(1:1).

Helvetica Chimica Acta – Vol. 96 (2013)
405
Procedure B. Selenosemicarbazide 7 (1 mmol) in MeOH (10 ml) was heated at reflux for 4 h under
N2. Then, the mixture was worked up as described in Procedure A.
2,4-Dihydro-4-(4-methoxyphenyl)-5-{[(1,4,5-trimethyl-1H-imidazol-2-yl)sulfanyl]methyl}-3H-1,2,4-
triazole-3-selone (9a). Yield: 0.260 g (64%; Procedure A). Colorless crystals. M.p. 190 – 1918 (MeOH).
IR (KBr): 3006m, 2917m, 2881m, 1515s, 1465s, 1251m, 1171m. 1H-NMR ((D6)DMSO): 7.45 – 6.70 (m, 4
arom. H); 3.95 (s, CH2); 3.85 (s, MeO); 3.30 (s, MeN); 2.05 (s, 2 Me). ESI-MS: 410 ([M þ H]þ), 432
([M þ Na]þ), 448 ([M þ K]þ).
2,4-Dihydro-4-(4-methoxyphenyl)-5-{[(1-methyl-4,5-diphenyl-1H-imidazol-2-yl)sulfanyl]methyl}-
3H-1,2,4-triazole-3-selone (9b). Yield: 0.301 g (57%; Procedure A); 0.317 g (60%; Procedure B).
1
Colorless crystals. M.p. 133 – 1358 (MeOH). IR (KBr): 3057m, 2928m, 1515s, 1454s, 1253m. H-NMR
((D6)DMSO): 14.20 (br. s, NH); 7.65 – 6.80 (m, 14 arom. H); 4.25 (s, CH2); 3.75 (s, MeO); 3.30 (s, MeN).
13C-NMR ((D6)DMSO): 160.3 (C¼Se); 157.8, 155.6, 150.1, 134.7, 131.4, 131.0, 130.9, 126.5 (triazol C(2), 4
arom. C, imidazol C(2’,4’,5’)); 129.6, 129.3, 128.5, 126.8, 126.6, 124.4, 119.1, 114.8 (14 arom. CH); 55.5
(MeO); 49.1 (MeN); 32.2 (CH2). HR-ESI-MS: 534.0859 ([M þ H]þ, C26H24N5OSSeþ; calc. 534.0862).
5-{[(1-Benzyl-4,5-dimethyl-1H-imidazol-2-yl)sulfanyl]methyl}-2,4-dihydro-4-(4-methoxyphenyl)-
3H-1,2,4-triazole-3-selone (9c). Yield: 0.410 g (86%; Procedure B). Colorless crystals. M.p. 164 – 1678
(MeOH). IR (KBr): 3066m, 2923m, 2857m, 1514s, 1254m, 1180m. 1H-NMR (CDCl3): 11.10 (br. s, NH);
7.35 – 6.70 (m, 9 arom. H); 5.05 (s, PhCH2); 3.80 (s, MeO); 3.75 (s, SCH2); 2.25, 1.95 (2s, 2 Me).
4-(4-Fluorophenyl)-2,4-dihydro-5-{[(1,4,5-trimethyl-1H-imidazol-2-yl)sulfanyl]methyl}-3H-1,2,4-tri-
azole-3-selone (9d). Yield: 0.104 g (25%; Procedure A). Colorless crystals. M.p. 154 – 1558 (MeOH). IR
1
(KBr): 3181m (NH), 3033m, 2893m, 1540s, 1508vs, 1227m. H-NMR ((D6)DMSO): 14.34 (br. s, NH);
7.45 – 7.38 (m, 4 arom. H); 4.02 (s, CH2); 3.28 (s, MeN); 2.04, 1.97 (2s, 2 Me). 13C-NMR ((D6)DMSO):
163.6 (C¼Se); 161.9, 151.3, 134.3, 133.9, 130.6, 126.7 (triazol C(2), 2 arom. C, imidazol C(2’,4’,5’)); 131.2,
116.6 (4 arom. CH); 31.1 (MeN); 28.9 (CH2); 13.0, 9.3 (2 Me). HR-ESI-MS: 398.0349 ([M þ H]þ,
C15H17FN5SSeþ; calc. 398.0348).
7. X-Ray Crystal-Structure Determination of 7a, 7d, and 9b (Table and Figs. 1 and 2)6). All
measurements were performed on a Nonius KappaCCD diffractometer [11] using graphite-monochro-
mated MoKa radiation (l 0.71073 ꢃ) and an Oxford Cryosystems Cryostream 700 cooler. The data
collection and refinement parameters are given in the Table, and views of the molecules 7d and 9b are
shown in Figs. 1 and 2, respectively. Data reduction was performed with HKL Denzo and Scalepack [12].
The intensities were corrected for Lorentz and polarization effects, and absorption corrections based on
the multi-scan method [13] were applied. Equivalent reflections, other than Friedel pairs in 9b, were
merged. The structures were solved by direct methods using SIR92 [14], which revealed the positions of
all non-H-atoms. In the case of 7a, the asymmetric unit contains two symmetry-independent molecules
7a and one disordered molecule of CHCl3. The solvent molecule could not be modelled satisfactorily, so
the SQUEEZE routine [15] of the program PLATON [16] was employed. This procedure, which allows
the disordered solvent molecules to be omitted entirely from the subsequent refinement model, gave
better refinement results, and there were no significant peaks of residual electron density to be found in
the voids of the structure. The procedure leaves one cavity of 303 ꢃ3 per unit cell. The electron count in
the disordered region was calculated to be 80 e per cavity. One molecule of CHCl3 per cavity
corresponded with the peaks of residual electron density observed prior to the application of the
SQUEEZE procedure. This yields 58 e and this estimate was used in the subsequent calculation of the
empirical formula, formula weight, density, linear absorption coefficient, and F(000). In all cases, the
non-H-atoms were refined anisotropically. In the case of 9b, the poor quality of the crystal and the
subsequent data meant that it was necessary to restrain atom C(15) to have pseudo-isotropic
displacement parameters. For 7a and 7d, the H-atoms of the NH groups were placed in the positions
indicated by a difference electron-density map, and their positions were allowed to refine together with
individual isotropic displacement parameters. All remaining H-atoms and all H-atoms of 9b were placed
in geometrically calculated positions and refined using a riding model where each H-atom was assigned a
6
)
CCDC-911592 – 911594 contain 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.cam.ac.uk/data_request/cif.

406
Helvetica Chimica Acta – Vol. 96 (2013)
Table. Crystallographic Data for Compounds 7a, 7d, and 9b
7a
7d
9b
Crystallized from
Empirical formula
CHCl3
acetone/EtOH
C21H23N5O2SSe
MeOH
C26H23N5OSSe ·
CH3OH
C16H21N5O2SSe ·
0.5 CHCl3
486.02
colorless, prism
0.20 ꢁ 0.25 ꢁ 0.30
160(1)
Formula weight [g molꢀ1
Crystal color, habit
Crystal dimensions [mm]
]
488.40
564.50
colorless, prism
0.15 ꢁ 0.17 ꢁ 0.20
160(1)
colorless, plate
0.05 ꢁ 0.12 ꢁ 0.25
160(1)
Temp. [K]
Crystal system
Space group
triclinic
P1
triclinic
P1
orthorhombic
Pna21
ꢀ
ꢀ
Z
4
2
4
Reflections for cell determination
2q Range for cell determination [8]
61134
4 – 55
19838
4 – 60
49048
4 – 50
Unit cell parameters:
a [ꢃ]
b [ꢃ]
c [ꢃ]
a [8]
10.3983(2)
12.7273(2)
15.9518(2)
84.0962(9)
88.1341(9)
82.6491(7)
2082.24(6)
1.550
9.5183(2)
9.7896(2)
12.7504(2)
95.948(1)
98.419(1)
114.092(1)
1055.20(4)
1.537
8.174(1)
46.768(7)
6.943(1)
90
90
90
2653.8(7)
1.413
1.526
f and w
50
b [8]
g [8]
V [ꢃ3]
Dx [g cmꢀ3
]
m(MoKa) [mmꢀ1
Scan type
]
2.117
f and w
55
1.906
f and w
60
2q(max) [8]
Transmission factors (min; max)
Total reflections measured
Symmetry independent reflections
Reflections with I > 2s(I)
Reflections used in refinement
Parameters refined; restraints
Final R(F) [I > 2s(I) reflections]
wR(F2) (all data)
0.610; 0.686
47740
9492
7535
9491
485; 0
0.0435
0.1090
0.0631; 0
1.070
0.585; 0.756
30512
6143
5412
6143
283; 0
0.0617
0.1739
0.1216; 0.7324
1.075
0.625; 0.934
11242
4008
2548
4008
329; 7
0.0876
0.2268
0.0825; 11.7070
1.152
Weighting parameters [a; b]a)
Goodness of fit
Secondary extinction coefficient
Final Dmax/s
0.0148(8)
0.003
0.63; ꢀ 0.52
–
0.027(2)
0.001
1.02; ꢀ 0.92
0.001
1.65; ꢀ 0.74
D1 (max; min) [e ꢃꢀ3
]
a) wꢀ1 ¼ s2(F2o ) þ (aP)2 þ bP where P ¼ (Fo2 þ 2F2c )/3
fixed isotropic displacement parameter with a value equal to 1.2 Ueq of its parent atom (1.5 Ueq for Me
groups). The refinement of each structure was carried out on F2 using full-matrix least-squares
procedures, which minimized the function Sw(F2o ꢀ Fc2 )2. In the cases of 7a and 9b, a correction for
secondary extinction was applied, and one reflection of 7a, whose intensity was considered to be an
extreme outlier, was omitted from the final refinement. For 9b, refinement of the absolute structure
parameter [17] yielded a value of ꢀ 0.02(3), which confidently confirms that the refined model
corresponds with the true absolute structure. Neutral atom-scattering factors for non-H-atoms were
taken from [18a], and the scattering factors for H-atoms were taken from [19]. Anomalous dispersion
effects were included in Fc [20]; the values for f’ and f’’ were those of [18b]. The values of the mass

Helvetica Chimica Acta – Vol. 96 (2013)
407
attenuation coefficients are those of [18c]. All calculations were performed using the SHELXL97 [21]
program.
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Received November 22, 2012