Synthesis and structure of thia and selena heterocycles containing cycloamidine substructures

Article abstract of DOI:10.1055/s-2007-983834

Cyclization of a bis-arylimidoyl chloride with an acylselenourea leads to the construction of a 1,3-selenazolidine with a heteroradialene structure. Another reaction of the bis-arylimidoyl chloride (hydrazinolysis) leads to the formation of Δ²-1,2-diazetines, which we have shown previously to be reactive precursors for ring transformation reactions that yield unusual heterocycles. We now demonstrate that the reaction of these Δ²- 1,2-diazetines with various isothio- or isoselenocyanates affords an efficient entry to highly substituted 1,3,4-thia- or -selenadiazines. The structures of these novel derivatives were confirmed by NMR and mass spectroscopy, elemental analysis, and X-ray structural analysis. Detailed multidimensional ⁷⁷Se NMR experiments as well as density functional theory (DFT) calculations show structural specifics of these compounds. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-983834

PAPER
2839
Synthesis and Structure of Thia and Selena Heterocycles Containing
Cycloamidine Substructures
a
a
a
a
a
a
T
J
hia and
S
a
e
lena
H
ete
n
rocycles Containin
F
g
Cycloamidi
l
S
ubs
e
tructures ischhauer, Rainer Beckert,* Wolfgang Günther, Stefan Kluge, Stefan Zahn, Jennie Weston,
b
c
Dorothea Berg, Helmar Görls
a
Institute of Organic and Macromolecular Chemistry, Friedrich Schiller University, Humboldtstrasse 10, 07743 Jena, Germany
Institute of Physical Chemistry, Friedrich Schiller University, Lessingstrasse 10, 07743 Jena, Germany
Institute of Inorganic and Analytical Chemistry, Friedrich Schiller University, Lessingstrasse 8, 07743 Jena, Germany
E-mail: Rainer.Beckert@uni-jena.de
b
c
Received 23 May 2007; revised 7 June 2007
Organic compounds containing selenium are much less
stable than their sulfur analogues. Classical synthetic pro-
cedures for thioderivatives thus often fail when applied to
Abstract: Cyclization of a bis-arylimidoyl chloride with an acylse-
lenourea leads to the construction of a 1,3-selenazolidine with a het-
eroradialene structure. Another reaction of the bis-arylimidoyl
2
chloride (hydrazinolysis) leads to the formation of D -1,2-diazet- their seleno counterparts. This is offset by the increasing
ines, which we have shown previously to be reactive precursors for demand for stable and nontoxic organic compounds con-
ring transformation reactions that yield unusual heterocycles. We
taining selenium, especially for potential pharmaceuti-
2
now demonstrate that the reaction of these D -1,2-diazetines with
cals. This dilemma requires a continuous expansion of
various isothio- or isoselenocyanates affords an efficient entry to
highly substituted 1,3,4-thia- or -selenadiazines. The structures of
these novel derivatives were confirmed by NMR and mass spectros-
copy, elemental analysis, and X-ray structural analysis. Detailed
3
preparative strategies. In this context we now present two
novel strategies for the synthesis of 1,3-selenazolidines
and 1,3,4-thia- or -selenadiazines containing highly vari-
multidimensional 77Se NMR experiments as well as density func- able substituent patterns.
tional theory (DFT) calculations show structural specifics of these
During the course of our past work, it has become increas-
compounds.
ingly clear that bis-arylimidoyl chlorides 1 of oxalic acid
are excellent (and selective) biselectrophilic C2-synthons
that can be employed in a wide range of heterocycliza-
tions as well as carbocyclizations.4
Key words: ring expansion, heterocycles, selenium, sulfur, non-
covalent chalcogen interactions
We are now investigating the potential of 1 for providing
further entry points for obtaining novel selenium- and sul-
fur-containing heterocycles (Schemes 1 and 2).
Selenium is an essential trace element and is incorporated
in organisms via the non-proteinogenic amino acid sele-
nocysteine and in the active site of redox enzymes such as
1
glutathione peroxidase. Ever since this discovery, there A bis-imidoyl chloride 1 condenses easily with an acylse-
has been increasing scientific interest in the synthesis of lenourea 2 to give a 1,3-selenazolidine (Scheme 1). Heat-
selenium compounds and investigation of their pharmaco- ing a mixture of 1 and 2 in acetonitrile in the presence of
logical potential. This has led to quite a few pharmaceuti- triethylamine thus leads to a red product 3 in acceptable
cal compounds and agricultural chemicals based on yield (Table 1).
selenium- or sulfur-containing organic compounds. Ex-
amples of this interest are the compounds selenazofurine
Elemental analysis and mass spectroscopy data of 3 indi-
cated a 1:1 cyclization product. A C=Se signal (ca. d =
and thiazofurine, which are potent antitumor and antiviral
5
13
1
85.5) was missing in the C NMR spectrum and only
2
drugs. The antithyroid activity of pharmaceuticals in the
77
one signal at d = 762.1 was detected in the Se NMR
spectrum. A single-crystal X-ray analysis showed that se-
lenium had been incorporated into the ring (Figure 1). The
methimazol series, based also on the thiazole/selenazole
substructure, should be mentioned in this context.2g
R1
O
O
Se
C
R2
Ar
N
N
R2
R1
N
N
Me
H
H /MeCN/Et3N/reflux
Cl
3
MeNH-NH2 /THF/Et N/0 °C
N
2
N N
Se
–
Et3N*HCl
3
– Et N*HCl
N
Cl
N
Ar
N
NH
Ar
Ar
N
Ar
Ar = R1 = Ph, R2 = Tol
Ar
3
1
4
2
Scheme 1 Synthesis of 1,3-selenazolidines 3 and D -1,2-diazetines 4a–c [Ar = 4-n-BuC H (4a), 4-t-BuC H (4b), 4-EtO CC H (4c)]
6
4
6
4
2
6
4
SYNTHESIS 2007, No. 18, pp 2839–2848
x
x.
x
x
.
2
0
0
7
Advanced online publication: 08.08.2007
DOI: 10.1055/s-2007-983834; Art ID: Z12507SS
Georg Thieme Verlag Stuttgart · New York
©

2
840
J. Fleischhauer et al.
PAPER
R1
E
R1
N
O
N
O
N
Me
Me
N
N
N
E
R1
N C
Me
1
N
N
R -N=C=E /THF/r.t.
E/acetone/r.t.
N
N
Ar
N
E = S, Se
E = S, Se
Ar
Ar
NH
Ar
NH
Ar
NH
Ar
5
6
E = S
E = Se
4
7 E = S
8 E = Se
Scheme 2 Synthesis of 1,3,4-thiadiazines 5 and 7 and 1,3,4-selenadiazines 6 and 8 from 4
unambiguous structural assignment of 3 is shown in Table 1 Synthesis of Sulfur- and Selenium-Substituted Heterocy-
Figure 1. The acyl moiety shows a cis arrangement with cles 3 and 5–8a
respect to the chalcogen atom (dSe–OAc = 2.591 Å), and the
77
Compound E
Ar
R1
d ( Se NMR) Yield
C1–Se–C3 bond angle is 86.6°. 1,3-Selenazolidines such
as 3 cannot be obtained by classical synthetic routes. Until
now, access to 3 as well as analogous 1,3,4-thia- or -sel-
enadiazines has been limited mainly to the cyclization of
a-halo ketones with thio- or selenoureas or thio- or sele-
(in 5–8)
(ppm)
762.1
–
(%)
68
89
80
63
84
92
96
49
95
89
51
80
83
62
90
86
79
81
57
97
92
88
83
90
86
54
81
3
–
Ph
Ph
5
S
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
PMP
PMP
3
b,6
nosemicarbazides.
6a
Se
Se
Se
S
499.72
497.52
596.28
–
6
6
7
7
7
7
7
b
4-BrC H
6
4
c
4-t-BuC H
6
4
a
b
c
Me
Et
S
–
S
i-Pr
t-Bu
–
d
e
S
–
S
cyclopropyl
cyclobutyl
CHPh2
Ph
–
Figure 1 Solid-state structure (X-ray analysis) of derivative 3
7f
S
–
7
g
S
–
We have previously shown that a controlled hydrazinoly-
2
7
7h
S
–
sis of 1 conveniently yields D -1,2-diazetines
4
(
Scheme 1), which are quite useful in a number of versa-
7
i
S
Tol
–
tile ring-transformation reactions due to their inherent
8
ring strain. Compounds 4 react with isocyanates to yield 7j
S
PMP
–
9
semicyclic urea derivatives. In contrast to this, isothiocy-
7
k
S
4-PhC H
–
6
4
anates immediately lead to ring-transformed products,
9
e.g. 1,3,4-thiadiazines 5 (Scheme 2). Animated by this 8b
Se
Se
Se
Se
Se
Se
Se
Se
Se
Se
Se
Et
594.09
501.26
594.41
596.05
598.20
497.52
597.19
609.10
597.73
594.30
595.32
different reactivity, we have now extended our investiga-
tions to include acylisothiocyanates, isoselenocyanates,
and acylisoselenocyanates.
8
c
i-Pr
8d
Cyclobutyl
t-Bu
There are very few existing procedures for obtaining iso-
8
8
8
8
8
e
1
0
selenocyanates. We used the protocol of Barton et al. in
which gray selenium is added to in situ generated isocya-
f
4-BrC H
t-Bu
6
4
1
0b
nides. The isoselenocyanates obtained in this manner
were unstable towards column chromatography and were
thus used directly, without further purification, in ring-
transformation reactions according to Scheme 2. Upon
workup of the reaction mixtures by repetitive crystalliza-
g
h
i
4-n-BuC H t-Bu
6
4
4-t-BuC H
t-Bu
6
4
4-EtO CC H t-Bu
2
6
4
tion (MeOH–H O), the 1,3,4-selenadiazines 6a–c were 8j
Tol
Tol
Tol
CHPh
Tol
2
2
obtained in good yields. The selenadiazine structure was
confirmed by elemental analysis, mass spectra, and NMR
experiments.
8
k
8l
PMP
a
See Schemes 1 and 2 for the reactions.
Synthesis 2007, No. 18, 2839–2848 © Thieme Stuttgart · New York

PAPER
Thia and Selena Heterocycles Containing Cycloamidine Substructures
2841
We then explored the reactivity of 4 towards acylhetero-
1
1
cumulenes such as R CON=C=E (R = alkyl, aryl; E = S,
Se) (Scheme 2). The acylheterocumulenes were generated
in situ by addition of the corresponding carboxylic chlo-
rides to a solution of sodium thiocyanate or potassium se-
1
1
lenocyanate in dry acetone at 0 °C. Addition of 4 to the
solution and stirring for one hour at room temperature
yielded the corresponding 1,3,4-thiadiazines 7 or 1,3,4-
selenadiazines 8. The success of this reaction depends sig-
Figure 3 Perspective drawings of the ring planes in 7g and 8j
nificantly on the purity of the carboxylic acid chloride em- The ring-bonding angles are significantly influenced by
ployed. The in situ generated isoselenocyanates the chalcogen atom. A relatively small C3–E–C2 angle
decompose rapidly in the presence of traces of hydrochlo- (7g, 101.93°; 8j, 97.72°) is compensated by a widening of
ric acid under extrusion of red amorphous selenium. the C1–C2–N1 and N1–N2–C3 angles (Figure 2). As in 3,
When the carboxylic acid chlorides were purged by distil- the acyl moiety shows a cis arrangement with respect to
lation and immediately used, good to excellent yields of the chalcogen. The distance between E and O1 is shorter
the acyl derivatives 7 or 8 were obtained (50–96%; not op- than expected when compared to classical van der Waals
timized).
radii [dEO1 = 2.603 Å (7g), 2.560 Å (8j)]. This noncova-
lent interaction has been rationalized by a simple p→s*
model between the chalcogen centers. The lone pair on the
donor chalcogen (occupied p orbital on O1) interacts
To test the scope and limitations of this reaction, a variety
2
of D -1,2-diazetines 4 as well as acylheterocumulenes
were employed. Table 1 demonstrates that we could vary
the chalcogen atom E, the aryl groups Ar, and substituents
‘
through space’ with a properly positioned s* orbital on
12
1
the acceptor (S/Se). Newer theoretical studies (Bleihol-
der et al.) show that noncovalent chalcogen interactions
can be described as the sum of several interactions: elec-
trostatics, induction, electronic dispersion, and exchange
correlation energies.13 Thus, electrostatics and ‘through
space’ hyperconjugation could possibly play a major
bonding role in acceptor-substituted systems such as these
R widely within this synthetic route. In addition, we suc-
2
ceeded in expanding the pool of accessible D -1,2-diazet-
ines 4 to include the 4-n-butylphenyl-, 4-tert-butylphenyl-,
and 4-(ethoxycarbonyl)phenyl-substituted derivatives 4a,
4
b, and 4c, respectively.
Compounds 5–8 are yellow crystalline solids that are re-
markably stable in solution. Even after standing in deuter-
ated chloroform for longer periods, decomposition of the
selenacycles 6 and 8 could not be detected by NMR-spec-
troscopy. Mass spectra of 5–8 show characteristic frag-
mentation patterns independent of the identity of the
chalcogen. The structures shown in Scheme 2 could be
confirmed by single-crystal X-ray structural analyses of
compounds 7g and 8j (Figure 2).
1
,3,4-thia- or -selenadiazines 7 and 8.
Animated by these results, we performed calculations of
1
the smallest system 7a/8a, in which R = Me. We opti-
mized both the cis and the trans isomers of these systems
at the TPSS(RI)/def2-TZVP (density functional) level of
theory (Figure 4).
Figure 4 Optimal structures of the cis and trans isomers of 7a, cal-
culated at the TPSS(RI)/def2-TZVP level of theory
Figure 2 Solid-state structures (X-ray analysis) of derivatives 7g
(
left) and 8j (right)
In accord with experiment, the cis isomer is with
DE = 33.9 kJ/mol for 7a (S) and 41.8 kJ/mol for 8a (Se)
In both 7g and 8j, the proton is located on the exocylic N5 clearly energetically favored (Table 2). An NBO analysis
and forms an intramolecular hydrogen bond to N4 [N4–H, carried out at the B3LYP/6-31++G(d,p) level of theory
2
.298 Å (7g) and 2.156 Å (8j)] (Figure 2). The central ring shows that the ‘through space’ p →s*
interaction be-
O1
C3–E
in 1,3,4-thiadiazine 7g is very slightly twisted in a boat tween the divalent chalcogen centers plays a major role
conformation in which the sulfur atom juts out ca. 10° and provides ca. 28 (S) or 50 (Se) kJ/mol of stabilization
more than N1 (Figure 3). In contrast, the ring in 1,3,4-se- energy. It is quite interesting that this interaction energy
lenadiazine 8j is nearly planar (Figure 3).
doubles upon exchanging S for Se, although the O1–E dis-
tance is somewhat less affected [2.535 Å (S) vs 2.516 Å
Synthesis 2007, No. 18, 2839–2848 © Thieme Stuttgart · New York

2
842
J. Fleischhauer et al.
PAPER
Table 2 Selected Structural and Electronic Interactions in Compounds 7a and 8a, Calculated at the TPSS(RI)/TZVP Level of Theory
(
B3LYP/6-31++G(d,p) Densities for the NBO Properties)
a
db (°)
0.2
dE–O1c (Å)
Ep→s*d (kJ/mol)
Epe (kJ/mol)
E
DE (kJ/mol)
7
7
8
8
7
7
acis
S
0.0
33.9
0.
2.535
–
28
–
129
65
atrans
acis
S
139.7
0.0
Se
Se
S
2.516
–
50
–
151
16
atrans
a¢cisf
a¢transf
41.8
0.
114.4
0.3
2.572
–
25
–
149
124
S
18.9
166.9
a
b
c
d
e
f
Energy difference between the cis and trans isomers.
Optimal O1–C4–N4–C3 dihedral angle.
E–O1 bond distance.
Energy (NBO) of the p→s* hyperconjugative interaction.
Energy (NBO) of the p
→p*
¥ p
→p*
delocalization interaction.
C3=N3
C3=N3
C4=O1
C4=O1
1
1
Modified model: R = H instead of R = Me.
(
Se)] This can be attributed to both the higher polarizabil-
ity of Se (increased transferability of accepted s* density
to other atomic orbitals) as well as a much larger s
*
C3–Se
lobe which increases the spatial overlap with p .
O1
A second factor, which stabilizes the cis isomer, is steric
1
repulsion between R (Me) and E in the trans conforma-
tion as observed from the fact that the optimal dO1–C4–N4–C3
dihedral angle strongly deviates from the ideal value of
1
80° [139.7° (S) vs 114.4° (Se)]. Replacement of the
methyl group by hydrogen (model 7a¢ in Table 2) relieves
this steric strain, and the dihedral angle relaxes to 166.9°.
Because the acyl functionality is turned out of the ring
plane, p-delocalization into the ring as measured by the
1
77
Figure 5 [ H, Se]-HMBC correlation spectrum of 8i (Ar = 4-
p
→p*
¥ p
→p*
hyperconjugative in-
C3=N3
C4=O1
C4=O1
C3=N3
1
EtO CC H ; R = t-Bu), showing a cross peak between selenium and
the ortho protons of the N4-aryl substituents
2
6
4
teraction (E ) is, especially in the trans isomer of the sele-
p
nium derivative 8a, disrupted.
1H NMR spectra of compounds 5–8 show no evidence for
compounds presented in this article would show interest-
possible prototropic forms of the semicyclic amidine sub-
ing follow-up chemistry; e.g., pyrazoles could possibly be
1
3
structure. C NMR spectra provide evidence for the acyl
functionality in 7 and 8 (d = 170–190). Two resonance
6c,e,14
obtained by a ring-contraction reaction.
The feasibil-
C=O
ity of these reactions will be topics of further articles. Fi-
nally, we would like to point out the structural relationship
of these new compounds with pharmaceuticals based on
groups of the selenium nuclei could be detected at d = 500
7
7
and 600 in the Se NMR spectra (Table 1).
Quite surprisingly, we detected fine coupling (J = 2–3 thiadiazines (potent matrix-metalloproteinase inhibi-
1
5
Hz) in the selenium signals due to proton coupling in the tors). We are now investigating the biological potential
7
7
Se NMR spectra. This coupling is eliminated when the of these compounds.
spectra are obtained in the proton-decoupled mode. This
observation is in direct contrast to our proposed struc-
tures, which contain no protons in the positions a or b to
All solvents were dried and purified by standard techniques. The re-
agents employed were of commercial quality (Aldrich, Lancaster,
Fluka, Merck). Reactions were monitored by TLC (aluminum
1
77
the selenium nucleus. However, [ H, Se]-HMBC corre-
lation experiments showed this to be due to the ortho pro- plates coated with alumina or silica, from Fluka). Melting points
tons of the N4-aryl substituents (see Figure 2), which are were measured on a KSPS 1000 digital detector system from Krüss
and a B-545 (Boetius system) from Büchi and are uncorrected. The
close enough to the selenium nucleus for through-space
coupling to occur (Figure 5).
1
13
H and C NMR spectra were obtained on a Bruker AC 250 (250
7
7
MHz) or Bruker DRC-400 (400 MHz) spectrometer. Se NMR
In summary, we have described two new synthetic routes spectra (76 MHz) were obtained on a Bruker DRC-400 spectrome-
7
7
for the preparation of selenacycles. Furthermore, we have ter, with Me Se used as external ( Se) standard. Mass spectra were
2
measured on a Trio 2000 spectrometer from Fisons. Elemental anal-
yses were carried out with a Varion EL III automatic analyzer from
Elementar Analysensysteme GmbH.
enlarged the pool of available ring transformations start-
2
ing from D -1,2-diazetines 4. We expect that the new
Synthesis 2007, No. 18, 2839–2848 © Thieme Stuttgart · New York

PAPER
Thia and Selena Heterocycles Containing Cycloamidine Substructures
2843
1
Quantum Chemical Methodology
The density functional programs provided by the ORCA suite
were used for all calculations except the NBO analyses. Geometry
H NMR (250 MHz, THF-d ): d = 9.03 (s, 1 H, NH), 7.42 (d, J = 8.4
8
1
6
Hz, 2 H, CH), 7.26–6.96 (m, 6 H, CH), 2.68–2.48 (m, 7 H, CH N,
CH ), 1.68–1.49 (m, 4 H, CH ), 1.45–1.25 (m, 4 H, CH ), 1.00–0.84
(m, 6 H, CH3).
13
3
1
7
2
2
2
1
8
optimizations were carried out employing the TPSS functional
with the def2-TZVP1 basis set featuring a split valence triple-z ba-
sis set with polarization functions on all atoms. For the TPSS calcu-
9
C NMR (63 MHz, THF-d ): d = 155.1, 154.1, 139.3, 138.6, 135.6,
8
1
3
34.2, 126.8, 126.7, 121.8, 115.7 (CH, C ), 37.8 (CH N), 33.1,
2
0
quat 3
lations the split resolution of identity approximation (Split-RI-J )
2.9, 31.9, 31.7, 20.3, 20.2 (CH ), 11.4 (CH ).
1
7
2
3
was employed. NBO analyses were carried out using an NBO5.0
+
2
1
22
MS (DEI): m/z = 362 [M ], 319, 263, 214, 203, 188, 131, 106, 91,
77.
augmented Gaussian03 version employing the B3LYP function-
2
3
al with the 6-31++G(d,p)-Basis set.
Anal. Calcd for C H N : C, 76.20; H, 8.34; N, 15.46. Found: C,
2
3
30
4
Crystal Structure Determination24
Intensity data for the compounds were collected on a Nonius Kappa
7
6.16; H, 8.46; N, 15.45.
CCD diffractometer using graphite-monochromated Mo-K radia-
tion. The data were corrected for Lorentz and polarization effects
a
1-Methyl-3-(4-tert-butylphenylamino)-4-(4-tert-butylphenyl-
imino)-D -1,2-diazetine (4b)
Yield: 64%; yellow crystals; mp 136.3 °C (dec).
2
2
5,26
but not for absorption effects.
The structures were solved using
2
7
direct methods (SHELXS ) and refined by full-matrix least-
1H NMR (250 MHz, THF-d
): d = 9.04 (s, 1 H, NH), 7.50–7.30 (m,
H, CH), 7.14 (d, J = 8.4 Hz, 2 H, CH), 2.61 (s, 3 H, CH N), 1.33,
2
28
8
squares techniques against Fo (SHELXL-97 ). For the amine
group N5 of compounds 7g and 8i the hydrogen atoms were located
by difference Fourier synthesis and refined isotropically. The other
hydrogen atoms were included at calculated positions with fixed
thermal parameters. All non-hydrogen atoms were refined anisotro-
pically.28 The program XP was used for structure representations.
6
1
3
.31 [2 s, 18 H, (CH ) C].
3
3
13C NMR (63 MHz, THF-d
135.3, 123.7, 123.6, 121.6, 115.4 (CH, Cquat), 37.9 (CH
): d = 155.2, 154.2, 146.8, 142.4, 139.1,
N), 32.3,
8
3
29
32.0 [(CH
)
C], 28.9, 28.8 [(CH ) C].
3
3
3 3
+
MS (DEI): m/z = 362 [M ], 337, 214, 203, 188, 173, 159, 131, 115,
N-[4,5-Bis(phenylimino)-3-p-tolyl-1,3-selenazolidin-2-
ylidene]benzamide (3)
A soln of 1 (2.77 g, 10 mmol), 2 (3.17 g, 10 mmol), and Et N (5 mL)
9
1, 77.
Anal. Calcd for C H N : C, 76.20; H, 8.34; N, 15.46. Found: C,
23 30
4
3
7
5.99; H, 8.36; N, 14.95.
in MeCN (80 mL) was heated under reflux for 4 h. Et N·HCl was
3
removed by filtration, the solvent was removed in vacuo, and the
1
-Methyl-3-[4-(ethoxycarbonyl)phenylamino]-4-[4-(ethoxycar-
residue was purified by recrystallization (CHCl –heptane).
3
2
bonyl)phenylimino]-D -1,2-diazetine (4c)
Yield: 50%; orange crystals; mp 128.4–130.8 °C (dec).
Yield: 68%; red crystals; mp 197.0–199.0 °C.
1
H NMR (400 MHz, CDCl ): d = 8.02 (d, J = 7.7 Hz, 2 H, CH),
1
3
H NMR (250 MHz, THF-d ): d = 9.60 (s, 1 H, NH), 8.08–7.91 (m,
8
7
.60–6.88 (m, 13 H, CH), 6.86 (d, J = 7.6 Hz, 2 H, CH), 6.81 (d,
4
H, CH), 7.56 (d, J = 8.9 Hz, 2 H, CH), 7.22 (d, J = 8.2 Hz, 2 H,
J = 7.6 Hz, 2 H, CH), 2.46 (s, 3 H, CH3).
CH), 4.39–4.25 (m, 4 H, CH ), 2.61 (s, 3 H, CH N), 1.40–1.31 (m,
6 H, CH ).
2
3
1
3
C NMR (100 MHz, CDCl ): d = 177.6 (C=O), 166.8, 151.9,
3
3
1
1
1
50.7, 149.1, 147.6, 139.1, 135.9, 135.6, 133.7, 130.6, 130.3, 129.9,
29.7, 128.8, 128.7, 128.5, 128.1, 127.5, 123.4, 120.0, 119.7, 119.3,
19.1, 109.5 (CH, Cquat), 21.0 (CH3).
13
C NMR (63 MHz, THF-d ): d = 163.2, 163.1 (C=O), 155.0, 145.8,
8
1
5
41.5, 128.7, 128.4, 126.0, 122.3, 120.7, 115.2 (CH, Cquat), 58.5,
8.2 (CH ), 37.8 (CH N), 11.8, 11.7 (CH ).
2
3
3
7
7
Se NMR (76 MHz, CDCl ): d = 762.1 (s).
+
3
MS (DEI): m/z = 394 [M ], 366, 351, 349, 338, 321, 293, 265, 230,
Anal. Calcd for C H N OSe: C, 66.79; H, 4.25; N, 10.74. Found:
219, 204, 190, 165, 159, 120.
29
22
4
C, 66.67; H, 4.16; N, 10.60.
Anal. Calcd for C H N O : C, 63.95; H, 5.62; N, 14.20. Found: C,
63.82; H, 5.80; N, 14.10.
2
1
22
4
4
2
4
–
X-ray crystallography data for 3: C H N OSe, M = 521.5 g·mol
2
9
22
3
4
1
,
red plate, size 0.08 × 0.08 × 0.06 mm , monoclinic, space group
1
P2 /n, a = 13.9378(12), b = 13.7489(20), c = 14.2802(12) Å,
Heterodiazines 5 and 6a–c; General Procedure
3
2
b = 116.460(6)°, V = 2450.0(1) Å , T = –90 °C, Z = 4, r
= 1.414
A THF soln (60 mL) of D -1,2-diazetine 4 (2 mmol) was cooled to
calcd
–
3
–1
g·cm , m (Mo-K ) = 15.32 cm , F(000) = 656, 7365 reflections in
–20 °C and a soln of the corresponding isothiocyanate or isoseleno-
cyanate (2 mmol) in 5 mL of THF was added dropwise. After the
addition, the reaction mixture was warmed to r.t. and stirred for 6 h.
The solvent was then removed in vacuo and the residue was purified
a
h(–13/13), k(–13/13), l(–14/14), measured in the range 2.10° £ Q £
2
7.42°, completeness Qmax = 99.5%, 2425 independent reflections,
Rint = 0.033, 1600 reflections with F > 4s(F ), 152 parameters, 0
o
o
restraints,
R1 = 0.0445,
wR2 = 0.146,
R1 = 0.0465,
by recrystallization (MeOH–H O).
2
obs
obs
all
wR2all = 0.174, GOOF = 1.025, largest difference peak and hole:
–
3
0
.441/–0.401 e·Å .
2-(4-Methoxyphenylimino)-3-methyl-N-p-tolyl-6-(p-tolylimi-
no)-3,6-dihydro-2H-1,3,4-thiadiazin-5-amine (5)
Yield: 89%; orange-yellow crystals; mp 150.4–157.4 °C.
1
2
D -1,2-Diazetines 4a–c; General Procedure
A THF soln (60 mL) of the appropriate 1 (5 mmol) and Et N (3 mL,
3
H NMR (400 MHz, CDCl ): d = 7.78 (s, 1 H, NH), 7.51 (d, J = 8.4
3
2
0 mmol) was cooled to 0 °C and a soln of MeNHNH (5 mmol) in
2
Hz, 2 H, CH), 7.20–7.10 (m, 4 H, CH), 6.85–6.72 (m, 6 H, CH),
THF (20 mL) was added dropwise. After complete conversion of 1
by TLC), the reaction mixture was filtered to remove the Et N·HCl.
3
.77, 3.74 (2 s, 6 H, CH N, CH O), 2.37, 2.34 (2 s, 6 H, CH ).
3
3
3
(
3
1
3
C NMR (100 MHz, CDCl ): d = 156.0, 144.6, 144.2, 141.8, 140.4,
The solvent was then removed in vacuo at r.t. and the residue was
3
1
37.4, 135.6, 134.6, 131.2, 130.1, 129.4, 122.8, 119.8, 118.5, 114.6
purified by recrystallization (MeOH–H O).
2
(
CH, Cquat), 55.4 (CH O), 43.4 (CH N), 21.0, 20.8 (CH ).
3 3 3
+
1
-2Methyl-3-(4-n-butylphenylamino)-4-(4-n-butylphenylimino)-
MS (DEI): m/z = 443 [M ], 326, 311, 235, 165, 161, 118, 91, 65.
D -1,2-diazetine (4a)
Yield: 58%; yellow crystals; mp 110.5–115.7 °C.
Anal. Calcd for C H N OS: C, 67.69; H, 5.68; N, 15.79; S, 7.23.
2
5
25
5
Found: C, 67.68; H, 5.79; N, 15.78; S, 7.15.
Synthesis 2007, No. 18, 2839–2848 © Thieme Stuttgart · New York

2
844
J. Fleischhauer et al.
PAPER
1
2
-(4-Methoxyphenylimino)-3-methyl-N-p-tolyl-6-(p-tolylimi-
H NMR (250 MHz, CDCl ): d = 8.08 (s, 1 H, NH), 7.55 (d, J = 8.4
3
no)-3,6-dihydro-2H-1,3,4-selenadiazin-5-amine (6a)
Hz, 2 H, CH), 7.26–7.13 (m, 4 H, CH), 6.88 (d, J = 8.2 Hz, 2 H,
Yield: 80%; orange-yellow crystals; mp 167.2 °C.
CH), 3.83 (s, 3 H, CH N), 2.37, 2.35 (2 s, 6 H, CH ), 2.18 (s, 3 H,
3
3
1
CH
3
).
H NMR (250 MHz, CDCl ): d = 7.71 (s, 1 H, NH), 7.49 (d, J = 8.6
3
1
3
Hz, 2 H, CH), 7.20–7.10 (m, 4 H, CH), 6.85–6.82 (m, 6 H, CH),
3
C NMR (63 MHz, CDCl ): d = 180.9 (C=O), 157.4, 152.9, 144.9,
3
.76 (s, 6 H, CH N, CH O), 2.34 (s, 6 H, CH ).
143.9, 138.4, 136.1, 136.0, 132.6, 130.3, 129.5, 119.6, 119.3 (CH,
3
3
3
1
3
C
quat), 45.7 (CH
3
N), 27.4, 21.0, 20.8 (CH ).
3
C NMR (63 MHz, CDCl ): d = 156.4, 146.0, 145.9, 141.4, 141.2,
3
+
1
37.6, 135.8, 134.0, 131.0, 130.2, 129.4, 122.7, 119.0, 118.5, 114.7
MS (DEI): m/z = 379 [M ], 336, 262, 247, 202, 200, 198, 177, 161,
(
CH, Cquat), 55.4 (CH O), 44.5 (CH N), 21.0, 20.8 (CH ).
118, 91, 65, 43, 28.
3
3
3
7
7
Se NMR (76 MHz, CDCl ): d = 499.72 (s).
Anal. Calcd for C H N OS: C, 63.30; H, 5.58; N, 18.46; S, 8.45.
Found: C, 63.30; H, 5.51; N, 18.29; S, 8.11.
3
20 21
5
+
80
MS (DEI): m/z = 491 [M ( Se)], 374, 359, 248, 235, 197, 161, 118,
5, 43.
6
N-[3-Methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-dihydro-2H-
1,3,4-thiadiazin-2-ylidene]propionamide (7b)
Yield: 96%; pale-yellow crystals; mp 175.0 °C.
1
Anal. Calcd for C H N OSe: C, 61.22; H, 5.14; N, 14.28. Found:
C, 61.14; H, 5.16; N, 14.31.
25
25
5
H NMR (250 MHz, CDCl ): d = 8.08 (s, 1 H, NH), 7.51 (d, J = 8.4
3
2
3
-(4-Bromophenylimino)-3-methyl-N-p-tolyl-6-(p-tolylimino)-
,6-dihydro-2H-1,3,4-selenadiazin-5-amine (6b)
Hz, 2 H, CH), 7.25–7.11 (m, 4 H, CH), 6.88 (d, J = 8.4 Hz, 2 H,
CH), 3.83 (s, 3 H, CH N), 2.47 (q, J = 7.5 Hz, 2 H, CH ), 2.37, 2.34
3
2
Yield: 63%; yellow crystals; mp 179.8–182.3 °C.
(
2 s, 6 H, CH ), 1.12 (t, J = 7.5 Hz, 3 H, CH ).
3
3
1
H NMR (250 MHz, CDCl ): d = 7.71 (s, 1 H, NH), 7.49 (d, J = 8.5
3
13
C NMR (63 MHz, CDCl ): d = 184.4 (C=O), 152.9, 145.0, 144.0,
3
Hz, 2 H, CH), 7.35 (d, J = 8.8 Hz, 2 H, CH), 7.22–7.10 (m, 4 H,
CH), 6.77 (d, J = 8.5 Hz, 2 H, CH), 6.71 (d, J = 8.8 Hz, 2 H, CH),
3
1
4
38.3, 136.2, 136.0, 132.5, 130.3, 129.5, 119.6, 119.2 (CH, Cquat),
5.7 (CH N), 33.5 (CH ), 21.0, 20.8, 9.6 (CH ).
3
2
3
.75 (s, 3 H, CH N), 2.36, 2.35 (2 s, 6 H, CH ).
3
3
3
+
1
MS (DEI): m/z = 393 [M ], 364, 336, 276, 247, 235, 161, 118, 91,
7, 29.
C NMR (63 MHz, CDCl ): d = 147.2, 145.8, 145.4, 141.0, 137.4,
3
5
1
36.1, 134.2, 132.5, 131.3, 130.4, 129.4, 123.6, 118.9, 118.6, 116.9
(
CH, Cquat), 44.4 (CH N), 21.1, 20.8 (CH ).
Anal. Calcd for C H N OS: C, 64.10; H, 5.89; N, 17.80; S, 8.15.
21 23 5
3
3
7
7
Found: C, 64.03; H, 5.66; N, 17.72; S, 7.94.
Se NMR (76 MHz, CDCl ): d = 497.52 (t, J = 2.6 Hz).
3
+
80
79
MS (DEI): m/z = 539 [M ( Se Br)], 422, 260, 198, 161, 118, 91,
5.
N-[3-Methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-dihydro-2H-
6
1
,3,4-thiadiazin-2-ylidene]isobutyramide (7c)
Yield: 49%; pale-yellow crystals; mp 173.0 °C.
Anal. Calcd for C H BrN Se: C, 53.45; H, 4.11; Br, 14.82; N,
2
4
22
5
1
2.99. Found: C, 53.28; H, 4.16; Br, n.d.; N, 12.87.
1
H NMR (250 MHz, CDCl ): d = 8.08 (s, 1 H, NH), 7.51 (d, J = 8.5
3
Hz, 2 H, CH), 7.26–7.10 (m, 4 H, CH), 6.88 (d, J = 8.3 Hz, 2 H,
2
-(4-tert-Butylphenylimino)-3-methyl-N-p-tolyl-6-(p-tolylimi-
CH), 3.84 (s, 3 H, CH N), 2.63 (quin, J = 6.9 Hz, 1 H, CH), 2.37,
3
no)-3,6-dihydro-2H-1,3,4-selenadiazin-5-amine (6c)
Yield: 84%; yellow crystals; mp 208.7–212.3 °C.
2
.35 (2 s, 6 H, CH ), 1.16 (d, J = 6.9 Hz, 6 H, CH ).
3
3
1
3
C NMR (63 MHz, CDCl ): d = 187.4 (CO), 153.3, 145.1, 144.0,
3
1
H NMR (250 MHz, CDCl ): d = 7.26 (s, 1 H, NH), 7.50 (d, J = 8.4
3
138.2, 136.2, 135.9, 132.5, 130.3, 129.5, 119.6, 119.2 (CH, C ),
quat
Hz, 2 H, CH), 7.36 (d, J = 8.8 Hz, 2 H, CH), 7.22–7.10 (m, 4 H,
4
5.7 (CH N), 38.7 (CH), 21.0, 20.8, 19.5 (CH ).
3 3
CH), 6.81–6.66 (m, 4 H, CH), 3.77 (s, 3 H, CH N), 2.35, 2.34 (2 s,
3
+
MS (DEI): m/z = 407 [M ], 364, 336, 280, 247, 219, 177, 161, 132,
31, 91, 65, 43.
6
H, CH ), 1.30 [s, 9 H, C(CH ) ].
3 3 3
1
1
3
C NMR (63 MHz, CDCl ): d = 146.8, 145.8, 145.7, 145.2, 140.0,
3
Anal. Calcd for C H N OS: C, 64.84; H, 6.18; N, 17.18; S, 7.87.
2
2
25
5
1
37.6, 135.8, 134.0, 131.0, 130.2, 129.4, 126.3, 121.1, 119.1, 118.5
Found: C, 64.68; H, 6.36; N, 17.08; S, 7.79.
(
CH, Cquat), 44.4 (CH N), 34.3 [C(CH ) ], 31.4 [C(CH ) ], 21.0,
3 3 3 3 3
2
0.8 (CH3).
N-[3-Methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-dihydro-2H-
1,3,4-thiadiazin-2-ylidene]pivalamide (7d)
Yield: 95%; yellow crystals; mp 174.0 °C.
1
7
7
Se NMR (76 MHz, CDCl ): d = 596.28 (t, J = 2.5 Hz).
3
+
80
MS (DEI): m/z = 517 [M ( Se)], 502, 400, 385, 248, 197, 173, 161,
18, 91, 65.
1
H NMR (250 MHz, CDCl ): d = 8.08 (s, 1 H, NH), 7.51 (d, J = 8.4
3
Hz, 2 H, CH), 7.25–7.11 (m, 4 H, CH), 6.88 (d, J = 8.2 Hz, 2 H,
Anal. Calcd for C H N Se: C, 65.11; H, 6.05; N, 13.56. Found: C,
6
2
8
31
5
CH), 3.85 (s, 3 H, CH N), 2.37, 2.35 (2 s, 6 H, CH ), 1.20 [s, 9 H,
4.90; H, 6.18; N, 13.64.
3
3
C(CH ) ].
3
3
Acylheterodiazines 7a–k and 8b–l; General Procedure
13
C NMR (63 MHz, CDCl ): d = 189.2 (CO), 153.4, 145.1, 144.0,
3
To an acetone soln (30 mL) of NaSCN or KSeCN (2 mmol) the ap-
propriate carboxylic chloride (2 mmol) was added at 0 °C and the
1
4
38.1, 136.2, 135.9, 132.4, 130.4, 129.5, 119.6, 119.2 (CH, Cquat),
5.8 (CH N), 41.4 [C(CH ) ], 27.7 [C(CH ) ], 21.0, 20.8 (CH ).
3
3
3
3 3
3
2
mixture was stirred for 15 min. Then the D -1,2-diazetine 4 (2
+
MS (DEI): m/z = 421 [M ], 364, 247, 177, 132, 118, 91, 57, 41.
mmol) was added and the soln was stirred for 1 h. The reaction mix-
ture was diluted with CHCl (25 mL) and filtered. The solvent was
Anal. Calcd for C H N OS: C, 65.53; H, 6.46; N, 16.61; S, 7.61.
3
23 27
5
removed in vacuo and the residue was purified by column chroma-
Found: C, 65.40; H, 6.13; N, 16.73; S, 7.63.
tography (alumina, CHCl –heptane, 2:1). Recrystallization
3
(
CHCl –heptane) yielded the acylheterodiazines 7 and 8.
N-[3-Methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-dihydro-2H-
3
1
,3,4-thiadiazin-2-ylidene]cyclopropanecarboxamide (7e)
N-[3-Methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-dihydro-2H-
,3,4-thiadiazin-2-ylidene]acetamide (7a)
Yield: 92%; pale-yellow crystals; mp 201.4–203.9 °C.
Yield: 89%; pale-yellow crystals; mp 186.0–188.0 °C.
1
1
H NMR (250 MHz, CDCl ): d = 8.08 (s, 1 H, NH), 7.51 (d, J = 8.5
3
Hz, 2 H, CH), 7.26–7.10 (m, 4 H, CH), 6.87 (d, J = 8.3 Hz, 2 H,
Synthesis 2007, No. 18, 2839–2848 © Thieme Stuttgart · New York

PAPER
Thia and Selena Heterocycles Containing Cycloamidine Substructures
2845
+
CH), 3.83 (s, 3 H, CH N), 2.36, 2.34 (2 s, 6 H, CH ), 1.85–1.74 (m,
MS (DEI): m/z = 441 [M ], 336, 324, 247, 161, 105, 77, 65.
3
3
1
H, CH), 1.04–0.97 (m, 2 H, CH ), 0.93–0.86 (m, 2 H, CH ).
2
2
Anal. Calcd for C H N OS: C, 68.00; H, 5.25; N, 15.86; S, 7.26.
Found: C, 67.82; H, 5.26; N, 15.89; S, 7.13.
2
5
23
5
1
3
C NMR (63 MHz, CDCl ): d = 183.9 (CO), 152.6, 145.0, 143.9,
3
1
4
38.2, 136.2, 135.9, 132.5, 130.3, 129.5, 119.6, 119.2 (CH, C ),
quat
5.7 (CH N), 21.0, 20.8 (CH ), 18.9 (CH), 9.5 (CH ).
4-Methyl-N-[3-methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-di-
hydro-2H-1,3,4-thiadiazin-2-ylidene]benzamide (7i)
Yield: 62%; pale-yellow crystals; mp 238.0 °C (dec).
1
3
3
2
+
MS (DEI): m/z = 405 [M ], 364, 336, 288, 247, 220, 161, 118, 91,
9, 41, 39.
6
H NMR (250 MHz, CDCl ): d = 8.15–8.05 (m, 3 H, NH, CH), 7.54
3
Anal. Calcd for C H N OS: C, 65.16; H, 5.72; N, 17.27; S, 7.91.
Found: C, 65.16; H, 5.72; N, 17.17; S, 7.74.
2
2
23
5
(
d, J = 8.5 Hz, 2 H, CH), 7.27–7.10 (m, 6 H, CH), 6.91 (d, J = 8.3
Hz, 2 H, CH), 3.98 (s, 3 H, CH N); 2.39, 2.36 (2 s, 9 H, CH ).
3
3
1
3
N-[3-Methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-dihydro-2H-
C NMR (63 MHz, CDCl ): d = 174.2 (CO), 154.0, 145.0, 144.0,
3
1
,3,4-thiadiazin-2-ylidene]cyclobutanecarboxamide (7f)
Yield: 51%; pale-yellow crystals; mp 163.0 °C.
142.5, 138.5, 136.1, 136.0, 133.9, 132.6, 130.4, 129.6, 129.5, 128.8,
119.6, 119.3 (CH, Cquat), 46.1 (CH N), 21.6, 21.1, 20.8 (CH ).
3
3
1
+
H NMR (250 MHz, CDCl ): d = 8.08 (s, 1 H, NH), 7.51 (d, J = 8.4
MS (DEI): m/z = 455 [M ], 364, 348, 338, 280, 247, 235, 161, 119,
91, 65.
3
Hz, 2 H, CH), 7.26–7.10 (m, 4 H, CH), 6.88 (d, J = 8.3 Hz, 2 H,
CH), 3.83 (s, 3 H, CH N), 3.25 (m, 1 H, CH), 2.40–2.10 (m, 10 H,
3
Anal. Calcd for C H N OS: C, 68.55; H, 5.53; N, 15.37; S, 7.04.
Found: C, 68.40; H, 5.39; N, 15.23; S, 6.90.
2
6
25
5
CH , CH ), 2.10–1.80 (m, 2 H, CH ).
3
2
2
1
3
C NMR (63 MHz, CDCl ): d = 185.4 (CO), 153.3, 145.0, 144.0,
3
1
4
38.3, 136.2, 136.0, 132.5, 130.3, 129.5, 119.6, 119.2 (CH, Cquat),
5.7 (CH N), 43.6 (CH), 25.8, 18.1 (CH ), 21.0, 20.8 (CH ).
4-Methoxy-N-[3-methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-
dihydro-2H-1,3,4-thiadiazin-2-ylidene]benzamide (7j)
Yield: 90%; pale-yellow crystals; mp 230.0 °C.
1
3
2
3
+
MS (DEI): m/z = 419 [M ], 364, 336, 280, 269, 247, 235, 161, 131,
18, 91, 55, 29.
1
H NMR (250 MHz, CDCl ): d = 8.15 (d, J = 9.0 Hz, 2 H, CH), 8.11
3
(
s, 1 H, NH), 7.54 (d, J = 8.4 Hz, 2 H, CH), 7.28–7.13 (m, 4 H, CH),
Anal. Calcd for C H N OS: C, 65.84; H, 6.01; N, 16.69; S, 7.64.
Found: C, 65.74; H, 5.83; N, 16.58; S, 7.52.
2
3
25
5
6
2
.95–6.85 (m, 4 H, CH), 3.97 (s, 3 H, CH N), 3.84 (s, 3 H, CH O),
.38, 2.35 (2 s, 6 H, CH3).
3
3
1
3
N-[3-Methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-dihydro-2H-
C NMR (63 MHz, CDCl ): d = 173.7 (C=O), 162.8, 153.7, 145.1,
3
1
,3,4-thiadiazin-2-ylidene]-2,2-diphenylacetamide (7g)
Yield: 80%; yellow crystals; mp 166.0 °C.
144.0, 138.4, 136.2, 135.9, 132.5, 131.6, 130.4, 129.5, 129.3, 119.6,
119.3, 113.3 (CH, Cquat), 55.3 (CH O), 46.0 (CH N), 21.1, 20.8
3
3
1
(CH ).
3
H NMR (250 MHz, CDCl ): d = 8.12 (s, 1 H, NH), 7.50 (d, J = 8.4
3
+
Hz, 2 H, CH), 7.38–7.12 (m, 14 H, CH), 6.88 (d, J = 8.2 Hz, 2 H,
MS (DEI): m/z = 471 [M ], 354, 235, 161, 135, 118, 91, 77, 65.
CH), 5.19 (s, 1 H, CH), 3.75 (s, 3 H, CH N), 2.38, 2.35 (2 s, 6 H,
CH3).
3
Anal. Calcd for C H N O S: C, 66.22; H, 5.34; N, 14.85; S, 6.80.
Found: C, 65.98; H, 5.42; N, 14.90; S, 6.63.
2
6
25
5
2
1
3
C NMR (63 MHz, CDCl ): d = 181.6 (CO), 153.9, 144.6, 143.9,
3
1
1
40.6, 138.5, 136.1, 136.0, 132.7, 130.4, 129.5, 129.0, 128.3, 126.6,
19.6, 119.4 (CH, Cquat), 62.4 (CH), 46.0 (CH N), 21.1, 20.9 (CH ).
N-[3-Methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-dihydro-2H-
1,3,4-thiadiazin-2-ylidene]biphenyl-4-carboxamide (7k)
Yield: 86%; yellow crystals; mp 238.0 °C.
1
3
3
+
MS (DEI): m/z = 531 [M ], 501, 364, 337, 321, 247, 177, 165, 131,
1, 65.
9
H NMR (250 MHz, CDCl ): d = 8.26 (d, J = 8.5 Hz, 2 H, CH), 8.14
3
(
s, 1 H, NH), 7.68–7.13 (m, 13 H, CH), 6.93 (d, J = 8.3 Hz, 2 H,
Anal. Calcd for C H N OS: C, 72.29; H, 5.50; N, 13.17; S, 6.03.
3
2
29
5
CH), 4.02 (s, 3 H, CH N), 2.39, 2.36 (2 s, 6 H, CH ).
3
3
Found: C, 72.21; H, 5.54; N, 13.20; S, 6.15.
13C NMR (63 MHz, CDCl
143.9, 140.4, 138.6, 136.1, 135.4, 132.7, 130.4, 130.0, 129.5, 128.8,
): d = 173.9 (CO), 154.1, 144.8, 144.6,
X-ray crystallography data for 7g:24 C H N OS, M = 531.6 g·mol ,
–1
3
3
2
29
5
3
yellow prism, size 0.06 × 0.06 × 0.05 mm , orthorhombic, space
group P2 2 2 , a = 8.8334(4), b = 14.2969(3), c = 21.4786(7) Å,
1
27.8, 127.2, 126.8, 119.6, 119.4 (CH, Cquat), 46.1 (CH N), 21.1,
3
1
1 1
3
20.9 (CH ).
3
a = 90.00, b = 90.00, g = 90.00°, V = 2712.54(16) Å , T = –90 °C,
–
3
–1
+
Z = 4, r
= 1.302 gcm , m (Mo-K ) = 1.55 cm , F(000) = 1120,
MS (DEI): m/z = 517 [M ], 400, 333, 318, 280, 247, 181, 152, 118,
calcd
a
1
9570 reflections in h(–11/9), k(–18/17), l(–27/27), measured in the
range 2.71° £ Q £ 27.50°, completeness Qmax = 99.8%, 6230 inde-
pendent reflections, Rint = 0.0676, 4493 reflections with Fo
restraints, R1obs = 0.0494,
91, 65.
Anal. Calcd for C H N OS·0.33CHCl : C, 67.51; H, 4.94; N,
3
1
27
5
3
>
1
2.56; S, 5.75. Found: C, 67.53; H, 4.71; N, 12.82; S, 5.61.
4
s(Fo), 359 parameters,
0
wR2obs = 0.1058, R1all = 0.0871, wR2all = 0.1246, GOOF = 0.923,
N-[3-Methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-dihydro-2H-
,3,4-selenadiazin-2-ylidene]propionamide (8b)
Flack parameter –0.05(8), largest difference peak and hole: 0.175/
1
–3
–
0.248 e·Å .
Yield: 79%; pale-yellow crystals; mp 153.0 °C.
1
H NMR (250 MHz, CDCl ): d = 8.06 (s, 1 H, NH), 7.52 (d, J = 8.6
N-[3-Methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-dihydro-2H-
,3,4-thiadiazin-2-ylidene]benzamide (7h)
Yield: 83%; pale-yellow crystals; mp 229.1 °C.
3
Hz, 2 H, CH), 7.26–7.10 (m, 4 H, CH), 6.84 (d, J = 8.2 Hz, 2 H,
CH), 3.91 (s, 3 H, CH N), 2.51 (q, J = 7.5 Hz, 2 H, CH ), 2.38, 2.34
(
1
1
3
2
2 s, 6 H, CH ), 1.13 (t, J = 7.5 Hz, 3 H, CH ).
1
3
3
H NMR (250 MHz, CDCl ): d = 8.17 (d, J = 8.1 Hz, 2 H, CH), 8.12
3
3
C NMR (63 MHz, CDCl ): d = 185.3 (CO), 155.3, 149.7, 145.8,
(
s, 1 H, NH), 7.54–7.42 (m, 5 H, CH), 7.25–7.15 (m, 4 H, CH), 6.90
3
1
4
38.6, 136.6, 136.0, 132.4, 130.5, 129.5, 119.3, 118.8 (CH, C ),
(
d, J = 8.3 Hz, 2 H, CH), 3.99 (s, 3 H, CH N), 2.37, 2.34 (2 s, 6 H,
quat
3
7.1 (CH N), 33.3 (CH ), 21.0, 20.8, 9.5 (CH ).
CH3).
3
2
3
7
7
1
3
Se NMR (76 MHz, CDCl ): d = 594.09 (t, J = 2.6 Hz).
C NMR (63 MHz, CDCl ): d = 174.1 (C=O), 154.2, 144.8, 143.9,
3
3
1
1
38.6, 136.6, 136.1, 136.0, 132.6, 132.0, 130.3, 129.5, 129.5, 128.0,
19.6, 119.3 (CH, Cquat), 46.1 (CH N), 21.1, 20.8 (CH ).
+ 80
MS (DEI): m/z = 441 [M ( Se)], 412, 384, 324, 295, 243, 199, 155,
118, 91, 57, 29.
3
3
Synthesis 2007, No. 18, 2839–2848 © Thieme Stuttgart · New York

2
846
J. Fleischhauer et al.
PAPER
7
7
Anal. Calcd for C H N OSe: C, 57.27; H, 5.26; N, 15.90. Found:
C, 57.08; H, 5.28; N, 15.78.
Se NMR (76 MHz, CDCl ): d = 598.20 (t, J = 2.5 Hz).
21
23
5
3
+ 80
79
81
MS (DEI): m/z = 599 [M ( Se Br Br)], 542, 517, 491, 397, 359,
76, 229, 199, 171, 155, 91.
2
N-[3-Methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-dihydro-2H-
Anal. Calcd for C H Br N OSe: C, 42.16; H, 3.54; Br, 26.72; N,
1
1
,3,4-selenadiazin-2-ylidene]isobutyramide (8c)
21 21
2
5
1.71. Found: C, 42.27; H, 3.55; Br, 26.95; N, 11.62.
Yield: 81%; pale-yellow crystals; mp 164.0 °C.
1
H NMR (250 MHz, CDCl ): d = 8.06 (s, 1 H, NH), 7.52 (d, J = 8.5
3
N-[5-(4-Butylphenylamino)-6-(4-butylphenylimino)-3-methyl-
,6-dihydro-2H-1,3,4-selenadiazin-2-ylidene]pivalamide (8g)
Yield: 88%; yellow crystals; mp 104.0 °C.
Hz, 2 H, CH), 7.25–7.10 (m, 4 H, CH), 6.84 (d, J = 8.3 Hz, 2 H,
3
CH), 3.93 (s, 3 H, CH N), 2.67 (quin, J = 6.9 Hz, 1 H, CH), 2.38,
3
2
.35 (2 s, 6 H, CH ), 1.17 (d, J = 6.9 Hz, 6 H, CH ).
3
3
1
H NMR (250 MHz, CDCl ): d = 8.08 (s, 1 H, NH), 7.54 (d, J = 8.4
1
3
3
C NMR (63 MHz, CDCl ): d = 188.3 (CO), 155.7, 149.7, 145.8,
3
Hz, 2 H, CH), 7.24–7.09 (m, 4 H, CH), 6.86 (d, J = 8.0 Hz, 2 H,
1
4
38.5, 136.4, 135.9, 132.3, 130.5, 129.5, 119.3, 118.8 (CH, Cquat),
7.2 (CH N), 38.5 (CH), 21.0, 20.8, 19.5 (CH ).
CH), 3.93 (s, 3 H, CH N), 2.68–2.54 (m, 4 H, CH ), 1.70–1.53 (m,
3
2
3
3
4
H, CH ), 1.48–1.28 (m, 4 H, CH ), 1.22 [s, 9 H, C(CH ) ], 1.01–
2 2 3 3
7
7
Se NMR (76 MHz, CDCl ): d = 501.26 (s).
0.89 (m, 6 H, CH3).
3
+
80
13
MS (DEI): m/z = 455 [M ( Se)], 412, 338, 294, 248, 235, 161, 118,
1, 65, 43.
C NMR (63 MHz, CDCl ): d = 190.2 (CO), 155.8, 149.3, 145.8,
3
9
141.0, 138.4, 137.4, 136.6, 129.8, 128.8, 119.2, 118.9 (CH, C ),
quat
4
7.2 (CH N), 41.2 [C(CH ) ], 35.2, 35.0, 33.7, 33.5, 22.4, 22.3
3 3 3
Anal. Calcd for C H N OSe: C, 58.15; H, 5.55; N, 15.41. Found:
C, 58.10; H, 5.62; N, 15.41.
22
25
5
(
CH ), 27.6 [C(CH ) ], 14.0 (CH ).
2 3 3 3
7
7
Se NMR (76 MHz, CDCl ): d = 497.52 (s).
3
N-[3-Methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-dihydro-2H-
+ 80
MS (DEI): m/z = 553 [M ( Se)], 496, 394, 337, 267, 203, 160, 131,
9
1
,3,4-selenadiazin-2-ylidene]cyclobutanecarboxamide (8d)
1, 57.
Yield: 57%; pale-yellow crystals; mp 151.0 °C.
Anal. Calcd for C H N OSe: C, 63.03; H, 7.11; N, 12.67. Found:
C, 63.08; H, 7.11; N, 12.62.
1
29 39
5
H NMR (250 MHz, CDCl ): d = 8.06 (s, 1 H, NH), 7.52 (d, J = 8.5
3
Hz, 2 H, CH), 7.26–7.10 (m, 4 H, CH), 6.85 (d, J = 8.3 Hz, 2 H,
CH), 3.92 (s, 3 H, CH N), 3.29 (m, 1 H, CH), 2.40–2.10 (m, 10 H,
3
N-[5-(4-tert-Butylphenylamino)-6-(4-tert-butylphenylimino)-3-
methyl-3,6-dihydro-2H-1,3,4-selenadiazin-2-ylidene]pival-
amide (8h)
Yield: 83%; yellow crystals; mp 156.0 °C.
CH , CH ), 2.10–1.83 (m, 2 H, CH ).
3
2
2
1
3
C NMR (63 MHz, CDCl ): d = 186.2 (CO), 155.7, 149.7, 145.8,
3
1
38.6, 136.4, 136.0, 132.4, 130.5, 130.0, 129.5, 119.3, 118.8 (CH,
Cquat), 47.1 (CH N), 43.4 (CH), 29.7, 18.2 (CH ), 21.0, 20.8 (CH ).
1
3
2
3
H NMR (250 MHz, CDCl ): d = 8.10 (s, 1 H, NH), 7.57 (d, J = 8.8
3
7
7
Se NMR (76 MHz, CDCl ): d = 594.41 (s).
Hz, 2 H, CH), 7.47–7.33 (m, 4 H, CH), 6.90 (d, J = 8.0 Hz, 2 H,
CH), 3.94 (s, 3 H, CH N), 1.47, 1.36, 1.22 [3 s, 27 H, C(CH ) ].
3
+
80
3
3
3
MS (DEI): m/z = 467 [M ( Se)], 412, 350, 294, 269, 235, 161, 132,
18, 91, 55.
1
3
1
C NMR (63 MHz, CDCl ): d = 190.2 (CO), 155.8, 150.3, 149.3,
3
1
49.1, 145.6, 145.5, 138.4, 136.4, 126.8, 125.8, 118.9, 118.6 (CH,
Anal. Calcd for C H N OSe: C, 59.22; H, 5.40; N, 15.01. Found:
23
25
5
Cquat), 47.2 (CH N), 41.2, 34.6, 34.0 [C(CH ) ], 31.4, 31.4, 27.7
[
3
3 3
C, 59.20; H, 5.40; N, 15.12.
C(CH ) ].
3 3
7
7
N-[3-Methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-dihydro-2H-
Se NMR (76 MHz, CDCl ): d = 597.19 (t, J = 2.5 Hz).
3
1
,3,4-selenadiazin-2-ylidene]pivalamide (8e)
+ 80
MS (DEI): m/z = 553 [M ( Se)], 496, 394, 337, 203, 159, 131, 83,
5
Yield: 97%; yellow crystals; mp 167.0 °C.
7, 41.
1
H NMR (250 MHz, CDCl ): d = 8.06 (s, 1 H, NH), 7.52 (d, J = 8.6
3
Anal. Calcd for C H N OSe: C, 63.03; H, 7.11; N, 12.67. Found:
C, 62.73; H, 7.21; N, 12.42.
2
9
39
5
Hz, 2 H, CH), 7.25–7.11 (m, 4 H, CH), 6.84 (d, J = 8.2 Hz, 2 H,
CH), 3.93 (s, 3 H, CH N), 2.38, 2.35 (2 s, 6 H, CH ), 1.22 [s, 9 H,
3
3
C(CH ) ].
3
3
N-{5-[4-(ethoxycarbonyl)phenylamino]-6-[4-(ethoxycarbon-
yl)phenylimino]-3-methyl-3,6-dihydro-2H-1,3,4-selenadiazin-
2-ylidene}pivalamide (8i)
1
3
C NMR (63 MHz, CDCl ): d = 190.2 (CO), 155.9, 149.8, 145.9,
3
1
38.4, 136.4, 135.9, 132.8, 130.5, 129.5, 128.2, 119.3, 118.8 (CH,
Cquat), 47.2 (CH N), 41.2 [C(CH ) ], 27.6 [C(CH ) ], 21.0, 20.8
Yield: 90%; yellow crystals; mp 169.0 °C.
3
3 3
3 3
(
7
CH3).
1
H NMR (250 MHz, CDCl ): d = 8.28 (s, 1 H, NH), 8.11 (d, J = 8.8
3
7
Se NMR (76 MHz, CDCl ): d = 596.05 (t, J = 2.7 Hz).
Hz, 2 H, CH), 8.04 (d, J = 8.8 Hz, 2 H, CH), 7.67 (d, J = 9.0 Hz, 2
H, CH), 6.96 (d, J = 8.8 Hz, 2 H, CH), 4.46–4.31 (m, 4 H, CH
3
C(CH ) ].
13
3
+
80
2
),
MS (DEI): m/z = 469 [M ( Se)], 412, 384, 352, 295, 235, 225, 199,
61, 132, 118, 91, 57.
.96 (s, 3 H, CH N), 1.46–1.35 (m, 6 H, CH ), 1.19 [s, 9 H,
3
3
1
3
3
Anal. Calcd for C H N OSe: C, 58.97; H, 5.81; N, 14.95. Found:
C, 59.02; H, 5.68; N, 14.87.
23
27
5
C NMR (63 MHz, CDCl ): d = 190.6, 166.2, 165.8, (CO), 155.7,
3
1
52.2, 151.1, 142.8, 137.2, 131.7, 130.8, 128.2, 124.3, 118.6, 118.1
(
[
7
CH, Cquat), 61.0, 60.7 (CH ), 47.4 (CH N), 41.3 [C(CH ) ], 27.5
2
3
3 3
N-[5-(4-Bromophenylamino)-6-(4-bromophenylimino)-3-meth-
yl-3,6-dihydro-2H-1,3,4-selenadiazin-2-ylidene]pivalamide (8f)
Yield: 92%; pale-yellow crystals; mp 204.0 °C.
1
C(CH ) ], 14.4, 14.4 (CH ).
3
3
3
7
Se NMR (76 MHz, CDCl ): d = 609.10 (t, J = 2.0 Hz).
3
+ 80
H NMR (250 MHz, CDCl ): d = 8.06 (s, 1 H, NH), 7.55–7.43 (m,
MS (DEI): m/z = 585 [M ( Se)], 528, 410, 353, 325, 219, 176, 145,
83, 57.
3
6
H, CH), 6.81 (d, J = 6.8 Hz, 2 H, CH), 3.93 (s, 3 H, CH N), 1.21
3
[
1
s, 9 H, C(CH ) ].
3 3
Anal. Calcd for C H N O Se: C, 55.48; H, 5.35; N, 11.98. Found:
C, 55.53; H, 5.35; N, 11.89.
2
7
31
5
5
3
C NMR (63 MHz, CDCl ): d = 190.5 (C=O), 155.5, 151.0, 147.1,
3
1
37.9, 137.7, 133.1, 131.9, 120.7, 120.7, 120.7, 119.4, 115.2 (CH,
Cquat), 47.3 (CH N), 41.3 [C(CH ) ], 27.5 [C(CH ) ].
3
3
3
3 3
Synthesis 2007, No. 18, 2839–2848 © Thieme Stuttgart · New York

PAPER
Thia and Selena Heterocycles Containing Cycloamidine Substructures
2847
+
80
N-[3-Methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-dihydro-2H-
MS (DEI): m/z = 519 [M ( Se)], 402, 296, 235, 191, 161, 135, 119,
1
,3,4-selenadiazin-2-ylidene]-2,2-diphenylacetamide (8j)
91, 77, 65.
Yield: 86%; yellow crystals; mp 180.0 °C (dec).
Anal. Calcd for C H N O Se: C, 60.23; H, 4.86; N, 13.51. Found:
C, 60.09; H, 4.99; N, 13.41.
2
6
25
5
2
1
H NMR (250 MHz, CDCl ): d = 8.10 (s, 1 H, NH), 7.52 (d, J = 8.4
3
Hz, 2 H, CH), 7.39–7.10 (m, 14 H, CH), 6.85 (d, J = 8.2 Hz, 2 H,
CH), 5.24 (s, 1 H, CH), 3.85 (s, 3 H, CH N), 2.39, 2.36 (2 s, 6 H,
CH3).
3
Acknowledgement
1
3
C NMR (63 MHz, CDCl ): d = 182.6 (CO), 156.3, 149.2, 145.8,
We thank AlzChem Trostberg GmbH, Clariant GmbH, and Syngen-
ta Crop Protection AG for support in donating chemicals.
3
1
1
40.5, 138.7, 136.2, 136.1, 132.5, 130.6, 129.5, 129.1, 128.3, 126.7,
19.4, 118.8 (CH, Cquat), 62.1 (CH), 47.4 (CH N), 21.1, 20.9 (CH ).
3
3
7
7
Se NMR (76 MHz, CDCl ): d = 597.73 (t, J = 2.6 Hz).
3
References
+
80
MS (DEI): m/z = 579 [M ( Se)], 501, 441, 411, 332, 295, 198, 167,
55, 91
(
1) (a) Schwarz, K.; Foltz, C. M. J. Am. Chem. Soc. 1957, 79,
292. (b) Ursini, F.; Bindoli, A. Chem. Phys. Lipids 1987,
44, 255. (c) Stadtman, T. Annu. Rev. Biochem. 1990, 59,
11. (d) Forchhammer, K.; Böck, A. Naturwissenschaften
1
3
Anal. Calcd for C H N OSe: C, 66.43; H, 5.05; N, 12.10. Found:
32
29
5
C, 66.49; H, 5.02; N, 12.04.
1
2
4
X-ray crystallography data for 8j: C H N OSe, M = 578.5
1991, 78, 497. (e) Stadtman, T. J. Biol. Chem. 1991, 266,
16257. (f) Stadtman, T. Annu. Rev. Biochem. 1996, 65, 83.
3
2
29
5
–1
3
g·mol , yellow prism, size 0.05 × 0.04 × 0.04 mm , triclinic, space
group P-1, a = 10.4484(4), b = 12.0024(5), c = 12.2689(5) Å,
a = 109.661(2), b = 105.576(2), g = 91.844(3)°, V = 1382.89(10)
Å , T = –90 °C, Z = 2, r
cm , F(000) = 596, 9958 reflections in h(–13/13), k(–15/15), l(–15/
(2) (a) Kirsi, J. J.; McKernan, P. A.; Burns, N. J. III; North, J.
A.; Murray, B. K.; Robins, R. K. Antimicrob. Agents
Chemother. 1984, 26, 466. (b) Robins, R. K.; Revankar, G.
R.; McKernan, P. A.; Murray, B. K.; Kirsi, J. J.; North, J. A.
Adv. Enzyme Regul. 1985, 24, 29. (c) Gebeyehu, G.;
Marquez, V. E.; Van Cott, A.; Cooney, D. A.; Kelley, J. A.;
Jayaram, H. N.; Ahluwalia, G. S.; Dion, R. L.; Wilson, Y.
A.; Johns, D. G. J. Med. Chem. 1985, 28, 99.
3
–3
= 1.389 g·cm , m (Mo-K ) = 13.92
calcd
a
–
1
1
5), measured in the range 2.54° £ Q £ 27.46°, completeness
Qmax = 98.9%, 6261 independent reflections, Rint = 0.0292, 5008 re-
flections with Fo > 4s(F ), 357 parameters, 0 restraints,
o
R1obs = 0.0397, wR2obs = 0.0853, R1all = 0.0589, wR2all = 0.0927,
–
3
GOOF = 1.023, largest difference peak and hole: 0.446/–0.429 e·Å .
(d) Natsumeda, Y.; Yamada, Y.; Yamaji, Y.; Weber, G.
Biochem. Biophys. Res. Commun. 1988, 153, 321.
4
-Methyl-N-[3-methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-di-
(e) Franchetti, P.; Cappellacci, L.; Abu Sheikha, G.;
Jayaram, H. N.; Gurudutt, V. V.; Sint, T.; Schneider, B. P.;
Jones, W. D.; Goldstein, B. M.; Perra, G.; De Montis, A.;
Loi, A. G.; La Colla, P.; Grifantini, M. J. Med. Chem. 1997,
hydro-2H-1,3,4-selenadiazin-2-ylidene]benzamide (8k)
Yield: 54%; pale-yellow crystals; mp 235.0 °C.
1
H NMR (250 MHz, CDCl ): d = 8.16–8.05 (m, 3 H, NH, CH), 7.54
d, J = 8.4 Hz, 2 H, CH), 7.28–7.13 (m, 6 H, CH), 6.88 (d, J = 8.4
3
4
(
1
0, 1731. (f) Parker, W. B. Virus Res. 2005, 107, 165.
g) Sarma, B. K.; Mugesh, G. J. Am. Chem. Soc. 2005, 127,
5207.
(
Hz, 2 H, CH), 4.06 (s, 3 H, CH N), 2.39, 2.35 (2 s, 9 H, CH ).
3
3
1
3
C NMR (63 MHz, CDCl ): d = 175.1 (CO), 156.1, 149.6, 145.8,
3
(3) (a) Shinkai, I.; Larsen, R. D. In Comprehensive Heterocyclic
Chemistry II, Vol. 3; Pergamon: New York, 1996, 493–510.
(b) Boulton, A. J.; Smalley, R. K.; Sainsbury, M. In
Comprehensive Heterocyclic Chemistry II, Vol. 6;
Pergamon: New York, 1996, 737–783, 987–1018.
1
1
42.7, 138.7, 136.4, 136.0, 133.6, 132.4, 130.5, 129.6, 129.5, 128.9,
19.4, 118.9 (CH, Cquat), 47.4 (CH N), 21.7, 21.0, 20.9 (CH ).
3
3
7
7
Se NMR (76 MHz, CDCl ): d = 594.30 (t, J = 2.8 Hz).
3
+
80
MS (DEI): m/z = 503 [M ( Se)], 386, 235, 198, 161, 132, 119, 91,
5.
(c) Młochowski, J.; Kloc, K.; Lisiak, R.; Potaczek, P.;
6
Wójtowicz, H. Arkivoc 2007, (vi), 14. (d) Garud, D. R.;
Anal. Calcd for C H N OSe: C, 62.15; H, 5.01; N, 13.94. Found:
Koketsu, M.; Ishihara, H. Molecules 2007, 12, 504.
26
25
5
C, 61.91; H, 4.89; N, 13.90.
(4) (a) Beckert, R.; Mayer, R. J. Prakt. Chem. 1982, 324, 227.
(
b) Beckert, R.; Gruner, M.; Seidel, I.; Kuban, R.-J.
4
-Methoxy-N-[3-methyl-5-(p-tolylamino)-6-(p-tolylimino)-3,6-
Monatsh. Chem. 1989, 120, 1125. (c) Beckert, R.; Gruner,
M. J. Prakt. Chem. 1990, 332, 65. (d) Brandenburg, J.;
Käpplinger, C.; Beckert, R. Synthesis 1996, 1302.
(e) Brandenburg, J.; Beckert, R.; Fehling, P.; Döring, M.;
Görls, H. J. Prakt. Chem./Chem.-Ztg. 1996, 338, 430.
dihydro-2H-1,3,4-selenadiazin-2-ylidene]benzamide (8l)
Yield: 81%; pale-yellow crystals; mp 220.0 °C.
1
H NMR (250 MHz, CDCl ): d = 8.17 (d, J = 9.0 Hz, 2 H, CH), 8.09
s, 1 H, NH), 7.54 (d, J = 8.4 Hz, 2 H, CH), 7.28–7.12 (m, 4 H, CH),
3
(
(
f) Beckert, R.; Gruner, M. Z. Naturforsch., B: Chem. Sci.
6
2
.96–6.83 (m, 4 H, CH), 4.05 (s, 3 H, CH N), 3.85 (s, 3 H, CH O),
3
3
1
997, 52, 1245. (g) Billert, T.; Beckert, R.; Fehling, P.;
.39, 2.35 (2 s, 6 H, CH3).
Döring, M.; Görls, H. Tetrahedron 1997, 53, 5455.
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1
3
C NMR (63 MHz, CDCl ): d = 174.6 (CO), 162.9, 155.8, 149.7,
3
1
1
45.8, 138.6, 136.4, 135.9, 132.4, 131.6, 130.5, 129.5, 129.0, 119.4,
18.8, 113.4 (CH, Cquat), 55.4 (CH O), 47.4 (CH N), 21.0, 20.8
3
3
(
CH3).
7
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2
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