Thia- and Selena-heterocycles containing cycloamidine substructures: Ring contraction reactions of 1,3,4-thia-/selenadiazines

Article abstract of DOI:10.1515/znb-2008-0408

1,3,4-Thia/selena-diazines proved to be suitable starting materials for ring contraction reactions. Treatment with acetic acid/water mixtures leads to highly substituted 1,3,4-thia/selenadiazoles. In addition, the selenadiazoles formed undergo a fast Dimroth-rearrangement to finally yield derivatives of 1,2,4-triazole. The structures of all new derivatives were confirmed by NMR experiments, mass spectroscopy, elemental analysis and X-ray structural analysis.

Full text of DOI:10.1515/znb-2008-0408

Thia- and Selena-Heterocycles Containing Cycloamidine Substructures:
Ring Contraction Reactions of 1,3,4-Thia-/Selenadiazines
Jan Fleischhauera, Rainer Beckerta, David Horniga, Wolfgang Gu¨nthera, Helmar Go¨rlsb,
and Vera Klimesovac
a Institute of Organic and Macromolecular Chemistry, Friedrich Schiller University,
Humboldtstraße 10, D-07743 Jena, Germany
b Institute of Inorganic and Analytical Chemistry, Friedrich Schiller University,
Lessingstraße 8, D-07743 Jena, Germany
c Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University,
500 05 Hradec Kralove, Czech Republic
Reprint requests to Prof. Dr. R. Beckert. E-mail: Rainer.Beckert@uni-jena.de
Z. Naturforsch. 2008, 63b, 415 – 424; received January 8, 2008
In memoriam to Ariane Beutler (1978 – 2007)
1,3,4-Thia/selena-diazines proved to be suitable starting materials for ring contraction reactions.
Treatment with acetic acid/water mixtures leads to highly substituted 1,3,4-thia/selenadiazoles. In
addition, the selenadiazoles formed undergo a fast Dimroth-rearrangement to finally yield derivatives
of 1,2,4-triazole. The structures of all new derivatives were confirmed by NMR experiments, mass
spectroscopy, elemental analysis and X-ray structural analysis.
Key words: Ring Contraction, Dimroth Rearrangement, Triazoles, Thiadiazoles, Selenadiazoles
Introduction
Being part of the heterocarbonyl systems in deriva-
tives 2 and 3, the imino substructures allow partial
modifications of their backbones. Therefore one aim
of our work was the formation of the corresponding
oxo derivatives. Due to the different electronic and
steric environments of the imino groups, several
regioisomers 4, 5 as well as the dioxo derivatives 6
could be expected [5]. In addition, these functional-
ities are often the subject of 1,3-acyl rearrangement
reactions, finally resulting in derivatives of types 7
and 8. During the course of our previous research,
we have studied such Dimroth rearrangements on
different five-membered heterocycles. As an important
result we showed that they can be employed in the
synthesis of new conjugated thioxo systems [6].
∆2-1,2-diazetines of type 1 are easily accessible
by cyclization reactions of monoalkyl-hydrazines with
bis-imidoylchlorides of oxalic acid [1]. Such four-
membered heterocycles, which contain two nitrogen
atoms in the ring positions 1 and 2, are quite rare, and
only a few examples were reported. Therefore their ap-
plication in synthetic chemistry is rather limited [2].
Previously, we showed that due to their inherent ring
strain and weak bonds, ∆2-1,2-diazetines 1 are quite
useful in a number of versatile ring transformation re-
actions [3]. For example, compounds of type 1 react
with isothiocyanates and isoselenocyanates in a ring
enlargement reaction to yield 1,3,4-thiadiazines 2 and
1,3,4-selenadiazines 3, respectively, with a wide vari-
ability of substitution patterns (Scheme 1) [4].
Furthermore, the ring contraction reactions of 1,3,4-
thiadiazines 2 are well studied in the literature. The
R
R
N
O
N
O
N
H3C
H3C
N
N
E
H3C
N
N
/acetone/rt
E
R
N
C
R-N=C=E /THF/rt
E = S, Se
N
N
E
Ar
N
Ar
E = S, Se
Ar
N
NH
Ar
NH
Ar
NH
Scheme 1. Ringtransformations
of 1,2-diazetines 1 to yield 1,3,4-
thia(selena)diazines 2, 3.
Ar
2
3
E = S
E = Se
1
2 E = S
3 E = Se
c
0932–0776 / 08 / 0400–0415 $ 06.00 ꢀ 2008 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com
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J. Fleischhauer et al. · Thia- and Selena-Heterocycles Containing Cycloamidine Substructures
4 E = S/Se, Y = NAr, Z = O
9 Y = NR,
Z = N-NHMe
11
5 E = S/Se, Y = O Z = NR 10 Y = N-NHMe, Z = NR
6 E = S/Se, Y = O Z = O
Scheme 2. Possible products of hydrolysis
and ring contraction reactions starting from 2
and 3.
7 E = NR, Y = NAr, Z = S/Sc
8 E = NAr, Y = S/Sc,Z = NR
2a E = S, Ar/Arꢀ = Tol,
2b E = S, Ar/Arꢀ = Tol,
2c E = S, Ar/Arꢀ = Tol,
2d E = S, Ar/Arꢀ = Tol,
2e E = S, Ar/Arꢀ = Tol,
R = Me
R = Et
R = Bn
R = PMP
R = Bz
12a
12b
12c
12d
12e
E = S, Ar = Tol,
E = S, Ar = Tol,
E = S, Ar = Tol,
E = S, Ar = Tol,
E = S, Ar = Tol,
R = Me
R = Et
R = Bn
R = PMP
R = Bz
2f E = S, Ar = 4-Br-Ph, Arꢀ = Mesityl,R = 4-tBu-Ph 12f
E = S, Ar = 4-Br-Ph, R = 4-tBu-Ph
Scheme 3. Hydrolysis
reaction of heterodi-
azines 2a – f/3a – c.
3a E = Se, Ar/Arꢀ = Tol,
3b E = Se, Ar/Arꢀ = Tol,
3c E = Se, Ar/Arꢀ = Tol,
R = PMP
13a/15a E = Se, Ar = Tol,
R = PMP
R = 4-Br-Ph 13b/15b E = Se, Ar = Tol,
R = 4-Br-Ph
R = 4-tBu-Ph 13c/15c E = Se, Ar = Tol,
R = 4-tBu-Ph
products obtained show a remarkable dependence on
the reaction conditions as well as on their substi-
tution patterns [7]. For example, different 1,3-thiaz-
oles were synthesized by the acid-catalyzed hydrolysis
of 2 [8]. Similarly, 2-aminothiazoles 9 or thiazolyl-2-
hydrazines 10 proved to be possible products in a ring
contraction reaction. This useful method was recently
employed by Pfeiffer et al. in order to make pyrazoles
accessible which possess an unusual pattern of sub-
stituents [9]. In our case, this protocol should lead to
pyrazoles of type 11 allowing further transformations
which offer good requirements for the formation of
metal chelate complexes (Scheme 2). These heterocy-
cles should be of interest with respect to biological and
pharmaceutical applications [10]. However, difficulties
in the preparation of such compounds hamper their ap-
plication.
Fig. 1. Molecular structure of derivative 12b in the solid state
as determined by X-ray analysis.
any of the expected products listed in Scheme 2. In
a complex reaction, not only the 1,3,4-thia-/selenadi-
azoles 12/13 were isolated as main products but also
the 1,3,4-triazoles 15/16 were formed. Nearly the same
product distribution was observed upon treatment of
the starting materials 2/3 in glacial acetic acid. The
acetylated arylamines 14 were formed as byproducts in
equimolar amounts (Scheme 3). The structural assign-
ment shown in Scheme 3 was confirmed by NMR and
MS data, elemental analysis and single crystal X-ray
structural analysis for the compounds 12b, 12e, 13a
and 15a (Figs. 1 – 3).
Results and Discussion
Surprisingly, the hydrolysis reaction of 2 or 3 in
acetic acid/water mixtures (10 : 1) did not result in
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J. Fleischhauer et al. · Thia- and Selena-Heterocycles Containing Cycloamidine Substructures
417
Fig. 2. Molecular structure of derivative 13a in
the solid state as determined by X-ray analysis.
Common synthetic methods to obtain 2-imino-
substituted 1,3,4-thia-/selenadiazoles often apply the
[2+3]-cycloaddition reaction between hydrazonoyl
halides and thio-/selenocarbonyl derivatives [11]. Re-
cently, Firsova et al. reported a 2-thioxo-1,3-thiazole
as dipolarophile, which strongly limited the variability
of substituents at the imino group [11f]. Other authors
used carbodithioates and thiocarbamates, respectively,
as thioxo components in order to prepare 2-imino-
substituted 1,3,4-thiadiazoles [11a– e]. To the best of
our knowledge, only one example exists in the litera-
ture: the ring contraction reaction of 6-hydroxyimino-
tetrahydro-l,3,4-thiadiazine-2-thiones to 3-methyl-5-
phenyl-1,3,4-thiadiazole-2(3H)-thiones [12]. Analo-
gous ring transformation reactions finally leading to
highly substituted 1,3,4-thiadiazoles 12 and 1,3,4-
selenadiazoles 13 are unknown.
Fig. 3. Molecular structure of derivative 15a in the solid state
as determined by X-ray analysis.
In order to test the scope and limitations of this
mild ring contraction reaction, a variety of aliphatic
as well as aromatic substituted thia/selenadiazines was
remarkably stable in solution. Even after standing in
CDCl3 for a prolonged period, no decomposition of the
employed. As demonstrated in Scheme 3, this method selenacycles 13 was detected by NMR spectroscopy.
can be applied to a wide range of substituents at the In contrast, the selenones 15 decompose by irradiation
educts. Due to different electronic and steric effects,
the achieved yields and the reaction times differ. In
the case of 1,3,4-selenadiazines 3, a second side re-
action was observed. Under the conditions applied for
hydrolysis of derivatives 3, a further product was iso-
lated in a yield of approximately 20 %. The X-ray
crystal structural analysis revealed that an additional
Dimroth rearrangement leading to 4-aryl-1-methyl-5-
selenoxo-1,2,4-triazole-3-carboxamide 15 took place
(Scheme 3, Fig. 3). The easy cleavage of the C(2)–Se
bond, which is considerably elongated compared to
the C(2)–S bond, might be the explanation for this
final rearrangement. Similarly, 3-selenoxo-1,2,4-triaz-
oles were obtained by reactions of isoselenocyanates
with phenylhydrazinesor S-methyl-isothiosemicarbaz-
ides [13].
with UV light under the loss of selenium.
In both 12b and 13a, the proton is located at the ex-
ocylic atom N(3) and forms a very weak intramolecu-
˚
lar hydrogen bond to N(2) [N(2)–H = 2.42 A (12b);
˚
2.39 A (13b)]. The ring bonding angles are signifi-
cantly influenced by the chalcogen atom. A relatively
small C1–E–C2 angle (12b = 88.29◦; 13b = 83.83◦)
is compensated by a widening of the C1–N1–N2 and
N2–C2–E angles. The arylamide moiety as well as the
imine substituent at N4 show a cis-arrangement with
respect to the chalcogen atom. The arylamide moiety is
slightly twisted out of plane of the heterodiazole sub-
structure. In the 13C NMR spectra, the carbon of the
N–C=Se group in 15 resonates at a significantly lower
field than the one of the Se–C=N in 13 (δ ≈ 140 ppm
[13], 170 ppm [15]). In their 77Se NMR spectra the sig-
Compounds 12/13 are colorless (R = aliphatic) or nals for the selenium nucleus appear at about 500 ppm
pale yellow (R = aromatic) crystalline solids that are for 13 and 100 ppm for 15.
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418
J. Fleischhauer et al. · Thia- and Selena-Heterocycles Containing Cycloamidine Substructures
Scheme 5. Postulated mechanism of the hydrolysis reaction
of heterocycles 2/3.
position. Then the attack of water at C(6) causes a bond
cleavage between C(6) and the chalcogen atom E. The
resulting semicyclic aminal B is not stable under these
Scheme 4. Regioselective ring transformation reactions of 1a
and 2f.
In view of mechanistic investigations for these ring conditions and quickly decomposes under acid catal-
ysis into H+/Arꢀ-NH2 and 12 or 13. The transforma-
contraction reactions, unsymmetrically substituted ∆2-
1,2-diazetines 1a with respect to their aromatic sub- tion of 13 into 15 can easily be explained by a Dimroth
stituents (Ar = Arꢀ) were used. These derivatives could rearrangement reaction which often takes place under
acidic catalysis or at higher temperatures. Finally, the
eliminated arylamine (Arꢀ-NH2) is acetylated to yield
be obtained by a four-step protocol starting from ethyl
(chlorocarbonyl) formate and 2,4,6-trimethylbenzen-
amine. The four-membered ring system of 1a proved derivative 14.
to be unstable and was thus applied directly in the ring
transformation reaction with 4-tert-butylphenyl isoth-
iocyanate without further purification. The structure of
product 2f was confirmed by NMR and mass spec-
troscopy, elemental analysis and X-ray structural anal-
ysis. The arrangement of substituents in 2f clearly un-
derlines the regioselectivity of this cycloacylation re-
action (Scheme 4).
The hydrolysis reaction of 2f (Ar = Arꢀ) resulted in
only one product with the 4-bromophenyl substituent
(Ar = 4-BrC6H4) at the position of the aromatic amide.
Consequently, in the course of the hydrolysis, the mesi-
dine moiety is liberated (Ar = 2,4,6-(CH3)3C6H2). This
important experimental finding suggests the following
mechanism (Scheme 5): First, a protonation reaction
under formation of the iminium salt A takes place. Due
to the existence of amino/imino as well as amidine sub-
structures in the molecules of 2/3, dynamic protonation
and deprotonation equilibria in acidic media exist. The
iminium salt A can be regarded as a key intermediate
Generally, the hydrolysis reaction could be applied
to acyl-substituted derivatives as shown in example 2e.
However, influenced by the higher electrophilicity of
the ring carbon atoms, an increasing number of side
reactions was observed. The products and mechanisms
of their formation have not yet been fully investi-
gated. For example, no thiadiazole derivatives could
be isolated upon hydrolysis of the acetyl derivative 2g
(Scheme 6).
We assume that in this case a desacetylation reaction
is the first step which generates the free NH group (C)
followed by the nucleophilic attack of water and a ring-
opening/ring-closure sequence (D). The final cycliza-
tion product 16, a derivative of 1,2,4-triazole with an
exocyclic thiocarboxamide substructure (Scheme 6),
was isolated in about 40 % yield. The result of a sin-
gle crystal X-ray analysis clearly demonstrated that
the NH nitrogen was integrated into the five-membered
ring (Fig. 4).
Biological tests of similar compounds such as 3-
in which the chalcogen atom attacks the activated C(5)- phenyl-2-N-arylimino-2,3-dihydro-1,3,4-thiadiazoles
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J. Fleischhauer et al. · Thia- and Selena-Heterocycles Containing Cycloamidine Substructures
419
were isolated as additional products. This new ring
contraction method is applicable to a wide range of
substituents R as well as Ar in the starting materials.
We are currently investigating further ring transforma-
tion reactions, especially those of corresponding acyl
derivatives. The results will be reported in a forthcom-
ing article.
Experimental Section
All solvents were dried and purified by standard tech-
niques. The reagents employed were of commercial qual-
ity (Aldrich, Lancaster, Fluka, Merck). Reactions were mon-
itored by TLC using aluminum plates coated with Al2O3
or SiO2 from Fluka. Melting points were measured with a
digital detector system KSPS 1000 from Kru¨ss and with a
B-545 (Boetius system) from Bu¨chi and are uncorrected.
The 1H and 13C NMR spectra were obtained on a Bruker
AC 250 (250 MHz) or Bruker DRC-400 (400 MHz) spec-
trometer. 77Se NMR spectra (76 MHz) were obtained on
a Bruker DRC-400 spectrometer using Me2Se as external
(
77Se) standard. Mass spectra were measured on a spectrom-
Scheme 6. Acidic hydrolysis of thiadiazine 2g.
eter Trio 2000 from Fisons. Elemental analyses were carried
out with an automatic analyzer Varion EL III from Elementar
Analysensysteme GmbH.
Crystal structure determinations
Intensity data for the compounds were collected on a No-
nius KappaCCD diffractometer using graphite-monochrom-
atized MoKα radiation. The data were corrected for Lorentz
and polarization effects but not for absorption [14, 15].
The structures were solved by Direct Methods (SHELS-
Fig. 4. Molecular structure of derivative 16 in the solid state
as determined by X-ray analysis.
2
97) and refined by full-matrix least-squares methods on Fo
(SHELXL-97) [16, 17]. In all cases the hydrogen atom of the
amino group N(3) was located in a difference Fourier syn-
thesis and refined isotropically. The other hydrogen atoms
were included at calculated positions with fixed thermal pa-
rameters. All non-hydrogen atoms were refined anisotrop-
ically. The program XP was used for structure represen-
tations [18]. Crystal data and refinement details are sum-
marized in Table 1, selected bond lengths and angles in
Table 2.
N1-(4-Bromo-phenyl)-N2-mesityl-oxalodiimidoyl dichlo-
ride was prepared starting from ethyl (mesitylamino)oxo-
acetate [19a] which was heated under reflux with 4-bromo-
aniline in xylene for several days to give the N1-(4-bromo-
phenyl)-N2-mesityloxalamide [19b]. The latter was chlori-
nated following the general protocol [19c] for bis-imido-
ylchlorides (in toluene with phosphorus pentachloride) to
give the N1-(4-bromo-phenyl)-N2-4-mesityl-oxalodiimidoyl
[10c] have shown that they exhibit antibacterial
and fungicide activity. First biological tests of our
compounds showed activity against M. tuberculosis,
M. avium und M. kansasii which is similar to that
of the reference standard (INH). The modification
of these derivatives with respect to new leading
structures, especially against resistant bacterial and
fungicide strains, will be the subject of further
studies.
Conclusions
A new and useful method for the synthesis of 1,3,4-
thia-/selenadiazoles 12/13 was presented employing
easily accessible heterodiazines 2, 3 (E = S, Se). In
the series of selenacycles, 1,3,4-triazoles of type 15 dichloride [19d].
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420
J. Fleischhauer et al. · Thia- and Selena-Heterocycles Containing Cycloamidine Substructures
Table 1. Crystal data and refinement details for the X-ray structure determinations.
Compound
Formula
2f
12b
C13H16N4OS
276.36
−90(2)
monoclinic
P21/n
9.7860(4)
11.7752(4)
12.2790(5)
90.00
100.585(2)
90.00
1390.86(9)
4
1.320
2.31
12e
13a
15a
16
C29H32BrN5S
562.57
C18H16N4O2S
352.41
C18H18N4O2Se
401.32
C18H18N4O2Se
401.32
C11H12N4OS
248.31
−90(2)
orthorhombic
Pbca
Mw, g · mol−1
T, ◦C
−90(2)
−90(2)
monoclinic
P21/c
7.9533(3)
20.0780(6)
10.5065(4)
90.00
94.331(2)
90.00
1672.95(10)
4
1.399
2.13
11808
2778
3836/0.0427
0.047
0.127
−90(2)
monoclinic
P21/n
8.4055(3)
19.0862(4)
10.9646(4)
90.00
96.430(2)
90.00
1747.97(10)
4
1.525
21.67
12217
3097
3986/0.0483
0.034
0.078
−90(2)
monoclinic
P21/c
5.6757(5)
28.302(3)
11.5359(9)
90.00
104.148(5)
90.00
1796.8(3)
4
1.484
21.09
6761
2093
3565/0.0715
0.061
0.132
Crystal system
Space group
triclinic
¯
P1
˚
a, A
9.3843(4)
11.5017(7)
13.9601(7)
104.602(2)
98.079(3)
101.403(3)
1400.26(13)
2
1.334
15.69
9917
4524
8.8695(3)
9.1237(2)
30.2125(8)
90.00
90.00
90.00
2444.88(12)
8
1.349
2.54
14828
1962
2797/0.0620
0.045
0.123
1.033
˚
b, A
˚
c, A
α, deg
β, deg
γ, deg
3
˚
V, A
Z
ρ, g · cm−3
µ, cm−1
Measured data
Data with I ≥ 2σ(I)
Unique data / Rint
R1 [I ≥ 2σ(I)]a
wR2 (all data, on F2)a
Sb
9182
2316
3149/0.0408
0.040
0.109
6347/0.0324
0.045
0.096
1.008
1.008
1.007
1.005
1.015
−3
˚
∆ρfin (max/min), e A
0.33/−0.50
0.21/−0.22
0.58/−0.22
0.38/−0.45
0.50/−0.54
0.32/−0.34
CCDC No.c
671007
671008
671009
671010
671011
671012
Definition of the R indices: R1 = (ΣꢂFo| − |Fcꢂ)/Σ|Fo|; wR2 = {Σ[w(Fo − Fc2)2]/Σ[w(Fo2)2]}
with w−1 = σ2(Fo2) + (aP)2; S =
a
2
1/2
b
{Σ[w(Fo −Fc2)2]/(No −Np)}
;
CCDC 671007 – 671012 contain the supplementary crystallographic data for this paper. These data can
2
1/2 c
be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data request/cif.
Table 2. Selected bond lengths
Compound
2f
12b
12e
13a
15a
16
˚
(A) and angles (deg) for 2, 12,
E = S1
1.780(2)
1.766(2)
E = S
E = S1
E = Se1
E = N4
E = N3
13, 15 and 16 with estimated
standard deviations in paren-
theses.
(C1)–(E)
(C2)–(E)
1.7773(16) 1.7488(19) 1.932(2)
1.7401(17) 1.735(2)
1.283(2)
1.383(2)
1.271(2)
1.374(6) 1.365(2)
1.378(6) 1.367(3)
1.298(6) 1.305(3)
1.336(6) 1.359(3)
1.879(2)
1.281(3)
1.386(3)
1.272(3)
1.357(2)
(C2)–(N2)
(C1)–(N1)
(C1)–(N4)
(N1)–(N2)
(C1)–(Se1)
(C1)–(O1)
(C3)–(S1)
(C3)–(N2)
(C3)–(C2)
1.290(3)
1.355(2)
1.308(2)
1.365(3)
1.387(3)
1.3573(18) 1.364(2)
1.375(5) 1.381(2)
1.844(5)
1.241(2)
1.650(2)
1.289(3)
1.473(3)
(C1)–(E)–(C2)
103.17(11) 88.29(8)
87.67(9)
83.83(9)
107.1(4) 107.82(18)
(C1)–(N1)–(N2) 126.93(19) 117.30(13) 117.35(16) 119.64(18) 112.6(4) 112.34(16)
(N2)–(C2)–(Y)
116.28(12) 116.76(14) 116.43(16) 111.3(4) 112.04(17)
(N2)–(C3)–(C2) 126.5(2)
1-Methyl-3-(mesitylamino)-4-(4-bromophenylimino)-∆2-
1,2-diazetine (1a)
Ring transformation reaction of 1a with 4-tert-butylphen-
yl-isothiocyanate to yield 2-(4-tert-butylphenylimino)-6-(4-
bromophenylimino)-3,6-dihydro-N-mesityl-3-methyl-2H-
1,3,4-thiadiazin-5-amine (2f)
A THF solution (30 mL) of the bis-imidoyl chloride de-
scribed above (0.8 g, 2 mmol) and TEA (1.5 mL, 10 mmol)
was cooled to 0 ◦C, and a solution of methylhydrazine
To the cooled THF solution (30 mL) of 1a (0.74 g,
(0.11 mL, 2 mmol) in 10 mL of THF was added drop- 2 mmol) was added dropwise a solution of 4-tert-butylphen-
wise. After complete conversion (as monitored by TLC), yl-isothiocyanate (0.39 g, 2 mmol) in 5 mL of THF. The
the reaction mixture was filtered to remove the TEA · HCl reaction mixture was warmed up to r. t. and stirred for 6 h.
and was used without further purification for the following The solvent was removed in vacuo, and the residue was puri-
reaction.
fied by column chromatography (Al2O3, chloroform/heptane
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J. Fleischhauer et al. · Thia- and Selena-Heterocycles Containing Cycloamidine Substructures
421
2 : 1). Recrystallization from chloroform/heptane gives the 56. – C13H16N4OS (276.4): calcd. C 56.50, H 5.84, N 20.27,
heterodiazine 2f as yellow needles (0.87 g, 77 % yield), m. p. S 11.60; found C 56.52, H 5.95, N 20.22, S 11.46.
◦
1
186.8 – 187.1 C. – H NMR (250 MHz, CDCl3): δ = 7.47
(d, J = 8.8 Hz, 2H, CH), 7.29 (d, J = 8.8 Hz, 2H, CH),
6.95 (s, 2H, CH), 6.90 – 6.71 (m, 5H, NH, CH), 3.78 (s, 3H,
CH3N), 2.33, 2.31 (2s, 9H, CH3), 1.31 (s, 9H, C(CH3)3). –
13C NMR (63 MHz, CDCl3): δ = 146.5, 146.0, 145.4, 144.2,
140.9, 135.8, 135.5, 135.0, 133.6, 132.5, 128.8, 126.2, 121.8,
121.2, 118.9 (Caryl, Cimin), 43.5 (CH3N), 34.3 (C(CH3)3),
31.4 (C(CH3)3), 21.0, 18.7 (CH3). – MS (DEI): m/z = 563
[M, 81Br]+, 546, 380, 365, 247, 189, 176, 146, 131, 117,
91, 77, 41. – C29H32BrN5S (562.6): calcd. C 61.91, H 5.73,
N 12.45, S 5.70; found C 61.85, H 5.68, N 12.46, S 5.80.
5-Benzylimino-4,5-dihydro-4-methyl-N-p-tolyl-1,3,4-thiadi-
azole-2-carboxamide (12c)
This compound was obtained as colorless prisms (192 mg,
◦
57 % yield), m. p. 140 C. – 1H NMR (250 MHz, CDCl3):
δ = 8.29 (s, 1 H, NH), 7.50 (d, J = 8.4 Hz, 2 H, CH), 7.33
(m, 5 H, CH), 7.18 (d, J = 8.2 Hz, 2 H, CH), 4.37 (s, 2 H,
CH2), 3.73 (s, 3 H, CH3N), 2.34 (s, 3 H, CH3). – 13C NMR
(63 MHz, CDCl3): δ = 158.0, 155.6, 141.6, 139.1, 134.6,
134.3, 129.7, 128.4, 127.6, 127.0, 119.7 (Caryl, Cimin), 60.6
(CH2), 36.0 (CH3N), 20.9 (CH3). – MS (DEI): m/z = 338
[M]+, 261, 204, 160, 133, 106, 91, 65, 56. – C18H18N4OS
(338.4): calcd. C 63.88, H 5.36, N 16.56, S 9.47; found
C 63.70, H 5.39, N 16.54, S 9.43.
Hydrolysis reaction of heterodiazines 2a – g and 3a – c to
yield the heterodiazoles 12a – f/13a – c and heterotriazoles
15a – c/16
General procedure
4,5-Dihydro-4-methyl-5-(4-methoxyphenylimino)-N-p-tolyl-
1,3,4-thiadiazole-2-carboxamide (12d)
A solution of 1 mmol of the corresponding heterodiazine,
10 mL of glacial acetic acid and 1 mL of water was stirred
for approx. 2 h at 100 – 110 C. After complete conversion
(monitored by TLC; Al2O3; toluene/acetone 20 : 1), the sol-
vent was removed in vacuo, and the residue was purified
by column chromatography (Al2O3, toluene/acetone 50 : 1).
Recrystallization from chloroform/heptane gives heterodia-
zoles 12/13 and triazoles 15/16.
This compound was obtained as pale yellow prisms
◦
◦
1
(227 mg, 64 % yield), m. p. 109 C. – H NMR (250 MHz,
CDCl3): δ = 8.32 (s, 1 H, NH), 7.50 (d, J = 8.4 Hz, 2 H,
CH), 7.16 (d, J = 8.2 Hz, 2 H, CH), 7.02 (d, J = 9.2 Hz, 2 H,
CH), 6.91 (d, J = 9.2, 2 H, CH), 3.81 (s, 3 H, CH3O), 3.75
(s, 3 H, CH3N), 2.33 (s, 3 H, CH3). – 13C NMR (63 MHz,
CDCl3): δ = 156.7, 156.3, 155.5, 144.1, 141.5, 134.6, 134.3,
129.7, 121.6, 119.7, 114.9 (Caryl, Cimin), 55.5 (CH3O), 36.2
(CH3N), 20.9 (CH3). – MS (DEI): m/z = 354 [M]+, 338,
206, 165, 147, 106, 91, 78, 65. – C18H18N4O2S (354.4):
calcd. C 61.00, H 5.12, N 15.81, S 9.05; found C 60.95,
H 5.06, N 15.69, S 8.75.
4,5-Dihydro-4-methyl-5-(methylimino)-N-p-tolyl-1,3,4-thia-
diazole-2-carboxamide (12a)
This compound was obtained as colorless prisms (150 mg,
◦
57 % yield), m. p. 143 C. – 1H NMR (250 MHz, CDCl3):
δ = 8.28 (s, 1 H, NH), 7.50 (d, J = 8.4 Hz, 2 H, CH), 7.17 (d,
J = 8.0 Hz, 2 H, CH), 3.66, 3.09 (2 s, 6 H, CH3N), 2.34 (s, 3
H, CH3). – 13C NMR (63 MHz, CDCl3): δ = 159.1, 155.5,
141.9, 134.6, 134.2, 129.7, 119.7 (Caryl, Cimin), 43.1, 36.0
(CH3N), 20.9 (CH3). – MS (DEI): m/z = 262 [M]+, 174,
146, 133, 106, 102. – C12H14N4OS (262.3): calcd. C 54.94,
H 5.38, N 21.36, S 12.22; found C 54.98, H 5.36, N 21.33,
S 12.09.
5-Benzoylimino-4,5-dihydro-4-methyl-N-p-tolyl-1,3,4-thia-
diazole-2-carboxamide (12e)
This compound was obtained as pale yellow prisms
(140 mg, 40 % yield), m. p. 200 ◦C (dec.). – 1H NMR
(250 MHz, CDCl3): δ = 8.41 (s, 1 H, NH), 8.32 (m, 2 H,
CH), 7.48 (m, 5 H, CH), 7.16 (d, J = 8.2 Hz, 2 H, CH), 4.09
(s, 3 H, CH3N), 2.32 (s, 3 H, CH3). – 13C NMR (63 MHz,
CDCl3): δ = 174.4, 167.1 (C=O), 155.3, 151.9, 135.5, 135.0,
134.0, 132.4, 129.7, 129.6, 128.2, 119.8 (Caryl, Cimin), 38.1
(CH3N), 20.9 (CH3). – MS (DEI): m/z = 352 [M]+, 275,
218, 164, 142, 105, 77, 51. – C18H16N4O2S (352.4): calcd.
C 61.35, H 4.58, N 15.90, S 9.10; found C 61.11, H 4.60,
N 15.84, S 9.32.
5-Ethylimino-4,5-dihydro-4-methyl-N-p-tolyl-1,3,4-thiadi-
azole-2-carboxamide (12b)
This compound was obtained as colorless prisms (259 mg,
◦
97 % yield), m. p. 129 C. – 1H NMR (400 MHz, CDCl3):
δ = 8.29 (s, 1 H, NH), 7.51 (d, J = 8.6 Hz, 2 H, CH),
7.17 (d, J = 8.3 Hz, 2 H, CH), 3.65 (s, 3 H, CH3N), 3.18
(q, J = 7.3 Hz, 2 H, CH2), 2.35 (s, 3 H, CH3), 1.31 (t,
J = 7.3 Hz, 3 H, CH3) – 13C NMR (100 MHz, CDCl3):
5-(4-tert-Butylphenylimino)-4,5-dihydro-4-methyl-N-(4-
bromophenyl)-1,3,4-thiadiazole-2-carboxamide (12f)
δ = 156.7, 155.7, 141.5, 134.5, 134.4, 129.7, 119.7 (Caryl
,
This compound was obtained as pale yellow needles
Cimin), 52.2 (CH2), 35.9 (CH3N), 20.9, 15.4 (CH3). – MS (285 mg, 64 % yield), m. p. 182.5 – 182.9 ◦C (dec.). –
(DEI): m/z = 276 [M]+, 261, 174, 160, 146, 133, 106, 91, 69, 1H NMR (250 MHz, CDCl3): δ = 8.37 (s, 1H, NH),
Unauthenticated
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422
J. Fleischhauer et al. · Thia- and Selena-Heterocycles Containing Cycloamidine Substructures
7.60 – 7.30 (m, 6H, CH), 7.02 (d, J = 8.8 Hz, 2H, CH), 77Se NMR (76 MHz, CDCl3): δ = 521.2 (s). – MS (DEI):
3.77 (s, 3H, CH3N), 1.34 (s, 9H, C(CH3)3). – 13C NMR m/z = 428 [M, 80Se]+, 413, 224, 206, 173, 158, 145, 133,
(63 MHz, CDCl3): δ = 156.3, 155.6, 147.7, 147.2, 141.3, 117, 106, 91, 77, 65, 28. – C21H24N4OSe (427.4): calcd.
135.9, 132.2, 126.5, 121.3, 120.0, 117.5 (Caryl, Cimin), 36.4 C 59.01, H 5.66, N 13.11; found C 59.09, H 5.73, N 13.19.
(CH3N), 34.4 (C(CH3)3), 31.4 (C(CH3)3). – MS (DEI):
m/z = 446 [M, 81Br]+, 431, 232, 215, 173, 145, 91, 44, 28. –
4,5-Dihydro-4-(4-methoxyphenyl)-1-methyl-5-selenoxo-N-
C20H21BrN4OS (445.4): calcd. C 53.94, H 4.75, Br 17.94,
N 12.58, S 7.20; found C 53.91, H 4.72, Br 18.40, N 12.61,
S 7.31.
p-tolyl-1H-1,2,4-triazole-3-carboxamide (15a)
This compound was obtained as colorless needles (64 mg,
16 % yield), m. p. 233.4 – 234.6 ◦C (dec.). – 1H NMR
(250 MHz, CDCl3): δ = 8.48 (s, 1H, NH), 7.42 (d, J =
8.6 Hz, 2H, CH), 7.27 (d, J = 8.8 Hz, 2H, CH), 7.12 (d,
J = 8.2 Hz, 2H, CH), 7.03 (d, J = 9.0 Hz, 2H, CH), 4.03
(s, 3H, CH3N), 3.85 (s, 3H, CH3O), 2.31 (s, 3H, CH3). –
13C NMR (63 MHz, CDCl3): δ = 167.4 (C=Se), 160.4,
151.6, 144.2, 135.2, 133.7, 129.7, 128.7, 128.2, 119.9, 114.6
(Caryl, Cimin), 55.4 (CH3O), 38.9 (CH3N), 20.9 (CH3). –
77Se NMR (76 MHz, CDCl3): δ = 92.3 (s). – MS (DEI):
m/z = 402 [M, 80Se]+, 387, 360, 314, 296, 290, 268, 227,
213, 188, 161, 147, 133, 108, 91, 82, 77, 59, 44, 28. –
C18H18N4O2Se (401.3): calcd. C 53.87, H 4.52, N 13.96;
found C 53.85, H 4.42, N 13.92.
4,5-Dihydro-4-methyl-5-(4-methoxyphenylimino)-N-p-tolyl-
1,3,4-selenadiazole-2-carboxamide (13a)
This compound was obtained as pale◦ yellow prisms
(221 mg, 55 % yield), m. p. 101.6 – 102.8 C. – 1H NMR
(250 MHz, CDCl3): δ = 8.32 (s, 1H, NH), 7.51 (d, J = 8.4 Hz,
2H, CH), 7.16 (d, J = 8.4 Hz, 2H, CH), 7.06 – 6.88 (m, 4H,
CH), 3.81, 3.79 (2s, 6H, CH3O, CH3N), 2.33 (s, 3H, CH3). –
13C NMR (63 MHz, CDCl3): δ = 158.8, 157.0, 156.6, 146.0,
143.0, 142.1, 134.5, 134.4, 129.7, 120.9, 119.7, 115.1 (Caryl
C
,
imin), 55.5 (CH3O), 37.0 (CH3N), 20.9 (CH3). – 77Se NMR
(76 MHz, CDCl3): δ = 520.4 (s). – MS (DEI): m/z = 402 [M,
80Se]+, 385, 254, 213, 162, 147, 133, 121, 106, 91, 77, 28. –
C18H18N4O2Se (401.3): calcd. C 53.87, H 4.52, N 13.96;
found C 53.87, H 4.51, N 13.88.
4-(4-Bromophenyl)-4,5-dihydro-1-methyl-5-selenoxo-N-p-
tolyl-1H-1,2,4-triazole-3-carboxamide (15b)
This compound was obtained as colorless needles (77 mg,
17 % yield), m. p. 245.2 – 246.5 ◦C (dec.). – 1H NMR
(250 MHz, CDCl3): δ = 8.46 (s, 1H, NH), 7.68 (d, J =
8.6 Hz, 2H, CH), 7.41 (d, J = 8.4 Hz, 2H, CH), 7.24 (d,
J = 8.6 Hz, 2H, CH), 7.14 (d, J = 8.4 Hz, 2H, CH), 4.03
(s, 3H, CH3N), 2.32 (s, 3H, CH3). – 13C NMR (63 MHz,
CDCl3): δ = 167.3 (C=Se), 151.5, 143.7, 134.7, 133.5, 132.7,
129.7, 129.4, 124.4, 112.0 (Caryl, Cimin), 38.9 (CH3N), 20.9
(CH3). – 77Se NMR (76 MHz, CDCl3): δ = 101.7 (s). –
MS (DEI): m/z = 450 [M, 80Se79Br]+, 371, 344, 316, 263,
236, 209, 196, 184, 157, 133, 106, 91, 82, 77, 44, 28. –
C17H15BrN4OSe (450.2): calcd. C 45.35, H 3.36, Br 17.75,
N 12.45; found C 45.38, H 3.39, Br 17.90, N 12.41.
5-(4-Bromophenylimino)-4,5dihydro-4-methyl-N-p-tolyl-
1,3,4-selenadiazole-2-carboxamide (13b)
This compound was obtained as pale◦ yellow prisms
(194 mg, 43 % yield), m. p. 181.5 – 182.3 C. – 1H NMR
(250 MHz, CDCl3): δ = 8.31 (s, 1H, NH), 7.60 – 7.42 (m,
4H, CH), 7.17 (d, J = 8.2 Hz, 2H, CH), 6.94 (d, J = 8.8 Hz,
2H, CH), 3.81 (s, 3H, CH3N), 2.34 (s, 3H, CH3). – 13C NMR
(63 MHz, CDCl3): δ = 159.8, 156.7, 151.5, 143.8, 134.6,
134.3, 132.9, 129.7, 121.8, 119.7, 117.3 (Caryl, Cimin), 37.1
(CH3N), 20.9 (CH3). – 77Se NMR (76 MHz, CDCl3): δ =
526.8 (s). – MS (DEI): m/z = 450 [M, 80Se79Br]+, 402, 344,
290, 261, 210, 196, 174, 161, 146, 133, 118, 106, 91, 83, 77,
56, 28. – C17H15BrN4OSe (450.2): calcd. C 45.35, H 3.36,
Br 17.75, N 12.45; found C 45.37, H 3.35, Br 18.40, N 12.59.
4-(4-tert-Butylphenyl)-4,5-dihydro-1-methyl-5-selenoxo-
N-p-tolyl-1H-1,2,4-triazole-3-carboxamide (15c)
5-(4-tert-Butylphenylimino)-4,5dihydro-4-methyl-N-p-tolyl-
1,3,4-selenadiazole-2-carboxamide (13c)
This compound was ob◦tained as colorless needles (90 mg,
21 % yield), m. p. 225.0 C (dec.). – 1H NMR (250 MHz,
CDCl3): δ = 8.46 (s, 1H, NH), 7.55 (d, J = 8.4 Hz, 2H, CH),
7.40 (d, J = 8.4 Hz, 2H, CH), 7.28 (d, J = 8.4 Hz, 2H, CH),
7.12 (d, J = 8.4 Hz, 2H, CH), 4.03 (s, 3H, CH3N), 2.31 (s, 3H,
CH3), 1.37 (s, 9H, C(CH3)3). – 13C NMR (63 MHz, CDCl3):
δ = 167.1 (C=Se), 152.9, 151.7, 144.2, 135.3, 133.7, 133.0,
129.7, 127.0, 126.3, 120.1 (Caryl, Cimin), 38.9 (CH3N),
This compound was obtained as pale◦ yellow prisms
(286 mg, 67 % yield), m. p. 117.9 – 118.8 C. – 1H NMR
(250 MHz, CDCl3): δ = 8.34 (s, 1H, NH), 7.52 (d, J = 8.4 Hz,
2H, CH), 7.41 (d, J = 8.6 Hz, 2H, CH), 7.17 (d, J = 8.2 Hz,
2H, CH), 7.01 (d, J = 8.6 Hz, 2H, CH), 3.81 (s, 3H, CH3N),
2.34 (s, 3H, CH3), 1.35 (s, 9H, C(CH3)3). – 13C NMR
(63 MHz, CDCl3): δ = 158.4, 157.0, 149.7, 147.4, 143.2, 34.9 (C(CH3)3), 31.3 (C(CH3)3), 20.9 (CH3). – 77Se NMR
134.5, 134.4, 129.7. 126.7, 119.7, 119.3 (Caryl, Cimin), 37.0 (76 MHz, CDCl3): δ = 91.7 (s). – MS (DEI): m/z = 428 [M,
(CH3N), 34.4 (C(CH3)3), 31.4 (C(CH3)3), 20.9 (CH3). – 80Se]+, 413, 322, 306, 294, 278, 238, 214, 199, 187, 173,
Unauthenticated
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J. Fleischhauer et al. · Thia- and Selena-Heterocycles Containing Cycloamidine Substructures
423
159, 133, 106, 91, 82, 77, 65, 28. – C21H24N4OSe (427.4): 175.9 (C=S), 154.3, 142.2, 137.3, 135.2, 129.8, 122.7 (Caryl
,
calcd. C 59.01, H 5.66, N 13.11; found C 58.99, H 5.75, C=O, Cimin), 32.8 (CH3N), 21.30 (CH3). – MS (DEI): m/z =
N 12.99.
248 [M]+, 215, 175, 149, 124, 106, 91, 65. – C11H12N4OS
(248.3): calcd. C 53.21, H 4.87, N 22.56, S 12.91; found
C 53.10, H 4.80, N 22.52, S 12.95.
4,5-Dihydro-1-methyl-5-oxo-N-p-tolyl-1H-1,2,4-triazole-3-
carbothioamide (16)
Acknowledgements
This compound was obtained as yellow prisms (109 mg,
44 % yield), m. p. 206 – 210 ◦C. – 1H NMR (250 MHz,
CDCl3): δ = 10.27, 9.89 (2s, 2H, NH), 7.74 (d, J = 8.4 Hz,
2H, CH), 7.24 (d, J = 8.2 Hz, 2H, CH), 3.55 (s, 3H, CH3N),
2.37 (s, 3H, CH3). – 13C NMR (63 MHz, CDCl3): δ =
We thank AlzChem Trostberg GmbH, Clariant GmbH and
Syngenta Crop Protection AG for support by chemicals. Fur-
thermore, this work was supported by the Ministry of Educa-
tion of Czech Republic (MSM 0021620822).
[1] D. Pufky, R. Beckert, M. Do¨ring, O. Walter, Heterocy-
cles 2002, 57, 1257 – 1264.
fer, K. Lachmann, U. Epperlein, Pharmazie 1994, 49,
401 – 406.
[9] a) T. Jira, A. Stelzer, W. D. Pfeiffer, C. Schopplich,
S. Siegert, M. Kindermann, Pharmazie 1997, 52, 831 –
835; b) W. Pfeiffer, E. Dilk, H. Rossberg, P. Langer,
Synlett 2003, 2392 – 2394.
[2] a) E. C. Taylor, H. M. L. Davies, R. J. Clemens,
H. Yanagisawa, N. F. Haley, J. Am. Chem. Soc. 1981,
103, 7660 – 7661; b) E. C. Taylor, H. M. L. Davies,
W. T. Lavell, N. D. Jones, J. Org. Chem. 1984, 49,
2204 – 2208; c) E. C. Taylor, H. M. L. Davies, J. S. Hin-
kle, J. Org. Chem. 1986, 51, 1530 – 1536; d) E. C.
Taylor, D. M. Sobieray, Tetrahedron 1991, 47, 9599 –
9620.
[3] a) J. Fleischhauer, R. Beckert, W. Gu¨nther, H. Go¨rls,
Synthesis 2006, 2885 – 2890; b) J. Fleischhauer,
R. Beckert, J. Weston, M. Schmidt, H. Flammersheim,
H. Go¨rls, Synthesis 2006, 514 – 518.
[4] a) R. Beckert, J. Fleischhauer, A. Darsen, J. Weston,
S. Schenk, A. Batista, E. Anders, H. Go¨rls, M. Do¨ring,
D. Pufky, O. Walter, Heterocycles 2005, 65, 1311 –
1320; b) J. Fleischhauer, R. Beckert, W. Gu¨nther,
S. Kluge, S. Zahn, J. Weston, D. Berg, H. Go¨rls, Syn-
thesis 2007, 2839 – 2848.
[10] a) M. Morvan, G. Nadler, R. G. Zimmermann, J. Het-
erocycl. Chem. 1991, 28, 1365 – 1368; J. Schro¨der,
A. Henke, H. Wenzel, H. Brandstetter, H. G. Stamm-
ler, A. Stammler, W. D. Pfeiffer, H. Tschesche, J.
Med. Chem. 2001, 44, 3231 – 3243; c) A. M. Mahran,
N. A. Hassan, Arch. Pharm. Res. 2006, 29, 46 – 49;
d) J. Matysiak, Eur. J. Med. Chem. 2007, 42, 940 – 947.
[11] a) H. M. Hassaneen, A. Shetta, A. S. Shawali, J. Het-
erocycl. Chem. 1980, 17, 1185 – 1187; b) A. O. Ab-
delhamid, S. M. Abdelgawad, S. F. El-Sharnoby, Phos-
phorus, Sulfur Silicon Relat. Elem. 2002, 177, 2699 –
2709; c) A. T. S. Omer, N. M. Rateb, A. O. Abdel-
hamid, Phosphorus, Sulfur Silicon Relat. Elem. 2003,
178, 2363 – 2371; d) S. M. Abdel-Gawad, M. S. El-
gendy, A. O. Abdelhamid, J. Sulfur Chem. 2005, 26,
21 – 31; e) N. Rateb, Phosphorus, Sulfur Silicon Relat.
Elem. 2005, 180, 2361 – 2372; f) O. V. Firsova, T. S.
Dolgushina, V. A. Polukeev, E. M. Ioannisyan, V. E.
Zavodnik, A. I. Stash, V. K. Bel’skii, V. A. Galishev,
Russ. J. Org. Chem. 2005, 41, 762 – 768.
[5] R. Beckert, R. Mayer, J. Prakt. Chem. 1982, 324, 227 –
236.
[6] a) R. Beckert, M. Gruner, I. Seidel, R. J. Kuban,
Monatsh. Chem. 1989, 120, 1125 – 37; b) R. Beck-
ert, M. Gruner, J. Prakt. Chem. 1992, 334, 611 – 18;
c) C. Kaepplinger, R. Beckert, A. Darsen, W. Gu¨nther,
Sulfur Letters 2001, 24, 281 – 289.
[7] a) G. I. Kornis in Comprehensive Heterocyclic Chem-
istry. II, Vol. 4 (Ed.: R. C. Storr), Pergamon Press Inc.,
New York 1996, chapter 4.10, pp. 379 – 408; b) R. K.
Smalley in Comprehensive Heterocyclic Chemistry. II,
Vol. 6 (Ed.: A. J. Boulton), Pergamon Press Inc., New
York 1996, chapter 6.17, pp. 737 – 781.
[12] U. Petersen, H. Heitzer, Justus Liebigs Ann. Chem.
1973, 944 – 960.
[13] a) M. Koketsu, Y. Yamamura, H. Ishihara, Heterocycles
2006, 68, 1191 – 1200; b) G. L. Sommen, A. Linden,
H. Heimgartner, Helv. Chim. Acta 2007, 90, 641 – 651.
[14] COLLECT, Nonius Kappa-CCD Software, Nonius,
B. V., Delft, (The Netherlands) 1998.
[8] a) H. Beyer, E. Bulka, F. W. Beckhaus, Chem. Ber.
1959, 2593 – 2599, b) H. Beyer, Z. Chem. 1969, 9,
361 – 369; c) W. D. Pfeiffer, J. Buhrow, E. Bulka, Wis-
sensch. Z. der Ernst-Moritz-Arndt-Universita¨t Greif-
swald, Math.-Nat.wiss. Reihe 1988, 37, 38 – 41;
d) R. E. Busby, T. W. Dominey, J. Chem. Soc., Perkin
Trans. 1980, 2, 890 – 899; e) T. Jira, W. D. Pfeif-
[15] HKL DENZO, SCALEPACK: Z. Otwinowski, W. Mi-
nor, Methods in Enzymology, Vol. 276, Macromolec-
ular Crystallography, Part A (Eds.: C. W. Carter Jr,
R. M. Sweet), Academic Press, New York 1997, pp.
307 – 326.
[16] G. M. Sheldrick, Acta Crystallogr. 1990, A46, 467.
[17] G. M. Sheldrick, SHELXL-97, Program for the Refine-
Unauthenticated
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424
J. Fleischhauer et al. · Thia- and Selena-Heterocycles Containing Cycloamidine Substructures
ment of Crystal Structures, University of Go¨ttingen,
Go¨ttingen (Germany) 1997.
[18] XP (version 4.1). Siemens Analytical X-ray Instru-
ments Inc., Madison, Wisconsin (USA) 1990.
[19] a) O. J.-C. Nicaise, D. M. Mans, A. D. Morrow, E. V.
Hefti, E. M. Palkovacs, R. K. Singh, M. A. Zukowska,
M. D. Morin, Tetrahedron 2003, 59, 6433 – 6443;
b) 1H NMR (250 MHz, [D6]DMSO): δ = 10.90, 10.30
(2s, 2 H, NH), 7.86 (d, J = 8.8 Hz, 2 H, CH), 7.55 (d,
J = 8.8 Hz, 2 H, CH), 6.91 (s, 2 H, CH), 2.23, 2.11 (2s,
9 H, CH3); c) R. Bauer, Ber. Dtsch. Chem. Ges., 1907,
40, 2653; d) 1H NMR (250 MHz, CDCl3): δ = 7.60 (d,
J = 8.8 Hz, 2 H, CH), 7.07 (d, J = 8.8 Hz, 2 H, CH),
6.94 (s, 2 H, CH), 2.33, 2.11 (2s, 9 H, CH3).
Unauthenticated
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